Unanticipated Cleavage of 2-Nitrophenyl-Substituted N-Formyl Pyrazolines under Bechamp Conditions: Unveiling the Synthesis of 2-Aryl Quinolines and Their Mechanistic Exploration via DFT Studies

Abstract

We herein report for the first time an unusual decomposition of 2-nitrophenyl-substituted N -formyl pyrazolines under Bechamp reduction condition employed to yield 2-aryl quinolines exclusively instead of pyrazolo[1,5- c ]quinazolines. The reaction investigation suggests acid-mediated cleavage of 1 followed by a retro-Michael addition, and a subsequent in situ intramolecular reductive cyclization through a modified Friedlander mechanism afforded 2-aryl quinolines ( 2 ) in good yields. The proposed mechanistic pathways were supported via experimental evidence and density functional theory studies. B3LYP/6-31+G(d) analysis indicated the involvement of trans-2-hydroxyaminochalcone as a key intermediate and its isomerization and cyclization, leading to unusual product formation.

Design, Synthesis and Biological Evaluation of New 5‐(2‐Nitrophenyl)‐1‐aryl‐1H‐pyrazoles as Topoisomerase Inhibitors

“…Recently our research group reported 2‐nitro substituted N‐acetyl/formyl pyrazolines [22,32] as effective anticancer agents, and interestingly compound 29 [22] showed topoisomerase inhibition as well. However, their chemical instability [33] warrants the development of more stable and potent anticancer agents. We herein rationally designed 5‐(2‐nitrophenyl)‐1‐aryl‐1 H‐ pyrazole compounds ( 5 ) by incorporating the following changes in 29 after considering its interaction model with Topo II and preliminary docking studies of 5 at the ATP binding domain of Topo II (Figure 2).…”