Nucleophilic Substitution Reactions of α-Bromoacetanilides with Benzylamines

Kinetic studies of the reactions of α-bromoacetanilides [YC6H4NHC(=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.