Bromination of pyrroles

Treatment of pyrrole, 1-methyl-, 1-benzyl- and 1-phenyl-pyrrole with one mole of A -bromosuccinimide in THF results in the regiospecific formation of 2-bromopyrroles. Chlorination with IV-chlorosuccinimide is less selective (8UOC2221). Bromination of pyrrole with bromine in acetic acid gives 2,3,4,5-tetrabromopyrrole and iodination with iodine in aqueous potassium iodide yields the corresponding tetraiodo compound. 

If the pyrrole is substituted with an electron-withdrawing group, then more vigorous halogenation conditions are required, but the products are usually more stable than simple halogenated pyrroles. For example, the bromination of pyrrole-2-carboxylic acid (12) yields the 4,5-dibromo isomer (13) in excellent yield [22]. Similarly, the bromination of 4-chloropyrrole-2-carboxylic acid furnishes 5-bromo-4-chIoropyrrole-2-carboxylic acid in 90% yield [23]. 

Regioselective bromination. This reagent is superior to NBS for bromination of pyrrole to provide 2-bromopyrrole. After conversion to the N-boc derivative,... 

Unlike the violent bromination of pyrrole or indole, which leads to polybrominated products, the bromination of pyrrolopyridines proceeds readily to a monobrominated product. Table 39 lists some of the pyrrolopyridine derivatives that have been brominated. Common solvents for these bromination reactions are chloroform, dioxane, or acetic acid. 

Bromination of pyrrole with bromine gives mainly the thermodynamically more stable 3-bromo derivative, which is produced from the 2-isomer, formed initially under kinetic control, through isomerization catalyzed by the reaction product HBr. If N-bromosuccinimide is used for bromination, no HBr is produced and the 2-isomer dominates (8IJOC222I). Bromination of furan gave cis- and frans-2,5,-dibromo-2,5-dihydrofurans (isolated as the dimethoxy derivatives) in a ratio of 3 I (67BCJ130). A spectroscopic study carried out at low temperature (- 50°C) confirmed this ratio and also showed that 20% of trans-2,3-dibro-mo-2,3-dihydrofuran was formed (75CC875). It is not known whether these adducts (which demonstrate the competition between 1,4- and 1,2-addition) are intermediates along the pathway for bromine substitution, or whether they are produced in a separate equilibrium as is the case for bromination of benzo[6]furan. 

Bromopyrrole 339, as a precursor of the compound 340, was easily prepared by bromination of pyrrole 338 with Bt2 in chloroform (Scheme 76) <1997J(P1)1443>. 

Another application of CuBrj to bromination of pyrroles was described. 2-(o-Hydroxybenzoyl)pyrrole can be converted to either the 4-bromo or 4,5-dibromo product, depending upon reaction conditions. Use of 3 equiv. of CuBrj gave l27as the major product (72%) whereas 6-6.5 equiv. gave mainly 128(95%). Still higher amounts of CuBrj result in bromination of the phenol ring. <94JHC941>... 

Radical bromination of pyrrole and indole methyl substituents continues to be investigated, as does the substitution of the resulting bromo compound. Selective bromination of the 2-methyl group in 1-acetyl-2,3-dimethylindole can be achieved and the bromide ion displaced by malonate <85TL5253>. A recent example of an effective sequence of bromination and substitution is shown in Scheme 116 <928743, 930PP249,93TL3215>. 

Bromination of 1-substituted pyrroles with one equivalent of Brj in CCI4 leads to a mixture of 2-and 3-monobromination products, as well as di-, tri- and tetrabromo derivatives. Use of NBS improves selectivity so that 75-100% yields of 2-bromination products can be obtained from 1-substituted pyrroles. With two equivalents, high yields of 2,5-dibromo products are obtained <8lJOC222i>. 2-Bromopyrrole can be obtained by bromination of pyrrole with 1,3-dibromo-5,5-dimethylhydantoin in the presence of a catalytic amount of AIBN at — 50°C and is isolated as the Boc derivative <9208(70)151 >. 

The aforementioned regioisomer formation is showcased by bromination of pyrroles. The C2(a)-bromination is prevalent for bromination of the liV-Boc protected pyrrole. ... 

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