The role of the carboxy-group in intramolecular catalysis of acetal hydrolysis. The hydrolysis of substituted 2-methoxymethoxybenzoic acids

Abstract

Separating the effects of substituents on the carboxy and leaving groups of 4- and 5-substituted 2-methoxymethoxybenzoic acids, by means of the extended Hammett equation, reveals the expected moderate sensitivity to the leaving group. But the Brönsted coefficient α is zero for intramolecular general acid catalysis. The mechanism proposed to account for this insensitivity to the pK_a of the carboxy-group is analogous to that proposed previously for the hydrolysis of the dianion of salicyl phosphate, and depends on the electronic interaction between the carboxy and leaving groups which occurs in reactions in which the salicylate anion is displaced. The suitability of salicylic acid derivatives as models for enzyme–substrate reactions in which the carboxy and leaving groups are in separate molecules is therefore questionable.