Experimental and Theoretical Mechanistic Study on the 6‐Iodo‐2‐pyridone‐Catalyzed Aminolysis of Esters

Abstract

A rigorous evaluation of 6‐halo‐2‐pyridone in the catalytic aminolysis of esters revealed that 6‐iodo‐2‐pyridone exhibits high catalytic activity, particularly in the presence of phenyl esters. In this reaction, a series of amines and aromatic esters gave the corresponding amides in high yield. To elucidate the reaction mechanism of the 6‐iodo‐2‐pyridone‐catalyzed aminolysis of esters, ¹H NMR experiments, kinetic studies, and density functional theory (DFT) calculations were conducted. The combined results demonstrate that the reaction proceeds via the formation of a 1:1:1 complex comprising the catalyst, the amine, and the phenyl ester. In this context, 6‐iodo‐2‐pyridone thus works as an acid–base bifunctional catalyst, successfully activating both the ester and the amine. Notably, a π–π interaction was observed between the catalyst and the phenyl ester in the transition state. The stereoelectronic effect of iodine most likely contributes to a favorable degree of this π–π interaction, facilitating a smooth transition to the subsequent leaving of phenol. The low energy barrier for the tautomerization between 6‐iodo‐2‐pyridone and 6‐iodo‐2‐hydroxypyridine also facilitates the process.