Nucleophilic Substitution Reactions of N-Methyl α-Bromoacetanilides with Benzylamines in Dimethyl Sulfoxide

Kinetic studies of the reactions of N-methyl-Y-alpha-bromoacetanilides with substituted X-benzylamines have been carried out in dimethyl sulfoxide at 25.0 degrees C. The Hammett plots for substituent X variations in the nucleophiles (log k(N) vs sigma(X)) are slightly biphasic concave upwards/downwards, while the Bronsted plots (log k(N) vs pk(a)) are biphasic concave downwards with breakpoints at X = H. The Hammett plots for substituent Y variations in the substrates (log k(N) vs sigma(Y)) are biphasic concave upwards/downwards with breakpoints at Y = H. The cross-interaction constant rho(XY) values are all negative: rho(XY) = -0.32 for X = Y = electron-donating; -0.22 for X = electron-withdrawing and Y = electron-donating; -1.80 for X = electron-donating and Y = electron-withdrawing; -1.43 for X = Y = electron-withdrawing substituents. Deuterated kinetic isotope effects are primary normal (k(H)/k(D) > 1) for Y = electron-donating, while secondary inverse (k(H)/k(D) < 1) for Y = electron-withdrawing substituent. The proposed mechanisms of the benzylaminolyses of N-methyl-Y-alpha-bromoacetanilides are a concerted mechanism with a five membered ring TS involving hydrogen bonding between hydrogen (deuterium) atom in N-H(D) and oxygen atom in C = O for Y = electron-donating, while a concerted mechanism with an enolate-like TS in which the nucleophile attacks the alpha-carbon for Y = electron-withdrawing substituents.