organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J. ...

, the Nef reaction is an

organic reaction Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemic ...

describing the acid

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolys ...

of a

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quantiti ...

of a primary or secondary nitroalkane () to an

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...

() or a

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bon ...

() and

nitrous oxide Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or nos, is a chemical compound, an oxide of nitrogen with the formula . At room temperature, it is a colourless non-flammable gas, and has ...

(). The reaction has been the subject of several literature reviews. The reaction was reported in 1894 by the chemist John Ulric Nef, who treated the sodium salt of

nitroethane Nitroethane is an organic compound having the chemical formula C2H5NO2. Similar in many regards to nitromethane, nitroethane is an oily liquid at standard temperature and pressure. Pure nitroethane is colorless and has a fruity odor. Preparati ...

with

sulfuric acid Sulfuric acid ( American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular fo ...

resulting in an 85–89% yield of nitrous oxide and at least 70% yield of

acetaldehyde Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the m ...

. However, the reaction was pioneered a year earlier in 1893 by Konovalov, who converted the potassium salt of 1-phenylnitroethane with sulfuric acid to

acetophenone Acetophenone is the organic compound with the formula C6H5C(O)CH3. It is the simplest aromatic ketone. This colorless, viscous liquid is a precursor to useful resins and fragrances. Production Acetophenone is formed as a byproduct of the cumene p ...

Reaction mechanism

The

reaction mechanism In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs. A chemical mechanism is a theoretical conjecture that tries to describe in detail what takes place at each stage of ...

starting from the nitronate salt as the

resonance structure In chemistry, resonance, also called mesomerism, is a way of describing bonding in certain molecules or polyatomic ions by the combination of several contributing structures (or ''forms'', also variously known as ''resonance structures'' or ...

s 1a and 1b is depicted below: The salt is protonated forming the nitronic acid 2 (in some cases these nitronates have been isolated) and once more to the

iminium In organic chemistry, an iminium cation is a polyatomic ion with the general structure . They are common in synthetic chemistry and biology. Structure Iminium cations adopt alkene-like geometries. The central C=N unit is nearly coplanar with al ...

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 Hyponitrous acid is a chemical compound with formula or HON=NOH. It is an isomer of nitramide, H2N−NO2; and a formal dimer of azanone, HNO. Hyponitrous acid forms two series of salts, the hyponitrites containing the N=NOsup>2− anion, and t ...

6 (forming

6c through 6b) and the

oxonium ion In chemistry, an oxonium ion is any cation containing an oxygen atom that has three bonds and 1+ formal charge. The simplest oxonium ion is the hydronium ion (). Alkyloxonium Hydronium is one of a series of oxonium ions with the formula R''n''H3 ...

7 which loses a proton to form the

carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...

compound. Note that formation of the nitronate salt from the nitro compound requires an alpha hydrogen atom and therefore the reaction fails with tertiary nitro compounds.

Scope

The Nef reaction is frequently encountered in

organic synthesis Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...

. It has been applied in

carbohydrate chemistry Carbohydrate chemistry is a subdiscipline of chemistry primarily concerned with the detection, synthesis, structure, and function of carbohydrates. Due to the general structure of carbohydrates, their synthesis is often preoccupied with the select ...

as a chain-extension method for

aldose An aldose is a monosaccharide (a simple sugar) with a carbon backbone chain with a carbonyl group on the endmost carbon atom, making it an aldehyde, and hydroxyl groups connected to all the other carbon atoms. Aldoses can be distinguished from ket ...

s for example in the

isotope labeling Isotopic labeling (or isotopic labelling) is a technique used to track the passage of an isotope (an atom with a detectable variation in neutron count) through a reaction, metabolic pathway, or cell. The reactant is 'labeled' by replacing specific ...

of C¹⁴-D-

mannose Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation ar ...

and C¹⁴-D-

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...

from D-

arabinose Arabinose is an aldopentose – a monosaccharide containing five carbon atoms, and including an aldehyde (CHO) functional group. For biosynthetic reasons, most saccharides are almost always more abundant in nature as the "D"-form, or structurally ...

and C14-

nitromethane Nitromethane, sometimes shortened to simply "nitro", is an organic compound with the chemical formula . It is the simplest organic nitro compound. It is a polar liquid commonly used as a solvent in a variety of industrial applications such as in ...

(the first step here is a Henry reaction): The opposite reaction is the Wohl degradation. The reaction is also used in combination with the

Michael reaction In organic chemistry, the Michael reaction or Michael addition is a reaction between a Michael donor (an enolate or other nucleophile) and a Michael acceptor (usually an α,β-unsaturated carbonyl) to produce a Michael adduct by creating a carbon ...

in the synthesis of γ-keto-carbonyls such as: or ''2,5-heptanedione'' Hydrolysis of nitro compounds with strong acid without the intermediate salt stage results in the formation of

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...

s and hydroxylamine salts. The hydrolysis step of the Nef reaction can also be performed with

Lewis acid A Lewis acid (named for the American physical chemist Gilbert N. Lewis) is a chemical species that contains an empty orbital which is capable of accepting an electron pair from a Lewis base to form a Lewis adduct. A Lewis base, then, is any sp ...

s such as tin(IV) chloride and

iron(III) chloride Iron(III) chloride is the inorganic compound with the formula . Also called ferric chloride, it is a common compound of iron in the +3 oxidation state. The anhydrous compound is a crystalline solid with a melting point of 307.6 °C. The colo ...

oxidizing agent An oxidizing agent (also known as an oxidant, oxidizer, electron recipient, or electron acceptor) is a substance in a redox chemical reaction that gains or " accepts"/"receives" an electron from a (called the , , or ). In other words, an oxi ...

s, such as oxone.

References

{{Reflist Substitution reactions Name reactions