The Gassman indole synthesis is a series of chemical reactions used to synthesize substituted indoles by addition of an aniline and a ketone bearing a thioether substituent.
The Gassman indole synthesis
This is a one-pot chemical reaction, and none of the intermediates are isolated. R1 can be hydrogen or alkyl, while R2 works best with aryl, but can also be alkyl. Electron-rich anilines, such as 4-methoxyaniline, tend to fail in this reaction.
The 3-position thiomethyl group is often removed using Raney nickel to give the 3-H-indole.
Reaction mechanismedit
The reaction mechanism of the Gassman indole synthesis
The reaction mechanism of the Gassman indole synthesis is divided among three steps.
The second step is the addition of the keto-thioether to give the sulfoniumion3, and is typically done at low temperatures (−78 °C).
The third and final step is the addition of a base, which in this case is triethylamine. Upon warming to room temperature, the base will deprotonate the sulfonium ion creating the sulfonium ylide4, which quickly undergoes a [2,3]-sigmatropic rearrangement to give the ketone 5. The ketone 5 will undergo a facile condensation to give the desired 3-thiomethylindole 6.
Referencesedit
Gassman, P. G.; Gruetzmacher, G.; van Bergen, T. J. (1973). "Use of halogen-sulfide complexes in the synthesis of indoles, oxindoles, and alkylated aromatic amines". J. Am. Chem. Soc.95 (19): 6508. doi:10.1021/ja00800a088.
Gassman, P. G.; van Bergen, T. J.; Gilbert, D. P.; Cue, B. W. Jr. (1974). "General method for the synthesis of indoles". J. Am. Chem. Soc. 96 (17): 5495. doi:10.1021/ja00824a028.
Gassman, P. G.; van Bergen, T. J. (1974). "Oxindoles. New, general method of synthesis". J. Am. Chem. Soc. 96 (17): 5508. doi:10.1021/ja00824a029.
Gassman, P. G.; Gruetzmacher, G.; van Bergen, T. J. (1974). "Generation of azasulfonium salts from halogen-sulfide complexes and anilines. Synthesis of indoles, oxindoles, and alkylated aromatic amines bearing cation stabilizing substituents". J. Am. Chem. Soc. 96 (17): 5512. doi:10.1021/ja00824a030.
gassman, indole, synthesis, series, chemical, reactions, used, synthesize, substituted, indoles, addition, aniline, ketone, bearing, thioether, substituent, this, chemical, reaction, none, intermediates, isolated, hydrogen, alkyl, while, works, best, with, ary. The Gassman indole synthesis is a series of chemical reactions used to synthesize substituted indoles by addition of an aniline and a ketone bearing a thioether substituent The Gassman indole synthesis This is a one pot chemical reaction and none of the intermediates are isolated R1 can be hydrogen or alkyl while R2 works best with aryl but can also be alkyl Electron rich anilines such as 4 methoxyaniline tend to fail in this reaction The 3 position thiomethyl group is often removed using Raney nickel to give the 3 H indole Reaction mechanism edit nbsp The reaction mechanism of the Gassman indole synthesis The reaction mechanism of the Gassman indole synthesis is divided among three steps The first step is the oxidation of the aniline 1 using tert butyl hypochlorite tBuOCl to give the chloramine 2 The second step is the addition of the keto thioether to give the sulfonium ion 3 and is typically done at low temperatures 78 C The third and final step is the addition of a base which in this case is triethylamine Upon warming to room temperature the base will deprotonate the sulfonium ion creating the sulfonium ylide 4 which quickly undergoes a 2 3 sigmatropic rearrangement to give the ketone 5 The ketone 5 will undergo a facile condensation to give the desired 3 thiomethylindole 6 References editGassman P G Gruetzmacher G van Bergen T J 1973 Use of halogen sulfide complexes in the synthesis of indoles oxindoles and alkylated aromatic amines J Am Chem Soc 95 19 6508 doi 10 1021 ja00800a088 Gassman P G van Bergen T J Gilbert D P Cue B W Jr 1974 General method for the synthesis of indoles J Am Chem Soc 96 17 5495 doi 10 1021 ja00824a028 Gassman P G van Bergen T J 1974 Oxindoles New general method of synthesis J Am Chem Soc 96 17 5508 doi 10 1021 ja00824a029 Gassman P G Gruetzmacher G van Bergen T J 1974 Generation of azasulfonium salts from halogen sulfide complexes and anilines Synthesis of indoles oxindoles and alkylated aromatic amines bearing cation stabilizing substituents J Am Chem Soc 96 17 5512 doi 10 1021 ja00824a030 Organic Syntheses Coll Vol 6 p 601 Vol 56 p 72 Article Retrieved from https en wikipedia org w index php title Gassman indole synthesis amp oldid 1215902342, wikipedia, wiki, book, books, library,
