3- Methylindole-2-carbaldehyde

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). 

Indole and various 2-substituted indoles give the 3-formyl derivative in generally excellent yields under Vilsmeier-Haack conditions (79HC(25-3)357, B-70MI30609). 3-Methylindole gives the 2-carbaldehyde, but in rather poor yield (63JPS645). 

The oxidation of 2,3-dimethylindole with peroxodisulfate and peroxomonosulfate has been shown to yield 3-methylindole-2-carbaldehyde <88JCS(P2)1065>. Mechanistic studies have established that the reaction proceeds in three steps, namely electrophilic attack of the peroxide at C-3 to give an indolenine intermediate (194), peroxide attack on the enamine tautomer (195), and hydrolysis (Scheme 61) <93JOC7469>. 

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