Japp-Klingemann reaction

The Japp-Klingemann reaction is a chemical reaction used to synthesize hydrazones from β-keto-acids (or β-keto-esters) and aryl diazonium salts. [cite journal
title = Ueber Benzolazo- und Benzolhydrazofettsäuren
author = Francis Robert Japp, Felix Klingemann
journal = Berichte der deutschen chemischen Gesellschaft
volume = 20
issue = 2
pages = 2942–2944
year = 1887
url =
doi = 10.1002/cber.188702002165 ] [cite journal
title = Zur Kenntniss der Benzolazo- und Benzolhydrazopropionsäuren (p 3284-3286)
author = F. R. Japp, F. Klingemann
journal = Berichte der deutschen chemischen Gesellschaft
volume = 20
issue = 2
pages = 3284–3286
year = 1887
url =
doi = 10.1002/cber.188702002234 ] [cite journal
title = Ueber sogenannte »gemischte Azoverbindungen
author = F. R. Japp, F. Klingemann
journal = Berichte der deutschen chemischen Gesellschaft
volume = 20
issue = 2
pages = 3398–3401
year = 1887
url =
doi = 10.1002/cber.188702002268 ] [cite journal
title = Ueber die Constitution einiger sogenannten gemischten Azoverbindungen
author = F. R. Japp, F. Klingemann
journal = Liebigs Annalen der Chemie
volume = 247
issue = 2
pages = 190–225
year = 1888
url =
doi = 10.1002/jlac.18882470208 ] [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). ( [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv4p0633 Article] )] 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. [cite journal
title = 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)
author = Bowman, R. E.; Goodburn, T. G.; Reynolds, A. A.
journal = J. Chem. Soc. Perkins Trans 1
volume =
issue =
pages = 1121
year = 1972
url =
doi = 10.1039/P19720001121 ] [cite journal
title =
author = Meyer, M. D.; Kruse, L. I.
journal = J. Org. Chem.
volume = 49
issue =
pages = 3195–3199
year = 1984
url =
doi = 10.1021/jo00191a028 ]

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.

References