:Trichloroacetonitrile

The production of trichloroacetonitrile by dehydration of trichloroacetamide was first described in 1873 by L. Bisschopinck at the Katholieke Universiteit Leuven.{{cite journal | doi = 10.1002/cber.187300601227| title = Ueber die gechlorten Acetonitrile| journal = Berichte der Deutschen Chemischen Gesellschaft| volume = 6| pages = 731–734| year = 1873| last1 = Bisschopinck| first1 = L.| url = https://zenodo.org/record/1425042}}

:Trichloroacetonitrile via trichloracetamide

Trichloroacetonitrile can be obtained by chlorination of acetonitrile on a zinc, copper and alkaline earth metal halide-impregnated activated carbon catalyst at 200–400 °C with a 54% yield.

{{Cite patent | country = US | number = 2375545 | status = patent | title = Process for the preparation of trichloroacetonitrile | fdate = 1943-10-07 | gdate = 1945-05-08 | invent1 = R. T. Foster | assign1 = Imperial Chemical Industries}}

:Trichloroacetonitrile via acetonitrile

The high temperatures required by this process favours the formation of byproducts, such as tetrachloromethane. In contrast, the chlorination of acetonitrile saturated with hydrogen chloride leads to pure trichloroacetonitrile even at 50–80 °C in good yields.{{Cite patent | country = US | number = 2745868 | status = patent | title = Process for the production of trichloroacetonitrile | fdate = 1954-02-08 | gdate = 1956-05-15

| invent1 = G. Käbisch | assign1 = Deutsche Gold- und Silber-Scheideanstalt, formerly Roessler}}

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.{{cite book|title=Guidelines for Drinking Water Quality|edition=3rd|volume=1|series=Recommendations|publisher=World Health Organization|location=Geneva|date=2004|isbn=9-2415-4638-7|url=https://www.who.int/water_sanitation_health/dwq/chemicals/halogenatedacetonit.pdf}}{{cite book|surname1=Frank Bernsdorff|title=Untersuchungen zur abiotischen Bildung von Acetonitril, Haloacetonitrilen und Trichlornitromethan|trans-title=Investigations into abiotic formation of acetonitrile, haloacetonitriles and trichloronitromethane|publisher=GRIN|page=5|date= 2007|language=German|url=https://books.google.com/books?id=3pgcYVOS_t4C|isbn=9783638383431}}

File: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).{{cite book|editor-first=David R.|editor-last=Lide|title=CRC Handbook of Chemistry and Physics|edition=90th|date=2010|publisher=CRC Press/Taylor and Francis|location=Boca Raton, FL|chapter=Structure of Free Molecules in the Gas Phase|pages=9–46}}

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) to convert allylic alcohols into the corresponding allylic chlorides.{{cite journal|first=E. D.|last=Matveeva|display-authors=etal|title=Regioselective and stereoselective substitution of hydroxyl group for halogen in allyl alcohols|journal=Russian Journal of Organic Chemistry|volume=31|issue=8|pages=1121–1125|date=1995}}

:Allyl chloride via propenol

With carboxylic acids, acyl chlorides are obtained.{{cite journal|first=D. O.|last=Jang|display-authors=etal|title=A mild and efficient procedure for the preparation of acid chlorides from carboxylic acids|journal=Tetrahedron Letters|volume=40|issue=29|pages=5323–5326|date=1999|doi=10.1016/S0040-4039(99)00967-3 }}

Due to the mild reaction conditions, the Cl₃CCN/PPh₃ system is also suitable for the activation of carboxylic acids and their linkage with supported amino compounds to amides (peptides) in solid-phase syntheses.{{cite journal|first1=J.|last1=Vago|first2=J.|last2=Greiner|title=A useful acylation method using trichloroacetonitrile and triphenylphosphine for solid phase organic synthesis|journal=Tetrahedron Letters|volume=43|issue=34|pages=6039–6041|date=2002|doi=10.1016/S0040-4039(02)01241-8 }} From sulfonic acids, the corresponding sulfochlorides are formed analogously.{{cite journal|first=O.|last=Chantarasriwong|display-authors=etal|title=A practical and efficient method for the preparation of sulfonamides utilizing Cl₃CCN/PPh₃|journal=Tetrahedron Letters|volume=47|issue=42|pages=7489–7492|date=2006|doi=10.1016/j.tetlet.2006.08.036 }} In an analogous manner, the activation of diphenylphosphoric acid with Cl₃CCN/PPh₃ and reaction with alcohols or amines proceeds to the corresponding phosphoric acid esters or amides in a gentle and efficient one-pot reaction.{{cite journal|first=A.|last=Kasemsuknimit|display-authors=etal|title=Efficient amidation and esterification of phosphoric acid using Cl₃CCN/Ph₃P|journal=Bulletin of the Korean Chemical Society|volume=32|issue=9|pages=3486–3488|date=2011|doi=10.5012/bkcs.2011.32.9.3486 |doi-access=free}}

Also, phenolic hydroxy groups in nitrogen-containing aromatics can be converted into the chlorine compounds.{{cite journal|first=W.|last=Kijrungphaiboon|display-authors=etal|title=Cl₃CCN/PPh₃ and CBr₄/PPh₃: two efficient reagent systems for the preparation of N-heteroaromatic halides|journal=Tetrahedron Letters|volume=53|pages=674–677|date=2006|issue=6 |doi=10.1016/j.tetlet.2011.11.123 }}

:2-Chloropyridine via trichloroacetonitrile

In a Hoesch reaction, 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.{{citation|first=R.|last=Martin|title=Aromatic Hydroxyketones: Preparation and Physical Properties. Vol. 1 Hydroxybenzophenones|edition=3rd|publisher=Springer|isbn=978-1-4020-9787-4|date=2011|language=German|doi=10.1007/978-1-4020-9787-4}}

:Hydroxyketones via trichloroacetonitrile

The electron-withdrawing effect of the trichloromethyl group 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,{{cite journal|first=J. U.|last=Nef|journal=Annalen der Chemie|volume=287|page=274|date=1895}} which can be isolated as stable and less hydrolysis-sensitive adducts.

:Trichloroacetimidate formation

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.{{Cite journal|last1=Grivas|first1=John C.|last2=Taurins|first2=Alfred|date=1958|title=Reaction of trichloroacetonitrile with primary and secondary amines. Part I. Preparation of some trichloroacetamidines|journal=Canadian Journal of Chemistry|volume=36|issue=5|pages=771–774|doi=10.1139/v58-113|issn=0008-4042|doi-access=free}} Reaction with ammonia and then with anhydrous hydrogen chloride 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, converting allylic alcohols into allylic amines.{{cite journal |first1=T. |last1=Nishikawa |first2=M. |last2=Asai |first3=N. |last3=Ohyabu |first4=M. |last4=Isobe | journal = The Journal of Organic Chemistry | year = 1998 | volume = 63 | pages = 188–192 | doi = 10.1021/jo9713924 | pmid = 11674062 | title = Improved Conditions for Facile Overman Rearrangement | issue = 1}}{{cite web | url = https://www.organic-chemistry.org/namedreactions/overman-rearrangement.shtm | work = Organic Chemistry Portal | publisher = organic-chemistry.org |title = Overman Rearrangement | accessdate = 2012-11-15}}{{cite journal | first1 = Y. K.|last1= Chen |first2=A. E. |last2=Lurain |first3=P. J. |last3=Walsh | journal = Journal of the American Chemical Society | year = 2002 | volume = 124 | pages = 12225–12231 | doi = 10.1021/ja027271p | pmid = 12371863 | title = A general, highly enantioselective method for the synthesis of D and L alpha-amino acids and allylic amines | issue = 41|bibcode= 2002JAChS.12412225C }} The reaction is based on a [3,3]-sigmatropic and diastereoselective rearrangement.

Benzyl trichloroacetimidate is easily accessible from benzyl alcohol and trichloroacetonitrile.{{cite journal | doi = 10.1021/jo01061a034| title = Base-Catalyzed Reaction of Nitriles with Alcohols. A Convenient Route to Imidates and Amidine Salts| journal = The Journal of Organic Chemistry| volume = 26| issue = 2| pages = 412–418| year = 1961| last1 = Schaefer| first1 = Fred C.| last2 = Peters| first2 = Grace A.}} Benzyl trichloroacetimidate is useful as a benzylating reagent for sensitive alcohols under mild conditions and to preserve chirality.{{cite journal|first1=E. P.|last1=Eckenberg|display-authors=etal|title=A useful application of benzyl trichloroacetimidate for the benzylation of alcohols|journal=Tetrahedron|volume=49|pages=1619–1624|date=1993|issue=8 |doi=10.1016/S0040-4020(01)80349-5 |url=http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-47218 }}

R. R. Schmidt and co-workers{{cite journal|first1=R. R.|last1=Schmidt|first2=J.|last2=Michel|title=Einfache Synthese von α- und β-O-Glycosylimidaten. Herstellung von Glykosiden und Disacchariden|trans-title=Simple synthesis of α- and β-O-glycosylimidates. Manufacture of glycosides and disaccharides|journal=Angewandte Chemie|volume=92|pages=763–764|date=1980|issue=9 |doi=10.1002/ange.19800920933 |bibcode=1980AngCh..92..763S }} have described the selective anomeric activation of O-protected hexopyranoses (glucose, galactose, mannose, glucosamine, galactosamine), hexofuranoses and pentopyranoses with trichloroacetonitrile in the presence of a base, as well as glycosylations under acid catalysis.{{cite journal|first=R. R.|last=Schmidt|title=Neue Methoden zur Glycosid- und Oligosaccharidsynthese – gibt es Alternativen zur Koenigs-Knorr-Methode?|trans-title=New methods for glycoside and oligosaccharide synthesis – are there alternatives to the Koenigs–Knorr method?|journal=Angewandte Chemie|volume=98|pages=213–236|date=1986|issue=3 |doi=10.1002/ange.19860980305 |bibcode=1986AngCh..98..213S }}{{cite journal|first1=R. R.|last1=Schmidt|first2=W.|last2=Kinzy|title=Anomeric-oxygen activation for glycoside synthesis – the trichloroacetimidate method|journal=Advances in Carbohydrate Chemistry and Biochemistry|volume=50|pages=21–123|date=1994|doi=10.1016/S0065-2318(08)60150-X |pmid=7942254 |isbn=9780120072507 }}{{cite book|first1=R. R.|last1=Schmidt|first2=K.-H.|last2=Jung|chapter=Oligosaccharide synthesis with trichloroacetimidates|title=Preparative Carbohydrate Chemistry|editor-first=S.|editor-last=Hanessian|publisher=Marcel Dekker|location=New York, NY|pages=283–312|date=1997|isbn=0-8247-9802-3}}

Under kinetic control{{cite journal|first1=R. R.|last1=Schmidt|first2=J.|last2=Michel|title=Glycosylimidate, 12 Direkte Synthese vonO-α- undO-β-Glycosyl-imidaten |journal=Liebigs Annalen der Chemie|pages=1343–1357|date=1984|volume=1984|issue=7 |doi=10.1002/jlac.198419840710 }} with potassium carbonate as the base, β-trichloroacetimidates are formed selectively, whereas with sodium hydride, caesium carbonate or potassium hydroxide{{cite journal|first=F. J.|last=Urban|title=Synthesis of tigogenyl β-O-cellobioside heptaacetate and glycoside tetraacetate via Schmidt's trichloroacetimidate method; some new {{sic|nolink=y|observatons}} |display-authors=etal|journal=Tetrahedron Letters|volume=31|pages=4421–4424|date=1990|issue=31 |doi=10.1016/S0040-4039(00)97637-8 }} and in the presence of phase-transfer catalysts{{cite journal|first=V. J.|last=Patil|title=A simple access to trichloroacetimidates |journal=Tetrahedron Letters|volume=37|pages=1481–1484|date=1996|issue=9 |doi=10.1016/0040-4039(96)00044-5 }} only α-trichloroacetimidates are obtained (thermodynamically controlled).

:α-Glycosyltrichloracetimidate

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.

:Octaacetyltrehalose

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.{{cite journal|first=A.|last=Jegorov|display-authors=etal|title=1-Thio-β-D-galactose as a chiral derivatization agent for the resolution of D,L-aminoacid enantiomers|journal=Journal of Chromatography A|volume=673|issue=2|pages=286–290|date=1994|doi=10.1016/0021-9673(94)85045-3 }}

:Thiogalactose synthesis

Trichloroacetonitrile was an important fumigant in the first half of the 20th century, but today it has become obsolete for this application.{{cite book|editor1-first=N. M.|editor1-last=Sax|editor2-first=R. J.|editor2-last=Lewis|title=Hawley's Condensed Chemical Dictionary|edition=11th|publisher=Van Nostrand Reinhold|location=New York, NY|pages=261, 1175|date=1987}}

• Acetonitrile
• Trichloroacetic acid
• Chloral

{{Reflist}}

Category:Nitriles

Category:Reagents for organic chemistry

Category:Trichloromethyl compounds

Category:Foul-smelling chemicals