Studies in asymmetric transformation

The equilibrium set up between the different forms of four related acids, benzylmalonanilic acid I, benzylmaloa-o-toluidie acid II, N-ethyl-benzylmalonanilic acid III and benzylmalonpiperi-dinic acid IV, (optically unstable by virtue of a keto-enol group in the molecule) has been investigated by kinetic and other means, in presence of basic reagents of varying strength from weakly basic alkaloids, pyridine, ammonia, piperidine to sodium and potassium hydroxides, in non-hydroxylic and hydroxylic solvents. The acids I, II and IV, were prepared by a modification of Chattaway's method for malonanilic acid ( J., 1910, 97 649). III could not be prepared by this method and with considerable difficulty a successful synthesis was worked out in 3 stages from ethyl cyanoacetate as follows: - CN.CH2.CO2Et -> CN.CH2.CONPhET -> CN CHCH2PhCONPhet -> CO2HCHCH2PhCONPhet. The existence of cyclic in addition to acyclic structures was made evident by the isolation from each acid of a covalent sodium salt, cyclic and acyclic forms from one diastereoisomeride are associated with opposite signs of rotation, the predominance of either form depending on (1) the nature of the solvent and (2) the base forming the salt. Second order asymmetric transformation was observed for the acids I and II. The absence of demonstrable first order asymmetric transformation is attributed to the existence of stable optically inactive end intermediates which, in this case, is the determining factor in the establishment of equilibrium. The acids III and IV containing tertiary nitrogen differ in properties from I and II. No optical activity has yet been detected. It is suggested that this fact, together with the observed difficulty of salt formation and ease of solubility in chloroform indicates an increased tendency of these acids to exist in the cyclic form.