Inorganic chemistry, anitrile is anyorganic compound that has a−C≡Nfunctional group. The name of the compound is composed of a base, which includes the carbon of the−C≡N, suffixed with "nitrile", so for exampleCH3CH2C≡N is called "propionitrile" (or propanenitrile).[1] The prefixcyano- is used interchangeably with the termnitrile in industrial literature. Nitriles are found in many useful compounds, includingmethyl cyanoacrylate, used insuper glue, andnitrile rubber, a nitrile-containingpolymer used inlatex-free laboratory andmedical 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 ascyanocarbons.
Inorganic compounds containing the−C≡N group are not called nitriles, butcyanides instead.[2] Though both nitriles and cyanides can be derived from cyanide salts, most nitriles are not nearly as toxic.
The N−C−C geometry is linear in nitriles, reflecting the sp hybridization of the triply bonded carbon. The C−N distance is short at 1.16 Å, consistent with atriple bond.[3] Nitriles are polar, as indicated by high dipole moments. As liquids, they have highrelative permittivities, often in the 30s.
The first compound of the homolog row of nitriles, the nitrile offormic acid,hydrogen cyanide was first synthesized byC. W. Scheele in 1782.[4][5] In 1811J. L. Gay-Lussac was able to prepare the very toxic and volatile pure acid.[6] Around 1832benzonitrile, the nitrile ofbenzoic acid, was prepared byFriedrich Wöhler andJustus von Liebig, but due to minimal yield of the synthesis neither physical nor chemical properties were determined nor a structure suggested. In 1834Théophile-Jules Pelouze synthesizedpropionitrile, suggesting it to be an ether of propionic alcohol and hydrocyanic acid.[7]The synthesis of benzonitrile byHermann Fehling in 1844 by heating ammonium benzoate was the first method yielding enough of the substance for chemical research. Fehling determined the structure by comparing his results to the already known synthesis of hydrogen cyanide by heating ammoniumformate. He coined the name "nitrile" for the newfound substance, which became the name for this group of compounds.[8]
Industrially, the main methods for producing nitriles areammoxidation andhydrocyanation. Both routes aregreen in the sense that they do not generate stoichiometric amounts of salts.
Inammoxidation, ahydrocarbon is partiallyoxidized in the presence ofammonia. This conversion is practiced on a large scale foracrylonitrile:[9]
In the production of acrylonitrile, a side product isacetonitrile. On an industrial scale, several derivatives ofbenzonitrile,phthalonitrile, as well as Isobutyronitrile are prepared by ammoxidation. The process is catalysed bymetal oxides and is assumed to proceed via the imine.
Hydrocyanation is an industrial method for producing nitriles from hydrogen cyanide and alkenes. The process requireshomogeneous catalysts. An example of hydrocyanation is the production ofadiponitrile, a precursor tonylon-6,6 from1,3-butadiene:
Twosalt metathesis reactions are popular for laboratory scale reactions. In theKolbe nitrile synthesis,alkyl halides undergonucleophilic aliphatic substitution with alkali metalcyanides. Aryl nitriles are prepared in theRosenmund-von Braun synthesis.
In general, metal cyanides combine with alkyl halides to give a mixture of the nitrile and theisonitrile, although appropriate choice ofcounterion andtemperature can minimize the latter. Analkyl sulfate obviates the problem entirely, particularly in nonaqueous conditions (thePelouze synthesis).[5]
Thecyanohydrins are a special class of nitriles. Classically they result from the addition of alkali metal cyanides to aldehydes in thecyanohydrin 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 additiontrimethylsilyl cyanide in the presence of a catalyst (silylcyanation). Cyanohydrins are also prepared by transcyanohydrin reactions starting, for example, withacetone cyanohydrin as a source of HCN.[10]
Nitriles can be prepared by thedehydration of primaryamides. Common reagents for this includephosphorus pentoxide (P2O5)[11] andthionyl chloride (SOCl2).[12] In a related dehydration, secondaryamides give nitriles by thevon Braun amide degradation. In this case, one C-N bond is cleaved.
Numerous traditional methods exist for nitrile preparation byamine oxidation.[13] In addition, several selective methods have been developed in the last decades forelectrochemical processes.[14]
The conversion ofaldehydes to nitriles viaaldoximes is a popular laboratory route. Aldehydes react readily withhydroxylamine salts, sometimes at temperatures as low as ambient, to give aldoximes. These can be dehydrated to nitriles by simple heating,[15] although a wide range of reagents may assist with this, includingtriethylamine/sulfur dioxide,zeolites, orsulfuryl chloride. The relatedhydroxylamine-O-sulfonic acid reacts similarly.[16]
In specialised cases theVan Leusen reaction can be used. Biocatalysts such asaliphatic aldoxime dehydratase are also effective.
Aromatic nitriles are often prepared in the laboratory from the aniline viadiazonium compounds. This is theSandmeyer reaction. It requires transition metal cyanides.[17]
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.
Thehydrolysis of nitriles RCN proceeds in the distinct steps under acid or base treatment to first givecarboxamidesRC(O)NH2 and thencarboxylic acidsRC(O)OH. The hydrolysis of nitriles to carboxylic acids is efficient. In acid or base, the balanced equations are as follows:
Strictly speaking, these reactions are mediated (as opposed tocatalyzed) 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 ofacetonitrile toacetamide is 1.6×10−6 M−1 s−1, which is slower than the hydrolysis of the amide to the carboxylate (7.4×10−5 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.[28] The classical procedure to convert a nitrile to the corresponding primary amide calls for adding the nitrile to cold concentratedsulfuric acid.[29] 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.Nitrilases hydrolyze nitriles to carboxylic acids:
Nitrile hydratases aremetalloenzymes that hydrolyze nitriles to amides.
These enzymes are used commercially to produceacrylamide.
The "anhydrous hydration" of nitriles to amides has been demonstrated using an oxime as water source:[30]
Nitriles are susceptible tohydrogenation over diverse metal catalysts. The reaction can afford either the primary amine (RCH2NH2) or the tertiary amine ((RCH2)3N), depending on conditions.[31] In conventionalorganic reductions, nitrile is reduced by treatment withlithium aluminium hydride to the amine. Reduction to theimine followed by hydrolysis to the aldehyde takes place in theStephen aldehyde synthesis, which usesstannous chloride in acid.
Alkyl nitriles are sufficiently acidic to undergo deprotonation of the C-H bond adjacent to theC≡N group.[32][33] Strong bases are required, such aslithium diisopropylamide andbutyl lithium. The product is referred to as anitrile anion. These carbanions alkylate a wide variety of electrophiles. Key to the exceptional nucleophilicity is the small steric demand of theC≡N unit combined with its inductive stabilization. These features make nitriles ideal for creating new carbon-carbon bonds in sterically demanding environments.
The carbon center of a nitrile iselectrophilic, hence it is susceptible tonucleophilic addition reactions:
Nitriles are precursors totransition metal nitrile complexes, which are reagents and catalysts. Examples includetetrakis(acetonitrile)copper(I) hexafluorophosphate ([Cu(MeCN)4]+) andbis(benzonitrile)palladium dichloride (PdCl2(PhCN)2).[40]
2.jpg)
Cyanamides areN-cyano compounds with general structureR1R2N−C≡N and related to the parentcyanamide.[41]
Nitrile oxides have thechemical formulaRCNO. Their general structure isR−C≡N+−O−. The R stands for any group (typicallyorganyl, e.g., acetonitrile oxideCH3−C≡N+−O−,hydrogen in the case offulminic acidH−C≡N+−O−, orhalogen (e.g., chlorine fulminateCl−C≡N+−O−).[42]: 1187–1192
Nitrile oxides are quite different from nitriles: they are highly reactive1,3-dipoles, and cannot be synthesized from the direct oxidation of nitriles.[43] Instead, they can be synthesised bynitroalkane dehydration,oxime dehydrogenation,[44]: 934–936 or halooxime elimination in base.[45] They are used in1,3-dipolar cycloadditions,[42]: 1187–1192 such as toisoxazoles.[44]: 1201–1202 They undergo type 1dyotropic rearrangement toisocyanates.[42]: 1700
The heavier nitrile sulfides are extremely reactive and rare, but temporarily form during thethermolysis ofoxathiazolones. Theyreact similarly to nitrile oxides.[46]
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 ofBrassica crops (such as cabbage, Brussels sprouts, and cauliflower), which release nitriles through hydrolysis.Mandelonitrile, acyanohydrin produced by ingesting almonds or some fruit pits, releases hydrogen cyanide and is responsible for the toxicity of cyanogenic glycosides.[47]
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, fromvildagliptin, an antidiabetic drug, toanastrozole, 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.[48] The nitrile functional group is found in several drugs.
{{cite journal}}: CS1 maint: multiple names: authors list (link);Collected Volumes, vol. 6, p. 307.