Chlorination of arenes

A catalyst—solvent system containing a PIL and HCI or two PILs was used for the chlorination of arene compounds to replace conventional Lewis acid catalysts. The PILs trialed were [HMImJNOs and [HMImJCI. The best selectivity was obtained using [HMImJNOs with HCI, with 99% conversion and 96% selectivity toward the monochloro derivative after 48 h. The nitrate anion was determined to be involved in the reaction, with the IL being reformed afterward and being reusable. 

Chlorination of Aromatic Compounds. NCS can be used for the chlorination of electron-rich aromatic compounds, such as phenol and xylene derivatives under the microwave conditions. Palladium-catalyzed directing group-assisted chlorination of arenes has also been reported (eq 48). ... 

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... 

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. 

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]. 

Aiyl chlorides and bromides can be easily prepared by electrophilic substitution of arenes with chlorine and bromine respectively in the presence of Lewis acid catalysts like iron or Iron(III) chloride. 

Carboxylic acid fluorides, intermediates in the pathway to trifluoromethyl derivatives, are readily formed in reactions of all types of carboxylic acids with sulfur tetrafluoride derivatives (see Section 8.2.4.). Little attention has been paid to fluorination of other carboxylic acid halides. Aroyl chlorides are converted into aroyl fluorides by treatment with sulfur tetrafluoride, e.g. formation of l,41 or to (trifluoromethyl)arenes, e.g. 2 and 3. in the presence of hydrogen fluoride.45 Chlorination of the aromatic ring occurs in some cases.41... 

A powerful electrophilic species is obtained from C120 and a strong protic acid xuch as trifluoroacetic acid. This reagent effects exclusive ring chlorination of deactivated arenes in high yield with the usual regioselectivity. 

One of the most important reactions in arene synthesis is the halogenation of arenes. Conventionally, these reactions are performed directly by bromine or chlorine [7]. However, on the laboratory scale chlorine is not easily manageable and is a toxic gas. Therefore, it is not often used in academic research. For iodinations normally a strong oxidizing agent is required. In halogenations, often unintentional side-chain... 

The direct chlorination of iodoarenes is a very effective and convenient method to obtain (dichloroiodo)arenes in good yield this approach was recommended for the purification of arenes. The method described in Organic Syntheses [13] is also suitable for a wide number of iodoarenes. An alternative new method involved the... 

Photochemical remote chlorination of steroids through (dichloroiodo)arenes... 

Photoreactions involving benzoic add are not common, but it is now reported that the arene moiety is susceptible to substitution in the presence of sodium hypochlorite in aqueous alkali at pH > 12. At ratios of the order of 0.1 for [Q0 ] [PhC02 l, hydroxylation and chlorination of the aromatic ring occur simultaneously with ipso substitution at the carboxylate group (which yields phenol). At high relative concentrations of hypochlorite, the photo-products react further in the dark to yield polychlorinated derivatives. The reaction is discussed in terms of the initial steps being the generation of the active species 0( P), 0( D), O, and Cl from irradiation of C10 . 

Much of the research on the SbCls-catalyzed halogenation of arenes has focused on the chlorination and bromination of perfluoroalkyl-substituted aromatics [14]. The reaction of organic disulfides with electron-rich aromatic compounds under catalysis with SbCls and AgSbFg affords unsymmetrical aryl sulfides in modest yields [15a]. Electrophilic sulfinylation and sulfonation can be similarly effected by SbCls [15a-c]. Alkyl- and halobenzenes give thiocyano derivatives when treated with a mixture of SbCls and Pb(SCN)2 in CCI4 [16],... 

Haiogenation of arenes (Section 12.5) Aryl chlorides and bromides are conveniently prepared by electrophilic aromatic substitution. The reaction is limited to chlorination and bromination. Fluorination is difficult to control iodi-nation is too slow to be useful. 

Chlorination of thiophenols leads, with cleavage of the S-H bond, to arene-sulfenyl chlorides,659-661 the first example of the series having been prepared by Zincke as early as 1911 662... 

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. ... 

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... 

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