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Updated: Feb 25, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Superacidic Cyclization of Activated Anthranilonitriles into 2-Unsubstituted-4-aminoquinolines
Hubert Lavrard1, Paolo Larini2, Florence Popowycz1
1Université Lyon 1, CNRS, INSA , CPE, UMR 5246, ICBMS, COB, 20 Avenue Albert Einstein, F-69621 Villeurbanne Cedex, France.
Abstract:
4-Aminoquinolines were prepared in a three-step synthesis starting from substituted anthranilonitriles. The condensation on 1,1,1-trichloro-4-ethoxybut-3-enone proceeded efficiently either neat or in refluxing EtOH. Cyclization in superacidic trifluoromethanesulfonic acid provided unstable intermediate, which upon treatment with NaOEt in ethanol, afforded the expected esters. Theoretical investigations pointed out a monoprotonated nitrilium as the reactive species during the cyclization process.
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