Bentonite catalyzed solvent-free synthesis of N′-(2-oxoindolin-3-ylidene) benzohydrazide derivatives under microwave irradiation

Abstract

Isatin-derived Schiff bases are widely explored pharmacologically, however, their production is still mainly based on syntheses under organic solvents, which make the process more expensive and result in the production of residues. To overcome these obstacles, this work describes a new methodology for the synthesis of a series of N′-(2-oxoindolin-3-ylidene)benzohydrazide derivatives, using bentonite clay as catalysts under microwave irradiation. The methodology was optimized studying the type and loading of the catalyst, solvent, and heating source. The solvent-free reaction in the presence of bentonite as a catalyst was the best experimental condition, and this methodology was applied to several isatin-derived substrates with yields up to 96% for isolated products, and reaction times between 15-60 minutes. All these results were comparable or superior to those found in the literature, however with an environmentally compatible methodology using heterogeneous catalysis. Finally, the catalyst shows recyclability for at least three cycles without significant losses in yields and reaction time, demonstrating the applicability of this clay as a low-cost and cleaner alternative. Considering yet the biological potential of the molecules studied, preliminary molecular docking analyzes were performed to verify their affinities against DNA-gyrase, a bacterial target previously recognized by analogous compounds.