Trichloroacetonitrile is an
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...
with the formula CCl
3CN. It is a colourless liquid, although commercial samples often are brownish. It is used commercially as a precursor to the fungicide
etridiazole. It is prepared by dehydration of
trichloroacetamide.
As a
bifunctional compound
In organic chemistry, when a single organic molecule has two different functional groups, it is called a bifunctional molecule . A bifunctional molecule has the properties of two different types of functional groups, such as an alcohol (), amide ...
, trichloroacetonitrile can react at both the trichloromethyl and the nitrile group. The
electron-withdrawing effect of the
trichloromethyl group
The trichloromethyl group is a functional group that has the formula –CCl3. The naming of is group is derived from the methyl group (which has the formula –CH3), by replacing each hydrogen atom by a chlorine atom. Compounds with this group are ...
activates the nitrile group for nucleophilic additions. The high
reactivity makes trichloroacetonitrile a versatile
reagent, but also causes its susceptibility towards
hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolys ...
.
Synthesis
The production of trichloroacetonitrile by dehydration of
trichloroacetamide was first described in 1873 by L. Bisschopinck at the
Katholieke Universiteit Leuven.
:
![TCAN via Trichloracetamid](https://upload.wikimedia.org/wikipedia/commons/d/db/TCAN_via_Trichloracetamid.svg)
Trichloroacetonitrile can be obtained by
chlorination Chlorination may refer to:
* Chlorination reaction
In chemistry, halogenation is a chemical reaction that entails the introduction of one or more halogens into a compound. Halide-containing compounds are pervasive, making this type of transform ...
of
acetonitrile on a
zinc
Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
,
copper
Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...
and
alkaline earth metal
The alkaline earth metals are six chemical elements in group 2 of the periodic table. They are beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra).. The elements have very similar properties: they are all ...
halide-impregnated
activated carbon catalyst at 200–400 °C with a 54% yield.
:
![TCAN via Acetonitril](https://upload.wikimedia.org/wikipedia/commons/c/cf/TCAN_via_Acetonitril.svg)
The high temperatures required by this process favours the formation of byproducts, such as
tetrachloromethane
Carbon tetrachloride, also known by many other names (such as tetrachloromethane, also recognised by the IUPAC, carbon tet in the cleaning industry, Halon-104 in firefighting, and Refrigerant-10 in HVACR) is an organic compound with the chemica ...
. In contrast, the chlorination of acetonitrile saturated with
hydrogen chloride
The compound hydrogen chloride has the chemical formula and as such is a hydrogen halide. At room temperature, it is a colourless gas, which forms white fumes of hydrochloric acid upon contact with atmospheric water vapor. Hydrogen chloride ga ...
leads to pure trichloroacetonitrile even at 50–80 °C in good yields.
Like other halogenated acetonitriles, trichloroacetonitrile is produced from organic substances such as
algae,
humic acids and proteinaceous material in the disinfecting chlorination of water from natural sources.
Properties
![Trichloroacetonitrile dimensions](https://upload.wikimedia.org/wikipedia/commons/2/26/Trichloroacetonitrile_dimensions.svg)
Freshly-distilled trichloroacetonitrile is a colorless, liquid with a pungent odor that discolours rapidly yellowish to light brown. It is sensitive towards water, acids and bases.
The
bond lengths are 146.0
pm (C–C), 116.5 pm (C≡N) and 176.3 pm (C–Cl). The bond angle is 110.0° (Cl–C–Cl).
Use
The substitution of all electronegative substituents in trichloroacetonitrile by nucleophilic attack of
alkoxide anions produces
orthocarbonic acid esters in high yield.
Due to the high reactivity of the chlorine atoms, trichloroacetonitrile can be used (especially in combination with
triphenylphosphine
Triphenylphosphine (IUPAC name: triphenylphosphane) is a common organophosphorus compound with the formula P(C6H5)3 and often abbreviated to P Ph3 or Ph3P. It is widely used in the synthesis of organic and organometallic compounds. PPh3 exists ...
) to convert allylic alcohols into the corresponding allylic chlorides.
:
![Allylchloride via Allylalkohole](https://upload.wikimedia.org/wikipedia/commons/a/a4/Allylchloride_via_Allylalkohole.svg)
With carboxylic acids,
acyl chlorides are obtained.
Due to the mild reaction conditions, the Cl
3CCN/PPh
3 system is also suitable for the activation of
carboxylic acids and their linkage with supported amino compounds to
amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...
s (
peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
...
s) in solid-phase syntheses. From
sulfonic acids, the corresponding
sulfochlorides are formed analogously. In an analogous manner, the activation of
diphenylphosphoric acid with Cl
3CCN/PPh
3 and reaction with alcohols or amines proceeds to the corresponding phosphoric acid esters or amides in a gentle and efficient one-pot reaction.
Also,
phenolic hydroxy groups in nitrogen-containing aromatics can be converted into the chlorine compounds.
:
![2-Chlorpyridin via TCAN](https://upload.wikimedia.org/wikipedia/commons/3/34/2-Chlorpyridin_via_TCAN.svg)
In a
Hoesch reaction
The Hoesch reaction or Houben–Hoesch reaction is an organic reaction in which a nitrile reacts with an arene compound to form an aryl ketone. The reaction is a type of Friedel-Crafts acylation with hydrogen chloride and a Lewis acid catalyst.
...
, aromatic hydroxyketones are formed in the reaction of substituted phenols with trichloroacetonitrile, for example from
2-methyl phenol the 2-trichloroacyl derivative in 70% yield.
:
![Hydroxyketone via TCAN](https://upload.wikimedia.org/wikipedia/commons/b/be/Hydroxyketone_via_TCAN.svg)
The
electron-withdrawing effect of the
trichloromethyl group
The trichloromethyl group is a functional group that has the formula –CCl3. The naming of is group is derived from the methyl group (which has the formula –CH3), by replacing each hydrogen atom by a chlorine atom. Compounds with this group are ...
activates the nitrile group of trichloroacetonitrile for the attack of nucleophilic oxygen, nitrogen and sulfur compounds. For example, alcohols give ''O''-alkyltrichloroacetimidates under basic catalysis in a direct and reversible addition, which can be isolated as stable and less hydrolysis-sensitive
adduct
An adduct (from the Latin ''adductus'', "drawn toward" alternatively, a contraction of "addition product") is a product of a direct addition of two or more distinct molecules, resulting in a single reaction product containing all atoms of all co ...
s.
:
![Trichloracetimidat-Bildung](https://upload.wikimedia.org/wikipedia/commons/b/b5/Trichloracetimidat-Bildung.svg)
With primary and secondary amines, ''N''-substituted trichloroacetamidines are formed in a smooth reaction with good yields, which can be purified by vacuum distillation and are obtained as colorless, malodorous liquids. Reaction with
ammonia
Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous wa ...
and then with anhydrous
hydrogen chloride
The compound hydrogen chloride has the chemical formula and as such is a hydrogen halide. At room temperature, it is a colourless gas, which forms white fumes of hydrochloric acid upon contact with atmospheric water vapor. Hydrogen chloride ga ...
gives the solid trichloroacetamidine hydrochloride, the starting compound for the
fungicide etridiazole.
In academic research, trichloroacetonitrile is used as a
reagent in the
Overman rearrangement The Overman rearrangement is a chemical reaction that can be described as a Claisen rearrangement of allylic alcohols to give allylic trichloroacetamides through an imidate intermediate. The Overman rearrangement was discovered in 1974 by Larry Ove ...
, converting
allylic alcohols into allylic
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen
Hydrogen is the chemical element wi ...
s. The reaction is based on a
,3 sigmatropic and
diastereoselective
In stereochemistry, diastereomers (sometimes called diastereoisomers) are a type of stereoisomer. Diastereomers are defined as non-mirror image, non-identical stereoisomers. Hence, they occur when two or more stereoisomers of a compound have dif ...
rearrangement.
Benzyl trichloroacetimidate is easily accessible from
benzyl alcohol
Benzyl alcohol is an aromatic alcohol with the formula C6H5CH2OH. The benzyl group is often abbreviated "Bn" (not to be confused with "Bz" which is used for benzoyl), thus benzyl alcohol is denoted as BnOH. Benzyl alcohol is a colorless liquid w ...
and trichloroacetonitrile. Benzyl trichloroacetimidate is useful as a benzylating reagent for sensitive alcohols under mild conditions and to preserve chirality.
''O''-Glycosyl-trichloroacetimidates for the activation of carbohydrates
R. R. Schmidt and co-workers have described the selective
anomeric activation of ''O''-protected hexopyranoses (
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
,
galactose
Galactose (, '' galacto-'' + ''-ose'', "milk sugar"), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epimer of glucose. A galactose molecu ...
,
mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation ...
,
glucosamine
Glucosamine (C6H13NO5) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of two polysaccharides, chitosan and chitin. Glucosamine is one of the most ...
,
galactosamine
Galactosamine is a hexosamine derived from galactose with the molecular formula C6H13NO5. This amino sugar is a constituent of some glycoprotein hormones such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
Precursors such ...
), hexofuranoses and pentopyranoses with trichloroacetonitrile in the presence of a base, as well as
glycosylations under acid catalysis.
Under kinetic control with
potassium carbonate
Potassium carbonate is the inorganic compound with the formula K2 CO3. It is a white salt, which is soluble in water. It is deliquescent, often appearing as a damp or wet solid. Potassium carbonate is mainly used in the production of soap and gl ...
as the base, β-trichloroacetimidates are formed selectively, whereas with
sodium hydride
Sodium hydride is the chemical compound with the empirical formula Na H. This alkali metal hydride is primarily used as a strong yet combustible base in organic synthesis. NaH is a saline (salt-like) hydride, composed of Na+ and H− ions, in co ...
,
caesium carbonate
Caesium carbonate or cesium carbonate is a white crystalline solid compound. Caesium carbonate has a high solubility in polar solvents such as water, alcohol and DMF. Its solubility is higher in organic solvents compared to other carbonates l ...
or
potassium hydroxide
Potassium hydroxide is an inorganic compound with the formula K OH, and is commonly called caustic potash.
Along with sodium hydroxide (NaOH), KOH is a prototypical strong base. It has many industrial and niche applications, most of which exp ...
and in the presence of
phase-transfer catalyst
In chemistry, a phase-transfer catalyst or PTC is a catalyst that facilitates the transition of a reactant from one phase into another phase where reaction occurs. Phase-transfer catalysis is a special form of heterogeneous catalysis. Ionic r ...
s only α-trichloroacetimidates are obtained (thermodynamically controlled).
:
![Alpha-Glycosyltrichloracetimidat](https://upload.wikimedia.org/wikipedia/commons/4/49/Alpha-Glycosyltrichloracetimidat.svg)
The trichloroacetimidates are reacted between −40 °C and room temperature with
boron trifluoride etherate in
dichloromethane with ''O''-protected sugars. This method usually gives better results than the Koenigs–Knorr method using silver salts or the Helferich method which uses problematic
mercury salts. Since an inversion occurs at the anomeric center, the reaction leads to β-''O''-glycosides (when using α-trichloroacetimidates). The trichloroacetimidate method often produces sterically uniform glycosides under mild reaction conditions in very good yields.
:
![Octaacetyl-Trehalose](https://upload.wikimedia.org/wikipedia/commons/a/ac/Octaacetyl-Trehalose.svg)
Thioacetic acid reacts with acetyl-protected α-galactosyl trichloroacetimidate even without additional acid catalysis to thioglycoside, from which (after cleavage of the protective groups) 1-thio-β-
D-galactose is easily accessible, which is useful for the separation of
racemates of
amino acids.
:
![Thiogalactose-Synthese](https://upload.wikimedia.org/wikipedia/commons/b/b9/Thiogalactose-Synthese.svg)
Trichloroacetonitrile was an important
fumigant
Fumigation is a method of pest control or the removal of harmful micro-organisms by completely filling an area with gaseous pesticides—or fumigants—to suffocate or poison the pests within. It is used to control pests in buildings (s ...
in the first half of the 20th century, but today it has become
obsolete for this application.
See also
*
Acetonitrile
*
Trichloroacetic acid
Trichloroacetic acid (TCA; TCAA; also known as trichloroethanoic acid) is an analogue of acetic acid in which the three hydrogen atoms of the methyl group have all been replaced by chlorine atoms. Salts and esters of trichloroacetic acid are calle ...
*
Chloral
Chloral, also known as trichloroacetaldehyde or trichloroethanal, is the organic compound with the formula Cl3CCHO. This aldehyde is a colourless oily liquid that is soluble in a wide range of solvents. It reacts with water to form chloral hydrate ...
References
{{Reflist
Nitriles
Reagents for organic chemistry
Trichloromethyl compounds
Foul-smelling chemicals