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Updated: Jun 17, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Direct C4-H amination of pyridines and quinolines under benign conditions
Tong Han1, Fenlian Xu1, Xinqiao Nie1
1State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, College of Chemistry, Xinjiang University, Urumqi 830017, Xinjiang, China. chem_wd@hotmail.com.
Abstract:
Existing methods for the para-C-H amination of pyridines and quinolines are scarce and rely exclusively on indirect approaches. These typically involve initial installation of an amine surrogate or an aryl phosphine at the para position, followed by subsequent conversion to the amine functionality-a process that suffers from low atom economy and generates substantial waste. Herein, we report a straightforward and environmentally benign method for the direct C4-H amination of azines. This transition-metal-free protocol, employing a base and an activating agent in ethyl acetate, enables mild and efficient C4-H amination of a wide range of 2-substituted pyridines and quinolines. Furthermore, we demonstrate that regioselectivity is strongly influenced by both substrate structure and solvent, and provide practical guidelines for optimal substrate selection.
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