Imidazole-assisted intramolecular nucleophilic attack of the amide oxygen at ester linkages in aryl or alkyl esters of ( Z)-α-(acetylamino)cinnamic acid

Abstract

The intramolecular nucleophilic attack by the amide oxygen atoms of various aryl or alkyl esters of ( Z)-α-(acetylamino)cinnamate leads to the cyclization of the esters producing ( Z)-4-benzylidene-2-methyloxazolin-5-one. Kinetics of the cyclization reactions were measured in the presence and absence of imidazole (Im), N-methylimidazole (MeIm), or substituted pyridines. From the slopes of the plots of the logarithmic values of various rate constants against p K lg values (p K a of the leaving groups), β lg values were calculated. The β lg values indicate that the hydroxide-assisted cyclization involves rate-determining expulsion of the leaving phenols or alcohols. The Im-assisted reaction consisted of two paths: one involving the participation of Im only and the other involving that of Im together with hydroxide ion. When MeIm was added, only the reaction path involving MeIm was observed. The β lg values for the reaction paths involving Im or MeIm were ca. 0 in the cyclization of the aryl esters, while they were quite large in the reaction of the alkyl esters. When pyridine bases were added, the cyclization reactions were not catalyzed. Based on these kinetic data, it is proposed that Im- or MeIm-assisted cyclization reactions involve the initial attack of Im or MeIm at the amide carbon followed by the attack of the oxyanion of the consequently formed tetrahedral intermediate at the ester carbon.