Kinetic and Mechanistic Studies of Oxidation of an Antiallergic Drug with Bromamine-T in Acid and Alkaline Media

摘要

Cetrizine dihydrochloride (CTZH) is widely used as an anti-allergic drug. Sodium N-bromo-p-toluenesulfon-amide or bromamine-T (BAT) is the bromine analogue of chloramine-T (CAT) and is found to be a better oxidizing agent than CAT. In the present research, the kinetics of oxidation of CTZH with BAT in acid and alkaline media was studied at 313 K. The experimental rate laws obtained are: -d[BAT]/dt = k[BAT] [CTZH]~(0.80) [H~+]~(-0.48) in acid medium and -d[BAT]/dt = k[BAT][CTZH]~(0.48)[OH~-]~(0.52)[PTS]~(-0.40) in alkaline medium where PTS is p-toluenesulfonamide. Activation parameters and reaction constants were evaluated. The solvent isotope effect was studied using D2O. The dielectric effect is positive. The stoichiometry of the reaction was found to be 1:1 and the oxidation products were identified as 4-chlorobenzophenone and (2-piperazin-1-yl-ethoxy)-acetic acid in both media. The rate of oxidation of CTZH is faster in acid medium. Suitable mechanisms and related rate laws have been worked out.