Trichloroacetonitrile

545-06-2 Systematic name-. Trichloroacetonitrile 

2 Structural and molecular formulae and relative molecular mass 

Halogenated acetonitriles are not produced on an industrial scale. Trichloroacetonitrile has been used on a limited basis in the past as a pesticide. Several halogenated acetonitriles have been detected in chlorinated drinking-water in a number of countries as a consequence of the reaction of chlorine with natural organic substances. The only known route of human exposure is through chlorinated drinking-water (lARC, 1991). 

Trichloroacetonitrile was tested in a limited carcinogenicity study in female SEN mice by skin application, in an initiation/promotion study in female SEN mice by skin application and in a screening assay for lung tumours in female strain A mice by oral administration. No skin tumour was produced after skin application in mice or in the initiation/promotion study, in which trichloroacetonitrile was applied topically as six equal doses over a two-week period, followed by repeated doses of 12-G-tetradecanoyl-phorbol 13-acetate for 20 weeks. A small, significant increase in the proportion of mice with lung tumours and in the number of tumours per mouse was observed control, 3/31 and 0.1 treated group (10 mg/kg bw, three times per week, eight weeks), 9/32 and 0.38 p 0.05) (lARC, 1991). 

Other Data Relevant to an Evaluation Carcinogenicity and its Mechanisms 

Catalysis of Ring Formation. 1,2,4-Triazole can induce the formation of isoxazole rings from conjugated ketones and hydrox-ylamine (eq 5).  

Oligonucleotide Synthesis. Sulfonyl derivatives of 1,2,4-triazole, e.g. (1), are used as efficient coupling reagents in oligonucleotide synthesis by the phosphotriester method. A nitro derivative (2) allows esterification of amino acids onto hydroxymethyl polymers.  

Jean-Claude Gesquiere Institut Pasteur, Lille, France 

Physical Data mp —42°C bp 83-84 °C d 1.440gcm . Solubility sol most organic solvents. 

Handling, Storage, and Precautions toxic lachrymator use only in a fiime hood. Reagent can be absorbed through the skin. Always wear gloves when handling this reagent. 

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Trichloroacetonitrile reacts with glycosidic hydroxy groups of protected sugars to form glycosyl trichloroacetimidates (R. R. Schmidt, 1980, 1984,1985,1986 B. Wegmann, 1988). The imidate is substituted by alcohols in the presence of trimethylsilyl trifluoromethanesulfonate... 

The reaction of ethyleneimine with nittiles in the presence of HBF gives A -imidazolines (229). If trichloroacetonitrile [545-06-2] (R = Cl) is used as the nitrile component, the intermediate amidine can be isolated (230). 

Trichloroacetamido-l-hexene, 58,9,11 Trichloroacetonitrile, 58,5, 7, 10,11 2,3,5-Trichloro-3,6-di-/a-f-butyl-5-cyclo-hexene-l,4-dione, 55, 33 2- 2,2,2-T richloroethoxy)carbonyl-... 

The effect of sodium nitride on trichloroacetonitrile in the presence of ammonium chloride was used to make tetrazole. The operation was interrupted by the medium detonating. 

Benzyl groups are usually introduced by the Williamson reaction (Section 3.2.3). They can also be prepared under nonbasic conditions if necessary. Benzyl alcohols are converted to trichloroacetimidates by reaction with trichloroacetonitrile. These then react with an alcohol to transfer the benzyl group.183... 

O-Allyl imidate esters undergo [3,3]-sigmatropic rearrangements to /V-allyl amides. Trichloromethyl imidates can be made easily from allylic alcohols by reaction with trichloroacetonitrile. The rearrangement then provides trichloroacetamides of IV-allylamines.260... 

The later publication [1] reveals that the title compound is in fact a relatively stable compound. The previously attempted preparation of the then unknown compound from trichloroacetonitrile, sodium azide and ammonium chloride (0.14 0.42 0.2 mol) by an analogous established method [2], but at lower initial temperature because of the exothermic reaction, gave, after vacuum evaporation of solvent, an oily product. When sampled with a pipette, this evolved gas and then exploded violently. It was thought that an azidomethyltetrazole may have been formed by displacement of chloro-substituent(s) by the excess azide employed [3], An alternative hypothesis which involved isomerisation of the title compound to the open chain azidoazomethine [4] was discounted, because no trace of this could be detected [1]. 

Thermal decomposition of the salt in nitriles produces 2-substituted quinazolines. In trichloroacetonitrile it proceeded explosively. 

The Mukaiyama-Hoshino reaction between a nitroalkane and phenyl isocyanate generates a nitrile oxide, and this method has been used in the synthesis of 1,2,4-oxadiazoles as discussed in CHEC-II(1996) <1996CHEC-II(4)179>. In a more recent advance, nitroethane undergoes ultrasound-mediated cycloaddition with trichloroacetonitrile to give the extremely useful (see Equation 11) 5-trichloromethyl-l,2,4-oxadiazole 228 (Equation 45) <1995TL4471>. 

CF3CN and CCI3CN leads to the corresponding substituted oxadiazolines (74, 829). Thus, reactions of (746) and (747), derived from 1-deoxynojirimycin with trichloroacetonitrile in toluene at room temperature leads to bicyclic compounds (748) and (749) (Scheme 2.308). 

However, the successful isolation of an iminoborane derivative in the reaction of trichloroacetonitrile with diborane indicated that the stability of imino-boranes is not only a function of the nature of the borane but also of that of the imine 16>. 

A B-Cl bond of pentafluorophenyldichloroborane adds quantitatively across the C=N group of trichloroacetonitrile and yields an equilibrium mixture of the monomeric and dimeric iminoborane derivative 26>. In contrast, benzon-itrile does not react at all with trichloroacetonitrile under comparable conditions 26 ... 

The reaction of tris(organothio)boranes with nitriles leads to B—S substituted iminoboranes. 1,2-addition of tris(methylthio)borane or tris(phenylthio) borane to trichloroacetonitrile yields the monomeric products (XIV) or (XV)32). 

Closure of the oxadiazole ring is still achieved through cycloaddition between pyridine iV-oxides and isocyanates, affording adducts such as 142 (Scheme 38) <1995T6451>. Nonaromatic imine fV-oxides exhibited similar reactivities, since azasugar-derived fV-oxides as a mixture of 143 and 144 underwent cycloaddition reactions in the presence of phenyl isocyanate or trichloroacetonitrile. Compounds 145 and 146 (Scheme 39) were obtained from the aldoxime W-oxide 143 two other regioisomeric heterocycles arose from the ketoxime derivative 144 <1996T4467>. 

Electron-deficient nitriles, such as for instance trichloroacetonitrile and trifluoroacetonitrile (A=B A = N B = CCC13, CCF3), are known to undergo direct and reversible, base-catalyzed addition of alcohols providing O-alkyl trichloroacetimidates (1,50). This imidate synthesis has the advantage that the free imidates can be isolated as stable adducts, which are less sensitive to hydrolysis than their corresponding salts. 

A detailed study of the addition of trichloroacetonitrile to 2,3,4,6-tetra-O-benzyl-D-glucose (la, Scheme 4) revealed (1 - 3,45) that, from the equatorial... 

Unprotected galactose derivatives may be readily transformed into the trichloroacetimidates 8a-8g, as shown in Table VIII. Again, as demonstrated for the O-benzyl-protected compounds 8a, either the a-trichloroace-timidate 8a-a or the / -trichloroacetimidate 8a -/ may be obtained highly selectively, depending on the base used for the catalysis of the addition to the trichloroacetonitrile. 

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