Benzothiophenes

Patent Pentacyclic Compounds, Intermediates, Processes, Compositions, 

To 2-dimethylamino-6-methoxybenzo-[b]-thiophene (96.5 mmol) dissolved in 200 ml tetrahydrofuran was added 200 ml 1M HCl and the mixture refluxed 3 hours. Once cooled, the layers were separated, the aqueous layer extracted with 300 ml CH2CI2, washed with 250 ml water, dried, and concentrated. The residue was recrystallized using ethyl alcohol and the product isolated in 80% yield, mp = 80-82°C. H- and C-NMR, IR, and elemental analysis data supplied. 

To a solution of the product from Step 1 (111 mmol) dissolved in 100ml ethyl alcohol and 50 ml CH2CI2 was added 4-methoxy-salicylaldehyde (115 mmol) and triethylamine (5.6 mmol) and the mixture stirred at ambient temperature overnight. The mixture was diluted with 1L cold hexane, filtered, recrystallized, and the product isolated in 82% yield. and C-NMR, IR, and elemental analysis data supplied. 

The product from Step 2 (14.3 mmol) and 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (15mmol) were dissolved in 100ml dichloroethane, heated briefly to 80°C, and filtered hot. The precipitate was rinsed with CH2CI2, combined, and concentrated. The residue was dissolved in hot CH2CI2, filtered, and re-concentrated. The product was isolated in 88% yield after being recrystallized from toluene. H- and C-NMR, IR, and elemental analysis data supplied. 

The product from Step 3 (38.4 mmol) was dissolved in 220 ml CH2CI2 and ethanethiol (192 mmol) followed by the portionwise addition of AICI3 (288 mmol). The mixture stirred at ambient temperature 5 hours, cooled to 0°C, and was then quenched with 250 ml apiece THF and NaHCOj. The mixture was further diluted with IL THF, the layers separated, and the aqueous layer washed with THF. The combined organic layers were dried, concentrated, and 102% of crude diphenol intermediate isolated. Thereafter, the crude product was slurried in 200 ml CH2CI2 and triethylamine (200 mmol), t-butyldimethylsilylchloride (134.4 mmol) added, and the mixture stirred 5 hours at ambient temperature. After dilution with 600 ml hexane, the mixture was washed with brine and the aqueous layer extracted with 300 ml hexane. 

Raloxifene (Evista ) has been developed by Lilly and is considered a second-generation SERM. The compound can be regarded as a planar variant of the 

Piperazine analogs of raloxifene were described by the Shanghai Institute for Biological Sciences [124]. The unsubstituted piperazine 94 showed 19-fold selectivity 

Synthesis of functionalized benzo[fo]thiophenes is of substantial interest as this heterocyclic framework is often found in biologically active compounds and 

Nakamura reported a single example of the fairly efficient Rh(II)-catalyzed 4 + 1 benzothiophene synthesis, utilizing a one-pot reaction initiated by the S-H insertion of thiophenol 83 into the metallocarbenoid center derived from a-diazophosphonate 84. A subsequent base-mediated intramolecular Horner-Wadsworth-Emmons 

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The presence of thiophene and its derivatives in crude oils was detected in 1899, but until 1953, the date at which the methyl-thiophenes were identified in kerosene from Agha Jari, Iran crude oil, it was believed that they came from the degradation of sulfides during refining operations. Finally, their presence was no longer doubted after the identification of benzothiophenes and their derivatives (Table 8.9), and lately of naphthenobenzothiophenes in heavy cuts. 

The major part of the sulfur contained in crude petroleum is distributed between the heavy cuts and residues (Table 8.10) in the form of sulfur compounds of the naphthenophenanthrene or naphthenoanthracene type, or in the form of benzothiophenes, that is, molecules having one or several naphthenic and aromatic rings that usually contain a single sulfur atom. 

Analogous compounds derived by fusion of a benzene ring to a pyrrole furan or thio phene nucleus are called indole benzofuran and benzothiophene... 

Biological processes are also being studied to investigate abiHty to remove sulfur species in order to remove potential contributors to acid rain (see Air pollution). These species include benzothiophene-type materials, which are the most difficult to remove chemically, as weU as pyritic material. The pyrite may be treated to enhance the abiHty of flotation processes to separate the mineral from the combustible parts of the coal. Genetic engineering (qv) techniques are being appHed to develop more effective species. 

Benzo[b]thiophene-2,3-quinone, 5-chloro-oxidation, 4, 824 Benzothiophenes, 4, 863-934 biological activity, 4, 911-913 intramolecular acylation, 4, 761 mass spectrometry, 4, 739 metabolism, 1, 242 phosphorescence, 4, 16 reactivity, 4, 741-861 spectroscopy, 4, 713-740 structure, 4, 713-740 substituents reactivity, 4, 796-839... 

Thiophene-2-carbaldehyde, 3-bromo-synthesis, 4, 81 Thiophenecarbaldehydes benzothiophene synthesis from, 4, 906 reactions, 4, 807 synthesis, 4, 148 Wittig reactions, 4, 807 Thiophene-2-carb aldehydes bromination, 4, 753 conformation, 4, 33 halogenation, 4, 753 reactions, 4, 72-73 reactivity, 4, 72-73 reduction, 4, 776 Thiophene-3-carb aldehydes conformation, 4, 33 reactivity, 4, 72... 

Thiurets — see 1,2,4-Dithiazolidines, diimino-Thonzylamine antihistamine, 3, 153 Thorpe reaction benzothiophenes from, 4, 876 Thorpe-Ziegler cyclization, 2, 74 Three-membered heterocyclic compounds basicity, 7, 23... 

The only known reaction of a furan with a dihalocarbene is that recently reported between benzofuran and dichlorocarbene in hexane at 0°. The initial adduct (7) could not be isolated but on hydrolysis gave the ring-expanded product 8, possibly via 9, in 15% yield. Benzothiophene was recovered in 92% yield under the same conditions. 2,5-Dihydrofuran reacted with dichloro- and dibromo-carbene to give the products of allylic insertion, 2-dihalogenomethyl-2,5-dihydrofuran, as well as the normal addition products. ... 

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