Replacement of hydrogen by halogen in heterocycles

For the mechanism of halogenation of heterocycles and the influence of the medium (solvent, addition of acid to convert A-heterocycles into their conjugated acids, and addition of base for production of the anions from acidic heterocycles such as imidazole and pyrrole), as well as the influence of temperature a review by Eisch717 should be consulted. 

Thiophene is readily brominated at positions 2 and 5. A-Bromosuccinimide gives a very poor yield of 2-bromothiophene,721 but it is better when bromine is used. 

2-Bromothiophene 722 Bromine (1.1 mole) in CC14 (300 ml) is dropped during 4h into a stirred mixture of thiophene (1 mole) and CC14 (100 ml), cooled in an ice-bath. The residue left on removal of the solvent is heated with powdered NaOH (15 g) for 4 h on the steam-bath with occasional stirring. The solution is decanted from NaOH and the latter is washed with CC14. Distillation through a column affords 55% of 2-bromothiophene, b.p. 153-154°, and 29.2 g of 2,5-dibromothiophene, b.p. 95-98°/16 mm. 

5- Dibromothiophene 723 Bromine (950 g) is added to a mixture of thiophene (297 g) with an equal volume of benzene as quickly as is possible without escape of bromine vapor. When evolution of HBr has become slow, ethanol (700 ml) and NaOH (250 g) are added and the mixture is boiled under reflux for 16 h. Then, after dilution with water, the organic layer is separated and distilled through a column it gives 2-bromothiophene (152 g), b.p. 158-162°, and 2,5-dibromothiophene (425 g), b.p. 200-210°. 

5- Tribromo-724 and tetrabromo-thiophene725 are readily obtained by using larger amounts of bromine. 

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