Eco-friendly solvent-free synthesis of thiazolylpyrazole derivatives

Highly versatile ethyl 3-thiosemicarbazidobutanoate was ball-milled with phenacyl bromide to afford the corresponding ethyl 3-[(4-phenyl-2-thiazolyl)hydrazono]butanoate which underwent heterocyclization by heating in ethanolic sodium acetate to give thiazolylpyrazolone that coupled chemoselectively with aromatic diazonium salts to furnish arylhydrazonothiazolylpyrazoles. Vilsmeier-Haack reaction of ethyl 3-thiosemicarbazidobutanoate furnished selectively thiazolylpyrazole. A series of pyrazolylthiosemicarbazones were synthesized by solid-state technique which allowed waste-free production. The reaction of pyrazolylthiosemicarbazones with phenacyl bromide afforded the corresponding 2-(arylidenehydrazino)-4-phenylthiazoles in quantitative yields.