Srikanth Danaboina, Shejul Gayatri Diliprao, Joshi Swanand Vinayak, Kalam Abdul, Jahnavi Avvaru Subha, Dikundwar Amol G, Chopra Sidharth, Yaddanapudi Madhavi Venkata, Nanduri Srinivas
Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
Org Biomol Chem. 2025 Jun 18;23(24):5812-5820. doi: 10.1039/d5ob00610d.
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.
开发了一种连二亚硫酸钠（NaSO）介导的5-（2-硝基苯基）-1-吡唑与醛/二硫化碳的串联化学选择性还原环化反应，用于合成吡唑并[1,5 - ]喹唑啉。该方法包括一锅法还原5-（2-硝基苯基）-1-吡唑，然后与醛或二硫化碳进行分子内环化以得到吡唑并[1,5 - ]喹唑啉。该方法进一步扩展用于从3-（2-硝基苯基）-1-苯基-1-吡唑-4-甲醛一锅法还原后进行分子内环化合成吡唑并[4,3 - ]喹啉。值得注意的是，使用连二亚硫酸钠作为还原剂实现了无金属、无配体和无添加剂的方法，底物范围广，可扩展至克级规模。研究了合成化合物在乙腈和甲醇中的光物理性质，含有供电子甲氧基的化合物7c表现出更大的红移。值得注意的是，吡唑并[1,5 - ]喹唑啉-5(6)-硫酮衍生物5a和5d表现出对……的选择性抑制，最小抑菌浓度（MIC）分别为2和4 μg/mL。进行了电喷雾电离质谱（ESI-MS）和密度泛函理论（DFT）研究以鉴定关键中间体并阐明可能的反应机理。
