PdCl2 Catalyzed and Uncatalyzed N-Oxidation of Naratriptan with Alkaline Chloramine-T: Delineation of Reaction Mechanisms and Kinetic Modelings

摘要

Naratriptan (NTT), chemically known as N-methyl-2-[3-(1-methyl piperidin-4-yl)-1-H-indol-5-yl] ethane sulfonamide, is an indole derivative widely used in the treatment of migraine headaches. The literature survey indicates that there is no report on the oxidation of NTT from the view point of its kinetic and mechanistic aspects. Also none has examined the task of platinum group metal ions as catalysts in the oxidation of this drug. Therefore, in the present research, oxidation of NTT with chloramine-T (CAT) in alkaline medium has been investigated at 298 K through systematic kinetic study in order to explore the mechanistic picture of this redox system in presence and absence of palladium (II) chloride (Pd(II)) catalyst. The reaction shows a first-order dependence of rate each on [CAT]0 and [NTT]0, and an inverse-fractional-order dependence on [NaOH] for both the Pd(II) catalyzed and uncatalyzed reactions. The order with respect to Pd(II) catalyst is fractional. Addition of P-toluenesulfonamide decreases the rate. The dielectric effect is negative. 2-[3-(1-methyl-1-oxidopiperidin-4-yl)-1H-indol-5-yl]ethanesulfonic acid and methylamine were identified as oxidation products of NTT. Activation parameters were deduced. The Pd(II) catalyzed reactions are about five-fold faster than the uncatalyzed reactions. The observed results have been explained by plausible mechanisms and the related rate laws have been worked out.