Quinone methide phosphodiester alkylations under aqueous conditions

by Zhou, Q. B.; Turnbull, K. D.

A detailed analysis of the alkylation of phosphodiesters with a P-quinone methide under aqueous conditions has been accomplished. The relative rates of phosphodiester alkylation and hydrolysis have been examined by H-1 NMR analysis of the reaction of 2,6-dimethyl-p-quinone methide in a buffered diethyl phosphate/acetonitrile solution (1:9 v/v, pH 4.0). The rate of hydrolysis of the quinone methide was confirmed by UV analysis in 28.5% solutions of aqueous inorganic phosphate in acetonitrile at pH 4.0 and 7.0. Similarly, the rate of phosphodiester alkylations by the quinone methide was also confirmed by UV analysis in 28.5% solutions of aqueous dibenzyl, dibutyl, or diethyl phosphate in acetonitrile at pH 4.0 and 7.0. These kinetic studies further establish that the phosphodiester alkylation reactions are acid-catalyzed, second-order processes. The rate constant for phosphodiester alkylation was found to range from approximately 370-3700 times the rate constant of quinone methide hydrolysis with diethyl and dibenzyl phosphate, respectively (pH 4.0, 28.5% aqueous acetonitrile).

Journal
Journal of Organic Chemistry
Volume
66
Issue
21
Year
2001
Start Page
7072-7077
URL
https://dx.doi.org/10.1021/jo015792+
ISBN/ISSN
1520-6904; 0022-3263
DOI
10.1021/jo015792+