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In organic chemistry, a nitrile is any organic compound that has a functional group. The name of the compound is composed of a base, which includes the carbon of the , suffixed with "nitrile", so for example is called "propionitrile" (or propanenitrile).IUPAC Gold Book nitriles The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, including methyl cyanoacrylate, used in super glue, and nitrile rubber, a nitrile-containing polymer used in latex laboratory and medical gloves. Nitrile rubber is also widely used as automotive and other seals since it is resistant to fuels and oils. Organic compounds containing multiple nitrile groups are known as .
Inorganic compounds containing the group are not called nitriles, but instead.NCBI-MeSH Nitriles Though both nitriles and cyanides can be derived from cyanide salts, most nitriles are not nearly as toxic.
In general, metal cyanides combine with alkyl halides to give a mixture of the nitrile and the isonitrile, although appropriate choice of counterion and temperature can minimize the latter. An alkyl sulfate obviates the problem entirely, particularly in nonaqueous conditions (the Pelouze synthesis).
In specialised cases the Van Leusen reaction can be used. Biocatalysts such as aliphatic aldoxime dehydratase are also effective.
Strictly speaking, these reactions are mediated (as opposed to catalyzed) by acid or base, since one equivalent of the acid or base is consumed to form the ammonium or carboxylate salt, respectively.
Kinetic studies show that the second-order rate constant for hydroxide-ion catalyzed hydrolysis of acetonitrile to acetamide is 1.6 M−1 s−1, which is slower than the hydrolysis of the amide to the carboxylate (7.4 M−1 s−1). Thus, the base hydrolysis route will afford the carboxylate (or the amide contaminated with the carboxylate). On the other hand, the acid catalyzed reactions requires a careful control of the temperature and of the ratio of reagents in order to avoid the formation of polymers, which is promoted by the exothermic character of the hydrolysis. The classical procedure to convert a nitrile to the corresponding primary amide calls for adding the nitrile to cold concentrated sulfuric acid. The further conversion to the carboxylic acid is disfavored by the low temperature and low concentration of water.
Two families of enzymes catalyze the hydrolysis of nitriles. hydrolyze nitriles to carboxylic acids:
The "anhydrous hydration" of nitriles to amides has been demonstrated using an oxime as water source:
Nitrile oxides are quite different from nitriles: they are highly reactive 1,3-dipoles, and cannot be synthesized from the direct oxidation of nitriles. Instead, they can be synthesised by nitroalkane dehydration, oxime dehydrogenation, or halooxime elimination in base., alluding to a large-scale modification later detailed in They are used in 1,3-dipolar cycloadditions,
The heavier nitrile sulfides are extremely reactive and rare, but temporarily form during the thermolysis of oxathiazolones. They react similarly to nitrile oxides.
Over 30 nitrile-containing pharmaceuticals are currently marketed for a diverse variety of medicinal indications with more than 20 additional nitrile-containing leads in clinical development. The types of pharmaceuticals containing nitriles are diverse, from vildagliptin, an antidiabetic drug, to anastrozole, which is the gold standard in treating breast cancer. In many instances the nitrile mimics functionality present in substrates for enzymes, whereas in other cases the nitrile increases water solubility or decreases susceptibility to oxidative metabolism in the liver. The nitrile functional group is found in several drugs.
Cyanohydrins
The are a special class of nitriles. Classically they result from the addition of alkali metal cyanides to aldehydes in the cyanohydrin reaction. Because of the polarity of the organic carbonyl, this reaction requires no catalyst, unlike the hydrocyanation of alkenes. O-Silyl cyanohydrins are generated by the addition trimethylsilyl cyanide in the presence of a catalyst (silylcyanation). Cyanohydrins are also prepared by transcyanohydrin reactions starting, for example, with acetone cyanohydrin as a source of HCN.
Dehydration of amides
Nitriles can be prepared by the dehydration of primary . Common reagents for this include phosphorus pentoxide () and thionyl chloride (). In a related dehydration, secondary give nitriles by the von Braun amide degradation. In this case, one C-N bond is cleaved.
Oxidation of primary amines
Numerous traditional methods exist for nitrile preparation by amine oxidation. Common methods include the use of potassium persulfate, Trichloroisocyanuric acid, or anode electrosynthesis. In addition, several selective methods have been developed in the last decades for electrochemical processes.
From aldehydes and oximes
The conversion of aldehydes to nitriles via is a popular laboratory route. Aldehydes react readily with hydroxylamine salts, sometimes at temperatures as low as ambient, to give aldoximes. These can be dehydrated to nitriles by simple heating, although a wide range of reagents may assist with this, including triethylamine/sulfur dioxide, , or sulfuryl chloride. The related hydroxylamine-O-sulfonic acid reacts similarly.
Sandmeyer reaction
Aromatic nitriles are often prepared in the laboratory from the aniline via diazonium compounds. This is the Sandmeyer reaction. It requires transition metal cyanides." o-Tolunitrile and p-Tolunitrile" H. T. Clarke and R. R. Read Org. Synth. 1941, Coll. Vol. 1, 514.
Other methods
Reactions
Nitrile groups in organic compounds can undergo a variety of reactions depending on the reactants or conditions. A nitrile group can be hydrolyzed, reduced, or ejected from a molecule as a cyanide ion.
Hydrolysis
The hydrolysis of nitriles RCN proceeds in the distinct steps under acid or base treatment to first give Amide and then . The hydrolysis of nitriles to carboxylic acids is efficient. In acid or base, the balanced equations are as follows:
Nitrile hydratases are that hydrolyze nitriles to amides.
These enzymes are used commercially to produce acrylamide.
Reduction
Nitriles are susceptible to hydrogenation over diverse metal catalysts. The reaction can afford either the primary amine () or the tertiary amine (), depending on conditions. In conventional organic reductions, nitrile is reduced by treatment with lithium aluminium hydride to the amine. Reduction to the imine followed by hydrolysis to the aldehyde takes place in the Stephen aldehyde synthesis, which uses stannous chloride in acid.
Deprotonation
Alkyl nitriles are sufficiently acidic to undergo deprotonation of the C-H bond adjacent to the group. (1984). 9780471264187 ISBN 9780471264187 Strong bases are required, such as lithium diisopropylamide and butyl lithium. The product is referred to as a nitrile anion. These carbanions alkylate a wide variety of electrophiles. Key to the exceptional nucleophilicity is the small steric demand of the unit combined with its inductive stabilization. These features make nitriles ideal for creating new carbon-carbon bonds in sterically demanding environments.
Nucleophiles
The carbon center of a nitrile is electrophilic, hence it is susceptible to nucleophilic addition reactions:
(2010). 9780470638859, John Wiley & Sons, Inc.. ISBN 9780470638859 While not a classical Grignard reaction, it may be considered one under broader modern definitions.
Miscellaneous methods and compounds
Complexation
Nitriles are precursors to transition metal nitrile complexes, which are reagents and catalysts. Examples include tetrakis(acetonitrile)copper(I) hexafluorophosphate () and bis(benzonitrile)palladium dichloride ().
Nitrile derivatives
Organic cyanamides
Cyanamides are N-cyano compounds with general structure and related to the parent cyanamide.
Nitrile oxides
Nitrile oxides have the chemical formula . Their general structure is . The R stands for any group (typically organyl, e.g., acetonitrile oxide , hydrogen in the case of fulminic acid , or halogen (e.g., chlorine fulminate ).
(2025). 9780471720911, John Wiley & Sons. ISBN 9780471720911 such as to . They undergo type 1 dyotropic rearrangement to .
Occurrence and applications
Nitriles occur naturally in a diverse set of plant and animal sources. Over 120 naturally occurring nitriles have been isolated from terrestrial and marine sources. Nitriles are commonly encountered in fruit pits, especially almonds, and during cooking of Brassica crops (such as cabbage, Brussels sprouts, and cauliflower), which release nitriles through hydrolysis. Mandelonitrile, a cyanohydrin produced by ingesting almonds or some fruit pits, releases hydrogen cyanide and is responsible for the toxicity of cyanogenic glycosides.Natural Product Reports Issue 5, 1999 Nitrile-containing natural products
See also
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