Indole synthesis Bischler-Mohlau

3-Arylindoles from the cyclization of co-arylamino-ketones and anilines. 

Sundberg, R. J. The Chemistry of Indoles Academic Press New York, 1970, p 164. (Book). 

The Chemistry of Heterocyclic Compounds, Indoles (Part 1), Houlihan, W. J., ed. Wiley Sons New York, 1972. (Review). 

The Bischler-MOhlau indole synthesis, also known as the Bischler indole synthesis, refers to the synthesis of 2-aiylindoles from the cyclization of a-aiylamino-ketones and excess anilines. 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 26, Springer International Publishing Switzerland 2014 

Example 5, Microwave-assisted, solvent-free Bischler indole synthesis 

Mohlau, R. Ber. 1881, 14, 171-175. Mohlau, a German chemist, worked extensively 

Bischler, A. Fireman, P. Ber. 1893, 26,1346-1349. Augustus Bischler (1865-1957) was bom in Southern Russia. He studied in Zurich with Arthur Hantzsch. He discovered the Bischler-Napieralski reaction while studying alkaloids at Basel Chemical Works, Switzerland with his coworker, B. Napieralski. 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 22, Springer-Verlag Berlin Heidelberg 2009 

Example 4, Mierowave-assisted, solvent-free Bisehler indole synthesis  

Heating excess of aniline with 2-bromo-l-phenyl-ethanone to afford 2-arylindoles. 

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BERNTHSEN Acndine synthesis 32 BIGINELLI Pynmidone synthesis 33 BIRCH - HUCKEL - BENKESER Reduction 34 BISCHLER Benzomarine synthesis 35 BISCHLER - MOHLAU Indole synthesis 35 BISCHLER - NAPIERALSKI Isoquinoline synthesis 36... 

BISCHLER - MOHLAU Indole synthesis Indole synthesis from a aminoacetophenones... 

Bischler-Mohlau indole synthesis. Formation of 2-substituted indoles by heating o-halogeno-... 

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. ... 

A Bischler-Mohlau indole synthesis was also pivotal in constructing the indole ring of bazedoxifene acetate (Viviant), Wyeth s novel and highly selective indole estrogen. It is a selective estrogen receptor modulator (SERM) for the treatment of and prevention of osteoporosis. It was found... 

Instead of using a-haloketones, an unsymmetrical benzoin can be utilized as starting material for the Bischler-Mohlau indole synthesis. RWJ 68354, a potent inhibitor of the p38 MAP kinase, was prepared via a variation of the Bischler-Mohlau indole synthesis under mild conditions with 55% isolated yield only 2-3% regioisomer could be isolated from the mother liquor. ... 

Like the venerable Fischer, Madelung, and Nenitzescu indole syntheses, the Bischler indolization has stood the test of time and continnes to find utihty in indole synthesis. This method, which is also known as the Bischler-Mohlau indole synthesis, was discovered by both of these German chemists within the span of a decade [1 ]. Other early pioneers... 

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... 

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