Nitrile

A nitrile in any organic compound that has a-C≡N functional group. The prefixcyano- 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 butadiene rubber, a nitrile-containing polymer  used in latex-free laboratory and medical gloves. Organic compounds containing multiple nitrile groups are known as cyanocarbons. Inorganic compounds containing the -C ≡ N group are not called nitriles, but cyanides instead. Though both nitriles and cyanides can be derived from cyanide salts, most nitriles are not nearly as toxic.

History

The first compound of the homolog row of nitriles, the nitrile of formic acid , hydrogen cyanide was first synthesized by CW Scheele in 1782. In 1811 JL Gay-Lussac was able to prepare the very toxic and volatile pure acid. The nitrile of benzoic acids was first 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. 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

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.

Ammoxidation

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

CH ₃ CH=CH ₂ + 3/2 O ₂ + NH ₃ → NCCH=CH ₂ + 3 H ₂ O

A side product of this process is acetonitrile . Most derivatives of bensonitrile as well as Isobutyronitrile are prepared by ammoxidation.

Hydrocyanation

An example of hydrocyanation is the production of adiponitrile from 1,3-butadiene :

CH ₂ =CH-CH=CH ₂ + 2 HCN → NC(CH ₂ ) ₄ CN

From organic halides and cyanide salts

Often for more specialty applications, nitriles can be prepared by a wide variety of other methods. For example, alkyl halides undergonucleophilic aliphatic substitution with alkali metal cyanides in the Kolbe nitrile synthesis . Aryl nitriles are prepared in the Rosenmund-von Braun synthesis.

Cyanohydrins

The cyanohydrins are a special class of nitriles that result from the addition of 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

Dehydration of amides and oximes

Nitriles can be prepared by the 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 . In a related dehydration, secondary amides give nitriles by the von Braun amide degradation . In this case, one CN bond is cleaved.The dehydration of aldoximes (RCH=NOH) also affords nitriles. Typical reagents for this transformation arewith triethylamine / sulfur dioxide , zeolites , or sulfuryl chloride. Exploiting this approach is the One-pot synthesis of nitriles from aldehyde with hydroxylamine in the presence of sodium sulfate.

from aryl carboxylic acids ( Letts nitrile synthesis)

Sandmeyer reaction

Aromatic nitriles are often prepared in the laboratory form the aniline via diazonium compounds. This is the Sandmeyer reaction . It requires transition metal cyanides.

ArN ₂ ⁺ + CuCN → ArCN + N ₂ + Cu ⁺

Other methods

·                   A commercial source for the cyanide group is diethylaluminum cyanide Et₂AICN which can be prepared from triethylaluminium and HCN. It has been used in nucleophilic addition to keton. For an example of its use see: Kuwajima Taxol total synthesis

·                   Cyanide ions facilitate the coupling of dibromes. Reaction of α,α'-dibromo adipic acid with sodium cyanide in ethanol yields the cyano cyclobutane

In the so-called Franchimont Reaction (APN 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 syntesis