Synthesis of Indole

Synthesis of Indole covers Fischer indole, Madelung, Bartoli, and Nenitzescu methods with key steps for medicinal chemistry.

1. Fischer (Most common method)

   • Reactants: Phenylhydrazine + Aldehyde or Ketone
   • Conditions: Acidic, heat
   • Example:
     • Phenylhydrazine  +  Acetone  →  Indole (after cyclization and rearrangement)
   • 
   • Mechanism:
     • Hydrazone formation
     • [3,3]-Sigmatropic rearrangement (Fischer)
     • Cyclization and aromatization

2. Bischler–Möhlau Indole Synthesis

   • Reactants: Aniline + α-haloketone
   • Conditions: Heat
   • Reaction:
     • • Aniline  +  α-haloketone  →  Indole derivative
     • Used for substituted indoles

3. Madelung Synthesis

   • Reactants: o-Toluidine + Acid chloride (intramolecular cyclization)
   • Reagents: Base (e.g., NaOMe), high temperature

4. Leimgruber–Batcho Synthesis

   • Used in pharmaceutical industry for high-yield synthesis of substituted indoles
   • 

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