Thiophene-S-oxides

The 1,3-dipolar cycloaddition of mesitonitrile oxide 575 to benzo[h]thiophene S-oxides 576 in non-stereoselective and both syn and anti adducts 577 are obtained674,675 (equation 366). 

Mansuy D, Valadon P, Erdelmeier I, et al. Thiophene S-oxides as new reactive metabolites formation by cytochrome P450 dependent oxidation and reaction with nucleophiles. J Am Chem Soc 1991 113(20) 7825—7826. 

Only [4 + 2] cycloadducts 155 a, b were formed and isolated in 48 and 43% yield, respectively, in the reaction of bicyclopropylidene (1) with thiophene S-oxide derivatives 154 a, b under high pressure (Scheme 33) [128]. 

The rearrangement (automerization) of Dewar thiophene S-oxide (61), observed by 19F NMR, occurs so much more rapidly than that of the corresponding episulfide that special mechanisms have been invoked. The one which involves a zwitterionic intermediate (Scheme 108) is favored over a pseudopericyclic sulfur-walk mechanism in which the electrons of the carbon-sulfur cr-bond and the pair of electrons on sulfur exchange places as the sulfur atom migrates around the ring (80JA2861). 

When standing in solution, a slow conversion of the thiophene S-oxide takes place and after some time a noticeable amount of the corresponding thiophenes is formed, among other products. The conversion is accelerated upon exposure to light. In order to understand the conversion processes under these conditions, the authors undertook a study on the photochemistry of thiophene S-oxide. 

The photolysis of 682 in carefully dried and distilled CD2CI2 yielded a mixture of products, which is a little different in relative composition from that of the photoreaction in nondried CD2CI2. Most noticeable is the higher yield of the purely deoxygenated products, 683 (25%), and a lower yield in the total amount of hydroxylated products, 684 and 685 (27 and 12%). The formation of hydroxylated products in dried solvents, however, means that oxygen in the hydroxyl/alkoxymethyl moieties of the products stems from thiophene S-oxides. The addition of ethanol (5 equiv.) to the reaction mixture in nondried CD2C12 leads to the formation of 2-ethoxymethyl-5-... 

Piperidine and dibenzylamine as well as p-methoxythiophenol have been examines as readily oxidizable additives. In the case of the amines, no product resulting from the oxidation of the amines can be isolated. However, the conversion of the thiophene S-oxide to the thiophene is quantitative. 

The photoirradiation of tetrakis(p-tolyl) thiophene S-oxide (686) in the presence of triphenylphosphine was carried out. Here, again the corresponding thiophene 687 was formed, but also significant amount of tri-phenylphosphide oxide could be isolated, giving evidence of a direct transfer of the oxygen from a thiophene S-oxide to another species of molecule. 

When tetrakis(p-tolyl)thiophene S-oxide is use, no furan could be isolated from the reaction. When photoirradiated 693-6955 deoxygenate readily. The bis(thiophene S,S-dioxide 696 is not photoreactive under the condition and does not deoxygenate. 

Figure 6 Selected calculated bond lengths (A) of thiophene and thiophene S-oxides <1996JOC1275>.

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. 

Dansette, P. M., Thang, D. C., el Amri, H., Mansuy, D. Evidence for thiophene-S-oxide as a primary reactive metabolite of thiophene in vivo formation of a dihydrothiophene sulfoxide mercapturic acid. Biochem. Biophys. Res. Common. 1992, 186, 1624-1630. 

Ab initio MO calculations on 3-formyl-(5 2-isoxazoline-BF3-complex suggests that s-trans conformation is preferred over s-cis conformation. Nucleophiles attack the stable s-trans conformer from the opposite side of the C-4 substituent, giving the respective anti adducts <93T7637>. The regioselectivity of the 1,3-dipolar cycloadditions of mesitonitrile oxide with benzo[b]thiophene S-oxide and S,S-dioxide yielding only 2,3-dihydrobenzo[b]thieno[2,3-d]isoxazolines, is discussed in terms of frontier MO interactions on the basis of photoelectron spectra and CNDO/S calculations <82JOC2461>. 

Elimination from dihydrobenzo[c]thiophene S -oxides has been successfully applied, as for isoindoles, for the preparation of benzo[c]thiophenes, including the parent compound and isolable 4,6,7-tri-t-butylbenzo[c]thiophene. ... 

Benzolb]thiophen S-Oxides. Benzolb]thiophen 1,1-dioxide... 

Zirconium metallacycles were found to serve as the precursor compound for the preparation of a variety of main group heterocycles including thiophenes and their 5 -oxides. The zirconium metallacycles (275) and (277) were prepared by treatment of 2,8-decadiyne and diphenylethyne with zirconocene dichloride in the presence of Bu"Li and allowed to react with disulfur dichloride and thionyl chloride, respectively, to give the bicyclic thiophene (276) and the thiophene S -oxide (278)... 

Thiophene is an aromatic heterocycle thiophene-1-oxide (or thiophene-S-oxide) is stiU aromatic, whereas thiophene-1,1-dioxide (or thiophene-S,S-dioxide), having both electron pairs engaged in the formation of sulfur-oxygen bonds, is no longer aromatic [1-3]. 

Thiophene-S-oxides are less stable than thiophene-5,5-dioxides and have been used as synthons for a wide range of pharmaceutical applications and investigated for their biological activity [6], Whereas the parent unsubstituted thiophene-5,5-dioxide has been isolated and characterized at low temperature [4], the corresponding unsubstituted thiophene-5-oxide has never been prepared, due to spontaneous dimerization. 

Dimerization of thiophene S-oxide (23) via a Diels-Alder reaction was observed when ticlodipine (22) was oxidized by CYP2C19 or CYP2D6 [68] (Scheme 12.7). 

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