Japp-Klingemann reaction
From Wikipedia, the free encyclopedia
The Japp-Klingemann reaction is a chemical reaction used to synthesize hydrazones from β-keto-acids (or β-keto-esters) and aryl diazonium salts.[1][2][3][4][5][6] The Reaction is named after the chemists Francis Robert Japp and Felix Klingemann.
The hydrazone products of the Japp-Klingemann reaction are most often used as intermediates in syntheses of more complex organic molecules. For example, a phenylhydrazone product can be heated in the presence of strong acid to produce an indole via the Fischer indole synthesis.[7][8]
[edit] Reaction mechanism
To illustrate the mechanism, the Japp-Klingemann ester variation will be considered. The first step is the deprotonation of the β-keto-ester. The nucleophilic addition of the enolate anion 2 to the diazonium salt produces the azo compound 3. Intermediate 3 has been isolated in rare cases. However, in most cases, the hydrolysis of intermediate 3 produces a tetrahedral intermediate 4, which quickly decomposes to release the carboxylic acid 6. After hydrogen exchange, the final hydrazone 7 is produced.
[edit] References
- ^ Francis Robert Japp, Felix Klingemann (1887). "Ueber Benzolazo- und Benzolhydrazofettsäuren". Berichte der deutschen chemischen Gesellschaft 20 (2): 2942–2944. doi:.
- ^ F. R. Japp, F. Klingemann (1887). "Zur Kenntniss der Benzolazo- und Benzolhydrazopropionsäuren (p 3284-3286)". Berichte der deutschen chemischen Gesellschaft 20 (2): 3284–3286. doi:.
- ^ F. R. Japp, F. Klingemann (1887). "Ueber sogenannte »gemischte Azoverbindungen". Berichte der deutschen chemischen Gesellschaft 20 (2): 3398–3401. doi:.
- ^ F. R. Japp, F. Klingemann (1888). "Ueber die Constitution einiger sogenannten gemischten Azoverbindungen". Liebigs Annalen der Chemie 247 (2): 190–225. doi:.
- ^ Phillips, R. R. Org. React. 1959, 10, 143.
- ^ Reynolds, G. A.; VanAllan, J. A. Org. Syn., Coll. Vol. 4, p.633 (1963); Vol. 32, p.84 (1952). (Article)
- ^ Bowman, R. E.; Goodburn, T. G.; Reynolds, A. A. (1972). "". J. Chem. Soc. Perkins Trans 1: 1121. doi:.
- ^ Meyer, M. D.; Kruse, L. I. (1984). "". J. Org. Chem. 49: 3195-3199. doi:.
