Reissert indole synthesis

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Reissert indole synthesis
Named after Arnold Reissert
Reaction type Ring forming reaction

The Reissert indole synthesis is a series of chemical reactions designed to synthesize indole or substituted-indoles (4 and 5) from ortho-nitrotoluene 1 and diethyl oxalate 2.[1][2]

The Reissert indole synthesis

Potassium ethoxide has been shown to give better results than sodium ethoxide.[3]

Reaction mechanism[edit]

The first step of the synthesis is the condensation of o-nitrotoluene 1 with a diethyl oxalate 2 to give ethyl o-nitrophenylpyruvate 3. The reductive cyclization of 3 with zinc in acetic acid gives indole-2-carboxylic acid 4. If desired, 4 can be decarboxylated with heat to give indole 5.

Variations[edit]

Butin modification[edit]

In an intramolecular version of the Reissert reaction, a furan ring-opening provides the carbonyl necessary for cyclization to form an indole. A ketone side chain is present in the final product, allowing further modifications.[4]

Butin modification to Reissert indole synthesis.png

See also[edit]

References[edit]

  1. ^ Reissert, A. (1897). "Einwirkung von Oxalester und Natriumäthylat auf Nitrotoluole. Synthese nitrirter Phenylbrenztraubensäuren". Berichte der deutschen chemischen Gesellschaft. 30: 1030. doi:10.1002/cber.189703001200. 
  2. ^ Noland, W. E.; Baude, F. J. Organic Syntheses, Coll. Vol. 5, p. 567 (1973); Vol. 43, p. 40 (1963). (Article)
  3. ^ Johnson, J. R.; Hasbrouck, R. B.; Dutcher, J. D. & Bruce, W. F. (1945). "Gliotoxin. V. The Structure of Certain Indole Derivatives Related to Gliotoxin1,2". J. Am. Chem. Soc. 67 (3): 423. doi:10.1021/ja01219a023. 
  4. ^ Butin, Alexander; Stroganova, Tatyana; Lodina, Irina; Krapivin, Gennady (2001). "Furan ring opening—indole ring closure: a new modification of the Reissert reaction for indole synthesis". Tetrahedron Letters. 42 (10): 2031–3. doi:10.1016/S0040-4039(01)00066-1. Retrieved June 19, 2018.