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AKBANGEMENT

ATOMS IN SPACE

THE AEEANGBMBNT

ATOMS IN SPACE

J. H. VAN 'T HOFF

SECOND REVISED AND ENLARGED EDITION

WITH A PKEFACE BY JOHANNES WISLICENUS

Professor of Chemistry at the University of Leipzig
AND AN APPENDIX

STEREOCHEMISTRY AMONG INORGANIC SUBSTANCES

ALFEED WEENEB

Professor of Chemistry at the University of ZUrich
TRANSLATED AND EDITED BY

ABNOLD EILOAET

LONGMANS, GEEEN, AND CO,

89 PATERNOSTER ROW, LONDON

NEW YORK AND BOMBAY

1898

PBEFACE

THE FIKST EDITION

THE first edition of this little book appeared in
1877, in the form of Dr. F. Herrmann's free render-
ing of my brochure, ' La Chimie dans 1'Espace,' and
Wislicenus, as long ago as that, helped the work
by a warm recommendation.

As the original views still survive in Stereo-
chemistry, this second edition presents once more
a freely revised version of that brochure ; but a
section on nitrogen derivatives has been added.
Besides this, in the part devoted to carbon, the
greatly increased number of facts has been taken
into account, and finally the amount of the rota-
tion of active bodies has received special attention.
Accordingly the book may serve as a reference
book for stereochemistry and optical activity.

At the publishers' wish, I have studied brevity
as far as compatible with thorough treatment.

J. H. VAN 'T HOFF.

AMSTERDAM : February 1894.

PREFACE

THE SECOND EDITION

FOR this second edition of the ' Arrangement of
Atoms in Space,' as for the first, the publishers and
the author desire a short preface from my pen.
This can have now no such purpose as in the case of
Dr. Herrmann's edition. Then I had to address to
German chemists a letter of recommendation in
favour of the little-known hypothesis of a very
young colleague ; now the name of the author has
a renown so high, based on such an extraordinary
series of important and far-reaching researches, that
my recommendation would be altogether superfluous
for his book, even if the theory here set forth had not
acquired for itself the position in chemistry which in
fact it possesses.

Indeed, the old opposition to the principle has
almost died out ; where it still lives it is directed

PREFACE TO THE SECOND EDITION vii

against the ultimate basis— against the Atomic
Hypothesis itself — and does not deny that the doc-
trine of atomic arrangement in three dimensions is
a logical and necessary stage, perhaps the final
stage, in the chemical theory of atoms. For the
most part the opposition is directed — often quite
rightly — against special applications of the principle
to the explanation of particular facts, leaving the
principle itself untouched. That the hypothesis
itself has proved its own justification — at least, as
much as any other scientific theory — none can
dispute.

It has already effected to the full all that can be
effected by any theory ; for it has brought into
organic connection with the fundamental theories
of chemistry facts which were before incomprehen-
sible and apparently isolated, and has enabled us to
explain them from these theories in the simplest
way. By propounding to us new problems the hy-
pothesis has stimulated empirical investigation on
all sides ; it has caused a vast accumulation of facts,
has led to the discovery of new methods of observa-
tion, has become amenable to the test of experiment,
and has at the same time started in our science
a movement full of significance — in a certain sense,
indeed, a new epoch.

How and to what extent the hypothesis has
effected this, is told in this book, briefly, clearly, com-

Vlll PREFACE TO THE SECOND EDITION

pletely. Tne book is now not so much a new edition
of the first German work, as a German revision of
van 't Hoff's ' Dix Annees dans 1'Histoire d'une
Theorie,' enriched by the growth of our knowledge
during the last seven years. In this new form,
also, the book will win many friends, and be a wel-
come guide to the comprehension of stereochemistry
and to its already very extensive literature.

I may well be pardoned if I find an especial
satisfaction in this new edition of van 't Hoff's pioneer
publication. When it first appeared as ' La Chimie
dans 1'Espace ' it bore as motto a sentence uttered
by me as early as 1869. l I was then able to do
something towards making known the new theory,
and later to contribute to its development and to
the experimental testing of it. Accordingly it is
with great pleasure that I accept the honour of in-
troducing the new revision, and send my thanks and
regards to my honoured friend at Amsterdam.

JOHANNES WISLICENUS.

LEIPZIG : April 1894.

1 Bcr. 2, 550, and especially p. 620.

CONTENTS

PAGE

INTRODUCTION . i

STEREOCHEMISTRY OF CARBON
CHAPTER I

THE ASYMMETRIC CARBON ATOM

I. Statement of the fundamental conception .... 5
I. Experimental confirmation of the fundamental conception . 9

A. Character of the isomerism due to the asymmetric carbon 9

B. Observed coincidence of optical isomerism with the

presence of asymmetric carbon 13

CHAPTER II

DIVISION OF THE INACTIVE MIXTURE. TEMPERATURE

OF CONVERSION

Inactivity of compounds containing asymmetric carbon . . 27

1. Division by means of active compounds . . . . 28

2. Division by means of organisms 30

3. Spontaneous division. Temperature of conversion . . 34

4. Proof of divisibility by synthesis of the inactive mixture 40
Indivisibility in absence of asymmetric carbon . . . 40
Transformation of active bodies into each other. The

point of equilibrium . . . . . . . 47

Inactive indivisible type 50

X CONTENTS

CHAPTER III

COMPOUNDS WITH SEVERAL ASYMMETRIC
CARBON ATOMS

PAGE

I. Application of the fundamental conception . . 54

II. Experimental confirmation 57

A. Number and character of the isomers to be expected 57

B. Formation of isomers containing several asymmetric

carbon atoms 65

C. Transformation of isomers with several asymmetric

carbon atoms 70

D. Simplification through symmetry of the formula.

Inactive indivisible type 74

CHAPTER IV

DETERMINATION OF THE POSITION OF THE RADICALS

IN STEREOMERS 81

CHAPTER V

THE UNSATURATED CARBON COMPOUNDS

I. Statement of the fundamental conception .... 93

II. Confirmation of the fundamental conception . . . 99

III. Determination of the position of the radicals in unsaturated
compounds 105

CHAPTER VI

RING FORMATION 114

CHAPTER VII

NUMERICAL VALUE OF THE ROTATORY POWER

I. Conditions in which the results are comparable. Examina-
tion in dilute solution, having regard to the molecular
weight, indispensable , 134

CONTENTS XI

PAGE

II. Rotatory power of electrolytes. Law of Oudemans-Landolt 136

III. Rotation of imperfect electrolytes. Organic acids . . 141

IV. Influence of ring formation on rotation .... 146
V. Rotation of non-electrolytes. Hypotheses of Guye and

Crum Brown . . 153

VI. More complicated cases 160

STEBEOCHEMISTRY OF NITROGEN
COMPOUNDS

I. Trivalent nitrogen 169

- A. Trivalent nitrogen without double linkage . . . 169

B. Trivalent nitrogen doubly linked with carbon . . . 171

C. Trivalent nitrogen in closed rings .... 176

D. Configuration in the case of doubly linked nitrogen . . 178

II. Compounds containing pentavalent nitrogen . . . 180

APPENDIX

Stereochemical isomerism of inorganic compounds . . . 185

INDEX . 201

INTKODUCTION

EVERY time I write on stereochemistry a new name
has to be added to complete the history of its
development. In my ' Dix Annees dans 1'Histoire
d'une Theorie ' I mentioned Gaudin and his ' Archi-
tecture du Monde ' (1873) ; then Meyerhoffer in his
1 Stereochemie ' added Paterno,1 who in 1869 pro-
posed to explain isomeric bromethylenes by a tetra-
hedral grouping round carbon ; and Rosenstiehl,2
who in the same year represented benzene by six
tetrahedra ; and now Eiloart, in his ' Guide to
Stereochemistry,' goes back to Swedenborg's 'Pro-
dromus Principiorum Rerum Naturalium sive
Novorum Tentaminum Chymicam et Physicam
Experimentalem geometrice explicandi.' 3 Certainly,
then, we were not over-hasty, Le Bel and I, when we
published our ideas (November and September 1874)
in the ' Bulletin de la Societe Chimique ' and in the
' Voorstel tot Uitbreiding der Structuur-Formules in
de Euimte ' respectively. That shortly before this

1 Giorn. di Scienze Naturali cd Econ. vol. v., Palermo ; Gazz
Chim. 1893, 35.

2 Bull. Soc. Chim. 11, 393. 3 Jan Ostenvyk, Amsterdam, 172].

tfl STEREOCHEMISTRY OF CARBON

we had been working together in Wurtz's laboratory
was purely fortuitous ; we never exchanged a word
about the tetrahedron there, though perhaps both of
us already cherished the idea in secret. To me it
had occurred the year before, in Utrecht, after read-
ing Wislicenus' paper on lactic acid. ' The facts
compel us to explain the difference between isomeric
molecules possessing the same structural formulae by
the different arrangement of their atoms in space ' :
this was the sentence which remained in my memory,
and which I have since used as a motto ; on trying
to refer to it I could not find it again, and so cannot
give the reference here.

On the whole, Lie Bel's paper and mine are in
accord ; still, the conceptions are not quite the same.
Historically the difference lies in this, that Le Bel's
starting point was the researches of Pasteur, mine
those of Kekule.

The researches of Pasteur had made plain the
connection between optical activity and crystal-form,
and had led to the idea that the isomers of opposite
rotatory power correspond to an asymmetric group-
ing and to its mirrored image. Indeed, the possi-
bility of a tetrahedral grouping was suggested.1 Le
Bel closely follows Pasteur, then, when he sees this
grouping in the four atoms or radicals — inactive
bodies all different — united to carbon.

My conception is, as Baeyer pointed out at the
Kekule festival, a continuation of Kekule's law of the
quadrivalence of carbon, with the added hypothesis
1 Lemons sur la Dissymdtric MoUculaire.

INTRODUCTION 3

that the four valences are directed towards the
corners of a tetrahedron, at the centre of which is
the carbon atom.

Practically our ideas, so far as they concern the
asymmetric carbon, amount to the same thing — ex-
planation of the two isomers by means of the tetra-
hedron and its image, disappearance of this
isomerism when two groups become identical,
through the resulting symmetry and identity of the
two tetrahedra.

In the case of doubly linked carbon, however,
"there arises the possibilty of a difference. Here, too,
four groups are connected, and Le Bel considers that
a priori only so much is known about their position,
that of the two pairs one pair lies nearer to one
carbon, the other pair to the other carbon. It may
happen, then, that ethylene derivatives may have no
symmetry in their molecules — they may be active.
Carrying out my tetrahedral grouping I concluded
that the four groups are in one plane with the car-
bon, this being accordingly the plane of symmetry of
all ethylene derivatives ; therefore no optical activity
can occur. As regards this, Le Bel [ at first altered
his opinion in my favour, but later 2 altered it back
again.

Of course, the facts must decide ; as, however,
Liebermann informs me, specially for this edition,
that bromocinnamic acid from active cinnamic acid
dibromide is inactive, and Walden states that fumaric
acid from active bromosuccinic acid is inactive, it

1 Bull. Soc. Chim. 37, 300. " Ibid. [3], 7, 164, 1892.

B 2

4 STEEEOCHEMISTRY OF CARBON

appears that, in accordance with facts previously
known, the simple conception of the tetrahedral
grouping and of the development of structural
chemistry to stereochemistry on these lines is still
permissible.

STEREOCHEMISTRY OF CARBON

CHAPTEK I
THE ASYMMETRIC CARBON ATOM

I. STATEMENT OF THE FUNDAMENTAL
CONCEPTION

The molecule a stable system of material points.—

When we arrive at a system of atomic mechanics
the molecule will appear as a stable system of
material points ; that is the fundamental idea which
continually becomes clearer and clearer when one is
-treating of stereochemistry ; for what we are dealing
with here is nothing else than the spatial — i.e. the
real — positions of these points, the atoms.

I choose this fundamental conception as the
starting point for this reason, that there is already
evident in the rough outlines of this future system
of atom mechanics a very considerable simplification,
which I will here discuss.

One might suppose that the arrangement of the\
atoms in the molecule would be something like that
in a system of planets, equilibrium being maintained
by attraction and motion, by equality between
centripetal and centrifugal force. I will try to show

6 STEREOCHEMISTRY OF CARBON

that we must exclude this motion ; and this as a
necessary consequence of simple thermodynamic
considerations.

As the partial decomposition of salts containing
water of crystallisation shows, and, generally, as the

formula ~ •'-- = ~L requires, the alteration of
d.JL ^J-2

any dissociation phenomenon with the temperature
is always of this nature, that while on cooling the
decomposition gradually becomes less, yet it ceases
only at absolute zero (T=0). But this is as much
as to say that the internal stability of the molecule
is attained only at absolute zero, i.e. in the absence
of all internal motion. Otherwise interaction with
another molecule is an essential condition of equi-
librium.

This law is seen to be perfectly general when we
consider that every compound would undergo visible
dissociation at a sufficiently high temperature, thus
fulfilling the above conditions.

We may add, as a necessary consequence, that the
state of things at absolute zero is to be explained
solely by atomic mechanics, thermodynamics having
nothing to do with this explanation, because thermo-
dynamics comes into play only when, at a tempera-
ture above zero, dissociation begins ; and we may
add further that, to render equilibrium possible,
instead of the centrifugal force which ordinarily acts,
there must be a repulsion, for the action of matter
(atoms) alone appears insufficient, and there must
be something else, perhaps electricity.

THE ASYMMETRIC CARBON ATOM 7

For stereochemistry the above considerations are
important as showing that motion of the atoms may
for the present be neglected, the state of things
being tacitly assumed to be as it would be at absolute
zero. Indeed, the phenomena of isomerism are in a
certain sense opposed to motion ; they are certainly
not a consequence thereof ; for when the tempera-
ture rises they ultimately disappear, and become
constantly more marked as it falls. He who
chooses to assume motion, however, may conceive
^the motionless systems here to be described as the
expression of the position of certain points about
which the motion, doubtless a periodical motion,
takes place.

Insufficiency of structural chemistry. The asym-
metric carbon atom. — Everyone is now familiar
with the fact, only occasionally observed in 1874,
that the simple structural formulae are insufficient
to explain the existing cases of isomerism; and
that, to consider first carbon-compounds of the
type C(E1K2E3E4) — i.e. compounds in which four
separate groups or atoms are combined with the
carbon — an extra isomerism occurs when these four
groups are different, and disappears if but two of
them become the same. Assuming a fixed position
of the groups round the carbon atom, only a tetra-
hedral grouping brings us to the same conclusion,
as figs. 3 and 4 show : these become identical
when E3 and B4 become the same ; while this leaves
the isomerism unaffected if we represent the formula
in one plane (figs. 1. and 2).

STEREOCHEMISTRY OF CARBON

To illustrate the matter with models we may
use the cardboard tetrahedra, the different groups
being represented by attaching caps made of coloured
paper : e.g. Kt white ; E2 yellow ; R3 black ; R4 red ;
to make the two tetrahedra alike an extra pair, say a
pair of black caps, may be used, and may be placed
on R4, for instance. The Kekule models, improved by
v. Baeyer, and sold by Sendtner (Schillerstrasse 22,
Miinchen), may be used for the same purpose.

Fig. 3.

Fig. 4.

A word as to the shape of the tetrahedra. If we
wish to represent only the two possible formulae
given above, their peculiar lack of symmetry, their
object-and-image relation, and the way they may be
rendered identical, the regular tetrahedron with
variously coloured corners quite suffices. But if the
mechanics of the atoms is to be taken into account,
we must admit, without making any hypothesis as
to the nature of the forces acting, that in general

THE ASYMMETKIC CAKBON ATOM 9

these forces will be different between different
groups, and the same between similar groups ; and
then the difference between fig. 3 and fig. 4 must
be expressed in the dimensions also. The edges
E! E4, E! K3, &c., will then be different in the
two figures, but the corresponding dimensions in
each, E1 E4 in fig. 3, ^ E4 in fig. 4, &c., will be
equal. The two tetrahedra then express by their
shape their object-and-image relation (so-called en-
antiomorphism) , and at the same time a mechanical
^necessity is satisfied. It is now superfluous to vary
the colours of the corners ; but the way in which
identity arises can now be shown only by two more
models in which, in accordance with the funda-
mental requirement of mechanics, E4 and E3 take
corresponding positions which are equally distant
from the plane of symmetry now called into ex-
istence, and passing through E1 E2 ; for we now have

E4 E1 = E3 E! and E4 E2=E3 E2.

II. EXPEEIMENTAL CONFIRMATION OF THE

FUNDAMENTAL CONCEPTION

A. CHARACTER OF THE ISOMERISM DUE TO THE
ASYMMETRIC CARBON

Optical activity. — The isomerism expressed by the
difference between the two enantiomorphous forms
is characterised in the first place by this, that it is
to be expected when the carbon is united to four
different groups, and only then.

But in the second place all the molecular dimen-

10 STEREOCHEMISTRY OF CAEBON

sions being equal in the two forms, we must expect
a kind of isomerism distinguished by a near
approach to identity. This state of things fully
coincides with the facts, and may be summed up as
follows.

All physical properties depending on molecular
dimensions and attractions (mathematically speaking,
on the quantities a and b of Van der Waals' theory)
are identical in the two isomers ; thus, sp. gr., crit.
temp., maximal tension, boiling point, melting point,
latent heat of fusion and vaporisation, &c. The same
holds for the physical properties which manifest them-
selves as the expression of these fundamental quan-
tities, on contact with other bodies, e.g. solubility.

As regards chemical properties we must expect
exactly equal stability, the same speed of formation
and of conversion in given reactions, equilibrium
when equal quantities of each are present together,
no heat of transformation when one is converted
into the other, and accordingly equal heat of forma-
tion in both cases.

Finally, the only difference is due to the lack of
symmetry, and this is manifested physically in the
opposite optical activity, the so-called right- and
left-handed rotation, shown by the isomers in the
dissolved state — in the state, that is, when the
rotation must arise from molecular, not from crystal-
line structure. It is important to note that a
corresponding enantiomorphous structure causes the
opposite activity in other cases also, as may be
deduced empirically from active crystals, e.g. quartz,

THE ASYMMETRIC CARBON ATOM 11

in which opposite rotatory power as regards light
accompanies enantiomorphism of crystalline form.
The same holds for elastic bodies wound in a right-
or left-handed spiral, and finally for the active mica
combinations of Reusch, formed of a pile of thin
plates of binaxial mica placed at an angle of 60° one
above another.1 And Sarrau 2 has shown the theo-
retical necessity for this optical phenomenon in the
case of asymmetric structures in general.

Crystalline form. — In the second place the
asymmetry manifests itself crystallographically,3
isomers due to asymmetric carbon showing an
enantiomorphism of crystalline form corresponding
to their molecular structure, as illustrated by the
following woodcuts of right- and left-handed
ammonium bimalate : —

Fig. 5. Fig. 6.

We may add that Soret 4 has shown this result
to be a general necessity.

In the third place there is the difference in chemical
and consequently in physiological properties. — The

1 Wyrouboff, Ann. de Chim. et de Phys. [6J, 8, 340.

2 Journ. de Math.pures et appliquees [2], 12, 1867.

3 But see Walden, Ber. 29, 1692, and H. Traube's reply, I.e. 2446.

4 Arch, de Geneve, 24, 592, 1890.

12 STEREOCHEMISTRY OF CARBON

chemical identity emphasised above ceases directly
the asymmetric isomers have to do with a substance
which is itself asymmetric. And it is just in this
case that mechanical reasons show the impossibility
of equality in action (mathematically in the quan-
tities a of Van der Waals for the two substances).
The affinities are accordingly different, and doubtless
the solubilities also ; the resulting compounds have
not the same composition, e.g. salts, as regards
water of crystallisation ; sometimes indeed one
isomer can exist, while the other is incapable of
existing. Finally the physiological action, particu-
larly the nutritive value for the lower organisms, is
altogether different for the two isomers, doubtless
owing to the difference above mentioned, for in these
organisms asymmetric bodies, e.g. proteids, play a
great part. Also poisoning power, in the case of
tartaric acid, and taste, in the case of asparagine, are
different.

We may add that Pasteur ! long ago expressed
the view that the above-mentioned optical, crystal-
lographical, chemical, and physiological properties
must arise from an asymmetric grouping in the
molecule ; indeed, he even mentioned the tetra-
hedron as a possibility.

' Are the atoms of tartaric acid arranged along
the spiral of a right-handed screw, or are they situ-
ated at the corners of an irregular tetrahedron, or
have they some other asymmetric grouping? Time
must answer the question. But of this there is no
1 Lemons de Chimie, 1860, 25.

THE ASYMMETRIC CAKBON ATOM 13

doubt, that the atoms possess an asymmetric
arrangement like that of an object and its mirrored
image. Equally certain is it that the atoms of the
left-handed acid possess just the opposite asym-
metric arrangement.'

B. OBSEEVED COINCIDENCE OF OPTICAL ISOMEEISM
WITH THE PEESENCE OF ASYMMETEIC CAEBON

Enumeration of the active compounds. — In order
now to show that the above-mentioned properties
really accompany the asymmetric carbon atom
wherever it occurs, we may confine our attention to
the optical activity, since all the above-mentioned
peculiarities, crystallographical, chemical, and physio-
logical, regularly coincide therewith. Another sim-
plification : it is no matter whether both isomers
have been found or not, since if a compound has
been found which in solution rotates to the right
(e.g.), it is perfectly certain that the corresponding
compound of opposite activity will sooner or later be
discovered.

We will therefore simply enumerate the active
bodies, of known structure, indicating the asym-
metric carbon by italics. In order to give these
important data as completely as possible without
occupying too much space I will here confine myself
to the active compounds containing only one asym-
metric carbon, as the others will be discussed later ;
and in each group only the principal members (and
not, e.g., salts and esters) will be included, since
these derivatives also will be treated of specially.

14 STEREOCHEMISTRY OF CARBON

1. Compounds with three carbon atoms. — (an indi-
cates the directly observed rotation for sodium light ;
[a]D is the so-called specific rotation, i.e. calculated
for one decimetre and unit density.)

Propylene glycol,1 (7H.OH.CH3.CH2OH an
= - 5° for 22 cm.

Propylene oxide,1 CH.CH3.OCH2 aD = + 1° for
22 cm. ' | J

Propylene diamine, CH.CH3.NH2.CH2NH2.'2

Ethylidene lactic acid,3 CH.OH.CH3.C02H. Bo-
tation in aqueous solution varying much with time
and concentration (c).

Maximal value \_a~\D = + 3° (c = 7-38). The
somer of opposite activity has also been obtained.4

Lactid,3 (7H.CH3.CO.O [a],, = - 86°.

Cystine,5 O.SH.NH2.CH3.C02H [a], = - 8°.

Glyceric acid,6 CH.OH.CH2OH.C02H. ' Eotation
in aqueous solution varying much with time and
concentration. Both isomers have been obtained.

2. Compounds with four carbon atoms.

Butyl alcohol,7 (7H.OH.CHa.C2H5.

1 Le Bel, Bull. Soc. Chim. [2], 34, 129.

2 Baumann, Ber. 28, 1177.

3 Wislicenus, Ann. 167, 302.

4 Nencki and Sieber, Ber. 22, Ref . 695 ; Schurdinger, Chem.
Soc. J. Abstr. 1891, p. 666; Purdie and Walker, Trans. 1892,
p. 754 ; Lewkowitsch, Ber. 16, 2720 ; Linossier, 24, Ref. 660.

5 Baumann, Zeitschr. f. Physiol. Chem. 8, 305.

6 Lewkowitsch, I.e. ; Frankland and Appleyard, Chem. Soc. J.
Trans. 1893, p. 296.

7 Combes and Le Bel, Chem, Soc. J. Abstr. 1893, p. 246.

THE ASYMMETKIC CA

'Oxybutyric acid,1 (7H.OH.CH,
= - 21°.

Malic acid, CH.OH.C02H.CH2C02H. Kotationin
aqueous solution varying much with the concentration.
[a]n = - 2-3° (c = 8-4) ; [a\D = + 3'34° (c = 70). 2

The isomer of opposite activity has also been
obtained.3

Chlorosuccinic acid, CHCLC02H.CH2CO2H 4
[a]5J = + 20° (c= 3-2 to 16).

Methoxysuccinic acid,

CH.OCH3.C02H.CH2C02H 5

[a]i?=33° (c = 5-5 to 10-8).

Both isomers were obtained.

Ethoxysuccinicacid, CH.OC2H5.C02H.CH2C02H G
[a]i8 = 33° (c = 5-6 to 11-2).

Propoxysuccinic acid,

(7H.OC3H7.C02H.CH2C02H 7 [a]J? = 36-2°.
Isopropoxysuccinic acid,

OH.OCH(CH3)2.C02H.CH2C02H.8

Aspartic acid, CH.NH2.C02H.CH2C02H [a]7,
= — 4° to — 5° 9 in aqueous solution. The isomer of
opposite activity is also known.10

1 Minkowski and Kiilz, Ber. 17, Eef. 334, 534, 535.

2 Schneider, Ann. 207, 257.

3 Bremer, Bull. Soc. Chim. 25, 6 ; Piutti, Ber. 19, 1693.
1 Walden, Ber. 26, 215.

5 Purdie and Marshall, Chem. Soc. J. Trans. 1893, p. 217.
B Purdie and Walker, I.e. p. 229.

7 Purdie and Bolam, ibid. 1895, p. 955 ; Cook, Ber. 30, 294.

8 Purdie and Lander, Chem. Soc. Proc. 1896, p. 221.
» Becker, Ber. 14, 1031.

10 Piutti, Compt. Bend. 103, 134 ; Marshall, Chem. Soc. Trans.
1896, p. 1023.

16 STEREOCHEMISTRY OF CARBON

Malamide, CH.OH.C01OT2.CH2CONH2.

Asparagine, CH.NH2.C02H.CH2CONH2 [a]D
— — 8° to — 5° l in aqueous solution. The isomer of
opposite activity is also known.2

Uramidosuccinamide,

CH.NHCONH2.C02H.CH2CONH2,

also obtained in the two modifications.2

3. Compounds with five carbon atoms.

Amyl alcohol, (7H.CH3.C2H5.CH2OH [o]S = - 5°.3
The isomer of opposite activity is also known.4 All
the derivatives are mentioned later.

Valeric acid, (7H.CH3.C2H5.C02H \_a~\D = +
17° 30'.5

Amyl alcohol, OH.OH.CH3.C3H7 aD = - 8° 7'
for 22 cm.6

Amyl iodide, CHI.CH3.C3H7 aD = + 1° 8' for
22 cm.6

Amyl chloride, CHC1.CH8.C3H7 aD = - 0° 5'
for 20 cm.7

Oxyglutaric acid, CH.OH.C02H.C2H4C02H [a],,
= — 2° 8 in aqueous solution.

Methylmalic acid, C.OH.CH3.C02H.CH2C02H.9

1 Becker, Ber. 14, 1031.

2 Piutti, Compt. Rend. 103, 134 ; Marshall, Chern. Soc. Trans.
1896, p. 1023.

3 Rogers, Chem. Soc. J. Trans. 1893, p. 1130.

4 Le Bel, Compt. Rend. 87, 213 ; cf. Schiitz and Marckwald, Ber.
29, 52.

5 Taverne, Rec. des Trav. Chim. des Pays-Bas, 1894, p. 201 ;
Schiitz and Marckwald, Z. c.

6 Le Bel, Bull. Soc. Chim. 33, 106.

7 Guye, Th&ses, 1891, p. 55.

8 Ritthausen, J.f.prakt. Cfcew.[2], 5, 354; Scheibler, Ber. 17, 1728.

9 Le Bel, Bull. Soc. Chim. [3], 11, 292.

THE ASYMMETKIC CARBON ATOM 17

Glutamic acid, CHNH2.C02H.C2H4C02H [a]D
= ._+ 35° l in dilute nitric acid.

4. Fatty substances with more than five carbon atoms.
Hexyl alcohol,2 CH.CH3.C2H5.CH2CH2OH [a],, = 8°.

Hexylic acid,2 GH..CHyCfLs.CHjCOJS. [a]B = 9°.
The isomer of opposite activity has been prepared
from amyl alcohol.3

l4f<7H.OH.CH,.C4H9, left-handed.

Hexylalc°holtcH.OH.C2H,C3H7,right-handed.

Hexyl chloride,4 CH.C1.C2H5.C3H7, left-handed.

Hexyl iodide,4 CH.I.C2H5.C3H7, right-handed.

Leucine,5 CH.CH2CH(CH3)2.NH2.C02H [a]D
= + 18° in hydrochloric acid solution.6 The isomer
of opposite activity has also been discovered.7

Ethyl amyl,8 CH.CH3.C2H5.C3H7 aD = + 5° for
20 cm.

5. Pyridine derivatives.

a-Pipecoline = a-methylpiperidine 9 [a]D = 35°.
a-Ethylpiperidine 9 [a]D = 7°.
Conine = a-propylpiperidine 9 [a]D = 14°.
CH2

H0C CH,

H0C

1 Bitthausen, J.f.prakt. Chem. [1], 107, 238.

2 Van Bomburgh, Rec. des Trav. Chim. des Pays-Bas, 6, 150.

3 Wurtz, Ann. Chim. Phys. [3], 51, 358.

4 Combes and Le Bel, Chem. Soc. J. Abstr. 1893, p. 246.

5 Schulze and Likiernik, Ber. 24, 669 ; 26, Bef. 500.
d Mauthner, Zeitschr. f. physiol. Chem. 7, 222.

7 Schulze, Barbieri, and Bosshard, ibid. 9, 103.

8 Just, Ann. 220, 157. ° Ladenburg, Ber. 19, 2584, 2975.

18 STEREOCHEMISTRY OF CARBON

Copellidine = methylethylpiperidine.1
Methylconine 2 [a]* = 81'33°.
Nicotine 3[a]/>= -161°.

CH CH

HC C OH CH2

II I I I
HC CH N CH2

Y <k

6. Aromatic compounds.

Mandelic acid,4 OH.CGHVOH.C02H [a]D = ±156°.

Tropic acid,5 OH.C6H5.CH2OH.C02H [>],, = 71°
in aqueous solution. Both isomers were obtained.

Phenylcystine,6 O.CH3.NH2.SC6H5.C02H [a]D
= - 4°.
Bromophenylcystine,6O.CH3.SCGH4Br.NH2.C02H.

Phenylbromomercapturic acid 6 [a]D = — 7°.
O.CH3.SC6H4Br.NH(COCH3).C02H.

Phenylamidopropionic acid,7

OH.NH2.CH2C6H5.C02H.

Tyrosine,8 CH.NH2.CH2.CGH4OH.C02H [a]D
= -8°.

Isopropylphenylglycollic acid,9
OH.OH.CGH4C3H7.C02H. Both isomers were pre-
pared. [a]D = 135°.

1 Levy and Wolffenstein, Ber. 28, 2270 ; 29, 43, 1959.

2 Wolffenstein, ibid. 27, 2614. 3 Ladenburg, ibid. 26, 293.
•» Lewkowitsch, ibid. 16, 1565, 2721.

3 Ladenburg, ibid. 22, 2590.

« Baumann, ibid. 15, 1401, 1731.

7 Schulze and Nageli, Zcitschr. f. physiol. Chem. 11, 201.

8 Mauthner, Wien. Akad. Ber. [2], 85, 882. 9 Ber. 26, Ref. 89.

THE ASYMMETRIC CARBON ATOM 19

Leucinephthaloylic acid,1

CH.C4H9.NHCOC6H4(C02H).C02H.
Phthalylamidocapro'ic acid,1

CH.C4H9.N(C202)C6H4.C02H.

Limonene.2

Carvol.3

Camphor.4

[a>=±1050

[a\D= ±62°

[a]D= ±55°

C3H7

HC CH

H2C CH

II 1
HC CH2

II 1
HC CO

H2C CO

HCH,

Tetrahydronaphthylenediamine 5 [a]D — — 7° and + 8°.
H H.NH2

H/Y\H,
HC C CH2

NH2 H2

Phenyl amyl,6 CH.CH3.C2H5.CH2C6H, aD=l° 4'.

Predictions of activity confirmed. — Thus in all

active bodies the asymmetric carbon occurs ; indeed,

1 Reese, Ann. 242, 9 ; Ber. 21, 277.

2 Ber. 21, 166. 3 Ibid. 20, 486, 2071.

4 Landolt, Opt. Drehungsvermogen, p. 83.

5 Bamberger, Ber. 23, 291. 6 Guye, Thtees, 1891.

' o 2

20 STEREOCHEMISTRY OF CARBON

in many cases activity was first suspected from the
constitution, and subsequently discovered. This
was the case with leucine, tyrosine, cystine, propy-
leneglycol, glyceric and mandelic acids, secondary
butyl-, amyl-, and hexyl-alcohol, isopropylphenyl-
glycollic acid, hydronaphthalenediamine, &c.

Doubtful statements. — A fact which inspires special
confidence is that in seven cases the supposed
activity of bodies containing no asymmetric carbon
atom has been disproved.

Propyl alcohol, C^CH.CH.OH.1

Styrolene, C6H5CHCH2.2

Trimethylethylstibineiodide, (CH3)3C2H5SbI.3

/3-Picoline = /3-methylpyridine.4

Papaverine.5

Chlorofumaric and chloromaleic acids,6
C02HCC1CHC02H.

It must then be considered doubtful whether
oxypyroracemic acid 7 with the constitution ascribed
to it, C02H.COCH2OH, really possesses the activity
discovered by Will.

1 Chancell, Compt. Rend. 68, 659, 726. Inactive according to a
private communication from Henninger.

2 Berthelot, ibid. 63, 518 ; van 't Hoff, Maandblad voor Natuur-
ivetenschappen, 6, 72 ; Ber. 9, 5 ; Krakau, Ber. 11, 1259 ; Weger,
Ann. 221, 68.

3 Friedlander, Journ. f. prakt. Chem. 70, 449 ; Le Bel, Bull.
Soc. Chim. 27, 444.

4 Hesekiel, Ber. 18, 3091 ; Landolt, ibid. 19, 157.

5 Hesse, Ann. 176, 198 ; Goldschmidt, Wien. Akad. Ber.
January 1888.

6 Perkin, Chem. Soc. Journ. 1888, 695 ; van 't Hoff, Ber. 10, 1620;
Walden, I.e. 26, 210, 508.

' Ber. 24, 400.

THE ASYMMETKIC CAKBON ATOM 21

Disappearance of the activity in derivatives. — It is
of special importance to note the activity in different
groups of derivatives, for it is found that the activity
regularly vanishes with C, the asymmetric carbon
atom. This proof is specially pertinent, because
Colson l has recently given prominence again to the
conception of an active type or radical as the cause
of rotation ; this conception, however, lacks sufficient
precision, the precision which renders it possible to
decide beforehand in which cases this type vanishes.

In the amyl series, in the derivatives of active
amyl alcohol, H3C (C2H5) CHCH2OH, the activity
persists in the ethers and amyl sulphates, in the
chloride, bromide, and iodide, in amylamine and
its salts, in the aldehyde and in valeric acid, in
diamyl ; in short, in more than sixty compounds
recently examined by Guye 2 and others. Unaided by
the theory, one would be inclined to maintain that
the activity exists in all the derivatives ; but, relying
on the theory, Le Bel3 and Just4 examined the
nearest derivatives in which the asymmetric car-
bon is lacking, the former testing methylamyl,
(H5C2)2CHCH3, and amylene, H3C(C2H5)CCH2, the
latter amylhydride. No rotatory power could be
detected in any of these three compounds.

In the derivatives of tartaric acid the same

1 Etude sur la Sttreochimie, 1892 ; Journ. de Pharm. et de
Chimie, 1893.

2 Theses, Paris, 1891 ; Walden, Zeitschr. physik. Chem. 15, 638 ;
I. Welt, Compt. Rend. 119, 885 ; Guye andChavanne, I.e. 119, 906 ;
120, 452.

3 Bull. Soc. Chim. [2], 25, 565. 4 Ann. 220, 146.

22 STEREOCHEMISTRY OF CARBON

peculiarity occurs. Starting with the right-handed
acid we find the rotatory power preserved in the
salts and esters, in tartraniic acid and tartraniide ;
in short, in forty-one derivatives recently enumerated
by Guye, in malic acid, its salts, its esters, and
its amide. But Pasteur himself did not suspect
that the activity would disappear in succinic acid,1
C02HCH2CH2C02H, obtained by the reduction of
malic acid ; the same holds for chlorofumaric acid,2
C02HCC1CHC02H, obtained by treating tartaric
acid with phosphorus pentachloride.

Starting from malic acid in the contrary direction
we have active methoxy- and ethoxy-succinic acids,
chlorosuccinic acid, asparagine, aspartic acid with
the two series of salts, uramidosuccinic acid ; 3 but
the succinic acid made from asparagine is inactive.

Further confirmation is afforded by the follow-
ing isolated cases, which will find an application
later.

Oxalic acid made from active sugar4 or active
tartaric acid 5 is inactive ; so is furfurol from active
arabinose or xylose.5

Active phenylcystine gives on treatment with
baryta inactive phenylmercaptan.6

The active oxybutyric acid of Minkowski and
Kiilz gives an inactive crotonic acid.7

Bremer and van 't Hoff, Ber. 9, 215.

Van 't Hoff, ibid. 10, 620 ; Walden, Z.c. 26, 210.

Piutti, Compt. Bend. 103, 134.

Van 't Hoff, Ber. 10, 620. 5 Ibid. 1620.

Baumann and Preusse, Z.c.

Deichmuller, Szymansky, and Tollens, Ann. 228, 95.

THE ASYMMETEIC CAKBON ATOM 23

Among observations of this kind those cases in
which compounds without the asymmetric atom are
obtained by fermentation — i.e. by the action of living
organisms — deserve special attention, because this
action specially favours the formation of active
compounds. When therefore in these circumstances
an inactive body is formed from an active one, it is
surely very probable that its inactivity arises from
its constitution being incompatible with rotatory
power. For this reason we mentioned in 1875 the
inactivity of ethyl-, propyl-, butyl-, and amyl-alcohols,
which result from the fermentation of active carbo-
hydrates.

Succinic acid l made by fermentation of active
malate and tartrate of calcium, of asparagine, and
of starch, is inactive. Further, Beyerinck, to whom
I am indebted for these samples of succinic acid
(made by Fritz), has placed at my disposal some
ethylacetate prepared by fermenting active maltose.
Van Deventer showed that this was inactive.

Finally, one might add all inactive vegetable pro-
ducts, which for the most part are made from active
material under the influence of the organism. The
inactivity of citric acid, e.g., rendered probable the
formula C02H.CH2COH(C02H)CH2C02H. This was
pointed out long ago and has since been proved.

Does any difference in the groups attached to the
carbon suffice to cause activity ? — This question arose
in the first edition. Some reserve was still necessary
as long as cases were lacking in which even the dif-

1 Ber. 10, 1620 ; 11, 142 ; 12, 474.

24 STEREOCHEMISTRY OF CARBON

ference between halogen and hydrogen — i.e. between
the simplest possible groups of only one atom —
sufficed for activity.1 There was room for doubt,
because in many cases the activity was lost on sub-
stituting one group for another — e.g. chlorine for
hydroxyl — although all the groups were still different.
Thus the following inactive halogen derivatives were
obtained from active bodies :—

Bromosuccinic acid from malic acid.2

Dichlorosuccinic acid from tartaric acid.3

lodohexyl from mannite.4

Phenyl-brom- and chlor-acetic acids from phenyl-
glycollic acid.5

Isopropylphenylchloracetic acid from isopropyl-
phenylglycollic acid.6

Since then, however, the following thoroughly
decisive cases have become known in which the
activity is retained or present.

Chloro- and bromo-propionic acids from lactic
acid.7

Chlorosuccinic acid from malic acid.3

Chloro- and bromo-malic acids from tartaric acid.7

Iodide and chloride of secondary amyl alcohol,
CH.OH.CH3.C3H7.8

Iodide and chloride of secondary hexyl alcohol,
CH.OH.C2H5.C3H7.9

1 See Guye's work below.

2 Ann. 130, 172 ; Ber. 24, 2687. 3 Walden, Ber. 26, 212.

4 Ann. 135, 130. 5 J. Chem. Soc. 59, 71 ; Proc. 1891, 152.

8 Fileti, Oazz. Chim. [2], 22, 395. 7 Walden, Ber. 28, 1287.

s Le Bel, Bull. Soc. Chim. [2], 33, 106 ; Guye, Theses, 1891.
" Combes and Le Bel, J. Chem. Soc. Abstr. 1893, 246.

THE ASYMMETKIC CARBON ATOM 25

Hexachlorhydrin of mannite,

Cinnamic acid dibromide and dichloride,2
C6H5(CHBr)2C02H.

Finally, the above-mentioned phenyl-brom- and
chlor-acetic acids, which had been known only in the
inactive form, were obtained active from mandelic
acid.

The unexpected occurrence of the inactive de-
rivatives will be explained presently.

TKANSLATOE'S NOTE

A final restriction has yet to be acknowledged.
At present we do not know a single active molecule
containing less than two carbon atoms united with
the asymmetric carbon.

Thus no activity has been observed in the follow-
ing compounds :—

Containing one carbon atom.
Chlorobromomethanesulphonic acid, (7HClBr.S03H.

Containing two carbon atoms.

Bromnitroethane, CHBr.N02.CH3.
Sodiumnitroethane, CHNa.N02.CH3.
Aldehyde ammonia, CH.OH.NH2.CH3.
Chloralsulphydrate, (7H.OH.SH.CC13.
Chloral alcoholate and hydrocyanide.
Bromoglycollic acid, CH.OH.Br.COOH.
Hydrogen silver fulminate, CHAg.N02.CN.
Ethylidene iodobromide, CHIBr.CH3.

1 Mourgues, Compt.Rend. Ill, 112.
- Liebermann, Ber. 26, 245, 833.

26 STEREOCHEMISTRY OF CARBON

Ethylidenemethethylate, CH.OCH3.OC2H5.CH3.
Ethylidenechlorosulphinic acid, (7HC1.S02H.CH3.
Chlorethylidene oxide, CH8.CHC1.0.C1HC.CH3.

The verdict of observation, then, up to the
present time, is that an asymmetric carbon alone is
not sufficient to cause optical activity, but that the
presence of the group C.C.C is essential.1 It seems
probable, however, that the inactivity of the mole-
cules just mentioned is due to an intramolecular
transformation, favoured by the mobility of the
small radicals attached to the asymmetric carbon.
The same thing is observed in the case of asymmetric
nitrogen (p. 181 post).

1 Compare Moller, Cod Liver Oil and Chemistry, p. 462
(London : Moller).

CHAPTER II
DIVISION OF THE INACTIVE MIXTURE1

INACTIVITY OF COMPOUNDS CONTAINING AN
ASYMMETRIC CARBON ATOM

EVERY active compound, then, occurring in the
two characteristic isomers contains an asymmetric
carbon atom ; on the other hand, there are many
substances which possess this peculiar constitution
and yet show no activity ; indeed, they are perfectly
certain to be inactive when prepared in the laboratory
from inactive substances.

.. From the first, Le Bel and I considered this
difficulty to be merely apparent. The exactly cor-
responding internal constitution of the two isomers,
CR^RgR^ demands that when they are formed
from CRjRgRgRg (where the similar groups R3
occupy exactly corresponding positions on each side
of the plane of symmetry passing through CR^),
the reaction should proceed with equal velocity in
two directions ; the product will consist of equal
quantities of two isomers, one resulting from the
conversion of the one R3 group into R4, the other

1 Compare Chr. Winther, Bar. 28, 3000. Tables showing the
results so far obtained and a theoretical explanation are given.

IE~OS/

OF TrfB

UNIVERSITY

>n\K

28 STEEEOCHEMISTEY OF CARBON

from the conversion of the other B3 group into R4.
Thus we get an inactive mixture, and a mixture
which, owing to the complete agreement in the
chemical and physical properties of the components,
can be separated only by special means. If we add
that, on the other hand, the two isomers, like right-
and left-handed tartaric acid, may join together to
form a so-called racemic compound, everything
justifies the expectation that the isomers may be
obtained from the product of this reaction, as Pasteur
obtained tartaric from racemic acid.

And this has gradually been done in more than
thirty cases. We have now, then, to describe the
methods, which may be briefly indicated as—

Division by the use of active compounds ; divi-
sion by the use of organisms ; spontaneous division ;
proof of divisibility by synthesis of the inactive
mixture or compound.

1. DIVISION BY THE USE OF ACTIVE COMPOUNDS

This method was based on the observation of
Pasteur that when a solution of racemic acid is
neutralised with (active) cinchonine, the salt of the
left-handed tartaric acid is the first to crystallise out.
Since that time the method has been employed with
success in many cases, and seems advantageous for
procuring a large quantity of pure substance ; but it
is limited to the division of acids and bases, because
other active bodies lack the requisite combining
power.

DIVISION OF THE INACTIVE MIXTUKE

Substance
Racemic acid,
CO,H CHOHCHOHC02H

Malic acid,
CO^HCHOHCHCO.^

a-Oxybutyric acid,

Pyrotartaric acid,

C02HC'H.CH3.CH2CO,H

Mandelic acid,
C6H5.CHOHC02H

i-Mannonic acid,
CH2OH(CHOH)4C02H

i-Galactonic acid,

CH,OH(CHOH)4C02H

Phenylbromolactic acid,
C6H5CHBrCHOHCO,H

Means
Cinchonine

Cinchonine

Brucine

Strychnine
Cinchonine

Strychnine,
Morphine

Strychnine
Cinchonine

•Ethoxysuccinic acid, Cinchonine

C02HCH(OC2H5)CH2C02H

Lactic acid, CH8CHOHC02H Strychnine

Isopropylphenylglycollic Quinine, Cincho-
acid, C3H7C<5H4CHOHC02H nine, Codeine

Cinnamic acid dibromide Strychnine

C6H5(CHBr)2C02H

Cinnamic acid dichloride Strychnine

Phenyldibromobutyric acid Brucine

Author

Pasteur.

Bremer, 'Ber.' 13,
351;'Rec.desTrav.
Chim. des Pays-
Bas,' 4, 180.

Guye and Chavanne,
' Compt. Kend.'
120, 565, 632.

Ladenburg, 'Ber. '28,
1171.

Lewkowitsch, ' Ber.'
16, 1573.

Fischer, 'Ber.' 23, 379.

Fischer, 'Ber.' 25, 124.

Purdie and Marshall,
' Chem. Soc. J.
Trans.' 1893, 218.

Purdie and Walker,
' Chem. Soc. J.
Trans.' 1892, 754.

Fileti, 'Gazz. Chi-
mica,' [2], 22, 395.

Erlenmeyer, jun., and
Lothar Meyer, jun.,
' Ann.' 271, 137;
'Ber.' 25, 3121.

Liebermann, ' Ber.' 26,
833.

L. Meyer, jun., and 0.
Stein, 'Ber.' 27, 890.

STEREOCHEMISTRY OF CARBON

Substance

Nitrosohexahydroquinolic
acid

Conine, HNC5H,,C3H7
o-Pipecoline, HNC5H9CHg
a-Ethylpiperidine,

1, 5-Tetrahydronaphthylene-
diamine

Diphenyldiethylenediamine

Copellidine (hydroaldehyde-
collidine)

Means
Strychnine

Tartaric acid
Tartaric acid
Tartaric acid
Tartaric acid
Tartaric acid
Tartaric acid

Author

Besthorn, ' Ber.' 28,
3156.

Ladenburg, ' Ber.' 19,
2975.

Ladenburg, 'Ber.' 19,
2975.

Ladenburg, ' Ber.' 19,
2975.

Bamberger, ' Ber.' 23,
291.

Feist and Arnstein,
' Ber.' 28, 3169.

Levy and Wolffen-
stein, 'Ber.' 28,
2270 ; 29, 43.

2. DIVISION BY THE USE OF ORGANISMS

In this case it may be said that the division is
due to the same causes as in the last — namely, to the
different deportment of the active isomers towards
the active compounds (proteids) of the organism.
The origination of this method is also due to Pasteur,
who observed that a dilute solution of ammonium
racemate with a trace of phosphate-leaves, after the
growth of penicillium, finally a solution of the left-
handed salt.

For stereochemical purposes the method has the
advantage that it is not limited to acids and bases ;
on the other hand, one of the isomers is lost, whereas
the former method yielded both. Moreover the pre-
paration of a pure product is not so easy, because

DIVISION OF THE INACTIVE MIXTURE

continued vegetation often destroys the other isomer
also. The process seems specially suitable in cases
where a qualitative test of possible activity is re-
quired ; accordingly it was used in all Le Bel's
investigations. In this way we may divide —

Substance
Racemic acid,

COaHCHOHCHOHCO-jH

Amyl alcohol,

CH.CH3.C.2H5CH2OH

Amyl alcohol,
CHOHCH3C3H7

Butyl alcohol,

Hexyl alcohol,
CHOHCH3C4H9

Butyleneglycol,
CHOHCH3CH,OH

Mandelic acid,

Gly eerie acid,

CHOH.CH2OH.C0.2H

Lactic acid,

CH.OH.CHj.CO.pI

Means and Product

Penicillium,
L-tartaric acid

Penicillium,
R-alcohol

Penicillium,
L-alcohol

Bacterium termo,
L-alcohol

Aspergillus, Mucor,
Penicillium,

R-acid ;
Saccharomyces

ellipsoi'deus,
Schizomycetes,
L-acid

Penicillium,

L-acid ;

Bacillus ethaceticus,
R-acid

Penicillium,

L-acid [?]

R-acid

Author

Pasteur.

Le Bel, ' Compt.
Rend.' 87, 213.

Le Bel, ' Compt.
Rend.' 89, 312.

Combes and Le Bel,
' Bull. Soc. Chim.'
[3], 7, 551.

Le Bel, * Compt.
Rend.' 92, 532.

Lewkowitsch, 'Ber.'

15, 1505.

Lewkowitsch, ' Ber.'

16, 1569.

Lewkowitsch, ' Ber.
16, 2721.

Lewkowitsch, 'Ber.

16, 2721.
Linossier, ' Bull. Soc.

Chim.' [3], 6, 10 ;

Schardinger, ' Mon.

fur Chem.' 11, 545.

82 STEREOCHEMISTRY OF CARBON

Substance Means and Product Author

Leucine, Penicillium, Schulze and Boss-

CH.NH,.C4H(J.CO.,H left-handed in hard, 'Ber.' 18, 388.

hydrochloric acid

Glutamic acid, Penicillium, Schulze and Boss-

CH.NH2.C02H.C2H4CO,H left-handed in hard, ' Ber.' 18, 388.
hydrochloric acid

Aspartic acid, Penicillium, Schulze and Boss-

CH.NH2.C02H.CH2CO,H left-handed in hard, I.e. ; Engel,
hydrochloric acid ' Compt. Rend.' 106,
1734.

o-Acrose, Beer yeast, Fischer, 'Ber.' 23,

CH.,OH(CHOH)8COCH2OH L-fructose 389.

i-Mannose, Beer yeast, Fischer, ' Ber.' 23,

CH,OH(CHOH)4COH L-mannose 382.

Ethoxysuccinic acid, Penicillium, Purdie and Walker,

CH.OC2H5.CO,H.CH2C02H L-acid ' Chem. Soc. J.

Trans.' 1893, 230.

TRANSLATOR'S NOTE

Fischer and Thierfelder ] have shown that micro-
organisms not only distinguish between isomers of
completely opposed activity, but that the transposi-
tion of two groups, attached to a single one of a
number of asymmetric carbon atoms in a molecule,
is of moment to them.

Thus the following sugars are fermentable by
various species of yeast :—

H H OH H

d-Glucose CH2OH C C C C COH
OH OH H OH

1 Ber. 27, 2031 ; see also Fischer, ibid. 27, 2985, 3228, 3479 ;
28, 1429.

DIVISION OF THE INACTIVE MIXTURE 33

H H OH OH

d-Mannose, CH2OH C C C C COH
OH OH H H

H OH OH H

d-Galactose, CH2OH C C C C COH
OH H H OH

But the same yeast species are incapable of attacking
d-talose,

H HO OH OH
CH2OH C C C C COH

OH H H H

which differs from mannose and galactose only by
the transposition of the groups attached to a single
asymmetric carbon atom.

This result is the more surprising, since changes
in the composition of the sugar, though much more
marked, do not affect these ferments, which act on
sugars with three as well as on those with nine
carbon atoms.

Similar results have been obtained with unorgan-
ised ferments. To insure fermentation, then, the
substance to be fermented and the ferment must
have their configurations adjusted to one another
like lock and key. It follows that ferments which
act on the same substance must resemble one
another in configuration like two keys ; and they
may act on one another to their mutual destruction
if the keys turn opposite ways. Experiments made
by me showed, however, no such destructive action
in the case of human and pig pepsins.

34 STEREOCHEMISTRY OF CARBON

3. SPONTANEOUS DIVISION. TEMPERATURE OF
CONVERSION

While the method of division last mentioned
depends on the action of the living organism, and
the first method is also connected therewith, in that
the active compounds employed are mostly products
of the organism, the method now to be described
does not demand the aid of life. It is a purely
chemical one, which isolates the active compound
without assistance from animate nature. This
method, too, was discovered by Pasteur, who, on
crystallising a solution of sodium ammonium race-
mate, found the two tartrates separated. Although
the method has been rarely used since (first by
Purdie to divide lactic acid ]), yet the researches
which brought to light the facts on which the method
is based have a special interest.

As a matter of history we may remark that
Stadel,2 when he evaporated the solution which in
Pasteur's hands had yielded the two tartrates, ob-
tained crystals of a double racemate of sodium and
ammonium.

This apparent contradiction was harmonised by
Scacchi,3 who showed by a thorough investigation of
the racemate in question that a high temperature
of crystallisation favours the formation of the race-
mate, while at the ordinary temperature one obtains

1 Trans. Chem. Soc. 1893, 1143. 2 Ber. 11, 1752.

3 Bendiconti delV Accademia di Napoli, 1865, p. 250.

DIVISION OF THE INACTIVE MIXTURE 35

chiefly the two tartrates. Indeed, Wyrouboff ' suc-
ceeded in showing that the phenomenon is very
simple when supersaturation is avoided. There is
then a perfectly definite limiting temperature, viz.
about 28° ; on evaporation one obtains the racemate
or the tartrate, according as the crystallisation takes
place above or below this temperature.

Temperature of transformation. — The researches
wilich I conducted with van Deventer 2 have shown
that we have here to do with a peculiar phenomenon
which may occur also outside the solution. The
mixture of the two tartrates, when heated a little
above 27°, loses a part of its water of crystallisation
and is quantitatively converted into the racemate
according to the following equation :
2C406H4NaNH44H20
= (C406H4NaNH4)22H20 + 6H20 ;
while below this temperature the reverse takes place.
The temperature mentioned is that noticed by
Wyrouboff, and the transformation observed gives
therefore a complete explanation of his results.

This conversion is also to be detected in the
following ways :

1. On mixing the racemate with the above-men-
tioned proportion of water, the originally soft mass
becomes hard, until finally a perfectly dry mixture of
the two tartrates remains.

2. A mixture of the two tartrates in equal quan-
tities, heated above 27° in sealed tubes, is partly

1 Bull. Soc. ChimAl, 210; 45, 52 ; Compt. Rend. 102, 627.

2 Zeitschr. f. phys. Chem. 1, 173.

D 2

36 STEREOCHEMISTRY OF CARBON

liquefied through loss of water of crystallisation and
formation of the racemate.

3. The expansion on formation of the racemate
renders possible an exact study of the phenomenon.
The dilatometer used consisted of a huge thermometer,
in the bulb of which was placed the mixture of the
two tartrates, this being covered with oil. .The
height of the oil in the stem of the thermometer was
read off on a scale. On heating this dilatometer for
a sufficiently long time at definite temperatures, one
observes, between 26'7° and 27'7°, a slow but persis-
tent and very considerable expansion, accompanied
by a complete change in the contents of the bulb ;
partial liquefaction takes place, together with pro-
duction of the racemate in well-formed crystals. On
cooling, the reverse phenomenon is observed.

This process of division is of special interest,
because it represents the first case of a class of
phenomena of chemical equilibrium,1 much studied
of late, and characterised by a definite temperature,
the ' conversion temperature,' above and below
which only one of the two systems can exist.

Recently van 't Hoff,2 H. Goldschmidt, and
Jorissen have adopted another method for investi-
gating phenomena of this kind. Taking the case
already studied, at the temperature of transformation
equality will exist in the vapour tension of (1) the

1 Van 't Hoff and van Deventer, Ber. 19, 2142 ; Zeitschr. f. physik.
Chem. I, 165, 227 ; Bakhuis Roozeboom, Bee. Trav. Chim. Pays-Bas,
6, 36, 91, 137 ; Zeitschr.f. physik. Chem. 2, 336.

2 Vorlesungen iiber Bildung und Spaltung von Doppelsalzen
(Leipzig, 1897, Engelmann).

DIVISION OF THE INACTIVE MIXTURE 37

water of crystallisation of the dextro- and Igevo-
tartrates, (2) a saturated solution of the above salts,
(3) a saturated solution of the salt of Scacchi,

(C4H1NaNH40(i.H20)2.

Accordingly the bulbs attached to the two limbs
of a differential tensimeter were charged with mix-
tures representing (1) and (2), and the temperature
was observed at which the tension in the two limbs
became equal. It was 26-6°.

If the temperature be raised a few degrees another
transformation takes place, the double racemate of
Scacchi now breaking up to form the single racemates :

2(NaNH4H4C406.H20)2

= (Na2H4C406)2 + ((NH4)2H4C406)2 + 4H20.

At the temperature of conversion there is equality
in the vapour tension of

(1) A saturated solution of Scacchi's salt and
'sodium racemate.

(2) A saturated solution of Scacchi's salt and
ammonium racemate.

(3) A saturated solution of sodium and ammonium
racemate.

(4) The water of crystallisation of Scacchi's salt.
To represent (4) one division of the tensimeter

was filled with 4 gm. of the salt of Scacchi which
had been dried till it lost half its water (J mol.).
Thus was formed the acid ammonium salt which is
necessary in order to reduce the ammonia tension to
a minimum. The other division contained the same
filling, with the addition of one molecule of water ;

38 STEEEOCHEMISTEY OF CARBON

that is, it was Scacchi's salt plus a mixture of dextro-
and- Igevo-tartrates. This was first heated to about
30° so as to form a saturated solution of the salt of
Scacchi with one of the two single racemates. The
tensions became equal at 34- 5°. On account of the
presence of the acid ammonium salt this temperature
is a little lower than that found by the dilatometer,
viz. 36°. It was found, further, that by heating at
once above 27° the conversion of the double tartrates
to the Scacchi salt could be avoided and the single
racemates could be obtained direct. The tempera-
ture of this transformation was found to lie, as ex-
pected, between the other two, viz. at 29°.

For sodium potassium racemate also, the exist-
ence of such a temperature of conversion had been
indicated by WyroubofTs researches.1 And it is
found by van 't Hoff and H. Goldschmidt that at
— 6° C. this salt is formed from the two tartrates :

2NaKH4C406.4H20=(NaKH4C406.3H20)2 + 2H20.

Wyrouboff's salt.

This double racemate divides at 41° into the single
racemates :

2(NaKH4C4O(5.3H20)2

= (Na2H4C406.2H20)2+ (K2H4C406.)2 + 8H20.
And at an intermediate temperature, viz. 33°, the
direct conversion takes place :

4NaKH4C4Orr4H20

= (Na2H4C406.2H20)2 + (K2H4C406.)2 + 12H20.
A similar conversion is undergone, e.g. by

1 Ann. de Cliim. et de Phys. [6], 9, 221.

DIVISION OF THE INACTIVE MIXTURE 39

magnesium sulphate, S04Mg7H20, and sodium sul-
phate, S04Na210H20, these being converted at 21°
into a double salt, astracanite, according to the
equation :

S04Mg7H20 + S04Na210H20
= (S04)2MgNa24H20 + 13H2O.

Below 21°, on the other hand, the double salt
treated with 13 molecules of water yields the two
single salts.

This case, then, is quite analogous to the forma-
tion of the racemate from the two constituents, the
right- and left-handed tartrates, at 27°.

This third method of division has been employed
successfully with racemic and lactic acids. It has
been observed l also that inactive asparagine, obtained
by the action of ammonia on maleic or fumaric ether,
crystallises in hemihedral, enantiomorphous forms,
of which the two kinds are present in equal quan-
tity. So also with homoaspartic acid.2 Also the
lactone of gulonic acid 3 divides on crystallising into
the two crystals of opposite activity ; while an indi-
cation of the same thing occurs in the case of
dimethyldioxyglutaric acid, but has not yet been
utilised for actually dividing it.

More recently Fischer and Beensch have ob-
served a similar transformation in the case of a
substance free from water, viz. methyl mannoside,
which above 15° exists only in the racemic form,
but below 8° only as the two active forms. The

1 Korner and Menozzi, Bcr. 21, Ref. 87.

- Accad. Lined, 1893, ii. 368. 3 Fischer, tier. 25, 1026.

40 STEEEOCHEMISTEY OF CAEBON

exact temperature of conversion has not been de-
termined.

4. PEOOF OF DIVISIBILITY BY SYNTHESIS OF THE
INACTIVE MIXTUEE

While in the above cases direct proof of
divisibility was afforded by actual division, the
observations now to be mentioned are not less
convincing. In these, by bringing together two
isomers of opposite activity, an inactive body was
produced which could then be identified with the
inactive product otherwise obtained. Thus the
inactive mandelic acid was obtained by Lewko-
witsch from the right and left modifications and
found to be identical with the synthesised inactive
acid, which in fact was afterwards divided. Since
then, whole groups of such racemic mixtures have
been prepared by Montgolfier, Haller, Jungfleisch, and
Friedel : in the camphor series — camphor, borneol,
bornylphenylurethane, camphoric acid, &c. ; in the
terpene series — dipentene and derivatives, limonene,
camphene, &c., by Wallach ; and finally in the
sugar group, by Fischer — arabite, mannite, mannose,
glucose, levulose, &c.

Since the result of bringing together two opposed
active bodies varies according as this occurs below or
above the temperature of transformation — in the one
case a mixture resulting, in the other a compound — it
is found that, in general, there is a difference in the
deportment of active mixtures at a given temperature,
say the ordinary temperature. These mixtures

DIVISION OF THE INACTIVE MIXTUKE 41

belong to two categories. On the one hand an
inactive substance is produced which, excepting in
optical properties, is exactly similar to the original
bodies as regards specific weight, and also chemically ;
in the other case, however, the product obtained is
entirely different from them. Probably the most
remarkable examples of this double behaviour are
those discovered by Wallach in the terpene series,
and by Fischer in the sugar group.

To show the way in which racemic compounds
differ from their components, the following list, given
by Walden,1 may be cited.

I. Inactive malic acid, C02H.CH2.CHOH.C02H
M.P. 130°-131°. Specific gravity, 2°C (d) = 1-601.
Molecular volume, Vm = 83 -70. Affinity constant,
(K) = 0-040.

L- or natural malic acid. M.P. 100°. d = 1-595.
Vm = 84-01. K =0-040. Solubility greater than the
inactive.

II. I-chlorosuccinicacid, C02H.CH2.CHC1.C02H.
M.P. 153°-154°. d = 1-679. Ym=90-83. K=0-294.
Solubility (20° C.), 1 in 2-3.

D-chlorosuccinic acid. M.P. 176°. d = 1-687.
Vm = 90-40. K = 0-294. Solubility, 1 in 4-5.

L-chlorosuccinic acid. M.P. 176°. d = 1-687.
Vm = 90-40. K = 0-294. Solubility, 1 in 4-6.

III. I-bromosuccinic acid, C02H.CH2.CHBrC02H.
M.P. 160°-161°. d=2-073. Vm=95«03. K=0'268.
Solubility, 1 in 5-2.

1 Ber. 29, 1692 ; compare J. Traube, I.e. p. 1394 ; H. Traube,
I.e. p. 2446. See also Kipping and Pope on ' Bacemism and Pseudo-
racemism,' J. Chem. Soc. 1897, p. 989.

42 STEREOCHEMISTRY OF CARBON

L-bromosuccinic acid. M.P. 172°. d = 2-093.
Vm = 94-12. K = 0-268. Solubility, 1 in 6-3.

IV. I-mandelic acid, C6H5.CHOH.C02H. M.P.
118°-119°. d = 1-300. Vm = 116-9. K = 0-043.
Solubility, 15-97 in 100.

L-mandelic acid. M.P. 130°. d = 1-341. Vm
= 113-3. K = 0-043. Solubility, 8-64 in 100.

V. I-glutamic acid,

C02H.CH2.CH2.CH(NH2).C02H.

M.P. 198°. d = 1-511. Vm = 97-29. K, see Walden,
1 Z. physik. Chem.' 8, 489. Solubility, 1 in 591.

D-glutamic acid. M.P. 202°. d = 1-538. Ym
= 95-58. K, see Walden, I.e. Solubility, 1 in 100.

VI. I-camphoric acid, C8H14(C02H)2. M.P. 202°-
203°. d =,1-228. Vm = 162-9. K = 0-00229. Solu-
bility, 0-239 in 100.

D-camphoric acid. M.P. 187°. d = 1-186. Vm
= 168-6. K=0-00229. Solubility, 6-96 in 100.

L-camphoric acid. M.P. 187°. d= 1-190. Vm
= 168-1. K= 0-00228. Solubility, 6-95 in 100.

VII. I-isocamphoric acid. M.P. 190°-191°. d
= 1-249. Vm=160-l. K=0-00174. Solubility, 0-203
in 100.

D-isocamphoric acid. M.P. 171°. d= 1-243. Vm
= 160-9. K = 0-00174. Solubility, 0-357 in 100.

L-isocamphoric acid. M.P. 171°. d= 1-243. Vm
= 160-9. K= 0-00174. Solubility, 0-337 in 100.

VIII. Eacemic acid,
C02H.CHOH.CHOH.C02H + H20.

M.P. 204°. d=l-697. Vm = 99«00. K = 0-097. Solu-
bility less than the active acids.

DIVISION OF THE INACTIVE MIXTURE 43

D-tartaric acid, C02H.CHOH.CHOHC02H.
M.P. 170°. d=l-755. Vm = 85-47. K = 0-097.

L-tartaric acid. M.P. 170°. d = 1-754. Vm
= 85-52. K=0-097.

Mesotartaric acid,

C02H.CHOH.CHOH.C02H + H20.

M.P. 140°. d=l-666. Vm = 100-8. K=0-060. More
soluble than racemic acid.

As to the melting point, it was to be expected
that the mixture should melt lower than its con-
stituents, addition of foreign bodies always lowering
the melting point. But from the above examples
we see that the racemic form has sometimes a
higher, sometimes a lower melting point than its
components ; the form of higher melting point being
less soluble, and having the smaller molecular
volume. (See also Kipping and Pope, * Proc. Chem.
Soc.' 1895, p. 39.)

As to the boiling point, it is similarly to be ex-
pected that the compound will have a higher boiling
point, but the mixture the same as the constituents,
corresponding to the halving of their maximal tension.

If we take this halving of the maximal tension as a
basis for calculating the extent to which the melting
point is lowered in the cases given above, we have

where T is the absolute melting temperature, W the
latent heat of liquefaction per kilogram-molecule.
In fact this equation gives values which fairly

44 STEEEOCHEMISTEY OF CAEBON

correspond with the observations in the case of the
gulonic acid lactones. Taking the known heat of
liquefaction for organic compounds,1 we get numbers
between 15° and 45°. This could be exactly tested
by determining the heat of liquefaction of the
gulonic lactones, and so perhaps we should arrive at
a new means of determining racemic 'character.

Proof of divisibility without direct division. — In
the above cases it was possible to prove divisibility
indirectly, by synthesis of the inactive compounds ;
but even if only one of the products of division is
known, we may obtain the desired proof, in the case
of acids at least, by examining the conductivity.
Since the divisible compounds, such as racemic
acid, are decomposed in solution,2 and the conduc-
tivity of the two active components is the same, it
is sufficient to prove that the conductivity of the
inactive body is equal to that of the active one.
As is well known, the electrical deportment varies
so strongly with the constitution, that identity in
one respect makes identity in the other extremely
probable.

That inactive malic acid 3 showed in Ostwald's
research the same conductivity as the active acid,
convinces us therefore of the divisibility of the
former. The same conclusion is to be drawn from
Eykman's4 examination of inactive quinic acid,
which also was found to be equal to the active acid.

The peculiar behaviour of compounds containing

1 Eylsm.Kn.)Zeitschr.physik. Chem. 3, 209. 2 Kaoult, ibid. 371.
3 Zeitschr. physik. Chem. 3, 370. 4 Ber. 24, 1289.

DIVISION OF THE INACTIVE MIXTURE 45

an asymmetric carbon atom, resulting from sym-
metrical bodies in ordinary laboratory experiments,
is now explained, and it only remains to mention
that, in what may be called asymmetric conditions
of formation, we may expect another and a simpler
state of things, and that we find it. The speed of
formation of the two isomers is in this case gene-
rally different and the product directly active. This
is illustrated by the direct formation of active bodies
in the organism, an apparatus consisting essentially
of active materials ; thus, from inactive carbonic
acid, water, ammonia, and nitrates, the plant forms
the innumerable active compounds with which we
are familiar — terpenes, carbohydrates, alkaloids. In
the animal organism, which consumes principally
active material, the opportunity for such observa-
tions is evidently more limited ; yet Baumann and
Preusse l were able to show that inactive bromo-
benzene is converted in the body into bromophenyl-
mercapturic acid.2

It is exceedingly probable that in other asym-
metric conditions of experiment the same direct
formation of active bodies will result ; e.g. in trans-
formations taking place under the action of right or
left circular polarised light, or caused by active com-

1 Zeitschr. physiol Chem. 5, 309 ; Ber. 15, 1731.

2 The production of the active acid may, however, be due to
preliminary formation of active alanine, and therefore cannot be
taken as proof of the production of active from inactive compounds
by the animal organism (J. f. physiol. Chem. 21, 255). On the
other hand it has been observed that, after poisoning by carbon
monoxide, the injection of inactive sodium lactate produces separa-
tion of active acid (I.e. 19, 455 ; 20, 374).

46 STEREOCHEMISTRY OF CARBON

pounds, perhaps even if only taking place in active
solvents.1

Indivisibility when the asymmetric carbon atom is
absent. — If on the one hand it may be said that
up till now no compound with an asymmetric car-
bon atom, when suitably treated, has escaped divi-
sion (with the exception of certain compounds of
symmetrical type which will be considered later), it
is important on the other hand to observe that
division has been repeatedly attempted in the absence
of dissymmetry, but so far without success.

We may again mention here the compounds
enumerated on page 23, obtained from active bodies
by fermentation &c., and yet inactive ; we may add
the inactive vegetable products. Of special impor-
tance, however, are the experiments undertaken with
the express purpose of obtaining division : e.g. of
oxalic acid by Anschiitz and Hintze ; 2 of fumaric
acid 3 by the same ; of orthotoluidine 4 by Le Bel ;
of inosite 5 by Maquenne ; of homosalicylic acid,
C6H3(CH3)(C02H)OH(1, 2, 3), of homo-oxybenzoic
acid, C6H3(OH)(CH3)C02H(1, 2, 3), and of methoxy-

1 Pope and Kipping (Proc. Chem. Soc. December 1896) find that
substances active only in the solid form, which ordinarily deposit
from solution dextro- and Isevo-gyrate crystals in equal numbers,
may be made to yield an excess of one form by dissolving an active
substance with them. Thus 5 per cent, of dextrose in the solu-
tion caused a preponderance of 1-sodium chlorate in the separated
crystals, while 5 per cent, of isodulcite caused the dextro-chlorate
to preponderate. They suggest that racemic bodies may be divided
in this way. (Compare Eakle, Chem. Centralbl. 1896, ii. 649.)

2 Ber. 18, 1394. 3 Ann. 239, 164.

4 Bull. Soc. Chim. 38, 98. 5 Compt. Eend. 104, 225.

DIVISION OF THE INACTIVE MIXTUKE 47

toluylic acid, C6H3(OCH3)(CH3)C02H(1, 2, 3), by
Lewkowitsch.1 All these attempts were unsuccessful.
Mutual conversion of active bodies. Position of
equilibrium.— From the exactly corresponding con-
figuration of the two isomers, it is at once clear that
the stability of both is the same. Now this stability
is, in general, slight ; it has long been known that
on warming sufficiently the activity is lost while
the composition remains the same. It has gradu-
ally become certain that we have here to do with
the formation of the racemic mixture. On heating
tartaric acid, racemic acid 2 is formed ; on heating
active amylalcohol (as sodium derivative) the result
is an inactive product, which Le Bel 3 has divided ;
mandelic acid yields an inactive mixture, divided by
Lewkowitsch ; 4 Schulze and Bosshard 5 obtained by
heating active leucine an inactive isomer, which
was also divided by them ; Michael and Wing 6
obtained aspartic acid, divided by Engel ; 7 Wallach
the divisible dipentene from active isomers. In
short, we have here a general method for preparing
from one isomer a derivative of opposed activity —
viz. racemising by heat and dividing the product.
Further, Walden 8 has made the curious observa-
tion that laevomalic acid produces with PC15 the

J. Chem. Soc. Trans. 1888, 781.

Jungfleisch, Compt. fiend. 75, 439, 1739.

Bull. Soc. Chim. 31, 104 ; Compt. Rend. 87, 213.

Ber. 15, 1505.

Ibid. 18, 588; Zeitschr. physiol. Chem. 10,134.

Ber. 18, 2984. 7 Compt. Rend. 106, 1734.

Ber. 28, 2766 ; 29, 133.

48 STEREOCHEMISTRY OF CARBON

chlorosuccinic acid corresponding to dextromalic
acid ; ethyl lactate behaves in the same way.1
Similarly Anschiitz, on treating fumaric acid with
bromine, observed the formation of the dibromo-
succinic acid corresponding to inactive tartaric acid ;
whereas, according to page 107 post, the racemic
compound was to have been expected.

It is important to add that so-called catalytic
influences may bring about a similar racernising, as
in the conversion of hyoscyamine into atropine by
bases,2 and of tartaric into racemic acid by the oxides
of iron and aluminium ; 3 in fact these catalytic in-
fluences occasionally cause the formation of racemic
acid in the commercial preparation of tartaric acid.

Further, the isomerisation in question, leading to
the production of inactive bodies, takes place more
easily during their formation than with the ready-
formed bodies, which is in perfect accord with all
our conceptions of the nascent state. Thus on heat-
ing albuminoids with baryta, the result was inactive
tyrosine, leucine, and inactive glutamic acid, while
when Schulze and Bosshard used hydrochloric acid
for the conversion, all the derivatives were obtained
in the active state ; in the former case, then, isomeri-
sation with loss of activity was brought about by the
united action of heat, alkali, and the nascent con-
dition. In those cases which have not yet been
cleared up by direct experiment there is yet hardly
room for doubt. That nitro- and pyro-tartaric acid

1 Purdie, J. Chem. Soc. 1896, p. 818.

2 Ber. 21, 2777. 3 Jungfleisch, Compt. Rend. 85, 805.

DIVISION OF THE INACTIVE MIXTURE 49

are inactive, although asymmetrical and prepared
from tartaric acid, is probably due to the same cause.
Hence also arises the inactivity of bromosuccinic
acid made from malic acid ; it has already been
mentioned on p. 24 that in the corresponding re-
action the chlorine product was obtained active. It
should be specially mentioned here that, when halo-
gens are brought into union with the asymmetric
carbon, isomerisation takes place very readily, as is
shown by the substances mentioned on p. 24 —
dichlorosuccinic acid, iodohexyl, phenylchlor-, brom-,
and isopropylphenylchlor-acetic acid.

The case is of course quite otherwise with Hart-
mann's l anhydride of active camphoric acid, which
changes back into the active camphoric acid ; it
chanced to be inactive under the particular con-
ditions, as, according to Colson,2 may be the case
with the isobutylamyl ester.

- Finally, it is of special interest to consider the
matter from a more general kinetic and thermo-
dynamic point of view. The state of equilibrium of
active isomers in a racemic mixture is the simplest
conceivable. Kinetically it is evident that, if the
stability is slight and leads to conversion, equilibrium
will be attained when the inactive mixture is formed.
Since, from the complete mechanical symmetry, the
tendency to conversion is equal in the two isomers,
the one present in larger quantity will always be
converted in larger quantity, until equal quantities
of each are present.3

1 Ber. 1888, 221. 2 Compt. Bend. February 1893.

3 Van 't Hoff, Ber. 10, 1620.

50 STEREOCHEMISTRY OF CARBON

Thermodynamically we have here a case most
remarkable for its simplicity. Seeing that the
equilibrium depends upon the work, E, which can
be performed by the conversion, and which in our
case, owing to the mechanical symmetry, is evidently
nil, the equilibrium-constant K, which determines
the proportion of the two active substances, must be
unity, according to the equation :

where T is the absolute temperature.1

A word in parenthesis. We have here one of
those rare cases in which alteration of the tempera-
ture does not change the equilibrium-constant ; and
this is simply because this change depends on the
heat of conversion, q (which is here nil — again
owing to the mechanical symmetry), according to
the equation :

d log K q
~dT = 2T*'

This is the simplest form of equilibrium.

INACTIVE, INDIVISIBLE TYPE

When Le Bel's paper and mine were laid before
the Societe Chimique in Paris, Berthelot 2 observed
that our views took no account of the ' indivisible
nactive type.' It was Pasteur who described this

1 Van 't Hoff, Arch. NcerL 1886 ; Kongl. SvensUa Akad. HandL
1886.^

2 Etudes de dynamique chimique.

DIVISION OF THE INACTIVE MIXTURE 51

modification in the case of tartaric acid, an indivisible
inactive tartaric acid being known, as representative
of the fourth type, in addition to the two active acids
and the combination of these two. In fact, in this
special case, in the presence of two asymmetric
carbon atoms our theory foresees the existence of
an indivisible inactive compound.

Since then some chemists have assumed the
existence of this indivisible inactive modification as
quite general. This type is, indeed, not to be ex-
plained by the theory in cases where the constitu-
tional formula contains only one asymmetric carbon
atom. In this respect the objection of Berthelot
was perfectly justified. The next thing was to find
a representative of the inactive type in bodies con-
taining only a single asymmetric carbon atom, and
Berthelot instanced the inactive malic acid, which
was, indeed, the only compound presenting a serious
objection to our theory. This malic acid had been
obtained by Pasteur from the inactive aspartic acid
of Dessaignes. This malic acid was inactive, and
Pasteur mentions it as indivisible.1 But his paper
did not give me the impression that he wished to
bind himself very strongly to this statement.

Nevertheless, the existence of the indivisible
inactive malic acid, in addition to the inactive com-
pound resulting from compensation, had from that
time been generally accepted.2

1 Ann. de Chim. et de Phys. [3], 34, 46.

' a See, e.g. Landolt, Das optische Drehungsvermogen organischer
Substanzen, p. 20.

K 2

52 STEREOCHEMISTRY OF CARBON

Through the more recent researches of Bremer,
Anschiitz, and H. J. van 't Hoff, this difficulty has
now been removed. Not only has Pasteur's acid
been studied afresh, but all inactive malic acids,
prepared according to the methods at present known,
were identified with the inactive acid which results
from mixing equal quantities of right- and left-
handed acids ; while more than one of these acids
was found capable of division. My brother l proved
the identity of the synthesised inactive acid with
that of Pasteur. He prepared its acid ammonia
salt in the two forms which are observed in the case
of Pasteur's acid, according as the salt is anhydrous
or hydrated. He proved 2 the same thing for the
inactive acid which had been obtained by Loydl by
heating fumaric acid with caustic soda, and this
identity was confirmed by the division effected by
Bremer.3 The same crystalline form was observed
in Kekule's acid ammonium malate prepared from
bromosuccinic acid.

Anschiitz4 found on a crystallographic com-
parison of these salts, made from the acids of
Pasteur, Kekule, and Jungfleisch (the last obtained
by heating fumaric acid with water), that here also
identity exists. Jungfleisch,5 too, found his acid
ammonium malate to be crystallographically identical
with that of Pasteur, though he does not give the
measurements.

1 Maandblad voor Natuurwetenschappen, 1885, Bijdrage to
de kennis der inaktieve Appelzuren. Diss. 1885.

2 Ber. 18, 2170. 3 Bee. Trav. Chim. Pays-Bas, 4, 180.
4 Ber. 18, 1949. a Butt. Soc. Chim. 30, 147.

DIVISION OF THE INACTIVE MIXTURE 53

This evidence has been strengthened by an
observation of Piutti,1 who recognised in the in-
active aspartic acid, obtained by mixing the right
and left isomers, the acid prepared by Dessaignes,
which was the one used by Pasteur for making
malic acid. We may add that the malic acid 2
prepared by heating maleic acid with caustic soda
has been found identical with the divisible malic
acid, an observation which has since been confirmed
by the probable identity of the methyl- and ethyl-
-malic acids which Purdie 3 obtained on treating
fumaric and maleic acids with sodium methylate
and ethylate. Thus the isomerism of these acids
disappears in the malic acid derivatives formed from
them.

Then, too, what Fischer observed in the case of
galactonic acid is most important. From mucic
acid, which in accordance with its symmetrical
formula, C02H(CHOH)4C02H, can be inactive and
indivisible, as indeed it is, he obtained a galactonic
acid, C02H(CHOH)4CH2OH, not of the inactive
indivisible type, but a product which was capable
of division ; surely a proof that even under the most
favourable conditions no inactive indivisible type
results, unless its existence is justified by the sym-
metrical constitution.

1 Compt. Rend. 103, 134. 2 Ber. 18, 2173.

3 Chem. Soc. J. 1885, 855,

STEREOCHEMISTRY OF CARBON

CHAPTEK III

COMPOUNDS WITH SEVERAL ASYMMETRIC
CARBON ATOMS

I. APPLICATION OF THE FUNDAMENTAL
CONCEPTION

Spatial arrangement. Free rotation. — From the
hypothesis that the groups attached to an asym-
metric carbon atom correspond to an unsymmetric
tetrahedron, it follows at once that for a compound
with two asymmetric carbon
atoms joined to each other,
CGE^KaB,, 0B4B5B6, the arrange-
ment is determined as far as this :
each carbon atom must form at
once the centre of one and the
corner of the other tetrahedron,
as shown in the accompanying
figure.

Every other arrangement,
however, obtained by rotation (of
the lower tetrahedron, e.g.) round the axis C — C
must be equally in harmony with the fundamental
conception. But in order to avoid this idea of an
infinite isomerism, no additional hypothesis is

Fig. 7.

UNIVERSITY
SEVEEAL ASYMMETEIC cbssfiSmS 55

necessary. Free rotation being admitted by the
fundamental conception, the mutual action of the
groups Ej E2 E3 on the one hand, and E4 E5 E6 on the
other will lead to a single ' favoured configuration.'
It is for the present indifferent which we call the
' favoured configuration,' and we may take as such
the arrangement represented by the figure, where E!
is above E4, E2 above E5, E3 above E6.

We may use now either the model recommended
on p. 8, or, following Friedlander, we may improvise
one from caoutchouc tubes and sealing-wax, each
tetrahedral grouping being represented by four short
tubes meeting at equal angles.1 Or, instead of
models, we may, as has been proposed by Fischer
and also by myself, choose as the most suitable way
of representing these isomers, a projection, in which
the front groups E3 and E6 are turned upwards or
downwards, and so appear on paper thus :

E, C B2
E4 C E5

These projections may conveniently be used for
illustrating the possible isomers. That there are
four of these is at once evident, since each asym-
metric carbon involves a doubling.

These differences are represented by changing
the order of the groups Ej E2 E3. But if, without

1 It is convenient to attach the tubes to a hollow caoutchouc
ball (Jowett's model).

56 STEREOCHEMISTRY OF CARBON

changing this order, we simply move E, to E2,
K2 to K3, E3 to E4, we only bring about the above-
mentioned rotation and no isomerism results. But
if E! and E2 change places we get a new isomer ;
also by transposing E4 and E3 ; hence the following
symbols represent the four isomers :

No. 1 No. 2 No. 3 No. 4

E3 E3 E3 E3

E! C E2 E2 C Et E! C E2 E2 C ^

E4 C E5 E4 C E;. E5 C E4 E5 C E4

E(, Eg Eg E6

It is plain that these are reduced to two directly
the asymmetry of one of the carbon atoms ceases
through E. and E4 becoming identical ; the difference
between No. 1 and No. 3 on the one hand, and
between No. 2 and No. 4 on the other, then vanishes.
Several asymmetric carbon atoms. — The special
advantage of these projections lies in the fact that
they may almost be said to gain in simplicity when
the cases become more complicated. For represent-
ing the isomerism in the simplest cases they are not
well adapted ; here they have to compete with the
cardboard model. For three asymmetric carbons
they are decidedly superior. The number being then
again doubled we have to expect eight isomers ; in
general, 271 for n asymmetric carbons. The middle
carbon atom then holds two groups :

If now the configurations are worked out in three
dimensions — according to Friedlander, e.g. — and then

SEVERAL ASYMMETRIC CARBON ATOMS 57

utilising the free rotation, one of the simplest pos-
sible positions is chosen, where B! B2, B7 B8, and
B4 B5 are in parallel lines, the projection leads to a
formula like that below, and the eight isomers result
on simply transposing B, and B2, B7 and B8, B4 and

9 *No. 1 No. 2 No. 3 No. 4

R~D ~D ~R

a -"a -^3 -"a

BI 0 B2 B2 0 Ej JLij O ' -Qi2 JAi2 O -tvj

B. C B8 B7 C B8 B7 C B8 B7 C B8

B4 C B5 B4 C B5 B5 C B4 B5 C B4

E6> E6 B6 E6

No. 5 No. 6 No. 7 No. 8

Bj C E2 E2 C Bj Bj C B2 B2 C Et
Eg Q B7 Eg O E7 Eg O E7 Eg O Jixi7

E/^i T> *D f^ T? T? (~^ T? T? /^ T?

4 l^ JIX- XV4 V>< -L\J5 -LV5 W _LV4 JQjg \J JAi4

B6 B6 E6 B6

II. EXPERIMENTAL CONFIRMATION

A. NUMBER AND CHARACTER OF THE ISOMERS
TO BE EXPECTED

The actual preparation of the isomers (which, as
we have seen, should number four, eight, or sixteen,
according as two, three, or four asymmetric carbon
atoms are present) is simple, provided this can be
effected by combining several compounds, each con-
taining one asymmetric carbon. Let us take, for
instance, as a starting point, the two active malic
acids ; with these and the two active amylalcohols
we can evidently prepare four amylmalic acids. If
now we introduce in place of the hydroxyl hydrogen

58 STEEEOCHEMISTEY OF CAEBON

atom the radical of any acid obtainable in two forms
of opposite activity, e.g. lactic acid, we should have
the eight bodies, which, on saturating with the two
conines of opposite activity, would give us the
required number of sixteen.

As to the characters of the isomers, a considera-
tion of the above, as well as a glance at the formulae
Nos. 1 to 4 and Nos. 5 to 8, shows that the isomers
would be grouped in pairs. The symbols No. 1 and
No. 4, No. 2 and No. 3, in the first series, and those
which may easily be found in the second series, are
reflections one of the other, and stand to each other
therefore as the two isomers with one asymmetric
carbon atom, and are, like them, so similar that one
might be taken for the other. The existence of the
second asymmetric carbon atom only betrays itself
by the appearance of a second type, which is also
present in two forms, but in general differs from the
first type in activity, melting point, and solubility.
For example, in the case of the experiment which we
have supposed to be carried out, No. 1 and No. 4
would correspond to left-amyl left-malic acid and
right-right acid ; No. 2 and No. 3 to right-amyl left
acid and left-amyl right acid.

The following have been obtained :

Two asymmetric carbon atoms.— The four active
borneols and their derivatives, obtained by Mont-
golfier1 and Haller 2 by reduction of camphor,
exactly correspond with the above.

1 Thdses sur les Isomdres et les Ddrivds du Camphre et du BorneoL

2 Compt. Rend. 105, 227 ; 109, 187 ; 110, 149 ; 112, 143.

SEVERAL ASYMMETRIC CARBON ATOMS 59

Camphor Borneol

HC C

HC CO H2C CH(OH)

HCH3 HCH3

r- and 1-Borneol (a) [a]D = + and - 37° (in

alcohol), + and - 38°
(in toluene)

r- and 1-Borneol (/3) [>]„ = + and - 33° (in

alcohol), + and - 19°
(in toluene)

Borneolphenylurethane (a) [a]D = + and — 35°

" (M.P. 137°)

Borneolphenylurethane (/9) [a]D = + and - 57°

(M.P. 130°)

A second example is afforded by limonenenitroso-
chloride and its derivatives : l

Limonene Nitrosochloride

C,H,
HCT "cH HC CHC1

I II II

H2C OH H2C CNOH

V V

HCH3 HCH3

1 Wallach and Conrady, Ann. 252, 144.

60 STEREOCHEMISTRY OF CARBON

r- and 1-a-Nitrosochloride [a]D = + and — 313°

(M.P. 103°)

r- and l-/3-Nitrosochloride [a]n = 4- and — 241°

r- and 1-a-Nitrolepiperidine [a]D = + and — 68°

(M.P. 94°)

r- and l-/3-Nitrolepiperidine [a]7, = + and — 60°

(M.P. 110°)

Perhaps the four camphoric acids come in the
same category :

HC = C (C3H7) C02H CH2C(CH3) C02H

H2CCH(CH3)C02H CH2C(C3H7)C02H

(Kekule ') (Bamberger 2)

r- and 1-Camphoric acid (a) [a]D = + and — 46°

(M.P. 180°), dissolves
in 160 parts of water
at 15°

r- and 1-Camphoric acid (J3) 3 [a]7; = + and — 46°

(M.P. 113°), dissolves
in 268 parts of water
at 15°

The constitution being here uncertain, however,
the possibility of an isomerism like that of fumaric
and maleic acids is not excluded, and this would
explain the remarkable equality in the rotating
power of the a and /3 modifications. This occurs,
however, in other cases and will be discussed later.

1 Ber. 6, 932. 2 Ibid. 23, 218.

3 Friedel, Campt. Rend. 108, 978 ; Jungfleisch, I.e. 110, 790 ;
Marsh, Ber. 23, Eef. 229.

SEVERAL ASYMMETRIC CARBON ATOMS 61

In the case of atropine, which, from its decom-
position products, tropine and tropic acid,1 contains
at least two asymmetric carbons :

CH2

HC CH2

HC (7HCH2CH2OCCH(CH2OH)C6H6

\X o

N
CH3

there have been obtained the left- and right-rotating
atrophies,2 [a]D = 10°, M.P. 110° ; of the two other
modifications only one is known, viz. hyoscyamine,
[a]j, = - 21°, M.P. 109°. The atropine formed from
this by the action of bases, which according to
Hesse 3 is active, may belong to a third type.4

There is still another point on which more light
is required. The left-handed atropine, resulting from
left-atropic acid and inactive tropine, could also exist
in several modifications, since this tropine must be
considered as a racemic mixture.

In the case of the allied substance, cocaine ( [a]D
= - 16° ; 5 as HC1 salt [a]7, = - 68°), and of ecgonine
(as HC1 salt [a]D = - 62° 6):

1 Ladenburg, Ber. 21, 3065 ; Einhorn, I.e. 23, 1338.
- Ladenburg, Ber. 22, 2591.
3 Ann. Chem. 271, 100.

1 Pseudohyoscyamine, [<*]/> = — 21°, gives on decomposition an
isomeric tropine, like hyoscine (J. Chem. Soc. Abstr. 1893, p. 491).
5 Ber. 20, 320. 6 Einhorn, Ber. 22, 1495.

62 STEREOCHEMISTRY OF CARBON

Cocaine

CH2

!TT

HC CH

HC CHCH(OC7H50)CH2C02CH3

N
CH3

Ecgonine

CH0

HC CH2

HC CHCH(OH)CH2C02H

N
CH3

the transformation which the latter undergoes when
treated with alkalies corresponds to that undergone
by hyoscyamine, only there results here a right
ecgonine l (as HC1 salt \_a]D — + 20°) which yields a
right cocaine (as HC1 salt [a]7, = + 42°). Both are
therefore representatives of the (3 type.

However, here too the constitution is doubtful.
If we were to accept Merling's 2 tropine formula :

CH2 XC\

/^ \ TT rt r\1\

HC CH2

II I
HC CHCH9CH9OH

C'JIOH

H.C

CH8 \N

(Ladenburg) ^-jjj

(Merling)

1 Einhorn, Ber. 23, 468 ; Liebermann, I.e. 511.

2 Liebermann, Ber. 25, 929.

SEVERAL ASYMMETRIC CARBON ATOMS 63

we should expect to find four asymmetric carbons in
atropine and cocaine, and accordingly sixteen isomers.1
And Merling's formula has been rendered the more
probable, since Willstatter has found two inactive
tropines (probably racemic). Ladenburg's formula
admits of only one.

Three asymmetric carbon atoms. — Here there should
be eight isomers, in four pairs. If we take the left
and right tartaric acids as corresponding to sub-
stances with a single asymmetric carbon atom, then
we find that a not inconsiderable proportion of these
eight isomers has been prepared by Wallach and
Conrady 2 from limonene :

r- and 1-a-Nitrolebenzylamine

right tartrate [a]D - 50° and + 70°

r- and 1-a-Nitrolebenzylamine

left tartrate \a\j, - 70° and + 50°

but the four isomers of the /3 type are lacking.
Also, Haller has obtained chloralbornylates,

CC13.CH(OH)C10H170,

in four modifications, r- and 1- (a), and r- and 1- (13) ;
while it is quite possible that in each of the four
methods of preparation, e.g. from chloral and r-
borneol (a), two isomers were formed.

In the sugar series, in the pentose group,

COH(CHOH)3CH2OH,

1 Ber. 29, 936. * Ann. Chem. 252, 144.

64 STEREOCHEMISTRY OF CARBON

we have :

r- and 1-Arabinose l [a],, = + and — 104° (at

first 157°)

Xylose [a]l} = + 19° (at first 79°)

Eibose 2

Here, then, three types have been experimentally
realised, which also have been found to recur in the
corresponding acids :

Arabonic acid [a]D < — 8° ; as lactone [a\n = — 74°
Xylonic „ [ojj, = - 7° ; „ „ [a]/, = + 21°
Eibonic „ ? „ „ [a],, = - 18°

Four asymmetric carbon atoms. — Of the sixteen
isomers (eight types) there have been prepared, in
the case of the glucoses,

COH(CHOH)4CH2OH,

and particularly by Fischer : 3

1- and r-Glucose [a]w = 53° (at first 105°)

1- and r-Mannose4 [a]D = 13°

1- and r-Gulose

Galactose [a]D = 80° (at first 118°)

Talose

Idose

Of the corresponding acids,

C02H(CHOH)4CH2OH,

and their lactones, there have been obtained :

1- and r-Gluconic acid [a]D — 8° ; as lactone, 68°
1- and r-Mannonic acid [a]D = 3° ; „ „ 54°

1 Ber. 26, 740. - Fischer, Ber. 24, 4220.

3 Ber. 24, 1840, 3622. 4 I.e. 22, 368, 3218.

SEVERAL ASYMMETRIC CARBON ATOMS 65

1- and r-Gulonic acid l [a\n — 14° ; as lactone, 55°
Galactonic acid [a]D < — 11; ,, „ —71°

Talonic acid,2 as lactone, strongly left-handed.

B. FORMATION OF THE ISOMERS WITH SEVERAL
ASYMMETRIC CARBON ATOMS

Whereas the formation of a compound with
several asymmetric carbon atoms by the union of
two substances, each containing one such atom,
leads to results which can easily be foreseen, the
.case is altered when the number of the asymmetric
carbon atoms increases through a transformation
taking place within the molecule.

First case. — Theoretically the simplest case is
that in which we start from a single compound with
an asymmetric carbon atom, that is, a compound
active and not racemic.3 If we introduce into such
a compound a new asymmetric carbon atom, as in
the transformation of camphor to borneol, we may
in general expect the production of two isomers.
But this case is quite distinct from that in which the
original compound contained no asymmetric carbon
atom, where the resulting isomers are images of
each other and possess that identity of internal
structure which causes the formation of equal
quantities of each. Here the case is different. We
have now to do with conditions like those which

. ' Lc. 24, 526. * Z.c. 24, 3625.

3 To indicate a compound rendered inactive by the mutual
counterbalancing of two active isomers, it is as well to use the word
chosen by Pasteur, with whom this conception originated.

66 STEREOCHEMISTRY OF CARBON

determine, e.g. the formation of the right malate of
right and of left conine. The formation of equal
quantities of the two isomers, which will in general
possess unequal stability, is by no means to be pre-
dicted ; indeed, one isomer may predominate to such
a degree that the other escapes detection ; further,
the two isomers may be separated by ordinary
means, e.g. by crystallisation, without necessitating
a resort to the special means of dividing optical
isomers.

The researches of Montgolfier and Haller men-
tioned above afford the most suitable illustration of
all this. On conversion into borneol, camphor gives
two isomers, the right-handed, stable, ordinary
modification (a), and a left-handed unstable
modification (/3). These may be separated from
each other by simple crystallisation, and yield on
oxidation the same original camphor. The left-
handed matricaria camphor also forms two com-
plementary compounds, as shown in the following
table :
Ordinary camphor Bright stable borneol [a]D = +37°

aD= + 55° [left unstable „ [a}D = - 33°
Left camphor deft stable ,, [a]D = — 37°

an=— 55° 1 right unstable „ [a]D=+33°

We may add that turpentine oil also yields two
isomeric borneols l on treatment with sulphuric
acid, and that there are two camphoric acids corre-
sponding to each camphor.

1 Bouchardat and Lafont, Compt. Rend. 105, 49.

SEVERAL ASYMMETRIC CARBON ATOMS 6?

Similarly, E. Fischer,1 by addition of hydrocyanic
acid, has formed two acids, 1-mannonic and
1-gluconic acids, from arabinose ; a- and y8-gluco-
heptonic acid from glucose ; and a- and /3-gluco-
octonic acid from heptose, the asymmetric group,
XCH(OH)C02H, being introduced in place of the
aldehyde group. Glucose yields, moreover, two
isomeric methylglucosides.2 Finally, by reduction of
levulose: CH2OH(CHOH)3COCH2OH, asymmetry
is introduced into the CO group, and the result
is the simultaneous formation of two isomeric
alcohols, mannite and sorbite.3

There is every reason to class in this category
the formation of the isomeric nitrosochlorides which
were obtained by Wallach4 from limonene (p. 60),
by means of amylnitrite and hydrochloric acid ;
the right limonene gives, e.g. an a- and /3-nitrosyl-
chloride (chlorinated oxime). It seems indeed, at
the first glance, somewhat strange that each of
these chlorides should yield with amines — e.g.
piperidine — a mixture of a- and #-nitrosamine ; but
this is probably due to an isomerisation taking place
during the transformation, such as, according to
p. 49, is especially apt to occur in the case of halogen
derivatives.

Finally, in the fact that left and right ecgonine

1 Ber. 23, 2611 ; 24, 2685 ; Ann. 270, 64.

2 Alberda v. Ekenstein, Rec. des Trav. Chim. des Pays-Bast
1894, p. 183.

3 Ber. 23, 3684; Meunier, Campt. Rend. Ill, 49.

4 Ann. 252, 106 ; Ber. 23, 3687 ; 24, 1653, 2687.

68 STEREOCHEMISTRY OF CARBON

(p. 62) yield the same active anhydrecgonine and
the same ecgonic and tropic acid, we may see another
example of the disappearance of isomerism conse-
quent on the elimination of an asymmetric carbon
atom.1

Second case. — A case theoretically more compli-
cated, but often realised in the laboratory, occurs
when two asymmetric carbon atoms are introduced
into an inactive or racemic compound, as in the
addition of bromine to cinnamic acid, forming
C(JH5(CHBr)2C02H, and in the addition of nitrosyl-
chloride to dipentene (= racemic limonene) . In both
cases we have to expect the formation of an inactive
mixture, consisting of two racemic pairs, represented

by:

First pair : + A + B and — A — B

Second pair : + A — B and — A + B
The ordinary methods of separation yield, then, two
(racemic) isomers, the special methods yielding
four.

It is only lately that such cases have been experi-
mentally demonstrated. Wallach was able to follow
them out in detail by preparing from 1- and
r-limonene-a-nitrosylchloride the inactive, or i-nitro-
sylchloride (a), and then in the same way the
i-nitrosylchloride (J3) . On treating dipentene he then
obtained and isolated the i-(a)- and i-(/3) -products.

Erlenmeyer, jun., Lothar Meyer, jun., and Lieber-
mann have broken up the cinnamic acid bromide
(00=68°) and the last named the dichloride also

1 Ber. 24, 611.

SEVEKAL ASYMMETKIC CAKBON ATOMS 69

(aD= 67°) . The division of bromophenyl-lactic acid is
the third example of division in presence of two asym-
metric carbon atoms. But the third and fourth
isomers are still lacking. On the other hand, there is a
whole series of as yet undivided racemic com-
pounds, which have already been obtained in the
two isomers foreseen by the theory. Such are : bro-
mine addition products of crotonic and isocrotonic
acids, CH^CHBrJjCOjH,1 angelic and tiglic acids,
CH3CHBrCBrCH3C02H,2 hypogaeic and gaidinic
acids, CH3((7HBr)2C13H2502, oleic and elaidic acids,
CH3(CHBr)2C1-H2902, erucic and brassidic acids,
CH3 (CHBr)2C19H3702, mesaconic and citraconic
acids, CH3CBr (C02H) CHBrC02H. Such also are the
bi-substituted succinic acids, all of which have been
obtained in two modifications : brommethyl-,3
methylallyl-, allylethyl-, benzylmethyl-, benzyl-
ethyl-, methylphenyl-succinic acid4 ; further, methyl-
ethyl and methylpropyl-glutaric acids, and isomeric
glycols, X(CHOH)2Y, like phenylmethylglycol,5
which, according to Zincke,6 constantly occur in
two modifications.

Interesting, too, is the fact lately established by
Schiff,7 that crotonchloral gives with amides (acet-

1 Melikoff, Ber. 16, 1268 ; Wislicenus, 20, 1010.

2 Puckert, Ann. 250, 244 ; Fittig, 259, 1.

3 Bischoff, Ber. 23, 3622.

4 Ibid. 24, 1876 ; Zeitschr. f. physiol. Chem. 8, 465.

5 Zincke, Ber. 17, 708. 6 Ber. 20, 339.

7 Ibid. 26, 446; see also Griner, Ann. de Chim. et de Phys.
2], 26, 305.

70 STEEEOCHEMISTEY OF CARBON

amide, benzamide, formamide) two isomers ; this
would be expected from the formula .

CH3(7HC1CC12CH(OH)NHC2H30.

But that crotonchloral should be recovered from
this in two isomeric forms is inexplicable.

C. TEANSFOEMATION OF ISOMEES WITH SEVEEAL
ASYMMETEIC CAEBON ATOMS

As has been stated, compounds containing a
single asymmetric carbon, form, on heating, an
inactive mixture corresponding to the state of stable
equilibrium.

It is otherwise with compounds containing two
or more asymmetric atoms. It is evident that here
too the inactive mixture corresponds to the state of
equilibrium ultimately attained ; but this final state is
reached in two phases, since in general one of the
two asymmetric groups is converted faster than the
other. Sometimes, indeed, the conversion of one
group may be complete when the other is still
unaltered. Beginning, then, with the compound
+ A + B, we shall get first a mixture of + A + B and
+ A — B. It is by no means necessary that the
quantities of the two products formed at the end of
the first phase should be equal, for the two molecules
which are not images of each other are in general of
different stability. It is therefore not strange if
almost the whole mass becomes converted into
+ A— B, the direction of the rotation being perhaps
reversed. In fact, this has been found to take place.

SEVEKAL ASYMMETRIC CAKBON ATOMS 71

And first let us recall Pasteur's l words concerning
the transformations in the quinine group :

' Let us consider the three isomers, quinine, quini-
dine, and quinicine. Quinine is left-handed, quini-
dine right-handed, both to a considerable degree.
Quinicine is right-handed, but, compared with the
others, very slightly so. . The logical, I had almost
said the inevitable, explanation of these results is
the following : The quinine molecule is double, and
consists of two active bodies, of which one is strongly
left-handed, the other very slightly right-handed.
This latter is stable on heating, resists transformation
into the isomeric group, and, persisting unaltered in
quinicine, imparts to this the weak right rotation.
The other group, which, on the contrary, is strongly
active, becomes inactive when quinine becomes
converted by heating into quinicine. Accordingly
quinicine would be nothing else than a quinine in
which one group has become inactive. Similarly
quinicine would be a quinidine in which one group
has become inactive ; but in quinidine this strongly
active group is right-handed instead of left-handed
as in quinine, and still combined with that slightly
active and stable group which, persisting in quinicine,
imparts to this the slight right rotation. I could
repeat this word for word with reference to the
isomers, cinchonine, cinchonidine, and cinchonicine,
which are constituted like the related quinine
isomers; for they present exactly the same relations.'

The only difference between these views and those

1 Compt. Rend. 37, 110.

72 STEKEOCHEMISTBY OF CAEBON

developed above is that in the latter nothing has
been said about the so-called groups.

As examples of transformations resulting from
change in one of the asymmetric atoms, may be
mentioned :

Borneol. — Prepared from ordinary camphor, the
product is a mixture in .which the left borneol
predominates; on heating, almost the whole of this
modification is transformed (this is the reason why
Moiitgolfier called it unstable) and produces ordinary
right-handed borneol, the sign of the rotation being
reversed.

Menthol. — This compound, which contains two
asymmetric carbon atoms,

HCC3H7

H2C CH2

H2C CO

H(7CH3

behaves in the same way. Beckmann l observed a
transformation from left to right rotation on heating
to 30° in presence of sulphuric acid.

Gluconic and mannonic acids present, according
to Fischer,2 the same peculiarities, an analogous
transformation occurring on heating them with
quinoline. Only here in the final condition both
isomers are present together, whereas in the former
examples one of them almost vanished. Here, too,

1 Ann. 250, 322. -' Ber. 23, 800.

SEVERAL ASYMMETRIC CARBON ATOMS 73

we must class camphoric acid, if, with Bamberger,1
we assume in it two asymmetric carbon atoms. The
conversion of right into left acid,2 which takes place
on heating, would then be traceable to the same
cause.

We may add, also, the conversion of arabonic
into ribonic 3 acid, of galactonic into talonic,4 of a- into
/3-gluco-octonic acid,5 and finally, in all probability,
that of left into right ecgonine (p. 62) and of hyos-
cyamine into atropine (p. 61), both under the influence
of alkalies. In the last case the complete disappear-
'ance of the activity is remarkable, as in the case of
such a slightly active body we might expect trans-
formation in only one of the asymmetric groups ; and
recently Hesse 6 has announced the activity of atro-
pine, which is especially evident in the sulphate.

It is to be observed further that, so far as is
known, the transformation takes place in the part of
the molecule richest in oxygen, that is, as near as
possible to the carboxyl group when this is present.
This is rendered probable in the case of the conversion
of left into right ecgonine by the formation of the
same anhydrecgonine and of the same tropic acid
from both isomers ; in the case of the conversion of
mannonic into gluconic acid, and of a- and /3-gluco-
octonic acids by the relations to arabinose and
heptose. Moreover, it is well known that in general
the presence of oxygen in organic compounds brings

1 Ber. 23, 218. 2 Jungfleisch, Compt. Rend. 110, 790.

3 Fischer, Ber. 24, 4216. 4 Ibid. 2622.

5 Ann. 270, 64. 6 Ibid. 271, 100.

74 STEREOCHEMISTRY OF CARBON

about a certain loosening, which often determines the
point at which the molecule is attacked and also the
breaking up into ions.

It is remarkable that in the transformations con-
sidered above, the reverse rotation is in several cases
equal to the original rotation :

Stable borneol (a) + 37° (/3) - 37°

Camphoric acid (a) + 46° (£) - 46°

Limonenenitropiperidine (a) —68° (/3) + 60°
Mannite and sorbite, both rotating feebly.
Gluconic and mannonic acid, the same.
Arabonic and ribonic acid, the same.
Left menthone, — 28° ; right menthone, + 28°.
This equality is not to be confounded with that
observed in the case of a single asymmetric carbon
atom, and in derivatives it is lacking.

D. SIMPLIFICATION THROUGH SYMMETRY OF THE
FORMULA. INACTIVE INDIVISIBLE TYPE

Tartaric acid type. — If we have to do with the
presence of asymmetric carbon in a symmetrical
formula, the case is simplified. To begin with the
simplest case, CEjE^gCEjEgCg, the four symbols
given above (p. 57) assume the following form :

No. 1 No. 2 No. 3 No. 4

Ej O E3 E3 0 Ej Ej 0 E3 E3 \j Ej
E, O Eo E, 0 Eo E., C> E, En 0 E,

1 o 1 o o 1 o 1

E2 E2 E2 E2

Here, however, No. 1 and No. 4 are identical, as

SEVEEAL ASYMMETRIC CARBON ATOMS 75

may be shown with the models, but is evident also
from these symbols if we consider that a projection
of this kind may be moved round in the plane of the
drawing, and therefore may be turned upside down,
by turning it through 180° in the direction of the
hands of a watch ; when this is done No. 1 coincides
with No. 4. This configuration is also characterised
by the fact that it is symmetrical, as is also shown
by the model, but is again expressed in very simple
fashion by the symmetry of the projections. There
is accordingly no activity to be expected here ; it is,
"then, the ' inactive indivisible type ' which results
from the symmetry of the formula. The symbols
No. 2 and No. 3 are evidently asymmetrical images
of each other, and correspond therefore to bodies
of opposite activity.

A perfect illustration of this occurs in the isomer-
ism of the tartaric acids. In this group we are, in
fact, acquainted with the two isomers of equal and
opposite activity, which are represented by the for-
mulae:

C02H C02H

HOCH and HCO H

HCOH HOCH

C02H

as well as the inactive mixture of the two — racemic
acid — which was divided by Pasteur. But what
especially characterises this case is the existence of
an indivisible inactive isomer, which was also dis-
covered by Pasteur, and which some years ago

76 STEREOCHEMISTKY OF CARBON

Przibytek l tried in vain to divide. In fact, such a
compound was to be predicted from the formula :

C02H
HCOH
HCOH

C02H

Erythrite, CH2OH(CHOH)2CH2OH, maybe cited
as a second instance of this inactive indivisible type,
since Przibytek 2 has shown that this yields on oxi-
dation the inactive non-racemic tartaric acid. From
the constitution of erythrite the possibility of in-
activity without divisibility was, in fact, to be expected.
Thirdly, we must now add erythrene- or pyrrolylene-
bromide, CH2Br(CHBr)2CH2Br (tetrabromobutane),
since Griner 3 has converted this into erythrite ; the
liquid isomeric bromine compound 4 would then
represent the racemic mixture.

Here, too, we must mention several compounds
whose constitution resembles that of tartaric acid in
that they possess a symmetrical formula with two
asymmetric carbon atoms. These compounds possess
a special interest because they all present a case of
isomerism, which, inexplicable according to the old
views, is a self-evident necessity of our theory. As
in the case of erythrenetetrabromide, these isomers
correspond to the inactive indivisible tartaric acid
and to racemic acid. Most of these compounds

1 Ber. 17, 1412. 2 Ibid. 20, 1233.

3 Compt. Rend. 116, 823.

4 Henninger, Compt. Rend. 104, 144 ; Ciamician, Ber. 19, 569 ;
20, 3061 ; 21, 1430.

SEVERAL ASYMMETRIC CARBON ATOMS 77

have been investigated by Bischoff in his study of the
bisubstituted succinic acids possessing the sym-
metrical formula, C02H(CHX)2C02H. Such are the
dibromo- and isodibromo-succinic acids, dimethyl-,1
diethyl-,2 diisopropyl-,3 and diphenyl-succinic 4 acids,
with their derivatives, ethers, anhydrides, &c., which
also form isomers. Eecent additions to the list are the
dimethyldioxyadipic acids,5 (C02H.CH3.C.OH.CH2)2,
and the thiodilactylic acids6 (CO2H.CH3.C'H)2S.

Although up to the present none of these isomers
has been divided, yet there is such an intimate con-
nection between their formulae and those of the
tartaric acids that it is difficult to doubt of ultimate
success. We have only to substitute methyl, &c.,
for the hydroxyl of the tartaric acids, and it is more
than probable that the isomeric relations of these
acids will survive the substitution.

To this class belong also hydro- and isohydro-
benzoin, C6H5(CHOH)2C6H5, with some derivatives
and homologues.7 These are comparable with tar-
taric acid, the carboxyl group being now replaced.
Finally, we must mention the bromides of nitrostil-
bene, N02C6H4(CHBr)2C6H4N02,8 and also bi- and
isobi-desyl, C6H5(CHCOC6H5)2C6H5.9

1 Ber. 18, 846, 2368 ; 20, 2736 ; 21, 3170 ; 22, 66, 1821.

2 Bischoff and Hjelt, Ber. 20, 2988, 3078 ; 21, 2089 ; 22, 67 ;
23, 650.

3 Hell and Mayer, Ber. 22, 56.

1 Reimer, Ber. 14, 1802 ; 15, 2628 ; Ossipoff, Compt. Rend. 109,
223 ; Tillmanns, Ann. 258, 87 ; 259, 61.

5 Zelinsky and Isajew, Ber. 29, 819. 6 Loven, I.e. 1132.

7 Auwers, Ber. 24, 1778. 8 Bischoff, Ber. 21, 2074.

9 Knovenagel, Ber. 21, 1359 ; Garett, 21, 3107 ; Fehrlin, 22, 553.

78 STEREOCHEMISTBY OF CARBON

Glutaric acid type. — What has been said above
refers to two asymmetric carbons directly connected.
If they are joined by an intermediate atom, we must
make a distinction according as this atom is con-
nected with similar or dissimilar groups.

In the first case, for the type (X)2C((7K1K2E3)2,
what has been said above applies equally. We may
therefore apply it to the two isomeric dimethyl-1 and
dimethyldioxy-glutaric acids, H2C(CHCH3C02H)2
and H2C((70HCH3C02H)2,2 to the dimethyladipic
acids,2 C2H4(CHCH3C02H)2, as well as to the
isomeric bromides of piperylene, H2C(CHBrCH2Br)2,3
and of diallyl, C2H4(CHBrCH2Br)2.4

But if there is a difference between the two groups
joined to the middle carbon atom. CXY (CE^Eg)^
then, as Fischer 5 has remarked, a second inactive
indivisible modification occurs ; this is shown by the
difference in the formulae :

E3 E3

Ej C E2 E! C E2

X C Y and Y C X

E, C E2 E! C E2

E3 E3

This modification has, in fact, been found in the case
of the trioxyglutaric acids, C02H((7HOH)3C02H,
and of the corresponding alcohols,

CH2OH(CHOH)3CH2OH.

1 Zelinsky, Ber. 22, 2823 ; Auwers, 23, 1600 ; 26, 4012.

2 Zelinsky, Ber. 22, 2823 ; Auwers and V. Meyer, 23, 295.

3 Ciamician and Magnanini, Ber. 21, 1434 ; Wagner, Ber. 22,
3057 ; Oazz. Chim. 16, 390.

4 Ciamician and Anderlini, Ber. 22, 2497, 3056.

5 Ber. 24, 1839.

SEVERAL ASYMMETRIC CAKBON ATOMS 79

In the former case we have, besides the active
acid (\_a]D= — 23°) from arabinose, the inactive acid
(M.P. 152°) from xylose,1 and the isomeric unstable
inactive acid from ribonic acid, which readily changes
into the lactone.

In the case of the alcohols we have side by side
the corresponding isomers xylite 1 and adonite.2

Also, Zelinsky 3 has prepared three inactive modi-
fications of dimethyltricarballylic acid :

C02H

I
HCCH3

I
HCC02H

HCCH

C02H

Saccharic acid type. — Finally we come to the sym-
metrical compounds, which contain four asymmetric
carbon atoms, such as saccharic acid. A conspectus
of their isomeric relations is afforded by the follow-
ing symbols, in which the two groupings, HCOH and
HOCH, possible with each asymmetric carbon, are
indicated by + and — . The sixteen isomers, divided
into eight types, are then these :

No. 1 No. 2 No. 3 No. 4

Ber. 26, 635. 2 Ibid. 24, 538. 3 Ibid. 29, 616.

80 STEREOCHEMISTRY OF CARBON

No. 5 No. 6 No. 7 No. 8

If symmetry exists the two isomers marked No. 1
become identical and inactive ; the same with No. 8 ;
the pair No. 2 coincides with No. 5, and No. 3 with
No. 4. Hence we have ten isomers, of which two
are inactive and indivisible, while the other eight be-
long to four types. Now, in the case of mannite,
CH2OH(CHOH)4CH2OH, we have :

Left and right (ordinary) mannite,1 [a]/,= + 0-03 ;
with boric acid, more strongly right-handed.

Left and right (ordinary) sorbite,2 slightly active ;
with borax, [a]fl=l-4.

Dulcite, inactive, indivisible.3

In the case of the corresponding saccharic acids,
indeed, all the six types exist :

Left and right (ordinary) saccharic acid, [a]D=8° ;
as lactone, 38°.4

Left and right mannosaccharic acid, slightly
active ; as double lactone, 202°. 5

Talomucic acid,6 [a]n> +24° ; as lactone, < +7°.

Mucic acid, inactive, indivisible.7

Allomucic acid, inactive, indivisible.8

1 Kiliani, Ber. 20, 2714. 2 Fischer and Stahel, Ber. 26, 2144.
3 Ber. 25, 2564, 1247. 4 Tollens's Kohlehydrate.

5 Ber. 24, 541, 3628. 6 Fischer, Ber. 24, 3622.

7 Fischer, I.e. 25, 1247. 8 Fischer, Lc. 24, 2136

CHAPTEK IV

DETERMINATION OF THE POSITION OF THE
RADICALS IN STEREOMERS

WHEN the number of the isomers actually existing
(which, in the cases we have been considering, may
be called stereomers) agrees with the theory, we are
confronted with a problem like that which we have
to solve in the aromatic series, when we assign to
each of three derivatives one of the three symbols 1, 2,
1, 3, 1, 4. At present this problem can be solved only
partially : which of the two enantiomorphous formulae
corresponds to, say, the left-rotating compound, is
undecided. When, however, there are several
carbon atoms the case is different. We have already
mentioned such types. In the case of tartaric acid,
e.g. (p. 75), the symbol

C02H

HCOH

HCOH
C02H

was chosen on account of its symmetry as the ex-
pression for the 'inactive indivisible type/ while the
two other formulae remained for the right- and left-
acids ; to decide between these last is, however,

82 STEREOCHEMISTRY OF CARBON

impossible. It is especially in the sugar group that
the determination of configuration, in this sense, has
been carried out by Fischer.1 In now discussing the
special data and results, since we can choose the
formula for the type only, and not for the right- or
left-handed product in question, we find that the
number of symbols to be distributed is reduced by
half, which greatly simplifies the discussion. In
what follows, therefore, the mirror-images, such as

C02H C02H

HCOH HOCH

HOCH HCOH

C02H C02H

represent the same tartaric acid — in this case the
active one.

In order now to facilitate the review of the sugar-
derivatives we will take in succession first the
simplest, the tetroses, COH(CHOH)2CH2OH, then
the pentoses, COH((7HOH)3CH2OH, and finally the
glucoses, COH(CH.OH)4CH2OH. Then we have 4,
8, and 16 isomers, or 2, 4, and 8 types, and the first
two are directly connected with the tartaric acids,
their symbols being

H2COH H2COH

HCOH HCOH

HCOH HOCH

COH COH

and the substances represented by the first symbol
giving inactive, indivisible tartaric acid, those re-
presented by the other giving the left- or right-

1 Ber. 24, 1836, 2684.

POSITION OF THE RADICALS IN STEREOMERS 83

acid. This tetrose has been recently obtained from
arabinose.1

The following table gives, so to speak, the develop-
ment of the pentoses and glucoses from these two
tetroses, according to the experimental results of
Kiliani and Fischer.

Tetroses (C4H804)
I

H2COH
HCOH
HCOH
OCH
(corresponds to inactive

HCOH
HOCH
OCH
(corresponds to active

tartaric acid)

Pentoses (C5H1005)

H.,COH
HCOH
HCOH
HCOH
OCH
Ribose

H.2COH
HCOH
HCOH
HCOH
HCOH
OCH

Allomucic
acid

H2COH
HCOH
HCOH

HOCH
OCH

Arabinose

HCOH
HOCH
HOCH

OCH

Lyxose

H2COH

HCOH

HOCH

HCOH

OCH

Xylose

Glucoses (C6H1206)

H2COH

HCOH

HOCH

HCOH

HOCH

OCH

Talomucic

Saccharic acid

Manno-

acid

Glucose

saccharic

Talose ?

Sorbite

Mannose

Mannite

1 Fischer, .$er. 56, 740.

UNIVERSITY

STEREOCHEMISTRY OF CAEBON

II A

Glucoses (C6H1206)— continued.

II B

H2COH

HCOH

HOGH

HOCH

HCOH

HOCH

HCOH

HOCH

OCH

Talomucic acid

Saccharic acid

Idosaccharic

Talose

Gulose

acid

Sorbite

Idose

Idite

H2COH
HCOH
HOCH
HOCH
HCOH
OCH

Mucic acid
Galactose
Dulcite

The respective tetrose or pentose is enriched by
CHOH, by addition of hydrogen cyanide, conversion
of cyanogen into carboxyl, and, finally, reduction of
the resulting acid (or rather of its lactone) , the group
OCH being converted successively into HOCHCN,
HOCHC02H, and HOCHCOH. The formation of
two isomers is then indicated by the symbols ; they
are distinguished in the case of the pentoses
by A and B, in the case of the glucoses by a
and/3.

It is noteworthy that, thanks to the recent re-
searches of Wohl,1 the process has been carried out
in the opposite direction, the oxime HOCHNOH
being formed, and hydrogen cyanide removed from
this by ammoniacal silver oxide.

We have now to find for each of the known
isomers its place in the table.

Pentose group. — In the first place we have to refer
the four pentose types to the symmetrical acids. Of
the three possible types,

' Ber. 26, 740.

POSITION OF THE RADICALS IN STEREOMERS 85

C02H
HCOH

HCOH

HOCH

HCOH

HOCH

HCOH

C02H

only the second is active, accordingly, for arabinose,
which on oxidation yields this acid, the choice lies
between :

CH2OH COH

HCOH HCOH

HCOH and HCOH

HOCH HOCH

COH CH2OH

i.e. between I B and II A in the table.

Now, in the Kiliani-Fischer reaction arabinose
yields glucose and mannose,1 which therefore are
represented either by I B a, ft, or by II A a, ft. By
oxidising these to the symmetrical acids,

C02H(OHOH)4C02H,

we get saccharic and mannosaccharic acids 2 respec-
tively ; both are active, which agrees only with
I B a, ft, since II A a would give an inactive isomer.
Accordingly the arabinose formula must be I B :

H2COH

HCOH

HOCH

OCH

1 Ber. 23, 799. - Ibid. 24, 539.

86 STEREOCHEMISTRY OF CARBON

while to the recently discovered lyxose l which yields
mucic acid (II A a) on oxidation we assign the for-
mula II A :

H2COH
HCOH
HOCH
HOCH
OCH

Now, from arabonic acid, H2COH(HCOH)3C02H,
which corresponds to arabinose, we get, on heating,
ribonic acid,2 and we must assume that the trans-
formation takes place in the neighbourhood of the
highly oxygenated carboxyl-group. Eibonic acid is,
then :

H2COH

HCOH

HCOH
C02H

Further, the configuration of adonite,3
CH2OH(CHOH)3CH2OH,

the reduction-product of ribose, must be taken as
corresponding with the above ; while for xylite 4 and
xylose the last possibility remains :

H2COH

HCOH
HOCH

HCOH

OCH

1 Bcr. 29, 581. 2 Ibid. 4214. a Ibid. 26, 636. 4 Ibid. 24, 528.

POSITION OF THE KADICALS IN STEREOMERS 87

As for lyxonic acid, which corresponds to lyxose,
it is obtained from xylonic acid just as ribonic from
arabonic acid, by a transformation in the neighbour-
hood of the carboxyl group. The formula above
given for lyxose is thus confirmed.

In the group of the pentoses, of the correspond-
ing pentatomic alcohols, alcohol acids, and trioxy-
glutaric acids, all the configurations are, then, deter-
mined :

Ribose. Arabinose.

Ribonic acid. Arabonic acid.

Adonite (inact.). Arabite (act.).

Inact. trioxygl. Act. trioxygl.

H2COH H2COH

HCOH HCOH

HCOH HOCH

OCH OCH

Lyxose. Xylose.

Lyxonic acid. Xylonic acid.

Xylite (inact.).
Act. trioxygl. Inact. isomeric trioxygl.

H2COH H2COH
HCOH HCOH

HOCOH HOCH
HOCOH HCOH

OCH OCH

Glucose group. — It has already been mentioned
that glucose and mannose have the formulae I B a,
@. The choice is rendered possible by the fact that
the same saccharic acid which results from the
oxidation of glucose is obtained also from an

88 STEREOCHEMISTRY OF CARBON

isomeric gulose ; l only the formula I B a admits of
such an isomer, and therefore the configuration of
mannose and gulose, of mannosaccharic and sac-
charic acid, is at once settled, as well as that of the
corresponding mannite and sorbite, which are formed
on reducing mannose 2 and glucose 3 respectively.

Glucose. Mannose. Gulose.

Saccharic acid. Manno-saccharic acid. Saccharic acid.
Sorbite. Mannite. Sorbite.

H2COH H2COH H2COH
HCOH HCOH HCOH

HCOH HCOH HOCH

HOCH HOCH HCOH

HCOH HOCH HCOH
OCH OCH OCH

At the same time this determines the configura-
tion of levulose. The constitution is, according to
Kiliani, H2COH(HCOH)3COCH2OH. Now, as this
yields on reduction sorbite and mannite 4 :

H2COH H2COH H2COH

HCOH

HOCH

HCOH

HOCH

H2COH

Sorbite.

H2COH

Mannite.

H2COH

Levulose.

it must possess the third formula.

Glucose group, mucic acid derivatives. — Since it is

1 Fischer, Ber. 24, 521. 2 Ber. 22, 365 ; 24, 539.

3 Meunier, Delachanal, Compt Rend. Ill, 49, 51.

4 Ber. 23, 2611.

POSITION OF THE RADICALS IN STEREOMERS 89

proved that mucic acid, C02H(H(70H)4C02H, and
the corresponding dulcite belong to the ' inactive
indivisible type,' l we have only to choose between
the two following configurations for the acid :

C02H C02H

HCOH HCOH

HCOH -, HOCH

HCOH HOCH

HCOH HCOH

C02H C02H

Then we have for galactonic acid,
CH2OH(CHOH)C02H

(and galactose), two possibilities. Now, this acid is
converted into talonic acid (and talose) by heating
the quinoline- and pyridine-salt,2 and the trans-
formation must be supposed to take place in the
HCOH group next to the carboxyl. Talonic acid is
accordingly :

H2COH H2COH

HCOH HCOH

HCOH HOCH

HOCH HOCH

C02H C02H

But this determines the configuration of the
talomucic acid obtained by oxidation. Of the four
active types we have now determined three, saccharic
acid by the configuration of glucose, mannosaccharic

1 Ber. 25, 1247. 2 Ibid. 24, 1841.

STEREOCHEMISTRY OF CARBON

acid by that of mannose, and also talomucic acid.
We have then :

CO.,H

CO,H

C0.2H

CO,H

HCOH

HOCH

HCOH

HOCH

HCOH

HOCH

HCOH

HOCH

HCOH

HOCH

CO,H

COJ3

CO,H

C02H

CO.,H

Inactive

Talo-

Saccharic

Manno-

Inactive

ido-

allo-

mucic (?)

acid

saccharic

mucic

saccharic

mucic

acid.

(Sorbite).

acid

acid.

(Mannite).

(Dulcite).

(Idite).

Finally, the following table is appended to afford
a conspectus of the relations thus established. It
contains, of course, only half of the possible isomers ;
the other half corresponds to the mirror-images.
Fischer has proposed to distinguish by the letters d-
and Z- the two groups which belong together, and has
chosen d- for that which contains the long-known
dextroglucose ; the rotations given in the table are
based on this plan.

It must be added that some compounds have
been included of which only the enantiomorphous
form is known, e.g. xylose, arabonic and ribonic
acid ; in such cases, however, we need not scruple to
reverse the sign of the rotation. The formulae thus
obtained have done excellent service as guides in
following out the relations of these compounds.
They explain, e.g. :

1. That levulose is broken up on oxidation into
gly collie acid and inactive tartaric acid.1

1 Kiliani, Ber. 14, 2530.

POSITION OF THE RADICALS IN STEREOMEKS 91

H.,COH

H2COH

H,COH

HCOH

HOCH

HCOH

HOCH

HCOH

H2COH

H,COH

H2COH

Xylite (inact.)

Arabite (act.)

Adonite (inact.)

•I'

OCH

H.,COH

H2COH

HCOH

HOCH

HCOH

HOCH

HCOH

H2COH

OCH

Xylose ( * qoj

(157°\
-1040/

Ribose (W^go )

I .

C02H

H2COH

HCOH

HOCH

HCOH

HOCH

H2COH

CO-^H

C02H

Gulonic acid \c'ao)

Gluconic Aveak\
acid V 68° /

Mannonic /weak\
acid V 54° /

H2COH

HCOH

HOCH

HCOH

H2COH

HOCH

H2COH

HCOH

H2COH

Sorbite (act.)

HCOH

Mannite (act.)

HOCH

t— J

~* CO

H2COH

Levulose (lJSp°te90°!

)

;

CO-jH

HCOH

CO,H

Tartaric acid (inact.)

92 STEREOCHEMISTRY OF CARBON

2. That glucose, by means of its osazone, can be
changed into levulose.1

3. That mannite forms on oxidation mannose and
levulose.2

4. That glucose, on being treated according to the
method of Kiliani-Fischer, gives a glucoheptonic acid
in two isomers, of which one forms on oxidation
an inactive, indivisible pentoxypimelic acid,3 and so
on.

1 Ber. 22, 94. 2 Dafert, ibid. 17, 227.

3 Fischer, Ann. 270, 64.

CHAPTEK V

THE UNSATUBATED CARBON COMPOUNDS

I. STATEMENT OF THE FUNDAMENTAL IDEA

Historical. — In planning this chapter for the new
edition, it was of special importance to make plain
the present position of the theory.

Having hitherto considered chiefly the derivatives
of methane, CH4, we have now to do with those of
ethylene, C2H4. The problem is here more compli-
cated, since there are now six atoms whose relative
position is to be considered, whereas before there
were only five ; and accordingly we find the position
of affairs less satisfactory.

With regard to the asymmetric carbon atom, Le
Bel's conceptions and mine led to the same result.
There was here at least the possibility of a difference.
My fundamental idea was the tetrahedral grouping,
that is to say, any force — cause so far unknown-
proceeding from the carbon atom and tending to
drive the groups united with carbon as far away
from one another as possible, that is, to bring them
into the tetrahedral position. Although it did not
necessarily follow that the tetrahedron must be
regular because the mutual action of the different

94 STEREOCHEMISTRY OF CARBON

groups might vary its form somewhat, yet the ten-
dency to form the regular tetrahedron remained, and
in the case of identity among the groups, as in CH4,
the tendency was realised.

To Le Bel, the asymmetry of the tetrahedron
with different, and the symmetry with identical
groups, seemed established, CH4, e.g. might be a
regular four-sided pyramid, with carbon at the sum-
mit and the hydrogens at the corners of the square
base.1

At present this cannot be decided. So that as
regards methane derivatives we are practically
agreed.

With substituted ethylenes the case is different.
I had at once concluded, as will presently be set forth
in detail, that the four groups are in one plane, in
which lie the carbon atoms also ; here, then, there
is never any possibility of dissymmetry but only of
another kind of isomerism, like that of fumaric and
malei'c acid. To Le Bel the question seemed an
open one ; experiment would have to decide. It was
only after some time 2 that, influenced by the re-
searches of Kekule and Auschiitz, he declared himself
in favour of my view.

But later another change occurred. Doubts arose
in Le Bel's mind on account of indications of
asymmetry, i.e. optical activity among substituted
ethylenes. He had observed3 that a solution of
citraconic acid, CH3C(C02H)=CH(C02H), acquires

1 Bull. Soc. Chim. [3] 3, 788 ; Compt. Rend. 114, 304.

2 Bull. Soc. Chim. 37, 300. 3 Ibid. [3] 7, 164.

THE UNSATURATED CARBON COMPOUNDS 95

activity through the growth of fungi. If active
citraconic acid had been thus formed, the activity of
ethylene derivatives was proved ; it was found,1
however, that the activity was due to the formation,
by addition of water, of methylmalic acid
COS. CH3. C02H

I
OH. OH. C02H,

and this no doubt accounts for the active product
formed in the case of mesaconic acid also; allyl
alcohol and a-crotonic acid gave no active product ;
the results in the case of fumaric and maleic acid
were doubtful.

There could be adduced then only the supposed
activity of styrolene, C6H5.HC = CH2, and of chloro-
fumaric and chloromaleic acid, C02H.C1C = CH.C02H
(Perkin).2 My researches (p. 20) had, however,
already rendered the activity of styrol very doubtful,
and presently Walden's 3 investigation showed the
observation of Perkin to be positively incorrect. It
remains only to state the facts which make the
activity of ethylene derivatives seem to me improb-
able.

In the first place there are numerous ethylene
derivatives occurring in nature, among them such
as have two different groups attached to each of the
two carbon atoms ; tiglic acid,

CH3CH = C(CH3)C02H,
and numerous compounds of the oleic series, fumaric

1 Le Bel, Bull Soc. Chim. [3] 11, 292.

2 /. Chem. Soc. Trans. 1888, 695. * Ber. 26, 508.

96 STEBEOCHEMISTKY OF CAKBON

acid, cinnamic acid, coumaric acid, anethole, asarone,
pipeline. They are all inactive.

In the second place I may mention the statements
published long since as to the formation of ethylene
derivatives from active compounds ; the activity
uniformly disappears :

Inactive fumaric and maleic acids from active
malic acid ;

Inactive chloro-fumaric and maleic acids from
active tartaric acid ; l

Inactive crotonic acid from active /3-oxybutyric
acid ; 2

Inactive furfurol from active arabinose and
xylose ; 1

Inactive coniferyl alcohol from active coniferine.

In the third place, fumaric acid could not be
divided by Auschiitz and Hintze,3 while, according to
a private communication from Walden, the growth
of microbes in maleic acid gave a similar negative
result.

Finally, at my request, Liebermann has converted
his active cinnamic acid dibromide,

C,;H5(CHBr)2C02H,

at a low temperature, into bromo-cinnamic acid,
C6HfiCBrCHC02H, and Walden his active chloro-
succinic acid into fumaric acid. Both derivatives
proved inactive. At present, then, no reason for a
change of opinion is apparent.

1 van 't Hoff, Ber. 10, 1620. Walden, I.e.

2 Deichmiiller, Szymanski, Tollens, Ann. 228, 95.
a Ibid. 239, 164.

THE UNSATUEATED CARBON COMPOUNDS

Relative position of the groups attached to doubly
linked carbon ; cessation of free rotation. — The funda-
mental idea that the four groups connected with
carbon occupy the corners of a tetrahedron, requires,
in order that it may be applied to doubly linked

FIG. 9.

FIG. 10.

carbon, a clear conception of the nature of this
linkage. As to this, we assume that the relative
position of the two connected tetrahedra corresponds
with that which we assumed in the case of the
single bond ; but now two corners of the tetrahedron
play the part which formerly was reserved for one

98 STEBEOCHEM1STKY OF CAKBON

Farther, having regard to the now universally
assumed equality of the carbon affinities, each of the
two tetrahedron corners must play in the act of
combination a perfectly identical part. In order to
arrive at the grouping corresponding to this view,
we must find that relative position of the tetrahedra
which lies half-way between the two cases of single
linking in which the one or the other pair of corners
is joined. Let us consider, then, a compound,
CE^rCE-^r, and represent it in the two different
forms which are obtained if we leave the group CE,E.2
in the same position, but attach to it the groups r
and CK3R4r in two different ways, as shown in figs.
SA and SB.

Passing now to the unsaturated compound
CR1E2 = CE3E4, we have to eliminate the two r
groups and to place CE3E4 in a position half-way
between the two cases. This position is easily
perceived if we unite the two cases in a single
figure (9). In fact we arrive at the intermediate
position shown in fig. 10, in which the groups E3
and E4, and R,, E2 are in one plane, with regard to
which the two positions shown in fig. 9 are sym-
metrical.

Graphic representation. — The grouping thus arrived
at can be represented with the utmost simplicity by
using the following formula :

E3CE4
Prediction of cases of isomerism, — Besides .the

THE UNSATUKATED CAEBON COMPOUNDS 99

above-described relative position of the four groups
Bj, B2, B3, B4, there is another, which also satisfies the
conditions laid down, but yet is not identical with
the first. The groups Bj and B2 may lie in one
plane with B3 and B4, each joined to the same
carbon atom as before, but with the difference that
Bj is opposite B4, and B2 opposite B3 :

B4CB3

Consequently there must be here an isomerism
unforeseen by the old formulae, and it is clear that this
isomerism must be expected in every case where the
groups attached to the same carbon, B15 B2 and B3, B4,
are different, and this whether the groups attached to
different carbons are alike or not, so that e.g. the same
isomerism would occur in the case of

II. CONFIRMATION OF THE FUNDAMENTAL IDEA

General character of the isomerism to be expected
in the case of doubly linked carbon. — In the first
place we must call attention to the nature of this
isomerism, because a marked difference is to be ex-
pected between this and the isomerism due to the
presence of asymmetric carbon. For, according to
the views just set forth, there is here neither
dissymmetry nor enantiomorphism in structure,
so that we should not expect either the rotatory
power, in opposite directions in the two cases, nor
the peculiar hemihedral crystalline form which

100 STEREOCHEMISTRY OF CARBON

accompanies this optical behaviour ; and, as we shall
see, these two properties are altogether lacking. But
we must expect to find a profound difference in the
other properties of the two isomers. Whereas there
was in this respect complete identity between the
two isomers of opposite activity, an identity
harmonising perfectly with the assumed equality of
their molecular dimensions, this identity must for
the very same reasons be lacking in the present case,
because on the one hand we must assume a difference
in the physical properties in general (difference in
the quantities a and b of van der Waals' theory), in
specific gravity, melting- and boiling-point, solubility,
&c., while, on the other hand, a chemical difference is
to be expected, that is to say a difference in stability,
heat of formation, &C.1

We may classify the cases coming within this
category as follows :

A. SIMPLE ETHYLENE DERIVATIVES

Monochloropropylene - . . . CH3CHC1 = CH,

Bromopseudobutylene 3 . . . CH3CBr = CHCH3

Crotonylenebromide 3 . . . CH3CH,CBr = CHBr

1 CH3CBr = CBrCH3

Tolanechloride5 .... C6H3CC1 = CClCtiH5

Tolanebromide 5 .... C6H5CBr = CBrCtiH5

1 A marked physiological difference has been observed by Fodera
(Ref. Ghent. Ztg. 19, Repertorium 407). Injection of maleic acid
kills a dog quickly, whereas the like quantity of fumaric acid has no
poisonous action. As to differences in refractive and dispersive
power, see Briihl, Ber. 29, 2902.

2 Wislicenus, Ber. 20, 1008. :i Holz, Ann. 250, 230.

4 Faworsky, Journ. f. prakt. Ghent. 1890, 149.

5 Zinin, Ber. 4, 288 ; Limpricht, ibid. 379 ; Blank, Ann. 248,
20 ; Eiloart, Am. Ghent. J. 12, 231.

THE UNSATURATED CARBON COMPOUNDS 101

o-Dinitrostilbene ' . C6H4N02CH = CHC6H4NO2

Apiol and Isapiol - . C9H904CH = CHCHS

Anethol3 C6H4OCH3CH = CHCH3

Nitrostyrol 4 C6H5CH = CHN02

B. UNSATURATED MONOBASIC ACIDS (ACRYLIC ACID

SERIES)

£-bromacrylic acid 5 CHBr = CHCOjjH

0-iod6 „ „ . CHI=CHC02H

Furfuracrylic acid .... CHC4H30 = CHCO^

Crotonic and isocrotonic acid . . CH3CH = CHC02H

j3-chloro- „ „ „ 7 CH3CC1 = CHC02H

a-chloro- „ „ „ 8 CH3CH = CC1CO2H

a- and 0-brom-acid 7 CH3CH = CBrCO-jH
8-thioethyl, thiophenyl, and thio-

benzylacid9 .... CH3C(SC,,H5) = CHCO^

Bromomethacrylic acid 10 . . CHBr = C(CHa)COM

Tiglic and angelic acid " . . . CH3CH = C(CHS)CO2H

Hydrosorbic acid 12 . . . . C3H7CH = CHCO.JI

Hypogaeic and gaidic acid . . CH8CH = CH(C,3H2502)

Oleic and elaidic acid . . . . CH3CH = CH^C^H^OJ

Erucic and brassic acid I3 . . CHSCH = CH(Ci9H37O2)

C. AROMATIC MONOBASIC ACIDS (CINNAMIC ACID

SERIES)

Cinnamic and isocinnamic acid 14 . C6H5CH = CHCOJB.

a-bromocinnamic acid 7 ls . . C6HSCH = CBrCO-jH

IB- „ „ „ 7 15 . . C6H3CBr = CHC02H

Dibromocinnamic acid 16 . . . C6H5CBr = CBrC02H

1 Bischoff, Ber. 21, 2073 ; Thiele and Dimroth, ibid. 28, 1411.

2 Ciamician, ibid. 1621. 3 Beilstein. 4 Ber. 19, 1936.
5 Michael, ibid. 1385. 6 Stolz, ibid. 542.

7 Mirbach, ibid. 1384 ; Authenrieth, ibid. 29, 1645, 1670.

8 Wislicenus, ibid. 20, 1008.

11 Authenrieth, ibid. 1531 ; 29, 1639.

10 Fittig, Ann. 206, 16. » Ibid. 216, 16.

12 Ibid. 200, 51 ; Ber. 15, 618.

13 Holt, ibid. 24, 4126. M Liebermann, ibid. 23, 141.

15 Erlenmeyer, ibid. 19, 1936. 16 Roser, ibid. 20, 1576.

102 STEKEOCHEMISTKY OF CAKBON

a-chlorocinnamic acid ' . . . C6H5CH = CC1CO..H
o-, m- and p-nitrophenylcinnamic

acid NOoC6H4CH = C(CeH5)CO,H

Cumaric acid 2 C6H4(OH)CH = CHCO,H

Methyl- and ethyl-cumaric acid3 . C6H4(OMe)CH = CHC02H

a- and £-hydropiperic acid 4 . . (C7H502)CH = CH(C2H4C02H)

benzalhevulic acid 5 . . . C6H5CH = C(COCH3)CH2C02H

D. DIBASIC ACIDS (FUMAEIC ACID SERIES)

Fumaric and maleic acid . . . CO2HCH = CHC02H

Halogen derivatives .... C02HCX = CYC02H

Hydroxyl derivatives 6 . C02HC(OH) = C(OH)CO,H

Citra- and mesaconic acid . . CH3CC02H = CHC02H

Dimethylfumaric 7 and maleic 8 acid CH3.CC02H = C.CH3.C02H

Diphenylfumaric and maleic acid9 . C02HC(C6H5) = C(C6H5)C02H
Camphoric acid (p. 60).

Perhaps in some of the above cases it is not
established to the satisfaction of everyone that both
isomers possess the same constitution ; and in a few
cases the existence of the isomerism is questioned.
On the other hand some isomers have probably been
overlooked, and all chemists, even those who are
opposed to stereochemical conceptions, are convinced
that with doubly linked carbon, when the attached
groups are different, isomerism results.

Camphoric acid (see p. 60) is included in the list
because it is possible that the four known isomers
are due to a combination of asymmetry with double
linkage.

Plochl, Ber. 15, 1946. 2 Koser, ibid. 2348.

Fittig, Ann. 206, 16. 4 Ibid. 216, 171.

Erdmann, ibid. 258, 130.

Fenton, J. Chem. Soc. 1896, 546. 7 Fittig, Ber. 29, 1842.

Exists only as the anhydride, pyrocinchonic acid.
Riigheimer, Ber. 15, 1625.

THE UNSATURATED CARBON COMPOUNDS 103

ALLYLENE TTPE — SECOND CASE OF OPTICAL
ACTIVITY

The following prediction may here be repeated
verbatim from the earlier edition.

The combination (K,E2)C = C = C(K3E4) is
represented in fig. 11. Here, too, we shall have
two isomers, as follows from the difference between

R4
FIG. 12.

FIG. 11. Fia. 13.

figs. 12 and 13, figures which result from the applica-
tion of the graphic method above mentioned. The
conditions with regard to the equality or difference of
the attached groups are the same as in the preceding
case. The models of the isomers are in this case
e nant iomorphous .

It is evident that the case of

(E,E2)C = C = C=C(E3E4),
or, in general,

(E,E2)C=C2» = C(E3E4),

104 STEREOCHEMISTRY OF CARBON

is the same as the case of

(R.igc = C(K3E4).

Of combinations of this kind there always exist

two isomers when there is a difference between the

groups E, and E2, as well as between E3 and K4.

The models of the isomers are not enantiomorphous.

On the other hand, the case of

(EtE2)C = 0 = 0 = 0 = C(E3E4),
or, in general,

(R.iyC = C21, t , = C(E3K4),
is the same as the case of

(E1E2)C = C=C(E3E4).

Thus, of these combinations also, there are
always two isomers when there is a difference between
Ej and E2 as well as between E3 and E4. The
models of the isomers are enantiomorphous.

Treble linkage. — Two carbon atoms, trebly linked,
which, according to the ordinary formulae, are ex-
pressed by the symbol 0 = 0, may,
on the hypothesis of the equality of
the bonds, be represented by two
tetrahedra having three corners in
common, and therefore having a
surface of each coinciding, so that
they form a double three-sided
pyramid (fig. 14). Et and E2 are
the monad groups by which the two
free affinities of the system are
saturated. In this case a differ-
ence in the relative position of the saturating

THE UNSATURATED CARBON COMPOUNDS 105

groups is not possible, and the possibility of iso-
merism is, in accordance with the prevalent views,
excluded.

III. DETERMINATION OF KELATIVE POSITION IN
UNSATURATED COMPOUNDS

Whereas, for the isomers of opposite rotatory
power, it is at present impossible to decide which
structure a given modification possesses, the state of
things is much more favourable in this respect for
isomers which have a double bond, like fumaric and
male'ic acid. For these substances the question
was settled at the outset, and it is due principally to
the development of the subject by J. Wislicenus *
that considerations of this kind have met with
general recognition. We have to do in particular with
two principles which seem capable of solving this
problem, viz. with the mechanism of addition which
forms and transforms the isomers, and with the
mutual influence of the groups within the molecule.

As regards the mechanism of addition we can
use the same principle which governs every deter-
mination of chemical structure by the aid of the for-
mation and transformation of known compounds, and
which consists in the assumption that in chemical
processes the atomic structure remains as far as
possible unaltered.

According to this principle, then, it must be
expected that on making an addition to bodies with
a triple carbon linkage, two of the three connected

1 Ablutndl. der KonigL Sachs. Oes. 1887.

106 STEEEOCHEMISTEY OF CARBON

pairs of corners will remain unaltered.1 Hence
follows that acetylene dicarboxylic acid,

C(C02H)C(C02H),
e.g. on addition of bromine, will yield the compound

C02HCBr

H •
C02HCBr

In opposition to this Bandrowski 2 had proved the
formation of dibromofumaric acid. But Wislicenus,
guided by these theoretical views, repeated the
experiments and showed that, in fact, dibromomaleic
acid is formed.

Later these experiments were taken up by
Michael ; 3 in a detailed paper, where the theory in
question is critically discussed, the formation of
dibromomaleic acid up to 28 or 33 per cent, is con-
firmed, but there was found also about double the
quantity of the isomeric substance. The objection
arising from the formation of this latter is, however,
as Wislicenus also observes, not important ; it is
well known, in fact, with what ease male'ic acid
changes into fumaric ; 4 under the influence of light
and a trace of bromine, I have myself seen this
transformation ensue so rapidly that it was possible
to take a photograph in fumaric acid from the solu-
tion of male'ic acid ; moreover, in Michael's experi-
ments the status nascens has to be taken into
account.

1 van 't Hoff, Etudes de dyn. chim. 1884, 100.

2 Ber. 12, 2122. 3 /. prakt. Chem. 46, 210.
4 Compare Wislicenus, Ber. 29, Eef. 1080.

THE UNSATURATED CARBON COMPOUNDS 107

In the case of addition to substances with a
double linkage, the principle above-mentioned de-
mands that, of the two connected pairs of corners,
one shall remain unaltered. If, then, we add
hydroxyl to fumaric and maleic acid we obtain l
from

C02HCH

HCC02H

and

C02HCH

C02HCH
the compounds

OH
C02HCH

HCCO2H
OH

and

C02HCH
C02HCH

C02HCH

HCC02H

II
HCC02H

HCC02H
C02HCH
OH

HCC02H
HCC02H

—that is to say, we get racemic acid in the first case,
and inactive tartaric acid in the second case. And
this has actually been proved to be the case by
oxidation with permanganate of the acids men-
tioned.2

If, on the other hand, a saturated compound
becomes unsaturated, the constitution of the resulting

1 Lagerung der Atome im Raume, p. 40.

2 Kekul6 and Anschiitz, Ber. 13, 2150 ; 14, 713.

108 STEREOCHEMTSTKY OF CARBON

body may be foreseen in an analogous way. We
may consider the isodibromosuccinic acid 1 which is
prepared by the addition of bromine to malei'c acid,
and hence has the formula :

HCC02H
HCC02H "

Let us abstract hydrobromic acid, writing the above
formula in a slightly different way, in order the
better to follow the result :

C02HCBr
HCC02H '
Br

it is then clear that we shall obtain bromofumaric
acid :

C02HCBr

II
HCC02H

The result is noteworthy. By addition of bromine,
and subsequent splitting off of hydrobromic acid,
one passes from the maleic to the fumaric series.
This transition is perfectly general and has been
uniformly confirmed by observation.

Of course, as in other cases where molecular
structure is to be determined, this reasoning, which
is based on the stability of a molecule undergoing
partial rearrangement, encounters facts apparently
contradictory. Of these some, as in the above
observation by Bandrowski, have been explained by

1 Etudes de dyn. cliim. p. 100.

THE UNSATUKATED CAKBON COMPOUNDS 109

the discovery of a secondary change. For other
cases the explanation is yet to be found. We may
mention, as of special interest, the conversion of the
isodibromosuccinic acid, made from maleic acid into
racemic acid,1 and that of right-handed tartaric acid
into chlorofumaric acid2 (by the action of phos-
phorus pentachloride 3) .

Such objections, to the number of forty-six, have
been recently collected in the above-mentioned paper
by Michael. But their value as a means of judging
what has just been said is considerably diminished by
the two following observations :

1. All the objections amount to this, that instead
of the product to be expected, another results which
is more stable under the conditions of the experiment,
but in such a case a secondary transformation,
masking the main result, is always possible, even in
cases where this secondary action cannot be directly
realised, for we have to take into account the status
nascens.

2. All the objections refer to halogen derivatives.
Now, the experiments with active compounds men-
tioned on p. 49, and also the reactions on p. 67,
show that when e.g. dichlorosuccinic acid is formed
from tartaric, phenylbrom- and chlor-acetic acid
from malic acid, a transformation occurs. Here, too,

1 Anschiitz, Ann. Chem. Pharm. 226, 191 ; V. Meyer, Ber. 21,
264.

2 Kauder, J.prakt. Chem. 31,33; Perkin, J. Chem. Soc. 1888,
645.

3 This substance has, however, a peculiar property of reversing
the position of groups in a molecule. See ante, p. 47.

110 STEREOCHEMISTRY OF CARBON

the chlorine compounds once formed are stable, as
is shown by the fact that activity is possible (p. 24) ;
during their formation, however, transformation
occurs. The practical conclusion to be drawn from
Michael's work amounts to this, that in the cases
investigated by him transformation easily takes place,
and this is always to be expected where halogens are
concerned ; proof ' for ' or ' against ' the views above
stated is therefore to be sought in cases where
halogens are as far as possible excluded. Fischer in
the cases mentioned (p. 82) has done this with most
favourable results.

Let us now consider the mutual influence of the
groups forming the molecule, so far as this can
contribute to a determination of the structure of the
isomers.

First, there is the question of stability. Just as
our theory explained the perfectly equal stability of
the two isomers of opposite activity by the absolute
identity in the dimensions of the molecule, so it
foresees that in general the unsaturated isomers will
differ in stability, because it assumes a difference in
their analogous dimensions.

Of the formulae :

B3CB4 B4CB3

.it may, generally speaking, be maintained that, say,
the second represents the more stable modification if
there is reason to suppose that B1 exerts a stronger

THE UNSATUEATED CAEBON COMPOUNDS 111

attraction on R4 and K2 on B3. Thus, for fumaric
acid, stable in comparison with the isomeric malei'c
acid, the formula :

HCC02H
COJHCH

seems justified.

Apart from the difficulty of comparing these
attractions, we have here to take the temperature
into account. Since a rise in temperature is
generally opposed to the ordinary action of chemical
affinities, it may happen that at a given temperature,
possibly at the ordinary temperature, a transforma-
tion occurs in the sense opposed to that expected,
the latter occurring only at lower temperatures.
The absolute criterion of stability is, therefore, not
the transformation at a given temperature, but the
larger heat of formation. As is well known, on
lowering the temperature the isomer with the
greater heat of formation will always predominate.

Moreover there are reactions which enable us to
judge as to the distance of two groups in a molecule.
If in one isomer two of these groups easily undergo
a simultaneous conversion, while in the other the
opposite takes place, we may assume that these
groups are nearer together in the first case. For
example, malei'c acid readily forms an anhydride
through the interaction of its two carboxyl groups,1

1 Substitution of a methyl group for one or more of the hydrogens
attached to carbon in maleic acid facilitates the closing of the ring,
—formation of an anhydride. The same thing is observed in the
case of succinic and glutaric acids. In other cases, however, the

112 STEREOCHEMISTRY OF CARBON

and is thus distinguished in a very striking way
from the isomeric fumaric acid. The former, there-
fore, has the formula

C02HCH

II ,
CO,HCH

in which the two carboxyls are near together.

presence of methyl prevents the ring formation, Sometimes, indeed,
in a compound containing several methyl groups, it is easier to bring
about a molecular rearrangement than a simple ring formation.
Thus, instead of

CH3
CH3-.Cv

I >0
CH3-C/
CH3

we may obtain

CH, -
CH3-g-CH3
CH3-C:0
II

To account for such apparently irreconcilable observations Bischoff
has applied his ' dynamic hypothesis,' according to which those con-
gurations are the most favoured in which the components can
oscillate most freely. Now, like atoms will have like paths of oscil-
lation, and will therefore be the most prone to collide ; in a favoured
configuration, then, they must be far removed from one another.
Hence configuration II above, in which this condition is fulfilled as
regards the methyl groups, is more stable than configuration I.

Where, on the other hand, the methyl groups cause closure of
the ring (e.g. pyrocinchonic acid, CH3CCOv it is again their

II >0)
CH3CCO/

effort to gain room for their oscillations which causes them to crowd
together the hydroxyl groups, so that expulsion of water with ring
formation follows. For an account of the dynamic hypothesis, see
Bischoff and Walden, Handbuch der Stercochemic, Frankfurt a. M.
1893-94. Bechhold.-Tr.

?iS

I UNIVERSITY^
THE UNSATURATED CARBON COMPOUNDS 118

Also the formation of certain bodies may help to
make clear these relationships. Thus it is plain
that the closed chains occurring in benzene, cincho-
meronic acid, pyromuconic acid, and pyrrol, approxi-
mate to the arrangement of the four carbon atoms in
maleic acid, and differ from the arrangement in the
isomeric compound. In fact, in energetic decomposi-
tions it is maleic acid (or its derivatives) which
results in such cases.1

There is, finally, another, though a less direct,
proof of the neighbouring position of the carboxyls
in maleic acid. This acid is the stronger : its dissocia-
tion constant is 1-17, that of its isomer only 0*093. 2
It is uniformly observed that this constant is raised
by the neighbourhood of a negative group.

1 Kekule and Strecker, Ann. Chem. Pharm. 228, 170 ; Hill, Her.
13, 734 ; Bischoff and Each, Ann. Chem. Pharm. 234, 86 ; Cia-
mician and Silber, Ber. 20, 2594.

2 Ostwald, Zeitschr. physik. Chem. Ill, 380.

114

STEREOCHEMISTRY OF CARBON

CHAPTEK VI
EING F OEM AT ION

THE chapter devoted to ring formation in the
original pamphlet was omitted in the first German
edition, for at that time the isomerism of v. Baeyer's
hydro- and isohydro-mellitic acids was the only case
in point. Since then, however, this branch of the
subject has, especially through v. Baeyer's researches,
gained so much in extent and interest that an
approximately systematic treatment of the whole is
possible. We observe that here too the historical
development has kept pace with the complexity of
the problem. After the methane derivatives had
been dealt with, came the ethylene and finally the
polymethylene compounds.

Rings of three members. Tri-
and trithio-methylene. — Starting
from the tetrahedral grouping,
I developed, in the pamphlet
referred to, the annexed con-
figuration for the trimethylene
derivatives, remarking that a
transposition of the two groups
B! and B2, which are attached to the same carbon,
would bring about an isomerism approximating to

RING FORMATION

115

that of fumaric and maleic acids, i.e. to that of di-
methylene derivatives.

Since then two isomeric trimethylene dicarboxylic
acids,1 CH2.CHC02H.CHC02H, and three isomeric
phenyltrimethylenedicarboxylic acids,2

CHC6HtVCHC02H.CHC02H,
have in fact been discovered.

To render the discussion clearer the scheme given
above may be transformed in a way readily intel-
ligible, and the isomerism possible in the case of the
trimethylenecarbonic acids may be represented in
the following way :

C02II

C02H

CO,H

C02H

C02H
HC

Thus we have three possibilities, of which the
second and third are non-superposable images, and
must therefore possess opposite activity. Of the two
known isomers, it is possible then that one may be
divisible. If now a methylenehydrogen be replaced
by phenyl, as in phenyltrimethylenecarboxylic acid,
the first scheme leads evidently to two possibilities
according as phenyl is placed above or below ; the
second and third schemes give, in this case, only a

1 Buchner, Ber. 23, 702.

2 Buchner and Dessauer, ibid. 25, 1148.

i 2

116 STEREOCHEMISTRY OF CARBON

single isomer each, and these also are mirror images
of each other. Of the three isomers found, then, one
should be divisible.

Thus, although the isomerism is not analogous
to that of fumaric and maleic acid, but rather, in the
first case at least, to that of inactive tartaric acid
and racemic acid, it must be remembered that the
first kind of isomerism is to be expected, as the
figure indicates, only when all the methylene groups
have undergone similar substitution. Such deriva-
tives have not been prepared from methylene ; but
in the case of trithiomethylene they have been
thoroughly investigated, and in accordance with the
above figure they may be represented thus :

H
H ^4^ K

H H

And Baumann and Fromm ] have been led by their
work on the trebly polymerised thioaldehydes and
thioacetones, which probably have the constitution
(E,K2)C - S --

to the following conclusions :

1. When the groups Et and E2 are alike, as in tri-
thiomethylene (from methylaldehyde) and trithiodi.
methylmethylene (from acetone), no isomerism occurs.

1 Per. 24, 1419.

RING FORMATION 117

2. Two isomers occur when the groups are dif-
ferent, as in the aldehyde thio-derivatives of acetyl,
benzoyl, anisyl, methylsalicyl, isobutylsalicyl, and
cinnamyl.1

The observed isomers would in this case exactly
correspond to the configurations given in my first
pamphlet, of which one is reproduced above (fig. 15),
and the other here (fig. 16) . The main point to notice
is that here isomerism exists
without asymmetry; that is, as
with fumaric and maleic acids,
no division is to be expected.
The plane of symmetry lacking
in the second and third tri-
methylenedicarboxylic acids re-
presented above is here present.2 FIG. 16.

1 But later researches show that for substituted aromatic alde-
hydes this holds good only when the substituting group is positive
or indifferent. When it is negative no isomerism is observed. Thus
there exists only one tri-thio derivative of the following : methoxy-
benzaldehyde, benzoylmethoxybenzaldehyde, methylmetoxybenz-
aldehyde, paroxybenzaldehyde, benzoylparoxybenzaldehyde, vanillin
(but methylvanillin yields the isomers), benzoylvanillin, gentisin-
aldehyde, metanitro-, anis-, and cumin-aldehyde, dinitroanisaldehyde
(Worner, Ber. 29, 139).

2 It is evident that if the radicals R,R2 are in the plane of the
trimethylene ring there must be three inactive trimethylenedicar-
boxylic acids, of the formula CH2.CHCOOH.CHCOOH.

COoH. ,H Hv xCO-JI COM.

H /- -^-H H-/- \H C02H_

CO.H H C0.2H H H H

Whereas we have seen that according to the tetrahedron hypothesis
there can be only two inactive isomers, of which one should be

118

STEEEOCHEMISTEY OP CARBON

Rings of four members. Tetramethylene deriva-
tives.— Here too, especially through Liebermann's l
investigation of the truxillic acids, cases of isomerism
have been discovered which may well be classed with
those above mentioned. The acids named, which
from their transformation must be considered as
dicinnamic acids, and from their saturated character
as tetramethylene derivatives, correspond to the two
formulae :

C6H5CH— CHC02H C6H5CH— CHC02H

'II II

C6H5CH— CHC02H C02HCH— CHC6H5

and have been obtained in four, if not in five, isomeric
forms.

The first formula alone presents the following
possibilities :

divisible. Buchner's later results are all in favour of this hypothesis.
He has also prepared the stereomers of the tri- and tetra-carboxylic
acids (Ann. 286, 197). ' Ber. 23, 2516.

KING FOKMATION

119

C6H5

'COaH

of which the figures bracketed
together are mirror images
without symmetry. We have
to expect, then, six isomers, of
which four are divisible — that
is, altogether, ten different
isomers.

Next we have to mention
the so-called a-7-diacipipera-
zines,1 substitution products
and homologues of the com-
pound

COCH2
C6H5N NC6H5.

CH2CO

Disregarding for the present the possibility, which
will be discussed later, that the nitrogen may cause

1 Bischoff, Ber. 25, 2950.

120

STEREOCHEMISTRY OF CARBON

isomerism, there is none to be expected in the
derivatives investigated, which belong to the type

COCH2
XN NX

CH2CO
and, in fact, for

X=C6H5, C6H4CH3 (p and o), C10H7 (a and /3),
none was found ; nor even when the X groups were
different (C6H5 and C7H7).

But if in the two methylene groups a hydrogen
is replaced by CH3 or C2H5, giving the type

COCHK

XN NX,

(7HECO

isomerism results, and may be considered as due to
the two asymmetric carbon atoms.

The isomers found for

X=C6H5, C6H4CH3 (p and o), C10H7 (a and £),
which have been prepared in ten cases, would corre-
spond to the two possible racemic mixtures :

Rings of six members. Hexamethylene derivatives,

In the case of the derivatives of hexamethylene the
observations are no less convincing. While among
the monosubstituted hexamethylene derivatives, such

RING FORMATION 121

as hexahydrobenzoic acid, no case of isomerisni is as
yet known, it is otherwise with the products which
have undergone several substitutions ; and we owe
to Baeyer's l researches a knowledge approximately
complete of all the details in at least one case. This
is the hydroterephthalic acid, especially the hexa-
hydro derivative, C6H10(C02H)2 1, 4. Of this two
modifications have been discovered which correspond
to the cases foreseen :

C02H

C02II C02H

In these figures the twelve groups linked in pairs
with carbon or the atoms of the ring form the corners
of a hexagonal prism the edges of which are indicated
by the vertical lines. For simplicity the carbon atoms
of the ring, as well as the hydrogen atoms remain-
ing unsubstituted, are again omitted in the figure.

Here, too, the hexahydrophthalic acids,

C6H10(C02H)2 1, 2,

which likewise occur in two modifications, may be
mentioned :

C02H C02H C02H

C02H

1 Ann. Chem. Pharm. 245, 103 ; 251, 258 ; 258, 1, 145.

122 STEREOCHEMISTRY OF CARBON

In this case, however, it must be added that the
first arrangement corresponds to an enantiomorphous
form, and that accordingly a division into two active
isomers must be possible.1 The two compounds
obtained would be comparable to racemic acid and
inactive tartaric acid, for they contain two asym-
metric carbon atoms in a symmetrical formula. The
recent discovery of the two isomeric hexaisophthalic
acids by Perkin 2 has supplemented the above.

Finally, we may mention the a- and /3-tetra-
hydroterpenes, the terpines, and the pinenedihydro-
chlorides and bromides,3 which perhaps correspond
in structure to the hexahydroterephthalic acids.

If more than two hydrogen atoms are substituted
in hexamethylene, the number of possible isomers
will be increased. On this point, however, the
number of researches is limited : as cases of treble
substitution, only the bromides of tetrahydrobenzoic
acid 4 can be mentioned.

It is only when we come to the sixfold substitu-
tion products that the number of compounds
investigated increases ; hydro- and isohydro-mellitic
acids, C6H6(C02H)6, having been the first cases

1 Such a division has since been effected in the case of the
analogous compound cis-trans-hexahydroquinolic acid,

H2 H
H2C— C-CCOOH

H2C— N— CH

H COOH

(Besthorn, Ber. 28, 3153).
- J. Chem. Soc. 1891, 814.

3 Beilstein, 2nd ed. 1, 182 ; Baeyer, Ber. 26, 2861.

4 Ber. 24, 1867.

RING FORMATION 123

investigated.1 With regard to the isomeric hexa-
chlorbenzenes, C6H6C16, on which so much work has
been done recently, since the identity of their
molecular weights has been proved 2 the assumption
of a structural difference is scarcely tenable, and
accordingly Friedel 3 and Matthews 4 resorted to the
stereochemical explanation. This is included in
what has been said above.

Activity among hexamethylene derivatives. Inosite.
It has already been repeatedly stated that among
polymethylene derivatives optical activity is to be
expected. And it has been proved to exist in several
cases, viz. :

Hydroshikimic acid, [a]^ = - 18° Quinic acid, [a]^ = - 44°

CHOH CHOH

H2C CHOH H2C OHOH

HOHC CH2 HOHC CH2

y y

HC02H HOC02H

This might have been at once foreseen as a con-
sequence of the asymmetric carbon atoms which are
evidently present. The case of inosite, however,
demands special attention :

1 Baeyer, Ann. Chem. Pharm. Suppl. 7, 43.

2 Paterno, Qazz. Chim. 19, 195.

3 Bull. Soc. Chim, [3], 5, 130.

4 Chem. Soc. J. 1891, 165 ; the same author has recently pre-
pared two isomeric chlorbenzenehexachlorides. Recently, too,
Orndorff and Howells (Am. Chem. J. 18, 312) announce the discovery
of stereomerism in the case of hexabromobenzene.

124

STEREOCHEMISTRY OF CARBON

CHOH
HOHC CHOH

HOHC C

HOH

Here the absence of symmetry due to the presence
of the asymmetric carbon is not evident, or at least
not sufficiently so. It shows itself in these cases
only on consideration of the scheme developed as
above, which is therefore applied here. The ordinary
long-known inosite is inactive and indivisible (p. 46),
and therefore possesses a symmetrical constitution :

The right and left inosites, [a]D = 65°, prepared
by Maquenne,1 the first from pinite and /3-pinite, the
second from quebrachite — that is to say, both from iso-
meric methylinosites, C6H6(OH)5OCH3 — will then cor-
respond to the asymmetric mirror images, such as, e.g. :

HL/OH H
HI\OH H/loH

H OH OH H

Ann. Chim. Phys. [6], 22, 264 ; Compt. Rend. 109, 812.

KING FORMATION 125

These diagrams explain also how it is that the
same inosite can result from isomeric methyl deriva-
tives, pinite and /3-pinite. It may be observed
parenthetically that isomers in considerable variety
are to be foreseen here, and are perhaps to be found
in scyllite, in phenose, &c.

Finally, hexahydro-o-toluylic acid,

y<cofi

has been obtained by Goodwin and Perkin jun.1 in
two modifications representing the cis 2 and trans 2
configurations.

Tetrahydrobenzene derivatives. — Starting from the
derivatives of hexamethylene, to which the application
of stereochemical conceptions is simple, we gradually
arrive — using Baeyer's investigations on the tetra-and
di-hydrides of terephthalic acid — at the complicated
state of things presented by the benzene nucleus.

Thus, if in the isomeric tetrahydro derivatives we
assume a double bond, it is easy to see that the
following two forms must exist :

C02H HC02H

H2 H H2 H

I I I II

TT TT TT TT

\/2

HC02H HC02H

1 J. CJiem. Soc. 1895, i. 119.

- These terms were introduced by Baeyer to distinguish the
isomer in which the substituents are on the same side, from that in
which they are on opposite sides of the ring.

126

STEREOCHEMISTRY OF CARBON

Of the latter formula, the two following isomers
are to be expected :
C02H

And, in fact, three tetrahydroterephthalic acids are
known. Again, we observe that the last diagram is
enantiomorphous, and therefore it is to be expected
that two of the acids should stand to one another in
the relation of inactive tartaric acid and racemic
acid ; for the formula to which they correspond
contains two asymmetric carbon atoms, the constitu-
tion of the whole being symmetrical.

Dihydrobenzene derivatives. — Here, too, we find
theory and observation in accord. Assuming two
double bonds, the following four structural formulae
are to be expected :

C02H HC02H

H/Nl H/\H

C02H

H/NE

1H,

HC02H

C02H

C02H HC02H

Again, we may expect from the last an isomerism,

C02H

GOaH

RING FORMATION 127

which probably corresponds to the fumaric-maleic
isomerism. In fact, Baeyer has described five di-
hydroterephthalic acids.

Benzene derivatives. — When finally we come to
the derivatives of non-hydrogenated benzene, the
ethylene character is lacking and with it the condition
determining isomerism ; the acetylene character is
now assumed, and thus all ground for stereochemical
speculations vanishes. This point must be specially
emphasised. Everything forces on us the conclusion
that in these non-hydrogenated derivatives of benzene
rotatory power is lacking, unless the side chain con-
tains an asymmetric atom. This assumption is based
in the first place on the fact that the numerous
benzene derivatives occurring in nature, such as
salicylic aldehyde, vanillin, cumarin, are without
exception inactive ; and in the next place all attempts
at ' doubling ' have been in vain. Le Bel l has made
such attempts with orthotoluidine ; Lewkowitsch 2
with /3-meta-homosalicylic acid,

CGH3(CH3)(C02H)(OH)(1, 2, 3,),
with ^-ortho-homomethoxybenzoic acid,

CGH3(OH)(CH3)(C02H)(1, 2, 3,),
and with methoxytoluylic acid,

C6H3(OCH3)(CH3)(C02H)(1, 2, 3) ;
and V. Meyer and F. Liihn3 with nitro- and
formyl-thymotic acids,

C6H.OH.COOH.CH3.C3H7.N02

1 Bull. Soc. Chim. 38, 98.

2 Chem. Soc. J. 1888, p. 791 ; see also Ber. 16, 1576.

3 Ber. 28, 2795

128 STEREOCHEMISTRY OF CARBON

and C6H.OH.COOH.CH3C3H7.CHO, without effecting
a division.1 Now, only those benzene formulae which
contain the carbon and hydrogen atoms in one plane
can be free from enantiomorphism, which in the
prism formula, indeed, would manifest itself even in
the bisubstitution products.

Objection. — The ring-linkage has here been treated
in such a way that, starting from methylene deriva-
tives, we advanced gradually to benzene. In this
way, however, a difficulty is concealed which must
now be mentioned. The construction of the con-
figurations by means of models does very well in the
case of methylene derivatives, as is shown by the
figures sketched. In constructing benzene, however,
we encounter, if we take Kekule's doctrine as a
basis, the well-known difference2 between 1, 2, and
1, 6 ; while, with Ladenburg's prism, activity is to
be expected even in bisubstituted products. This
objection is met, however, if we consider the tetra-
hedral grouping as only the cause of the final
arrangement of the atoms, which, in benzene,
adopting a plane arrangement, would be

H H

C C
H C C H

C C
H H

The tetrahedra, then, are to be considered as the
cause of the grouping, not as anything really present.

1 According to Riigheimer, however, active m-methylic-p-oxy-
benzoic acid possibly exists (Ber. 29, 1967).

2 See Graebe, Ber. 29, 2802.

KINO FOEMATION 129

Stability of the ring formation. — Let us apply,
finally, the tetrahedron theory from a point of view
somewhat different. It is now some years since
Victor Meyer,1 on the occasion of a general review
of the essential properties of carbon compounds,
referred to the peculiar readiness of this element to
form closed chains consisting of six atoms, and to
the extraordinary stability of these compounds. In
view of the difficulty of obtaining closed chains with,
for example, three atoms — such bodies were at that
time not even known — this was all the more re-
markable. And Victor Meyer urged with justice that
such an essential property should be deducible as an
immediate consequence from clearer views as to the
structure of organic compounds.

I took this occasion to point out 2 that the new
tetrahedron theory was capable of explaining this
peculiarity up to a certain point. However, these
considerations attracted no further notice ; and there
would be no reason to produce here those rather
tentative remarks, but that recently Baeyer,3
Wunderlich,4 and Wislicenus,5 each from his own
standpoint, have developed ideas of a perfectly
analogous nature. It seems therefore desirable to
repeat here the observations referred to.

For the various observations which have led to
analogous conceptions on the part of the chemists

1 Ann. Chem. Pharm. 180, 192.

2 Maandblad voor Natuurwetenschappen, 6, 150.

3 Ber. 18, 2278.

4 Konfiguration organischer Molekille, Wiirzburg, 1886.

5 Abh. der Konigl. Sachs. Akad. 1887, 57.

130 STEREOCHEMISTEY OF CARBON

named, possess one characteristic in common.
Bodies containing a chain of several connected
carbon atoms are sometimes capable of remarkable
transformations, arising from a preference for inter-
action between distant groups. To give an example.
Among the oxybutyric acids it is precisely that one
which most readily forms a lactone which has the
carboxyl and hydroxyl groups apparently furthest
removed from one another, namely, 7-oxybutyric
acid, C02HCH2CH2OH. The anhydride results,
then, from the interaction of the two outermost
groups with loss of water. This phenomenon is
general ; the ^-oxy-acids, which have three carbon
atoms between hydroxyl and carboxyl, are always
those which display a special tendency to lactone
formation.

Now, our theory, so far from seeing any difficulty
in the interaction of groups attached to the carbon
atoms of a long chain, finds here,
if not a direct confirmation, at
least the indication of such.
Let us represent the grouping of
several carbon atoms according
to our views. The first carbon
atom, Cj, with the two groups it
connects, will be at the corners
of an isosceles triangle, the angle
at A being, according to the dimensions of the tetra-
hedron, 35°. The second carbon atom, C2, with the
connected Cl and C2, will be arranged in an abso-
lutely identical fashion. The same holds for a third

KING FORMATION 131

atom, C3, for a fourth, C4, and so on. Now, it is plain
that the distances A C2, A C3, A C4, which represent
the distances of the groups connected with the first,
with the first and second, and with the first and
third atoms, do not continually increase.

On the contrary, since the ratio of these distances
is expressed by

sin2A: sin3A: sin 4A : sin 5A=1 : 1-02 : 0-67 : 0-07,
there must ensue, as the figure also shows, a consider-
able decrease in the distances in question.

After these general considerations, let us pass on
to the discussion of details.

With regard to Baeyer's l views, we note first
that this author assumes in the closed-chain poly-
methylenes a symmetrical arrangement of the carbon
atoms, and compares the angle which two carbon
atoms make with a third connected with them, with
the angle C2 C1 A of fig. 17. Now, according as we
have to do with hexa-, penta-, tetra-, tri-, or di-
methylene, this angle is 120°, 106°, 90°, 60°, or 0°,
while the angle C2 Cl A of fig. 17 is about 109°. The
difference is, then, 11°, 3°, 19°, 49°, and 109° respec-
tively, and in this difference the author sees an
approximate expression of the tendency to satura-
tion. In support of this view may be mentioned
the extraordinary difficulty of saturating hexa-
and tetra-methylene ; whereas trimethylene unites
with bromine, though not with hydrobromic acid.
In the case of dimethylene even the action of iodine
suffices to bring about saturation.

1 Ber. 18, 2278.

K 2

132

STEREOCHEMISTEY OF CAEBON

The benzene derivatives admit of similar treat-
ment,1 which, however, is influenced by the fact that
the relative position of the six carbon atoms is here
not quite settled. We assume Kekule's hypothesis,
according to which double and single bonds alternate,
and compare with benzene those analogous closed
chains of five to eight carbon atoms, which may be
assumed from the valence of carbon, namely,
(CH)4, (CH)4CH2, (CH)6, (CH)6CH2, and (CH)8.

To this end let us place side by side the sums of
the angles which our theory requires when two
carbon atoms are joined to a third (about 109° in
the case of a single, and 125° in the case of a double
bond), with the sums of the angles of a closed poly-
hedron :

Formula

Sum of the angles

Polyhedron
angles

Difference

(CH)4 . .
(CH)4CH2 .
(CH)6 . .
(CH).OH2 .
(OH). . .

4x125 = 500
4x125 + 109= 609
6x125 = 750
6x125 + 109= 859
8 x 125 = 1000

300
540

720
900
1080

140
69
30
-41

-80

We see that, in fact, the greatest approximation
occurs in the case of benzene, which accounts for the
stability of this substance as well as for the fact
that up to the present the others have not been
prepared.

1 Wunderlich, Konfiguration organischer Molekiile ; van 't Hoff
Maandblad voor Natuurwetenschappen, 7, 150.

133

CHAPTEE VII
NUMERICAL VALUE OF THE ROTATORY POWER

WHEREAS thus far we have spoken only of the
absence or presence of rotatory power, we have
now to do with the magnitude of the rotation. It is
already a considerable time since such determinations
began to be made, and (as the expression of the
quantitative relation) the so-called molecular rotation
was chosen — that is, the specific rotation, a,1
multiplied by the molecular weight (and for short-
ness divided by 100) . The chief results so obtained
are, firstly, the statement of Mulder, Krecke, and
Thomson2 that the molecular rotations within
certain groups of substances bear a simple ratio to
one another ; and, secondly, the observation of
Oudemans and Landolt that different salts of the
same active base or acid in dilute aqueous solution
possess the same molecular rotation. Such con-
siderations have gained a new interest for stereo-
chemistry since Guye 3 and Crum Brown 4 attempted

1 Eotation caused by 1 decim., the substance being supposed
present in this column with the density one.

2 Zeitschr.f. Chemie, 1868, 58 ; Zeitschr. f. prakt. Chem. 1872, 5
6 ; Ber. 1880, 1881.

3 Theses, 1891 ; Ann. Chim. et Phys. [6], 25, 145.

4 Proc. Roy. Soc. Edinb. 17, 181.

134 STEREOCHEMISTRY OF CARBON

to connect the magnitude of the rotation with the
nature of the groups attached to the asymmetric
carbon atom ; accordingly the facts bearing on the
question are here given in detail.

I. COMPAEISON OF THE NUMERICAL KESULTS.
NECESSITY OF AN EXAMINATION IN DILUTE
SOLUTION AND OF TAKING INTO ACCOUNT THE
MOLECULAR WEIGHT

It was a priori certain that the relation between
the groups attached to the asymmetric carbon and
the rotation must be such that when two groups
become identical the rotation vanishes ; but in at-
tempting to go beyond this we are at once met by
the difficulty that the magnitude of the rotation
depends on the wave-length of the light, on the
solvent, and on the temperature. The first thing is,
then, to determine the conditions in which com-
parable numbers may be obtained.

And here it seems most essential to avail our-
selves of the light thrown on the subject by the new
conception of the nature of solutions.

It is certainly inadmissible to use simply the
figures obtained by an examination of the substance
without special precautions, because the size of the
molecule is then uncertain, and the magnitude of
the rotation seems to be specially influenced by every
change of constitution. In this connection it is
important to remember the fact recently discovered
by Eamsay,1 that, of fifty-seven liquids examined, no
1 Chem. Soc. J. 1893, 1098.

NUMERICAL VALUE OF THE ROTATORY POWER 135

less than twenty-one possessed double molecules,
among them the alcohols, acids, nitro- ethane, aceto-
nitrile, and acetone. Another objection is that the
rotation is generally influenced by the solvent, and,
indeed, by every solvent differently, perhaps in con-
sequence of the four groups attached to carbon being
differently attracted. If the substance be used alone,
without solvent, its own molecules may be supposed
to exert a similar influence, an influence displayed
most prominently in the formation of crystals, and
which, in the case of strychnine sulphate, e.g., leads
to the almost complete annihilation of the rota-
tion.

The objections mentioned disappear completely
only when the substance is examined in the state of
rarefied gas. As this is impracticable we are driven
to adopt some other means, and thus arrive naturally
at the state of dilute solution. It is also indispens-
able, of course, to take into account the molecular
weight, which can then easily be determined ; while
the comparability of the results will evidently be by
far the greatest when the same solvent is chosen for
the different cases.

The influence of wave-length and of temperature
seems not to be important if the circumstances of
each case are duly taken into account. The anoma-
lous rotation-dispersion in the case of, say, tartaric
acid in aqueous solution — which is such that the
rotation changes its direction with the colour — is
evidently connected with phenomena of equilibrium
which affect the tartaric acid in the solution ; it was

136 STEREOCHEMISTRY OF CARBON

also found by Biot in a mixture of right- and left-
handed substance. The same holds for the great
alteration in the rotation of tartaric acid when the
temperature, the concentration, or the solvent is
changed. All these phenomena are connected to-
gether and only make necessary a careful use of the
figures obtained, but are no argument against the
existence of relations between rotation and constitu-
tion in general.

II. KOTATORY POWER OF ELECTROLYTES. LAW

OF OUDEMANS-LANDOLT

Active bases. — In perfect harmony with the new
views of the nature of aqueous solutions — according
to which electrolytes undergo, at a sufficient degree
of dilution, a division into ions until, as Arrhenius
pointed out, a limit is reached — stands Oudemans'
observation concerning salts of active bases and
acids. At a sufficient degree of dilution the mole-
cular rotation of quinine, e.g., is independent of
the salt observed. The following table (p. 137) gives
the results obtained by Oudemans l and also by
Tykociner ; 2 it gives the specific rotation [a]L^,
observed at 16° C., and calculated for the base.

It may be remarked here that the equality of
rotation which Wyrouboff3 recently showed to exist
in solutions of isomorphous sulphates and selenates

1 Bee. des Trav. Chim. des Pays-Bas, 1, 18, 184.
- I.e. I, 144. For nicotine, Schwebel, Ber. 15, 2850 ; Carrara,
Gazz. Chim. 23, [2], 593. 3 Compt. Rend. 115, 832.

NUMERICAL VALUE OF THE ROTATORY POWER 137

I I I I

•^ CO CO GO O5
CO CD GO rH <M
CO (M rH (M (N

I S i

I rH

OS O »O O5 O
d 00 C^l *O 00
<N iN CO (M rH

ua TH o

U5 *O -Tfl GO . ?

CO CO CO <M PH

<N rH "

CD TH 00

co cq !H

t^* O5 O5 d O5 O CO !>• "^ ^O 00 "^
rH(MC^<MXOGOrH (M COCOlMCO
rH(M(MCO<MrHC<J(M rHrH

00 CO
rH <M
rH <M

§ g S

Ol rH O5

CO O5 O5 GO rH -«^ CD
rH (M d CO IN rH (M

CO CO iM CO

CO <M rH

I I I I
I CO <?Q CO

O 00 O5 CD O5 CD 'M I —

rHCqt>-<MU5t>rH <M

rHC<J(MCO<Mi-l(M Cq

f + I + I I + +

I I I I *

•a • • « .a a e •

a <D .S 'S '8 'o 3.S

'3 ° 12 j j .S o §

fl 21 '3 'S o q '§ ^_fl P

: § 'B 3 .S .2

O O" O* O O

M 02

a> ®

2 -S

I §

o £

138 STEREOCHEMISTRY OF CARBON

of strychnine and cinchonine, is by no means to be
considered, as he says, as a consequence of a connec-
tion between rotation and isomorphism ; it is simply
a confirmation of Oudemans' law.

Active acids. — The same holds for the salts of
active acids as Landolt found for tartaric acid,
and as is proved by Table II., where the specific
rotation, calculated for the acid, is given (see
p. 139).

The salts of shikimic acid, with alkalies and
alkaline earths, also exhibit equal rotation, according
to Eykman ; l and the same holds, according to
Colson, for acetylmalic acid.2

Finally, it must be mentioned, with regard to
the remarkably low figure obtained for the barium
and calcium salts of methoxy- and ethoxy-succinic
acid, that the very great influence of concentration
is here to be taken into consideration. The specific
rotation of the methoxybarium salt is, e.g., for the
percentage given :

26-1 per cent. 12-4 per cent. 5-7 per cent. 1-15 per cent.

— 14.3 _ 7-4 _ 2-2 + 3-2

Evidently the limit of dissociation is not yet
reached, and this is probably true also for the
gly cerates of the polyvalent metals. With the
monovalent metals the maximum seems to be
reached sooner. The gly cerates were investigated
in ten per cent, solution.

In these investigations the theory of electrolytic
dissociation is a valuable guide ; it enables the

1 Ber. 26, 1281. 2 Compt. Rend. 116, 818.

NUMERICAL VALUE OF THE ROTATORY POWER 139

Mill

IMS

1 1 1 <f S

1 5 1 1 1

ilia

1 1 1 1 1

GO GO (M

| i> | os Aj

1 1 . ! 83

1 ' ' <M

1 1 1 1 1

CO O5

i J S i

| «, | CO

| « } « |

A |

i i i i i

Ml*

1 1 1 1 1

i S i S i

ills

1 3 1 1 1

ss^

CO t- I CJ <M GO i— I

O5 CO C-

I s c I

+ I

»p cp »p os cp

II I O5 GO GO CO CO Ol

I I T-H CO 01 rH (M

+ + + ! I I

n-i i=« --i .S .z; ^ o ••

S3 .2.2 'o c3 s*i
' fl o3 o

' <T3 ' 'd <P O '

N .S ^ "S

I .s - a * s * . s s §

•9 ? § .2 § s fg = § g g

& 2 ^ ^ -g §

' u 'S c8 ft S o

i O fl »— ' 3-5 r '**

2 12 II 1

." ^ -§S2

O ->

1 1

"o S - * o "C

CG CQ C3 rl £f

p, >» 5 a ^3

§§^S fr

STEREOCHEMISTRY OF CARBON

Diff. 14

Oudemans-Landolt law to be predicted, and sees
in the equality of rotation of the different salts
the consequence of the existence of the same ions.
Table II., then, may be condensed thus :

[a]/, for the ion COO(CHOH),COO 43°

COO(CHOH)2C02H 29°

COOCHOHCH2COO 14°

COOGHOHCH2CO_2H 9°

CH2OHCHOHCOO 22°

COOCHOCH3CH,COO 15°

COOCHOCH3CH,C02H 29°

COOCHOC2H.CH2COO 23°

COOCHOC,H5CH2CO,H 37° ,

From this we see at once that, when the rotation
alters on dilution, only the values at the limit are to
be taken, and doubtful cases may be decided by a
determination of the conductivity — i.e. of the mole-
cular weight — accompanying the observation of the
polarisation. Then the objection recently brought
by Frankland against Oudemans' law, based on the
abnormally large rotation of tartar emetic, at once
breaks down ; for this salt, according to determina-
tions of the molecular weight and to the chemical
reactions, is present in solution in a form quite
different from the other tartrates.1

Alcoholic solutions of electrolytes. — Of alcoholic
solutions, at least some have been investigated. It is
probable that here division into ions is not of such
frequent occurrence. Also, the results vary more (for
quinates,2 e.g., they lie between —9° and —40°, while
in water the extremes are —43° and —49°) ; how-

1 Hadrich, Zeitschr. f. physik. Chem. 12, 476.

2 Cerkez, Conipt. Bend. 117, 173.

NUMERICAL VALUE OF THE ROTATOEY POWER 141

ever, the hydriodide, perchlorate, and nitrate of
quinamine are equal. All that is to be inferred from
this is that here, as in other instances, bodies capable
of undergoing division into ions often, without being
actually divided, show in their physical properties
an approximation to the products of division.

The influence which may be exerted by electro-
lytic dissociation is evident from the following
conspectus of the results in alcohol and in water?
which contains the limiting values obtained for
various salts :

Alcohol

Diff.

Water

Diff.

Quinamine salts

130 to 135

117 to 118

Conquinamine

200 , 234

228 „ 229

Quinidine .

233 , 255

322 „ 329

Cinchonine .

206 , 240

258 „ 289

Cinchonidine

-114 , -161

176 „ 180

Quinic acid salts

-9 , -40

-43 ,,-49

Quinine sulphate

-212

—

-279

—

Nicotine acetate .

- 65

—

+ 13-8

—

The change of sign in the case of nicotine salts
(with the sulphate ] also) is of especial interest.

III. KOTATION OF IMPERFECT ELECTROLYTES.
ORGANIC ACIDS

These substances demand separate treatment
because, representing as they do the transition stage
between electrolytes and non-electrolytes, they
exhibit — in aqueous solution at least— complicated
phenomena, which, however, have already been
partially accounted for. In view of the alteration of
1 Nasini, Gazz. Chim. 1893, 43,

142 STEREOCHEMISTRY OF CARBON

the molecular conductivity and of the lowering of
the freezing-point with the concentration of their
solutions, it is evident that water effects a funda-
mental change in their molecular structure — dissocia-
tion, in fact. The salts, especially those of strong
acids and bases, show this at degrees of dilution
which admit of an optical examination, and then
Oudemans' law holds. With the acids this is not
the case.

While, e.g., the non-electrolyte sugar,1 at a
strength of from 70 to O2 per cent., shows a scarcely
noticeable alteration of [a]z,=64'5 to 65-2, and for
disodium tartrate2 the rotation for concentrations
(c) between 5 and 15 per cent, is expressed by

[ay°=27-85-O17c (25-3 to 27),
for tartaric acid 3 we have

0]^=: 14-98 - 0-1303 c (8*5 to 14-3)

between c = 50 and 5 ; while the rotation between
4-7 per cent, and 0'35 per cent, rose from 14*2 to 16'3
(at 20°) . Malic acid even changes from left to right
according as dilute or concentrated solutions are used.4

The laws which govern these complex phenomena
are the following :

1. The alteration in rotation effected by change
of concentration is parallel with that effected by
change of temperature, dilution and rise of tempera-

1 Schmitz, Tollens, Ber. 10, 1414, 1403; Pribram, Sitz.-Ber.
preuss. Akad. 1887, 505.

2 Hesse, Ann. Chem. (Liebig), 176, 122.

3 Arndtsen, Ann. Chim. et Phys. [3], 54, 403 ; Pribram, l.c.

4 Schneider, Ann. Chem. 207, 257.

NUMEKICAL VALUE OF THE EOTATOEY POWER 143

ture acting in the same direction, as in general both
have the same effect on dissociation. For sugar l
and the tartrates 2 the alteration with the tempera-
ture is scarcely perceptible.

With tartaric acid,3 warming, like dilution, effects
a rise :

Temp. 40 per cent. 20 per cent. 10 per cent.

0° an= 5-53 aD= 8-66 a0= 9-95
100° „ =17-66 „ =21-48 „ =23-97

In the case of malic acid, Pasteur found in the
dilute left-handed solution an increase of rotation to
the left on warming, which is the result Schneider
obtained by dilution. With mandelic acid Lewko-
witsch 4 observed a decrease in the rotation on
diluting and on warming ; with rhamnose Tollens
found the same thing.

2. The change of rotation with the concentration
is parallel with that effected by the solvent, so that
the rotations in other solvents approximate to those
in concentrated aqueous solution. Tartaric acid,
which in water gradually rotates less to the right as
the concentration increases, exhibits in other solvents
now a weak right-handed rotation, now even left-
handed rotation, as in alcohol.5

3. The change of rotation on dilution is in the
direction of the numbers obtained for the (acid) salt,
and appears to be limited by these numbers. It is,
again, in the case of tartaric acid that the subject has

1 Tuchschmid, J. prakt. Chem. [2], 2, 235.

2 Krecke, Arch. NecrL 7, 97. 3 Ber. 16, 1567.

4 Ann. Chem. (Liebig), 271, 64.

5 Pfibram, Wien. Acad. 97, 460.

144 STEREOCHEMISTKY OF CAKBON

been most thoroughly investigated. The gradual
increase of [a]/,25 from 8- 5° to 14' 3° between 50 and
5 per cent, is evidently in the direction of the value
found for the acid salt, 29° ; Pf ibram, indeed, obtained
for 0-35 per cent. [a]7,20 = 16-3°, and Krecke at 100°
and 10 per cent, observed 23-97°.

Malic acid, right-handed in the concentrated
solutions (70 per cent. [a]D= +3*34) and left-handed
in dilute solutions (8-4 per cent. [a]n= — 2*3), also
shows an approximation to its (left-handed) salts ;
though their (extreme) value (\_a]D= — 9) is not
attained.

Lactic acid, the right rotation of which is
diminished by dilution (21-24 per cent. [a]^ = 2-66 :
15-75 per cent. [«.]# = 2-06), possesses accordingly
left rotation in its salts.

4. The acids which undergo no change of rotation
on dilution are also those which rotate as strongly
as their acid salts. Methoxy- and ethoxy-succinic
acids l exhibit rotations which scarcely alter with
the concentration :

Methoxy-acid 11 per cent. [o]D = 33-3° 5-6 per cent. [d]D = 33°
Ethoxy-acid 11 „ „ = 33° 5-6 „ „ = 32-5°

These numbers are almost the same as those ob-
tained for the acid salts, viz. [a]y>=29° and 37°
respectively.

For quinic acid,2 also, the rotation is the same,
from 2 to 53 per cent. [a]D= — 43*9°, while for the
salts it is -49°.

1 Chem. Soc. J. Trans. 1893, 217, 229.

2 Hesse, Ann. Chem. (Liebig), 176, 124.

NUMERICAL VALUE OF THE ROTATOKY POWER 145

The rotation of shikimic acid ] also alters but
little (36-26 per cent. \a\D= -204° ; 4'03 per cent.
[a]7>= — 183'8°), while for the ammonium salt it is
-189°.

The hypothesis of electrolytic dissociation ex-
plains these facts to this extent, that it demands
that dilution of an acid and salt formation shall bring
about equal activity, since both cause the formation
of the same ion. For dibasic acids the same holds
for the acid salts, because dilution of these acids first
liberates a single hydrogen atom.

Evidently, however, there is something else con-
cerned besides electrolytic dissociation, and that is
the point of attack offered to the carboxyl group in
another part of the molecule, as appears from the
following.

5. Great change of rotation on dilution manifests
itself specially with the oxy-acids. Malic acid is
remarkable in this respect. The change of rotation
which we have observed to characterise this acid is
no longer found in methoxysuccinic acid and in the
corresponding ethyl derivative, nor in chlorosuccinic 2
and acetylmalic 3 acids*.

C02HCHOHCH,C02H 70%[a]Z)=+ 3-34° 8-4%[a]1,= - 2-3°

C02HCHOCH3CH2CO,H .11 „ „ = 33-3° 5-6 „ „ 33°

C02HCHOC2H5CH2C02H 11 „ „ = 33° 5-6 „ „ 32-5°

C02HCHC1CH2C02H 16 „ „ = + 20-6° 3-2 „ „ + 21-3°

CO,HCHOC2H3OCH2C02H 16 „ „ =-11° 3-2 „ „ -10°

Thus when the hydroxyl group disappears the

1 Eykman, Ber. 24, 1280, 1297. 2 Ber. 26, 215.

3 Guye, Arch. Sc.phys. nat. [3], 29, 430 ; Colson, Compt. Rend.
116, 818.

146 STEEEOCHEMISTRY OF CARBON

rotation becomes more constant. The peculiar part
played by this group is, however, still more plainly
manifested in the gradual change which often occurs
in oxy-acids after a change of concentration or of
temperature. This was first observed in the case of
lactic acid,1 the rotation of which decreased on
simple standing of the freshly prepared solution ; it
was recently proved in the case of glyceric acid,2 and
is due to etherification or lac tone formation, as
Wislicenus showed. This will be considered in the
next section.

In the oxy-acids, then, the alteration of the rota-
tion on dilution may be due to a phenomenon akin
to lactone formation, which also is probably in-
fluenced by electrolytic dissociation. Finally, several
acids, and not oxy-acids only, possess a double mole-
cule,3 and accordingly on changing the concentration
they may break up in a way which will affect the
optical examination. Comparable results for acids
are therefore scarcely to be obtained except by an
investigation of dilute solutions of the alkali salts.

IV. INFLUENCE OF EING FORMATION ON KOTATION

The interaction of several of the groups attached
to the asymmetric carbon atom, which may be accom-
panied by ring formation, appears to have a quite
extraordinary influence on the magnitude and the sign
of the rotation. In the phenomena mentioned above

1 Wislicenus, Ann. 167, 302.

2 Chem. Soc. J. Trans. 1893, 296.

3 Bineau, Ramsay, ibid. 1893, 1098.

NUMERICAL VALUE OF THE ROTATORY POWER 147

we have already had indications of this, and below
the fundamental facts are given.

Lactone formation. — The change of rotation was
first observed in the case of lactic acid,

CH3CHOHC02H [>]„= +2° and +3°,
while the lactone CH3CH— CO (lactid) has the

enormous rotation [a]D=— 86°. * The same change
has been observed for glyceric acid,2 and in the sugar
group has indeed become a simple test to distinguish
between the isomeric saccharic acids,3 e.g., of which
one forms a lactone, a second a double lactone, a
third no lactone. The following table illustrates this :

Lactone formation

[a] D of the acid

[a]jr> of the lactone

Arabonic acid,

C02H(CHOH)3CH.,OH

< - 8-5 4

- 73-9° 5

Ribonic acid, „ Cd salt + 0*6° 5

- 18° 5

Xylonic acid, „

-7°

+ 21° "

Gluconic acid,

CO,H(CHOH)4CH2OH

_ 1-740 e

+ 68-2° 7

Galactonic acid, „

< - 10-56° ti

- 70-7° 8

Mannonic acid, ,,

weak 7

+ 53-8° 9

Saecharinic acid, CtiH12Ou .

Na salt - 17-2°

+ 93-6° 10

Isosaccharinic acid, ,,

left-handed

+ 62° 10

Rhamnonic acid, ,,

- 7-67°

- 38-7° 8

Talomucic acid,

C02H(CHOH)4C02H

> + 24°

< 7on

Saccharic acid, „

+ 8°

-f 38° 12

Mannosaccharic acid, „

weak5

+ 201-8°

(Double lactone) "

I Wislicenus, Ann. 167, 302. 2 Chem. Soc. J. Trans. 1893, 296.
3 Ber. 23, 2614. 4 Ann. Chem. (Liebig), 260, 313.

5 Ber. 24, 4217-4219. 6 Ann. Chem. (Liebig), 271, 78-85.

7 Ber. 23, 2626. s Ibid. 23, 2992.

9 Ibid. 22, 3218. 10 Tollens, Kohlehydrate, 293-295.

II Ber. 24, 3628. 12 Tollens, Kohlehydrate, 309. 13 Ber. 24, 541.

L 2

148

STEEEOCHEMISTEY OF CAEBON

Where the figures, especially those 'for the acid,
are uncertain, because they are strongly influenced
by the time and probably also by the concentration,
we cannot avoid the conclusion that lactone forma-
tion exerts an influence equally profound ; for lactic
acid the difference amounts to about 90°, for arabonic
acid to 70° or more, the same for gluconic acid, for
saccharinic acid 100°, and for the double lactone 200°.
If the acids had been investigated as sodium salts,
and the lactones pure, some relation would perhaps
have been found.1

Multi-rotation. — The phenomenon at first known
as bi-rotation — where immediately after solution a
rotation is observed, which for glucose is twice as
large as afterwards — has been shown by further in-

1 As the result of an investigation made in accordance with this
suggestion, the following table has been published. Here the
' molecular rotation ' is the specific rotation multiplied by the mole-
cular weight and divided by 1000.

Acid

Molecul
Ion

ir rotation
Lactone

Difference

Bibonic

+ 0-2

- 3-0

3-2

Gluconic (d)

+ 1-3 to + 1-8

+ 11 to 12-1

10-8 to 9-2

Mannonic (d and 1)

+ 2

- 9-5 to - 9-8

11-7

Saccharinic .

- 1-1

+ 15-3 to + 15-1

16-3

Isosaccharinic

- 1-1

+ 10-2

11-3

Saccharic (d)

- 2-6

+ 7-3 to + 8-0 9-9 to 10-6

Mannosaccharic .

+ 0-2

+ 35-1 to + 35-6 35-2

(Double lactone)

a-Khamnohexonic

+ 1-3

+ 16-1 to + 16-5

15-0

o-Glucoheptonic .

+ 1-6

- 10-9 to - 11-5

12-8

Gulonic (d and 1) .

± 2-7

± 9-9

12-6

See W. Alberda van Ekenstein, W. P. Jorissen, and L. Th. Eeicher,
Zeitschr. physik. Chem. 21, 383.

NUMEKICAL VALUE OF THE ROTATORY POWEE 149

vestigations, especially those of Tollens,1 to be a
change of rotation which only in the case of glucose
amounts to a decrease of about one-half ; in other
cases there is, indeed, an increase.

Rotation

Initial

Final

Dextrose, CH2OH(CHOH)4COH .

105-2

52-6

Galactose, „

117-5

80-3

Levulose, CH2OHCO(CHOH)3CH2OH

- 104

- 92-1

(- 53 at 90°)

Lactose, C^H^On

82-9

52-5

Maltose, „ ...

118-8

136-8

Arabinose, CH2OH(CHOH)3COH .

156-7

104-6

Xylose, „

78-6

19-2

Bhamnose, C6H1206

-3-1

+ 8-6

+ 92-7

+ 87-5

The phenomenon of multi-rotation corresponds
completely to that observed in the case of the lactone-
forming acids ; if these (galactonic acid, e.g.) are set
free from their salts in solution, the gradual change of
rotation manifests itself here also,2 only it proceeds
faster in the case of the acids. Moreover, the lactone-
forming bodies and those possessing multi-rotation
are most intimately related to one another ; the'
aldehydes exhibiting multi-rotation — glucose, galac-
tose, arabinose, xylose, rhamnose — correspond to the
lactone-forming acids, gluconic and saccharic, galac-
tonic, arabonic, xylonic, and rhamnonic acids.

Then the multi-rotating compounds and the oxy-
acids have the hydroxyl and carboxyl groups in com-
mon. Finally, since the lactone formation, which is
accompanied by the closing of a ring, in general

1 Ann., 257, 160 ; 271, 61.

2 Tollens, Ber. 23, 2991.

150 STEREOCHEMISTRY OF CARBON

brings about an increase of rotation, and in the cases
now under consideration (maltose excepted) there is
a decrease, there is perhaps here a ring opened up.
Thus xylose may have been at first

CH2OHCH(CHOH)2C(OH)H,
1 0-

and later, HOCH2(OHOH)3C(OH)2H, corresponding
to CH2OH(OHOH)3COH.1

And it may be observed that the marked changes
of rotation with the concentration and temperature,
observed with glucose, galactose, and rhamnose,2
and especially with levulose and the lactone-forming
acids, are to be attributed to changes of equilibrium.

Other internal anhydrides. — There are other
isolated cases of great change of rotation through
ring formation which are also related to lactone
formation.

Propyleneglycol ( -- 4° 55' 22 mill.) changes the
sign of the rotation on being transformed into
propyleneoxide ( + 1° 10' 22 mill.).3 The same is
the case with left diacetyltartaric acid, aD=— 19-23,
which forms a right-handed anhydride, an= + 62-04. 4
Finally, phenylbromolactic acid yields a much
stronger phenoxacrylic acid of reverse rotation.5

1 In the case of glucose, according to Trey, hydration does not
take place (Zeitschr. physik. Chem. 18, 193).
- Tollens, Kohlehydrate, and Ann. 271, 61.

3 Jahresber. 1881, 513.

4 Ibid. 1882, 856. [This change of sign does not occur with
acetylmalic acid. (Bcr. 26, K. 371, 492.)]

5 Ber. 24, 2830.

NUMERICAL VALUE OF THE ROTATORY POWER 151

The dibromoshikimic acid, C7H10Br205 aD = — 58,
gives a right-handed bromo-lactone,

C7H9Br05( + 22°).1

Boric acid and polyatomic alcohols, — Now that the
increase of rotation through ring formation has been
established, the very considerable rise of rotation
observed on addition of boric acid is seen in another
light. Such is the effect of this addition that, as is
well known, it was only by this means that activity
could be demonstrated in the case of mannite,
sorbite, arabite, &c. If we consider now the more
recent observations,2 especially those of Magnanini,
we see in the first place that the proved diminution
of the number of molecules involves the hypothesis
that an addition product is formed. In the next
place, in view of the fact that only polyatomic
alcohols (including erythrite) 3 and oxy-acids are
affected by boric acid, while mannite with six
hydroxyl groups demands three molecules of boric
acid, there must be two hydroxyl groups connected
with one boric acid molecule, and we come of
necessity to the hypothesis that the following ring is
formed :

| \B_0-H,
C— (K

1 Eykman, Ber. 24, 1293. See also the high rotation of methyl-
glucoside, &c. (Fischer, Ber. 26, 2400).

2 Zeitschr.physik. Chem. 6, 58 ; Gazz. Chim. 11, 8, 9 ; 1891. <Ref.
Zeitschr. physik. Chem. 9, 230.)

3 Klein, Compt. Rend. 86, 826 ; 99, 144.

152 STEKEOCHEMISTKY OF CAKBON

which is in harmony with the other properties (acid
character, depression, conductivity).

Tartar emetic and analogous substances.— The
enormous increase of rotation which tartaric acid in
its salts ([«]#= 20 to 30) undergoes on transforma-
tion into tartar emetic, and the analogous pheno-
menon in the case of malic acid (salts, [a]z,= —10 to
20 ; antimony derivative, + 115 l) suggest similar
considerations. The fact that only oxy-acids yield
compounds of this kind, the formula of tartar emetic
(C4H406K)2Sb202.H20,2 the anomalous reactions, the
depression (^ = li)3 are in the most perfect harmony
with the following hypothesis as to the constitution :

C02K C02K

HOOH CHOH

HC— Ox /O— CH + 2H20.

| \sb-0— Sb< |
OC— (X \0-CO

Salts of polyvalent metals and polybasic acids,— The

change of rotation in the salts of polyvalent metals,
to which we have already called attention, is partly
due to the fact that in general they do not undergo
electrolytic dissociation to the same extent as the
alkali salts.

But this change of rotation is especially notice-
able when the acid is polybasic, so that here too
interaction of the two carboxyl groups (ring forma-
tion) is possible. The observed alterations in such

1 Landolt, Opt. Dreh.-vermogen. 221. - Ber. 16, 2386.

3 Zeitschr. physik. Chem. 9, 484.

NUMERICAL VALUE OF THE ROTATORY POWER 153

cases are therefore collected here. First we have
Schneider's values for aD for malates :

20 per cent.

Na2

Li, (NH4)2

> +15 - 9-6 - 8-2 - 8-6 - 8-7
- 5 -11-5 -13-1 -13-9 -11-2

Then the striking results with methoxy- and ethoxy-
succinic acid :

Salts

Methoxy-acid

Ethoxy-acid

(NH4)2

5-76 per cent.

15-2

5-22 per cent.

22-2

2-82

15-1

1*48 „

22-8

K2.

12-16

14-3

5-02

14-2

—

5-31

- 12-7

3-04 per cent.

+ 10-4

2-21

+ 5-2

1-79

+ 14-1

26-12

-27-3

25-08

- 8

1-15

+ 6-1

4-56

+ 11-7

V. ROTATION OF NON-ELECTROLYTES. HYPOTHESES

OF GUYE AND CRUM BROWN

In the case of non-electrolytes, the most important
fact concerning the material that has been collected
is that as a rule all exact comparison of results is
impossible. These compounds have not yet been
examined in the same solvent, diluted, and with due
regard to the molecular weight and to the possible
action of the solvent.

That a determination of molecular weight must be
made follows from the observation of Haller,1 who
finds for left isocamphol (borneol) in alcohol, a^=33° ;
in benzene and its homologues, a^=19°. According
to Paterno, hydroxyl derivatives possess in benzene a

1 Compt. Bend. 112, 143.

STEKEOCHEM1STBY OF CAEBON

double molecule. The known borneol according to
Beckmann,1 does not do this, and has also the same
rotation in benzene as in alcohol, a7, = 37°. And
Freundler 2 has recently shown that in the case of
ethereal tartrates the change of rotation by the
solvent is accompanied by a change of molecular
weight.

The views of Guye and of Crum Brown deserve
especial notice. The latter3 proposes to establish
by experiment a function, K (which perhaps alters
for the temperature, &c.), for each of the groups
attached to the asymmetric carbon ; the rotation
would be determined by the difference of these
functions. From the material at hand he thinks it
may be concluded that the function for any group
rises as the group increases.

The objection to this hypothesis is, as the author
himself observes, that in it the mutual action of the
groups plays no part. But in view of what has just
been said about the influence of the solvent, and of
ring formation on the rotation, this mutual action
must be essential. Guye 4 starts on a broader basis,
viz. the whole configuration of the molecule, and he
proceeds to determine numerically its degree of
disymmetry, by the displacement of its centre of

1 Zeitschr. physik. Chem. 6, 440. In accordance with this view
the hydroxyl-free phenylurethane, obtained from isocamphole, shows
no change of rotation.

2 Compt. Rend. 117, 556. •• Proc. Roy. Soc. Edinb. June 1890.
4 Compt. Rend. March 1890 ; Ann. Chim. phys. [6], 25, 145 ;

Arch. Sc. phys. Nat. [3], 26, 97, 201, 333; Rev. scientifique,
49, 265.

NUMEKICAL VALUE OF THE ROTATORY POWER 155

gravity in relation to the six planes of symmetry of
the regular tetrahedron. Six values, dl . . . . d6, are
thus obtained, the product of which, called product
of asymmetry, determines the rotation :

P=dl d2d3d4d5d6.

This product satisfies the main condition, that when
only two of the groups are equal, one of the dis-
placements (the one referred to the plane of sym-
metry between the two groups) becomes nil, and
consequently P is also nil, which corresponds with
inactivity.

These values d, however, are difficult to
determine ; they are certainly influenced by the
weights of the groups and by their distances,1 and
the first thing is to determine the part played by the
weight. The displacement is then determined by
the difference of weight, and we have as a concrete
expression of this :

-P =(0i—02) (ffi—gj (9 \— #4) (9—gJ (#2—04) (03—04)*

where gl . . . . g4 are the group-weights in
question.

This expression is not a necessary consequence of
Guye's conception, but only a formulation of it upon
certain assumptions made for the sake of simplicity.
It is to be regarded as a special case of the view
of Crum Brown, according to which K and g
are identical. Finally, we may repeat that the

1 Compare Frankland and Wharton (./. Chem. Soc. 1896, 1309)
on the methyl and ethyl esters of o-, m-, and p-ditoluyltartaric acid ;
also Guye, Bull. Soc. Chim. Paris, [3], 15, 1187.

156 STEEEOCHEMISTEY OF CAKBON

essential requisite, that P=o when two groups are
identical, is fulfilled ; and that if two groups,
<73 and g4, e.g., change places, the sign of P is
simply reversed, its numerical value remaining the
same.

From this view the following novel and essential
consequences result. If the groups are in the
following order :

9, > £3 > £2 > ffi,

and the substance is, say, right-handed, then when
g4 is replaced by smaller and smaller groups, we may
expect :

1. Diminution of the right rotation for g4>g3 ;

2. Inactivity when g4=g3 ;

3. Left rotation, increasing to a maximum and
then diminishing, when gz > g4 > g2 ;

4. Inactivity when <74 = <?2 ;

5. Eight rotation, increasing to a maximum, and
then diminishing, when g^>g4>g} ',

6. Inactivity when g4 = gl ;

1 . Left rotation, increasing, when g± gr
Thus, when one of the groups gradually passes
from the maximum to the minimum the sign of the
rotation will change four times.

Let us consider first the derivatives of active
amylalcohol, C2H5(=29)CH3.CH.CH2OH. The sub-
stances are arranged in the order of the magnitude
of the radical replacing CH2OH, and it is seen
that, in general, increase of the largest group leaves
the sign of the rotation unaltered :

NUMERICAL VALUE OF THE ROTATORY POWER 157

1. Aldehyde, COH = 29 oJD=+0° 42' (10 Dec.)

2. Ainine, CH2NH2=30 aD=-3° 30' (10 Dec.)

3. Alcohol, CH2OH = 31 [«]„=- 5° 2'.

4. Nitrile, CH2CN = 40 an = +1° 16' (10 Dec.)

5. About sixty compounds between 4 and 6, all
right-handed.

6. Iodide, CH2I=141 an= 4- 8° 20' (10 Dec.)
The change of sign observed in the case of the

amine and the alcohol should, however, not occur
till below 29°.

It follows that change of sign can be brought
about by causes other than change of weight. In
this connection the cases where, as in amylaldehyde,
there are two groups of equal weight are especially
convincing. Here we do not find inactivity, which
Guye's formula wrould demand. Such cases are :
Dimethylic diacetyl tartrate,

C02CH3(CHOC2H30)2C02CH3 :
C02CH3 = OC2H30 = 59 (left-handed) .
Diethylic dipropionyl tartrate,
C02C2H5 = OC3H50 = 73 (slightly right-handed).

Dipropylic dibutyryl tartrate,
C02C3H7 = OC4H70 = 87 (right-handed) .

Acetylmalic acid, C02HCHOC2H3OCH2C02H :

OC2H30 = CH2C02H=59 (left-handed).
Ethylmalic acid, C02HCHOC2H5CH2C02H :

C02H=OC2H5 = 45 (right-handed).
The following table of such esters of tartaric,1

1 Pictet, Arch, des Sc. phys. ct nat. [3], 7, 82 ; Freundler, Compt.
Rend. 115, 509.

158

STEREOCHEMISTRY OF CAEBON

glyceric,1 and valerianic2 acids as have been investi-
gated yields the same result, namely, that the weight
of the groups acts in the sense demanded by Guye's
fundamental conception, but not strictly according to
the formula chosen by him as a first approximation.3

i
CH:1 C.,H3 O.H, C£JJ»

C4HU

iso'J

C7H7

Tartaric acid
Acetyltartaric acid
Propionyltartaric acid
Butyryltartaric acid .

2-1 7-7 1 12-4 14-9
-14-3 5 13-5
— 12 0-8 7-9
- 13 - 1 5-4 —

15-9
17-8

11-3
9-2
7-1

—

Benzoyltartaric acid .

- 88-8 - 60 | -<~!J9 [

—

-42

—

Glyceric acid
Valerianic acid

- 6-8 - 9-2 -12-9 '-11-8
16-8 13-4 | 11-7 —

- 11 -14-2
10-6 IU'5

' 5-31

In the glyceric acid derivatives, CH2OHCHOHC02X,
the rotation is seen to rise as the largest group,
C02X, becomes larger.

The case of tartaric acid is somewhat more
complicated. In the first place there are two
asymmetric carbon atoms, but these being perfectly
identical we may confine ourselves to the considera-
tion of one. But, further, in the derivatives there
are always two groups which alter. If we set out
the groups thus :

H = l cOH = 17 <C02H = 45<CHOHC02H = 75,
we see that, in the esters in which carboxyl hydro-

1 Frankland and MacGregor, Chem. Soc. J. Trans. 1893, 524.

- Guye, Compt. Rend. 116, 1454. Is the decrease of rotation with
the group-weight due to the increased formation of the racemoid
form on distillation, caused by the higher boiling-point ?

3 In confirmation of this see Walden, Zeitschr. physik. Chem. 15,
638 ; I. Welt, Compt. Rend. 119, 885 ; Ann. Chim. Phys. [7], 6, 115 ;
Ph. A. Guye and L. Chavanne, Compt. Rend. 119, 906 ; 120, 452.
Compare J. W. Walker, J. Chem. Soc. 67, 914, and Purdie and Wil-
liamson, I.e. p. 957.

NUMERICAL VALUE OF THE ROTATORY POWER 159

gen is replaced, the two largest groups increase, and
therefore the rotation ; in those in which hydroxyl
hydrogen undergoes substitution, OH = 17 increases,
and also the largest group : a change of sign is
therefore to be expected, and at the same time an
increase in the numerical value. Both occur ; only
the change of sign does not exactly correspond with
the equality of the group-weights.

Further, we must emphasise the fact that, in
isomeric compounds, groups of equal weight do not
correspond to equal rotations. Among gly eerie esters,
propyl- and iso-propyl, butyl- and iso-butyl have not
the same action ; with tartaric acid the case is the
same, but not with valerianic acid. But whether in
the first two cases the difference is as great as the
figures indicate is uncertain, as it is doubtful how far
they can be compared. Thus Freundler found that
ethylic diacetyl tartrate rotates, in alcohol, + 1-02
instead of + 5.

Finally, it is a striking fact, in agreement with
Guye's conception, that the very high rotations
are observed among compounds of high molecular
weight. One example of this is seen in methylic
benzoyl tartrate, —88-8°. Then we have the small
rotation of + 2° for lactic acid, as compared with
— 21° for oxybutyric, and— 11° for leucic acid, 71°
for tropaic acid, —156° for mandelic acid, and —135°
for isopropylphenylglycollic acid. Perhaps in the
last the effect of ring formation is superadded. It
ia a fact that the highest known rotations are found
among the alkaloids and santonine derivatives (over

UNIVERSITY

160 STEREOCHEMISTEY OF CARBON

300° for quinidine, 700° for santonine) , where several
rings and high molecular weight coexist. Of course,
the converse of this rule does not hold. Even when
the molecular weight is high, identity among the
groups annihilates the rotation, and similarity among
the groups perhaps reduces it to small proportions.

VI. MORE COMPLICATED CASES
Several asymmetric groups in one molecule. — So far

we have dealt chiefly with the simplest cases, with
a single asymmetric carbon atom. It remains to
add a few words on more complicated compounds,
which may throw some light on the subject. In the
first place we may consider the idea expressed in
my former pamphlet l that when there are several
asymmetric carbon atoms their action is to be added
or subtracted. Thus for the four pentose types,
COH(CHOH)3CH2OH, we should have the following
rotations :

No. 1 No. 2 No. 3 No. 4

+ A + A + A -A

+ B + B - B + B

+ C - G + C + C

and since the sum of No. 2, No. 3, and No. 4 is equal
to A + B -j- C, the rotation of arabinose (probably the
highest) should be equal to the rotations of xylose,
ribose, and the expected fourth type 2 taken together.
For the asymmetric compounds of the saccharic
acid group a similar conclusion may be drawn. The
four active types would have the following rotations :

1 See Preface.

2 Discovered since, and called lyxose.

NUMEKICAL VALUE OF THE ROTATORY POWER 161

No. 1

No. 2

No. 3

No. 4

+ A

+ B

-B

+ B

- B

-B

+ A

- A

+ A

C02H
HCOH

C02H

HCOH

C02H
HCOH

HOCH

HCOH

HOCH

HCOH

HOCH

C02H

Idosaccharic
acid

Saccharic
acid

8°

Talomucic
acid
29°

Manno-
saccharic
acid ; weak.

The large rotation 2(A+B) might belong to the
first type and would amount to 37°. This corre-
sponds to the constitution in that neither the inner
nor the outer asymmetric carbon atoms are sym-
metrically opposed. Then saccharic acid corresponds
to 2.B, because in its configuration the two outer
carbon atoms are symmetrically opposed ; for similar
reasons talomucic acid corresponds to %A. For
mannosaccharic acid we should then have about 20°
(29° — 8°) ; all that is known is that it possesses
slight activity. Since the acids readily form lactones
an exact investigation of the sodium salts in not too
concentrated solution seems to be the only way to
arrive at definite results.

Further, it is to be noted that the outer asym-
metric carbon atoms cause a rotation of 29°, the

162 STEREOCHEMISTKY OF CARBON

inner a rotation of 8°, and this greater influence of
the excentric carbons accords with Guye's theories.

Influence of the type. — In the second place we
must note the fact that the magnitude of the
rotation is to a certain extent determined by the
type of the compound.

We have already observed (p. 147) what an effect
lactone formation has on the rotation, an effect which
often amounts to about 80° ; and how ring formation
in other cases causes a fairly definite change of rota-
tion. We saw, further, that in many cases stereomers
though not enantiomorphous possess equal rotation
(p. 74). Now it has been observed that in chemically
related compounds there are often found rotations
of a similar order of magnitude.

1. Thus, the alcohols of the type

CH2OH(CHOH)nCH2OH

have a remarkably small rotation, often noticeable
only after addition of borax :

Arabite . . . CH,OH(CHOH)3CH,OH - 5° in borax

Mannite . . . CH~OH(CHOH)4CH,OH almost nil

Sorbite ... „ 1°

Perseite > . . . CH,OH(CHOH)5CH,OH 8° in borax

a-Glucosectite - . CR!OH(CHOH)6CH,OH 2°

It is very remarkable that in the hexatomic alcohol
inosite, C6H6(OH)6--which in composition resembles
mannite, but as a hexamethylene derivative belongs
to another type — we observe at once a compara-
tively strong rotation of 65° (caused by the ring
formation) .

1 Bcr. 23, 2226. 2 Ann. 270, 64.

NUMEKICAL VALUE OF THE KOTATORY POWER 163

2. The amido-acids exhibit rather low rotations :

Leucine . . C4H9CHNH,CO,,H 14°HC1;6°NH3

Phthalyl deriva-
tive . . C4H9CHN(C6H4C202)C02H - 22° C2H60

Cystine . . CH3C(NH2)(SH)C02H - 8° H2O

Phenylcystine . CH3CS(C6H5)NH2C02H < - 4° NaOH

Bromine deriva-
tive . . CH3CS(C6H4Br)NH.)C02H - 4° NaOH

Acetyl derivative CH3CS(CeH5)NHAcCO,H - ? C,H60; 5° NaOH

Bromacetyl de-
rivative . . CH3CS(C6H4Br)NHAcC02H - 7° C2H60 ; 8° NaOH

Tyrosine . . C6H4OHCH,CHNH2CO,,H - 8° HC1 ; - 9° KOH

Phenylamido-

propionic acid C(jH5CH.,OHNH.,CO.,H - 35° H2O

Asparagine . C02HCHNH2CH2CONH2 - 8° H20; + 37° HC1

Aspartic acid . COoHCHNH.CH.CO^ - 4° H20 ; + 25° HC1

Glutamic acid . CO,HCHNH2C2H4C02H 10° H20 ; 26° HC1 ;

- 5° CaO,H2

Glutamine . CO.,H(C3H5NH2)CONH2 slightly right-handed,

H2SO,

Chitamic acid . C6H,3N06 + 1-5° H20

The weak activity of the amido-acids is probably the
reason why no rotation has as yet been discovered in
the case of serine, alanine, &c.

3. Among the lactones of the sugar group, &c.,
larger variations occur ; the values, however, do not
exceed 90°, which amount is attained by the simplest,
lactid. This is probably due to the fact that the
oxy-acids have generally a low rotation, and that
between acid and lactone there is usually a difference
of 80°. The lactones of the following oxy-acids may
be cited :

Lactic acid .... CH2CHOHC02H - 86°

Arabonic acid . . . CH2OH(CHOH)3C02H - 74°
Ribonic acid .... „ - 18°

Xylonic acid .... „ + 21°

M 2

164

STEREOCHEMISTRY OF CARBON

Saccharinic acid .
Isosaccharinic acid
Rhamnonic acid
Gluconic acid
Galactonic acid
Mannonic acid
Talomucic acid
Saccharic acid
Mannoheptonic acid
o-Glucoheptonic acid
j3-Glucoheptonic acid
Gluco-octonic acid
Mannononic acid .

For the double lactone of mannosaccharic acid the
more than double value of 202° is attained.

The small rotations of the oxy-acids are shown
in the following table :

C6H,A

+ 94°

+ 62°

- 38°

CH2OH(CHOH)4CO,H

+ 68°

- 71°

+ 54°

C02H(CHOH)4C02H

7°

38°

CH,OH(CHOH)5CO,H

- 74°

- 68°

+ 23°

CH,OH(CHOH)6C02H

+ 46°

CH,OH(CHOH);C02H

_ 41°

Malic acid .
Tartaric acid
Oxyglutaric acid .
Trioxyglutaric acid
Arabonic acid
Ribonic acid
Xylonic acid
Isosaccharinic acid
Rhamnonic acid .
Gluconic acid
Galactonic acid .
Mannonic acid
Talomucic acid
Saccharic acid
Mannosaccharic acid

. CO,HCHOHCH2CO,H weak + or -
. CojH(CHOH),CCvH
. C02HCHOHC2H4CO,H - 2°
. C02H(CHOH)"3CO.,H~ - 23°
. CH,OH(CHOH)3cb,H less than - 8°
Cd salt + 1°

- 7°

Na salt - 17°

- 8°

- 2°

less than - 11<

weak

29°

8°

weak

. C6H1407

. CH2OH(CHOH)4CO.,H

. CO,H(CHOH)1CO,H

For the acids of the type CH4OH((7HOH)4C02H,
beginning with gluconic acid, the rotations seem to
be extremely small. It is a striking fact that if a

NUMERICAL VALUE OF THE ROTATORY POWER 165

benzene nucleus (ring formation) is introduced into
these oxy-acids relatively high values result :

Lactic acid .... CI^CHOHCO^ + 2°

Oxybutyric acid . . . CH3CHOHCH2C02H - 21°
Leucic acid .... C4H9CHOHC02H - 4°

Mandelic acid . . . C6H5CHOHCO2H ± 156°

Tropaic acid . . . C6H5CH(CH2OH)C02H + 71°
Propylmandelic acid . . C^C^CROUCO^i ± 135°

4. Among the aldehyde sugars, pentoses, glucoses,
heptoses, &c., a difference amounting frequently to
50° is caused by multi-rotation, and the maximum
value, somewhat above 150°, is thus attained ; other-
wise the values are below 100°, as with the lactones :

Arabinose . . . COH(CHOH)3CH2OH 105° (158°)

Xylose .... „ 19° (79°)

Dextrose . . . COH(CHOH)4CH,OH 53° (105°)

Galactose ... „ 80° (118°)

a-Glucoheptose . . COH(CHOH)5CH2OH - 20° (- 25°)

Mannoheptose . . „ 85°

a-Gluco-octose . . COH(CHOH)6CH2OH - 50°

Manno-octose . „ — 3°

Mannononose . . COH(CHOH)7CH2OH 50°

5. Remarkable cases. Cystine derivatives, — The

determinative action of the type is especially striking
in the case of cystine, CH3C.NH2.SH.C02H. The
small rotation (—8°) characteristic of the amido-
acids is maintained when the hydrosulphyl hydrogen
is replaced by phenyl, and by bromophenyl (group
weight, C6H4Br=156), also .in the corresponding
acetyl derivatives ( — 7°, p. 163). Upon oxidising to
cystin,1 CH3CNH2.C02H.SSC02H.NH2.CCH3, how-

1 Baumann, Zeitschr. physiol. Cliem. 8, 305; Mauthner, I.e.
7, 222.

166 STEREOCHEMISTKY OF CARBON

ever, we get at once the enormous value [a]n= —214°
(group weight, S.C02H.NH2.CCH3 = 120).

Shikimic acid,1 — The remarkably high rotation of
the derivatives of this acid—

HC70H

iCHOH

HOHCl JCH

C
C02H

appears to be connected with the partial saturation
of the benzene ring, as the following table shows :

Without saturation [a]7; After saturation [a]D

Acid .... - 184° Dihydrogen product . - 18°

Ammonium salt . . — 166° Dibromine . . . — 58°

Triacetyl acid . . 191° Bromolactone . . . + 22°

Triacetylethylic ester . - 174° Dioxy-acid . . . - 28°

It is noteworthy that here, too, the lactone forma-
tion has the very considerable influence already men-
tioned (p. 147), and indeed to about the same extent.

Limonenenitroso chloride and derivatives,2 — The
striking fact here is that substitution of amine
residues for the chlorine in

C1CCH

HCCH

1 Eykman, Ber. 24, 1285.

2 Wallach, Ann. 252, 151.

NUMERICAL VALUE OF THE ROTATORY POWER 167
reduces the remarkably high rotation :

o-Nitrosylchloride - 315° a-Nitrolepiperidine - 68°

a-Nitrolebenzylamine — 164°
0-Nitrosylchloride - 242° 0-Nitrolepiperidine + 60°

Nitro-camphor and derivatives.1 — In connection
with the amount of the rotation, the nitro-derivative
of camphor, perhaps,

H.C

HCCH3

is highly interesting.

Probably no compound undergoes such a sudden
change of rotation with the solvent and the concen-
tration :

a} = — 140° (O7 per cent, in benzene)
a, = - 102° (5-2 „ „ „ )
a} = - 7° (3 „ „ alcohol)

Further, the salts rotate very strongly, and in the
opposite direction :

Zinc salt . . . a, = + 275°
Sodium salt . .«,•=+ 289°

Santonine derivatives,2 — Although their constitu-
tion has not yet been sufficiently investigated, the

1 Cazeneuve, Compt. Rend. 103, 275 ; 104, 1522 ; Jahresber. 1888,
1636.

2 Carnelutti, Nasini, Per. 13, 2210 ; 22, Ref. 732 ; 24, Ref. 909 ;
25, Ref. 938.

168 STEREOCHEMISTEY OF CAKBON

members of this group are remarkable on account
of their enormous rotations, which in the case of
santonid and parasantonid are as high as [a]^=745
and 892. Lactone formation plays here, as in the
whole santonine group, its usual part, raising the
rotation, as the following table shows :

Acids aD Lactones a.D

Santoninic acid, C15H.WO4 - 26° Santonine, CHHi803 - 174°

Santonic acid, C^H^O, - 70° Santonid, CJ5H1803 + 745°

Santononic acid, C30H3806 + 37° Santonone, C30H3404 + 129°

Isosantononic acid, „ — 40° Isosantonone, „ + 265°

Finally, it may be observed that the cause of the
remarkably high rotation appears to be akin to the
cause of the colour of organic compounds.

STEREOCHEMISTRY OF NITROGEN
COMPOUNDS

SINCE on the one hand the isomeric benzildioxine
discovered by Goldschmidt l was proved by Meyer
and Auwers 2 to be structurally identical with the
one formerly known, and since on the other hand
Le Bel 3 obtained active ammonium derivatives, the
stereochemistry of nitrogen compounds, which I
have already had occasion to deal with,4 has acquired
practical interest.

To begin with that which is simplest, let us in
the first place consider the compounds of trivalent
nitrogen.

I. TRIVALENT NITROGEN

A. TRIVALENT NITROGEN WITHOUT DOUBLE LINKAGE

Here, where we have to do with the configuration
of four atoms or groups, NXYZ, the case is still
simpler than with carbon, where there were five,
C(K1K2K3K4), to consider. Putting the matter quite

1 Bar. 16, 1616, 2176. 2 Ibid. 21, 784.

3 Compt. Rend. 112, 724.

4 Maandblad voor Natuurwetenschappen, 1877; Ansichten itber
org. Chemie, 80, 1878.

170 STEREOCHEMISTRY OF NITROGEN COMPOUNDS

generally — that is, without for the present calling in
the aid of the tetrahedron — we may say in the latter
case that, given the identity of two groups, e.g.
E3 and E4, a mechanical necessity demands that
these two groups shall be similarly situated with
regard to the whole, which only happens if they are
symmetrically arranged with regard to the plane
passing through CEjEg. This brings us at once to
the tetrahedral arrangement ; only it may as well be
Ej or E2 as the carbon which occupies the centre.
The latter is only the case on the assumption of
directive forces proceeding from the carbon atom.

In the case of nitrogen derivatives, NXYZ, we
should from general mechanical considerations arrive
at a tetrahedron of some form, which of course
would be unsymmetrical and would lead to optical
isomerism. Attempts at ' doubling,' made by Kraft l
and by Behrend and Konig with NH(C2H5)=C7H7,
p-tolylhydrazine, hydroxylamine bases (NHEOH),2
gave negative results. It is therefore not improbable
that the groups NXYZ lie in one plane,3 which

1 Ber. 23, 2780.

- Ann. 263, 184. Also Ladenburg (Ber. 26, 864) tried in vain to
obtain optically active methylaniline, tetrahydroquinoline, and tetra-
hydropyridine.

3 Further evidence of this has been supplied by the discovery of
two stereomeric compounds of the ammonia type, which proved to be
inactive.

Isomers having the plane formulae,

X\ /Y X\ /Z

\N/ \N/

I I

Z Y

are of course impossible, because these configurations are identical.

STEREOCHEMISTRY OF NITROGEN COMPOUNDS 171

again points to the existence of directive forces, in
this case proceeding from the nitrogen.

B. TEIVALENT NITROGEN DOUBLY LINKED WITH
CARBON

The oximes. — The first remarkable isomerism
among nitrogen isomers, which indicated the ex-
istence of stereochemical relations, was that of the
oximes, which are known to contain the group
C=NOH.

It was found to be a perfectly general rule that
isomerism occurs when the groups attached to carbon
are different, as the following table shows :

Aldoximes HXCNOH

Ethylaldoxime ' . . . . CH3HCNOH
Propionaldoxime 2 . . . C2H5HCNOH

But if X, Y, Z are bunched together by their mutual attraction, then

X -TT X, r/

I/Y and |/Z

N— Z N— Y

represent two different configurations. Accordingly the stereomers
in question, which are condensation products of acetaldehyde with
asyni. m-xylidene, may be represented by the formulas :

CH(CH3).CH2CHO CH(CH3).CH2CHO

N.C6H3(CH3)2 and N.H

H C6H3(CH3)2

(v. Miller and Plochl, Ber. 29, 1462, 1733). The presence of an
asymmetric carbon indicates that each isomer should be divisible
into two active forms. It must be noted that the persistence of the
isomerism in the compounds of the two substances has not yet been
established.

1 Franchimont, Versl. Kon. Akad. Amsterdam, 1892 ; Bee. Pays-
Bas, 10, 236.

2 Dunstan, Chem. Soc. J. Proc. 1893, 76 ; Ber. 26, 2856.

172 STEREOCHEMISTRY OF NITROGEN COMPOUNDS

Aldoximes HXCNOH

Furfuraldoxime ' . . . . C4H3OHCNOH
Thiophenaldoxime ' . . . C4H3SHCNOH
Aldoximeacetic acid 2 . . . C02HCH2HCNOH
Benzaldoxime 3 . . . . C6H5HCNOH
p-, o-, and m-Nitrobenzaldoxime 4 C6H4(N02)HCNOH
o-, m-, and p-Chlorbenzaldoxime 5 C6H4C1HCNOH
3-, 4-Dichlorbenzaldoxime 6 . C,;H3C12HCNOH
Cuminaldoxime 7 . . . . C6H4(C3H7)HCNOH
Anisaldoxime 8 .... C6H4(OCH3)HCNOH

Ketoximes XYCNOH

Oxiraidosuccinic acid !) . . C02HCNOHCH,C02H
Phenylchlorphenyl 10 . . . C6H5.C6H4C1CNOH
„ bromphenyl 10 . . . C6H5.C6H4BrCNOH
„ lolyl11 .... CGH5.C7H7CNOH
„ anisyl8 .... CfiH5.C6H4(OCH3)CNOH
„ ethylphenyl . . . C.H^C.H.C.H.CNOH
„ propylphenyl . . . CUH5.C6H4C3H7CNOH
,, isopropylphenyl . . ,,

„ araidophenyl . . . C6H5C6H4NH2CNOH
„ oxyphenyl >2 . . . C0H5.C6H4OHCNOH
„ xylylphenyl >3 . . . Cfa.H5.C8H9CNOH

Benzoin14 C6H5.CNOHCH,C6H5

Benzil15 C6H5.CNOHCOC6H5

1 Goldschmidt and Zanoli, Bar. 25, 2573.

2 Hantzsch, ibid. 25, 1904.

3 Beckmann, Ber. 22, 429, 514 ; 23, 1531, 1588.

4 Goldschmidt, ibid. 23, 2163 ; 24, 2547 ; Behrend, I.e. 3088 ;
Hantzsch, I.e. 23, 2170 ; Goldschmidt and v. Rietschoten, I.e. 26, 2100.

5 Behrend and Niessen, Ann. 269, 390 ; Erdmann and Schwech-
ten, ibid. 260, 60.

6 Ibid. 260, 63.

7 Goldschmidt and Behrend, Ber. 23, 2175.

8 Beckmann, Ber. 23, 1687 ; vide also Goldschmidt, ibid. 23, 2163 ;
Hantzsch, ibid. 24, 36, 3479.

9 Cramer, ibid. 24, 1198.

10 Auwers and Meyer, ibid. 23, 2063. n Wegerhof, Ann. 252, 11.

12 Hantzsch, Ber. 24, 5, 3479.

13 Smith, ibid. 24, 4029. I4 Werner, ibid. 23,

15 Auwers and Meyer, ibid. 22, 537 ; Beckmann, ibid. 22, 514.

STEKEOCHEMISTKY OF NITROGEN COMPOUNDS 173

Ketoxiraes XYCNOH

Carvoxime1 .... C9HUCNOH

Thienylphenyl2 .... C4H,8CNOHCfH,

Acetacetic ester 3 . . . . CH3CNOHCO,C,H5
Papaveraldoximes 4 . C6H3(CH30),CN6HC(JNH5(CH30),

Phenylketoximepropionic acid 5 . CUH5CNOHCH,CH,C02H
Phenylketoximecarboxylic acid 6 . CtiH5CNOHC02H
Hydroxamic acid . . . HOXCNOH
Ethylbenzhydroxamic acid 7 . C2H5O.C6H3CNOH

It must be mentioned that the only possible
aldoxime which contains two similar atoms attached
to carbon, H2CNOH, exhibits no isomerism, nor
does the diphenyl derivative among the ketoximes.
But if substitution occurs in one of the phenyl
groups, the two forms regularly appear.8

The dioximes. — When the peculiar oxime group-
ing occurs several times in the molecule, the number
of the isomers rises, amounting to three when the
formula is symmetrical, as with benzildioxime,
(C6H5CNOH)2. Dioximidosuccinic acid,

(C02HCNOH)2,

camphor-, anisyl-, nitrobenzil-, and ditolyl-dioxime,
probably also the simplest gly oxime, (HCNOH)2,
and phenylgly oxime,9 occur in two forms. Kecent

Goldschmidt, Ber. 26, 2084. - Hantzsch, ibid. 24, 5, 3479.

Jovitschitsch, ibid. 28, 2683.

Hirsch, Monatsh.f. Chem. 16, 831.

Ber. 24, 41. 6 Dollfus, ibid. 25, 1932.

Lessen, Ann. 175, 271 ; 186, 1 ; 252, 170.

With the oximes must be ranked the anil compounds,
XYC:NC6H5, since v. Miller and Plochl (Ber. 27, 1296) have pre-
pared, by the action of acetaldehyde on aniline, twoisomeric ethylidene
anilines (CH3.HC : NC6H5)2. See also Ber. 29, 1733. L. Simon, how-
ever, attempted in vain to prepare these isomers (Bull. Soc. Ckim.
[3], 13, 334). » Ber. 24, 25.

174 STEKEOCHEMISTKY OF NITROGEN COMPOUNDS

additions to this list are the dioximes of quinone
and thymoquinone.

The facts concerning the oximes are, then, very
simple : regular occurrence of two isomers 1 for
compounds of the formula XYCNOH ; disappearance
of this isomerism when X and Y become identical ;
increase in the number of isomers when the above-
mentioned group occurs more than once in the same
molecule.

The observations concerning allied bodies may
now be given. The groups to be considered where
nitrogen occurs doubly -linked with carbon are these :

The hydrazones 2 and carbazides.3 — Just as oximes
are formed by the action of hydroxylamine on alde-
hydes or ketones, &c., i.e. on compounds containing
the group CO, so the hydrazones are formed by a
corresponding action of hydrazines on these com-
pounds. And if the group CO is first replaced by
CC12, there are again formed two isomers, provided
the groups linked with carbon are different. The

1 There are, however, many exceptions — cases in which only one
isomer has been isolated. There is only one oxime of pyruvic acid,
of thienylglyoxylic acid, of the ortho-substituted aromatic acids, of
the mixed ketones containing an aliphatic and an aromatic radical
(Glaus and Hafelin, J. -prakt. Cliem. 54, 391). But if we compare
this single oxime with two stereomers of analogous constitution and
of known configuration, we find that in its chemical and physical
properties it resembles one of the two isomers, and totally differs
from the other. These are, then, extreme cases of the instability of
one isomer.

2 Fehrlin and Krause, Ber. 23, 1574, 3617 ; Hantzsch and Kraft,
ibid. 24, 3511 ; Hantzsch and Overton, ibid. 26, 9, 18.

3 Marckwald, ibid. 24, 2880; Dixon, J. Chem. Soc. Trans.
1892, 1012.

STEREOCHEMISTRY OF NITROGEN COMPOUNDS 175

substances at present known have been prepared
from phenyl- and diphenyl-hydrazine, and correspond
therefore to the formulae

XYCNNHC6H5 and XYCNN(C6H5)2.

The following derivatives of this kind have been
obtained in two forms :

Phenylhydrazone of XYCNNHC6H5

o-Nitrophenylglyoxylic acid . . . CaH4NO,(C0.2H)CNNHC6H5
Anisylphenylketone .... C6H5(CtiH4OCH3)CNNHC6H5

Carbazide ... . . . C6H3NH(SH)CNNHC,.H5

p-Tolylcarbazide ...... C7H7NH(SH)CNNHC,.H5

Phenyl-p-tolylcarbazide '. . . C6H5NH(SH)CNNHC7H7
o-Tolyl-p-tolylcarbazide . . . C.H.NH(SH)CNNHC7H7
Di-p-tolylcarbazide . . . . . , ,,

Benzylphenylcarbazide . . . C7H7NH(SH)CNNHCtiH5

Diphenylhydrazones of , XYCNN(C6H5),

Anisylphenylketone .... CtiH5(C6H4OCHa)NN(C6H5),
Tolylphenylketone . . . . C6H5(C(jH4CH3)NN(CtjH5)2

The carbodi-imides. — By abstracting hydrogen
sulphide from sulphocarbanilide, SC(NHC6H5)2,
Weith l obtained a carbodiphenylimide, C(NC6H5)2,
which according to Schall's 2 researches occurs in
three modifications of equal molecular weight.
According to Miller and Plochl,3 however, there are
only two modifications, of which one has thrice the
molecular weight of the other.

The diazotates.

C6H5.N2.X.(X=C1, OMe, S03Me, CN).
Besides the structural isomers,

(1) C6H5.N.X and (2) C6H5N : NX,

1 Ber. 7, 1306.

2 Ibid. 25, 2880 ; 26, 3064 ; Zeitschr. physik. Chem. 12, 145.

3 Ber. 28, 1004.

176 STEEEOCHEMISTKY OF NITEOGEN COMPOUNDS

there is evidence l to show that the compounds
possessing the formula (2) exist in two forms, to
which Hantzsch attributes the stereomeric formulae

CBHaN C6H5N

XN and NX

syn-diazotate anti-diazotate

The question of the constitution of these substances
is still in dispute.2

The isomerism of the bodies H2N2O2 is also
attributed by Hantzsch 3 to doubly linked nitrogen :

HO.N HO.N

(1) HO.N (2) N.OH

syn- anti-hyponitrous acid

The isomer (1) is that which readily breaks up into
N20 and water.

C. TEIVALENT NITROGEN IN CLOSED EINGS

Just as in the case of carbon the double linkage
and the fumar-maleic isomerism were treated in
connection with ring linkage and the isomerism of
the hydrophthalic acids, so here some remarkable
observations by Ladenburg and by Giustiniani should
be mentioned.

The former, having shown that there are pro-
bably five isomeric piperidinemonocarboxylic acids,4

1 Hantzsch, Ber. 28, 1734 ; Hantzsch and Gerilowski, ibid. 28,
2002 ; 29, 743, 1059.

- Bamberger, Ber. 29, 564, 1388 ; Blomstrand, J. prakt. Chem.
54, 305.

3 Ann. 292, 340 ; Hantzsch and Kaufmann, ibid. 292, 317.

* Ber. 25, 2775.

STEREOCHEMISTRY OF NITROGEN COMPOUNDS 177

proved1 that conine (an = ~L&8°) , on heating the
chlorhydrate with zinc dust, is transformed into an
isomer (a/)=8'20),2 and that this was also the case
with the active a-methylpiperidine.3

As the rotation alone indicates, it may be sup-
posed that this is not a case of isomerism caused by
the asymmetric carbon atom.

Giustiniani 4 found that benzylmalimide occurs
in two isomeric forms, of which one is distinguished
from the other by having about double the rotation :

a-Imide aD= -24-3° (2-28 %) £-Imide aD = -48-2° (2-255 %)
aD= -21-4° (0-244%) „ a^^-430 (0-226%)

This isomerism is maintained in the acetyl and
benzoyl derivatives, but is lacking in the benzyl-
malamic acid, which is formed by treatment with
potash.

If we compare the constitutional formulae

CH2— CH2 H2C— CO

HC/ \NH \NC7H7

CH2— CHX UOHC— CO

we find here a structure analogous to the above cases
of double linkage, since here symmetry is lacking in
the carbon radical attached to the nitrogen. Perfectly
analogous cases of isomerism have been recently

1 Preuss. Akad. 1892, 1057.

2 Wolffenstein accounts this a mixture of inactive and dextro-
conine (Bar. 27, 2616 ; 29, 195). But see Ladenburg, ibid. 29,
2706.

3 But see Marckwald, Ber. 29, 43, 1293; and Ladenburg, I.e.
p. 422.

4 Gazz. Chim. 1893, 168.

11 '8 STEREOCHEMISTRY OF NITROGEN COMPOUNDS

discovered by Ladenburg l among the imides of
tartaric acid.

D. CONFIGURATION IN THE CASE OF DOUBLY LINKED
NITROGEN 2

Combining the two ideas, that from carbon there
proceed four directive forces as divergent as possible—
that is, directed to wards the tetrahedron corners — and
also from nitrogen three forces in one
plane directed towards the corners of
a triangle, we arrive at the annexed
fig. 18 in the same way as we deduced
the figure for doubly linked carbon.
The essence of this arrangement is
that, as in ethylene derivatives, all the
components, ANCXY, must be arranged
in one plane. Under the influence of
the attractive forces proceeding from
X and Y, the radical at A appears to
find its position of equilibrium either nearer to X or
nearer to Y ; but as one of these positions will be
more favoured than the other, we can always dis-
tinguish a stable and a labile modification. Hantzsch
and Werner represent this very suitably thus : 3

1 Ber. 29, 2710.

2 Willgerodt, J. prakt. Ghent. 37, 449 ; Marsh, J. Chem. Soc.
1889, 654 ; Hantzsch and Werner, Ber. 23, 11 ; Werner, Raumliche
Anordnung der Atome in stickstoffhaltigen Molekulen, 1890 ;
Beitrdge zur Theorie der Affinitat und Valenz, 1891 ; Vaubel, Das
Stickstoffatom, 1891 ; V. Meyer and Auwers, Ber. 24, 4229 ; 26, 16.

3 But compare Behal, Actualitts Chimiques, 1, 76 ; Jovitschitsch,
I.e. 167.

STEREOCHEMISTRY OF NITROGEN COMPOUNDS 179

NA AN

II and ||

XCY XCY

The three isomers of benzildioxime would then be
represented thus :

... xc- — cx xc- — ex xc— -ex

AN NA

AN AN

NA AN

For the corresponding isomerism in ring com-
pounds the relations would be expressed, according
to Ladenburg, by the symbols used on p. 121, as
follows :

and

C3H7

Nitrogen linked with nitrogen. — It must not be
overlooked that Willgerodt l has observed in the case
of the picrylhydrazines formed from dinitrochloro-
benzene and phenylhydrazine,

C6H3(N02)HNNH(C6H5)

— as well as in the case of picryl-a- and -/3-naphthyl-
hydrazine,2 which are constituted according to the
formula EjHNNEgH — an isomerism which, on
oxidising these compounds to the azo-derivative
g, disappears.

J. prakt. Cliem. 37, 449.

2 Ibid. 43, 177.

N 2

180 STEREOCHEMISTRY OF NITROGEN COMPOUNDS^

The explanation given, which is based upon the
difference between the symbols

and !

K2NH HNK2

would indicate that free rotation is stopped by a
single nitrogen-nitrogen linkage, as by a double
carbon linkage.

The cause of this might be found in the supple-
mentary valences, and doubly linked nitrogen would
then be analogous to trebly linked carbon and cause
no isomerism.

II. COMPOUNDS CONTAINING PENTAVALENT
NITEOGEN

Besides these researches on derivatives where the
nitrogen is trivalent, there are some observations of
Le Bel's on ammonium compounds. In the first
place he succeeded l in obtaining two isomeric
trimethylisobutylammonium chlorides, a result
which calls to mind the isomerism which Ladenburg2
stated to exist in the trimethylbenzyl derivative,
but which Meyer 3 doubted. The isomerism dis-
covered by Le Bel shows itself in the chloroplatinate,
which at first forms in needles, but after recrystallisa-
tion from alcohol in octahedra. This second type is
regained unaltered after treatment with silver oxide
and reconversion to chloroplatinate ; but if the ex-
periment lasts some time the needles result on re-

1 Compt. Rend. 110, 144. 2 Ber. 10, 43, 561, 1152, 1634.

3 Ibid. 309, 964 978 (Corrp.), 1291.

STEKEOCHEMISTKY OF NITROGEN COMPOUNDS 181

formation of the platinate. One compound there-
fore is the more stable as chloroplatinate, the other
as hydroxide. It is to be observed that if the sub-
stituted groups are smaller (trimethylpropyl, tri-
propylmethyl) the isomerism in question does not
occur, probably in consequence of an intra-molecular
transformation, which, in fact, is favoured by the
mobility of the smaller groups. The same thing is
observed among the oximes ; ethylaldoxime is easily
transformed, and probably for the same reasons the
simplest members of the ketoximes are lacking (e.g.
phenylmethylketoxime) . Schry ver l made similar
observations. While the corresponding ethyl and
methyl derivatives showed no isomerism, it was
found that on treating methylethylisoamylamine
with ethyliodide a chloroplatinate results, which on
warming is converted into the compound obtained
direct from methyl iodide or amyl iodide and the
appropriate amine. Here, then, we have isomerism
in the case of

(H3C)3C4H9NC1 and (H3C)(C2H5)2C5HUNC1.

Finally, Le Bel 2 has made the most impor-
tant observation, that isobutylpropylethylmethyl-
ammonium chloride may be ' doubled,' and yields
active compounds, numbering probably four. The
chlorides of ethylpropyldimethyl, ethyldipropyl-
methyl, ethyldipropylisobutyl, and ethylpropyldiiso-
butyl ammonium could not be ' doubled.'

The only conclusion at present to be drawn from

1 J. Chem. Soc. Proc. 1891, 39. ~ Compt. Rend. 112, 724.

182 STEKEOCHEMISTEY OF NITKOGEN COMPOUNDS

what has just been said is that in ammonium
chloride, in view of the activity among its deriva-
tives, all the atoms do not lie in one plane ; while in
view of the isomerism of the trimethylisobutyl
derivative, the four hydrogen atoms have not identi-
cal positions in the molecule. The inactivity
observed when two groups are identical would indi-
cate that the similar groups are symmetrically
situated with regard to the plane passing through the
two others, the nitrogen and the chlorine.

For graphic representation I will reproduce here
that cube which I long ago proposed (p. 169). The
nitrogen is supposed to be in the
centre and the five connected
groups in five of the corners (fig.
19). Of these 1, 2, and 3, which
have equivalent positions, corre-
spond to the alkyls attached to
FIG. 19. the three chief valences. When

the nitrogen is trivalent they lie in
one plane with it ; here they are somewhat displaced
through the influence of the chlorine situated in 4 ;
in 5 lies the fourth alkyl.

If one of the alkyls is different from the three
others, which are identical, so that the type

(E,)3E2NC1

results, as in (H3C)3C4H9NC1, there is the possibility
of isomerism according as C4H9 is in 5 or in 1 to 3.
And this isomerism has actually been observed. As
yet there is no reason to expect optical activity.

STEKEOCHEMISTKY OF NITKOGEN COMPOUNDS 183

The stability of one isomer has been found to be very
slight.

If two different alkyls have entered the molecule,
which would give the type (K1)2R2R3NC1, then be-
sides asymmetric (i.e. active) configurations (Rj in 5),
there is always a symmetrical configuration possible
(R2 or R3 in 5) ; and the slight stability above men-
tioned leads to the symmetrical type, which always
corresponds to the favoured position of equilibrium.
Accordingly ' doubling ' has not succeeded here, e.g.
in the case of

C2H5(CH3)2C3H7NC1.

If three different radicals have entered the mole-
cule (type R1R2R3R4NC1), internal symmetry is
impossible. The ' doubling ' succeeded here in the
case of (C4H9)(C3H7)(C2H5)(CH3)NC1, of which
already several isomers have been prepared. Of these,
four types should exist, according as one or the
other of the four different groups occupies 5 ; each
of the four types would be divisible into two isomers
of opposite activity.

185

APPENDIX

STEREOCHEMICAL ISOMEEISM OF
INOEGANIC COMPOUNDS

NOTE BY ALFBED WERNEB

Professor of Chemistry in the University of Zurich

To facilitate the study of the stereochemical isomerism
presented by certain classes of inorganic compounds, we
must glance briefly at the constitution of these substances.
They are molecular compounds whose constitution can
hardly be represented with the aid of the idea of
valence, unless we resort to several secondary hypotheses,
each applicable to only a limited number of compounds.

The constitution of the molecular compounds may be
established on the basis of a relation between those known
as ammoniacal metallic compounds and the double salts,
such as the double chlorides, fluorides, nitrites, &c.
Indeed, the two extreme groups may be connected by a
certain number of intermediate bodies of mixed character,
thus forming a continuous series in which the molecular
combinations of the first class gradually pass into the
double salts.

Let us consider this remarkable transition in one of
the most simple series. In the study of the compounds
in question the fact that certain electro-negative radicals
in the molecule behave in a peculiar, an abnormal manner,

186 APPENDIX

is of great importance. To emphasise this peculiarity, let
us take a special case. We are acquainted with two
ammoniacal compounds of cobalt, the one corresponding
to the formula Co(NH3)6Cl3, the other to the formula
Co(NH3)5Cl3. It is seen that the two bodies differ only
by a molecule of ammonia, and yet their chemical
properties are very different and characterised by the
following reactions. On adding a solution of nitrate of
silver to a solution of the first salt, it is found that the
three atoms of chlorine are precipitated as silver chloride,
a nitrate, Co(NH3)6(N03)3, being formed. In the case of
the second salt, the nitrate of silver precipitates only two
atoms of chlorine, the third differs entirely in its chemical

(~n

function ; a chloronitrate, Co(NH3)5/1VTr> v , results.

(1NU3J2

This difference in reaction is observed also in the case
of other reagents. Thus, when acted on by concentrated
sulphuric acid, the first salt loses its three atoms of
chlorine as hydrochloric acid, while the second in the
same circumstances loses only two molecules of hydro-
chloric acid.

Thus the three chlorine atoms of the second salt have
not the same chemical function ; one of them behaves in
a special way like the chlorine in certain organic com-
pounds. Arrhenius' hypothesis of electrolytic dissociation
accounts for this anomaly. The two atoms of chlorine
which have the same properties as the chlorine in the
ordinary chlorides (chloride of potassium, &c.) behave as
ions, while the third does not.

As is well known, one of the factors of the electric
conductivity of a saline solution is the number of ions
which it contains ; the properties of the two salts
Co(NH3)6Cl3 and Co(NH3)5Cl3 indicated, then, that there
would be a difference in the conductivity of the solutions
of these compounds. Experiment confirms this prevision.

APPENDIX 187

For a dilution of 1,000 litres the molecular conductivity
of the first salt has been found equal to 432'6, and that of
the second to 261'3.

There can then be no doubt that the first salt contains
three atoms of chlorine identical in properties and acting
as ions, while the second contains only two which can
act in this way.

What chiefly interests us is to find the difference of
constitution to which we should refer the various pro-
perties of the negative groups forming part of the mole-
cules in question.

All the chemists who have worked at this subject,
whatever their theories as to the constitution of the
ammoniacal metallic compounds, consider this difference
of constitution as the consequence of a different connection
of the negative group with the metallic atom, which
connection may be either direct or indirect.

When the connection is direct — that is, when the
negative group is directly united with the metal — this
group does not behave as an ion. When the connection is
indirect — that is, when the negative group is united to the
metal indirectly by means of anjmoniacal molecules — this
group behaves as an ion. The difference between the two
kinds of connection is indicated by the following formula :

r ^Cl
0<NH3C1

Although this way of looking at the constitution of
these compounds does not harmonise very well with the
ideas which we ordinarily hold concerning the state of
salts in solution, it is so thoroughly confirmed by all the
facts observed with regard to the class of ammonio-
metallic compounds, that it is hardly possible to doubt it,
and we shall adopt it in the following discussion.

One of the simplest series of bodies which we have to
consider is that of the derivatives of bivalent platinum.

188 APPENDIX

The platinum atom combines with four molecules of
ammonia to form a compound, Pt(NH3)4X2, the letter X
representing a monovalent acid radical. The reactions of
these salts, and their molecular conductivity, prove that
the two acid groups act as ions ; they represent the acid
radicals of a salt of which the positive part is the radical
Pt(NH3)4.

The second term of the series is a compound,
Pt(NH3)3X2 ;

the old constitutional formula Pt < 'v Hs'X is

JN±i3X

not at all in accord with the observed molecular con-
ductivity, which indicates that only one of the chlorine
atoms behaves as an ion. The formula should then be

Pt(NH3)3X
X

The third term of the series, Pt(NH3)2X2, is found in
two isomeric forms, the salts of platosammine and the
salts of platosemidiammine. The formulae attributed by
Cleve and Jorgensen to these salts are the following :

p NH3.C1 , p NH3.NH3.C1

<NH3.C1 <C1

Now, neither of these formulae accounts for the chemical
properties and the electric conductivities of these salts.
Indeed, these substances no longer behave at all like salts
of strong bases ; but the chlorine, in such salts as

has properties analogous to those possessed by this
element in chlorinated organic bodies ; the electric
conductivity approaches zero, and it is with great difficulty
that any chemical reactions can be brought about. From
all this it follows that their formulae must be

APPENDIX 189

the two negative radicals being in direct union with the
platinum ; in this case the ammonia molecules must be
united similarly ; the rational formula will be then :

The negative groups being attached by means of
valences, as it is usually called, the ammonia molecules
by means of secondary forces, I shall indicate this
difference by saying that the molecules of ammonia are
co-ordinated, that is to say, that they must be directly
connected with the metallic atom, the platinum, although
this linkage is not due to what are ordinarily called
valences.

The next term of the series is a compound,

PtNH3Cl2ClE,

E representing a monovalent positive group ; it is a double
salt in the ordinary sense of the word. Supposing E to
represent an atom of potassium, the formula would

ordinarily be written thus : Pt^3 + KC1. But the sub-

stance does not behave at all as this formula would
indicate; on the contrary, its molecular conductivity proves

that it contains a complex radical, Ft™ 3, which acts as

a negative ion, the potassium being the electro-positive
ion. The compound in question is a salt of a peculiar

kind, of which the acid radical is the group Ft™ 3 and

the basic radical the potassium.

The final term of the series is the compound
PtCl2-f2KCl,

the addition product formed by platinous chloride and
potassium chloride. This salt, again, has not the properties

190 APPENDIX

which the above formula assigns to it, th& molecular
conductivity proving beyond doubt that we have to do
with a salt of which the acid radical is formed by the
group PtCl4, the basic radicals being the two potassium
atoms ; the negative ion is PtCl4, the positive ions are
K2, and the rational formula is (PtCl4)K2.

To resume. These substances form the following
series :

[Pt(NH3)4]Cl2;

In this series we observe that all the compounds
contain a special radical (PtA4), of which the character
varies with the nature of the groups A. In the first
terms this radical has a basic function ; in the middle of
the series it is neutral, and in the last terms it has an acid
function. The constitution of this radical PtA4 is of
much interest. Everything tends to show, as we have
pointed out, that the four groups A are directly connected
with the platinum atom. If these four radicals are in
the same plane with the platinum atom the constitution
of these complex radicals will be represented by

Admitting this arrangement of groups in one plane,
we get, when two of the radicals A are different from the
other two, a case of geometrical isomerism expressed by
the formulae :

We must refer to these theoretical formulae certain cases
of isomerism observed among the compounds of platinum.

One of the most characteristic examples is the

isomerism of the salts of platosemidiammine,

•jr

with the salts of platosammine, Pt /-J TT \ .

ViN±13J2

The two series of compounds correspond to the same
formula,' PtL 3'?, and we can explain their isomerism

only by the stereochemical formulae,
and

We can even allot the proper formula to each of the two
series.

Let us assume that, say, the first formula represents
the compounds of platosemidiammine, the second formula
the compounds of platosammine,

01>PWNH3 C1>Pt<;NH=

Cl>Pt<NH3 NH^ t<:Cl

Chloride of platosemidiammine Chloride of platosammine

then the analogous compounds formed by platinous
chloride with pyridine will have the formulas :

ClPy Py

By treating the chloride of platosemidiammine with
pyridine, and the chloride of platosemidipyridine with

ammonia, we obtain the same compound, Ptjp 3^2 C12,
which we shall call a and which is formed thus :

•a

Similarly, by treating the chloride of platosammine
with pyridine, and the chloride of platopyridine with

192 APPENDIX

ammonia, we obtain a compound, P^p 3'2 C12, differ-

ing from a, and which we shall call (3 ; this is stereo-
meric with a.

It is formed thus :

NHCl

< 4-m-FM -

PyCl H3)2- Py

On warming the compounds a and /3 they lose ammonia
and pyridine and change into compounds of the platos-
ammine series, that is, into bodies corresponding to the
general formula :

On considering the formulae of a and /3, it will readily
be seen that the substance « will undergo such a trans-
formation, on losing a molecule of ammonia and a mole-
cule of pyridine according to the equation :

FNH3 p Py-|cl NH3 NH3 p Cl
[NH3>It<PyJU2 ~ Py cP <Py

The compound a should yield, then, in this reaction a

substance, Pt.NH3

C12

The compound /?, on the other hand, could undergo
the transformation into salts of the platosammine series
in two different ways, either by losing two molecules of
ammonia, or by losing two molecules of pyridine, as
shown by the following equations :

APPENDIX 193

On warming /?, then, we should obtain a mixture of two
substances, A > Pt < MTr and

These reactions, which may be deduced from the
stereochemical formulae of the compounds of platosam-
mine and of platosemidiammine, are in fact those which
occur on warming the substances « and /?, of which the
formulae are thus settled.

It can be shown that if we give to the platosammine

A X

salts the formula ^>Pt<y, and to the platosemidiam-

X A

mine salts the formula ^ > Pt < -^- , we shall arrive at con-

clusions which are no longer in accord with the facts.
For, on adding to platosammine chloride,

Cl NH

two molecules of pyridine, and to platopyridine chloride,
™>Pt <p^» two molecules of ammonia, we should get a

compound -^ g3 > Pt < p^ C12 ; but this compound could

change into salts of the platosammine series in three
different ways : first, by losing two molecules of ammonia ;
second, by losing two molecules of pyridine ; third, by
losing one molecule of ammonia and one molecule of
pyridine ; we should obtain, then, a mixture of the .three

substances, Pt ^2, Pt^H^2, Pt.NH3. Now, this has never
A2 A2 Xa

been observed in a single case, even when the amines of

a-2
the compound. Ptb2 are quite analogous in character, e.g.

X2
ethylamine and propylamine.

194 APPENDIX

The two isomeric series must, then, correspond with
the following formulae :

X ^ Pf ^ A
x>Pt<A

Salts of platosemidiamraine Salts of platosammine

The number of stereomeric compounds of dyad
platinum is already considerable. A special interest
attaches to the compounds of sulphurous acid, having the
formulae :

Cl NH3 d Cl^ NH3

and to the compounds

H03S p NH3 d HO.,S p NH3

H03S>I <NH3 NH3> t<:S03H

The substances thus far considered contain a radical
MA4. There exists also a large number of inorganic com-
pounds whose molecules are characterised by the pre-
sence of a radical MA6, and which may be arranged in
series having characters analogous to those which we
have developed in detail for dyad platinum.

To give an idea of these series, here are the formulae
of the compounds of tetrad platinum and of dyad cobalt :

[Pt(NH3)6]Cl4,

[Pt$H3),]C1'

[PtCl6]K2 Co(NH3)6Cl3,

2)2-|n rr(N02)

(NH3)4JC1' L (NH4)3- (NH3)2

2) [Co(N02)6]K3..
Just as in the radicals MA., the four groups A are

APPENDIX

195

directly connected with the atom of the metal, so in the
compounds containing the complex radical MA6 the six
groups are in direct union with the metal ; the proof is
afforded by the amount of the molecular conductivity.

We have now to get an idea of the configuration of
these groups MAG ; the most simple hypothesis that can
be formulated is an octahedral arrangement ; the metallic
atom occupying the centre of the octahedron, the six
groups A will have their places at the corners.

It is evident that this arrangement should give rise to
certain cases of stereomerism, of which we shall consider
at present only one, which experiment confirms.

Let us consider a radical MA6 of which four groups
are alike and the two others different : we have then a

group M * / . In this case the two radicals A' may

occupy different positions ; they may occupy two corners
of the octahedron joined by an axis, or two corners
joined by an edge, as the following figures show :

that is to say that the compounds containing a radical
M A j , should present two isomeric forms.

The radical M^/ is found in certain ammoniacal

196

APPENDIX

derivatives of cobalt, salts of praseocobaltammine,
answering to the general formula CO/-NTTT \ X ; these

salts should, then, if our theory is correct, present a
special isomerism. And, as a matter of fact, this is what
we find. We know by the beautiful researches of Jorgen-
sen that there exist two series of salts of the formula

The two series scarcely differ, from a

chemical point of view ; of the three acid radicals, only
one acts as an ion. But the two series are distinguished
by a characteristic property ; the salts of the praseo-
cobaltammine series are green, while the salts of the
isomeric series, the salts of the violeocobaltammines, are
violet, as their name indicates (see figs. 22 and 23).

1TH

This interesting case of isomerism is a first proof in

favour of the stereomerism of the radicals

Mt:

another series, also, cobalt presents this special isomerism.
For a long time there has been known a group of salts of
cobaltammine, called salts of croceocobaltammine, and

answering to the formula Co^H) X ; these also, then,

APPENDIX 197

contain a radical M ^ 2 . Quite recently Jorgensen
has discovered a new series of compounds having the
same formula, ^°(jirf) r^' an(^ Differing fr°m the

first only in physical properties. He calls them salts of
flaveocobaltammine, and it is impossible to doubt that
this isomerism of the two series arises from the presence

of two isomeric radicals, ^o/-^-g-2y . To represent

the positions occupied by the two NO2 groups, one may
imagine the following formulae :

Among the ammoniacal derivatives of tetrad platinum
we find a case of isomerism perfectly analogous to those
observed among the cobalt compounds.

We know, in fact, two series of bodies answering to

the general formula Pt' v ; they are the salts of
platinosemidiammine and the salts of platinammine ; here
again, then, we encounter the radical M^ .

Here, too, the isomerism is doubtless due to the
same cause as with the cobalt compounds, and would be
represented by the following formulae :

198

APPENDIX

We can even determine, with a certain degree of proba-
bility, the space formula corresponding to each of the two
series.

The compounds of the platinosemidiammine series
and of the platinammine series are formed by the addition
of two negative groups to the salts of platosemidiammine
and of platosammine; the dyad platinum transforming
itself into tetrad platinum :

For the compounds of bivalent platinum WQ have
arrived at plane formulae ; for those of tetravalent platinum
wre have given octahedral formulae. The most simple
hypothesis is, then, that the negative groups add them-
selves to the salts of divalent platinum, so as to occupy two
corners united by the diagonal of an octahedron, which
is formed by the four radicals joined to the platinum, and

APPENDIX 199

by the two added radicals which complete the mole-
cule.

This transformation is explained by the above formulae,
which also give us the stereochemical formulae of the two
isomeric series.

In the short sketch here given of the stereochemical
isomerism of certain classes of inorganic compounds
we have been able to consider only the principal points
of the new theory ; we believe, however, that we have
proved, by well-established facts, that it is possible to
explain these cases of isomerism only by stereochemical
conceptions.

BlBLIOGEAPHY

A. Werner, ' Contribution to the Constitution of Inorganic Com-
pounds,' Zcitsclir. f. anorg. Chcm. 3, 267.

A. Werner and A. Miolati, Zeitschr. f. pliysik. Chem. 12, 35 ;
13, 506.

INDEX

ACETYLMALIC ACID, 117, 138, 157

Acetylene dicarboxylic acid, on

addition of bromine yields di-

bromomalei'c acid, 106
o-Acrose, divided by means of

yeast, 32

Acrylic acid series, 101
Active derivatives formed by the

action of hydrochloric acid on

albuminoids, 48

— substances, list, 14

Activity, disappearance of, in
derivatives, 21

— in which compounds it is re-

tained, 21

— optical, 9, 10

— prediction of, confirmed, 19

— refutation of supposed, 20

— what is a sufficient cause for, 23,

25
Addition, mechanism of, in the

formation and transformation of

isomei's, 105
Adonite, 79, 86
Alanine, no rotation as yet observed,

163
Aldehyde ammonia, 25

— thio derivatives of acetyl-, &c.,

117

Aldoximes, stereomeric, 172
Alkaloids exhibit the highest known

optical rotation, 159
Allyl alcohol, inactivity, 95
Allylene type, second case of optical

activity, 103

Amido acids, slight activity, 163
Ammonium bimalate, 11, 52

— chlorides, substituted, inactive

(except methylethylpropyliso-
butyl), 181

Ammonium chlorides, trimethyliso-
butyl, two isomers, 180

— — methyldiethylisoamyl, two

isomers, 181

— compounds, substituted, stereo-

merism of, 180
Ammoniums, substituted, stereo-

merism of salts of, 180
Amyl alcohol, 16, 31
active rotation of derivatives,

Guye's theory, 156
chloride of secondary, active,

iodide of secondary, active, 24

secondary, 20

— alcohols, inactive, obtained from

active carbohydrate by fermen-
tation, 23

— chloride, 16

Amyl hydride, found to be inactive,
21

— iodide, 16

Amylmalic acids, preparation of
four, 57

Amyl series, activity among mem-
bers, 21

Amylene, found to be inactive, 21

Anethol, 101

Angelic acid, 101

Anil compounds, 173

Apiol, 111

Apocinchonine, specific rotation,
137

— hydrochlorate, specific rotation,

101
Arabinose, 85, 86

— r- and 1-, 64

— multi-rotation, 149

Arabite, its strikingly small rotation,
162

202

INDEX

Arabonic acid, 64

— its rotation and that of its

lactone, 148
- — conversion into ribonic acid,

Asparagine, poisoning power of r-
and 1-, 12

— inactive, doubling by crystallisa-

tion, 39

Aspartic acid, 15, 22, 32, 47
inactive, obtained by mixing

the dextro- and lasvo-rotatory,

— rotation, 163
Astracanite, formation from the

simple salts, 39

Asymmetric carbon, character of
the isomerism due to the, 9 .

— conditions of formation of com-

pounds, 45

Asymmetry, manifested in chemi-
cal, crystallographical, physical,
and physiological properties, 10,

Atropine, its activity, 73

— contains at least two asymmetric

carbon atoms, 61

— its modifications, 61
Atrophies, dextro- and laavo-rota-

tory, 61

BENZALLEVTJLIC acid, 102
Benzene, configuration, 1, 128

— derivates, 127

— its acetylene nature, hence no

prospect of stereomers, 127

— the problem of the relative posi-

tion of the six carbon atoms is
not yet completely solved, 128

— stability of, accounted for, 132
Benzildioximes, configurations of

the three isomers, 179

Benzoin, hydi'o- and isohydro-, their
constitution, 77

Benzylmalimide, two isomers, 177

Bi- and isobi-desyl, constitution, 77

Bi-rotation, 148

Boiling point, of racemic com-
pounds, 43

Boric acid, effect on rotation of
polyatomic alcohols, 151

Borneol as example of a transforma-
tion caused by changing one of
the asymmetric atoms, 72, 74

Borneol, rotation in benzene and

in alcohol, 153

Borneols, four active, and their de-
rivates prepared by reducing
camphor, 58, 59
Brassic acid, 101
j8-Bromacrylic acid, 101
Bromethylenes, Paterno's explana-
tion of their isomerism, 1
Bromine, addition of, to cinnamic
acid, giving an example of race-
mic compound containing two
asymmetric atoms, 68

— addition products (of crotonic and

iso-crotonic acids, hypogeeic and
gaidic acids, oleic and elaidic
acids, erucic and brassic acids,
mesaconic and citraconic acids),
as examples of racemic com-
pounds as yet undivided, 69
Bromnitroethane, 25
Bromobenzene, inactive, converted
in the animal organism into
active bromophenylmercapturic
acid, 45

Bromocinnamic acid from cinnamic
acid dibromide, 96

— inactivity of, 3, 96

a- and ^-Bromocinnamic acids, 101

a- and |8-Bromocrotonic, and brom-
isocrotonic acids, 101

Bromoglycollic acid, 25

Bromomalic acid, 24

Bromomethacrylic acid, 101

Bromophenylcystine, 18
j Bromopheiiyl-lactic acid, division
of, as example of division of a
compound containing two asym-
metric carbon atoms, 69
I Bromopropionic acid, 24

Bromopseudobutylene, 100

Bromosuccinic acid, 24

— formation from malic acid, 24

— from malic acid, inactivity, 49
Butyl alcohol, 14

— secondary, division, 31

— alcohols, inactive, obtained

from active carbohydrate by
fermentation, 23
Butylene glycol, division. 31

CAMPHOK, 19

— modifications, two camphoric
acids coiresponding to each, 66

INDEX

208

Camphor series, synthesis of
racemic bodies, 40

— yields two isomeric borneols, 6C>
Camphoric acid, 60, 102

anhydride of the active, 49

— specific rotation, 139

— acids, GO, 0(5
Carbazides, 174
Carbodi-imides, probably not stereo-

ineric, 175

Carbohydrates, formed by plants
from inactive material, 45

— conspectus, 91

Carbon atom, asymmetric, represen-
tation by models, 8

— atoms, graphic representation of

several connected, 54

asymmetric, formation of iso-

mers containing several, 65

— doubly linked, 99

— graphic representation, 98

— prediction of isomerism,

Carboxyls, proof of their neighbour-
ing position, 113

Carvol, 19

Catalytic influence, bringing about
inactivity, 48

Catalysis, racemising by, 48

Chitamic acid, 163

Chloral alcoholate, 25

— bornylates, prepared in four

modifications, 63

— hydrocyanide, 25

— sulphydrate, 25
Chlorethylidene oxide, 26
Chlorobromomethanesulphonic

acid, 25

a-Chlorocinnamic acid, 102
a- and j8-Chlorocrotonic and chlori-

socrotonic acids, 100
Chlorofumaric acid, 20, 96

obtained by treatment of tar-

taric acid with PCI,-,, 22
Chloromalei'c acid, 20, 96
Chloromalic acid, 24
Chloroplatinates of substituted

ammoniums, isomeric, 180
Chloropropionic acid, 24
Chlorosuccinic acid, 15, 22, 48, 96
Cholalic acid, specific rotation, 139
rhmamic acid, 101

— addition of bromine to, 68
dibromide, 68

division, 25

Cinnamic acid, dichloride, 25

— series, 101
Cinchonicine, rotatory power an

constitution, 71

Cinchonidine, rotation in alcoho
and in aqueous solution, 141

— rotatory power and constitution,

— specific rotation, 137
Cinchonine, rotation in alcoholic

and in aqueous solution, 141

— rotatory power and constitution,

— equal rotation of the sulphate

and selenate not due to their
isomorphism, 136

— specific rotation, 137

Cis and trans isomerism, 125

Citraconic acid, 94, 102

Citric acid, 23

Cobalt, ammoniacal compounds of,

186, 196
Cocaine, 61

Codeine, specific rotation, 137
Conductivity, electric, of ammonia-
cal compounds of cobalt, 186

— of ammoniacal compounds of

platinum, 188

— of racemic compounds, 44
Configuration, favoured, 55
Configurations, determination of,

in the sugar group, 81
Coniferyl alcohol, from inactive

. coniferine, inactive, 96
Conine, 17, 30

— conversion into an isomer,

177

— r-malate of r- and 1-, 66
Conquinamine, rotation in alco-
holic and in aqueous solution,
141

— specific rotation, 137
Conversion, mutual, of active

bodies, 47
i Copellidine, 18, 30

Croceocobaltammine, salts of, 196
Crotonchloral, gives with amides

two isomer s, 69
Crotonic acid, 22, 95, 96
Crotonylene bromide, 100
Cumarine, inactive, 127
Cumaric acid, 102
Cystin, 165
Cystine, 14

— derivatives, rotation, 165

204

INDEX

DEXTROSE, multirotation, 149, 10. r>

Diacetyltartaric acid and anhydride,
150

methylic ester, rotation,

157

a-7-Diacipiperazines, 119

Di-allyl, isomeric bromides, 78

Diazotates, 175

Dibromocinnamic acid, 48, 101

Dibromoshikimic acid, 151

Dibutyryltartaric acid, propylic es-
ter, rotation, 157

Dichlorosuccinic acid, as an ex-
ample of isomerisation on bring-
ing halogens into union with the
asymmetric carbon atom, 24,
49

Diethylic dipropionyl tartrate, ro-
tation, 157

Dihydrobenzene derivatives, 120

Dihydroterephthalic acids, 127

Dilatometer, 30

Dimethyladipic acids, 78

Dimethyldioxyadipic acids, two
modifications, 77

Dimethyldioxyglutaric acid, 78

Dimethylene, ease with which it is
saturated, 131

Dimethyl-fumaric and -malei'c
acids, 102

Diphenyl-fumaric and -malei'c
acids, 102

Dimethylglutaric acid, 78

Dimethylic diacetyl tartrate, rota-
tion, 157

Dimethylmalei'c acid, 102

Dimethyltricarballylic acids, three
inactive, 79

o-Dinitrostilbene, 101

Di-oximes, isomeric, 173

Dipentene, 47, 08

Diphenyldiethylenediamine, 30

Diphenylfumaric acid, 102

Diphenylmalei'c acid, 102

Dipropionyltartaric acid, ethylic
ester, rotation, 157

Dipropylic dibutyryl tartrate, ro-
tation, 157

Dissociation by heat, theory of
universal, 0

— constants of fumaric and malei'c

acids, 113

— electrolytic, 130, 138

— its bearing on the theory of
rotation, 130, 145

Ditoluyltartaric acid, rotation of

esters, 155

Divisibility of racemic compounds,
by active compounds, 28

— by organisms, 30
by synthesis, 40

— spontaneous, 34
Division into optical isomers, vain

attempts, 21, 40, 77, 127, 170, 181
Double linkage of carbon atoms,

nature of, 97
— molecules, liquids composed of,

134, 135

Dulcite, inactive indivisible, 89
Dynamic hypothesis, 112

ECGOXIXE, 01

— 1-, transformation into r-, 73

— 1- and r- yield the same active

anhydrecgonine and the same
ecgonic and tropic acids, 08
Elaidic acid, 101

Electrolytes, rotatory power, 130
Electrolytic dissociation, 180

— and rotatory power, 130, 138
Enantiomorphism of optical iso-
mers, 11

— causing opposite activity, 10
Equilibrium between active iso-

mers, conditions of, 49
Erucic acid, 101
Erythrene bromide, 70
Erythrite, 74
Ethoxysuccinic acid, 15, 29, 32

rotation of salts, 138

Ethyl alcohol, inactive, obtained

by fermentation from active

carbohydrate, 23

— amyl, 17

— cumaric acid, 102

Ethylene derivatives, inactivity of,

90
plane or three-dimensional

configuration of, 82
Ethylidene anilines, 173

— chlorosulphinic acid, 20

— iodobromide, 25

— lactic acid, 14

— methethylate, 20
Ethylmalic acid, rotation, 157

— obtained by heating fumaric

and malei'c acids with sodium
ethylate, 53
a-Ethyl piperidine, 17, 30

INDEX

205

FAVOUKED configuration, 55
Formylthymotic acid, 127
Fumaric acid, 96

— inactivity of, 3
indivisibility, 46

— series, 102
Furfuracrylic acid, 101
Furfurol, from active arabinose or

xylose, is inactive, 22, 96

GAIDIC acid, 101
Galactonic acid, 29, 65, 89

rotation compared with the

lactone, 147, 149, 164

from mucic acid, divisible, 53

converted into talonic acid,

73
Galactose, 89

— multi-rotation, 149, 165

a- and /3-Glucoheptonic acids,
formed from glucose, 67
— rotation, 164

— acid, rotation compared with

that of the lactone, 148
a-Gluco-heptose, rotation, 165
Gluconic acid, 64

its rotation compared with

the lactone, 147, 164 «*
1-Gluconic acid, formed with 1-
mannonic acid from arabinose,
67

Gluco-octonic acid, rotation, 164
a- and )8- Gluco-octonic acids, formed
from heptose, 67

transformation of a- into j8-,

o-Gluco-octose, rotation, 165
Glucose, 64

— gives two isomeric glucoheptonic

acids, 67

— converted into levulose, 92

— multi-rotation, 149
o-Glucosectite, rotation, 161
Glucoses, isomeric, 64, 82, 87, 165
Glutamine, rotation, 163
Glutamic acid, 17, 32, 163

- — formed on heating al-
buminoids with baryta, 48
Glutaric acid, type 78
— acids, the two isomeric dimethyl-
and dimethyldoxy-, 78

methylethyl- and methyl-

propyl, two modifications, 78
Glyceric acid, 14, 31

Glyceric acid, change in rotation,

146
— specific rotation, 138, 139

esters rotation, as evidence

for Guye's hypothesis, 158
Glycols, substituted, two modi-
fications, 69
Gulonic acid, 1- and r-, 65

lactone, division, 39

rotation, compared with that

of the lactone, 148
Gulose, configuration, 88
— 1- and r-, 64

HALOGEN, derivatives containing
asymmetric carbon, active, 24

inactive, 25

Halogens, attached to the asym-
metric carbon atom cause isomer-
isation, 24, 49

Hexabromobenzenes, isomeric, 123

Hexachlorbenzenes, isomeric, 123

Hexahydrophthalic acids, two
modifications, 121

Hexaisophthalic acids, two modifi-
cations, 122

Hexahydroterephthalic acids, two
modifications, 121

Hexamethylene derivatives, 120

activity among, 123

Hexyl alcohol, 17

secondary, 17, 31

chloride, 24

iodide, 24

— chloride, 17

— iodide, 17
Hexylic acid, 17
Homoaspartic acid, division, 39
Homometa-oxybenzoic acid, indi-
visible, 46

/3-o-Homomethoxybenzoic acid,

visible, 127

Homosalicylic acid, indivisible, 46
Hydrazones, isomeric, 174
Hydrobenzoi'n, 77
Hydrochlorapocinchonine, specific

rotation, 137

Hydrogen, silver fulminate, 25
Hydromellithic acid, and iso-, 122
Hydronaphthalenediamine, 20
Hydropiperic acid, a- and /3-> 102
Hydroshikimic acid, 123
Hydrosorbic acid,, 101
Hydroterephthalic acids, 121

206

INDEX

Hyoscyamine, conversion into

atropine, 48

Hypogaeic acid, isoniers, 101
Hyponitrous acid, 176

IDOSACCHARIC acid, rotation and
configuration, 161

Idose, 64

Inactive indivisible type, 50, 74

Inactivity among compounds con-
taining the asymmetric carbon
atom, 27

— of a body arising from the

incompatibility of its constitu-
tion with rotatory power,
23

Indivisible inactive type, 50, 74
Indivisibility, in absence of the

asymmetric carbon atom, 46
Influence, mutual, of the groups

forming a molecule, 93, 110
Inorganic compounds, stereomerism

of, 185
Inosite, 123

— its strong rotatory power caused

by ring formation, 161

— indivisibility, 46

Inosites, r- and 1-, configuration,

124

/3-Iodacrylic acid, 101
lodohexyl, 49

— from mannite, 24
Ions, rotation of acid, 140
Isapiol, 101
Isocinnamic acid, 101
Isocrotonic acid, 101
Isodibromosuccinic acid, prepared

from malei'c acid by addition of
bromine, 108

— from malei'c acid, converted into

racemic acid, 109
Isohydrobenzoi'n, 77
Isohydromellithic acid, 122
Isomerism, due to the asymmetric
carbon atom, character of, 9

— due to doubly linked carbon,

character of, 99

Isomerisation, on attaching halo-
gens to the asymmetric carbon,
24, 49

Isomers, number due to several
asymmetric carbons, 56

— optical properties of, 10
Isopropoxysuccinic acid, 15

Isopropylphenylchloracetic acid,

24,49

Isopropylphenylglycollic acid, 18,
24, 29

— rotation, 159
Isosaccharinic acid, rotation, 164

KETOXIMEK, stereomeric, 173
Kinetics of racemising, 49

LACTIC acid, 58

— division, 29, 31

— rotation, 159, 163

— alteration of, on dilution,

144

— decrease on standing, 146
Lactid, 14

— rotation, 147
Lactone formation, 130

— and rotatory power, 147
Lactose, multi-rotation, 149
Levulose, configuration, 88

— yields on reduction the isomers

mannite and sorbite, 67

— multi-rotation, 149

— breaks up on oxidation into gly-

collic acid and inactive tartaric

acid, 90

Leucic acid, rotation, 159
Leucine, 17, 32, 47, 163

— inactive, formed on heating albu-

minoids with baryta, 48
Leucinephthaloylic acid, 19
Limonene, 18, 40

— iiitrosochloride and its deriva-

tives, 60, 67

rotation, 166

Linkage, treble, graphic representa-
tion, 104
Lyxose, 86, 160
Lyxonic acid, 87

MALAMIDK, 16

Malei'c acid, 96

dissociation constant, 113

— easy conversion into fumaric

acid, 106

— proof of configuration, 111
Malic acid, 15, 22

acetyl, and Guye's theory, 117,

157

and its anhydride, rota-
tion, 150

INDEX

207

Malic acid, acetyl, salts of, their

equal rotatory power, 138
alteration of rotation on dilut-
ing, 145

rotation of salts, 153

amylic esters, preparation of

four, with two active malic
acids, and two active amyl
alcohols, 57

behaviour in solution, with

regard to rotation, 143

conductivity of active and

inactive the same, 44

activity among derivatives of,

increase of Isevo-rotatioii in

the diluted solution on
warming, 144

inactive, 51

its acid ammonium salt,

prepared by heating fumaric

or malei'c acid with soda,
identity of this with the
divisible malic acid, 52, 53
remarkable change in its rota-
tion on diluting, 145

salts of, their equal rotatory

power, 139

Maltose, multi-rotation, 149
Mandelic acid 18, 29, 31

rotation, 143, 159

inactive from the r- and 1-

modifications, identical with
synthetic, 40
Mannice configuration, 88

— hexachlorhydrin of, 25

— isomers, 80

— rotation, 161

— yields on oxidation mannose and

levulose, 92

Mannoheptonic acid, rotation, 164
Mannoheptose, rotation, 165
Mannonic acid, 29, 64

1-, formed from arabinose, 67

— 1- and r-, 64
— rotation, 164

— compared with that of the

lactone, 147

Mannononose, rotation, 165
Manno-octose, rotation, 165
Mannosaccharic acid, configuration,
161

rotation, compared with that

of the lactone, 147, 164

Mannose, configuration, 88

— divided, 32

Mechanism of addition in forming
and transforming isomers, 105

Mechanics of the atoms, 5

Melting point, quantitative expres-
sion for lowering of, 43

Menthol, 72

Mesaconic acid, 95, 102

(8-Metahomosalicylic acid, indivi-
sible, 127

Methoxysuccinic acid, 15
— rotation of salts, 138

Methoxytoluylic acid, indivisible,
46, 127

Methylamyl, 21

Methylcumaric acid, 102

Methyl coriine, 18

Methylethylpiperidine (copellidine),
18

Methyl glucoside, high rotation of,
151

— glucosides from glucose, 67
Methylic benzoyltartrate, high rota-
tion, 159

Methylmalic acid, 16

formed by the action of fungi

on citraconic acid, 95

— — formed by heating fumaric

and malei'c acids with
sodium methylate, 53
a-Methylpiperidine (pipecoline), 17

— active, conversion into an

isomer, 177

j8-Methylpiperidine, 20
Mica, active combinations of, 11
Models, 8, 55

Molecular dimensions, equality of,
in optical isomers, 10

— rotation, 133
Monochloropropylene, 100
Morphine, specific rotation, 137
Mucic acid derivatives, 89
Multi-rotation, 148

NICOTINE, 18

— specific rotation, 137

- - acetate, rotation in alcoholic and

in aqueous solution, 141
Nitro-camphor and derivatives, ro-
tation, 167
Nitrogen, combined with carbon,

configuration, 178
— nitrogen, 179

208

INDEX

Nitrogen compounds, stereochem-
istry of, 169

— trivalent, 169
— in rings, 176

— pentavalent, 180

graphic representation of

isomers, 182

Nitrolepiperidine, 60

o- m- and p-Nitrophenylcinnamic
acids, 102

Nitrosohexahydroquinolic acid, divi-
sion, 30

Nitrostilbene, constitution of bro-
mides, 77

Nitrostyrolene, 101

Nitrotartaric acid, inactivity, 48

Nitrothymotic acid, 127

OBJECTIONS to the representation of
benzene by tetrahedra, 128

— to the theory of unsaturated

isomers, 109
Oleic acids, 101

Optical isomerism and the asym-
metric carbon atom, 13

— isomers, properties of, 10
Organism, formation of active com-
pounds in the, 65

Organisms, division of racemic com-
pounds by, 30

— action of modified, by trans-

position of groups, 32
Oxalic acid formed from active
sugar or active tartaric acid
is inactive, 22

indivisible, 46

Oximes, isomerism of, 171
Oxy-acids, small rotation of, 163
- • — change of rotation on diluting,
145

— high rotation on introducing

a benzene residue, 165
Oxybutyric acid, 15, 139, 159
a-Oxybutyric acid, division, 29
7-Oxybutyric acid most readily

forms a lactone, 130
Oxyglutaric acid, 16

— rotation, 164
Oxy-pyroracemic acid, 20
Oxy-pyrotartaric acid, 20

PAPAVERINE, 20
Pentose group, 63, 82, 84

Pentoses, rotation, 160

Perseite, rotation remarkably small,

161

Phenose, 125
Phenoxacrylic acid, 150
Phenylamidopropionic acid, 18, 163
Phenylamyl, 19
Phenylbromacetic acid from man-

delic acid, 25, 49
— from phenylglycollic acid, 24
Phenylbromolactic acid 29, 150
Phenylbromomercapturic acid, 18
Phenylchloracetic acid, 24, 25, 49
Phenylcystine, 18, 163
Phenyldibromobutyric acid, divi-
sion, 29

Phenylmercaptan, 22
Phenyltrimethylenecarboxylic

acids, three isomeric, 115
Phenylurethane, rotation in various

solvents, 154

Phthalylamidocaproic acid, 19
Physiological properties of optical

isomers, 12

— different, of the two optical iso-
mers, 12
j8-Picoline, 20
Picryl a- and £-naphthyl hydra-

zines, 179

Picrylhydrazines, isomerism, 179
Pinenedihydro-chlorides and -bro-
mides, 122
a-Pipecoline, 17, 30
Piperidine monocarboxylic acids,

five isomeric, 176
Piperylene, isomeric bromides of,

Platinum, bivalent, 187
Platopyridine chloride, 193
Platosammine salts, 188, 191
Platosemidiammine salts, 188, 191
Podocarpic acid, specific rotation,

139

Polymethylene rings, Baeyer's hy-
pothesis, 131

— derivatives, 114
Polymethylenes, relative stability,

131

Praseocobaltammine, salts of, 196
Product of asymmetry, 155
Projections of models, 55
Propionaldoxime, 171
Propoxysuccinic acid, 15
Propylene diamine, 14

— glycol, 14, 150

INDEX

209

Propylene oxide, 14, 150
Propylic alcohol, 20, 23
Propylmandelic acid, rotation, 165
a-Propylpiperidine (conine), 17
Pyrotartaric acid, 29

inactivity, 48

Pyrrolylene bromide, example of
inactive indivisible type, 76

QUINAMINE salts, rotation of al- j
coholic and aqueous solutions, i
141

— specific rotation, 137
Quinic acid, 123

— as an example of constancy j

of rotation on dilution, 144
-- inactive, divisibility, 44

— salts, rotation in alcoholic and

in aqueous solution, 140, 141
-- specific rotation, 139
Quinicine, rotatory power and con-

stitution, 71

Quinidine, rotation in alcoholic and i
in aqueous solution, 141

— rotatory power and constitu-

tion, 71

— specific rotation, 137, 160
Quinine group, transformations in,

— rotatory power and constitution,

— specific rotation, 137

— sulphate, rotation in alcoholic

and in aqueous solution, 141 j

RACEMATE of sodium and ammo-

nium, 34
— potassium, 38
Racemic acid, 74

— division, 29, 81, 74
— compounds, 28
-- characteristics, 41

-- properties of, 41
Racemising by heat, by catalysis,

47, 48

Rhamnonic acid, rotation com-
pared with that of the lactone,
147 •

Rhamnose, multi-rotation, 149
Ribonic acid, 64, 163, 164
-- rotation compared with that

of the lactone, 147
Ribose, 160

Ring formation, stability of, 129
connection with unsaturated

isomers of malei'c type,

118
influence on rotation, 146,

150, 164
with boric acid and hydroxyl

groups, 151

— stability, 129
Rings, four carbon, 118

— three carbon, 114

— six carbon, 120
Rotation, free, 55

cessation of, in the case of

doubly linked carbon, 97

— optical, causes which influence,

184

— influence of concentration,

142, 156
influence of groups attached

to the asymmetric carbon

atom, 154
influence of group weights,

155

— influence of ring formation,

146, 150, 164

influence of solvent, 135

influence of type, 162

molecular, 133

raised by addition of boric

acid, 161

— relative, of singly linked carbon

atoms, 54

Rotatory power and electrolytic
dissociation, 136, 138

— and lactone formation, 147

— — of non-electrolytes, 158
and ring formation, 146

— Guye's hypothesis, 154
of electrolytes, 13(5

— of imperfect electrolytes

141

remarkable cases, 165

numerical value of, 188

in relation to con-
stitution, 184

tables, 187, 139

variation with vary

ing conditions, 134

varying, of tartaric acid

solutions, 136

SACCHAUIC acid, configuration, 161
group, rotation, 160, 164

210

INDEX

Saccharic acid, rotation compared
with that of t-he lactone, 147, 164

type, 70, 79

Saccharic acids, 80
Saccharin, multi-rotation, 149
Saccharinic acid, rotation com-
pared with that of the lactones,
147, 164

Salicylic aldehyde, inactive, 127
Salts of active bases and acids,
rotatory power, 136, 188

multivalent metals with

glyceric acid, rotation, 138
— polyatomic acids, ro-
tation, 152

Santonine derivatives, rotation,
160, 167

— the highest known, 159
Scacchi's salt, 37

Scyllite, 125

Serine, no rotation as yet observed,

163
Shikimic acid, rotation, constancy

on dilution, 145
— of derivatives, 166

— of salts, 108, 138
Sodium ammonium racemate, 34

— nitro-ethane, 25

— potassium racemate, 38
Sorbite, configuration, 88

— rotation, remarkably small, 162
Spontaneous division of racemic

compounds, 34
Stability, absolute criterion of, 111

— of un saturated stereomers, un-

equal, 100

— • equal, of active isomers, 47
Strychnine, specific rotation, 137

— isomorphous sulphate and sele-

nate, equal rotation of, 136
Styrolene, 20, 95
Succinic acid, inactive, 22

— formed from asparagine, is

inactive, 22, 23

— obtained by reduction of

malic acid, 22

— acids, bisubstituted, obtained in

two modifications, 69, 77
Sugars, configuration, 82

— conspectus, 91

TALOMUCIC acid, rotation, 161, 164
— compared with that of the
' lactone, 147, 164

I Talomucic acid, configuration, 161
I Talonic acid, 65, 89

Talose, 89

Tartar emetic, abnormally large
rotation of, 140, 152

Tartaric acid, 81

— activity among derivatives, 21
conversion into racemic acid

by oxide of iron or of alu-
minium, 48

— derivatives, 22

— esters, rotation in different

solvents, 154

— formation, from racemic acid,

by Pasteur, 28

— imides, isomeric, 178

inactive, indivisible, 51, 74,

— rotation and Guye's hypo-

thesis, 158

— rotation specific, 139, 142, 164

- — many circumstances

affecting, 135, 143
— in tartar emetic, 140

— type, 74

Temperature, effect on equilibrium,

— of conversion of active sub-
stances, 35
Tensimeter, 37
Terephthalic acid, di- and tetra-

hydrides of, 125
Terpenes, 122
( Terpines, structure, 122
Tetrabromobutane, 76
Tetrahedron theory, 129
Tetrahydrobenzene derivatives, 125
Tetrahydrobenzoic acid, bromides

of, 122
Tetrahydronaphthyleiie diamine,

19,30

Tetrahydroterephthalic acids, 126
Tetrahydroterpenes, a- and )8-

structure, 122

Tetramethylene derivatives, 118
I Tetroses, 82

Thermodynamics of racemising, 49,

Thiacetones, polymeric, configura-
tion, 116

Thialdehydes, polymeric, configura-
tion, 116

Thiobenzylcrotonic acid, 101
Thiodilactylic acids, two modifica-
tions, 77

INDEX

211

£-, Thio-ethylcrotonic acid, 101
$-Thio-phenylcrotonic acid, 101
Tiglic acid, 95, 101
Tolane bromides, 100

— chlorides, 100
o-Toluidine, indivisible, 46, 127
Treble linkage of carbon atoms,

representation of, 104
Trimetliylene, 114
Trimethylene dicarboxylic acids,

isomeric, 115, 117
Trimethylethylstibine iodide, 20
Tri-oxyglutaric acid, a second in-
active indivisible type, 78
— rotation, 164

— acids, 87

Trithiodimethylmethylene, 116
Trithiomethylene, 114
Tropaic acid, 18, 159

rotation, 159

Tropine, 62
Truxillic acids, 118
Turpentine yields two borneols,
66

Tyrosine, 18, 163

— inactive, obtained on heating
albuminoids with baryta, 48

UBAMIDOSUCCINAMIDE, 16
Uramidosuccinic acid, active, 22

VALEBIC acid, 16
- — esters, rotation and Guye's

theory, 158, 159
Vanilline, inactive, 127
Violeocobaltammines, salts of, 196

XYLITE, 79, 86
Xylonic acid, 64, 87, 164

— rotation compared with that

of the lactone, 147, 164
Xylose, 86, 160
— multi-rotation, 149, 165

YEAST, action on various sugars, 32

Errata.

Page 52, line 11 from top, for ammonia read ammonium.
Page 87, the formula of lyxose should be as on page 83.
Page 95, line 12 from bottom, for styrol read styrolene.
Page 101, line 4 from top, for nitrostyrol read nitrostyrolene.
Page 166, line 3 from bottom, for limonenenitroso chloride
limonene nitrosochloride.

read

I'lUNTEj") HY

SPOTTWWOOntf AND CO., XI-.W-SrUEKT SQUARE
LOXDOV

14 DAY

TJTTTITRN TO DESK FROM *

LOAN DEPT.

T2003

-r,T)21 A-60w-3,'70
(N5382tlO)476-A-32

General Library

LD21-100m-7,'33

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