Mechanistic investigation of oxidation of metronidazole and tinidazole with N-bromosuccinimide in acid medium: A kinetic approach

Abstract

Metronidazole (MTZ) and tinidazole (TNZ) belong to nitroimidazole group of drugs used to treat infections such as ameobiasis, giardiasis and trichomoniasis. The kinetics of oxidation of MTZ and TNZ with N-bromosuccinimide (NBS) in perchloric acid medium has been investigated at 308 K. A 1:1 stoichiometry has been observed in both MTZ and TNZ cases. The oxidation reactions of both MTZ and TNZ follow the same rate law, -d[NBS]/dt = [NBS][Sub][H+]. However, in case of MTZ, at higher concentrations of H+ (0.006–0.01 mol dm−3), the rate law obtained is -d[NBS]/dt = [NBS][MTZ][H+]−1. Accelerating effect of [Cl-] and retardation of the added succinimide on the reaction rate have been observed in the case of MTZ. The reactions were examined with reference to changes in concentration of added neutral salt, ionic strength and dielectric permittivity of the medium. The overall activation parameters have been evaluated from the Arrhenius plot. The reactive oxidizing species of NBS have been determined. The main oxidation products were identified by IR and 1H NMR spectral analyses. The observed results have been explained by plausible mechanisms and the relative rate laws have been deduced.