Reissert indole synthesis

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]

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

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

Reaction mechanism

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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

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Butin modification

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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]

 

See also

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References

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  1. ^ Reissert, A. (1897). "Einwirkung von Oxalester und Natriumäthylat auf Nitrotoluole. Synthese nitrirter Phenylbrenztraubensäuren". Berichte der deutschen chemischen Gesellschaft. 30: 1030–1053. 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.