Iodination electrophilic aromatic

Chlorination is carried out in a manner similar to bromination and follows a similar mechanism to give aryl chlorides. Fluorination and iodination of arenes are rarely performed. Fluorine is so reactive that its reaction with benzene is difficult to control. Iodination is very slow and has an unfavorable equilibrium constant. However, iodine, in the presence of a powerful oxidizing agent can be used for electrophilic aromatic iodination. In the following example, the oxidant peroxyacetic acid reacts with iodine to... 

Electrophilic aromatic substitution of the 4-aminobenzofuran 1103 with the complex salt 602 afforded the iron complex 1109 in quantitative yield. Cyclization of the complex 1109 with concomitant aromatization was achieved by oxidation with an excess of iodine in pyridine at 90 °C in air to afford directly furostifoline (224) (688,689) (Scheme 5.179). 

Cyclization of 265 to give 266 involves an initial rearrangement followed by S-iodination and electrophilic aromatic substitution (Scheme 54) <2001JOC1026>. 

Iodine is reactive toward unsaturated aliphatic hydrocarbons and the iodine number is a well-known measure for the degree of unsaturation of fatty acids [164]. The electroiodination of unsaturated and aromatic hydrocarbons also is well known and can be achieved, for example, by electrogeneration of I" in acetonitrile [165] (Eq. 13). The reaction has been proposed to be consistent with a conventional homogeneous electrophilic aromatic substitution. 

These equations show the general theoretical basis for the empirical order of rate constants given earlier for electrophilic attack on an aromatic ligand L, its metal complex ML, and its protonated form HL, one finds kt > n > hl. Conflicting reports in the literature state that coordination can both accelerate electrophilic aromatic substitution (30) and slow it down enormously (2). In the first case the rates of nitration of the diprotonated form of 0-phenanthroline and its Co(III) and Fe(III) complexes were compared. Here coordination prevents protonation in the mixed acid medium used for nitration and kML > h2l. In the second case the phenolate form of 8-hydroxyquinoline-5-sulfonic acid and its metal chelates were compared. The complexes underwent iodination much more slowly, if at all, and kL > kML ... 

The first preparations of diaryliodonium salts have been reported in the 19th century, but refinements and improvements keep appearing to date. In most cases an iodoaryl species containing iodine(III) is coupled with an arene or a derivative of it in a typical electrophilic aromatic substitution. Lithiated, stannylated or silylated aryls and arylboronic acids or borates have been introduced recently in order to avoid harsh conditions and to improve yields. The iodoaryl species may be also formed in situ from arenes and iodine(III) reagents. 

Anodic iodination 24°) involves an iodonium intermediate, probably N-iodo-acetonitrilium perchlorate (29) undergoing electrophilic aromatic substitition (Eq. (100) ). A radical cation (28) as intermediate is improbable in this case. Electrolysis of iodine and aromatics in CH3CN/LiC104 yields the corresponding... 

More involved studies of the oxidation of plant phenols [27], as well as the introduction of thallium and hypervalent iodine complexes and the use of electrochemical methods, have emphasized the importance of another intermediate involved in oxidative coupling reactions, namely the phenoxonium ion 8 [28-30]. Due to its ionic nature, reaction through an oxo-nium ion can improve the regioselectivity of bond formation and lead to fewer unwanted products (for example, no coupling via the oxygen atom). The coupling reaction can then be viewed as an electrophilic aromatic substitution between 17 and a nucleophilic aromatic unit 15 (Scheme 5). 

Iodination probably involves an electrophilic aromatic substitution with the iodine cation (I+) acting as the electrophile. The iodine cation results from oxidation of iodine by nitric acid. 

IC1 can be represented as I Cl because chlorine is a more electronegative element than iodine. Iodine can act as an electrophile in electrophilic aromatic substitution reactions. 

Iodination of arenes2 Iodination of arenes can be effected by reaction with HgO HBF4 in the presence of iodine. The orientation conforms to that observed in electrophilic aromatic substitution except that ortho-attack is favored over para-attack in activated arenes. The method is particularly useful for meta-iodination of deactivated arenes (99% selectivity). 

A good example of a back titration involving iodine and thiosulfate is the assay of resorcinol in Resorcinol Solution BP. Resorcinol is an antiseptic that was widely used in the past, although less so now. The assay of resorcinol involves a quantitative electrophilic aromatic substitution reaction using bromine as the reagent, as shown in Figure 6.4. 

An excellent alternative to the classical Hunsdiecker reaction and its variants, which totally avoids the use of heavy metal salts and potent electrophilic reagents, consists of the simple photolysis or thermolysis of Barton esters in refluxing bromotri-chloromethane for the bromides or tetrachloromethane for the chlorides [4], The analogous decarboxylative iodination can also be achieved using iodoform as the reagent in a benzene/cyclohexene solvent system (Scheme 5). For the cases of vinylic and aromatic acids, where the usual problems of chain efficiency are encountered, the addition of azobisisobutyronitrile (AIBN) is also required [10]. Nevertheless, since this method can operate on both electron-rich and electron-poor aromatic systems, and moreover does not suffer from the competitive electrophilic aromatic bromination found with electron rich aromatics under normal Hunsdiecker conditions, this route to synthetically useful aryl iodides and bromides should find widespread application. 

The reaction exhibits other characteristics typical of an electrophilic aromatic substitution.Examples of electrophiles that can effect substitution for silicon include protons and the halogens, as well as acyl, nitro, and sulfonyl groups.The fact that these reactions occur very rapidly has made them attractive for situations where substitution must be done under very mild conditions.One example is the introduction of radioactive iodine for use in tracer studies. 

Electrophilic Substitution Iodine labeling can be obtained by using molecular iodine and oxidation reagents, such as peracetic acid, imides and amides, which increase the electrophilic reactivity of the halogen toward aromatic compounds. 

The electrophilic aromatic substitution of the pyridine ring continues to be explored as a way to prepare substituted pyridines. Bw-( 5y w-collidine)-iodine(I) and bromine (I) are effective iodinating or brominating agents, respectively, of pyridinols, although the di- or tri-halogenated products are obtained <97TL2467>. lodination of 3-pyridinol produces 5-hydroxy-... 

Another interesting contribution to the problem of the intermediate in electrophilic aromatic substitutions is Grimison and Ridd s (1958, 1959) investigation of isotope effects in diazo-coupling and iodination of imidazole. Imidazole reacts in the form of its conjugate base (4) which couples with p-diazobenzenesulphonic acid at carbon atom 2 without an... 

Iodine in combination with [bis(acyloxy)iodo]arenes is a classical reagent combination for the oxidative iodination of aromatic and heteroaromatic compounds [99], A typical iodination procedure involves the treatment of electron-rich arenes with the PhI(OAc)2-iodine system in a mixture of acetic acid and acetic anhydride in the presence of catalytic amounts of concentrated sulfuric acid at room temperature for 15 min [100,101]. A solvent-free, solid state oxidative halogenation of arenes using PhI(OAc)2 as the oxidant has been reported [102]. Alkanes can be directly iodinated by the reaction with the PhI(OAc)2-iodine system in the presence of f-butanol under photochemical or thermal conditions [103]. Several other iodine(in) oxidants, including recyclable hypervalent iodine reagents (Chapter 5), have been used as reagents for oxidative iodination of arenes [104-107]. For example, a mixture of iodine and [bis(trifluoroacetoxy)iodo]benzene in acetonitrile or methanol iodinates the aromatic ring of methoxy substituted alkyl aryl ketones to afford the products of electrophilic mono-iodination in 68-86% yield [107]. 

A noteworthy example of electrophilic aromatic substitution in nature, as mentioned in the introduction, is biosynthesis of the thyroid hormone thyroxine, where iodine is incorporated into benzene rings that are derived from tyrosine. 

The structure of thyroxine, a thyroid hormone that helps to regulate metabolic rate, was determined in part by comparison with a synthetic compound believed to have the same structure as natural thyroxine. The final step in the laboratory synthesis of thyroxine by Harington and Barger, shown helow, involves an electrophilic aromatic substitution. Draw a detailed mechanism for this step and explain why the iodine substitutions occur ortho to the phenolic hydroxyl and not ortho to the oxygen of the aryl ether. [One reason iodine is required in our diet (e.g., in iodized salt) is for the biosynthesis of thyroxine.]... 

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