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Updated: Sep 11, 2025

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Catalyst-Free Regioselective 1,6-Aza-Michael Addition of para-Quinone Methides with Tetrazoles in Water
Yanan Li1,2, Chenpei Yang1, Jianan Sun3
1School of Chemical and Blasting Engineering, Anhui Province Key Laboratory of Specialty Polymers, The First Affiliated Hospital of Anhui University of Science and Technology, Anhui University of Science and Technology, Huainan 232001, China.
Abstract:
A facile catalyst-free regioselective 1,6-aza-Michael addition of para-quinone methides with tetrazoles was efficiently developed using water as a green solvent. This process exhibited broad substrate compatibility, including benzotriazole, pyrazole, and indazole, yielding the corresponding N-substituted azoles with excellent efficiency and regioselectivity. To demonstrate the practicality of this methodology, gram-scale reactions were successfully conducted. The possible mechanistic pathway is elucidated based on the preliminary results from control experiments as well as discrete fourier transform (DFT) calculations, which reveal that the solvent water plays a crucial role in facilitating the reaction by forming hydrogen bonds with the substrate, thereby enhancing the reaction progress.
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