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Full text of "Chemical addresses delivered at the second decennial celebration of Clark University, in September, 1909"

CLARK UNIVERSITY 

'"lebration Lectures 




"> With flie compliments of the 
Department of Chemistry, 
C-LAKK UNTFER8IXY, 
Worcester, - Mass, 



fr 




THE LIBRARY 

OF 

THE UNIVERSITY 
OF CALIFORNIA 






PRESENTED BY 

PROF. CHARLES A. KOFOID AND 
MRS. PRUDENCE W. KOFOID 



CHEMICAL ADDRESSES 

Delivered at the Second Decennial Celebration of 

CLARK UNIVERSITY, 

ii 

in September, 1909, 
BY 



Professor THEODORE W. RTCHA.RDS, of Harvard University; Professor WIUJAM A. 
NOYBS, of the University of Illinois; Dr. WIMJS R. WHITNEY, Director of the Re- 
search laboratory of the 'General Electric Company; Professor JOHN E. BUCHER, of 
Brown University; Professor Juuus STiEGUTZ, of the University of Chicago; Dr. P. 
A. SEVENS, of the Rockefeller Institute for Medical Research; Dr. EDWARD W. 
WASHBURN, of the University of Illinois; Professor MARSTON TAYLOR BOGERT, of 
Columbia University; Dr. C. S. HUDSON, of the U. S. Department of Agriculture; 
Professor ARTHUR MiCHAKi,, sometime Director of the Department of Chemistry 
in Clark University; Professor S. P. MULUKEN, of the Massachusetts Institute of 
Technology; Professor H. P. TAiyBOT, of the Massachusetts Institute of Technology; 
Mr. JESSE E. WHITSIT, of the DeWitt Clinton High School, New York; Mr. MICHAKI, 
D. SOHON, of the Morris High School, New York; and Dr. ANDR DEBIERNK, of the 
University of Paris. 



With a Preface by 

M. A. ROSANOFF, Sc.D. 

Professor of Chemistry and Director of the Chemical Laboratories in Clark 

University 



Published jointly by Clark University, Worcester, Mass., and the American Chem- 
ical Society. 



1911. 



. i. 



I 



PREFACE. 

Clark University was founded in 1889 as a research university, an insti- 
tution in which the best part of the teaching and studying should be car- 
ried on through original investigation. On the one hand, and primarily, 
the University was to devote its activities to the advancement of scien- 
tific knowledge. On the other hand, it was believed that genuine 
knowledge and habits of independent thought can in no way be acquired 
by the mature university student as surely as through the labor of finding 
new truth. 

While the new university has not perhaps attracted such attention 
from the public at large as it would have received had it been attended 
by large numbers of students, it soon gained a high reputation among 
men of science both at home and abroad. It has been stated by good 
authorities that the example of Clark University has had a profound in- 
fluence on the ideals and organization of the American graduate schools 
established since 1889.* 

At the time of its foundation Clark University was almost unique in 
this country in its ideals and methods. Even at present it can boast the 
distinction of having none but research professorships : chairs unhampered 
by the burdens of elementary teaching and routine administrative work. 
If any member of the University, professor or student, fails to contribute 
his share to the advancement of his science and thus himself gain greater 
and greater mastery over it, the fault is not that of the University's 
organization. 

It seemed appropriate that the anniversary celebration of Clark Uni- 
versity should consist in a series of research conferences, and the present 
volume reproduces most of the chemical addresses of the Celebration. In 
organizing the conferences, an effort was made to have all the more im- 
portant chapters of American chemical research represented, and the effort 
was in large measure successful, owing to the generosity with which a 
majority of our chemical investigators responded to the Department's in- 
vitation. 

The technical addresses have been gradually publisned in the Journal 
of the American Chemical Society, the educational addresses in Science. 

*For example, Professor Stieglitz, reviewing the progress of American chemical 
research, says: "The greatest recent impetus to all branches of research, including 
chemistry, came, in my opinion, from the founding of Clark University, with research 
as its chief and almost exclusive field...." (See Science, Vol. XXVI, p. 700, for 
the year 1907.) 



M3679G3 



The Chemical Department of the University wishes to again express its 
deep appreciation of the honor bestowed upon it by the brilliant lecturers, 
and its confidence that their joint effort here will not have been without 
fruit. 

The Department, which has recently been placed under the director- 
ship of the present writer, also wishes to assure the chemists of the 
country that it is making a veritable effort to grow to the ideal of 
Clark University, which is the ideal of all sincerely scientific men. 

M. A. ROSANOFF. 

November. 1911. 



7 

TABLE OF CONTENTS. 

Page.* 
I. Recent Investigations in Thermochemistry. By Professor Theodore W. 

Richards X 

II. Molecular Rearrangements. By Professor William A. Noyes 9 

III. Organization of Industrial Research. By Dr. Willis R. Whitney 16 

IV. The Acids of the Phenylpropiolic Series and Their Condensation to Naph- 

thalene Derivatives. By Professor John E. Bucher 23 

V. Catalysis on the Basis of Work with Imido Esters. By Professor Julius 

Stieglitz 32 

VI. On the Biochemistry of Nucleic Acids. By Dr. P. A. Levene 42 

VII. The Fundamental Law for a General Theory of Solutions. By Dr. Edward 

W. Washburn 52 

VIII. A Review of Some Recent Investigations in the Quinazoline Group. By 

Professor Marston Taylor Bogert 70 

IX. A Review of Discoveries on the Mutarotation of the Sugars. By Dr. C. S. 

Hudson 8 1 

X. Outline of a Theory of Organic Chemistry Founded on the Law of Entropy. 

By Professor Arthur Michael 87 

XI. Progress in Systematic Qualitative Organic Analysis. By Professor S. P. 

Mulliken 104 

XII. The Outlook for a Better Correlation of Secondary School and College In- 
struction in Chemistry. By Professor H. P. Talbot 113 

XIII. High School Chemistry: The Content of the Course. By Mr. Jesse E. 

Whitsit 125 

XIV. Chemistry in Secondary Schools. By Mr. Michael D. Sohon 130 

XV. Radioactivity. By Dr. Andre Debierne 135 

*The numbers of this column arc to be found at the bottom of pages. 



RECENT INVESTIGATIONS IN THERMOCHEMISTRY. 1 

BY THEODORE W. RICHARDS. 
Received September 17, 1909. 

Within a brief space of time, the world has lost two masters of thermo- 
chemistry, Marcellin Berthelot and Julius Thomsen. To these great 
men chemical science owes much ; their places in its history are forever se- 
cure. Each, by his indefatigable labors, added both new methods and 
new data to the sum of human knowledge; and upon the broad founda- 
tion which they laid, all the subsequent development of thermochemistry 
must be built. All honor to their memories! It is no discredit to their 
faithful work that as science progresses many of their methods must be 
subjected to revision and refinement, for mankind approaches precision only 
little by little, and those workers who come later have the benefit of all 
that has gone before, with fresh energy and new years with which to im- 
prove upon it. In the same way, a few decades hence, others will perhaps 
remodel the not yet perfect work of the present generation, may possibly 
marvel at inaccuracies which have escaped our detection, and will have 
opportunities for the exercise of charity similar to those which fall to our 
own lot. 

It is not necessary to emphasize the importance of thermochemistry, 
or to trace in detail its history. You know that the first law of energy 
was applied in this science by Lavoisier and Laplace, and by Hess, before 
it was generalized by Mayer, Joule and Helmholtz. You are familiar 
with the fact that Berthelot and Thomsen and Stohmann and others 
utilized this principle to determine the heats of formation of most com- 
mon substances with some degree of approximation; and that these data 
constitute the sum and substance of our knowledge of the heat evolved 
during chemical reaction. 

Before we consider the revision of these multifarious data which is now 
in progress, it is worth while to pause for a moment and think of their 
significance. 

Thermochemistry is concerned with the total energy-change of a chemical 
reaction, and not with the change of the free energy, hence it cannot 
serve as an infallible guide to the tendency of a reaction, for preponder- 
ance of free energy, not of total energy, determines the path which a change 
will take. Nevertheless, in spite of this limitation, thermochemistry 
includes some of the most important facts of the universe within its scope, 
both for the theorist and the practical man. 

The total heat given out during any chemical change is one of the funda- 
mental thermodynamic data concerning that change. Its exact evalua- 
tion is necessary to the complete understanding of the thermodynamics 
of any reaction, and without an understanding of the thermodynamics 
of a reaction, the phenomena are only half interpreted. Although free 
energy change is that which determines the tendency of the reaction, 
bound energy is also significant, and the interpretation of bound energy 
is being realized more and more generally as one of the coming problems 
in thermodynamics. But bound energy is the difference between total 

1 Presented at the Second Decennial Celebration of Clark University, Worcester, 
Mass., on Sept. 16, 1909. 

I 



1276 GENERAL, PHYSICAL, AND INORGANIC. 

energy-change and the free energy-change, so that all these three quan- 
tities are as closely connected together as is possible. In short, the ac- 
curate determination of thermochemical data is essential to the precise 
application of thermodynamics to chemistry. 

To the practical man, perhaps, the matter takes on a different aspect 
although ultimately he, too, will profit more than he can now appreciate 
from the growth of pure thermodynamics. He is more immediately 
concerned with the every-day applications of thermochemistry, espe- 
cially the developments of heat by combustion. Our text-books of 
chemistry discuss the union of carbon and oxygen with chief emphasis 
upon the formation of carbon dioxide, but that is the least important 
practical aspect of the matter. The really essential thing is the libera- 
tion of energy, a fact which falls within the province of the thermochemist. 
Numerous other reactions less striking but no less important, including 
the maintenance of our own bodily heat, are concerned with the same 
principles and methods. Hence it is not too much to say that thermo- 
chemistry is intimately related with every breath we draw. The ac- 
curate evaluation of its fundamental quantities is, therefore, one of the 
most important fields of scientific advance, because accurate data are 
needed to provide an adequate basis for precise thinking in an inductive 
science. 

Let us consider systematically the dimensions concerned, in order that 
we may more clearly appreciate the advances which have been made 
possible in thermochemical work during the years which have elapsed 
since Berthelot and Thomsen carried out most of their work. The energy 
of heat is, of course, calculated as the product of two factors, temperature 
and heat capacity, and the accuracy of its determination is directly pro- 
portional to the accuracy of measurement of each of these dimensions. 

The advances in the accurate measurement of temperature during the 
last thirty years have been very great. In the first place the standard 
of reference, namely the hydrogen scale, has been fixed with much greater 
accuracy than at that early time. There is very little evidence as to what 
the centigrade degree, as used by Thomsen or Berthelot, really meant. 
In the next place, the vagaries of the glass-mercury thermometer have 
been studied by Crafts and others with much greater completeness and 
understanding than in those earlier days. We know now how uncertain 
its indications may be when it is not properly handled ; and we know, also, 
how to obtain very accurate results from this instrument when it is prop- 
erly made and carefully used. Again, thermometry has gained through 
the introduction of new fixed points between the old classic ones of the 
early history of thermometry; I mean the transition temperatures of 
bi-component systems. These give a firm basis for a thermometric scale 
in their neighborhood and thereby contribute to its certainty and defi- 
niteness. All these things must be considered in the thermochemistry 
of to-day and all contribute to an accuracy exceeding that of olden times. 

A further gain has to be found in the introduction of the new methods 
of measuring temperature electrically, which, when properly manipulated, 
may exceed in accuracy the readings of the mercury thermometer. One 
must not forget, however, that these methods are subject to their own 
peculiar and somewhat elusive sources of inaccuracy, and that their use 
does not yield the unqualified gain which is sometimes attributed to them. J 
1 Emil Fischer and F. Wrede have made some excellent determinations in this way. 



RECENT INVESTIGATIONS IN THERMOCHEMISTRY. 1277 

Turning now to heat capacity, we find that to some extent the same 
considerations apply. Heat capacity is, of course, determined by com- 
parison with a standard substance, and the comparison is made by means 
of some kind of thermometer. The sources of error are partly eliminated 
here, however, because the determination is a purely relative one and does 
not hark back to the absolute standard, as in the case of temperature 
change. Specific heats are reckoned by finding the rise of temperature 
in two approximately equivalent masses of substance, one the standard 
substance and the other the substance to be determined. If the same 
thermometer is used in each and the quantities of substance are so ad- 
justed that the temperature changes produced by a known quantity of 
heat energy are nearly the same, the inaccuracies of the thermometer 
are largely eliminated when the same thermometer is used as a standard 
in each set of determinations. Errors of reading the thermometer still 
appear, and indeed the range of inaccuracy here is doubled, because a 
specific heat determination depends upon four thermometer readings 
whereas temperature change depends upon only two. Obviously, how- 
ever, an error in the standard interval makes no difference. The degree 
might really be two degrees and its inaccuracy would cancel. Hence, 
although the thermometer is used for determining heat capacity, the 
uncertainties of the determination arise in part from a different source 
and are chiefly to be traced to the errors of calorimetry, which deserve 
and will receive detailed consideration in a few minutes. 

Before discussing the errors of calorimetry let us for a moment discuss 
the means of calculating the heat capacity of a given system which have 
been used in the determinations now accepted by the chemical world. 
We find upon studying the literature of the subject, that there has been 
considerable variety of usage, but that the usage has rarely, if ever, 
been precise. Marignac determined a number of specific heats by means 
of a kind of calorifer, and Thomsen also determined many by means 
of his combustion calorimeter, but these were seldom in either case within 
two-tenths of one per cent. Therefore the values calculated from them 
could not be expected to be closer than this, if as close, to the truth. 
Work of others has not yet actually been used. Berthelot relied largely 
on Marignac' s determinations or more commonly adopted very rough 
approximations by assuming that the heat capacity of the solution is 
equal to that of a like volume of water in other words, that the specific 
heat of a solution is inversely proportional to its specific gravity. This 
method of calculating may easily yield results several per cent, aside 
from the truth with concentrated solutions. 

Moreover, we find a general haziness concerning the question as to 
whether the heat capacity of the factors or of the product of reaction is 
to be used in the calculation. Should one multiply the temperature 
rise by the heat capacity of the factors in order to obtain the heat evolved, 
or is it the products which must be considered as having been raised 
through the range of temperature in question? Only very recently has 
this question been answered scientifically, and its answer is simply this: 
either the one or the other may be used, provided that it is used intelli- 
gently. When the heat capacity of the factors is used in calculating 
the result, this result corresponds to the heat evolved by the reaction 
occurring isothermally at the final temperature attained when the adiabatic 
change is completed, whatever that may be. On the other hand, when the 



1278 GENERAL, PHYSICAL AND INORGANIC. 

heat capacity of the products is used, the result corresponds to the heat of 
isothermal reaction at the initial temperature. When there is no change 
of heat capacity during the reaction, the results of the two methods 
will, of course, be identical. In other words, in this last case the heat 
evolved will be independent of the temperature at which the reaction 
takes place, according to the well-known thermodynamic rule of Kirch- 
hoff. 1 

Further uncertainty concerning heat capacity arises from the fact that 
the specific heat of the standard substance, water, changes with the 
temperature and that therefore no expression for heat capacity is definitely 
fixed without a qualifying phrase. In order to overcome this disadvan- 
tage a proposition of Ostwald's to use the absolute C. G. S. scale has been 
revived and a convenient standard of heat capacity, namely the capacity 
raised one centigrade degree by one joule of energy, has been chosen. 
This unit fixes the dimension of heat capacity much more definitely than 
the old uncertain and changing one. Out of respect to the memory of 
one of the founders of the first law of energy, the name "mayer" has been 
suggested for this unit and its introduction seems to afford help in teach- 
ing as well as to add precision to scientific statement. 2 

In the coming revision of thermochemical data all the early incomplete- 
nesses in these respects will be eradicated, and the matter will be put 
upon the best basis possible to-day. 

What now are the chief errors of calorimetry, which affect both the 
determination of specific heat and of reaction heat? 

Any one with any calorimetric experience whatsoever will recognize 
that the greatest cause of uncertainty in results of this kind is the cooling 
effect of the surroundings of the calorimeter. The errors of thermometric 
reading, of the lag of the thermometer behind the temperature of the 
surrounding medium, and all other uncertainties are trifling compared 
with this. Therefore precise calorimetry is largely a question of properly 
correcting for this cause of uncertainty, or else avoiding it altogether. 
The well-known methods of Rumford and of Regnault as amplified by 
Pfaundler, serve to a certain extent to correct for the effect of the ex- 
change of heat with the environment. But the former, although it has 
been much used in thermochemical work, is greatly at fault; and the latter, 
although far better, is still imperfect. Rumford started his determination 
as much below the temperature of the air around as he finished above 
this temperature, supposing that the intake of heat during the first part 
of the operation would balance the outgo during the latter part. We 
have been able to show that this is by no means the case at any rate 
in a vessel containing a solution and enclosed in a jacket of definite tem- 
perature. Hence Rumford's method is not a very close approximation. 
The Regnault-Pfaundler method depends upon Newton's law of cooling, 
which under certain circumstances has been shown to be fairly accurate. 
We must remember, however, that the cooling of the vessel is due to 
convection and conduction as well as to radiation, so that the exact 
fulfilment of Newton's law is hardly to be expected. Moreover the 
evaluation of the rate of cooling depends upon the taking of a number 
of thermometric readings which are "caught on the wing," as it were, 
while the thermometer is moving. Hence, although the Regnault- 

1 Richards, THIS JOURNAL, 25, 209 (1903). 
1 Proc. Amer. Acad., 36, 327 (1901). 



RECENT INVESTIGATIONS IN THERMOCHEMISTRY. 1279 

Pfaundler method may serve with sufficient approximation for quick 
reactions, it still leaves much uncertainty in reactions which extend over 
many minutes ; and even in quick reactions the lag of the cooling correction 
may introduce some error. Further, many fundamental processes are 
slow; and among them must be catalogued the determination of specific 
heat, or heat capacity, because considerable time is needed as a rule to 
communicate the heat to the substance to be studied. 

It was with a view to eliminating these disadvantages that there has 
recently been put into practice at Harvard a method of calorimetry 
which wholly eliminates the correction for cooling by causing the tem- 
perature of the environment around the calorimeter to change at the 
same rate as the calorimeter itself. It is surprising that this obvious 
and easily carried out device had not been applied before. It had, indeed, 
been suggested by S. W. Holman 1 in 1895, although this paper was un- 
known to me at the time of the first Harvard work. The somewhat 
similar device used in the respiration calorimeter of Atwater and Benedict, 
suggested perhaps even before this, is not exactly comparable. In the 
respiration calorimeter the environment is not essentially changed in 
temperature. It is merely kept constant, as is also that of the calorim- 
eter, by a suitable quantitative cooling device. Hence, so far as I am 
aware, the Harvard device was the first one in which the surroundings 
of the calorimeter were changed in temperature by any considerable 
amount during the progress of the experiment. 

If the surrounding jacket about a calorimeter is thus changed in tem- 
perature at exactly the same rate as the temperature of the calorimeter 
itself, it is obvious that the calorimeter will neither gain nor lose heat 
from its equally hot surroundings, excepting for the negligible quantity 
of heat required to warm the small quantity of air immediately in contact 
with it inside the jacket. Thus a calorimetric reaction may be made 
really adiabatic. 

Obviously there are several ways in which the outside water jacket in 
a calorimeter might be heated in order to accomplish this purpose. The 
simple device of pouring in hot water might be employed, or the water 
might be warmed by an electrically heated resistance coil, or the jacket 
itself might be made the scene of a chemical reaction of the same speed 
and thermal intensity as that within the calorimeter itself. 

Of these and other methods which suggested themselves the last named 
seemed the most convenient and suitable for a chemical laboratory. 
It has the special advantages that before the beginning of operations 
all the apparatus and material employed may be at the temperature of 
the room; that the maximum temperature attained may be easily cal- 
culated with great nicety; that no point in the system can ever exceed 
this maximum temperature, if the reaction is suitably chosen; and that 
the speed of the reaction may be simply regulated by a stop cock ad- 
mitting one of the reacting substances. A reaction easily regulated 
and well suited to this purpose, namely, the neutralization of an alkali 
with an acid, was chosen for this purpose. 

The form of apparatus originally devised consisted of a lower jacket 

containing alkali and a separate movable lid. More recently we have 

found it convenient to enclose the calorimeter wholly in a water-tight 

vessel a sort of submarine, provided with suitable conning towers or 

1 Proc. Am. Acad., 31, 252 (1895). 



1280 GENERAL, PHYSICAL AND INORGANIC. 

periscopes. 1 This water-tight compartment is wholly immersed in the 
alkali to which is added, little by little, sulphuric acid in order to keep 
the bath precisely at the same temperature as the interior, however 
much this may be changed. Violent agitation of the warming alkali 
is necessary in order that the heat may be quickly distributed throughout 
the whole mass, and the interior of the calorimeter must be agitated also 
more energetically than has usually been the custom, if great precision is 
needed. In passing, I may state that we have evidence showing that 
in the past no one has stirred his calorimeter violently enough. The 
burettes delivering the sulphuric acid into the alkaline environment 
are graduated in tenths of degrees, instead of in cubic centimeters, so 
that a small deficiency in temperature may be instantly corrected with a 
minimum of mental arithmetic. 

This form of chemical calorimeter serves not only to determine with great 
accuracy specific heats, but also to estimate the thermal output of all 
forms of chemical reactions. With it series of determinations of many 
kinds are in progress. 

In the first place let me describe somewhat more closely the determina- 
tion of specific heat with this apparatus, because upon this determination 
the calculation of all other thermochemical results must depend. Within 
the platinum calorimeter, enclosed in its submarine, is immersed a small 
platinum bottle; and inside of this bottle a carefully measured chemical 
reaction is allowed to take place which communicates its heat to the 
calorimeter. By placing in the calorimeter, in the first place water, 
and in the next place the unknown liquid whose specific heat is to be 
determined, and each time allowing the measured reaction to occur 
within the innermost platinum bottle, a direct comparison of the specific 
heats of the standard and the unknown liquid is obtained. As the results 
agree within one-twentieth of one per cent., the average of many experi- 
ments must be much nearer than this, and it is not unreasonable to be- 
lieve that the results thus obtained are at least five times as accurate as 
those of Thomson or Marignac. 

Having used this device and method for determining the specific heats 
of liquids, it is now possible to proceed with the more accurate evaluation 
of reactions in which liquids take part. In two recent investigations 
the heats of neutralization of the acids and alkalis on the one hand and 
the heats of solution of metals in acids on the other hand have been studied. 
Time does not permit the detailed statement of the various precautions 
necessary in these determinations. The former problem is of special 
interest because of its relation to the theory of electrolytic dissociation, 
and our revision of this work was prompted by the desire to discover the 
extent of the deviation of the several results for strong acids from the 
constant value, 137 calories or 57 kilo joules. Several unexpected points 
were brought out in the investigation, the most important being the 
irregularities in the results produced by the unequal distribution in heat 
during mixing and also the grave errors caused in previous results by the 
presence of carbonate in the alkali. The investigation is not yet finished, 
but has already shown that many of the accepted results are much in 
error even for this simple process of neutralizing an acid by an alkali. 

The heats of solution of metals in acids are among the most essential 

1 A device of this kind was employed by Richards and Forbes, Publications of the 
Carnegie Inst., 56, 52 (1906). 



RECENT INVESTIGATIONS IN THERMOCHEMISTRY. 1 28 1 

and fundamental of thermochemical data. The heats of formation of 
all the metallic compounds depend upon them, because through them 
the heat values are referred back to the element. Hence it is highly 
important for exactness in thermochemistry that these values be deter- 
mined vrith great precision. 

As a matter of fact, in the past certain difficulties have interfered with 
the perfection of the measurements. First and foremost among these 
is the fact that the heat of solution of a metal requires much time, and 
therefore the always somewhat uncertain correction for cooling in the 
usual method becomes a serious fraction of the whole rise of temperature. 
In the second place, the method generally used namely, the plunging 
of a weigied sheet of metal into acid, and then withdrawing it, checking 
the reactbn as soon as possible, and determining the amount dissolved 
by loss k weight is open to serious criticism. It is impossible that 
the withdrawal should be so quick as to introduce no error in the result. 

The new method of adiabatic calorimetry, recently used at Harvard, 
seems to b; especially suitable for such cases as this. With it cadmium, 
zinc, magresium, aluminium and iron have already been investigated, 
and very concordant and satisfactory results have been obtained. Here 
again much greater purity of material than has been usual in work of 
this sort wa; sought, and the results justify the trouble thus taken. There 
can be no dcubt that in these cases also the older work was defective. 

The heats of combustion of organic substances form another very im- 
portant fiek for thermochemical research. These reactions carried 
out in the cdorimetric bomb of Berthelot seemed especially suitable for 
the application of the new method of calorimetry, and formed indeed 
one of the first series of experiments to which it was applied. The com- 
bustion of sold substances such as sugar presents no difficulty and imagi- 
nation can easily picture the way in which this process might be carried 
out in an aciabatic calorimeter. Several long series of experiments 
with typical sibstances of this sort have been made in order to test the 
method, with satisfactory results. * The combustion of liquids is a more 
difficult probhm. As you well know, Thomsen endeavored to burn 
liquids by firs; vaporizing them with the help of electrically generated 
heat in his socalled "universal burner." We now know that some of 
the superfluous heat from the electric coil must have found its way into 
the calorimete", so that these results are usually too high. Berthelot 
and Stohmann on the other hand, determined the heat of combustion 
of organic liquids by saturating cellulose with the liquid, which was then 
ignited in the lomb. This latter method of procedure is evidently open 
to the error catsed by a varying loss of the organic liquid by evaporation. 
Not all the vaoor of the organic liquid spread throughout the bomb is 
capable of beirg burnt, hence Berthelot's results for volatile liquids are 
probably all t>o low. The truth would be expected to lie somewhere 
between them Thomsen's results for the more volatile liquids being prob- 
ably the more accurate because there the accidental heating from his 
apparatus was unimportant, and Berthelot's results for the less volatile 
liquids being better because there the loss through evaporation would 
cause less error. 

We sought to overcome these difficulties by enclosing the organic liquid 
in a small, /ery thin glass bulb, flattened on the sides and completely 

1 Proc. Aner. Acad., 42, 573 (1907). 



1282 GENERAL, PHYSICAL AND INORGANIC. 

full of liquid. No difficulty is found in making such bulbs, and they 
will stand several hundred atmospheres of pressure without bursting, 
if completely full of liquid, because the glass of the flattened sides is suffi- 
ciently flexible to permit of considerable compression. These closed glass 
bulbs were put inside the bomb in a very small platinum crucible, and 
upon a thin glass shelf above them was placed a small weighed quantity 
of powdered sugar. The sugar was ignited first in the usual way. This 
exploded the bulb and instantly lighted the vapor of the liquid at all 
points so that none escaped combustion. In this way we have been able 
to show that the heat of combustion of volatile organic liquids is as a 
rule distinctly higher than Stohmann and Berthelot supposed ft to be. 
We have unquestionable evidence that complete combustion of their 
vapor has at last been attained. These methods open the way to an un- 
limited amount of further experimentation, and promise to afford results 
upon which interesting theoretical considerations may be founded. 

It is a pleasure to acknowledge my thanks to my several assistants, Pro- 
fessor A. B. Lamb, and Drs. L. J. Henderson, G. S. Forbes, H. I/. Frevert, 
A. W. Rowe, R. H. Jesse, Jr., and L. L. Burgess for their expert assistance 
in these protracted and often tiresome researches, as well as to express my 
obligations to the Cyrus M. Warren Fund of Harvard University, the 
Rumford Fund of the American Academy of Arts and Science and espe- 
cially to the Carnegie Institution of Washington, for generois pecuniary 
help in the prosecution of the work. 

Before closing let me review briefly the recent advance! in thermo- 
chemistry which I have attempted to enumerate. In the first place, 
the thermometric scale has been far more definitely fixed than it was 
thirty years ago. In the next place, the determination of specific heat 
and therefore of heat capacity has been put upon a scienlffic basis and 
its precise treatment in the calculation of thermochemical results has been 
pointed out. In the next place the most serious correction tor all thermo- 
chemical results in the past, namely the cooling correction has been en- 
tirely obviated by the use of the method preventing loss of my heat from 
the calorimeter by enclosing the latter in a jacket of similarly changing 
temperature. Again the necessity for more active agitatim of the con- 
tents of the calorimeter has been demonstrated, and the necessity of the 
use of very pure materials has been put beyond question. In every case 
the effort has been made to insure the completeness of tte reaction and 
to correct for any side reactions which may take place at the same time, 
so that the final results may represent truly the data sought. In short 
the effort has been made to apply to these fundamental figtres concerning 
chemical energetics the same kind of precision which has recently been 
attempted in the revision of atomic weights; and although on account 
of the greater complexity of the problem the percentage accuracy thus 
far reached has probably not equaled that in the case of atomic weights, 
one cannot help thinking that the proportional gain ovei the previous 
investigations is perhaps as great in this case as in the other. 

HARVARD UNIVERSITY, CAMBRIDGE, MASS. 



MOLECULAR REARRANGEMENTS. 1 

BY WILLIAM A. NOYES. 
Received September 16, 1909. 

"The end of chemistry is its theory. The guide in chemical research 
is a theory" (Phil. Mag. [4], 16, 104 (1858)). With these words A. S. 
Couper began one of the most remarkable papers in the history of chem- 
istry. At the time when he wrote the system of types advocated by 
Gerhardt had come into very general favor. Chemists were busy arrang- 
ing the compounds of carbon and of other elements as well, in classes 
according to a few simple types, especially in accordance with the type 
of water and its multiples. The advantages of the system in comparison 
with what had gone before were very evident and organic chemistry 
was making rapid progress with its aid. It answered very well for the 
classification of many of the compounds then known and as a guide in 
the discovery of a great many new ones. And most of the chemists of 
that day, as always, were satisfied in working away at the discovery of a 
vast array of new facts and marshaling these in accordance with a highly 
mechanical theory with very little thought about its philosophical basis. 

Under these conditions two master spirits, Couper and Kekul, suc- 
ceeded, entirely independently, in grasping those simple principles which 
lie at the foundation of our knowledge of the structure of compounds 
of carbon. Only as the result of an unfortunate accident was Kekul's 
paper published before that of Couper. 

It is interesting, and I think profitable, for us to recall that it was 
chiefly a consideration of the philosophical basis for Gerhardt's system 
which led Couper to reject it and propose something better. In criticizing 
the system he says of Gerhardt "He is led, not to explain bodies according 
to their composition and inherent properties, but to think it necessary 
to restrict chemical science to the arrangement of bodies according to 
their decomposition, and to deny the possibility of our comprehending their 
molecular constitution. Can such a view tend to the advancement of 
science? Would it not be only rational, in accepting this veto to renounce 
chemical research altogether?" 

I have dwelt thus on Couper's point of view because it carries with 
it, as it seems to me, a lesson which we chemists of to-day may well take 
to heart. Very few are gifted with the insight of a Dalton, a Faraday, 
a Couper or a Rutherford but when a glimpse of the real things which 
lie beneath the phenomena which we observe comes to such an one it 
may, guide the development of science for a decade, for a century, or 
even, if sufficiently true, for all time. And it seems possible that if we 
directed our thoughts more toward fundamental problems instead of 
towards the accumulation of compounds and of facts which are little 
more than permutations of compounds and facts already known, more 
real progress could be made. 

The new principles proposed by Couper were very simple: First, that 
atoms show "degrees of affinity" or as we should call it, valence, and 
second, that carbon atoms can combine with each other. But these two 
simple principles have been the foundation on which chemists have built 
a knowledge of the structure of one hundred thousand compounds of 
1 An address delivered at Worcester, Mass., September 14, 1909, at the celebra- 
tion of the twentieth anniversary of Clark University. 



1369 MOLECULAR REARRANGEMENTS. 

carbon. These principles involve a knowledge of the actual arrangement 
of atoms within the molecule in the sense of the order of their successive 
attachments to each other. Thus far, at least, they are accepted by all 
active workers in organic chemistry and there is, among these, a prac- 
tically universal belief that atoms and molecules actually exist and that 
there is something in the structure of the molecules which actually cor- 
responds to our formulas. The two principles just stated have been 
further extended, especially by the study of optically active and of cyclic 
compounds to include still more definite ideas with regard to the actual 
arrangement of atoms in space and this development of stereochemistry 
has also received very general, though not quite universal, acceptance. 

For a clearer understanding of molecular rearrangements we are in 
need of more definite knowledge with regard to the nature of those in- 
teratomic forces or attractions which hold atoms together in molecules 
and which also cause atoms of different molecules to react with each 
other. Many theories with regard to these forces have been proposed 
but none has, as yet, received any very general acceptance and the majority 
of chemists feel that any satisfactory knowledge of this sort is beyond 
our reach. But in 1858 nearly all chemists believed that any definite 
knowledge of the arrangement of atoms in chemical compounds was 
impossible, yet all of the facts for the acquirement of such knowledge 
were already in their hands and it only needed a clear statement of the 
simple principles proposed by Couper and by Kekule" and the application 
of those principles in the explanation of facts already known to make 
clear the structure of a large number of substances. Is it not possible 
that the answer to other, equally fundamental questions lies at our hands 
to-day? 

It is in the hope that this may be so that I shall venture to state some 
of these fundamental questions as they present themselves to me. 

The first of these is as to the nature of the attractive forces between 
atoms. The question is, perhaps, bound up with that of the nature of 
attraction between material bodies in general and may be equally far from 
a solution. Newton seems to have assumed an attractive force as an 
inherent property of matter and most of the discussion of atomic forces 
starts with a similar tacit assumption. But, as soon as the question is 
raised the mind revolts against the assumption of a force exerted through 
space without a medium. Physics has abandoned any idea of inherent 
attractive or repulsive forces in sound, light, heat or electricity and has 
accepted a kinetic explanation instead. Is it not probable that we must 
ultimately do the same for atomic forces? The discoveries in connection 
with radium have made us familiar with the notion that the atoms are 
very complex in their structure and that their parts may possess an almost 
inconceivable amount of kinetic energy. The spectroscope long ago 
demonstrated to us that such an atom as that of iron can send out im- 
pulses through the ether similar in complexity to those impulses of sound 
which come from a whole orchestra. It seems altogether probable that 
these impulses come from motions within the atom and not from vibra- 
tions of the atom as a whole. If we think of such intraatomic motions 
as general and that such motions within the atoms may produce effects 
which are transmitted through the ether, a kinetic explanation of atomic 
and molecular attraction seems possible. 

The second question with regard to the atomic forces is whether these 

10 



ORGANIC AND BIOLOGICAL. 1370 

forces are purely attractive, resembling gravitation, or polar, partly 
attractive and partly repulsive, resembling or identical with electrical 
forces. You are all familiar with the fluctuation of opinion on this point. 
During the first half of the nineteenth century chemists came gradually 
to a pretty general agreement that the atomic forces are electrical in their 
nature. Then came the discovery of the substitution of chlorine for hy- 
drogen in organic compounds and the overthrow of the old dualistic, 
electrochemical theory. Then for several decades the question of any 
connection between electrical and atomic forces was generally ignored 
and the attractions of the atoms were considered as direct and positive, 
though, of course, specific in character. During the last twenty years, 
as the theory of Arrhenius with regard to electrolytic dissociation or 
ionization has come into quite general favor, many different writers have 
proposed theories which identify atomic attractions with electrical forces. 
Faraday's law and the whole group of phenomena which find their most 
satisfactory explanation in the theory of ionization point very strongly 
toward an intimate relation between the two in the case of electrolytes. 
But if we assume that the forces which hold atoms together in electrolytes 
are electrical it is difficult to escape from the conclusion that the forces 
are electrical in the molecules of non-electrolytes also, for the two classes 
pass over into each other so gradually that it is very hard to believe that 
after the line is passed we are dealing with a radically different kind of 
atomic force. Further than this, an electrolyte may be formed in many 
cases by two different processes, by double decomposition in solution and 
by the direct union of the elements. Hydrochloric acid, acetylene and 
probably methane (from zinc methyl and by direct union of carbon and 
hydrogen) may be cited as illustrations. The nature of the compounds 
does not seem to depend at all on whether they are formed by the one 
process or by the other. 

The idea that organic reactions are all ionic in character enables us, 
also to understand many reactions not so easily understood otherwise. 
Thus ethyl alcohol gives with phosphorus pentachloride, chlorethane, 
while phenol gives with the same reagent partly chlorobenzene, partly 
phenyl phosphate. If we assume, as seems natural, that ethyl alcohol 
ionizes to ethyl and hydroxyl while phenol ionizes partly in the same 
way but chiefly to hydrogen and phenoxy ions these reactions become 
clear : 



4 C 2 H 5 + + 3 OH- + +H++P+++++ + 5C1- = 4 C 2 H 5 C1 + H S P 
or 

4C 2 H 5 ++ 4 OH- + PC1++++ + 4C1- = 4 C 2 H 5 C1 + PC1(OH) 4 
PC1(OH) 4 = H 3 PO 4 + HC1 

3 C 6 H 5 0- + 3 H+ + C 6 H 5 + + O + H+ + P+++++ + 5C1- = 

C 6 H 5 C1+(C 6 H 5 ) 3 P0 4 + 4 HC1. 

If we accept the reasons given and identify atomic and electrical forces 
we have still the question as to the real nature of these forces, for after 
we have called them electrical and even after we have identified them, 
perhaps, as residing in electrons (Faraday's law and many other things 
point that way) we still have the inherent difficulty of conceiving an at- 
traction existing between bodies at a distance without a medium and I 
can not help a strong belief that we must ultimately have a theory for 
the attractions as an effect produced by the motions of the electrons. 

ii 



137 1 MOLECULAR REARRANGEMENTS. 

Such a belief need not interfere with our use of the idea of positive and 
negative charges as a convenient present hypothesis. It may, perhaps, 
help us to a theory with regard to a reversal of the charge which it seems 
necessary to assume in certain cases and which has led to Abegg's theory of 
normal and contravalences. The hypothesis proposed by J. J. Thompson 1 
that combination is caused by the transfer of negative corpuscles from 
one atom to another has much in its favor but it assumes inherent at- 
tractions between negative corpuscles and positive atoms or parts of 
atoms. Although the distances are small such attractions are in as 
much need of further explanation as is the force of gravity. We assume 
that the attractions and repulsions between conductors conveying currents 
or between magnets are due to motions in the ether between them. Is it 
not possible that the attractions and repulsions between corpuscles and 
atoms amy be explained in a similar manner? 

The third and last question which I wish to raise is as to the nature of 
the forces which atoms already combined with other atoms exert in the 
attraction or repulsion of still other atoms. Are these residual forces 
merely the same forces which hold the atoms in combination still acting 
past those atoms which are nearest and upon others further away or are 
they different forces as seems to be implied rather indefinitely in the 
"partial valences" of Thiele? The former idea seems simpler and more 
logical. This question is intimately associated with the mechanism of chem- 
ical reactions, the causes for the stability or instability of compounds and 
especially with questions of molecular rearrangements. As illustrations 
of facts requiring an explanation by a more intimate knowledge of forces 
of this sort we may cite the stability of the union of carbon with carbon 
in ethane as compared with oxalic acid, in propionic and butyric as com- 
pared with malonic and acetoacetic acids and in the esters of these acids 
as compared with the free acids, in benzoic acid as compared with 2,6- 
dimethyl-4-aminobenzoic acid (Am. Chem. J., 20, 813 (1898)) in hydro- 
cinnamic as compared with phenyl propiolic acid and in acetic as compared 
with trichloracetic acid. The instability of compounds similar to those 
mentioned has long been accepted as an empirical fact and it is easy to 
predict many cases where such instability will occur but the reason for 
the instability has scarcely been discussed. With one exception the 
separation always occurs between two carbon atoms, one, at least, of 
which is united to a group or atom commonly designated as negative; 
and the exception may be only apparent, for the decomposition of 2,6- 
dimethyl-4-aminobenzoic acid takes place in an acid solution in which 
the amino group is combined with hydrochloric acid and may be con- 
sidered negative. 

It is very noticeable that acetoacetic acid, CH 3 COCH 2 CO 2 H, is much 
less stable than pyrotartaric acid, CH 3 COCO 2 H. This is some slight 
indication that the separation of the carbon atoms is ionic in character, 
taking place more readily when there is a greater contrast between the 
atoms united together. It may be that, in this connection, we have 

1 "The Corpuscular Theory of Matter," p. 126. See also the recent discussion by 
Falk, School 0} Mines Quarterly, 30, 179 (1909). My own discussion of the reaction 
between chlorine and ammonia, THIS JOURNAL, 23, 460(1901), also has an important 
bearing on Thompson's hypothesis of the transfer of electrons in the union of atoms of 
the same element, Loc. cit., p. 127. 

12 



ORGANIC AND BIOLOGICAL,. 



1372 



not sufficiently considered the difference between stability and reactivity. 
Thus sodium chloride and sodium nitrate are both instantaneously re- 
active in solutions, separating between the sodium and the chlorine or 
the sodium and the nitrate group but when heated the former compound 
is extremely stable while the latter decomposes between the nitrogen 
and oxygen rather than between the sodium and the nitrate group. 

This leads me to the consideration of some of those molecular rearrange- 
ments in which I have been especially interested. When camphor is 
heated with phosphorus pentoxide it gives cymene. 



CH, 



CH, 



-CO 



CH 3 C CH 3 



CH, 



-CH- 



-CH, 



CH 3 

CH C CH 

II I 

CH C = CH 



CH 3 CH CH 3 



H,O. 



The two carbon atoms which separate from each other in this rearrange- 
ment bear the same relation to the carbonyl group as do the two carbon 
atoms which separate in either the acid or ketonic decomposition of 
acetoacetic ester. This primary separation of carbon from carbon is fol- 
lowed by the wandering of four hydrogen atoms, two of these leaving 
the molecule entirely with the oxygen. 

When camphor is heated with sulphuric acid it undergoes a different 
rearrangement, giving -acetyl-o-xylene (Armstrong and Kipping, /. 
Chem. Soc., 63, 81). 



CH, 



CH 



CH 2 - 



CH, 



-c- 



-CO 



CH, 



CH, 



-CH- 



-CH 2 



CH 



CH 

II 
C-CH, 

C CH, 



4 H. 



Here the rearrangement is much more complex and we must assume 
two primary separations of carbon atoms, both of which are again in the 
same relation as before to the carbonyl group. We have then a different 
carbon atom uniting with one of those which has separated, forming a 
six- ring and a transfer of a methyl group from one carbon atom to another, 
a transfer that has been noticed so many times in other compounds that 
it can no longer be considered abnormal. Four hydrogen atoms are lost 
but it is not necessary to consider that more than one hydrogen atom 
has wandered within the molecule. 

When either dihydrohydroxycampholytic acid or a-campholytic acid 
is allowed to stand for a short time with dilute sulphuric acid (i : i) 
it is transformed into /?-campholytic acid. 



CH, 



-C CH 3 

II 
CH 



CO 2 H CH CH 2 
a-Campholytic acid. 




CO 2 H- 

j9-Campholytic acid. 



1373 



MOLECULAR REARRANGEMENTS. 



If /3-campholytic acid is allowed to stand with concentrated hydro- 
bromic acid it passes back to the hydrobromide of d/-a-campholytic 



acid : 



/ 



CH 8 
CH 



CO,H C- 



CH 2 
-CH, 



Vxiio\ 

>< 

CH/ 
CO 2 H ( 


/CH 3 

v Q/ 


CH 2 
^H CH 2 



/?-Campholytic acid. dZ-Hydrobromide of a-<5ampholytic acid. 

The latter compound may lose hydrobromic acid and give dl-a-cam- 
pholytic acid, or it may exchange its bromine for hydroxyl giving dl-a- 
hydroxydihydrocampholytic acid (Walker and Cormack, /. Chem. Soc., 
77, 380; Noyes and Blanchard, Am. Chem. J., 36, 285 ; Noyes and Patterson, 
Ibid., 27, 426). 

In both of these transformations the methyl group separates from a 
carbon atom adjacent to a carbon atom which is doubly united to a third, 
just as in the acetoacetic ester the separation is from a carbon atom adjacent 
to one which is doubly united to oxygen. A similar relation, but with 
some variation is found in the transformation of the nitroso derivative 
of the anhydroaminolauronic acid to laurolene (Noyes and Derick, /. Am. 
Soc., 31,669(1909)). 

CH 3 CH, 

^C 




CH, O 



CH 2 . 



H 



HNO 



CH 8 CH CH 3 



Here the carbonyl group leaves (as carbon dioxide) a carbon atom 
attached to another which is united only to carbon. Doubtless the 
vibrations set up in the molecule at the moment of decomposition are an 
important factor in this rearrangement. 

The pinacone-pinacolin rearrangement is, perhaps, the first of this 
type which was studied. 

OH 

CH,\ 

5i CH 3 ^c co CH S . 

CH/ 

Tiffeneau and his collaborators have recently studied very many re- 
arrangements similar to these, phenyl and other groups as well as methyl 
being transferred in many cases. 

These shiftings of groups seem to take away from under us one of the 
most important principles on which we rely for the determination of 
structure, the principle that groups of atoms pass from one compound 
to another without changing their mutual relations. But when we think 
of the matter a little further we see that in all chemical reactions we 
expect the atoms to separate from each other at some point, and the only 
thing which surprises us is that a separation has taken place at a point 




ORGANIC AND BIOLOGICAL. 1374 

where we did not expect it. We can already see some empirical relations 
between the compounds in which these separations and rearrangements 
take place and can predict to a certain extent where they are liable to 
occur. But we are still wholly in the dark as to the real forces which 
lie behind and are the cause of the transformations. 

J. J. Thomson, Rutherford and others have shown that in the phe- 
nomena of conductivity of gases and of radioactivity we have new and 
most powerful means of studying the properties of matter and energy 
which have thrown a flood of light upon the nature of atoms. Ostwald 
at the other extreme has wished to discard atoms altogether and to explain 
structural organic chemistry on the basis of thermodynamics. Richards, 
from a somewhat intermediate point of view but with distinctly more 
sympathy with Ostwald than with Thomson, has given us a conception of 
compressible atoms which is surprisingly like the latter's corpuscular theory 
of chemical combination as developed in his latest book. Michael wishes 
to explain phenomena of this sort by the law of entropy. Thiele, imbued 
with the ideas of structure, explains them in part by partial valences. 
Still others have attempted to study such problems from the properties 
of crystals, the absorption of light, and a great variety of other phenomena. 
The great number of properties which must finally be coordinated in 
any true explanation of atomic and molecular forces is discouraging and 
gives some basis for that agnostic point of view which considers the 
number of possibilities infinite and that we can never hope for a knowl- 
edge of the truth even as to the existence of atoms. Let us rather take 
the more hopeful view that some one, in a not too distant future, will 
give us a simple and comprehensive theory of the nature of atoms and of 
the forces which bind them together in compounds. The one who is 
to do this must not look at science as cut up into water-tight compart- 
ments but must be able to coordinate the evidence which conies from 
workers in many diverse fields of chemistry, of physics and of other 
sciences. 

URBANA, ILL. 



ORGANIZATION OF INDUSTRIAL RESEARCH. 1 

BY WILLIS R. WHITNEY. 
Received November 6, 1909. 

The intimate connection between the purely scientific research of a 
people and its advance in the art of good living cannot be too frequently 
discussed. The organization of industrial research involves arranging 
and maintaining a body of involute parts as an operative whole of high- 
est efficiency. It is never perfectly accomplished, and the fact that 
improvement can always be made is an incentive for its discussion. 

A recent copy of Life has this to say, which, without straining, bears 
direct upon industrial research: 

"This is the most interesting country in the world. The game here 
is the biggest that is being anywhere played. The problems of humanity 
that are being worked out here are the greatest problems under considera- 
tion, and the prospect of solving them is better than it is anywhere else." 

Lord Bacon said: "The real and legitimate goal of the sciences is the 
endowment of human life with new invention and riches." He, in turn, 
cited King Solomon, who said, "it is the glory of God to conceal a thing, 
but the glory of a king to search it out." 

Bacon distinguishes three degrees of ambition: 

First, that of men anxious to enlarge their own power in their own coun- 
try. This is "vulgar and degenerate." 

Second, that of men who strive to enlarge the power and empire of 
their country over mankind. This is "more dignified, but not less covet- 
ous." 

Third, that of those who strive to enlarge the power and empire of 
mankind in general over the universe. Evidently this is the best, and 
is the real ambition, whether recognized or not by himself, of any good 
experimenter. 

For purposes of systematic analysis, the subject, "Organization of In- 
dustrial Research," may be divided into two parts: 

Part one, the personal or mental organization, with its requirements, 
etc. 

Part two, the objective or material organization. 

For brevity, these may be called the mind and the matter organiza- 
tions. 

The former, or personal, I will subdivide into such parts as: 

Its training and characteristics. 

Division of its labors. 

Its records, etc. 

The objective or matter organization, I divide into : 

1 An address delivered at the Twentieth Anniversary of Clark University, 
Worcester, Mass., Sept. 17, 1909. 

16 



GENERAL, PHYSICAL AND INORGANIC. 72 

The fields for material research. 

The laboratory equipment and systems of its material co-operation. 

Naturally, the personal comes first, relatively and chronologically, 
and the mental precedes the material. The personal factor is everything 
in industrial research. Strangely enough, it is everywhere and always 
dominant, while every other factor is sometimes recessive. In an organ- 
ization "A" cannot work well with "B" because one is too slow, too 
fast, to egotistical, too jealous, too narrow, etc. Nowhere else do the 
personal traits protrude so much as in concerted research. And so I 
hold that above all, as an industrial experimenter, I should like as broad 
a human training as possible, before any other specific one. This proba- 
bly means little more than acquirement of a demonstrated desire to play 
fair, and it may be no more applicable to this field than to others. 

To one always in close touch with research, it seems as though there 
is an immutable law of nature which may be stated as follows: (It is 
an application of the principle of reversible reactions so as to include the 
reactions of the mind.) 

The equilibrium between mental and material conception is so sensi- 
tive that anything which, to the fair mind, seems possible, is to the trained 
persistence permissible. If this should be proven not strictly true, it 
would still be a good working hypothesis for a research organization. 

This theory requires, then, a certain characteristic in the generally 
successful research operator. This is recognized in optimistic activity 
and, to my mind, should be placed first among the requisites. It is placed 
above knowledge, because, without it, little that is new will ever be done 
except by accident. With active optimism, even in absence of more 
than average knowledge, useful discoveries are almost sure to be made. 

Speaking from personal analysis and from the observation of others, 
I would say that general-chemical and physical knowledge may some- 
times be as much a detriment as a help to one imbued only with a need 
of solving new problems. A possible explanation is this: We always 
reason deductively. We apply general laws in attempting to answer 
specific questions. To any specific problem of research there are usually 
general laws which may seem to forbid the solution. These laws are 
known and revered. Naturally, the unknown, specific ways by which 
it may be solved are more or less hidden. An illustration may not be 
out of place here : 

Cotton may be dissolved in a solution of zinc chloride. The solution 
may be squirted through a die into alcohol in such a way that a smooth, 
coagulated cellulose thread is thereby obtained. This may be heated 
so as to give a solid, compact and pure carbon filament. Many are thus 
made. But as a new problem, it would certainly appear quite imprac- 
ticable to one who might have a fairly extensive knowledge of the chem- 
istry of the materials. Generally speaking, zinc chloride solution does 
not dissolve cellulose. Only a strong solution, kept at a high temperature 
for a long time, will give the desired solution. In general, too, it could 
not be squirted and coagulated into a smooth thread. Very specific 
conditions are necessary. Finally, the treatment with gradually rising 
temperature, which alone succeeds in giving the compact carbon fila- 
ment, is a matter of specific detail. The places in this process where 
general reasoning points to failure are numberless. Years of multiplied 
effort are necessary to perfect such a process. Once established, it is 

17 



73 ORGANIZATION OF INDUSTRIAL RESEARCH. 

easily analyzed along the lines of understood reason and theories of re- 
actions may be based upon the facts. But such processes are not laid 
out greatly in advance of their accomplishment. The successful steps 
are found among the many which are actually attempted, and something 
more than general knowledge is necessary. This something is hopeful 
pertinacity, optimistic activity. To a chemist imbued with fair knowl- 
edge, it was recently apparently useless to attempt such an experiment 
as the continual removal of traces of hydrogen from oxygen by passing 
the gas through a red-hot iron pipe. He had seen iron wire burned 
rapidly in oxygen, he tried wrought iron and the iron was oxidized, and 
his knowledge was vindicated, but he also tried cast iron and found that 
it did not burn and that it would operate perfectly. A scramble for an 
explanation evolved the theory that the silicon burning to silica protected 
the iron. Ex. postfacto theories are permissible. 

As the mental world is constituted, optimists are greatly in the minority, 
when one counts those only who are also imbued with knowledge. There- 
fore, in practice, the optimist must be used to crystallize the efforts of 
others less optimistic. Thus, any large industrial research laboratory 
is soon perforce, systematized into organized clusters of people, working 
along distinct and different lines. This permits, in our case, of the 
combined use, to maximum efficiency, of the delicate hands of young 
women, the strength and skill of trained mechanics, the mind of the use- 
ful dreamer, the precision and knowledge of the skilful chemist, and the 
data of the accurate electrical engineer. 

Simple mathematical axioms make clear the fact that a group of opera- 
tors working together on a subject, are related to the same group opera- 
ting separately, as a power is related to a simple sum. This principle 
holds as well among a group of groups and to related subjects. It is evi- 
dent, for example, that knowledge gained along the line of insulation 
would be of use in a study of conduction, and that the man who had 
studied the reduction of tungstic oxide by carbon in vacua could help 
the one who is working with a pressure furnace, upon the equilibrium 
between carbon monoxide and carbon dioxide. Therefore, the strength 
of a research department, properly operated, should rise exponentially 
with its numbers. 

To this audience, the importance of highest advance in specific chem- 
ical and physical training will probably be apparent, but an expression 
of it may be of use. The supply of highly trained men is below the de- 
mand. There is a healthy supply of moderately trained men. This 
applies to all general, scientific training. Let me give more concrete 
ideas. There are a hundred chemists who can fill satisfactorily an analyst's 
position, to one who knows what J. J. Thomson has done or who reads 
Drude's Annalen. Reading the Annalen is not a "sine qua non," but it 
is an indicator of no little merit. If a chemist or a physicist is not suffi- 
ciently interested to keep informed, he is probably not going to work at 
high efficiency as an investigator. This does not preclude the possibility 
of splendid research work being done by some one who is confined to a 
very limited field of vision, but such cases are the exception and cannot 
be used as bases for common application. In general, the man with the 
best tools and with the best knowledge and experience in their use, will 
advance most rapidly in industrial research. In my own experience, 
we frequently have a line of work which demands the addition to the 

18 



GENERAL, PHYSICAL AND INORGANIC. 74 

force of well trained men. The difficulty which stands out most mark- 
edly when considering this problem is usually the scarcity of men who 
are highly enough trained along the line of pure research. While in many 
fields of industrial research new and brilliant discoveries will continue 
to be made suddenly and, as it were, out of new cloth, still many more 
are being made by the most careful application of highly refined methods 
and knowledge, to processes which already seem at first pretty well worked 
out. This intensive farming is most promising and demands the highest 
skill. It is to-day most difficult to find American trained men who can 
do this work. It is a German attribute which we would do well to make 
our own. 

If the chemist is only a chemist or the physicist confined to pure physics, 
he is liable to overestimation of the laws he learns. He should be some- 
thing of a "mental mixer," one who has enough history, enough psy- 
chology, and enough faith to read possibility of acquirement for the future 
out of knowledge of attainments in the past. 

As we have said, one of the most practical detriments to successful 
industrial research is that automatic action of the mind which recognizes 
the possible grounds for a failure quicker than it sees the probable ways 
to success. Research needs more aviators. Those of us who feel the 
work-horse brand on our work have a call to cultivate a flying spirit, 
and are to be condemned only if we stand still. 

In this connection, I am in favor of anything which helps train the 
American student in the path of sanguine research. It can be done Jay 
research men themselves, but probably not by others. It is not the 
knowledge which the student preparing for research needs, so much as the 
spirit of the investigator. His thoughts should not be fettered by laws, 
but helped by them to fly. This can be done best by those who are opti- 
mistic almost to the extinction of reason. 

A search in the research laboratories of the world to-day would dis- 
close large numbers of J. J. Thomson men, Ostwald men, Nernst men, 
van't Hoff men. The teacher probably made the school. The investi- 
gator probably endowed the students, not with facts alone, but with 
spirits. We are not of that hopeless class who assume that the sparks 
of genius are only Heaven-sent, but we are inclined to adopt as an axiom 
that man is flexible, auto-corrigible and mentally elastic beyond limit. 
Therefore the rare genius in research, as elsewhere, is the one most given 
to hopeful effort. 

To dwell for a moment upon points in a system for co-operation of a 
research force, I will describe our own scheme. 

The present corps comprises about eighty people, about thirty of whom 
are college men, mostly chemists. Every man or woman on the 
research staff is expected to give undivided effort to the work. 
Whatever invention results from his work becomes the property of 
the company. I believe that no other way is practicable. An attempt 
to reward systematically such labors by a scheme of royalty payment 
is more impracticable than the operation of a manufacturing plant upon 
a graded scheme of profit sharing. In this case an immediate and fairly 
equitable division of profits is sometimes possible. In research, the 
problem itself is an asset of the organization. Both the equipment 
and the risks belong to the organization. The accumulated experience 
of the force as a whole is its property. Finally, the privilege of direct- 

19 



75 ORGANIZATION OF INDUSTRIAL RESEARCH. 

ting the work of operators along lines where no direct financial benefit 
(or an immeasurable one) to the company could ever be determined, 
must belong to it. Every operator is expected to keep good notes and 
his books become a part of the laboratory files. In most cases weekly 
typewritten reports are made by each worker, and copies of these also 
become part of accessible library files. For purposes of establish- 
ment of dates, etc., witnesses who read and understand the notes also 
endorse them. Photographs of apparatus, curves, etc., are frequently 
added wherever useful, and each room of the laboratory is photographed 
regularly and the dated photographs are bound in books, to record stand- 
ing conditions. Wherever practicable, single sheets, of standard reporr 
size, are printed to cover oft-repeating data, so that the experimenter 
regularly fills in certain blanks, as, for example, in experiments on carbon 
motor brushes: the composition of the particular lot, temperature and 
time of drying and firing, hardness, resistivity, tensile strength, and all 
other tests of the product. The use of plotted curves on standard milli- 
meter paper, for use where one property of material is studied as a func- 
tion of some other variable, is very common in our reports. This occurs, 
for example, in practically all cases where electric furnace work is de- 
scribed, and where the changes undergone by incandescent lamps during 
their life are recorded. 

These conditions are the result of eight years of development. The 
system has been subjected to many changes and may still be greatly im- 
proved. It is possible to have such a complex system of record that 
efficiency is sacrificed. We have reached the present stage because of 
frequent indications of previous weakness in the simpler methods. Very 
few good investigators can keep good notes. The more interested the 
investigator becomes, the more difficult it seems for him to carefully 
record his passing work. His eyes and mind are always upon the ex- 
citing and more interesting advance. It seems not so tempting to actually 
make history by the writing as to metaphorically make it by the concep- 
tion or experiment. 

We now come to the material side of the subject. 

In the early days, the same hands which mined the iron ore and operated 
the bellows, also forged the sword and plowshare and touched the goods 
which were the equivalent in exchange. The records of the development 
through which the distribution of the steps of such processes has gone is 
what we call the history of man. It is not always easy to recognize the 
extent to which this development is progressing in our own time. Sta- 
tistics ought to show us, but these often fail to impress us. It may be 
that if used to a limited extent to armor an argument, a few data will be 
of interest in connection with industrial research. 

The known chemical compounds of the earth are myriads. The still un- 
known, but knowable, are certainly many myriads more, but any consid- 
eration of either great mass is too huge a task. We may, however, con- 
sider for a moment a part of the alphabet from which that language is 
made. We will consider research as applied to the metallic elements alone. 

There are about 75 elements. About two-thirds are metals. Of these, 
only a very few can be said to have been the subject of much industrial 
research. It is impossible to accurately measure the extent to which an 
element has been studied with a view to its possible use by the race, but 
we have no difficulty in recognizing that iron and copper have been much 

20 



GENERA!,, PHYSICAL AND INORGANIC. 76 

studied, while calcium and silicon have not. In these illustrations we have 
not selected rare elements. The calcium and silicon, which have been least 
used by man thus far, are more common than copper or iron. A natural 
explanation of the lack of development of such elements is a lack of need, 
but this is possibly incorrect. Copper, iron, etc. , were certainly first obtained 
by accident as distinct from design. The uses to which they could be put 
were later developed by trial. The finding of some uses established the 
further supply, which insured the subsequent discovery of new uses. This 
mirrors the history now being made by new elements such as silicon. 
Only in the past year the commercial production of this element has been 
begun, and about 500 tons were sold for a deoxidizer in steel-making. 
Thus a substance absolutely out of reach of almost every chemist a few 
years ago, can now be obtained as cheaply as zinc. 

Similarly, future needs, which only calcium, for example, can meet, 
are certain to be developed. More calcium will then be made. The cost 
of production will be reduced and the field of its usefulness will again 
and ever afterward continue to broaden. Never in the history of the 
world has the rate of iron production been so great as at present (nearly 
two million tons a month by the U. S. Steel Company alone). Copper is 
being mined more rapidly than ever before. We have ourselves seen the 
industrial birth and growth of a new metal which points to the great 
possibilities in case of the other unused elements. I refer to aluminium. 
Only two to three tons were made as late as 1884 while furnaces now 
exist which are capable of yielding three to four times this quantity every 
hour of the day and night. Its present uses could only have been, and 
were, very imperfectly predicted, before actual industrial research made 
tentative use of it. So it must be with other elements. One is not too 
bold who assumes that all the elements which are found in abundance 
will be industrially utilized when they have been economically isolated 
and thoroughly investigated. 

I am considering the metallic elements only in order to point out in a 
concrete manner the need of high-quality research, physical, chemical, 
electrical, etc., in the simplest field. Evidently this field, among com- 
pounds of the elements, is again bounded only by the infinite. I am im- 
pressed with the idea that the commonest elements in nature have not 
been studied with anything like the care which has been given to those for 
which the demands are already developed. 

In our age, a single investigator will probably not isolate, in large 
quantities, the metal tellurium, for example, and also put it to use to 
fill one of his individual needs, as did the warrior who first fashioned an 
iron blade or axe. The men who develop the myriad uses to which the 
common element titanium will be put, will have to rely upon the previous 
work of many investigators. It is in this respect that the conditions are 
continually changing, and always in one direction. I call it the direction of 
specific complexity. Our wants are very complex. We are learning to 
demand very specific properties. It is this fact which makes necessary 
the research work of the specialist, the specific or narrow investigation 
of the pure scientist, the pioneer work of the trail-blazer, the crude and 
hurried trials by the inventor, the long and exacting developments of 
the practical application in the factory, etc. Demands for new materials 
do not really precede the discovery of the product, any more than the 

21 



77 ORGANIZATION OF INDUSTRIAL RESEARCH. 

demand for high-speed tool steel preceded the discovery of the prop- 
erties of the chrome-tungsten-iron alloys. With the material dis- 
covered, its properties known, the world apparently could then hardly 
get along without it. This means that necessity is not the mother of 
invention. Knowledge and experiment are its parents. It sometimes 
happens that a successful search is made for unknown material to fill 
well recognized and predetermined requirements. It more often happens 
that the acquirement of knowledge of the previously unknown properties 
of a material suggests its trial for some new use. These facts strongly 
indicate the value of knowledge of properties of materials and indicate 
a way for research. 

Among the recently developed uses for modern metals which were 
certainly not surmised until the metal itself had been made easily available, 
are the use of aluminium and silicon as deoxidizers in steel-making, where 
all the silicon and a large part of the aluminium are now used. This 
discovery of utility by experiment, rather than the discovery of material 
by force of necessity, is again illustrated by the metals titanium and vana- 
dium. The former is used in arc lamps because it was found, by experi- 
ment, to give a good light. (Your Worcester streets are lighted by it.) The 
latter has been surprisingly useful in steel-making, where a fraction of 
i per cent, has been found to impart additional strength to the steel. 
In this way, about a thousand tons of vanadium are now used annually 
in America. 

When the first step is taken from the study of the supply, production 
and utilities of our metallic elements, the next step is apparently along 
the lines of alloys and we readily see how quickly the field widens. The 
recent great advances in scientific foundation for much study are to be 
attributed to the physical chemists, to such men as Tamman and his 
school. In their work we begin to see the magnitude of the alloy field. 
There are probably over a thousand pairs of metals whose properties as 
alloys are still absolutely unstudied, and for alloys of three or more metals 
the number is legion. 

It seems as though our advance could be quickened by a greater in- 
timacy with the newly cheapened elements. When sodium, chlorine, 
bromine, silicon, magnesium, chromium, cobalt, manganese, tungsten, etc., 
etc., are many times as available or cheap as they were only ten years 
ago, it is probable that the possible uses are not up-to-date. 

The field of material research really divides into two parts: the search 
for more economical production and the search for wider application. These 
two go hand in hand. If the one advances, the other is led along. In 
this way, in our laboratory, the knowledge of such elements as carbon, 
as in its forms of graphite in lamp filaments, in motor brushes, in electrodes, 
etc., has been widely and continually advanced. The result is not 
a conclusion that we know all about carbon, but rather that it still pre- 
sents a wonderful field for useful research. 

From the materials worked upon, to the tools is a step. Our experience 
here is concrete and clear, and we want to record our impressions. Good 
tools, new tools, rare tools, are most valuable. No good tool lives long 
for a single use alone. Many times we have questioned the advisability 
of installing some new apparatus a vacuum furnace, a pair of metal rolls, 
some special galvanometer, some microscope, an hydraulic press, a power 

22 



ORGANIC AND BIOLOGIC AL,. 78 

hammer, a steam digester, etc., etc. Never, after it became a part of the 
equipment, has it seemed possible to proceed without it. In the single 
case of the electric vacuum furnace, for example, our laboratory has made 
almost continual use of from three to eight for the past five years. The 
laboratory, piped several years ago with high vacuum and with electro- 
lytic hydrogen, besides steam, air, water and gas, will probably never 
operate without them. 

Similarly, this applies to a library. In general, the most useful and 
fertile of our investigators use the library the most. This is as it should 
be. The recorded research work in a library of a few thousand volumes 
frequently represents the work of millions of work-hours, and there is 
little excuse for not availing oneself of the published experience of others. 
A library containing ten of the leading research journals of the world 
may be said to have in each volume about 100,000 available brain-power- 
hours. So a library corresponds to a charged storage battery of great 
capacity. 

RESEARCH LABORATORY. GENERAL ELECTRIC Co., 

SCHBNBCTADY, N. Y. 



THE ACIDS OF THE PHENYLPROPIOLIC SERIES AND THEIR 
CONDENSATION TO NAPHTHALENE DERIVATIVES. 1 

BY JOHN E. BUCHER. 
Received December 9, 1909. 

In an investigation of the action of acetic anhydride on acids of the 
acetylene series in 1895, Michael and Bucher 2 obtained the anhydride 
of a new acid from phenylpropiolic acid. Three years later, 3 after a 
thorough study of the compound, they proved it to be the anhydride of 
i-phenyl-2,3-naphthalenedicarboxylic acid. It was found to have the 
composition corresponding to the formula C^H^Og and a molecular 
weight of 274. 

This corresponds to the composition of a phenylpropiolic anhydride 
(C 8 H 5 .C H= C.CO) 2 O, but the acid obtained from it was found to be sat- 
urated and entirely different from phenylpropiolic acid. This structural 
formula evidently does not represent its constitution. 

It seemed probable that three molecules of the acid might have 
polymerized to triphenyltrimesic acid in a manner analogous to the for- 

C.CO 2 H 




C 6 H 5 . 
H0 3 C.cl Jc.C0 2 H 

C.C 8 H 8 

1 Presented at the Second Decennial Celebration of Clark University, Worcester, 
Mass., September 14, 1909. 
7 Ber., 28, 2511 (1895). 
1 Am. Chem. ] ., 20, 89 (1898). 

23 



213 



ACIDS OF THE PHENYLPROPIOLIC SERIES. 



mation of benzene from acetylene. The resulting acid was found to be 
dibasic and to have only two-thirds of the required molecular weight. 
These facts showed conclusively that the compound is not the anhydride 
of triphenyltrimesic acid. 

It was then thought possible that the compound might be the anhy- 
dride of diphenyltetrenedicarboxylic acid. 

C 8 H 6 .C r -i C.C0 2 H 



C,H 8 .C 



C.CO 3 H 



This acid would contain two carboxyl groups in the ortho position and 
it would be dibasic. One might expect benzil among the oxidation 
products of such an acid but many experiments failed to show the slightest 
trace of this substance. It was not possible to find any evidence in 
favor of the tetrene formula. 

As none of these three formulas corresponded to the compound, it 
was evident that the polymerization of the phenylpropiolic acid must 
have proceeded in a very unusual manner. 



H0 2 C. 
H0 2 C. 




,C.CO 2 H 
.CO,H 



CH 



24 



ORGANIC AND BIOLOGICAL. 214 

They finally succeeded in isolating diphenyltetracarboxylic- and ortho- 
benzoylbenzoic acids from its oxidation products and in preparing its 
hydrocarbon. The hydrocarbon was also oxidized to orthobenzoyl- 
benzoic acid. The preceding formulas show these transformations. 

These facts can only be explained by the above constitutional formula 
and the compound is therefore the anhydride of i-phenyl-2,3-naph- 
thalenedicarboxylic acid. 

Later, several investigators who evidently had overlooked the above work 
obtained this compound. Basing their reasoning on insufficient experi- 
mental evidence, they described the substance first as the anhydride of 
triphenyltrimesic acid and afterwards as that of diphenyltetrenedicar- 
boxylic acid, representing structural formulas which had already been 
shown to be untenable by Michael and Bucher. For example, Lanser 1 
obtained the compound by heating phenylpropiolic acid with phosphorus 
oxychloride, and assigned the formula C^HgoOg for triphenyltrimesic 
anhydride without making molecular weight determinations. 

A little later Manthey 2 determined the molecular weight thus showing 
the formula to be C 18 H 10 O S and that the constitution must be different 
from that assigned by Lanser. This evidence together with the fact 
that the acid contains the two carboxyl groups in the ortho-position, 
led him to assign the tetrene formula. 

In a later paper, Lanser and Halvorsen 8 acknowledge the correctness 
of Manthey 's experimental work and they also accept the tetrene formula. 
The reactions which they study would, however, apply equally well to 
other ortho-dibasic acids. 

Ruhemann and Meriman 4 also obtained the anhydride in studying the 
action of phenylpropiolyl chloride on acetone in pyridine solution. 
They proved the identity of their compound with that of Lanser and 
regarded it as a terene compound as they did not investigate its con- 
stitution. 

Michael 5 next showed that the compound described by these investi- 
gators is i-phenyl-2,3-naphthalenedicarboxylic anhydride. He proved 
this by preparing a specimen by Lanser's method and finding it identical 
in every respect with a specimen prepared by the method of Michael 
and Bucher. 

Recently, Stobbe* obtained this anhydride by the action of light on 
dibenzalsuccinic anhydride. Failing to get diphenyltetracarboxylic 
acid by direct oxidation but obtaining ortho-benzoylbenzoic acid, he 
claimed to have shown the truth of the naphthalene formula of Michael 
and Bucher for the first time. 

These investigators 7 showed that his failure to get the diphenyltetra- 
carboxylic acid was due to incomplete oxidation 8 and that they had 

1 Ber., 32, 2478 (1899). 

2 Ibid., 33, 3083 (1900). 
1 Ibid., 35, 1407 (1902). 

4 J. Ckem. Soc., 87, 1389 (1905). 

8 Ber., 39, 1908 (1906). 

Ibid., 40, 3372 (1907). 

7 Ibid., 41, 70 (1908). 

1 Tins JOURNAL, 30, 1246 (1908). 

25 



215 



ACIDS OF THE PHENYIvPROPIOLIC SERIES. 



noticed the formation of ortho-benzoylbenzoic acid by the direct oxida- 
tion 1 of the anhydride as well as from the hydrocarbon. 

Pfeiffer and Moller 2 have polymerized phenylpropiolic ester to the 
ester of i-phenyl-2,3-naphthalenedicarboxylic acid by simply heating 
to 200. They point out that aromatic acetylene derivatives may thus 
be polymerized to naphthalene derivatives without the use of condensing 
agents. The earlier work of Lanser also shows this since Michael has 
shown that the so-called triphenyltrimesic acid is really a naphthalene 
derivative. Lanser obtained the anhydride of this acid by heating 
phenylpropiolic acid to a temperature above 200. Pfeiffer and Holler's 
work, however, illustrates the additional fact that anhydride formation is 
not essential for this naphthalene condensation. 

I have confirmed Lanser's experiment and have been able to get a 
much better yield of the ester of the naphthalene acid than Pfeiffer and 
Moller got. In my experiment, however, the phenylpropiolic ester was 
polymerized by heating it with acetic anhydride instead of heating it 
alone. 

These investigations show that phenyl propiolic acid and its ester or 
chloride can be polymerized in a number of different ways to naphthalene 
derivatives but that the original method of Michael and Bucher which 
gives a quantitative yield is still the best. The following formulas in- 
dicate how this change takes place : 



C.COjH 




CH 




This work has been continued in this laboratory for a number of years 
in order to determine whether this transformation is general or not. 
Besides phenylpropiolic acid, eleven of its substitution products 
have been examined thus far and in every case they polymerized, on 
heating with acetic anhydride, to derivatives of i-phenyl-2,3-naph- 
thalenedicarboxylic anhydride. The facts thus far obtained justify the 
statement 3 that phenylpropiolic acid and its substitution products show a 
strong tendency to polymerize, with the wandering of an ortho hydrogen atom, 
to phenylnaphthalene derivatives. 

1 Am. Chem. J., 20, 112 (1898). 

Bar., 40, 3839 (1907). 

THIS JOURNAL, 30, 1262 (1908). 

26 



ORGANIC AND BIOLOGICAL. 2l6 

In fact, this kind of polymerization is the only form which has been 
thus far obtained from aromatic propiolic acids. 

In this work much time was spent in preparing the aromatic propiolic 
acids as it was usually necessary to either prepare new compounds or 
else to improve the methods of preparation of acids which were already 
known. In most cases methods were found by which these interesting 
acids could be prepared readily from comparatively inexpensive materials 
providing that suitable precautions were observed. 

Phenylpropiolic acid was prepared in the usual way from cinnamic 
acid by making cinnamic ester dibromide. It is well known that alco- 
holic potash converts this into a mixture of the salts of allo-bromocinnamic 
acid and bromocinnamic acid and that the latter is easily converted into 
phenylpropiolic acid by the loss of hydrobromic acid. The former acid 
is so stable, however, that it is not practicable to convert it into phenyl- 
propiolic acid directly by further heating with alcoholic potash. It can, 
however, be converted into the isomeric acid by simply heating it. This 
acid can then be converted, in turn, into phenylpropiolic acid. This 
change of the labile bromo acids into the corresponding isomeric acids 
was found to be quantitative in several cases. In the case of the allo- 
bromocinnamic acid it was noticed that when it was heated with acetic 
anhydride to 100 its own anhydride was produced but at a higher tem- 
perature this was transformed into the bromocinnamic anhydride. The 
latter could then be transformed into phenylpropiolic acid. From this, 
it is evident that it is not necessary to use pure phenylpropiolic acid 
in this work. It generally seemed desirable, however, to separate the 
acids first. A very good way of doing this is to crystallize them from 
carbon disulphide or from carbon tetrachloride. In this way it is possible 
to separate much of the phenylpropiolic acid from the more soluble allo- 
bromocinnamic acid. 

In some other cases, the potassium salts of the propiolic acids were 
found to be very sparingly soluble in the alcoholic potash, thus yielding 
the pure acids at once. In all cases the potassium salts of the labile 
bromocinnamic acids were found quite soluble while the ammonium salts 
of the isomeric acids were very sparingly soluble. These properties were 
found very useful in separating the resulting phenylpropiolic acids from 
these labile substituted bromocinnamic acids which were formed. 

The meta- and para-nitrophenylpropiolic acids can be prepared from 
the corresponding nitrobenzoic aldehydes by Perkin's synthesis. In 
some other cases Claissen's synthesis was found preferable to that of Per- 
kin. 

It was also found that the ortho- and para-nitrophenylpropiolic acids 
could be converted into the corresponding halogen acids by means of the 
diazo reaction. 

Besides phenylpropiolic acid, the following substitution products were 
prepared : Piperonylpropiolic acid, o-chloro-, o-bromo-, w-nitro-, m-chloro-, 
p-nitro-, p-chloro-, p-bromo-, p-iodo-, />-methoxy-, and ^-methylphenyl- 
propiolic acids. These all polymerize readily to derivatives of i-phenyl-2,3- 
naphthalenedicarboxylic anhydride when they are heated with acetic 
anhydride. In the earlier work it was found very difficult to prove this 
constitution for these products. The method used in case of the first 
compound has already been described. The meta- and para-nitro 
compounds were oxidized and then converted into diphenyltetracar- 

27 



217 



ACIDS OF THE PHENYLPROPIOLIC SERIES. 



boxylic acid thus showing them to be naphthalene derivatives. By 
means of the diazo reaction, they were then converted into the halogen 
derivatives identical with those obtained by direct polymerization. This 
showed the latter to have the same constitution. The constitution of 
the product from the para-methylphenylpropiolic acid was established 
by oxidizing it to a diphenylpentacarboxylic acid. In more recent 
work the very efficient method of oxidizing to benzenepentacarboxylic 
acid described below was used. By means of this method, which depends 
on the catalytic action of manganese nitrate in fuming nitric acid, eleven 
of these acids were oxidized to benzenepentacarboxylic acids, thus con- 
firming the naphthalene constitution which had previously been assigned 
for some of the substances. 

The following description gives an idea of some of the transformations 
which these substances undergo: They are all ortho-dibasic acids from 
which water splits out easily on heating. In fact, the first acid obtained 
is partially converted into its anhydride even on crystallizing it from only 
moderately heated glacial acetic acid. In this way, I obtained eight 
grams of the anhydride from twenty grams of the acid. This loss of 
water in crystallizing the acid from hot solvents led to the statement, 
made in the first description, that the acid passed into the anhydride 
spontaneously. This statement was corrected in a later paper by Michael. 
All of these acids have this general property and some of them, as well as 
their oxidation products, may show properties similar to those noticed 
by Orndorff in the case of tetrachlorophthalic acid. 

The acids all necessarily contain a carboxyl group with both ortho 
positions substituted. According to V. Meyer's observations one might 
expect difficulty in esterifying these acids. This was found to be the 
case, little or no neutral ester being found, on heating the substances with 
alcohol and sulphuric acid under the usual conditions. If more sulphuric 
acid is used and the heating continued for a longer time from 40 to 60 
per cent, of neutral ester may be obtained. 

Sulphuric acid converts the i-phenyl-2,3-naphthalenedicarboxylic 
acid into red allo-chrysoketonecarboxylic acid. 



H 




CH 



.COjH 
.CO.H 



.00,11 



H 




JCH 



CH CH 

I. II. 

When this red acid is heated to 218 with potassium hydroxide, it is 

28 



ORGANIC AND BIOLOGICAL. 



218 



changed practically quantitatively into a new i-phenylnaphthalenedi- 
carboxylic acid. 

CH CH 
C 




Formulas I, II and III show a method of transferring a carboxyl 
group from the ortho position on one ring to the corresponding position 
on the other ring. When the new acid (III) is heated with sulphuric acid, 
a new red acid different from the allochrysoketonecarboxylic acid (II) is 
obtained. 

The oxidation of these naphthalene acids in alkaline potassium per- 
manganate solution has already been described. The yield of diphenyl- 
tetracarboxylic acid is usually small, since the intermediate ketonic acids 
are very stable towards alkaline potassium permanganate. 

HO,C.O~ 
/ \ 
HOC 



H0 2 C.C 





These ketonic acids are very easily oxidized to diphenyltetracarboxylic 
acids when the solution is acidified. Formulae I, IV, V and VIII 
indicate these reactions. These acids are obtained in the form of sirup- 
like solutions and they resemble phthalonic acid closely. Heated with 
caustic alkalies, they yield diphenyltricarboxylic acids and oxalic acid. 



29 



219 



ACIDS OF THE PHENYLPROPIOUC SERIES. 



On reduction with hydriodic acid, the weto-glyoxylic acid (V) first yields 
methyldiphenyltricarboxylic acid (VI) which then reduces at a higher 
temperature to a methylfluorenecarboxylic acid. The isomeric ortho- 
glyoxylic acid (IV), aven at the boiling point of hydriodic acid, reduces 
to a fluorenetricarboxylic acid (VII). 

CH CH 



H 8 C. 



HO 2 C. 




HO 2 C. 




C.CO 2 H 



C.CO,H 



VII. 

This shows the ease with which diphenylcarboxylic acids close the ring 
to form fluorene derivatives. The same tendency is shown by the action 
of sulphuric acid on diphenyltetracarboxylic acid (VIII) in forming the 
yellow diphenyleneketonetricarboxylic acid (IX), which can be reduced 
to the acid represented by formula VII. I have found this closing of the 
ring on heating to 100 with sulphuric acid, to take place when all the 
carboxyl groups were on the same ring but generally not when the car- 
boxyl groups were on different rings. In diphenyleneketonecarboxylic 
acids of the general form IX, the ring is broken in such a way, on heating 
with potassium hydroxide, that the carboxyl group is transferred from 
the ortho position on one ring to the corresponding ortho position on the 
other. 1 In this case, about 299 parts out of 300 are changed in this way 
making the process practically quantitative. The following formulas 
show these changes. 

The very sharp breaking of the ring at a in formula IX and in the 
similar case of the red acid (II) indicates a tendency to remove the 
carboxyl groups as far as possible from each other and suggests the pos- 
sibility of its giving a means of testing the constitution of the resulting 
acid. For example Bamberger and Hooker, 3 after heating a yellow 
diphenyleneketonedicarboxylic acid from retene with caustic alkali, 
represent the resulting white diphenylenetricarboxylic acid as having 
the three carboxyl groups on the same ring. This seemed scarcely pos- 
sible in view of the above facts and an examination showed the acid to 
have a different structure. 

The yellow diphenyleneketonetricarboxylic acid (IX) also furnishes 
a means of oxidizing these i-phenyl-2,3-naphthalenedicarboxylic acids 
or diphenylpolycarboxylic acids (like I and VIII) to benzenepentacar- 

1 THIS JOURNAL, 30, 1261 (1908). 
1 Ann., 229, 159 (1885). 



ORGANIC AND BIOLOGICAL. 



22O 



CH 




,C.CO 2 H 

ic.co 2 H 



C.CO 3 H 
XI. 



boxylic acids. The latter acid (VIII) is very stable towards alkaline potas- 
sium permanganate as on heating for six weeks I recovered 28 per cent, 
of unchanged acid and could not isolate any benzenepentacarboxylic acid. 
The yellow acid (IX), however, decolorized the theoretical quantity of 
permanganate in less than two hours. The very soluble acid product 
was not completely oxidized but it yielded benzene for the hydrocarbon. 
Many experiments were made in attempting to complete the reaction 
but without success. Even heating on the water bath with fuming nitric 
acid did not aid very much. A small quantity of manganese nitrate 
was then added to the hot nitric acid. Brisk effervescence began at once 
and in a few moments pure benzenepentacarboxylic acid separated front 
the liquid. The yield in this experiment was about 90 per cent, of the 
theory. The manganese nitrate is evidently a very efficient catalytic 
agent in this case. This method was also applied to the acids without 
first converting them into ketone derivatives, and, in eleven cases out of 
the twelve tested, benzenepentacarboxylic acid was found. Not only 
does this give a very powerful method for determining constitution but 



221 CATALYSIS ON THE BASIS OF WORK WITH IMIDO ESTERS. 

it gives a very easy method of preparing the hitherto almost inaccessible 
benzenepentacarboxylic acid. It also serves for the preparation of 
other benzene polycarboxylic acids. Bamberger and Hooker's diphenyl- 
eneketonedicarboxylic acid from retene can be oxidized in a few hours 
to two isomeric benzenetricarboxylic acids, thus showing that the constitu- 
tion given for retene and all its derivatives is incorrect. 

The above work dealing with the action of acetic anhydride led to the 
supposition that anhydrides 1 might be prepared from meta- and para- 
phthalic acids and their substitution products. On trying the experi- 
ment it was found that such anhydrides could be obtained quantitatively 
by heating a solution of the acid in acetic anhydride to 200 until the 
excess of reagent was distilled off. These products apparently have a 
very high molecular weight. A preliminary determination, in nitro- 
benzene by the boiling point method, for the anhydride from chlorotere- 
phthalic acid, [C 6 H B Cl(CO) 2 O]x, indicates that it may be as high as 1500 
or 2000. 

A part of this work has been carried on with the aid of my students 
and I wish especially to acknowledge the valuable assistance of G. F. 
Parmenter, N. A. Dubois, V. S. Babasinian, M. L. Dolt, W. C. Slade 
and F. Keyes. 

The more important results of this work thus far are as follows : 

1. Satisfactory methods for the preparation of a number of aromatic 
propiolic acids. 

2. The polymerization of these acids to derivatives of i-phenyl-2,3- 
naphthalenedicarboxylic acids giving a quantitative method of syn- 
thesis. 

3. Syntheses of acids of the diphenyl, fluorene and diphenyleneketone 
series and a study of their characteristic reactions. 

4. Syntheses of benzenepentacarboxylic acid and other benzene- 
polycarboxylic acids. 

5. The determination of the constitution of retene and its derivatives. 

6. The preparation of anhydrides from meta- and para-phthalic acids 
and their substitution products. 

BROWN UNIVERSITY, PROVIDENCE, R. I. 



CATALYSIS ON THE BASIS OF WORK WITH IMIDO ESTERS. 2 

BY JULIUS STIEGLITZ. 
Received December 2, 1909. 

I shall not attempt to discuss to-day the general subject of catalysis 
but shall use the short time rather to present briefly some results 3 in 
certain lines of our work which seem to shed some light on three funda- 
mental points of interest in catalysis, namely, on the questions how in 

1 THIS JOURNAL, 30, 1263 (1908) and 31, 1319 (1909). 

1 Presented at the Second Decennial Celebration of Clark University, Worcester, 
Mass., September 15, 1909. 

' Certain parts of the work are still being carried out as indicated below and 
for such parts this report is preliminary to a final one. Complete discussion of the 
several parts lay outside the limits of this paper and will be brought in in later special 
reports. 

32 



ORGANIC AND BIOLOGICAL. 222 

certain cases a catalytic agent does its work, why it does it, and what 
limitations there are to its action. 

It may be recalled that an imido ester, such as methyl imido benzoate, 
is very slowly decomposed by pure water. One of the decompositions 
it undergoes under these conditions is into ammonia and methyl benzoate 1 
as expressed in the equation 

C 6 H 5 C( : NH)OCH 3 + H 2 O > C 6 H 6 CO 2 CH 3 + NH 3 . (i) 
The addition of an acid, say hydrochloric acid, enormously accelerates 
this otherwise extremely slow action and we were able to show that the 
acceleration is due to the fact that the reacting component in this decom- 
position is the positive ion of the ester, 2 as expressed in the equation. 

C fl H 5 ( : NH 2 +)OCH 3 + H 2 O ^ C 6 H 5 CO 2 CH 3 + NH 4 +. (2) 
In arriving at this conclusion, account had to be taken of the so-called 
"salt-effect" or "salt-acceleration" produced by the presence of elec- 
trolytes, entirely analogous to the "salt-effect" in other decompositions 
in which water is a reacting component, as in the catalysis of esters by 
acids. This salt-effect being allowed for, the velocity of decomposition 
of an imido ester by water in the presence of acids is given in the equation 3 

dxfdi = K v(ion} X C^ M/ . * X [C H X C OH }. (3) 

I have not time more than to mention the fact that it was shown that 
the same fundamental equation may be applied to the saponification of 
ordinary esters under the influence of acids, the main difference being 
that for such exceedingly weak oxonium bases as esters are the con- 
centration of the positive ester ion is practically proportional to the 
concentrations of the ester and the hydrogen ion present at any moment, 
so that we may transform (3) into 4 

dx/dt = K V X C ester XC H X [C H X C OH ] (4) 

which is also the equation based on experience. 

The work on which the above conclusions were based was carried 
out wholly with the hydrochlorides of the imido esters. More recently 
we have also carried out measurements with the hydrobromides and 
nitrates, and begun work also with sulphates; if the positive ion is the 
reacting component, then, determining rigorously the degree of ionization 
and making rigorous allowance for the salt-effect, we should find that the 
velocity constant for the decomposition of the positive ion in the chloride 
solution should also satisfy the observed rates of decomposition of these 
other salts. For the rigorous treatment, the "salt-effect" produced by 
the chlorides, bromides, nitrates, etc., has to be determined experimen- 
tally and this has been carried out 5 with the chlorides and bromides, 6 
mixtures with varying amounts of the potassium and sodium salts being 
examined, the degrees of ionization of each salt in the mixture being 
1 Stieglitz, Report International Congress of Arts and Science, St. Louis, 4, 276 
(1904), and Am. Chem. J., 39, 29 (1908). 

* Stieglitz with Derby, McCracken, Schlesinger, Am. Chem. J., 39, 29, 166, 402, 
437, 586, 719. 

3 Cp os . est. ion 1S a function of x. 

* Cgster is a function of x. 

' W. W. Hickman, Dissertation, 1909. 

' Mr. Weatherby is completing the work begun by Mr. Hickman on the nitrates 
and sulphates. 

33 



223 CATALYSIS ON THE BASIS OF WORK WITH IMIDO ESTERS. 

determined with the aid of the principle of isohydric solutions, which 
was proved to apply to such mixtures. 1 The salt-effect is, except for 
minute quantities of salt, proportional to its concentration or rather, 
more probably, only to the concentration of the ionized part of the salt.. 
The salt-effect is an acceleration and if we call K V (i on ) the velocity of 
decomposition of the imido ester ion in the absence of any salt at all, 
this velocity will be increased proportionally to some specific acceleration 
factor A, and to the concentration ma of the ionized part of A salt. So we 
have 

K ,(M)ob,. = K ,<io)o (1 +Ama). (5) 

Kv(ion)obs. is the constant calculated according to equation (3) from 
the observations without any allowance for a salt-effect. 

Kv(ion)o, the velocity constant when the salt effect is eliminated, is easily 
found by extrapolation from the observations when imido ester salts 
are present without added salts, A from the results obtained when salts 
have been added. We arrived thus empirically at the rather unexpected 
result that the accelerating factor A is approximately the same for 
sodium, potassium and lithium chlorides and for the bromides as well 
as for the chlorides, viz., about 185 per cent, per gram molecule of fully 
ionized salt. Table I illustrates this fact for potassium chloride and 
potassium bromide. K v is the velocity coefficient calculated without 
regard to the degree of ionization of the imido ester salt, a is the degree 
of ionization of the salt calculated with the aid of the principle of iso- 
hydric solutions. In the columns headed "found" are given the values 
obtained for K v \ a by experiment; in the columns headed "calculated" 
are the values obtained according to equation (5), in which the velocity 
coefficient K v (i on ) in the absence of any salts at all is taken as 164 and the 
salt acceleration factor A is taken as 185 per cent, for both series. 

TABUJ I. 1 

KCl. KBr. 

43430 K-oja. 43430/S^/a. 



K Hal. 



m. Found. Calculated. Found. Calculated, 

o 176 176 176 177 

O.I 191 190 191 190 

0.2 213 214 209 215 

0.25 227 226 230 227 

0.333 247 245 (268) 247 

I wish to emphasize this result because the work of others, notably of 
Arrhenius and Euler, with cane-sugar and esters, shows varying specific 
accelerating factors for these salts. I believe our work has the advantage 
of our knowing from conductivity measurements the degrees of ioniza- 
tion of the imido ester salts as well as of the added electrolyte so that 
there seems to be no unknown factor left in our estimations. But we are 
simply presenting these results for the time being as an empirical contri- 
bution to the whole question of catalysis and we do not consider the 
very complex question of "salt catalysis" as at all settled. 3 

. * Edith E. Barnard, Dissertation, 1907. 
3 Taken from W. W. Hickman's dissertation. 

3 Work on "salt catalysis" is being continued by L. S. Weatherby, preliminary 
results by Mr. Hickman on the effect of sulphates indicated an abnormally high effect. 

34 



ORGANIC AND BIOLOGICAL. 224 

With the aid of the determination of the salt factor for chlorides and 
bromides we have been able to show that the positive ester ion shows 
indeed the same rate of decomposition irrespective of its origin from either 
of these salts and very probably also for the nitrate 1 (see the values for 
K v i a for the three salts in equi-molar concentrations as given in Table II). 
This is exactly what our theory would require, namely, that the simple 
reason why the addition of an acid accelerates this decomposition is that 
it forms a salt whose positive ion is the reacting component and that the 
concentration of the ion is enormously increased when the catalyzing 
acid is added to the free ester, which is a very weak and therefore little 
ionized base. . 

TABLE II.* ETHYL IMIDO BENZOATE. 

Hydrochloride. Hydrobromide. Nitrate. 

^. 0.8 K v .* JftjT * Kv* Kfa. o. K v * Kvla. 

0.05 77.8 136 175 75-9 133 i?6 75-1 133 177 

o.i 71.8 132 185 69.4 128 184 68.3 127 186 

0.2 64.5 121 188 61.7 119 193 60.4 118 195 

0-33 57-7 "4 198 54-7 108 198 52.7 107 201 

It was suggested by Arrhenius and emphasized by Euler that the 

salt acceleration is probably largely due to the increased ionization of 

water in the presence of electrolytes, but quantitative evidence in support 

of such a conclusion has not been brought, as far as I am aware. In view 

of the increase observed by Arrhenius arid others 5 in the strength of other 

acids in the presence of added foreign salts, e. g., of acetic, formic and 

carbonic acids in the presence of sodium chloride, it seems a sufficiently 

rational assumption that water should show a similar increased ionization. 6 

The imido esters, enabling us to measure the actual concentration of the 

reacting imido ester ion, gave us an opportunity to bring experimental 

evidence strongly supporting this view. From equation (3) it is obvious 

that if the salt acceleration is due to the increased ionization of water, 

viz., an increase in the value of the third factor, (C H X COM) then, Cp os . M <. i on 

being known by experiment, the velocity constant K v (io n ) calculated 

-without taking any increased value of [C# X COH] i nto account, should 

increase in the same proportion for all the imido esters for the same 

concentration of added salt ions, irrespective of the fact that, according 

to the ester used, the decomposition may be a comparatively slow or a 

very fast one. We have found this to be true 7 all the esters used show 

the same acceleration per gram molecule ionized salt i. e., close to 

185 per cent, per gram molecule ionized potassium chloride, etc. 8 

Having found that the reacting component in these and a number 
of other actions under the influence of acids is the positive ion of a salt 
formed with the acid, we were naturally most interested in the question 

1 The salt effect for nitrates is now being determined. 
1 Taken from W. W. Hickman's dissertation. 

3 Taken from Edith E. Barnard's dissertation. 

4 Taken from Schlesinger's results, Loc. cit. 

* E. J. Szyszkowski, Z. physik. Chem., 58, 419. 

See a discussion of the other side of this question by Acree, Am. Chem. J., 41, 474- 

7 Dissertation of Edith E. Barnard and W. W. Hickman. 

8 The investigation of the ionization of water in salt solutions is being continued 
with other substances and by other methods. 

35 



225 CATALYSIS ON THE BASIS OF WORK WITH IMIDO ESTERS. 

why the ion should be so reactive, why it should be so important a com- 
ponent. We can hardly consider the decompositions to be purely ionic 
reactions, 1 comparable with the hydrolysis of salts in aqueous solutions, 
as was mistakenly assumed, for instance, by Euler and by Kastle. Such 
assumptions run counter to the law of mass action applied rigorously in 
the analysis of the conditions. 1 The law is, however, in agreement with 
the assumption 2 based on experience gained in organic chemistry that the 
following are the stages for the action : 



. 

C,H s Cf +H+ + OH- *-C,H 6 C OIH *-t^H 5 CO,CH, + NH,+ (6) 

\OCH, 

Now, we may well ask why this should be an enormously faster action 
than the entirely analogous possible action of water on the non-ionized 
free ester, which, it is clear, could proceed in a very similar series of stages 
as expressed in the equations : 



C,H 6 C^ +H+ + OH- C,H S C O:H * C,H 6 CO,CH a +NH,,. (6') 
\OCH. \oj- 

For me, one of the most interesting and important features of our 
work is found in the unmistakable way in which the fact is brought out 
more and more clearly that the accelerating or catalytic effect of the 
acid is most intimately associated with the transformation, in acid solu- 
tion, of the positive ion of a weaker base into that of a stronger one 
the results no doubt of the principle of the loss of a maximum amount 
of free energy. 3 This is shown most strikingly in the following illustra- 
tion: whereas the above imido esters are very rapidly decomposed by 
water in the presence of acid, this is not the case for the closely related 
compounds, the urea ester salts, which, structurally considered, could 
react quite as easily with water but are as a matter of fact quite stable 
in acid solution. The transformation 



/NH 2 + 
NH 2 C< ' +HOH >NH 2 C OH -^ NH 4 ++H 2 NCOOCH 3 (7) 



only takes place to a very slight extent at 100, and at ordinary tempera- 
tures, where imido ester salts are completely decomposed in one to ten 
hours, the urea ester salts have not been observed to decompose at all. 4 
In this case we have the notable fact that such a transformation would 
involve the change of a salt of a stronger base into that of a much weaker 
one an ammonium salt and this does not take place. To test the 
legitimacy of our reasoning we recently examined the behavior of ben- 
zoyl urea ester salts: the benzoyl urea esters form very much weaker 

1 See a more complete discussion by Stieglitz, Am. Chem. J ., 39, 402. 

2 Stieglitz, Loc. cit. 
8 Ibid. 

* The degree of stability is being examined quantitatively. 

36 



ORGANIC AND BIOLOGICAL. 226 

bases than ammonia and our reasoning would lead us to expect that they, 
in turn, ought to be decomposed quite as smoothly in acid solution as the 
imido esters. Such is, in fact, the case; 1 urethanes and ammonium salts 
readily result according to the equation 



C 6 H 5 CO.NH.Cf + HOH > NH 4 + + C 6 H 5 CONHCOOCH 3 . (8) 
X OCH, 

We find then that perfect analogy in structure is of far less importance 
in determining the result of the action of water than a definite physico-chemical 
relation subject to quantitative measurement. 

This is again brought out beautifully by the behavior of the urea esters 
towards ammonia. The imido esters give with ammonia amidines and 
again the action is accelerated by the addition of an acid or an ammonium 
salt and, as we shall see presently, this is due to the fact that again it is 
the positive ester ion that reacts with ammonia, an amidine resulting 
according to the equation 

C 6 H 5 C( : NH 2 +)OCH, + NH, * C a H 6 C( : NH 2 +)NH 2 + HOCH 3 (9). 

Now, urea esters which, as explained above, would not react with water 
in acid solution because the salt of a stronger base would be converted 
into the salt of a weaker one if they did react, would give with ammonia 
guanidines which are still stronger bases than they are themselves. 
They should, therefore, according to this theory, react with ammonia in 
the presence of an acid ; as a matter of fact they do, producing guanidines 
very readily, and we were able to prove again that the velocity of the 
formation is proportional to the concentration of the positive ester ion; 2 
in fact, until our theory led us to recognize the importance of having a 
salt-forming acid present, all our efforts to prepare guanidines from 
urea esters by using ammonia alone had proved futile; so that this 
theory seems to agree equally well with the reactions of a given compound 
which do occur as with those which do not take place. 

We have found too that in series of structurally closely related esters 
where what might be called the structural and stereochemical resistances 
to the action are perhaps approximately the same, the transformation 
of the positive ion of a weaker base in the presence of acids into that of a 
given stronger base, say into the ammonium ion, proceeds with the greater 
velocity at a given temperature the weaker the original base is. 3 This brings, 
as far as I am aware, the first complete experimental proof of a theory 
which others, notably van't Hoff and Euler suspected to be true, 4 although 
there appeared so many marked contradictions to the assumption that 
the theory appeared at best a very uncertain one. For instance, Hemp- 
tinne 5 and Lowenherz, 6 working on this problem at van't Hoff's sug- 
gestion, obtained the following results for the saponification of esters by 
acids : 

1 J. C. Moore's dissertation, 1909. 

1 R. A. Hall's dissertation (1907). 

Cf. Stieglitz, Loc. cit., and McCracken, Loc. cit. 

4 See the discussion by Euler, Z. physik. Chem., 36, 410. 

8 Ibid., 13, 561. 

Ibid., 15, 395. 

37 



227 CATALYSIS ON THE BASIS OF WORK WITH IMIDO ESTERS. 

TABLE III. 1 

Ester. Velocity constant. loniz. const, of the acid. 

HCOOC 2 H 5 O.H 21 X 10- 

CH 3 COOC 7 H 5 0.0057 i. 8X10- 

C1CH 2 COOC 2 H S 0.0033 155 X io- 

C1 2 CHCOOC 2 H 5 0.0053 5ioo X io- 

CH 3 CH 2 COOC 2 H 5 0.0061 i .3 X io~ 

Assuming, as Euler did, that the strongest acids produce the weakest 
bases in their esters, one might expect the positive ions of the chloroacetic 
acid esters to be saponified most rapidly to give the positive ion of a 
given stronger base, the oxonium base of ethyl alcohol. As a matter of fact 
the velocity constants in the above table do not tell us anything at all 
as to whether that is so or not and that is why the theory, heretofore, has 
appeared as an unproved one; obviously it does not follow from the data 
in Table III, where the weakest bases, dichloroacetic ester and chloroacetic 
ester, have the smallest, not the largest, velocity constants of decomposi- 
tion. But the fact that, for instance, the velocity coefficient for the 
saponification of dichloroacetic ester is even smaller than that for ethyl 
acetate does not mean anything at all in regard to the real relative rates of 
transformation of their positive ions: there is a second factor involved, 
namely, the concentrations of the positive ions of the esters are 
dependent on the strength of the esters as oxonium bases, as expressed 
in our fundamental equations for the catalysis of an ester by an acid. 2 
In our fundamental equation 

dx/dt = K v(ion) X C^ M , ^ X [C H X C OH ] (io) 3 

we may substitute for C^j. est . ion the relation expressed in : 

Cpos. est. ion = **/*' X C esU , X C H (i l) 

and have 

dx/dt = K v(ion) X k aff jk' X C ester X C H X [C H X C OH ] (12) 

= K v X C ester X C H X C H X C OH (13) 

which is the ordinary equation representing the velocity of decomposition 
of esters by acids. What we determine with esters, for instance in Hemp- 
tinne's and Lowenherz's work as expressed in Table III is K v and not 
the more fundamental constant K V (i on ). Now 

K v = K,(M X hrfjk' (14) 

and it is obvious that if the basic strength of the ester as expressed in 
k a ff. grows very much smaller, as it undoubtedly does when we go from 
ethyl acetate to ethyl chloroacetate, K V (i on ) could easily grow very much 
larger and yet K v need not change appreciably or it might even grow smaller, 
without the result being in any disagreement whatever with the theory 
expressed. This means, of course, that determinations simply of the 
velocity constants K v of decomposition of such esters do not prove any- 

1 The table is taken from Euler, Loc. tit., p. 412. 

2 Stieglitz, International Congress of Arts and Science, St. Louis, 1904, 4, 276 
of the report, and Am. Chem. J., 39, 47 (1908). 

8 C pos . est . ion is a function of x. 

4 k' is the stability constant of the oxonium hydroxide. k a ftjk' may be considered 
the stability constant of the complex ester ion. Cf. Bredig, Z. Elektrochem., 9, 118 
(foot-note). 

38 



ORGANIC AND BIOLOGICAL. 228 

thing as to the principle at issue. A somewhat stronger base might 
well give a higher rate of change than a weaker one by virtue of the fact 
that a larger proportion of the base is present in its active form, the ion, 
and the real rate of decomposition of the ion may be much smaller than 
that of an ester giving a smaller velocity constant K v . The imido esters 
have the advantage that their affinity constants are easily ascertained 
and we do not deal with any such unknown quantity at all, and thus we were 
able to bring what I believe is the first experimental proof of the sound- 
ness of the theory. An apt illustration of the correctness of our argu- 
ment concerning the lack of data for a correct analysis of results like those 
given in Table III is found in the following facts: the formation of ami- 
dines from imido esters, as was stated, is greatly accelerated by the addition 
of acids or of an ammonium salt and we were able to show that the amidine 
formation may be considered essentially a function of the concentration 
of the positive ester ion, proceeding according to 



C 6 H 5 C< + NH 3 > C 6 H 5 C< + HOCH, (9) 

X 



OCH 3 
and 

dx/dt = K V X C pos _ est . ^ X C NHt 

Now, if we develop the expression for the concentration of the positive 
ion of a very weak base like an imido ester in the presence of a much 
stronger one like ammonium hydroxide we find that: 



.. , 

*~NH 3 K off. amm. 

and by substitution we get: 

fir I rlt - K V kaff - est - V CesUr X CNH * + V 

ax/at - K v(ion ) X , X 

K aff. amm. 

- a ft- est - / 



a/7. amm. 

Now, imido ethyl benzoate forms benzamidine considerably faster 
than does the methyl ester: in both cases the change is from the salt of 
the positive ion of a weaker base to that of a much stronger one, the 
amidine, but the ethyl ester is the stronger base and yet it reacts the faster 
and apparently contradicts our theory. A knowledge of the affinity 
constants shows, however, that it reacts the faster only because by virtue 
of its being a stronger base it takes a larger proportion of the catalytic 
agent, the acid, from the ammonium chloride, and forms a proportionally 
larger concentration of the active component, the ester ion, than does 
the methyl ester under the same conditions. Calculating with the aid 

1 Cpos. est. ion is a function of x. 

2 In passing, it may be remarked that this last form shows that the action may be 
considered one of the ion ammonium acting on the ester, but we believe our original 
assumption to be the right one for reasons found in the behavior of organic compounds 
which cannot be elaborated here ; it may be said, for instance, that we have found NH, 
and not NH 4 + to react with ordinary esters to form amides and are carrying out other 
more crucial experiments on this point. Vide Acree, Am. Chem. J., 38, 308. 
Fitzgerald and Lapworth, /. Chem. Soc., 93, 2163. 

39 



229 CATALYSIS ON THE BASIS OF WORK WITH IMIDO ESTERS. 

of the affinity constants the true velocities of transformation of the positive 
ions, we find the true relation: ^(ion) for the methyl ester is 140/0.434 
and for the ethyl ester only 69/0.434. * So the true relations resulting 
from an exact knowledge of all the quantitative constants involved agree 
perfectly with the fundamental principle given. 

This reaction shows other points of great interest: for instance, the fact 
that the concentration of ammonia cancels out of the mathematical 
equation leads to the conclusion that the velocity of decomposition is 
independent of the concentration of ammonia, one of the reacting com- 
ponents. 

This peculiar conclusion has been fully verified by experience; the 
velocity constant is as a matter of experiment almost, although not ab- 
solutely, independent of the concentration of ammonia ; in the case of the 
above methyl ester, the constant grows only about 10 per cent, with an 
increase of 400 per cent, in the concentration of the ammonia. This ap- 
parent contradiction with the law of mass action is readily understood 
if we remember that the concentration of ammonia has two effects which 
oppose each other; ammonia does accelerate the action in proportion to 
its mass as required by the law, but it also to the same degree retards 
the action by depriving the weaker base of the ionizing and therefore 
catalyzing acid. Within a year Lapworth 2 has made the extremely 
important discovery that water stands in exactly the same relation to 
the esters in the catalysis by acids only then the two bases competing 
for the acid are two oxonium bases, the ester and water. 

And now in conclusion I wish to call attention to one more result with 
these imido esters which has impressed us very much and which seems 
to me to throw a very clear light on the whole question of catalysis or 
acceleration by showing certain limitations to catalytic effects. It was 
mentioned a moment ago that the velocity of formation of benzamidine 
from methyl imido benzoate may be expressed as a function of the positive 
imido ester ion and that it is almost independent of the concentration of 
the ammonia; but it is not absolutely independent, there is a slight but 
steady rise in the value of the constants with increasing concentrations 
of ammonia. All other secondary reactions having been excluded (e. g., 
for fourfold increase of NH 3 , the constants rise gradually from 139/0.434 
to 154/0.434) as the cause of this increase by a knowledge of their velocity 
constants, we suspected that besides the main action of ammonia on the 
positive ester ion, there is a much slower action of ammonia also on the 
non-ionized free ester, namely, that we have two simultaneous actions: 
C 8 H 6 C( : NH 2 +)OCH, + NH, + C e H 6 C(' : NH 3 +)NH 2 + HOCH, (18) 

and 

C 6 H 6 C( : NH)OCH, + NH S > C 8 H 5 C( : NH)NH 2 + HOCH, (19) 
We had the more reason to suspect this as we had already found that 
water, besides decomposing the positive ion of an imido ester at a very 
high speed, also undoubtedly decomposes the non-ionized ester at a very 
slow rate. 8 It was found that the experimental results agree very well 
with this conception of two simultaneous actions in the formation of 

1 Miss Katharine Blunt's dissertation (1907). 

2 Loc. cit. 

* In this case the products are different. Vide Stieglitz, Derby and Schlesinger, 
Loc. cit. 

40 



ORGANIC AND BIOLOGICAL. 230 

benzamidine and that the velocity constant for the action of ammonia 
on the positive ester methyl ion at 25 is 325, while that on the ester 
molecule is only 0.0069. * That is, the positive ion is almost 50,000 times 
as reactive as the non-ionized molecule. It may appear somewhat 
surprising that such a small constant could still be detected side by side 
with such an enormous one, the whole action being completed in one 
to two hours. But we must remember that for the ion action with the 
enormously high rate of change we have at any moment only minute 
quantities of the reacting component, e. g., 0.000,005 gram ion at the 
beginning of a velocity measurement, which is used up at an enormous 
speed but always formed again instantly by the purely ionic action of 
imido ester on the ammonium chloride. On the other hand the transfor- 
mation of the non-ionized molecule has the advantage of relatively high 
concentrations of each of the reacting components, say 0.05 both for the 
ammonia and for the free ester at the beginning of an action. With a 
concentration many thousand times in its favor it is then not surprising 
to find this very slow action becoming perceptible in careful quantitative 
work. Now, if we should use a much weaker base still, we might easily 
find the action with the non-ionized ester taking a more and more promi- 
nent part in the total change, even if the actual rate of change of the 
positive ester ion should still be very much the greater. We have recently 
found such to be the case for the action of ammonia and ammonium 
chloride on benzoyl urea ester: 2 the velocity constants are so nicely 
balanced against the affinity constants that the observed changes did not 
agree even approximately with either conception used alone, viz., that 
the guanidine formation was due to the action of ammonia on the positive 
ester ion alone, or on the non-ionized ester alone. But they did agree 
well with the view that both actions occur simultaneously, the velocity 
coefficient for the action on the ion being 34.5 and the coefficient for the 
action on the non-ionized ester being 0.0015, a ratio of 23000 to i again. 
We were exceedingly pleased to find this case because it forms the con- 
necting link with what we have found to be true for the formation of 
ordinary acid amides from acid esters in the presence of ammonia and 
ammonium salts: 

CH 3 COOCH 3 + NH 3 -> CH 3 CONH 2 + HOCH 3 (20). 

This action seems to be essentially a function of the ester and ammonia 
and it is an extremely slow reaction. 3 We can easily understand this 
case now; the esters as extremely weak oxonium bases must be able to 
take only the faintest traces of acid from the ammonium chloride in the 
presence of ammonia and therefore the slow molecular transformation 
comes to the front as enormously favored by the concentrations of the 
reacting components. In the case of the actions of acids on esters and 
water, the esters compete only with an oxonium base of the same order 
of strength as they are themselves and rather weaker, 4 the oxonium base 
of water and here the reaction with the ion is again predominant. 

These studies then show us a whole range of organic compounds, obvi- 
ously of the same type and family but giving reactions which proceed quite 

1 Mr. Norton is collecting more data on these relations. 

1 J. C. Moore's dissertation (1909). 

* Unpublished work by J. Stieglitz and Dr. Barnard. 

4 Lap worth, Loc. cit. 

41 



231 ON THE BIOCHEMISTRY OF NUCLEIC ACIDS. 

differently with the imido esters the action of ammonia on the positive 
ion is the essential action and the use of a catalytic agent, 1 an acid is 
advisable, in fact, necessary ; with ordinary esters the action on the ion 
becomes negligible because the ion simply cannot be produced in sufficient 
quantity under these conditions and the action of ammonia on the non- 
ionized ester becomes the essential action. The addition of acid as a catalytic 
agent is practically ineffective and therefore inadvisable. But these ap- 
parently disconnected results are now easily understood as being per- 
fectly consistent and logical the one case representing an almost but 
not quite pure type of one of the two natural simultaneous reactions 
the enormously rapid action of the ammonia on the imido ester ion and 
the other case representing the almost pure type of the other simultaneous 
action, the extremely slow action of ammonia on the non-ionized ester 
molecule. And the connecting link is found when the adjustment of 
the affinity and the velocity constants involved bring both actions out 
prominently at the same time. Of course one must then expect every 
possible class of reactions lying between these extremes. The results 
show plainly then, I believe, why a catalytic agent will work smoothly 
in a number of cases, and why it will fail utterly in accelerating actions 
apparently of exactly the same organic type, differing only in the numer- 
ical value of the physico-chemical constants included in the final expres- 
sion governing the action of a catalytic agent. We have been using the 
imido esters simply as a kind of magnifying glass to measure all these 
constants and thus to enable us to recognize some of the general underly- 
ing principles which govern catalysis by such chemical agents, as acids, 
bases and salts. 



ON THE BIOCHEMISTRY OF NUCLEIC ACIDS. 2 

BY P. A.' LEVENE. 
Received December 2, 1909. 

Life is the most complex phenomenon in nature and its manifesta- 
tions are innumerable. They all mysteriously arise in the living organism 
and are all harmoniously centered in it. This, even in its simplest form 
is the most perfect laboratory, the seat of an infinite number of chem- 
ical reactions, none of them interfering with the equilibrium of the others. 
The substances produced by the most primitive of the living organisms 
are as large in number as they are varied in their properties. The dis- 
coveries of new substances manufactured by the plant or animal cell 
are not yet exhausted and for ages the chemist dreamed of no better 
reward for his labors than the finding in tissue juices of a new body with 
properties hitherto unknown. The living organism was the only retort, 
vital force the only reaction in his possession that could furnish him with 
carbon-containing substances. In that sense every chemist in those 
days was a biological chemist. 

In the year 1828 a startling discovery was announced. Wohler wrote 
to Berzelius: "I must tell you that I can make urea without the aid of 
the kidney, or generally without the living organism whether of man 
or dog," and four years later the divorce of biological and organic 

1 Loc cit. 

3 Presented at the Second Decennial Celebration of Clark University, Worcester, 
Mass., September 15, 1909. 

42 



ORGANIC AND BIOLOGICAL. 232 

chemistry was apparently accomplished when Wohler and Liebig laid 
the foundation of the organic chemistry of to-day by their work on the 
radicle of benzoic acid. However, the divorce was only apparent, for 
the reason that only the knowledge of molecular constitution made it 
possible to establish the relationship between the organism and the 
chemical bodies manufactured by it, only the knowledge of the dynamics 
of the chemical reactions could coordinate the observations of the func- 
tions of the living organism, and of the accompanying changes in the 
composition of the living cells. 

The attitude of the biological chemist was altered. He saw his new 
goal in disclosing the nature of chemical reactions occurring within the 
living cell and finding their bearing on the manifestations of life. 

If time permitted I would present to you the progress of all the work 
done in that direction in recent years. Within the narrow limits of this 
report, however, this is impossible to accomplish with any degree of 
justice to the subject and I shall, therefore, limit the discussion to only 
one phase, namely, to the work bearing on the chemical interpretation 
of one of the most cardinal properties of living matter. 

Living matter is distinguished from inanimate by the fact that it under- 
goes cleavage and oxidation at a very perceptible velocity, and that 
the restoration of the loss sustained in that manner takes place at approx- 
imately the same rate. Thus the function of automatic regeneration 
lends to living matter its principal peculiarity. 

Great credit is due to the biologist for the discovery that in an or- 
ganized cell this function is seated in a formation possessing definite 
chemical properties, named chromatin or nuclein. At a time when 
the process of regeneration is very active, namely, during the develop- 
ment of the fertilized egg, the rate of the new formation of nuclein rises 
to a very perceptible degree, and the observer is led to see a genetic re- 
lationship between these two processes. 

Our distinguished biologist, Jacques L/oeb, 1 was the first to express 
the function of reproduction in terms of chemical reactions. In his 
address to the International Congress of Zoologists held in Boston in 
September, 1907, he stated: "If the question be raised as to what is the 
mo t obvious chemical reaction which the spermatozoan causes in the 
egg, the answer must be an enormous synthesis of chromatin or nuclear 
material from constituents of the cytoplasm." Thus, it becomes evident 
that the knowledge of the mechanism of regeneration is dependent on the 
knowledge of the chemistry of nucleins. 

I shall for a moment forestall the systematic discussion of the chemical 
nature of nucleins by mentioning that at the time of Loeb's address we 
were in possession of considerable information on the composition of 
these substances. It was known that phosphoric acid entered into the 
formation of the molecule. Therefore, it became evident to Loeb that 
a supply of phosphoric acid was required in order to make a synthesis 
of nucleins possible. In a developing egg the phosphoric acid was fur- 
nished by the cell itself, for the formation of nucleins proceeded also 
when the eggs were placed in a medium free of phosphoric acid. The 
other components of the cell that are known to contain phosphoric acid 
in their molecule are the lipoids. In these substances phosphoric acid 

1 University of California Publications in Physiology, 3, 61-81 (1907). 

43 



233 ON THE BIOCHEMISTRY OP NUCLEIC ACIDS. 

is present in an ester-form combination, and Professor Loeb proceeded 
to argue that the first phase in cell reproduction a priori ought to consist 
in the saponification of its lipoids. This assumption was brilliantly verified 
in his experiments on artificial parthogenesis. He brought to light the 
fact that dissolution of the lipoids is actually the process which precedes 
the nuclein synthesis and the segmentation of the nucleus. He further 
demonstrated that agencies facilitating this saponification were able under 
favorable conditions to start the development of an unfertilized egg 
without the aid of spermatozoa. Thus only an elementary knowledge 
of the chemical nature of two cell components furnished Professor Loeb 
with the power at will to start or to impede cell development by chemical 
means, and in a way to furnish evidence that the function of regeneration 
was a chemical process. But the process of nuclein synthesis in the ac- 
tive cells is not yet disclosed in its harmonious entirety, and no one can 
entertain any hope of arriving at this knowledge without the discovery 
of the chemical constitution of nudeins. 

The considerations that attracted the attention of so many chemists 
to the work on the chemical nature of these substances, therefore, are 
becoming very obvious, and I shall attempt to present the results and the 
achievements of the numerous endeavors towards the solution of this 
very difficult problem. 

The first important contribution to the chemistry of nucleins was 
made by Altman, a biologist. 1 Altman was in possession of the infor- 
mation that nucleins were endowed with the properties of fairly strong 
acids, and further that they were quite resistant to the action of pepsin 
hydrochloric acid. The latter property enabled him to prepare con- 
siderable quantities of nuclein by removing the protein part of the tis- 
sues by means of peptic digestion, and the fats by the usual extractives. 
The remaining nuclein he found to consist of a protein combined with 
a conjugated phosphoric acid. The acid he named "nucleic acid." 
By means of alkaline hydrolysis, Altman succeeded in removing all the 
protein from his nuclein so that the final product analyzed by him re- 
fused to disclose any trace of protein even by the aid of the most sensitive 
color test. 

The further development of the chemistry of nucleic acid was accom- 
plished through the investigations of Miescher, of Schmiedeberg and his 
pupils, of Kossel and his school, by Haiser, G. H. Hammarsten and his 
pupil Ivar Bang, and in this country by the work of T. B. Osborne, of 
Walter Jones, and of my co-workers and myself. I must, however, add 
that the purest nucleic acid was obtained by the man who was first in 
so many lines of chemical activity, Liebig, although on this occasion 
he failed to discover the real significance of his finding. 

I shall make no attempt to present all the work on nucleic acid in its 
chronological order, but I shall refer to individual investigations in con- 
nection with the discussion of the development of the various phases in 
our knowledge of chemical structure of those complex acids. 

The three principal phases in the endeavors to reveal the nature of 
nucleic acid consist: first, of work aiming to obtain the substance in a 
convenient manner, and in a possibly unaltered condition with a 

1 Arch. Anat. und Physiol. Physiol. Abt., 1889, 524. 

44 



ORGANIC AND BIOLOGICAL. 234 

view to ascertain the elementary composition of the substance; second, 
in the work directed towards finding all the components of the various 
nucleic acids ; and third, in determining the actual structure of the molecule ; 
or in other words the manner of arrangement of the individual com- 
ponents within the molecule. 

Ultimate Analysis of Nucleic Acids. 

I shall touch only briefly on the first phase of the work, for the reason 
that it is of interest principally to the men personally engaged in it. The 
achievements obtained through that work are not very significant. Only 
in connection with the study of inosinic acid, a nucleic acid of beef muscle, 
the elementary analysis was of unmistakable service in ascertaining the 
composition of the substance. It was the first and thus far the only 
instance that a salt of a nucleic acid was obtained in a crystalline form. 
The fact that no other nucleic acid has been prepared in an absolutely 
pure condition renders the conclusions drawn from their analysis only 
of secondary value. The workers who contributed to the improvement 
in the methods of preparation of the substance are: Altman, Miescher, 
Schmiedeberg, Kossel, Neumann, Hammarsten, Bang, Haiser and myself. 1 

The methods of preparation and of purification of the substance 
employed by individual workers differed greatly either in principle or 
detail. Under such circumstances marked divergence was noted in 
the analytical figures obtained by different investigators for nucleic acids 
even of the same origin. The following table illustrates some of these 
discrepancies. 

TABLE SHOWING THE ELEMENTARY COMPOSITION OP VARIOUS NUCLEIC ACIDS. 

C. H. N. P. O. Base. 

I. Thymonucleic acids of animal 
origin: 

1 Fisch sperm: 

a Salmon (Miescher and 

Schmiedeberg) 37.8 4.5 15.8 9.7 33.2 

b Gadus (Levene) 34.8 5.2 16.8 9.1 

c Homo (Katsuji and 

Inouye) 37.5 4.4 16.0 9.7 

d Maifisch (Levene and 

Mandel) 36.3 5.0 15.9 8.1 

2 Pancreas: 

a Ivar Bang 34.2 4.4 18.2 7.7 35.6 

b v. Furth, and Jerusalem. .. 29.2 4.3 u.6 6.9 ... Cu = 14.2 

3 Spleen (Levene) 37.8 4.8 16.5 8.99 

4 Mammary gland (Levene and 

Mandel) 34.7 4.4 15.6 8.5 

5 Intestinal wall (Katsuji Inouye) 37.5 4.8 15.5 9.4 

6 Thymus gland: 

a (Ivar Bang) 35.8 4.2 15.3 9.3 ... Na 6.25 

1 Altmann, "Uber Nukleinsauren," Arch. /. Anat. u. Physiol. Physiol. Abt., 1889, 
524. Miescher, Verhand. der naturforschenden Ges. in Basel, 1874, 6, 138; Arch. exp. 
Path. Pharm., 37, (1896). Schmiedeberg, Arch. exp. Path. Pharm., 43, 57 (1900). 
Kossel u. Neumann, Ber., 27, 2215, (1894), Neumann, Arch. Anat. und Physiol. Physiol. 
Abt., 1899, 552. Bang, Z. physiol. Chem., 26, 133 (1898-9). Haiser, Monatsh. Chemic, 
16. Levene, Z. physiol. Chem., 32, 541 (1901); 37, 402 (1902-3); 45, 370 (1905). 

45 



235 ON THE BIOCHEMISTRY OF NUCLEIC ACIDS. 

C. H. N P. O. Base. 

b (Kostytschew) 3* -4 4-6 12.8 7.6 ... Ba 17.5 

c (Herlant) 37-534-9316.489.63 

d (Schmiedeberg) 35.82 4. 14 14.68 9. 17 

II. Guanylic acid (animal origin): 

a Ivar Bang 34 .28 4.39 18.21 7.64 34.48 

b Levene and Mandel 36.35 4.95 18.65 6.15 33.90 

III. Plant nucleic acid: 

1 Yeast: 

a Herlant 337 4.1 14.8 8.69 ... Cu 10 

b Levene 34-97 4-4* 15.21 8.6 

2 Wheat embryo (Osborne and 

Harris) 33.1 4.2 14.9 8.1 

In adopting an empirical formula for the nucleic acids the individual 
investigators were guided not only by the analytical figures, but also by 
considerations of a speculative nature based to some extent on information 
obtained on partial or complete hydrolysis of the acids. The basis for 
the speculations of the different workers varied considerably. This 
led to a great divergence in the views on the empirical formula of nucleic 
acid. The following table contains some illustrations of it: 

c. H. N. o. P. 

Schmiedeberg 1 (spermnucleic acid) 40 56 14 26 4 

Stetidel 2 (thymus nucleic acid) 43 57 15 26 4 

[54 71 20 37 5 



Levene 3 (spleen nucleic acid) 

{43 55 15 3i 4 

Osborne and Harris 4 (wheat embryo nucleic acid) 42 62 16 31 4 

117 26 6 14 2 



Kossel 5 (yeast nucleic acid) . 

25 36 9 20 3 

Boas* (yeast nucleic acid) 36 52 14 24 4 

Levene 7 (yeast nucleic acid) 38 50 15 29 4 

The Components of Nucleic Acids. 

It has been stated that the first knowledge of the chemical nature of 
nucleic acids was limited to the information that it was a conjugated 
phosphoric acid. The first work of Altmann was followed by that of 
Kossel. The efforts of this investigator were directed towards the analysis 
of the products of hydrolytic cleavage of nucleic acids. His first achieve- 
ment was the discovery of purine bases in the molecule of nucleic acids. 
These bases can be obtained on cleavage of nucleic acids with very dilute 
solutions of mineral acids. Kossel further devised methods for the 
separation of the individual bases. He arrived at the conclusion that 
four purine bases, namely, adenine, guanine, hypoxanthine and xanthine, 
enter into the molecule of nucleic acids. This view, however, was later re- 
vised as it was established that only two purine bases, adenine and guanine, 
actually enter into the composition of nucleic acids. Hypoxanthine and 

1 Arch. exp. Path. Pharm., 57, 309 (1907). 

2 Z. physiol. Chem., 46, 332 (1905). 
8 Biochem. Z., 17, 120 (1909). 

4 Z. physiol. Chem., 36, 85 (1902). 
' Arch. f. Anat. Physiol., p. 181 (1891). 
Arch exp. Path. Pharm., 55, 16 (1906). 
7 Biochem. Z., 17, 120 (1909). 

46 



ORGANIC AND BIOLOGICAL. 236 

xanthine are now regarded as secondary products. 1 However, it was 
evident from the figures obtained on elementary analysis of nucleic acids, 
that their molecule contained substances other than purine bases. On 
the basis of the observation that on hydrolysis with dilute mineral acids 
only the purine bases are liberated and the other components remain 
intact, there was advanced a theory that in nucleic acids the phosphoric 
acid is combined with a complex radicle forming a conjugated phosphoric 
acid, and that this in its turn combined with the purine bases. The 
manner of this combination was the subject of considerable discussion 
and disagreement. 

The efforts to elucidate the composition of the complex radicle resulted 
in the discovery of the following purine derivatives. 2 

N = C.NH 2 HN CO HN CO 

OC CH OC CH OC C.CH 3 

I II I II I II 

HN CH HN CH HN CH 

Cytosine. Uracil. Thyinine. 

However, in order to obtain these substances it was necessary to resort 
to the hydrolysis by means of mineral acids of considerable concentra- 
tion. This procedure caused many investigators to express doubt as 
to the presence of the pyrimidine bases in the nucleic acid molecule. 
The doubt was particularly great regarding the orgin of cytosine and 
uracil. R. Burian 3 with great persistence defended the view that these 
two bases took their origin in the partial cleavage of the purine ring. 
However, the majority of workers were inclined to consider cytosine 
also as a primary constituent of the molecule of nucleic acids, while uracil 
was considered a primary product in the acids of plant origin only. 

Besides the purine and pyrimidine bases the molecule of nucleic acid 
was found to contain carbohydrates. The complex nucleic acids of 
animal origin contain a hexose, the exact nature of which is not yet 
established. The nucleic acid of plant origin and the simpler nucleic 
acid of the animal tissues contain a pentose. On the basis of the work 
of Neuberg 4 the pentose was considered /-xylose. However, very recently 
Jacobs and I have succeeded in isolating the substance in crystalline form. 
This made it possible to establish the true nature of the substance as 
d-ribose. 5 

As the methods of analysis had improved, and as approximately quan- 
titative estimation of the components was made possible, it was found 
that in nearly all the acids the bases were present in approximately 
equimolecular proportions, that the number of molecules of phosphoric 

1 Levene, Z. physiol. Chem., 45, 370 (1905). W. Jones and Austrian, J. Biol. Chem., 
3, i (1907). 

2 Kossel and Neumann, Ber., 27, 2215 ( J 894). Ascoli, Z. physiol. Chem., 31, 161 
(1900-1). Kossel and Steudel, Ibid., 37, 177 (1902-3). Levene, Ibid., 37, 402, 527 
(1902-3). 

* R. Burian, Ergebnisse der Physiol. 3 Jahrg. i Abt., 98 (1904); Z. physiol. Chem., 
51, 438 (1907). Steudel, Z. physiol. Chem., 53, 508 (1907). Osborne and Heyl, Am. J. 
Physiol., 20, 157 (1908). Levene and Mandel, Biochem. Z., 9, 233 (1908). 

4 Neuberg, Ber., 32, 3386 (1899). 

Levene and Jacobs, Ibid., 42, 2102, 3247 (1909). 

47 



237 ON THE BIOCHEMISTRY Of NUCLEIC ACIDS. 

acid corresponded to that of the bases, and the number of molecules of 
carbohydrate was equal to that of phosphoric acid. 1 

On the basis of these calculations, and on the basis of the numbers of 
the character of the bases entering into the molecule of the individual 
nucleic acids the following classification could be established: 

1. Nucleic acids: Containing one purine base (no pyrimidine), a pen- 
tose and phosphoric acid. (Inosinic acid, guanylic acid.) 

2. Nucleic acids: Containing two purine bases (guanine and adenine), 
two pyrimidine bases (cytosine and uracil) and phosphoric acid. (Phy to- 
nucleic acids.) 

3. Nucleic acids: Containing two purine bases (guanine and adenine), 
two pyrimidine bases (thymine and cytosine), and a hexose and phos- 
phoric acid. (Nucleic acid of animal tissue thymonucleic acids.) 

The Constitution of Nucleic Acids. 

The early speculations regarding the constitution of nucleic acids were 
based on the results of partial hydrolysis by means of dilute acids or 
weak alkalies. Reference has been made already to the views expressed 
by Kossel. 2 By mere heating with water under increased pressure, this 
author thought he obtained a substance, which was free of purine bases, 
but contained all the other components of the original nucleic acid. The 
substance was named thymic acid. Nucleic acid was regarded therefore 
as a complex consisting of thymic acid and of purine bases. The author 
did not furnish any detailed information regarding the nature of thymic 
acid. Somewhat more definitely formulated was the view of Schmiede- 
berg. According to this author there existed a complex nucleotin, this 
complex combined with phosphoric acid to form nucleotin phosphoric acid, 
and this acid in its turn combined with purine bases thus forming nucleic 
acid. Schmiedeberg ascribed to the nucleotin the formula C 30 H 42 N 4 O 1S . 
Alsberg, 3 working in Schmiedeberg's laboratory, actually succeeded in 
obtaining a substance which had the composition of the hypothetic 
nucleotin. However, these writers also failed to disclose the constitution 
of the complex radicle. In fact, they failed to furnish evidence that 
their substance was not a mixture composed of several cleavage products 
of nucleic acids. 

Results of actual significance for the interpretation of the structure 
of the nucleic acid were obtained only recently. The point of de- 
parture for the work was the study of inosinic acid by Levene and Jacobs. 
As has already been pointed out this acid is comparatively simple in its 
composition. It is composed of phosphoric acid, a pentose and hy- 

1 Schmiedeberg, Arch. exp. Path. Pharm., 46, 57 (1900). Kossel u. Neumann, 
Ber., 27, 2215 (1894). Kossel u. Steudel, Z. physiol. Ckem., 37, 119, 120, 121, 131, 
177 (1902-3); 145, 377 (1903); 38, 49. Ascoli, Ibid., 31, 161 (1900-1). Steudel, 
Ibid., 42, 165 (1904); 43, 402 (1905); 44, 157 (1905); 46, 332 (1905); 48, 425 (1906). 
Osborne and Harris, Ibid., 36, 85 (1902). Jones, W., and Austrian, /. Biol. Chem., 3, 
i (1907). Levene, Z. physiol. Chem., 37, 402, 527 (1902-3); 38, 80 (1903); 39, 4, 479 
(1903); 43, 199 (1904); 45, 37 (1905)- Levene and Stookey, Ibid., 44, 404 (1904). 
Mandel u. Levene, Ibid., 46, 155 (1905); 47, 140 (1906). v. Furth u. Jerusalem, Beitrage 
Chem. Physiol. u. Pathol., 10, 174 (1907). 

1 Kossel and Neumann, Z. physiol. Chem., 22, 74 (1896-7). 

3 Schmiedeberg, Ach. exp. Path. Pharm., 43, 57 (1900). Alsberg, Ibid., 51, 239 
'1904). 

48 



ORGANIC AND BIOLOGICAL. 238 

poxanthine. Through prolonged action of dilute acid at the temperature 
of 50 it was possible to break up the molecule into hypoxanthine and 
a pentose-phosphoric acid. 1 This substance was obtained by Jacobs 
and myself in the form of its crystalline barium salt. This acid had all the 
properties of a conjugated phosphoric acid, and on cleavage yielded the 
phosphoric acid. The acid reduced Fehling's solution on heating without 
previous hydrolysis. It was concluded from this that in the molecule 
the phosphoric acid and the carbohydrate are bound in ester-form, and 
that the aldehyde group of the pentose phosphoric acid was free and that 
therefore in the inosinic acid the base and pentose were coupled in a gly- 
coside union. This assumption was strengthened by the fact that 
inosinic acid was found to be very resistant towards the action of alkalies 
even at fairly high temperatures, and even on prolonged boiling the 
acid underwent only partial hydrolysis with formation of phosphoric 
acid and of the complex: pentose-base. Furthermore, it was found that 
by hydrolysis at nearly neutral point the conditions for the reaction 
were more favorable and it was possible in this manner to isolate and to 
identify the pentoside-inosine (C^H^N^). On the basis of this we 
concluded that the order of combination of the components in the 
molecule of the inosinic acid was established. I could add here that 
only on hydrolysis of the pentoside was it possible to obtain the crystal- 
line sugar which was identified as d-ribose. The structure of the com- 
plex pentose-hypoxanthine may be represented in the following manner: 

N C N 

II II I 
HC 

H H H H | 

CH 2 OH C C C C N C CH 
| OH OH | || 

L O OC NH 

The same substance had been found by Haiser and Wenzel in beet 
extract. 2 

Regarding the place of the purine base which entered into union with 
the sugar, there still remains only the evidence of Burian that place 7 
is attached to the sugar and no information exists regarding the place 
of the hydroxyl in the pentose that is coupled with the phosphoric acid. 
The following step in the progress of the work was the application of 
the experience obtained on inosinic acid to the other nucleic acids. Jacobs 
and I next directed our attention to the remaining acid of comparatively 
simple composition, namely guanylic acid. Employing the same methods 
of hydrolysis as applied to inosinic acid, we obtained guanosine 
(C 10 H 13 N 5 O 5 ), a substance analogous to inosine; it possessed nearly the 
same crystalline form, differed in its physical constants, and on hydrolysis 
gave guanine and the same pentose as the inosine, namely d-ribose. This 
pentoside had the same properties as inosine in its behavior towards al- 
kalies and acids. 3 For the sake of convenience we named the substances of 
this order " nucleosides " and the combination of the nucleoside and phos- 
phoric acid we named "nucleotides." Thus according to that nomencla- 
1 Ber., 44, 2703 (1908). 

1 Haiser and Wenzel, Monatsh. Chem., 29, 157 (1908) 
Ber., 42, 2474 (1909). 

49 



239 



ON THE BIOCHEMISTRY OF NUCLEIC ACIDS. 



ture inosine and guanylic acid were to be regarded as mononucleotides of 
the following structure : 

N C N 



X)H 



CH 



H H H H l| 

O = P O CH 2 C C C C N C CH 






OH 



OH OH 
i o 

(Inosinic acid.) 



H H H H 



OC NH 



N C N 

!! II II 
CH 



O = P O CH 2 C C C C N C C (NH 2 ) 



\ 



OH 



OH OH 



(Guanylic acid.) 



OC NH 



The further application of the same methods to a more complex nucleic 
acid, to that of the yeast, led to the conviction that this also was com- 
posed in the same manner. Thus the same nucleoside-guanosine, as 
obtained from guanylic acid, was also found on hydrolysis of the yeast 
nucleic acid. When the proper conditions are observed the nucleoside 
can be chilled out and a nearly quantitative separation accomplished. 
In the filtrate from this nucleoside other substances of the same nature 
were expected. On the basis of considerations expressed by me in an 
earlier article on the composition of the yeast nucleic acid the molecule 
of the acid is composed of four nucleotides and therefore four nucleosides 
should be found on cleavage of the substance. The work in that direc- 
tion is of comparatively recent date, and a second nucleoside has already 
been obtained from the mother liquor of guanosine. 1 The second nucleo- 
side has practically the same crystalline appearance as inosine or guano- 
sine, and differs from these two only by its physical constants and by 
the fact that on hydrolysis it yields in place of guanine the base adenine, 
and is, therefore, named adenosine. Also on hydrolysis of this nucleo- 
side the crystalline d-ribose is obtained. The substance therefore had 
the following structure : 

N C N 



CH 



H H H H 



CH,OH C C C C N C CH 



OH OH 



NH,C = N 



It possesses the melting point of 229 and the rotation: [a] D = 67.30. 
On the ground of this the structure of the yeast nucleic acid may be 
presented in the following manner : 2 

1 Levene and Jacobs, Ber., 42, 2703 (1909). 

2 Bloch, Zeitsch., 120, 17 (1909). 



ORGANIC AND BIOLOGICAL. 



240 



OH H H H 

O = P O CH 3 C C C CH C 6 H 4 N 5 
| OH OH | 

O J O 

H H H 

O = P CH, C C C CH C 5 H 4 N 5 O 
| OH OH |! 

OH J O 

All this work is of comparatively recent date so that as yet it could 
not have been extended to the analysis of thymonucleic acid. But 
evidence had been furnished that this substance also has a structure 
analogous to that of the yeast nucleic acid. 1 In fact considerations 
based on the work on thymus nucleic acid were the first that led to 
formulating the structure of the complex nucleic acid as a polynucleotide, 
of which the individual mononucleotides were composed of phosphoric 
acid, sugar and base. Levene and Mandel have on hydrolysis of the 
spleen nucleic acid with dilute sulphuric acid obtained a substance which 
had the elementary composition (C U H 17 N 2 PO 10 ) of a complex consisting 
of phosphoric acid, hexose and thy mine. On cleavage with 25 per cent, 
sulphuric acid this body gave rise to phosphoric acid, levulinic acid and 
thymine. This assumption is in harmony with subsequent discoveries 
on the simple nucleic acid and on the yeast nulceic acid, and one feels justi- 
fied in formulating the structure of thymonucleic acid in the following 
manner : 

OH H OH OH H 
O CH 2 C C C C C- 



O = P OH 



H 



H H 



C 5 H 4 N S 



-O 

N 



/~ OH H OH OH 

= P O CH, C C C C C C 5 H 4 N 6 O 



OH 



H 



H H 



-O 



Thus the details in the structure of the molecule of nucleic acids are 
not yet known. But some general information is already obtained and 
the route is singled out, by which the solution of the problem will be 
reached. An indication is given for a point of departure for the work 
on the synthesis of these substances. Work in that direction is now in 
progress in our laboratory. 

THE ROCKEFELLER INSTITUTE FOR MEDICAL RESEARCH, 
NEW YORK CITY. 



THE FUNDAMENTAL LAW FOR A GENERAL THEORY OF 

SOLUTIONS. 1 

BY EDWARD W. WASHBURN. 
Received March 3, 1910. 

Nomenclature. 

C Volume concentration. 

(i) Cp, (2) Cp Molecular heat capacity of (i) a liquid, (2) a gas. 

ACp Decrease in molecular heat capacity attending a change in 

state of aggregation, 
(i) KC, (2) KN Equilibrium constant in terms of (i) volume concentrations, 

(2) mol fractions. (Products of the reaction in the denomi- 
nator.) 

KS Solubility product in terms of mol fractions, 

(i) LS (2) Lg (3) Lp Molecular heat of (i) sublimation, (2) vaporization, (3) fusion 

(under constant external pressure). 

(i) N, (2) N' Mol fraction of (i) solvent, (2) solute, 

(i) n, (2) n' Number of mols of (i) solvent, (2) solute. 

p Gas or vapor pressure. 

P External pressure on a liquid or solid. 

Q x Heat evolved when the reaction aA + bB + .... = mM. + 

N + . . . . takes place from left to right in a solution 

under osmotic equilibrium. 
R Gas constant. 

(i) T, (2) Tp, (3) T , (i) Absolute temperature, (2) absolute temperature of the 
(4) TB, (5) TB O freezing point of a solution, (3) of the freezing point of the 

pure solvent, (4) of the boiling point of a solution, (5) of the 

boiling point of the pure solvent. 
U Total energy decrease produced when the reaction aA. + bE + 

. . . . = mM. + nN + . . . takes place from left to right. 
(i) v, (2) V Molecular volume of (i) a gas, (2) a liquid. 

JT Osmotic pressure. 

p. Thermodynamic potential. 

tf> Fugacity. 

6 Activity. 

I. The Development of the Modern Theory of Solutions. 

Upon the foundations laid by the labors of van't Hoff and Arrhenius 
has arisen the structure which we know to-day as the Modern Theory of 
Solutions. Before van't Hoff's epoch-making discovery of the ther- 

1 Presented at the Second Decennial Celebration of Clark University, Worcester, 
Mass., September 16, 1909. 

52 



GENERAL, PHYSICAL AND INORGANIC. 654 

modynamic relations which bind together the colligative properties 2 of 
dilute solutions, our knowledge concerning these important quantities 
was confined to a set of apparently unconnected empirical laws. Van't 
Hoff's generalization of these laws, followed almost immediately by the 
Ionic Theory of Arrhenius, stimulated greatly the study of solutions and 
made possible the rapid development and perfection of our present theory. 
Investigation has, however, been confined chiefly to the domain of dilute 
solutions and the Modern Theory of Solutions has remained almost en- 
tirely a theory of dilute solutions. The reason for this is, I believe, due 
largely to one of those historical "accidents" which occur now and then 
in the development of science. The history of this "accident" and the 
manner in which it came about forms a chapter in physical chemistry of 
interest alike to the chemist and to the philosopher. 

Perhaps the best way to form a clear idea of the process of evolution 
of our present theory of solutions is to consider first the colligative prop- 
erties of solutions and the relations which connect them. These quan- 
tities the osmotic pressure, vapor pressure, freezing point, boiling point, 
etc. have played such an important and vital part in the development of 
our solution theory that a clear idea of their relations to one another is 
absolutely essential to a proper understanding of the theory and of its 
development. The nature of these relations is expressed by the follow- 
ing statement : The colligative properties of a solution are connected by a set of 
rigorous differential equations which involve no assumptions except the two 
laws of thermodynamics. The equations are as follows: 



(1) Osmotic Pressure and Freezing Point, 

dT F 
V~ 

(2) Vapor Pressure and Freezing Point, 



/ L F \ 

= [ - (82) 

\ V > - 



(92) 
(3) Osmotic Pressure and Vapor Pressure, 

(77) 



(4) Osmotic Pressure and Boiling Point, 

'L. 



(90) 

To these should be added a number of others, such as the relation be- 
tween the electromotive force of a concentration cell and either vapor 
pressure (74) or osmotic pressure (70), and (16 and 14) the mutual re- 
lations among the osmotic pressures or vapor pressures of the constituents 
of a physical mixture or (30 and 300) the substances concerned in a 

2 Following Ostwald, the term "colligative properties" is used to embrace such 
properties as osmotic pressure, boiling point raising, freezing point lowering, vapor 
pressure lowering, etc. 

53 



655 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 

chemical equilibrium, etc. 3 While the following discussion applies with 
equal force to all of these relations, it will perhaps be conducive to clear- 
ness, if we confine our attention chiefly to the four relations given above. 

From the method of derivation of these relations, it is clear that they 
do not involve any assumptions regarding the concentration of the solu- 
tion, nor do they depend in any way upon the nature of the dissolved 
solute or its degree of association, dissociation, or solvation. In fact, if 
one knows, for example, the vapor pressure, freezing point lowering or 
boiling point raising for a solution of any nonvolatile solute, he has the 
means of calculating the osmotic pressure for the same temperature with- 
out knowing either the concentration of the solution or the nature of the 
solute. There may be one or several solutes present and they may as- 
sociate, dissociate, or unite with each other or with the solvent in any 
manner and to any extent. These questions are in no way involved in 
the calculation. Since relations such as those existing among the collig- 
ative properties of a solution involve only the two laws of thermody- 
namics, it will be convenient to refer to them as "purely thermodynamic 
relations" to distinguish them from an important group of relations which 
involve the composition of the solution and the nature of its components, 
and which we will now proceed to consider. 

Let us consider a solution of any solute A in any solvent B, and let our 
problem be to express each of the colligative properties of the solution 
as a function of its composition or its "concentration." This problem 
can in general be solved only by direct experiment for the particular 
solvent and solute under consideration. From what has preceded, how- 
ever, it is evident that as soon as we know the relation between any one 
of the colligative properties and the composition of the solution, the other 
relations become thereby determined. If, for example, we determined 
the freezing point of the solution for a series of concentrations, we could 
calculate thermodynamically the osmotic pressure, the vapor pressure, 
etc., for the same concentrations and thus derive an equation connecting 
each of these quantities with the concentration. The colligative property 
which should be chosen for experimental study in a given case would 
depend upon the relative ease and accuracy with which the several quan- 
tities could be determined and the temperature range which it was desired 
to cover; also in some cases upon whether the requisite "caloric quan- 
tities" 4 were known with sufficient accuracy or could be determined readily. 

The relation between any one of the colligative properties and the con- 
centration of the solution for any given solvent and solute will obviously 
depend upon the degree of association, dissociation and solvation of the 
solute. 5 Since the magnitude of these effects and their dependence upon 

3 The derivations of these relations and a more detailed discussion of them are 
given in a previous paper, "A Simple System of Thermodynamic Chemistry Based 
upon a Modification of the Method of Carnot" (Tins JOURNAL, 32, 467 (1910)). For 
convenience in reference these equations are given the same number here as in the 
previous paper where the significance of the quantities appearing in the equations is 
explained in detail. 

4 Proposed by van der Waals to distinguish heat capacities, latent heats, heats of 
reaction, etc., from colligative properties. 

5 It is hardly necessary to remark that this statement tacitly assumes that the 
desired relation is to be one which involves the number of mols of the solute. 

54 



GENERA!,, PHYSICAL AND INORGANIC. 656 

the concentration are in general unknown quantities, the problem is too 
complex for any complete solution. In general, therefore, it is necessary 
to make a separate investigation for every solvent and solute in order to 
establish the desired relation connecting some one of the colligative proper- 
ties with the concentration. To leave the problem in this condition, how- 
ever, is naturally not very satisfactory, and the course usually followed 
by science when confronted with a problem which is too complex is first 
to simplify the problem. Let us try to trace the process of simplification 
which has been followed by science in the present instance. 

Since association or dissociation of either solvent or solute molecules 
introduces complications, the first step in the process of simplification is 
obviously to consider the simple case of a solution in which neither takes 
place. Since the union of a portion or all of the solute molecules with 
the solvent molecules (solvation) is also a complicating factor, the next 
step in the process of simplification would naturally be to eliminate this 
factor also by assuming no solvation. After making these simplifications 
our problem would read as follows: What are the relations connecting 
the colligative properties with the composition in the case of a solution 
in which the number of molecular species present is equal to the number 
of components? Let us call such a solution, provisionally, an "ideal 
solution," postponing until later a more definite and accurate description 
of the properties of the type of solution to which the term "ideal" should 
be applied. 

There is, however, another method by which the complicating factor 
of solvation can also be eliminated. Willard Gibbs, in his monumental 
work on thermodynamic chemistry, has taught us that the proper way 
to represent the composition of any phase is by the means of the mol 
fractions of its several components. 7 

Now in the case of a solution, the mol fraction of the solute (for ex- 
ample) will be altered if it becomes solvated on going into solution, owing 
to the consequent change in the number of solvent molecules. Such a 
complication can be eliminated from our problem, as explained above, 
by assuming no solvation; or it can be likewise eliminated by taking the 
solution sufficiently dilute. For, as the solution becomes more and more 
dilute, the limit approached by the mol fraction of the solute is the same 
whether solvation occurs or not. 8 

* For example, in the case of two components, a solvent and one solute, there 
would be only two different kinds of molecules; for a solvent and two solutes, only 
three different kinds of molecules, etc. 

7 This system has been consistently followed by all investigators who use systems 
of thermodynamics based upon Gibbs' thermodynamic potential. The reason that it 
has not been followed by others is because they have confined themselves to the region 
of dilute solutions, where it is possible to use one of the limiting forms approached by 
the mol fraction of the solute, as the concentration approaches zero. 

8 To illustrate, if we put n' mols of a solute in n mols of a solvent and no solvation 

n' 

(or dissociation or association) occurs, then the mol fraction of the solute is 

(n' + n) 

If, however, on the average x mols of solvent are combined with each mol of solute, 

n' n' 

the mol fraction of the (solvated) solute is or . As the 

[n' + n n'x] \n'(ix) + n] 

55 



657 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 

Owing to an "historical accident" the latter method of eliminating the 
complication of solvation has been the one followed by science, instead of 
the former and more logical one. The "historical accident" 9 in this 
instance was van't Hoff's brilliant discovery of the remarkably simple 
equation connecting osmotic pressure with temperature and concentration 
in very dilute solutions. Starting with this equation as a basis and using 
the principles of thermodynamics, he showed us how to construct a com- 
plete theory of dilute solutions. 

As the field of dilute solutions became more and more developed, both 
from the experimental and theoretical side, investigators began to turn 
their attention to the subject of concentrated solutions. Investigation 
in this direction has usually taken the direction of attempts to extend the 
osmotic pressure equation by the introduction of quantities corresponding 
to the a and b of van der Waals' condition equation for gases, upon the 
basis of kinetic conceptions derived from an assumed analogy between 
osmotic and gas pressure. Other investigators have sought to attribute 
all of the deviation of concentrated solutions from the equations of dilute 
solutions, to solvation, and have even gone so far as to compute on this 
basis the approximate degree of hydration in some very concentrated 
aqueous solutions, for example. Still other attempts have been taken in 
the direction of an extension of our present equations by the addition of 
a series of terms containing a number of constants intended to express 
the influence of the solute molecules upon one another and upon the 
solvent. 

Attempts to obtain a satisfactory theory of concentrated solutions in 
any of these directions give no promise of success. An attempt to "ex- 
plain" why, as a solution becomes more and more concentrated, it de- 
viates more and more from the equations of very dilute solutions is some- 
what analogous to an attempt to explain why the sine of angle, which 
for sufficiently small angles is equal to the angle, deviates more and more 
as the angle grows larger. The reason is, of course, a purely mathematical 
one. Similarly in the case of solutions there is first of all a purely mathe- 
matical reason why concentrated solutions should deviate from the equa- 
tions of the infinitely dilute solution. The equations of dilute solutions 
are the limiting forms assumed by more general equations, owing to the 
fact that certain terms become negligible as the concentration approaches 
zero. In other words we have in our dilute solution laws only a portion, 
the residue, so to speak, of a more general set of laws for solutions of all 

solution becomes more and more dilute, both expressions approach - as their limit. 

n 

This is the familiar ratio which appears in our boiling point and freezing point equations. 

(n'\ (RT\ 

In the case of our osmotic pressure equation, instead of writing it jr== l~)\ ) 

\n / \ r / 

where V is the molecular volume of the solvent, it is customary to substitute V s = 
nV and write nV s = n'RT. Here again, if the solution is sufficiently dilute, it is ob- 
viously immaterial whether we understand V t to mean the volume of the solution or 
the volume of pure solvent in which the n' mols of solute were dissolved in preparing 
the solution. 

* The expression, "historical accident," is, of course, used in the philosophical 
sense. 

56 



GENERAL, PHYSICAL AND INORGANIC. 658 

concentrations. Consequently before science can hope to make any 
progress in the region of concentrated solutions she must go back to the 
point where the simplifying assumption of a dilute solution was uncon- 
sciously introduced, and, in place of it, make the simplifying assumption 
of an "ideal solution" as we have denned it above. We come, therefore, to 

2. The Laws of the Ideal Solution. 

Owing to the simplicity of the thermodynamic treatment of solutions 
by what we may call the osmotic-cyclical-process method and the fact 
that it uses conceptions which are comparatively easy to grasp and pro- 
cesses which can be readily pictured in the mind, it has been the favorite 
system among physical chemists. The fact that the theories developed 
by the advocates of this method have been confined almost entirely to 
the domain of the dilute solution is not due to any inherent fault in the 
method. In addition to this method we have the systems of thermody- 
namics based upon the Gibbs thermodynamic potential and its related 
functions. These systems have been the favorite ones among physicists 
and those who by training and inclination were accustomed to the use of 
potential functions, and it is among the advocates of the thermodynamic 
potential that we find the first successful attempt to formulate a theory 
of solution which is free from the assumption that the solution must be 
dilute. 

This theory has been developed in Holland by van der Waals and his 
associates, especially by van Laar. The first attempt was made in 1893 
by Hondius Boldingh 10 in an Amsterdam Dissertation which so far as I 
have been able to learn has never been published elsewhere. In the 
following year van Laar 11 published two papers in which he derived a set of 
"exact formulae for osmotic pressure, change in solubility, freezing point, 
boiling point, etc." His results were expressed in a series of equations 
in which the concentration of the solution appeared in a term, In(i-N'), 
in which N' represents the mol fraction of the solute. The equations 
contained, in addition, an undetermined function of the molecular ther- 
modynamic potentials of the constituents. In numerous subsequent 
publications van Laar has advocated with great warmth and zeal, the 
use of the thermodynamic potential method and the introduction of the 
concentration of the solution into the equations by means of the expression 
ln(i-A 7/ ), instead of assuming that the solution is dilute. Van Laar has 
in fact advocated a theory of solution which is entirely free from the 
assumption that the solution must be dilute. The foundations for this 
theory have existed in the literature for the last fifteen years. If it occurs 
to any one to wonder why the theory has not come into general use in the 
chemical world, he has only to glance through some of van Laar's papers, 
especially his earlier ones, and the reason will be more or less obvious. 

It is my present purpose to free this theory from the language of the 
thermodynamic potential and to develop it in the so-called "osmotic 
language." 12 Stated in this language, our problem is to determine the 

10 Boldingh, "De Afwijkingen van de Wetten voor Verdunde Oplossingen." Dis- 
sertation, Amsterdam, 1893. 

11 van Laar, Z. physik. Chem., 15, 457 (1894). 

12 The "language of the colligative properties" would be a better term. Too 
much importance is usually ascribed to osmotic pressure in our solution theory. 

57 



659 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 

functional relation between some one of the colligative properties of the 
solution and its concentration in the case of an ideal solution. Theoreti- 
cally we can start with any one of the colligative properties we choose, but 
since our present theory of dilute solutions is usually assumed to start 
with the osmotic-pressure-concentration relation, it will perhaps be more 
interesting to develop our theory of the ideal solution from the same 
standpoint. 

Let us, therefore, turn to the equation which expresses the osmotic 
pressure 13 for a very dilute solution : 

_ n'RT _ n'RT 
~T7 "~nV 

In this equation, n' is the number of mols of solute in n mols of solvent 
and V is the molecular volume of the pure liquid solvent. Let us now 
make use of the method, introduced by Willard Gibbs, of expressing the 
composition of the solution by means of the equation N' + N = i ,[ where 
N' is the mol fraction of the solute and N that of the solvent. The 
above equation can now be written : 



RT 



n' N'RT 



n + n' 



We have long recognized the fact that our osmotic pressure equation 
expresses strictly only the limit approached by the osmotic pressure as 
the concentration of the solution approaches zero. Let us therefore 
write the equation itself so that it will indicate this fact. This gives us 

(*N'\(RT\ 

V1TAT/- 

Seeing the equation in this form it is natural to suspect that the real 
relation might possibly be 

dN'\ fRT\ 

AT AT/' (I 3) 

or since by definition dN' = dN, 

ft'p\ 

-Jd\nN. (104) 

Stated in words, this means that not only would the addition of dN' mols 
of solute to a pure solvent involve an increase (i. e., from o to ATT) of 
osmotic pressure which satisfies equation (104) but that it would also 
involve the same increase in osmotic pressure when added to a solution 
whose osmotic pressure is TT. If such proves to be the case (and we shall 
see that in many cases, at least, it does) , our Modern Theory of Solutions 

13 Throughout this paper, we shall understand by the term "osmotic pressure," 
the pressure difference TT as defined by the equation TT = P P A , where P A is the 
pressure upon the pure liquid solvent A when it is in equilibrium (through a membrane 
or medium permeable only to itself) with the solution under the constant pressure P. 
This has been discussed more fully in the previous paper (Tins JOURNAL, 32, 478 (1910)). 

58 



GENERAL, PHYSICAL AND INORGANIC. 660 

has remained a theory of infinitely dilute solutions, because we have 
failed to recognize the fact that we have been working with true differen- 
tial equations, and that in order to obtain the "theory of concentrated 
solutions" which we have been seeking, the only thing we needed to do was 
to integrate our equations. 

In the case of osmotic pressure, for example, if we integrate equation 
(104), we shall obtain an equation which contains no assumption whatever 
regarding the concentration. The solution may be infinitely dilute or 
infinitely concentrated or may have any concentration between these 
limits. In order to do this we have only to put V = V (i + OTT), where 
V is the molecular volume of the pure solvent under the standard pres- 
sure P and a is its coefficient of compressibility, and on integration we 
obtain the Boldingh-van Laar 1 * equation for osmotic pressure: 



_ '!D f T t \ 

Jln(i 

* O * 



(105) 



Having come to the conclusion that the integral of equation (104) should 
represent the osmotic pressure for an "ideal solution," whatever its con- 
centration, we naturally seek for experimental confirmation before adopt- 
ing it finally. 15 Owing to the great difficulty of making accurate and 

14 The history of this equation (105) is very interesting. The differential form 
as expressed by equation (104) was obtained by van der Waals as early as 1890 (Z. 
physik. Chem., 5, 163) but no attempt was made to integrate it, only the case of dilute 
solutions being discussed, for which case it assumes the form of equation (102) or 
(100). In 1893 Hondius Boldingh, a student of van der Waals, making use of the 
thermodynamic potential of Gibbs, derived equation (105) in the following form (Diss. 
Amsterdam, 1893, p. 57): 

xV = RT In (i N 1 ) + aN' 

This differs from equation (105) as we have obtained it above, only in the fact that 
the compressibility of the liquid is neglected and a small correction term aN' is added, 
a being a quantity which, according to the molecular theory of van der Waals, expresses 
the mutual influence of the components of the solution upon each other. For "ideal 
solutions" it is negligible. 

Boldingh apparently made no attempt to apply his equation. The same equation 
was obtained the following year by van Laar (Loc. cit.) and in numerous publications 
since then, this investigator has given various derivations of this equation usually by 
methods involving the thermodynamic potential (cf., however, note 15). In 1897 
an osmotic pressure equation in its essential points practically identical with equation 
(105) was derived by Willard Gibbs (Nature, 60, 461 (1897)) by a method of balanced 
columns. Finally G. N. Lewis, in a recent paper (Tins JOURNAL, 30, 675 (1908)), has 
obtained equation (105) by a derivation involving his "activity" function and based 
upon the assumption that the "activity" of the solvent is proportional to its mol 
fraction. Both van Laar (Proc. Acad. Sci., Amsterdam, 9, 55 (1906)) and Lewis 
(Loc. cit.) have discussed the relation of this equation to the van't Hoff equation and 
have made comparisons of the values of osmotic pressure given by it with those obtained 
by Morse and Fra/.er by direct measurement, in the case of aqueous solutions. 

15 In view of the fact that the van't Hoff equation for osmotic pressure is usually 
regarded as derivable from the kinetic theory by methods analogous to those used in 
the kinetic derivation of the perfect gas laws (that is, on the assumption that osmotic 
pressure is caused by the molecular bombardment of the solute molecules), it may 

59 



66 1 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 

reliable osmotic pressure measurements, it would be an unnecessary 
waste of time and effort to seek experimental confirmation in this direc- 
tion, especially as the equation can be tested just as satisfactorily by means 

not be without interest to include here a brief kinetic derivation of the differential 
form of equation (105). For this purpose I shall modify slightly the derivation given 
by van Laar (Sechs Vortrage, p. 20). 

Consider two solutions of the same solute in the same solvent, both under the ex- 
ternal pressure P and separated from each other by a membrane permeable only to the 
molecules of the solvent. According to a theorem of Boltzmann, the number of solvent 
molecules which diffuse per second through a unit surface of the membrane in the 
two directions is given by the expressions: 

(a) From the weaker solution to the stronger, 



UTB = (iN' w )eRT~ ( 107) 

(6) From the stronger solution to the weaker, 

i+PV f 

n s = (/ N' f )e~Rf- ( 108) 

In these equations e is the base of natural logarithms, N' w and N' s are the mol frac- 
tions of solute in the weaker and the stronger solutions respectively, V is the volume 
of the solution, R the gas constant, T the absolute temperature and A a quantity 
which is a function of the temperature and which depends upon the units of measure- 
ment. By adjusting the pressure on the two solutions we can make the number of 
molecules of solvent which pass in the two directions equal ; in other words the two solu- 
tions will be in equilibrium as respects the passage of the solvent from one to the 
other. Under these conditions the right-hand members of the above equations can be 
placed equal to each other, giving us the equation: 



Or - 

Let us now impose the condition that the "weaker solution" shall be the pure 
solvent and that the "stronger solution" shall be an infinitely dilute solution in this 
solvent and shall be under an external pressure P. Under these conditions the above 
equation assumes the form 



(i+PV) 
Dividing through by e RT and using the logarithmic instead of the exponential 

nomenclature, we obtain equation (104): 

_ /?T\ 

Jdln(z AT') (104) 

After giving a kinetic derivation for equation (105), van Laar follows it with what 
he terms a "rein thermodynamischer" proof. Such a proof is of course impossible, 
if by "purely thermodynamic" we are to understand that the equation can be shown 
to be a necessary consequence of the two laws of thermodynamics and nothing else. 
In his papers on the subject, van Laar does not distinguish carefully between purely 
thermodynamic relations and relations which involve additional assumptions. This 
makes it difficult for the reader, who has not had considerable experience in the use of 
the thermodynamic potential, to appreciate just what assumptions he is making and 
what grounds he has for making them. Van Laar also falls into the error of attributing 
the failure of the modern theory of solutions in the region of concentrated solutions, 
to an inherent weakness in the osmotic method which he condemns severely, at the 
same time advocating with great zeal the thermodynamic potential as the only quantity 

60 



GENERAL, PHYSICAL AND INORGANIC. 662 

of its thermodynamic derivatives. Of these we will consider first, the 
vapor pressure derivative. The thermodynamic relation connecting 
osmotic pressure and vapor pressure is 



dr.= \^}*P' (77) 

Combining this with equation (104) so as to eliminate it we obtain 

Vdp = RTdlnN. (in) 

RT 
If the vapor can be regarded as a perfect gas we can put v = and 

obtain 

dln/> = dlnN (112) 

which on integration gives 

p = Pot* (3) 

where p , the integration constant, is the vapor pressure of the pure 
solvent. Since the terms solvent and solute are quite arbitrary, we can 
state therefore in general that the partial vapor pressure of any constitu- 
ent of an "ideal solution" is proportional to its mol fraction, if the vapor 
obeys Boyle's law. We have therefore in equation (113) an excellent 
means of testing our fundamental osmotic equation. 

which is in a position to completely solve the problem (Sechs Vortrage, p. 19). 
This point of view is absolutely unjustified and is doubtless partially responsible for 
the fact that the many excellent and valuable features of this investigator's contribu- 
tions to this problem have not received from the chemical world the consideration 
which they deserve. Whether we should adopt a system of thermodynamic chemistry 
based upon the entropy function (as worked out by Horstmann), or upon one of the 
thermodynamic potentials of Gibbs or Planck, or upon the "fugacity" and "activity" 
as defined by Lewis or upon the "osmotic pressure" and its related colligative properties, 
is largely a philosophical question in which the personal equation is an important 
factor. The "best" system from one point of view is not the "best" from another, 
and instead of adopting one of these systems and severely condemning the others, we 
should rather rejoice that the problems of our science are being attacked from these 
different points of view. All of these systems rest upon the common ground of the 
first and second laws of thermodynamics and any chemical problem which can be 
solved in terms of one of them can be solved in terms of all. I cannot therefore agree 
with van Laar, that the so-called "osmotic" system "lauft auf seinen letzen Beinen" 
and "nach wenige Jahre wird abgereist sein." 

Van Laar also attacks the so-called "gas theory" of solutions, that is, the theory 
that what we call "osmotic pressure" is a real pressure which exists within an isolated 
solution due to a molecular bombardment by the solute molecules. On this question, 
I sympathize largely with van Laar's point of view. His exposition of the difficulties 
in the way of such a theory is clear and convincing and I shall not, therefore, attempt 
any further discussion of the question at this time. In this connection, however, it 
is interesting to recall the views held by Willard Gibbs upon this point. In speaking 
(Loc. cit.) of the osmotic pressure in the case of a solution A, containing a solute, D, 
he says: 

"But we must not suppose in any literal sense, that this difference of pressure 
represents the part of the pressure in A which is exerted by the D-molecules, for that 
would make the total pressure calculable by the law of Boyle and Charles." 

6l 



663 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 

The next question which confronts us is, where are we to look for 
solutions whose characteristics approach most closely those which we 
have assumed for our "ideal solution," or in other words where can we 
find solutions for which we have reason to believe that we know the mol 
fractions of the constituents in the solution? Our attention is naturally 
directed towards mixtures of the so-called "normal" liquids of which 
many examples are to be found among the hydrocarbons of the benzene 
series and their substitution products. These liquids possess the property 
of mixing with each other in all proportions, the process of solution being 
accompanied by little if any heat effects or volume changes, such as 
would, in general, necessarily occur, if the process of solution were ac- 
companied by chemical reactions such as solvation or changes in the de- 
gree of association or dissociation of any of the components. In general 
the physical properties of these solutions are additive with respect to the 
constituents. This behavior is, however, just what we should expect 
in the case of the "ideal solution" which we have assumed. We may 
therefore expect to find experimental confirmation of our osmotic pressure 
equation in the case of these solutions. Fortunately data are at hand 
in the vapor pressure measurements of Zawidski and others. These data 
show most conclusively that equation (113) expresses the partial vapor 
pressure for both constituents throughout the total concentration range 
from zero to infinity for some dozen or fifteen different mixtures. 18 Freez- 
ing point data furnish additional confirmation of the correctness of our 
fundamental equation. Van Laar finds, for example, that the "freezing 
point" curve for solutions of mercury in tin, throughout its entire range 
(from t = 232 C., N' = o to i = 19, N f = 0.9964), is satisfactorily 
represented by an equation which rests on the same basis as our funda- 
mental osmotic pressure equation. 

This perfect experimental confirmation, combined with the light which 
is thrown upon the subject by the historical criticism, constitutes a most 
convincing array of evidence in favor of the adoption of the Theory of the 
Ideal Solution, as the best provisional General Theory of Solution. Before 
turning to a more detailed consideration of the equations of the Ideal 
Solution, let us state clearly the general characteristics of such a solution. 

They are as follows : 

18 The mixtures which obey this vapor pressure law are as follows: 
(i) CO CH 8 C1; (2) C 6 H 14 C.H 18 ; (3) C 2 H 4 Cl 2 --C e H,; (3) C,H,Br, C.H.Br,; 
(2) CH S OH C^OH; (2) CH 3 COOC Z H 6 C.H.COOC.H.; (2) C.H. C.H 6 CH 3 ; (4) 
C.H 6 C 6 H 5 C1; ( 4 ) C.H.-C.H.Br; (2) C 8 H S CH 3 C 8 H 6 C V H 6 ; (4) C 6 H 6 CH S C.H.C1; 
(4) CFsCHi- C 6 H s Br; (2) C 6 H S C1 C fl H s Br. 
References: 

1 Kuenen, Z. physik. Chem., u, 38 (1893). 
1 Young, J. Chem. Soc., 81, 768; 83, 68 (1903). 

3 von Zawidski, Z. physik. Chem., 35, 129 (1900). 

4 Linebarger, THIS JOURNAL, 17, 615, 690 (1895). 

This experimental confirmation of the theory of the ideal or "perfect" solution 
was pointed out in a recent paper by G. N. Lewis (Loc. cit.) who has computed some 
tables which exhibit in a very striking manner the excellent agreement of equation 
(105) with the experimental data, even in the most concentrated solutions. 

62 



GENERAL, PHYSICAL, AND INORGANIC. 664 

I. The number of molecular species present is equal to the number of 
components. 

II. The physical properties of the solution are connected with the physi- 
cal properties of its components in the pure state by the equation 

X = xN + x'N' + x"N" + ... (114) 

in which X is the molecular property in question (e. g., molecular heat 
capacity, molecular volume, molecular refraction, molecular internal 
energy, etc.), x (x', x", etc.) the molecular property of a constituent in 
the pure state and N (N f , N", etc.) its mol fraction in the solution. 

III. The third and most important characteristic is that which describes 
the thermodynamic relations. The manner of stating this characteristic 
depends upon what system of thermodynamics one chooses to make use 
of. I shall therefore state it in three different "languages." 

(a) The Gibbs Thermodynamic Potential System. According to van 
Laar the thermodynamic characteristics of the "ideal solution" are ex- 
pressed by the equation 

ft = Ho + RTlnN (115) 

in which /j. is the molecular thermodynamic potential of a constituent in 
the solution, fio the molecular thermodynamic potential of the same 
constituent in the pure state and N its mol fraction in the solution. 

(6) The Fugacity- Activity System of Lewis. Lewis uses a system of 
thermodynamic chemistry based upon two quantities, the "fugacity" 
<j>, and the "activity" !;, whose relation to each other is expressed by the 
equation 

<!> = RT (116) 

and which are connected with the thermodynamic potential by the equa- 
tion 

H = C + RTlntp (117) 

where C is a function of the temperature only. According to Lewis 
the "perfect solution" is defined by the equation 

= SoN (118) 

or what amounts to the same thing, 

<p = (f> N. (119) 

That van Laar's and Lewis' methods of describing the "ideal" or "perfect" 
solution are identical is made evident by writing equation (i 19) in the form 

RT\n<{> = RTlnfa + RTlnN, (120) 

and combining it with equation (117) when we obtain at once equation 

(US). 

(c) The Colligati've Property System or the So-called Osmotic System. 
According to this system, the relation between the colligative properties 
of the Ideal Solution and its composition is expressed by a set of equations 
which is composed of the equation 

63 



665 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 

(I04 ) 

and its thermodynamic derivatives. 17 

Having established fundamental equations for the Ideal Solution, let 
us now derive a set of equations for such a solution similar to our present 
equations for dilute solutions, but free from any assumptions as to the 
concentration of the solution. In deriving such a set of equations we could 
start either with our osmotic pressure equation (104) or the vapor pressure 
derivative (112). In either case we should obtain the same set of equa- 
tions. There is not much reason for choosing one of these equations 
rather than the other as a starting point. Each possesses certain ad- 
vantages for this purpose. In the following derivations, however, I shall 
start with the osmotic pressure equation (104) in each case. This pro- 
cedure will allow of direct comparison with our corresponding derivations 
for dilute solutions and it moreover avoids the necessity of using the 
gaseous phase in the derivation of a relation which is independent of the 
properties of the vapor. The procedure for obtaining our set of equations 
is very simple. In each instance, it consists simply in combining equation 
(104) with the proper purely thermodynamic relation and then integrating 
the result. The purely thermodynamic relations have all been obtained 
by the author in the previous publication 3 to which the reader is referred 
for their derivation. For convenience in reference these equations will 
be designated by the same numbers as in the preceding publication. All 
numbers below 100 refer to the previous paper. 

3. Vapor Pressure. 

We have already derived this equation for which the integrated form 
is 

P = P N (113) 

where p is the partial vapor pressure of any molecular species from an 
ideal solution in which its mol fraction is N, and p is its vapor pressure 
in the pure liquid state at the same temperature. For a single non- 
volatile solute whose mol fraction is N r this can also be written in the form 

A* n' 

r = N' = - -. (121) 

Po (n + nO 

If in a mixture of say two liquids, polymerization of one or both con- 
stituents, or chemical combination between them occurs, we can obviously 
make use of equation (113) to determine the exact nature and extent of 
these processes if we know the necessary partial vapor pressure data. 
Derivatives of equation (113) for special cases of association and of chemi- 
cal combination have been applied recently with considerable success 

17 Regarding the general characteristics of the Ideal Solution as stated above, it 
should be noted that although in general the absence of heat effects or volume changes 
on mixing two liquids may be taken as evidence for the absence of accompanying 
chemical reactions, the reverse is not necessarily the case. Heat effects and volume 
changes may and doubtless do occur in the absence of any chemical reaction, although 
in such a case the heat effect will in the majority of cases be of quite a different order 
of magnitude from that which is caused by a chemical reaction. 

64 



GENERAL, PHYSICAL AND INORGANIC. 666 

by Ikeda 18 and by Dolezalek 19 to the elucidation of the chemical condition 
of several pure liquids and of their mixtures. The accumulation of 
accurate and reliable vapor pressure data is of the highest importance to 
a clearer and more complete knowledge of the nature of solutions. For 
reasons which I have stated elsewhere, 21 the vapor pressure equation is 
the relation best adapted to serve as a basis for the experimental attack 
on the problem of concentrated solutions. 

4. The Freezing Point Equation. 
If we combine the purely thermodynamic equation 

L F \ dT F 



(82) 

with our fundamental equation 



_ RT 



\ 

Jdlntf (104) 



so as to eliminate TT, we obtain the desired equation 2 



For -very dilute solutions, we can of course substitute the freezing point 

n' dN' 

lowering A*/r in place of dT F and in place of ^ and obtain the 

n jv 

familiar law of Raoult-van't Hoff for freezing point lowering in dilute 
solution : 



It is preferable, however, to integrate our differential equation and 
thus obtain a general equation for an ideal solution of any concentration. 
Before doing this we will substitute in equation (122) 

T Atp = T F , i N' = N and <*( A*/r) = dT F 

where A//r is the freezing point lowering in centigrade degrees and T 
is the freezing point of the pure solvent on the absolute scale. This gives 
us 

dN' L F (i N') 



In order to integrate, we must first express L F as a function of At F which 
is done by the following purely thermodynamic equation: 

L F = L Fo ACp A< F y,a(A*F) f V^A^)' .... (85) 



18 Ikeda, J. Coll. Sri. Imp. Univ. Tokyo, 25, Art. 10 (1908). 

19 Dolezalek, Z. physik. Chem., 64, 730 (1908) ; see also Moller, Ibid., 69, 449 (1909). 
zo This equation was obtained by Boldingh (Loc. tit., p. 61) in the following form: 



where a has the meaning explained in note (14). Boldingh integrated his equation 
under the assumption that L F is independent of T. 

65 



667 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 

In this equation Lp is the molecular heat of fusion of the pure solvent 
at its freezing point T , ACp is the attendant decrease in the heat capacity 
of the system and a, /?, etc., are constants expressing the dependence of 
ACp upon the temperature. Combining (85) with (125) we obtain finally 
(neglecting /?) : 

dN' [L Fo &Cpo l /,a(W](i N') 



This equation can now be integrated. A convenient way to do this 
is to integrate into a power series in the desired variable by applying 
McL/aurin's theorem directly to the differential equation, carrying the 
series only so far as the accuracy of the experimental data warrant for 
the particular case under consideration. For example, in the case of 
water solutions if A/ F be known to 0.001, then for values of Atp which 
do not exceed 7, the terms containing a, (3, etc., are negligible and 
the application of McL/aurin's theorem gives us the equations 21 



Fo F A t 

v L F ~ 



AT* ro I A j i / I "Til . r" I / A \ I / \ 

N' atp l /,{ H I ( A^ F ) a (127) 

>-T o I / I r-fc*nn A * r T^ / \ * ' 

and 



the remaining terms in the expansion not being significant. 

If we desire to follow a freezing point curve through a considerable 
range of temperature, the general integral of equation (126) is more ad- 
vantageous. The general integral is 



* o 
(AC Po + aT ) Afr + V 2 a Afr] L Fo 



Equations of this general character have been derived by several ob- 
servers 22 and the corresponding theoretical curves have been compared 
with the experimental curves for a number of systems with good agreement. 
In these comparisons, however, the constants of the theoretical equation 
have been evaluated from the freezing point data themselves, so that 
the agreement loses a good deal of its significance. 

5. The Boiling Point Equation. 
By combining the purely thermodynamic equation 

21 The application of equation (127) to the data for aqueous solutions and the 
interpretation of the results obtained have been discussed by the author in a previous 
paper (Technology Quarterly, 21, 370 (1908)). This application was made on the 
assumption that the molecular weight of liquid water is 18. Although the results ob- 
tained on this assumption were fairly satisfactory up to a concentration of i molal, it 
is clear that a complete study of the behavior of aqueous solutions from the stand- 
point of the laws of the Ideal Solution must take into account the degree of associa- 
tion of the solvent. Further investigations along this line are now in progress in 
this laboratory. 

22 e. g., van Laar (Versl. K. Akad. van Wet., Amsterdam, 1903 and 1904; several 
papers) Roozeboom ('Die Heterogene Gleichgewicht," 2, 267 et. seq.), and Yamamota 
(/. Cott. Sci. Imp. Univ. Tokyo, 25, Art. n (1908)). 

66 



GENERAL,, PHYSICAL, AND INORGANIC. 668 

with equation (104) so as to eliminate TT we obtain the desired equation 

' 



(I30) 



which for very dilute solutions takes the familiar form 



In order to integrate the differential equation (130) we have only to ex- 
press LT, as a function of the temperature. The First Law of Thermo- 
dynamics gives us the rigorous equation 

dL, L v /^W^\ 

&-*-**+-(-;)(&), 

by means of which we can calculate the temperature coefficient of L,. 
If the vapor behaves as a perfect gas this equation becomes 

^ = ACp (133) 

dl 

and the methods of integration of equation (130) become perfectly analo- 
gous in every respect to those followed in the case of the freezing point 
equation in the preceding section. It is not necessary therefore to discuss 
them in detail. The final equations have the same form as the corre- 
sponding ones for the freezing point lowering. 

6. Chemical Equilibrium. 

Two examples will be sufficient to illustrate the method of derivation 
of the laws which regulate chemical equilibrium in the ideal solution. 
Let the equilibrium be expressed by the equation : 

oA + 6B + ..... ^~ > mM + N + ... (134) 

(a) The Effect of Concentration. The purely thermodynamic equation 
for the effect of concentration upon chemical equilibrium in a liquid phase 
at constant temperature and pressure is 

aVfidittL bVzdxB ..... + mVud^M + nV^dify + ... == o . (300) 
According to equation (104) the osmotic pressure for each substance 
taking part in the equilibrium is 

Fxcfcrx = RTdlnN*. (135) 

Combining these two equations we obtain the relation 

j #!' 

-~=*" (136) 



where K v is a constant. This expression differs from the Guldberg- 
Waage Law only in the substitution of the mol fraction N, in place of 
the volume concentration C. Equation (136) was obtained by Planck 23 as 
early as 1887, and the reasons for adopting it in place of the Guldberg- 
Waage form and for expressing the composition of solutions in terms 
of mol fractions instead of mols per liter were clearly stated by him at the 
same time. 

(6) The Effect of Temperature. The purely thermodynamic relation is 

OxdT 
. . . + ml/ M rf~ M + nV^dr^ + . . . = . (380) 



Planck, Wied. Ann., 32, 489 (1887). 

6? 



669 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 

Combining this with equations (136) and (135) and introducing the First 
Law of Thermodynamics we obtain the equation 

d^Kff = U_ 
dT RT* 

which is identical with the van't Hoff Law, with the substitution of Kjy 
in place of the Guldberg-Waage constant KC- In general it may be 
stated that the laws for chemical equilibrium in an ideal solution may 
be obtained from our present dilute solution laws by substituting mol 
fractions in place of volume concentrations. This applies also to hetero- 
geneous equilibrium. The Solubility Product Law, for example, for a 
saturated solution of the solute BC which dissociates into B and C be- 
comes 24 

WB'NC = const. = KS. (138) 

7. Concluding Discussion. 

Lest any one from the perusal of the foregoing pages should gain the 
impression that the problem of a satisfactory general theory of solutions 
may be regarded as completely solved, it will be well to examine for a 
moment, in a general way, the characteristics of the Theory of the Ideal 
Solution with respect to its advantages and disadvantages when regarded 
as the basis for a general theory of solutions. When compared with the 
Theory of Dilute Solutions we must acknowledge that it constitutes a 
distinct and decided step forward. One requirement of a satisfactory 
general theory of solutions is that it shall represent the facts throughout 
the whole range of concentrations for some type of solution, at least. 
This requirement is fulfilled by the Theory of the Ideal Solution and we 
may feel considerable certainty that any deviation from the requirements 
of this theory, in a given case, is due to physical or chemical causes and 
capable of a physical or chemical explanation and is not simply the result 
of attempting to apply a set of incomplete laws which do not and could 
not be expected to hold for any kind of a concentrated solution no matter 
how simple its character. 

The success of the Theory of the Ideal Solution as an instrument for 
throwing light upon the processes occurring in solutions has already been 
demonstrated in several instances. In the case of several solutions which 
apparently exhibit a behavior contrary to the requirements of the Theory, 
Dolezalek 19 has shown that perfect agreement between theory and ex- 
periment exist if the assumption be made that a simple compound is 
formed between the two constituents or that one of them is partially 
associated. In the case of acetone and chloroform for example, the as- 
sumption of a single compound, CHC1 3 (CH 3 ) 2 CO, and the introduction 
of the corresponding equilibrium constant into the equations sufficed to 
produce complete agreement between theory and experiment. It is true 
that the value of the constant was computed from the vapor pressure 
data themselves, but in a recent paper 19 Holier has shown that the values 
of such constants may be obtained independently of the vapor pressure 
data of the solution under consideration and that they therefore possess 
24 This is obtained by combining equations (51) and (104). It does not involve 
the Mass Action Law [i. e., equation (136)], which is usually assumed as the basis for 
the derivation of the Solubility Product Law. This point, which was brought out in 
the previous paper, has been overlooked in all of the textbooks of physical chemistry, 
although it was explained clearly by Planck as early as 1887 (Loc. cit.). 

68 



GENERAL, PHYSICAL AND INORGANIC. 670 

the physical significance ascribed to them and are not simply empirical 
constants of an interpolation formula. 

In all the cases studied by Dolezalek he found that agreement between 
experiment and theory is produced if the assumption be made that what 
appears to be a deviation from the theory is simply due to the fact that 
the numbers assumed as the mol fractions of the two constituents 
in the solution are incorrect and that when the proper mol frac- 
tions are used, the apparent discrepancy disappears. If we were 
justified in assuming that all solutions are really ideal solutions and 
that what appear to be exceptions are merely due to our inadequate 
knowledge of the number and kind of the various molecular species present 
and their respective mol fractions, then the Theory of the Ideal Solution 
would constitute a general theory including all solutions and all con- 
centrations and would enable us to ascertain just what occurs chemically, 
when the solution is formed out of its constituents. Unfortunately such 
is not the case, for it can be easily shown mathematically that if certain 
liquids form an ideal solution with one another they must be miscible 
in all proportions. The solutions in a system composed of two or more 
liquid phases in equilibrium with one another cannot therefore be governed 
to the laws of the Ideal Solution. Moreover, these exceptions are not 
merely apparent but are real and cannot be explained on the grounds of 
association, dissociation or chemical combination. The explanation 
must be looked for in a radical difference in the physical nature of the 
medium. 

To illustrate by an extreme case, let us consider a system composed of 
a solution of benzene in mercury and a solution of mercury in benzene, 
both solutions in equilibrium with each other. The vapor pressure of 
benzene from the mercury layer is equal to its vapor pressure from the 
benzene layer and yet the mol fraction of benzene in the mercury layer 
is probably so small that we could not detect it by any analytical means, 
while in the benzene layer it is equal to i , within the limits of our ability to 
measure it. The equality of the vapor pressure from the two layers can 
only be due, therefore, to the fact that the nature of the medium between 
the molecules of mercury is such that the benzene molecules can penetrate 
it only with the greatest difficulty. This effect of the physical nature of 
the medium is therefore one which must be taken account of in all applica- 
tions of the Theory of the Ideal Solution. In order that the laws of the 
Ideal Solution shall apply, the nature of the medium or the field of force 
in which the molecules find themselves in the solution must not be -very 
different from that of the pure liquid itself. Although this restricts some- 
what the sphere of usefulness of the theory, there still remain a large 
number of cases where it should prove of the greatest value in the elucida- 
tion of the chemical nature of solutions. Even in cases where the theory 
cannot be extended over all concentrations because of a consequent 
radical change in the physical nature of the medium, we may still hope 
to obtain valuable results with its aid in solutions of moderate concen- 
trations. At all events, I believe that the Theory of the Ideal Solution 
is the one which should be adopted as the basis for reference, classification 
an interpretation of the experimental data on solutions in place of our 
present Theory of the Infinitely Dilute Solution which is only a special, 
though very important, case of the former theory. 

URBANA, ILLINOIS, Feb. i, 1910. 

6 9 



A REVIEW OF SOME RECENT INVESTIGATIONS IN THE QUIN- 

AZOLINE GROUP. 1 

BY MARSTON TAYLOR BOGERT. 
Received March 31, 1910. 

For several years past, the Organic Laboratory of Columbia Univer- 
sity has been engaged in the synthesis and study of compounds belonging 
to that group of organic heterocycles known as quinazolines or phen- 
miazines. 

To us, the work has been most interesting and enjoyable. The com- 
pounds obtained have been generally crystalline solids, quite readily 
purified, stable, and very satisfactory to work with. 

Our investigations have included A. Quinazolines, B. Thioquinazo- 
lines, and C. Naphthotetrazines of quinazoline structure : 

N N N 






N - NN 



(Quinazoline) (Thioquinazoline) (1,3,7,9-Naphthotetrazine) 

Incidentally, a great many new preparatory, intermediate and sub- 
sidiary products have been obtained. From the standpoint of new sub- 
stances, the field has been an unusually fruitful one. 

It is, therefore, not only an honor but also a pleasure to present on 
this occasion a brief synopsis of the major lines of the work to date. 

A. Quinazolines. 

Colby and Dodge, 2 as the result of their investigations of the inter- 
action of nitriles and organic acids, under conditions of heat and pres- 
sure, came to the following conclusions: 

I. Fatty nitriles and aromatic acids give fatty acids and aromatic 
nitriles. 

II. Aromatic nitriles and fatty acids give mixed secondary amides. 

III. Aromatic nitriles and aromatic acids give secondary amides, un- 
less the temperature is very high, when the nitrile of the higher radical 
may form. 

Mathews, 3 in continuation of this work, heated acetonitrile and an- 
thranilic acid together under pressure, hoping thereby to obtain the 

1 Presented at the Twentieth Anniversary Celebration of Clark University, Wor- 
cester, Mass., Sept. 14, 1909. 

2 Am. Chem. J ., 13, i (1891). 

3 THIS JOURNAL, 20, 654 (1898). 

70 



RECENT INVESTIGATIONS IN THE QUINAZOLINE GROUP. 785 

anthranilic nitrile. On examining the contents of the tube, he found 
not the nitrile desired but a colorless crystalline compound, melting 
at 232 (uncor.), which was not identified at the time. 

Later, Bogert and Gotthelf 1 made a more careful study of this reac- 
tion and found that the crystalline substance melting at 232 was identical 
with the 2-methyl-4-ketodihydroquinazoline first described by Weddige, 2 
and later obtained by Bischler and Burkart, 3 Bischler and Lang, 4 and 
Niementovskii. 5 By varying the nitrile, they obtained other quinazolines 
of analogous structure. 

Continuing this work, Gotthelf 8 heated anthranilic acid under pressure 
with a: 

IV. Fatty nitrile alone (using aceto-, propio-, w-butyro-, t-valero- and 
i-capronitriles). 

V. Fatty nitrile and the corresponding fatty acid (acetonitrile and 
acetic acid, propionitrile and propionic acid, etc.). 

VI. Fatty nitrile and a higher fatty acid (acetonitrile and propionic 
acid, n-butyronitrile and capric acid, etc.). 

VII. Fatty nitrile and a lower fatty acid (isocapronitrile and pro- 
pionic acid, etc.). 

VIII. Fatty nitrile and the corresponding acid anhydride (propioni- 
trile and propionic anhydride, valeronitrile and valeric anhydride, etc.). 

IX. Fatty nitrile and higher acid anhydride (acetonitrile and pro- 
pionic anhydride, etc.). 

X. Fatty nitrile and lower acid anhydride (acetonitrile and formic 
acid, etc.). 

In considering case IV, Bogert and Gotthelf at the time thought it 
probable that the production of a quinazoline was due to the formation 
of an intermediate secondary amide. 



,NH, X X = 3 

C.H 4 < + CH 8 CN = C.A 4 < fi 1 =C 6 H 4 < | + H,O 

VOOH X CONHCCH 3 X CO . NH 

just as acetonitrile and acetic acid when heated under pressure give 
diacetoamide. 7 

One objection to this explanation of the course of the reaction lies 
in the fact that it involves a lactam condensation, whereas Weddige's 
investigations in this very field have made it quite clear that these con- 
densations follow preferably the lactim course. If the intermediate 
secondary amide assumed by us passes directly into the quinazoline by 
loss of water, two different quinazolines should result according to whether 
the condensation is of lactam or lactim type : 



y 

C 6 H 4 < 
N 



O 



+H t O 



CONHCCH, CO . NH 

(a) 

1 THIS JOURNAL, 22, 129 (1900). 

2 J. prakt. Chem., [2] 31, 124 (1885). 

3 Ber., 26, 1350 (1893). 

4 Ibid., 28, 282 (1895). 

8 /. prakt. Chem., [2] 51, 564 (1895) and Ber., 29, 1360 (1896). 

THIS JOURNAL,., 23, 6n (1901). 

7 Kekuld, Lehrbuch (ist ed.), i, 574; Gautier, Ztschr. Chem., 1869, 127. 

71 



786 ORGANIC AND BIOLOGICAL. 



6 H 4 <( 



NH H OH .NH.CCH, 

+ H,0 



CON:CCH 3 CO.N 

(*) 
As a matter of fact, the product obtained by us is identical with (a). 

Another objection is that it is not in harmony with the conclusions 
of Colby and Dodge 1 cited above. According to their experiments, 
the first products of the action of a fatty nitrile upon an aromatic acid 
at high temperature and pressure are the aromatic nitrile and the fatty 
acid, which may and often do subsequently combine to a mixed secondary 
amide. That the secondary amide is not the first product seems established 
by their results, for in no case where a fatty nitrile acted upon an aro- 
matic acid was the secondary amide found unaccompanied by aromatic 
nitrile, while in many cases aromatic nitrile and fatty acids were found 
unaccompanied by any secondary amide. Thus, acetonitrile and benzoic 
acid at 220 gave no acetobenzamide, but only benzonitrile and acetic 
acid, whereas when the latter two were heated together at 220, only 
acetobenzamide was formed. 

It therefore seems probable that the first phase of the reaction be- 
tween anthranilic acid and a fatty nitrile is as follows: 
HH, /NH, 

+ RCN = c e H K + R.COOH 

COOH \CN 

As aniline when heated to sufficiently high temperatures with fatty 
acids yields the corresponding anilides, 2 the second phase of the reaction 
is probably 

.NH, .NH.COR 

C 6 H 4 < + R.COOH = C 9 H 4 < + H,0. 



/ 
4V 

\ 



As the ease with which this acylation takes place decreases with in- 
crease in the molecular weight of the fatty acid, the higher nitriles should 
give smaller yields of the quinazoline, and this was found to be the case. 
The yield with propionitrile, for example, was 22.5 per cent., while with 
valeronitrile it was only 5 per cent, of the theoretical. 

The acylanthranilic nitrile may then pass into the quinazoline by either 
of the following reactions: 

.NH.COR xNH.COR ,K = CR 

C 6 H 4 < + H 8 0=C 6 H,< = C 6 H 4 < I +H k O 

X CN \CONH, \CO . NH 

or 

xNH.COR X NH.COR /N = CR 

C 6 H 4 < + R.COOH = C 6 H 4 < =C 6 H 4 < | + R.COOH. 

\CN \CONHCOR X CO . NH 

That a simple molecular rearrangement of the acylanthranilic nitrile 
occurs, 

xNH.COR N = CR 



CN co . NH 

seems unlikely, for the reason that when acetoanthranilic nitrile was 
heated for some time above its melting point, or when its solution in 
dry toluene was heated to high temperatures in sealed tubes, no change 

1 Loc. cit. 

2 Williams, Ann., 131, 288; Pebal, Ibid., 91, 152. 

72 



. 

RECENT INVESTIGATIONS IN THE QUINAZOUNE GROUP. 787 

whatever occurred. 1 Moisture was, of course, rigidly excluded in these 
experiments, since a small amount of water, by successive addition and 
splitting off, would suffice to convert an indefinite amount of the nitrile 
to the quinazoline. 

In further support of the assumption that the acylanthranilic nitrile 
is an intermediate product, are the following facts: (i) Acetanilide is 
found as a by-product in the tubes. 2 (2) The presence of a small amount 
of acetic anhydride greatly increases the yield of quinazoline. (3) The 
same quinazoline results when acetoanthranilic acid is heated in a sealed 
tube with acetonitrile as when anthranilic acid itself is used. 3 (4) Aceto- 
anthranilic nitrile on partial hydrolysis changes immediately to the 
quinazoline. 4 

The by-products observed in the experiments were carbon dioxide, 
aniline, anilides, amides and ammonia. Of these, carbon dioxide and ani- 
line are normal decomposition products of anthranilic acid at high tem- 
peratures. Partial hydrolysis of the nitrile accounts for the presence of 
amide. Aniline acting on the latter, 5 or upon the fatty acid present, 
yields the anilide, the by-product in the former case being ammonia. 

In those cases (V, VI and VII) where the anthranilic acid was heated 
with both the fatty nitrile and the fatty acid, the results are confusing 
and the interpretation obscure. Quinazolines were formed, but the 
course of the reactions is not clear and additional work is needed before 
any satisfactory conclusions can be reached. 

When an acid anhydride was added to the tubes containing the an- 
thranilic acid and fatty nitrile (VIII, IX and X), the anhydride used 
determined the quinazoline formed in practically every case. In these 
experiments, the reaction is therefore probably as follows: 

y NH, .NH.COR 

C 6 H,< + O(CO.R) 2 = C 6 H 4 < + R.COOH 

X COOH X COOH 

/NH.COR /NH.COR 

C 6 H/ + R'CN = C 6 H/ 

X COOH X CONHCOR', 

the latter then~condensing in either of the following ways: 



N:C 



X ,N 



CONH 



OH 
COR 



).NH 



+ R'COOH (a) 



C 6 H/ 



N HCOR 



,N = CR' 



R' 



= C 8 H 4 / | + R.COOH 

VO . NH 



The nitrile was used with the corresponding acid anhydride (VIII), 
with a higher acid anhydride (IX), and with a lower anhydride (X). Of 
these, types VIII and IX invariably yielded pure quinazolines according 
to reaction (a) above. Only when a lower anhydride was used with the 

1 Bogert and Hand, THIS JOURNAL, 24, 1034 (1902). 

2 Bogert and Gotthelf, Ibid., 22, 528 (1900). 

3 Bogert and Gotthelf, Loc. cit. 

4 Bogert and Hand, Loc. cit. 

6 Kelbe, Ber., 16, 1200 (1883). 

73 



788 ORGANIC AND BIOLOGICAL. 

nitrile (X), were products encountered which were mixtures of quinazo- 
lines. 

Of these different sealed-tube reactions, much the best was that in 
which the anthranilic acid was heated with the fatty nitrile and the 
corresponding acid anhydride (VIII). The yield by this process was 
fair (30 to 50 per cent, of the theory) and, unless the heating was too 
high, the tube contents were invariably light-colored and crystalline. 

In the foregoing, it is assumed that the secondary amide is an inter- 
mediate product in the formation of the quinazoline. Such an amide, 
R.CO.NH.CO.R', being symmetrical, should be producible either from 
R.COOH and R'CN, or from R'COOH and RCN. In other words, 
since the formation of the CO.NH.CO group is due solely to the 
combination of the CN and COOH, it should make no difference which 
radical carries the CN and which the COOH. The same secondary amide 
and, therefore, the same quinazoline, should result whether the acylan- 
thranilic acid is heated with the fatty nitrile, or the acylanthranilic nitrile 
with the fatty acid (or its anhydride). On testing this practically, 1 such 
was indeed found to be the case, and a number of quinazolines were 
thus obtained from the acylanthranilic nitriles by heating them in sealed 
tubes with the fatty acid or, better, its anhydride. 

In experimenting with these acylanthranilic nitriles, a method of 
converting them into the quinazolines, far superior to any of the methods 
described above, was discovered. It consists in digesting the acylan- 
thranilic nitrile for a few minutes with a warm alkaline dioxide solution, 
and is really a beautiful method, being very rapid, simplicity itself in 
execution, and giving large yields of practically pure quinazolines. It 
depends upon the hydrolysis of the nitrile to the amide, the acylanthranil- 
amide then condensing to the quinazoline, as shown by Weddige. 2 

In those cases where the o-amino acid is best obtained from its nitrile 
by saponification, it is convenient to be able to pass direct from the 
nitrile to the quinazoline. Thus, homoanthranilic nitrile is readily 
prepared from ra-nitro-/>-toluidine, through w-nitro-/>-toluonitrile, and 
from the acyl derivatives of this homoanthranilic nitrile and an alkaline 
dioxide solution (hydrogen dioxide solution made alkaline with sodium 
hydroxide), the 7-methyl-4-quinazolones were prepared. 3 

By a number of different processes, including those already mentioned, 
starting with brominated anthranilic acdis, bromoquinazolines were pre- 
pared. 4 

Our attention was next turned to the nitroquinazolines, and many 
were made from nitroanthranilic acids by the methods already described, 
and also by heating the ammonium salt of the nitroanthranilic acid 
with formamide, 5 by the direct action of heat on the ammonium salts 
of nitroacylanthranilic acids, 6 and by the action of primary amines on 
nitroacetoanthranils. 7 The last is a very fine method indeed, and one 
we have developed quite extensively. 

1 Bogert and Hand, THIS JOURNAL, 24, 1031 (1902). 

2 J. prakt. Chem., [2] 31, 124 (1885); 36, 141 (1887). 

3 Bogert and Hoffman, THIS JOURNAL, 27, 1293 (1905). 

4 Bogert and Hand, Ibid., 25, 943 (1903); 28, 94 (1906). 

5 Niementovskii, /. prakt. Chem., [2] 51, 564 (1895). 
8 Bischler and Burkart, Ber., 26, 1349 (1893). 

7 Anschiitz, Schmidt and Griffenberg, Ber., 35, 3480 (1902). 

74 



RECENT INVESTIGATIONS IN THE QUINAZOLINE GROUP. 789 

By these various methods, we prepared 5-nitro-, 1 6-nitro- 2 , and y-nitro- 
4-quinazolones. 3 Of the four possible types of benzoylnitroquinazolines, 
representatives of the 6-nitro, 4 and 8-nitro, 5 were already known. The 
preparation of the 5-and y-nitro derivatives completed the series. 

Reduction of the nitroquinazolines yielded the corresponding benzoyl- 
aminoquinazolines, 6 in which, as might have been expected, the amino 
group shows the usual aniline reactions. 

Aminoquinazolines with the amino group on the miazine side of the 
nucleus were produced by condensing simple or substituted acylanthranils 
with primary hydrazines, 7 

N.COR /N = CR 

H,N.NHR' = C 6 H 4 < | + H S O. 

\CO . N.NHR' 

With hydrazine itself, it was also found possible to condense two mol- 
ecules of the anthranil with one of the hydrazine, thereby giving 3,3'- 
diquinazolonyls, 

= Cr RC = N, 



. N N. CC 

The same result can be accomplished, though less satisfactorily, by con- 
densing the 3-aminoquinazoline with a second molecule of the anthranil. 
The di-quinazolonyls so far isolated are all very difficultly soluble and 
inert. 

The 3-aminoquinazolines proved interesting because of their unsym- 
metrical secondary hydrazine structure, >N.NH 2 . In the main, their 
properties coincide with those of other N-amino heterocyclic compounds. 
Thus, nitrous acid does not diazotize the amino group, but replaces it 
by hydrogen; with diacetosuccinic esters, they often yield pyrrole de- 
rivatives; 8 with aromatic nitroso bodies, they do not give azo compounds; 
nor are they oxidized to tetrazones by mercuric oxide. On the other 
hand, they do not usually condense with ketones, while they do occasion- 
ally yield phenyluramino derivatives with phenyl isocyanate. 9 In the 
elimination of the N-amino group by the action of nitrous acid, there 
must be some unstable intermediate product formed, for if immediately 
after the addition of the nitrous acid the mixture be poured into an alkaline 
solution of alpha- or beta-naphthol, dyestuffs are formed of considerable 
tinctorial power, the structure of which has not been elucidated. 

Further experimentation with the acylanthranils showed that they 

1 Bogert and Chambers, THIS JOURNAL, 27, 649 (1905); Bogert and Sell, Ibid., 
2 7 1305 (1905) and 29, 532 (1907). 

2 Bogert and Cooke, Ibid., 28, 1449 (1906). 

3 Bogert and Steiner, Ibid., 27, 1327 (1905); Bogert and Sell, Ibid., 29, 532 (1907); 
Bogert and Klaber, Ibid., 30, 807 (1908). 

4 Dehoff, /. prakt. Chem., [2] 42, 347 (1890); Thieme, Ibid., 43, 441 (1891). 

5 Zacharias, Ibid., 43, 441 (1891). 

8 Bogert and Chambers, THIS JOURNAL, 28, 207 (1906); Bogert and Klaber, Ibid., 
30, 807 (1908). 

7 Bogert and Sell, Ibid., 28, 884 (1906); Bogert and Cook, lloc. cit.; Bogert and 
Klaber, Loc. cit. 

8 Billow, Ber., 35, 4312 (1902); 39, 2621 and 3372 (1906). 

9 Bogert and Gortner, THIS JOURNAL, 31, 943 (1909). 

75 



790 ORGANIC AND BIOLOGICAL. 

could also be condensed with amino nitrils or amino esters to the cor- 
responding quinazolines. 1 

The ease with which acylanthranils condense with primary amines to 
crystalline quinazolines suggests the utilization of this reaction for the 
separation and identification of easily soluble or sirupy amines difficult 
to handle otherwise. 

The same reaction was employed for the preparation of quinazoline 
carboxylic acids from acylanthranil carboxylic acids, 2 

X N.COR ,N = CR 

HOOC.C e H 3 < | + zR'NH, = R^NH 3 OOC.C 4 H 3 < | + H,O. 

N CO \CO . NR' 

These quinazoline benzoylcarboxylic acids are colorless crystalline 
solids, melting with decomposition above 300, more or less soluble in 
alcohol, but very difficultly soluble in other neutral organic solvents. 

From the oxalyl anthranils, quinazolinecarboxylic acids were pre- 
pared carrying the carboxyl group on the miazine side of the nucleus, 3 

.N.COCOOR .N = C.COOR 

C 6 H/ | + R'NH, == C 6 H 4 < | + H,0. 

N CO N CO . NR' 

The particular quinazolines described in the foregoing are for the most 
part of the type designated as 4-ketodihydroquinazolines or, more simply, 
4-quinazolone s, 




O 
(4) 

When there is an H at position 3 instead of a radical, there arises the 
possibility of keto-enolic tautomerism, 

.N = CR X N == CR 

C,H/ | ^ C 6 H/ | . 

X CO.NH \C(OH):N 

(4-Quinazolone) (4-Hydroxyquinazoline) 

All those 4-quinazolones (4-hydroxyquinazolines) which carry a hydro- 
gen at position 3 are easily soluble in aqueous solutions of the caustic 
alkalies and re-precipitable from such solutions by carbon dioxide or 
acetic acid. When these alkali salts are treated with alkyl halides, the 
3-(JV)alkyl derivative is the chief product. 4 The nitro derivatives furnish 
an apparent exception to this, in that the product with the higher alkyl 
halides is reported as chiefly the oxygen ether (i. e., the 4-(<9)alkyl, or 
-OR compound). 5 We are somewhat skeptical, however, of the accuracy 
of these results and feel that they should not be fully accepted until the 
pure oxygen ethers have been prepared by other processes and the two 

1 Bogert and Klaber, Loc. cit. 

2 Bogert, Wiggin and Sinclair, THIS JOURNAL, 29, 82 (1907); Bogert and Jouard, 
Ibid., 31, 489 (1909). 

3 Bogert and Gortner, Ibid., 32, 119 (1910). 

4 Bogert and May, Ibid., 31, 507 (1909). 

5 Bogert and Seil, Ibid., 29, 517 (1907). 

7 6 



RECENT INVESTIGATIONS IN THE QUINAZOLINE GROUP. 79 1 

products compared. One reason for this skepticism on our part is that 
certain of these suppositious oxygen ethers could not be hydrolyzed with 
concentrated mineral acids (hydrochloric), a result contrary to our ex- 
perience and to that of others working with true oxygen ethers. 

Pure 3-(A^)alkyl derivatives are easily obtained by the acylanthranil 
reaction already described. For the isomeric 4-OR derivatives, the 
best method appears to be the treatment of the 4-chloroquinazolines 
with sodium alcoholates. 1 In the case of the simple alkyl derivatives 
of unsubstituted 4-quinazolones (4-hydroxyquinazolines), the (3)-NR 
compounds are colorless, odorless solids, quite soluble in water, gen- 
erally very difficultly volatile with steam, of higher melting point than 
the 4-OR isomers, and are not hydrolyzed by strong hydrochloric acid. 
On the other hand, the 4-OR compounds are oily liquids or low-melting 
solids, usually of pleasant odor, readily volatile with steam, less soluble 
in water but more soluble in hydrochloric acid than the NR isomers, 
and are readily hydrolyzed by mineral acids to the hydroxyquinazoline 
(4-quinazolone) again. Some of the lower ones can even be distilled 
undecomposed at ordinary pressure. 

In the preparation of the 4-chloroquinazolines from the 4-hydroxy- 
quinazolines (4-quinazolones), 1 a methyl or ethyl group in position 2 
exerts a peculiar influence upon the course of the reaction with phos- 
phorus halides or similar halogenating reagents. In all such cases, it 
was found impossible to replace the OH at 4 by chlorine without simul- 
taneously introducing three chlorine atoms in the benzene part of the 
nucleus. Even when 2,3-dimethyl-4-quinazolone was heated with phos- 
phorus penta- and oxychlorides, 2 the 3-methyl group was split off, a Cl 
attached itself at 4, but again three Cl's entered the benzene nucleus. 

Our investigations in this 4-quinazolone group have led to the syn- 
thesis and study of derivatives carrying the following substitutions: 

1. At position, 2-, methyl, ethyl, normal and isopropyl, isobutyl, isoamyl, 
phenyl, m- and />-nitrophenyl, benzyl, p-to\yl, COOH, and various com- 
plex radicals and residues. 

2. At position, 3-, methyl, ethyl, normal and isopropyl, iso- and second- 
ary butyl, isoamyl, allyl, phenyl, o-tolyl, />-anisyl, benzyl, beta-naphthyl, 
CH 2 COOR, CH 2 CONH 2 , CH 2 CN, C 6 H 4 COOR, C 6 H 4 CONH 2 , C 6 H 4 CN, the 
amino group and its derivatives, quinazolonyls, and dimethyl dicarb- 
ethoxy pyrrole. 

3. At position, 4-, OH, Cl, and OR. 

4. On the benzene nucleus-, alkyls, halogens, nitro, amino (and deriva- 
tives), and COOH. 

In the various series, where homologs of analogous structure are com- 
pared, it will be found that the melting point falls quite steadily with 
rise in molecular weight, the iso compounds melting higher than the 
isomers carrying normal alkyls. This is perhaps not so surprising since 
many series of anthranilic compounds (for example, the alkyl and acyl- 
amino anthranilic acids, the acylanthranilic nitriles, etc.) exhibit a similar 
behavior. 

In addition to the 4-quinazolones, our studies have included also the 
2-quinazolones (2-hydroxyquinazolines), 2,4-dihydroxyquinazolines (2,4- 

1 Bogert and May, Loc. cit. 

2 Compare Fischer, Ber., 32, 1297 (1899). 

77 



792 ORGANIC AND BIOLOGICAL. 

dike tote trahydroquinazolines, or benzoylene ureas), and a few other 
types. 

B. Thioquinazolines. 

The work in the domain of the oxygenated quinazolines led quite natur- 
ally to the production of bodies of analogous structure carrying sulphur 
instead of oxygen, and known as the 4-thioquinazolone or quinazolthion (4) 
type, 1 

/N = Cr N===CR 

C 6 H/ ! I C 6 H 4 < | . 

\CS . NH \C(SH) : N 

Since anthranilamides, as noted, easily condense to quinazolines by 
loss of water, it seemed probable that the corresponding thioamides would 
yield thioquinazolines. 

/NH.COR X N = CR 

C,H/ =C 6 H 4 < | + H.O. 

\CS.NH, N CS . NH 

and the results corroborated this fully. 

The acylanthranilic thiamide was prepared either by first converting 
the anthranilic nitrile to the amide by the direct addition of hydrogen 
sulphide and then acylating, or by first acylatirig and then adding the H 2 S: 

/NH, 

C 6 H/ + O(COR), 

A \CSNH, , 

t+H,S I 

/NH, | /NH.COR /N = CR 

r\ TT s-\ TT S - , >. TT / I I TT \ 

*\CN A* 4 ^CS.NH 2 4 \CS . NH 

+ O(COR), 
NH.COR 

H,S 

CN 



By the use of thiol acids (for example, thioacetic acid) in sealed tubes, 
the thioquinazoline was obtained direct. The thiol acid first acylates 
the amino group. The by-product of this acylation, H 2 S, cannot escape 
from the tube and is thus forced to attach itself to the CN, thereby changing 
it to the thioamide. The acylaminothioamide then passes to the thio- 
quinazoline by loss of water. 

As comparatively few thiol acids are readily available, we made our 
reaction more widely applicable by substituting the acid anhydride with 
sodium sulphide for the thiol acid. Thus, when anthranilic nitrile is 
heated with acetic anhydride and sodium sulphide in open flasks or, 
better, in sealed tubes, the anhydride first acetylates the amino group 
with formation of acetic acid as the by-product. The latter then attacks 
the sodium sulphide, setting free hydrogen sulphide and forming sodium 
acetate. The hydrogen sulphide converts the acetoanthranilic nitrile 
to the thioamide, which then splits out water and gives the quinazoline, 
the sodium acetate possibly assisting in the elimination of this molecule 
of water. 

These thioquinazolines crystallize in beautiful yellow needles or prisms 

when alcohol is used as the solvent. By virtue of the CS.NH 7""^ 

C(SH) : N group, they dissolve freely in solutions of the caustic 

1 Bogert, Breneman and Hand, THIS JOURNAL, 25, 372 (1903); Bogert and Hand, 

Ibid., 25, 935 (1903)- 

78 



RECENT INVESTIGATIONS IN THE QUINAZOLINE GROUP. 793 

alkalies and are re precipitated therefrom by carbon dioxide or by acetic 
acid. 

Like the corresponding oxygen compounds, the melting point of the 
2-alkyl derivatives steadily falls with rise in molecular weight, the iso 
compounds melting higher than the isomers of normal structure. 

In the course of the investigation, we have used both simple and sub- 
stituted anthranilic acids. 

C. Naphthotetrazines. 

Our syntheses of the simple quinazolines having resulted so satis- 
factorily, we decided to attempt the synthesis of compounds of the follow- 
ing types, 

N N N 





N 
. \/ \/ 

N 
( 1,3,6,8-Naphthotetrazine) ( 1,3,7,9-Naphthotetrazine) 

and in this were equally fortunate. 

Naphthotetrazines of both types were prepared from the bis-acyl- 
anthranils of the appropriate diaminophthalic acid and various primary 
amines, 1 

RCO.Nv JST.COR RC:Nv .N = CR 

OCf *^CO R'N.CCK *\CO . NR' 

as well as from the diaminophthalic acids themselves by reactions similar 
to those employed for the synthesis of the simple quinazolines. The 
diaminophthalic acids used, which must be, of course, of anthranilic 
structure, were 



HO C \/\/ NH ' H,N NH, 




-_ Z -[ //NS//N ^COOH HOOC' S ^ \COOH 

(3,6-Diamino-i,4-phthalic acid) (4,6-Diamino-i,3-phthalic acid) 
These acids, as can be seen by a glance at their , graphic formulas, are 
only double anthranilic acids, and undergo similar reactions, the former 
yielding the 1,3,6,8-naphthotetrazines, and the latter the 1,3,7,9-isomers. 
1,3,6,8-Naphthotetrazines were also obtained by condensing suc- 
cinylosuccinic esters with amidines: 2 

HN .HJ*OjCO.C.CH,CJOH~H N : CR 

I " + ii ir ~+ i = 

RC : NH_HO C.CH a C.CO:QR HJNH 

HN.CO.C.CH..C.N: CR 

RC:N.C.CH,.CCONH 

All of these naphthotetrazine derivatives so far obtained by the above 
processes are either infusible or melt very high. They are insoluble in 
the ordinary neutral organic solvents. When they carry the NH.CO 

1 Bogert and Nelson, THIS JOURNAL, 29, 729 (1907); Bogert and Kropff, Ibid., 
31, 1071 (1910). 

2 Bogert and Dox, Ibid., 27, 1127 and 1302 (1905). 

79 



794 ORGANIC AND BIOLOGICAL. 

x > N : C(OH) group, they dissolve readily in solutions of the 
caustic alkalies, whence they are reprccipitated by carbon dioxide or 
by acetic acid. 

The naphthotetrazine prepared from guanidine and succinylosuccinic 
ester gives a sodium salt crystallizing in beautiful yellow needles or prisms 
which have a magnificent greenish fluorescence. 

This, in a very hasty and imperfect way, indicates the main lines along 
which this particular field of investigation has been developed. It would 
only weary you to refer even hurriedly to the many subordinate lines 
of investigation radiating from these main ones, necessitating or resulting 
in the synthesis of many hundreds of new organic substances. I can only 
say, as I did at the outset of this address, that it has all been most interest- 
ing to us, and that we are still carrying on the work. 



The articles published in the progress of these researches are listed 
below. They all have appeared in The Journal of the American Chemical 
Society, to which the volume numbers refer : 

1900 i. A new synthesis in the quinazoline group. M. T. Bogert and A. H. Gotthelf, 
THIS JOURNAL, 22, 129. 

2. The direct synthesis of ketodihydroquinazolines from orthoamino acids. 
M. T. Bogert and A. H. Gotthelf, Ibid., 22, 522. 

1901 3. The synthesis of alkyl ketodihydroquinazolines from anthranilic acid. A. 
H. Gotthelf, Ibid., 23, 611. 

1902 4. The synthesis of alkyl ketodihydroquinazolines from anthranilic nitrile. 
M. T. Bogert and W. F. Hand, Ibid., 24, 1031. 

I93 5- The synthesis of alkyl thio ketodihydroquinazolines from anthranilic nitrile. 
M. T. Bogert, H. C. Breneman and W. F. Hand, Ibid., 25, 372. 

6. 3,5-Bibrom-2-aminobenzoic acid; its nitrile and the synthesis of quinazolines 
from the latter. M. T. Bogert and W. F. Hand, Ibid., 25, 935. 

1905 7. The synthesis of 5-nitro-4- ketodihydroquinazolines from 6-nitro-2-amino- 
benzoic acid, 6-nitro-2-acetylaminobenzoic acid, and from the corresponding nitro 
acetylanthranil. M. T. Bogert and V. J. Chambers, Ibid., 27, 649. 

8. The condensation of succinylosuccinic acid diethyl ester with guanidine. 
A derivative of 1,3,5,7-naphthotetrazine, a new heterocycle. M. T. Bogert and A. 
W. Dox, Ibid., 27, 1127. 

9. Some acyl derivatives of homoanthranilic nitrile, and the 7-methyl-4-ketodi- 
hydroquinazolines prepared therefrom. M. T. Bogert and A. Hoffman, Ibid., 27, 
1293. 

10. The condensation of succinylosuccinic acid diethyl ester with acetamidine: 
2,6-dimethyl-4,8-dihydroxy-9,io-dihydro-i,3,5,7-napthotetrazine. M. T. Bogert and 
A. W. Dox, Ibid., 27, 1302. 

11. The synthesis of 2-methyl-5-nitro-4-ketodihydroquinazolines from 6-nitro 
acetanthranil and primary amines. M. T. Bogert and H. A. Seil, Ibid., 27, 1305. 

12. The synthesis of 7-nitro-2-alkyl-4-ketodihydroquinazolines from 4-nitro 
acetanthranilic acid and from 4-nitro acetanthranil. M. T. Bogert and S. H. Steiner, 
Ibid., 27, 1327. 

13. 5-Brom-2-aminobenzoic acid and some of its derivatives. M. T. Bogert and 
W. F. Hand, Ibid., 27, 1476. 

1906 14. The preparation of 6-brom-4-ketodihydroquinazolines from 5-brom-2 
aminobenzoic acid and certain of its derivatives. M. T. Bogert and W. F. Hand, 
Ibid,, 28, 94, 

80 



RECENT INVESTIGATIONS IN THE QUINAZOUNE GROUP. 795 

15. On 5-amino-4-ketodihydroquinazolines and 5-amino-2-methyl-4-ketodihy- 
droquinazolines. M. T. Bogert and V. J. Chambers, Ibid., 28, 207. 

16. On the condensation of succinylosuccinic esters with amidines. M. T. 
Bogert and A. W. Box, Ibid., 28, 398. 

17. On a 3-aminoquinazoline and the corresponding 3,3'-diquinazolyl, from 
6-nitro acetanthranil and hydrazine hydrate. M. T. Bogert and H. A. Sell, Ibid., 28, 
884. 

18. Synthesis of 6-nitro-2-methyl-4-ketodihydroquinazolines from 5-nitro acetan- 
thranil and primary amines. M. T. Bogert and E. P. Cook, Ibid., 28, 1449. 

1907 19. The synthesis of quinazoline carboxylic acids from 4-aminoisophthalic acid 
and from aminoterephthalic acid. M. T. Bogert, J. D. Wiggin and J. E. Sinclair, 
Ibid., 29, 82. 

20. A strange case of poisoning. M. T. Bogert, Ibid., 29, 239. 

21. On 2,3-dialkyl-4-quinazolones and the products obtained by alkylating 
2-alkyl-4-quinazolones (2-alkyl-4-hydroxyquinazolines). M. T. Bogert and H. A. 
Sell, Ibid., 29, 517. 

22. The synthesis of 1,3,6,8-naphthotetrazines from paradiaminoterephthalic 
acid and from certain of its derivatives. M. T. Bogert and J. M. Nelson, Ibid., 29, 
729. 

1908 23. On certain 7-nitro-2-methyl-4-quinazolones from 4-nitroacetanthranil. M. 
T. Bogert and W. Klaber, Ibid., 30, 807. 

1909 24. 3-Amino-o-phthalic acid and certain of its derivatives. M. T. Bogert and 
F. L. Jouard, Ibid., 31, 483. 

25. On certain quinazoline oxygen ethers of the type N:C(OR) and the 
isomeric NR.CO compounds. M. T. Bogert and C. E. May, Ibid., 31, 507. 

26. On some amino and nitroamino derivatives of benzoic, metatoluic and 
metaphthalic acids. M. T. Bogert and A. H. Kropff, Ibid., 31, 841. 

27. On 2-methyl-3-amino-4-quinazolone and certain of its derivatives. M. T. 
Bogert and R. A. Gortner, Ibid., 31, 943. 

28. On 6-methyl-7-aminoquinazolones, 7-nitroquinazolone-6-carboxylic acids, 
and 1,3,7,9-naphthotetrazines. M. T. Bogert and A. H. Kropff, Ibid., 31, 1071. 

1910 29. On oxalyl anthranilic compounds and quinazolines derived therefrom. M. T. 
Bogert and R. A. Gortner, Ibid., 32, 119. 

HAVEMEYBR LABORATORIES, COLUMBIA UNIVERSITY, 
March 2*, 1910. 



A REVIEW OF DISCOVERIES ON THE MUTAROTATION OF THE 

SUGARS. 1 

By C. S. HUDSON. 
Received May 9, 1910. 

Dubrunfaut 2 discovered in 1846 that the specific rotation of a freshly 
prepared cold solution of crystalline glucose decreases from an initial 
value of about 110 to become constant at 52. This phenomenon he 
named birotation but later discoveries have shown the name to be in- 
appropriate and the better term mutarotation, which was introduced by 
Lowry 3 in 1899, has generally replaced it, though the word muliirotation 

1 Presented at the Second Decennial Celebration of Clark University, Worcester, 
Mass., Sept. 15, 1909. 

2 Ann. chim. phys., 18, 99-107 (1846); 21, 178-80 (1847); Compt. rend., 23, 38-44 
(1846). 

8 /. Chem. Soc., 75, 212-5 (1899). 

8l 



890 ORGANIC AND BIOLOGIC AL,. 

is also in use. In addition to glucose the following crystalline sugars 
have been found to show mutarotation: lactose, 1 galactose, 2 arabinose, 3 
maltose, 4 xylose, 5 fructose, 6 fucose, 7 rhamnose, 8 mannose, 9 rhodeose, 10 
gentiobiose, 11 melibiose, 12 perseulose, 13 and several rare synthetic sugars. 
All of these sugars reduce Fehling's solution and combine with phenyl- 
hydrazine, proving that they are aldoses or ketoses and contain the 
carbonyl group; on the other hand such sugars as sucrose, raffinose, 
gentianose, and stachyose, and the polysaccharides starch, inulin, mannan, 
etc., and the glucosides salicin, amygdalin, helicin, arbutin, etc., none 
of which show the characteristic reactions for the carbonyl group, do not 
exhibit mutarotation. This proves that the mutarotation is in some 
way dependent upon the carbonyl group. 

After Dubrunfaut's great discovery the next important observation on 
mutarotation was made by E. O. Erdmann 14 in 1855, who noticed that 
lactose occurs in two crystalline modifications, one having a higher rota- 
tion (86) than that of the stable solutions (52), and the other a lower 
rotation (36), and each form showing mutarotation towards the same 
final rotation (52). Erdmann measured the rates at which each form 
changes in rotation to that of the stable solution, but did not notice 
that the rates are the same in value and that this fact is of much theoretical 
significance. Many years later, after the principles of chemical dynamics 
became better known, the author 15 showed that these equal rates prove 
that the two changes of rotation are not different reactions but are opposite 
parts of one balanced reaction. In this way the mutarotation of lactose, 
and what is true of this sugar is doubtless true of all which show mutarota- 
tion, was proved to belong to the great class of balanced reactions. 16 

In 1859 Anthon 17 noticed that crystalline glucose forms its saturated 
solutions in cold water very slowly even when the mixing is vigorous; 
this fact was discovered for lactose by Mills and Hogarth 18 in 1879. It 
is now known that this slowness of the process of solution is caused by the 
same slow balanced chemical reaction, involving the carbonyl group, 

1 E. O. Erdmann, Fortschritte Physik., p. 13; Fortschritte Chemie, p. 671 (1855). 

2 Pasteur, Compt. rend., 42, 347-51 (1856). 

3 Parcus and Tollens, Ann., 257, 160-78 (1890). 

4 Soxhlet, /. prakt. Chem., 21, 283 (1880). 

8 Koch, Pharm. Ztg. Riissland, 25, 619, 635, 651, 667, 683, 699, 730, 747, 763 
(1886). 

6 Jungfleisch and Grimbert, Compt. rend., 107, 390-3 (1888). 

7 Guenther and Tollens, Ber., 23, 2585-6 (1890). 

8 Parcus and Tollens, Loc. cit. 

9 Van Ekenstein, Rec. tra-v. chim., 15, 221-4 (1896). 

10 Z. Zuckerind. Bohmen, 25, 297 (1902). 

11 Bourquelot and H6rissey, Ann. chim. phys. 27, 397-432 (1902). 
11 Z. Ver. d. Zuckerind., 53, 1050-9 (1903). 

13 Bertrand, Compt. rend., 147, 201-3 (1908). 

14 Loc. cit. Also Ber., 13, 2180-4 (1880). 
18 Z. physik. Chem., 44, 487-94 (1903). 

18 Using the same method Meyer later proved this for glucose, Z. physik. Chem., 
62, 74 (1908). Cf. also Roux, Ann. chim. phys., 30, 422-32 (1903). 

17 Dingier** poly. /., 151, 213-23 (1859); 155, 386-8 (1860); 166, 69-71 (1862). 
11 Proc. Roy. Soc. London, 28, 273-9 (1879). 

82 



DISCOVERIES ON THE MUTAROTATION OF THE SUGARS. 89! 

which causes the mutarotation, and that it is a general property of all the 
aldehyde and ketone sugars. 1 

The first attempt to find the physical law which governs the rate of the 
mutarotation was made by Mills and Hogarth 2 in 1879, but the result was 
only an empirical formula and must be regarded as unsatisfactory. It 
is to Urech 3 that we owe the first real progress in this line. He showed 
by a series of experiments during 1882-5 that the mutarotation follows 
the law of unimolecular reactions. It is interesting, and to some minds 
instructive, to note that this correct beginning in the physico-chemical 
study of the long unsolved mutarotation reaction was coincident in time 
with the beginning of the modern theory of solutions and chemical dynam- 
ics. There can be little doubt that Urech's experiments, which are 
the starting point of all exact work on mutarotation, were suggested by 
the advances that were being made at that time in the study of chemical 
dynamics by the new physico-chemical school. 

In 1888 Brown and Morris 4 and Arrhenius 5 observed that the freezing 
temperatures of glucose solutions remain unchanged during the process of 
mutarotation, which proves that the reaction which causes mutarotation 
is not a polymerization or dissociation of the sugar. More recently 
Roth 8 has detected a slight change in freezing temperature of concentrated 
solutions of anhydrous glucose on standing but this is doubtless due to 
hydration and does not alter the conclusion from the work of Brown and 
Morris and Arrhenius, because a polymerization or dissociation would also 
affect the freezing point of dilute solutions, and the investigators are all 
agreed that such an effect is not discernible. 

In 1890 O'Sullivan and Tompson 7 noticed that the invert sugar which 
is produced by the hydrolytic action of the enzyme invertase on sucrose 
shows mutarotation; this fact was later investigated by E. F. Armstrong 8 
and has been precisely studied lately by the author. 9 These researches 
have shown that the glucose which is liberated from sucrose is a-glucose 
and the fructose is a hitherto unknown form of this hexose, a-fructose; 
these facts show that sucrose has the constitution a-glucose < > a-fructose. 
The new form of fructose has not as yet been obtained crystalline. This 
method for determining the constitution of the polysaccharides by study- 
ing the mutarotation of the sugars which are formed by their enzymotic 
hydrolysis was first used by E. F. Armstrong 2 in his correlation of the 
a- and /?-methylglucosides with the a- and /?-glucoses. In applying the 
method to other substances such as cane sugar where two mutarotating 
sugars are formed at the same time it is necessary to extend the theoretical 
considerations; a mathematical theory of the modified method of Arm- 

1 Hudson, Z. physik. Chem., 44, 487-94 (1903); THIS JOURNAL, 26, 1065-82 (1904). 
1 Loc. cit. 

* Ber., 15, 2130-3 (1882); 16, 2270-1 (1883); 17, I547~5O (1884); 18, 3047-60 
(1885). 

* J. Chem. Soc., 53, 610-21 (1888). 

6 Z. physik. Chem., 2, 491-505 (1888). 

* Ibid., 43, 539-64 (1903). 

7 /. Chem. Soc., 57, 920 (1890). 

8 Ibid., 83, 1305-13 (1903)- 

* THIS JOURNAL, 30, 1160-6, 1564-83 (1908); 31, 655-64 (1909). 

83 



892 ORGANIC AND BIOLOGICAL. 

strong and an experimental demonstration of it has recently been pub- 
lished by the author. 1 

In 1895 Charles Tanret 2 discovered a new form of crystalline glucose 
which was found to have a specific rotation lower than that of the stable 
solution (52), though its value increased to this on standing. This 
discovery is the complement to Dubrunfaut's and the two must cause 
chemists the world over to be grateful to French science, because more 
fruitful single discoveries in the chemistry of the carbohydrates have 
hardly been made. Tanret found the final rotation of glucose solutions 
to be the same whether the solution is made from the higher or the lower 
initially rotating form. He interpreted his results as proving that three 
forms of glucose exist, one of high rotation, one of low, and the third the 
form to which each of these changes in aqueous solution. About the same 
time Tanret isolated similar new crystalline forms of rhamnose, galactose 
and arabinose, and obtained Erdmann's lower rotating form of lactose 
practically pure. Tanret's striking discoveries immediately caused new 
interest to be taken in the problem of mutarotation. In 1899 Lowry 1 
advanced the view that the mutarotation of glucose is caused by a balanced 
reaction between the highest and lowest rotating forms of the sugar, a 
view which may be expressed by the equation a-glucose ~^~*' {3-glucose. 
This explanation is essentially different from any that preceded it and 
later investigations have proved it to be entirely correct. On the other 
hand, Lowry did not support this hypothesis with any direct proof and it 
remained without such proof for several years. In 1902* the author 
published the same view as an explanation of the mutarotation of lactose, 
being at that time unacquainted with the publication of Lowry. The 
explanation may be expressed by the equation a-lactose ~j~ > ' /?-lactose, 
and experimental evidence for the view was given by measurements on 
the heats of solution of the three forms of lactose, which showed that the 
stable form to which a- and ^-lactose change in solution is not a chemical 
individual, as Tanret had supposed, but is a mechanical mixture of a- 
and /Mactoses. In 1903 the author 4 measured the slow maximum rate of 
solution of a-lactose and showed that the slowness of dissolving, which 
had been discovered by Mills and Hogarth, 1 is caused by the balanced 
reaction which produces the mutarotation. By quantitative measure- 
ments the hypothesis of the balanced reaction was tested and proved, 
and the explanation which these measurements gave of the mutarotation 
of lactose was immediately accepted by such an authority as Nernst. 5 
In the same year Lowry 6 published similar experiments on glucose and 
proved the suggestion which he had advanced in 1899. These questions 
of priority are here stated for the reason that E. F. Armstrong 7 has recently 
claimed for Lowry the discovery of the balanced reaction which causes 
the mutarotation, a claim which in the opinion of the author is entirely 
too broad. 

1 Loc. cit. 

2 Bull. soc. chim., 15, 195-205, 349-61; 17, 802-5. 
* Princeton Univ. Bull., April, 1902. 

4 Z. physik. Chem., 44, 487-94 (1903). 
8 " Theoretische Chemie," ed. 1904. 

6 Proc. Chem. Soc., 19, 156-7 (1903); 20, 108-9 (1904). 

7 "The Simple Carbohydrates and Glucosides," p. 8. 

84 



DISCOVERIES ON THE MUTAROTATION OF THE SUGARS. 893 

A very fruitful idea was advanced by Llppmann 1 in 1895 in the sugges- 
tion that the lactonic formula for glucose predicts two possible forms of 
the sugar on account of the asymmetry of the end carbon atom, the two 
structures being 

, O -, /H 

CH 2 OH.CHOH.CH.CHOH.CHOH.C< and 

X OH 

r- O n /OH 

CH 2 OH.CHOH.CH.CHOH.CHOH.C<^ , 

This suggestion, after a slight development by Simon, 2 was made more 
probable by Armstrong's discovery, 3 that the a- and /9-forms of methyl 
glucoside are hydrolyzed by enzymes to give methyl alcohol and the 
a- and /?-forms of glucose respectively. As the methyl glucosides show no 
aldehyde reactions the lactonic formulas have always been chosen for 
them, the hydroxyl of the end carbon atom in the structures shown above 
being replaced by the group OCH 3 . Armstrong's discovery indicates 
that similar structures probably apply to the forms of glucose. This 
suggestion received final proof in 1909 when the author* showed that certain 
numerical relations which can only be explained by the assumption of 
such lactonic structures for the two forms of the sugar, hold all through 
the sugar group. If the rotation of the end carbon atom is B for one 
structure it must be B for the other, and if A is the rotation of the 
remaining asymmetric carbon atoms, which are common to both struc- 
tures, the total rotation of the one structure is A + B, and of the other 
structure A B, the difference between the two total rotations being 
then 2B. This rotation B applies to all the aldoses because they contain 
the same end asymmetric carbon, therefore the difference between the 
molecular rotations of the a- and /3-forms of all the aldose sugars should 
be a constant quantity if the sugars have the two isomeric lactonic struc- 
tures. The molecular rotatory powers of the two forms of lactose, glucose, 
arabinose and galactose were found indeed to differ by the quantities 
17600, 16000, 16200, and 15700, which are sufficiently alike to show that 
the theory is correct and that the two forms of each of the mutarotating 
sugars have the stereomeric lactonic structures. Certain other similar 
conclusions from the same theory were also found to agree with the 
rotatory powers of the sugars and their glucosidic derivatives. 

The catalytic action of various substances on the mutarotation reaction 
has been investigated by various chemists. 5 These researches have 
shown that only acids and alkalies have a strong action. Osaka 6 made 
the first quantitative study of the relation between acidity or alkalinity 
and catalytic action and found that the catalysis is proportional to the 
concentration of the hydroxyl ions and proportional to the square root 

1 " Die Chemie der Zuckerarten," ed. 1895, pp. 130, 990, 992. 

2 Compt. rend., 132, 487-90 (1901). 

3 Loc. cit. 

4 THIS JOURNAL, 31, 66-86 (1909). 

6 Levy, Z. physik. Chem., 17, 301-24 (1895); Trey, Ibid., 18, 193-218 (1895); 22, 
424-63 (1897); 46, 620-719 (1903); Simon and Benard, Compt. rend., 132, 564-6 (1901); 
Lowry, /. Chem. Soc., 83, 1314-23 (1903). 

6 Z. physik. Chem., 35, 661-706 (1898). 

85 



894 ORGANIC AND BIOLOGICAL. 

of that of the hydrogen ions. Later the author 1 showed that the pro- 
portionalities are somewhat different from this and that the rate of the 
mutarotation of glucose is related to the acidity and alkalinity of the 
solution by the expression rate = A + B(H') + C(OH'), where A, B, 
and C are constants at constant temperature. This formula has lately 
been used as the basis of a new method for measuring the electrolytic 
dissociation of water. 2 A satisfactory explanation of the fact that acids 
and alkalies are enormously powerful catalysts of the mutarotation while 
all other substances are without comparable action is lacking. 

The sugars glucose, lactose, galactose, rhamnose, melibiose, arabinose, 
maltose, xylose and some others occur as monohydrates and these have 
generally been regarded as hydrated aldehydes without lactonic structure 
and thus intermediate forms between the two lactonic a- and/3-forms 
of the sugars. The freshly prepared solutions of these monohydrates 
are identical in properties with such solutions of one of the anhydrous 
lactonic forms of the sugars and it is therefore to be concluded that the 
equilibrium between this lactonic form, whichever it may be, and the 
monohydrate is established instantly. For most of the sugars the lactonic 
form which is thus in instantaneous equilibrium with the monohydrate 
is the a-form, but for one sugar at least, maltose, it is the /3-form. The 
mutarotation reaction may then be considered to be the slow change of 
the monohydrate into the other lactonic form by a reversible reaction, 
or in the form of an equation, 

a-sugar + H 2 O "7"*' monohydrate ~^~^~ /?-sugar + H 3 O. 

(i) .(2) 

For most of the sugars the reaction i is instantaneous in comparison 
with 2, which is therefore the mutarotation reaction, but for maltose the 
relations are reversed. Why the monohydrate should change instantly 
to the a-form for some sugars, but to the /9-form for others is entirely 
unknown and is a most interesting problem. 

The mutarotation reaction is general to all the aldehyde and ketone 
sugars. It may indeed be called the fundamental reaction of the sugar 
group. While its cause remained unknown during the half century 
following its discovery, the last decade has brought a full explanation 
of it. The principal facts regarding it have been accurately measured 
and correlated. On the other hand the application of these facts to the 
elucidation of the chemical and biological reactions of the sugars, in 
every one of which mutarotation plays a part, has just begun, but it is 
even now apparent that the unfolding chemistry of the polysaccharides 
is to be largely a development of the mutarotation reaction. 

BUREAU OF CHEMISTRY, U. S. DEPARTMENT OF AGRICULTURE, 
WASHINGTON, D. C. 

1 THIS JOURNAL, 29, 1571-6 (1907). 
1 Ibid., 31, 1136-8 (1909). 



86 



OUTLINE OF A THEORY OF ORGANIC CHEMISTRY FOUNDED ON 
THE LAW OF ENTROPY. 1 

BY ARTHUR MICHAEL. 
Received June 27, 1910. 

There appears to be no generalization in science more firmly estab- 
lished than the second law of thermodynamics, which demands that 
every spontaneous chemical change shall be accompanied by an increase 
of entropy, and that the system shall endeavor to realize this increase 
to its maximum extent. 

Since the law of entropy represents the fundamental principle, under- 
lying and regulating all chemical phenomena occurring in nature, it must 
necessarily be the correct scientific basis for the theory of organic chemis- 
try. But it is a curious fact that there has been as yet little attempt 
to use this basic chemical principle in connection with organic theory; 
this theory has been developed along lines so mechanical in their charac- 
ter that it is perhaps no exaggeration to speak of them as essentially 
pictorial. This unilateral, mechanical development is due largely to 
the interpretation of the phenomenon called valency; and, if we are to 
incorporate the law of entropy into chemical theory, it is here that our 
theoretical conceptions will require a radical modification. 

Before entering a discussion of the subject of valency, we shall men- 
tion a conception of the chemical genesis of matter, since it prepares the 
way for the theoretical views which follow. A simple hypothesis is to 
assume that cosmos was originally made up of two kinds of matter, 
which were the carriers of two kinds of chemical energy, 2 and that the 
temperature of the system was inconceivably low. Chemical energy, 
as it now appears to us, exists in two conditions. One of these is freely 
and perfectly convertible into less active chemical energy and into various 
forms of physical energy ; and this less active chemical energy can be recon- 
verted into the active form only partially and then with comparative 
difficulty. We shall designate the active form free, the relatively inac- 
tive form, bound chemical energy, 3 and, as the transformations of 
chemical energy must have obeyed the law of entropy since the 
beginning of cosmos, the original corpuscles were exclusively carriers 
of free chemical energy, and the accumulation of bound chemical energy 
and the various forms of physical energy now existing have been grad- 
ually evolved from it. 

1 Address delivered at the Second Decennial Celebration of Clark University, 
Worcester, Mass., September 15,1909. 

1 To distinguish between them they will be called positive and negative, but this 
does not imply any connection with positive and negative electricity. 

8 The terms free and bound chemical energy, as here used, are not to be confused 
with the terms free and bound energy as used in physical chemistry, with which they 
are not identical. 

87 



991 THEORY OF ORGANIC CHEMISTRY. 

The permanence of the law of entropy justifies the conclusion that the 
chemical relations which existed between the corpuscles at the beginning 
were similar to those which now exist between the atoms and the mole- 
cules. We may, therefore, assume that the free chemical energy of unlike 
and like corpuscles united to form aggregations in which the corpuscles 
were held together by bound chemical energy. At first the chemical 
evolution of matter must have been accompanied by an enormous rise 
of temperature, but later, owing to the decreasing amount of free chemical 
energy in the cosmical system, a period must have come when the loss 
of heat through radiation was greater than its formation, and then the 
temperature of the system must have begun to decrease. We may 
assume, too, that the atoms of those elements, the molecules of which 
now show the greatest stability toward heat, were formed first and dur- 
ing the hottest period of cosmical evolution. Hence, the atoms of hy- 
drogen, and those of the non-metals, with small atomic weight, repre- 
sent the earliest forms of atomic matter. 

If we suppose that in the formation of the atoms of certain elements 
the free chemical energy of the corpuscles was very largely converted 
into bound chemical energy and heat, their atoms would be extremely 
inert toward other atoms and incapable of uniting with each other. Such 
elementary matter is represented by the so-called noble gases, in the 
atoms of which the relation of free corpuscular to free atomic chemical 
energy is analogous to that of free atomic to free molecular chemical 
energy in the atom and molecule of nitrogen. Further, if we suppose 
that thermic, or other conditions, toward the end of the corpuscular 
period of chemical evolution no longer permitted a sufficient conversion 
of free into bound chemical energy, we get a glimpse into the genesis of 
radioactive matter, the atoms of which contain so much free corpuscular 
chemical energy that they represent a reversible system and are, there- 
fore, gradually breaking down into smaller parts, which then rearrange 
according to the changed conditions of cosmos. 

Kekule", 1 in his memorable paper, "Ueber die Constitution und die 
Metamorphosen der chemischen Verbindungen, ' ' assumed that the first 
phase in chemical union consists in molecules attracting each other 
through their chemical affinity, and that a sort of loosely joined, larger 
molecule is thus formed. It is obvious that the formation of this 
"Kekule poly molecule" 2 is due to the attraction between the free chem- 
ical energy in the constituent molecules, and that it proceeds with the 
conversion of more or less free into bound chemical energy and heat 
the extent of this change determining its stability. 

Let us represent the free chemical energy in an atom by a point 

1 Ann., 106, 141. 

2 Michael, Ber., 34, 4028; 39, 2140, 2570. Am. Chem. J., 39, 3; 41, 120. 

88 



ORGANIC AND BIOLOGICAL. 992 

and the bound by a line, and let the number of the points and the length 
of the lines be a rough indication of the changes in the energy values 
occurring during the reaction. If we assume that the energies of un- 
like character in a molecule of sodium and of chlorine are approximately 
equal in value, we may represent the energy relations in sodium and 
chlorine by 

Na Na Cl Cl 

and the " polymolecule, " representing the first phase in their interaction, 

by 

Na Na 

Cl Cl 

which indicates that some of the free has been converted into bound 
chemical energy. The free chemical energies of unlike character would 
then strive to neutralize each other as completely as possible, a phase of 
the reaction that may be represented by 

Na Na 

I 

Cl Cl 

and then, certainly facilitated by the enormous " internal maximum heat 

of reaction," 1 the bound chemical energies between Na and Na and Cl 
and Cl would be converted into bound chemical energy between Na and 
Cl and Na and Cl ; finally, to realize a phase which may be represented by 

Na Na 

I I . 

Cl Cl 

At this point, the bound chemical energy between the atoms of like nature 
may be inadequate to hold them together, and the complex would then 
break down into two molecules of NaCl. 2 

What happens if we substitute magnesium in the place of sodium; 
that is, an element the atom of which contains much less positive energy? 
The formation of a "polymolecule," then the conversion of the free 
chemical energy in the metallic and non-metallic atoms into bound be- 
tween metal and halogen; but, although the energy in the sodium mole- 
cule suffices to neutralize that in the chlorine to an extent that the com- 
plex breaks down into two molecules, that in the much less positive mag- 

1 Wohl, Ber., 40, 2290. That part of the free and bound chemical energy is con- 
verted into heat has not been indicated. 

2 The energies in two unlike atoms are never capable of exactly neutralizing 
each other, so that a certain content of free chemical energy is invariably present in 
the atoms of every molecule. 

8 9 



993 THEORY OF ORGANIC CHEMISTRY. 

nesium molecule is insufficient to convert enough of the bound energy 
between the chlorine atoms into bound energy between metal and halo- 
gens, therefore the latter atoms separate. On the other hand, the greater 
energy in the chlorine atoms is capable of using up that in the magne- 
sium to an extent that these fall apart. In magnesium chloride, there- 
fore, the halogen has a considerably greater content of free chemical 
energy than it has in sodium chloride, and bound chemical energy exists 
not only between it and the metal, but between the chlorine atoms. We 
may represent these relations by: 



Mg<^ | " 



While the energy in a molecule of magnesium is not sufficient to 
separate the chlorine atoms, it obviously may be able to do so with the 
less negative oxygen, and, if the opposite energies in magnesium and 
oxygen approximately neutralize each other, two molecules of magne- 
sium oxide should be formed. But, if we take oxygen and a metal with 
considerably more positive energy than magnesium, say lithium, the 
oxygen is not able to separate the metallic atoms, while the latter can 
separate the oxygen atoms, thus leading to the formation of Li 2 O, in which 
the Li atoms are held together by bound chemical energy. The valency 
of an element, according to this interpretation, represents the resultant 
of the intramolecular chemical forces acting on the atom in terms of 
bound chemical energy, whether the action takes place directly, that is 
through direct union of the atoms or through space; or indirectly, that 
is, through other atoms. In as far as the free chemical energy in the 
atoms is not so converted into bound chemical energy, it will be able to 
exert readily a chemical attraction for such other atoms, either in the 
same or other molecules, for which it shows a chemical affinity. 

Although a spontaneous chemical change can proceed only with in- 
crease of entropy, the increment depends on free chemical energy and 
chemical affinity existing between those atoms, which in the reaction 
enter into direct union with each other. The atoms in a molecule are 
held together solely by bound chemical energy and, if their chemical nature 
is such that their free chemical energy has very largely disappeared in 
the formation of the molecule, the substance must be chemically inert; 
if not, it will be more or less chemically active. Thus, the well neutral- 
ized condition of NaCl and A1 2 O 3 , the superabundant positive energy 
in Na 2 O, and the negative in A1C1 3 , is reflected in the properties of those 
substances. 

Let us suppose that we could isolate and experiment with ele- 
ments other than the noble gases in atomic condition, and could pre- 
vent the formation of molecules by the union of like, but not unlike, 
atoms. In such a system free chemical energy would be amply present 

90 



ORGANIC AND BIOLOGICAL. 994 

and chemical union would therefore depend alone on the affinity relations 
of the atoms. Moreover, if an isomeric substance could be formed, it 
would be that particular isomer which would represent the maximum 
entropy of the system under the prevailing conditions. 

For instance, the present structure theory indicates the existence of 
two isomeric cyanogen chlorides, i. e., C1NC and C1CN, but leaves us 
entirely in doubt why only one is known. So great is the uncertainty 
in regard to its constitution that this has long been a subject of active 
discussion and investigation. 1 Chlorine, nitrogen and carbon in atomic 
condition would possess ample free chemical energy for union and the 
question which isomer would be formed would depend on the increase of 
entropy connected with the affinity relations of Cl for N and for C. Since 
we know that the affinity between Cl and N is exceedingly slight, and 
that between Cl and C is large, it is absolutely certain that the isomer 
in which the halogen is united directly to the C, i. e., C1CN, would be the 
direct product. Furthermore, a consideration of the energetic condi- 
tions enables us to predict the properties of the isomeric form (C1NC) ; 
it could exist only at a very low temperature and under ordinary condi- 
tion the rearrangement C1NC >-ClCN would occur so quickly, and 
with such a great increase of heat that the substance would be a violent 
explosive. 2 The matter we actually deal with is, however, in a molecular 
condition and all chemical changes that do not proceed solely through 
expenditure of free chemical energy involve an expenditure of energy 
due to overcoming bound chemical energy between atoms in the molecule. 
Chemical action is dependent, therefore, on a third factor, which con- 
stitutes a chemical hindrance, and it can proceed spontaneously only 
when the increase of entropy due to changes of free chemical energy 
and affinity is greater than the expenditure of energy necessary to over- 
come the chemical hindrance. That is, when the value of the equation : 
chemical affinity plus free chemical energy divided by chemical hin- 
drance, is positive. 

To ascertain quantitative values for the various factors that determine 
an organic reaction is at present impossible, but it is of the greatest im- 
portance for the development of organic theory to be able to connect 

1 See Michael and Hibbert, Ann., 364, 69. 

2 It is evident that the content of free chemical energy in C1NC would be vastly 
greater than that in C1CN, which implies a better condition of intramolecular neutral- 
ization of the chemical forces of the atoms in the latter structure. Since such chem- 
ical neutralization proceeds with increase of entropy, we may substitute chemical 
neutralization in the place of entropy in the second law of thermodynamics. Further, 
we may apply the Carnot principle to the activity of free chemical energy of unlike 
kinds, and conclude that the increase of entropy will be greatest when the chemical 
forces are able to neutralize each other exactly. This law of chemical neutralization 
has the advantage over that of entropy in a much wider application to organic 
reactions (Michael, /. prakt. Chem., [2] 60, 293; 68, 489. Ber., 38, 23). 

91 



995 THEORY OF ORGANIC CHEMISTRY. 

changes in these values with modifications in structure. This done, we 
shall then be able to predict relative changes in the factors that contribute 
to the entropy values and thus be able to understand and explain or- 
ganic reactions to a degree at present impossible. 

What are the properties of carbon on which the existence of this won- 
derful and intricate organic world mainly depend? First, its capacity 
to polymerize, to form stable chains of astonishing length; second, the 
extreme sensitiveness of its properties to the influence of other elements, 1 
which is shared in a 1 ke degree only by hydrogen, and which has been 
called its "chemical plasticity"; 2 and third, its high valence combined 
with its marked affinity for hydrogen and for most of the non-metals, 
to form more or less stable derivatives. 

The first of these properties stands clearly in a close relation to the 
position of the element in the periodic system. In the halogen group, 
the tendency to form greater than diatomic molecules is not shown, 
with the exception perhaps of iodine; in the oxygen group it is shown 
by that element, but in a far greater degree by the other members. From 
analogy, a similar tendency to form large molecules by conversion of 
free into bound chemical energy should be expected in passing from oxy- 
gen to nitrogen, but the latter element acts anomalously, although in 
the formation of its diatomic molecule its free is converted into bound 
chemical energy to a remarkable extent. 

The next member of this group, phosphorus, shows a marked capacity 
to polymerize to large molecules, and the conversion of ordinary into 
red phosphorus, which is accompanied by the evolution of only 19 calories, 
is one of the most salient illustrations in chemistry of how a change of 
free into bound chemical energy will radically change the properties of 
a substance. The very existence of organic life depends on carbon not 
sharing with nitrogen the property of polymerizing to a diatomic mole- 
cule, which is poor in free chemical energy. The actual change in pass- 
ing from N to C is similar to that in going from N to P, but it is in a de- 
gree much more highly developed, and carbon represents among elements 
the greatest capability to use the free chemical energy in its atom to form 
molecules containing a large number of atoms. The midway position 
of carbon in the second series of the periodic system indicates that there 
is an approximate balance of positive and negative corpuscles in the 
make-up of its atom. And, as the polymerizing capacity of non-metallic 
atoms increases, generally speaking, with a tendency toward this con- 
stitution of their atoms, it seems reasonable to connect this all-impor- 
tant property of the carbon atom with its corpuscular composition. 

A relation which is hardly less important for organic theory than the 

1 Van't Hoff, Ansichten iiber organische Chem., I, 280; II, 242. 

2 Michael, /. prakt. Chem. [2], 60, 325. 

92 



ORGANIC AND BIOLOGICAL,. 996 

foregoing, is to what extent the polymerizing power of carbon is modified 
by the presence of other elements in the molecule, and the influence 
which they exert on the affin ty of carbon for hydrogen and for non- 
metals. Without exception, every element joined to carbon decreases 
its polymerizing capacity, i. e., its affinity for itself, and the influence 
is in the order, H, halogen, N, S and O. To the influence of the last ele- 
ment carbon is so exceedingly sensitive that, through direct union with 
a single atom of oxygen, the enormous combining capacity of the carbon 
atom for itself is completely destroyed. 

Notwithstanding the considerable content of free chemical energy in 
the atoms of CO, this substance shows practically no tendency to polym- 
erize, but the characteristic property of carbon reappears at once, 
when the influence of oxygen is neutralized by the presence of other ele- 
ments. Thus, the action of potassium on CO leads not to COK, but to a 
polymerized product, derived from benzene. 

Not only does O decrease the affinity of C for C, but of C for H and for 
any non-metal to which carbon may be joined, whether the atoms are 
directly or indirectly oined. This is true to a degree directly propor- 
tionate to the extent of such negative influences acting on the atoms. 1 
The capacity of hydrogen to decrease the affinity of carbon for carbon 
is far less than that of oxygen, but it plays, nevertheless, an important 
role in many organic reactions. Thus, the pinacone >-pinaco- 
line rearrangement : (H 3 C) 2 = C(OH) (HO)C = (CH 3 ) 2 > (CH 3 ) 3 = 
C CO CH 3 + H 2 O, takes place on boiling with dilute mineral acid, and the 

1 Michael, /. prakt. Chem., 37, 473; 60, 286. Ber., 38, 28, 3221. The writer is 
unaware of any facts in organic chemistry which are not strictly in accordance with 
the above stated rule. W. A. Noyes (Tins JOURNAL, 31, 1371) believes that the 
greater instability of acetoacetic acid (CH 3 COCH 2 CO 2 H) over pyrotartaric acid 
(CH 3 COCO 2 H) "is some slight indication that the separation of the carbon atoms 
is ionic in character, taking place more readily when there is a greater contrast be- 
tween the atoms united together." In the first-named acid, the group C CO 2 H is 
under the influence of H 2 and a negative, acidic radical (CH 3 CO), in the second under 
a positive radical (CH 3 ) and O and it is quite in agreement with the above rule that 
acetoacetic acid splits off CO 2 much more readily than pyrotartaric acid. The writer, 
also, knows of no satisfactory evidence in favor of the view that any strictly organic 
reaction is ionic in character (see Michael, Ber., 38, 29; Am. Chem. J., 43, 322; Michael 
and Hibbert, Ber., 31, 1090); or of any facts that are more easily understood than 
otherwise by such an assumption. The formation of ethyl chloride from ethyl alcohol 
and phosphorus pentachloride, while phenol gives partly chlorobenzene, partly phenyl 
phosphate, is mentioned by Noyes (loc. tit., 1370) as confirming this view. However, 
when we consider that the chemical hindrance to the formation of a chloride, i. e., 
the energy necessary to separate hydroxyl from the hydrocarbon radical, is much 
greater with phenol than with ethyl alcohol, it is obvious that such assumptions as 
that phenol can ionize to the phenyl and hydroxyl group, and that ethyl alcohol 
can ionize to ethyl and hydroxyl, do not contribute in any way to make the subject 
more clear. 

93 



997 THEORY OF ORGANIC CHEMISTRY. 

reaction apparently should lead, with loss of water, to the formation of 
tetramethylethylene oxide. 

This compound contains a three-membered, cyclic chain, which is 
formed under considerable tension, and, besides, a large number (12) 
of hydrogen atoms, exerting in a very important position (3) their posi- 
tive influence on the cyclic carbons. Such a structure cannot represent 
a very stable substance. On the one hand, there is considerable tension, 
representing energy in a potential condition; on the other, an extremely 
insufficient, intramolecular chemical neutralization of the positive by 
the negative energy in its atoms. The compound may, indeed, be com- 
pared to sodium oxide, and shares with that substance a capacity to 
unite with water, most energetically, and with great increase of entropy. 
It is apparent that the oxide cannot possibly be formed from pinacone 
under the conditions of the reaction, but, if a rearrangement may lead 
to the formation of an intramolecularly well neutralized substance, this 
may be formed, provided the increase of entropy due to the intramol- 
ecular neutralization is greater than the decrease that is due to the 
chemical hindrance, *. e,, the energy necessary to effect the migration of 
a methyl group. These conditions are possible, for pinacoline repre- 
sents a fairly well neutralized structure and has, consequently, a con- 
siderable heat of formation; 1 and the expenditure of energy accompany- 
ing the migration of a methyl in pinacone is comparatively small, owing 
to the decrease of the affinity of carbon for carbon by the influence of the 
numerous hydrogens. 

That phenyl exerts an extremely strong positive influence on any atom 
joined directly to it 2 is evident from the fact that two such groups united 
directly with iodine, give that non-metal a metallic character. It might, 
therefore, have been expected, that the accumulation of phenyl groups 
would facilitate rearrangements of the nature of the pinacone > pina- 
coline reaction, as this has been especially proven by the investigations 
of Tiffeneau. We have, moreover, direct experimental evidence that 
hydrogen diminishes the affinity of carbon for carbon hi the observa- 
tion of Acree, 3 that in the rearrangement with di-/j-tolyldiphenylpinacone 
it is the more positive tolyl radical that migrates. 

Another interesting illustration of this influence of hydrogen is found 
in that much-discussed substance "triphenylmethyl" (hexaphenyl- 
ethane). Tshitshibabin 4 has shown that replacement of five of the 
hydrogens in ethane by phenyl groups materially lessens the affinity 
of the ethane carbon atoms for each other. It is, therefore, not surpris- 

1 Zoubuff, Chem. Centralbl. t 99, I, 516. 

2 Michael and Leigh ton, Ber., 39, 2792. 
8 Am. Chem. J., 33, 180. 

4 Ber., 40, 367. 

94 



ORGANIC AND BIOLOGICAL. 998 

ing that when the remaining hydrogen is likewise replaced, the mutual 
affinity of these carbons is so greatly diminished that the substance 
easily dissociates into two molecules of triphenylmethyl, 1 and that these 
carbons, or the. carbon, in "triphenylmethyl" joined to the three phenyl 
groups, have chemical properties similar to those of a very positive metal, 
for instance, sodium. 2 Nor is it surprising that hexaphenylethane may 
undergo easily a desmotropic rearrangement into the quinoid form : 

' 



- 

(C 6 H 5 ) 2 =C=< X 

'N 



or, since the difference in the entropy values of these two forms is slight, 
that the existence of one or the other form, or a derivative, will depend 
on the nature of a reagent or even of a solvent. 8 

The remaining fundamental properties of carbon, its high valency 
and its capability to combine not only with hydrogen but with most of 
the non-metals to form stable derivatives, are also related to the posi- 
tion of the element in the periodic system. An element acts as mono- 
valent towards H, or Cl, when its energy suffices to neutralize that of H, 
or Cl, to an extent that the system is incapable of uniting with further 

1 Since the above was written Schlenk (Ann., 372, i) has shown that with a more 
positive radical than phenyl, i. e., biphenyl, the affinity of carbon for carbon is reduced 
to such an extent that tribiphenylmethyl exists in solution in mono-molecular 
condition, which is a further confirmation of the above explanation. 

1 Michael, /. prakt. Chem., [2] 60, 423, 428; 64, 107; Ber., 39, 2791. 

'Michael and Hibbert, Ber., 41, 1091. A thermochemical investigation on 
intramolecular rearrangement will be published later; it may be stated that 
all our present experimental data on this subject confirm the view that the 
fundamental reason of the phenomenon is the increase of entropy proceeding 
with the change. In intramolecular changes it is the formation of an iso- 
mer with a greater heat of formation and in intermolecular rearrangements 
the increase of entropy is connected with a change in composition and the reagent 
uniting with a product of decomposition; in either case, slight chemical or physical 
forces may bring about the change, if the chemical hindrance is inconsiderable (see 
Michael and Hibbert, Ber., 41, 1091). The rearrangements of camphor on treatment 
with P.p 4 and H 2 SO 4 , to which W. A. Noyes (Tnis JOURNAL, 31, 1372) recently called 
attention, may be understood from the point of view here presented. In camphor 
the affinity of the central carbon to those with which it is directly joined has been di- 
minished considerably by the influence of hydrocarbon radicals and the central ring 
appears to exist in a condition of tension; moreover, such reduced benzene derivatives 
show a tendency to pass over into benzene derivatives, as the formation of the para- 
bonds in benzene is connected with a considerable increase of entropy (Michael, /. 
prakt. Chem., [2] 79, 418). Phosphoric anhydride is a powerful dehydrating agent 
and the formation of a benzene derivative (cymene) with the elimination of water 
and rupture of a central carbon bond represents the maximum increase of entropy. 
In its action on camphor sulphuric acid acts not only as a hydrolyzing, but also as an 
oxidizing agent; the formation of />-acetyl-o-xylene undoubtedly represents the max- 
imum entropy under such conditioms. 

95 



999 THEORY OF ORGANIC CHEMISTRY. 

atoms of these elements. In passing from F to O, from O to N, and from 
N to C, the valency for H, or Cl, increases, because the amount of energy 
in these atoms, able to neutralize that of H, or Cl, is successively de- 
creasing. CH 4 or CC1 4 represent stable substances, because the energy 
and affinity relations between C and H, or Cl, are such that, in the com- 
bination of four atoms of hydrogen or chlorine among themselves and 
with one atom of carbon, comparatively little free chemical energy re- 
mains in any of the atoms. 1 

Like the polymerizing capacity and the "chemical plasticity" of car- 
bon, its power to unite not only with hydrogen, but with most non- 
metals, is due to the approximate balance of the positive and negative 
corpuscular energies in its atom. The direction in which the affinity of 
carbon for such elements will vary under the influence of other atoms 
in the molecule must be toward those of elements adjacent to it in the 
periodic system. Thus, the effect of increasing the influence of H on C 
in relation to H, or to a non-metal, joined to it, must be to shift its affinity 
values toward those of silicon, i. e., there should be a decrease in the 
value for H and an increase for that of a non-metal. On the other hand, 
increasing the influence of O should shift them towards those of N, i. e., 
decrease the values both for H and a non-metal. Further, the effect of 
such changes on the content of free chemical energy of C, and of any 
atom joined to it, must stand in a direct relation to the changes in the 
affinity values; in fact, the free must respond to such changes before the 
bound chemical energy. 

According to van't Hoff, 2 two atoms in a molecule acting through di- 
rect union or through space, or indirectly, that is through intermediate 
atoms. This idea has been further developed 3 and shown to be of great 
importance in explaining organic reactions. If we number a certain 
atom in any fatty compound with a normal carbon chain by the figure i, 
our present knowledge of the combined mutual influence between this 
atom and others in the molecule is expressed by the following "scale of 
combined influence," the numbers indicating the degree of removal and the 
extent of the influence decreasing in the order given : 2 3 5 6 4 7 

1 Replacement of an H in CH 4 by Na gives a substance with preponderance of 
positive energy, and which is, therefore, poorly neutralized intramolecularly. Car- 
bon, a weak non-metal, in uniting with very positive metals, tends to form compounds 
of the type C 2 Me, in which the accumulated negative energy of several carbon atoms 
endeavors to neutralize the positive energy of the metal. Only with a weak positive 
metal like Al are metallic derivatives of methane formed, and it is doubtless owing 
to this relation between the energies of C and Al, the compounds of which are so widely 
distributed in nature, that we owe the occurrence of such enormous deposits of satura- 
ted hydrocarbons. 

2 Ansichten tieber die organische Chemie, I, 284-285; II, 252-254. 

Michael, /. prakt. Chem., [2] 60, 331. Ber., 39, 2138-2157, 2780-2790; 40, 
141. 

96 



ORGANIC AND BIOLOGICAL. IOOO 

(9 10 n) 8. It is to be strongly emphasized that the effect of an 
atom in position 2 or 3 is far greater than that of any similar atom less 
closely connected, and, in the case of atoms farther removed, the in- 
fluence must be largely direct, i. e., spatial. 

The principles developed above form a new basis for the theory of 
organic chemistry and may be applied to any problem arising in the 
science. 

Several important organic questions will be discussed from the new 
point of view. One of the weakest sides of the present structure theory 
is that it indicates the existence of a countless number of compounds, 
which are incapable of existence. One instance, that of an isomeric 
chloride of cyanogen (C1NC) has been already discussed, but this ques- 
tion is of such importance that it will be considered with substances of 
a different type. Nitrosomethane (H 3 CNO) does not exist, as it passes 
over spontaneously into the isomeric oxime: H 3 C NO > H 2 C= 
N(OH). If we add an oxygen to the nitroso group, we obtain nitro- 
methane (H 3 CNO 2 ), which is perfectly stable, but the tautomeric form of 
which (H 2 C = NO(OH)) is so unstable, that its existence can be proven 
only by indirect means. The thermochemical equation, 2 NO 4- O 2 = 
2NO 2 + 26.9 cal. proves conclusively that the nitroso group contains 
much more free chemical energy than the nitro, which is the reason why 
the nitroso group in nitrosobenzene is so much more reactive than the 
nitro group in nitrobenzene. In nitrosomethane, then, the following 
energetic and affinity relations exist: the oxygen has much free chem- 
ical energy and a strong affinity for the H of the methyl group, and by 
the change into the oxime, the great content of free chemical energy in 
the nitroso group is largely converted into bound chemical energy and 
heat. The transformation therefore proceeds with increase of entropy 
and the oxime represents an intramolecularly well neutralized structure, 
which agrees with its amphoteric properties and the slight additive capacity 
at the double bond. Since the nitro group in nitromethane has less free 
chemical energy than the nitroso in nitrosomethane, its oxygen has less 
capability to overcome the bound chemical energy holding the hydrogen 
to the carbon. A rearrangement to isonitromethane is barred for a sec- 
ond reason, viz., that it would proceed with a degradation of entropy, 
for it is evident that the neutral nitromethane, the nitro group of which 
carries but little free chemical energy, is vastly poorer in such energy 
than the strongly acidic, unstaturated isonitromethane. 1 

In order that a rearrangement should proceed spontaneously, the atom 

which receives the migrating atom, or group, must have sufficient affinity 

for it to be able to overcome the bound chemical energy between the 

migrating atom, or group, and the atom to which it is already joined. 

1 See Ann., 363, 21. 

97 



100 1 THEORY OF ORGANIC CHEMISTRY- 

If we increase through a structural change the bound chemical energy 
more than we do the affinity and free chemical energy factor; or if 
we decrease the latter without essentially altering the former, 
we obviously increase the relative stability of the new derivative and 
it may show an existence in a free state. Through certain structural 
changes the difference between the entropy values of the isomeric forms 
may be lessened, and we may arrive in this way to desmotropic sub- 
stances, the energy relations of which are so evenly balanced that the 
existence of one or the other form may be determined by a slight expen- 
diture of extraneous chemical, or physical energy. 1 

Before 1887 the substitution process in organic chemistry was uni- 
versally supposed to consist of the direct replacement of an atom, or 
group, by another. It was then shown, by an investigation on the con- 
stitution of acetoacetic ester and its sodium derivative, 2 that this view 
could be upheld no longer and that apparent substitution is often the re- 
sult of a combination of an addition and elimination process. Subse- 
quent researches 3 have shown that substitution, as represented by the 
old view is of comparatively rare occurrence, and that a rational inter- 
pretation of the process may be based on the entropy principle. Thus, 
by the use of a metal like sodium, which has considerable free chemical 
energy and a strong affinity for oxygen, the hydrogen in CH 2 = NOH 
attached directly to oxygen may be driven out, with the formation of 
CH 2 = NONa. 4 This change is only apparently a direct replacement 
of hydrogen by sodium, for what actually occurs is, that the energy and 
affinity values of the metal are such that it is able to overcome the bound 
chemical energy between the oxygen and hydrogen and that the latter 
element is driven out, not replaced. 

The distinction between replacing and driving out may seem from the 
above instance to be unimportant, but it is in reality of fundamental 
importance in organic reactions. Let us consider, for instance, the be- 
havior of nitromethane and hydrocyanic acid towards sodium from the 
new point of view! In the system 

1 Michael, Ann., 363, 27. 

2 Michael, /. prakt. Chem. [2], 37, 473. 

8 Michael, Loc. cit., 60, 316. Ber., 33, 3739; 34, 4028; 38, 22, 1922-1938, 2083, 
2097, 3218. Amer. Chem. ]., 43, 330. 

* It does not follow from the formation of this sodium derivative that the change 

as represented by CH 2 =NOH > CH Z =NONa designates an increase of entropy; 

indeed, a consideration of the well neutralized, amphoteric character of the oxime 
and the strong basic, easily hydrolyzed character of the sodium derivative, leaves no 
doubt that the free chemical energy in the latter is much greater than in the former 
structure. In the reaction much of the free chemical energy in sodium is converted 
into bound; it is the total change (2CH 2 =NOH + Na., = 2CH, =NONa + H 3 ) 
that proceeds with increase of entropy. 



ORGANIC AND BIOLOGICAL. IOO2 



/ 
H S C-N< | + Na, 

> 



the metal may be attracted either by the C or the O, but not only is the free 
chemical energy in the O larger than that in the C, but also the chemical 
affinity for Na. Moreover, according to the law of entropy, the system 
must strive to realize the maximum condition, which will be the formation 
of a sodium derivative, in which the free chemical energy existing in nitro- 
methane and in sodium is converted as completely as possible into bound 
chemical energy and heat. This condition is realized by the direct union 
of Na with O, since then an almost neutral salt will be formed, while the 
derivative containing the metal joined directly to C would be strongly 
basic and have positive energy in great excess. Indeed, if such a deriva- 
tive as NaCH 2 NO 2 could be obtained at a low temperature, it would pass 
over at ordinary temperature spontaneously and with an enormous in, 
crease of entropy into CH 2 = N(ONa)O. 1 The intramolecular hindrance- 
which nitromethane offers to attack, of the Na on the O is the energy 
necessary to overcome the bound chemical energy between a hydrogen 
and the carbon, which, owing to the strong negative character of the 
nitro group, is very considerably less than in methane and the reaction 
therefore proceeds readily. 

According to the old substitution theory, the action of Na on HCN 2 
proceeds by the direct replacement of the hydrogen by the metal, form- 
ing NaCN; according to the new theory, the Na may be attracted by 
the C or the N, and a salt may be formed if the metal is able to overcome 
the bound chemical energy between the H and the C and the reaction 
proceeds with an increase of entropy. The properties of the cyano group 
leave no doubt as to the existence of considerable free chemical energy 
in the C and the N, and there is also no doubt that Na has a greater affinity 
for N than for C: furthermore, N, being an element with more negative 
chemical energy than C, the energy of the metal in NaNC is much better 
neutralized than it would be in NaCN. The energy and affinity condi- 
tions permit, therefore, hi the direct formation of CH 2 = NO(ONa) and 
NaNC, the maximum possible increase of entropy, and any other con- 
ception of the structures of these salts, is as inconceivable from the new 
theory, as the older view leaves us wholly in the dark in regard to them. 

1 Although a "double" bond is usually an indication of the accumulation of free 
chemical energy, its symbolistic use for this purpose would be misleading. The free 
chemical energy in an atom must vary with the extent of intramolecular neutralization/ 
*'. e., in CH 2 = NO(ONa) the free chemical energy at C and N is used up indi- 
rectly to a very considerable extent in neutralizing the positive energy of the sodium. 
An approximate idea of the free chemical energy in the atoms of a molecule can usually 
be formed by a consideration of their chemical nature, the structure and the proper- 
ties of the substance. 

2 Michael and Hibbert, Ann., 364, 64. 

99 



ioo3 THEORY OF ORGANIC CHEMISTRY. 

We have seen that the positive energy in sodium has been largely 
converted into bound chemical energy, when the metal is introduced 
into nitromethane and that neither at the unsaturated carbon or nitrogen 
of H 2 C = N(ONa)O is there much free chemical energy. It follows from 
these energy conditions that this salt should not easily react with a re- 
agent, unless the latter contains atoms with much free chemical energy 
and a large affinity value for certain atoms in the salt. Hence, sodium 
isonitromethane is comparatively inert toward methyl iodide: but, if we 
make a change hi the structure of the salt, so that the metal is less well 
neutralized, we shall facilitate the reaction ; for, by doing so, we increase 
not only the free chemical energy of the unsaturated atoms, but the 
difference between the heats of formation of sodium iodide and the sodium 
salt, which is one of the largest factors in determining the entropy of 
the reaction. The conditions for an easy reaction are fulfilled, for instance, 
in sodium acetoacetic ester (CH 3 CONa = CH COOCsH 5 ), for in this 
derivative the positive energy of the metal is very inadequately neutral- 
ized by the weakly acidic organic radical to which it is joined, and the 
unequal balance between the positive and negative chemical forces must 
leave considerable free chemical energy in the unsaturated atoms. The 
reaction may proceed in two directions: 

CH, CONa > I 

I. || I = CH 3 CO-CH(CH S ) COOC 7 H 5 + Nal. 

H 5 C 2 OOC-CH < CH 5 

H S C Na > I 

II. Ill s=CH, C(OCH,)=CH COQC-Hj-fNat 

H 5 C,OOC CH=C O < CH S 

It is of interest to analyze the energy and affinity relations of the un- 
saturated carbon joined directly to the carbethoxyl group and those of 
the oxygen joined to sodium, since they determine the course of the re- 
action. Sodium iodide is formed in either case, and, as the heat of forma- 
tion of theC- is greater than that of theO-methyl derivative, 1 its forma- 
tion represents the maximum entropy of the system. The introduction 
of sodium into acetoacetic ester (CH 3 CO CH 2 COOC^) has the 
following effect on the energy and affinity relations of the carbonyl oxy- 
gen (in CO) and the methylene carbon (hi CH 2 ) : 

First, the free chemical energy in the O has been greatly decreased 
through direct union with the metal, while part of the bound chemical 
energy of the C (used before in holding the eliminated H) has been con- 
verted into free; second, the affinity of the O for CH 3 has been greatly 
reduced by the positive influence of the metal, which, on the other hand, 
has neutralized the effect of the two negative radicals (CH 3 CO and 
COOCjHj) and given the unsaturated a-C a large affinity value for methyl. 
It is evident that when we take the entropy, energy and affinity relations 
1 Experimental proof will be published later. 

IOO 



ORGANIC AND BIOLOGICAL. IOO4 

into consideration, the conversion of the O-sodium salt into the C-methyl 
derivative, *. e., the reaction represented by I, is not an abnormal, but a 
perfectly normal, reaction, 1 as, indeed is every chemical change hi which 
the condition of maximum entropy is realized. 

Finally, we shall discuss another fundamental organic process, that of 
addition, from the standpoint of the second law of thermodynamics. 

If we remove one hydrogen from two adjacent hydrocarbon groups 
in propane a compound is formed (CH 3 CH = CH 2 ) in which part of 
the bound chemical energy previously holding the eliminated hydrogen 
atoms hi chemical union appears as free chemical energy at the unsatura- 
ted C-atoms. 2 In the addition of a reagent to such a compound, the 
free chemical energy of the unsaturated atoms is more or less completely 
converted into bound chemical energy and heat, and the second law of 
thermodynamics compels the addition to take place hi such a manner 
that the maximum entropy will be realized, unless there is some chemical 
hindrance, which prevents this attainment of the ultimate goal of free 
chemical energy. 

The structure theory teaches us that in the addition of hydrobromic acid 
to propene, two isomers (propyl and isopropyl bromide) may be formed, but 
it fails altogether to give us any indication which of these products, or 
whether both of them, should result. The chemical hindrance hi this reac- 
tion is the energy necessary to overcome the bound chemical energy between 
the H and the Br of HBr to the extent to which it exists between them 
in the bromopropane that will be formed in the addition. 3 This hindrance 
is obviously quantitatively the same in the formation of either isomer. 
The maximum entropy hi this addition will be attained, therefore, hi 
the formation of the isomeric bromopropane with the greater heat of forma- 
tion. 

Obviously, it is of great importance in this and hi many other organic 
reactions to be able to trace the relation between the structure of iso- 
mers and their heat of formation. This is enabled by the following 
" thermochemical law of structure." 4 In isomers with normal chains 
and which contain a common negative radical as a nucleus, that isomer 
will have the largest heat of formation, the positive radicals of which to 
the greatest extent are under the influence direct and indirect of the 
negative nucleus. Thus, in propyl and isopropyl bromide the common 
negative nucleus is CBr, which hi the last compound is under the direct 
influence of two methyl groups, while in propyl bromide only one methyl 
is directly, the other indirectly, joined. The intramolecular neutraliza- 

1 Michael, Ber., 38, 129. 

1 /. prakt. Chem., [2] 60, 298. 

* Michael, Am. Chem. ] ., 43, 333 (foot-note). 

4 Michael, /. prakt. Chem., [2] 68, 499; 79, 418; Ber., 39, 2140. 

101 



1005 THEORY OP ORGANIC CHEMISTRY. 

tion, which finds an expression in the heat of formation, is therefore 
larger in the iso than in the normal bromide, and, since the thermic 
value of direct is very much greater than that of indirect chemical 
union, the heat of formation of the former compound is considerably 
larger than that of the latter. 

Not only does the system, propene and hydrobromic acid, realize its 
maximum condition of entropy in the formation of isopropyl bromide, but 
the affinity relations at the points of maximum concentration of the free 
chemical energy, i. e., at the unsaturated carbons, are such as to favor the 
course of the reaction in this direction, since the influence of methyl in 
this substance is positive to that of hydrogen in the same position. 1 This 
relation causes in propene a greater accumulation of positive energy at the 
middle than at the end unsaturated carbon and the middle carbon must 
have, therefore, the greater affinity for the strongly negative halogen of the 
acid. It seems theoretically probable that this coincidence of affinity and 
entropy values should lead exclusively to the formation of the iso deriva- 
tive, as, indeed, it would if chemical change depended solely on the free 
energy and the affinity values. When a mixture, containing an acid 
with a very large and a very small .acidity constant, is brought together 
with a quantity of a strong base inadequate for complete neutralization 
of the acids present, there is always an appreciable amount of salt de- 
rived from the weak acid formed. The chemical force in each acid en- 
deavors to its utmost capacity to contribute its share toward the increase 
of entropy, which depends not only on the values of the affinity constants 
but, although to a very much smaller degree, on the actual mass, by weight, 
of acid present. 

If the formation of normal propyl bromide from propene and hydro- 
bromic acid proceeds with an increase of entropy, which it undoubtedly 
does, we have in this addition reaction two chemical forces, each striving 
to increase the entropy, but, in this case, the mass by weight cannot be 
changed and the struggle is between energies. 2 Furthermore, since 
there is no difference in the chemical hindrance to the addition in 
either direction, it is extremely probable that the relative amounts of 
salts, or isomeric bromides, formed will stand in a direct relation to the 
increase of entropy, and as this is very much greater with the formation 
of isopropyl bromide, it agrees with the theory that the normal bromide 
is formed only to a very slight extent. 3 

The principle here involved was first used by Thomson 4 to determine 
the relative acidity constants, and has been called the "principle of 

1 Michael, /. prakt. Chem., [2] 60, 332; Ber., 39, 2142 (footnote). 

2 There is no practical difference, as matter from a chemical point of view should 
be considered only as a carrier of chemical energy. 

3 Michael and Leigh ton, /. prakt. Chem., 60, 443. 

4 Pogg. Ann., 138, 497. 

102 



ORGANIC AND BIOLOGICAL,. IOO6 

partition"; 1 it may be applied to every organic reaction where two or 
more isomers may be formed. 2 Let us take, as illustrations of the appli- 
cation of this principle, the addition of water by means of sulphuric acid 
to hexine-i and -2. In hexine-i (CH 3 CH 2 CH 2 CH 2 CEE CH), 
we have practically the same conditions as in propene, that is, the differ- 
ence between the energy and affinity values of the unsaturated carbons 
are due to the difference between the direct influence of an alkyl group 
and a hydrogen; hexanone-2 (CH 3 CH 2 CH 2 CH 2 CO CH 3 ) and 
probably a very slight amount of hexanal (CH 3 CH 2 CH 2 CH 2 
CH 2 CHO) are formed. The relations in hexine-2 (CH 3 CH 2 CH 2 
C EE C CH 3 ) are quite different; the unsaturated carbons are both joined 
directly to alkyl groups, and the change in their energy values is due 
not to direct, but to indirect, influences, which are largely spatial. This 
relation must cause the heats of formation of the products that may 
result, hexanone-2 and -3, to be much nearer together than the isomers 
that may be formed in the addition to hexine-i ; also an approximation 
in the energy and affinity values at the unsaturated carbons. 

According to the "principle of partition," the relative amounts of 
hexanone-2 and -3 formed should not fall very far apart. Moreover, 
we can approximately estimate the energy values of the unsaturated 
carbons in relative terms by the use of the "scale of combined influence" 
mentioned above. Applying this scale to the relations in hexine-2, 
omitting those atoms the influences of which on the unsaturated carbons 
are equal, 2 or very nearly so, we find that A^ C 3 (joined directly to 
methyl) is under the influence of one carbon in the 4th, one hydrogen in 
the 3rd, and three hydrogens in the 5th position, and A r C (joined di- 
rectly to butyl) has one carbon acting in the 3rd and 4 hydrogens in the 
4th position. Since atoms in the 3rd and 5th positions exert a greater 
influence than those in the 4th, it is obvious that the positive energy 
at A^ C is greater than that at A r C, and that a larger proportion 
of that ketone should be formed, when the negative part of the addenda 
adds to it, i. <?., hexanone-2. A re-investigation 4 of the reaction shows 
indeed that about 60 per cent, of hexanone-2 to 40 per cent, of -3 are 
formed in the reaction. 

The present structure theory has been, and always will be, of inestimable 
service to organic chemistry: it has taught us, until recently, 5 the possi- 
ble number of isomers that may exist of a given formula, and it has been 
a guide in determining the constitution of most of the substances that 

1 Michael, J. prakt. Chem., [2] 60, 341-354; Ber., 39, 2138-2156, 2569, 2786- 
2 795; 40, 140. 

2 See J. prakt. Chem., 60, 341. Ber., 39, 2141. 

* The capital "Delta" denotes unsaturation (Baeyer, Ann., 245, 112). 
4 Michael, Ber., 39, 2133. 
8 Ber., 39, 203. 

103 



1007 THEORY OF ORGANIC CHEMISTRY. 

have been discovered. But its weakness and limitations are inherent 
in its foundation on a mechanical conception of valency and an almost 
exclusive theoretical development along similar lines, for surely in nature 
there are no forces more intimately and indissolubly connected with 
changes in energy than the chemical. 

Largely for this reason, the structure theory fails to offer explanations 
for many of the simplest organic reactions and, for many years, it has 
failed in explaining and co-ordinating with theory much of the wonder- 
ful experimental progress that has been made in the science. 

It is true that innumerable attempts have been made to amplify or 
change the idea of valency and the structure theory so as to remedy 
these deficiencies, but they have always been along mechanical lines and 
have led to such impossible theoretical conceptions as new brands of 
valencies, dissociated and partial valencies, oxonium and carbonium 
theories, steric hindrance due to size of the atoms, etc., etc. 

All the forces in nature, whether mechanical or chemical, have the 
same goal in view, which is the realization of the maximum condition of 
entropy, and a scientific theory of chemistry must inevitably have this 
law as its basis. The present aim of organic theory is not to abandon 
the structure theory, but so to broaden and develop it that it becomes a 
consistent and harmonious part of nature. 

NEWTON CENTRE, MASS. 



PROGRESS IN SYSTEMATIC QUALITATIVE ORGANIC ANALYSIS. 1 

BY S. P. MULLIKEN. 

Received June 29, 1910. 

A general procedure in organic qualitative analysis that may be trusted 
to lead to the discovery of the proximate composition of any unknown 
organic substance whatever, whether this be a simple compound or a 
mixture, is demonstrably incapable of practical realization. Before pro- 
ceeding to the discussion of the main subject of this paper, it therefore 
behooves us to pause for a moment to note certain limits which Nature 
seems to have set against the too curious advances of the analyst. 

The most clearly insuperable of these limitations are associated with 
high molecular weight. If a paraffin hydrocarbon of the formula C 36 H 72 
were to be isolated in a state of perfect purity and in large quantity from 
some natural product, it would be impossible to absolutely identify it 
as a compound corresponding to any particular structural formula by 
any combination of methods of investigation now known, or whose 
future discovery appears probable. Such a hydrocarbon would not differ 
by one one-hundredth of one per cent, in its hydrogen or its carbon 
content from its adjoining homologues, while in chemical and physical 
properties there would be no measurable differences between it and 
1 An address delivered at the Second Decennial Celebration of Clark University, 
Worcester, Mass., Sept. 16, 1909. 

104 



ORGANIC AND BIOLOGICAL. 1050 

thousands of its four million undiscovered structural isomers, which, ac- 
cording to the calculations of Cayley, are theoretically possible. Indeed, 
in the case of the discovery of such a high hydrocarbon by any process 
other than one of simple synthesis, no proof could be contrived which 
would show that the substance might not well be a mixture of many iso- 
mers and neighboring homologues; for all finite methods of purification 
by fractional separation based on differences in properties must inevita- 
bly fail when the numerical odds against them are so great, and we have 
no choice in such a case but to resign ourselves with the best grace pos- 
sible to an inevitably partial solution of our problem. 

But without having ascended to such an altitude in the homologous 
scale as in the instance just cited, it is often necessary or expedient to 
accept incomplete answers in qualitative inquiries because of our thraldom 
to the rule that unknown compounds in mixtures cannot in general be 
fully identified without previous isolation in a state of purity. It is for 
this reason that it is so common a practice in technical analysis to ex- 
press the quantitative composition of familiar and important products 
in conventional or collective terms. L/ong and thoroughly as the animal 
fats have been studied, for example, there is probably no instance on 
record of a quantitative examination of any natural fat in which it could 
be safely claimed that the structural identity of all its fatty acids contain- 
ing less than eighteen carbon atoms had been irrefutably established. 
Nor would it be surprising under the circumstances if such a result were 
never accomplished. 

Thus handicapped, systematic qualitative organic analysis has de- 
veloped slowly when compared with the simpler qualitative analysis of 
the inorganic elements and salts. Yet, if we contrast the difficulties to 
be overcome in constructing an orderly scheme for the separation and 
identification of the list of less than one hundred elements with the diffi- 
culties to be met in any corresponding scheme for the organic compounds, 
and then recall what has already been accomplished in overcoming them, 
and also the imperfections which present-day inorganic qualitative 
schemes still exhibit when the rarer elements are included, the organic 
chemist will find little cause for pessimism. The greater part of the con- 
tributions to organic qualitative analysis have been made, however, with- 
out much thought of the part which they might be made to play in 
any comprehensive scheme of procedure, and have often owed their 
origin to incidental observations made during the execution of investiga- 
tions of broader scope and different purpose. Fischer's numerous char- 
acterizations of compounds in the sugar, purine and protein groups, by 
well chosen reactions and derivatives, and his ingenious separations 
for the amino acids formed in proteolysis are illustrations of this fact. 
Among the rather numerous handbooks of organic analysis, although 

105 



1 05 1 SYSTEMATIC QUALITATIVE ORGANIC ANALYSIS. 

many devote much space to qualitative testing, the speaker recalls only 
one whose author (Barfoed, 1878) has been sufficiently venturesome to 
incorporate the phrase "Organic Qualitative Analysis" in its title. Of 
the many commendable partial schemes for the isolation and identifica- 
tion, or the detection in certain classes of mixtures, of carbon compounds 
belonging to restricted groups, we owe the origin of a large proportion 
to an acute need of special analytical assistance in some department of 
industry, research, or governmental control. To such cause we owe 
much of what is most valuable in Allen's " Commercial Organic Analysis," 
Post's " Chemisch-technische Analyse," and the works of Vortmann, 
Dragendorff, Hoppe-Seyler, Konig, Leach, Sherman, and others. The 
investigation of methods for the detection and determination of constit- 
uent radicals has also proved a fruitful source of valuable material, much 
of which has been made accessible for ready reference in H. Meyer's 
"Analyse und Konstitutionermittelung organischer Verbindungen. " 

The resolution of mixtures is usually the first, and often the most 
difficult part of a qualitative analysis. Definite plans for correlation 
in a broad general procedure of the methods of separation that have 
proved effective in the study of restricted classes of mixtures have yet 
to be proposed. The speaker is not in accord with the rather prevalent 
view that it is useless to strive for broader and more systematic separa- 
tion procedures. But, on the other hand, as he is unprepared to play 
the prophet's role, it may be more profitable for him to confine the fol- 
lowing discussion to the topic of systematic procedures for the identifica- 
tion of pure compounds, this being an important division of the qualita- 
tive problem whose solution seems nearer accomplishment. 

Prior to 1831, the date of the inauguration of those revolutionary 
improvements in organic combustion methods by Liebig, which rendered 
it possible to determine the percentage composition of any carbon com- 
pound with considerable accuracy and comparative convenience, it does 
not appear that any comprehensive systematic methods for identifying 
previously described organic compounds had been formulated, or that 
the lack of them had been felt as a serious inconvenience. The num- 
ber of pure compounds that had been described was comparatively small, 
the possibility of laboratory syntheses for organic compounds having 
only just become recognized, and the descriptions of such compounds 
as were known were not scattered as to-day through an almost endless 
list of special journals and treatises. A chemist of this earlier period, 
if a man of extended practical experience, well read, and having access 
to a good library, rested more or less content in the knowledge that he 
could probably accomplish by a purely eclectic procedure, based on his 
miscellaneous sources of information, ingenuity, and common sense, 
all that was then analytically possible. 

1 06 



ORGANIC AND BIOLOGICAL. 1052 

Thanks to Liebig's writings and the influence of the students who passed 
from his Giessen laboratory, his simplified methods of ultimate analysis 
were not long in becoming widely known. In scientific laboratories 
they were everywhere welcomed and adopted. This welcome was richly 
deserved; for, besides serving as a means to determine percentage com- 
position values which will perhaps always remain the most funda- 
mental of chemical constants their use, in connection with the later 
widely adopted vapor density molecular weight determination meth- 
ods, furnished all information required for the calculation of empirical 
formulas. These, if we add knowledge of genetic relations and chemical 
behavior, become structural formulas with all the added information 
as to chemical characteristics and individuality which are inherent in 
the latter. The vapor density molecular weight determination methods 
reached their climax for the organic chemist in the air displacement 
form proposed by Victor Meyer in 1878. The prestige of the empirical 
formula as an aid in compound identification was soon still further en- 
hanced by the discovery of Raoult's principle, followed by the invention 
of the Beckmann thermometer in 1888, these aids to molecular weight 
determination finally enabling the inclusion among the compounds of di- 
rectly determined empirical formulas of a large share of the non-volatile 
compounds. Other causes about to be mentioned also conspired to bring 
the analytical importance of the empirical formula to extreme promi- 
nence. 

During the two decades closing in 1880, the unprecedented increase in 
newly described organic compounds had already begun to assume 
the dimensions of a threatening deluge. The synthesis responsible 
for the creation of a new species, being aware of its genetic relations, 
and having determined its empirical formula, was usually in a position 
to correctly interpret the chemical identity of his progeny; though 
to prove that his discovery was really an original one by a search 
through the swollen literature had become a task to be undertaken with 
fear and trembling. The time rapidly approached when the healthy 
future development of organic research seemed likely to receive a serious 
check from the confusion and discouragement in store for investigators 
who could only hope to escape plagiarism in recounting their alleged dis- 
coveries by well-nigh interminable bibliographical delvings. Those of us 
in the younger generation of organic chemists are not in a position to even 
faintly appreciate the sigh of relief that must have been breathed by 
hundreds of workers in many lands when these chaotic conditions were 
ameliorated in 1882 by the completion of the first edition of Friedrick 
Beilstein's great handbook of organic chemistry. With rare foresight 
Beilstein had in season anticipated the mission which this remarkable 
work had to fulfil, and its publication after twenty years of incessant 



1053 SYSTEMATIC QUALITATIVE ORGANIC ANALYSIS. 

labor, occurring as it did at this critical period in the development of 
organic chemistry, is of epoch-making importance to organic qualitative 
analysis as well as to all other departments of the science. 

Beilstein's "Handbuch" was a digest of the complete literature of the 
modes of formations, properties and reactions of all the analyzed com- 
pounds of carbon. It did not purport to be an analytical guide, and in 
its introduction the possibility of a qualitative organic analysis at all 
comparable to the inorganic is categorically denied. Nevertheless, 
because of the completeness and orderly arrangement of its concise de- 
scriptions, its importance as an aid in the identification of organic com- 
pounds may be fairly estimated as greater than that of all the special 
analytical treatises which have ever been issued. Its general classifica- 
tion for the compounds has sometimes been criticized as clumsy and 
confusing, but the division of species according to chemical function, 
saturation, and in homologous series, has, on the whole, served the in- 
terests of the analyst well; and the invention of a simple device for loca- 
ting in its pages the description of any desired compound of known em- 
pirical formula, which has been more recently made available through 
the ingenuity and cooperation of M. M. Richter, the manager of the 
Prinz Dye Works in Carlsruhe, has now long served in case of compounds 
of this class to greatly facilitate their identification. 

Richter's "Tabellen der Kohlenstoff-Verbindungen" with its 20,000 
brief references to the literature and properties of the analyzed organic 
compounds was issued in 1884. The first volume of the second edition 
appeared in 1900 under the altered title of "Lexikon der Kohlenstoff- 
Verbindungen." In its present completed form this edition registers 
more than one hundred thousand compounds of determined empirical 
formulas, and gives direct access to the full description and literature of 
each by citation of the proper volume and page number of Beilstein. 
As a bibliographical index for compounds of known empirical formula it 
is hard to imagine anything simpler or more complete than the Rich- 
terian classification. The exact position of every possible compound 
(if we exclude the arrangement of isomers with reference to one another) 
is automatically fixed by its formula alone, and is as easily found, and 
in much the same manner, as a word in a dictionary through a knowledge 
of the relative positions of its letters in the alphabet. The completeness 
of the tabulation is suggestively indicated by the author's remark that 
his guiding thought during its preparation was " Das Unwesentliche, 
d. h. die weniger bekannten Verbindungen, stets in erster L,inie und 
vollstandig hervorzuheben. " On the other hand, its use as the basis 
for a method of identification for unknown organic compounds is often 
attended with serious or prohibitive difficulties. 

It has been already pointed out that an absolute determination of 

1 08 



ORGANIC AND BIOLOGICAL. 1054 

species among the carbon compounds is theoretically impossible by any 
combination of tests in the case of compounds of extremely high molec- 
ular weight, and that the unavoidable errors of ultimate organic analysis 
with such substances are large enough to prevent analysts from making 
any selection between a large number of seemingly possible and equally 
probable empirical formulas. This unfortunate circumstance prohibits 
the use of the Richterian system in large and important fields where 
quantitative investigation by other methods may be conducted with good 
prospect of success. For example, the dyestuff tables of Schultz and 
Julius describe a hundred distinct tetra-azo dyestuffs having molecular 
weights above 500, and some of them exceeding 1000. These colors are 
many of them important, their constitutions well established by syn- 
thesis, and their identification through their physical and chemical 
properties, or at least their approximate identification which is often 
all that is required is not especially troublesome. The absurdity of 
an attempt to identify an unknown color of this class through its em- 
pirical formula which would usually involve the quantitative deter- 
mination of at least six elements with an impossible degree of precision 
is so patent from the mere mention of the stoichiometric conditions that 
it may be hoped it has never been made by any rational being. 

A second defect in the method of the empirical formula, which in the 
ordinary laboratory curtails its actual application even more than the 
absolute limitation just mentioned, is the fact that much special 
manipulation, skill and apparatus are necessary to insure trustworthy 
results in elementary organic analysis, and that so much time is always 
consumed in the preliminary arrangements for a combustion and in its 
conduct. In the larger organic laboratories where the combustion of 
new synthetic products is an almost daily incident of the routine of 
investigation, and the equipment of the combustion room is maintained 
at all times in a state of perfect preparedness for emergency calls, so that 
no time need ever be lost in the mobilization for an analysis, the organic 
combustion is not formidable to the initiated. But under other circum- 
stances and they are the prevalent ones chemists do not resort to 
the method of the empirical formula except under rather strong com- 
pulsion, and many identifications which ought to be made are not even 
attempted. 

In view of these defects and inconveniences, it is natural to inquire 
whether there is hope of securing in the future any scientific substitute 
for the method of the empirical formula. In the comprehensiveness 
and simplicity of its classification of compounds, it must be admitted 
that it will be vain to expect anything but loss from radical changes in 
the Richterian arrangement; but, if we accept the logician's definition 
of a scientific classification as "Nothing more than a system of division 

109 



1055 SYSTEMATIC QUALITATIVE ORGANIC ANALYSIS. 

carried out in such a way as to best serve a given purpose," and if our 
purpose is convenience and effectiveness in general qualitative investiga- 
tion, the possibility of other and more scientific classifications is not to 
be denied; and it has seemed to the speaker that the discovery of such 
methods of classification is at present one of the important and attractive 
fields for organic chemical research. What the final outcome of this 
quest will be if we have the right to speak of a final outcome in a prob- 
lem which from its nature permits of only progressive partial solution 
no one can as yet speak with full authority. Some of the general 
considerations bearing on the subject may, however, be brought to your 
attention. 

Scientific classifications are chiefly concerned with relations of resem- 
blance and contrast. To answer the question what points of resemblance 
and contrast must be regarded, and in what order, if we are to make a 
classification scientific, is to say that no basis of classification (" funda- 
mentum dimsionsis") is per se better than any other. All depends on 
the ultimate object. If the object of a classification is ready diagnosis 
of natural objects, it is evident that the characteristics used as differentiae 
for distinguishing between groups should permit of easy as well as cer- 
tain determination; and it is also a good quality in such a division to 
collect individuals in the lowest group for comparison which are on the 
whole most alike. Methods of subdivision which aim at discovering 
something without regard to whether the resemblances of adjacent 
species are fundamental or accidental, like the classification of words in a 
dictionary according to the accidental alphabetical sequence of their 
letters, are called artificial systems. The Linnaean and Richterean 
systems belong to this category. No comprehensive system of division in 
natural science is free from many artificial features. But these are more 
likely to be prominent in the early than in the later stages of the develop- 
ment of a classification, the pioneer in such work having to first bridge 
his rivers with such structural materials as lie nearest at hand. 

To the observant mind the discovery of possible differentiae for the 
classification of natural objects is an easy and fascinating pastime, though 
to make a wise selection may often be quite the reverse. Thus we read 
in the quaint diary of the botanist Linnaeus under the date of June 12, 
1632, in his "Lapland Observations": "Close to the road hung the under 
jaw of a horse, having six front teeth, much worn and blunted, two canines, 
and at a distance from the latter twelve grinders, six on each side. If 
I knew how many teeth and what peculiar form, as well as how many 
udders, and where situated, each animal has, I should perhaps be able 
to contrive a most natural methodical arrangement of quadrupeds." 
As with Linnaeus' quadrupeds, so with organic compounds we find a 
multitude of easily determined properties from which we may choose 

no 



ORGANIC AND BIOLOGICAL. 1056 

the differentiae for our classification, and by the exact coincidence of a 
sufficient number of these characteristics of different orders with those 
of an unknown compound, the identity of the latter may be proved. 
Qualitative elementary composition, color, melting and boiling point, 
specific gravity, odor, taste, solubility, refractive index, specific optical 
rotation, electrical conductivity, absorption spectra, color reactions, 
precipitations, and general chemical behavior especially simple chemical 
reactions that throw light on the nature of dominant atomic groups and 
structural peculiarities may all be thus used. 

Regarding the chemical compound, or individual, as the species of a 
chemical system, it appears most natural to group these species in such a 
way as to make the next higher unit or genus contain species which are 
most similar in general chemical behavior. This would, for example, 
tend to make congeners of members of all homologous series containing 
the aldehyde radical, provided we could find sufficiently reliable and 
simple chemical tests for showing the presence of the CHO group. Re- 
cent chemical literature abounds in suggestions for tests suitable for 
generic differentiae, though much additional work will be required in 
every instance to determine the real value and exact boundaries of the 
genera that their employment would create, there being ever-present 
danger that overconfidence in the constancy of behavior of a reagent 
towards a given radical in different structural environments may lead 
to false conclusions. Thus it is not safe to assume that under certain 
specified conditions all ketones will form oximes; all acids and phenols 
will dissolve in alkali; all esters will be saponified; or all unsaturated 
compounds will add bromine. In first delimiting a genus such assump- 
tions may be adopted, after preliminary experiments, as tentative 
working hypotheses ; but the contents and existence of the genus must be 
held to be strictly provisional and dependent on the positive outcome of 
the proposed genetic reaction when applied to a larger number of its care- 
fully selected species, and to its negative outcome when tried with numer- 
ous members of all genera of higher numerical designation in the same 
classificatory order. It will also be the duty of the classifier to indicate, 
in a manner that will leave no doubt in the minds of readers, all descrip- 
tions, or parts of descriptions, for which he is personally responsible; 
for unless some means is given for distinguishing between data which he 
has verified, and others which he has not, the authority is liable to be 
more or less implicated in the mistakes of others for which he need have 
assumed no responsibility, but which will now tend to vitiate the value 
of his classification as a whole. 

It would be premature at this time to present in all its minutiae any 
plan for such a classification as has just been suggested in its outlines. 
Details in illustration of the speaker's original conception and partial 

in 



IO57 SYSTEMATIC QUALITATIVE ORGANIC ANALYSIS. 

execution of such a plan are to be found in the already published first and 
third volumes of his "Method for the Identification of Pure Organic Com- 
pounds." All that is desired here is to lead to a discussion of the ad- 
vantages in the plan for Chemistry; and if it is sound, to arouse interest 
with a view to eventually bringing about a wider cooperation for 
furthering its future development. The difficulties to be overcome are 
considerable. Recorded descriptions of organic compounds, while fre- 
quently very complete for a few properties like melting and boiling 
points, are commonly equally deficient concerning others especially in 
exact data showing the extent of the influence of slight variations in chem- 
ical constitution on the results of the selected differential tests. The occa- 
sion hence arises for an investigation or partial reexamination of a con- 
siderable proportion of the species receiving locations. If one has the pure 
compounds with which to experiment, the tests are easily made. But 
as only a few thousand pure compounds can be procured through com- 
mercial channels, and most of these require some purification, sucess 
in the construction of a comprehensive diagnostic classification implies 
assistance from private collections throughout the world; for to syn- 
thesize any considerable part of the rarer species would overtax the 
facilities of the largest and best equipped of laboratories. 

To bring a majority of the carbon compounds referred to in Richter's 
Lexikon into an essentially "natural" classification of the kind sug- 
gested would, assuming the study of tests and revision of constants 
to be thoroughly done, perhaps involve a labor as great as the trans- 
formation of the "artificial" botanical classification of Linnaeus into 
the modern "natural" system as it was left by de Candolle. An 
undertaking of this magnitude and character might presumably in the 
present century be accomplished with greater benefit to science under the 
direction of some such organization as the committee entrusted with the 
periodical revision of Beilstein's "Handbuch" and the Richter "Lexikon" 
than under private auspices. 

MASSACHUSETTS INSTITUTE OF TECHNOLOGY, 
BOSTON, MASS. 



112 



THE OUTLOOK FOR A BETTER CORRELATION OF SECONDARY 
SCHOOL AND COLLEGE INSTRUCTION IN CHEMISTRY. 1 

If the question "Should more credit be allowed by institutions of col- 
lege grade for work in chemistry done by pupils in secondary schools?" 
were asked of any considerable number of teachers in those schools it is 
easy to believe that the majority would make an affirmative reply, and 
that all would at least be inclined to add to the query the traditional 
language of the examination paper, "If not, why not? Give reasons for 
your answer." Inasmuch as the present conditions with respect to the 
correlation of the work in the two grades of schools is admittedly unsatis- 
factory, and since these conditions are essentially determined by deci- 
sions on the part of the colleges, it is fitting that the situation should be 
occasionally reviewed, with the purpose of finding out, on the one hand, 
how far the present situation can be defended and, on the other hand, 
of seeking means by which better results can be attained. Others have 
dealt with this subject from various standpoints, and the statements 
which follow are made less with the expectation that anything like a 
final word will be said, than the hope that a contribution of the experi- 
ences of the teachers in one more laboratory, and a few of the conclu- 
sions which they have reached, may do something to aid in the compre- 
hension of one of the most perplexing problems which confront the teacher 
of elementary chemistry to-day. 

The experiences here recorded have been gathered from the routine of 
instruction in a technical school, and it may be considered doubtful by 
some whether observations made in the laboratory of a technical school 
in which the instruction in chemistry becomes a part of a "step up" 
system of requirements (that is, one in which successful work in subjects 
of later years is directly dependent upon a thorough grounding in earlier 
subjects to a degree that does not obtain in the less rigid sequence of 
studies in the college) should be taken as a basis for conclusions bearing 
also upon college work; but, while such doubts may be justified in the 
case of a limited number of institutions in which chemical instruction is 
merely a part of a general college course, it is increasingly true that more 
and more students from all colleges are seeking the technical schools to 
complete some of the professional courses which they offer. In the case 
of the university the technical school may well be a part of its own sys- 
tem; in the case of the college it means that its reputation for efficiency 
in teaching is to be unexpectedly tested by some other group of instruc- 
tors, and it should be as much a matter of concern to them to see that 
their students have an adequate preparation in the sciences as to see 
that they are soundly taught in mathematics or the humanities. Many 
of the colleges have much room for improvement in this respect. 

Let us first look at the situation as it apparently exists at present in 
some of our typical institutions as indicated by the following brief sum- 
maries. The term "entrance requirement" is assumed to represent 
the work of a year with the ordinary time allotment for chemistry in the 
preparatory schools. The data have been obtained through direct cor- 
respondence with representatives of the institutions mentioned. 

1 Presented at the second decennial celebration of Clark University, Worcester, 
Mass., September 17, 1909. 



1 . Yale College. Does not require chemistry for entrance. Students 
may take an examination for advanced standing, but rarely do so. 

2. Harvard College. Those who have passed the entrance requirement 
take the same lecture as those who have had no chemistry, but they have 
special laboratory work and more advanced instruction in a special divi- 
sion. They are also allowed to take a first course in organic chemistry 
in the freshman year. Admission of such students to work in qualita- 
tive analysis has not proved successful. Those' who present more chem- 
istry than the entrance requirement are individually considered, but are 
rarely excused from college work on the basis of secondary school work. 

3. Cornell University. The entrance requirement is nearly the same 
as that of the College Entrance Examination Board, but the passing of 
this examination does not secure credit for introductory inorganic chem- 
istry in the university. The student may take an examination for ad- 
vanced standing if he desires. 

4. Columbia University. Those who pass the College Entrance Ex- 
amination Board examination are admitted to a special course in lectures 
in chemistry, including a somewhat advanced treatment of the subject. 

5. Syracuse University. For one year of chemistry in a normal school 
credit is given for elementary chemistry in college, provided the student 
takes another course in chemistry and passes well. After one year of 
chemistry in a secondary school, pupils are allowed to take the regular 
examination in elementary chemistry, and if they pass, credit is given 
for that course. If chemistry is accepted for admission the student is 
admitted to second-year classes, but no credit is given for elementary 
chemistry. 

6. Washington and Lee University. Students from secondary schools 
with the equivalent of Remsen's "Briefer Course" are admitted to a 
course including physico-chemical topics and to qualitative analysis. 
If they do well, they are excused from the former at Christmas, and con- 
tinue with analytical chemistry; otherwise they continue the course in 
inorganic chemistry through the year. A few students from selected 
schools are admitted at once to qualitative analysis, but no college credit 
is given. 

7. Washington and Jefferson University. Students from a few selected 
schools are given credit for the first year of chemistry in college, provided 
they take a later course in chemistry and attain a high pass record. Others 
are required to pass an examination before any credit is given. Chemis- 
try is given in the sophomore year in this institution. 

8. Wellesley College. An advanced course is provided for those stu- 
dents who have had a year of chemistry. Smith's "College Chemistry" 
is used, and a somewhat exacting line of experiments is required. Some 
quantitative experiments, some volumetric analysis and some inorganic 
preparations are included. 

9. Chicago University. Students who have completed one year of 
chemistry in an accredited school are admitted to special courses and 
complete the work preparatory for qualitative analysis, or elementary 
organic chemistry, in about two-thirds of the time required by beginners; 
that is, they complete two majors in chemistry in place of three. The 
work of these two majors is carefully adapted to utilize and clarify the 
knowledge already gained. 

114 



10. University of Michigan. For a year of chemistry at an accredited 
school four hours of university credit are allowed (sixteen hours per 
semester is full credit). These students are admitted to a course some- 
what less elementary than that given to beginners. 

11. University of Illinois. A full year of chemistry in a secondary 
school is accepted in place of one semester in the university, provided no 
more chemistry is taken (and provided chemistry is not offered for en- 
trance). When the student continues in chemical subjects he is ad- 
vised to take the regular course of lectures in chemistry, but spends less 
time in the laboratory. 

12. University of Wisconsin.-*- Credit is given for entrance chemistry 
to the extent of one or two units out of fourteen. These students enter 
the same classes as the others, but have a slightly different laboratory 
course. In the course of two months they appear to be on about the 
same footing as those taking the subject anew. 

13. Lehigh University. Up to two years ago certain certificates were 
accepted from secondary schools but the results were so unsatisfactory 
that an examination has been substituted. Those who fail take elementary 
chemistry; those who pass are admitted to a course in theoretical chemis- 
try. 

14. Sheffield Scientific School. If the student passes entrance chemis- 
try, he is allowed to take an examination to pass off the elementary 
course in the scientific school, and if successful he is admitted to quali- 
tative analysis. Very few students are thus admitted. 

15. Stevens Institute of Technology. Students pass an entrance ex- 
amination like that of the College Entrance Examination Board, but the 
instructor finds that he cannot make use of the earlier work, and all stu- 
dents take a course in elementary chemistry. 

16. Worcester Polytechnic Institute. Earlier attempts to examine upon 
a limited portion of elementary chemistry with the purpose of definitely 
eliminating this from the college course were not successful. Note- 
books are now examined, and when these indicate a satisfactory course, 
the students are placed in separate divisions and given a different labora- 
tory course. They attend the same courses of lectures as the beginners. 

17. Massachusetts Institute of Technology. Students who have satisfied 
the entrance elective requirement are admitted to a special class during 
the first term, and the lecture and class-room instruction, as well as the 
work in the laboratory, are designed to take advantage of the work al- 
ready completed by the student in the preparatory school. The effort is 
made to introduce new lines of experimentation, as well as to reawaken 
interest in earlier work by encouraging the student to interpret the phe- 
nomena which he now studies in the light of his more extended expe- 
rience, and with the aid of such additional concepts as have been introduced 
into the lectures and recitations. The two divisions of the class are uni- 
ted for the work of the second term. 

Of these seventeen institutions one does not recognize chemistry for 
entrance, two make no specific provision for students who have had 
chemical instruction in the preparatory schools, three provide special 
laboratory instruction, but give no definite college credit, six provide 
special instruction in both lecture room and laboratory, but without 
giving college credit, while two give some college credit on certificate, 



and four excuse students from elementary college courses after special 
examination. 

These institutions are sufficiently varied as to locality and type to 
justify the assertion that they represent the present practise on the part 
of thoughtful college teachers. That there is apparently much duplica- 
tion of effort is at once evident, and that this must result in some loss of 
time, energy and enthusiasm hardly requires argument. Why, then, 
have we so long tolerated this apparent waste, and why do we not imme- 
diately take steps to avoid it? The answer seems to me to be this: It 
appears to be impossible to select any point in the chemical instruction 
received by the members of a college entering class at which they have 
such a sound understanding of the facts and principles already studied 
that this knowledge may safely be accepted as a foundation for further 
college instruction; or, if such a point may be selected, it lies so near to 
the beginning of the college course as to make a definite excuse from this 
small amount or work practically meaningless. There is, of course, a 
small proportion of students to whom this statement is not applicable, 
but it holds true to so large a proportion that it determines the character 
of the instruction which is given to all students who have had any pre- 
vious chemical instruction. The situation does not appear to be appre- 
ciably better in institutions having a definite entrance requirement in 
chemistry than in others. 

Some of the reasons for this state of affairs we will try to consider 
presently, but let us first look at the conditions as they confront the col- 
lege teacher who has an earnest desire to enable his students to utilize 
every advantage which they have gained, remembering, however, that in 
these days it is not a question of individual but of class instruction, so 
far as the main features of a course are concerned. The college teacher 
or the teacher in a technical school will find among the members of a 
single class students of each of the following types, with many varia- 
tions : 

Student A. An intelligent, reasonably thoughtful pupil from a school 
where there are small classes, a well-arranged one-year course and a 
judicious, helpful teacher. Such a student is a source of constant pleas- 
ure, and much can be done for and with him. 

Student B. The chemical enthusiast who, during a course of one or 
two years' duration has been permitted, because of his enthusiasm, to 
work extra hours or to assist his teacher. He has won high praise and 
occasionally merits it, but too often the college teacher learns to dread 
the expenditure of energy and tact which is necessary to retain the good 
will of such a student while bringing him to realize that a more profound 
knowledge than his own may be possible; yet, when the battle has been 
won, perhaps half of these men make excellent students. 

Student C. The student who has had two years of chemistry, in a 
course of ordinary excellence, under average conditions as to equipment 
and teaching. He feels, with some reason, that all this should count 
for a great deal, and no argument will wholly displace this notion. He 
works without interest, and generally badly, and is a heavy load to carry. 
You ask, Why not transfer him to the work of the higher years? We 
reply, Because experience has shown that he probably lacks adequate 
preparation for it, and will fail in it. The only practicable alternative 
lies in so arranging his laboratory practise that he shall have as large a 

116 



measure of new work assigned him as it is possible to oversee without 
disproportionate attention on the part of the instructors. 

Student D. A student of moderate ability from an average school 
with a year of experience. His credentials are clear, but he has perhaps 
had little personal instruction and his knowledge is ill-arranged and 
vague, as to both fact and principle. He has no confidence in himself, 
and there is very little which is final in his preparatory work. His is 
one of the most difficult cases to provide for at the start, but often turns 
out well in the end. 

Student E. A student who has spent a year, or more rarely two years, 
under inadequate instruction, which has been worse than useless. An 
entrance examination may exclude him, but under other systems he be- 
comes a troublesome factor in the complex problem and it may require 
some weeks to discover or be sure of his trouble. His place is with those 
students who take up the study of chemistry as beginners and his exclu- 
sion from the more advanced class is logical ; but a transfer to elementary 
classes when these are provided is almost certain to breed discontent 
in the individual, and often disarranges other work of the term which, 
by that time, is well advanced. 

But the confusion of interest does not end here! The types just re- 
ferred to have been selected essentially along the lines of general efficiency 
of instruction and length of courses. It must further be recalled that 
even efficient teachers vary widely in their conceptions of the ground to 
be covered, and the college receives students who, during a single year 
of chemical instruction, have had the chief emphasis laid upon descrip- 
tive chemistry; others where it has been laid chiefly on "theoretical 
chemistry;" again others where the course is largely one of physics rather 
than chemistry; and, finally, where considerable qualitative analysis 
has been included even in this brief time. 

The conditions appear, then, to be these, briefly stated: Experience 
indicates that the pupils who have had even two years of instruction in 
secondary schools are, in general, not in a condition to take up work in 
chemistry which is more advanced than that of the first year in the col- 
lege, and for students who have had but a single year there is at present 
so little that can be regarded as common knowledge that the present 
apparent duplication of work seems unavoidable. Regarding this dupli- 
cation more will be said presently. 

Let us next face the question, Why is it that secondary-school courses 
have failed, and, as it seems to me, are likely to fail, to serve as substi- 
tutes for any considerable amount of college instruction in chemistry? 
The reasons are far from simple, and they need some analysis. We may 
distinguish, I think, at once between certain factors which, since they are 
inherent in the nature of our science or in the period in the pupil's life 
in which the instruction is given, are common to all schools, and those 
elements in the situation which are the outcome of varying fitness on the 
part of the instructors. 

Is it not true that chemistry itself presents some peculiar difficulties? 
It is often said that "physics is taught better in the secondary schools 
than chemistry." I am inclined to think that, as a general statement, 
it is essentially true. But might not the full truth be better stated in 
this form: "Physics is more effectively taught than chemistry in the 
secondary schools because physics is an easier science to teach?" It 

117 



is true that chemical phenomena are plentifully at hand, and that our 
very life processes are dependent upon them; yet they are not recognized 
as such and are essentially unfamiliar. The teacher of chemical science, 
and the practitioner who seeks recognition for his achievements, are 
alike forced to realize that the tools which he employs, the working con- 
ditions which he establishes and the terms in which the results of his 
labors are to be expressed are unusual and strange and, because of this, 
more difficult of comprehension by his fellow-men. 

The beginner in chemistry is at a similar disadvantage as compared 
with the beginner in physics. In his work in physics the pupil handles, 
for example, the balance, the mirror, the pendulum or the battery, and 
he makes his measurements in units which are largely familiar to him; 
and the phenomena which he observes are not foreign to his daily life. 
On the other hand, the very test-tube and beaker to which the student 
of chemistry is immediately introduced are unaccustomed objects, the 
bottle of acid is still more so, and we often accentuate the situation by 
asking him to don breast-plate and armor for his personal protection, 
in the shape of aprons or rubber sleeves. While, on the other hand, the 
concepts and laws of physics may not be properly alluded to as "easy," 
yet it seems to me evident that they make less demands upon the intellect 
and the imagination than the fundamental principles of chemistry, if 
these principles are to mean more to the pupil than mere memorized 
statements. 

With the growth of the holes in the pupil's clothing the strangeness of 
the beaker, test-tube and acid bottle lessens, to be sure, but he is coinci- 
dently introduced to increasingly complicated phenomena; he is asked to 
conceive of molecules, atoms, ions, even of electrons; he is asked to form 
some notion of valence, to construct chemical equations, and to "state 
all that they express" a thing which you and I with our greater wis- 
dom and experience may well hesitate to attempt. He must master the 
principles of stoichiometry, that branch of chemical science which seems 
to baffle the human intellect to a degree that never ceases to amaze even 
experienced teachers. It may even happen that his course includes 
such concepts as those of chemical equilibrium, the mass law, or the phase 
rule which, in their relation to the proper subject matter of a secondary- 
school course, somehow remind one of the records of those early chemical 
processes found in the first chapter of Genesis in which it is quite inci- 
dentally stated that near the close of the fourth day the Lord created 
"the stars also." It is easier to forgive the ancient recorder for his lack 
of a due sense of proportion than to excuse the twentieth-century instruc- 
tor. 

Keeping in mind, then, the newness of the chemical processes and chem- 
ical concepts, and the fact that the latter necessarily make considerable 
demands upon immature imaginations, may we not fairly ask whether it 
is actually reasonable to expect that a young boy or girl of fifteen to seven- 
teen will gain a really clear insight into chemical science in one year; 
such an insight as will serve as a safe foundation for a chemical super- 
structure without further strengthening through review? I think I can 
hear teachers answering warmly in the affirmative. But, again, do they 
not have in mind the exceptional rather than the average pupil? It 
seems to me that experience indicates that the most that it is wise to at- 
tempt in the case of the large majority of pupils of the ages named is to 

118 



broaden their horizon by teaching them to interpret common phenomena 
in the terms of chemistry, and with the aid of only the simplest funda- 
mental principles to help in the understanding of those terms, leaving 
the meaning of the more abstract conceptions to be learned in a college 
course, or by later and more mature reading if the pupil is not destined 
for college, but has an inquiring mind. I believe that the disparity be- 
tween the immaturity of mind of the pupil and the demands of the sub- 
ject matter assumed to be taught has been far too much ignored. I 
think this is the more true in these days when it seems evident that our edu- 
cational system, through its multiplicity of subjects and the over-promi- 
nence of the baneful influence of the examination paper, tends to remove 
nearly all opportunity for concentrated or independent thought on the 
part of the pupil, or of originality in methods of instruction on the part 
ofthe teacher. 

I believe, then, that even the competent teacher, with adequate equip- 
ment and the usual time allotment must find great difficulty in teaching 
chemistry to even the more receptive pupils at the secondary-school age 
so thoroughly as to permit the college to substitute it for any considerable 
part of the college course, at least under present conditions. For, let it 
be said with all humility, we college teachers too often made a sad mess of 
it even with the advantages as to maturity and environment, which we 
presumably possess. 

The statement is sometimes made by college teachers that they would 
prefer to receive students without previous chemical experience, and the 
question may be raised whether or not it would be better to abandon 
entrance requirements in chemistry. I believe it is the opinion of the 
majority of college teachers, especially of those who have given the prob- 
lem the most careful thought, that this would be very unfortunate. I 
should consider it so far at least two important reasons: first, because, 
while formal excuse from a definite portion of the college work is not yet 
generally practicable, the experience already acquired by the student 
can be made very helpful if judiciously utilized, and second, because it 
is mainly through increased cooperation between the schools and the 
colleges in an effort to secure better working conditions for the teacher, 
and the adoption of a rational course of instruction in the secondary 
schools, which will take into account all of the pupils, rather than those 
alone who propose to enter college, that we may hope to attain better 
results. 

It is noticeable in the statements quoted above regarding the present 
practise in the various institutions, that the state colleges are apparently 
giving a greater amount of definite credit for work in the secondary 
school than the others. This is frankly stated by some of the college 
teachers to be due to the closer organic connection of the state university 
with the general school system, and is admittedly done under slight 
pressure. On the other hand, these institutions have, through the system 
of school inspection on the part of the state universities, a more direct 
means of influencing instruction in the preparatory schools. The outlook 
for better conditions in the future is generally regarded as favorable. 

Perhaps we may ask just here, What would these better conditions be 
like? It is probably fair to say that they would be such as to avoid 
duplication of work. Obviously repetition and duplication should be 
reduced to a minimum, and no one would welcome changes which tend 

119 



8 

to bring this about more than I. But I think it is possibly true that 
there is less actual duplication of work than is commonly supposed in 
those institutions in which the students who have had a year or more of 
chemical instruction are segregated in separate divisions. Let us take 
a concrete case by way of illustration. The pupil in the secondary school 
prepares chlorine, using salt, sulphuric acid and manganese dioxide, or 
hydrochloric acid and manganese dioxide. The time available rarely 
permits the use of any other method, and the chemical changes involved 
are sufficiently complex to present some little difficulty for their complete 
comprehension. Few pupils, as experience shows, really understand 
that this is a typical, and not an isolated or unique procedure, and the 
rdle played by the manganese dioxide is but vaguely grasped. It is 
true that such students are asked to again prepare chlorine from these 
materials in the college laboratory, but they are at the same time required 
to study the action upon hydrochloric acid of such agents as lead dioxide, 
barium dioxide, hydrogen dioxide, potassium permanganate or potassium 
dichromate, and to discuss the changes involved from the common point 
of view of the oxidation of the acid, and the proportion of actual duplica- 
tion of work is really small. Similarly, in the study of the action of acids 
upon metals, while it is desirable to ask the student for the sake of com- 
pleteness to repeat the familiar process for the preparation of hydrogen 
from zinc and sulphuric acid, this becomes a mere incident in the series 
of experiments and in the broader discussion of all phenomena observed 
which may well go so far as to include the principles of solution tension, 
in the case of such students. 

It is, apparently, work of this general character which many college 
teachers are offering to those who have had earlier chemical training. 
The laboratory work is, as we have seen, frequently accompanied by 
lecture demonstration and recitations of a corresponding grade, and while 
it does not, of course, appeal to the student as a step in advance, as would 
some other procedure which seemed to give a stamp of finality to his 
earlier studies, it may well be questioned whether it does not better foster 
his intellectual welfare than the more alluring plan could do. It should, 
however, be the purpose of the college teacher to keep closely in touch 
with the actual and probably increasing average attainments of the pupils 
sent to him, in order that he may take all proper advantage of the instruc- 
tion already given, and it is probably true that a larger number of insti- 
tutions should offer such moderately advanced courses than is at present 
the case. 

I propose next to refer briefly to one or two specific points at which it 
appears to me that the instruction in the secondary schools might be 
improved. I do this with much hesitation, for I realize that those very 
details or methods which perhaps fail to appeal to me may well be very 
dear to another, and I realize that I should be loath indeed to have the 
actual efficiency of my own instruction judged by certain alleged quota- 
tions on the part of some of my students, or even by the subsequent acts 
of many of them. A conspicuous instance of the failure of some of our 
hopes was afforded by a statement made by one of our students in a recent 
written test that "nitroglycerine is used as a lubricant." 

A question which many find difficult to answer is this: How far, 
taking into account existing and not idealized conditions, is it just to re- 
gard note-books as an index of the efficiency of the instruction as given 

120 



in a particular school, or college? I shall not be rash enough to under- 
take to answer this beyond expressing a conviction that while a note- 
book which is well kept and carefully corrected probably indicates care- 
ful, efficient teaching, a relatively poor note-book may represent more 
accurately an overburdened condition of the teacher, which prevents 
adequate inspection and correction, than actual inefficiency in instruc- 
tion. For it is often true that much of apparent error in the records 
may have been actually corrected in conference or class-room. This 
does not, however, apply to some of the atrociously bad specimens 
which are occasionally met with, nor, on the other hand, does it ignore 
those note-books which are obviously not records of work done, but stud- 
iedly prepared exhibits, executed through connivance of teacher and 
pupil at the expense of a fundamental principle of all scientific work, 
rigid honesty. 

Is it not true that too many teachers are contented to have their stu- 
dents perform more or less perfunctorily the magic "forty experiments" 
which are said by some one else to represent a suitable course, rather than 
to vitalize their instruction by devising ten, twenty-five, fifty-five or 
any other number of experiments of their own to illustrate the facts or 
principles which they themselves desire to fix in the pupils' minds, and 
to see that these are actually discerned. The busy, often overburdened 
teacher, will not always find time or energy to devise an entire course 
of instruction, but the introduction of even a limited amount of well- 
considered experiments or class-room instruction which represents the 
personal equation of the individual teacher does much to maintain en- 
thusiasm for the teaching which is often reflected in the work of the pupils 
as well. 

The deadening tendency of a mere following of a course of experiments 
laid down by others shows itself also in a disposition to regard each ex- 
periment as a thing apart, the nominal completion of which is a cause 
mainly for relief, is also reflected in many instances in the notes sub- 
mitted, which are long and minutely descriptive of really insignificant 
details, but miss the real point of the experiment. This, in turn, comes 
from the fact that the pupil is not sufficiently informed why he is asked 
to perform the experiment at all, and in the strangeness of the work he 
naturally confuses the important and the unimportant. For example, 
he is often apparently left to think that a description of "the apparatus 
used" is as essential when he pours silver nitrate solution from a bottle 
into a test-tube containing a halide solution, as when he is preparing 
nitric acid from saltpeter, and he elaborates his descriptions with the same 
fidelity in the former ease as in the latter, with a very considerable aggregate 
loss of good energy on his part and that of his instructor. But that is 
not the worst of it, for he gains an idea that all experiments are to be 
treated with similar uniformity in other respects, even including his 
search for their hidden meanings. I do not, of course, advocate telling 
the student what is to happen and then asking him to say that it did oc- 
cur, adding, possibly, the color of a precipitate; but I do believe that a 
great deal would be gained if nearly all experiments, or groups of experi- 
ments, were more carefully prefaced in the laboratory directions by a 
brief statement regarding the principles or the types of changes involved, 
and if, then, the student were encouraged to make his observations with 
reference to these statements and were required to show that he under- 

121 



IO 

stands how the given experiment actually confirms the points in ques- 
tion. This would do much to avoid what is at present a wasteful expendi- 
ture of time, muscular energy and eyesight all of which could be used 
to increase the pupil's experience, and it would partially, at least, elim- 
inate the vague groping which results as those appalling scientific mon- 
strosities which follow the words "I conclude" in the note-book of many 
a conscientious student. Have you ever recalled the bewilderment of 
your student days, when you had no idea what to look at among so many 
phenomena? Have you ever taken a half dozen experiments and can- 
didly asked yourself what you can legitimately conclude from what has 
been performed? It is very much like trying to answer some of one's 
own well-sounding examination questions: a procedure which often causes 
them to lose their attractiveness. 

Do we not then, tend to lay too much stress upon mere performance 
of experiments, and devote too much time to the making and reading 
of descriptive notes which are often copies of the experiment manual, 
and too little time to helping the pupil, through judicious suggestions 
regarding the experiments and through questioning at the work-table 
and in the recitation room, to comprehend what it is all about, and the 
relation of a given experiment to others already performed? 

In order that the perplexities of the college instructor may be brought 
more clearly to mind, and in order to illustrate certain types of note- 
books, I reproduce here a few pages from the books presented in connec- 
tion with the entrance elective requirement of the Massachusetts Insti- 
tute of Technology. The first (Fig. i) is a representative of a rather small 
number of superior books. The observations are carefully recorded, the 
deductions are valid and well expressed and there is evidence (not shown 
in the cut) that the note-book had been inspected and corrected. Un- 
der existing conditions as to numbers of pupils to be taught it is probably 
too much to expect that all will attain a standard which this note-book 
appears to represent. To all appearances the records are original and 
the instruction efficient. 

The pages reproduced in Figs. 2 and 3 are of a not uncommon type. 
The first leaves one in doubt as to what part of the work has been per- 
formed by the pupil, since the statements made regarding the physical 
properties could have been copied from a book, the records of experi- 
ments performed are distinctly wrong and, in the case of the alleged 
preparation of chlorine, would, if ever followed, lead more directly to a 
residence at a hospital than to any worthy scientific end. Fig. 3 shows 
a page which makes no pretense of being anything more than a mere 
record of a useless mixing of a few solutions, and moreover these records 
are also entirely wrong. 

The two pages just commented upon did not bear any evidence of in- 
spection on the part of the teacher ; that shown in Fig. 4 bore the stamped 
legend "approved," but a careful inspection leaves one in doubt as to 
what particular feature of the record warranted this, unless it may be 
the evidence of sympathy (?) on the part of the pupil with the tendency 
towards spelling reform. 

These are not exceptional pages; they are representatives of many 
that pass under our inspection each year, and I ask you, with all sym- 
pathy for the teachers concerned, what evidence does any but the first 
give that one may safely omit a review of the ground supposed to be 

122 




Fig. 1. 




Fig. 2. 




Fig. 3. 




Fig. 4. 



II 

covered by this work in a college course which is primarily expected to 
furnish a safe foundation on which there is afterwards to be erected a 
very considerable superstructure of chemical knowledge? Are we not 
justified in our perplexities? 

I should like also to appeal to the teachers in the preparatory schools 
to encourage the pupils to better economize their laboratory time. Too 
many are allowed to placidly watch a crucible heat, or a solution boil, 
when other experiments might be in progress at the same time, and these 
habits are difficult to overcome. I should like to suggest, too, that some 
of the most promising pupils are often seriously harmed by allowing them 
to work too much by themselves, or by encouraging them to go beyond 
their depth in a particular line in which they appear to be specially in- 
terested, to the detriment of their fundamental work. Some pupils 
usually come to college with an exaggerated sense of their own attain- 
ments and it frequently requires long and tactful persuasion on the part 
of the college instructor before they can be reduced to reasonable humility. 

On the other hand, I venture to plead that all proper encouragement 
be given to pupils to take advantage of such special privileges as the col- 
leges offer. It is not an infrequent occurrence to find a pupil who tells 
us that he has been advised by his teacher to take the elementary course 
for beginners as one in which he will incur less risk of failure. Were 
the examination the goal of the course, there obviously would be little 
to criticize in this suggestion; its effect upon the student as an embryo 
scientist is seldom happy. 

In conclusion let us ask, how can we make the work in chemistry in 
the various institutions more mutually helpful? 

1. By a more extensive cooperation on the part of the colleges and 
technical schools in the way of separate courses for those who have taken 
chemistry before entrance, a closer study of the problem on the part of 
all, and a readiness to recognize improved conditions. 

2. By an intelligent delimitation of the secondary-school course, so 
that it will only offer what the pupil can best assimilate at the age and in 
the environment in which he works. This is too large a topic for dis- 
cussion in this connection, and it is sadly complicated by the necessity 
for furnishing a course which shall be alike useful for the pupil who ex- 
pects to enjoy college opportunities and his less fortunate associate. I 
plead, as I have often done, for a course which is fundamentally descrip- 
tive in its character. I do not mean a mere catalogue of facts, but a course 
in which selected facts are taught for some specific reason, which is in- 
variably explained to the pupil, and in which these facts are interpreted 
for him in terms of the simplest of the fundamental principles and con- 
cepts, so often repeated and constantly utilized that they may ultimately 
mean more than memorized paragraphs from what he may later remem- 
ber only as "a book with a green cover." I think there can be no greater 
mistake than to suppose that such a course is a less worthy one than such 
as is often pointed to with pride as a "theoretical course," and no teacher 
should consider that it will demand less than his best efforts, supplemented 
by all his knowledge, to utilize the opportunities for helpful and thorough 
instruction which such a course affords. It is, of course, difficult to de- 
termine whether or by how much the instruction of the boy or girl destined 
for college should be differentiated from that of their fellow-students, 
but I venture to hope that a decision may yet be reached, through coflpera- 

123 



12 



tion, which may permit us to select a limited field which shall be so well 
covered as not to necessitate repetition in college, and that this may be 
done without prejudice to the candidate or non-candidate for college 
credits. How soon this will come, or how large this field may be, I do 
not venture to predict. 

3. By increasing the time allotted to chemistry in the secondary schools 
until it is more nearly commensurate with the dignity and difficulty of 
the subject. Whether such increase should amount to one third, or 
some larger fraction of the present time allotment is a point which those 
actively concerned in the teaching can best determine. The increase in 
time should be asked for mainly in the interests of those who will not pur- 
sue the study of chemistry further, but it will also presumably hasten 
the time when a definite point of articulation with the college work, as 
just suggested, can be fixed. 

Finally, there is the urgent need of decreasing the demands made upon 
the teacher of chemistry in the secondary school for duties other than 
those of chemical instruction, and also a critical need for relatively more 
instructors. I believe that a very large proportion of the unsatisfactory 
results now noticeable are due to the fact that in most of our schools it is 
not humanly possible for the teaching force to accomplish what should be 
expected of them, or to be at the desk of the pupil when he reasonably 
needs assistance. In some schools which have come under my observa- 
tion the distribution of supplies must be attended to by the senior (or 
often the only) instructor, an operation which consumes a half hour or 
more. 

Probably no science demands for its understanding by the beginner 
more individual instruction in laboratory and class-room than chemistry, 
and the school authorities should realize this. When they do we shall 
have much cause for rejoicing, and much of the present groping and be- 
wilderment on the part of the young student will give place to enjoyment 
in the study of a science which is really second to none in its attractive- 
ness or value when pursued under favorable conditions. 

It is a pleasure, in closing, to say that I feel that too much praise can 
hardly be given to the loyal, hard-working, intelligent and inspiring 
teachers who are accomplishing so much in behalf of our science in the 
training of the beginners. No thoughtful college teacher can fail to 
recognize the good work done in very many schools throughout the coun- 
try, and while many feel that more definite recognition in the college 
curriculum can not wisely be given to this work at the present time, I 
am sure from the messages which have recently come to me from many 
colleagues in many institutions that there is an increasing appreciation 
of the fact that the way to better things lies through a sympathetic ap- 
preciation and study of our common problem and our common difficul- 
ties. 1 

1 In a discussion which followed the presentation of this and other papers on 
educational topics, a statement was made by a secondary school teacher of recognized 
standing to the effect that many such teachers had become indifferent to the opinions 
of college instructors, since it is "impossible to satisfy them any way." While I 
heartily sympathize with the thoughtful teacher who desires to teach his subject in 
his own way and with his own ideals in view, and deplore any attitude of the colleges, 
collectively or individually, which tends to interfere with this, it seems to me that the 
common cause of greater total efficiency in instruction can hardly be served by ignoring 

124 



13 
i 

If there can be a determination, on the one hand, to undertake only 
so much as can be well taught and to give the largest practicable vitality 
to the instruction, and, on the other hand, a disposition to promptly 
recognize and utilize every bit of ground gained which offers a secure 
foundation for later work, a more satisfactory situation than that which 
exists at present can hardly fail to result, even though the degree of 
recognition of secondary school instruction may fall short of that which 
some desire. H. P. TALBOT. 

MASSACHUSETTS INSTITUTE 
OF TECHNOLOGY. 



HIGH SCHOOL CHEMISTRY: THE CONTENT OF THE COURSE. 1 

Every teacher in the high school of to-day finds himself in stimulating 
circumstances. He is obliged to question himself closely as to the part 
that his subject plays in the curriculum, for, at least in the large cities, 
the long-discussed change in the character of the high school is upon us. 
The reason for the change is found in a realization of the facts that in the 
past, high school education has been enormously wasteful; that eighty 
to ninety per cent, of our pupils do not complete the course; that only a 
small part of the remaining per cent, achieve the purpose for 
which the whole course has been framed, that of entering college. 
The evidence that the change has actually begun is found in the estab- 
lishment of trade and vocational schools, in the frequent discussion of 
questions pertinent to these points, and in the statements of principals 
and superintendents that something must be done to stop the enormous 
educational waste; and in their declaration that the high school must 
meet real needs, must give the boy or girl the education that is best for 
him or her, as a member of the human group, with little reference to col- 
lege entrance. 

Among the changes that are coming from a recognition of these facts, 
we find the importance of science in the high school largely increased. 
The fact that it is science that has produced the great material advance 
of the past century makes it certain that in the further turning from formal 
to practical education, science will play a larger part. It is the purpose 
of this paper to inquire into the manner in which these changing condi- 
tions are reacting on the high school course in chemistry, and to discuss 
some of the considerations that are determining, or should determine, 
a new course of study. The speaker wishes also to discuss, in general, 
the problem of high school chemistry, presenting personal and perhaps 
even extreme points of view. 

We may classify the various forces that are shaping the new course as 
external and internal. In the first class we find: (a) a lessening of the 
college influence, due to a realization of the necessity of educating for 
other purposes than college entrance; (6) a tendency to put chemistry 

the opinions of the colleges, even if they are mistaken. May it not be true that the 
secondary school teachers lack some courage, or at least some persistence, in forcing 
their convictions upon the college teacher? They have the privilege of speaking from 
a fullness of experience with the young pupil which the college instructor usually lacks. 
1 Presented at the second decennial celebration of Clark University, Worcester, 
Mass., September 16, 1909. 

125 



14 

earlier in the course and to give a second year of it; (c) what we may call 
the lay demand for practical education. 

The lessened college influence will give to the body of secondary teach- 
ers not only greater freedom in the selection and arrangement of their 
material, but what is of even more importance, because it serves as a 
stimulus to their creative ability, a realization of the importance of their 
own great work and their responsibility for it. The lack of this kind of 
freedom is in part responsible for the condition that exists to-day when 
the high school, paying comparatively high salaries, can not get enough 
good men, while the college apparently has more than it needs at a smaller 
compensation. This is not the least of the evils that have resulted from 
the college domination of the high school. Others have often been 
pointed out and are well known. The course of study can never be adapted 
to the real needs of the high school so long as it is framed by the college, 
at the best a force operating at a distance, at the worst a power acting 
for needs it cannot know. The college, as far as the high school was con- 
cerned, always had the idea of preparation, not growth, in mind. A 
thousand boys went through a course in chemistry whose nature was 
determined solely by the needs of the three or four who were to be trained 
to be expert chemists. It is often said at this point that the course which 
best prepares the pupil for advanced work is also best for every other 
boy. It is nearer the truth to say that the education which best meets 
the needs of the growing member of the human whole ought to be the 
best preparation for college. 

Chemistry earlier in the course and perhaps a second year of it; the first 
of these conditions may bring dismay to many teachers; the second, 
delight to all, surely. Certainly some changes in the traditional course 
are necessary in teaching chemistry in the second year. On this point 
the speaker can refer to an experience covering nearly seven years. During 
all that time chemistry has been taught to some second-year students. 
At times fourth-year students and second-year students have been taking 
nearly the same course simultaneously in separate classes; at other times 
the two terms of students have been mixed in the same class. In both 
cases a certain degree of success with the second-year students has been 
obtained, even if we judge by no other standards than results of college 
entrance and state board examinations. Speaking for the moment from 
the standpoint of the college entrance syllabus, but little change is neces- 
sary to adapt the chemistry to second-year students. A less rigorous 
insistence on the philosophical development of the atomic and other 
hypothesis seems to be the most necessary item of change. In any case, 
as far as the ability of the student to comprehend is concerned, the differ- 
ence between individuals is much greater than the difference between 
second- and fourth-year classes. The general average of work is consid- 
erably better in fourth-year classes, but this is explained largely by the 
dropping out of weak material. 

To meet the demand for practical education, we find that there is a 
decided tendency to introduce into the high school a great deal more of 
chemical technology than there was in the older course. There are some 
who go so far as to say that the high school ought to give the pupil a means 
of earning his living; that chemistry should be taught so as to fit him for 
some direct employment in practical occupations. While admitting 
this as a possible ideal, the view implies such an extreme change in the 

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15 

character of the high school that it is not advisable to take it into con- 
sideration in the present discussion, except to admit that, given time, it 
would be possible to accomplish this result. Along with the demand 
for technical education, we find a tendency to fill the course with a great 
deal of matter that is associated with the home and every-day life. These 
two demands have come largely from without. They have done great 
good and have added much to the human interest of our science. We 
teachers are very prone to an academic point of view, and the stimulus 
has been a needed one. Yet with the good, there is some danger. There 
is a tendency in some quarters to emphasize the technological details 
of processes, to fill the discussion with technical terms, so that the pupils' 
talk bristles with tuyeres and downcomers and the particular names of 
the many towers that find application in manufacturing chemistry. 
The chief evil of this kind of instruction is that it produces rather showy 
results, it seems to indicate more knowledge than really exists. More- 
over, a technical process of to-day is a very complicated thing. It is 
improved every year and we find to our discomfiture, on visiting the 
factory, that the process we have so carefully learned from the text- 
book differs in a hundred details from that actually employed. 

The chemical interpretation of the ordinary phenomena of the house- 
hold is a very interesting matter. Unfortunately many of these inter- 
pretations are very complex, others are unknown. Some are simple 
enough to be comprehended by a beginner, and certain food tests and 
the like can be taught so that the pupil can go through them in a more 
or less mechanical fashion. But surely these do not constitute a suita- 
ble vehicle for the transmission of that highly organized mass of knowl- 
edge and way of thinking which we know as chemistry. The intellec- 
tual and material advance that our science has brought to the world has 
not come from the knowledge of isolated test-tube reactions, but from 
the brilliant imaginings of the authors of its great hypotheses, from the 
realizations of its tremendous generalizations, from the perceptions of 
most deeply hidden relationships among the things that we call matter. 
If this that we teach our pupils is to bear the name of chemistry, it must 
give them at least a glimpse of these deeper things. Technological chem- 
istry and household chemistry have a very proper place in the high school 
course, but they should never be over-emphasized. They afford the 
illustrative material which the good teacher will constantly use to give 
interest to his work by showing what good the science has brought to 
mankind. But a course composed almost wholly of such material, as 
has been proposed, would not be chemistry, and it would probably not 
be science. There would be an absence of principles of relationships. 
A pupil might indeed learn that there exists a simple process for the 
manufacture of soda, but he would not share in any degree the kind of 
thinking that has made this and a thousand other processes possible. 
I hold that it is our chief duty to give him this kind of knowledge. 

Coming then to the internal considerations which shall help shape our 
new course of study, we must inquire what high school chemistry should 
seek to accomplish for the pupil. One way of answering this question is 
by asking ourselves what it has done for us as individuals. We know 
that it has made us broader men and freer human beings, and it is fitting 
that we should seek to have our pupils attain in some degree this high 
end. Again, it is certain that one who has been through a good course 

127 



i6 

in chemistry, who has learned the principles of chemical action, and com- 
prehended the great laws that the science has revealed, looks upon the 
world about him in an altogether new way, so much so that with the 
increase in the general knowledge of science there is being produced a 
new type of world mind. Our pupils must be taught so that they shall 
share in this new world mind. 

THE LABORATORY ASPECT OF THE COURSE. 

The course will continue to be based on experiment, the amount of 
laboratory work being limited only by the physical possibilities of the 
situation. The experiment will precede the class discussion in order 
that the pupil may conceive the things that he is talking about as reali- 
ties. Chemical thinking cannot go far without these definite concep- 
tions. It requires images of real things, and it is this point of view that 
should determine the character of our laboratory work. There seems 
to be considerable difference of opinion, if not confusion, on this point. 

There is the point of view which assumes that it is the purpose of the 
experiment to prove the statement of the teacher or the text. Because 
there was so much that was bad in reliance upon authority in older types 
of education, it is felt that science must have none of this, but must ac- 
company everything by rigorous proof. Following this method at its 
worst, the pupil is stimulated into a condition of perpetual doubt. He 
meets every statement with a but, and has rather the air of believing 
that some scientific charlatanry is being imposed on him. This is wrong; 
science does not have this attitude of perpetual doubt. It requires the 
most rigorous proof from discoverers of new things, but if each of us 
had demanded ocular demonstration at each step in our advancing knowl- 
edge, we should probably still be somewhere in the realm of descriptive 
inorganic chemistry. Moreover, it is a serious scientific mistake to let 
the pupil think that a single experiment performed under the ordinary 
condition of the beginner's laboratory proves much of anything. If it 
does, the speaker has seen many curious things proved in his time. Let 
us be frank: these experiments show at best the line of thought by which 
the proof is obtained. They illustrate the proof they do not give it. 

Nor does the theory that the pupil should, in the laboratory, rediscover 
the fundamental truths of the science, give us a right basis for experi- 
mental work. Followed to the extreme, this method soon reduces itself 
to an absurdity. Take, for example, the experiments of Lavoisier, which 
afford such an excellent starting point in the teaching of the subject. 
The pupil is given some metals and a balance, and is supposed, in an hour 
and a half, to rediscover what it took the best minds the world then pos- 
sessed several centuries to accomplish. The fact the pupil's laboratory 
record, duly attested by the teacher, indicates that he independently 
accomplished this prodigious feat is a comment on the system. All that 
is done in this method at its best, is the arousing of the pupil's curiosity, 
which is later gratified by judicious^ suggestions at the proper moment 
from the teacher. There is no rediscovery; the line of thought has sim- 
ply been retraced, and the big steps have ever been taken by the teacher. 
To be a discoverer you must be the author of your own curiosity. An- 
other trouble with this method is that once committed to it the teacher 
is driven to curious round-about expedients to prevent the pupil's hav- 
ing knowledge in advance of the thing he is going to see. l A here are 

128 



17 

hundreds of instances where the pupil should have this knowedge in ad- 
vance. 

The speaker is more and more convinced that while the laboratory 
should to a certain extent seek to accomplish the things which the hold- 
ers of two points of view consider desirable, its real purpose is to afford 
illustrative material, and by illustrative material he means that which 
will give concrete ideas images of things and processes. One might 
read hundreds of pages about chlorine, but if he had never seen it he 
would never know it. This is the great work of the laboratory method, 
to teach things and not literal symbols for them. We should seek this 
end, and let other considerations give way to it. 

And we shall not neglect to exercise the pupil's scientific imagination. 
Chemical thinking requires this faculty. After he has been well grounded 
in the method of the laboratory, we shall want the pupil to learn to fore- 
see chemical possibilities. The progress of the science has been by the 
working together of experiment and imagination, the one reacting upon 
the other and each suggesting in turn new steps in the advancing knowl- 
edge. 

THE CLASS-ROOM ASPECT OF THE COURSE. 

It is no longer being framed exclusively for the college entrance re- 
quirement; our course will not require us to cover so much material as 
it did formerly. Discussion of the rare elements and their compounds 
will give way to a more intensive study of those that show typical chem- 
ical actions, and establish the main lines of thought. We shall prefer to 
do this by reference to the things of the practical life where we can, but 
we will not go into the chemistry of foods, dyes, textiles and the like, 
knowing that this matter is far too complex for us to use in establishing 
the laws and relationships that are necessary for a comprehension of the 
science. We shall draw from every aspect of chemistry in our effort 
to establish the principles of chemical action. Our teaching may grow 
less descriptive and more dynamic. We may find it better to study 
types of chemical action than to study elements and compounds. As 
suggestion along this line, we might proceed, after reaching the defini- 
tions of chemical action, element and compound, to the general study of 
simple decompositions, using many experimental illustrations. We would 
bring in the ideas of stability and heat of formation. We would then 
proceed to direct combinations, simple replacements, and so on, until 
finally the pupil would have a very good idea of the comparatively few 
types of chemical action. He would acquire incidentally a very prac- 
tical descriptive knowledge. 

Our course will necessarily continue to pay a large amount of atten- 
tion to chemical theories, in order that we may have the means of seeing 
analogies and interpreting results. The mechanism of chemical changes 
is so far removed from direct observation by the senses that any attempt 
to comprehend these must be largely by aid of the imagination. The 
atomic theory has given us a splendid instrument for this purpose. We 
should retain it even if it had done nothing more than give us a system of 
chemical formulas, or made it possible to represent chemical actions by 
equations. Only one who has attempted to teach chemistry without the 
use of these symbols can fully appreciate what a tremendous aid they 
are. We shall therefore want to establish the atomic theory rationally, 
and to show how formulas are determined. This is perhaps the most 

129 



i8 

difficult part of our work, but the fact that many pupils fail utterly to 
comprehend this matter is no ground for its omission from the course. 
There are many who succeed, and we must not forget that those who fail 
at least learn that such knowledge was acquired by human reasoning 
and patient experimenting. We should make our pupils feel that these 
theories are very practical things indeed, since it is largely by their aid 
that the science has advanced and brought material benefits to mankind. 

We have in the past been given to considerable drill in certain types of 
chemical problems, largely because of the demands of college entrance 
examinations. There has been a good deal of mental gymnastics in the 
matter. These calculations should be taught in a less formal way; the 
laboratory is the best place to do it. Let the pupil calculate from the 
equations the quantities of substances he needs for his reaction, and 
then actually mix them in these proportions. Let him get practise in 
correcting gas volumes in the course of experiments involving simple 
gas measurements. Knowledge acquired in this way has a far greater 
staying quality than that obtained in formal class-room drill. 

As we have already said, chemical technology will find a place in the 
course, but it must be taught by principle too. In the Solvay process, 
for example, it is more important that the pupil should get the idea of 
precipitation by differences in solubility than that he should know the 
mechanical details of the carbonating towers. It is more important 
he should know that the process is only commercially profitable because 
the ammonia is recovered, thus getting hold of the principle of the utiliza- 
tion of by-products, than that he should know the factory terms for the 
machinery and operations. A good course in manufacturing equip- 
ment, in which different types of furnaces, towers and the like were 
grouped and compared, might be of great practical and educational im- 
portance. But isolated bits of such information have no such value. 

Our high school chemistry might well include a treatment of more 
organic compounds than it has in the past. This knowledge can readily 
be acquired by reference to inorganic types. So many of the simpler 
derivatives of the hydrocarbons are things of every-day life that in order 
to include them we can afford to sacrifice some of the things of the tra- 
ditional elementary course. The pupil needs, moreover, some intima- 
tion of the character and extent of the organic branch of the science. 

In conclusion, the speaker feels that the best hope for the improvement 
of high school chemistry lies in discussions of the kind we are engaged in 
this morning. The experimental end of our work has been so new and 
interesting that much of our time has been spent on these matters. But 
the time is at hand when a reconsideration of the course as a whole in 
its general relations would be of benefit to the teaching of the elementary 
science. JESSE E. WmTsiT. 

DKWITT CLINTON HIGH SCHOOL, 
NEW YORK CITY. 



CHEMISTRY IN SECONDARY SCHOOLS. 1 

It is not necessary in a gathering such as this to recount the stages in 
the history of chemistry teaching in secondary schools how, from the 

1 Presented at the second decennial celebration of Clark University, Worcester, 
Mass., September 16, 1909. 

130 



19 

purely descriptive natural philosophy of the early college we finally as- 
sayed the teaching of chemistry and physics as sciences; how the mis- 
cellaneous encyclopedic instruction has been replaced by courses, de- 
signed, in these latter days, to develop power for the pupil rather than 
to impart knowledge. 

The changes in content and method of formal secondary-school instruc- 
tion have been brought about by the colleges; by advice, by supplying 
the teachers and most drastically, by the requirements for admission. 
While the bulk of the class might pass from the school and not be heard 
from again, the failure of a pupil to pass the college examination is quickly 
brought home to the teacher, so that the entrance examinations have 
become the standard of the school. 

During the last fifteen years four syllabuses have been published which 
have decidedly affected the teaching of chemistry in schools; in 1894 
that of the Committee of Ten, descriptive and general; in 1898 a Harvard 
syllabus, largely quantitative and scientific in method; in 1900, the 
syllabus of the College Entrance Examination Board, a plan for a course 
I hesitate to classify; in 1905, the last revision of the syllabus of the New 
York Department of Education, a historico-systematic course. 

There is almost nothing in common to these four courses, and although 
the College Entrance Examination Board maintains and strengthens its 
hold upon the schools it has never, fortunately for the pupils, conducted 
its chemistry examination in accordance with its syllabus. 

If we examine the texts to find what is being taught in high schools 
we find the chemistry text-books to be descriptive or theoretical; very few 
have successfully combined the two. The descriptive texts usually 
become encyclopedic, try to include all the elements, strange compounds, 
the latest processes and weird discoveries, often curtailing or entirely 
displacing those common things we are too liable to take for granted 
that every one knows. The theoretic texts are largely the product of 
college men. These tend to become too abstract and sacrifice the 
pupil to the subject. One elementary text of very wide use devotes 
two pages to a discussion of the action of bleaching powder, but does not 
state how it is used or for what goods. 

If a subject is to be treated as a science many facts must be given 
and understood in order that the pupil may acquire a comprehensive 
idea of the subject. It is folly to expect thorough understanding of a 
part without a general knowledge of the whole. The high schools can- 
not train chemists or engineers. Time and cost do not admit of such 
intensive science teaching, even if it is desirable. Such teaching should 
be left to the college. 

If we take the pupils as we find them in our large city high schools 
they are not well informed and have little opportunity to be. They 
live in a complex environment. The city boy or girl is brought in con- 
tact with but few simple phenomena; a push of a button a bell is rung; 
another push a door is unlocked; another push a light appears. The 
modern apartment is a complicated structure operated by buttons. 
If we look for chemical actions within this pupil's sphere we find 
them to be rather few, too familiar to hold the attention or too 
complicated to tempt analysis. He comes in contact with but few 
elements and but few pure compounds. Steel is to him a specially 
pure iron, zinc is the metal used in batteries, tin used for cans, 



20 

sulphur smells bad. He has often been told that soda water 
contains no soda. Soap is useful in cleaning, as it eats dirt as an acid 
"eats metal." A material involving electric means is necessarily superior. 
The tendency to centralization in driving our small industrial estab- 
lishments has narrowed the child's opportunities for observation. The 
shops of the blacksmith, carpenter and soap-maker where he learned the 
art of critical observation and learned some things not taught in school 
have been withdrawn behind doors marked "no admission." 

The classes of our large schools are mixed as to sex, race and ability. 
It is often said with pride that our urban population is cosmopolitan, 
but that the second generation from the emigrant is acquainted with 
American ways. Admitting that the second generation may be some- 
what acquainted with American ways, we must also admit that the 
population of our large cities is becoming mongrel. The mongrel is never 
stable and is rarely successful. The psychology of the mongrel is analogous 
to that of the mob. Is it not then asking too much that children of one 
or two generations from barbarity should be put through the same course 
and be expected to meet the same educational standards as the natives 
of Massachusetts? 

The tendency of education at present is the development of power, 
of ability to reason, to think. We may, indeed, ask if the drill along 
this line has not been pushed so far at times as to neglect giving some- 
thing to think about. The school, unlike the college, works by the clock, 
the work must be cut to fit the time, thus we often find a few facts or 
questions are presented in such a way that but one conclusion is possible. 
This is called inductive teaching teaching to reason. 

It makes the work easier for the teacher if the work can be made to 
follow a mathematical model, so problems come to take an important 
place. The work becomes quantitative and is now held to develop 
thought, originality and logical reasoning. But the problem in ele- 
mentary chemistry is usually of type form, and is not the teacher largely 
sponging on the power drilled into the pupil by the mathematics teacher? 
The English of the schools is criticized by college and business men alike. 
I believe a clear, concise exposition of phenomena in correct language 
will be of more benefit to the pupil than any number of problems in 
chemical arithmetic. 

The pupils I have in mind are the ordinary ones in large schools, thir- 
teen to sixteen years of age, girls and boys. Only a small percentage will 
go to college, some will go to business, some to be clerks, some home 
makers, some teachers. They have been herded in elementary schools 
taught at in bulk. They are deficient in English and any correct notions 
of the activities of the world. It is the business of the high school to 
supplement the elementary school and by its specialization correct the 
errors of the grades and systematize the instruction. College prepara- 
tion is only incidental. 

A large amount of knowledge is not needed in practical life so much 
as the power to do things, but knowledge certainly increases power. 
While we must be able to do one thing well even a superficial knowledge 
of many things is not to be despised. Good judgment, ability to arrive 
at accurate conclusions from given data is most essential, but if we look 
closely a large part of what is commonly called reasoning is but rehearsing 
of formulae. Good judgment cannot be taught. So few of our pupils 

132 



21 

will ever be so situated that they need reason independently concerning 
chemical phenomena that it is scarcely justifiable to foist the time and 
cost of such instruction on the public. 

Where and how can chemistry accomplish the most good in the school? 
If the object of education is to develop a youth most completely, to make 
a well-rounded individual, to make him feel an intelligent interest in the 
activities of the world, it is not necessary that each factor in such a total 
should be well rounded. A number of smooth, well-rounded sticks will 
make a very insecure bundle, but if some of the tricks are somewhat 
rough the bundle may not appear so elegant but it will be more firm. 
Chemistry touches every phase of human activity. It requires language 
for its expression, mathematics for its determination, physics for its 
operation. Its history is the history of the world. 

It would be impossible to find a better subject than chemistry to bind 
together the school work, to systematically furnish splinters to make 
the bundle strong. The domestic science teacher, the biology teacher 
and the physics teacher give some splinters of information which they 
call chemistry and build their work upon this basis, usually indigestible 
definitions. A systematic course in elementary science should be placed 
in the first year of the high school, designed to impart that information 
of things and processes we might well expect every one to know. This 
might be followed later by a course more thorough. 

We now expect our pupils to specialize as soon as they leave the ele- 
mentary schools and to prepare for some life work. He or she knows 
nothing of human activities out in the every-day world ; there is practic- 
ally no place in the school curriculum where this is taught. We have 
trade schools, vocation schools, commercial schools, not to mention 
others all of which require him to specialize before showing him any 
general plan from which to choose or guiding his choice. 

The pupil who will receive no further school instruction can in a year 
be given a good knowledge, by a teacher with adequate equipment, of 
many of the facts of elementary chemistry relating to our daily life and 
its activities a knowledge sufficient in most cases to excite a lasting 
interest in natural phenomena and to cause the student to seek explana- 
tion. There is a multitude of chemical facts which concern the boy 
who goes into the shop or office or behind the counter, and which he 
should know. The girl who will stop at home or teaches others' chil- 
dren is also concerned with chemical phenomena, chemical information 
which has been crowded out of her curriculum to make room for more 
cultured and less mussy subjects. 

Adhering to traditional procedure, our science courses have become 
pseudotheoretical or pseudotechnical ; it is time we had one systematically 
informational and practical. Facts are as important as explanations 
and should precede them. Such a course need not pretend complete- 
ness in any line. It might be comparative rather than critical. It would 
not attempt to rediscover or verify natural laws, but would aim to culti- 
vate the powers of observation and of accuracy of description, to express 
ideas of phenomena in simple, direct English rather than to hide incoherent 
thought behind a big name or a slang expression. 

In a first course in chemistry, atoms, molecules, ions and many other 
terms might be omitted altogether. They are but words, the modern 
idea of an atom is incomprehensible to one without a wide knowledge of 
chemistry. Theory should be eliminated as much as possible, making 

133 



22 

the course treat of facts, their sequence and relation to one another. 
Numerical problem solving should take but a small part in recitation 
work. No more can come out of an equation than we put into it. It 
cannot develop originality. 

Such a course for children of twelve to thirteen years would need sim- 
plicity in its treatment. Faraday's lectures to children are a model in 
this respect. Ostwald's "Conversations" show how some complicated 
things may be dealt with simply. 

I would have such a course give information concerning natural phe- 
nomena and the work of man, show what is being done, and how, with- 
out technical detail. 

I would give the pupil something to know. Facts that are worth know- 
ing in and of themselves facts that concern himself, his food, his cloth- 
ing, his shelter and his work. Concerning the things he or she will meet 
in life, no matter whether the future be as a chemist, a bookkeeper or in 
the kitchen. The material is ample. 

The subject might be systematized by its applications rather than 
the traditional order. Study topics rather than elements; study deter- 
gents, not soap; study bleaching rather than peroxide or bleaching pow- 
der. The development of the race through the stone, bronze and iron 
age has depended largely upon his chemical knowledge. Let us study 
the metals in their metallic aspects rather than according to the periodic 
table. 

Foods, clothing, materials of utility and convenience or of commerce 
often can not be rationally treated by the present systems of our texts, 
but a suitable systematization might easily include these ; what they are, 
how they are produced and what they do. 

In its effects upon the pupil and school, we may be sure that pupils 
who have seen something of the general trend of the instruction through 
a systematic preliminary course will feel more interest to continue study 
and will accomplish more and better work in later courses. 

MICHAEL D. SOHON. 

MORRIS HIGH SCHOOL, 
NEW YORK, N. Y. 



134 



RADIOACTIVITY. 1 

BY ANDRE DEBiERNE. 2 
Received July i, 1911. 

Radioactivity comprises to-day a very large number of facts and theo- 
ries of which it would not be possible to give a complete survey in a brief 
address. Nevertheless, I shall make an effort to bring out all the chief 
points of interest of the new science, the birth of which may be consid- 
ered without exaggeration as the most important scientific event of the 
past few years. 

Not only has this new science revealed the existence of extremely curious 
substances and brought a rich harvest of new natural phenomena, but 
it has led us to the attack of a problem which seemed absolutely chimer- 
ical only a few years ago the problem of the transmutation of atoms 
or of the chemical elements; for it is now demonstrated that the phe- 
nomena of radioactivity are concomitants of the disintegration of atoms. 
Radioactivity may now be defined as the science of atomic transforma- 
tions; it is not impossible that in time radioactivity may become the art 
of changing chemical elements into one another. The facts known at 
present leave no doubt as to the reality of atomic disintegrations; if as 
yet these transformations are entirely beyond our control, possibly some 
day we may learn how to bring them about and to control them. 

The fundamental phenomenon, which was discovered by Henri Bec- 
querel and has served as the point of departure for the development of 
radioactivity, is as follows: Certain substances emit spontaneously a 
peculiar radiation whose properties are analogous to those of the rays 
obtained in a Crookes tube. The new rays render gases conductors of 
electricity, act on a photographic plate, and produce fluorescence in certain 
substances. This spontaneous emission of rays was first observed in the 
case of uranium and its compounds, later also in the case of thorium com- 
pounds. Then were discovered new substances possessing the same 
property in a very high degree. All these substances are said to be 
radioactive. They constitute a new source of energy. 

An apparently essential characteristic of the phenomenon of radio- 

1 A summary presented at the Second Decennial Celebration of Clark University, 
Worcester, Mass., September 17, 1909. 

2 Translated from the French by M. A. Rosanoff. 

135 



1389 RADIOACTIVITY. 

activity is its spontaneity : the emission of rays takes place without visi- 
ble external cause. This characteristic permits of distinguishing the 
phenomena of radioactivity from those that take place in the course of 
certain chemical reactions. For instance, the oxidation of phosphorus 
is accompanied by phosphorescence and by electrical conductivity of the 
gases surrounding the phosphorus. The same phenomena may be brought 
about by the action of heat upon the sulfate of quinine. But in all such 
cases the phenomenon is not spontaneous ; it is brought about by external 
causes which are easy to detect. Therefore, phosphorus and quinine 
sulfate are not considered as radioactive substances. 

Another essential characteristic was brought out by the early researches 
of Madame Curie. Radioactivity is an atomic property. The spon- 
taneous emission of rays is connected with the radioactive atom, and is 
not in the slightest degree influenced either by changes of state of aggre- 
gation of by chemical combination with the atoms of other elements. 
Thus, the intensity of the Becquerel rays emitted by the substances con- 
taining uranium, and measured by the conductivity of the surrounding 
gases, is always proportional to the number of uranium atoms contained 
in the substance and is independent of the form in which uranium may 
be present. Among the numerous other properties of matter, mass alone 
is so distinctly atomic in its nature. 

Our realization of the atomic character of the radioactive property has 
had a directing influence on the science of radioactivity and has led to 
the establishment of its present theories. But first of all it had led to 
the discovery of radium itself and of the other strongly radioactive sub- 
stances. I shall review briefly the genesis of the discovery of radium, 
which forms one of the most beautiful investigations ever carried out 
in the physical sciences, both as regards the logical keenness with which 
the research was carried on and as regards the material difficulties which 
had to be overcome. The novel method employed has since been con- 
stantly used in researches in radioactivity. 

Among the elements that had previously been known, only uranium 
and thorium were radioactive, and the activity of any substance con- 
taining one of these elements was found to be proportional to the quan- 
tity of the active element present. Certain minerals, however, contain- 
ing uranium showed a greater activity than metallic uranium itself. 
Pierre Curie and Madame Curie, thoroughly convinced of the atomic 
nature of radioactivity, assumed that these minerals contained new 
chemical elements, endowed with greater activity than uranium, and al- 
though physicists by profession, and with only rudimentary laboratory 
means at their disposal, they undertook a search after the new hypo- 
thetical elements. 

I cannot depict here all the difficulties that presented themselves in the 
search, which involved the chemical treatment of tons of material. Suffice 
it to recall the results obtained by Pierre Curie and Madame Curie after 
several years of uninterrupted effort. Those results fulfilled their expec- 
tations entirely. The minerals studied do contain strongly radioactive 
compounds, whose radioactivity is due to the presence of new chemical 
elements. In the case of one of these elements, namely radium, it has 
been possible to prepare a series of pure salts; further, its spectrum has 
been studied, its atomic weight determined and a place has been 

136 



GENERAL, PHYSICAL AND INORGANIC. 1390 

assigned to it in the periodic classification of the elements. Radium has 
become a marvelous instrument of research, and to it we owe all the 
most important discoveries in radioactivity. 

It was soon recognized that radioactive substances may differ from 
one another, not only in intensity of radiation, but also in the character 
of radiation and in certain peculiarities in the mode of emission of the 
rays. On the basis of these properties it is as easy to recognize a given 
radioactive element with certainty as it is to recognize one of the older 
elements with the aid of spectrum analysis. 

The principal new radioactive substances are polonium and radium, 
discovered by Pierre Curie and Madame Curie; actinium, discovered by 
myself shortly afterwards; radio-thorium, discovered by Hahn; and 
ionium, discovered by Rutherford and Boltwood. However, certain 
of these substances are really complex mixtures containing entire fami- 
lies of chemical elements: namely, the thorium family, the radium family, 
and the actinium family. 

The rays emitted by radioactive substances may be subdivided into 
three groups, viz., the a rays, the /? rays, and the ? rays, which are analo- 
gous to the three groups of rays emitted in a Crookes tube, viz., canal 
rays, cathode rays, and Roentgen rays. The a rays are constituted by 
the projection of positively charged particles ; the ft rays by a projection 
of negatively charged particles; the f rays are not charged at all. 

The particles of /? rays are electrons, and the rays are easily bent out of 
their path by a magnetic field. Certain /? rays are constituted by elec- 
trons projected with an extremely great velocity, a velocity approach- 
ing that of light, and it has been possible to verify on these rays an im- 
portant deduction from the electron theory. For very great velocities, 
namely, the inertia of a particle ceases to be a fixed quantity; it may 
greatly increase with increased velocity of motion, and so the particle no 
longer obeys the laws of Newtonian mechanics. Finally, comparing 
(3 rays and cathode rays, one finds them analogous, only the particles of 
ft rays move with greater velocity and are capable of penetrating a much 
thicker layer of matter (for instance, a plate of aluminium one mm. 
thick). 

The a rays are constituted by the projection of material particles, 
charged electro-positively, having the dimensions of atoms, and moving 
with a smaller velocity than the particles of /? rays. The a rays are bent 
by a magnetic field with considerable difficulty, and can penetrate only 
a very thin layer of matter (aluminium foil V 20 mm. thick absorbs them 
completely). They have the peculiarity of suddenly stopping after 
having traversed a certain well-determined path in a given medium. 
The length of this path in air is a very important quantity, for it permits 
of distinguishing from one another the different species of a rays and 
consequently also the different radioactive substances. The a particles 
play a very important part in radioactive transformations, and their 
nature seems now to be clearly understood. 

The f rays are not charged, and therefore are not deflected by a mag- 
netic field. They suffer but slight absorption in matter (a considera- 
ble proportion of the 7- rays from radium passes through a lead plate 
one centimeter in thickness). 

These several rays excite fluorescence in a number of substances (platino- 

137 



1391 RADIOACTIVITY. 

cyanide of barium, sulfide of zinc, uranyl salts, glass, paper, diamond, 
etc.). The action of a rays upon zinc sulfide produces the very peculiar 
phenomenon generally designated by the term scintillation; in this, the 
luminosity of the zinc sulfide screen is caused by an infinity of brilliant 
little points which appear and disappear continually and which are clearly 
distinguishable when the screen is examined with a lens. 

The radioactive substances constitute a new source of energy ; but dur- 
ing the earlier researches both the origin and the mechanism of this pro- 
duction were entirely unknown. Pierre Curie and Madame Curie ad- 
vanced two distinct hypotheses to explain the production of this energy. 
The first hypothesis assumed that the energy was furnished from outside 
in the form of a special radiation, causing in the radioactive substances 
a phenomenon analogous to phosphorescence. According to the second 
hypothesis, the energy comes from the active substance itself, and hence 
the emission of energy must be accompanied by a change in the substance. 
Pierre Curie and Madame Curie, who had demonstrated the atomic char- 
acter of the new property, believed thoroughly, even before radium had 
been discovered, that the transformation takes place in the radioactive 
atom itself, which must therefore change into a different atom and, con- 
sequently, gradually disappear in course of time. It is this hypothesis of 
atomic transmutation that has proved to be most fruitful and has formed 
the basis of the theories accepted at present. 

The principal fact which has led to these theories is as follows: With 
the aid of radioactive substances, whose activity appears constant and 
permanent, it is possible to produce phenomena of radioactivity whose 
intensity diminishes in time. These phenomena of temporary activity 
may be observed under various circumstances. Thus, if any substance 
whatever is placed near a salt of radium, thorium, or actinium, the sur- 
face of the substance becomes radioactive, and this activity diminishes 
more or less rapidly in time. This is the phenomenon of induced radio- 
activity discovered by Pierre Curie and Madame Curie. Similarly, any 
gaseous atmosphere surrounding radium, thorium, or actinium, becomes 
itself radioactive, and its activity likewise diminishes in time. Ruther- 
ford, the discoverer of this last phenomenon, gave the name "emana- 
tion" to the cause of the temporary activity of the gases. Finally, as 
first observed by myself, in the case of actinium, substances temporarily 
radioactive may also be obtained through certain chemical separations 
in mixtures containing permanently radioactive substances. 

These temporary radioactivities often follow complex laws of de- 
crease. The study of these laws has shown that there exist really several 
different kinds of radioactivity succeeding one another in time. When 
one kind of activity has died out, another replaces it, and this may grad- 
ually cease to exist in its turn. Each kind of radioactivity is character- 
ized by its own velocity of decrease and by a radiation peculiar to itself. 
Extraordinarily great temporary radioactivities may accumulate in an 
extremely slight quantity of matter. 

Applying to these temporary radioactivities the idea which had guided 
to the discovery of radium, namely, that radioactivity is an atomic prop- 
erty of the elements exhibiting it, one is led to think that the temporary 
radioactivities which have been separated from radium, thorium, and 
actinium characterize new radioactive atoms. And, accepting the 

138 



, PHYSICAL AND INORGANIC. 1392 

hypothesis of atomic transmutation as an explanation of the origin of 
radioactive energy, the decrease of a given radioactivity appears to re- 
sult from the gradual disappearance of a radioactive element and its 
transmutation into another element. 

The present theory of radioactive phenomena is based on these con- 
siderations. It was proposed by Rutherford and Soddy, who have 
published numerous observations in complete accord with it. At pres- 
ent the theory is accepted by all investigators of radioactivity. An 
extremely precious guide in research, it has again and again been con- 
firmed by discoveries of great importance. 

The various phenomena exhibited by radium may, then, be interpreted 
as follows : The radium atom, which emits a certain a radiation, produces 
continually a radioactive emanation. This emanation is considered 
to be a radioactive gaseous element resulting from the transmutation 
of radium, and hence the latter must gradually disappear in time. The 
emanation emits an a radiation different from that of radium and disap- 
pears quite rapidly (the decrease follows a simple exponential law and 
amounts to one-half in 3.8 days). The emanation produces deposits of 
induced radioactivity, which are considered as new elements resulting 
from the transmutation of the emanation. In these deposits it has been 
possible to identify a series of stages which have received the names of 
Radium A, Radium B, Radium C, and which succeed one another, radium 
A changing into radium B, which in turn changes into radium C. These 
different members of the group emit different radiations and undergo de- 
struction with considerable velocities. 

Following radium C is another sequence of terms, characterized by a much 
smaller rate of disappearance, viz., Radium D, Radium E t , Radium E 2 , 
and Radium F. The last-named has been shown by Rutherford to be 
identical with polonium. Polonium itself disappears little by little, but 
the element succeeding it is as yet unknown. 

It has been possible to determin with much precision the laws of forma- 
tion and destruction of the different transition terms of the series. These 
laws are exponential expressions analogous to those which hold for mono- 
molecular chemical reactions. Most of the terms have been isolated 
(by means of chemical reactions, electrolysis, heating, condensation at 
low temperatures, etc.), and the several exponential formulas followed by 
their rates of destruction have been determined separately, the formula 
corresponding to each term having a characteristic exponent, X, of its 
own. The rate of destruction of a given term is frequently characterized 
by specifying the time T required to diminish by one-half the original 
intensity of its radiation. The quantity i/^ may be considered as the 
mean duration of life of an atom of the substance under consideration; 
it is denoted by the symbol and is usually referred to briefly as "the 
mean life." We have, then, = i/k and T = @hi2. 

The numerous researches which have been carried out on radioactive 
substances have resulted in fairly complete knowledge concerning the 
series of radioactive transformations in the several families, the proper- 
ties of the different terms, and the properties of the rays emitted during 
the transformations. The knowledge gathered up to the present time is 
reproduced in the accompanying tables. 

139 



1393 



RADIOACTIVITY. 





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GENERAL, PHYSICAL AND INORGANIC. 



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RADIOACTIVITY. 



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GENERAL, PHYSICAL AND INORGANIC. 



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143 



1397 RADIOACTIVITY. 

The inter-relation between the different terms of one and the same 
family is not the result of theoretical interpretation. It is a thoroughly 
established experimental fact. According to present-day theory, each 
term represents a certain chemical element which differs from the ordi- 
nary elements only by its ephemeral existence and by its emitting a special 
radiation. The disappearance of the radioactive atom is the result of its 
transformation into another atom, the special radiation representing 
the energy which accompanies that transformation. According to this 
theory, then, the study of radioactivity has led to the discovery of some 
thirty new elements. 

The theory outlined above permits of an easy interpretation of all 
phenomena thus far known. Still, it was a matter of great importance to 
obtain a direct experimental demonstration of the reality of atomic 
transformations, and of the existence of chemical atoms having a very 
short life, corresponding to the ephemeral radioactivities. Such direct 
experimental demonstrations have actually been produced, and hence 
the theory rests on an extremely solid basis. 

The reality of atomic transformations accompanying the phenomena of 
radioactivity has been demonstrated by the experiments of Ramsay 
and Soddy on the production of helium from radium. Radium, whose 
character as a chemical element is established by its chemical properties, 
by its atomic weight, and by its spectrum, continually produces the gas 
helium, which is itself a well characterized chemical element. This pro- 
duction of helium cannot be reasonably interpreted in any other way 
than by recognizing atomic transformation. 

Some time after Ramsay and Soddy, I showed that the same phenom- 
enon takes place in actinium, which also continually produces helium 
gas. Recently, Soddy has discovered the production of helium also 
from uranium and from thorium. 

The production of helium from radioactive substances is the first 
case ever discovered of the transformation of chemical atoms. 

That an ephemeral radioactivity is due to the existence of a corre- 
sponding chemical element has been experimentally demonstrated in 
the case of the radium emanation. This emanation has been isolated 
in a pure state, its spectrum determined, and its volume measured. 
Somewhat numerous experiments were first carried out by Ramsay 
and his collaborators, and though the published results are not in per- 
fect agreement, they still leave no doubt whatever as to the material 
existence of the emanation, which is characterized by a spectrum of its 
own. The isolation of the substance was effected by utilizing its property 
of easily condensing at low temperatures. These experiments were later 
repeated by Rutherford and Royds, who obtained agreeing measure- 
ments of the volume occupied by the pure emanation produced by a given 
quantity of radium, and who described completely the spectrum of the 
emanation. Recently, I have carried out analogous experiments: my 
volume measurements agree perfectly with Rutherford's, and my spectro- 
photographs are identical with those of Rutherford and Royds. I have 
observed besides that the volume of gas produced does not increase pro- 
portionally to the time, owing to the spontaneous destruction of the 
substance. The observed volume is invariably proportional to the radio- 
activity of the emanation, no matter what the duration of its produc- 
tion from radium. In the experiments mentioned above, all investiga- 

144 



GENERAL, PHYSICAL AND INORGANIC. 1398 

tors have observed the production of helium from the emanation: the 
spectrum of helium gradually appears, while that of the emanation dis- 
appears. Finally, Rutherford, and also Ramsay, have succeeded in de- 
termining the point of liquefaction and the point of solidification of the 
emanation. 

It thus appears entirely certain that the emanation is a material gas 
a fact which corroborates very strongly Rutherford and Soddy's theory. 

The production of helium by radioactive substances is directly rela- 
ted to the emission of a particles, and the hypothesis early advanced 
by Rutherford, that each a particle is an atom of helium, is to-day con- 
firmed. In fact, Rutherford has shown that the a rays and the helium 
produced by the radium emanation pass through thin layers of matter 
in a similar manner. Other properties of the a particles are in complete 
accord with this conception of their nature. 

Now, if we assume that in all transformations accompanied by the 
emission of a. particles each radioactive atom changes into the next in 
order by loss of a single a particle or helium atom, it becomes possible 
to calculate the atomic weights of the several transition elements of the 
radium series. The atomic weight of helium being 4, we have, namely: 
Radium 226.5 > Emanation 222.5 > Radium A 218.5 * 
Radium B 214.5 > Radium C 214.5 > Radium D 210.5 > 
Radium E 210. 5 > Radium F, or Polonium, 210. 5 > a last unknown 
substance 206.5. This l as * number represents exactly the atomic weight 
of lead, which suggests the idea that this element is the final product 
of the transformation of radium. It is probable that this idea can be 
subjected to experimental verification. 

The mother substances, uranium, radium, actinium, and thorium, 
ought to gradually disappear in course of time, as they are transformed 
into other elements. But the destruction is certainly very slow, and no 
diminution of their activity has been directly detected. The laws of 
their destruction may, however, be determined indirectly. Since the 
transformation of each radioactive atom produces an emission of rays, 
it is natural to assume that the more intense the radiation produced by 
a gram-atom of the substance, the more rapid is the transformation. 
Thus, radium ought to have a much shorter life than uranium or thorium. 
The comparison of the radiations may be carried out quantitatively, 
and thus the ratio of the mean lives of two radioactive substances may 
be readily obtained. 

On the other hand, if it is assumed that the emission of a single a par- 
ticle corresponds to the transformation of a single atom, it will suffice 
to determin the number of particles emitted per second by a given mass 
of the active substance under consideration, in order to ascertain its 
velocity of transformation. Indirect determinations were first made by 
measuring the total positive charge emitted in the form of a rays by the 
active substance and making an assumptiion concerning the charge of a 
single particle. The results so obtained have been confirmed by directly 
counting the a particles emitted by a certain quantity of active sub- 
stance. 

The first direct results were yielded by the scintillations produced by 
a particles on a screen of zinc sulfide. Each scintillation being assumed 
to be produced by a single a particle, the number of scintillations was 

H5 



1399 RADIOACTIVITY. 

determined, produced in a given time by . known quantity of the active 
substance. This gave the number of a particles emitted by the sub- 
stance, and consequently the number of atoms transformed in a given 
time. Another, and very ingenious, method was first employed by 
Rutherford and Geiger, who utilized the ionization produced in a gas by a 
particles. These investigators succeeded in determining the ionizing 
effect produced in a rarefied gas by each a particle by making use of the 
phenomenon of ionization by shock. The entrance of each single a par- 
ticle into the gas affects the electrometer, and all that is necessary is to 
count the number of disturbances produced in a given time. The two 
methods have yielded well agreeing results, which indicate that radium 
ought to be one-half destroyed in about 2000 years. 

The destruction of radium is too slow to be capable of being detected 
by direct experiment. Nevertheless, in order to account for the presence 
of radium in minerals, it is necessary to assume that radium is continually 
produced in those minerals, the destruction being thus partly compensa- 
ted for. The element which appears evidently to be the most capable 
of changing into radium is uranium. 

In fact, radium is always found in uranium minerals and, furthermore, 
uranium is radioactive and hence in a state of decomposition. Since the 
radioactivity of uranium is much less intense than that of radium, its 
duration of life must be much greater than that of radium, and this ex- 
plains the occurrence of uranium in considerable quantities in nature. 

An extremely important argument in support of the accepted rela- 
tionship between uranium and radium lies in the constant ratio of the 
quantities of the two elements found in minerals. The constancy of this 
ratio, which has been principally affirmed by the experiments of Bolt- 
wood, is readily explained if we assume that radium is produced from 
uranium, and that the destruction of radium is much more rapid than that 
of uranium. The ratio permits of calculating the mean life of uranium. 

Attempts to demonstrate directly the formation of radium from ura- 
nium have shown that this transformation is certainly not immediate, 
and that there ought to exist at least one substance intermediate between 
uranium and radium. This has been confirmed by Rutherford and 
Boltwood's discovery of a new substance capable of producing radium. 
This new substance has been named ionium. The mean life of ionium 
being probably long, there is hope that this substance will be isolated 
without much difficulty. 

The question of the relationship between uranium and radium seemed 
to be definitly settled, when recently Mile. Gleditsch announced that 
the ratio of the quantities of uranium and radium was not the same in all 
minerals, contradicting the earlier results of Bolt wood. While the 
ratios found by Mile. Gleditsch are of the same order of magnitude, 
they nevertheless differ very materially from one another. The hypothesis 
of the formation of radium from uranium furnishes so simple an explana- 
tion of the presence of radium in minerals that one can hardly abandon 
it. As a matter of fact, however, the conditions of formation of radium 
appear to be complex and not yet completely elucidated. Unquestion- 
ably, further study of the relative quantities of the different active sub- 
stances in minerals will yield new and important results. Such study 
will also be of great usefulness in geology. 

146 



GENERAL, PHYSICAL AND INORGANIC. 1400 

If the phenomena of radioactivity indicate atomic transformation, one 
expects to find radioactive energy, corresponding to the transformation 
of atoms, to be far greater than the energy changes generally accompany- 
ing the transformation of molecules. That this is true is shown by Pierre 
Curie and Laborde's discovery of the enormous quantity of energy given 
off by radium. One gram of radium in radioactive equilibrium would 
produce about 1 20 calories of heat in an hour. The quantity of heat that 
would be set free by the complete transformation of one gram of radium 
is nearly the same as that produced by the combustion of a ton of coal. 
Most of this heat has been shown to come from the kinetic energy of the 
a particles. Heat has also been shown to be developed by actinium, 
thorium, and polonium. Radioactivity thus constitutes an extremely 
important source of energy. A very slight proportion of radium in the 
sun (about i gram per cubic meter) would be sufficient to account for 
all the energy radiated by it. The energy radiated by our own planet 
seems to be more than compensated for by the radium contained in its 
crust, so that the progressive cooling of the earth, once generally accepted, 
now seems to be problematic. It seems legitimate to assume that radio- 
activity constitutes one of the principal sources of the energy radiated 
in the universe. No other hypothesis is based on an equally serious ex- 
perimental foundation. 

The atomic transformation of radioactivity takes place under very pecul- 
iar conditions. As already stated, the phenomenon is spontaneous, 
apparently causeless. Moreover, no method is as yet known by which 
such transformations might be brought about or stopped, or even in the 
least degree hastened or slowed up. Elevation of temperature, which is 
so sure to increase the velocity of chemical reactions, seems to have no 
effect whatever on radioactive transformations. Thus, the characteris- 
tic constant of the destruction of radium emanation is the same at high 
temperatures as at the temperature of liquid air. Neither does the 
nature of an inactive chemical element combined with the radioactive 
atom seem to have any influence upon the velocity of its destruction. 
As yet, we are mere spectators, observing the transformation of atoms, 
but unable to interfere with it in any way. 

The transformation follows a probability law identical with the law of 
mass action followed by chemical reactions: the number of atoms trans- 
formed per unit of time is at any instant proportional to the total number 
of atoms present. No simple and satisfactory hypothesis, however, has 
been advanced explaining this fact. In the case of mono-molecular 
chemical reactions, the fact that the transformation takes place grad- 
ually is explained on the assumption that all the molecules present are 
not in the same condition, either owing to collisions between the mole- 
cules or because of differences in whatever motion may be going on within 
the molecules themselves. The transformation of a given molecule is 
instantaneous, but the molecule will not undergo transformation unless 
it happens to get into a certain condition necessary for it. The proba- 
bility law must then remain the same as long as the number of molecules 
remains very great and the external conditions of the reaction remain 
the same. In the case of radioactive transformations, external condi- 
tions (e. g., of temperature) and intermolecular collisions ought to have 
no effect. Therefore, only the motion within the interior of the atom 

147 



1401 RADIOACTIVITY. 

can be invoked in an effort to explain why, in one and the same substance, 
some atoms break down immediately after being formed, while others 
are destined to live hundreds or even thousands of years before under- 
going transformation. 

It is imaginable that there exists in space a special field of force which 
influences intra-atomic motion and is therefore capable of causing the 
disintegration of atoms. The action of such a force must then be inde- 
pendent of any translatory motion of the atoms. There is, however, at 
present absolutely no indication of the existence of such a force in space. 

If the transformation is not brought about by an external force, and if 
external conditions of pressure, temperature, etc., have really no influ- 
ence upon the progress of radioactive changes, one is led to assume 
that the destiny of a given atom is completely determined at the very 
moment of its formation, that at that moment it is already in such a state 
that its transformation must take place after exactly a certain interval 
of time. In that case a radioactive element must be considered as 
made up of atoms of different nature, some destined to very speedy de- 
struction, others to a more or less prolonged existence. It is not un- 
thinkable that these different atoms of one and the same radioactive ele- 
ment may some day be separated. 

In order to account for the exponential law of spontaneous destruction, 
it is necessary, in that case, to assume that the distribution of life dura- 
tions among the atoms at the moment of their formation is represented 
by a simple exponential function, the atoms of short life being much more 
numerous than those of long life. It is, however, difficult to imagine 
what can possibly be the cause of such a law of distribution, and con- 
siderations like the above only show that while the laws of radioactive 
transformations have been determined with precision and are well 
known, the initial cause of the phenomena is as yet altogether obscure. 

In concluding this summary, I will mention the attempts that have 
been made with a view to artificially bringing about atomic transforma- 
tions with the aid of radioactive energy. Some results in this connec- 
tion have been published by Ramsay and Cameron. They believed 
that by the action of radium emanation upon water they had succeeded 
in producing neon. They further believed that by the action of the 
emanation upon a salt of copper they had produced alkali metals: the 
formation of lithium appeared to have been especially well demonstrated. 

These results have, unfortunately, been shown to be erroneous. Mme. 
Curie and Mile. Gleditsch repeated the experiments on the formation of 
lithium and found that when no other than platinum vessels were used, 
the appearance of lithium could not be detected ; in Ramsay and Cameron's 
experiments the lithium came from the glass of the apparatus employed. 
Similarly, Rutherford and Royds have re-investigated the effect of emana- 
tion upon water and have failed to obtain any neon. I, too, have failed 
to find neon in the gases evolved by a solution of radium. The neon 
found by Ramsay and Cameron must have come from a small quantity 
of air introduced by accident. 

So it may be said that up to the present time no atomic transmutation 
has been produced artificially. All we can do is to subject to inquiry 
spontaneous transmutations which we cannot control. A long step, 

148 



GENERAL, PHYSICAL AND INORGANIC. 1402 

therefore, remains to be taken before the dream of the alchemists 
has been realized. 1 

CLARK UNIVERSITY. WORCESTER. MASS. 

1 New results have been published by Ramsay and Gray. According to these 
investigators, carbon dioxide may be produced by the action of radium emanation 
upon compounds of thorium, zirconium, silicon, etc. But inasmuch as carbon com- 
pounds may easily find their way into apparatus by accident, it is difficult to establish 
beyond doubt a transformation of the elements thorium or zirconium into carbon. 
The authors themselves admit that their experiments are not conclusive. 



149 



Duplicate 
Stanford Lib.