Quinone methide phosphodiester alkylations under aqueous conditions

A detailed analysis of the alkylation of phosphodiesters with a P-quinone m ethide under aqueous conditions has been accomplished. The relative rates o f phosphodiester alkylation and hydrolysis have been examined by H-1 NMR an alysis of the reaction of 2,6-dimethyl-p-quinone methide in a buffered diet hyl phosphate/acetonitrile solution (1:9 v/v, pH 4.0). The rate of hydrolys is of the quinone methide was confirmed by UV analysis in 28.5% solutions o f aqueous inorganic phosphate in acetonitrile at pH 4.0 and 7.0. Similarly, the rate of phosphodiester alkylations by the quinone methide was also con firmed by UV analysis in 28.5% solutions of aqueous dibenzyl, dibutyl, or d iethyl phosphate in acetonitrile at pH 4.0 and 7.0. These kinetic studies f urther establish that the phosphodiester alkylation reactions are acid-cata lyzed, second-order processes. The rate constant for phosphodiester alkylat ion was found to range from approximately 370-3700 times the rate constant of quinone methide hydrolysis with diethyl and dibenzyl phosphate, respecti vely (pH 4.0, 28.5% aqueous acetonitrile).