Trifluoroacetyl chloride

Formation - with trifluoroacetic anhydride or trifluoroacetyl chloride Cleavage - K2CO3, MeOH... 

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... 

The volatility of trifluoroacetyl chloride may explain the smooth reaction when preparing neodymium(tris)dichlorophosphate, which is of some interest for dye-lasers, from trifluoroacetate and POCI3 (79) ... 

Trifluoropropene, 20 241-242 3-Trifluoroacety 1-17 -camphorate, 6 98 Triflates, cross-coupling of organoboranes with, 73 651 Triflic acid, 22 598 Tri-Flo separator, 76 634 Trifluoroacetylacetone molecular formula, 5 712t Trifluoroacetyl chloride... 

In contrast, the reactivity of trifluoroacetyl chloride, the reactive metabolite of halothane discussed in Chapter 4 under oxidative dehalogenation (Fig. 8.7), is due to the electron-withdrawing effect of the carbonyl and trifluoromethyl groups, which makes it very electrophilic, more reactive than most other molecules that have chloride as the leaving group (Fig. 8.7). 

FIGURE 8.7 Oxidation of halothane to the highly reactive trifluoroacetyl chloride. 

The oxidative metabolism leads to the formation of reactive species (epoxides, quinone-imines, etc.), which can be a source of toxicity. Consequently, slowing down or limiting these oxidations is an important second target in medicinal chemistry. Thus, the metabolism of halothan (the first modern general anaesthetic) provides hepatotoxic metabolites inducing an important rate of hepatitis the oxidation of the non-fluorinated carbon generates trifluoroacetyl chloride. The latter can react with proteins and lead to immunotoxic adducts [54], The replacement of bromine or chlorine atoms by additional fluorine atoms has led to new families of compounds, preferentially excreted by pulmonary way. These molecules undergo only a very weak metabolism rate (1-3%) [54,55]. 

George, C J. Y. Saison, J. L. Ponche, and P. Mirabel, Kinetics of Mass Transfer of Carbonyl Fluoride, Trifluoroacetyl Fluoride, and Trifluoroacetyl Chloride at the Air/Water Interface, J. Phys. Chem., 98, 10857-10862 (1994b). 

Oxidative dehalogenation. Halogen atoms may be removed from xenobiotics in an oxidative reaction catalyzed by cytochromes P-450. For example, the anesthetic halothane is metabolized to trifluoroacetic acid via several steps, which involves the insertion of an oxygen atom and the loss of chlorine and bromine (Fig. 4.28). This is the major metabolic pathway in man and is believed to be involved in the hepatotoxicity of the drug. Trifluoroacetyl chloride is thought to be the reactive intermediate (see chap. 7). 

The aerobic pathway of metabolism (pathway 1) (Fig. 7.77) produces trifluoroacetyl chloride, a highly reactive acyl chloride, which can react with nucleophiles such as amino groups similar to those on proteins. Alternatively, reaction with water yields trifluoroacetic acid. Trifluoroacetylchloride is the probable reactive metabolite that trifluoroacylates protein, most probably at lysine residues (Fig. 7.77). Removal of the trifluoroacyl moiety from the... 

The resulting epitope density may depend on the number of lysine groups in the particular protein, and this will in turn affect the immunogenicity of the antigen. Trifluoroacyl adducts have been detected on the outer surface of hepatocytes, presumably as a result of the hapten-complex processing and delivery by MHC I, which is described above. The fact that the production of the trifluoroacetyl chloride is part of the major metabolic pathway and that the majority of patients produce trifluoroacylated proteins suggests that it is differences in the immune surveillance system or immune responsiveness, which determine which patients will succumb to the immunotoxic effect. 

Trifluoroacetyl chloride, CF3COCl. The reagent can be generated in situ from lithium chloride and trifluoroacetic anhydride. 

Olefin inversion (c/. 7, 338). Trifluoroacetyl chloride reacts with 1,2-dialkyl epoxides in DMF stereospeciflcally by trans opening to give u/c-chlorohydrin trifluoroacetates. These products are reduced stcrcospccifically by Nal to alkenes with. ryn-elimination to give inverted alkenes. Reductions with zinc arc less selective. Inversion of olefins is also possible by addition of NCS in CFjCOOH (actual reagent is trifluoroacetyl hypochlorite) followed by reduction with Nal. 

INVERSION, ALKENES Tellurium chloride. Trifluoroacetyl chloride. 

There is an interesting difference in properties between fluoro compounds and the corresponding hydrogen compounds that can be explained by the assumption of the formation of C—H---X bonds. For example, trifluoroacetyl chloride, F CC0C1, has a boiling point below 0°C, whereas that of acetyl chloride is 51°C similarly, trifluoroacetic acid anhydride, (FjCCO O, boils at 20°C and acetic acid anhydride at 137°C. 

Some acyl halides are reactive enough to effect Friedel-Crafts acylation on the neutral heterocycles without a catalyst. For pyrrole such reactions are known, for example, with trifluoroacetyl chloride and trichloroacetyl chloride. Indole reacts smoothly in cold ether with oxalyl chloride and on heating with acetic anhydride. Some examples of these types of acylation are collected in Table 10. 

BUTENOLIDES D i methylformamide dimethyl acetal. Dimethylsulfonium methylide. Peracetic acid. Phenylthiomethyllithium. Titanium(IV) chloride. Trifluoroacetyl chloride. 

Triethylsilyloxypentadienyllithium, 556 Trifluoroacetic acid, 557-559 Trifluoroacetyl chloride, 560 Trifluoromethanesulfonie anhydride, 560-561... 

Monosaccharides Electron capture Monosaccharides derivati vised with trifluoroacetyl chloride [501 ]... 

The primary oxidation product, chlorotrifluoroethylene oxide (compound K), can isomerize either to trifluoroacetyl chloride, or to chlorodi-fluoroacetyl fluoride (compound L). It is unfortunate that the isomerization occurs in this way, because the other possibility would lead to a very coveted compound, trifluoroacetic acid [18,19, 20],... 

Isocyanates of fluorinated compounds can readily be obtained either from trimethylsilyl isocyanate and, e.g. trifluoroacetyl chloride, with yields of isocyanate in the region of 64%. or more conveniently by Curtius degradation of fluorinated acid chlorides. ... 

Another method for the formation of Irilliioroacetyl-substitiited phosphanes such as 6 uses the coupling reaction between trifluoroacetyl chloride and silylphosphanes 5. ... 

A German patent describes a procedure for the production of trifluoroacetyl chloride by UV irradiation of dichlorohexafluorobutene and oxygen the reaction is possible between - 20 and 70 C, the yield is ca. 80%. 

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