Aryl-substituted thiophenes

Oxidation of cyclic sulfites to sulfates was accomplished with RuClj/aq. Na(IO )/CH3CN-CCiyO°C and a large-scale oxidation of D-mannitol-l,2 5,6-diacetonide-2,3-cyclic sulfite to the sulfate described (Fig. 5.17) [437]. The system RuO /aq. Na(10 )/CHCl3 converted cyclic sulfite diesters to the sulfates (Fig. 5.18) [438]. Oxidations of thiophene and aUcyl- and aryl-substituted thiophenes by RuCyaq. Na(ClO) were compared with similar reactions effected by stoich. [MnOJ- [439]. 

Oxidations of a number of thiophenes and a wide variety of alkyl- and aryl-substituted thiophenes by RuCyaq. Na(ClO) have been compared with similar oxidations effected stoicheiometrically by [MnO ]", the aim being the destruction of these compounds for environmental reasons. Some were totally oxidised to sulfate, but in many cases end-products were not identified, though 2-ethylthiophene gave 2-acetylthiophene and 2-n-butylthiophene gave 2-butyroylthiophene [115],... 

Substituted Thiophens. Aryl-substituted thiophens cannot be planar, and several theoretical studies have been made to predict preferred conformations. EHT computations for 2- and 3-phenylthiophen (40) predict an angle of distortion of 37° between the two planes of the cyclic ir-systems the electron distribution in these conformations was calculated by the CNDO/2-approach and comparison was made between the theoretical and experimental dipole moments. The calculations were later extended to (41) and its hetero-analogues. Bond-length calculations predict a very long bond between the heterocycles, which largely preserves the geometries of individual furan and thiophen ring systems. 

A number of cycloalkyl-, vinyl-, aryl-, and benzyllithium compounds (predominantly benzyl-lithiums) are converted into fluoro derivatives in good to excellent yields, e.g. formation of 4, 5, and 6 19 however, when this method was applied to the synthesisof 3-fluorobenzocyclobutene from the lithium salt a violent explosion occurred when the reaction mixture was warmed from — 70 C to room temperature.20 Various fluoro-substituted thiophenes 7 are obtained when the starting compounds (thiophene, 2-methylthiophene, etc.) arc transformed with al-kyllithium compounds to the corresponding lithium derivatives then fluorinated with perchloryl fluoride at 0 C.21 Potassium tricyanomethanidc is converted at —15 C in triglyme into tricyanofluoromethane in 81 % yield.22... 

Methyl- and 2-aryl-substituted benzo[fc]thiophenes (26) can be synthesized starting from o-toluenethiol in three steps, which involves the intramolecular addition of thiols, produced by acid hydrolysis, to the carbonyl group followed by dehydration as the final step (Scheme 3) (91JHC173). 

Hinsburg first reported that various a-dicarbonyl compounds (256) condensed with thiodiglycolic esters in the presence of alcoholic sodium ethoxide to give various substituted thiophene-2,5-dicarboxylic esters (257). R1 and R2 in (256) could be H, OH, alkyl, OR, aryl or carboxyl groups o-quinones will also condense. If the condensation is carried out in aqueous alcohol, as is the case when glyoxal (256 R1 = R2 = H) is used, the thiophene-2,5-dicarboxylic acid is isolated directly. Pyruvic acid gives the half-ester of (257 R1 = Me, R2 = OH). The earlier work has been reviewed (52HC(3)l). 

When benzyl halides, benzylidene halides, benzotrichloride, or aryl-substituted haloethanes are heated with sulfur, complex mixtures containing thiophenes, benzo[6]thiophenes, and other condensed... 

In 1949, Werner187 announced the synthesis of several 3-alkyl- and 2,3-dialkylbenzo[6]thiophenes by the cyclodehydration of (arylthio)-acetones with phosphorus pentoxide or zinc chloride [Eq. (5)]. The reaction has since been widely used to synthesize alkyl- and aryl-substituted benzo[6]thiophenes (Table IV). Cyclodehydration proceeds most conveniently with PPA,297 298 but concentrated sulfuric acid,299,300 hydrofluoric acid, 299 aluminum chloride in benzene301 or chlorobenzene,302 zinc chloride and hydrochloric acid,303 a melt of aluminum and sodium chlorides,304 and phosphorus pentoxide in boiling o-dichlorobenzene 305 have been less widely used. 

Ravikanth and coworkers have synthesized (S-pyrrole-substituted 21,23-dithiaporphyrins by refluxing 21,23-dithiaporphyrin with NBS in chloroform. (5-Aryl-substituted thiaporphyrin 238 (Scheme 94) has been obtained by condensing 3,4-disubstituted pyrroles 237 with thiophene diol 222 (X=S) under mild acid conditions (00CL480). 

Arylation of furan and thiophene with arylhydrazine (40) and Mn(OAc)3 gives 2-aryl substituted furan and thiophene (41) as shown in eq. 5.22. 

Cation 6 adds to furan, pyrrole, thiophene and some of their 2,4-dimethyl derivatives bearing a free a-position, in MeCN as solvent. Furan is the least reactive substrate giving 2-arylated product in 32% yield, whereas under the same reaction conditions the sulfur analogue provides 54% of 2-substituted-thiophene 9c (Scheme 10.37). Pyrroles are the most reactive heterocycles, and 2-arylated products 9a-b are found with 64% and 75% yields using pyrrole and 2,4-dimethyl-pyrrole, respectively. Only with 2,5-dimethylated furan and pyrrole, will arylation... 

The photoisomerization of 2-substituted thiophenes into the corresponding 3-substituted derivatives is a common pathway observed for both 2-aryl and 2-alkylthiophenes [4]. However, for synthetic applications, a significant example can be recognized in the photoisomerization of 2-arylthiophenes 33 into the corresponding 3-aryl derivatives 34 by the large-scale irradiation in Et20 with a high-pressure Hg lamp (Scheme 12.10) [28]. 

The direct arylation (Heck) of thiophene by means of aryl halides and substituted thiophenes has been extensively studied by Lemaire and co-workers <1997TL8867, 1998JOM(567)49,2002TL1829, 2004T3221>. EWGs facilitate the reaction. With a 3-substituted thiophene, the major product was the 2-aryl derivative with 2-substituted thiophenes, the only product was the 5-aryl derivative. Yields ranged from 40% to 95%. The reaction has been extended to the synthesis of 2-arylbenzo[3]thiophenes as well (Equations 22 to 25). The yield improved on replacing the quaternary ammonium bromide by dicyclohexyl-18-crown-6. 

The boroxines could then be subjected to Suzuki coupling with aryl, vinyl, or benzyl halides. Suzuki coupling with tri- -butylstannyl chloride also gave the tri- -butylstannyl-substituted thiophenes 221. These can form the starting materials for further transformations. The carbonylative coupling with halides resulted in the formation of ketones tin-lithium exchange followed by reaction with electrophiles led to a host of other useful products (Scheme 65). 

In the same manner 2-phenylthiazole and 2,3-substituted thiophene derived imino-phosphoranes react with one eqivalent of aryl isocyanate to give fused 1,3-diazepines in 50-72 % yield, while with two equivalents aryl isocyanate the [2-1-2] cycloadducts are obtained in 50-61% yield. ... 

Solid phase synthesis of highly substituted thiophene derivatives 15 using a cyclic malonic acid ester resin 14 was also reported. Highly pure thiophene derivatives were reported to have been prepared by this solid phase synthesis <0314851>. While alkyl or aromatic substitutions on the P position to the carbonyl yielded the corresponding 5-alkyl/aryl substituted 2-acyl aminothiophene, acetaldehyde did not produce the corresponding 2,3- disubstituted thiophene. 

In the presence of hexafluoro-2-butyne, 2,3-di(trifluoromethyl) thiophene was isolated in addition to the above products, formed by the addition of C2H2S to the triple bond of 2-butyne. Methyl substitution either in the 4- or 5-position leads to the formation of only one thiophene, viz. 2,3-trifluoromethyl 5-methylthiophene in the presence of hexafluoro-2-butyne, suggesting the intermediacy of methyl thiirene. Aryl-substituted 1,2,3-thiadiazoles have been investigated by Kirmse and Horner and by Huisgen . 

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