Indole, 1,2-dimethyl-, bromination

Related reactions have been observed in the indole series. Bromination of 1-acetyl-2,3-dimethyl-indole in methanol first generates the adduct (33) which is dehydrohalogenated to (34) by tri-ethylamine. Exposure to HBr then generates (35) (Scheme 105) <82CJC1233, 85TL5253>. 

When 1-methyl-, 1,2- and 1,3-dimethyl-indoles were oxidized on a platinum electrode in methanolic ammonium bromide solution, in addition to the oxidation products, products of nuclear bromination at the 3-and 5-positions were observed. 1,2- Dimethylindole (20) gave 3-bromo-1,2-dimethylindole (81CCC3278) [bromine in chloroform gave the same product (85CHE786)]. In acidic conditions the amidinium cation formed from 20 was brominated in the 5-position (Scheme 14). Acylated 2-aminoindoles reacted similarly in neutral media to give 3-bromo derivatives and when protonated to give 5-bromo products. Bromine in chloroform transformed l-methyl-2-dimethylaminoindole (21) into the 3-bromo derivative (85CHE782) (Scheme 15). 

The use of mixtures of trimethylbromosilane and dimethyl sulfoxide to brominate indoles is more successful than analogous chlorinations since the bromine atom increases the rate of transformation of Me2S+OSiMe3 to Me2S+Br and shows a stronger electrophilic character than the chloro intermediate. Sulfonium products do not form in such reactions [89JCR(S)182],... 

Non-brominated indoles also underwent the 2-tert-prenyl migration induced by NBS and methylation of the side chain nitrogen was not necessary. N, Ni,-Dimethyl-2-tert-prenyltryptamine (238) afforded the AAi -dimethylamidinium salt 239, which precipitated from EtOAc (63% yield. Scheme 46). When the side chain was monoformylated, no cyclisation was observed. In the case of AbWb-dimethyl-2-Icrt-prenyltryptamine (240), oxidation with NBS was carried out in acetone for solubility reasons affording 3-bromoindole 242 (21%) via bromoin-dolenine 241, which was observed on NMR control. Loss of the side chain of the 3-bromoindolenine on alkaline work-up can be explained by nucleophilic attack of hydroxide at the imine (3-position. 

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