Iodination of thiophenes

Procedures have been worked out which increased the yield of 2-bromothiophene to 78% on direct bromination in acetic acid-ether mixtures and to 67% in carbon tetraehlorided With the mild brominating agent, dioxane dibromide, quantitative yields of 2-bromothiophene are obtained. A very convenient procedure for the iodination of thiophenes consists of the acid-catalyzed (HzSOi) reaction with iodine and HIO3, giving 2-iodothiophene in 75% yieldd In contrast to the HgO method, all the iodine is utilized. 

Although chlorination, bromination and iodination of thiophenes by polyhalide salts require forcing conditions with the addition of zinc chloride [52], halogenation of acridine and acridone has been recorded to yield both 3-halo and 3,7-dihalo derivatives under relatively mild reaction conditions [53], However, whereas chloro-, bromo- and iodo-compounds are readily obtained from acridone, acridine only forms the bromo derivatives, as it produces stable complexes with the dichloroiodate and tetrachloroiodate salts [53]. 

The destruction of thiophene by its treatment with iodine was noted already by Meyer in 1884 [77], Application of HgO to capture HI has been known from Meyer s time and is still applied nowadays. Several other oxidants which can convert hydroiodic acid into iodine have been described. Lead(lV) acetate serves as useful oxidant to support iodination of thiophene with iodine (Scheme 76) [114]. The lead acetate was obtained in this case in situ from commercial red lead (minium), Pb304 [114]. 

Iodination of thiophene with iodine in the presence of orthoperiodic acid H5IO6 used as oxidant was performed either with conventional heating, giving 2-iodothiophene (60°C, 69%), or with microwave irradiation in only 5 min (Scheme 77) [115]. 

Thiophene was converted into 2-iodothiophene in 58% yield in only 10 min using iodine in the presence of silica-supported bismuth(III) nitrate pentahydrate under solvent-free conditions at room temperature [116]. A(-Iodosuccinimide (NIS) in acetic acid and methanol is also an effective agent for iodination of thiophenes (Scheme 78) [117, 118]. 

Scheme 81 Use of benzyltrimethylammonium dichloroiodate for chlorination/iodination of thiophene [123]...

The iodination of thiophene rings attached to a borane has been achieved using only NIS as the iodinating agent (Scheme 7.96) [155], The chemistry was carried out under mild conditions in a mixture of acetic acid and chloroform. The reaction was regioselective for the position adjacent to the sulfur center, and simply stirring at room temperature for a few hours generated moderate yields of the diiodinated compound. 

Further evidence for the mechanism suggested for the iodination of thiophens by iodine and nitric acid has been presented. For 2-phenylthiophen the kinetic... 

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