Intramolecular catalysis of phosphate triester hydrolysis. Nucleophilic catalysis by the neighbouring carboxy-group of the hydrolysis of diaryl 2-carboxyphenyl phosphates

Abstract

2-Carboxyphenyl diphenyl phosphate is rapidly hydrolysed to salicylic acid and diphenyl phosphate, in a reaction subject to highly efficient catalysis by the ionised carboxy-group. A rate enhancement of the order of 108 is observed, and there is convincing evidence that the reaction involves intramolecular nucleophilic catalysis. The stereochemistry of this non-linear displacement at phosphorus is in striking contrast to the corresponding reaction of the monophenyl ester, in which selective exocyclic displacement occurs, but is consistent with Westheimer's rules for pseudorotation. Kinetic and product studies with five aryl 2,3-dicarboxyphenyl phenyl phosphates support the proposed mechanism, and show that intramolecular displacements on these phosphate triesters depend exclusively on the basicity of the leaving group, and not at all on geometry. Linear free-energy relationships show that the sensitivity to the basicity of the leaving group is the largest yet measured for a displacement reaction, and allow order-of-magnitude calculations of rate constants for the breakdown of pentacovalent intermediates.