13C nuclear magnetic resonance study of acid–base tautomeric equilibria

Abstract

Acid–base tautomerisation equilibria are reported for o-, m-, and p-aminobenzoic acids, p-aminophenylacetic acid, pyridine-3-carboxylic (nicotinic) acid, and pyridine-4-carboxylic (isonicotinic) acid. These equilibria are determined by modelling the displacements of 13C n.m.r. chemical shifts of each carbon due to protonation of basic sites. The models are based on the corresponding displacement due to protonation of as many as twelve related compounds. Each such model compound yields several independent estimates of the tautomeric partitioning ratio corresponding to the several carbon resonances. It is observed that the mean tautomeric partitioning ratio and its estimated uncertainty are independent of the nature or the location of ring substituents and are unaffected by heteroatom substitution in the aromatic ring. This observation has led to the development of generic models for 13C n.m.r. chemical shift protonation displacements based on collections of similar model compounds. The use of generic models summarises and simplifies the determination of tautomeric equilibria.