Reactions of Indoles with Electrophiles

Nitration of Indole

• Nitration of indole with benzoyl nitrate in acetonitrile or with ethyl nitrate in the presence of sodium ethoxide at low temperature yields 3-nitroindole.
• Reaction conditions affect the products of nitration of indoles with different nitrating agents.

Nitrosation of Indole

• Nitrosation of 2-methylindole with sodium nitrite in the presence of acetic acid occurs at position-3, forming 3-oximino-2-methylindole (or 3-nitroso-2-methylindole).
• Nitrosation of 3-methylindole yields N-nitroso-3-methylindole.

Halogenation of Indole

Chlorination

• Chlorination of indole with sulfuryl chloride produces 3-chloroindole.
• Excess sulfuryl chloride leads to the formation of 2,3-dichloroindole via 3,3-dichloro-3H-indole.

Bromination

• Bromination of indole occurs at position-3, forming 3-bromoindole.
• If position-3 is already substituted, bromination takes place at position-2.

Sulfonation of Indole

• Indole is sulfonated with pyridine-sulfur trioxide complex, yielding indole-3-sulfonic acid.
• If position-3 is already occupied, sulfonation occurs at position-2 via an initial reversible sulfonation at position-3.

Vilsmeier-Haack Formylation

• Indole undergoes Vilsmeier-Haack formylation with N,N-dimethylformamide (DMF) in the presence of phosphorus oxychloride, forming 3-formylindole.

This quiz covers the reactions of indoles with electrophiles, specifically nitration and nitrosation reactions, including the effects of different reaction conditions and agents.