Intramolecular general base catalysis of intramolecular nucleophilic catalysis of ester hydrolysis

Abstract

The hydrolysis of the anion of 2-carboxyphenyl 4-hydroxybutyrate at 39° is 85 times faster than that of aspirin anion, and some 500 times faster than the spontaneous hydrolysis of phenyl 4-hydroxybutyrate. The expected mechanism is concerted intramolecular general base–intramolecular nucleophilic catalysis, by the carboxylate and hydroxy-groups, respectively, and the expected products are salicylate and γ-butyrolactone. All the evidence is consistent with this mechanism, which constitutes the first clear-cut example of bifunctional catalysis of ester hydrolysis.