Enzymatic synthesis of isoniazid in non-aqueous medium

The reaction of ethyl isonicotinate (ethyl 4-pyridine carboxylate) with hydrazine hydrate as a nucleophile was conducted in 1,4-dioxane as a solvent to produce 4-pyridine carboxylic acid hydrazide (isoniazid) with different immobilized lipases. Isoniazid is an important agent in the treatment of tuberculosis and it can be synthesized via Novozym 435 as the catalyst. Equimolar quantities of reactants (3.33 × 10−4 mol/cm3 each) in 30 mL solution with 1.67 × 10−3 g/cm3 Novozym 435 leads to 52% conversion in 24 h. Based on the initial rate studies and concentration profiles (progress curve) analysis, a complete rate equation is proposed taking into account the irreversible inactivation caused by ethyl isonicotinate at very high concentrations. The kinetic model follows the ternary complex mechanism with dead end inhibition by ethyl isonicotinate.