Kinetics and mechanism of the aminolysis of aryl ethyl chloro and chlorothio phosphates with anilines

Abstract

The reactions of ethyl Y-phenyl chloro (1) and chlorothio (2) phosphates with X-anilines in acetonitrile at 55.0 °C are studied kinetically and theoretically. Kinetic results yield the primary kinetic isotope effects (k_H/k_D = 1.07–1.80 and 1.06–1.27 for 1 and 2, respectively) with deuterated aniline (XC₆H₄ND₂) nucleophiles, and the cross-interaction constants ρ_XY = −0.60 and −0.28 for 1 and 2, respectively. A concerted mechanism involving a partial frontside attack through a hydrogen-bonded, four-center-type transition state is proposed. The large ρ_X (ρ_nuc = −3.1 to −3.4) and β_X (β_nuc = 1.1–1.2) values seem to be characteristic of the anilinolysis of phosphates and thiophosphates with the Cl leaving group. Because of the relatively large size of the aniline nucleophile, the degree of steric hindrance could be the decisive factor that determines the direction of the nucleophilic attack to the phosphate and thiophosphate substrates with the relatively small-sized Cl leaving group.