Intra- and inter-molecular catalysis in the halogenation of some oxocarboxylic acids

Abstract

The dissociation constants of twelve oxo-carboxylic acids have been measured, and also the catalytic effect of the anions of eight of them in the decomposition of nitramide. The results are used to deduce the equilibrium fraction of the cyclic lactol isomers in aqueous solution: this fraction is considerable only for 2,2-dimethyl-(50% lactol) and 2,2,3-trimethyl-levulinic acid (87% lactol).

The rates of iodination of the twelve acids were measured in self-buffered solutions and in acetate buffers. The reaction is of zero order with respect to iodine, and the observed rates are interpreted in terms of ionization or enolization: both intra- and inter-molecular acid–base catalysis could be evaluated. For four acids the relative rates of reaction at different sites were measured by a ¹H n.m.r. study of exchange in deuterium oxide.

In the two series MeCO·[CH₂]_n·CO₂H and PhCO·[CH₂]_n·CO₂H the intramolecular rate has its maximum value when n= 3, corresponding to a cyclic transition state containing six atoms including the proton. For two acids it was shown that analogous inter- and intra-molecular processes have indistinguishable activation energies, thus confirming the view that the efficiency of the latter depends upon entropic factors. The detailed results for seven alkyl-levulinic acids were difficult to interpret, but abnormally low intramolecular rates were found for the two acids which have appreciable lactol contents in solution.