- Benzo-Fused 1,4-Heterocycles via Dialkyl Carbonate Chemistry
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A novel halogen-free synthesis of benzo-fused six-membered 1,4-heterocycles through the chemistry of dialkyl carbonates is reported. Commercially available catechol, 2-aminophenol, and 2-aminothiophenol were reacted first with ethylene carbonate in an autoclave to give O -hydroxyethyl, N -hydroxyethyl, and S -hydroxyethyl derivatives respectively, through a B Al 2 mechanism. Then 2-(2-hydroxyethoxy)phenol and 2-(2-hydroxyethylamino)phenol were cyclized in excellent yields by reaction with dimethyl carbonate (DMC) and DABCO as a bicyclic organic base to give the corresponding benzodioxine and benzoxazine derivative, respectively. Moreover, 2-(2-aminophenylthio)ethanol afforded the benzothiazine derivative in good yield by reaction with DMC with an excess of a strong base such as NaH. The investigation on the cyclization reaction has highlighted that several equilibria are involved leading to the formation of carbonate and carbamate intermediates through B Ac 2 mechanisms. Depending on the reaction conditions employed, these intermediates may undergo either kinetic-controlled ring closure by a B Al 2 mechanism or by-product formation.
- Musolino, Manuele,Aricò, Fabi
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supporting information
p. 1770 - 1778
(2019/04/05)
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- Revisiting Hydroxyalkylation of Phenols with Cyclic Carbonates
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Described is a tetrabutylammonium fluoride-mediated hydroxyalkylation reaction of phenols with cyclic carbonates. This operationally simple method enables the synthesis of a variety of aryl β-hydroxyethyl ethers in good to excellent yields with a very small amount of catalyst loading (0.1–1 mol%). Of particular note is the efficient conversion of aromatic diols and phloroglucinol to the corresponding bis- and tris-hydroxyethylated products. To further showcase the versatility of this protocol, guaifenesin was prepared with a single step by the condensation of guaiacol and glycerol carbonate. We also developed a flow ethoxylation process permitting the continuous synthesis of multiflorol. (Figure presented.).
- Kao, Shih-Chieh,Lin, Yi-Ching,Ryu, Ilhyong,Wu, Yen-Ku
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supporting information
p. 3639 - 3644
(2019/07/10)
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- Harnessing C?H Activation of Benzhydroxamates as a Macrocyclization Strategy: Synthesis of Structurally Diverse Macrocyclic Isoquinolones
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Macrocycles are arising considerable interest in medicinal chemistry. With the goal of harnessing C?H activation reactions for the development of efficient macrocyclization processes, the ruthenium(II)-catalyzed cyclization of O-methyl benzhydroxamates possessing an ω-acetylenic chain was investigated to access new structurally diverse macrocyclic isoquinolones. A slow addition of the substrate and the presence of Cu(OAc)2?H2O as an additive were crucial for the success of the macrocyclization that features an excellent functional-group compatibility, as illustrated by the successful synthesis of a library of 21 macrocyclic isoquinolones of different ring sizes and substitution patterns. These results contribute to significantly highlight the synthetic interest of C?H activation-mediated processes for the synthesis of new macrocyles incorporating heterocyclic scaffolds of potential interest in medicinal chemistry.
- Krieger, Jean-Philippe,Ricci, Gino,Lesuisse, Dominique,Meyer, Christophe,Cossy, Janine
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supporting information
p. 13469 - 13473
(2016/09/13)
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- The toluene o-xylene monooxygenase enzymatic activity for the biosynthesis of aromatic antioxidants
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Monocyclic phenols and catechols are important antioxidant compounds for the food and pharmaceutic industries; their production through biotransformation of low-added value starting compounds is of major biotechnological interest. The toluene o-xylene monooxygenase (ToMO) from Pseudomonas sp. OX1 is a bacterial multicomponent monooxygenase (BMM) that is able to hydroxylate a wide array of aromatic compounds and has already proven to be a versatile biochemical tool to produce mono- and dihydroxylated derivatives of aromatic compounds. The molecular determinants of its regioselectivity and substrate specificity have been thoroughly investigated, and a computational strategy has been developed which allows designing mutants able to hydroxylate non-natural substrates of this enzyme to obtain high-added value compounds of commercial interest. In this work, we have investigated the use of recombinant ToMO, expressed in cells of Escherichia coli strain JM109, for the biotransformation of non-natural substrates of this enzyme such as 2-phenoxyethanol, phthalan and 2-indanol to produce six hydroxylated derivatives. The hydroxylated products obtained were identified, isolated and their antioxidant potential was assessed both in vitro, using the DPPH assay, and on the rat cardiomyoblast cell line H9c2. Incubation of H9c2 cells with the hydroxylated compounds obtained from ToMO-catalyzed biotransformation induced a differential protective effect towards a mild oxidative stress induced by the presence of sodium arsenite. The results obtained confirm once again the versatility of the ToMO system for oxyfunctionalization reactions of biotechnological importance. Moreover, the hydroxylated derivatives obtained possess an interesting antioxidant potential that encourages the use of the enzyme for further functionalization reactions and their possible use as scaffolds to design novel bioactive molecules.
- Donadio, Giuliana,Sarcinelli, Carmen,Pizzo, Elio,Notomista, Eugenio,Pezzella, Alessandro,Di Cristo, Carlo,De Lise, Federica,Di Donato, Alberto,Izzo, Viviana
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- NOVEL PROCESS FOR THE SYNTHESIS OF PHENOXYETHYL DERIVATIVES
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The present invention provides an improved process for the synthesis of 2-[2- (2,2,2-trifluoroethoxy)phenoxy]ethanol intermediate, its derivatives and/or its pharmaceutically acceptable salts, useful in the synthesis of α-1 adrenoceptor blockers such as silodosin.
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Page/Page column 22
(2011/09/19)
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- Aromatic ethers and process for producing aromatic ethers
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According to a production process, aromatic ethers are producible by reacting phenols with an oxirane compound with use of an anion exchange resin as a catalyst. According to another production process, aromatic ethers having an alcoholic hydroxyl group are producible by a crystallization-purification step of using a solvent having a solubility parameter ranging from 7.5 to 12.5 for purification by crystallization. Further, according to still another production process, producible are aromatic ethers having an alcoholic hydroxyl group, wherein the content of a metal in the aromatic ethers is less than 100 ppm by mass, and the content of a halogen element in the aromatic ethers is less than 100 ppm by mass.
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- Process for the synthesis of oligomeric compounds
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Synthetic processes are provided wherein oligomeric compounds are prepared having phosphodiester, phosphorothioate, phosphorodithioate, or other covalent linkages. Also provided are synthetic intermediates useful in such processes.
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- Undesirable deprotection of O-TBDMS groups by Pd/C-catalyzed hydrogenation and chemoselective hydrogenation using a Pd/C(en) catalyst
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In general, O-TBDMS protective groups have been believed to be stable toward Pd/C-catalyzed hydrogenation conditions. In practice, however, frequent and unexpected loss of the TBDMS protective group of a variety of hydroxyl functions occurred under neutral and mild hydrogenation conditions using 10% Pd/C in MeOH. When a 10% Pd/C-ethylenediamine complex catalyst [10% Pd/C(en)] was used instead of 10% Pd/C, the undesirable problem was perfectly overcome and the chemoselective hydrogenation of reducible functionalities leaving intact the TBDMS protective group was achieved.
- Hattori, Kazuyuki,Sajiki, Hironao,Hirota, Kosaku
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p. 2109 - 2114
(2007/10/03)
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- Crown calix[4]arenes, method of preparation and use for selective extraction of caesium
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PCT No. PCT/FR98/00401 Sec. 371 Date Jan. 27, 1999 Sec. 102(e) Date Jan. 27, 1999 PCT Filed Mar. 2, 1998 PCT Pub. No. WO98/39321 PCT Pub. Date Sep. 11, 1998The invention relates to new calixarenes of formula: in which R1 represents a crown ether chain that includes at least two aryl or cycloalkyl rings, R2 is a hydroxyl or alkoxy group, or the two R2 groups together form a crown ether chain such as R1, and R3 represents a hydrogen atom or an alkyl group. The calixarenes are used to selectively extract caesium from aqueous solutions that notably have high concentrations of sodium.
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- The undesirable lability of tert-butyldimethylsilyl ethers under Pd/C- catalyzed hydrogenation conditions and solution of the problem by using a Pd/C(en) catalyst
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While the frequent and unexpected loss of the TBDMS protective group of a variety of hydroxylic functions was demonstrated under neutral and mild hydrogenation conditions using 10% Pd/C, the undesirable problem was perfectly overcome by using a 10% Pd/C-ethylenediamine complex catalyst. (C) 2000 Elsevier Science Ltd.
- Hattori, Kazuyuki,Sajiki, Hironao,Hirota, Kosaku
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p. 5711 - 5714
(2007/10/03)
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- Studies on quinones. Part. 33. Synthetic approach to podands containing quinone fragments
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The preparation and oxidative demethylation attempts of podands 3-5, and 9 containing the 2,5-dimethoxyphenyl substituent are described. The reaction of alizarine 13 with chloroethanol afforded compounds 14 and 15. The pathway formation of heterocycle 15 from 14 is proposed. The synthesis of podand 16 containing the cytotoxic 1-hydroxy-9,10-anthraquinone fragment as the terminal groups is reported.
- Valderrama, Jaime A.,Leiva, Hilda,Tapia, Ricardo
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p. 737 - 749
(2007/10/03)
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- A new calix[4]arene-bis(crown ether) derivative displaying an improved caesium over sodium selectivity: Molecular dynamics and experimental investigation of alkali-metal ion complexation
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In the light of computational studies suggesting enhanced cation-binding abilities for various benzo derivatives of calix[4]arene-bis-crown-6 macrocycles, the synthesis and properties of one of these ligands, BC6B2, have been investigated. In this compound, di(1,2-phenylene)-annelated glycolic chains link the 1,3- and 2,4-phenyl rings of the calixarene, thereby forcing it into the 1,3-alternate conformation. The detailed structures of BC6B2·CH3NO2 1 and Cs2(NO3)2BC6B2·CHCl 3·H2O 2 have been established by X-ray crystallography. Studies of coordination and solvent extraction of the alkali-metal ions have been used to compare this ligand with a number of related systems known previously.
- Lamare, Veronique,Dozol, Jean-Francois,Fuangswasdi, Saowarux,Arnaud-Neu, Francoise,Thuery, Pierre,Nierlich, Martine,Asfari, Zouhair,Vicens, Jacques
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p. 271 - 284
(2007/10/03)
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- Cyclotriveratrylene models for proteins: 3:1 subsite differentiation and modulation of the redox potential
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The potential of cyclotriveratrylene (ctv) (2,3,7,8,12,13-hexamethoxy-10,15-dihydro-5H-tribenzocyclo-nonene) trithiols as ligands that can easily be functionalised and show subsite differentiation in their complexes with clusters has been explored.The cluster complexes of tris(2-sulfanylethoxy)- and tris(3-sulfanyl-methylbenzyloxy)-functionalised ctvs have been studied by core-extrusion experiments, spectroscopy and electrochemical techniques.With 2- as starting material a cluster complex was obtained in which the unique Fe and its co-ordinating Cl was turned into the cavity and show no reactivity.Starting with the more bulky t)4>2- the unique iron points outwards and is susceptible to substitution reactions.The effects of hydrogen bonding and electron density on the redox potential of the cluster complex have been investigated.The redox potential becomes more negative when the length of the spacer between the ctv and cluster core is increased, which is explained by the longer distance between the cluster and the electron-withdrawing phenoxy moiety of the ctv.The synthesis of ctv derivatives with one thiol and one alcohol functionality per phenyl unit, and comparison with corresponding derivatives where hydrogen bonding is not possible, showed that no significant differences were found.The effects of a substituent in an aromatic amide group that could hydrogen bond to the co-ordinated thiol were investigated.A weak effect, in the direction expected, was found upon substitution of methyl for H.
- Strijdonck, Gino P. F. van,Haare, John A. E. H. van,Hoenen, Paulus J.M.,Schoor, Roger C. G. M. van den,Feiters, Martinus C.,et al.
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p. 449 - 462
(2007/10/03)
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- N-Arylpiperazinyl-N'-propylamino derivatives of heteroaryl amides as functional uroselective α1-adrenoceptor antagonists
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Novel arylpiperazines were identified as α1-adrenoceptor (AR) subtype- selective antagonists by functional in vitro screening. 3-[4-(ortho- Substituted phenyl)piperazin-1:yl]propylamines were derivatized with N,N- dimethyl anthranilamides, nicotinamides, as well as carboxamides of quinoline, 1,8-naphthyridine, pyrazolo[3,4-b]pyridine, isoxazolo[3,4- b]pyridine, imidazo[4,5-b]pyridine, and pyrazolo[1,5-a]pyrimidines. Strips of rabbit bladder neck were employed as a predictive assay for antagonism in the human lower tract. Rings of rat aorta were used as a 'negative screen' for the test antagonists. Binding to α1-ARs was relatively sensitive to size and electronic features of the arylpiperazine portion of the antagonists and permissive to these features on the heteroaryl carboxamide side. These structure-affinity findings were exploited to produce nicotinamides (e.g. 13ii and 25x) and pyrazolo[3,4-b]pyridines (e.g. 37f and 37y) ligands with nanomolar affinity at the α1-AR subtype prevalent in the human lower urinary tract (pA2 values: 8.8, 10.7, 9.3, and 9.9, respectively) and displaying 2-3 orders of magnitude selectivity over the α(1D)-AR.
- Elworthy, Todd R.,Ford, Anthony P. D. W.,Bantle, Gary W.,Morgans Jr., David J.,Ozer, Rachel S.,Palmer, Wylie S.,Repke, David B.,Romero, Magarita,Sandoval, Leticia,Sjogren, Eric B.,Talamás, Francisco X.,Vazquez, Alfredo,Wu, Helen,Arredondo, Nicolas F.,Blue Jr., David R.,DeSousa, Andrea,Gross, Lisa M.,Kava, M. Shannon,Lesnick, John D.,Vimont, Rachel L.,Williams, Timothy J.,Zhu, Quan-Ming,Pfister, Jürg R.,Clarke, David E.
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p. 2674 - 2687
(2007/10/03)
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- Radiochemical stability of the dicyclohexano-18-crown-6 ether (DCH18C6): Synthesis and tests in radioactive medium of the DCH18C6 radiolytic products
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The cis-syn-cis isomer of the dicyclohexano-18-crown-6 ether (DCH18C6) was subjected to hydrolysis and radiolysis with a 137Cs gamma source, at different doses of irradiation. The cis-syn-cis DCH18C6 radiolytic products previously identified [1], were synthesized in their different configurations. These radiolytic products, all of cis configuration, were tested on aqueous synthetic solutions of spent nuclear fuels. Experiments in radioactive medium showed that, under continuous extraction conditions, the cis-syn-cis DCH18C6 radiolytic products cannot perturb a reprocessing process using the DCH18C6 as selective extractant. Good prospects for the application of DCH18C6 to spent nuclear fuel reprocessing were therefore demonstrated. An X-ray crystallographic study of the DCH18C6 cis-syn-cis-isomer with uranyl nitrate was investigated. Elsevier,.
- Draye, Micheline,Favre-Reguillon, Alain,Chomel, Rodolph,Faure, Rene,Guy, Alain,Foos, Jacques,Lemaire, Marc
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p. 183 - 197
(2007/10/03)
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- Acid Catalysed ipso Photosubstitution of Alkoxy-substituted Benzenes in Aqueous Acid Solution
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The first examples of acid catalysed ipso photosubstitution of alkoxy-substituted benzenes by solvent water, with observed quantum yields in the range 0.03-0.14 are reported, the mechanism of which is believed to involve initial photoprotonation of the aromatic ring in the excited singlet state.
- Wan, Peter,Wu, Pin
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p. 822 - 823
(2007/10/02)
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