Chlorinated arenes

The transformation of chlorotolnenes has been studied in Ralstonia (Pseudomonas) sp. strain PS12, and important reasons that limit their biodegradability have emerged (Poltmann et al. 2001). 

Mutations at the active site of CYPlOl (cytochrome P450j,j jj) from a strain of Pseudomonas putida made possible the monooxygenation of chlorinated benzenes with less than three substituents to chlorophenols, with concomitant NIH shifts for 1,3-dichlorobenzene (Jones et al. 2001). Further mutations made it possible to oxidize even pentachlorobenzene and hexachlorobenzene to pentachlorophenol (Chen et al. 2002). Integration of the genes encoding cytochrome PTSO. into Sphingobium chlorophenolicum enabled this strain to partially transform hexachlorobenzene to pentachlorophenol (Yan et al. 2006). 

Attention has been directed to the dechlorination of polychlorinated benzenes by strains that use them as an energy source by dehalorespiration. Investigations using Dahalococcoides sp. strain CBDBl have shown its ability to dechlorinate congeners with three or more chlorine substituents (Holscher et al. 2003). Although there are minor pathways, the major one for hexachlorobenzene was successive reductive dechlorination to pentachlorobenzene, 1,2,4,5-tetrachlorobenzene, 1,2,4-trichlorobenzene, and 1,4-dichlorobenzene (Jayachandran et al. 2003). The electron transport system has been examined by the use of specific inhibitors. lonophores had no effect on dechlorination, whereas the ATP-synthase inhibitor A,A -dicyclohexylcarbodiimide (DCCD) was strongly inhibitory (Jayachandran et al. 2004). 

This is discussed in some detail both on account of the importance of the degradation of PCBs, which are widely distributed contaminants, and since it illustrates a number of important principles. 

In this section, the strains used have been given to minimize confusion because there have been a number of changes in the nomenclature of some organisms, for example, 

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Aerobic degradation of chlorinated arene hydrocarbons, including the important group PCBs, and chlorobenzoates that are produced from them as metabolites, is generally initiated by dihy-droxylation of the rings to dihydrodiols followed by dehydrogenation to catechols. Halide may be lost simultaneously and for 2-halogenated benzoates, both halide and carboxyl. Salient aspects are summarized, and attention drawn to selected aspects of enzyme inhibition. 

Dehalogenation of chlorinated arenes.3 Palladium (10%) on carbon catalyzes the rapid transfer of hydrogen from ammonium formate to aryl chlorides to provide the parent arene. Dehalogenation of 2,4,6-trichlorophenol proceeds through di-chloro- and chlorophenol and is complete within 10 minutes at ambient temperature and pressure. 

Chlorinated arenes are cheap to manufacture and therefore play a vital role as intermediates in chemical industry. However, in contrast to their - much more expensive - brominated and iodinated counterparts chloroarenes are quite unreactive in subsequent reactions. Classical functionalizations of the C-Cl- bond in non-activated arenes usually require harsh conditions and side reactions may produce environmentally hazardous oxygenated chloroarenes. 

Chlorination.1 In combination with A1C13, this reagent chlorinates alkenes to provide vinyl chlorides and chlorinates arenes, but not benzene, to provide aryl chlorides. Anisole, diphenyl ether, and N,N-dimethylaniline are chlorinated exclusively in the para-position. Bromination can be effected by the combination of 1 with aluminum bromide. 

Sulfuryl chloride also chlorinates arenes in the nucleus if silica gel is present in small amounts. Silica gel is also a satisfactory catalyst for condensation of arenes with p-toluenesulfenyl chloride, TsSCl, and CeHs SCH2C1. ... 

On prolonged heating, the complexes decompose [43, 44d] to produce biaryls, chlorinated arenes and platinum(II) derivatives. The process of formation of the CT-tolyl complex of platinum(IV) is accompanied by its para-meta isomerization [43, 44e, 47], If in the initial instant the substitution takes place mainly (to extent of 90%) in the />ara-position in toluene, then the statistical distribution metaipara = 2 1 is gradually attained (Figure VII.4). 

Hydroxylation of arenes. The reagent behaves as though it is polarized in the sense HO +—F " in contrast to HOCl, which is polarized HO —CF +. Thus HOCl chlorinates arenes, whereas HOF hydroxylates arenes. Benzene is converted into phenol (18.77o) and o-catechol (3.97 ). p-Xylene gives 35.27. of... 

Voss J, Altrogge M, Golinske D, Kranz O, Ntinnecke D, Petersen D, Waller E. (2001). Degradation of chlorinated arenes by electroreduction. In Treatment of Contaminated... 

Later, Yu et al. reported the first example of Ru(n)-catalysed direct C-H amination of benzamides with N-benzoyloigramines at room temperature. This reaction is compatible with halogenated arenes, which are usually prone to react in cross-coupling reactions. Both fluorinated and chlorinated arenes reacted and provided the corresponding aminated products in 40-69% yields. Whereas, brominated arenes were less compatible giving lower yields. Other heteroarenes including pyrazole. 

The reduction of chlorinated arenes to arenes represents an important chemical transformation because of the deleterious environmental and health impact of these compounds, and nickel reagents have shown higher efficiencies in this reaction compared to other metals. Fort and co-workers reported the first use of NHC-Ni for the reduction of C-Cl bonds. In this approach, stable [(NHC)2Ni ] species were formed in situ, by NaH-induced reduction of [Ni(acac)2]. Interestingly, transmission electron microscopy of the obtained mixture revealed a homogeneous distribution of uniformly sized amorphous and subnanometric (<0.5 nm) Ni nanoparticles (NPs). NMR analysis of the reaction medium revealed a spectrum comparable to the reported spectra for [(IPr)2Ni ] prepared from [Ni(COD)2]. This procedure was recently adapted by Matsubara to prepare free [(IPr)2Ni] and [(IPr)Ni(acac)2] complexes in the absence of NaOt-Bu. This structural study also showed... 

Chlorination is carried out m a manner similar to brommation and provides a ready route to chlorobenzene and related aryl chlorides Fluormation and lodmation of benzene and other arenes are rarely performed Fluorine is so reactive that its reaction with ben zene is difficult to control lodmation is very slow and has an unfavorable equilibrium constant Syntheses of aryl fluorides and aryl iodides are normally carried out by way of functional group transformations of arylammes these reactions will be described m Chapter 22... 

Halogenation (Section 12 5) Chlorination and bromination of arenes are carried out by treatment with the appropriate halogen in the presence of a Lewis acid catalyst Very reactive arenes undergo halogenation in the absence of a catalyst... 

In another study in this field, Deligbz et al. [50], synthesized a polymeric calixarenes by combining 25,26,27-tribenzoyloxycalix[4]arene with the oligomer 1 in the presence of NaH. Based on the chlorine analysis of this product, it was observed that compound 2 did not attach to each consecutive (CH2-CI) groups in a regular array. 

The symmetric series provides functional cyclohexadienes, whereas the non-symmetric one serves to build deuterated and/or functional arenes and tentacled compounds. In both series, several oxidation states can be used as precursors and provide different types of activation. The complexes bearing a number of valence, electrons over 18 react primarily by electron-transfer (ET). The ability of the sandwich structure to stabilize several oxidation states [21] also allows us to use them as ET reagents in stoichiometric and catalytic ET processes [18, 21, 22]. The last well-developed type of reactions is the nucleophilic substitution of one or two chlorine atoms in the FeCp+ complexes of mono- and o-dichlorobenzene. This chemistry is at least as rich as with the Cr(CO)3 activating group and more facile since FeCp+ activator is stronger than Cr(CO) 3. 

When the nucleophile is a stabilized carbanion such as the enolate of acetylacetone, 1-benzoylacetophenone, diethylmalonate, or ethyl acetatoacetone, the reaction proceeds similarly. The monosubstituted complex is isolated as long as it contains an acidic hydrogen in the benzylic position. In addition, for the case of diketones CH2(COR)2 (R = Me, Ph, OEt), a deacetylation is observed in an acidic medium [92,93]. These features are the same as described above in the case of the substitution of Cl by stabilized carbanions in monochloroaromatics (the second chlorine being an inert arene substituent [99] Scheme XVII, Eq. (31) and Tables 10 and 11. 

The substituent effect of vinylsilanes is similar to that of allylsilanes. The reactivity of vinylsilanes increased as the number of chlorine atoms on the silicon increased, but decreased as the number of methyl groups increased. However, vinyltrimethylsilane does not react with benzene to give alkylated products. " In the aluminum chloride-catalyzed alkylation of arenes with allylsilanes or vinylsilanes, one or more chlorine substituents on the silicon atom of silanes are required. 

PART 1 HALOGENATED ARENES AND CARBOXYLATES WITH CHLORINE, BROMINE, OR IODINE SUBSTITUENTS... 

The only reported X-ray structure of a it-bonded diiodine exists in the 12/coronene associate [75], which shows the I2 to be located symmetrically between the aromatic planes and to form infinite donor/acceptor chains. -Coordination of diiodine over the outer ring in this associate is similar to that observed in the bromine/arene complexes (vide supra), and the I - C separation of 3.20 A is also significantly contracted relative to the stun of their van der Waals radii [75]. For the highly reactive dichlorine, only X-ray structures of its associates are observed with the n-type coordination to oxygen of 1,4-dioxane [76], and to the chlorinated fullerene [77]. 

Additional publications from Sanford et al. describe the full exploration of palladium-catalyzed chelate-directed chlorination, bromination, and iodination of arenes using N-halosuccinimides as the terminal oxidant <06T11483>. Moreover, an electrophilic fluorination of dihalopyridine-4-carboxaldehydes was reported by Shin et al. <06JFC755>. This was accomplished via transmetalation of the bromo derivative, followed by treatment with A-fluorobenzenesulfinimide as the source of electrophilic fluorine. 

The data in Table 10.1 suggest that the reactivity of epoxide hydrolase toward alkene oxides is highly variable and appears to depend, among other things, on the size of the substrate (compare epoxybutane to epoxyoctane), steric features (compare epoxyoctane to cycloalkene oxides), and electronic factors (see the chlorinated epoxides). In fact, comprehensive structure-metabolism relationships have not been reported for substrates of EH, in contrast to some narrow relationships that are valid for closely related series of substrates. A group of arene oxides, along with two alkene oxides to be discussed below (epoxyoctane and styrene oxide), are compared as substrates of human liver EH in Table 10.2 [119]. Clearly, the two alkene oxides are among the better substrates for the human enzyme, as they are for the rat enzyme (Table 10.1). 

The anodic chlorination in some cases allows one to achieve better regioselec-tivities than chemical alternatives (p/o ratio of chlorotoluene in chlorination of toluene anodic 2.2, chemical alternative 0.5-1.0) [215]. Anodic oxidation of iodine in trimethyl orthoformate afforded a positive iodine species, which led to a more selective aromatic iodination than known methods ]216]. Aryliodination is achieved in good yield, when an aryhodide is oxidized in HOAc, 25% AC2O, 5% H2SO4 in the presence of an arene ]217, 218]. Alkyl nitroaromatic compounds, nitroaromatic ketones, and nitroanihnes are prepared in good yields and regioselectivity by addition of the corresponding nucleophile to a nitroarene and subsequent anodic oxidation of the a-complex (Table 13, number 11) ]219, 220]. 

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