Nitrile
Encyclopedia
A nitrile is any organic compound
that has a -C
≡N
functional group
. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, one example being super glue (methyl cyanoacrylate).
Inorganic compound
s 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.
, 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.
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.
Nitriles occur naturally in a diverse set of plant and animal sources. Over 120 naturally occurring nitriles have been isolated from terrestrial and marine sources. Nitriles are commonly encountered in fruit pits, especially almonds, and during cooking of Brassica crops (such as cabbage, brussel sprouts, and cauliflower), which release nitriles being released through hydrolysis. Mandelonitrile, a cyanohydrin produced by ingesting almonds or some fruit pits, releases hydrogen cyanide and is responsible for the toxicity of cyanogenic glycosides.
Over 30 nitrile-containing pharmaceuticals are currently marketed for a diverse variety of medicinal indications with more than 20 additional nitrile-containing leads in clinical development. The nitrile group is quite robust and, in most cases, is not readily metabolized but passes through the body unchanged. The types of pharmaceuticals containing nitriles is diverse, from Vildagliptin an antidiabetic drug to Anastrazole which is the gold standard in treating breast cancer. In many instances the nitrile mimics functionality present in substrates for enzymes, whereas in other cases the nitrile increases water solubility or decreases susceptibility to oxidative metabolism in the liver.
and hydrocyanation
. Both routes are green in the sense that they do not generate stoichiometric amounts of salts. In ammonoxidation, a hydrocarbon is partially oxidized in the presence of ammonia. This conversion is practiced on a large scale for acrylonitrile:
An example of hydrocyanation is the production of adiponitrile
from 1,3-butadiene
.
Usually for more specialty applications in organic synthesis
, nitriles can be prepared by a wide variety of other methods:
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:
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
at the carbon atom in a nucleophilic addition
reactions:
. For an example see: von Braun reaction
.
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
that has a -C
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
≡N
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
functional group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, one example being super glue (methyl cyanoacrylate).
Inorganic compound
Inorganic compound
Inorganic compounds have traditionally been considered to be of inanimate, non-biological origin. In contrast, organic compounds have an explicit biological origin. However, over the past century, the classification of inorganic vs organic compounds has become less important to scientists,...
s 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 acidFormic acid
Formic acid is the simplest carboxylic acid. Its chemical formula is HCOOH or HCO2H. It is an important intermediate in chemical synthesis and occurs naturally, most notably in the venom of bee and ant stings. In fact, its name comes from the Latin word for ant, formica, referring to its early...
, hydrogen cyanide was first synthesized by C.W. Scheele
Carl Wilhelm Scheele
Carl Wilhelm Scheele was a German-Swedish pharmaceutical chemist. Isaac Asimov called him "hard-luck Scheele" because he made a number of chemical discoveries before others who are generally given the credit...
in 1782. In 1811 J. L. Gay-Lussac
Joseph Louis Gay-Lussac
- External links :* from the American Chemical Society* from the Encyclopædia Britannica, 10th Edition * , Paris...
was able to prepare the very toxic and volatile pure acid.
The nitrile of benzoic acids was first prepared by Friedrich Wöhler
Friedrich Wöhler
Friedrich Wöhler was a German chemist, best known for his synthesis of urea, but also the first to isolate several chemical elements.-Biography:He was born in Eschersheim, which belonged to aau...
and Justus von Liebig
Justus von Liebig
Justus von Liebig was a German chemist who made major contributions to agricultural and biological chemistry, and worked on the organization of organic chemistry. As a professor, he devised the modern laboratory-oriented teaching method, and for such innovations, he is regarded as one of the...
, but due to minimal yield of the synthesis neither physical nor chemical properties were determined nor a structure suggested. Théophile-Jules Pelouze
Théophile-Jules Pelouze
Théophile-Jules Pelouze was a French chemist. He was born at Valognes, and died in Paris....
synthesized propionitrile
Propionitrile
Propanenitrile, Propionitrile or ethyl cyanide, is a nitrile with the molecular formula C2H5CN. It is a clear liquid with an ethereal, sweet odor.-Production:...
in 1834 suggesting it to be an ether of propionic alcohol and hydrocyanic acid.
The synthesis of benzonitrile
Benzonitrile
Benzonitrile is the chemical compound with the formula C6H5CN, abbreviated PhCN. This aromatic organic compound is colourless, with a sweet almond odour. It is prepared by the dehydration of benzamide, or by the reaction of sodium cyanide with bromobenzene....
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
Formate
Formate or methanoate is the ion CHOO− or HCOO− . It is the simplest carboxylate anion. It is produced in large amounts in the hepatic mitochondria of embryonic cells and in cancer cells by the folate cycle Formate or methanoate is the ion CHOO− or HCOO− (formic acid minus one hydrogen ion). It...
to his results. He coined the name nitrile for the newfound substance, which became the name for the compound group.
Nitriles occur naturally in a diverse set of plant and animal sources. Over 120 naturally occurring nitriles have been isolated from terrestrial and marine sources. Nitriles are commonly encountered in fruit pits, especially almonds, and during cooking of Brassica crops (such as cabbage, brussel sprouts, and cauliflower), which release nitriles being released through hydrolysis. Mandelonitrile, a cyanohydrin produced by ingesting almonds or some fruit pits, releases hydrogen cyanide and is responsible for the toxicity of cyanogenic glycosides.
Over 30 nitrile-containing pharmaceuticals are currently marketed for a diverse variety of medicinal indications with more than 20 additional nitrile-containing leads in clinical development. The nitrile group is quite robust and, in most cases, is not readily metabolized but passes through the body unchanged. The types of pharmaceuticals containing nitriles is diverse, from Vildagliptin an antidiabetic drug to Anastrazole which is the gold standard in treating breast cancer. In many instances the nitrile mimics functionality present in substrates for enzymes, whereas in other cases the nitrile increases water solubility or decreases susceptibility to oxidative metabolism in the liver.
Synthesis
Industrially, the main methods for producing nitriles are ammoxidationAmmoxidation
In chemistry, ammoxidation is an industrial process for the production of nitriles using ammonia and oxygen. The usual substrates are alkenes. It is sometimes called the Sohio process, acknowledging that ammoxidation was commercialized by Standard Oil of Ohio...
and hydrocyanation
Hydrocyanation
Hydrocyanation is, most fundamentally, the process whereby H+ and –CN ions are added to a molecular substrate. Usually the substrate is an alkene and the product is a nitrile. When –CN is a ligand in a transition metal complex, its basicity makes it difficult to dislodge, so, in this...
. Both routes are green in the sense that they do not generate stoichiometric amounts of salts. In ammonoxidation, a hydrocarbon is partially oxidized in the presence of ammonia. This conversion is practiced on a large scale for acrylonitrile:
- CH3CH=CH2 + 3/2 O2 + NH3 → NCCH=CH2 + 3 H2O
An example of hydrocyanation is the production of adiponitrile
Adiponitrile
Adiponitrile is the organic compound with the formula 42. This dinitrile, a viscous, colourless liquid, is an important precursor to the polymer nylon 66. In 2005, about one billion kilograms were produced annually.-Early routes:...
from 1,3-butadiene
1,3-Butadiene
1,3-Butadiene is a simple conjugated diene with the formula C4H6. It is an important industrial chemical used as a monomer in the production of synthetic rubber. When the word butadiene is used, most of the time it refers to 1,3-butadiene....
.
- CH2=CH-CH=CH2 + 2 HCN → NC(CH2)4CN
Usually for more specialty applications in organic synthesis
Organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
, nitriles can be prepared by a wide variety of other methods:
- Nucleophilic aliphatic substitution reactions of alkyl halides with metal cyanideCyanideA cyanide is a chemical compound that contains the cyano group, -C≡N, which consists of a carbon atom triple-bonded to a nitrogen atom. Cyanides most commonly refer to salts of the anion CN−. Most cyanides are highly toxic....
s in the Kolbe nitrile synthesisKolbe nitrile synthesisThe Kolbe nitrile synthesis is a method for the preparation of alkyl nitriles by reaction of the corresponding alkylhalide with a metal cyanide . A side product for this reaction is the formation of an isonitrile because the cyanide ion is an ambident nucleophile and according to Kornblum's rule is...
. Aryl nitriles are prepared in the Rosenmund-von Braun synthesisRosenmund-von Braun synthesisThe Rosenmund-von Braun synthesis is an organic reaction in which an aryl halide reacts with cuprous cyanide to an aryl nitrile..The reaction was named after Karl Wilhelm Rosenmund who together with his Ph.D. student Erich Struck discovered in 1914 that aryl halide reacts with alcohol water...
. - DehydrationDehydration reactionIn chemistry and the biological sciences, a dehydration reaction is usually defined as a chemical reaction that involves the loss of water from the reacting molecule. Dehydration reactions are a subset of elimination reactions...
of primary amideAmideIn chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
s. Many reagents are available, the combination of ethyl dichlorophosphate and DBUDBU (chemistry)1,8-Diazabicyclo[5.4.0]undec-7-ene, or more commonly DBU, is a chemical compound and belongs to the class of amidine compounds. It is used in organic synthesis as a catalyst and complexing ligand and a strong non-nucleophilic base.It is used as a curing agent for epoxy; it is used as a protecting...
just one of them in this conversion of benzamideBenzamideBenzamide is an off-white solid with the chemical formula of C6H5CONH2. It is a derivative of benzoic acid. It is slightly soluble in water, and soluble in many organic solvents.- External links :* *...
to benzonitrileBenzonitrileBenzonitrile is the chemical compound with the formula C6H5CN, abbreviated PhCN. This aromatic organic compound is colourless, with a sweet almond odour. It is prepared by the dehydration of benzamide, or by the reaction of sodium cyanide with bromobenzene....
:
- Two intermediates in this reaction are amide tautomerTautomerTautomers are isomers of organic compounds that readily interconvert by a chemical reaction called tautomerization. This reaction commonly results in the formal migration of a hydrogen atom or proton, accompanied by a switch of a single bond and adjacent double bond...
A and its phosphateOrganophosphateAn organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...
adduct B.- dehydrationDehydration reactionIn chemistry and the biological sciences, a dehydration reaction is usually defined as a chemical reaction that involves the loss of water from the reacting molecule. Dehydration reactions are a subset of elimination reactions...
of secondary amideAmideIn chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
s (von Braun amide degradationVon Braun amide degradationThe Von Braun amide degradation is the chemical reaction of a monosubstituted amide with phosphorus pentachloride to give a nitrile and an organohalide....
) - dehydrationDehydration reactionIn chemistry and the biological sciences, a dehydration reaction is usually defined as a chemical reaction that involves the loss of water from the reacting molecule. Dehydration reactions are a subset of elimination reactions...
of aldoximes with triethylamineTriethylamineTriethylamine is the chemical compound with the formula N3, commonly abbreviated Et3N. It is also abbreviated TEA, yet this abbreviation must be used carefully to avoid confusion with triethanolamine, for which TEA is also a common abbreviation....
/sulfur dioxideSulfur dioxideSulfur dioxide is the chemical compound with the formula . It is released by volcanoes and in various industrial processes. Since coal and petroleum often contain sulfur compounds, their combustion generates sulfur dioxide unless the sulfur compounds are removed before burning the fuel...
, zeoliteZeoliteZeolites are microporous, aluminosilicate minerals commonly used as commercial adsorbents. The term zeolite was originally coined in 1756 by Swedish mineralogist Axel Fredrik Cronstedt, who observed that upon rapidly heating the material stilbite, it produced large amounts of steam from water that...
s, or sulfuryl chlorideSulfuryl chlorideSulfuryl chloride is an inorganic compound with the formula SO2Cl2. At room temperature, it is a colorless liquid with a pungent odor. Sulfuryl chloride is not found in nature, as can be inferred from its rapid hydrolysis.... - One-pot synthesisOne-pot synthesisIn chemistry a one-pot synthesis is a strategy to improve the efficiency of a chemical reaction whereby a reactant is subjected to successive chemical reactions in just one reactor...
of aldehydeAldehydeAn aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
with hydroxylamineHydroxylamineHydroxylamine is an inorganic compound with the formula NH2OH. The pure material is a white, unstable crystalline, hygroscopic compound. However, hydroxylamine is almost always provided and used as an aqueous solution. It is used to prepare oximes, an important functional group. It is also an...
and sodium sulfateSodium sulfateSodium sulfate is the sodium salt of sulfuric acid. When anhydrous, it is a white crystalline solid of formula Na2SO4 known as the mineral thenardite; the decahydrate Na2SO4·10H2O has been known as Glauber's salt or, historically, sal mirabilis since the 17th century. Another solid is the...
.
- dehydration
- In one study an aromatic or aliphatic aldehyde is reacted with hydroxylamine and anhydrousAnhydrousAs a general term, a substance is said to be anhydrous if it contains no water. The way of achieving the anhydrous form differs from one substance to another...
sodium sulfate in a dry media reactionDry media reactionA dry media reaction or solid-state reaction or solventless reaction is a chemical reaction system in the absence of a solvent. The drive for the development of dry media reactions in chemistry is* economics...
for a very small amount of time under microwave irradiationMicrowave chemistryMicrowave chemistry is the science of applying microwave irradiation to chemical reactions. Microwaves act as high frequency electric fields and will generally heat any material containing mobile electric charges, such as polar molecules in a solvent or conducting ions in a solid...
through an intermediate aldoxime.- reaction of metal cyanides with aldehydes in the cyanohydrin reactionCyanohydrin reactionA Cyanohydrin reaction is an organic chemical reaction by an aldehyde or ketone with a cyanide anion or a nitrile to form a cyanohydrin. This nucleophilic addition is a reversible reaction but with aliphatic carbonyl compounds equilibrium is in favor of the reaction products. The cyanide source...
- from arylArylIn the context of organic molecules, aryl refers to any functional group or substituent derived from an aromatic ring, be it phenyl, naphthyl, thienyl, indolyl, etc....
carboxylic acidCarboxylic acidCarboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
s (Letts nitrile synthesisLetts nitrile synthesisThe Letts nitrile synthesis is the chemical reaction of aromatic carboxylic acids with metal thiocyanates to form nitriles.-References:# Letts, E. A. Ber. 1872, 5, 669.# Mowry, D. T. Chem. Rev. 1948, 42, 264....
) - aromatic nitriles from diazonium compounds in the Sandmeyer reactionSandmeyer reactionThe Sandmeyer reaction is a chemical reaction used to synthesize aryl halides from aryl diazonium salts. It is named after the Swiss chemist Traugott Sandmeyer....
- A commercial source for the cyanide group is diethylaluminum cyanide Et2AlCN which can be prepared from triethylaluminiumTriethylaluminiumTriethylaluminium is an organoaluminium compound. This volatile, colorless liquid is highly pyrophoric, igniting immediately upon exposure to air. It is normally stored in stainless steel containers either as a pure liquid or as a solution in hydrocarbon solvents such as hexane, heptane, or ...
and HCN. It has been used in nucleophilic additionNucleophilic additionIn organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a π bond is removed by the creation of two new covalent bonds by the addition of a nucleophile....
to ketoneKetoneIn organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
s. For an example of its use see: Kuwajima Taxol total synthesisKuwajima Taxol total synthesisThe Kuwajima Taxol total synthesis by the group of Isao Kuwajima of the Tokyo Institute of Technology is one of several efforts in taxol total synthesis published in the 1990s... - cyanide ions facilitate the coupling of dibromides. Reaction of α,α'-dibromo adipic acidAdipic acidAdipic acid is the organic compound with the formula 42. From the industrial perspective, it is the most important dicarboxylic acid: About 2.5 billion kilograms of this white crystalline powder are produced annually, mainly as a precursor for the production of nylon...
with sodium cyanideSodium cyanideSodium cyanide is an inorganic compound with the formula NaCN. This highly toxic colorless salt is used mainly in gold mining but has other niche applications...
in ethanolEthanolEthanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
yields the cyano cyclobutaneCyclobutaneCyclobutane is an organic compound with the formula 4. Cyclobutane is a colourless gas and commercially available as a liquefied gas. Derivatives of cyclobutane are called cyclobutanes...
:
- reaction of metal cyanides with aldehydes in the cyanohydrin reaction
- In the so-called Franchimont Reaction (A. P. N. Franchimont, 1872) an α-bromocarboxylic acid is dimerized after hydrolysis of the cyanogroup and decarboxylationDecarboxylationDecarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...
- Aromatic nitriles can be prepared from base hydrolysis of trichloromethyl aryl ketimines (RC(CCl3)=NH) in the Houben-Fischer synthesis
Reactions
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 hydrolysisHydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
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 acetonitrileAcetonitrileAcetonitrile is the chemical compound with formula . This colourless liquid is the simplest organic nitrile. It is produced mainly as a byproduct of acrylonitrile manufacture...
and acetamideAcetamideAcetamide is an organic compound with the formula CH3CONH2. It is the simplest amide derived from acetic acid. It finds some use as a plasticizer and as an industrial solvent...
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 hydrogenHydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...
with a nickel
Nickel
Nickel is a chemical element with the chemical symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel belongs to the transition metals and is hard and ductile...
catalyst; an amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
is formed in this reaction (see nitrile reduction
Nitrile reduction
In nitrile reduction a nitrile is reduced to either an amine or an aldehyde with a suitable chemical reagent .Reagents for the conversion to amines are lithium aluminium hydride, Raney nickel / hydrogen / or diborane This organic reaction is one of several nitrogen-hydrogen bond forming...
). Reduction to the imine followed by hydrolysis to the aldehyde takes place in the Stephen aldehyde synthesis
Stephen aldehyde synthesis
Stephen aldehyde synthesis, a named reaction in chemistry, was invented by Henry Stephen . This reaction involves the preparation of aldehydes from nitriles using tin chloride , hydrochloric acid and quenching the resulting iminium salt with water .Overall, the reaction scheme is as...
Nucleophiles
A nitrile is an electrophileElectrophile
In general electrophiles are positively charged species that are attracted to an electron rich centre. In chemistry, an electrophile is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile...
at the carbon atom in a nucleophilic addition
Nucleophilic addition
In organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a π bond is removed by the creation of two new covalent bonds by the addition of a nucleophile....
reactions:
- with an organozinc compoundOrganozinc compoundOrganozinc compounds in organic chemistry contain carbon to zinc chemical bonds. Organozinc chemistry is the science of organozinc compounds describing their physical properties, synthesis and reactions....
in the Blaise reactionBlaise reactionThe Blaise reaction is an organic reaction that forms a β-ketoester from the reaction of zinc metal with a α-bromoester and a nitrile. The final intermediate is a metaloimine, which is hydrolyzed to give the desired β-ketoester.... - and with alcoholAlcoholIn chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
s in the Pinner reactionPinner reactionThe Pinner reaction is an organic reaction of a nitrile with an alcohol under acid catalysis for instance hydrochloric acid. The product formed is the hydrochloric acid salt of an imino ester or an alkyl imidate, which sometimes is called a Pinner salt...
. - likewise, the reaction of the amineAmineAmines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
sarcosineSarcosineSarcosine, also known as N-methylglycine, is an intermediate and byproduct in glycine synthesis and degradation. Sarcosine is metabolized to glycine by the enzyme sarcosine dehydrogenase, while glycine-N-methyl transferase generates sarcosine from glycine. Sarcosine is a natural amino acid found in...
with cyanamideCyanamideCyanamide is an organic compound with the formula CN2H2. This white solid is widely used in agriculture and the production of pharmaceuticals and other organic compounds. It is also used as an alcohol deterrent drug in Canada, Europe and Japan. The molecule features a nitrile group attached to an...
yields creatineCreatineCreatine is a nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to all cells in the body, primarily muscle. This is achieved by increasing the formation of Adenosine triphosphate... - Nitriles react in Friedel-Crafts acylation in the Houben-Hoesch reaction to ketones
Alkylation
Deprotonating nitriles generates exceptionally powerful nucleophiles that alkylate a wide variety of electrophiles. Key to the exceptional nucleophilicity is the extremely small steric demand of the CN unit combined with the unusual inductive stabilization. These features make nitriles ideal for creating new carbon-carbon bonds in sterically demanding environments and is used in several syntheses of medicinal targets as well as in the synthesis of pharmaceutical medicines. Recent developments have shown that the nature of the metal counter-ion causes different coordination to either the nitrile nitrogen or the adjacent nucleophilic carbon, often with profound differences in reactivity and stereochemistry.Miscellanea
- In reductive decyanation the nitrile group is replaced by a proton. An effective decyanation is by a dissolving metal reduction with HMPA and potassiumPotassiumPotassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
metal in tert-butanolTert-Butanoltert-Butanol, or 2-methyl-2-propanol, is the simplest tertiary alcohol. It is one of the four isomers of butanol. tert-Butanol is a clear liquid with a camphor-like odor. It is very soluble in water and miscible with ethanol and diethyl ether...
. α-Amino-nitriles can be decyanated with lithium aluminium hydrideLithium aluminium hydrideLithium aluminium hydride, commonly abbreviated to LAH or known as LithAl, is an inorganic compound with the chemical formula LiAlH4. It was discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic synthesis, especially for the reduction of esters,...
. - Nitriles self-react in presence of base in the Thorpe reactionThorpe reactionThe Thorpe reaction is a chemical reaction described as a self-condensation of aliphatic nitriles catalyzed by base to form enamines. The reaction was discovered by Jocelyn Field Thorpe.-Thorpe–Ziegler reaction:...
in a nucleophilic additionNucleophilic additionIn organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a π bond is removed by the creation of two new covalent bonds by the addition of a nucleophile.... - In organometallic chemistryOrganometallic chemistryOrganometallic chemistry is the study of chemical compounds containing bonds between carbon and a metal. Since many compounds without such bonds are chemically similar, an alternative may be compounds containing metal-element bonds of a largely covalent character...
nitriles are known to add to alkyneAlkyneAlkynes are hydrocarbons that have a triple bond between two carbon atoms, with the formula CnH2n-2. Alkynes are traditionally known as acetylenes, although the name acetylene also refers specifically to C2H2, known formally as ethyne using IUPAC nomenclature...
s in carbocyanation:
Organic cyanamides
Cyanamides are N-cyano compounds with general structure R1R2N-CN and related to the inorganic parent cyanamideCyanamide
Cyanamide is an organic compound with the formula CN2H2. This white solid is widely used in agriculture and the production of pharmaceuticals and other organic compounds. It is also used as an alcohol deterrent drug in Canada, Europe and Japan. The molecule features a nitrile group attached to an...
. For an example see: von Braun reaction
Von Braun reaction
The Von Braun reaction is an organic reaction in which a tertiary amine reacts with cyanogen bromide to an organocyanamide. An example is the reaction of dimethyl-α-naphthylamine :...
.
Nitrile oxides
Nitrile oxides have the general structure R-CNO.See also
- For the polymerPolymerA polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
used to make safety gloves, see Nitrile rubberNitrile rubberNitrile rubber, also known as Buna-N, Perbunan, or NBR, is a synthetic rubber copolymer of acrylonitrile and butadiene. Trade names include Nipol, Krynac and Europrene....
. - Protonated nitriles: NitriliumNitriliumA nitrilium ion is a nitrile that has been protonated, [RCNH]+, or alkylated, [RCNR′]+.-Synthesis:Nitriles are only weakly basic and are poor nucleophiles, but they will attack very reactive electrophiles such as carbocations....
- Deprotonated nitriles: Nitrile anionNitrile anionNitrile anions are nitriles lacking a proton at the position α to the nitrile group. They undergo nucleophilic addition and substitution reactions with various electrophiles....
- CyanocarbonCyanocarbonCyanocarbons are a chemical compounds that contain several cyanide groups. Such substances generally are classified as organic compounds, since they are formally derived from hydrocarbons by replacing one or more hydrogen atoms with a cyanide. The parent member is C4. Organic chemists often...
- Nitrile ylideNitrile ylideNitrile ylides also known as nitrilium ylides, or nitrilium methylides are generally reactive intermediates. Usually, they cannot be isolated. However, a structure has been determined on a by X-ray crystallography. As ylides, they possess a negative charge and a positive charge on adjacent atoms....