Jacobus Henricus van 't Hoff

“ This connexion of isomerism with resistant linking, and of this with high valency, explains, in considerable measure, why inorganic compounds afforded, as a rule, no phenomena of this kind until the systematic investigation of metallic compounds by Werner brought to light many instances of isomerism in inorganic compounds. Whereas carbon renders isomerism possible in organic compounds, cobalt and platinum are the determining elements in inorganic chemistry, the phenomena being exhibited especially by complex ammoniacal derivatives. ”

“ Phenomena analogous to those observed in carbon compounds might also exist in derivatives of other quadrivalent elements ; and only the relative stability of carbon-compounds makes every form of isomer, which often is unstable, more easily obtainable in organic chemistry. Nevertheless it has been possible to obtain stereo-isomers with different elements, but, as expected from the above, especially in derivatives containing carbon. Some of them have the character of optical antipodes and are more easily considered from a theoretical point of view ; others have not. ”

“ Polymorphism in the case of an element is illustrated in the case of sulphur, whereas metamerism in the case of elements has so far as yet not been observed; and is hardly probable, as most elements are built up, like the metals, from molecules containing only one atom per molecule; here metamerism is absolutely excluded, and a considerable number of the rest, having diatomic molecules, are about in the same condition. It is only in cases like sulphur with octatomic molecules, where a difference of internal structure might play a part. ”

“ But the crystalline form, which may show enantiomorphism, indeed shows this difference in the isomers in question; and especially the behaviour (in the amorphous state) towards polarized light differs in the sense that the plane of polarization is turned to the left by the one isomer, and exactly as much to the right by the other, so that they may be termed " optical antipodes." All these differences disappear with the asymmetric carbon, and the succinic acid, HO2C·CH2·CH2·CO2H, from tartaric acid is optically inactive and shows no stereo-isomerism. ”

“ The use of optically active compounds in separating antipodes is of the greatest value. The general principle is that the compounds which the d- and l-form give with a different active compound, for instance d producing dd and ld, are by no means antipodes and so exhibit the ordinary differences, e.g. in solubility, which allow separation. It was in this way that Pasteur split up racemic acid by cinchonine. ”

“ Isomerism.—Certain investigations on isomerism which have become especially prominent in recent times bear on the possibility of the mutual transformation of isomers. As soon as this reversibility is introduced, general laws related to thermodynamics are applicable (see Chemical Action; Energetics) . These laws have the advantage of being applicable to the mutual transformations of isomers, whatever be the nature of the deeper origin, and so bring polymerism, metamerism and polymorphism together. ”

“ One of the most simple examples is offered by the trimethylene- dicarboxylic acids
for which three formulae can be deduced:—
the first, where the carboxyl groups ⋅CO2H lie on the same side of the carbon ring, called, as Von Baeyer proposed, the cis-form, the others trans-forms. The trans-forms show enantiomorphism and correspond to optical antipodes, whereas the first symbol may be considered as corresponding to mesotartaric acid, symmetrical in configuration and inactive; this third stereo-isomer has also been met with. ”

“ C – is one of the most difficult to loosen.
The conception of metamerism, or isomerism in restricted sense, has been of the highest value for the development of our notions concerning molecular structure, i.e. the conception as to the order in which the atoms composing a molecule are linked together. In this article we shall confine ourselves to the fatty compounds, from which the fundamental notions were first obtained; reference may be made to the article Chemistry: Organic, for the general structural relations of organic compounds, both fatty and aromatic. ”

“ Configuration of Stereo-isomers.—The conception of asymmetric carbon not only opens the possibility of determining when and how many stereo-isomers are to be expected, but also allows a deeper insight into the relative position of atoms in each of them. The chief indication here lies in the configuration of the meso-type, already given for mesotartaric acid ”

“ These phenomena were quite in accordance with the atomic conception of matter, since a compound containing the same number of atoms of carbon, nitrogen, oxygen and hydrogen as another in the same weight might differ in internal structure by different arrangements of those atoms. ”

“ The method called “spontaneous separation” was first observed by Pasteur with racemic acid, which in its double sodium and am- monium salt crystallized from its aqueous solution in two enantio- morphic forms, which could be separated on examination. One of the two proved to be the ordinary sodium-ammonium-tartrate, the other its laevogyre antipode; thus /-tartaric acid wasdiscovered, and racemic acid proved to be a combination of d- and /-tartaric acid. ”

“ Consequently, of each pair of isomers we may establish beforehand which is the more stable; either in particular circumstances, a direct change taking place, as, for instance, with maleic acid, which when exposed to sunlight in presence of a trace of bromine, yields the isomeric fumaric acid almost at once, or, indirectly, one may conclude that the isomer which forms under greater heat-development is the more stable, at least at lower temperatures. Now, whether a real, though undetected, change occurs is a question to be determined from case to case ”

“ A special feature, however, wanting with carbon, is that compounds with one atom only of the element in question have been obtained as antipodes. A second observation of some interest is that the compounds in question are electrolytes and that, as in solutions, where they are split up into ions, activity must be due to the last, the ionic complex, for instance, RiR 2 R s S, must cause optical rotation. ”

“ That this particular feature belongs to carbon compounds is due to a property of carbon which characterizes the whole of organic chemistry, i.e. that atoms attached to carbon, to express it in the atomic style, cling more intensely to it than, for instance, when combined with oxygen. ”

“ Mutual Transformation of Antipodes.—Thus far we have supposed the molecule to be stable with atoms in fixed places, as may be the case at absolute zero ; in reality, at ordinary temperatures, atoms probably are endowed with movement, and this may be supposed to take place along the fixed places just mentioned as centres, which movement can go so far as to lead to total transformation, the one stereo-isomer changing over into the other. ”

“ It is the limit where the possibility of spontaneous separation begins, and is relatively rare, so that this way of separation is an exceptional one, most antipodes forming a racemic compound stable at all temperatures that come into question. ”

“ In the divalent oxygen we meet with the modification called ozone, which, although unstable, changes but slowly into oxygen. Similarly the trivalent phosphorus in the ordinary white form shows such resistance as if it were practically stable; on the other hand the red modification is in reality also stable, being formed, for instance, under the influence of light. In the case of the quadrivalent carbon, diamond seems to be the stable form at ordinary temperatures, but one may wait long before it is formed from graphite. ”

“ A different way of using active compounds in producing antipodes consists in the so-called asymmetric synthesis. The method consists in the introduction of an active complex before that of the asymmetric carbon ; both stereo-isomers need not then form in the same quantity. W. Marckwald and A. McKenzie, who chiefly worked out this method, found, for example, that the salt of methylethylmalonic acid, C (CH3) (C2H5) (CO2H) 2 , with the active brucine forms on heating the corresponding salt of d- and /-methylethylacetic acid C (CH 3 ) (C 2 H 5 ) H (C0 2 H) , with the /-antipode in slight excess. ”

“ In ordinary isomers indications of mutual transformation often occur; and among these the predominant fact is that denoted as tautomerism or pseudomerism. It exhibits itself in the peculiar behaviour of some organic compounds containing the group – C·CO·C – , e.g. CH3CO·CHX·CO2C2H5, derivatives of acetoacetic ester. These compounds generally behave as ketones; but at the same time they may act as alcohols, i.e. as if containing the OH group; this leads to the formula H3C·C (OH) :CX·CO2C2H5. ”

“ Unsaturated compounds generally show larger rotative powers; amyl alcohol with −5° produces an aldehyde with 15 ; succinic (diamyl) ether with −9° produces fumaric ether with 15°, &c. Cyclic configuration especially leads to the highest values known: the lactic acid with 3 leads to a lactone with −86°,
H3C-CH-COO
I I
OOC-HC-CH 3 ;
mannosaccharic acid, H0 2 C (CHOH) 4CO 2 H, to a dilactone (with two rings, formed by the loss of two molecules of water) with 202°, whereas the original acid only shows a small rotation. ”

“ This temperature is somewhat different from the ordinary melting-point, the latter corresponding to atmospheric pressure, the former to the maximum vapour-pressure; and so we come to a third relation for polymorphism. Just as the melting-point changes with pressure, the transition-point also changes; even the same quantitative relation holds for both, as L. J. Reicher proved with sulphur: aT/aP = AvT/q, v being the change in volume which accompanies the change from rhombic to prismatic sulphur, and q the heat absorbed. ”

“ The formation of a racemic compound built up from dd and ld has also been observed in the so-called partial racemate. An example is the racemate of strychnine. It is in this case also that the transition-point forms the limit of possible separation, determined by Ladenburg and G. Doctor to be 30°. ”

“ These isomers, having some relation to those in cyclic compounds, may be also denoted as cw- (maleic) and trans- (fumaric) forms, a close analogy existing indeed in those ring systems of which the simplest type is:—
this has been realized in the 1, 3-tetramethylene dicarboxylic acids, which exist in a trans- and cis-form:—
When two double carbon Unkings are present, as in H 2 C:C:CH 2 , the four hydrogen atoms form the summits of a tetrahedron according to the development in fig. 4 ; and consequently the introduction of different groups may bring enantiomorphism and optical antipodes. ”

“ The last group of stereo-isomers, in which insight is most difficult yet, is that of Werner's complex metallic compounds, observed with cobalt, platinum and chromium. No enantiomorphous character throws light here, and there is no relation to ethylene derivatives. ”