Home > 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 the triptan class are often synthesized by this method.1 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 SNAr attack of the phenyl ring. The resulting aniline/ imineAn imine is the functional group or compound containing the functional group of a carbon- nitrogen double bond. Reactions Synthesis (by nucleophilic addition) # ketone or aldehyde + ammonia or primary amine ↔ tetrahedral carbonyl addition compound # forms a cyclic aminoacetal (or aminal) under acid catalysisEnthalpy profile for catalysed and uncatalysed reactions. A is the activation energy for an uncatalysed reaction, A is the reduced activation energy for the same reaction when catalysed. I represents the point at which a chemical intermediate has been for that splits off NH3Ammonia is a chemical compound with the formula. The molecule is not flat, but has the shape of a flattened tetrahedron known as a trigonal pyramid''. In solution it forms the positively charged ammonium ion , which has the shape of a regular tetrahedron., resulting in the energetically favorable aromatic indole system.
The reaction is catalyzed by dilute acids like sulfuric acidProperties General Name Sulfuric acid Chemical formula H SO Appearance Colorless liquid Physical Formula weight 98. 1 amu Melting point 283 K (10 °C) Boiling point 610 K (337 °C) Density 1. 8 ×103 kg/ m3 Solubility miscible Thermochemistry ΔH0 -814, hydrochloric acidProperties General Name Hydrogen chloride Chemical formula H Cl Appearance Colourless liquid Physical Formula weight 36. 5 amu Melting point 203. 15 K (-70 °C) Boiling point 382 K (109 °C) Density 1. 2 ×103 kg/ m3 (liquid) Solubility 70 g in 100g water Th, phosphoric acidPhosphoric(V) acid is a weak mineral acid with the chemical formula HPO. Fertilizer use It is used as a component in fertilizer. Large supplies of phosphorus are found in Guano, the defecations of bats or birds. Some pacific islands are so largely compose, or polyphosphoric acid .
2 See also
- Japp-Klingemann indole synthesis
- Abramovitch-Shapiro tryptamine synthesis
- Indole
