Anilines Bischler-Mohlau indole synthesis

The Bischler-Mohlau indole synthesis, also known as the Bischler indole synthesis, is the formation of a 2-arylindole from an a-bromoacetophenone and excess aniline.Although not widely used in making indoles, one of the syntheses of fluvastatin sodium (Lescol) took advantage of the Bischler-Mohlau indole synthesis to assemble its indole core. As shown below, reaction of a-chloroketone with A-/-Pr-aniline at elevated temperature generated the tertiary amine. The resulting A-/-Pr-aniline underwent a ZnCb-mediated Bischler-Mohlau indole synthesis also at an elevated temperature to afford the indole core structure of fluvastatin. ... 

The Bischler-Mohlau indole synthesis, also known as the Bischler indole synthesis, refers to the synthesis of 3-arylindoles from the cyclization of ca-arylamino-ketones and excess anilines. 

The Bischler-Mohlau indole synthesis is a classical chemical reaction that forms substituted indoles. The reaction involves heating excess anilines 1 with a-haloketones 2 (or a-haloacetals), followed by acid-catalyzed (aniline HX salt, X = Br or Cl, and Lewis acid) cyclization of the resulting intermediate 2-arylaminoketone. 

The Bischler-Mohlau indole synthesis was applied in the synthesis of fluvastatin sodium (Lescol) to assemble its indole core. As shown below, reaction of a-chloroketone with iV-/-Pr-aniline at elevated temperature generated a tertiary amine. The resulting A-/-Pr-aniline tertiary amine... 

A Bischler-Mohlau indole synthesis was also used in constructing the indole ring of bazedoxifene acetate (Viviant), a novel and highly selective indole estrogen. It is a selective estrogen receptor modulator (SERM) for the treatment of and prevention of osteoporosis. Condensation between a-bromopropiophenone and 4-(benzyloxy)-aniline hydrochloride generated the 3-methyl indole core. ... 

In 1881, Mohlau first disclosed this reaction, which was followed by further study carried out by Bischler in 1892-1893. Typically, this indole synthesis of heating excess anilines with a-haloketones is referred to as the Bischler reaction, however naming the transformation the Bischler-Mdhlau indole synthesis is more appropriate. Despite its long history, this classical reaction... 

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