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 -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 Benzolhydrazofettsuren". 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.