Japp Klingemann Reaction

Submitted toDr. Ibrahim

• Submitted by

• Muhammad Sajid Majeed

• Roll No # 2295

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.

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.

General 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.

Mechanism

Example

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

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.

Conclusion

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

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.