Oxidation of tricyclic antidepressant drugs with chloramine-T in acidic solutions: kinetic, mechanistic and thermodynamic studies

The kinetics of the oxidation of two tricyclic antidepressants (TCA) namely, imipramine (IMP) and clomipramine (CLM) with sodium N-chloro-p-toluenesulfonamide or chloramine-T (CAT) in HClO(4) medium was studied at 300 K. The two reactions followed identical kinetics with a first-order dependence of rate on [CAT](o) and fractional order dependence on [TCA](o). The reaction is catalyzed by H(+) ions with a fractional order dependence. The reaction was studied at different temperatures and activation parameters were evaluated. The reaction constants involved in the mechanism were computed. The solvent isotope effect was studied using D(2)O. Addition of p-toluenesulfonamide retards the reaction rate. The rate increased with decreasing dielectric constant of the medium. Variation of ionic strength of the medium and addition of halide ions (Cl(-) or Br(-)) showed no effect on the rate. The stoichiometry of the reaction was found to be 1:1 and the oxidation products were identified as imipramine-5-N-oxide and clomipramine-5-N-oxide. The rate of oxidation of IMP is faster than CLM. The observed results have been explained in terms of a mechanism and a relevant rate law has been deduced.