Reactions of Indole

Reactions of Indole include electrophilic substitution, oxidation, reduction, and cyclization pathways vital in drug synthesis.

Reactions of Indole

1. Electrophilic Substitution (EAS)

   • Very reactive at C-3 (due to resonance stabilization of carbocation intermediate).
   • Secondarily reactive at C-2.
   • Examples:
     • Nitration: dilute HNO₃ → 3-nitroindole
     • Halogenation: Br₂ → 3-bromoindole
     • Friedel–Crafts acylation: at C-3
     • Vilsmeier–Haack Reaction: POCl₃/DMF → 3-formylindole

2. N-Substitution

   • Indole nitrogen can be acylated, alkylated to form:
   • N-methylindole
   • N-benzylindole
   • These modulate reactivity and are important in drug design.

3. Oxidation

   • Indoles can oxidize at C-2 or C-3:
     • KMnO₄ → isatin (important building block)
     • Oxygen + light → peroxides (decomposition)

4. Reduction

   • Mild hydrogenation → indoline (saturated pyrrole ring)
   • Stronger → octahydroindole

5. Nucleophilic Attack

   • Indole is less reactive to NAS but can undergo attack at electrophilic centers when substituted.

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