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

Article abstract of DOI:10.1021/jo00063a028

Catalytic amounts of 70percent perchloric acid (0.1 - 10, mostly 0.1 - 1, mol percent, based on substrate) initiate the regioselective halogenation of activated aromatics and heteroaromatics 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 82-98percent) using 1 or 2 equiv of NXS, respectively.Unsymmetrical 2,5-dihalothiophenes are obtained in 70-82percent yield by reacting 2-halothiophenes with an appropriate NXS.The reaction of 3-bromothiophene with NBS affords 2,3-dibromothiophene in 93-99percent yield. 1,3-Dimethoxybenzene and 2,3-dimethylanisole are halogenated regiospecifically at the 4-position to give the corresponding products in 81-94percent yield.