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

Abstract

A sodium dithionite (Na₂S₂O₄) mediated tandem chemoselective reductive cyclization of 5-(2-nitrophenyl)-1H-pyrazoles with aldehydes/carbon disulfide is developed for the synthesis of pyrazolo[1,5-c]quinazolines. The protocol involves one pot in situ reduction of 5-(2-nitrophenyl)-1H-pyrazoles, followed by intermolecular cyclization with aldehydes or carbon disulfide to afford the pyrazolo[1,5-c]quinazolines. The protocol is further expanded for the synthesis of pyrazolo[4,3-c]quinolines from 3-(2-nitrophenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde via one pot in situ reduction followed by intramolecular cyclization. Notably, the use of Na₂S₂O₄ 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-c]quinazoline-5(6H)-thione derivatives 5a and 5d demonstrated selective inhibition of Staphylococcus aureus, with minimum inhibitory concentrations (MICs) of 2 and 4 μg mL⁻¹, respectively. ESI-MS and DFT studies were conducted for the identification of the key intermediates and to elucidate the plausible reaction mechanism.