Trichloromethyl radical intermediate

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 hypothesized transformation pathways of CT and CF to methane are shown in Figure 2. The transformation of CT and CF to methane in the Pd/alumina system, despite the low reactivity of MeCl, indicates that the reactions do not involve sequential dehalogenation of CF to methane (i.e. MeCl is not an intermediate). The formation of C2 and C3 compounds during the transformation of both CT and CF indicates the existence of a radical pathway. However, the production of ethane (12-14%) and CF (18-23%) from CT was much lower than that of methane (51-60%). This implies that the main transformation pathway is a direct reaction of CT to methane, with a secondary pathway involving a trichloromethyl radical which then reacts to form CF and C2 and C3 species. Similarly, the relatively low production of ethane (<1%) from CF indicates that the major pathway for the reaction of CF to ethane occurs through direct transformation to methane, rather than through a dichloromethyl radical species. (Lowry and Reinhard 1999)... 

The use of carbon tetrachloride as a solvent in diketone irradiations is dangerous since intermediate radicals can abstract chlorine giving trichloromethyl radicals which can result in formation of complex mixtures. In a study 146) of the irradiation of 68 in CCI4, products included (inter alia) reduced 68 and the trichloromethyl compound 186. 

The radical reaction of carbon tetrachloride with aliphatic double bonds involves addition of the trichloromethyl radical to the double bond, followed by chlorine atom abstraction from carbon tetrachloride by the intermediate radical to give the product. After the addition of the trichloromethyl radical to /3-pinene, a fragmentation occurs prior to formation of the product. 

According to this analysis, the weakening of the C—H bonds in isobutane and toluene is largely due to the stabilization of the resulting radicals. However, even though trichloromethyl radicals are quite stable, there is also considerable stabilization in the starting material chloroform, and the C—H bond in chloroform is not weakened as much as that in isobutane. More is said about separating structural effects in reactant and intermediate radicals in Topic 11.1. 

The fran -fused decalin system is conformationally rigid and the stereochemistry of the product indicates that the initial addition of the trichloromethyl radical is from an axial direction. This is expected on stereoelecfronic grounds because the radical should initially interact with the ir orbital. The axial trichloromethyl group then shields the adjacent radical position and directs the bromine abstraction in the trans sense. Addition of bromotrichloromethane to norbornene is also anti. This is again the result of steric shielding by the trichloromethyl group, which causes the bromine atom to be abstracted from the endo face of the intermediate radical. 

The alkali metals are easily vaporized at temperatures of 300—500"C, and most studies of this group have been reviewed in Sections 2 and 3. The reactivity of alkali metals in co-condensation reactions is high, but little different from that in diffusion flame studies. However, the alkali metals have been used in a number of low-temperature reactions, largely to produce radicals or intermediates of spectroscopic interest. For example, the trichloromethyl radical has been produced in a solid argon matrix by reaction of lithium atoms with carbon tetrachloride [294]. A similar technique has been used to produce the CBr2H radical from bromoform [295], the CCljH radical from chloroform [296], and the methyl radical from methyl iodide and methyl bromide [297]. In all these cases the corresponding lithium halide is produced. 

The radical nature of this reaction has been confirmed by Griffin (118, 119), Crofts and Downie (87), and Cadogan and co-workers (71,77). These latter workers favor an alternative mechanism involving chain propagation by reaction of the phosphoranyl radical with carbon tetrachloride to give a phosphonium intermediate capable of valency expansion and a free trichloromethyl radical. 

The highly reactive intermediate, dichlorocarbene, was identified and quantified by means of trapping with 2,3-dimethylbutene. Evidence for involvement of the trichloromethyl radical was also obtained and was indirectly... 

The formation of the reactive intermediate, dichlorocarbene, is confirmed by die selective trapping of the carbene with 2,3-dimethyl-2-butene to form l,l-dichloro-2,2,3,3-tetramethylcyclopropane. In a similar fashion, die trichloromethyl radical is trapped by 2,3-dimethyl-2-butene to yield 2-methyl-2-trichloromethyl-1-butene. These trapped intermediates can be identified and quantified by gas chromatography/mass spectroscopy (GC/MS) techniques. 

On the experimental front, by the early 1960s, thermal reactions exhibiting fall-off with pressure were no longer a rarity, but I could not see at that time how further study of the shapes of fall-off curves would be helpful on the theoretical front so I started to look for other useful experiments. I thought that if we could react methyl radicals with trichloromethyl radicals at various pressures, we might be able to probe the k(E) function for the elimination of HQ from the vibrationally excited methylchloroform intermediates which would be formed, i.e. 

This result shows than the initially added trichloromethyl group has little influence on the stereochemistry of the subsequent bromine atom-abstraction. The intermediate 2-(trichlor-omethyl)cyclohexyl radical presumably relaxes to the equatorial conformation faster than bromine-atom abstraction occurs. In contrast with addition to A -octahydronaphthalene, the addition is exclusively /ran -diaxial ... 

This is again the result of steric shielding by the trichloromethyl group, which causes the bromine atom to be abstracted from the endo face of the intermediate radical. 

The degradation of tetrachloromethane by a strain of Pseudomonas sp. presents a number of exceptional features. Although was a major product from the metabolism of CCI4, a substantial part of the label was retained in nonvolatile water-soluble residues (Lewis and Crawford 1995). The nature of these was revealed by the isolation of adducts with cysteine and A,A -dimethylethylenediamine, when the intermediates that are formally equivalent to COClj and CSClj were trapped—presumably formed by reaction of the substrate with water and a thiol, respectively. Further examination of this strain classified as Pseudomonas stutzeri strain KC has illuminated novel details of the mechanism. The metabolite pyridine-2,6-dithiocarboxylic acid (Lee et al. 1999) plays a key role in the degradation. Its copper complex produces trichloromethyl and thiyl radicals, and thence the formation of CO2, CS2, and COS (Figure 7.64) (Lewis et al. 2001). 

The metabolism of carbon tetrachloride proceeds via cytochrome P-450-dependent dehalogenation (Sipes et al. 1977). The first step involves cleavage of one carbon-chlorine bond to yield Cl- and a trichloromethyl free radical, which is then oxidized to the unstable intermediate trichloromethanol, the precursor of phosgene. Hydrolytic dechlorination of phosgene yields C02 and HC1 (Shah et al. 1979). Although there are similarities in the metabolism of chloroform and carbon tetrachloride, metabolic activation of chloroform produces primarily phosgene, whereas the level of phosgene production from... 

To explain the presence of a trichloromethyl and an iodine atom at the bridgehead atoms, two photochemically generated radicals were postulated to react with propellane leading to an unstable organoiodine(III) derivative (165). This iodane intermediate underwent ligand coupling to afford eventually the iodopropellane derivative.268 (Scheme 5.22)... 

This is the result of a strong steric factor working against syn addition. The trichloromethyl group will provide steric resistance to approach from the exo direction and thereby favor abstraction of bromine from the endo side of the intermediate radical. 

Halomethyl compounds are subdivided into monohalomethyls, which are alkylating agents, and polyhalomethyls, which must be metabolized to an ultimate species. Reductive dechlorination of carbon tetrachloride 353) to chloroform by rabbit liver microsomes parallels the concentration of cytochrome P-450 in the microsomes but requires anaerobic conditions and NADPH. The identification of hexachloroethane after incubation of NADPH-reduced microsomes with carbon tetrachloride is indicative of homolytic formation of the free radicals of chlorine and trichloromethyl and supports the hypothesis that such species initiate an autocatalytic peroxidation of lipid membranes that results in the observed hepatotoxicity. A similar scheme for radical formation and lipid destruction has been described by Reynolds and Moslen for halothane. In contrast to the reductive dechlorination of carbon tetrachloride, the metabolism of chloroform to carbon dioxide in vitro requires oxygen and produces carbonyl chloride (phosgene) as an intermediate. That this also... 

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