Kinetic Study on Aminolysis of 4-Nitrophenyl Isonicotinate in Acetonitrile: Effect of Amine Basicity on Reactivity and Reaction Mechanism

Abstract

A kinetic study is reported on nucleophilic substitution reactions of 4-nitrophenyl isonicotinate (7) with a series of cyclic secondary amines in MeCN. The plots of kobsd vs. [amine] curve upward for the reactions with weakly basic amines (e.g., morpholine, 1-(2-hydroxyethyl)piperazine, and piperazine) but are linear for those with strongly basic amines (e.g., piperidine and 3-methylpiperidine). The curved plots for the reactions with the weakly basic amines are typical for reactions reported previously to proceed through uncatalyzed and catalyzed routes with two intermediates (e.g., a zwitterionic tetrahedral intermediate T ± and its deprotonated form T – ). In contrast, the linear plots for the reactions with the strongly basic amines indicate that the catalytic route (i.e., the deprotonation process to yield T – from T ± by a second amine molecule) is absent. The Bronsted-type plots for Kk2 and Kk3 (i.e., the rate constants for the uncatalyzed and catalyzed routes, respectively) exhibit excellent linear correlations with βnuc = 0.99 and 0.69, respectively. The effect of amine basicity on the reaction mechanism is discussed in detail.