Elimination-addition mechanisms of acyl group transfer: hydrolysis and aminolysis of aryl phenylmethanesulfonates

Abstract

The following evidence is consistent with an ElcB mechanism involving a sulfene intermediate for the alkaline hydrolysis and aminolysis of aryl phenylmethanesulfonates in water: (1) The Brjinsted plot of hydroxide rate constant vs. phenol acidity possesses a sharp break at pKa~6.5. (2) Alkaline hydrolysis of the esters of weakly acidic phenols possesses a high selectivity (βLG=2.4) compared with that for esters (1.2) undergoing an addition-elimination mechanism. (3) The rate constant for phenol release is not linearly dependent on amine buffer concentration. (4) Trapping experiments with amines indicate a common intermediate for aminolysis of the esters. (5) The hydroxide rate constant for the 4-nitrophenyl ester is 1000-fold larger than for the corresponding benzene- and methanesulfonates. (6) Esters of the acidic phenols hydrolyze with general base catalysis and a high primary deuterium isotope effect. (7) Esters of the weakly acidic phenols undergo only specific base-catalyzed hydrolysis and involve no primary isotope effect. The lifetime of the conjugate base from esters of phenols with pKa < 6 is too short (< 10~13 s) for it to exist as a discrete intermediate and an E2 elimination occurs with an unsymmetrical transition state involving no S-OAr bond cleavage and half advanced proton transfer. The inactivation of a-chymotrypsin by phenyl-methanesulfonyl fluoride is shown not to be via a sulfene intermediate.