Solvent effect on preferred protonation sites in nicotinate and isonicotinate anions

Abstract

Potentiometric determinations of the two successive acidities of nicotinic and isonicotinic acids (AH2+) have been carried out in aqueous dimethyl sulfoxide mixtures containing up to 95% Me2SO by volume. In both systems, the results reveal that the addition of Me2SO induces a proton transfer from the pyridinium ring to the carboxylate group, the tautomeric equilibrium between the neutral forms of the two acids being displaced toward the zwitterionic form (AH±) in aqueous solution, but toward the molecular form (AH°) in Me2SO. An analysis of the data by means of Hammett relationships previously established for benzoic acids over the whole range of H2O/Me2SO mixtures allowed the four microscopic acidity constants as well as the tautomeric equilibrium constant KTpertaining to the complete ionization scheme of the two acids to be determined. At 20 °C, there are equal populations of the tautomeric AH° and AH±species in the mixtures containing 38 and 47% Me2SO for the nicotinic and isonicotinic systems, respectively. Hammett relationships describing the ionization behaviour of a number of substituted pyridinium cations in H2O/Me2SO mixtures are also discussed. Possible reasons accounting for the peculiar effects exerted by the NH2, CONH2, and COOH substituents on the process are suggested. Key words: nicotinic and isonicotinic acids, substituted pyridines, acidities, tautomeric equilibrium, protonation sites, water – dimethyl sulfoxide mixtures.