Mechanism of hydrolysis of phosphorylethanolamine diesters. Intramolecular nucleophilic amine participation

Abstract

Intramolecular displacement reactions at phosphorus have been examined in a series of N-alkyl-O-arylphosphorylethanolamines in water at 35 °C. The examination of the pH–rate profiles and the direct observation by ³¹P n.m.r. of the reaction products implicate a nucleophilic role for the amine. A rate enhancement of 10⁶–10⁷ is observed. Structure–reactivity correlations derived by changing the pK_a of the amine and leaving group yield values for β_nuc≃ 0.7 and β_1g≃–1.25 and support an uncoupled concerted mechanism. A discussion of the mechanisms of nucleophilic reactions involving amines and oxyanions with inter- and intra-molecular phosphate di- and tri-esters is presented.