The document summarizes the Japp-Klingemann reaction, which was discovered in 1887 by Francis Robert Japp and Felix Klingemann. They attempted to prepare an azo ester by coupling benzenediazonium chloride with sodium salt of ethyl-2-methylacetoacetate, but instead produced the phenylhydrazone of ethyl pyruvate, which contained two fewer carbon atoms than expected. The reaction involves the deprotonation of a β-keto-ester followed by nucleophilic addition to the diazonium salt, producing an unstable azo compound that hydrolyzes to release the carboxylic acid. The Japp-Klingemann reaction is

1. Japp Klingemann
Reaction

2. Submitted to
Dr. Ibrahim
• Submitted by
• Muhammad Sajid Majeed
• Roll No # 2295

3. history
• Francis Robert Japp (1848-1925) Scottish, born in Dundee, Scotland
• Felex Klingemann (1863-1944), British, born in London, England
• In 1887 F.R Japp and Klingemann attempted to prepare an azo ester by
coupling benzenediazonium chloride with sodium salt of ethy-2-
methylacetoacetate. However, the isolated product turned out to be the
phenylhydrazone of ethyl pyruvate, which contained two carbon atoms less
than expected azo easter.

4. Principle
• In an attempt to prepare an azo ester by coupling benzendiazonium
chloride with ethyl-2-methylacetoacetate, Japp and Klingemann obtained a product,
which was soon recognized as the phenylhydrazone of ethyl pyruvate. It thus
appears that the acetyl group is displaced, actually the coupling product was unstable
under the conditions of its formation, undergoing hydrolytic scission of the acetyl
group and rearrangement of the azo structure. It was later discovered that, if the
substituted acetoacetic ester was saponified and the cocoupling carried out on the
sodium salt, the carboxylic function rather than the acetyl group, was lost and the
product isolated was the phenylhydrazone of biacetyl. This reaction was extended to
other systems containing methinyl groups.

5. General reaction

6. 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.

7. Mechanism

8. Example
• A phenylhydrazone product can be heated in the presence of strong acid to
produce an indole via the Fischer indole synthesis

9. Applications
• =>Japp-Klingemann reaction used In synthesis of (-)-gillbertine.
• =>Japp-Klingemann reaction used in synthesis of Amoamine A.
• => Japp-Klingemann reaction used in synthesis of Lactone degradation
product of soraphen A.
• => Japp-Klingemann reaction used in synthesis of 5H,12H-[1]Benzoxepino
[4,3-b]indole-6-one.

10. Conclusion
• Japp-Klingemann reaction is used to prepare phenylhydrazone of ethyl
pyruvate.

11. References
• Francis Robert Japp, Felix Klingemann (1887). "Ueber Benzolazo- und
Benzolhydrazofettsäuren". Berichte der deutschen chemischen Gesellschaft
• Name reaction By Kurti.
• Phillips, R. R. Org. Reaction
• P. M. Jackson and C. J. Moody, J. Chem. Soc., Perkin Trans. 1, 1990, 2156–
2158.