Nitrile

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Categories: Functional groups | Nitriles

The structure of the nitrile group

A nitrile is any organic compound which has a -C≡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 bonded 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⁻. 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 cyanides.

Nitriles sometimes release the highly toxic CN⁻ cyanide ion. See the article on cyanide for a discussion of biological effects and toxicity.

1 History
2 Synthesis of nitriles
3 Reactions of nitriles
4 Organic cyanamides
5 See also
6 External links
7 References

History

The first compound of the homolog row of nitriles, the nitrile of formic acid, hydrogen cyanide was first synthesized by K.W. Scheele in 1782.^[1] It took several years until 1811 J. L. Gay-Lussac was able to prepare the very toxic volatile pure acid. The nitrile of benzoic acids has been 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.^[2] 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 was coined the name nitrile for new found substance, which became the name for the compound group. ^[3]

Synthesis of nitriles

Nitriles can be prepared in organic synthesis by the following methods:

Nucleophilic aliphatic substitution reactions of alkyl halides with metal cyanides in the Kolbe nitrile synthesis. Aryl nitriles are prepared in the Rosenmund-von Braun synthesis.

dehydration of primary amides. Many reagents are available, the combination of ethyl dichlorophosphate and DBU just one of them in this conversion of benzamide to benzonitrile:^[4]

Image:Amidedehydration.png

Two intermediates in this reaction are amide tautomer A and its phosphate adduct B.

dehydration of secondary amides (von Braun amide degradation)
dehydration of aldoximes with triethylamine/sulfur dioxide, zeolites, or sulfuryl chloride
One-pot synthesis of aldehyde with hydroxylamine and sodium sulfate.

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In one study ^[5] 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 irradiation through an intermediate aldoxime.

reaction of metal cyanides with aldehydes in the cyanohydrin reaction
from aryl carboxylic acids (Letts nitrile synthesis)
aromatic nitriles from diazonium compounds in the Sandmeyer reaction
from alkenes and alkynes in hydrocyanation

A commercial source for the cyanide group is diethylaluminum cyanide Et₂AlCN which can be prepared from triethylaluminium and HCN ^[6]. It has been used in nucleophilic addition to ketones.^[7] 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:^[8]

Image:CyclobutaneByCyanideMediatedDibromideCoupling.png

In the so-called Franchimont Reaction (A. P. N. Franchimont, 1872) an α-bromocarboxylic acid is dimerized after hydrolysis of the cyanogroup and decarboxylation ^[9]

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.

In hydrolysis the nitrile is reacted with an acid and water at a high temperature, or with a base and water. The acid hydrolysis forms a carboxylic acid, the alkali hydrolysis forms a carboxylate.
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 alcohols in the Pinner reaction.

likewise, the reaction of the amine sarcosine with cyanamide yields creatine ^[10]

In reductive decyanation the nitrile group is replaced by a proton ^[11]. 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 alkynes in carbocyanation:^[12]

Image:Carbocyanation.png

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.

External links

International Union of Pure and Applied Chemistry. "nitrile". Compendium of Chemical Terminology Internet edition.
International Union of Pure and Applied Chemistry. "cyanide". Compendium of Chemical Terminology Internet edition.

References

^ David T. Mowry (1948). "The Preparation of Nitriles.". Chemical reviews 42 (2): 189 - 283. doi:10.1021/cr60132a001.
^ J. Pelouze (1834). "Notiz über einen neuen Cyanäther". Annalen der Chemie und Pharmacie 10 (2): 249. doi:10.1002/jlac.18340100302.
^ Hermann Fehling (1844). "Ueber die Zersetzung des benzoësauren Ammoniaks durch die Wärme". Annalen der Chemie und Pharmacie 49 (1): 91 - 97. doi:10.1002/jlac.18440490106.
^ Chun-Wei Kuo, Jia-Liang Zhu, Jen-Dar Wu, Cheng-Ming Chu, Ching-Fa Yao and Kak-Shan Shia (2007). "A convenient new procedure for converting primary amides into nitriles". Chem. Commun. 2007: 301 - 303. doi:10.1039/b614061k.
^ Sharwan K, Dewan, Ravinder Singh, and Anil Kumar (2006). "One pot synthesis of nitriles from aldehydes and hydroxylamine hydrochloride using sodium sulphate (anhyd) and sodium bicarbonate in dry media under microwave irradiation" (open access). Arkivoc: (ii) 41-44.
^ W. Nagata and M. Yoshioka (1988). "Diethylaluminum cyanide". Org. Synth.; Coll. Vol. 6: 436.
^ W. Nagata, M. Yoshioka, and M. Murakami (1988). "PREPARATION OF CYANO COMPOUNDS USING ALKYLALUMINUM INTERMEDIATES: 1-CYANO-6-METHOXY-3,4-DIHYDRONAPHTHALENE". Org. Synth.; Coll. Vol. 6: 307.
^ Reynold C. Fuson, Oscar R. Kreimeier, and Gilbert L. Nimmo (1930). "RING CLOSURES IN THE CYCLOBUTANE SERIES. II. CYCLIZATION OF α,α′-DIBROMO-ADIPIC ESTERS". J. Am. Chem. Soc. 52 (10): 4074 - 4076. doi:10.1021/ja01373a046.
^ Franchimont Reaction
^ Smith, Andri L.; Tan, Paula (2006). "Creatine Synthesis: An Undergraduate Organic Chemistry Laboratory Experiment". J. Chem. Educ. 83: 1654.
^ 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 Article
^ Yoshiaki Nakao, Akira Yada, Shiro Ebata, and Tamejiro Hiyama (2007). "A Dramatic Effect of Lewis-Acid Catalysts on Nickel-Catalyzed Carbocyanation of Alkynes" (Communication). J. Am. Chem. Soc. 129 (9): 2428 - 2429. doi:10.1021/ja067364x.