Nef reaction
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The Nef reaction is an organic reaction describing the acid hydrolysis of a salt of a primary or secondary nitroalkane to an aldehyde or a ketone and nitrous oxide [1].
The reaction was reported by the chemist J.U. Nef in 1894 [2]who treated the sodium salt of nitroethane with sulfuric acid resulting in a 85-89 chemical yield of nitrous oxide and at least 70% yield of acetaldehyde but the reaction was pioneered a year earlier in 1893 by Konovalov [3] who converted the potassium salt of l-phenylnitroethane with sulfuric acid to acetophenone.
[edit] Reaction mechanism
The reaction mechanism starting from the nitro salt as the resonance structures 1a and 1b is depicted below:
The salt is protonated forming the nitronate 2 (in some cases these nitronates have been isolated) and once more to the iminium ion 3. This intermediate is attacked by water in a nucleophilic addition forming 4 which loses a proton and then water to the 1-nitroso-alkanol 5 which is believed to be responsible for the deep-blue color of the reaction mixture in many Nef reactions. This intermediate rearranges to hyponitrous acid 6 (forming nitrous oxide 6c through 6b) and the oxonium ion 7 which loses a proton the the carbonyl compound.
Note that the reaction requires an alpha hydrogen atom and therefore the reaction fails with tertiary nitro compounds.
[edit] Scope
The Nef reaction is frequently encountered in organic synthesis. It has been applied in carbohydrate chemistry as a chain-extension method for aldoses for example in the isotope labeling of C14-D-mannose and C14-D-glucose from D-arabinose and C14-nitromethane.
The reaction is also used in combination with the Michael reaction in the synthesis of γ-keto-carbonyls such as [4]:
or 2,5-heptanedione [5] Hydrolysis of nitro compounds with strong acid without the intermediate salt stage results in the formation of carboxylic acids and hydroxylamine salts.
The Nef reaction can also be performed with lewis acids such as tin(IV) chloride [6]
[edit] References
- ^ The NEF Reaction Wayland E. Noland Chem. Rev.; 1955; 55(1) pp 137 - 155; DOI:10.1021/cr50001a003
- ^ Nef JU: Liebigs Ann Chem 1894:280.
- ^ Konovalov.,: J. Russ. Phys. Chem. SOC2. 6, I, 509 (1893);
- ^ A convenient synthesis of γ-functionalized cyclopentenones Nour Lahmar, Taïcir Ben Ayed , Moncef Bellassoued and Hassen Amri Beilstein Journal of Organic Chemistry 2005, 1:11 DOI:10.1186/1860-5397-1-11
- ^ Organic Syntheses, Coll. Vol. 6, p.648 (1988); Vol. 56, p.36 (1977) Link.
- ^ Organic Syntheses, Coll. Vol. 7, p.414 (1990); Vol. 60, p.117 (1981) Link.
