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Nef Reaction

The conversion of nitro compounds into carbonyls is known as the Nef Reaction. Various methodologies have been developed, but the most important is the standard procedure: a preformed nitronate salt is poured into strong aqueous acid (pH < 1). Some oxidative variations have also found wide application, and some reductive methods have even been developed.

Mechanism of the Nef Reaction

Nitroalkanes are relatively strong carbon acids, and deprotonation leads to the nitronate salt. The hydrolysis of this intermediate must take place in strong acid, to prevent the formation of side products such as oximes or hydroxynitroso compounds:

The procedure using the commercial reagent Oxone is mechanistically interesting:

P. Ceccherelli, M. Curini, M. C. Marcotullio, F. Epifano, O. Rosati, Synth. Commun., 1998, 28, 3057-3064.

The reductive method leads to oximes, which may be hydrolyzed to the corresponding carbonyl compound. Ti(III) serves to reduce the N-O bond, and titanium's strong affinity towards oxygen facilitates the hydrolysis to complete the conversion:

Recent Literature

Unprecedented, selective Nef reaction of secondary nitroalkanes promoted by DBU under basic homogeneous conditions
R. Ballini, G. Bosica, D. Fiorini, M. Petrini, Tetrahedron Lett., 2002, 43, 5233-5235.

Silicon-Catalyzed Conversion of Nitro Compounds into Ketones and Poly(1,3-diketones)
J. R. Hwu, T. Josephrajan, S.-C. Tsay, Synthesis, 2006, 3305-3308.

KMnO4-Mediated Oxidation as a Continuous Flow Process
J. Sedelmeier, S. V. Ley, I. R. Baxendale, M. Baumann, Org. Lett., 2010, 12, 3618-3621.

Cu-Catalyzed Enantioselective Conjugate Addition of Alkylzincs to Cyclic Nitroalkenes: Catalytic Asymmetric Synthesis of Cyclic α-Substituted Ketones
C. A. Luchaco-Cullis, A. H. Hoveyda, J. Am. Chem. Soc., 2002, 124, 8192-8193.

One-Pot Synthesis of γ-Diketones, γ-Keto Esters, and Conjugated Cyclopentenones from Nitroalkanes
R. Ballini, L . Barboni, G. Bosica, D. Fiorini, Synthesis, 2002, 2725-2728.

Electrochemical Oxidative Cleavage of Alkynes to Carboxylic Acids
Q. Feng, Y. Wang, B. Zheng, S. Huang, Org. Lett., 2023, 25, 293-297.

Boron Trifluoride Mediated Ring-Opening Reactions of trans-2-Aryl-3-nitro-cyclopropane-1,1-dicarboxylates. Synthesis of Aroylmethylidene Malonates as Potential Building Blocks for Heterocycles
T. Selvi, K. Srinivasan, J. Org. Chem., 2014, 79, 3653-3658.