Substituent effects on the thioamide group in thiobenzanilides: simultaneous conformational and acid-base equilibria

Substituent effects in substituted thiobenzanilides were investigated by th e acid dissociation constants in water and the half-wave potentials of the anodic oxidation in acetonitrile; the substituents were chosen with respect to related pharmacological research. The pK values are well correlated by the Hammett equation, and the effects of substituents in the two benzene ri ngs are additive. Since the acid-base equilibrium is combined with an equil ibrium of conformers Z reversible arrow E, the general mathematical consequ ences for a Hammett correlation were calculated. In the common case, a Hamm ett correlation is not obeyed for the apparent dissociation constants even when it is obeyed for all partial processes. In the present case, the effec t of conformation is relatively slight and insufficient to disturb the over all Hammett correlation of the acidities. The half-wave potentials gave bad correlations, only an additive relationship is roughly valid. Copyright (C ) 2000 John Wiley & Sons, Ltd.