Nef Rearrangement

1. BY
Dr. Gurumeet.C.Wadhawa
DEPARTMENT OF CHEMISTRY
K. B. P. College,Vashi,Navimumbai
Nef reaction

2. INTRODUCTION
3
Interconversion of functional groups represents an
important aspect in every process leading to the
synthesis of structurally defined compounds
Nef reaction involves acid hydrolysis of a salt of
primary or secondary nitroalkane to yield carbonyl
compounds.
It was first reported by Nef in 1894

3. In 1893, M. Konovalov observed that the treatment of the potassium
salt of 1-phenylnitroethane with dilute acid (AcOH, H2SO4) led to the
formation of 1-phenylnitroethane and acetophenone.
In 1894, J.U. Nef systematically studied the acidic hydrolysis of
several nitroparaffin sodium salts, while he was completely unaware of
Konovalov's experiments, and showed that the major product of all
these reactions were the corresponding carbonyl compounds.
Since Nef demonstrated the generality of this transformation, which he
discovered independently, the conversion of nitroalkanes into the
corresponding carbonyl compounds is known as the Nef reaction

4. GENERAL TRANSFORMATIONS OF NITRO
GROUP
4
Tetrahedron, 2004 ,60 ,1017–1047.

5. HISTORY
5
Nef reaction is named after the
John Ulric Nef
He was graduated from
harvard university
The discovery of nef reaction
and papers concerned with the
divalent carbon are his major
acheivements
June 14, 1862 – August 13,
1915

6. MECHANISM
6

8. Side reactions
7
 Self condensation
 Dimerization
 Formation of pseudonitroles
J. Am. Chem. Soc. 1955, 77,2622

9.  Dehydration
8
 Nitrocompounds which fail to react under nef conditions
J. Am. Chem. Soc. 1948, 70,746

10. The general features of the
reaction are: 1) the product distribution is strongly influenced by the acid
concentration, and for best results the pHneed to be smaller than unity;
2) when the pH>1, a number of by-products such as oximes and hydroxynitroso
compounds can be formed; and
3) original reaction conditions required the addition of the nitronate salt to the
solution of the acid to avoid the formation of undesired products.
To make the reaction more chemoselective and tolerant toward many functional
groups, several modifications have been developed during the past three
decades: 1)
oxidative methods allow the conversion of primary nitroalkanes into aldehydes
or carboxylic acids, while secondary nitroalkanes are converted to ketones;
2) reductive methods are available for the direct preparation of
nitroalkanes to aldehydes, ketones, or oximes;
3) carbonyl compounds and oximes can also be prepared
from nitroolefins (nitroalkenes) using various reducing agents

11. 9
MODIFIED NEF REACTIONS

12. OXIDATIVE METHODS
10
DMD
Synlett 1998, 1335

13. 11
Oxone
Synth. Commun. 1998, 28, 3054
MECHANISM

14. 12
Mc murry method
REDUCTIVEMETHODS
J. Org. Chem. 1973, 38, 4367

15. 13
J. Org. Chem. 1973, 38, 4367.
MECHANISM

16. 14
Other methods
Tetrahedron Lett. 2002, 43, 5233

20. 15
APPLICATIONS

21. In carbohydrate chemistry
16
Used as chain extension method of
aldoses
J. Biol. Chem. 1949, 180,55-58

22. 17
Synthesis of α-amino acids
Tetrahedron Lett. 1999, 40, 4449

23. 18
Synthesis of allylrethrone
It is an important component of insecticidal pyrethroid
Synthesis. 1993,687
18

24. Synthesisof β-lactum building blocks
19
J. Org. Chem. 1990, 55, 2070

25. Conclusion
 Nef reaction dates back a century ago but still it has
significance due to its applicability in conversion of
nitrocompounds to carbonyl compounds
 Modified nef reactions uses oxidising and reducing agents which helps in the
synthesis ofvarious biologically active
compounds
 It also has applications in carbohydrate chemistry as a
 chain-extension method of aldoses
20

26. References
1. Nef, J. U. Ann. 1894, 280, 263-342. John Ulrich Nef (186-1915) was born in
Switzerland
and immigrated to the US at the age of four with his parents. He went to Munich,
Germany to study with Adolf von Baeyer, earning a Ph.D. In 1886. Back to the
States, he served as a professor at Purdue University, Clark University, and the
University
of Chicago. The Nef reaction was discovered at Clark University in Worcester,
Massachusetts. Nef was temperamental and impulsive, suffering from a couple of
mental breakdowns. He was also highly individualistic, and had never published with
a coworker save for three early articles.
2. Pinnick, H. W. Org. React. 1990, 38, 655. (Review).
3. Adam, W.; Makosza, M.; Saha-Moeller, C. R.; Zhao, C.-G. Synlett 1998, 1335–
1336.
4. Thominiaux, C.; Rousse, S.; Desmaele, D.; d’Angelo, J.; Riche, C. Tetrahedron:
Asymmetry 1999, 10, 2015–2021.
5. Capecchi, T.; de Koning, C. B.; Michael, J. P. J. Chem. Soc., Perkin Trans. 1 2000,
2681–2688.
6. Ballini, R.; Bosica, G.; Fiorini, D.; Petrini, M. Tetrahedron Lett. 2002, 43, 5233–
5235.
7. Chung, W. K.; Chiu, P. Synlett 2005, 55–58.
8. Wolfe, J. P. Nef reaction. In Name Reactions for Functional Group
Transformations;
Li, J. J., Ed.; Wiley: Hoboken, NJ, 2007, pp 645􀀐652. (Review).
9. Burés, J.; Vilarrasa, J. Tetrahedron Lett. 2008, 49, 441–444.

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