- An Efficient One-Pot Method for the Preparation of Polysubstituted Benzothiophenes
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A one-pot method for the transformation of an aryl bromide, an internal alkyne, and sulfur dichloride into a polysubstituted benzothiophene, in high yield, is described.The method involves the generation and trapping of a zirconocene complex of a substituted benzyne.
- Buchwald, Stephen L.,Fang, Qun
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- Cascade radical reactions in synthesis: A new and general approach to condensed thiophenes
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A novel cascade radical sequence is described for the direct conversion of ketenedithioacetals into condensed thiophenes. A noteworthy feature of this approach is its generality with respect to substituents.
- Harrowven, David C.
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- Chiral Benzothiophene Synthesis via Enantiospecific Coupling of Benzothiophene S-Oxides with Boronic Esters
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Benzothiophenes are valuable heterocycles that are widely used in medicines, agrochemicals, and materials science. Herein, we report a general method for the synthesis of enantioenriched 2,3-disubstituted benzothiophenes via a transition-metal-free C2-alkylation of benzothiophenes with boronic esters. The reactions utilize benzothiophene S-oxides in lithiation-borylations to generate intermediate arylboronate complexes, and subsequent Tf2O-promoted S?O bond cleavage to trigger a Pummerer-type 1,2-metalate shift, which gives the coupled products with complete enantiospecificity. Primary, secondary and tertiary alkyl boronic esters and aryl boronic esters are successfully coupled with a range of C3-substituted benzothiophenes. Importantly, this transformation does not require the use of C3 directing groups, therefore it overcomes a major limitation of previously developed transition-metal-mediated C2 alkylations of benzothiophenes.
- Aggarwal, Varinder K.,Noble, Adam,Sang, Ruocheng
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supporting information
p. 25313 - 25317
(2021/11/09)
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- Nickel-Catalyzed Asymmetric Hydrogenation of Cyclic Alkenyl Sulfones, Benzo[ b]thiophene 1,1-Dioxides, with Mechanistic Studies
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A highly efficient catalytic system based on the cheap transition metal nickel for the asymmetric hydrogenation of challenging cyclic alkenyl sulfones, 3-substituted benzo[b]thiophene 1,1-dioxides, was first successfully developed. A series of hydrogenation products, chiral 2,3-dihydrobenzo[b]thiophene 1,1-dioxides, were obtained in high yields (95-99%) with excellent enantioselectivities (90-99% ee). According to the results of nonlinear effect studies, deuterium-labeling experiments, and DFT calculation investigations, a reasonable catalytic mechanism for this nickel-catalyzed asymmetric hydrogenation was provided, which displayed that the two added hydrogen atoms of the hydrogenation products could be from H2 through the insertion of Ni-H and subsequent hydrogenolysis.
- Liu, Gongyi,Tian, Kui,Li, Chenzong,You, Cai,Tan, Xuefeng,Zhang, Heng,Zhang, Xumu,Dong, Xiu-Qin
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supporting information
p. 668 - 675
(2021/02/06)
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- Thiophene compounds and applications of thiophene compounds serving as USP7 inhibitors and antitumor drugs
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The invention discloses compounds shown in the formula I or nitrogen oxides, pharmaceutically acceptable salt or solvate of the compounds, a preparation method of the compounds, and applications of the compounds in pharmacy, and particularly provides the applications of the compounds serving as USP7 inhibitors and antitumor drugs. Pharmacodynamic experiment results show that the compounds in the formula I have inhibition effects on a USP7 enzyme and also have proliferation inhibition effects on human colon cancer cells HCT-116. Therefore, the compounds can be used for preparing the drugs for preventing or treating diseases related to tumors. The formula I is shown in the description.
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Paragraph 0066; 0070; 0071
(2019/01/16)
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- Oxygen Activated, Palladium Nanoparticle Catalyzed, Ultrafast Cross-Coupling of Organolithium Reagents
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The discovery of an ultrafast cross-coupling of alkyl- and aryllithium reagents with a range of aryl bromides is presented. The essential role of molecular oxygen to form the active palladium catalyst was established; palladium nanoparticles that are highly active in cross-coupling reactions with reaction times ranging from 5 s to 5 min are thus generated in situ. High selectivities were observed for a range of heterocycles and functional groups as well as for an expanded scope of organolithium reagents. The applicability of this method was showcased by the synthesis of the [11C]-labeled PET tracer celecoxib.
- Heijnen, Dorus,Tosi, Filippo,Vila, Carlos,Stuart, Marc C. A.,Elsinga, Philip H.,Szymanski, Wiktor,Feringa, Ben L.
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supporting information
p. 3354 - 3359
(2017/03/17)
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- A simple protocol for Cu-catalyzed protodecarboxylation of (hetero)aromatic carboxylic acids
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A simple and practical protodecarboxylation of o-nitrobenzoic acids as well as heteroaromatic carboxylic acids with various substituents via using CuI/Et3N has been established. This transformation provides a viable and low-cost approach to generating previously unavailable substituted arenes from readily accessible aryl carboxylic acids as the starting materials.
- Li, Zhaojie,Fu, Zhengjiang,Zhang, Haixia,Long, Jiao,Song, Yuanyuan,Cai, Hu
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supporting information
p. 3014 - 3018
(2016/05/09)
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- Preparation and pharmacological evaluation of a novel series of 2-(phenylthio)benzo[b]thiophenes as selective MT2 receptor ligands
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A series of N-(2-(5-fluoro-2-(4-fluorophenylthio)benzo[b]thiophen-3-yl) ethyl)acylamides was synthesized and evaluated for binding affinity and intrinsic activity at melatonin receptors. The affinity of each compound for the melatonin receptors was determined by binding studies on cloned human MT 1 and MT2 receptors expressed in CHO cells. Agonist and antagonist potency was measured on the [35S]GTPγS binding assay for the most interesting compounds. The new derivatives 8-14 showed modest to high selectivity (between 4 and 220) for MT2 receptors. The most selective compound, N-(2-(5-fluoro-2-(4-fluorophenylthio)benzo[b]thiophen-3-yl) ethyl)but-3-enamide (14), an MT2 ligand with affinity for the MT 2 receptor similar to that of melatonin and a 220-fold preference over MT1 receptors, acts as a partial agonist. In addition, N-(2-(5-fluoro-2-(4-fluorophenylthio)benzo[b]thiophen-3-yl)ethyl)propionamide (9), a nanomolar MT2 ligand with a good selectivity ratio (MT 1/MT2 = 51) shows antagonist activity on both melatonin receptors.
- Mésangeau, Christophe,Fraise, Mika?l,Delagrange, Philippe,Caignard, Daniel Henri,Boutin, Jean Albert,Berthelot, Pascal,Yous, Sa?d
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scheme or table
p. 1835 - 1840
(2011/05/06)
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- Decarboxylative homocoupling of (hetero)aromatic carboxylic acids
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A variety of hetero(aromatic) carboxylic acids are shown to undergo decarboxylative homocoupling, mediated by a Pd/Ag system. This novel methodology for the synthesis of symmetrical biaryls avoids the use of haloarenes and organometallic compounds as starting materials.
- Cornella, Josep,Lahlali, Hicham,Larrosa, Igor
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supporting information; experimental part
p. 8276 - 8278
(2010/12/19)
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- Synthesis of 3-substituted benzo[b]thiophenes via the reaction of α-substituted 2-lithio-β-methoxystyrenes with sulfur
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3-Substitued benzo[b]thiophenes were synthesized in reasonable overall yields from α-substituted 2-bromo-β-methoxystyrenes. Thus, the bromine-lithium exchange between these bromostyrenes with butyllithium in diethyl ether at 0 °C followed by reaction with sulfur afforded the corresponding a-substituted β-methoxy-2-sulfanylstyrenes. These were then treated with an equimolar amount of concentrated hydriodic acid in acetonitrile at room temperature to give the desired products. The Japan Institute of Heterocyclic Chemistry.
- Kobayashi, Kazuhiro,Nakai, Daisuke,Fukamachi, Shuhei,Konishi, Hisatoshi
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p. 1703 - 1709
(2011/04/15)
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- Silver-catalyzed protodecarboxylation of heteroaromatic carboxylic acids
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[Chemical Equation Presented] A simple and highly efficient protodecarboxylation procedure for a variety of heteroaromatic carboxylic acids catalyzed by Ag2CO3 and AcOH in DMSO is described. This methodology can also perform the selective monoprotodecarboxylation of several aromatic dicarboxylic acids.
- Lu, Pengfel,Sanchez, Carolina,Cornella, Josep,Larrosa, Igor
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supporting information; experimental part
p. 5710 - 5713
(2010/02/28)
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- Convenient synthesis of 3-substituted benzo[b]thiophenes by iodine-mediated cyclization of α-substituted 2-(1-Phenylethylthio)styrenes
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A new and convenient method for the preparation of 3-substituted benzo[b]thiophenes was developed. α-Substituted 2-(1-phenylethylthio) styrenes, which could easily be prepared from 2-mercaptophenyl ketones or benzenethiols in two or three steps, respectively, underwent 5-endo cyclization on treatment with iodine in the presence of sodium hydrogencarbonate in acetonitrile at room temperature to give 3-substituted benzo[b]thiophenes in fair to good yields.
- Kobayashi, Kazuhiro,Nakamura, Daizo,Miyamoto, Kazuna,Morikawa, Osamu,Konishi, Hisatoshi
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experimental part
p. 1780 - 1784
(2009/07/25)
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- Phenyl migration to thiophene ring in photolysis of 1-phenylbenzo[b]thiophenium salts
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Photolysis of 1-phenylbenzo[b]thiophenium salts was conducted by use of a Pyrex-filtered high pressure Hg lamp. The major products in most cases were the phenyl-migrated ones, i.e., 2-phenylbenzo[b]thiophenes and 3-phenylbenzo[b]thiophenes, together with the dephenylated benzo[b]thiophenes. This photochemical behavior is quite different from the thermal ones that provide the ring-opened olefins. The selective phenyl migration to the thiophene ring and the absence of the ionic products are characteristic of benzothiophenium systems.
- Kitamura, Tsugio,Morizane, Kunihiko,Taniguchi, Hiroshi,Fujiwara, Yuzo
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p. 5157 - 5160
(2007/10/03)
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- Electrophilic Reactions of Carbenoids. Synthesis of Fused Heterocyclic Systems via Intramolecular Nucleophilic Substitution of Carbenoids
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Intramolecular nucleophilic substitution of carbenoids with oxygen, nitrogen, and sulfur nucleophiles leading to the synthesis of fused heterocyclic compounds has been studied.For the purpose of this investigation styryl type gem-dihalides 4, 8, 18, 20, 28 containing a nucleophilic substituent in the ortho position of the aromatic ring have been synthesized.Carbenoids have been generated in those systems by the halogen - metal exchange reaction and shown to readily undergo intramolecular nucleophilic substitution by the properly located nucleophilic group (OH, SH, or NH2).As a result a new synthetic route to benzofurans, thianaphthenes, and indoles has been established based on nucleophilic substitution of vinyl halides by an ortho substituent.The dramatic increase of reactivity of vinyl halides upon introduction of lithium has been explained as being due to metal-assisted ionization.
- Topolski, Marek
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p. 5588 - 5594
(2007/10/03)
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- Molecular recognition in aqueous media. new binding studies provide further insights into the cation-π interaction and related phenomena
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We describe a large number of binding studies in aqueous media designed to provide new insights into noncovalent binding interactions, especially the cation-π interaction. The studies include 7 different hosts, over 70 guests, and over 150 new binding constants. In addition to the now standard NMR methods, circular dichroism has proven to be an especially useful tool for determining aqueous binding constants. We have found that, in addition to the alkyliminium and tetraalkylammonium guests we have studied previously, sulfonium and guanidinium guests also show substantial cation-π effects. Bromination of the host greatly enhances its binding ability in a general fashion, primarily as a result of hydrophobic interactions. Addition of methoxy groups did not enhance binding, apparently as a result of a collapse of the host into a conformation that is not suitable for binding. Replacement of two benzene rings of the host by furans or thiophenes also did not enhance binding. Ab initio calculations provide a rationalization for this effect and suggest a clearer model for the cation-π interaction.
- Kearney, Patrick C.,Mizoue, Laura S.,Kumpf, Robert A.,Forman, Jonathan E.,McCurdy, Alison,Dougherty, Dennis A.
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p. 9907 - 9919
(2007/10/02)
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- Preparation of Benzothiophenes by Pd(0)-Catalyzed Intramolecular Cyclization of Allyl (and Propargyl) o-Iodophenyl Sulfides
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Benzothiophenes are prepared by intramolecular Pd(0)-catalyzed Heck reaction of allyl o-iodophenyl sulfides.Pd(0)-Catalyzed intramolecular cyclization of o-iodophenyl propargyl sulfide in the presence of a hydride donor gives 3-methylene-2,3-dihydrobenzothiophene, which reacts with several enophiles in ene type reactions.However, allyl (and propargyl) aryl sulfides react with palladium(II) chloride to afford polymeric 2.
- Arnau, Narcis,Moreno-Manas, Marcial,Pleixats, Roser
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p. 11019 - 11028
(2007/10/02)
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- HIGH-TEMPERATURE ORGANIC SYNTHESIS. XXXI. REACTION OF PHENYLTHIYL RADICALS WITH ACETYLENE, PHENYLACETYLENE, AND PROPARGYL ALCOHOL
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Thiophenol reacts with acetylene at 550-590 deg C and diphenyl disulfide reacts at 500 deg C with the selective formation of benzothiophene.The reaction of phenylacetylene with diphenyl disulfide (450-550 deg C) leads to a mixture of 2- and 3-phenylbenzothiophenes.The products from the reaction of thiophenol with propargyl alcohol (450-630 deg C) are benzothiophene and 3-methylbenzothiophene.Diphenyl sulfide is formed as a side product, and thiophenol is formed in addition in the reaction of diphenyl disulfide with propargyl alcohol.The reaction mechanisms, involving the participation of phenylthiyl radicals, are discussed.
- Sukhomazova, E. N.,Russavskaya, N. V.,Korchevin, N. A.,Deryagina, E. N.,Voronkov, M. G.
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p. 1360 - 1364
(2007/10/02)
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- Metalation Reactions; Part XI. A Novel, One-Step Synthesis of Benzothiophene Derivatives
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A novel one-step synthesis of 3-substituted benzothiophene derivatives was achieved by dilithiation of (methylthio)benzene followed by reaction with various aliphatic and aromatic carboxylic acid chlorides.
- Cabiddu, S.,Cancellu, D.,Floris, C.,Gelli, G.,Melis, S.
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p. 888 - 890
(2007/10/02)
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- Halogeno-Substituted 2- and 3-Methylbenzothiophenes: Use of 1H NMR Spectral Analysis and 1H Nuclear Overhauser Effect for Locating the Halogen Substituent
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Thirty-seven halogeno-substituted 2- and 3-methyl-(or halogenomethyl)-benzothiophenes, including 17 new compounds, were prepared.The constitution of 14 of these was confirmed by full analysis (LAOCOON) of their 80 MHz 1H NMR spectra and by 1H NOE measurements.In this way a by-product from the preparation of 4- and 6-bromo-3-bromomethylbenzothiophenes was shown conclusively to be 5-bromo-3-bromomethylbenzothiophene.The 3-substituted benzothiophenes showed greater NOE enhancement factors at H-4 than at H-2 when the 3-methyl or halogenomethyl substituent was irradiated.
- Cuberes, M. Rosa,Moreno-Manas, Marcial,Sanchez-Ferrando, Francisco
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p. 814 - 821
(2007/10/02)
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- HIGH-TEMPERATURE ORGANIC SYNTHESIS. INVESTIGATION OF THE MECHANISM OF PYROLYSIS OF DIORGANIC SULFIDES BY THE CHLOROBENZENE TRAP METHOD
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The copyrolysis of various diorganic sulfides with chlorobenzene in the gas phase at 600-650 deg C was investigated.The degree of conversion of the chlorobenzene, which is a trap for thiyl radicals, increases with increase in the reaction temperature and depends significantly on the nature of the sulfide.The copyrolysis of chlorobenzene with branched dialkyl sulfides (secondary and tertiary) takes place more slowly than the reaction with the corresponding di(n-alkyl) sulfides.Alkyl vinyl sulfides are similar to the latter in reactivity.Ethyl β,β-dichlorovinyl sulfide and bis(ethylthio)acetylene have low reactivity.The main products from copyrolysis of all the diorganic sulfides with chlorobenzene are benzene, thiophenol, diphenyl sulfide, thiophene, and benzothiophene.The ratio between the products depends on the nature of the initial sulfide and an the temperature.The ratio between the thiophene and benzothiophene makes it possible to form an opinion about the mechanism of the formation of thiophene during the pyrolysis of the sulfides.Several paths were determined for the formation of the thiophene molecule through the thiyl radicals, and they supplemented the known mechanism of the pyrolysis of dialkyl sulfides, i.e., intermolecular cyclization of ethenethiol, intramolecular cyclization of butenethiol, cyclization of divinyl sulfide, and thermal dissociation of bis(ethylthio)acetylene.Intramolecular heterocyclization of the thiyl radicals is realized at a higher rate than intermolecular cyclization.
- Voronkov, M. G.,Deryagina, E. N.,Sukhomazova, E. N.,Mirskova, A. N.,Seredkina, S. G.
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p. 1453 - 1458
(2007/10/02)
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