Acetonitrile - Misplaced Pages

Acetonitrile, often abbreviated MeCN (methyl cyanide), is the chemical compound with the formula CH₃CN and structure H₃C−C≡N. This colourless liquid is the simplest organic nitrile (hydrogen cyanide is a simpler nitrile, but the cyanide anion is not classed as organic). It is produced mainly as a byproduct of acrylonitrile manufacture. It is used as a polar aprotic solvent in organic synthesis and in the purification of butadiene. The N≡C−C skeleton is linear with a short C≡N distance of 1.16 Å.

Acetonitrile was first prepared in 1847 by the French chemist Jean-Baptiste Dumas.

Applications

Acetonitrile is used mainly as a solvent in the purification of butadiene in refineries. Specifically, acetonitrile is fed into the top of a distillation column filled with hydrocarbons including butadiene, and as the acetonitrile falls down through the column, it absorbs the butadiene which is then sent from the bottom of the tower to a second separating tower. Heat is then employed in the separating tower to separate the butadiene.

In the laboratory, it is used as a medium-polarity non-protic solvent that is miscible with water and a range of organic solvents, but not saturated hydrocarbons. It has a convenient range of temperatures at which it is a liquid, and a high dielectric constant of 38.8. With a dipole moment of 3.92 D, acetonitrile dissolves a wide range of ionic and nonpolar compounds and is useful as a mobile phase in HPLC and LC–MS.

It is widely used in battery applications because of its relatively high dielectric constant and ability to dissolve electrolytes. For similar reasons, it is a popular solvent in cyclic voltammetry.

Its ultraviolet transparency UV cutoff, low viscosity and low chemical reactivity make it a popular choice for high-performance liquid chromatography (HPLC).

Acetonitrile plays a significant role as the dominant solvent used in oligonucleotide synthesis from nucleoside phosphoramidites.

Industrially, it is used as a solvent for the manufacture of pharmaceuticals and photographic film.

Organic synthesis

Acetonitrile is a common two-carbon building block in organic synthesis of many useful chemicals, including acetamidine hydrochloride, thiamine, and 1-naphthaleneacetic acid. Its reaction with cyanogen chloride affords malononitrile.

As an electron pair donor

Acetonitrile has a free electron pair at the nitrogen atom, which can form many transition metal nitrile complexes. Being weakly basic, it is an easily displaceable ligand. For example, bis(acetonitrile)palladium dichloride is prepared by heating a suspension of palladium chloride in acetonitrile:

PdCl₂ + 2 CH₃CN → PdCl₂(CH₃CN)₂

A related complex is tetrakis(acetonitrile)copper(I) hexafluorophosphate [Cu(CH₃CN)₄]. The CH₃CN groups in these complexes are rapidly displaced by many other ligands.

It also forms Lewis adducts with group 13 Lewis acids like boron trifluoride. In superacids, it is possible to protonate acetonitrile.

Production

Acetonitrile is a byproduct from the manufacture of acrylonitrile. Most is combusted to support the intended process but an estimated several thousand tons are retained for the above-mentioned applications. Production trends for acetonitrile thus generally follow those of acrylonitrile. Acetonitrile can also be produced by many other methods, but these are of no commercial importance as of 2002. Illustrative routes are by dehydration of acetamide or by hydrogenation of mixtures of carbon monoxide and ammonia. In 1992, 14,700 tonnes (16,200 short tons) of acetonitrile were produced in the US.

Acetonitrile shortage in 2008–2009

Starting in October 2008, the worldwide supply of acetonitrile was low because Chinese production was shut down for the Olympics. Furthermore, a U.S. factory was damaged in Texas during Hurricane Ike. Due to the global economic slowdown, the production of acrylonitrile used in acrylic fibers and acrylonitrile butadiene styrene (ABS) resins decreased. Acetonitrile is a byproduct in the production of acrylonitrile and its production also decreased, further compounding the acetonitrile shortage. The global shortage of acetonitrile continued through early 2009.

Safety

Toxicity

Acetonitrile has only modest toxicity in small doses. It can be metabolised to produce hydrogen cyanide, which is the source of the observed toxic effects. Generally the onset of toxic effects is delayed, due to the time required for the body to metabolize acetonitrile to cyanide (generally about 2–12 hours).

Cases of acetonitrile poisoning in humans (or, to be more specific, of cyanide poisoning after exposure to acetonitrile) are rare but not unknown, by inhalation, ingestion and (possibly) by skin absorption. The symptoms, which do not usually appear for several hours after the exposure, include breathing difficulties, slow pulse rate, nausea, and vomiting. Convulsions and coma can occur in serious cases, followed by death from respiratory failure. The treatment is as for cyanide poisoning, with oxygen, sodium nitrite, and sodium thiosulfate among the most commonly used emergency treatments.

It has been used in formulations for nail polish remover, despite its toxicity. At least two cases have been reported of accidental poisoning of young children by acetonitrile-based nail polish remover, one of which was fatal. Acetone and ethyl acetate are often preferred as safer for domestic use, and acetonitrile has been banned in cosmetic products in the European Economic Area since March 2000.

Metabolism and excretion

Compound	Cyanide, concentration in brain (μg/kg)	Oral LD₅₀ (mg/kg)
Potassium cyanide	700 ± 200	10
Propionitrile	510 ± 80	40
Butyronitrile	400 ± 100	50
Malononitrile	600 ± 200	60
Acrylonitrile	400 ± 100	90
Acetonitrile	28 ± 5	2460
Table salt (NaCl)	—	3000
Ionic cyanide concentrations measured in the brains of Sprague-Dawley rats one hour after oral administration of an LD₅₀ of various nitriles.

In common with other nitriles, acetonitrile can be metabolised in microsomes, especially in the liver, to produce hydrogen cyanide, as was first shown by Pozzani et al. in 1959. The first step in this pathway is the oxidation of acetonitrile to glycolonitrile by an NADPH-dependent cytochrome P450 monooxygenase. The glycolonitrile then undergoes a spontaneous decomposition to give hydrogen cyanide and formaldehyde. Formaldehyde, a toxin and a carcinogen on its own, is further oxidized to formic acid, which is another source of toxicity.

The metabolism of acetonitrile is much slower than that of other nitriles, which accounts for its relatively low toxicity. Hence, one hour after administration of a potentially lethal dose, the concentration of cyanide in the rat brain was 1⁄20 that for a propionitrile dose 60 times lower (see table).

The relatively slow metabolism of acetonitrile to hydrogen cyanide allows more of the cyanide produced to be detoxified within the body to thiocyanate (the rhodanese pathway). It also allows more of the acetonitrile to be excreted unchanged before it is metabolised. The main pathways of excretion are by exhalation and in the urine.

References

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^ Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 902. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4.
^ NIOSH Pocket Guide to Chemical Hazards. "#0006". National Institute for Occupational Safety and Health (NIOSH).
^ "Acetonitrile". Immediately Dangerous to Life or Health Concentrations (IDLH). National Institute for Occupational Safety and Health (NIOSH).
^ "Archived copy" (PDF). Ashford's Dictionary of Industrial Chemicals, Third edition. p. 76. Archived from the original (PDF) on 2011-05-16. Retrieved 2011-03-31.{{cite web}}: CS1 maint: archived copy as title (link)
Karakida, Ken'ichi; Fukuyama, Tsutomu; Kuchitsu, Kozo (1974). "Molecular Structures of Hydrogen Cyanide and Acetonitrile as Studied by Gas Electron Diffraction". Bulletin of the Chemical Society of Japan. 47 (2): 299–304. doi:10.1246/bcsj.47.299.
Dumas, J.-B. (1847). "Action de l'acide phosphorique anhydre sur les sels ammoniacaux" [Action of anhydrous phosphoric acid on ammonium salts]. Comptes rendus. 25: 383–384.
Steiner, P. A.; Gordy, W. (1966). "Journal of Molecular Spectroscopy". 21: 291. {{cite journal}}: Cite journal requires |journal= (help)
^ Spanish Ministry of Health (2002), Acetonitrile. Summary Risk Assessment Report (PDF), Ispra (VA), Italy: European Chemicals Bureau, Special Publication I.01.65, archived from the original (PDF) on 2008-12-17
DiBiase, S. A.; Beadle, J. R.; Gokel, G. W. "Synthesis of α,β-Unsaturated Nitriles from Acetonitrile: Cyclohexylideneacetonitrile and Cinnamonitrile". Organic Syntheses; Collected Volumes, vol. 7, p. 108.
^ Philip Wexler, ed. (2005), Encyclopedia of Toxicology, vol. 1 (2nd ed.), Elsevier, pp. 28–30, ISBN 0-12-745354-7
Jürgen-Hinrich., Fuhrhop (2003). Organic synthesis : concepts and methods. Li, Guangtao, Dr. (3rd, completely rev. and enl. ed.). Weinheim: Wiley-VCH. p. 26. ISBN 9783527302727. OCLC 51068223.
B. Swanson, D. F. Shriver, J. A. Ibers, "Nature of the donor-acceptor bond in acetonitrile-boron trihalides. The structures of the boron trifluoride and boron trichloride complexes of acetonitrile", Inorg. Chem., 2969., volume 8, pp. 2182-2189, {{doi:10.1021/ic50080a032}}
Haiges, Ralf; Baxter, Amanda F.; Goetz, Nadine R.; Axhausen, Joachim A.; Soltner, Theresa; Kornath, Andreas; Christe, Kalr O. (2016). "Protonation of nitriles: isolation and characterization of alkyl- and arylnitrilium ions". Dalton Transactions. 45 (20): 8494–8499. doi:10.1039/C6DT01301E. PMID 27116374.
Pollak, Peter; Romeder, Gérard; Hagedorn, Ferdinand; Gelbke, Heinz-Peter. "Nitriles". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a17_363. ISBN 978-3527306732.
US 4179462, Olive, G. & Olive, S., "Process for preparing acetonitrile", published 1979-12-18, assigned to Monsanto Company
Lowe, Derek (2009). "The Great Acetonitrile Shortage". Science Translational Medicine.
A. Tullo (2008). "A Solvent Dries Up". Chemical & Engineering News. 86 (47): 27. doi:10.1021/cen-v086n047.p027.
^ Institut national de recherche et de sécurité (INRS) (2004), Fiche toxicologique no. 104 : Acétonitrile (PDF), Paris: INRS, ISBN 2-7389-1278-8, archived from the original (PDF) on 2011-07-28, retrieved 2008-08-19
^ International Programme on Chemical Safety (1993), Environmental Health Criteria 154. Acetonitrile, Geneva: World Health Organization
^ Greenberg, Mark (1999), Toxicological Review of Acetonitrile (PDF), Washington, DC: U.S. Environmental Protection Agency
Caravati, E. M.; Litovitz, T. (1988). "Pediatric cyanide intoxication and death from an acetonitrile-containing cosmetic". J. Am. Med. Assoc. 260 (23): 3470–73. doi:10.1001/jama.260.23.3470. PMID 3062198.
"Twenty-Fifth Commission Directive 2000/11/EC of 10 March 2000 adapting to technical progress Annex II to Council Directive 76/768/EEC on the approximation of laws of the Member States relating to cosmetic products". Official Journal of the European Communities. L65: 22–25. 2000-03-14.
^ Ahmed, A. E.; Farooqui, M. Y. H. (1982), "Comparative toxicities of aliphatic nitriles", Toxicol. Lett., 12 (2–3): 157–64, doi:10.1016/0378-4274(82)90179-5, PMID 6287676
Pozzani, U. C.; Carpenter, C. P.; Palm, P. E.; Weil, C. S.; Nair, J. H. (1959), "An investigation of the mammalian toxicity of acetonitrile", J. Occup. Med., 1 (12): 634–642, doi:10.1097/00043764-195912000-00003, PMID 14434606

External links

WebBook page for C₂H₃N
International Chemical Safety Card 0088
National Pollutant Inventory - Acetonitrile fact sheet
NIOSH Pocket Guide to Chemical Hazards
Chemical Summary for Acetonitrile (CAS No. 75-05-8), Office of Pollution Prevention and Toxics, U.S. Environmental Protection Agency
Simulation of acetonitrile
How Did Organic Matter Reach Earth? Cosmic Detectives Trace Origin of Complex Organic Molecules, on: SciTechDaily. September 10, 2020. Source: Tokyo University of Science: Acetonitrile found in molecular cloud Sgr B2(M) at the center of our galaxy.

Molecules detected in outer space

Molecules

Diatomic	Aluminium monochloride Aluminium monofluoride Aluminium(II) oxide Argonium Carbon cation Carbon monophosphide Carbon monosulfide Carbon monoxide Cyano radical Diatomic carbon Fluoromethylidynium Helium hydride ion Hydrogen chloride Hydrogen fluoride Hydrogen (molecular) Hydroxyl radical Iron(II) oxide Magnesium monohydride Methylidyne radical Nitric oxide Nitrogen (molecular) Imidogen Sulfur mononitride Oxygen (molecular) Phosphorus monoxide Phosphorus mononitride Potassium chloride Silicon carbide Silicon monoxide Silicon monosulfide Sodium chloride Sodium iodide Sulfanyl Sulfur monoxide Titanium(II) oxide
Triatomic	Aluminium(I) hydroxide Aluminium isocyanide Amino radical Carbon dioxide Carbonyl sulfide CCP radical Chloronium Diazenylium Dicarbon monoxide Disilicon carbide Ethynyl radical Formyl radical Hydrogen cyanide (HCN) Hydrogen isocyanide (HNC) Hydrogen sulfide Hydroperoxyl Iron cyanide Isoformyl Magnesium cyanide Magnesium isocyanide Methylene N₂H Nitrous oxide Nitroxyl Ozone Methylidynephosphane Potassium cyanide Trihydrogen cation Sodium cyanide Sodium hydroxide Silicon carbonitride c-Silicon dicarbide SiNC Sulfur dioxide Thioformyl Thioxoethenylidene Titanium dioxide Tricarbon Water
Four atoms	Acetylene Ammonia Isocyanic acid Cyanoethynyl Formaldehyde Fulminic acid HCCN Hydrogen peroxide Hydromagnesium isocyanide Isocyanic acid Isothiocyanic acid Ketenyl Methylene amidogen Methyl cation Methyl radical Propynylidyne Protonated carbon dioxide Protonated hydrogen cyanide Silicon tricarbide Thioformaldehyde Tricarbon monoxide Tricarbon monosulfide Thiocyanic acid
Five atoms	Ammonium ion Butadiynyl Carbodiimide Cyanamide Cyanoacetylene Cyanoformaldehyde Cyanomethyl Cyclopropenylidene Formic acid Isocyanoacetylene Ketene Methane Methoxy radical Methylenimine Propadienylidene Protonated formaldehyde Silane Silicon-carbide cluster
Six atoms	Acetonitrile Cyanobutadiynyl radical E-Cyanomethanimine Cyclopropenone Diacetylene Ethylene Formamide HC₄N Ketenimine Methanethiol Methanol Methyl isocyanide Pentynylidyne Propynal Protonated cyanoacetylene
Seven atoms	Acetaldehyde Acrylonitrile Vinyl cyanide Cyanodiacetylene Ethylene oxide Glycolonitrile Hexatriynyl radical Propyne Methylamine Methyl isocyanate Vinyl alcohol
Eight atoms	Acetic acid Aminoacetonitrile Cyanoallene Ethanimine Glycolaldehyde Hexapentaenylidene Methylcyanoacetylene Methyl formate Acrolein
Nine atoms	Acetamide Cyanohexatriyne Dimethyl ether Ethanol Methyldiacetylene Octatetraynyl radical Propene Ethanethiol Propionitrile N-Methylformamide
Ten atoms or more	Acetone Benzene Benzonitrile Buckminsterfullerene (C₆₀, C₆₀, fullerene, buckyball) C₇₀ fullerene Cyanodecapentayne Ethylene glycol Ethyl formate Methyl acetate Methyl-cyano-diacetylene Methyltriacetylene Propionaldehyde Butyronitrile Pyrimidine Heptatrienyl radical