TheNef Reaction

Abstract

The Nef reaction is usually defined as the conversion of a primary or secondary nitroalkane into the corresponding carbonyl compound. This reaction was reported by the Swiss chemist J. U. Nef in 1894. Hydrochloric and sulfuric acid give the same result. The conversion of a nitro group to a carbonyl group has become an important synthetic tool because of the ease of preparation of substituted nitro compounds by condensation of nitroalkanes with aldehydes (the Henry reaction), conjugate addition of nitroalkanes to electrophilic alkenes, or carbon alkylation of the dianion of primary nitroparaffins. The Nef reaction is one of the better examples of “umpolung” reactivity in which the original nitro compound anion functions as an acyl anion equivalent. This chapter discusses the Nef reaction and modifications of the original process that extend the variety of compounds which are useful as substrates. Each modification is considered according to general mechanistic type and is organized in a “reagent” approach. The Tabular Survey lists all known examples of both the Nef reaction and these modifications so that specific comparison of methods can be made.

The Nitro to Carbonyl Conversion (Nef Reaction): New Perspectives for a Classical Transformation

“…Since its discovery at the endo ft he nineteenth century,t he Nef reactionh as been widely exploited for the generation of carbonyls ystems in simple and functionalized molecules. [2][3][4][5] Ther elationship which connects nitroalkanes and the corresponding carbonyl systems fairly resembles that existing between alcohols and their oxidized counterparts.A samatter of fact, primary nitroalkanes can be converted into aldehydeso rc arboxylic acids depending on the adopted reactionc onditions,w hiles econdary nitro compounds are transformedi nto ketones.T his reactionw as originally designed as the hydrolysiso fn itronic acids,g enerated from the corresponding nitronate anions under strongly acidic conditions.O ver the years the Nef reaction has progressively modified its nature being nowadays carriedo ut under different reactionc onditions.C leavage of the C=Ns ystem can be performed under oxidative conditions on nitronates 2 obtained from nitroalkanes 1 using basic promoters (Scheme 1). [6] Reducing reagents can also be applied directlyo nn itroalkanesa si nt he classicalM cMurry procedure using aqueous solutions of TiCl 3 .T his may resulti nt he formation of the oxime 3 or the carbonyl derivative 4.…”

Novel non-classical C9-methyl-5-substituted-2,4-diaminopyrrolo[2,3-d]pyrimidines as potential inhibitors of dihydrofolate reductase and as anti-opportunistic agents

“…There are numerous Nef reaction conditions available for converting nitro adducts to carbonyl intermediates. 31 However the one-pot conditions reported by Taylor and Liu. 14,15 were particularly appealing.…”

The Chemistry of Flammable Gas Generation

“…The decomposition of the nitro compound in aqueous media provides an oxidized organic product with a carbonyl group and the reduced nitrosyl anion, which spontaneously produces nitrous oxide (Noland, 1955;Hawthorne 1957;Pinnick 1990;March 1992). This reaction usually is carried out in acidic solution, hut there are many examples of the reaction in alkaline media (Pinnick 1990 The chemistry of the nitrosyl anion, which leads directly to nitrous oxide, is discussed in Section 4.3.…”

“…This reaction usually is carried out in acidic solution, hut there are many examples of the reaction in alkaline media (Pinnick 1990 The chemistry of the nitrosyl anion, which leads directly to nitrous oxide, is discussed in Section 4.3.…”