Spectroscopic Study on Kinetics of Oxidation of Doxycycline Hydrochloride by N-Chlorosuccinamide in Acidic Medium

Abstract

A tetracycline antibiotic doxycycline hydrochloride (DOX) has been oxidized by N-chlorosuccinamide (NCS) in sulphuric acid medium at 303 K and the kinetics have been investigated. The stoichiometry of the reaction was found to be 1:1 where one mole doxycycline reacted with one mole of NCS and the product of oxidation of doxycycline, 1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,4,11-trioxotetracene-2-carboxamide is identified by the spot tests and confirmed by LC-MS spectral analysis. The titled reaction exhibited first-order kinetics with reference to concentration of NCS and doxycycline a fractional order kinetics was observed with respect to [H2SO4] and doxycycline. The changes in the reaction rate on the addition of halide ions and reduction product was studied. The influence of added product, p-toluene sulfonamide was studied and found no significant effect. The influence of ionic strength (NaClO4) and dielectric constant of the medium was investigated on the reaction rate. All the experimental values were compiled together and a mechanism was proposed. The temperature effect was studied for calculating the activation parameters with reference to the rate determining step in the mechanism and the thermodynamic parameters were also discussed.