The uncatalysed, and the imidazole and o-mercaptobenzoic acid catalysed, hydrolysis of p-nitrophenyl N-benzyloxycarbonylglycinate

Abstract

The uncatalysed hydrolysis of p-nitrophenyl N- benzyloxycarbonylglycinate has been studied in 40% (v/v) ethanol-water over the pH range 7.6-8.5. The reaction shows a first-order dependence on the hydroxide ion concentration. The quite rapid hydrolysis (k = (4.4±0.4) x 10⁴ 1. mole^-1 min^-1 at 20°) may possibly indicate the formation of a 2-benzyloxyoxazoline-5-one intermediate.     Unlike the hydrolysis of the p-nitrophenyl esters of α-amino acids, the hydrolysis of the N-protected derivatives is not catalysed by carbon dioxide. The hydrolysis of p-nitrophenyl N- benzyloxycarbonylglycinate is, however, catalysed by imidazole in 40% v/v ethanol-water. Unprotonated imidazole (Im) is the catalytically active species. N-Benzyloxycarbonylaminoacetylimidazole has been detected spectrophotometrically as an intermediate in the reaction, indicating nucleophilic catalysis by the base. o-Mercaptobenzoic acid was also found to catalyse the hydrolysis of p-nitrophenyl N- benzyloxycarbonylglycinate. pH-rate profile studies indicate that the dianion of o-mercaptobenzoic acid is the catalytically active species, the substrate presumably hydrolysing via the thioester intermediate Z- NHCH₂COSC₆H₄COO^-, although efforts to detect such an intermediate have been unsuccessful. Some evidence for a thioester intermediate in the L- cysteine-catalysed reaction has been obtained.