Chlorinations, with arenes

The most useful compounds of this type are (dichloroiodo)arenes. The method of choice for their preparation remains the old, direct combination of elemental chlorine with the corresponding iodide, as originally applied by Willgerodt. The usual procedure for iodoarenes is to dissolve them in a suitable solvent (preferably chloroform or dichloromethane) and pass chlorine at 0°C (Scheme 2) [5]. 

The contribution of polar structures reduces the barrier and also the intrinsic barrier. This results for non thermoneutral reaction in a reduction of isotope effect. This has been a controversial subject for several years it is extensively covered by Russell29. The variation with substituents in the low isotope effects for the reaction of aryl radical with arene thiols were explained using such an effect. We may possibly further account for the lower intrinsic barrier for the R-H-Cl system (3.8 Kcal) than for the R-H—S system (5 Kcal) in terms of the greater electronegativity of chlorine. 

Chlorination. Activated arenes are chlorinated with (salen)manganese(III) complex, and moist alumina in dichloromethane. 

Dichloroiodo)arenes can also be used for the chlorination of aromatic compounds. Aminoacetophenone 73 is selectively chlorinated with (dichloroiodo)benzene to give product 74 in good yield (Scheme 3.25). This process can be scaled up to afford 24.8 kg of product 74 with 94% purity [58]. 

Kodomari et al. [8] report the chlorination of alkoxybenzenes in chlorobenzene with copper(II) chloride on neutral alumina. The reactions are typically carried out at 100°C within 3 h, giving excellent yields and para to ortho product ratios greater than 30. Higher substituted arenes have been chlorinated with sulfuryl chloride and silica gel in hexane at room temperature [9]. 1,2,4,5-Tetramethylbenzene yields 73% of the mono-chloro product and 10% of the dichloro product. The system has been applied to a wide range of substituted benzenes and naphthalenes. 

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 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. 

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). 

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. 

Allylchlorosilanes undergo Friedel-Crafts alkylation with aromatic compounds such as benzene derivatives and ferrocene to give [p-(chlorosilyl)alkyl]arene compounds in the presence of Lewis acid catalyst. Allylsilanes containing two or more chlorine atoms on silicon react smoothly with benzene under mild conditions to give alkylation products in good yields [Eq. (15)]. In alkylations of benzene, the reactivity of the allylsilanes increases as the number of chlorine atoms on the silicon increases, but decreases as the number of methyl groups increases. Because the reactivity of allylsilanes is sensitive to the electronic nature of the substituents on the silicon atom, allylsilane selection is an important factor for alkylation reactions. 

The preparation of functionalized aryllithium compounds bearing an oxygen- or sulfur-containing functionality in a benzylic position is also possible by arene-catalyzed lithiation. When chlorinated materials 239 were deprotonated (for Y = OH, SH) with n-butyllithium in THF at —78 °C and then lithiated using DTBB as the catalyst at the same temperature. 

The corresponding catalytic version of this reaction was performed using either naphthalene- or biphenyl-supported polymers 594 or 595, respectively, which were prepared by cross-coupling copolymerization of 2-vinylnaphthalene or 4-vinylbiphenyl with vinyl-benzene and divinylbenzene promoted by AIBN in THF and polyvinyl alcohoP . These polymers have been used as catalysts (10%) in lithiation reactions involving either chlorinated functionalized compounds or dichlorinated materials in THF at —78°C and were re-used up to ten times without loss of activity, which is comparable to the use of the corresponding soluble arenes. 

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