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Updated: Aug 6, 2025

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Polyphosphoric Acid Esters Promoted Synthesis of Quinazolin-4(3H)-imines from 2-Aminobenzonitrile
Natalia B Kilimciler1, Nicolás M Palavecino1, Nadia Gruber1
1Cátedra de Química Orgánica II, Departamento de Ciencias Químicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Junín 956, 1113 Buenos Aires, Argentina.
Abstract:
A novel method for the synthesis of quinazolin-4(3H)-imines (QIs) by trimethylsilyl polyphosphate (PPSE) promoted reaction of 2-aminobenzonitrile with secondary amides is reported. The reaction is general and allows for the synthesis of N-aryl and N-alkyl QIs with variable 2-substituents affording high yields. The procedure was extended to derivatives bearing additional functional groups. The method is operationally simple, involves easily available starting materials and a mild dehydrating agent, with wide functional group tolerance. The reaction procedure proved to be suitable for scaling-up. A possible reaction path via an intermediate nitrilium ion is proposed on the basis of literature data and experimental observations.
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