The
Nef reaction is an
organic reactionOrganic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions and redox reactions. In organic synthesis, organic reactions are used...
describing the
acidIn acid catalysis and base catalysis a chemical reaction is catalyzed by an acid or a base. The acid is often the proton and the base is often a hydroxyl ion. Typical reactions catalysed by proton transfer are esterfications and aldol reactions. In these reactions the conjugate acid of the carbonyl...
hydrolysisHydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions, which may go on to participate in further reactions. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization...
of a salt of a primary or secondary nitroalkane (
1) to an
aldehydeAn aldehyde is an organic compound containing a terminal carbonyl group. This functional group, which consists of a carbon atom bonded to a hydrogen atom and double-bonded to an oxygen atom , is called the aldehyde group...
or a
ketoneIn organic chemistry, a ketone is a type of compound that features a carbonyl group bonded to two other carbon atoms, i.e., R3CCO-CR3 where R can be a variety of atoms and groups of atoms...
(
3) and
nitrous oxideNitrous oxide, commonly known as happy gas or laughing gas, is a chemical compound with the chemical formula N
2O. At room temperature, it is a colorless non-flammable gas, with a pleasant, slightly sweet odor and taste. It is used in surgery and dentistry for its anesthetic and analgesic...
(
4).
The reaction was reported in 1894 by the chemist
John Ulric NefJohn Ulric Nef was a Swiss-born American chemist and the discoverer of the Nef reaction.-Life:...
, who treated the sodium salt of
nitroethaneNitroethane 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 colourless and has a fruity odor...
with
sulfuric acidSulfuric acid, , is a strong mineral acid. It is soluble in water at all concentrations. Sulfuric acid has many applications, and is one of the top products of the chemical industry. World production in 2001 was 165 million tonnes, with an approximate value of US$8 billion...
resulting in a 85-89% yield of nitrous oxide and at least 70% yield of
acetaldehydeAcetaldehyde is an organic chemical compound with the formula CH3CHO or MeCHO. It is a flammable liquid. Acetaldehyde occurs naturally in ripe fruit, coffee, and bread, and is produced by plants as part of their normal metabolism...
. However, the reaction was pioneered a year earlier in 1893 by Konovalov, who converted the potassium salt of 1-phenylnitroethane with sulfuric acid to
acetophenoneAcetophenone is the organic compound with the formula C6H5CCH3. It is the simplest aromatic ketone. This colourless, viscous liquid is a precursor to useful resins and fragrances.-Production:...
.
The
Nef reaction should not be confused with the Nef synthesis.
The
reaction mechanismIn chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs .Although only the net chemical change is directly observable for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in...
starting from the nitro salt as the resonance structures
1a and
1b is depicted below:
The salt is protonated forming the
nitronateA nitronate in organic chemistry is a functional group with the general structure R1R2C=N+. It is a tautomeric form of a nitro group. A nitronate is also called a aci form. In the Nef reaction Nitronates are degraded to ketones.They can be alkylated on oxygen and...
2 (in some cases these nitronates have been isolated) and once more to the
iminiumAn iminium salt or cation in organic chemistry has the general structure [R1R2C=NR3R4]+ and is as such a protonated or substituted imine . It is an intermediate in many organic reactions such as the Beckmann rearrangement,...
ion
3.
The
Nef reaction is an
organic reactionOrganic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions and redox reactions. In organic synthesis, organic reactions are used...
describing the
acidIn acid catalysis and base catalysis a chemical reaction is catalyzed by an acid or a base. The acid is often the proton and the base is often a hydroxyl ion. Typical reactions catalysed by proton transfer are esterfications and aldol reactions. In these reactions the conjugate acid of the carbonyl...
hydrolysisHydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions, which may go on to participate in further reactions. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization...
of a salt of a primary or secondary nitroalkane (
1) to an
aldehydeAn aldehyde is an organic compound containing a terminal carbonyl group. This functional group, which consists of a carbon atom bonded to a hydrogen atom and double-bonded to an oxygen atom , is called the aldehyde group...
or a
ketoneIn organic chemistry, a ketone is a type of compound that features a carbonyl group bonded to two other carbon atoms, i.e., R3CCO-CR3 where R can be a variety of atoms and groups of atoms...
(
3) and
nitrous oxideNitrous oxide, commonly known as happy gas or laughing gas, is a chemical compound with the chemical formula N
2O. At room temperature, it is a colorless non-flammable gas, with a pleasant, slightly sweet odor and taste. It is used in surgery and dentistry for its anesthetic and analgesic...
(
4).
The reaction was reported in 1894 by the chemist
John Ulric NefJohn Ulric Nef was a Swiss-born American chemist and the discoverer of the Nef reaction.-Life:...
, who treated the sodium salt of
nitroethaneNitroethane 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 colourless and has a fruity odor...
with
sulfuric acidSulfuric acid, , is a strong mineral acid. It is soluble in water at all concentrations. Sulfuric acid has many applications, and is one of the top products of the chemical industry. World production in 2001 was 165 million tonnes, with an approximate value of US$8 billion...
resulting in a 85-89% yield of nitrous oxide and at least 70% yield of
acetaldehydeAcetaldehyde is an organic chemical compound with the formula CH3CHO or MeCHO. It is a flammable liquid. Acetaldehyde occurs naturally in ripe fruit, coffee, and bread, and is produced by plants as part of their normal metabolism...
. However, the reaction was pioneered a year earlier in 1893 by Konovalov, who converted the potassium salt of 1-phenylnitroethane with sulfuric acid to
acetophenoneAcetophenone is the organic compound with the formula C6H5CCH3. It is the simplest aromatic ketone. This colourless, viscous liquid is a precursor to useful resins and fragrances.-Production:...
.
The
Nef reaction should not be confused with the Nef synthesis.
Reaction mechanism
The
reaction mechanismIn chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs .Although only the net chemical change is directly observable for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in...
starting from the nitro salt as the resonance structures
1a and
1b is depicted below:
The salt is protonated forming the
nitronateA nitronate in organic chemistry is a functional group with the general structure R1R2C=N+. It is a tautomeric form of a nitro group. A nitronate is also called a aci form. In the Nef reaction Nitronates are degraded to ketones.They can be alkylated on oxygen and...
2 (in some cases these nitronates have been isolated) and once more to the
iminiumAn iminium salt or cation in organic chemistry has the general structure [R1R2C=NR3R4]+ and is as such a protonated or substituted imine . It is an intermediate in many organic reactions such as the Beckmann rearrangement,...
ion
3. This intermediate is attacked by water in a
nucleophilic additionIn organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a π bond is removed by the creation of two new covalent bonds by the addition of a nucleophile....
forming
4 which loses a proton and then water to the 1-
nitrosoNitroso refers to a functional group in organic chemistry which has the general formula RNO. Nitroso compounds can be prepared by the reduction of nitro compounds or by the oxidation of hydroxylamines...
-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 acidHyponitrous acid is the chemical compound H2N2O2. This can be formulated as HON=NOH and is an isomer of nitramide, . It forms white crystals that are explosive when dry...
6 (forming
nitrous oxideNitrous oxide, commonly known as happy gas or laughing gas, is a chemical compound with the chemical formula N
2O. At room temperature, it is a colorless non-flammable gas, with a pleasant, slightly sweet odor and taste. It is used in surgery and dentistry for its anesthetic and analgesic...
6c through
6b) and the
oxonium ionThe oxonium ion in chemistry is any oxygen cation with three bonds. The simplest oxonium ion is the hydronium ion H
3O
+. Another oxonium ion frequently encountered in organic chemistry is obtained by protonation or alkylation of a carbonyl group e.g...
7 which loses a proton to form the
carbonylIn organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom : C=O.The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex In organic chemistry, a carbonyl group is a functional group...
compound.
Note that the reaction requires an alpha hydrogen atom and therefore the reaction fails with tertiary nitro compounds.
Scope
The Nef reaction is frequently encountered in
organic synthesisOrganic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
. It has been applied in
carbohydrate chemistryCarbohydrate chemistry is a subdiscipline of chemistry primarily concerned with the synthesis, structure, and function of carbohydrate structures. Due to the general structure of carbohydrates, their synthesis is often preoccupied with the selective formation of glycosidic linkages and the...
as a chain-extension method for
aldoseAn aldose is a monosaccharide containing one aldehyde group per molecule and having a chemical formula of the form Cnn.With only two carbon atoms, glycolaldehyde is the simplest of all aldoses....
s for example in the isotope labeling of C
14-D-
mannoseMannose is a sugar monomer of the aldohexose series of carbohydrates.-Metabolism:Mannose is not well metabolized in humans.Therefore, it does not significantly enter the carbohydrate metabolism when taken orally, and although traces of exogeneously introduced mannose have been detected in all body...
and C
14-D-
glucoseGlucose , a monosaccharide also known as - grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate...
from D-
arabinoseArabinose is an aldopentose – a monosaccharide containing five carbon atoms, and including an aldehyde functional group.For biosynthetic reasons, most saccharides are almost always more abundant in nature as the "
D"-form, or structurally analogous to...
and C14-
nitromethaneNitromethane is an organic compound with the chemical formula CH3NO2. It is the simplest organic nitro compound. It is a slightly viscous, highly polar liquid commonly used as a solvent in a variety of industrial applications such as in extractions, as a reaction medium, and...
.
The opposite reaction is the
Wohl degradationThe Wohl degradation in carbohydrate chemistry is a chain contraction method for aldoses. The classic example is the conversion of glucose to arabinose as shown below. The reaction is named after the chemist Alfred Wohl....
.
The reaction is also used in combination with the
Michael reactionThe Michael reaction or Michael addition is the nucleophilic addition of a carbanion to an alpha, beta unsaturated carbonyl compound. It belongs to the larger class of conjugate additions. This is one of the most useful methods for the mild formation of C-C bonds...
in the synthesis of
γGamma uppercase Γ, lowercase γ; ) is the third letter of the Greek alphabet. In the system of Greek numerals it has a value of 3. It was derived from the Phoenician letter Gimel . Letters that arose from Gamma include the Roman C and G and the Cyrillic letters Ge Г and Ghe Ґ.In Modern Greek, it...
-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 acidCarboxylic acids are organic acids characterized by the presence of a carboxyl group, which has the formula -COH, usually written -COOH or -CO2H. Carboxylic acids are Brønsted-Lowry acids — they are proton donors. Salts and anions of carboxylic acids are called...
s and
hydroxylamineHydroxylamine is a reactive chemical with formula NH2OH. It can be considered a hybrid of ammonia and water due to parallels it shares with each...
salts.
The hydrolysis step of the Nef reaction can also be performed with
lewis acidA Lewis acid, A, is a chemical compound that can accept a pair of electrons from a Lewis base, B, that acts as an electron-pair donor, forming an adduct, AB:
A + :B → A—B...
s such as
tin(IV) chlorideTin chloride, also known as tin tetrachloride or stannic chloride is a chemical compound with the formula SnCl4.At room temperature it is a colourless liquid, which fumes on contact with air, giving a stinging odour...
, or oxidants such as oxone.