f— n_ ru.
REESE LIBRARY
UNIVERSITY OF CALIFORNIA.
Deceived
No. 7& 0 V(o . Class No.
AKBANGEMENT
OF
ATOMS IN SPACE
THE AEEANGBMBNT
OF
ATOMS IN SPACE
BY
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
BY
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
All rights reserved
PBEFACE
TO
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
TO
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].
B
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
2
H
o
H
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.
C
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 |
C3H7 |
C3H7 |
|
C |
C |
C |
|
/% |
X\ |
/N |
|
HC CH |
HC CH |
H2C CH |
|
II 1 HC CH2 |
II 1 HC CO |
H2C CO |
|
V |
\/ C |
\/ C |
|
HCH, |
HCH, |
HCH, |
Tetrahydronaphthylenediamine 5 [a]D — — 7° and + 8°. H H.NH2
H/Y\H, HC C CH2
'V
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).
27
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
29
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.
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.
30
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
31
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
Penicillium, L-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.
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,
54
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 :
E3
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
H2
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.
F
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.
99
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
81
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,
G
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
II
HCOH HOCH OCH (corresponds to active
tartaric acid)
tartaric acid)
Pentoses (C5H1005)
A
H.,COH HCOH HCOH HCOH OCH Ribose
a
H.2COH HCOH HCOH HCOH HCOH OCH
Allomucic acid
B
H2COH HCOH HCOH
HOCH OCH
Arabinose
HCOH HOCH HOCH
OCH
Lyxose
B
H2COH
HCOH
HOCH
HCOH
OCH
Xylose
Glucoses (C6H1206)
IA
IB
|
0 |
a |
3 |
|
H2COH |
H2COH |
H2COH |
|
HCOH |
HCOH |
HCOH |
|
HCOH |
HCOH |
HCOH |
|
HCOH |
HOCH |
HOCH |
|
HOCH |
HCOH |
HOCH |
|
OCH |
OCH |
OCH |
|
Talomucic |
Saccharic acid |
Manno- |
|
acid |
Glucose |
saccharic |
|
Talose ? |
Sorbite |
Mannose |
|
Mannite |
1 Fischer, .$er. 56, 740.
UNIVERSITY
84
STEREOCHEMISTRY OF CAEBON
II A
|
Glucoses (C6H1206)— continued. |
||
|
II B |
||
|
ft |
a |
0 |
|
H2COH |
H2COH |
H2COH |
|
HCOH |
HCOH |
HCOH |
|
HOGH |
HOCH |
HOCH |
|
HOCH |
HCOH |
HCOH |
|
HOCH |
HCOH |
HOCH |
|
OCH |
OCH |
OCH |
|
Talomucic acid |
Saccharic acid |
Idosaccharic |
|
Talose |
Gulose |
acid |
|
Sorbite |
Idose |
|
|
Idite |
a
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 |
C02H HCOH |
C02H HCOH |
|
HCOH |
HCOH |
HOCH |
|
HCOH |
HOCH |
HCOH |
|
C02H |
C02H |
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
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
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 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 |
HCOH |
HCOH |
|
HCOH |
HCOH |
HCOH |
|
HOCH |
HOCH |
HOCH |
|
HCOH |
HOCH |
CO |
|
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
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.
90
STEREOCHEMISTRY OF CARBON
acid by that of mannose, and also talomucic acid. We have then :
|
CO.,H |
CO,H |
CO,H |
C0.2H |
CO,H |
CO,H |
|
HCOH |
HCOH |
HCOH |
HCOH |
HCOH |
HCOH |
|
HCOH |
HCOH |
HCOH |
HCOH |
HOCH |
HOCH |
|
HCOH |
HCOH |
HOCH |
HOCH |
HOCH |
HCOH |
|
HCOH |
HOCH |
HCOH |
HOCH |
HCOH |
HOCH |
|
CO,H |
COJ3 |
CO,H |
CO,H |
C02H |
CO.,H |
|
Inactive |
Talo- |
Saccharic |
Manno- |
Inactive |
ido- |
|
allo- |
mucic (?) |
acid |
saccharic |
mucic |
saccharic |
|
mucic |
acid. |
(Sorbite). |
acid |
acid |
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 |
HCOH |
HCOH |
|
HOCH |
HCOH |
HCOH |
|
HCOH |
HOCH |
HCOH |
|
H2COH |
H,COH |
H2COH |
|
Xylite (inact.) |
Arabite (act.) |
Adonite (inact.) |
|
^ |
i |
•I' |
|
OCH |
H.,COH |
H2COH |
|
HCOH |
HCOH |
HCOH |
|
HOCH |
HCOH |
HCOH |
|
HCOH |
HOCH |
HCOH |
|
H2COH |
OCH |
OCH |
|
Xylose ( * qoj |
(157°\ -1040/ |
Ribose (W^go ) |
|
i |
I . |
\ |
|
C02H |
H2COH |
H2COH |
|
HCOH |
HCOH |
HCOH |
|
HCOH |
HCOH |
HCOH |
|
HOCH |
HOCH |
HOCH |
|
HCOH |
HCOH |
HOCH |
|
H2COH |
CO-^H |
C02H |
|
Gulonic acid \c'ao) |
Gluconic Aveak\ acid V 68° / 1 |
Mannonic /weak\ acid V 54° / |
|
H2COH |
H2COH |
|
|
HCOH |
HCOH |
|
|
HCOH |
HCOH |
|
|
HOCH |
HOCH |
|
|
HCOH |
H2COH |
HOCH |
|
H2COH |
HCOH |
H2COH |
|
Sorbite (act.) |
HCOH |
Mannite (act.) |
|
1 |
HOCH |
t— J |
|
~* CO |
||
|
H2COH |
||
|
Levulose (lJSp°te90°! |
) |
|
|
; |
||
|
CO-jH |
||
|
HCOH |
||
|
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.
93
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
97
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.
R,
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
H2
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.
R1
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
HCC02H
and
C02HCH
C02HCH the compounds
OH C02HCH
or
or
HCCO2H OH
or
and
OH
C02HCH C02HCH
OH
or
C02HCH
HCC02H
II HCC02H
OH
HCC02H C02HCH OH
OH
HCC02H HCC02H
OH
—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 :
Br
HCC02H HCC02H "
Br
Let us abstract hydrobromic acid, writing the above formula in a slightly different way, in order the better to follow the result :
H
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
c
H
H
c
CO,H
C02H
H
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
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 :
H
OH
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. :
OH
OH
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
H
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
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.
K
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
GO
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 a ^ ° ,2 a>
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
|
5 |
Mill |
IMS |
1 |
1 1 1 <f S |
|
I |
||||
|
N |
1 5 1 1 1 |
ilia |
1 |
1 1 1 1 1 |
|
bo |
GO GO (M | i> | os Aj |
1 1 . ! 83 1 ' ' <M |
1 |
1 1 1 1 1 |
|
a! |
CO O5 i J S i |
| «, | CO |
CO |
| « } « | |
|
n |
||||
|
A |
A |
A | |
||
|
b 00 |
i i i i i |
Ml* |
1 |
1 1 1 1 1 |
|
g |
i S i S i |
ills |
CO |
1 3 1 1 1 |
|
A |
A |
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
Diff. 14
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 |
5 |
117 to 118 |
1 |
|
Conquinamine |
200 , 234 |
34 |
228 „ 229 |
1 |
|
Quinidine . |
233 , 255 |
22 |
322 „ 329 |
7 |
|
Cinchonine . |
206 , 240 |
34 |
258 „ 289 |
1 |
|
Cinchonidine |
-114 , -161 |
47 |
176 „ 180 |
4 |
|
Quinic acid salts |
-9 , -40 |
31 |
-43 ,,-49 |
6 |
|
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
V
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, |
1 |
|
|
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 :
Ba
K,
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 |
|
M |
2-82 |
15-1 |
1*48 „ |
22-8 |
|
K2. |
12-16 |
14-3 |
|
|
|
5-02 |
14-2 |
— |
|
|
|
Ca |
5-31 |
- 12-7 |
3-04 per cent. |
+ 10-4 |
|
2-21 |
+ 5-2 |
1-79 |
+ 14-1 |
|
|
Ba |
26-12 |
-27-3 |
25-08 |
- 8 |
|
n |
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» I |
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 |
+ A |
+ A |
+ A |
|
+ B |
+ B |
+ B |
-B |
|
+ B |
+ B |
- B |
-B |
|
+ A |
- A |
+ A |
+ A |
ZA
|
C02H HCOH |
C02H HCOH |
C02H HCOH |
C02H HCOH |
|
HOCH |
HOCH |
HOCH |
HCOH |
|
HCOH |
HCOH |
HOCH |
HOCH |
|
HOCH |
HCOH |
HOCH |
HOCH |
|
C02H |
C02H |
C02H |
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° |
|
t1 |
- 38° |
|
CH2OH(CHOH)4CO,H |
+ 68° |
|
,, |
- 71° |
|
55 |
+ 54° |
|
C02H(CHOH)4C02H |
7° |
|
55 |
38° |
|
CH,OH(CHOH)5CO,H |
- 74° |
|
55 |
- 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
HC
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
CO
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,
N
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.
N
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
2
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 :
NH
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
V
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
A2
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 :
L2
•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
?y
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
Pv
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,
24
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,
73
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,
53
— 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,
99
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,
71
— specific rotation, 137 Cinchonine, rotation in alcoholic
and in aqueous solution, 141
— rotatory power and constitution,
71
— 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-,
73
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,
22
increase of Isevo-rotatioii in
the diluted solution on warming, 144
inactive, 51
its acid ammonium salt,
52
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,
78
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,
71
— rotatory power and constitution,
71
— 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,
81
— 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,
50
— 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,
50
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.
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