Intramolecular catalysis of amide hydrolysis by carboxyl and metal ion/proton agents: I. Intramolecular reactions of imidazole or pyridine derivatives of maleamic acid

Abstract

Kinetic studies on the hydrolysis of N-(2-imidazolylethyl)maleamic acid, N-(2-pyridylethyl)maleamic acid, and N-(2-pyridylmethyl)maleamic acid were carried out. In these maleamic acid derivatives, the amide nitrogens together with the heterocyclic nitrogens form bidentate ligands. The compounds were hydrolyzed through nucleophilic catalysis by carboxyl groups. The pH profiles for the hydrolysis at 65°C were descending sigmoids and were unaffected by the ionization of the heterocyclic nitrogens. The absence of rate enhancement due to the added divalent metal ions revealed that chelate formation by the bidentate leaving groups is not efficient. N-(2-Pyridylmethyl)maleamic acid underwent a dual intramolecular nucleophilic reaction through participation of both the carboxyl and the pyridyl groups.