General base catalysis of ester hydrolysis

Article abstract of DOI:10.1021/ja00067a020

The hydrolysis of alkyl formates with leaving groups in the range pK_a = 12-16 is catalyzed by substituted acetate anions. There is an increase in the Br?nsted β value for general base catalysis with decreasing pK_a of the leaving alcohol and a complementary increase in -β_1g with decreasing pK_a of the catalyzing base, both of which are consistent with a value of p_xy = ?β/-pK_1g = ?β_1g/-?pK_BH ? 0.11. This result supports a class n mechanism of general base catalysis, in which a proton is abstracted from the nucleophilic water molecule by the base catalyst in the transition state; it is not consistent with the kinetically equivalent class e mechanism of electrophilic catalysis by general acids of a reaction with hydroxide ion, by proton donation to the leaving alcohol. Solvent deuterium isotope effects in the range k_H2O/k_D2O = 3.6-5.3 for the buffer-independent reaction and 2.5-2.8 for catalysis by CHaCOO^- support concerted proton transfer and O-C bond formation. The secondary isotope effect for catalysis of the hydrolysis of LCOOMe by acetate ion is k_D/k_H = 1.05. Both nucleophilic and general base mechanisms of catalysis by acetate anions are observed for the hydrolysis of substituted phenyl formates with leaving groups of pK_a = 7.1-10.1. A small value of β = 0.12 for general base catalysis of the hydrolysis of phenyl formate and p-methylphenyl formate represents catalysis of the addition of water by hydrogen bonding of water to the base catalyst. On the other hand, a larger value of β = 0.35 and a decrease in k_H2O/k_D2O to 1.2 were observed for general base catalysis of the hydrolysis of p-nitrophenyl formate. It is suggested that the increase in β with decreasing pK_1g (an apparent "anti-Hammond effect") may be accounted for by a change in mechanism, from catalysis of a stepwise reaction of phenyl and p-methylphenyl formates to concerted general base catalysis of formyl transfer to water for the reaction of p-nitrophenyl formate.