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-oxazaphospholidine 2-sulfide (3) with substituted anilines (<TEX>$XC_6H_4NH_2$</TEX>) and deuterated anilines (<TEX>$XC_6H_4ND_2$</TEX>) are investigated kinetically in acetonitrile at <TEX>$5.0^{\circ}C$</TEX>. The anilinolysis rate of 3 involving a cyclic five-membered ring is considerably fast because of small negative value of the entropy of activation (<TEX>${\Delta}S^\neq=-2cal\;mol^{-1}\;K^{-1}$</TEX>) over considerably unfavorable enthalpy of activation (<TEX>${\Delta}H^\neq=18.0\;kcal\;mol^{-1}$</TEX>). 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 <TEX>$S_N2$</TEX> mechanism with a backside nucleophilic attack is proposed on the basis of the secondary inverse deuterium kinetic isotope effects, <TEX>$k_H/k_D$</TEX> < 1.