Kinetic Study on Aminolysis of 4-Nitrophenyl Nicotinate and Isonicotinate: Factors Influencing Reactivity and Reaction Mechanism

Abstract

A kinetic study is reported on nucleophilic substitution reactions of 4-nitrophenyl nicotinate (7) and 4-nitrophenyl isonicotinate (8) with a series of cyclic secondary amines in H2O containing 20 mol % DMSO at 25.0 oC. The Brønted-type plots for the reactions of 7 and 8 are linear with βnuc = 0.90 and 0.92, respectively, indicating that the reactions proceed through a stepwise mechanism with expulsion of the leaving group occurring in the rate-determining step. Comparison of the reactivity of 7 and 8 with that of 4-nitrophenyl benzoate (2a) and 4-nitrophenyl picolinate (6) has revealed that their reactivity toward the amines increases in the order 2a < 7 < 8 < 6, although the reactions of these substrates proceed through the same mechanism. Factors that control reactivity and reaction mechanism have been discussed in detail (e.g., inductive and field effects, H-bonding interaction, solvent effect, etc.)