Efficient MW-Assisted synthesis, spectroscopic characterization, x-ray and antioxidant properties of indazole derivatives

Abstract

A small series of tetrahydroindazoles was prepared, starting from 2-acetylcyclohexanone and different hydrazines using reflux and a focused microwave reactor. Microwave irradiation (MW) favored the formation of the desired products with improved yields and shortened reaction times. This is a simple and green method for the synthesis of substituted tetrahydroindazole derivatives. The in vitro antioxidant activity was evaluated using the DPPH and ABTS methods. In these assays, 2-(4-fluorophenyl)-3-methyl-4,5,6,7-tetrahydro-2H-indazole (3f) showed moderate DPPH decoloring activity, while 3-methyl-4,5,6,7-tetrahydro-1H-indazole (3a), 3-methyl-2-phenyl-4,5,6,7-tetrahydro-2H-indazole (3b) and 2-(4-fluorophenyl)-3-methyl-4,5,6,7-tetrahydro-2H-indazole (3f) were the most active in the ABTS assay. All compounds were well characterized by IR, 1H-, 13C-NMR and GC-MS spectroscopy and physical data, while the structure of 4-(3-methyl-4,5,6,7-tetrahydro-2H-indazol-2-yl)benzoic acid (3e) was also determined by single crystal X-ray analysis.