| Nef reaction | |
|---|---|
| Named after | John Ulric Nef |
| Reaction type | Substitution reaction |
| Identifiers | |
| Organic Chemistry Portal | nef-reaction |
| RSC ontology ID | RXNO:0000157 |
Inorganic chemistry, theNef reaction is anorganic reaction describing the acidhydrolysis of asalt of a primary or secondarynitroalkane (R−NO2) to analdehyde (R−CH=O) or aketone (R2C=O) andnitrous oxide (N2O). The reaction has been the subject of several literature reviews.[1][2][3]
The reaction was reported in 1894 by the chemistJohn Ulric Nef,[4] who treated the sodium salt ofnitroethane withsulfuric acid resulting in an 85–89%yield of nitrous oxide and at least 70% yield ofacetaldehyde. However, the reaction was pioneered a year earlier in 1893 by Konovalov,[5] who converted the potassium salt of 1-phenylnitroethane with sulfuric acid toacetophenone.
Thereaction mechanism starting from thenitronate salt as theresonance structures1a and1b is depicted below:
The salt is protonated forming thenitronic acid2 (in some cases these nitronates have been isolated) and once more to theiminium ion3. This intermediate is attacked by water in anucleophilic addition forming4 which loses a proton and then water to the 1-nitroso-alkanol5 which is believed to be responsible for the deep-blue color of the reaction mixture in many Nef reactions. This intermediate rearranges tohyponitrous acid6 (formingnitrous oxide6c through6b) and theoxonium ion7 which loses a proton to form thecarbonyl compound.
Note that formation of the nitronate salt from the nitro compound requires analpha hydrogen atom and therefore the reaction fails with tertiary nitro compounds.
Nef-type reactions are frequently encountered inorganic synthesis, because they turn theHenry reaction into a convenient method for functionalization at the β and γ locations.[6] Thus, for example, the reaction is combined with theMichael reaction in the synthesis of theγ-keto-carbonylmethyl 3-acetyl-5-oxohexanoate, itself acyclopentenone intermediate:[7][8]
Incarbohydrate chemistry, they are a chain-extension method foraldoses, as in theisotope labeling of C14-D‑mannose and C14-D‑glucose fromD‑arabinose and C14‑nitromethane (the first step here is aHenry reaction):
The opposite reaction is theWohl degradation.
Nef's original protocol, using concentratedsulfuric acid, has been described as "violent".[9] Strong-acid hydrolysis without the intermediate salt stage results in the formation ofcarboxylic acids andhydroxylamine salts,[citation needed] butLewis acids such astin(IV) chloride[10] andiron(III) chloride[11] give a clean hydrolysis. Alternatively, strongoxidizing agents, such asoxone,[12]ozone, orpermanganates, will cleave thenitronate tautomer at the double bond to form a carbonyl andnitrate.Oxophilic reductants, such astitanium salts, will reduce the nitronate to a hydrolysis-susceptibleimine, but less selective reductants give the amine instead.[9]