Nitrile

This article is about the group of organic compounds. For the polymer used for making safety gloves, see Nitrile rubber.

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.

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. In 1811 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 nor chemical properties were determined nor a structure suggested. Théophile-Jules Pelouze synthesized propionitrile in 1834 suggesting it to be an ether of propionic alcohol and hydrocyanic acid. 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 formate to his results. He coined the name nitrile for the newfound substance, which became the name for the compound group.

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:

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.

In one study 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 . It has been used in nucleophilic addition to ketones. 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:

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

• Aromatic nitriles can be prepared from base hydrolysis of trichloromethyl aryl ketimines (RC(CCl₃)=NH) in the Houben-Fischer synthesis

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.

Hydrolysis

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 RCOOH. 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:

• 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^–5M^–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.
• 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.

Reduction

In organic reduction the nitrile is reduced by reacting it with hydrogen with a nickel catalyst; an amine is formed in this reaction (see nitrile reduction). Reduction to the imine followed by hydrolysis to the aldehyde takes place in the Stephen aldehyde synthesis

With nucleophiles

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
• Nitriles react in Friedel-Crafts acylation in the Houben-Hoesch reaction to ketones

Other

• In reductive decyanation the nitrile group is replaced by a proton . An effective decyanation is by a dissolving metal reduction with HMPA and potassium metal in tert-butanol. 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:

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.

Nitrile oxides

Nitrile oxides have the general structure R-CNO.

See also

• For the polymer used to make safety gloves, see Nitrile rubber.
• Protonated nitriles: Nitrilium

External links

• IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "nitrile". doi:10.1351/goldbook.N04151
• IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "cyanide". doi:10.1351/goldbook.C01486