Benzothiophene derivatives

A remarkable case of a Meerwein reaction of phenylacetylene was reported by Leardini et al. (1985) in a new synthetic route to benzothiophene derivatives. Aryldi-azonium salts with a thioether group in the 2-position add phenylacetylene and substituted phenylacetylenes in the presence of metallic copper or iodide ion in acetone, or of FeS04 in DMSO (Scheme 10-60). The radical 10.21 formed initially is attacked intramolecularly by the sulfur atom of the thioether group to give the benzothiophene 10.22 in high yields (55-95%) as shown in (Scheme 10-60). Lear-... 

Dimethylene-2,3-dihydrothiophene (37, Figure 2.3) is the thiophene analog [38] of o-quinodimethanes and has been used to develop a Diels-Alder-based synthetic approach to benzothiophene derivatives. Generated in situ by treating the trimethylsylyl ammonium derivatives 38 or 39 with Bu4N F , it... 

We studied the effect of replacing the indole nucleus by other non-basic ring systems and prepared the benzofuran and benzothiophen derivatives by the standard route from the appropriate ketone. It may be seen from Table 7.5 that both derivatives were less active than ondansetron. 

Non-peptide inhibitors of thrombin (obtained by random screening procedures) include compounds based around benzothiophene (e.g. 155) and other ring systems and cyclic and linear oligocarbamate derivatives (e.g. 156). The benzothiophene derivative 155 showed antithrombotic efficacy in a rat model of thrombosis after infusion (ED50 2.3 mg/kg/h). The cyclic oligocarbamate tetramer 156 inhibited thrombin with an apparent K[ of 31 nM. 

SUMMARY OF PRACTICAL SYNTHESES OF THIOPHENE AND BENZOTHIOPHENE DERIVATIVES... 

The purpose of this section is to call attention to the best laboratory synthetic methods of producing thiophene and benzothiophene derivatives in yields satisfactory for utility. Since methods of constructing the parent ring systems have been surveyed earlier in the chapter, and the introduction of substituents on the parent ring systems has been discussed in Chapter 3.14, specific examples of the synthetic reactions have been discussed earlier. Industrial processes for the parent ring systems, thiophene and benzothiophene, have been adequately covered <52HC(3)i, 54HC(7)l). 

Irradiation of a benzothiophene derivative 63 gave the corresponding Dewar isomer 64 (95TL3177). 

The sulfur-heterocyclic compounds in the mid-distillate range are primarily the thiacyclane derivatives, benzothiophene derivatives and dibenzothiophene derivatives. with lesser amounts dialkyl-, diaryl- and aryl-alkyl sulfides. Sulfur compounds are significant contributors to the vacuum gas oil fraction (Ma et al., 1997). The major sulfur species are alkyl benzothiophene derivatives, dibenzo-... 

Brilliant blue dyes such as C.I. Disperse Blue 354, 48480 [74239-96-6] (12) [32] are produced from aminobenzaldehydes and benzothiophene derivatives. 

Sulfur removal still remains a useful synthetic tool for the preparation of important molecules. A benzothiophene derivative was the staiting point for the prepaition of 1,11-epithio steriod 52 that was converted to estradiol by the stereoselective removal of sulfur (W-7 Raney Ni) to provide the necessary 9a-H configuration <95TL4467>. Desulfurization of the thienothiophene derivative 53... 

The benzothiophene derivative raloxifene (Evista /Lilly) is a selective estrogen receptor modulator (SERM). Raloxifene produces its biological actions via modulation (both activation and blockade) of estrogen receptors that ultimately results in decreased resorption of bone. The bisphosphonate derivative alendronate (Fosamax /Merck), an inhibitor of osteoclast-mediated bone resorption, is also useful in the treatment of osteoporosis. Both raloxifene and alendronate are useful in the treatment of osteoporosis in postmenopausal women. 

Queiroz and coworkers [130] have devised a sequential Pd-catalyzed borylation-Suzuki coupling as the key step to thienocarbazole precursors. This one-pot processes begins with a Pd-catalyzed borylation using pinacolb-orane and a bromo benzothiophene derivative and concludes with the add-... 

It was known that 2-arylthio-3-methylcyclohexen-l-ones 15 underwent photocyl-ization in solution via the thiocarbonyl ylide intermediates 16 to yield the dihydro-benzothiophene derivatives 17 [42]. However, asymmetric induction was difficult... 

The 12-promoted cyclisation of o-(vinyl)thiobenzamides produces benzothiophene derivatives at 0 °C, but at reflux in MeCN these are converted into 1-imino-177-2-benzothiopyrans (Scheme 45) <07BCJ763>. 

The thiophene-bridged 4,4 -bipyridinium salts 149 and 150 can be prepared by alkylation of bis-bipyridinium cations <1999T4709>. The order of alkylation is crucial. Whereas in the thiophene derivative the xylene core is introduced in the last step, it is not possible to obtain the benzothiophene derivative in the same way due to the less stable bis-cation. Therefore, the benzothiophene unit is introduced in the last ring-closing step. 

In an earlier investigation by Kim [1] benzothiophene derivatives, (I), were prepared and used as components in photochromic polymers. 

Several groups have used this reaction in recent years to prepare biologically active molecules. Benzothiophene derivatives 93, prepared from Gewald products 92 in three steps via a palladium-mediated aromatization reaction, (Scheme 21) were tested for their antiproliferative activity and inhibition of tubulin polymerization [55]. Several compounds showed inhibitory effects against murine leukemia (L1210), murine mammary carcinoma (FM3A) and human T-lymphoblastoid (Molt/4 and GEM) cells. For most of the compounds, there was a positive... 

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