Biphasic Electrophilic Halogenation of Activated Aromatics and Heteroaromatics with N-Halosuccinimides Catalyzed by Perchloric Acid

Abstract

Catalytic amounts of 70% perchloric acid (0.1–10, mostly 0.1–1, mol %, based on substrate) initiate the regioselective halogenation of activated aromatics [mesitylene, 1,3-dimethoxybenzene, 2,3-dimethylanisole, o-xylene] and heteroaromatics [thiophene, its 2-methyl, 2-halo (chloro, bromo, iodo), and 3-bromo derivatives] with N-halosuccinimide (NXS, X = Cl or Br) in two-phase solid-liquid systems (NXS/hexane or NXS/CCl4) at room temperature to give ring-halogenated products in high yields. For example, thiophene is transformed to 2-halo or 2,5-dihalo derivatives (yield 82–98%) using 1 or 2 equiv of NXS, respectively. Unsymmetrical 2,5-dihalothiophenes are obtained in 70–82% yield by reacting 2-halothiophenes with an appropriate NXS. The reaction of 3-bromothiophene with NBS affords 2,3-dibromothiophene in 93–99% yield. 1,3-Dimethoxybenzene and 2,3-dimethylanisole are halogenated regiospecifically at the 4 position to give the corresponding products in 81–94% yield. © 1993, American Chemical Society. All rights reserved.