Sustainable access to (E)-2-(2-benzylidenehydrazinyl)-4-phenylthiazoles using a ruthenium(ii) catalyst via dehydrogenative coupling of alcohols

Abstract

Medicinally important (E)-2-(2-benzylidenehydrazinyl)-4-phenylthiazoles are derived via the acceptorless dehydrogenative coupling (ADC) of readily available alcohols using a new ruthenium(II) catalyst. An areneruthenium(II)-N^O chelating complex is synthesised and structurally characterized using elemental analysis, IR and NMR spectroscopies and single-crystal XRD technique. A wide range of 2,4-disubstituted thiazole derivatives (15 examples) is constructed via the dehydrogenative coupling of alcohols with thiosemicarbazide, followed by cyclization with 2-bromoacetophenone under mild reaction conditions. The reactions proceed well under low catalyst loading (1 mol%) with a maximum yield of 92% and produce eco-friendly H₂O and H₂ gas as the only by-products. Various control experiments and mechanistic studies reveal that the reactions proceed via alcohol dehydrogenation. In addition, the successful large-scale synthesis of one of the derivatives highlights the catalytic efficiency of the proposed methodology.