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Bischler–Möhlau indole synthesis

Lianyungang Klinechem Co.,Ltd | Updated: Nov 30, 2018

The Bischler–Möhlau 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 Richard Möhlau [1][2][3][4][5]

The Bischler-Möhlau indole synthesis

In spite of 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.[6][7][8]

Reaction mechanism[8]

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.

The mechanism of the Bischler-Möhlau indole synthesis

See also

  • Fischer indole synthesis

  • Bischler–Napieralski reaction

References

  1. ^ Bischler, Aug. (1892). "Ueber die Entstehung einiger substituirter Indole". Berichte der deutschen chemischen Gesellschaft25 (2): 2860–2879. doi:10.1002/cber.189202502123. ISSN 0365-9496.

  2. ^ Bischler, Aug.; Fireman, P. (1893). "Zur Kenntniss einiger α-β- Diphenylindole". Berichte der deutschen chemischen Gesellschaft26 (2): 1336–1349. doi:10.1002/cber.18930260232. ISSN 0365-9496.

  3. ^ Möhlau, R. (1881). "Ueber die Einwirkung primärer aromatischer Aminbasen auf Acetophenonbromid". Chemische Berichte14: 171. doi:10.1002/cber.18810140146.

  4. ^ Möhlau, R. (1882). "Ueber Diphenyldiisoindol". Chemische Berichte15 (2): 2480. doi:10.1002/cber.188201502204.

  5. ^ Fischer, Emil Hermann; Schmitt, T. (1888). "Ueber Pr-2-Phenylindol". Chemische Berichte21: 1071. doi:10.1002/cber.188802101200.

  6. ^ Pchalek, K.; Jones, A. W.; Wekking, M. M. T.; Black, D. S. C. (2005). "Synthesis of activated 3-substituted indoles: An optimised one-pot procedure". Tetrahedron61: 77. doi:10.1016/j.tet.2004.10.060.

  7. ^ Sridharan, V.; Perumal, S.; Avendaño, C.; Menéndez, J. C. (2006). "Microwave-Assisted, Solvent-Free Bischler Indole Synthesis". Synlett: 91. doi:10.1055/s-2005-922760.

  8. Jump up to:a b Vara, Yosu; Aldaba, Eneko; Arrieta, Ana; Pizarro, José L.; Arriortua, María I.; Cossío, Fernando P. (2008). "Regiochemistry of the microwave-assisted reaction between aromatic amines and α-bromoketones to yield substituted 1H-indoles". Organic & Biomolecular Chemistry6 (10): 1763. doi:10.1039/B719641E.

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