A Rapid, Greener, and Sustainable Synthesis of N-Acylhydrazones of Isoniazid in a Deep-Eutectic Solvent

Abstract This study introduces an efficient, environmentally friendly, and sustainable method for synthesizing N-acylhydrazone analogues by engaging isoniazid in a condensation reaction with variously substituted benzaldehydes. The deep-eutectic solvent (ZnCl2/urea) employed in this study acted not only as a solvent but also as a catalyst to facilitate the synthesis of the target compounds within two to six minutes without the requirement of any lengthy purification techniques. The synthetic protocol is operationally simple and offers other remarkable advantages such as a short reaction time, good to excellent yields, a scalable protocol, and a recyclable and reusable catalyst. Additionally, green metrics calculations suggest the present method to be environmentally benign. Finally, the frontier molecular orbitals and the global reactivity parameters of the synthesized compounds were predicted by using density functional theory calculations.