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.