Nitration and Nitrosation of Indoles

Nitration

• Nitration of indoles with different nitrating agents depends on reaction conditions due to acid sensitivity of indole nucleus.
• 3-Nitroindole is produced when indole is nitrated with benzoyl nitrate in acetonitrile or with ethyl nitrate in the presence of sodium ethoxide at low temperature.

Nitrosation

• 2-Methylindole is nitrosated with sodium nitrite in the presence of acetic acid, forming 3-oximino-2-methylindole (a form of 3-nitroso-2-methylindole).
• 3-Methylindole is nitrosated to form N-nitroso-3-methylindole.

Halogenation

• Chlorination of indole with sulfuryl chloride produces 3-chloroindole.
• Excess sulfuryl chloride reacts with 3-chloroindole to form 2,3-dichloroindole via 3,3-dichloro-3H-indole.
• Bromination of indole occurs at the position-3, forming 3-bromoindole.
• If position-3 is already substituted, bromination takes place at the position-2.

Sulfonation

• Indole is sulfonated with pyridine-sulfur trioxide complex to form indole-3-sulfonic acid.
• If position-3 is already occupied, sulfonation occurs at the position-2 via 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.