Hemetsberger indole synthesis explained
The Hemetsberger indole synthesis (also called the Hemetsberger–Knittel synthesis) is a chemical reaction that thermally decomposes a 3-aryl-2-azido-propenoic ester into an indole-2-carboxylic ester.[1] [2]
Yields are typically above 70%. However, this is not a popular reaction, due to the lack of stability and difficulty in synthesizing the starting material.
Reaction mechanism
The mechanism is unknown. However, azirine[3] intermediates have been isolated. The mechanism is postulated to proceed via a nitrene intermediate.[4]
Notes and References
- Hemetsberger, H. . Knittel, D. . Monatshefte für Chemie. 1972. 103. 194–204. 10.1007/BF00912944. Synthese und Thermolyse von α-Azidoacrylestern. 91741917 .
- Gribble, G. W.. Recent developments in indole ring synthesis-methodology and applications . . 2000. 1045–1075. 10.1039/a909834h. 7.
- Gilchrist, T. L. . Activated 2H-Azirines as Dienophiles and Electrophiles . . 2001 . 34 . 2 . 51 . dead . https://web.archive.org/web/20130515054311/http://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Aldrich/Acta/al_acta34_2.pdf . 15 May 2013 . dmy-all.
- Knittel, D. . Synthesis. 1985. 186–188. 10.1055/s-1985-31149. Verbesserte Synthese von α-Azidozimtsäure-estern und 2H-Azirinen. 1985. 2.