Transition metal-free one-pot tandem chemoselective reduction and cyclization of 3/5-(2-nitrophenyl)-1-pyrazoles using sodium dithionite.

A sodium dithionite (NaSO) mediated tandem chemoselective reductive cyclization of 5-(2-nitrophenyl)-1-pyrazoles with aldehydes/carbon disulfide is developed for the synthesis of pyrazolo[1,5-]quinazolines. The protocol involves one pot reduction of 5-(2-nitrophenyl)-1-pyrazoles, followed by intermolecular cyclization with aldehydes or carbon disulfide to afford the pyrazolo[1,5-]quinazolines. The protocol is further expanded for the synthesis of pyrazolo[4,3-]quinolines from 3-(2-nitrophenyl)-1-phenyl-1-pyrazole-4-carbaldehyde one pot reduction followed by intramolecular cyclization. Notably, the use of NaSO as the reducing agent enables a metal, ligand, and additive-free approach, wide substrate scope, and scalability up to gram scale. The synthesized compounds were studied for photophysical properties in ACN and MeOH, the compound 7c, which contains an electron-donating methoxy group, exhibited a greater bathochromic shift. Notably, the pyrazolo[1,5-]quinazoline-5(6)-thione derivatives 5a and 5d demonstrated selective inhibition of , with minimum inhibitory concentrations (MICs) of 2 and 4 μg mL, respectively. ESI-MS and DFT studies were conducted for the identification of the key intermediates and to elucidate the plausible reaction mechanism.