Kinetics of the oxidation of isoniazid with the hypochlorite ion

Abstract

The stoichiometry and kinetics of the reaction between isoniazid (isonicotinic hydrazide, INH) and the hypochlorite ion was studied in a basic aqueous medium (pH > 10) by spectrophotometric, hydrogen-1 nuclear magnetic resonance, electrospray mass spectrometric and stopped-flow methods. At oxidant excess, the sole organic product was confirmed to be isonicotinic acid. At isoniazid excess, a coupled condensation product formed from isoniazid and isonicotinic acid was also detected in relatively high amounts. The stoichiometric ratio of the two reactants (INH/OCl⁻) was 0.46 or 0.67 depending on which of the reagents was in excess initially. Under all conditions, the rate determining step of the overall reaction was confirmed to be the rapid bimolecular reaction between the neutral from of isoniazid and the anionic hypochlorite ion. The second order rate constant of the process was estimated to be (3.4 ± 0.7) × 10⁴ M⁻¹ s⁻¹ at 25.0 °C.