Nitrile

{{Short description|Organic compound with a –C≡N functional group}} {{about|the class of organic compounds|the synthetic rubber product|Nitrile rubber}} {{distinguish|Cyanide}} {{Use dmy dates|date=January 2023}} thumb|class=skin-invert-image|The structure of a nitrile: the functional group is highlighted blue

In organic chemistry, a '''nitrile''' is any organic compound that has a {{chem2|\sC\tN}} functional group. The name of the compound is composed of a base, which includes the carbon of the {{chem2|\sC\tN}}, suffixed with "nitrile", so for example {{chem2|CH3CH2C\tN}} is called "propionitrile" (or propanenitrile).<ref>IUPAC Gold Book [http://goldbook.iupac.org/N04151.html ''nitriles'']</ref> 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-free 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 cyanocarbons.

Inorganic compounds containing the {{chem2|\sC\tN}} group are not called nitriles, but cyanides instead.<ref>NCBI-MeSH [https://www.ncbi.nlm.nih.gov/mesh/68009570 ''Nitriles'']</ref> Though both nitriles and cyanides can be derived from cyanide salts, most nitriles are not nearly as toxic.

==Structure and basic properties== 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 a triple bond.<ref>{{cite journal | last1 = Karakida | first1 = Ken-ichi | last2 = Fukuyama | first2 = Tsutomu | last3 = Kuchitsu | first3 = Kozo | year = 1974 | title = Molecular Structures of Hydrogen Cyanide and Acetonitrile as Studied by Gas Electron Diffraction | journal = Bulletin of the Chemical Society of Japan | volume = 47 | issue = 2| pages = 299–304 | doi=10.1246/bcsj.47.299| doi-access = free }}</ref> Nitriles are polar, as indicated by high dipole moments. As liquids, they have high relative permittivities, often in the 30s.

==History== thumb|Joseph Louis Gay-Lussac was the first to produce dicyan in 1815The first compound of the homolog row of nitriles, the nitrile of formic acid, hydrogen cyanide was first synthesized by C. W. Scheele in 1782.<ref>See: *Carl W. Scheele (1782) [https://books.google.com/books?id=mHVJAAAAcAAJ&pg=PA264 "Försök, beträffande det färgande ämnet uti Berlinerblå"] (Experiment concerning the colored substance in Berlin blue), ''Kungliga Svenska Vetenskapsakademiens handlingar'' (Royal Swedish Academy of Science's Proceedings), 3: 264–275 (in Swedish). *Reprinted in Latin as: [https://books.google.com/books?id=BLo5AAAAcAAJ&pg=PA148 "De materia tingente caerulei berolinensis"] in: Carl Wilhelm Scheele with Ernst Benjamin Gottlieb Hebenstreit (ed.) and Gottfried Heinrich Schäfer (trans.), ''Opuscula Chemica et Physica'' (Leipzig ("Lipsiae"), (Germany): Johann Godfried Müller, 1789), vol. 2, pages 148–174.</ref><ref name="CR48">{{cite journal | title = The Preparation of Nitriles | journal = Chemical Reviews | pages = 189–283 | author = David T. Mowry | doi = 10.1021/cr60132a001 | volume = 42 | issue = 2 | year = 1948 | pmid=18914000}}</ref> In 1811 J. L. Gay-Lussac was able to prepare the very toxic and volatile pure acid.<ref>Gay-Lussac produced pure, liquified hydrogen cyanide in: {{cite journal | last1 = Gay-Lussac | first1 = J | year = 1811 | title = "Note sur l'acide prussique" (Note on prussic acid) | url = https://books.google.com/books?id=uJs5AAAAcAAJ&pg=PA128 | journal = Annales de chimie | volume = 44 | pages = 128–133 }}</ref> Around 1832 benzonitrile, the nitrile of benzoic acid, was prepared by Friedrich Wöhler and Justus von Liebig, but due to minimal yield of the synthesis neither physical nor chemical properties were determined nor a structure suggested. In 1834 Théophile-Jules Pelouze synthesized propionitrile, suggesting it to be an ether of propionic alcohol and hydrocyanic acid.<ref name="Pelouze1834">{{cite journal |title=Notiz über einen neuen Cyanäther |trans-title=Note on a new cyano-ether |url=https://books.google.com/books?id=P0s9AAAAcAAJ&pg=PA249 |journal=Annalen der Pharmacie |page=249 |author=J. Pelouze |doi=10.1002/jlac.18340100302 |volume=10 |issue=3 |year=1834}}</ref> The synthesis of benzonitrile by Hermann 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 ammonium formate. He coined the name "nitrile" for the newfound substance, which became the name for this group of compounds.<ref name=":21">{{citation|author=David T. Mowry |date=1948-04-01 |doi=10.1021/cr60132a001 |issue=2 |pages=189–283 |journal=Chemical Reviews |title=The Preparation of Nitriles. |volume=42 |pmid=18914000 }}</ref><ref>{{cite journal |journal=Annalen der Chemie und Pharmacie |volume=49 |issue=1 |pages=91–97 |year=1844 |title=Ueber die Zersetzung des benzoësauren Ammoniaks durch die Wärme (On the decomposition of ammonium benzoate by heat) |author=Hermann Fehling |url=https://books.google.com/books?id=2U09AAAAcAAJ&pg=PA91 |doi=10.1002/jlac.18440490106}} On page 96, Fehling writes: "Da Laurent den von ihm entdeckten Körper schon Nitrobenzoyl genannt hat, auch schon ein Azobenzoyl existirt, so könnte man den aus benzoësaurem Ammoniak entstehenden Körper vielleicht Benzonitril nennen." (Since Laurent named the substance that was discovered by him "nitrobenzoyl" – also an "azobenzoyl" already exists – so one could name the substance that originates from ammonium benzoate perhaps "benzonitril".)</ref>

In 1903, Arthur Lapworth investigated the formation of cyanohydrins by addition of hydrocyanic acid to aldehydes and ketones and discovered that the actual nucleophile is the cyanide ion, such that the addition of a base increases the reaction rate. This work represented one of the earliest investigations of an organic reaction mechanism.<ref>{{citation|author=Arthur Lapworth |date=1903 |doi=10.1039/CT9038300995 |pages=995–1005 |journal=J. Chem. Soc., Trans. |title=XCVI.—Reactions involving the addition of hydrogen cyanide to carbon compounds |volume=83}}</ref><ref name=":9">{{citation|author=Robert J. H. Gregory |date=1999-12-08 |doi=10.1021/cr9902906 |issue=12 |pages=3649–3682 |journal=Chemical Reviews |title=Cyanohydrins in Nature and the Laboratory: Biology, Preparations, and Synthetic Applications |volume=99 |pmid=11849033 |bibcode=1999ChRv...99.3649G }}</ref>

For a long time, nitriles were primarily of academic interest. Between the First and Second World War, however, research activity increased significantly.<ref name=":21" /> By the second half of the 20th century, several large-scale industrial processes had been developed in which nitriles were either produced or utilized. An important example is the development of polyamides (polyamide 6.6) in the 1930s, as adiponitrile is a key intermediate in its manufacture and is produced by hydrocyanation of butadiene with hydrogen cyanide.<ref>{{citation|date=1977 |isbn=0-8247-2452-6 |location=New York |publisher=Dekker |title=Encyclopedia of chemical processing and design. 2: Additives to alpha}}</ref><ref name=":26">{{citation|author=Ji Yang, Peng Wang, Helfried Neumann, Ralf Jackstell, Matthias Beller |date=2023 |doi=10.1039/D3IM00009E |issue=2 |pages=155–174 |journal=Industrial Chemistry & Materials |title=Industrially applied and relevant transformations of 1,3-butadiene using homogeneous catalysts |volume=1|doi-access=free }}</ref> Acrylonitrile polymers have been known since the 1920s but gained greater importance as synthetic fibers toward the late 1940s.<ref name=":0">{{citation|date=2016 |isbn=978-0-429-10162-5 |pages=157–186 |journal=Handbook of Thermoplastics |publisher=CRC Press |title=Polyacrylonitrile}}</ref> Superglues based on cyanoacrylates have also been available since the late 1940s.<ref name=":22" />

== Nomenclature == [[File:Butyronitrile StructureV2.svg|thumb|Butyronitrile, according to IUPAC: Butanenitrile ('''blue''' marked C atom belongs to the main chain), formally also propanecarbonitrile ('''blue''' marked C atom belongs to the substituent)]]

The functional group of nitriles containing the {{chem2|C\tN}} triple bond is referred to as the nitrile or cyano group.<ref name="Beyer">Hans Beyer und Wolfgang Walter: ''Organische Chemie'', S. Hirzel Verlag, Stuttgart, 22. Auflage, 1991, ISBN 3-7776-0485-2, S. 266–269.</ref> If the nitrile is the highest-ranking functional group, the suffix ''-nitrile'' is added to the name of the parent compound. The triply bonded carbon atom is, as always, included in the parent chain.<ref>{{GoldBookRef|title=nitriles|file=N04151}}</ref> Alternatively, the ending ''-carbonitrile'' may be used (analogous to ''-carboxylic acid''), in which case the carbon atom is ''not'' counted as part of the parent chain.<ref>{{GoldBookRef|title=carbonitriles|file=C00838}}</ref> This ending must be used if the nitrile group is attached to a ring (as in {{ill|cyclopentanecarbonitrile|qid=Q28973667|s=1}}) or if not all carbon atoms are part of the parent chain, which is necessarily the case when more than two nitrile groups are present, as these can only be located at the termini of the chain.<ref name=":23">{{citation|author=Karl-Heinz Hellwich |date=1998 |edition=3., überarb. Aufl |isbn=3-7741-1095-6 |location=Eschborn |publisher=Govi-Verl |title=Chemische Nomenklatur: die systematische Benennung organisch-chemischer Verbindungen ; ein Lehrbuch für Pharmazie- und Chemiestudenten}}</ref> Due to their relationship to carboxylic acids (the nitrile carbon has the same oxidation state as the carboxyl carbon), trivial names are often derived from the corresponding carboxylic acids using the ending ''-onitrile'' (for example, benzoic acid to benzonitrile).<ref name=":16">{{citation|author=Kurt Peter C. Vollhardt, Neil Eric Schore |date=2011 |edition=5. Aufl |isbn=978-3-527-32754-6 |location=Weinheim |publisher=Wiley-VCH |title=Organische Chemie. Hauptbd.}}</ref> If the nitrile function is ''not'' the principal functional group in the molecule, the prefix ''cyano-'' is used together with the appropriate locant. In this case as well, the triple-bonded carbon atom is ''not'' counted as part of the parent chain.<ref name=":23" />

== Synthesis == Numerous methods are available for the preparation of nitriles. These include Kolbe nitrile synthesis, dehydration of carboxylic acid amides and oximes, and oxidation of primary amines.

Industrially, the main methods for producing nitriles are ammoxidation and hydrocyanation. Both routes are green in the sense that they do not generate stoichiometric amounts of salts.

===From organic halides and cyanide salts=== Two salt metathesis reactions are popular for laboratory scale reactions. In the Kolbe nitrile synthesis, alkyl halides undergo nucleophilic aliphatic substitution with alkali metal cyanides. Aryl nitriles are prepared in the Rosenmund-von Braun synthesis.

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).<ref name="CR48" />

In the Kolbe nitrile synthesis (a nucleophilic substitution reaction), an alkanonitrile and an alkali halide are formed from a reactive halocarbons and an alkali cyanide (sodium cyanide or potassium cyanide). The reaction is particularly suitable for primary, allylic, and benzylic halides. Secondary alkyl halides provide lower yields, whereas tertiary halides undergo exclusively elimination reaction instead of substitution. In addition to halides, substrates bearing other good leaving groups may also be employed. In contrast to alkali cyanides, silver cyanide is unsuitable for nitrile synthesis, as it preferentially forms isonitriles.<ref name=":8">{{citation|author=Thomas Laue, Andreas Plagens |date=1994 |doi=10.1007/978-3-322-94726-0 |journal=Teubner Studienbücher Chemie |title=Namen- und Schlagwort-Reaktionen der Organischen Chemie |isbn=978-3-519-03526-8 }}</ref> An example of the Kolbe nitrile synthesis is the reaction of methyl iodide with sodium cyanide to yield acetonitrile and sodium iodide:<ref>{{citation|author=K. R. Lynn, Peter E. Yankwich |date=January 1961 |doi=10.1021/ja01462a010 |issue=1 |pages=53–57 |journal=Journal of the American Chemical Society |title=Cyanide Carbon Isotope Fractionation in the Reaction of Cyanide Ion and Methyl Iodide. Carbon Isotope Effect in the Hydrolysis of Methyl Iodide |volume=83 |bibcode=1961JAChS..83...53L }}</ref>

<math>\mathrm{CH_3I + NaCN \longrightarrow CH_3CN + NaI}</math>

Similarly, 1,3-dibromopropane reacts with sodium cyanide to form glutaronitrile<ref>{{citation|author=G. E. Ham, Jane Stevens |date=December 1962 |doi=10.1021/jo01059a504 |issue=12 |pages=4638–4639 |journal=The Journal of Organic Chemistry |title=Reaction of 1,2-Dihaloethanes with Sodium Cyanide |volume=27}}</ref>, and 1-iodooctane reacts with potassium cyanide to give nonannitrile.<ref>{{citation|author=Cinzia Chiappe, Daniela Pieraccini, Paola Saullo |date=2003-08-01 |doi=10.1021/jo026838h |issue=17 |pages=6710–6715 |journal=The Journal of Organic Chemistry |title=Nucleophilic Displacement Reactions in Ionic Liquids: Substrate and Solvent Effect in the Reaction of NaN 3 and KCN with Alkyl Halides and Tosylates |volume=68 |pmid=12919037 }}</ref> Cyanations can also be carried out using hydrogen cyanide in combination with triethylaluminum or with diethylaluminum cyanide; for example, in the ring opening of an epoxide to a β-cyanohydrin or in the 1,4-addition of cyanide to an enone.<ref>{{citation|author=W. Nagata, M. Yoshioka, S. Hirai |date=June 1972 |doi=10.1021/ja00768a037 |issue=13 |pages=4635–4643 |journal=Journal of the American Chemical Society |title=Hydrocyanation. IV. New hydrocyanation methods using hydrogen cyanide and an alkylaluminum, and an alkylaluminum cyanide |volume=94 |bibcode=1972JAChS..94.4635N }}</ref><ref>{{citation|author=W. Nagata, M. Yoshioka, T. Okumura |date=1970 |doi=10.1039/j39700002365 |issue=17 |page=2365 |journal=Journal of the Chemical Society C: Organic |title=Hydrocyanation. Part X. Cleavage of epoxides with hydrogen cyanide and triethylaluminium and with diethylaluminium cyanide}}</ref> Trimethylsilylcyanide is another cyanating reagent capable of opening epoxides to β-cyanohydrins, with concomitant silylation of the oxygen atom.<ref>{{citation|author=Jeffrey C. Mullis, William P. Weber |date=July 1982 |doi=10.1021/jo00136a011 |issue=15 |pages=2873–2875 |journal=The Journal of Organic Chemistry |title=Regiospecificity of reactions of epoxides and oxetanes with trimethylsilyl cyanide |volume=47}}</ref> Trimethylsilyl cyanide also enables substitution of tertiary alkyl halides, which is not feasible under Kolbe nitrile synthesis conditions.<ref name=":8" />

In the presence of suitable transition metal catalysts, hydrocyanation allows addition of hydrogen cyanide to the multiple bonds of alkenes and alkynes to afford nitriles. Nickel catalysts are typically employed. Direct handling of hydrogen cyanide is often unnecessary, as synthetic equivalents such as acetone cyanohydrin or isovaleronitrile may be used.<ref>{{citation|author=Hongru Zhang, Xin Su, Kaiwu Dong |date=2020 |doi=10.1039/C9OB02374G |issue=3 |pages=391–399 |journal=Organic & Biomolecular Chemistry |title=Recent progress in transition-metal-catalyzed hydrocyanation of nonpolar alkenes and alkynes |volume=18}}</ref> An important industrial process is the hydrocyanation of butadiene to adiponitrile.<ref name=":26" />

=== Hydrocyanation === Hydrocyanation is an industrial method for producing nitriles from hydrogen cyanide and alkenes. The process requires homogeneous catalysts. An example of hydrocyanation is the production of adiponitrile, a precursor to nylon-6,6 from 1,3-butadiene: :{{chem2|CH2\dCH\sCH\dCH2 + 2 HC\tN -> NC(CH2)4C\tN}}

=== Dehydration of amides and others === Nitriles can be prepared by the dehydration of primary amides. Common reagents for this include phosphorus pentoxide ({{chem2|P2O5}})<ref>{{cite journal |title=ISOBUTYRONITRILE |journal=Organic Syntheses |date=1945 |volume=25 |page=61 |doi=10.15227/orgsyn.025.0061 |doi-access=}}</ref> and thionyl chloride ({{chem2|SOCl2}}).<ref>{{cite journal |date=1952 |title=2-ETHYLHEXANONITRILE |journal=Organic Syntheses |volume=32 |page=65 |doi=10.15227/orgsyn.032.0065 |doi-access=}}</ref> In a related dehydration, secondary amides give nitriles by the von Braun amide degradation. In this case, one C-N bond is cleaved.

:class=skin-invert-image|200px|Amide dehydration thumb|350px|Production of nitriles (center) by dehydration. Suitable starting materials are carboxylic acid amides (left) or aldoximes (right). The atoms of the eliminated water molecule are highlighted in blue

Specifically, carboxamides and oximes can be converted to nitriles by dehydration (elimination of water). Numerous reagents and methodologies are available for this transformation.<ref name=":4">{{citation|author=Muthupandian Ganesan, Paramathevar Nagaraaj |date=2020 |doi=10.1039/D0QO00843E |issue=22 |pages=3792–3814 |journal=Organic Chemistry Frontiers |title=Recent developments in dehydration of primary amides to nitriles |volume=7}}</ref><ref name=":5">{{citation|author=Dilip Konwar, Monalisa Boruah, Gautom Kumar Sarmah, Nayan Kamal Bhattacharyya, Naleen Borthakur, Birendra Nath Goswami, Kumar Ranjan Boruah |date=November 2001 |doi=10.3184/030823401103168604 |issue=11 |pages=490–492 |journal=Journal of Chemical Research |title=Aluminium Chloride and Sodium Iodide (AlCl3-NaI): A Versatile Dehydrating Agent |volume=2001}}</ref><ref name=":6">{{citation|author=Imen Talbi, Mohamed Lotfi Efrit, Soufiane Touil |date=2018-05-31 |doi=10.1021/acsomega.8b00544 |issue=5 |pages=5078–5082 |journal=ACS Omega |pmc=6641971 |pmid=31458722 |title=Efficient New Protocols for Converting Primary Amides into Nitriles Initiated by P(NMe 2 ) 3 , PCl 3 , or P(OPh) 3 |volume=3 |doi-access=free }}</ref> Methods for nitrile synthesis via dehydration of nitroalkanes have also been described.<ref>{{citation|author=Muthupandian Ganesan |date=2021-12-22 |doi=10.2174/1385272825666211126124835 |issue=24 |pages=2990–3003 |journal=Current Organic Chemistry |title=Methods for Direct Conversion of Primary Nitroalkanes to Nitriles |volume=25}}</ref>

Phosphorus pentoxide, known since the mid-19th century, is a classical reagent for amide dehydration.<ref name=":4" /> Amides can also be dehydrated using trivalent phosphorus reagents such as phosphorus trichloride or triphenyl phosphite;<ref name=":6" /> as well as diethyl chlorophosphate,<ref>{{citation|author=Z. Shahsavari-Fard, A. R. Sardarian |date=March 2011 |doi=10.1007/BF03246217 |issue=1 |pages=204–208 |journal=Journal of the Iranian Chemical Society |title=Diethyl chlorophosphate: A new alternative reagent for dehydration of primary amides to nitriles in solvent and solvent-free conditions |volume=8}}</ref> thionyl chloride<ref>{{citation|date=1952 |doi=10.15227/orgsyn.032.0065 |page=65 |journal=Organic Syntheses |title=2-ETHYLHEXANONITRILE |volume=32}}</ref>, or phosgene.<ref>{{citation|author=Harry Babad, Andrew G. Zeiler |date=1973-02-01 |doi=10.1021/cr60281a005 |issue=1 |pages=75–91 |journal=Chemical Reviews |title=Chemistry of phosgene |volume=73 |bibcode=1973ChRv...73...75B }}</ref> In the presence of specific palladium complexes or other suitable catalysts, acetonitrile can function as a dehydrating agent, converting an amide into a nitrile while being transformed into acetamide. Similarly, dichloroacetonitrile may be employed.<ref>{{citation|author=Mohammed H. Al-Huniti, Mitchell P. Croatt |date=October 2019 |doi=10.1002/ajoc.201900343 |issue=10 |pages=1791–1799 |journal=Asian Journal of Organic Chemistry |title=Metal-Catalyzed Dehydration of Primary Amides to Nitriles |volume=8}}</ref><ref>{{citation|author=Hiroyuki Okabe, Asuka Naraoka, Takahiro Isogawa, Shunsuke Oishi, Hiroshi Naka |date=2019-06-21 |doi=10.1021/acs.orglett.9b01657 |issue=12 |pages=4767–4770 |journal=Organic Letters |title=Acceptor-Controlled Transfer Dehydration of Amides to Nitriles |volume=21 |pmid=31184196 }}</ref> Related systems utilize iron(II) chloride tetrahydrate, zinc trifluoromethanesulfonate, or uranyl nitrate as catalysts in combination with ''N''-methyl-''N''-trimethylsilyltrifluoroacetamide as the dehydrating reagent.<ref>{{citation|author=Stephan Enthaler |date=September 2011 |doi=10.1002/ejoc.201100754 |issue=25 |pages=4760–4763 |journal=European Journal of Organic Chemistry |title=Straightforward Iron-Catalyzed Synthesis of Nitriles by Dehydration of Primary Amides |volume=2011}}</ref><ref>{{citation|author=Stephan Enthaler |date=2011-08-16 |doi=10.1002/chem.201101478 |issue=34 |pages=9316–9319 |journal=Chemistry: A European Journal |title=Straightforward Uranium-Catalyzed Dehydration of Primary Amides to Nitriles |volume=17 |pmid=21728201 }}</ref><ref>{{citation|author=Stephan Enthaler, Shigeyoshi Inoue |date=2012-01-02 |doi=10.1002/asia.201100493 |issue=1 |pages=169–175 |journal=Chemistry: An Asian Journal |title=An Efficient Zinc-Catalyzed Dehydration of Primary Amides to Nitriles |volume=7 |pmid=21956861 }}</ref> Carboxylic acid amides can also be dehydrated using a system comprising triphenylphosphane, iodine, and 4-methylmorpholine.<ref>{{citation|author=Shekharappa, L. Roopesh Kumar, C. Srinivasulu, Vommina V. Sureshbabu |date=March 2021 |doi=10.1007/s10989-020-10101-y |issue=1 |pages=497–502 |journal=International Journal of Peptide Research and Therapeutics |title=Dehydration of Chiral α-Amides to Chiral α-Nitriles Under the Appel Reaction Conditions |volume=27}}</ref> Another approach involves high-temperature dehydration (220–240 °C) in hexamethylphosphoramide (HMPA).<ref>{{citation|author=Richard S. Monson, Deggary N. Priest |date=1971-09-01 |doi=10.1139/v71-480 |issue=17 |pages=2897–2898 |journal=Canadian Journal of Chemistry |title=Dehydration of Amides to Nitriles Initiated by Hexamethylphosphoric Triamide |volume=49}}</ref> Dehydration of primary amides with zinc chloride under microwaves is reversible. In aqueous acetonitrile, an amide can be converted to a nitrile; however, in a water–tetrahydrofuran system with added acetamide, the reverse conversion of nitrile to amide occurs.<ref>{{citation|author=Krishnappa Manjula, Mohamed Afzal Pasha |date=May 2007 |doi=10.1080/00397910701230147 |issue=9 |pages=1545–1550 |journal=Synthetic Communications |title=Rapid Method of Converting Primary Amides to Nitriles and Nitriles to Primary Amides by ZnCl 2 using Microwaves under Different Reaction Conditions |volume=37}}</ref>

Both carboxamides and aldoximes can be dehydrated using aluminum chloride and sodium iodide in acetonitrile.<ref name=":5" /> Likewise, both classes can be dehydrated with oxalyl chloride and catalytic dimethyl sulfoxide in a reaction analogous to the Swern oxidation.<ref>{{citation|author=Rui Ding, Yongguo Liu, Mengru Han, Wenyi Jiao, Jiaqi Li, Hongyu Tian, Baoguo Sun |date=2018-10-19 |doi=10.1021/acs.joc.8b02190 |issue=20 |pages=12939–12944 |journal=The Journal of Organic Chemistry |title=Synthesis of Nitriles from Primary Amides or Aldoximes under Conditions of a Catalytic Swern Oxidation |volume=83 |pmid=30240220 }}</ref> Conversion to nitriles under catalysis by heptavalent rhenium species (perrhenic acid or trimethylsilyl perrhenate) is effective for both amides and aldoximes; the water formed can be removed by azeotropic distillation.<ref>{{citation|author=Kazuaki Ishihara, Yoshiro Furuya, Hisashi Yamamoto |date=2002-08-16 |doi=10.1002/1521-3757(20020816)114:16<3109::AID-ANGE3109>3.0.CO;2-K |issue=16 |page=3109 |journal=Angewandte Chemie |title=Rhenium(VII) Oxo Complexes as Extremely Active Catalysts in the Dehydration of Primary Amides and Aldoximes to Nitriles |volume=114 |bibcode=2002AngCh.114.3109I }}</ref>

The conversion of aldehydes to nitriles via aldoximes 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,<ref>{{cite journal |last1=Chill |first1=Samuel T. |last2=Mebane |first2=Robert C. |date=18 September 2009 |title=A Facile One-Pot Conversion of Aldehydes into Nitriles |journal=Synthetic Communications |volume=39 |issue=20 |pages=3601–3606 |doi=10.1080/00397910902788174 |s2cid=97591561}}</ref> although a wide range of reagents may assist with this, including triethylamine/sulfur dioxide, zeolites, or sulfuryl chloride. The related hydroxylamine-O-sulfonic acid reacts similarly.<ref>{{cite journal |year=1974 |title=Hydroxylamine-''O''-sulfonic acid: A convenient reagent for the oxidative conversion of aldehydes into nitriles |language=German |volume=15 |issue=36 |pages=3187–3188 |doi=10.1016/S0040-4039(01)91857-X |surname1=C. Fizet |surname2=J. Streith |journal=Tetrahedron Lett.}}</ref>

:[[Image:2,5-Diformylfuran Bildung von 2,5-Dicyanofuran.svg|360px|thumb|class=skin-invert-image|One-pot synthesis from aldehyde (Amberlyst is an acidic ion-exchange resin.) ]]

In specialised cases the Van Leusen reaction can be used. Biocatalysts such as aliphatic aldoxime dehydratase are also effective.

Aldoximes may also be dehydrated with cyanuric chloride,<ref>{{citation|author=Jiban K. Chakrabarti, Terrence M. Hotten |date=1972 |doi=10.1039/c39720001226 |issue=22 |page=1226 |journal=Journal of the Chemical Society, Chemical Communications |title=A new route to nitriles. Dehydration of aldoximes using 2,4,6-trichloro-s-triazine (cyanuric chloride)}}</ref> the Burgess reagent,<ref>{{citation|date=2000 |doi=10.1055/s-2000-6752 |issue=8 |pages=1169–1171 |journal=Synlett |title=Mild and Efficient Dehydration of Oximes to Nitriles Mediated by the Burgess Reagent |volume=2000}}</ref> or a combination of trifluoromethanesulfonic acid anhydride and triphenylphosphine, the latter being oxidized to triphenylphosphine oxide.<ref>{{citation|author=Ziad Moussa, Saleh A. Ahmed, Ahmad S. ElDouhaibi, Shaya Y. Al-Raqa |date=April 2010 |doi=10.1016/j.tetlet.2010.01.119 |issue=14 |pages=1826–1831 |journal=Tetrahedron Letters |title=NMR Studies and electrophilic properties of triphenylphosphine–trifluoromethanesulfonic anhydride; a remarkable dehydrating reagent system for the conversion of aldoximes into nitriles |volume=51}}</ref> Catalytic dehydrogenation is likewise possible, for example with {{ill|iron(III) triflate|qid=Q72484900|s=1}},<ref>{{citation|author=Kengo Hyodo, Saki Kitagawa, Masayuki Yamazaki, Kingo Uchida |date=2016-05-06 |doi=10.1002/asia.201600085 |issue=9 |pages=1348–1352 |journal=Chemistry: An Asian Journal |title=Iron-Catalyzed Dehydration of Aldoximes to Nitriles Requiring Neither Other Reagents Nor Nitrile Media |volume=11 |pmid=26910510 }}</ref> copper(II) acetate,<ref>{{citation|author=Philipp Rommelmann, Tobias Betke, Harald Gröger |date=2017-10-20 |doi=10.1021/acs.oprd.7b00169 |issue=10 |pages=1521–1527 |journal=Organic Process Research & Development |title=Synthesis of Enantiomerically Pure N -Acyl Amino Nitriles via Catalytic Dehydration of Oximes and Application in a de Novo Synthesis of Vildagliptin |volume=21}}</ref> mixed hydroxides of tin and tungsten,<ref name=":7">{{citation|author=Kazuya Yamaguchi, Hiroshi Fujiwara, Yoshiyuki Ogasawara, Miyuki Kotani, Noritaka Mizuno |date=2007-05-18 |doi=10.1002/ange.200605004 |issue=21 |pages=3996–3999 |journal=Angewandte Chemie |title=A Tungsten–Tin Mixed Hydroxide as an Efficient Heterogeneous Catalyst for Dehydration of Aldoximes to Nitriles |volume=119 |bibcode=2007AngCh.119.3996Y }}</ref> or a bimetallic palladium–manganese catalyst.<ref>{{citation|author=Dongliang Zhang, Yaping Huang, Erlei Zhang, Rong Yi, Chao Chen, Lei Yu, Qing Xu |date=2018-02-15 |doi=10.1002/adsc.201701154 |issue=4 |pages=784–790 |journal=Advanced Synthesis & Catalysis |title=Pd/Mn Bimetallic Relay Catalysis for Aerobic Aldoxime Dehydration to Nitriles |volume=360}}</ref> Enzymatic dehydration of aldoximes using aldoxime dehydratases has also been achieved. These bacterial enzymes, including those from ''Pseudomonas chlororaphis'', have been applied repeatedly in nitrile synthesis.<ref>{{citation|author=Tobias Betke, Jun Higuchi, Philipp Rommelmann, Keiko Oike, Taiji Nomura, Yasuo Kato, Yasuhisa Asano, Harald Gröger |date=2018-04-16 |doi=10.1002/cbic.201700571 |issue=8 |pages=768–779 |journal=ChemBioChem |title=Biocatalytic Synthesis of Nitriles through Dehydration of Aldoximes: The Substrate Scope of Aldoxime Dehydratases |volume=19}}</ref>

=== Preparation from aldehydes and ketones === thumb|The Van Leusen reagent enables conversion of carbonyl compounds into nitriles

Aldehydes can be converted into oximes using hydroxylamine hydrochloride and subsequently dehydrated to nitriles (e.g., with oxalyl chloride).<ref>{{citation|author=Liyuan Lan, Shuai Huang, Yongguo Liu, Baoguo Sun, Hongyu Tian |date=July 2020 |doi=10.1002/ffj.3581 |issue=4 |pages=425–434 |journal=Flavour and Fragrance Journal |title=Preparation and odor characteristics of nitriles derived from aldehydes |volume=35}}</ref> Direct transformation of aldehydes to nitriles is also possible using hydroxylamine-O-sulfonic acid<ref>{{citation|author=Dylan J. Quinn, Graham J. Haun, Gustavo Moura-Letts |date=August 2016 |doi=10.1016/j.tetlet.2016.07.047 |issue=34 |pages=3844–3847 |journal=Tetrahedron Letters |title=Direct synthesis of nitriles from aldehydes with hydroxylamine-O-sulfonic acid in acidic water |volume=57}}</ref> or {{ill|O-(4-trifluoromethylbenzoyl)hydroxylamine|lt=''O''-(4-trifluoromethylbenzoyl)hydroxylamine|qid=Q125548236|s=1}}.<ref>{{citation|author=Xiao-De An, Shouyun Yu |date=2015-10-16 |doi=10.1021/acs.orglett.5b02547 |issue=20 |pages=5064–5067 |journal=Organic Letters |title=Direct Synthesis of Nitriles from Aldehydes Using an O -Benzoyl Hydroxylamine (BHA) as the Nitrogen Source |volume=17}}</ref> Such conversions can also be accomplished with hydroxylamine in the presence of titanium(IV) chloride or mixed tin–tungsten hydroxides as catalysts<ref name=":7" /><ref>{{citation|author=Antonella Leggio, Emilia Lucia Belsito, Sonia Gallo, Angelo Liguori |date=April 2017 |doi=10.1016/j.tetlet.2017.03.007 |issue=15 |pages=1512–1514 |journal=Tetrahedron Letters |title=One-pot conversion of aldehydes to nitriles mediated by TiCl 4 |volume=58}}</ref>, or by addition of sulfuryl fluoride or selenium dioxide.<ref>{{citation|date=1999-04-15 |doi=10.1021/op990022+ |issue=4 |pages=292 |journal=Organic Process Research & Development |title=Lewis Acid Reagents Edited by H. Yamamoto. Oxford University Press:  Oxford, UK. 1999. 270 pp. £75.00, ISBN 0 19 850099 8. |volume=3}}</ref><ref>{{citation|author=Jitendra Gurjar, Jorick Bater, Valery V. Fokin |date=2019-02-06 |doi=10.1002/chem.201805175 |issue=8 |pages=1906–1909 |journal=Chemistry: A European Journal |title=Sulfuryl Fluoride Mediated Conversion of Aldehydes to Nitriles |volume=25 |bibcode=2019ChEuJ..25.1906G }}</ref> Tosylmethylisocyanide (Van Leusen reagent) enables direct conversion of ketones into nitriles via the Van Leusen reaction, introducing the entire nitrile group and thus an additional carbon atom.<ref>{{citation|author=Albert M. van Leusen, Piet G. Oomkes |date=January 1980 |doi=10.1080/00397918008061830 |issue=5 |pages=399–403 |journal=Synthetic Communications |title=One-Step Conversion of Aldehydes to Nitriles. Introduction of a One-Carbon Unit |volume=10}}</ref><ref>{{citation|author=Otto H. Oldenziel, Daan Van Leusen, Albert M. Van Leusen |date=September 1977 |doi=10.1021/jo00439a002 |issue=19 |pages=3114–3118 |journal=The Journal of Organic Chemistry |title=Chemistry of sulfonylmethyl isocyanides. 13. A general one-step synthesis of nitriles from ketones using tosylmethyl isocyanide. Introduction of a one-carbon unit |volume=42}}</ref><ref>{{citation|author=Niamh Disney, Megan Smyth, Scott Wharry, Thomas S. Moody, Marcus Baumann |date=2024 |doi=10.1039/D3RE00458A |journal=Reaction Chemistry & Engineering |title=A cyanide-free synthesis of nitriles exploiting flow chemistry|volume=9 |issue=2 |pages=349–354 |doi-access=free }}</ref>

=== Oxidation of primary amines === thumb|TEMPO is suitable as a catalyst for the catalytic oxidation of primary amines to nitriles

Numerous traditional methods exist for nitrile preparation by amine oxidation.<ref>{{cite journal |last1=Schümperli |first1=Martin T. |last2=Hammond |first2=Ceri |last3=Hermans |first3=Ive |date=2021 |title=Developments in the Aerobic Oxidation of Amines |journal=ACS Catal. |volume=2 |issue=6 |pages=1108–1117 |doi=10.1021/cs300212q |doi-access=}}</ref> Common methods include the use of potassium persulfate,<ref>{{cite journal |last1=Yamazaki |first1=Shigekazu |last2=Yamazaki |first2=Yasuyuki |date=1990 |title=Nickel-catalyzed dehydrogenation of amines to nitriles |journal=Bulletin of the Chemical Society of Japan |volume=63 |issue=1 |pages=301–303 |doi=10.1246/bcsj.63.301 |doi-access=free}}</ref> Trichloroisocyanuric acid,<ref>{{cite journal |last1=Chen |first1=Fen-Er |last2=Kuang |first2=Yun-Yan |last3=Hui-Fang |first3=Dai |last4=Lu |first4=Liang |date=2003 |title=A Selective and Mild Oxidation of Primary Amines to Nitriles with Trichloroisocyanuric Acid |journal=Synthesis |volume=17 |issue=17 |pages=2629–2631 |doi=10.1055/s-2003-42431}}</ref> or anodic electrosynthesis.<ref>{{cite journal |last1=Schäfer |first1=H. J. |last2=Feldhues |first2=U. |date=1982 |title=Oxidation of Primary Aliphatic Amines to Nitriles at the Nickel Hydroxide Electrode |journal=Synthesis |volume=1982 |issue=2 |pages=145–146 |doi=10.1055/s-1982-29721 |s2cid=97172564}}</ref> In addition, several selective methods have been developed in the last decades for electrochemical processes.<ref>{{cite journal |last1=Xu |first1=Zhining |last2=Kovács |first2=Ervin |date=2024 |title=Beyond traditional synthesis: Electrochemical approaches to amine oxidation for nitriles and imines |journal=ACS Org Inorg Au |volume=4 |issue=5 |pages=471–484 |doi=10.1021/acsorginorgau.4c00025 |pmc=11450732 |doi-access=free |pmid=39371318 }}</ref>

Several procedures employ nitroxyl radicals such as TEMPO or 4-acetamido-TEMPO as catalytic oxidants. These catalysts can be regenerated either by potassium peroxymonosulfate as the stoichiometric oxidant or electrochemically under applied potential.<ref>{{citation|author=M. F. Semmelhack, Christopher R. Schmid |date=October 1983 |doi=10.1021/ja00360a042 |issue=22 |pages=6732–6734 |journal=Journal of the American Chemical Society |title=Nitroxyl-mediated electro-oxidation of amines to nitriles and carbonyl compounds |volume=105 |bibcode=1983JAChS.105.6732S }}</ref><ref>{{citation|author=Kyle M. Lambert, James M. Bobbitt, Sherif A. Eldirany, Liam E. Kissane, Rose K. Sheridan, Zachary D. Stempel, Francis H. Sternberg, William F. Bailey |date=2016-04-04 |doi=10.1002/chem.201600549 |issue=15 |pages=5156–5159 |journal=Chemistry: A European Journal |title=Metal-Free Oxidation of Primary Amines to Nitriles through Coupled Catalytic Cycles |volume=22 |pmid=26868873 }}</ref> Another approach utilizes copper(I) chloride or copper(II) chloride as catalyst, molecular oxygen as the stoichiometric oxidant, and a molecular sieve to remove the water formed.<ref>{{citation|author=Yasunari Maeda, Takahiro Nishimura, Sakae Uemura |date=December 2003 |doi=10.1246/bcsj.76.2399 |issue=12 |pages=2399–2403 |journal=Bulletin of the Chemical Society of Japan |title=Copper-Catalyzed Oxidation of Amines with Molecular Oxygen |volume=76}}</ref>

=== Ammoxidation === In ammoxidation, a hydrocarbon is partially oxidized in the presence of ammonia. This conversion is practiced on a large scale for acrylonitrile:<ref>{{Ullmann|doi=10.1002/14356007.a17_363|chapter=Nitriles|year=2000|last1=Pollak|first1=Peter|last2=Romeder|first2=Gérard|last3=Hagedorn|first3=Ferdinand|last4=Gelbke|first4=Heinz-Peter|isbn=3527306730}}</ref>

:2 {{chem2|CH3CH\dCH2}} + 3 {{chem2|O2 + 2 NH3 -> 2 N\tCCH\dCH2 + 6 H2O}}

In the production of acrylonitrile, a side product is acetonitrile. On an industrial scale, several derivatives of benzonitrile, phthalonitrile, as well as Isobutyronitrile are prepared by ammoxidation. The process is catalysed by metal oxides and is assumed to proceed via the imine.

Ammoxidation is a heterogeneously catalyzed gas-phase reaction in which aliphatic or methyl-substituted aromatic compounds react with oxygen (air) and ammonia to form nitriles, with water as a by-product. Reaction temperatures exceed 300 °C, and oxides of vanadium, chromium, or molybdenum serve as catalysts.<ref>{{citation|author=Christiane Janke, Jörg Radnik, Ursula Bentrup, Andreas Martin, Angelika Brückner |date=2009-11-30 |doi=10.1002/cctc.200900180 |issue=4 |pages=485–491 |journal=ChemCatChem |title=Vanadium-Containing Oxynitrides: Effective Catalysts for the Ammoxidation of 3-Picoline |volume=1}}</ref> Acrylonitrile, an important precursor for polymer production (see Use section), is primarily manufactured by ammoxidation of propene.<ref name=":0" /> The principal industrial route to hydrogen cyanide is the Andrussov process, i.e., ammoxidation of methane over a platinum catalyst. However, a significant proportion of global hydrogen cyanide production arises as a by-product of acrylonitrile manufacture.<ref name=":25">{{citation|author=David Nakles, Richard Luthy, George Wong-Chong |date=2005-12-09 |pages=41–55 |journal=Cyanide in Water and Soil |publisher=CRC Press |title=Manufacture and the Use of Cyanide}}</ref>

=== Preparation of aromatic nitriles === thumb|300px|Preparation of aryl nitriles from quinones by reductive aromatization of silylated cyanohydrin intermediates

Aryl nitriles can be synthesized via the Sandmeyer reaction of diazonium salts with copper(I) cyanide<ref>{{citation|author=Irina P. Beletskaya, Alexander S. Sigeev, Alexander S. Peregudov, Pavel V. Petrovskii |date=November 2004 |doi=10.1016/j.jorganchem.2004.07.019 |issue=23 |pages=3810–3812 |journal=Journal of Organometallic Chemistry |title=Catalytic Sandmeyer cyanation as a synthetic pathway to aryl nitriles |volume=689}}</ref> or by the Rosenmund-von Braun reaction (direct reaction of an aryl bromide with copper(I) cyanide).<ref>{{citation|author=C. Frederick Koelsch |date=August 1936 |doi=10.1021/ja01299a004 |issue=8 |pages=1328–1330 |journal=Journal of the American Chemical Society |title=Some Applications of the Rosenmund-v. Braun Nitrile Synthesis |volume=58 |bibcode=1936JAChS..58.1328K }}</ref> Conversion of thiocyanate with aromatic carboxylic acids, known as Letts nitrile synthesis, can be carried out using potassium thiocyanate; lead thiocyanate generally provides higher yields.<ref name=":21" />

Aryl iodides can be converted into aromatic nitriles under palladium catalysis with trimethylsilyl cyanide. For example, iodobenzene reacts with trimethylsilyl cyanide in the presence of tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4) to form benzonitrile.<ref>{{citation|author=Naoto Chatani, Terukiyo Hanafusa |date=November 1986 |doi=10.1021/jo00374a041 |issue=24 |pages=4714–4716 |journal=The Journal of Organic Chemistry |title=Transition-metal-catalyzed reactions of trimethylsilyl cyanide. 4. Palladium-catalyzed cyanation of aryl halides by trimethylsilyl cyanide |volume=51}}</ref> Another palladium-catalyzed route (also employing Pd(PPh3)4) is the decarbonylation of aromatic acyl cyanides.<ref>{{citation|author=Shunichi Murahashi, Takeshi Naota, Nobuyuki Nakajima |date=March 1986 |doi=10.1021/jo00356a029 |issue=6 |pages=898–901 |journal=The Journal of Organic Chemistry |title=Palladium-catalyzed decarbonylation of acyl cyanides |volume=51}}</ref> Palladium-catalyzed cyanation of aryl chlorides with potassium cyanide<ref>{{citation|author=Mark Sundermeier, Alexander Zapf, Matthias Beller, Jürgen Sans |date=September 2001 |doi=10.1016/S0040-4039(01)01390-9 |issue=38 |pages=6707–6710 |journal=Tetrahedron Letters |title=A new palladium catalyst system for the cyanation of aryl chlorides |volume=42}}</ref> or potassium hexacyanidoferrate(II)<ref>{{citation|author=Todd D. Senecal, Wei Shu, Stephen L. Buchwald |date=2013-09-16 |doi=10.1002/ange.201304188 |issue=38 |pages=10219–10223 |journal=Angewandte Chemie |title=A General, Practical Palladium-Catalyzed Cyanation of (Hetero)Aryl Chlorides and Bromides |volume=125 |bibcode=2013AngCh.12510219S |hdl=1721.1/94498 |hdl-access=free }}</ref> has likewise been reported. Quinones can react with trimethylsilyl cyanide to give silylated cyanohydrins, which are subsequently aromatized using phosphorus tribromide.<ref>{{citation|author=Florian Glöcklhofer, Markus Lunzer, Johannes Fröhlich |date=2015-04-01 |doi=10.1055/s-0034-1380150 |issue=7 |pages=950–952 |journal=Synlett |title=Facile Synthesis of Cyanoarenes from Quinones by Reductive Aromatization of Cyanohydrin Intermediates |volume=26}}</ref> A further approach involves reaction of aryl Grignard or aryllithium reagents with dimethylmalonitrile.<ref>{{citation|author=Jonathan T. Reeves, Christian A. Malapit, Frederic G. Buono, Kanwar P. Sidhu, Maurice A. Marsini, C. Avery Sader, Keith R. Fandrick, Carl A. Busacca, Chris H. Senanayake |date=2015-07-29 |doi=10.1021/jacs.5b06136 |issue=29 |pages=9481–9488 |journal=Journal of the American Chemical Society |title=Transnitrilation from Dimethylmalononitrile to Aryl Grignard and Lithium Reagents: A Practical Method for Aryl Nitrile Synthesis |volume=137 |pmid=26151426 |bibcode=2015JAChS.137.9481R }}</ref>

Aromatic nitriles are often prepared in the laboratory from the aniline via diazonium compounds. This is the Sandmeyer reaction. It requires transition metal cyanides.<ref>"''o''-Tolunitrile and ''p''-Tolunitrile" H. T. Clarke and R. R. Read ''Org. Synth.'' 1941, Coll. Vol. 1, 514.</ref> :{{chem2|ArN2+ + CuC\tN -> ArC\tN + N2 + Cu+}}

=== Preparation of cyanohydrins === thumb|class=skin-invert-image|Synthesis of aromatic nitriles via silylated cyanohydrins The cyanohydrins 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.<ref>{{Cite journal |author=Gregory, Robert J. H. |year=1999 |title=Cyanohydrins in Nature and the Laboratory: Biology, Preparations, and Synthetic Applications |journal=Chemical Reviews |volume=99 |issue=12 |pages=3649–3682 |doi=10.1021/cr9902906 |pmid=11849033 |bibcode=1999ChRv...99.3649G }}</ref>thumb|Production of cyanohydrins: An aldehyde or ketone reacts with an alkali cyanide. M denotes an alkali metal

Cyanohydrins can also be prepared by addition of an alkali cyanide to an aldehyde or ketone in the presence of acetic acid. For less reactive substrates, diethylaluminum cyanide provides a suitable alternative. Another approach is transhydrocyanation, in which hydrogen cyanide is transferred from acetone cyanohydrin to an aldehyde or ketone.<ref name=":9" /> Suitable catalysts for this transformation include lanthanide alkoxides such as {{ill|lanthanum(III) isopropoxide|qid=Q72487196|s=1}}, {{ill|cerium(III) isopropoxide|qid=Q125558694|s=1}}, {{ill|samarium(III) isopropoxide|qid=Q72515210|s=1}}, and {{ill|ytterbium(III) isopropoxide|qid=Q72515207|s=1}}.<ref>{{citation|author=Hiroshi Ohno, Atsunori Mori, Shohei Inoue |date=February 1993 |doi=10.1246/cl.1993.375 |issue=2 |pages=375–378 |journal=Chemistry Letters |title=Lanthanoid(III) Alkoxides as Novel Catalysts for a Rapid Transhydrocyanation from Acetone Cyanohydrin to Aldehydes and Ketones |volume=22}}</ref>

Addition of trimethylsilyl cyanide to aldehydes or ketones affords cyanohydrins as their trimethylsilyl ethers.<ref>{{citation|author=David A. Evans, Gary L. Carroll, Larry K. Truesdale |date=April 1974 |doi=10.1021/jo00921a012 |issue=7 |pages=914–917 |journal=The Journal of Organic Chemistry |title=Synthetic applications of trimethylsilyl cyanide. Efficient synthesis of β-aminomethyl alcohols |volume=39}}</ref><ref>{{citation|author=Shu Kobayashi, Yoshikazu Tsuchiya, Teruaki Mukaiyama |date=April 1991 |doi=10.1246/cl.1991.537 |issue=4 |pages=537–540 |journal=Chemistry Letters |title=A Facile Synthesis of Cyanohydrin Trimethylsilyl Ethers by the Addition Reaction of Trimethylsilyl Cyanide with Aldehydes under Basic Condition |volume=20}}</ref> Suitable catalysts include zinc iodide, potassium cyanide in combination with 18-crown-6, or ytterbium(III) cyanide.<ref name=":9" /> Under appropriate conditions, such reactions can be rendered enantioselective. Vanadium- or titanium-based catalysts bearing chiral salen-type ligands are suitable, as is the combination of tetraisopropyl orthotitanate with a chiral imine.<ref>{{citation|author=Yuri N. Belokon', Susana Caveda-Cepas, Brendan Green, Nicolai S. Ikonnikov, Viktor N. Khrustalev, Vladimir S. Larichev, Margarita A. Moscalenko, Michael North, Charles Orizu, Vitali I. Tararov, Michela Tasinazzo, Galina I. Timofeeva, Lidia V. Yashkina |date=1999-04-01 |doi=10.1021/ja984197v |issue=16 |pages=3968–3973 |journal=Journal of the American Chemical Society |title=The Asymmetric Addition of Trimethylsilyl Cyanide to Aldehydes Catalyzed by Chiral (Salen)Titanium Complexes |volume=121 |bibcode=1999JAChS.121.3968B }}</ref><ref name=":10">{{citation|author=Nobuhito Kurono, Takeshi Ohkuma |date=2016-02-05 |doi=10.1021/acscatal.5b02184 |issue=2 |pages=989–1023 |journal=ACS Catalysis |title=Catalytic Asymmetric Cyanation Reactions |volume=6}}</ref>

=== Preparation of acyl cyanides === Acyl cyanides (α-oxonitriles) can in certain cases be prepared by reacting carboxylic acid halides with transition metal cyanides (e.g., copper cyanide or silver cyanide). This approach is particularly effective for aromatic carboxylic acid halides and aliphatic acyl bromides, whereas aliphatic acyl chlorides are unreactive. Aliphatic acyl cyanides can instead be synthesized by reacting carboxylic acid chlorides with trimethylsilyl cyanide.<ref>{{citation|author=Siegfried Hünig, Rainer Schaller |date=January 1982 |doi=10.1002/anie.198200361 |issue=1 |pages=36–49 |journal=Angewandte Chemie International Edition in English |title=The Chemistry of Acyl Cyanides |volume=21}}</ref>

=== Enantioselective synthesis of chiral nitriles === Using chiral pool starting materials, enantioselective synthesis enables access to α-chiral nitrile-containing compounds in eutomeric form, such as vildagliptin and saxagliptin. Conventional transformations can introduce the nitrile functionality; for example, an enantiomerically pure amide or oxime derived from naturally enantiopure proline may be dehydrated. The applicability of such strategies depends on the specific target molecule. Asymmetric cyanation reactions are also established.<ref>{{citation|author=Harald Gröger, Yasuhisa Asano |doi=10.1021/acs.joc.9b02773 |journal=The Journal of Organic Chemistry |title=Cyanide-Free Enantioselective Catalytic Strategies for the Synthesis of Chiral Nitriles |date=2020 |volume=85 |issue=10 |pages=6243–6251 |pmid=32250626 }}</ref> Of particular importance is the asymmetric hydrocyanation of carbonyl compounds (see section on cyanohydrin preparation). In addition, numerous asymmetric hydrocyanations of imines have been developed, affording enantiomerically pure α-aminonitriles.<ref name=":10" />

=== Other methods ===

*A commercial source for the cyanide group is diethylaluminum cyanide {{chem2|Et2AlCN}} which can be prepared from triethylaluminium and HCN.<ref>{{OrgSynth|collvol=6|collvolpages=436|year=1988|title=Diethylaluminum cyanide|author=W. Nagata and M. Yoshioka|prep=cv6p0436}}</ref> It has been used in nucleophilic addition to ketones.<ref>{{OrgSynth|collvol=6|collvolpages=307|year=1988|title=Preparation of cyano compounds using alkylaluminum intermediates: 1-cyano-6-methoxy-3,4-dihydronaphthalene|author=W. Nagata, M. Yoshioka, and M. Murakami|prep=cv6p0307}}</ref> For an example of its use see: Kuwajima Taxol total synthesis * Cyanide ions facilitate the coupling of dibromides. Reaction of α,α′-dibromoadipic acid with sodium cyanide in ethanol yields the cyano cyclobutane:<ref>{{cite journal |author1=Reynold C. Fuson |author2=Oscar R. Kreimeier |author3=Gilbert L. Nimmo |name-list-style=amp |year=1930 |title=Ring Closures in the Cyclobutane Series. II. Cyclization Of α,α′-Dibromo-Adipic Esters |journal=J. Am. Chem. Soc. |volume=52 |issue=10 |pages=4074–4076 |doi=10.1021/ja01373a046}}</ref> center|class=skin-invert-image|300px * Aromatic nitriles can be prepared from base hydrolysis of trichloromethyl aryl ketimines ({{chem2|RC(CCl3)\dNH}}) in the Houben-Fischer synthesis<ref>J. Houben, Walter Fischer (1930) "Über eine neue Methode zur Darstellung cyclischer Nitrile durch katalytischen Abbau (I. Mitteil.)," ''Berichte der deutschen chemischen Gesellschaft'' (A and B Series) 63 (9): 2464 – 2472. {{doi|10.1002/cber.19300630920}}</ref> * α-Amino acids form nitriles and carbon dioxide via various means of oxidative decarboxylation.<ref>{{cite journal |last1=Hiegel |first1=Gene |last2=Lewis |first2=Justin |last3=Bae |first3=Jason |date=2004 |title=Conversion of α-Amino Acids into Nitriles by Oxidative Decarboxylation with Trichloroisocyanuric Acid |journal=Synthetic Communications |volume=34 |issue=19 |pages=3449–3453 |doi=10.1081/SCC-200030958 |s2cid=52208189}}</ref><ref>{{cite journal |last1=Hampson |first1=N |last2=Lee |first2=J |last3=MacDonald |first3=K |date=1972 |title=The oxidation of amino compounds at anodic silver |journal=Electrochimica Acta |volume=17 |issue=5 |pages=921–955 |doi=10.1016/0013-4686(72)90014-X}}</ref> Henry Drysdale Dakin discovered this oxidation in 1916.<ref>{{cite journal |last1=Dakin |first1=Henry Drysdale |date=1916 |title=The Oxidation of Amino-Acids to Cyanides |journal=Biochemical Journal |volume=10 |issue=2 |pages=319–323 |doi=10.1042/bj0100319 |pmc=1258710 |pmid=16742643}}</ref> * From aryl carboxylic acids (Letts nitrile synthesis)

* Carbocyanation enables addition of a nitrile group across a multiple bond to yield a further nitrile. Aryl nitriles can be added to alkynes under catalysis by bis(cyclooctadiene)nickel(0) and trimethylphosphine, affording α,β-unsaturated nitriles. Modification of the reaction conditions, for example by employing a different phosphane or adding a frustrated Lewis pair such as trimethylaluminum or triphenylborane, allows addition of non-aromatic nitriles, both saturated and α,β-unsaturated.<ref>{{citation|author=Yoshiaki Nakao, Tamejiro Hiyama |date=2008-01-01 |doi=10.1351/pac200880051097 |issue=5 |pages=1097–1107 |journal=Pure and Applied Chemistry |title=Nickel-catalyzed carbocyanation of alkynes |volume=80|hdl=2433/84649 |hdl-access=free }}</ref> Carbocyanation reactions that couple two molecules while introducing a nitrile group are also known, using hexabutyldistannane and tosyl cyanide as the cyanide source.<ref>{{citation|author=Haitham Hassan, Vincent Pirenne, Maren Wissing, Chahinaz Khiar, Ashique Hussain, Frédéric Robert, Yannick Landais |date=2017-04-03 |doi=10.1002/chem.201605946 |issue=19 |pages=4651–4658 |journal=Chemistry: A European Journal |title=Free-Radical Carbocyanation of Olefins |volume=23 |pmid=28094885 }}</ref> * Carboxylic acids can be converted to the corresponding nitriles by reaction with indium(III) chloride in acetonitrile at 200 °C. In this process, acetonitrile functions both as solvent and nitrogen source and is converted into acetic acid. The reaction proceeds via multiple Mumm rearrangements.<ref>{{citation|author=Laurent Vanoye, Ahmad Hammoud, Hélène Gérard, Alexandra Barnes, Régis Philippe, Pascal Fongarland, Claude de Bellefon, Alain Favre-Réguillon |date=2019-11-01 |doi=10.1021/acscatal.9b02779 |issue=11 |pages=9705–9714 |journal=ACS Catalysis |title=Direct Synthesis of Nitriles from Carboxylic Acids Using Indium-Catalyzed Transnitrilation: Mechanistic and Kinetic Study |volume=9}}</ref> Alcohols can be transformed into nitriles by a Mitsunobu reaction, employing cyanomethylidene trimethyl phosphorane in the presence of acetone cyanohydrin.<ref>{{citation|author=Tetsuto Tsunoda, Kaori Uemoto, Chisato Nagino, Megumi Kawamura, Hiroto Kaku, Shô Itô |date=October 1999 |doi=10.1016/S0040-4039(99)01509-9 |issue=41 |pages=7355–7358 |journal=Tetrahedron Letters |title=A facile one-pot cyanation of primary and secondary alcohols. Application of some new Mitsunobu reagents |volume=40}}</ref> ''N''-Alkylamides can be converted to nitriles via the von Braun degradation using phosphorus pentachloride.<ref>{{citation|author=Walter-Georg Veeck, Manfred Regitz |date=1995 |pages=1151–1160 |journal=Comprehensive Organic Functional Group Transformations |publisher=Elsevier |title=Triple-bonded Heteroatom Derivatives Other Than Nitriles with Another Heteroatom Attached to the sp-Carbon Atom}}</ref> Alternative reagents include phosphorus pentabromide and carbonyl bromide.<ref>{{citation|author=B.A. Phillips, G. Fodor, J. Gal, F. Letourneau, J.J. Ryan |date=January 1973 |doi=10.1016/S0040-4020(01)93483-0 |issue=21 |pages=3309–3327 |journal=Tetrahedron |title=Mechanism of the von Braun amide degradations with carbonyl bromide or phosphorus pentabromide |volume=29}}</ref>

== 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 carboxamides {{chem2|RC(O)NH2}} and then carboxylic acids {{chem2|RC(O)OH}}. The hydrolysis of nitriles to carboxylic acids is efficient. In acid or base, the balanced equations are as follows:

:{{chem2|RC\tN + 2 H2O + HCl -> RC(O)OH + NH4Cl}} :{{chem2|RC\tN + H2O + NaOH -> RC(O)ONa + NH3}}

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{{x10^|-6}} M−1 s−1, which is slower than the hydrolysis of the amide to the carboxylate (7.4{{x10^|-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.<ref>{{cite journal|first1=V. Yu. |last1=Kukushkin |first2=A. J. L. |last2=Pombeiro |title=Metal-mediated and metal-catalyzed hydrolysis of nitriles |journal=Inorg. Chim. Acta |volume=358 |date=2005 |pages=1–21 |doi=10.1016/j.ica.2004.04.029}}</ref> The classical procedure to convert a nitrile to the corresponding primary amide calls for adding the nitrile to cold concentrated sulfuric acid.<ref>{{Cite journal|last=Abbas|first=Khamis A.|date=2008-01-01|title=Substituent Effects on the Hydrolysis of p-Substituted Benzonitriles in Sulfuric Acid Solutions at (25.0± 0.1) °C|journal=Zeitschrift für Naturforschung A|volume=63|issue=9|pages=603–608|doi=10.1515/zna-2008-0912|issn=1865-7109|bibcode=2008ZNatA..63..603A|doi-access=free}}</ref> The further conversion to the carboxylic acid is disfavored by the low temperature and low concentration of water. :{{chem2|RC\tN + H2O -> RC(O)NH2}}

Two families of enzymes catalyze the hydrolysis of nitriles. Nitrilases hydrolyze nitriles to carboxylic acids: :{{chem2|RC\tN + 2 H2O -> RC(O)OH + NH3}} Nitrile hydratases are metalloenzymes that hydrolyze nitriles to amides. :{{chem2|RC\tN + H2O -> RC(O)NH2}} These enzymes are used commercially to produce acrylamide.

The "anhydrous hydration" of nitriles to amides has been demonstrated using an oxime as water source:<ref>{{cite journal |doi=10.15227/orgsyn.089.0066|author=Dahye Kang |author2=Jinwoo Lee |author3=Hee-Yoon Lee |title =Anhydrous Hydration of Nitriles to Amides: ''p''-Carbomethoxybenzamide|journal=Organic Syntheses|year=2012|volume=89|page=66|doi-access=free}}</ref> :{{chem2|RC\tN + R'C(H)\dNOH -> RC(O)NH2 + R'C\tN}}

=== Reduction === {{Main|Nitrile reduction}}

Nitriles are susceptible to hydrogenation over diverse metal catalysts. The reaction can afford either the primary amine ({{chem2|RCH2NH2}}) or the tertiary amine ({{chem2|(RCH2)3N}}), depending on conditions.<ref>{{cite journal|first1=J. |last1=Barrault |first2=Y. |last2=Pouilloux |title=Catalytic Amination Reactions: Synthesis of fatty amines. Selectivity control in presence of multifunctional catalysts |journal=Catalysis Today |date=1997 |volume=1997 |issue=2 |pages=137–153 |doi=10.1016/S0920-5861(97)00006-0}}</ref> 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 {{chem2|C\tN}} group.<ref>{{cite book |doi=10.1002/0471264180.or031.01|chapter=Addition and Substitution Reactions of Nitrile-Stabilized Carbanions |title=Organic Reactions |year=1984 |last1=Arseniyadis |first1=Siméon |last2=Kyler |first2=Keith S. |last3=Watt |first3=David S. |pages=1–364 |isbn=978-0-471-26418-7 }}</ref><ref>{{cite journal |doi=10.1021/acs.accounts.7b00329|title=C- and N-Metalated Nitriles: The Relationship between Structure and Selectivity |year=2017 |last1=Yang |first1=Xun |last2=Fleming |first2=Fraser F. |journal=Accounts of Chemical Research |volume=50 |issue=10 |pages=2556–2568 |pmid=28930437 }}</ref> 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 {{chem2|C\tN}} 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: * with an organozinc compound in the Blaise reaction * with alcohols in the Pinner reaction. * with amines, e.g. the reaction of the amine sarcosine with cyanamide yields creatine<ref>{{cite journal |author1=Smith, Andri L. |author2=Tan, Paula | title = Creatine Synthesis: An Undergraduate Organic Chemistry Laboratory Experiment | journal = J. Chem. Educ. | year = 2006 | volume = 83 | page = 1654 | doi = 10.1021/ed083p1654|bibcode = 2006JChEd..83.1654S | issue = 11 }}</ref> * with arenes to form ketones in the Houben–Hoesch reaction via an imine intermediate. * with Grignard reagents to form primary ketimines in the Moureau-Mignonac ketimine synthesis.<ref>{{Cite book|date=2010-09-15|chapter=Moureau-Mignonac Ketimine Synthesis|title=Comprehensive Organic Name Reactions and Reagents|language=en|location=Hoboken, NJ, USA|publisher=John Wiley & Sons, Inc.|pages=1988–1990|doi=10.1002/9780470638859.conrr446|isbn=978-0-470-63885-9}}</ref> While not a classical Grignard reaction, it may be considered one under broader modern definitions.

=== Miscellaneous methods and compounds === * In reductive decyanation the nitrile group is replaced by a proton.<ref name=DecyanationReview>''The reductive decyanation reaction: chemical methods and synthetic applications'' Jean-Marc Mattalia, Caroline Marchi-Delapierre, Hassan Hazimeh, and Michel Chanon Arkivoc (AL-1755FR) pp. 90–118 2006 [http://www.arkat-usa.org/ark/journal/2006/I04_Lattes/1755/AL-1755FR%20as%20published%20mainmanuscript.asp Article]{{Dead link|date=January 2020 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Decyanations can be accomplished by dissolving metal reduction (e.g. HMPA and potassium metal in ''tert''-butanol) or by fusion of a nitrile in KOH.<ref>{{cite journal|last1=Berkoff|first1=Charles E.|last2=Rivard|first2=Donald E.|last3=Kirkpatrick|first3=David|last4=Ives|first4=Jeffrey L.|title=The Reductive Decyanation of Nitriles by Alkali Fusion|journal=Synthetic Communications|date=1980|volume=10|issue=12|pages=939–945|doi=10.1080/00397918008061855}}</ref> Similarly, α-aminonitriles can be decyanated with other reducing agents such as lithium aluminium hydride.<ref name=DecyanationReview /> * In the so-called Franchimont Reaction (developed by the Belgian doctoral student Antoine Paul Nicolas Franchimont (1844-1919) in 1872), an α-cyanocarboxylic acid heated in acid hydrolyzes and decarboxylates to a dimer.<ref>{{Cite journal | first = Antoine Paul Nicholas |last=Franchimont | title = Ueber die Dibenzyldicarbonsäure |trans-title= On 2,3-diphenylsuccinic acid | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 5 | issue = 2 | pages = 1048–1050 | date = 1872 | doi = 10.1002/cber.187200502138 | url = https://babel.hathitrust.org/cgi/pt?id=uc1.b3481750;seq=1012}}</ref> * Nitriles self-react in presence of base in the Thorpe reaction in a nucleophilic addition * In organometallic chemistry nitriles are known to add to alkynes in carbocyanation:<ref>{{cite journal | title = A Dramatic Effect of Lewis-Acid Catalysts on Nickel-Catalyzed Carbocyanation of Alkynes |author1=Yoshiaki Nakao |author2=Akira Yada |author3=Shiro Ebata |author4=Tamejiro Hiyama |name-list-style=amp | journal = J. Am. Chem. Soc. | year = 2007 | volume = 129 | issue = 9 | pmid = 17295484 | pages = 2428–2429| type = Communication | doi = 10.1021/ja067364x |bibcode=2007JAChS.129.2428N }}</ref> :400px|class=skin-invert-image|Carbocyanation Nakao 2007

===Complexation=== Nitriles are precursors to transition metal nitrile complexes, which are reagents and catalysts. Examples include tetrakis(acetonitrile)copper(I) hexafluorophosphate ({{chem2|[Cu(MeCN)4]+}}) and bis(benzonitrile)palladium dichloride ({{chem2|PdCl2(PhCN)2}}).<ref>{{cite journal|author1=Rach, S. F. |author2=Kühn, F. E. |title=Nitrile Ligated Transition Metal Complexes with Weakly Coordinating Counteranions and Their Catalytic Applications|journal=Chemical Reviews|year=2009|volume=109|issue=5|pages=2061–2080|doi=10.1021/cr800270h|pmid=19326858}}</ref>

==Nitrile derivatives== thumb|Compound classes containing a {{chem2|C\tN}} triple bond. Left (from top to bottom): hydrogen cyanide, nitriles, isonitriles. Center: cyanates, thiocyanates, cyanamides. Right: nitrile oxides, nitrile sulphides, nitrilimines, nitrilium ions

Nitriles are isomeric with isonitriles (isocyanides). These also contain a {{chem2|C\tN}} triple bond; however, the substituent is bonded via the nitrogen atom, which results in a zwitterionic structure.<ref>{{cite journal |last1=Moss |first1=G. P. |last2=Smith |first2=P. A. S. |last3=Tavernier |first3=D. |title=Glossary of class names of organic compounds and reactivity intermediates based on structure (IUPAC Recommendations 1995) |journal=Pure and Applied Chemistry |date=1995-01-01 |volume=67 |issue=8–9 |pages=1307–1375 |doi=10.1351/pac199567081307 |bibcode=1995PApCh..67.1307M }}</ref>

Compounds in which an oxygen atom is bonded to the carbon atom of a {{chem2|C\tN}} group are referred to as cyanates.<ref>{{GoldBookRef|title=cyanates|file=C01485}}</ref> If the oxygen atom is replaced by a sulfur or selenium atom, the compounds are termed thiocyanates or {{ill|selenocyanates|qid=Q2268086|s=1}}.<ref>{{GoldBookRef|title=thiocyanates|file=T06353}}</ref><ref>{{GoldBookRef|title=selenocyanates|file=S05573}}</ref> If the cyano group is bonded to a nitrogen atom, the compound is referred to as a cyanamide.<ref>{{cite journal |last1=Prabhath |first1=M. |last2=Williams |first2=Luke |last3=Bhat |first3=Shreesha |last4=Sharma |first4=Pallavi |title=Recent Advances in Cyanamide Chemistry: Synthesis and Applications |journal=Molecules |date=2017-04-12 |volume=22 |issue=4 |page=615 |doi=10.3390/molecules22040615 |doi-access=free |pmc=6154562 |pmid=28417938}}</ref>

In addition to nitriles, other classes of compounds are known that contain a {{chem2|C\tN}} triple bond in which the nitrogen atom forms a fourth bond and is therefore positively charged. In nitrile oxides, an oxygen atom is additionally bonded to the nitrogen atom.<ref>{{GoldBookRef|title=nitrile oxides|file=N04150}}</ref> If this atom is sulfur or another nitrogen atom instead, the compounds are referred to as {{ill|nitrile sulfides|qid=Q131762237|s=1}} or nitrilimines, respectively.<ref>{{GoldBookRef|title=nitrile sulfides|file=N04152}}</ref><ref>{{GoldBookRef|title=nitrile imides|file=N04148}}</ref> If the nitrogen atom of the nitrile is protonated or carries an additional organic substituent, the compound is a nitrilium ion.<ref>{{GoldBookRef|title=nitrilium ions|file=N04156}}</ref> If the nitrogen atom carries an organic substituent bearing a negatively charged carbon atom, the species is a nitrile ylide, a subclass of ylides.<ref>{{GoldBookRef|title=nitrile ylides|file=N04153}}</ref>

===Organic cyanamides=== {{See also|von Braun reaction|Cyanamide#Cyanamide functional group}} Cyanamides are ''N''-cyano compounds with general structure {{chem2|R^{1}R^{2}N\sC\tN}} and related to the parent cyanamide.<ref>{{March4th|page=436–7}}</ref>

===Nitrile oxides=== Nitrile oxides have the chemical formula {{chem2|RCNO}}. Their general structure is {{chem2|R\sC\tN+\sO-}}. The R stands for any group (typically organyl, e.g., acetonitrile oxide {{chem2|CH3\sC\tN+\sO−}}, hydrogen in the case of fulminic acid {{chem2|H\sC\tN+\sO−}}, or halogen (e.g., {{ill|chloroformonitrile oxide|qid=Q138297303|s=1}} {{chem2|Cl\sC\tN+\sO−}}).<ref name=March/>{{rp|1187–1192}}

Nitrile oxides are quite different from nitriles and do not arise from direct oxidation of the latter.<ref>{{cite book|page=794|doi=10.1002/9780470771242.ch14|title=The Chemistry of the Cyano Group|editor-first=Zvi|editor-last=Rappoport|year=1970|first=Ch.|last=Grundmann|chapter=Nitrile oxides|series=PATai's Chemistry of Functional Groups |isbn=978-0-471-70913-8 }}</ref> Instead, they can be synthesised by nitroalkane dehydration, oxime dehydrogenation,<ref name="Clayden">{{Clayden}}</ref>{{rp|934–936}} or halooxime elimination in base.<ref>{{cite journal|doi=10.1016/S0040-4039(00)71175-0|journal=Tetrahedron Letters|volume=21|pages=229–230|publisher=Pergamon|year=1980|location=Great Britain|title=Direct synthesis of the antitumor agent ''erythro''-α‑amino-3‑bromo-4,5‑dihydrooxazole-5‑acetic acid|first1=Alfred A.|last1=Hagedorn|first2=Bryan J.|last2=Miller|first3=Jon O.|last3=Nagy|orig-date=12 Oct 1979|postscript=none}}, alluding to a large-scale modification later detailed in {{cite journal|doi=10.1016/S0040-4039(00)99918-0|journal=Tetrahedron Letters|volume=25|issue=5|at=fn. 10|location=Great Britain|year=1984|publisher=Pergamon|title=A short, efficient total synthesis of (&pm;) acivicin and (&pm;) bromo-acivicin|first1=D. M.|last1=Vyas|first2=Y.|last2=Chiang|first3=T. W.|last3=Doyle}}</ref> They are highly reactive in 1,3-dipolar cycloadditions,<ref name="March">{{cite book | first1 = Michael B. | last1 = Smith | first2 = Jerry | last2 = March | title = March's Advanced Organic Chemistry | publisher = John Wiley & Sons | year = 2007 | edition=6th | isbn = 978-0-471-72091-1 }}</ref>{{rp|1187–1192}} such as to isoxazoles,<ref name="Clayden" />{{rp|1201–1202}} and undergo type I dyotropic rearrangement to isocyanates.<ref name="March" />{{rp|1700}}

The heavier nitrile sulfides are extremely reactive and rare, but temporarily form during the thermolysis of oxathiazolones. They react similarly to nitrile oxides.<ref>{{cite book|pages=506–507|last=Argyropoulos|first=Nikolaos G.|chapter=1,4-Oxa/thia-2-azoles|year=1996|title=Comprehensive Heterocyclic Chemistry|volume=4: Five-membered rings with more than two heteroatoms and fused carbocyclic derivatives|doi=10.1016/B978-008096518-5.00092-7|isbn=978-0-08-096518-5|editor-first1=Alan R.|editor-last1=Katritzky|editor-link1=Alan Katritzky|editor-first2=Charles W.|editor-last2=Rees|editor-first3=Eric F. V.|editor-last3=Scriven}}</ref>

== Occurrence == More than 100 naturally occurring nitriles were known as early as the 1990s,<ref name=":11">{{citation|author=Fraser F. Fleming, Fraser F. Fleming |date=1999 |doi=10.1039/a804370a |issue=5 |pages=597–606 |journal=Natural Product Reports |title=Nitrile-containing natural products |volume=16}}</ref> and several hundred have since been identified.<ref name=":12">{{citation|author=Camille Scotti, James W. Barlow |date=May 2022 |doi=10.1177/1934578X221099973 |issue=5 |pages=1934578X2210999 |journal=Natural Product Communications |title=Natural Products Containing the Nitrile Functional Group and Their Biological Activities |volume=17|article-number=1934578X221099973 |doi-access=free }}</ref> These compounds occur in bacteria, fungi, plants, and arthropods and sponges.<ref name=":11" /><ref name=":12" /> The biosynthesis of naturally occurring nitriles frequently begins with amino acids. Their ''N''-hydroxylation followed by decarboxylation (cleavage of the carboxylic acid group as carbon dioxide) yields oximes, which serve as the direct precursors of nitriles.<ref name=":11" />

=== Occurrence in plants === Numerous nitriles occur as secondary metabolites in plants.

In Ricinus communis (''Ricinus communis''), in addition to the highly toxic protein ricin, the alkaloid ricinin is present, which contains a nitrile functional group.<ref>{{citation|author=Anete C Ferraz, Miriam Elizabeth M Angelucci, Mariana L Da Costa, Ilza R Batista, Bras H De Oliveira, Claudio Da Cunha |date=July 1999 |doi=10.1016/S0091-3057(99)00007-6 |issue=3 |pages=367–375 |journal=Pharmacology Biochemistry and Behavior |title=Pharmacological Evaluation of Ricinine, a Central Nervous System Stimulant Isolated from Ricinus communis |volume=63 |pmid=10418776 }}</ref> The structurally closely related nudiflorin occurs in ''Trevia nudiflora'' (family spurge family).<ref>{{citation|author=R. Mukherjee, A. Chatterjee |date=January 1966 |doi=10.1016/S0040-4020(01)99443-8 |issue=4 |pages=1461–1466 |journal=Tetrahedron |title=Structure and synthesis of nudiflorine |volume=22}}</ref> In brown mustard, indoleacetonitrile is present; it is formed from indoleacetaldoxime and presumably functions in defense against pathogenic fungi.<ref>{{citation|author=M.Soledade C Pedras, Corwin M Nycholat, Sabine Montaut, Yiming Xu, Abdul Q Khan |date=March 2002 |doi=10.1016/S0031-9422(02)00026-2 |issue=6 |pages=611–625 |journal=Phytochemistry |title=Chemical defenses of crucifers: elicitation and metabolism of phytoalexins and indole-3-acetonitrile in brown mustard and turnip |volume=59 |pmid=11867093 |bibcode=2002PChem..59..611P }}</ref> In jojoba, various nitriles are found, including simmondsin, a glycoside containing an α,β-unsaturated nitrile moiety in the aglycone.<ref>{{citation|author=A. Bellirou, A. Bouali, B. Bouammali, N. Boukhatem, B.N. Elmtili, A. Hamal, M. El-Mourabit |date=March 2005 |doi=10.1016/j.indcrop.2004.04.007 |issue=2 |pages=229–233 |journal=Industrial Crops and Products |title=Extraction of simmondsin and oil in one step from jojoba seeds |volume=21}}</ref> A similar compound, menis daurin, occurs in European holly (''Ilex aquifolium'').<ref>{{citation|author=Adolf Nahrstedt, Victor Wray |date=1990 |doi=10.1016/0031-9422(90)85364-L |issue=12 |pages=3934–3936 |journal=Phytochemistry |title=Structural revision of a putative cyanogenic glucoside from Ilex aquifolium |volume=29 |bibcode=1990PChem..29.3934N }}</ref> α,β-Unsaturated nitriles are also present in several species of the genus ''Acacia'', including Sutherlandin and Acacipetalin.<ref>{{citation|author=Wendy K. Swenson, John E. Dunn, Eric E. Conn |date=January 1987 |doi=10.1016/S0031-9422(00)82299-2 |issue=6 |pages=1835–1836 |journal=Phytochemistry |title=Cyanogenesis in Acacia sutherlandii |volume=26 |bibcode=1987PChem..26.1835S }}</ref><ref>{{citation|author=Martin G. Ettlinger, Jerzy W. Jaroszewski, Søren Rosendal Jensen, Bent Juhl Nielsen, Frederick Nartey |date=1977 |doi=10.1039/c39770000952 |issue=24 |page=952 |journal=Journal of the Chemical Society, Chemical Communications |title=Proacacipetalin and acacipetalin}}</ref> The horseradish tree (''horseradish tree'') contains niazirine, a glycoside of 4-hydroxyphenylacetonitrile.<ref>{{citation|author=K Shanker, M Gupta, S Srivastava, D Bawankule, A Pal, S Khanuja |date=2007 |doi=10.1016/j.foodchem.2006.12.034 |issue=1 |pages=376–382 |journal=Food Chemistry |title=Determination of bioactive nitrile glycoside(s) in drumstick (Moringa oleifera) by reverse phase HPLC |volume=105}}</ref> The fragrant sweet pea (''Lathyrus odoratus'') causes the disease lathyrism, for which N-glutamyl-3-aminopropionitrile and its degradation product 3-aminopropionitrile are responsible.<ref>{{citation|author=F. W. Stamler |date=1955-10-01 |doi=10.3181/00379727-90-22013 |issue=1 |pages=294–298 |journal=Experimental Biology and Medicine |title=Reproduction in Rats Fed Lathyrus Peas or Aminonitriles |volume=90 |doi-broken-date=30 March 2026 |pmid=13273428 }}</ref><ref>{{citation|author=E. D. Schilling, F. M. Strong |date=May 1954 |doi=10.1021/ja01639a084 |issue=10 |pages=2848 |journal=Journal of the American Chemical Society |title=ISOLATION, STRUCTURE AND SYNTHESIS OF a LATHYRUS FACTOR FROM L. ODORATUS1 |volume=76 |bibcode=1954JAChS..76Q2848S }}</ref> The essential oil of ''Heracleum transcaucasicum'' (genus hogweed) contains geranylnitrile.<ref>{{citation|author=Mohammadali Torbati, Hossein Nazemiyeh, Farzaneh Lotfipour, Solmaz Asnaashari, Mahboob Nemati, Fatemeh Fathiazad |date=2013 |doi=10.5681/APB.2013.066 |journal=Advanced Pharmaceutical Bulletin |pmc=3848220 |pmid=24312869 |title=Composition and Antibacterial Activity of Heracleum Transcaucasicum and Heracleum Anisactis Aerial Parts Essential Oil |volume=3 |issue=2 |pages=415–418 }}</ref> 3-cyanopyridine is found in annual bindweed.<ref>{{citation|author=Peter Lorenz, Sarina Duckstein, Jürgen Conrad, Matthias Knödler, Ulrich Meyer, Florian C. Stintzing |date=February 2012 |doi=10.1002/cbdv.201100341 |issue=2 |pages=282–297 |journal=Chemistry & Biodiversity |title=An Approach to the Chemotaxonomic Differentiation of Two European Dog's Mercury Species: Mercurialis annua L. and M. perennis L. |volume=9}}</ref> Cyanolipids are a class of lipids that occur exclusively in soap tree plants (Sapindaceae). Their alcohol component is an unsaturated nitrile with five carbon atoms and one or two hydroxy groups, in contrast to glycerol in glycerides. Soap tree plants containing cyanolipids include soapnut tree and guarana.<ref>{{citation|author=K.L. Mikolajczak |date=January 1977 |doi=10.1016/0079-6832(77)90013-1 |issue=2 |pages=97–130 |journal=Progress in the Chemistry of Fats and Other Lipids |title=Cyanolipids |volume=15 |pmid=327513 }}</ref><ref>{{citation|author=David S. Seigler, Wanda Kawahara |date=January 1976 |doi=10.1016/0305-1978(76)90050-8 |issue=4 |pages=263–265 |journal=Biochemical Systematics and Ecology |title=New reports of cyanolipids from sapindaceous plants |volume=4 |bibcode=1976BioSE...4..263S }}</ref> Hydrogen cyanide is released by many plants containing corresponding cyanogenic compounds, particularly cyanogenic glycosides and cyanolipids.<ref>{{citation|author=E E Conn |date=June 1980 |doi=10.1146/annurev.pp.31.060180.002245 |issue=1 |pages=433–451 |journal=Annual Review of Plant Physiology |title=Cyanogenic Compounds |volume=31}}</ref> In plants, hydrogen cyanide also functions as a signaling molecule.<ref name=":27">{{citation|author=Pablo Díaz-Rueda, Laura Morales de los Ríos, Luis C Romero, Irene García |date=2023-10-13 |doi=10.1093/jxb/erad317 |issue=19 |pages=6040–6051 |journal=Journal of Experimental Botany |pmc=10575699 |pmid=37586035 |title=Old poisons, new signaling molecules: the case of hydrogen cyanide |volume=74}}</ref>

<gallery class="center" perrow="4" widths="200"> Blomstrende Ricinus communis med nogle frø.jpg|Ricinus plant Ricinin.svg|Ricinin Guaraná (Paullinia cupana) fruits (29055398276).jpg|Guaraná, a soap tree plant, contains cyanolipids Cyanolipid type 1 alcohol.svg|An alcohol component of cyanolipids, found for example in guaraná </gallery>

==== Nitriles from glucosinolates in cruciferous plants ==== An important group of natural products that serve as precursors of nitriles are the mustard oil glycosides (glucosinolates), which are biosynthesized analogously to direct nitrile formation via an aldoxime intermediate.<ref name=":11" /> Glucosinolates constitute a major class of secondary metabolites produced by plants of the cruciferous family (Brassicaceae) for defense against herbivores and microorganisms. Normally, glucosinolates are hydrolyzed by myrosinase to isothiocyanates; however, in the presence of an additional protein (''epithio specifier protein''), nitriles are formed instead.<ref>{{citation|author=Hieng-Ming Ting, Boon Huat Cheah, Yu-Cheng Chen, Pei-Min Yeh, Chiu-Ping Cheng, Freddy Kuok San Yeo, Ane Kjersti Vie, Jens Rohloff, Per Winge, Atle M. Bones, Ralph Kissen |date=2020-03-10 |doi=10.3389/fpls.2020.00257 |journal=Frontiers in Plant Science |pmc=7076197 |pmid=32211010 |title=The Role of a Glucosinolate-Derived Nitrile in Plant Immune Responses |volume=11 |article-number=257 |doi-access=free |bibcode=2020FrPS...11..257T }}</ref><ref>{{citation|author=Adam M. Wentzell, Daniel J. Kliebenstein |date=2008-04-28 |doi=10.1104/pp.107.115279 |issue=1 |pages=415–428 |journal=Plant Physiology |pmc=2330308 |pmid=18359845 |title=Genotype, Age, Tissue, and Environment Regulate the Structural Outcome of Glucosinolate Activation |volume=147 |bibcode=2008PlanP.147..415W }}</ref> Sinigrin is found primarily in horseradish, wasabi, and brown mustard, but also in head cabbage, kale, cauliflower, and Brussels sprouts; in addition to allyl isothiocyanate, it can be degraded to allyl cyanide (3-butenenitrile).<ref>{{citation|author=Hideji Tanii |date=March 2017 |doi=10.1539/joh.16-0147-RA |issue=2 |pages=104–111 |journal=Journal of Occupational Health |pmc=5478528 |pmid=28132970 |title=Allyl nitrile: Toxicity and health effects |volume=59}}</ref><ref>{{citation|author=Jinghua Yang, Zhangping Li, Jinmin Lian, Guoning Qi, Pibiao Shi, Jiawei He, Zhongyuan Hu, Mingfang Zhang |date=2020-12-16 |doi=10.1038/s42003-020-01523-x |issue=1 |journal=Communications Biology |pmc=7745032 |pmid=33328568 |title=Brassicaceae transcriptomes reveal convergent evolution of super-accumulation of sinigrin |volume=3 |article-number=779 }}</ref> Glucotropaeolin, present in garden cress, is degraded to phenylacetonitrile; gluconasturtiin, found in watercress, is degraded to 3-phenylpropionitrile.<ref>{{citation|author=David J. Williams, Christa Critchley, Sharon Pun, Mridusmita Chaliha, Timothy J. O'Hare |date=July 2009 |doi=10.1016/j.phytochem.2009.07.035 |issue=11–12 |pages=1401–1409 |journal=Phytochemistry |title=Differing mechanisms of simple nitrile formation on glucosinolate degradation in Lepidium sativum and Nasturtium officinale seeds |volume=70 |pmid=19747700 |bibcode=2009PChem..70.1401W }}</ref> Sinalbin, occurring in ''Lepidium draba'', can analogously be degraded to 4-hydroxyphenylacetonitrile.<ref>{{citation|author=Ani Radonić, Ivica Blažević, Josip Mastelić, Marina Zekić, Mirjana Skočibušić, Ana Maravić |date=June 2011 |doi=10.1002/cbdv.201000370 |issue=6 |pages=1170–1181 |journal=Chemistry & Biodiversity |title=Phytochemical Analysis and Antimicrobial Activity of Cardaria draba (L.) Desv . Volatiles |volume=8 |pmid=21674789 }}</ref>

<gallery class="center" perrow="4" widths="200"> Nasturtium officinale kz12.jpg|Watercress Gluconasturtiin Structural Formulae V.4.svg|Structure of gluconasturtiin Phenylpropionitrile.svg|Structure of phenylpropionitrile </gallery>

==== Cyanohydrins and cyanogenic glycosides ==== Cyanohydrins and their glycosides, referred to as cyanogenic glycosides, are widespread in nature and occur in several thousand plant species.<ref name=":9" /><ref name=":12" /> More than one hundred naturally occurring cyanogenic glycosides have been identified.<ref name=":12" /> Plants utilize cyanogenic glycosides for defense and possibly also as a nitrogen storage buffer. They are biosynthesized from a limited number of amino acids and various carbohydrates.<ref name=":9" /> Upon tissue damage, the glycosides come into contact with enzymes (Β-glucosidase and hydroxynitrillyase), which first release the aglycone (a cyanohydrin) and subsequently cleave it into a carbonyl compound and toxic hydrocyanic acid. Amygdalin is a glycoside of mandelonitrile and one of the most widespread cyanogenic glycosides; it occurs particularly in the seeds of the rose family (Rosaceae), including cultivated apple, apricot, peach, plum, cherry, and almond tree.<ref>{{citation|author=Islamiyat F. Bolarinwa, Caroline Orfila, Michael R.A. Morgan |date=June 2014 |doi=10.1016/j.foodchem.2013.11.002 |pages=133–139 |journal=Food Chemistry |title=Amygdalin content of seeds, kernels and food products commercially-available in the UK |volume=152 |pmid=24444917 |bibcode=2014FoodC.152..133B }}</ref> Whereas amygdalin is confined to the seeds of peaches, other parts of the plant predominantly contain prunasin.<ref>{{citation|author=C.J Graham |date=May 2002 |doi=10.1016/S0304-4238(01)00345-4 |issue=1–2 |pages=21–32 |journal=Scientia Horticulturae |title=Nonstructural carbohydrate and prunasin composition of peach seedlings fertilized with different nitrogen sources and aluminum |volume=94 |bibcode=2002ScHor..94...21G }}</ref> Prunasin is likewise a glycoside of mandelonitrile; however, its sugar moiety is a monosaccharide (rather than a disaccharide as in amygdalin). In almonds and bitter almonds, prunasin serves as a biosynthetic precursor of amygdalin.<ref>{{citation|author=C.J Graham |date=May 2002 |doi=10.1016/S0304-4238(01)00345-4 |issue=1–2 |pages=21–32 |journal=Scientia Horticulturae |title=Nonstructural carbohydrate and prunasin composition of peach seedlings fertilized with different nitrogen sources and aluminum |volume=94 |bibcode=2002ScHor..94...21G }}</ref> Prunasin is also present in laurel cherry.<ref>{{citation|author=Jandirk Sendker, Therese Ellendorff, Aljoscha Hölzenbein |date=2016-07-22 |doi=10.1021/acs.jnatprod.5b01090 |issue=7 |pages=1724–1729 |journal=Journal of Natural Products |title=Occurrence of Benzoic Acid Esters as Putative Catabolites of Prunasin in Senescent Leaves of Prunus laurocerasus |volume=79 |pmid=27331617 |bibcode=2016JNAtP..79.1724S }}</ref> Prunasin and sambunigrin, along with several other cyanogenic glycosides, occur in passion flower; in papaya, prunasin predominates.<ref>{{citation|author=David Chassagne, Jean C. Crouzet, Claude L. Bayonove, Raymond L. Baumes |date=1996-01-01 |doi=10.1021/jf960381t |issue=12 |pages=3817–3820 |journal=Journal of Agricultural and Food Chemistry |title=Identification and Quantification of Passion Fruit Cyanogenic Glycosides |volume=44 |bibcode=1996JAFC...44.3817C }}</ref><ref>{{citation|author=David S. Seigler, Guido F. Pauli, Adolf Nahrstedt, Rosemary Leen |date=August 2002 |doi=10.1016/S0031-9422(02)00170-X |issue=8 |pages=873–882 |journal=Phytochemistry |title=Cyanogenic allosides and glucosides from Passiflora edulis and Carica papaya |volume=60 |pmid=12150815 |bibcode=2002PChem..60..873S }}</ref> Sambunigrin, also a glycoside of mandelonitrile, is found in several species of the genus elderberry (''Sambucus''), including black elderberry and Canadian elderberry,<ref>{{citation|author=Mateja Senica, Franci Stampar, Robert Veberic, Maja Mikulic-Petkovsek |date=June 2017 |doi=10.1002/jsfa.8085 |issue=8 |pages=2623–2632 |journal=Journal of the Science of Food and Agriculture |title=The higher the better? Differences in phenolics and cyanogenic glycosides in Sambucus nigra leaves, flowers and berries from different altitudes |volume=97 |pmid=27734518 |bibcode=2017JSFA...97.2623S }}</ref><ref>{{citation|author=Rex A. Buhrmester, John E. Ebinger, David S. Seigler |date=August 2000 |doi=10.1016/S0305-1978(99)00105-2 |issue=7 |pages=689–695 |journal=Biochemical Systematics and Ecology |title=Sambunigrin and cyanogenic variability in populations of Sambucus canadensis L. (Caprifoliaceae) |volume=28 |pmid=10854744 |bibcode=2000BioSE..28..689B }}</ref> as well as in ''Ximenia americana''.<ref>{{citation|author=Nhat Hao Tran Le, Karl Egil Malterud, Drissa Diallo, Berit Smestad Paulsen, Cecilie Sogn Nergård, Helle Wangensteen |date=February 2012 |doi=10.1016/j.jep.2011.12.031 |issue=3 |pages=858–862 |journal=Journal of Ethnopharmacology |title=Bioactive polyphenols in Ximenia americana and the traditional use among Malian healers |volume=139 |pmid=22212502 }}</ref> Vicianin, another mandelonitrile glycoside, occurs in ferns of the genus ''Davellia'' (family Davalliaceae).<ref>{{citation|author=H. Kofod, R. Eyjólfsson |date=August 1969 |doi=10.1016/S0031-9422(00)85922-1 |issue=8 |pages=1509–1511 |journal=Phytochemistry |title=Cyanogenesis in species of the fern genera Cystopteris and Davalla |volume=8 |bibcode=1969PChem...8.1509K }}</ref> Dhurrin is a cyanogenic glycoside of 4-hydroxymandelonitrile found in sorghum millet and other species of the genus ''sorghum millet'', including ''Sorghum halepense''.<ref>{{citation|author=Gilles F. Nicollier, Daniel F. Pope, Alonzo C. Thompson |date=July 1983 |doi=10.1021/jf00118a016 |issue=4 |pages=744–748 |journal=Journal of Agricultural and Food Chemistry |title=Biological activity of dhurrin and other compounds from Johnson grass (Sorghum halepense) |volume=31 |bibcode=1983JAFC...31..744N }}</ref><ref>{{citation|author=Tomas Laursen, Jonas Borch, Camilla Knudsen, Krutika Bavishi, Federico Torta, Helle Juel Martens, Daniele Silvestro, Nikos S. Hatzakis, Markus R. Wenk, Timothy R. Dafforn, Carl Erik Olsen, Mohammed Saddik Motawia, Björn Hamberger, Birger Lindberg Møller, Jean-Etienne Bassard |date=2016-11-18 |doi=10.1126/science.aag2347 |issue=6314 |pages=890–893 |journal=Science |title=Characterization of a dynamic metabolon producing the defense compound dhurrin in sorghum |volume=354 |pmid=27856908 |bibcode=2016Sci...354..890L |url=https://research.birmingham.ac.uk/en/publications/90ddc888-b558-4034-a64e-4984a6708865 }}</ref> Linamarin (with the aglycone acetone cyanohydrin) and lotaustralin (with the aglycone butanone cyanohydrin) occur in the genera ''Linum'' (for example in common flax) and ''lotus flowers'', as well as in the common bean.<ref>{{citation|author=G.W. Butler |date=February 1965 |doi=10.1016/S0031-9422(00)86154-3 |issue=1 |pages=127–131 |journal=Phytochemistry |title=The distribution of the cyanoglucosides linamarin and lotaustralin in higher plants |volume=4 |bibcode=1965PChem...4..127B }}</ref> Both compounds are also present in cassava.<ref>{{citation|author=M. P. Cereda, M.C.Y. Mattos |date=1996 |doi=10.1590/S0104-79301996000100002 |issue=1 |pages=06–12 |journal=Journal of Venomous Animals and Toxins |title=Linamarin: The Toxic Compound of Cassava |volume=2|hdl=11449/64711 |hdl-access=free }}</ref> The mistletoe species ''Loranthus micranthus'' (genus ''Loranthus'') contains linamarin gallate, a derivative in which linamarin is additionally esterified with gallic acid.<ref>{{citation|author=Matthias Onyebuchi Agbo, Daowan Lai, Festus B.C. Okoye, Patience O. Osadebe, Peter Proksch |date=April 2013 |doi=10.1016/j.fitote.2013.02.006 |pages=78–83 |journal=Fitoterapia |title=Antioxidative polyphenols from Nigerian mistletoe Loranthus micranthus (Linn.) parasitizing on Hevea brasiliensis |volume=86 |pmid=23422225 }}</ref> The rubber tree also contains linamarin; studies indicate that in this case the compound likely serves as an important storage substance in addition to its defensive function. The seeds contain particularly high concentrations, and during seedling development the compound is metabolized without releasing hydrocyanic acid, suggesting utilization in other biosynthetic pathways.<ref>{{citation|author=R. Lieberei, D. Selmar, B. Biehl |date=1985 |doi=10.1007/BF00985567 |issue=1–2 |pages=49–63 |journal=Plant Systematics and Evolution |title=Metabolization of cyanogenic glucosides in Hevea brasiliensis |volume=150 |bibcode=1985PSyEv.150...49L }}</ref>

<gallery class="center" perrow="4" widths="200"> Prunus persica - Peach Hungary.jpg|Peach tree Amygdalin structure.svg|Structure of amygdalin Prunasin.svg|Struktur des Prunasins (R)-mandelonitrile-2D-skeletal.svg|Mandelonitrile, the aglycone of amygdalin and prunasin </gallery>

=== Occurrence in animals === Numerous arthropods (Arthropoda) contain cyanogenic (hydrogen cyanide-releasing) nitrile compounds, including centipedes (Chilopoda), bipedes (Diplopoda), beetles (Hemiptera), beetles (Coleoptera), and butterflies (Lepidoptera).<ref name=":13">{{citation|author=Mika Zagrobelny, Érika de Castro, Birger Møller, Søren Bak |date=2018-05-03 |doi=10.3390/insects9020051 |issue=2 |page=51 |journal=Insects |pmc=6023451 |pmid=29751568 |title=Cyanogenesis in Arthropods: From Chemical Warfare to Nuptial Gifts |volume=9 |doi-access=free }}</ref> The gooseberry moth (''Abraxas grossulariata'') contains the nitrile-bearing glycoside sarmentosin, which likely functions in defense.<ref>{{citation|author=Ritsuo Nishida, Miriam Rothschild, Rosemary Mummery |date=May 1994 |doi=10.1016/S0031-9422(00)97007-9 |issue=1 |pages=37–38 |journal=Phytochemistry |title=Acyanoglucoside, sarmentosin, from the magpie moth, Abraxas grossulariata, geometridae: Lepidoptera |volume=36 |bibcode=1994PChem..36...37N }}</ref> Sarmentosin is also present in several species of the genus ''Parnassius''.<ref>{{citation|author=Nanna Bjarnholt, Mirosław Nakonieczny, Andrzej Kędziorski, Diane M. Debinski, Stephen F. Matter, Carl Erik Olsen, Mika Zagrobelny |date=May 2012 |doi=10.1007/s10886-012-0114-x |issue=5 |pages=525–537 |journal=Journal of Chemical Ecology |title=Occurrence of Sarmentosin and Other Hydroxynitrile Glucosides in Parnassius (Papilionidae) Butterflies and Their Food Plants |volume=38 |pmid=22527055 |bibcode=2012JCEco..38..525B }}</ref> Several species of glass-winged bug (including ''Jadera haematoloma'') contain cyanolipids or cardiospermine, which they may acquire from their host plants through sequestration of toxins, i.e., uptake and storage.<ref name=":13" /><ref>{{citation|author=J. R. Aldrich, S. P. Carroll, W. R. Lusby, M. J. Thompson, J. P. Kochansky, R. M. Waters |date=January 1990 |doi=10.1007/BF01021279 |issue=1 |pages=199–210 |journal=Journal of Chemical Ecology |title=Sapindaceae, cyanolipids, and bugs |volume=16 |pmid=24264907 |bibcode=1990JCEco..16..199A }}</ref><ref>{{citation|author=J.C. Braekman, D. Daloze, J.M. Pasteels |date=December 1982 |doi=10.1016/0305-1978(82)90010-2 |issue=4 |pages=355–364 |journal=Biochemical Systematics and Ecology |title=Cyanogenic and other glucosides in a neo-guinean bug Leptocoris isolata: Possible precursors in its host-plant |volume=10 |bibcode=1982BioSE..10..355B |hdl=2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/81447 |hdl-access=free }}</ref> Six-spotted damselflies are butterflies capable of both sequestering the cyanogenic glycosides linamarin and lotaustralin from their host plants and synthesizing them de novo.<ref>{{citation|author=Mika Zagrobelny, Karsten Scheibye-Alsing, Niels Bjerg Jensen, Birger Lindberg Møller, Jan Gorodkin, Søren Bak |date=December 2009 |doi=10.1186/1471-2164-10-574 |issue=1 |journal=BMC Genomics |pmc=2791780 |pmid=19954531 |title=454 pyrosequencing based transcriptome analysis of Zygaena filipendulae with focus on genes involved in biosynthesis of cyanogenic glucosides |volume=10 |article-number=574 |doi-access=free |bibcode=2009BMCG...10..574Z }}</ref> Other species of the same genus (''Zygaena''), such as the Marsh Hornwort, also contain cyanogenic glycosides.<ref>{{citation|author=Adolf Nahrstedt |date=1993 |isbn=0-19-857762-1 |pages=107–129 |journal=Phytochemistry and Agriculture |publisher=Oxford University Press Oxford |title=Cyanogenesis and foodplants}}</ref> The defensive secretion of the centipede ''Himantarium gabrielis'' contains benzoyl cyanide, phenylacetonitrile, mandelonitrile (benzaldehyde cyanohydrin), and mandelonitrile benzoate.<ref>{{citation|author=Ljubodrag V. Vujisić, Ivan M. Vučković, Slobodan E. Makarov, Bojan S. Ilić, Dragan Ž. Antić, Milka B. Jadranin, Nina M. Todorović, Ivan V. Mrkić, Vlatka E. Vajs, Luka R. Lučić, Božidar P. M. Ćurčić, Bojan M. Mitić |date=September 2013 |doi=10.1007/s00114-013-1086-6 |issue=9 |pages=861–870 |journal=Naturwissenschaften |title=Chemistry of the sternal gland secretion of the Mediterranean centipede Himantarium gabrielis (Linnaeus, 1767) (Chilopoda: Geophilomorpha: Himantariidae) |volume=100 |pmid=23907296 |bibcode=2013NW....100..861V }}</ref> Phenylacetonitrile also functions as a hormone in the desert locust (''Schistocerca gregaria'').<ref>{{citation|author=Karsten Seidelmann, Heike Weinert, Hans-Jörg Ferenz |date=December 2003 |doi=10.1016/j.jinsphys.2003.08.005 |issue=12 |pages=1125–1133 |journal=Journal of Insect Physiology |title=Wings and legs are production sites for the desert locust courtship-inhibition pheromone, phenylacetonitrile |volume=49 |pmid=14624884 |bibcode=2003JInsP..49.1125S }}</ref> In various tapeworms (Polydesmida), the defensive secretion likewise contains benzoyl cyanide.<ref>{{citation|author=S. S. Duffey, M. S. Blum, H. M. Fales, S. L. Evans, R. W. Roncadori, D. L. Tiemann, Y. Nakagawa |date=1977 |doi=10.1007/BF00988137 |issue=1 |pages=101–113 |journal=Journal of Chemical Ecology |title=Benzoyl cyanide and mandelonitrile benzoate in the defensive secretions of millipedes |volume=3 |bibcode=1977JCEco...3..101D }}</ref> The mite species ''Oribatula tibialis'' (order horn mite, Oribatida) contains mandelonitrile hexanoate.<ref>{{citation|author=Adrian Brückner, Günther Raspotnig, Katja Wehner, Reinhard Meusinger, Roy A. Norton, Michael Heethoff |date=2017-03-28 |doi=10.1073/pnas.1618327114 |issue=13 |pages=3469–3472 |journal=Proceedings of the National Academy of Sciences |pmc=5380029 |pmid=28289203 |title=Storage and release of hydrogen cyanide in a chelicerate ( Oribatula tibialis ) |volume=114 |doi-access=free |bibcode=2017PNAS..114.3469B }}</ref> Hydrogen cyanide also occurs in arthropods as a degradation product of cyanogenic compounds.<ref name=":27" />

<gallery class="center" perrow="4" widths="200"> (1884) The Magpie (Abraxas grossulariata) (14502341918).jpg|Gooseberry moth SGR laying.jpg|Desert locust Himantarium gabrielis 77427992.jpg|''Himantarium gabrielis'' Benzoylcyanide.svg|Benzoyl cyanide is found in the defensive secretions of various arthropods </gallery>

In addition to arthropods, marine animals also contain nitrile compounds. These include bursatellin from broad-footed snails of the genus ''Bursatella''<ref>{{citation|author=Guido Cimino, Margherita Gavagnin, Guido Sodano, Aldo Spinella, Giuseppe Strazzullo, Francis J. Schmitz, Gopichand Yalamanchili |date=May 1987 |doi=10.1021/jo00387a037 |issue=11 |pages=2301–2303 |journal=The Journal of Organic Chemistry |title=Revised structure of bursatellin |volume=52}}</ref> and the calyculins isolated from sponges.<ref>{{citation|author=Annika Fagerholm, Damien Habrant, Ari M. Koskinen |date=2010-01-21 |doi=10.3390/md80100122 |issue=1 |pages=122–172 |journal=Marine Drugs |pmc=2817927 |pmid=20161975 |title=Calyculins and Related Marine Natural Products as Serine-Threonine Protein Phosphatase PP1 and PP2A Inhibitors and Total Syntheses of Calyculin A, B, and C |volume=8 |doi-access=free }}</ref> The albanitriles from sponges of the genus ''Mycale'' are linear compounds (chain length 16 to 18 carbon atoms) bearing a nitrile group at one or both termini and several additional C≡C triple bonds.<ref>{{citation|author=Samuele Sala, Jane Fromont, Oliver Gomez, Daniel Vuong, Ernest Lacey, Gavin R. Flematti |date=2019-12-27 |doi=10.1021/acs.jnatprod.9b00840 |issue=12 |pages=3450–3455 |journal=Journal of Natural Products |title=Albanitriles A–G: Antiprotozoal Polyacetylene Nitriles from a Mycale Marine Sponge |volume=82 |pmid=31833368 |bibcode=2019JNAtP..82.3450S }}</ref>

=== Occurrence in fungi === Many fungi produce hydrogen cyanide from glycine. These include representatives of the genera funnel mushrooms (''Clitocybe''), dwindlers (''Marasmius''), stem porcini (''Polyporus''), and Ritterlinge (''Tricholoma'').<ref>{{citation|author=C J Knowles |date=September 1976 |doi=10.1128/br.40.3.652-680.1976 |issue=3 |pages=652–680 |journal=Bacteriological Reviews |pmc=413975 |pmid=791236 |title=Microorganisms and cyanide |volume=40}}</ref> The epurpurins are a group of yellow phenolic pigments, each bearing two nitrile groups, occurring in ''Emericella purpurea''.<ref>{{citation|author=Hideyuki Takahashi, Koohei Nozawa, Ken-ichi Kawai |date=1996 |doi=10.1248/cpb.44.2227 |issue=12 |pages=2227–2230 |journal=Chemical and Pharmaceutical Bulletin |title=Isolation and Structures of Dicyanide Derivatives, Epurpurins A to C, from Emericella purpurea. |volume=44}}</ref> Diatretin II occurs in Fleshy Fungus (''Clitocybe diatreta'')<ref>{{citation|author=Marjorie Anchel |date=November 1958 |doi=10.1016/0003-9861(58)90318-7 |issue=1 |pages=100–110 |journal=Archives of Biochemistry and Biophysics |title=Metabolic products of Clitocybe diatreta. I. Diatretyne amide and diatretyne nitrile |volume=78 |pmid=13595907 }}</ref> and in the purple reddish bolete.<ref>{{citation|author=N. G. Heatley, J. S. Stephenson |date=May 1957 |doi=10.1038/1791078a0 |issue=4569 |pages=1078 |journal=Nature |title=Identity of 'Nudic Acid B' and 'Diatretyne II' |volume=179 |bibcode=1957Natur.179Q1078H }}</ref> In the clove dwarf mushroom, the cyanohydrin of glyoxylic acid is present; it is formed from two glycine molecules and releases hydrocyanic acid upon tissue damage.<ref>{{citation|author=Jan Caspar, Peter Spiteller |date=2015-03-02 |doi=10.1002/cbic.201402453 |issue=4 |pages=570–573 |journal=ChemBioChem |title=A Free Cyanohydrin as Arms and Armour of Marasmius oreades |volume=16 |pmid=25630401 }}</ref>

=== Occurrence in bacteria === Hydrogen cyanide is produced by various soil bacteria, including cyanobacteria and representatives of the genera ''Aeromonas'', ''Bacillus'', and ''Pseudomonas''. Biosynthesis proceeds from glycine.<ref>{{citation|author=Anju Sehrawat, Satyavir S. Sindhu, Bernard R. Glick |date=February 2022 |doi=10.1016/S1002-0160(21)60058-9 |issue=1 |pages=15–38 |journal=Pedosphere |title=Hydrogen cyanide production by soil bacteria: Biological control of pests and promotion of plant growth in sustainable agriculture |volume=32 |bibcode=2022Pedos..32...15S }}</ref> A group of alkanenitriles was isolated from ''Pseudomonas veronii'': dodecannitrile, tridecannitrile, tetradecanenitrile, pentadecannitrile, and hexadecannitrile, as well as compounds of similar chain length containing a double bond. From ''Micromonospora echinospora'', structurally related compounds were also isolated, differing by a terminal methyl branch, a double bond, or both.<ref>{{citation|author=Diogo Montes Vidal, Anna-Lena von Rymon-Lipinski, Srinivasa Ravella, Ulrike Groenhagen, Jennifer Herrmann, Nestor Zaburannyi, Paulo H. G. Zarbin, Adithi R. Varadarajan, Christian H. Ahrens, Laure Weisskopf, Rolf Müller, Stefan Schulz |date=2017-04-03 |doi=10.1002/anie.201611940 |issue=15 |pages=4342–4346 |journal=Angewandte Chemie International Edition |title=Long-Chain Alkyl Cyanides: Unprecedented Volatile Compounds Released by Pseudomonas and Micromonospora Bacteria |volume=56 |pmid=28276609 }}</ref> A cyanohydrin containing a phosphonic acid moiety is known from ''Streptomyces regensis''.<ref>{{citation|author=Joel P. Cioni, James R. Doroghazi, Kou-San Ju, Xiaomin Yu, Bradley S. Evans, Jaeheon Lee, William W. Metcalf |date=2014-02-28 |doi=10.1021/np400722m |issue=2 |pages=243–249 |journal=Journal of Natural Products |pmc=3993929 |pmid=24437999 |title=Cyanohydrin Phosphonate Natural Product from Streptomyces regensis |volume=77 |bibcode=2014JNAtP..77..243C }}</ref> The aetokthonotoxin from the cyanobacteria ''Aetokthonos hydrillicola'' is a brominated indole derivative bearing a nitrile group. It is a potent neurotoxin that frequently causes mortality in bald eagles that ingest it.<ref>{{citation|author=Sanjoy Adak, April L. Lukowski, Rebecca J. B. Schäfer, Bradley S. Moore |date=2022-02-23 |doi=10.1021/jacs.1c12778 |issue=7 |pages=2861–2866 |journal=Journal of the American Chemical Society |pmc=9004672 |pmid=35142504 |title=From Tryptophan to Toxin: Nature's Convergent Biosynthetic Strategy to Aetokthonotoxin |volume=144 |bibcode=2022JAChS.144.2861A }}</ref>

=== Occurrence in space === Nitriles are among the most abundant organic molecules in space, and more than ten distinct compounds have been unequivocally detected.<ref name=":28" /> Hydrogen cyanide was one of the first polyatomic species identified in space and occurs there relatively frequently and in substantial quantities.<ref>{{citation|author=S Green |date=October 1981 |doi=10.1146/annurev.pc.32.100181.000535 |issue=1 |pages=103–138 |journal=Annual Review of Physical Chemistry |title=Interstellar Chemistry: Exotic Molecules in Space |volume=32 |bibcode=1981ARPC...32..103G }}</ref> Other nitriles detected in space include acetonitrile and aminoacetonitrile,<ref name=":28">{{citation|author=Max P. Bernstein, Samantha F. M. Ashbourn, Scott A. Sandford, Louis J. Allamandola |date=2004-01-20 |doi=10.1086/380306 |issue=1 |pages=365–370 |journal=The Astrophysical Journal |title=The Lifetimes of Nitriles (CN) and Acids (COOH) during Ultraviolet Photolysis and Their Survival in Space |volume=601 |bibcode=2004ApJ...601..365B }}</ref> as well as butyronitrile,<ref>{{citation|author=Richard Carter, Mary M. Nijhout |date=1977-01-28 |doi=10.1126/science.12566 |issue=4276 |pages=407–409 |journal=Science |title=Control of Gamete Formation (Exflagellation) in Malaria Parasites |volume=195 |pmid=12566 |bibcode=1977Sci...195..407C }}</ref> cyanoacetylene, and cyanopolyins containing two to five conjugated triple bonds.<ref>{{citation|author=Jean-Claude Guillemin, Miloud Bouyahyi, El Hassan Riague |date=January 2004 |doi=10.1016/j.asr.2003.07.015 |issue=1 |pages=81–87 |journal=Advances in Space Research |title=Prebiotic, planetary and interstellar chemistry starting from compounds detected in the interstellar medium |volume=33 |bibcode=2004AdSpR..33...81G }}</ref> Hydrogen cyanide, cyanoacetylene, and cyanogen are present in the atmosphere of Saturn's moon Titan.<ref name=":15" />

=== Significance for the origin of life === Nitriles may have played a significant role in chemical evolution on Earth.<ref name=":14">{{citation|author=Yannick Vallee, Ibrahim Shalayel, Kieu-Dung Ly, K. V. Raghavendra Rao, Gael De Paëpe, Katharina Märker, Anne Milet |date=2017 |doi=10.1387/ijdb.170028yv |issue=8–9 |pages=471–478 |journal=The International Journal of Developmental Biology |title=At the very beginning of life on Earth: the thiol-rich peptide (TRP) world hypothesis |volume=61 |pmid=29139533 }}</ref><ref name=":15">{{citation|author=Nicholas F. Wogan, David C. Catling, Kevin J. Zahnle, Roxana Lupu |date=2023-09-01 |doi=10.3847/PSJ/aced83 |issue=9 |page=169 |journal=The Planetary Science Journal |title=Origin-of-life Molecules in the Atmosphere after Big Impacts on the Early Earth |volume=4 |doi-access=free |arxiv=2307.09761 |bibcode=2023PSJ.....4..169W }}</ref> Experimental studies have demonstrated that hydrogen cyanide can form under a wide range of plausible prebiotic conditions. Possible starting materials include gas mixtures of methane, carbon dioxide, nitrogen, ammonia, and/or hydrogen. Various energy sources, such as electrical discharges or ultraviolet radiation, are likewise conceivable. Under simple conditions, hydrogen cyanide can give rise to numerous additional organic molecules.<ref name=":29">{{citation|author=James P. Ferris, William J. Hagan |date=January 1984 |doi=10.1016/S0040-4020(01)99315-9 |issue=7 |pages=1093–1120 |journal=Tetrahedron |title=HCN and chemical evolution: The possible role of cyano compounds in prebiotic synthesis |volume=40 |pmid=11541961 |bibcode=1984Tetra..40.1093F }}</ref> Hydrogen cyanide and other nitriles, such as cyanoacetylene and dicyan, are considered potential precursors of nucleic bases.<ref name=":15" /><ref name=":29" /> Aminonitriles, in turn, are regarded as likely precursors of amino acids and peptides; for example, aminoacetonitrile is a precursor of glycine. An analogous process to the Strecker synthesis is proposed, in which α-aminopropionitrile initially forms from cyanide, acetaldehyde, and ammonia and is subsequently hydrolyzed to alanine.<ref name=":14" /><ref>{{citation|author=L. Chimiak, J. Eiler, A. Sessions, C. Blumenfeld, M. Klatte, B.M. Stoltz |date=March 2022 |doi=10.1016/j.gca.2022.01.015 |pages=78–98 |journal=Geochimica et Cosmochimica Acta |title=Isotope effects at the origin of life: Fingerprints of the Strecker synthesis |volume=321 |bibcode=2022GeCoA.321...78C |osti=1844259 }}</ref><ref>{{citation|author=Ibrahim Shalayel, Seydou Coulibaly, Kieu Ly, Anne Milet, Yannick Vallée |date=2018-10-19 |doi=10.3390/life8040047 |issue=4 |page=47 |journal=Life |pmc=6316830 |pmid=30347745 |title=The Reaction of Aminonitriles with Aminothiols: A Way to Thiol-Containing Peptides and Nitrogen Heterocycles in the Primitive Earth Ocean |volume=8 |doi-access=free |bibcode=2018Life....8...47S }}</ref>

== Use == Hydrogen cyanide is used on a large scale in the chemical industry as an intermediate for the production of other compounds. Acrylonitrile is an important feedstock for the manufacture of nitrile polymers. Acetonitrile is an important solvent. Other nitriles are employed as fragrances, pesticides, and chemical reagents. The nitrile group also plays a significant role in the development of active pharmaceutical ingredients.

=== Use of hydrogen cyanide === thumb|450px|Hydrogen cyanide (HCN) downstream products: acetone cyanohydrin, methyl methacrylate and its polymer PMMA (top row); cyanuric chloride (top center); methionine (bottom center); adiponitrile, hexamethylene diamine and polyamide 6.6 (bottom row)

Hydrogen cyanide is a bulk chemical; global production in 2001 was approximately 2.6 million tons. Key derivatives produced from it include adiponitrile, acetone cyanohydrin, sodium cyanide, and cyanuric chloride.<ref name=":25">{{citation|author=David Nakles, Richard Luthy, George Wong-Chong |date=2005-12-09 |pages=41–55 |journal=Cyanide in Water and Soil |publisher=CRC Press |title=Manufacture and the Use of Cyanide}}</ref><ref name=":32">{{citation|date=2005 |doi=10.1007/0-306-48639-3_19 |isbn=0-306-48225-8 |location=Boston |pages=347–360 |journal=Synthetic Nitrogen Products |publisher=Kluwer Academic Publishers |title=Hydrogen Cyanide |volume=19}}</ref> Chelating agents are also synthesized from hydrogen cyanide,<ref name=":32" /> for example ethylenediaminetetraacetic acid from formaldehyde, ethylenediamine, hydrogen cyanide, and sodium hydroxide.<ref>{{citation|date=2005 |doi=10.1007/0-306-48639-3_16 |isbn=0-306-48225-8 |location=Boston |pages=325–331 |journal=Synthetic Nitrogen Products |publisher=Kluwer Academic Publishers |title=Ethylenediamine and Chelating Agents |volume=16}}</ref> An important industrial route to amino acids is the Strecker synthesis, in which hydrogen cyanide serves as a starting material.<ref>{{citation|author=Harald Gröger |date=2003-08-01 |doi=10.1021/cr020038p |issue=8 |pages=2795–2828 |journal=Chemical Reviews |title=Catalytic Enantioselective Strecker Reactions and Analogous Syntheses |volume=103 |pmid=12914481 }}</ref> A quantitatively important amino acid is methionine, which is produced from acrolein, hydrogen cyanide, and hydrogen sulphide and is used primarily in animal feed.<ref name=":32" /><ref>{{citation|author=Thomas Willke |date=December 2014 |doi=10.1007/s00253-014-6156-y |issue=24 |pages=9893–9914 |journal=Applied Microbiology and Biotechnology |title=Methionine production—a critical review |volume=98 |pmid=25381187 }}</ref>

=== Plastics production === Several widely used polymers contain acrylonitrile as a monomer and therefore incorporate nitrile groups. Pure polyacrylonitrile (PAN) is difficult to process; consequently, during its production, 85 to 99% acrylonitrile is almost always copolymerized with small amounts of other monomers.<ref name=":0" /> Copolymers containing 35 to 85% acrylonitrile, together with other monomers such as vinyl acetate and methyl methacrylate, are also employed.<ref name=":0" /><ref name=":1">{{citation|author=Arman Sedghi, Reza Eslami Farsani, Ali Shokuhfar |date=March 2008 |doi=10.1016/j.jmatprotec.2007.06.052 |issue=1–3 |pages=60–67 |journal=Journal of Materials Processing Technology |title=The effect of commercial polyacrylonitrile fibers characterizations on the produced carbon fibers properties |volume=198}}</ref> Nitrile polymers are among the most important fully synthetic materials for textile fibers, alongside polyesters and polyamidess.<ref name=":0" /><ref>{{citation|author=Md Abdullah Al Faruque, Rechana Remadevi, Joselito Razal, Xungai Wang, Maryam Naebe |date=2020-02-15 |doi=10.1002/app.48370 |issue=7 |journal=Journal of Applied Polymer Science |title=Investigation on structure and characteristics of alpaca-based wet-spun polyacrylonitrile composite fibers by utilizing natural textile waste |volume=137 |article-number=48370 |url=https://figshare.com/articles/journal_contribution/20745766 }}</ref> These fibers, known as ''acrylic fibers'', are produced on the scale of several million tons per year. In 2000, global production was approximately 2.7 million tons.<ref name=":0" /><ref>{{citation|author=B. E. Geller |date=2002 |doi=10.1023/A:1020525628197 |issue=3 |pages=151–161 |journal=Fibre Chemistry |title=Status and Prospects for Development of Polyacrylonitrile Fibre Production. A Review |volume=34}}</ref> Acrylic fibers are used in garments (such as socks and sweaters), blankets, carpets, and knitting yarn, among other applications.<ref name=":0" /><ref>{{citation|author=P. Bajaj, Surya Kumari |date=May 1987 |doi=10.1080/07366578708081915 |issue=2 |pages=181–217 |journal=Journal of Macromolecular Science, Part C: Polymer Reviews |title=Modification of Acrylic Fibers: An Overview |volume=27}}</ref> PAN is also the principal precursor for the production of carbon fiber, which is used as an exceptionally lightweight yet strong material in automotive and aircraft construction.<ref name=":0" /><ref name=":1" /><ref>{{citation|author=T.A. Adegbola, O. Agboola, O.S.I. Fayomi |date=September 2020 |doi=10.1016/j.rineng.2020.100144 |article-number=100144 |journal=Results in Engineering |title=Review of polyacrylonitrile blends and application in manufacturing technology: recycling and environmental impact |volume=7|doi-access=free }}</ref><ref>{{citation|author=Xing Jin, Chunfang Feng, Claudia Creighton, Nishar Hameed, Jyotishkumar Parameswaranpillai, Nisa V. Salim |date=2021-04-01 |doi=10.1016/j.polymdegradstab.2021.109536 |article-number=109536 |journal=Polymer Degradation and Stability |title=On the structural evolution of textile grade polyacrylonitrile fibers during stabilization and carbonization: Towards the manufacture of low-cost carbon fiber |volume=186 |url=https://figshare.com/articles/journal_contribution/26252870 }}</ref> Global production of the monomer acrylonitrile was approximately 3.2 million tons in 1988.<ref name=":25" />

Acrylonitrile butadiene rubbers are known as nitrile rubbers and exhibit advantageous properties such as high tensile strength, high abrasion resistance, and resistance to hydrocarbons (oils and fuels). They are therefore used for sealing rings and for oil and fuel hoses.<ref name=":0" /> Another important application of nitrile rubber is protective gloves, which are frequently used in healthcare instead of latex clothing gloves, as the latter often cause latex allergies.<ref>{{citation|author=J. Sawyer |date=2005-12-12 |doi=10.1093/annhyg/mei066 |issue=3 |pages=289–296 |journal=Annals of Occupational Hygiene |title=Comparing the Level of Dexterity offered by Latex and Nitrile SafeSkin Gloves |volume=50 |pmid=16357028 }}</ref> Such gloves are also commonly used when handling hazardous chemicals, including organic solvents.<ref>{{citation|author=Keh-Ping Chao, Pak-Hing Lee, Min-Jet Wu |date=April 2003 |doi=10.1016/S0304-3894(03)00042-6 |issue=2 |pages=191–201 |journal=Journal of Hazardous Materials |title=Organic solvents permeation through protective nitrile gloves |volume=99 |pmid=12719151 |bibcode=2003JHzM...99..191C }}</ref>

Another important polymer is the terpolymer of acrylonitrile, butadiene, and styrene (acrylonitrile-butadiene-styrene copolymer). This material is widely used for the outer housings of electronic devices (computers, monitors, and keyboards).<ref>{{citation|author=L. B. Brennan, D. H. Isaac, J. C. Arnold |date=2002-10-17 |doi=10.1002/app.10833 |issue=3 |pages=572–578 |journal=Journal of Applied Polymer Science |title=Recycling of acrylonitrile–butadiene–styrene and high-impact polystyrene from waste computer equipment |volume=86 |bibcode=2002JAPS...86..572B }}</ref> Other applications include automotive plastic components (e.g., headlight and mirror housings), refrigerator liners, housings for kitchen appliances, vacuum cleaners, and power tools, as well as suitcases, snack containers,<ref name=":2">{{citation|date=2006 |location=New York, NY |page=22 |journal=Encyclopedic Dictionary of Polymers |publisher=Springer New York |title=Acrylonitrile-butadiene-styrene copolymers}}</ref> and toys, including Lego.<ref>{{citation|author=Francesca Sabatini, Silvia Pizzimenti, Irene Bargagli, Ilaria Degano, Celia Duce, Laura Cartechini, Francesca Modugno, Francesca Rosi |date=2023-07-31 |doi=10.3390/polym15153267 |issue=15 |page=3267 |journal=Polymers |title=A Thermal Analytical Study of LEGO® Bricks for Investigating Light-Stability of ABS |volume=15 |doi-access=free |pmid=37571161 |pmc=10422395 |hdl=11568/1221334 |hdl-access=free }}</ref><ref>{{citation|author=Zhijuan Wang, Hongyan Li, Tao Li, Qing Zhang, Yaqi Cai, Hua Bai, Qing Lv |date=March 2023 |doi=10.1016/j.ecoenv.2023.114570 |article-number=114570 |journal=Ecotoxicology and Environmental Safety |title=Application of validated migration models for the risk assessment of styrene and acrylonitrile in ABS plastic toys |volume=252 |pmid=36706528 |bibcode=2023EcoES.25214570W |doi-access=free }}</ref> ABS is also produced on the scale of several million tons annually; for example, about 2.7 million tons were manufactured in 1992.<ref name=":2" />

Polyamide (nylon) is not a nitrile polymer; however, a key intermediate in its production is adiponitrile. Adiponitrile is obtained by hydrocyanation of butadiene or by dimerization of acrylonitrile and is converted by catalytic hydrogenation into hexamethylenediamine, one of the monomers used to produce nylon. The second monomer, adipic acid, is produced by oxidation of cyclohexane.<ref>{{citation|author=Alex Tullo |date=2018-10-08 |doi=10.1021/cen-09640-feature3 |issue=40 |pages=22–23 |journal=C&EN Global Enterprise |title=Industry braces for nylon 6,6 shortage |volume=96}}</ref><ref>{{citation|author=Younghyun Lee, Sung Woo Lee, Hyung Ju Kim, Yong Tae Kim, Kun-Yi Andrew Lin, Jechan Lee |date=2020-10-26 |doi=10.3390/app10217506 |issue=21 |page=7506 |journal=Applied Sciences |title=Hydrogenation of Adiponitrile to Hexamethylenediamine over Raney Ni and Co Catalysts |volume=10 |doi-access=free }}</ref> Acetone cyanohydrin is an important intermediate in the production of methyl methacrylate, which in turn is used to manufacture polymethyl methacrylate.<ref>{{citation|author=Mohammad Jaber Darabi Mahboub, Jean-Luc Dubois, Fabrizio Cavani, Mohammad Rostamizadeh, Gregory S. Patience |date=2018 |doi=10.1039/C8CS00117K |issue=20 |pages=7703–7738 |journal=Chemical Society Reviews |title=Catalysis for the synthesis of methacrylic acid and methyl methacrylate |volume=47 |pmid=30211916 }}</ref>

<gallery class="center" perrow="4" widths="200"> Cotton-acrylic yarn.jpg|Polyacrylonitrile is used in knitting yarn Carbonsheetwiki1.png|Carbon fibers are often made from polyacrylonitrile Syringe Glove 01.jpg|Protective gloves made from nitrile rubber Lego Color Bricks.jpg|Lego bricks are made from acrylonitrile butadiene styrene copolymer (ABS) </gallery>

=== Chemical-pharmaceutical industry and laboratories === Acetonitrile is used as a solvent, particularly in the pharmaceutical industry.<ref name=":3">{{citation|author=Ian F. McConvey, Dean Woods, Moira Lewis, Quan Gan, Paul Nancarrow |date=2012-04-20 |doi=10.1021/op2003503 |issue=4 |pages=612–624 |journal=Organic Process Research & Development |title=The Importance of Acetonitrile in the Pharmaceutical Industry and Opportunities for its Recovery from Waste |volume=16 |url=https://pure.qub.ac.uk/en/publications/de533647-f193-49f2-b6e7-9eee75cf765f }}</ref> According to a market analysis, approximately 180,000 tons of acetonitrile were produced worldwide in 2022, of which around 70% was consumed by the pharmaceutical sector.<ref>{{cite web|access-date=2024-01-11 |title=Acetonitrile Market Size, Growth, Analysis & Forecast, 2032 |url=https://www.chemanalyst.com/industry-report/acetonitrile-market-721}}</ref> It is also one of the most important solvents for analyses performed by high-performance liquid chromatography.<ref name=":3" /><ref>{{citation|author=Cristiano Soleo Funari, Renato Lajarim Carneiro, Manish M. Khandagale, Alberto José Cavalheiro, Emily F. Hilder |date=May 2015 |doi=10.1002/jssc.201401324 |issue=9 |pages=1458–1465 |journal=Journal of Separation Science |title=Acetone as a greener alternative to acetonitrile in liquid chromatographic fingerprinting |volume=38 |pmid=25708832 }}</ref> The thermal decomposition of azobisisobutyronitrile (AIBN) and related compounds (e.g., azobis(cyclohexanecarbonitrile)) generates relatively stable radicals; accordingly, these compounds are used as radical initiators in radical reactions, particularly polymerizations.<ref>{{citation|author=Ladislav Androvič, Jan Bartáček, Miloš Sedlák |date=June 2016 |doi=10.1007/s11164-015-2351-4 |issue=6 |pages=5133–5145 |journal=Research on Chemical Intermediates |title=Recent advances in the synthesis and applications of azo initiators |volume=42}}</ref> The quinone DDQ, which contains two nitrile groups, is a widely used oxidizing agent, including in pharmaceutical synthesis.<ref>{{citation|author=Bao Li, Alison E. Wendlandt, Shannon S. Stahl |date=2019-02-15 |doi=10.1021/acs.orglett.9b00111 |issue=4 |pages=1176–1181 |journal=Organic Letters |pmc=6413530 |pmid=30702297 |title=Replacement of Stoichiometric DDQ with a Low Potential o -Quinone Catalyst Enabling Aerobic Dehydrogenation of Tertiary Indolines in Pharmaceutical Intermediates |volume=21}}</ref> Nitrile groups can be incorporated into biomolecules as probes for infrared spectroscopic investigations.<ref>{{citation|author=Jun-Ho Choi, Kwang-Im Oh, Hochan Lee, Chewook Lee, Minhaeng Cho |date=2008-04-07 |doi=10.1063/1.2844787 |issue=13 |journal=The Journal of Chemical Physics |title=Nitrile and thiocyanate IR probes: Quantum chemistry calculation studies and multivariate least-square fitting analysis |volume=128 |article-number=134506 |pmid=18397076 |bibcode=2008JChPh.128m4506C }}</ref> Some nitriles serve as starting materials for the synthesis of pharmaceuticals.<ref name=":30">{{citation|author=Fritz Ullmann, Barbara Elvers, Stephen Hawkins, Gail Schulz |date=1991 |edition=5th |isbn=3-527-20117-3 |location=Weinheim New York |publisher=VCH |title=Ullmann's encyclopedia of industrial chemistry}}</ref> Ketoprofen is an anti-inflammatory agent approved in some EU countries; propionitrile is used in its industrial synthesis.<ref>{{citation|author=S. DAWSON |display-authors=etal. |date=2005-08-01 |publisher=Office of Scientific and Technical Information (OSTI) |title=THE HIGGS WORKING GROUP: SUMMARY REPORT.}}</ref><ref>{{citation|author=Lili Song, Zhigang Liu, Minjie Liu, Pei Tang, Fener Chen |date=2023-05-19 |doi=10.1021/acs.oprd.3c00049 |issue=5 |pages=922–927 |journal=Organic Process Research & Development |title=Efficient and Scalable Synthesis of Ketoprofen: A Pyrolytic Aromatization Approach |volume=27}}</ref>

=== Nitriles in medicine === Nitriles occur in numerous classes of drugs. Between 2010 and 2020, at least one drug containing a nitrile function was approved annually by the US Food and Drug Administration. The nitrile group exhibits characteristic physicochemical properties that are important in drug design. Structurally, it has a linear geometry and occupies very little space—approximately one eighth of the volume of a methyl group. As a ligand substituent, it is therefore well suited to occupying narrow and deep cavities within the binding site of a target protein that are otherwise difficult to access. Incorporation of a nitrile group into a molecule generally reduces its octanol-water partition coefficient or increases its aqueous solubility. This often favorably influences bioavailability, plasma half-life, and thus the duration of action of lipophilic compounds. In medicinal products, the nitrile group is typically metabolically stable.<ref name=":33">{{citation|author=Xi Wang, Yuanxun Wang, Xuemin Li, Zhenyang Yu, Chun Song, Yunfei Du |date=2021 |doi=10.1039/D1MD00131K |issue=10 |pages=1650–1671 |journal=RSC Medicinal Chemistry |pmc=8528211 |pmid=34778767 |title=Nitrile-containing pharmaceuticals: target, mechanism of action, and their SAR studies |volume=12}}</ref> The nitrile group is isosteric with the carbonyl group, the hydroxy group, and the chlorine atom. It therefore exhibits similar electronic and steric properties and can be exchanged with these groups to fine-tune molecular characteristics.<ref name=":35">{{citation|author=Xi Wang, Yuanxun Wang, Xuemin Li, Zhenyang Yu, Chun Song, Yunfei Du |date=2021 |doi=10.1039/D1MD00131K |issue=10 |page=1651 |journal=RSC Medicinal Chemistry |pmc=8528211 |pmid=34778767 |title=Nitrile-containing pharmaceuticals: target, mechanism of action, and their SAR studies |volume=12}}</ref>

The hydrogen bond represents the principal pharmacodynamic interaction of the nitrile group, which acts as a proton acceptor due to the electronegativity of its nitrogen atom, in contrast to the ethynyl group.<ref>{{citation|author=Xi Wang, Yuanxun Wang, Xuemin Li, Zhenyang Yu, Chun Song, Yunfei Du |date=2021 |doi=10.1039/D1MD00131K |issue=10 |pages=1650–1671 |journal=RSC Medicinal Chemistry |pmc=8528211 |pmid=34778767 |title=Nitrile-containing pharmaceuticals: target, mechanism of action, and their SAR studies |volume=12}}</ref> For example, the nitrile group of the competitive PDE-3 inhibitor milrinone forms an affinity-relevant hydrogen bond via a histidine residue located at the binding site of these phosphodiesterases.<ref name=":33" /> Nitriles can form a coordinative bond with calcium cations, which is essential for the activity of calcium antagonists of the verapamil type. These agents inhibit calcium influx by forming, through ligand–calcium complex chemistry, a salt bridge with one of the glutamic acid residues in the selectivity filter within the pore of the calcium channel.<ref>{{citation|author=Xi Wang, Yuanxun Wang, Xuemin Li, Zhenyang Yu, Chun Song, Yunfei Du |date=2021 |doi=10.1039/D1MD00131K |issue=10 |pages=1651f |journal=RSC Medicinal Chemistry |pmc=8528211 |pmid=34778767 |title=Nitrile-containing pharmaceuticals: target, mechanism of action, and their SAR studies |volume=12}}</ref><ref>{{citation|author=Ricky C.K. Cheng, Denis B. Tikhonov, Boris S. Zhorov |date=October 2009 |doi=10.1074/jbc.M109.027326 |issue=41 |pages=28332–28342 |journal=Journal of Biological Chemistry |pmc=2788883 |pmid=19700404 |title=Structural Model for Phenylalkylamine Binding to L-type Calcium Channels |volume=284 |doi-access=free }}</ref> Verapamil is used in cardiovascular diseases such as arterial hypertension and angina pectoris.<ref>{{citation|author=Natalija Popović, Nicanor Morales-Delgado, David Vidal Mena, Antonia Alonso, María Pascual Martínez, María Caballero Bleda, Miroljub Popović |date=2020-05-05 |doi=10.3389/fphar.2020.00562 |journal=Frontiers in Pharmacology |pmc=7214748 |pmid=32431612 |title=Verapamil and Alzheimer's Disease: Past, Present, and Future |volume=11 |article-number=562 |doi-access=free }}</ref>

Nitrile substituents decrease the electron density of aromatic compounds through a strong inductive effect. In this manner, π-π interactions between a drug molecule and suitable amino acid residues of a target protein, such as phenylalanine, tyrosine, tryptophan, and histidine, are modulated.<ref name=":35" /> Such π-π interactions are observed with the aromatase inhibitors letrozole and anastrozole, which act as antiestrogens and are used in breast cancer.<ref>{{citation|author=Xi Wang, Yuanxun Wang, Xuemin Li, Zhenyang Yu, Chun Song, Yunfei Du |date=2021 |doi=10.1039/D1MD00131K |issue=10 |page=1654 |journal=RSC Medicinal Chemistry |pmc=8528211 |pmid=34778767 |title=Nitrile-containing pharmaceuticals: target, mechanism of action, and their SAR studies |volume=12}}</ref><ref>{{citation|author=Junmei Cairns, James N. Ingle, Tanda M. Dudenkov |display-authors=etal. |date=2020-08-20 |doi=10.1172/jci.insight.137571 |issue=16 |journal=JCI Insight |pmc=7455128 |pmid=32701512 |title=Pharmacogenomics of aromatase inhibitors in postmenopausal breast cancer and additional mechanisms of anastrozole action |volume=5 |article-number=e137571 }}</ref> Many androgen receptor antagonists contain a markedly electron-deficient aromatic ring, which is particularly important for supramolecular receptor binding.<ref name="pmid15833816">{{cite journal |author=Bohl CE, Gao W, Miller DD, Bell CE, Dalton JT |title=Structural basis for antagonism and resistance of bicalutamide in prostate cancer |journal=Proc Natl Acad Sci U S A |volume=102 |issue=17 |pages=6201–6 |date=2005 |pmid=15833816 |pmc=1087923 |doi=10.1073/pnas.0500381102 |doi-access=free |bibcode=2005PNAS..102.6201B |url=}}</ref> In bicalutamide, enzalutamide, and other analogs used to treat prostate cancer, a nitrile group contributes to this electronic effect.<ref>{{citation|author=Xi Wang, Yuanxun Wang, Xuemin Li, Zhenyang Yu, Chun Song, Yunfei Du |date=2021 |doi=10.1039/D1MD00131K |issue=10 |page=1653 |journal=RSC Medicinal Chemistry |pmc=8528211 |pmid=34778767 |title=Nitrile-containing pharmaceuticals: target, mechanism of action, and their SAR studies |volume=12}}</ref>

In some cases, nitriles form a reversible yet pharmacologically relevant covalent bond with a target molecule.<ref name=":35" /> Under appropriate conditions, an addition reaction can occur between serine or cysteine residues of the target protein and the nitrile group to form imidic acid esters or thioimidates. This mechanism applies to the dipeptidyl peptidase 4 inhibitor vildagliptin used in diabetes mellitus,<ref>{{citation|author=Mahnoor Pasha, Ammara Zamir, Waseem Ashraf, Imran Imran, Hamid Saeed, Anees Ur Rehman, Majid Aziz, Faleh Alqahtani, Muhammad Fawad Rasool |date=2023-11-26 |doi=10.1080/17425255.2023.2288252 |pages=991–1003 |journal=Expert Opinion on Drug Metabolism & Toxicology |title=A systematic review on the clinical pharmacokinetics of vildagliptin in healthy and disease populations |volume=19 |issue=12 |pmid=38008954 }}</ref> as well as to saxagliptin.<ref>{{citation|author=Mika Nabeno, Fumihiko Akahoshi, Hiroyuki Kishida, Ikuko Miyaguchi, Yoshihito Tanaka, Shinichi Ishii, Takashi Kadowaki |date=May 2013 |doi=10.1016/j.bbrc.2013.03.010 |issue=2 |pages=191–196 |journal=Biochemical and Biophysical Research Communications |title=A comparative study of the binding modes of recently launched dipeptidyl peptidase IV inhibitors in the active site |volume=434 |pmid=23501107 |bibcode=2013BBRC..434..191N }}</ref> The antibacterial antibiotic cefmetazole also acts as a covalent inhibitor, in this case targeting a bacterial peptidase.<ref>{{citation|author=Xi Wang, Yuanxun Wang, Xuemin Li, Zhenyang Yu, Chun Song, Yunfei Du |date=2021 |doi=10.1039/D1MD00131K |issue=10 |page=1660 |journal=RSC Medicinal Chemistry |pmc=8528211 |pmid=34778767 |title=Nitrile-containing pharmaceuticals: target, mechanism of action, and their SAR studies |volume=12}}</ref> The calcium sensitizer levosimendan is presumed to react with the cardiac troponin protein complex.<ref>{{citation|author=Sandra E. Pineda-Sanabria, Ian M. Robertson, Yin-Biao Sun, Malcolm Irving, Brian D. Sykes |date=March 2016 |doi=10.1016/j.yjmcc.2016.02.003 |pages=174–184 |journal=Journal of Molecular and Cellular Cardiology |pmc=4831045 |pmid=26853943 |title=Probing the mechanism of cardiovascular drugs using a covalent levosimendan analog |volume=92}}</ref> Such a reactive functional group is also referred to as a warhead.

In certain cases, nitrile groups exert their effect primarily through steric interactions (i.e., spatial complementarity) by forming van der Waals forces with amino acid residues. This applies to the tyrosine kinase inhibitor bosutinib, which is used in chronic myeloid leukemia. Crystal structures have been reported in which bosutinib is complexed with various tyrosine kinases. Inhibitors of reverse transcriptase, such as Etravirin and Rilpivirin, are used in combination therapies against HIV. The acrylonitrile substructure of rilpivirine penetrates an aromatic cage composed of tyrosine, phenylalanine, and tryptophan, as demonstrated by the corresponding three-dimensional structure published in 2008.<ref name="pmid18230722">{{cite journal |author=Das K, Bauman JD, Clark AD, Frenkel YV, Lewi PJ, Shatkin AJ, Hughes SH, Arnold E |title=High-resolution structures of HIV-1 reverse transcriptase/TMC278 complexes: strategic flexibility explains potency against resistance mutations |journal=Proc Natl Acad Sci U S A |volume=105 |issue=5 |pages=1466–71 |date=2008 |pmid=18230722 |pmc=2234167 |doi=10.1073/pnas.0711209105 |doi-access=free |url=}}</ref> The serotonin reuptake inhibitor citalopram, used in the treatment of depression, was the most frequently prescribed psychotropic drug in Germany in 2016, with 290 million defined daily doses. The nitrile group of escitalopram exhibits optimal complementarity to both the central and an additional allosteric binding site of the transporter protein, as evidenced by crystal structure analysis.<ref name="pmid27049939">{{cite journal |author=Coleman JA, Green EM, Gouaux E |title=X-ray structures and mechanism of the human serotonin transporter |journal=Nature |volume=532 |issue=7599 |pages=334–9 |date=2016 |pmid=27049939 |pmc=4898786 |doi=10.1038/nature17629 |bibcode=2016Natur.532..334C |url=}}</ref> <gallery class="center" perrow="4" widths="200"> Levosimendan Structural Formula V1.svg|Levosimendan Letrozole.svg|Letrozole Saxagliptin structure.svg|Saxagliptin Milrinone.svg|Milrinone Cefmetazole.svg|Cefmetazole Escitalopram 2.svg|Citalopram Rilpivirine.svg|Rilpivirine </gallery>

=== Pharmaceuticals ===

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.<ref>{{cite journal |last1=Fleming |first1=Fraser F. |last2=Yao |first2=Lihua |last3=Ravikumar |first3=P. C. |last4=Funk |first4=Lee |last5=Shook |first5=Brian C. |title=Nitrile-containing pharmaceuticals: efficacious roles of the nitrile pharmacophore |journal=J Med Chem |volume=53 |issue=22 |pages=7902–17 |date=November 2010 |pmid=20804202 |pmc=2988972 |doi=10.1021/jm100762r |bibcode=2010JMedC..53.7902F }}</ref> The nitrile functional group is found in several drugs.

<gallery class="skin-invert-image"> File:Periciazine.svg|Structure of periciazine, an antipsychotic studied in the treatment of opiate dependence File:Citalopram structure.svg|Structure of citalopram, an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) class File:Cyamemazine.svg|Structure of cyamemazine, an antipsychotic drug File:Fadrozole.png|Structure of fadrozole, an aromatase inhibitor for the treatment of breast cancer File:Letrozole.svg|Structure of letrozole, an oral nonsteroidal aromatase inhibitor for the treatment of certain breast cancers </gallery>

=== Other uses === thumb|130px|Geranyl nitrile is used as a fragrance

A few dozen nitriles are used as fragrance ingredients in cosmetics. These include cinnamic acid nitrile, dodecanitrile, benzonitrile, and geranyl nitrile.<ref>{{citation|author=David R Bickers, Peter Calow, Helmut A Greim, Jon M Hanifin, Adrianne E Rogers, Jean-Hilaire Saurat, I Glenn Sipes, Robert L Smith, Hachiro Tagami |date=April 2003 |doi=10.1016/S0273-2300(03)00003-5 |issue=2 |pages=218–273 |journal=Regulatory Toxicology and Pharmacology |title=The safety assessment of fragrance materials |volume=37 |pmid=12726755 }}</ref><ref>{{citation|author=S.P. Bhatia, V.T. Politano, A.M. Api |date=September 2013 |doi=10.1016/j.fct.2013.04.040 |pages=784–792 |journal=Food and Chemical Toxicology |title=Evaluation of genotoxicity of nitrile fragrance ingredients using in vitro and in vivo assays |volume=59 |pmid=23643699 }}</ref><ref>{{citation|author=K.R. Brain, D.M. Green, J. Lalko, A.M. Api |date=February 2007 |doi=10.1016/j.tiv.2006.08.005 |issue=1 |pages=133–138 |journal=Toxicology in Vitro |title=In-vitro human skin penetration of the fragrance material geranyl nitrile |volume=21 |pmid=17045775 |bibcode=2007ToxVi..21..133B }}</ref> Some nitriles possess fragrances similar to those of the corresponding aldehydes but are considerably more stable, making them suitable substitutes. For example, geranyl nitrile provides a citrus note and, unlike the structurally analogous citral, is resistant to oxidation.<ref>{{citation|author=David Pybus, Charles Sell |date=1999 |isbn=0-85404-528-7 |location=Cambridge |page=66 |publisher=Royal Society of Chemistry |series=RSC paperbacks |title=The chemistry of fragrances}}</ref>

Various nitriles are employed as pesticides. Cyano groups are present in certain pyrethroids. Pyrethroids are carboxylic acid esters; by using 3-phenoxymandelonitrile as the alcohol component, as in deltamethrin and cypermethrin, a class of particularly potent derivatives has been developed.<ref>{{citation|author=J E Casida, D W Gammon, A H Glickman, L J Lawrence |date=April 1983 |doi=10.1146/annurev.pa.23.040183.002213 |issue=1 |pages=413–438 |journal=Annual Review of Pharmacology and Toxicology |title=Mechanisms of Selective Action of Pyrethroid Insecticides |volume=23 |pmid=6347050 }}</ref> Azoxystrobin became the world's best-selling agricultural fungicide in 1999, only a few years after its introduction, with sales exceeding 400 million US dollars, and it has retained its market significance for more than 15 years, remaining the leading fungicide in 2016.<ref>{{citation|author=Thomas C. Sparks, James E. Hunter, Beth A. Lorsbach, Greg Hanger, Roger E. Gast, Greg Kemmitt, Robert J. Bryant |date=2018-10-10 |doi=10.1021/acs.jafc.8b03484 |issue=40 |pages=10337–10346 |journal=Journal of Agricultural and Food Chemistry |title=Crop Protection Discovery: Is Being the First Best? |volume=66 |pmid=30205003 |bibcode=2018JAFC...6610337S }}</ref><ref name=":24">{{citation|author=Dave W Bartlett, John M Clough, Jeremy R Godwin, Alison A Hall, Mick Hamer, Bob Parr-Dobrzanski |date=July 2002 |doi=10.1002/ps.520 |issue=7 |pages=649–662 |journal=Pest Management Science |title=The strobilurin fungicides |volume=58 |pmid=12146165 |bibcode=2002PMSci..58..649B }}</ref> Azoxystrobin was developed on the basis of the naturally occurring strobilurin. Key structural modifications relative to the parent compound include replacement of double bonds with aromatic rings and introduction of a cyano group onto the pre-existing ring system.<ref name=":24" /> A widely used nitrile-containing insecticide is fipronil.<ref>{{citation|author=Ngangbam Sarat Singh, Ranju Sharma, Sandeep Kumar Singh, Dileep Kumar Singh |date=August 2021 |doi=10.1016/j.envres.2021.111316 |article-number=111316 |journal=Environmental Research |title=A comprehensive review of environmental fate and degradation of fipronil and its toxic metabolites |volume=199 |pmid=33989624 |bibcode=2021ER....19911316S }}</ref>{{Multiple images | Direction = horizontal | footer = tube with cyanoacrylate adhesive and structure of ethyl cyanoacrylate, which is often used in cyanoacrylate adhesives | Width1 = 80 | Width2 = 194 | Image1 = Akfix 303 Super Glue.jpg | Image2 = Ethyl cyanoacrylate.png }}

cyanoacrylates are used as adhesives because, as single-component formulations, they cure rapidly under ambient conditions and can bond a wide range of materials. By far the most widely used compound in this field is 2-cyanoacrylic acid ethyl ester, while 2-cyanoacrylic acid methyl ester and allyl cyanoacrylate are used to a lesser extent.<ref>{{citation|author=H. W. Coover, D. W. Dreifus, J. T. O'Connor |date=1990 |doi=10.1007/978-1-4613-0671-9_27 |isbn=1-4612-8019-2 |location=Boston, MA |pages=463–477 |journal=Handbook of Adhesives |publisher=Springer US |title=Cyanoacrylate Adhesives}}</ref> Cyanoacrylate adhesives are also applied in medicine for wound closure as an alternative to suturing. However, short-chain alkyl esters (e.g., methyl cyanoacrylate) frequently cause adverse effects, particularly inflammation; therefore, different compounds are employed in medical applications than in technical uses. In particular, butyl cyanoacrylate and 2-octyl cyanoacrylate are predominantly used.<ref name=":22">{{citation|author=David García Cerdá, Antonio Martín Ballester, Alicia Aliena-Valero, Anna Carabén-Redaño, José M. Lloris |date=August 2015 |doi=10.1007/s00595-014-1056-4 |issue=8 |pages=939–956 |journal=Surgery Today |title=Use of cyanoacrylate adhesives in general surgery |volume=45 |pmid=25344231 }}</ref>

Nitriles are used as electrolyte additives in lithium batterys. For example, the addition of 1,3,6-hexanetricarbonitrile leads to a significant performance improvement compared with a corresponding battery without such an additive. The mechanism of action of nitrile additives has not yet been fully elucidated.<ref>{{cite web|access-date=2022-09-29 |date=2022-09-28 |publisher=Chemie.de |title=Wie ein gewöhnlicher Zusatzstoff Lithium-Ionen-Batterien einen Schub verleiht |url=https://www.chemie.de/news/1177889/wie-ein-gewoehnlicher-zusatzstoff-lithium-ionen-batterien-einen-schub-verleiht.html?xing_share=news}}</ref><ref>{{citation|author=Chao Tang, Yawei Chen, Zhengfeng Zhang, Wenqiang Li, Junhua Jian, Yulin Jie, Fanyang Huang, Yehu Han, Wanxia Li, Fuping Ai, Ruiguo Cao, Pengfei Yan, Yuhao Lu, Shuhong Jiao |date=2022 |doi=10.1007/s12274-022-4955-5 |journal=Nano Research |title=Stable cycling of practical high-voltage LiCoO2 pouch cell via electrolyte modification |volume=16 |issue=3 |pages=3864–3871 }}</ref>

==See also== * Protonated nitriles: Nitrilium * Deprotonated nitriles: Nitrile anion * Cyanocarbon * Nitrile ylide

== References == {{reflist}}

== External links == * {{GoldBookRef | file = N04151 | title = nitrile}} * {{GoldBookRef | file = C01486 | title = cyanide}}

Category:Nitriles Category:Functional groups

Nitrile

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