4.6- Dibromo-2-methylindole

Pyridinium bromide perbromide efficiently brominates pyrroles already substituted by electron-withdrawing substituents and also gives a high yield of 3-bromoindole in its reaction with indole. In conjunction with sulfuryl chloride, it has been used in the synthesis of 3-bromo-2-chloro-, 2-bromo-3-chloro- and 2,3-dibromo-indole (81SC253). 3-Methylindole reacts with A-bromosuccinimide in acetic acid to give the 2-bromo derivative which reacts further with an excess of A-bromosuccinimide to yield 2,6-dibromo-3-methylindole (B-70MI30500, 72HC(25-2)127) whilst in aqueous or alcoholic media, 3-bromo-3-methylox-indole is produced (cf. Scheme 15). All of these reactions proceed via the 3-bromo-3A-indolium cation, but the course of the reaction depends not only upon the orientation or... 

Wang and coworkers have explored and extended the utility of halogenations of indoles by Cu(II)Cl2 and Cu(II)Br2 [50]. The best results were obtained in dichloro-methane or acetonitrile in the presence of NaOH and silica gel. Similar conditions were successfully applied to C-ring substituted 1-methylindoles. When the reaction mixture included water and fefra-butylammonium bromide, the 2,3-dibromo products were formed. 1,3-Dimethylindole gave a good yield of the 2-bromo product under the latter conditions. 1-Unsubstituted indoles often present problems, but by using NaOH/sihca and CuCU, 2-chlorination of 3-methylindole was achieved in 86% yield. 

Bromoindole can be prepared by indirect bromination through A-(lithiocar-boxy)-2-lithioindole [51]. Subsequent 3-bromination followed by A-methylation gives 2,3-dibromo-l-methylindole in 92% yield. C-Ring bromination can then be carried out with one or two equivalents of bromine, giving the 2,3,6-tribromo and 2,3,5,6-tetrabromo derivatives [52]. 

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