Acetonitrile

Template:Short description Template:Distinguish Template:Chembox

Acetonitrile, often abbreviated MeCN (methyl cyanide), is the chemical compound with the formula Template:Chem2 and structure Template:Chem2. 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.<ref name="ashford">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The Template:Chem2 skeleton is linear with a short Template:Chem2 distance of 1.16 Å.<ref>Template:Cite journal</ref>

Acetonitrile was first prepared in 1847 by the French chemist Jean-Baptiste Dumas.<ref>Template:Cite journal</ref>

ApplicationsEdit

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,<ref>Template:Cite journal</ref> 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.<ref name="ecb"/>

Organic synthesisEdit

Acetonitrile is a common two-carbon building block in organic synthesis<ref>Template:OrgSynth</ref> of many useful chemicals, including acetamidine hydrochloride, thiamine, and 1-naphthaleneacetic acid.<ref name="encyc-toxic">Template:Citation</ref> Its reaction with cyanogen chloride affords malononitrile.<ref name = "ashford" />

As an electron pair donorEdit

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:<ref>Template:Cite book</ref>

Template:Chem2

A related complex is tetrakis(acetonitrile)copper(I) hexafluorophosphate Template:Chem2. The Template:Chem2 groups in these complexes are rapidly displaced by many other ligands.

It also forms Lewis adducts with group 13 Lewis acids like boron trifluoride.<ref>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}}</ref> In superacids, it is possible to protonate acetonitrile.<ref name="Christe">Template:Cite journal</ref>

ProductionEdit

Acetonitrile is a byproduct from the manufacture of acrylonitrile by catalytic ammoxidation of propylene. Most is combusted to support the intended process but an estimated several thousand tons are retained for the above-mentioned applications.<ref name=Ullmann>Template:Ullmann</ref> 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.<ref>Template:Cite patent</ref> In Template:As of, Template:Convert of acetonitrile were produced in the US.

Acetonitrile shortage in 2008–2009Edit

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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref>Template:Cite journal</ref> The global shortage of acetonitrile continued through early 2009.Template:Update inline

SafetyEdit

ToxicityEdit

Acetonitrile has only modest toxicity in small doses.<ref name="encyc-toxic" /><ref name="inrs">Template:Citation</ref> It can be metabolised to produce hydrogen cyanide, which is the source of the observed toxic effects.<ref name="ecb">Template:Citation</ref><ref name="who">Template:Citation</ref><ref name="epa">Template:Citation</ref> 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).<ref name="encyc-toxic" />

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.<ref name="who" /> 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.<ref name="who" />

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.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>

Metabolism and excretionEdit

Compound	Cyanide, concentration in brain (μg/kg)	Oral Template: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)	align="center" Template:N/a	3000
Ionic cyanide concentrations measured in the brains of Sprague-Dawley rats one hour after oral administration of an Template:LD50 of various nitriles.<ref name="ratdata">Template:Citation</ref>

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.<ref>Template:Citation</ref> 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.<ref name="inrs" /><ref name="who" /> 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 Template:Frac that for a propionitrile dose 60 times lower (see table).<ref name="ratdata" />

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.<ref name="inrs" /><ref name="who" /><ref name="epa" />