Jacobus Henricus van 't Hoff

“ 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. ”

“ 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. ”

“ 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 ”

“ 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. ”

“ 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. ”

“ 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. ”

“ 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. ”

“ 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. ”

“ 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°. ”

“ 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. ”

“ 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. ”

“ 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. ”