Intramolecular Aminolysis of Esters. O-Acetylserine and γ-Esters of Glutamic Acid

Article abstract of DOI:10.1021/jo00321a011

The kinetics of the concurrent hydrolysis and intramolecular aminolysis of γ-ethyl glutamate have been studied in aqueous solution (40 deg C) in range of pH 7.6-10.4.While hydrolysis contributes only 3percent to the overall rate of reaction of γ-ethyl glutamate at pH 10.4, its importance relative to aminolysis increases with decreasing pH; at pH 8, the hydrolysis pathway accounts for 32percent of the rate of disapperance of the ester.The pH-rate profile for the aminolysis pathway indicates the presence of water and a hydroxide-catalyzed reaction and provides no evidence for intermediates.The conversion of diethyl glutamate to pyrrolidone-5-carboxylate may occur through either of two competing pathways: (a) rate-determining aminolysis to ethyl pyrrolidone-5-carboxylate, followed by rapid hydrolysis of the ester; (b) rate-determining hydrolysis to γ-ethylglutamate, followed by rapid cyclization.The pH-rate profile for the intramolecular aminolysis of O-acetylserine, determined at zero buffer concentration (30 deg C), has the complex appearance characteristic for acyl-transfer reactions involving neutral and anionic tetrahedral intermediates.Quantitative support for the interpretation of the pH-rate profile comes from the analysis of the nonlinear increases in the rate of aminolysis observed in the presence of increasing concentrations of phosphate buffers.The results of this and earlier studies suggest that there may not be major differences in the mechanisms of the intra- and intermolecular aminolysis of weakly acidic alcohols.