Evidence for a Catalytic Six-Membered Cyclic Transition State in Aminolysis of 4-Nitrophenyl 3,5-Dinitrobenzoate in Acetonitrile: Comparative Brønsted-Type Plot, Entropy of Activation, and Deuterium Kinetic Isotope Effects

A kinetic study for reactions of 4-nitrophenyl 3,5-dinitrobenzoate (1a) with a series of cyclic secondary amines in acetonitrile is reported. Plots of the pseudo-first- order rate constant (kobsd) vs (amine) curve upward, while those of kobsd /(amine) vs (amine) exhibit excellent linear correlations with positive intercepts, indicating that the reaction proceeds through both uncatalyzed and catalyzed routes. Bronsted-type plots for uncatalyzed and catalyzed reactions are linear with βnuc = 1.03 and 0.69, respectively. The ΔH ⧧ and ΔS ⧧ values measured for the catalytic reaction with morpholine are −0.80 kcal/mol and −61.7 cal/(mol K), respectively. The negative ΔH ⧧ with a large negative ΔS ⧧ suggests that the reaction proceeds through a highly ordered transition state (i.e., a six-membered cyclic transition state, which includes a second amine molecule that accepts a proton from the aminium moiety of the zwitterionic tetrahedral intermediate and simultaneously donates a proton to the aryloxyl oxygen of the nucleofuge with concomitant C−OAr bond scission). This proposal is consistent with the smaller βnuc value for the catalyzed reaction as compared to the uncatalyzed reaction. An inverse deuterium kinetic isotope effect (DKIE) value of 0.93 and a contrasting normal primary DKIE value of 3.23 for the uncatalyzed and catalyzed routes, respectively, also support the proposed cyclic transition state.