The first catalyst and solvent-free synthesis of 2-arylimidazo[2,1-b][1,3,4]thiadiazoles: a comparative assessment of greenness

A concise and efficient one pot synthesis of bicyclic imidazo[2,1-b][1,3,4]thiadiazoles via the three component Groebke-Blackburn-Bienayme (GBB) reaction utilizing 5-aryl-1,3,4-thiadiazol-2-amines, aromatic aldehydes and isonitriles has been developed. The reactions were carried out under microwave irradiation and ultimate green conditions excluding both catalysts and solvents. Furthermore, the greenness of the protocol was evaluated within the ambits of green metrics and the method exhibited an excellent score in the defined parameters such as atom economy, E-factor, reaction mass efficiency, process mass intensity and carbon efficiency. This environmentally benign GBB methodology paves easy access towards the synthesis of pharmacologically significant scaffolds.