Nitrile#Organic cyanamides

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.{{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 }} Nitriles are polar, as indicated by high dipole moments. As liquids, they have high relative permittivities, often in the 30s.

The first compound of the homolog row of nitriles, the nitrile of formic acid, hydrogen cyanide was first synthesized by C. W. Scheele in 1782.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.{{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}} In 1811 J. L. Gay-Lussac was able to prepare the very toxic and volatile pure acid.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 }}

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.{{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}}

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.{{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".)

== Synthesis ==

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.

In ammoxidation, a hydrocarbon is partially oxidized in the presence of ammonia. This conversion is practiced on a large scale for acrylonitrile:{{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}}

:CH3CH=CH2 + 3/2 O2 + NH3 -> N#CCH=CH2 + 3 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.

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}}

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).

File:Synthesis of Cyanoarenes.png

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.{{Cite journal|title=Cyanohydrins in Nature and the Laboratory: Biology, Preparations, and Synthetic Applications|author=Gregory, Robert J. H.|journal=Chemical Reviews|year=1999|volume=99|issue=12|pages=3649–3682|doi=10.1021/cr9902906|pmid=11849033}}

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

:Image:7 Dehydratisierung-2.svg

Numerous traditional methods exist for nitrile preparation by amine oxidation. {{cite journal |title=Developments in the Aerobic Oxidation of Amines |journal=ACS Catal. |date=2021 |volume=2 |pages=1108–1117 |doi=10.1021/cs300212q |doi-access= |last1=Schümperli |first1=Martin T. |last2=Hammond |first2=Ceri |last3=Hermans |first3=Ive |issue=6 }} In addition, several selective methods have been developed in the last decades for electrochemical processes. {{cite journal |title=Beyond traditional synthesis: Electrochemical approaches to amine oxidation for nitriles and imines |journal=ACS Org Inorg Au |date=2024 |doi=10.1021/acsorginorgau.4c00025 |doi-access=free |last1=Xu |first1=Zhining |last2=Kovács |first2=Ervin |volume=4 |issue=5 |pages=471–484 |pmc=11450732 }}

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,{{cite journal |last1=Chill |first1=Samuel T. |last2=Mebane |first2=Robert C. |title=A Facile One-Pot Conversion of Aldehydes into Nitriles |journal=Synthetic Communications |date=18 September 2009 |volume=39 |issue=20 |pages=3601–3606 |doi=10.1080/00397910902788174|s2cid=97591561 }} 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.{{cite journal|surname1=C. Fizet|surname2=J. Streith|periodical=Tetrahedron Lett.|title=Hydroxylamine-O-sulfonic acid: A convenient reagent for the oxidative conversion of aldehydes into nitriles|volume=15|issue=36 |year=1974|pages=3187–3188|language=German|doi=10.1016/S0040-4039(01)91857-X}}

:Image:2,5-Diformylfuran Bildung von 2,5-Dicyanofuran.svg.) ]]

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

Aromatic nitriles are often prepared in the laboratory from the aniline via diazonium compounds. This is the Sandmeyer reaction. It requires transition metal cyanides."o-Tolunitrile and p-Tolunitrile" H. T. Clarke and R. R. Read Org. Synth. 1941, Coll. Vol. 1, 514.

:{{chem2|ArN2+ + CuC\tN -> ArC\tN + N2 + Cu+}}

• A commercial source for the cyanide group is diethylaluminum cyanide {{chem2|Et2AlCN}} which can be prepared from triethylaluminium and HCN.{{OrgSynth | collvol = 6 | collvolpages = 436 | year = 1988 | title = Diethylaluminum cyanide | author = W. Nagata and M. Yoshioka | prep = cv6p0436}} It has been used in nucleophilic addition to ketones.{{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}} 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:{{cite journal | title = Ring Closures in the Cyclobutane Series. II. Cyclization Of α,α′-Dibromo-Adipic Esters |author1=Reynold C. Fuson |author2=Oscar R. Kreimeier |author3=Gilbert L. Nimmo |name-list-style=amp | journal = J. Am. Chem. Soc. | year = 1930 | volume = 52 | issue = 10 | pages = 4074–4076 | doi = 10.1021/ja01373a046}} Image:Cyclobutane by cyanide mediated dibromide coupling.svg
• Aromatic nitriles can be prepared from base hydrolysis of trichloromethyl aryl ketimines ({{chem2|RC(CCl3)\dNH}}) in the Houben-Fischer synthesisJ. 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}}
• Nitriles can be obtained from primary amines via oxidation. Common methods include the use of potassium persulfate,{{cite journal|last1=Yamazaki|first1=Shigekazu|last2=Yamazaki|first2=Yasuyuki|title=Nickel-catalyzed dehydrogenation of amines to nitriles|journal=Bulletin of the Chemical Society of Japan|date=1990|volume=63|issue=1|pages=301–303|doi=10.1246/bcsj.63.301|doi-access=free}} Trichloroisocyanuric acid,{{cite journal|last1=Chen|first1=Fen-Er|last2=Kuang|first2=Yun-Yan|last3=Hui-Fang|first3=Dai|last4=Lu|first4=Liang|title=A Selective and Mild Oxidation of Primary Amines to Nitriles with Trichloroisocyanuric Acid|journal=Synthesis|date=2003|volume=17|issue=17|pages=2629–2631|doi=10.1055/s-2003-42431}} or anodic electrosynthesis.{{cite journal|last1=Schäfer|first1=H. J.|last2=Feldhues|first2=U.|title=Oxidation of Primary Aliphatic Amines to Nitriles at the Nickel Hydroxide Electrode|date=1982|volume=1982|issue=2|pages=145–146|doi=10.1055/s-1982-29721|journal=Synthesis|s2cid=97172564 }}
• α-Amino acids form nitriles and carbon dioxide via various means of oxidative decarboxylation.{{cite journal|last1=Hiegel|first1=Gene|last2=Lewis|first2=Justin|last3=Bae|first3=Jason|title=Conversion of α-Amino Acids into Nitriles by Oxidative Decarboxylation with Trichloroisocyanuric Acid|journal=Synthetic Communications|date=2004|volume=34|issue=19|pages=3449–3453|doi=10.1081/SCC-200030958|s2cid=52208189}}{{cite journal|last1=Hampson|first1=N|last2=Lee|first2=J|last3=MacDonald|first3=K|title=The oxidation of amino compounds at anodic silver|journal=Electrochimica Acta|date=1972|volume=17|issue=5|pages=921–955|doi=10.1016/0013-4686(72)90014-X}} Henry Drysdale Dakin discovered this oxidation in 1916.{{cite journal|last1=Dakin|first1=Henry Drysdale|title=The Oxidation of Amino-Acids to Cyanides|journal=Biochemical Journal|date=1916|volume=10|issue=2|pages=319–323|pmc=1258710|pmid=16742643|doi=10.1042/bj0100319}}
• From aryl carboxylic acids (Letts nitrile synthesis)

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.

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.{{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}} The classical procedure to convert a nitrile to the corresponding primary amide calls for adding the nitrile to cold concentrated sulfuric acid.{{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}} 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:{{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}}

:{{chem2|RC\tN + R'C(H)\dNOH -> RC(O)NH2 + R'C\tN}}

{{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.{{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}} 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.

Alkyl nitriles are sufficiently acidic to undergo deprotonation of the C-H bond adjacent to the {{chem2|C\tN}} group.{{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 }}{{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 }} 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.

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{{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 }}
• 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.{{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=9780470638859}} While not a classical Grignard reaction, it may be considered one under broader modern definitions.

• In reductive decyanation the nitrile group is replaced by a proton.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 }} 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.{{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}} Similarly, α-aminonitriles can be decyanated with other reducing agents such as lithium aluminium hydride.
• 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.{{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}}
• 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:{{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}}

:Image:Carbocyanation.png

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}}).{{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}}

File:Sample of PdCl2(PhCN)2.jpg

{{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.{{March4th|page=436–7}}

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., chlorine fulminate {{chem2|Cl\sC\tN+\sO−}}).{{rp|1187–1192}}

Nitrile oxides are quite different from nitriles: they are highly reactive 1,3-dipoles, and cannot be synthesized from the direct oxidation of nitriles.{{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 }} Instead, they can be synthesised by nitroalkane dehydration, oxime dehydrogenation,{{Clayden}}{{rp|934–936}} or halooxime elimination in base.{{cite journal|doi=10.1016/S0040-4039(00)71175-0|journal=Tetrahedron Letters|volume=21|pp=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 (±) acivicin and (±) bromo-acivicin|first1=D. M.|last1=Vyas|first2=Y.|last2=Chiang|first3=T. W.|last3=Doyle}} They are used in 1,3-dipolar cycloadditions,{{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 }}{{rp|1187–1192}} such as to isoxazoles.{{rp|1201–1202}} They undergo type 1 dyotropic rearrangement to isocyanates.{{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.{{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}}

Nitriles occur naturally in a diverse set of plant and animal sources. Over 120 naturally occurring nitriles have been isolated from terrestrial and marine sources. Nitriles are commonly encountered in fruit pits, especially almonds, and during cooking of Brassica crops (such as cabbage, Brussels sprouts, and cauliflower), which release nitriles through hydrolysis. Mandelonitrile, a cyanohydrin produced by ingesting almonds or some fruit pits, releases hydrogen cyanide and is responsible for the toxicity of cyanogenic glycosides.Natural Product Reports Issue 5, 1999 [http://pubs.rsc.org/en/Content/ArticleLanding/1999/NP/a804370a Nitrile-containing natural products]

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.{{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 }} The nitrile functional group is found in several drugs.

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

• Protonated nitriles: Nitrilium
• Deprotonated nitriles: Nitrile anion
• Cyanocarbon
• Nitrile ylide

{{reflist}}

• {{GoldBookRef | file = N04151 | title = nitrile}}
• {{GoldBookRef | file = C01486 | title = cyanide}}

{{Functional Groups}}

{{Nitrogen compounds}}

Category:Functional groups