Synthesis of benzothiophene derivatives by pdcatalyzed or. Preparation of 3amino6fluoro benzothiophene 2carbohydrazide 2 to a stirred solution of methyl3amino6fluoro benzothiophene 2carboxylate 1 2. The bocprotected intermediate resin r1 was synthesized using previously described solidphase peptide synthesis methods figure 9. Benzobthiophene is used in the preparation of 2thianapthenylphenyllithium, via metalation by nbutyllithium. The reaction of substituted buta1enes with potassium sulfide enables an atom economical, and transitionmetalfree synthesis of thiophenes via cleavage of multiple ch bonds. Synthesis and biological evaluation of novel benzothiophene. A new synthetic method for 1 benzothieno 3,2b1 benzothiophene derivatives btbts was developed.
A new synthetic method for 1benzothieno3,2b1 benzothiophene derivatives btbts was developed. Iodinecatalyzed cascade reactions of substituted thiophenols with alkynes under metal and solvent free conditions enable the synthesis of benzothiophene derivatives in good yields. Benzothiophene finds use in research as a starting material for the synthesis of larger, usually bioactive structures. Synthesis, molecular docking, and pharmacological evaluation. A new domino reaction between thioaurones and malononitrile has been reported. Expeditious synthesis of 3aryl benzothiophene a raloxifene. The construction of heterobiaryls was carried out through electrophilic activation of the arylheteroaryl.
May 2017, accepted 07 jul 2017, published 06 sep 2017. Dibenzothiophene dbt is the organosulfur compound consisting of two benzene rings fused to a central thiophene ring. It is also used in the manufacturing of dyes such as thioindigo. Benzothiophene and its derivatives have been reported to show activity in treating various medical conditions, such as hyperlipidemia, breast cancer, and uterus cancer charles et al. Synthesis and evaluation of a series of benzothiophene. A convenient synthesis of benzothiophene derivatives. Synthesis and biological evaluation of novel benzothiophene derivatives article pdf available in journal of chemical sciences 9 september 2018 with 151 reads how we measure reads. A metalfree approach combining sulfoxidedirected metalfree ch crosscouplings with tuneable electrophilemediated heterocyclizations and carbocyclative dimerizations, allows expedient access to benzothiophenebased systems that are components of important materials or are proven organic materials in thei. Synthesis of benzothiophene carboxamide derivatives from unsubstituted aminobenzophenones. Synthesis of benzothiophene and indole derivatives through metalfree propargylallene rearrangement and allyl migration. Gadada naganagowda, patchanita thamyongkit, amorn petsom research center for bioorganic chemistry, department of chemistry, faculty of science, chulalongkorn university, bangkok 10330, thailand. Sulfoxidedirected metalfree crosscouplings in the expedient synthesis of benzothiophenebased components of materials andrewj. A novel and efficient method for the synthesis of difluoroalkylated benzofuran, benzothiophene, and indole derivatives via palladiumcatalyzed aryldifluoroalkylation of 1,6enynes with ethyl difluoroiodoacetate and arylboronic acids has been established. Evaluation of benzothiophene carboxamides as analgesics.
Pdf benzothiophene derivatives were synthesized regioselectively using coupling reactions and electrophilic cyclization. Synthesis of benzothiophene and indole derivatives through metalfree. Removal of benzothiophene from organic solution by a combined photodegradationadsorption method 17 1. A metalfree approach combining sulfoxidedirected metalfree ch crosscouplings with tuneable electrophilemediated heterocyclizations and carbocyclative dimerizations, allows expedient access to benzothiophenebased systems that are components of important materials or are proven organic materials in their own right. Benzothiophenes heterocyclic building blocks sigmaaldrich. Thiophene is ppt on a modest synthesis of around alkylthiols to provide thiophene trifluoroborates in high pdf with. Regioselective synthesis of c3 alkylated and arylated benzothiophenes. Beilstein journal of organic chemistry 2017, , 18661870. Phosphinefree palladiumcatalysed direct c2arylation of. These findings suggest that compounds 4, 6, 8, and 9 inhibit cox. College of biological, chemical sciences and engineering, jiaxing university, jiaxing 314001, p. The present work details the journey towards development of a simple, cost effective, environmentally friendly synthesis of raloxifene hydrochloride 1. Specialized thiophenes can be synthesized similarly using lawessons reagent such as a bright counter and display endosymbiotic hypothesis quizlet medical terminology on a synthesis than pdf. Synthesis and physical properties of thiophene and its homologs.
Metalfree c3 ch arylation of benzothiophene soxides. We anticipated that a lewis acidtransition metal free synthesis of acyl benzothiophenes could provide an easy access to a library of benzothiophene based analogues of potential biological interest. Encouraged by these results, we decided to adopt a similar strategy for the acylation of benzothiophene. This paper deals with the sonochemical water treatment of polycyclic aromatic sulfur hydrocarbons pashs, one of the most common impurities found in waste water coming from petroleum industry. The present method consists of iodocyclization of 1,2bis2methylthiophenylethynes and photolysis of 3iodo2methylthiophenylbenzobthiophenes. Here we set out an unprecedented procedure for the formation of benzothiophenes by the twofold vicinal c. Benzothiophene is regarded as a privileged class of structure showing a wide spectrum of biological activities. Synthesis of c2 substituted benzothiophenes via an. The reaction proceeds via basepromoted propargylallenyl rearrangement followed by cyclization and allyl migration. A benzothiophene in which the benzene ring is fused to the thiophene ring across positions 3 and 4.
The reaction of substituted buta1enes with potassium sulfide enables an atom economical, and transitionmetal free synthesis of thiophenes via cleavage of multiple ch bonds. Their aminolysis resulted in opening of the 1,3dioxane ring and formation of 4carbamoyl7methyl2,3,3a,4,5,6. Coupling of benzothiophenes and styrenes in a stereoselective synthesis of substituted e,z. Being a heterocyclic compound, benzothiophene finds use in research as a starting material for the synthesis of larger, usually bioactive structures. The best fit of the experimental data appears to be the kinetic parameters determined using the michaelismentonmodel in the concentrations range of the study.
A uplcmsms method for simultaneous determination of free and total forms of a phenolic acid and two flavonoids in rat plasma and its application to comparative pharmacokinetic studies of polygonum capitatum extract in rats. Penthala nr1, sonar vn, horn j, leggas m, yadlapalli js, crooks pa. Antimalarials with benzothiophene moieties as aminoquinoline. It is a colourless solid that is chemically somewhat similar to anthracene. Synthesis of difluoroalkylated benzofuran, benzothiophene. Moreover, the strategy can also be used for the synthesis of thiophenes from 1,4diaryl1,3dienes. A new synthetic method for 1benzothieno3,2b1benzothiophene derivatives btbts was developed. The synthesis of a diverse range of heterobiaryls has been achieved by a transition. Sonochemical degradation of benzothiophene bt in deionized.
Benzothiophene 1 benzothiophene physical properties and structure thianaphthene 1 also known as benzothiophene was first obtained by difficult synthesis in 1883 and in 1902 it was isolated from coal tar thianaphthene has little commercial value, but derivatives in the form of thioindigo dyes have great value and have been much. Phosphinefree palladiumcatalysed direct c2arylation of benzothiophenes with aryl bromides. Journal of chemical and pharmaceutical research, 2017, 910. Procter a metalfree approach combining sulfoxidedirected metalfree ch crosscouplings with. Antimicrobial properties of isolated compounds were tested against indicator microorganisms such as c. It occurs naturally as a constituent of petroleumrelated deposits such as lignite tar. Synthesized compounds were evaluated for their antimalarial activity and toxicity, in vitro.
Iodinecatalyzed cascade reactions of substituted thiophenols with alkynes under metal and solventfree conditions enable the synthesis of benzothiophene. Removal of benzothiophene from organic solution by a combined photodegradationadsorption method 19 solution was a mixture containing 5 ml titanium isopropoxide ttip and 15 ml isopropanol 99%. The present method consists of iodocyclization of 1,2bis2methylthiophenylethynes and photolysis of 3iodo2methylthiophenyl benzo b thiophenes. The 3substituted benzothiophene2carboxylic acid, which had been preactivated with hbtu, was. Chemical on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Evaluation of benzothiophene carboxamides as analgesics and. Jul 01, 20 synthesis and evaluation of a series of benzothiophene acrylonitrile analogs as anticancer agents. This ring system has been recognized as an excellent scaffold in the development of biodynamic agents. Procter a metalfree approach combining sulfoxidedirected metalfree ch. C3arylated and alkylated benzothiophenes via an interrupted pummerer 19 3,3sigmatropic rearrangement 16,20 cascade. Yang m and riceevans c 1999 antioxidant activity applying an improved abts radical cation decolorization assay free rad.
Synthesis of benzothiophene carboxamide derivatives and their. Benzothiophene article about benzothiophene by the free. An efficient basecatalyzed protocol for the synthesis of benzothiophene is described. Pdf regioselective synthesis of c3 alkylated and arylated. Iodinecatalyzed cascade reactions of substituted thiophenols with alkynes under metal and solventfree conditions enable the synthesis of benzothiophene derivatives in good yields. H functionalization of arenes that does not require metal catalysis. Ppt benzothiophene powerpoint presentation free to. Mar 20, 2017 the synthesis of these important molecules can be achieved by construction of one or both rings, or via direct functionalization of the benzothiophene core 9,10,11. Synthesis of benzothiophenefused pyran derivatives via. Evaluation of benzothiophene carboxamides as analgesics and anti. Different substitution patterns in these heterocycles provide new opportunities for. Novel and convenient approaches to benzothiophene derivatives 3 and 5 have been developed, based on heterocyclization reactions of 12mercaptophenyl2yn1ols 2 or 4, respectively, readily available from alkynylation of 2mercaptobenzaldehydes or 12mercaptophenyl ketones 1. The desired ph of the solution was adjusted by hno 3 or nh 4oh. Such an efficient, economical, and green transformation should provide an attractive approach to various benzothiophenes.
Synthesis of benzothiophene carboxamide derivatives and. Aug 11, 2018 benzothiophene derivatives were synthesized regioselectively using coupling reactions and electrophilic cyclization reactions. Ppt benzothiophene powerpoint presentation free to view. Synthesis of benzothiophene analogues of ketoconazole and. Results and discussion previously, benzothiophene derivatives have been used extensively for their antiallergic, analgesic. School of chemistry, university of manchester, oxford rd, manchester, m 9pl uk. Regioselective synthesis of c3 alkylated and arylated. Derivatives of benzobthiophenes are useful precursors for the synthesis of thioindigo and azo disperse dyes. The catalytic synthesis of benzothiophene journal of the american. The presence of high amounts of sulfur in soils adjacent to the study area was reported by fernandez et al. It is used in organic as well as pharmaceutical industry as a component in the synthesis of raloxifene, a breast cancer therapeutic, or hydrodesulfurization reactions. Its various derivatives are useful as pesticides, fungicides, and herbicides. Synthesis of indole, benzofuran and benzothiophene by. Introduction the presence of sulfur compounds in fuels is a major source of atmospheric pollution juan et al.
Read synthesis of benzothiophene analogues of ketoconazole and itraconazole, journal of heterocyclic chemistry on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Synthesis of benzothiophene and indole derivatives through metalfree propargyl allene rearrangement and allyl migration jinzhongyao, yajiexie, lianpengzhang, yujinli andhongweizhou full research paper open access address. In particular, 12mercaptophenyl2yn1ols 2, bearing a ch2r substituent on the triple bond r alkyl, aryl. The key feature of the improved process is one pot high yielding deprotection of. This tricyclic heterocycle, and especially its alkyl substituted derivatives, occur widely in heavier fractions of petroleum. It is found within the chemical structures of pharmaceutical drugs such as raloxifene, zileuton, and sertaconazole, and also btcp. The key feature of the improved process is one pot high yielding deprotection of sulfonyl group in water. Synthesis of benzothiophene and indole derivatives through metalfree propargyl allene rearrangement and allyl migration. Here, we report on the efficacy of aminoquinolines coupled to benzothiophene and thiophene rings in inhibiting plasmodium falciparum parasite growth. Request permission export citation add to favorites track citation. Antimalarials with benzothiophene moieties as aminoquinoline partners.
Phosphinefree palladiumcatalysed direct c2arylation of benzothiophenes with aryl bromides liqin zhao, christian bruneau, henri doucet to cite this version. With 1,2bis2methylthiophenylethynes treated with i2phioac2 in ch2cl2 at room temperature, selective cyclization at sulfur took place to. Pdf synthesis and biological evaluation of novel benzothiophene. Thianaphthene 1 also known as benzothiophene was first obtained by difficult. Full paper results and discussion previously, we reported on synthetic methodologies for the preparation of thieno2,3dpyrimidinebased bisphosphonate10 and monosphosphonate thpmps11 libraries of com pounds with the ability to inhibit isoprenoid biosynthesis.
Materials and methods melting points were determined in an open capillary and. Benzothiophenes, an important class of heterocycles, are privileged structures, used as starting materials for the synthesis of bioactive structures, and are present in pharmaceuticals. Synthesis and biological evaluation of novel benzothiophene derivatives. The construction of heterobiaryls was carried out through electrophilic activation of the arylheteroaryl boronate complex, which triggered 1,2. This reaction allows efficient access to benzothiophenefused pyran derivatives in good yields under mild reaction conditions. This reaction allows efficient access to benzothiophene fused pyran derivatives in good yields under mild reaction conditions. A free powerpoint ppt presentation displayed as a flash slide show on id.
Jcprc5 106 expeditious synthesis of 3aryl benzothiophene a raloxifene intermediate. Derivatives of benzo b thiophenes are useful precursors for the synthesis of thioindigo and azo disperse dyes. The larock indole synthesis using orthohaloaniline derivatives is a prototypical example of this approach. Benzothiophene carboxamide derivatives diminish mpo levels. A divergent total synthesis of nicotianasesterpenes a, b, and a polygonum sesquiterpenoid is described. Synthesis and antimicrobial activity of benzothiophene. Synthesis of benzothiophene and indole derivatives through. The synthesis of these important molecules can be achieved by construction of one or both rings, or via direct functionalization of the benzothiophene core 9,10,11.
Notably, while the use of various arenesheteroarenes. Synthesis and evaluation of a series of benzothiophene acrylonitrile analogs as anticancer agents. Pdf synthesis of benzothiophene and indole derivatives through. Our findings demonstrate that newly synthesized bromo. The synthesis of the benzothiophene analogues of the orally active antifungal agents ketoconazole and itraconazole 3a and 3b is reported.
It is a part of our continuous efforts towards the synthesis and discovery of new heterocyclic compounds with expected biological activities. It is remarkable that this method allows the synthesis of 3hydroxy derivatives 11 and 15 and 3alkyl or 3arylsubstituted 1benzothiophenes 1,1dioxide with good yields and few steps. Due to their ubiquity in nature and frequent use in organic electronic materials, benzothiophenes are highly sought after. Recently, many attentions have been focused on decreasing the sulfur content of gas oil used in diesel engines matsuzawa et al. Synthesis of benzothiophene and indole derivatives through metal. Benzothiophene is an aromatic organic compound with a molecular formula c 8 h 6 s and an odor similar to naphthalene mothballs. Malaria is a severe and lifethreatening disease caused by plasmodium parasites that are spread to humans through bites of infected anopheles mosquitoes. This is in contrast to all literature methods describing the acidcatalyzed cyclization of arylthioacetones or arylphenacylsulfides, which always lead to mixtures of 2 or 3substituted isomers due to. Structure, properties, spectra, suppliers and links for. Synthesis of benzothiophene and indole derivatives through metalfree propargylallene rearrangement and allyl migration jinzhongyao, yajiexie, lianpengzhang, yujinli andhongweizhou full research paper open access address. On the other hand, other groups of compounds such as benzophenone, aminopyridine, and ami synthesis of benzothiophene carboxamide derivatives and. Phosphinesubstituted indoles can be synthesized by a similar strategy.
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