Chloro-1,1,1 -trifluoroethane

2 Structural and molecular formulae and relative molecular mass 

2-Chloro-1,1,1-trifluoroethane is used as a chemical intermediate in the production of the anaesthetic halothane. Human exposure occurs due to its presence as a low-level impurity in, and as a metabolite of, halothane (lARC, 1986). 

No data were available to the Working Group (lARC, 1986). 

Other Data Relevant to an Evaluation of Carcinogenicity and its Mechanisms 

Male Fischer 344 rats were exposed by inhalation to 1% 2-chloro-1,1,1 -trifluoroethane for 2 h and then urine was collected for 24 h. Urinary metabolites identified by 19F nuclear magnetic resonance and gas chromatography/mass spectrometry were 2,2,2-trifluoroethyl glucuronide (16%), trifluoroacetic acid (14%), trifluoroacetaldehyde hydrate (26%), trifluoroacetaldehyde-urea adduct (40%) and inorganic fluoride (3%). A minor, unidentified metabolite was also detected. No covalent binding of fluorine-containing metabolites was observed in the liver and kidney from the exposed rats (Yin et al., 1995). In-vitro incubation of 2-chloro-1,1,1-trifluoroethane with rat liver microsomes and an NADPH-generating system has been shown to involve a dechlorination reaction (Salmon et al., 1981) that produced trifluoroacetaldehyde hydrate as the only metabolite (Yin et al., 1995). 

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M. K. Ellis, J.L. Naylor, T. Green, M.A. Collins, Identification and quantification of fluorine-containing metabolites of 1-chloro-2,2,2-trifluoroethane (Hcfc133a) in the rat by F-19-Nmr spectroscopy. Drug Metab. Dispos. 23 (1995) 102-106. 

Halothane was introduced into clinical practice in 1956. It was not the first fluorinated anaesthetic— fluoroxene (Fluoromar) holds that distinction—but it was the first to achieve widespread acceptability. Halothane is a fluorinated alkane 1-bromo, 1-chloro -2,2,2-trifluoroethane (Figure 3.2). It has a characteristic odour, similar to chloroform, and requires a stabiliser, thymol (0.01%), to prevent degradation by light. Halothane has a blood/gas partition coefficient of 2.4 able 3.2) but its lack of irritant qualities makes possible the use of relatively high inspired concentrations (2-4%). For that reason, inhalation induction is characteristically smooth and rapid. Compared to sevoflurane, and possibly isoflurane, recovery from halothane anaesthesia is delayed. 

Synonyms/Trade Names 1-Bromo-1-chloro-2,2,2-trifluoroethane 2-Bromo-2-chloro-1.1.1-trifluoroethane ... 

In most cases, however, the liquid-phase fluorination processes require a halogenated (Cl or F) Lewis-acid catalyst. For example, the first addition of HF on trichlorethylene followed by two subsequent Cl exchanges to reach the 1-chloro-2,2,2-trifluoroethane (F133a, which is an intermediate for F134a), are catalyzed by SbCl [Eqs. (2) and (3)]. 

Wu K, Chen Q-Y (2003) A fadle synthetic method for 2-fluoroindolizines from 1-chloro-2,2,2-trifluoroethane (HCFC-133a) and 1,1,1.2-tetrafluoroethane (HFC-134a). J Huor Chem 2 171-174... 

Trademark for a series of fluorocarbon polymers, especially poly(chloro-trifluoroethane) and copolymers, available as oils, waxes and greases... 

Trifluoroethanol was first prepared by the catalytic reduction of trifluoroacetic anhydride [407-25-0] (58). Other methods iaclude the catalytic hydrogeaatioa of trifluoroacetamide [354-38-1] (59), the lithium aluminum hydride reductioa of trifluoroacetyl chloride [354-32-5] (60) or of trifluoroacetic acid or its esters (61,62), and the acetolysis of 2-chloro-l,l,l-trifluoroethane [75-88-7] followed by hydrolysis (60). More recently, the hydrogenation of... 

Preparation. Thermal elimination of HCl from l-chloro-l,l-difluoroethane (HCFC-142b) [75-68-3] is the principal industrial route to VDF covered by numerous patents (8—19). Dehydrohalogenation of l-bromo-l,l-difluoroethane (20), or 1,1,1-trifluoroethane (HFC-143a) (21—25), or dehalogenation of l,2-dichloro-l,l-difluoroethane (26—28) are investigated alternative routes (see Fluorine compounds, organic-fluorinated aliphatic compounds). 

Halothane. Halothane or Fluothane, 2-bromo-2-chloro-l,l,l-trifluoroethane [151 -67-7] is a colorless Hquid with a pleasant odor. Its lower flammability limit, 4.8% in 70% N2O/30% O2, renders it essentially nonflammable. It has a vapor pressure of 32.5 kPa (244 mm Hg) at 20 °C and is stable to soda lime. However, it is photochemicaHy reactive. 

In the presence of catalysts, trichloroethylene is readily chlorinated to pentachloro- and hexachloroethane. Bromination yields l,2-dibromo-l,l,2-trichloroethane [13749-38-7]. The analogous iodine derivative has not been reported. Fluorination with hydrogen fluoride in the presence of antimony trifluoride produces 2-chloro-l,l,l-trifluoroethane [75-88-7] (8). Elemental fluorine gives a mixture of chlorofluoro derivatives of ethane, ethylene, and butane. 

Conversion of 2-chloro-2-difluoromethoxy-l,lJ trifluoroethane to 2-difluo-romethoxy-l,l,l,2-tetrafluoroethane (98% purity) is accomplished with bromine trifluoride. The starting material is the major impurity [7] (equation 4)... 

With successive equivalents of chlonne monofluonde 1,1 1,2 tetrachloroethane gives 1 -fluoro-1,1,2-tnchloroethane, 1,2 dichloro-1,1 -difluoroethane, 2-chloro 1,1,1-trifluoroethane with some 1-chloro-1 1,2 tnfluoroethane, and finally 1,1,1,2 tetra-fluoroethane (equation 13)... 

Chloromethoxy-1,2,2 2-tetrafluoroethane is converted by triethylammonium fluoride or piperidine hydrogen fluoride to fluoromethoxy 1 2,2,2-tetra-fluoroethane in greater than 60% yield Piperidine hydrogen fluoride or butyl-ammonium fluoride can convert methoxy-l-chloro-2,2,2-trifluoroethane to methoxy-1,2,2,2-tetrafluoroethane in 80% yield [79]... 

Difluoromethoxy-2-chloro-l,l,l-trifluoroethane and potassium fluoride produce 2-difluoromethoxy-1,1,1,2-tetrafluoroethane [50] The yield of the latter reaction is improved by adding a phase transfer catalyst or crown ether, tetra-methylammonium chlonde, tetrabutylammonium chloride, or 18-crown-6 with a solvent like sulfolane can be used for this purpose [5/] (equation 32)... 

A nonconventional synthesis of the known inhalation anaesthetic, 2-bromo-2 chloro-l,l,l-trifluoroethane (Halothane), based on the reaction of ethyl 1,2 di bromo-1,2-dicliloroethyl ether with anhydrous hydrogen fluoride and sulfur tetrafluoride, has been patented The reaction presumably involves cleavage of the ether linkage, followed by fluorination of the intermediate bromochloroacetyl halide with sulfur tetrafluoride, ethyl halides are the by-products [2] (equation 2)... 

Alcoholysis of 1 -chloro-2-acyl-1,1,2-trifluoroethane, available from trifluoro-ethylene, an acyl chloride, and aluminum chloride, leads to 1-fluoro- 1-acylacetates [/] (equation 1) It is surpnsing that the remaining carbon-tluorine bond resists hydrolysis. 

Table 4. Rates of Dehydrofluorination of l-Phenyl-2,2,2-trifluoroethane and l-Chloro-l-phenyI-2,2,2-trifIuoroethane 42 ...

Chemical Name 2-chloro-1-(difluoromethoxy)-1,1,2-trifluoroethane Common Name —... 

Figure 7.1.7 The molecular structure of halothane (fluothane or 2-bromo-2-chloro-1,1,1- trifluoroethane).

HFC-134a is produced commercially by (1) the hydrofluorination of trichloroethylene via l-chloro-l,l,l-trifluoroethane, (2) isomerization and... 

Bis(fluorooxy)tetrafluoroethane, 0641 2-Chloro-1,1 -bis(fluorooxy)trifluoroethane, 0595 1, l,4,4-Tetrakis(fluoroxy)hexafluorobutane, 1374 See Fluorine Fluorocarboxylic acids, etc., 4310 See related HYPOHALITES... 

Haloalkanes can be regarded as substituted alkanes in which one or more of the hydrogen atoms is replaced by a halogen atom. They are named in a similar fashion to branched-chain alkanes with the halogen atoms treated like branches. For example, the anaesthetic halothane has the structure shown in the diagram and is called 2-bromo-2-chloro-l,l, 1-trifluoroethane. 

Complex formation equilibria in binary mixtures of chloroform with dipropyl ether (PE), diisopropyl ether (IPE), methyl tert-butyl ether(MBE), tetrahydrofuran (THE), 1,4-dioxane (DOX), acetone (AC), and methyl acetate (MA) have been analyzed in detail. The complex formation equilibria in chloroform mixtures was compared to those previously examined for halothane (2-bromo-2-chloro-l,l,l-trifluoroethane) mixed with the same oxygenated solvents. It was found that the H-bonds formed by halothane are stronger than those formed by chloroform (Dohnal and Costas, 1996). 

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