Kinetic and Mechanistic Investigation of S-Oxidation of Ranitidine Hydrochloride with Chloramine-t in Acid and Alkaline Media

Abstract

Ranitidine hydrochloride (RNH), chemically known as A-dimethyl-5-[2-(l- methylamino-2-nitro-vinyl)-ethylthiomethyl]furfuryl amine hydrochloride, is an antiulcer drug and its oxidation-kinetic study is of much significant in understanding its mechanistic chemistry in redox reactions. Consequently, the kinetics of oxidation of RNH by sodium N-chloro-p-toluenesulfonamide (chloramine-T or CAT) have been examined in HC104 and NaOH media at 298 K. The stoichiometry and oxidation products of RNH - CAT reaction are the same in both media, however, their kinetic patterns were found to be different. The reaction rate exhibits first-order kinetics with respect to [CAT]O and [RNH]O in both media. The rate of reaction increases with increase in [H+], but it decreases with respect to [OH -] with a slope of unity in both the cases. Decrease of the dielectric constant of the medium decreases the reaction rate in both media. Variation of the ionic strength of the medium, and addition of /7-tolucncsul foil amide or NaCl, have no significant effect on the rate. The reaction was studied at different temperatures and activation parameters have been deduced. Ranitidine-S'-oxide was identified as the oxidation product of RNH by GC-MS in both media. The conjugate free acid CH3C6H4S02NHC1 of CAT is postulated as the reactive oxidizing species in both cases. The observed results have been explained by plausible mechanisms and related rate laws have been deduced.