Acetonitrile is the chemical compound with the formula CH
3CN. This colourless liquid is the simplest organic nitrile. 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. In the laboratory, it is used as a medium-polarity
solvent that is miscible with water and range of organic solvents, but not saturated hydrocarbons.
It has a convenient liquid range 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. 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. 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.
Acetonitrile plays a significant role as the dominant solvent used in the manufacture of
DNA oligonucleotides from monomers. 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 α-napthaleneacetic acid. 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, PdCl
2(CH 3CN)
2 is prepared by heating a suspension of palladium chloride in acetonitrile:
PdCl 2 + 2 CH
3CN → PdCl 2(CH
3CN) 2
A related complex is [Cu(MeCN)4]+. The CH 3CN groups in these complexes are rapidly
displaced by many other ligands. Production
Acetonitrile is a by-product 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. The main distributors of acetonitrile in the
world are: INEOS, Purification Technologies Inc, BioSolve BV, Carlo Erba Reagents, Panreac,
J.T. Baker Chemical, VWR, Sigma Aldrich, and Petrolchem Trading Ltd. In 1992, 32.3 million
pounds 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. Owing to the global economic
slowdown, the production of acrylonitrile that is used in acrylic fibers and acrylonitrile-butadiene-styrene
resins decreased. Because acetonitrile is a byproduct in the production of acrylonitrile,
its production has also decreased. The global shortage of acetonitrile continued through
early 2009. Safety
Toxicity Acetonitrile has only a 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.
Cases of acetonitrile poisoning in humans are rare but not unknown, by inhalation, ingestion
and 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 remedies. It has been used in formulations for nail
polish remover, despite its low but significant toxicity. 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
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 one-twentieth that for
a propionitrile dose 60 times lower. The relatively slow metabolism of acetonitrile
to hydrogen cyanide allows more of the cyanide produced to be detoxified within the body
to thiocyanate. 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
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, Office of Pollution Prevention and Toxics, U.S. Environmental
Protection Agency Simulation of acetonitrile