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

Gaurav Joshi; Aabid Abdullah Wani; Sahil Sharma; Priyadeep Bhutani; Prasad V Bharatam; Atish T Paul; Raj Kumar

doi:10.1021/acsomega.8b02682

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

ACS Omega. 2018 Dec 28;3(12):18783-18790. doi: 10.1021/acsomega.8b02682. eCollection 2018 Dec 31.

Authors

Gaurav Joshi¹, Aabid Abdullah Wani², Sahil Sharma³, Priyadeep Bhutani⁴, Prasad V Bharatam², Atish T Paul⁴, Raj Kumar^{1

3}

Affiliations

¹ Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda 151001, Punjab, India.
² Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Mohali 160062, India.
³ Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga 142001, India.
⁴ Laboratory of Natural Product Chemistry, Department of Pharmacy, Birla Institute of Technology and Science, Pilani (BITS Pilani), Pilani Campus, Pilani 333031, Rajasthan, India.

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.