Thiophenes halogenation

TABLE 14. Reaction of furans and halogenated thiophene 1,1-dioxides117... 

Thienyliodomium salts (e.g., 28, 29) can be made by direct oxidation of thiophene with iodine in either the +5 or the +3 oxidation states (58JA4279), or by iodination of thienyl-lithium species (77JHC281 80CS(15)135). Such compounds are, however, of limited use only for the synthesis of halogenated thiophenes (Scheme 11). 

FIGURE 24. (a) Correlation of observed ionization energies for mono-halogenated thiophenes with the parent compound, (b) Correlation of observed ionization energies for 2,5- and 3,4-di-halo (chloro, bromo, iodo) substituted thiophenes, (c) Correlation of observed ionization energies for tetra-halo (chloro, bromo, iodo) substituted thiophenes with the parent compound. Reproduced by permission of Elsevier Science from Reference 172... 

When halogenated thiophenes are irradiated in benzene as a solvent, both arylation and dehalogenation reactions are observed (Scheme 2) <1997H(45)1775>. Irradiation of 5-iodo-2-cyanothiophene 44 gave the dehalogenated... 

Title Halogenated Thiophene Monomer for the Preparation of Regioregular Polythiophenes... 

The reaction of thienyllithium with organic halides to form C—C bonds has been discussed in Section 2.10.4.7.2. This cannot, however, be extended to aryl, alkenyl or heteroaryl halides in which the halogen is attached to an sp carbon. Such cross-coupling can be successfully achieved by nickel or palladium-catalyzed reaction of the unsaturated organohalide with a suitable thienyl metal derivative. The metal is usually zinc, magnesium, boron or tin occassionally lithium, mercury, copper, and silicon derivatives of thiophene have also found application in such reactions. In addition to this type, the Pd-catalyzed reaction of halogenated thiophenes with suitable alkenes and alkynes, usually referred to as the Heck reaction, is also discussed in this section. Besides these, a few other miscellaneous Pd-catalyzed substitution reactions on thiophene will also be referred to. 

The reaction of thiophenes and other related sulfur heterocycles with low-valent metal fragments has importance in relation to the catalytic hydrodesulfurization (HDS) process (see Section 8.02.4.1). Oxidative addition of halogenated thiophenes can involve C-S bond cleavage (Equation (40)) or oxidative addition of the G-X bond... 

Halogenated thiophenes are undoubtedly the most often used thiophene derivatives. They can be further converted into various substituted thiophenes through metal-halogen exchange reactions, electrophilic or nucleophilic substitutions or any of several types of palladium(0)-catalysed chemistry [21, 22, 74-76]. 

Soon after thiophene was discovered by Victor Meyer, reports from his group gave the first examples of halogenated thiophenes - dibromothiophene (now known to be 2,5-dibromothiophene) and monoiodothiophene [77]. Monoiodothiophene (now known to be 2-iodothiophene) was synthesised from a mixture with benzene isolated from coal tar containing 50-60% of thiophene ( raw thiophene ). Here the higher reactivity of thiophene in comparison to benzene in halogenations was observed and used. Thus for benzene, iodination requires elevated temperatures, but thiophene was iodinated at room temperature. It was found that 2-iodothiophene can be synthesised either by the treatment with a mixture of iodine and iodic acid or... 

P-Halogenated thiophenes unsubstituted at a-positions are not directly accessible by substitution. However, exhaustive bromination, with regioselective dehalo-genation at a-positions is often used as a means to prepare p-halothiophenes. In the example in Scheme 68, the 3,4-disubstituted thiophene was obtained via reaction with -BuLi then water [106]. 

The introduction of hydrogen or deuterium atoms into thiophenes is possible via the treatment of thienyUithiums with alcohols, water, deuterated alcohols, or deuterium oxide (Scheme 30) [24, 173, 174]. The combination of this method with a prior halogen-metal exchange reaction is a powerful tool for the regioselective partial dehalogenation of halogenated thiophenes [20, 174—190]. 

Halogenated thiophenes, which are important intermediates for the synthesis of further substitution patterns, can be generated by the reaction of thienyllithium derivatives with sources of electrophilic halogens. Fluorination is possible using perchloryl fluoride forming the corresponding product 95 in moderate yield (Scheme 39) [20, 238-240]. Chlorine can be introduced by the reaction of thienyllithium with chlorine, hexachloroethane, trichloroacetonitrile, or sulfonyl chloride [20, 173, 180, 226, 229, 240-244]. Tetrabromomethane is used for bromi-nations [245] and aUcyl iodides for iodinations (Scheme 40) [24, 123, 246-250]. 

Scheme 91 Addition-rearrangement reactions of furan derivatives with halogenated thiophene 1,1-dioxides [101]...

The previous three examples involved the couplings of halogenated thiophenes with different substrates. However, it is also possible to perform coupling between thiophene and halogen-substitnted arenes. The reaction of thiophene derivatives 223, 224 with pentafluoroiodobenzene proceeded in the presence of bis(triphenylphosphine)palladium(ll) dichloride and silver nitrate [116],... 

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