Kinetic Study on Aminolysis of Y-Substituted-Phenyl Picolinates: Effect of H-Bonding Interaction on Reactivity and Transition-State Structure

Abstract

A kinetic study is reported on nucleophilic substitution reactions of Y-substituted-phenyl picolinates (7a-7h) with a series of cyclic secondary amines in 80 mol % <TEX>$H_2O$</TEX>/20 mol % DMSO at <TEX>$25.0{\pm}0.1^{\circ}C$</TEX>. Comparison of the kinetic results with those reported previously for the corresponding reactions of Y-substituted-phenyl benzoates (1a-1f) reveals that 7a-7h are significantly more reactive than 1a-1f. The Br<TEX>${\o}$</TEX>nsted-type plot for the aminolysis of 4-nitrophenyl picolinate (7a) is linear with <TEX>${\beta}_{nuc}=0.78$</TEX>, which is typical for reactions proceeding through a stepwise mechanism with expulsion of the leaving group being the rate-determining step. The Br<TEX>${\o}$</TEX>nsted-type plots for the piperidinolysis of 7a-7h and 1a-1f are also linear with <TEX>${\beta}_{lg}=-1.04$</TEX> and -1.39, respectively, indicating that the more reactive 7a-7h are less selective than the less reactive 1a-1f to the leaving-group basicity. One might suggest that the enhanced reactivity of 7a-7h is due to the inductive effect exerted by the electronegative N atom in the picolinyl moiety, while the decreased selectivity of the more reactive substrates is in accord with the reactivity-selectivity principle. However, the nature of intermediate (e.g., a stabilized cyclic intermediate through the intramolecular H-bonding interaction for the reactions of 7a-7h, which is structurally not possible for the reactions of 1a-1f) is also responsible for the enhanced reactivity with a decreased selectivity.