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Updated: Sep 12, 2025

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
HFIP mediated transition metal-free synthesis of C4-aryl-substituted quinolines
Tae Kyung Ko1, Hyung Min Chi1,2,3
1Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, South Korea. hmchi@postech.ac.kr.
Abstract:
A transition metal-free method for C4-arylated quinolines synthesis from propargylic chloride and aniline was developed using 1,1,1,3,3,3,-hexafluoroisopropanol (HFIP). During the N-alkylation process, overalkylation was effectively resolved by hydrogen bonding interaction in HFIP. The cyclized intermediates were oxidized to quinolines under ambient air without additional oxidants. A cosolvent system was found to expand the substrate scope to include unstable electron-rich propargyl substrates by preventing acid-induced decomposition.
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