Japp–Klingemann reaction

{{Reactionbox

| Name = Japp–Klingemann reaction

| Type = Coupling reaction

| NamedAfter = Francis Robert Japp
Felix Klingemann

| Section3 = {{Reactionbox Identifiers

| RSC_ontology_id = 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.{{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 = https://zenodo.org/record/1425485 | doi = 10.1002/cber.188702002165}}{{cite journal | title = Zur Kenntniss der Benzolazo- und Benzolhydrazopropionsäuren (p 3284-3286)|author1=F. R. Japp |author2=F. Klingemann | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 20 | issue = 2| pages = 3284–3286 | year = 1887 | url = https://zenodo.org/record/1425489| doi = 10.1002/cber.188702002234}}{{cite journal | title = Ueber sogenannte »gemischte Azoverbindungen |author1=F. R. Japp |author2=F. Klingemann | journal = Berichte der deutschen chemischen Gesellschaft | volume = 20 | issue = 2 | pages = 3398–3401 | year = 1887 | url = https://zenodo.org/record/1425491 | doi = 10.1002/cber.188702002268}}{{cite journal | title = Ueber die Constitution einiger sogenannten gemischten Azoverbindungen |author1=F. R. Japp |author2=F. Klingemann | journal = Liebigs Annalen der Chemie | volume = 247 | issue = 2 | pages = 190–225 | year = 1888 | doi = 10.1002/jlac.18882470208|url=https://zenodo.org/record/1427427 }}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)([http://www.orgsyn.org/orgsyn/prep.asp?prep=cv4p0633 Article] {{Webarchive|url=https://web.archive.org/web/20120716191722/http://www.orgsyn.org/orgsyn/prep.asp?prep=cv4p0633 |date=2012-07-16}}) The reaction is named after the chemists Francis Robert Japp and Felix Klingemann.

:File: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.{{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) |author1=Bowman, R. E. |author2=Goodburn, T. G. |author3=Reynolds, A. A. | journal = J. Chem. Soc. Perkin Trans. 1 | pages = 1121 | year = 1972 | doi = 10.1039/P19720001121}}{{cite journal | title = 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 |author1=Meyer, M. D. |author2=Kruse, L. I. | journal = J. Org. Chem. | volume = 49 | issue = 17 | pages = 3195–3199 | year = 1984| doi = 10.1021/jo00191a028}}

:File:Japp-Klingemann Fischer Indole Combination.png

If there is a leaving group elsewhere in the Japp–Klingemann product, the hydrazone instead can cyclize at that site via a substitution reaction to give a pyrazole. This process is a key part of the synthesis of {{ill|pyraclofos|de}} and related compounds:{{cite journal |title= An improved procedure for the preparation of 1-aryl-4-hydroxy-1H-pyrazoles |first= Clemens |last= Lamberth |pages= 98–102 |journal= Organic Preprarations and Procedures International |volume= 34 |issue= 1 |year= 2002 |doi= 10.1080/00304940209355748 }}

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