Solvent-Free and Catalysis-Free Approach to the Solid State in Situ Growth of Crystalline Isoniazid Hydrazones

The isonicotinoylhydrazones and their coordination compounds have antibacterial, antifungal, antitubercular, antitumor, and anticonvulsant activities. A typical method employed in the preparation of isonicotinoylhydrazones involves the usage of the volatile organic solvents during the condensation reaction between isonicotinic acid hydrazide and carbonyl compounds. It has been shown that the solvent-free technique can be applied to obtain crystalline compounds. Reaction of isoniazid with carbonyl compound under solvent-free conditions results in microcrystalline solid state isonicotinoylhydrazones. The influence of solvent effect on the mechanism of condensation reaction was evaluated and the most significant intermediates and transition states, in the gas phase and in the presence of water and methanol were resolved. The solvent has positive effect on the reaction mechanism, but the organic solvent is unnecessary during the synthesis of crystalline isonicotinoylhydrazones derived from aldehydes. Mixing solid/liquid reactants together without additional solvent reduce the time of reaction and can be used to obtain microcrystalline compounds, which are synthesized for example to evaluate biological properties.