Acetonitrile

Acetonitrile
IUPAC name	Acetonitrile
Other names	Methyl cyanide; cyanomethane; ethanenitrile
Identifiers
CAS number	75-05-8 Y
PubChem	6342
RTECS number	AL7700000
SMILES	CC#N
InChI	1/C2H3N/c1-2-3/h1H3
Properties
Molecular formula	C2H3N
Molar mass	41.05 g mol−1
Appearance	colorless liquid
Density	0.786 g/mL liquid
Melting point	−45 °C
Boiling point	82 °C
Solubility in water	miscible
Solubility	organic solvents
Acidity (pKa)	25
Hazards
MSDS	External MSDS
EU classification	Flammable, harmful
R-phrases	R11, R20/21/22, R36
S-phrases	(S1/2), S16, S36/37
NFPA 704	3 2 0
Flash point	2 °C
Related compounds
Related nitriles	propionitrile, butyronitrile
Related compounds	acetic acid, acetamide, ethylamine
Supplementary data page
Structure and properties	n, εr, etc.
Thermodynamic data	Phase behaviour Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
Y (what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Acetonitrile is the chemical compound with formula CH₃CN. This colourless liquid is the simplest organic nitrile. It is produced mainly as a byproduct of acrylonitrile manufacture. It is widely used as a polar aprotic solvent in synthetic chemistry, and as a medium-polarity solvent in HPLC.

Production

Acetonitrile is a by-product from the manufacture of acrylonitrile.^[1] 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.^[2] The four main producers of acetonitrile in the world are: INEOS, DuPont, Panreac, and J.T. Baker Chemical. In 1992^[update], 32.3 million pounds (14,700 t) of acetonitrile were produced in the US.

The Acetonitrile Shortage of 2008-2009

As of October 2008, there has been a worldwide shortage of acetonitrile. The shortage results from an attenuated output from China, as production was shut down for the Olympics as well as damage to a U.S. factory in Texas during Hurricane Ike.

During the 2008 Summer Olympics in Beijing, "The industrial production that the Chinese government shut down to improve Beijing’s air quality seems to have included a disproportionate amount of the country’s acetonitrile production".^[3]

Due to the global economic slowdown, the production of acrylonitrile that is used in acrylic fibers and acrylonitrile-butadiene-styrene (ABS) resins has also decreased (used to make plastic moldings from car parts to Lego bricks). Because acetonitrile is a byproduct in the production of acrylonitrile, its production has also decreased.^[4] The global shortage of acetonitrile continued to be exacerbated through early 2009.

Applications

Acetonitrile is used mainly as a solvent that is miscible with water and has a convenient liquid range. With a dipole moment of 3.84 D, acetonitrile dissolves a wide range of ionic and nonpolar compounds, and, with its low reactivity, it does so with minimal complications.

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 low viscosity and low chemical reactivity make it a popular choice for liquid chromatography. Acetonitrile plays a significant role as the dominant solvent used in the manufacture of DNA oligonuleotides from monomers. Industrially, it is used as a solvent in the purification of butadiene and in the manufacture of pharmaceuticals and photographic film.^[5]

Organic synthesis

Acetonitrile is a common two-carbon building block in organic synthesis^[6] as in the production of pesticides to perfumes. Its reaction with cyanogen chloride affords malononitrile.

Ligand in coordination chemistry

In inorganic chemistry, acetonitrile is employed as a solvent and often an easily displaceable ligand. For example, PdCl₂(CH₃CN)₂ is prepared by heating a suspension of (polymeric) palladium chloride in acetonitrile:

PdCl₂ + 2 CH₃CN → PdCl₂(CH₃CN)₂

The CH₃CN groups undergo rapid displacement by many other ligands.

Safety

Toxicity

Acetonitrile has only a modest toxicity,^[7] but it can be metabolised to produce hydrogen cyanide (see below), which is the source of the observed toxic effects.^[5][8][9] 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.^[8] 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 remedies.^[8]

It has been used in formulations for nail polish remover, despite its low but significant toxicity.^[10] 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.^[11]

Metabolism and excretion

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.^[13] The first step in this pathway is the oxidation of acetonitrile to glyconitrile by an NADPH-dependent cytochrome P450 monooxygenase. The glyconitrile then undergoes a spontaneous decondensation to give hydrogen cyanide and formaldehyde.^[7][8]

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 one-twentieth that for a propionitrile dose 60 times lower (see table).^[12]

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. ^[7][8][9]

References

1. ^ Peter Pollak, Gérard Romeder, Ferdinand Hagedorn, Heinz-Peter Gelbke "Nitriles" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, 2002: Weinheim. DOI: 10.1002/14356007.a17_363
2. ^ US patent 4179462, "Process for preparing acetonitrile", granted , assigned to Monsanto Company 
3. ^ Lowe, Derek (2009), The Great Acetonitrile Shortage, Corante, http://pipeline.corante.com/archives/2009/01/22/the_great_acetonitrile_shortage.php 
4. ^ Chemical & Engineering News, 86(47), p. 27 November 24, 2008
5. ^ ^{a b} Spanish Ministry of Health (2002), Acetonitrile. Summary Risk Assessment Report, Ispra (VA), Italy: European Chemicals Bureau, Special Publication I.01.65, http://ecb.jrc.it/DOCUMENTS/Existing-Chemicals/RISK_ASSESSMENT/SUMMARY/acetonitrilesum006.pdf 
6. ^ DiBiase, S. A.; Beadle, J. R.; Gokel, G. W., "Synthesis of α,β-Unsaturated Nitriles from Acetonitrile: Cyclohexylideneacetonitrile and Cinnamonitrile", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv7p0108 ; Coll. Vol. 7: 108 
7. ^ ^{a b c} Institut National de Recherche et de Sécurité (INRS) (2004), Fiche toxicologique nº 104 : Acétonitrile, Paris: INRS, ISBN 2-7389-1278-8, http://www.inrs.fr/inrs-pub/inrs01.nsf/IntranetObject-accesParReference/FT%20104/$File/ft104.pdf 
8. ^ ^{a b c d e} International Programme on Chemical Safety (1993), Environmental Health Criteria 154. Acetonitrile, Geneva: World Health Organization, http://www.inchem.org/documents/ehc/ehc/ehc154.htm 
9. ^ ^{a b} Greenberg, Mark (1999), Toxicological Review of Acetonitrile, Washington, D.C.: U.S. Environmental Protection Agency, http://www.epa.gov/NCEA/iris/toxreviews/0205-tr.pdf 
10. ^ At least two cases have been reported of accidental poisoning of young children by acetonitrile-based nail polish remover, one of which was fatal: Caravati, EM; 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 
11. ^ 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. OJEC L65 of 2000-03-14, pp. 22–25.
12. ^ ^{a b} Ahmed, AE; Farooqui, MYH (1982), "Comparative toxicities of aliphatic nitriles", Toxicol. Lett. 12: 157–64, doi:10.1016/0378-4274(82)90179-5 
13. ^ Pozzani, UC; Carpenter, CP; Palm, PE; Weil, CS; Nair, JH (1959), "An investigation of the mammalian toxicity of acetonitrile", J. Occup. Med. 1: 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