The Bischler–Möhlau indole synthesis, also often referred to as the Bischler indole synthesis, is a chemical reaction that forms a 2-aryl-indole from an α-bromo-acetophenone and excess aniline; it is named after August Bischler and
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center|500px|The Bischler-Möhlau indole synthesis
Despite its long history, this classical reaction had received relatively little attention in comparison with other methods for indole synthesis, owing to the reactions harsh conditions, poor yields and unpredictable regioselectivity. Recently, milder methods have been developed, including the use of lithium bromide as a catalyst and an improved procedure involving the use of microwave irradiation.
History
What is now known as the Bischler-Möhlau indole synthesis was discovered and formulated through the separate, but complimentary, findings of German Scientist Richard Möhlau in 1882 and Russia-born German chemist August Bischler (with partner H. Brion) in 1892. These two researchers did not collaborate with each other, but instead independently developed very similar procedures starting from an aromatic ketone structure with an excess of some aniline and ultimately producing a product. Modified Indole Synthesis
- Japp and Murray Modified Indole Synthesis
Reaction mechanism
The first two step involve the reaction of the α-bromo-acetophenone with molecules of aniline to form intermediate 4. The charged aniline forms a decent enough leaving group for an electrophilic cyclization to form intermediate 5, which quickly aromatizes and tautomerizes to give the desired indole 7.