Japp–Klingemann reaction
Japp–Klingemann reaction | |
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Named after | Francis Robert Japp Felix Klingemann |
Reaction type | Coupling reaction |
Identifiers | |
RSC ontology ID | RXNO:0000158 |
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 .
![The Japp-Klingemann reaction](http://upload.wikimedia.org/wikipedia/commons/thumb/4/49/Japp-Klingemann_Reaction_Scheme.png/500px-Japp-Klingemann_Reaction_Scheme.png)
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]
![The Japp-Klingemann reaction used to synthesize indoles](http://upload.wikimedia.org/wikipedia/commons/thumb/7/77/Japp-Klingemann_Fischer_Indole_Combination.png/550px-Japp-Klingemann_Fischer_Indole_Combination.png)
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.
![The Japp-Klingemann reaction mechanism](http://upload.wikimedia.org/wikipedia/commons/thumb/1/12/Japp-Klingemann_Ester_Mechanism.png/1440px-Japp-Klingemann_Ester_Mechanism.png)
References[]
- ^ Francis Robert Japp, (1887). "Ueber Benzolazo- und Benzolhydrazofettsäuren". Berichte der deutschen chemischen Gesellschaft. 20 (2): 2942–2944. doi:10.1002/cber.188702002165.
- ^ 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:10.1002/cber.188702002234.
- ^ F. R. Japp; F. Klingemann (1887). "Ueber sogenannte »gemischte Azoverbindungen". Berichte der deutschen chemischen Gesellschaft. 20 (2): 3398–3401. doi:10.1002/cber.188702002268.
- ^ F. R. Japp; F. Klingemann (1888). "Ueber die Constitution einiger sogenannten gemischten Azoverbindungen". Liebigs Annalen der Chemie. 247 (2): 190–225. doi:10.1002/jlac.18882470208.
- ^ Phillips, R. R. Org. React. 1959, 10, 143.
- ^ Reynolds, G. A.; VanAllan, J. A. Org. Synth., Coll. Vol. 4, p.633 (1963); Vol. 32, p.84 (1952)(Article Archived 2012-07-16 at the Wayback Machine)
- ^ Bowman, R. E.; Goodburn, T. G.; Reynolds, A. A. (1972). "1,3,4,5-Tetrahydrobenz[cd]indoles and related compounds. Part I. A new synthesis of 3,4-dihydrobenz[cd]indol-5(1H)-one (Uhle's ketone)". J. Chem. Soc. Perkin Trans. 1: 1121. doi:10.1039/P19720001121.
- ^ Meyer, M. D.; Kruse, L. I. (1984). "Ergoline synthons: Synthesis of 3,4-dihydro-6-methoxybenz[cd]indol-5(1H)-one (6-methoxy-Uhle's ketone) and 3,4-dihydrobenz[cd]indol-5(1H)-one (Uhle's ketone) via a novel decarboxylation of indole-2-carboxylates". J. Org. Chem. 49 (17): 3195–3199. doi:10.1021/jo00191a028.
- Coupling reactions
- Substitution reactions
- Name reactions