Nitrile

In organic chemistry, a nitrile is any organic compound that has a functional group. The name of the compound is composed of a base, which includes the carbon of the , suffixed with "nitrile", so for example is called "propionitrile" (or propanenitrile). The prefix cyano- 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 rubber, a nitrile-containing polymer used in latex-free laboratory and medical gloves. Nitrile rubber is also widely used as automotive and other seals since it is resistant to fuels and oils. Organic compounds containing multiple nitrile groups are known as cyanocarbons. For the organic compounds of the form instead of , they are referred to as isonitriles, or isocyanides. Inorganic compounds containing the 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.

Structure and basic properties

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

History

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. In 1811 J. L. Gay-Lussac was able to prepare the very toxic and volatile pure acid. 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. 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. In 1903, Arthur Lapworth investigated the formation of cyanohydrins by addition of hydrocyanic acid to aldehydes and ketones and discovered that the actual nucleophile is the cyanide ion, such that the addition of a base increases the reaction rate. This work represented one of the earliest investigations of an organic reaction mechanism. For a long time, nitriles were primarily of academic interest. Between the First and Second World War, however, research activity increased significantly. By the second half of the 20th century, several large-scale industrial processes had been developed in which nitriles were either produced or utilized. An important example is the development of polyamides (polyamide 6.6) in the 1930s, as adiponitrile is a key intermediate in its manufacture and is produced by hydrocyanation of butadiene with hydrogen cyanide. Acrylonitrile polymers have been known since the 1920s but gained greater importance as synthetic fibers toward the late 1940s. Superglues based on cyanoacrylates have also been available since the late 1940s. , according to IUPAC: Butanenitrile ( blue marked C atom belongs to the main chain), formally also propanecarbonitrile ( blue marked C atom belongs to the substituent)]] The functional group of nitriles containing the triple bond is referred to as the nitrile or cyano group. If the nitrile is the highest-ranking functional group, the suffix -nitrile is added to the name of the parent compound. The triply bonded carbon atom is, as always, included in the parent chain. Alternatively, the ending -carbonitrile may be used (analogous to -carboxylic acid), in which case the carbon atom is not counted as part of the parent chain. This ending must be used if the nitrile group is attached to a ring (as in ) or if not all carbon atoms are part of the parent chain, which is necessarily the case when more than two nitrile groups are present, as these can only be located at the termini of the chain. Due to their relationship to carboxylic acids (the nitrile carbon has the same oxidation state as the carboxyl carbon), trivial names are often derived from the corresponding carboxylic acids using the ending -onitrile (for example, benzoic acid to benzonitrile). If the nitrile function is not the principal functional group in the molecule, the prefix cyano- is used together with the appropriate locant. In this case as well, the triple-bonded carbon atom is not counted as part of the parent chain.

From organic halides and cyanide salts

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). In the Kolbe nitrile synthesis (a nucleophilic substitution reaction), an alkanonitrile and an alkali halide are formed from a reactive halocarbons and an alkali cyanide (sodium cyanide or potassium cyanide). The reaction is particularly suitable for primary, allylic, and benzylic halides. Secondary alkyl halides provide lower yields, whereas tertiary halides undergo exclusively elimination reaction instead of substitution. In addition to halides, substrates bearing other good leaving groups may also be employed. In contrast to alkali cyanides, silver cyanide is unsuitable for nitrile synthesis, as it preferentially forms isonitriles. An example of the Kolbe nitrile synthesis is the reaction of methyl iodide with sodium cyanide to yield acetonitrile and sodium iodide: \mathrm{CH_3I + NaCN \longrightarrow CH_3CN + NaI} Similarly, 1,3-dibromopropane reacts with sodium cyanide to form glutaronitrile, and 1-iodooctane reacts with potassium cyanide to give nonannitrile. Cyanations can also be carried out using hydrogen cyanide in combination with triethylaluminum or with diethylaluminum cyanide; for example, in the ring opening of an epoxide to a β-cyanohydrin or in the 1,4-addition of cyanide to an enone. Trimethylsilylcyanide is another cyanating reagent capable of opening epoxides to β-cyanohydrins, with concomitant silylation of the oxygen atom. Trimethylsilyl cyanide also enables substitution of tertiary alkyl halides, which is not feasible under Kolbe nitrile synthesis conditions. In the presence of suitable transition metal catalysts, hydrocyanation allows addition of hydrogen cyanide to the multiple bonds of alkenes and alkynes to afford nitriles. Nickel catalysts are typically employed. Direct handling of hydrogen cyanide is often unnecessary, as synthetic equivalents such as acetone cyanohydrin or isovaleronitrile may be used. An important industrial process is the hydrocyanation of butadiene to adiponitrile.

Complexation

Nitriles are precursors to transition metal nitrile complexes, which are reagents and catalysts. Examples include tetrakis(acetonitrile)copper(I) hexafluorophosphate ( ) and bis(benzonitrile)palladium dichloride ( ).

Nitrile derivatives

Nitriles are isomeric with isonitriles (isocyanides). These also contain a triple bond; however, the substituent is bonded via the nitrogen atom, which results in a zwitterionic structure. Compounds in which an oxygen atom is bonded to the carbon atom of a group are referred to as cyanates. If the oxygen atom is replaced by a sulfur or selenium atom, the compounds are termed thiocyanates or . If the cyano group is bonded to a nitrogen atom, the compound is referred to as a cyanamide. In addition to nitriles, other classes of compounds are known that contain a triple bond in which the nitrogen atom forms a fourth bond and is therefore positively charged. In nitrile oxides, an oxygen atom is additionally bonded to the nitrogen atom. If this atom is sulfur or another nitrogen atom instead, the compounds are referred to as or nitrilimines, respectively. If the nitrogen atom of the nitrile is protonated or carries an additional organic substituent, the compound is a nitrilium ion. If the nitrogen atom carries an organic substituent bearing a negatively charged carbon atom, the species is a nitrile ylide, a subclass of ylides.

Organic cyanamides

Cyanamides are N-cyano compounds with general structure and related to the parent cyanamide.

Nitrile oxides

Nitrile oxides have the chemical formula . Their general structure is . The R stands for any group (typically organyl, e.g., acetonitrile oxide , hydrogen in the case of fulminic acid , or halogen (e.g., ). Nitrile oxides are quite different from nitriles and do not arise from direct oxidation of the latter. Instead, they can be synthesised by nitroalkane (nitronate) dehydration, oxime dehydrogenation, or halooxime elimination in base. They are highly reactive in 1,3-dipolar cycloadditions, such as to isoxazoles, and undergo type I dyotropic rearrangement to isocyanates. The heavier nitrile sulfides are extremely reactive and rare, but temporarily form during the thermolysis of oxathiazolones. They react similarly to nitrile oxides. Blomstrende Ricinus communis med nogle frø.jpg|Ricinus plant Ricinin.svg|Ricinin Guaraná (Paullinia cupana) fruits (29055398276).jpg|Guaraná, a soap tree plant, contains cyanolipids Cyanolipid type 1 alcohol.svg|An alcohol component of cyanolipids, found for example in guaraná Nasturtium officinale kz12.jpg|Watercress Gluconasturtiin Structural Formulae V.4.svg|Structure of gluconasturtiin Phenylpropionitrile.svg|Structure of phenylpropionitrile Prunus persica - Peach Hungary.jpg|Peach tree Amygdalin structure.svg|Structure of amygdalin Prunasin.svg|Struktur des Prunasins (R)-mandelonitrile-2D-skeletal.svg|Mandelonitrile, the aglycone of amygdalin and prunasin (1884) The Magpie (Abraxas grossulariata) (14502341918).jpg|Gooseberry moth SGR laying.jpg|Desert locust Himantarium gabrielis 77427992.jpg|Himantarium gabrielis Benzoylcyanide.svg|Benzoyl cyanide is found in the defensive secretions of various arthropods In addition to arthropods, marine animals also contain nitrile compounds. These include bursatellin from broad-footed snails of the genus Bursatella and the calyculins isolated from sponges. The albanitriles from sponges of the genus Mycale are linear compounds (chain length 16 to 18 carbon atoms) bearing a nitrile group at one or both termini and several additional C≡C triple bonds. Cotton-acrylic yarn.jpg|Polyacrylonitrile is used in knitting yarn Carbonsheetwiki1.png|Carbon fibers are often made from polyacrylonitrile Syringe Glove 01.jpg|Protective gloves made from nitrile rubber Lego Color Bricks.jpg|Lego bricks are made from acrylonitrile butadiene styrene copolymer (ABS) Levosimendan Structural Formula V1.svg|Levosimendan Letrozole.svg|Letrozole Saxagliptin structure.svg|Saxagliptin Milrinone.svg|Milrinone Cefmetazole.svg|Cefmetazole Escitalopram 2.svg|Citalopram Rilpivirine.svg|Rilpivirine 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

Names in other languages