Thiophene oxidative dimerization

The thiophene ring is opened and sulfur extruded as hydrogen sulfide when 3,4-dinitrothiophene is reacted with piperidine. The product contains two nitroenamine units coupled to each other (Scheme 140). Other secondary amines react similarly (69CC549). Secondary aliphatic amines also react with 2-nitrothiophene to form the nitrodienamines (426) in 50-80% yield. It is believed that the reaction involves addition of the amine at position 5, followed by proton transfer and ring opening to give the thiol which, in the presence of air, oxidatively dimerizes to (426) (Scheme 141). In one case the thiol has been trapped as the silver salt and methylated (74JCS(P1)2357). 

Treiber, A., Dansette, P.M., ElAmri, H., Girault, J.P., Ginderow, D., Mornon, J.P., and Mansuy, D. Chemical and biological oxidation of thiophene Preparation and complete characterization of thiophene S-oxide dimers and evidence for thiophene S-oxide as an intermediate in thiophene metabolism in vivo and in vitro. Journal of American Chemical Society, 1997, 119, 1565. 

C.N.-4. Salts, oxides, sulfides, imines, and ylides of the parent. Here cyclic delocalization is not possible since the lone pair on phosphorus is used in a fourth bond. Most of the oxides and some of the other functions are unstable at or slightly above room temperature, forming Diels-Alder dimers in the manner of thiophene oxides. 

Oxidation of N-aromatic methanesulfonamides 321 with (diacetoxyiodo)benzene in the presence of thiophene in trifluoroethanol or hexafluoroisopropanol (HFIP) affords the respective coupling products 322 in good yield (Scheme 3.131) [380]. The head-to-tail thiophene dimers 324 can be selectively prepared by the hypervalent iodine oxidation of 3-substituted thiophenes 323 [381,382] and bipyrroles 326 can be regios-electively synthesized by oxidative dimerization of pyrroles 325 with [bis(trifluoroacetoxy)iodo]benzene in the presence of bromotrimethylsilane [383]. Likewise, bithiophenes 328 have been synthesized from 3,4-disubstituted thiophenes 327 using [hydroxy(tosyloxy)iodo]benzene in the presence of bromotrimethylsilane in hexafluoroisopropanol [384]. 

The involvement of thiophene 1 -oxide as the key intermediate in the metabolism of the parent thiophene was directly validated by the isolation of thiophene 1-oxide dimers both in vitro (oxidation of thiophene with rat liver microsomes) and in vivo (isolation of 14 from rat urine) (Scheme 13) [22]. 

Scheme 13 Isolation of thiophene 1-oxide dimers both in vitro and in vivo in rats [22]...

The stability of o-sulfonylbenzonitrile oxides and their thiophene analogs probably depends on electronic factors. The same factors do not prevent dimerization, as can be seen from data concerning several differently substituted nitrile oxides of the thiophene series (103). Sterically stabilized 3-thiophenecarbonitrile oxides 18 (R = R1 = R2 = Me R = R2 = Me, R1 = i -Pr), when boiled in benzene or toluene, isomerized to isocyanates (isolated as ureas on reaction with aniline) while nitrile oxides 18 with electron-withdrawing substituents (R1 and/or R2 = SOiMe, Br) dimerized to form furoxans 19. 

The phenylation of thiophene with benzoyl peroxide gave a considerable amount of 2,2 -dithienyl one suggested mechanism involved the formation of 2-thienyl radicals by oxidation, and their subsequent dimerization. More recent studies indicate that the 2,2 -dithienyl is formed through an initial addition of benzoyloxy radicals to the thiophene nucleus followed by dimerization of the resulting radical and loss of two molecules of benzoic acid (Scheme 15). 

Novel tetrameric 7t-conjugated oligomers are produced by an intramolecular benzoin condensation from the dimeric thiophene, followed by air oxidation to give 28 <2003SM(135)85> in low yields (Equation 84). 

Although thermally allowed, the [2 + 4] cycloaddition of thiophene with nitrile oxides leads to low yields of products, even when thiophene itself is used as solvent (77JCS(P2)706, 78T3545). The yield is improved if the dimerization of the nitrile oxide is retarded. Both mono- and bis-adducts have been isolated. The most important feature of the cycloaddition, however, is the regiospecificity (Scheme 77). In contrast, benzo[6]thiophene gave a mixture of both possible regioisomers, although not in equal amounts. 

Photolysis of 3-methylbenzo[6]thiophene 1-oxide in benzene results in [2+2] cycloaddition-dimerization. Both products (Scheme 191) result from head-to-head dimerization. The yield is increased on using benzophenone sensitization (78TL999). The photodimerization proceeds from a triplet state precursor (81JOC4258). 

Photodimerizations have been observed in a variety of sulfur-containing heterocycles notable examples include the photodimerization of 2- and 3-ary lbenzo[b]thiophens,287 benzo[h]thiophen 1-oxide,288 benzo[h]thiophen 1,1-dioxide,289 and its 2-bromo289 and 2-methyl derivatives.290 All four possible dimers were obtained on irradiation of thio-chromone in aromatic solvents,291 and 1-thiauracil (345) is converted into... 

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