Thiophenes sulfonation

In a commercially useful reaction, sulfuric acid can be used to sulfonate thiophene at room temperature Benzene is not attacked under these conditions, and needs a reaction with oleum at 60 °C before it is sulfonated. Thiophene-2-sulfonic acid, formed in this way, dissolves in dilute alkali, allowing thiophene in coal tar distillate to be easily removed from benzene. Thiophene can be generated from its sulfonic acid by heating the latter in steam. 

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. 

ISOPRENE CYCLIC SULFONE (Thiophene, 2,5-dihydro-3-methyl-, 1-dioxide)... 

One of the problems associated with PEDOT-PSS is that the exact composition is generally difficult to determine. The blend that is obtained using poly(sodium-p-styrenesulfonate) (PSSNa), either chemically via Fe(III) salts [103] or electrochemically [134], has been investigated by means of energy dispersive x-ray (EDX) analyses, but the results were rather uncertain. The sulfonate/thiophene molar ratio J s/t was found to be in the range of 0.2-3 for samples made chemically [103] and —0.2 for those made electrochemically [134]. The electrical conductivity appears to increase with a decrease of Ps/n with typical values around 1 and 10 S cm for Rs/r = 2.5 and 0.25, respectively [103]. 

As unsaturated sulfones, thiophene-S,S-dioxides are employed as dienophiles and Michael acceptors as dienes, they undergo a variety of synthetically useful Diels-Alder reactions and cycloadditions [4], The reaction pathway is related to the structure of the dioxide, which can behave either as a diene or as a dienophile depending on the substitution pattern [5]. 

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. 

A/-sulfonated ayiridines have also been used in Friedel-Crafts reactions (qv) (63). The successful C-alkylation of the heteroaromatic compounds indole (qv) [120-72-9] (64—66) and thiophene [110-02-1] (67) with a2itidines has also been reported ... 

The classical structures of pyrrole, furan and thiophene (31) suggest that these compounds might show chemical reactions similar to those of amines, ethers and thioethers (32) respectively. On this basis, the initial attack of the electrophile would be expected to take place at the heteroatom and lead to products such as quaternary ammonium and oxonium salts, sulfoxides and sulfones. Products of this type from the heteroaromatic compounds under consideration are relatively rare. 

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... 

Thiophene, which is more stable to acid, is readily sulfonated by shaking with concentrated sulfuric acid at room temperature. Benzene is not reactive under these conditions and this is the basis for the purification of benzene from thiophene contamination. With all three heterocycles, if the a-positions are blocked, then sulfonation occurs at the /3-position. 

Indole is sulfonated under similar conditions to pyrrole though in this case the 3-sulfonic acid is formed. Benzo[Z>]thiophene is also sulfonated in the 3-position (71AHC(13)235). 

The principal electrophiles to attack ring sulfur are either oxidants or alkylating reagents. Thiophene sulfoxide and sulfone formation is discussed in Section 3.02.2.6. Alkylating agents capable of forming thiophenium salts include trimethyloxonium tetrafluoroborate (MeaO BF ) and alkyl fluorosulfonates (ROSO2F). The salts e.g. 87) are conveniently isolated as hexafluorophosphates (88). 

Thiophene-2-sulfonic acid is a strong acid, similar to benzenesulfonic acid. It forms a sulfonyl chloride with phosphoryl chloride which on reduction with zinc yields thiophene-2-sulfinic acid. 

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). 

Benzo[h]thiophene sulfone (229) reacts as a vinyl sulfone and forms adducts (228) and (230) when treated with mercury(II) acetate in methanol and with cyclopentadiene, respectively. 

Benzo[6]thiophene, methoxynitro-Meisenheimer complexes, 4, 816 Benzo[6]thiophene, 2-methyl-cycloaddition reactions, 4, 793 protonation, 4, 47 sulfonation, 4, 764 synthesis, 4, 879, 915 Benzo[6]thiophene, 3-methyl-cycloaddition reactions, 4, 793 1-oxide... 

Thiophene, 3,5-di-t-butyl-2-methyl-sulfonation, 4, 764 Thiophene, 2,4-dicarboxy-synthesis, 4, 870 Thiophene, 2,3-dichloro-synthesis, 4, 933 Thiophene, 2,5-dichloro-synthesis, 4, 933 Thiophene, 3,4-dichloro-... 

Thiophene-2-sulfonic acid, 5-acetamido-synthesis, 4, 932 Thiophene-3-sulfonic acid synthesis, 4, 932 Thiophene-2-sulfonyl chloride, synthesis, 4, 932... 

D. ci - -Thiabicyclo[4 .. Q]nonan S,S-Dioxide [Benzo[c]thiophene 2,2-dioxide, cis-octahydro-]. A solution of the sulfide (43.0 g., 0.303 mole) in 11. of ether is cooled to 0° and treated dropwise while magnetically stirred with 1.01. of 0.65iV ethereal monoperphthalic acid (0.65 mole). The mixture is kept overnight at 0°, after which time the precipitated phthalic acid is separated by filtration and the filtrate concentrated with a rotary evaporator. Bulb-to-bulb distillation of the residual oil at 0.05-0.1 mm. affords the sulfone as a eolorless liquid (48.5-50 g., 92-95%) (Note 11). This product is crystallized from ether-hexane to give a colorless solid, m.p. 39-41° (Note 12). 

Sulfonation with sulfur trioxide, pyridine sulfur trioxide, pyridine bis-sulfur trioxide, and dioxane sulfur trioxide, which are useful sul-fonating agents for acidophobic substances, have been applied to the thiophene seriesd At room temperature the 2-monosulfonic acid (isolated as the barium salt) is obtained in 86% yield. Higher temperatures lead to a disulfonic acid. However, sulfonation with chloro-sulfonic acid appears to be more convenient,as the sulfonyl chloride obtained can be used directly for the preparation of derivatives. 

Finally, certain 3-substituted compounds can be prepared by utilizing the - meta) directing powet (cf. Section IV,B) of some groups in the 2-position which afterward can be removed. 3-Nitrothiophene is prepared by nitration of 2-thiophenesulfonyl chloride and by removal of the sulfonic acid group of the 4-nitro-2-sulfonyl chloride formed with superheated steam. Another approach to 3-nitrothio-phene is to nitrate 2-cyanothiophene, separate the 4-nitro-2-cyano-thiophene from the 5-isomer, hydrolyze, and decarboxylate. A final method of preparation of 3-nitrothiophene is by simultaneous de-bromination and decarboxylation of 5-bromo-4-nitro-2-thiophene-carboxylic acid obtained through the nitration of methyl 5-bromo-2-thiophenecarboxylate. 

With weakly directing — I + M-substituents such as the halogens, the a-directing power of the ring sulfur dominates and substitution appears to occur exclusively in the 5-position. 2-Chloro-, 2-bromo-, and 2-iodo-thiophene are sulfonated both with chlorosulfonic aeid and in the 5-position. In the chlorination of chloro-... 

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-... 

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