Nucleophilic substitution reactions of α-bromoacetanilides with benzylamines

Abstract

Kinetic studies of the reactions of α-bromoacetanilides [YC 6H4NHC(=O)CH2Br] with substituted benzylamines (XC6H4CH2NH2) have been carried out in dimethyl sulfoxide at 35.0 °C. The Hammett plots for substituent (Y) variations in the substrate (log kN vs. σY) are biphasic concave upwards/downwards with breaks at Y = 4-Cl (σY = 0.23). The Hammett coefficients ρY and the cross-interaction constant ρXY (= +0.16) are positive for σY ≤ 0.23, while the ρY values are positive/negative [ρY > 0 for X = (4-MeO and 4-Me) and ρY < 0 for X = (H, 4-Cl and 3-Cl)] and the ρXY (= ?1.51) value is negative for σY ≥ 0.23. Based on these and other results, the benzylaminolyses of α-bromoacetanilides are proposed to proceed through rate-limiting expulsion of the bromide leaving group from a zwitterionic tetrahedral intermediate, T±, with a bridged transition state for σY ≤ 0.23, while the reaction proceeds through concerted mechanism with an enolate-like TS in which the nucleophile attacks the α-carbon for σY ≥ 0.23.