Nef reaction

The Nef reaction is a name of reaction in organic chemistry. Named the reaction after the American chemist John Ulric Nef ( 1862-1915 ). In the Nef reaction, a primary or a secondary nitroalkane is converted into the appropriate aldehyde or ketone and nitrous oxide under acid catalysis.

John Ulric Nef discovered the reaction when he, the sodium salt of nitroethane offset 1894 with sulfuric acid and obtained with a yield of 85-89 % nitrous oxide and 70 % acetaldehyde. But a year before Konovalov had already published a similar reaction. He relied to the potassium salt of 1- Phenylnitroethan with sulfuric acid to acetophenone.

Reaction mechanism

The nitroalkane 1 is deprotonated. The resulting salt is then protonated to nitronate 4 and a further protonation to the iminium ion 5 takes place. The nucleophilic attack of water at 5 and deprotonation now yields the 1- Nitrosoalkanol 8, which is believed that it is responsible for the blue color of the reaction solution. Rearrangement and cleavage of the final product 9 and the Hyposalpetrige acid is formed. This is split off and falls into nitrous oxide and water.

The reaction requires an acidic hydrogen in the α -position (ie the carbon atom to which the nitro group is bonded ), and therefore not containing tertiary nitro compounds can be carried out.

Application Examples

In carbohydrate chemistry, the Nef reaction is sometimes used for chain extension of aldose. An example is the radiolabeling of 14C- D-mannose and D - 14C -glucose from D -arabinose and 14C nitromethane.

The reaction is also sometimes used in combination with the Michael reaction for the synthesis of γ -keto carbonyls: