Kinetics and mechanism of the anilinolysis of (2R,4R,5S)-(+)-2-chloro-3,4- dimethyl-5-phenyl-1,3,2-oxazaphospholidine 2-sulfide in acetonitrile

Abstract

The nucleophilic substitution reactions of (2R,4R,5S)-(+)-2-chloro-3,4- dimethyl-5-phenyl-1,3,2-oxazapho-spholidine 2-sulfide (3) with substituted anilines (XC 6H 4NH 2) and deuterated anilines (XC 6H 4ND 2) are investigated kinetically in acetonitrile at 5.0 °C. The anilinolysis rate of 3 involving a cyclic five-membered ring is considerably fast because of small negative value of the entropy of activation (ΔS ≠ = -2 cal mol -1 K -1) over considerably unfavorable enthalpy of activation (ΔH ≠ = 18.0 kcal mol -1). Great enthalpy and small negative entropy of activation are ascribed to sterically congested transition state (TS) and bulk solvent structure breaking in the TS. A concerted S N2 mechanism with a backside nucleophilic attack is proposed on the basis of the secondary inverse deuterium kinetic isotope effects, k H/k D < 1.