Chemometrical Analysis of Substituent Effects. III. Additivity of Substituent Effects in Dissociation of 3,4-Disubstituted Benzoic Acids in Organic Solvents

Abstract

Sixteen 3,4-disubstituted benzoic acids (with all combinations of CH3O, CH3, Cl/Br, and NO2 substituents) have been synthesized and their dissociation constants measured in seven organic solvents (methanol, acetone, dimethyl sulfoxide, dimethylformamide, acetonitrile, pyridine, 1,2-dichloroethane). The effect of disubstitution and the validity of additive correlation relationships based on the Hammett equation have been analyzed by means of the analysis of variance, comparison of overall residual standard deviations of correlation equations of additive and additive multiplicative type, and application of the Hammett equation with internal (latent, defined in various ways) parameters and external (taken from literature) parameters describing the substituent effects. The effect of disubstitution has been found to be additive and describable within the validity range of the substituent constants adopted - by applying the additivity principle without any additional correction for interactions between the two substituents. The same conclusion has been drawn from the comparison of overall residual deviations in correlation equations for mono- and disubstituted derivatives. The analysis of differences between the reaction constants of the Hammett equation applied to mono- and disubstituted benzoic acids has shown that in organic solvents the solvation of substituents makes various contributions. The substituent influence is stronger in polar aprotic solvents (acetone, dimethyl sulfoxide, dimethylformamide, acetonitrile) than that in the protic, basic, and less polar ones in which the stabilization by hydrogen bond becomes important, the role of proton donor being played either by the solvent itself (methanol) or by its conjugated acid (pyridine) or by a molecule of the dissociating acid as a consequence of homoconjugation (1,2-dichloroethane).