Fischer indole synthesis
| Fischer indole synthesis | |
|---|---|
| Named after | Hermann Emil Fischer
|
| Reaction type | Ring forming reaction |
| Identifiers | |
| Organic Chemistry Portal | fischer-indole-synthesis |
| RSC ontology ID | RXNO:0000064 |
The Fischer indole synthesis is a
aromatic heterocycle indole from a (substituted) phenylhydrazine and an aldehyde or ketone under acidic conditions.[1][2] The reaction was discovered in 1883 by Emil Fischer. Today antimigraine drugs of the triptan
class are often synthesized by this method.
This reaction can be catalyzed by
.Several reviews have been published.[3][4][5]
Reaction mechanism
The reaction of a (substituted) phenyl
catalysis eliminates NH3
, resulting in the energetically favorable aromatic indole.
Isotopic labelling studies show that the aryl nitrogen (N1) of the starting phenylhydrazine is incorporated into the resulting indole.[6][7]
Buchwald modification
Via a palladium-catalyzed reaction, the Fischer indole synthesis can be effected by cross-coupling aryl bromides and hydrazones.[8] This result supports the previously proposed intermediacy as hydrazone intermediates in the classical Fischer indole synthesis. These N-arylhydrazones undergo exchange with other ketones, expanding the scope of this method.
Application
- Indometacin preparation.
- Triptan synthesis
- suberone→ 2,3-Cycloheptenoindole).
See also
- Bartoli indole synthesis
- Japp–Klingemann indole synthesis
- Leimgruber–Batcho indole synthesis
- Larock indole synthesis
Related reactions
References
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