Substitution, electrophilic with iodine

The heats of formation of Tt-complexes are small thus, — A//2soc for complexes of benzene and mesitylene with iodine in carbon tetrachloride are 5-5 and i2-o kj mol , respectively. Although substituent effects which increase the rates of electrophilic substitutions also increase the stabilities of the 7r-complexes, these effects are very much weaker in the latter circumstances than in the former the heats of formation just quoted should be compared with the relative rates of chlorination and bromination of benzene and mesitylene (i 3 o6 x 10 and i a-Sq x 10 , respectively, in acetic acid at 25 °C). 

In reactions with azides, ketones are directly converted to 5-hydroxytriazolines. Ketone enolate 247, generated by treatment of norbornanone 246 with LDA at 0°C, adds readily to azides to provide hydroxytriazolines 248 in 67-93% yield. Interestingly, l-azido-3-iodopropane subjected to the reaction with enolate 247 gives tetracyclic triazoline derivative 251 in 94% yield. The reaction starts from an electrophilic attack of the azide on the ketone a-carbon atom. The following nucleophilic attack on the carbonyl group in intermediate 249 results in triazoline 250. The process is completed by nucleophilic substitution of the iodine atom to form the tetrahydrooxazine ring of product 251 (Scheme 35) <2004JOC1720>. 

Only a little 3,5-di- and penta-iodopyridine is obtained when pyridine reacts with iodine in the vapour phase. Treatment of pyridine with iodine in 50% oleum furnishes 3-iodo-(18%) and some 3,5-di-iodo-pyridine. This is probably the result of electrophilic substitution by I+, with oleum performing in the role already discussed (57JCS387). The products of iodination of quinoline are not well defined however, a reviewer (77HC(32-1)319) has pointed out that one such product (formed by heating quinoline with iodine and potassium iodide at 160-170 °C in the presence of mercury(II) chloride) has a melting point identical with that of 3-iodoquinoline. 

The reaction of IODO-GEN with iodide ion in solution results in oxidation with subsequent formation of a reactive, mixed halogen species, IC1 (Fig. 266). Either 125I or 13 1 can be used in this reaction. The IC1 then rapidly reacts with any sites within target molecules that can undergo electrophilic substitution reactions. Within proteins, any tyrosine and histidine side-chain groups can be modified with iodine within... 

Aryl-A3-iodanes 1 are electrophilic at iodine and undergo ligand exchange with a variety of nucleophilic species, including organic functional groups (Scheme 1). Such reactions may be regarded as nucleophilic substitutions at trivalent... 

Arenes usually undergo electrophilic substitution, and are inert to nucleophilic attack. However, nucleophile attack on arenes occurs by complex formation. Fast nucleophilic substitution with carbanions with pKa values >22 has been extensively studied [44]. The nucleophiles attack the coordinated benzene ring from the exo side, and the intermediate i/2-cvclohexadienyl anion complex 171 is generated. Three further transformations of this intermediate are possible. When Cr(0) is oxidized with iodine, decomplexation of 171 and elimination of hydride occur to give the substituted benzene 172. Protonation with strong acids, such as trifluoroacetic acid, followed by oxidation of Cr(0) gives rise to the substituted 1,3-cyclohexadiene 173. The 5,6-trans-disubstituted 1,3-cyclohexadiene 174 is formed by the reaction of an electrophile. 

The parallels observed between CM) solubility and electrophilic substitution products are regular if C6o dissolution in aromatic hydrocarbons is considered as acid-base relationships. According to the theoretical research and experimental results, double bonds of aromatic hydrocarbons with mobile Tt-electrons are Lewis base. Consequently, they react with acids and Lewis acids to form complexes. It has been established that these complexes cannot be to a marked extent electrostatic. It has been found that they are often colored. Complexes with iodine (Lewis acid) give absorption bands at 300 nm in the UV region. These complexes are not true chemical compounds. According to Dewar, all the above facts are due to the formation of Tt-complexcs between an acid or Lewis acid and the entire Ji-electron system of an unsaturated compound which should be considered as Lewis base. Because in these complexes a double bond is an electron donor and Lewis acid is an electron acceptor, they are known as donor-acceptor complexes. The decrease in energy in complexing is conditioned by quantum-mechanical reasons. 

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. 

Similarly, the enamine salt 15 is obtained by lithiation of 14 (equation 5). In both cases the lower steric hindrance leads to higher stability of the enaminic system33 where the double bond is formed on the less substituted carbon. The Af-metalated enamines 11 and 15 are enolate analogs and their contribution to the respective tautomer mixture of the lithium salts of azomethine derivatives will be discussed below. Normant and coworkers34 also reported complete regioselectivity in alkylations of ketimines that are derived from methyl ketones. The base for this lithiation is an active dialkylamide—the product of reaction of metallic lithium with dialkylamine in benzene/HMPA. Under these conditions ( hyperbasic media ), the imine compound of methyl ketones 14 loses a proton from the methyl group and the lithium salt 15 reacts with various electrophiles or is oxidized with iodine to yield, after hydrolysis, 16 and 17, respectively (equation 5). 

The Se2 cleavage of tetramethyltin with iodine is an aliphatic electrophilic substitution reaction which is subject to strong solvent dependence [507-509], The rate of iodinolysis of (CH3)4Sn in acetonitrile at 25 °C is more than 10 times faster than that in tetrachloromethane (carried out at 50 °C owing to its slow rate in this solvent) [509],... 

Subsequent protic workup releases the aromatic compound. The metalative Reppe reaction can also be used to prepare iodo-substituted or homologated aromatics by treatment of the titanium aryl compound with iodine or an aldehyde, respectively. This procedure has recently been extended to include pyridine derivatives (254 and 255), where the titanacyclopentadiene intermediate can be treated with sulfonylnitriles to afford pyridines after protic workup.192 As with the alkyne cyclotrimerizations, treatment with the appropriate electrophiles affords iodo- and homologated pyridines. 

Electrophilic substitution of 4-(tributystannyl)pyridazines, prepared from tributylstannyl acetylenes and tetrazines, has been demonstrated (Scheme 80) with iodination, and palladium-catalyzed benzoylation and phenylation <91H(32)1387>. 

The electrophilic substitution of indoxazene-3-acetic acid and its derivatives has been investigated extensively. Chlorination with chlorine in acetic acid or with a slight excess of N-chlorosuccinimide produces a mixture of the a-chloroacetic acid (30 R1 = Cl, R2 = H) (48.6%) and 3-(dichloromethyl)-indoxazene (5%), whereas with a large excess of N-chlorosuccinimide a mixture of 3-(dichloromethyl)- and 3-(trichloromethyl)indoxazene results 47 Iodination with iodine monochloride in acetic acid, or bromination with an equivalent of bromine in the same medium, yields only the monohalogeno acids (30 R2 = H, R1 = I and Br, respectively).47-49 With an excess of bromine, 3-(tribromomethyl)indoxazene is formed.48 49 Surprisingly, bromination of the methyl ester (30 R1 = H, R2 = Me), even with an excess of... 

The first report of an attempt to carry out an electrophilic substitution in this group was by Sheehan and Leitner,30 who found that treatment of 3-hydroxythieno[3,2-6]pyridine with iodine monochloride gave... 

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