2- Methylindoles, formation

The first proton to be removed from iV-methylpyrrole by w-butyllithium is from an a-position a second deprotonation occurs to give a mixture of 2,4- and 2,5-dilithiated derivatives. The formation of a 2,4-dilithio derivative is noteworthy since in the case of both furan and thiophene initial abstraction of a proton at C-2 is followed by proton abstraction from C-5 (77JCS(P1)887). iV-Methylindole, benzo[6]furan and benzo[6]thiophene are also deprotonated at C-2. Selenophene and benzo[6]selenophene and tellurophene and benzo[6]tellurophene similarly yield 2-lithio derivatives (77AHC(21)119). 

The possibility of activating the indole nucleus to nucleophilic substitution has been realized by formation of chromium tricarbonyl complexes. For example, the complex from TV-methylindole (215) undergoes nucleophilic substitution with 2-lithio-l,3-dithiane to give a product (216) which can be transformed into l-methylindole-7-carbaldehyde (217) (78CC1076). 

The oxidation of indole magnesium bromide and its 2- and 3-methyl derivatives at room temperature with p-nitroperbenzoic acid, in the absence of light and air, results in the formation of 3-bromoindole (370), 3-bromo-2-methylindole (371), and 2-bromo-3-methylindole (372), respectively. ... 

Mainly based on the failure of 2-methylindole to form a dimer, Schmitz-DuMont proposed structure (24) for indole dimer, the argument being that a methyl group in position 2 would effectively hinder the formation of a skeleton of type (24), whereas one in position 3 would not. ... 

Treatment of l-ethylideneamino-3-methylindole 95 with p-toluene sulfonic acid in boiling benzene gave l,2-dihydro[l,2,4]triazino[l,6-a]indole 96 (75CPB2891). The reaction was said to be due to an initial formation of a Diels-Alder-type adduct followed by the liberation of 3-methylindole. Compound % was oxidized either on exposure to air or by the action of chloranil to give 97 (Scheme 24). 

The coupling reaction of 3-methylindole (Scheme 12-21) is complex, as it involves an initial ipso-addition at the 3-position followed by rearrangement of the arylazo group to the 2-position (Jackson and Lynch, 1987 Jackson et al., 1987). However, under slightly different conditions Spande and Glenner (1973) isolated the unusual triazene 12.41. Based on the change in the UV spectrum of the reaction mixture with time, Sarma and Barooah (1977) proposed a mechanism involving initial formation... 

Thornton-Manning, J. Appleton, M. L. Gonzalez, F. J. Yost, G. S. Metabolism of 3-methylindole by vaccinia-expressed P450 enzymes correlation of 3-methyleneindolenine formation and protein binding. J. Pharmacol. Exp. Ther. 1996, 276, 21-29. 

Iminium-catalyzed nucleophilic addition of N-methylindole to 2-hexenal, followed by enamine-catalyzed formation of product Star polymer encapsulation... 

Condensation of 3-(lH-pyrrol-l-yl)propylamine 391 with acetylbenzoic acids and formyl benzoic acids such as 392 under Dean and Stark water-removal conditions results in the formation of the fused angular 5 6 5 system 393 in good yield (Equation 105) <2002TL2831>. In a similar manner, l-(3-aminoethyl)-3-methylindole reacts with 2-formyl-benzoic acid to give the cyclized product in 82% yield <2002TL2831>. 

The related reaction of 10 with ferrocenylmethylamine affords, in addition to the C3 adduct (as the minor product), a 2-ferrocenylethyl(dimethylamino)allenyli-dene complex as the major product, formed by migration of the resonance-stabilized [FcCH2] carbenium ion to the terminal carbon atom of the chain (Scheme 3.24) [46], The formation of pyrrolyl- and indolyl-substituted allenylidene complexes by reaction of complex 10 with various pyrroles and N-methylindole [47] has also been rationalized as involving initial attack of the electron-rich heterocyde on C3 of 10 followed by proton migration to the terminal =CH2 entity of the intermediate butenynyl-substituted a-complex (Scheme 3.25). 

It is interesting to point out, that the analogous reaction of 1,4-dichlorophthalazine and 1-methylindole (7.86.), when run under classical Friedel-Crafts conditions in the presence of A1C13 in dichloroethane, resulted in the selective formation of the 3-hetarylindole derivative in good yield.109... 

The red color of adrenochrome methyl ether (8) solutions is rapidly discharged on addition of alkali, with the formation of a dirty brown, essentially non-fluorescent, solution from which an unidentified dark grey amorphous product was obtained on acidification,110 possibly 5,6-dihydroxy-3-methoxy- -methylindole (35) and not 5,6-dihy-... 

The non-oxidative formation of melanin from adrenochrome in acid solution, reported by Harley-Mason,6 has recently been shown by Bu Lock to be controlled by a second-order reaction between adrenochrome and acid.107 It was suggested that the initial product (not isolated) was probably l-methylindole-5,6-quinone, which polymerized rapidly to melanin via dimers and oligomers.107 (The intermediate monomer quinone also gave a melanin-like copolymer with indole.107)... 

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