Nef reaction

Nef Rearrangement

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

2. INT R O D U C TION 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. HIS T O R Y 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

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

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

9. 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

10. 9 MODIFIED NEF REACTIONS

11. OXIDATIVE METHODS 10 D M D Synlett 1998, 1335

12. 11 O x o n e Synth. Commun . 1998 , 28 , 3054 MECHANISM

13. 12 Mc murry method REDUCTIVE METHODS J. Org. Chem . 1973 , 38 , 4367

14. 13 J. Org. Chem . 1973 , 38 , 4367 . MECHANISM

15. 14 Other methods Tetrahedron Lett. 2002 , 43 , 5233

16. 15 APPLICATIONS

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

18. 17 Synthesis of α-amino acids Tetrahedron Lett. 1999 , 40 , 4449

19. 18 Synthesis of allylrethrone It is an important component of insecticidal pyrethroid Synthesis. 1993, 687 18

20. Synthesis of β-lactum building blocks 19 J. Org. Chem. 1990 , 55 , 2070

21. 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 a g e n ts which hel p s in t h e s y n thesis o f v arious biol o gi c ally active compounds It also has applications in carbohydrate chemistry as a chain-extension method of aldoses 20

22. 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. 10. Felluga , F.; Pitacco , G.; Valentin , E.; Venneri , C. D. Tetrahedron: Asymmetry 2008, 19, 945–955. 11. Chinmay Bhat , C.; Tilve , S. G. Tetrahedron 2013, 69, 6129–6143.

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