Related Experiment Video
Updated: Jun 6, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Triflic Anhydride-Mediated Friedel-Crafts Arylation of Quinazolin-4(3H)-ones
Zhenying Yao1, Zhanyong Tang1, Depeng Zhao1
1Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
Abstract:
Since the initial report, the Friedel-Crafts reaction has become a powerful tool to functionalize arenes. Nevertheless, the use of nitrogen heterocycles as electrophiles in Friedel-Crafts reactions has been less explored. Here, we show a Friedel-Crafts-like reaction of electron-rich arenes with quinazolin-4(3H)-ones, enabling late-stage C2-H arylation of quinazolin-4(3H)-ones via triflic anhydride (Tf2O) activation. A series of substrates can be efficiently coupled under mild reaction conditions, affording C(sp3)-C(sp2) coupling product 2-aryl dihydroquinazolinones that can be further converted into the corresponding quinazolinone in the presence of base. This methodology offers efficient access to 2-aryl quinazolin-4(3H)-ones and exhibits good functional group compatibility and site selectivity. Mechanistic investigations reveal the formation of highly electrophilic iminium intermediates upon Tf2O activation of quinazolin-4(3H)-ones, which serve as the key reactive species, enabling the Friedel-Crafts reaction to proceed efficiently.
More Related Videos
10:10Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes
Published on: July 28, 2018
07:56Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyltroponeiron
Published on: August 12, 2019
Related Concept Videos
Electrophilic Aromatic Substitution: Friedel–Crafts Acylation of Benzene
Limitations of Friedel–Crafts Reactions
Electrophilic Aromatic Substitution: Friedel–Crafts Alkylation of Benzene
Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo,...
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
Nucleophilic Aromatic Substitution: Elimination–Addition