Water-Mediated One-pot Three-Component Synthesis of Hydrazinyl-Thiazoles Catalyzed by Copper Oxide Nanoparticles Dispersed on Titanium Dioxide Support: A Green Catalytic Process

The present work describes the catalytic activity of copper oxide nanoparticles dispersed on titanium dioxide in water for one-pot synthesis of a library of hydrazinyl-thiazoles via a three-component reaction of various aldehydes/ketones with thiosemicarbazide and different phenacyl bromides. The structure of the synthesized compound, (E)-4-(4-bromophenyl)-2-(2-(4-methoxybenzylidene) hydrazinyl)thiazole is confirmed by single crystal X-ray diffraction studies. The catalyst prepared by a molten-salt method is characterized by X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, Auger electron spectroscopy and electron spin resonance spectroscopy. The noteworthy advantages of this method include its broad substrate scope, clean reaction profile, short reaction times and high yields at low catalyst loading. Further, the product does not require any chromatographic purification and the method has the potential for large-scale applications in pharmaceutical industries. In addition, the developed catalyst can be recovered and reused for 5 times without significant loss of activity. Mechanistic studies suggest that the reaction begins with the activation of the carbonyl group of both aldehyde/ketone and phenacyl bromide by copper oxide nanoparticles supported on titanium dioxide in water. These studies reveal that the reaction proceeds via the formation of thiosemicarbazone intermediate.