:Reissert indole synthesis
{{Reactionbox
| Name = Reissert indole synthesis
| Type = Ring forming reaction
| NamedAfter = Arnold Reissert
}}
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.{{cite journal|author=Reissert, A. |doi=10.1002/cber.189703001200|title=Einwirkung von Oxalester und Natriumäthylat auf Nitrotoluole. Synthese nitrirter Phenylbrenztraubensäuren|year=1897|journal=Berichte der deutschen chemischen Gesellschaft |volume=30|pages=1030–1053|url=https://zenodo.org/record/1425858}}Noland, W. E.; Baude, F. J. Organic Syntheses, Coll. Vol. 5, p. 567 (1973); Vol. 43, p. 40 (1963). ([http://www.orgsyn.org/orgsyn/prep.asp?prep=cv5p0567 Article])
File:Reissert Indole Synthesis.png
Potassium ethoxide has been shown to give better results than sodium ethoxide.{{cite journal|author1=Johnson, J. R.|author2=Hasbrouck, R. B.|author3=Dutcher, J. D.|author4=Bruce, W. F.|name-list-style=amp |journal=J. Am. Chem. Soc. |year=1945|volume=67|pages=423|doi=10.1021/ja01219a023|title=Gliotoxin. V. The Structure of Certain Indole Derivatives Related to Gliotoxin1,2|issue=3}}
Reaction mechanism
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
=Butin modification=
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.{{cite journal |last1=Butin |first1=Alexander |last2=Stroganova |first2=Tatyana |last3=Lodina |first3=Irina |last4=Krapivin |first4=Gennady |date=2001 |title=Furan ring opening—indole ring closure: a new modification of the Reissert reaction for indole synthesis |journal=Tetrahedron Letters |volume=42 |issue=10 |pages=2031–3 |doi=10.1016/S0040-4039(01)00066-1}}
