Intramolecular general acid catalysis of phosphate monoester hydrolysis. The hydrolysis of salicyl phosphate

Abstract

The effects of substituents in the 4- and 5-positions on the rate of hydrolysis of the salicyl phosphate dianion are entirely inconsistent with a mechanism involving a preliminary proton transfer to the leaving group. A mechanism is proposed in which the rate-determining step involves cleavage of the P–O bond concerted with a conformation change, but no significant amount of proton transfer. This mechanism accounts satisfactorily for all the known properties of the reaction, and predicts that intramolecular general acid catalysis by the carboxy-group in this system should be available for S_N2(P) reactions also. It is found that the reactions of substituted pyridines with the salicyl phosphate dianion are indeed subject to catalysis, with rate enhancements as high as 10⁸-fold.