Sulfonation of Thiophene

Sulfonation of thiophene by sulfuric acid is very well known [144]. Thiophene-2-sulfonic acid was one of the first isolated compounds in the thiophene family 

Various reagents for sulfonation are described in reviews [21,22]. Nowadays the most usual method for thiophene sulfonation is application of chlorosulfonic acid, in many cases together with PCI5 [148]. 

Several thiophene-2- and thiophene-3-sulfonamides were synthesised and investigated as potent compounds against HCTl 16 tumour cells (compounds 64 and 65 in Fig. 3) [150]. Thiophene-2-sulfonamides 66 and 67 were obtained as bioisosters for investigation of CXCR2 and CXCRl chemokine receptor antagonists [151]. 

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The text states that electrophilic aromatic substitution in furan, thiophene, and pyrrole occurs at C-2. The sulfonation of thiophene gives thiophene-2-sulfonic acid. 

When benzene is prepared from coal tar it is contaminated thiophene from which it cannot be separated by distillation because of very similar boiling points Shaking a mixture of benzene and thiophene with sulfuric acid causes sulfonation of the thiophene ring but leaves benzene untouched The sulfonation product of thiophene dissolves m the sulfuric acid layer from which the benzene layer is separated the benzene layer is then washed with water and distilled Give the structure of the sulfonation product of thiophene... 

Sulfonated styrene—divinylbensene cross-linked polymers have been appHed in many of the previously mentioned reactions and also in the acylation of thiophene with acetic anhydride and acetyl chloride (209). Resins of this type (Dowex 50, Amherljte IR-112, and Permutit Q) are particularly effective catalysts in the alkylation of phenols with olefins (such as propylene, isobutylene, diisobutylene), alkyl haUdes, and alcohols (210) (see Ion exchange). Superacids. 

The range of preparatively useful electrophilic substitution reactions is often limited by the acid sensitivity of the substrates. Whereas thiophene can be successfully sulfonated in 95% sulfuric acid at room temperature, such strongly acidic conditions cannot be used for the sulfonation of furan or pyrrole. Attempts to nitrate thiophene, furan or pyrrole under conditions used to nitrate benzene and its derivatives invariably result in failure. In the... 

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

The sulfonation of 2-acetamidomcthylthiophene and of 2-acetami-dothiophene attracted considerable interest in connection with work on potential thiophene chemotherapeutics, although from this point of view these investigations have given little reward. Sulfonation of 2-acetamidomethylthiophene with chlorosulfonic acid occurs in the 5-position. At room temperature 100% sulfuric acid yields 80% 5-acetamido-2-thiophcnesulfonic acid. With chlorosulfonic acid sulfonation cannot be stopped at the monosubstitution stage and 2-acetamido-3,5-thiophene disulfonyl chloride is obtained. - In recent Russian work the isolation of a monosulfonated product is claimed, however. With the activating -f-M-substituents, disubstitution, which is easily achieved, always leads exclusively to 3,5-disub-... 

Melles and Backer " found, from a study of the oxidation of substituted thiophenes with perbenzoic or peracetic acid, that sulfones could be obtained from polysubstituted methyl- and phenyl-thiophenes and that the presence of electron-attracting groups, such as nitro, hindered the oxidation. Oxidation of thiophene - led to a product which was formed through a Diels-Alder reaction between the intermediate thiophene sulfoxide (211) and thiophene sulfone (212) and for which two alternative structures, (213) or (214), were suggested. Similar sesquioxides were also obtained from 2- and 3-methylthiophene and 3-phenylthiophene. The structures were not proved. Bailey and Cummins synthesized thiophene-1,1-dioxide... 

Oxidation of thiophene with Fenton-like reagents produces 2-hydroxythiophene of which the 2(570 One isomer is the most stable (Eq. 1) <96JCR(S)242>. In contrast, methyltrioxorhenium (Vn) catalyzed hydrogen peroxide oxidation of thiophene and its derivatives forms first the sulfoxide and ultimately the sulfone derivatives <96107211>. Anodic oxidation of aminated dibenzothiophene produces stable radical cation salts <96BSF597>. Reduction of dihalothiophene at carbon cathodes produces the first example of an electrochemical halogen dance reaction (Eq. 2) <96JOC8074>. 

Rhodococcus sp. Strain T09 A Rhodococcus strain T09 was isolated by enrichment on media-containing BT. The desulfurization mechanism of this organism was reported to be similar to Gordonia sp. 213E due to the observation of similar intermediates however, the substrate specificity was different. The strain T09 could use 2-methyl, 3-methyl and 5-methyl BT apart from BT as sole source of sulfur for growth, but not 7-methyl or ethyl derivatives. Additionally, it could also use methyl thiobenzothiazole, marcaptobenzothiazole, as well as benzene sulfide, benzene sulfonate, biphenyl sulfinate, dimethyl sulfate, dimethyl sulfone, dimethyl sulfide, methane sulfonic acid, thiophene, and taurine as sole sulfur sources. However, it could not grow on DBT or DBT sulfone. 

Oxidation of thiophene and its derivatives was studied using hydrogen peroxide (H2O2), t-butyl-hydroperoxide and Ti-Beta redox molecular sieve as selective oxidation catalysts. A new reaction pathway was discovered and investigated using C-13 NMR, GC, GC-MS, HPLC, ion chromatography, and XANES. The thiophene oxidized to thiophene-sesquioxide [3a,4,7,7a-tetrahydro-4,7-epithiobenzo[b]-thiophene 1,1.8-trioxide] and the sesquioxide oxidized mostly to sulfate. 2-Methyl-thiophene and 2,5 dimethylthiophene also oxidized to sulfate and sulfone products. The Benzothiophene oxidation product was sulfone. This proposed new reaction pathway is different from prior literature, which reported the formation of thiophene 1,1-dioxide (sulfone ) as a stable oxidation product... 

Organic sulfur compounds are present in gasoline and diesel. With the increased emphasis on the requirement for more environmentally friendly transportation fuels [1], oxidative desulfurization, using H202 and redox-molecular sieves [2,5,6,7], has been studied and shown to significantly reduce the sulfur content of gasoline and diesel. The reaction of thiophene and its derivatives were successfully converted to oxidized compounds, but the identification of oxidized compounds was not simple because the concentrations of individual sulfur compounds were low. Most of the previous literature has reported sulfone formation. 

The oxidation of thiophene and its derivatives with H202 was studied using a Ti-Beta molecular sieve. The oxidation product is very dependent from the aromaticity of model compounds. The thiophene oxidation product was mostly sulfates and the benzothiophene oxidation product was benzothiophene sulfone. Oxidation of mono and di-alkyl thiophenes also produced sulfates and sulfones. The diffusivity and aromaticity of the relevant sulfur compounds, intermediates and stable product, as well as the proposed new mechanism of oxidation will be discussed. This proposed new reaction pathway is different from current literature, which reports the formation of sulfones as a stable oxidation product. 

Thiophene-1-oxide and 1 -substituted thiophenium salts present reduced aromaticity.144 A variety of aromaticity criteria were used in order to assess which of the 1,1-dioxide isomers of thiophene, thiazole, isothiazole, and thiadiazole was the most delocalized (Scheme 46).145 The relative aromaticity of those molecules is determined by the proximity of the nitrogen atoms to the sulfur, which actually accounts for its ability to participate in a push-pull system with the oxygen atoms of the sulfone moiety. The relative aromaticity decreases in the series isothiazole-1,1-dioxide (97) > thiazole-1,1 -dioxide (98) > thiophene-1-dioxide (99) then, one has the series 1,2,5 -thiadiazole-1,1 -dioxide (100) > 1, 2,4-thiadiaz-ole-1,1-dioxide (101) > 1,2,3-thiadiazole-1,1 -dioxide (102) > 1,3,4-thiadiazole-l,1-dioxide (103) in the order of decreasing aromaticity. As 1,2,5-thiadiazole-1,1-dioxide (100) was not synthesized, the approximations used extrapolations of data obtained for its 3,4-dimethyl-substituted analogue 104 (Scheme 46). 

The reaction of butadiene with the sulfone of 3-benzo[6]thiophene-carboxylic acid under Diels-Alder conditions gives the adduct (32). Catalytic reduction over platinum oxide removes the 2,3-double bond. 

Calculations of the UV spectra of the isomeric thieno-thiophenes " indicate that, as in the case of thiophene,3d and higher sulfur orbitals hardly affect the electronic spectra of sulfur-containing condensed heteroaromatics. In the case of sulfones of thienothiophene 2 and dithienothiophenes 5-10 in which the sulfur... 

The by far more common and preparatively valuable dioxirane oxidation of divalent sulfur substrates is that of sulfides, to produce either sulfoxides or sulfones . Since sulfoxides are considerably less reactive than sulfides, the reaction outcome may be conveniently controlled by the stoichiometry of the oxidant For example, in the low-temperature oxidation of thiophene by an excess of DMD, the corresponding 1,1-dioxide (sulfone) has been obtained, albeit in low yield (equation 20). This is the first preparatively useful method for isolating this elusive sulfone, which also accentuates the importance of the neutral and anhydrous conditions under which the oxidations with the isolated DMD may be conducted. 

Thiophene is very easily sulfonated 95% H2SO4 at 30-40 °C converts it to the 2-sulfonic acid in a few minutes. Thiophene-2-sulfonyl chloride can be easily prepared by the action of chlorosulfonic acid on thiophene. Mono- and di-sulfonic acids of thiophene have been prepared by sulfonating thiophene with S03 or pyridine-sulfur trioxide (63AHCd)t). Sulfon-ation of 2-methyl-3,5-di-t-butylthiophene gives 2-methyl-5-t-butylthiophene-3-sulfonic acid (63AHC(l)l). However, 2,5-di-r-butylthiophene is monosulfonated normally at the 3-position (63AHC(l)l) under forcing conditions 2-(-butylthiophene-3,5-disulfonic acid is obtained. 

Sulfonation of benzo[6]thiophene seems to give the 3-sulfonic acid as the major monosulfonated product, with minor amounts of the 2-isomer (70AHQ11)177). Sulfonation or chlorosulfonation of 2- or 3-methylbenzo[6]thiophene takes place in the free thiophene position. 

Hydroxylamine-O-sulfonic acid converts thiophene-2-carbaldehyde into the nitrile in high yield under mild conditions. 3-Azidothiophene-2-carbonitrile has been prepared thus and used for synthesizing many types of fused thiophenes (80JHC1765). Vapour-phase ammoxidation of thiophene-2-carbaldehyde to the nitrile has also been described (78CPB2838) the Mo-Bi-Sb (molar ratio 3 5 2) mixed oxide catalyst was found most suitable. 

Sulfonic acid and sulfone derivatives of thiophenes and benzo[b]thiophenes 932... 

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