Nitrile
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[[Image:Nitrile-group-2D.png|thumb|150px|The structure of the nitrile group]]
A '''nitrile''' is any [[organic compound]] which has a -[[Carbon|C]]'''≡'''[[Nitrogen|N]] [[functional group]]. The -C'''≡'''N functional group is called a '''nitrile group'''. In the -CN group, the [[carbon]] atom and the [[nitrogen]] atom are [[triple bond]]ed together. The prefix '''cyano''' is used in chemical nomenclature to indicate the presence of a nitrile group in a molecule. A [[cyanide]] ion is a negative ion with the formula CN<sup>−</sup>. The -CN group is sometimes, less properly, referred to as a ''cyanide group'' or ''cyano group'' and compounds with them are sometimes referred to as [[cyanide]]s.
Nitriles sometimes release the highly toxic CN<sup>−</sup> cyanide ion. See the article on [[cyanide]] for a discussion of biological effects and toxicity.
==History==
The first compound of the homolog row of nitriles, the nitrile of [[formic acid]], [[hydrogen cyanide]] was first synthesized by [[Carl Wilhelm Scheele|K.W. Scheele]] in 1782.<ref>{{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
| url = http://pubs.acs.org/cgi-bin/abstract.cgi/chreay/1942/42/i02/f-pdf/f_cr60132a001.pdf}} </ref> In 1811 [[Joseph Louis Gay-Lussac|J. L. Gay-Lussac]] was able to prepare the very toxic and volatile pure acid.
The nitrile of benzoic acids was first prepared by [[Friedrich Wohler]] and [[Justus von Liebig]], but due to minimal yield of the synthesis neither physical or chemical properties where determined nor a structure was suggested. [[Théophile-Jules Pelouze]] synthesized [[propionitrile]] in 1834 suggesting it to be an ether of propionic alcohle and hydrocyanic acid.<ref>{{cite journal
| title = Notiz über einen neuen Cyanäther
| journal = [[Annalen der Chemie und Pharmacie]]
| pages = 249
| author = J. Pelouze
| doi= 10.1002/jlac.18340100302
| volume = 10
| issue = 2
| 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.
He determined the structure by comparing it to the already known synthesis of hydrogen cyanide by heating ammonium [[formiate]] to his results. He coined the name nitrile for the newfound substance, which became the name for the compound group. <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
| author = Hermann Fehling
| doi = 10.1002/jlac.18440490106 }}</ref>
<!--==History==
[[Hydrogen cyanide]] was first synthesized by [[Carl Wilhelm Scheele|K.W. Scheele]] in 1782 and he was killed in an attempt to get the [[anhydrous]] compound <ref>{{cite journal | title = The Preparation of Nitriles | author = David T. Mowry | journal = [[Chem. Rev.]] | year = 1948 | volume = 42 | issue = 2 | pages = 189–283 | doi = 10.1021/cr60132a001}}</ref>. [[Joseph Louis Gay-Lussac|J. L. Gay-Lussac]] was the first to prepare the pure acid in 1811 and [[Friedrich Wohler]] and [[Justus von Liebig]] were the first to prepare the first nitriles ''benzoyl cyanide'' and [[benzonitrile]] in 1832. [[Théophile-Jules Pelouze]] synthesized [[propionitrile]] in 1834.<ref>{{cite journal
| title = Notiz über einen neuen Cyanäther
| journal = [[Annalen der Chemie und Pharmacie]]
| pages = 249
| author = J. Pelouze
| doi= 10.1002/jlac.18340100302
| volume = 10
| issue = 2
| year = 1834}}</ref>
Word by word coppy of the article {{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
| url = http://pubs.acs.org/cgi-bin/abstract.cgi/chreay/1942/42/i02/f-pdf/f_cr60132a001.pdf}}-->
== Synthesis of nitriles ==<!-- This section is linked from [[Organic reaction]] -->
Nitriles can be prepared in [[organic synthesis]] by the following methods:
* [[Nucleophilic aliphatic substitution]] reactions of [[alkyl halide]]s with metal [[cyanide]]s in the [[Kolbe nitrile synthesis]]. Aryl nitriles are prepared in the [[Rosenmund-von Braun synthesis]].
* [[Dehydration reaction|dehydration]] of primary [[amide]]s. Many reagents are available, the combination of [[ethyl dichlorophosphate]] and [[DBU (chemistry)|DBU]] just one of them in this conversion of [[benzamide]] to [[benzonitrile]]:<ref>{{cite journal | title = A convenient new procedure for converting primary amides into nitriles | author = Chun-Wei Kuo, Jia-Liang Zhu, Jen-Dar Wu, Cheng-Ming Chu, Ching-Fa Yao and Kak-Shan Shia | journal = [[Chem. Commun.]] | year = 2007 | volume = 2007 | pages = 301–303 | doi = 10.1039/b614061k}}</ref>
:[[Image:Amidedehydration.png|400px|Amide dehydration]]
:Two intermediates in this reaction are amide [[tautomer]] '''A''' and its [[Organophosphate|phosphate]] adduct '''B'''.
* [[Dehydration reaction|dehydration]] of secondary [[amide]]s ([[von Braun amide degradation]])
* [[Dehydration reaction|dehydration]] of [[aldoxime]]s with [[triethylamine]]/[[sulfur dioxide]], [[zeolite]]s, or [[sulfuryl chloride]]
* [[One-pot synthesis]] of [[aldehyde]] with [[hydroxylamine]] and [[sodium sulfate]].
:[[Image:Aldehyde to nitril conversion.png|400px|one-pot synthesis from aldehyde]]
:In one study <ref>{{cite journal | title = One pot synthesis of nitriles from aldehydes and hydroxylamine hydrochloride using sodium sulfate (anhyd) and sodium bicarbonate in dry media under microwave irradiation | author = Sharwan K, Dewan, Ravinder Singh, and Anil Kumar | journal = [[Arkivoc]] | year = 2006 | pages = (ii) 41–44 | url = http://www.arkat-usa.org/ark/journal/2006/I02_General/1646/05-1646D%20as%20published%20mainmanuscript.pdf | format = [[open access]]}}</ref> an aromatic or aliphatic aldehyde is reacted with hydroxylamine and [[anhydrous]] sodium sulfate in a [[dry media reaction]] for a very small amount of time under [[microwave chemistry|microwave irradiation]] through an intermediate aldoxime.
* reaction of metal cyanides with aldehydes in the [[cyanohydrin reaction]]
* from [[aryl]] [[carboxylic acid]]s ([[Letts nitrile synthesis]])
* aromatic nitriles from [[diazonium compounds]] in the [[Sandmeyer reaction]]
* from [[alkene]]s and [[alkyne]]s in [[hydrocyanation]]
* A commercial source for the cyanide group is '''diethylaluminum cyanide''' Et<sub>2</sub>AlCN 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 [[ketone]]s.<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'-dibromo [[adipic acid]] with [[sodium cyanide]] in [[ethanol]] yields the cyano [[cyclobutane]]:<ref>{{cite journal | title = Ring Closures In The Cyclobutane Series. Ii. Cyclization Of Α,Α′-Dibromo-Adipic Esters | author = Reynold C. Fuson, Oscar R. Kreimeier, and Gilbert L. Nimmo | journal = [[J. Am. Chem. Soc.]] | year = 1930 | volume = 52 | issue = 10 | pages = 4074–4076 | doi = 10.1021/ja01373a046}}</ref>
:[[Image:CyclobutaneByCyanideMediatedDibromideCoupling.png|300px]]
: In the so-called '''Franchimont Reaction''' (A. P. N. Franchimont, 1872) an α-bromocarboxylic acid is dimerized after hydrolysis of the cyanogroup and [[decarboxylation]] <ref>[http://www.drugfuture.com/OrganicNameReactions/ONR143.htm Franchimont Reaction<!-- Bot generated title -->]</ref>
* Aromatic nitriles can be prepared from base hydrolysis of trichloromethyl aryl ketimines (RC(CCl<sub>3</sub>)=NH) in the '''Houben-Fischer synthesis''' <ref>''Über eine neue Methode zur Darstellung cyclischer Nitrile durch katalytischen Abbau'' (I. Mitteil.) (p 2464-2472) J. Houben, Walter Fischer '''Berichte der deutschen chemischen Gesellschaft''' (A and B Series)
Volume 63, Issue 9 , Pages 2464 - 2472 {{DOI|10.1002/cber.19300630920}}</ref> <ref>http://www.drugfuture.com/OrganicNameReactions/ONR197.htm Merck & Co., Inc., Whitehouse Station</ref>
== Reactions of nitriles ==
Nitrile groups in organic compounds can undergo various reactions when subject to certain 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 achieve carboxamides RC(=O)NH2 and then carboxylic acids RCO2H. The hydrolysis of nitriles is generally considered to be one of the best methods for the preparation of carboxylic acids. However, these base or acid catalyzed reactions have certain limitations and/or disadvantages for preparation of amides. The general restriction is that the final neutralization of either base or acid leads to an extensive salt formation with inconvenient product contamination and pollution effects. Particular limitations are as follows: (i) The base catalyzed reactions. The kinetic studies allowed the estimate of relative rates for the hydration at each step of the reaction and, as a typical example, the second-order rate constants for hydroxide-ion catalyzed hydrolysis of acetonitrile and acetamide are 1.6•10–6 and 7.4•10–5 M–1s–1, respectively. Comparison of these two values indicates that the second step of the hydrolysis for the base-catalyzed reaction is faster than the first one, and the reaction should proceed to the final hydration product (the carboxylate salt) rather than stopping at the amide stage. This implies that amides prepared in the conventional metal-free base-catalyzed reaction should be contaminated with carboxylic acids and they can be isolated in only moderate yields. (ii) The acid catalyzed reactions. Application of strong acidic solutions 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 [V. Yu. Kukushkin, A. J. L. Pombeiro, Metal-mediated and metal-catalyzed hydrolysis of nitriles (a review), Inorg. Chim. Acta, 358 (2005) 1–21].
* In [[organic reduction]] the nitrile is reduced by reacting it with [[hydrogen]] with a [[nickel]] [[catalyst]]; an [[amine]] is formed in this reaction. Reduction to the imine followed by hydrolysis to the aldehyde takes place in the [[Stephen aldehyde synthesis]]
* A nitrile is an [[electrophile]] at the carbon atom in a [[nucleophilic addition]] reactions:
** with an [[organozinc compound]] in the [[Blaise reaction]]
** and with [[alcohol]]s in the [[Pinner reaction]].
** likewise, the reaction of the [[amine]] [[sarcosine]] with [[cyanamide]] yields [[creatine]] <ref>{{cite journal | author = Smith, Andri L.; Tan, Paula | url = http://jchemed.chem.wisc.edu/Journal/Issues/2006/Nov/abs1654.html | title = Creatine Synthesis: An Undergraduate Organic Chemistry Laboratory Experiment | journal = [[J. Chem. Educ.]] | year = 2006 | volume = 83 | pages = 1654}}</ref>
* Nitriles react in Friedel-Crafts acylation in the [[Houben-Hoesch reaction]] to ketones
* In '''reductive decyanation''' the nitrile group is replaced by a proton <ref>''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]</ref>. An effective decyanation is by a [[dissolving metal reduction]] with [[HMPA]] and [[potassium]] metal in [[tert-butyl alcohol]]. α-Amino-nitriles can be decyanated with [[lithium aluminium hydride]].
* Nitriles self-react in presence of base in the [[Thorpe reaction]] in a [[nucleophilic addition]]
* In [[organometallic chemistry]] nitriles are known to add to [[alkyne]]s in '''carbocyanation''':<ref>{{cite journal | title = A Dramatic Effect of Lewis-Acid Catalysts on Nickel-Catalyzed Carbocyanation of Alkynes | author = Yoshiaki Nakao, Akira Yada, Shiro Ebata, and Tamejiro Hiyama | journal = [[J. Am. Chem. Soc.]] | year = 2007 | volume = 129 | issue = 9 | pages = 2428–2429| format = Communication | doi = 10.1021/ja067364x}}</ref>
:[[Image:Carbocyanation.png|400px|Carbocyanation Nakao 2007]]
==Organic cyanamides==
'''Cyanamides''' are N-cyano compounds with general structure R1R2N-CN and related to the inorganic parent [[cyanamide]]. For an example see: [[von Braun reaction]].
==See also==
* [[:Category:Nitriles]]
* For the [[polymer]] used to make safety gloves, see [[Nitrile rubber]].
* [[Thorpe reaction]]
== External links ==
* {{GoldBookRef | file = N04151 | title = nitrile}}
* {{GoldBookRef | file = C01486 | title = cyanide}}
== References ==
{{reflist}}
{{Functional Groups}}
[[Category:Functional groups]]
[[Category:Nitriles]]
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