Fischer indole synthesis

The Fischer indole synthesis is a chemical synthesis of the aromatic heterocycle indole from a (substituted) phenylhydrazine and an aldehyde or ketone under acidic conditions. The synthesis was discovered in 1883 by Hermann Emil Fischer. Today antimigraine drugs of the triptan class are often synthesized by this method.

Reaction Mechanism

On reaction of a (substituted) phenylhydrazine with an aldehyde or ketone a phenylhydrazone forms and isomerizes into the respective enamine (or 'ene-hydrazine'). After protonation a cyclic rearrangement occurs, involving a nucleophilic aromatic S_NAr attack of the phenyl ring. The resulting aniline/imine forms a cyclic aminoacetal (or aminal) under acid catalysis that splits off NH₃, resulting in the energetically favorable aromatic indole system.

The reaction is catalyzed by dilute acids like sulfuric acid, hydrochloric acid, phosphoric acid, or polyphosphoric acid .

See also

• Japp-Klingemann indole synthesis
• Abramovitch-Shapiro tryptamine synthesis
• Indole