Radical trichloromethyl

Degradation of carbon tetrachloride by photochemical, x-ray, or ultrasonic energy produces the trichloromethyl free radical which on dimeri2ation gives hexachloroethane. Chloroform under strong x-ray irradiation also gives the trichloromethyl radical intermediate and hexachloroethane as final product. 

The /rans-fiised decalin system is conformationally rigid, and the stereochemistry of the product indicates that the initial addition of the trichloromethyl radical is from the axial direction. This would be expected on stereoelectronic grounds, because the radical should initially interact with the n orbital. The axial trichloromethyl group then shields the adjacent radical position enough to direct the bromine abstraction in the trans sense. 

Primary alkyl chlorides are fairly stable to fluorine displacement. When fluorinated, 1-chloropropane is converted to 1-chloroheptafluoropropane and 1-chloto-2-methylbutane produces 39% l-chlorononafluoro-2-methylbutane and 19% perfluoro-2-methylbutane. Secondary and tertiary alkyl chlorides can undergo 1,2-chlorine shifts to afford perfluonnated primary alkyl chlorides 2-Chloro-2-methylpropane gives l-chlorononafluoro-2-methylpropane, and three products are obtained by the fluorination of 3-chloropentane [7] (equation 1). Aerosol fluorina-tion of dichloromethane produces dichlorodifluoromethane which is isolated in 98% purity [4 (equation 2). If the molecule contains only carbon and halogens, the picture is different. Molecular beam analysis has shown that the reaction of fluorine with carbon tetrachlonde, lodotrichloromethane, or bromotrichloromethane proceeds first by abstraction of halogen to form a trichloromethyl radical [5]... 

First examine the geometry of methyl radical. Is it planar or puckered Examine the geometries of 2-methy 1-2-propyl radical, trifluoromethyl radical, trichloromethyl radical and tricyanomethyl radical. Classify each of the substituents (methyl, fluoro, chloro and cyano) as a n-electron donor or as a Tt-electron acceptor (relative to hydrogen). Does replacement of the hydrogens by 7t-donor groups make the radical center more or less puckered Does replacement by Jt-acceptor groups make the radical center more or less puckered Justify your observations. 

Both 2-chloro- and 2,6-dichloro-quinoxalines can be made by ring expansion of 1-methylimidazole using trichloromethyl radicals (91MI5). 

The overall trend of reactivities for t-butoxy radicals with the fluoro-olcfins more closely parallels that for methyl radicals than that for the electrophilic trifluoromethyl or trichloromethyl radicals. 

Irichloromethyl-I unctional initiators, as ATRP macroinitiators 546 trichloromethyl radicals Hammett parameters... 

We see that the effect of multidipole interaction plays an important role in all reactions of abstraction and addition of polar reactants. This interaction can increase or decrease the activation energy of the reaction. However, the multidipole interaction does not influence the reactions of nonpolar trichloromethyl radicals with mono- and polyatomic esters due to the nonpolar character of the attacking radical [89]. 

On the other hand, microsomes may also directly oxidize or reduce various substrates. As already mentioned, microsomal oxidation of carbon tetrachloride results in the formation of trichloromethyl free radical and the initiation of lipid peroxidation. The effect of carbon tetrachloride on microsomes has been widely studied in connection with its cytotoxic activity in humans and animals. It has been shown that CCI4 is reduced by cytochrome P-450. For example, by the use of spin-trapping technique, Albani et al. [38] demonstrated the formation of the CCI3 radical in rat liver microsomal fractions and in vivo in rats. McCay et al. [39] found that carbon tetrachloride metabolism to CC13 by rat liver accompanied by the formation of lipid dienyl and lipid peroxydienyl radicals. The incubation of carbon tetrachloride with liver cells resulted in the formation of the C02 free radical (identified as the PBN-CO2 radical spin adduct) in addition to trichoromethyl radical [40]. It was found that glutathione rather than dioxygen is needed for the formation of this additional free radical. The formation of trichloromethyl radical caused the inactivation of hepatic microsomal calcium pump [41]. 

A similar reaction of 1,5-cyclooctadiene with trichloromethyl radicals, produced from carbon tetrachloride and dibenzoyl peroxide, leads to 2-chloro-6-trichloromethylbicyclo-[3.3.0]octane (94), with chloroform and dibenzoyl peroxide the analogue 95 is obtained and iV-t-butylfonnamide affords compound 96 (equation 57)62,63. 

TABLE 4. Relative rate constants for the addition of the trichloromethyl radical to substituted styrenes and butadiene in BrCCl3 at 80 °C12... 

Carbon tetrachloride is a solvent that is chemically inert, highly resistant to oxidation, but biologically toxic. Despite its chemical stability, P450 is able to convert carbon tetrachloride to several reactive species. Reduced P450 transfers an electron to chloride leading to the elimination of a chloride anion and the generation of the reactive trichloromethyl radical (10). Trichloromethyl radical can undergo a second one-electron reduction to... 

FIGURE 5.5 P450-mediated reduction of carbon tetrachloride and subsequent reactions of the trichloromethyl radical. 

Laser flash photolysis at wavelengths within the charge-transfer absorption bands of 2,2,6,6-tetramethylpiperidine-./V-oxyl (TEMPO) and carbon tetrachloride yields theoxoam-monium chloride of TEMPO 291 (Xmax = 460 nm) and the trichloromethyl radical in an essentially instantaneous 18 ps) process152. The primary photochemical reaction is an electron transfer from TEMPO to carbon tetrachloride followed by immediate decomposition of the carbon tetrachloride anion radical to chloride and trichloromethyl radical (equation 140). The laser flash photolysis of TEMPO and of other nitroxides in a variety of halogenated solvents have confirmed the generality of these photoreactions152. 

Finally, chain transfer is undesirable except when it is used intentionally to limit molecular weight by adding good chain transfer agents such as carbon tetrachloride. Here transfer of a chlorine atom limits the size of one chain and at the same time initiates formation of a new chain by the trichloromethyl radical. Instead of (3), (3), (3), etc., we get (3), (3), (7), (8), (3), (3), (7), (8), etc., with a lower average chain length. 

Administration of hyperbaric oxygen following exposure to carbon tetrachloride improved survival from 31 to 96% in rats (Ellenhorn and Barceloux 1988). Hyperbaric oxygen has also been used in treating overdoses of carbon tetrachloride in humans and may correct regional tissue hypoxia and damage, as well as inhibit the P-450-dependent reductive dehalogentation of carbon tetrachloride to the metabolically active acute trichloromethyl radical in the liver. However, the effectiveness of this method has not been established in humans (Burkhart et al. 1991 Ellenhorn and Barceloux 1988). 

Dose and duration dependence of free radical generation during carbon tetrachloride metabolism in the endoplasmic reticulum relation between trichloromethyl radical formation and lipid radical format on. 

Methods for Determining Biomarkers of Exposure and Effect. Covalent adducts between reactive carbon tetrachloride metabolites (e.g., the trichloromethyl radical) and cellular proteins, lipids and nucleic acids are known to occur, but at present these can only be measured using radiolabeled carbon tetrachloride. Development of immunological or other methods to detect such adducts in humans exposed to carbon tetrachloride could be of value in estimating past exposures to carbon tetrachloride. 

Lai EK, McCay PB, Noguchi T, et al. 1979. In wVo spin-trapping of trichloromethyl radicals formed from Carbon tetrachloride. Biochem Pharmacol 28 2231-2235. 

Noguchi T, Fong K-L, Lai EK, et al. 1982a. Specificity of a phenobarbital- induced cytochrome P-450 for metabolism of carbon tetrachloride to the trichloromethyl radical. Biochem Pharmacol 31 615- 624. 

Poyer JL, Floyd RA, McCay PB, etal. 1978. Spin-trapping of the trichloromethyl radical produced during enzymic NADPH oxidation in the presence of carbon tetrachloride or bromotrichloromethane. Biochim Biophys Acta 539 402- 409. 

Tezuka M, Ishii S, Okada S. 1991a. Chromium (III) decreases carbon tetrachloride-originated trichloromethyl radical in mice. J Inorganic Biochem 44 261-265. 

It is clear from Table III that addition of methyl radicals occurs 1.5 to 3 times as often as abstraction, while for the peroxy radical addition occurs only 0.1 to 2 times as often. Despite this large variation in the proportions reacting by addition, the relative rates of addition of these two radicals to cyclic olefins are about the same. In fact, the reactivity of cyclohexene relative to cyclopentene in these systems agrees with that observed (25) for the trichloromethyl radical (0.14 to 0.30). However,... 

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