Quantitative Kinetics of the Rapid Bromination of Isoxazole in Bromide-Free Aqueous Medium using Hydrodynamic Voltammetry

Abstract

The kinetics of rapid bromination of isoxazole by molecular bromine at pH 4.7 have been studied quantitatively. Bromination of isoxazole is an electrophilic substitution reaction where the inductive effect and resonance effect govern reactivity and orientation respectively. Isoxazoles have a broad range of applications in pharmaceuticals and therapeutics. Hence the quantitative kinetic study will help in these applications. The bromination reactions are rapid electrophilic substitution reactions with a half-life of a few seconds, therefore the kinetic data regarding the bromination was lacking thus far. A distinct technique known as hydrodynamic voltammetry was used to perform the kinetics of the reaction. Only molecular bromine gets reduced on the working electrode during the reactions. As the solution lacked bromide ions, a decrease in the concentration of molecular Br2 was measured with reference to diffusion current using a rotating platinum electrode (RPE). During the work, a saturated calomel electrode (SCE) was used as a reference electrode. Bromination of isoxazole followed second-order kinetics with an equal initial concentration of reactants. Thermodynamic parameters were obtained based on rate constants at five different temperatures. The obtained rate constants and activation energy were used to comment on the mechanism of the electrophilic substitution reaction. Thus, the present work quantitatively verifies the reactivity of the isoxazole in the bromination reaction.