Zwitterion formation and subsequent carboxylate–pyridinium NH synthon generation through isomerization of 2-anilinonicotinic acid

Abstract

Through structural modification of 2-anilinonicotinic acid by isomerization, the ΔpK_a between the carboxylic acid and pyridinium NH increased dramatically over the threshold to form zwitterions in the newly designed 4-anilinonicotinic acids. This in turn led to the formation of a hydrogen bond between carboxylate and pyridinium NH, and the absence of two commonly observed synthons, i.e., the acid–acid homosynthon and acid–pyridine heterosynthon. The new synthon has a stronger hydrogen bond than the acid–acid homosynthon and the acid–pyridine heterosynthon, as suggested by theoretical calculations. This, together with the much larger ΔpK_a, explains its formation.