- Preparation method of eltrombopag intermediate and preparation method of eltrombopag diethanolamine salt
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The invention provides a preparation method of an eltrombopag intermediate and a preparation method of eltrombopag diethanolamine salt, and relates to the technical field of medicinal chemistry. According to the preparation method of the eltrombopag intermediate, p-bromophenol is taken as a raw material, and the problem of poor selectivity of nitration reaction is solved. After iodination, the coupling reaction yield of the intermediate compound as shown in a formula (I) and phenylboronic acid is high. Subsequently reduction reaction is carried out, the debromination reaction is complete, the yield is 90% or more, the refining is simpler, and the synthesis yield of the compound of the formula (I) is higher and the operation is simple. Through the improvement, the yield of the key compound shown as the formula (I) is relatively high, the subsequent treatment operation is simple, the process is easy for amplified production, the yield of the whole synthesis process of the eltrombopag diethanolamine salt is 48.1%, the operation is simple, less three wastes are generated, and the synthesis process is suitable for amplified production.
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Paragraph 0038; 0043-0044
(2021/06/22)
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- (±)-trans-2-phenyl-2,3-dihydrobenzofurans as leishmanicidal agents: Synthesis, in vitro evaluation and SAR analysis
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Leishmaniasis, a neglected tropical disease caused by parasites of the genus Leishmania, causes a serious burden of disease around the world, represents a threat to the life of millions of people, and therefore is a major public health problem. More effective and non-toxic new treatments are required, especially for visceral leishmaniasis, the most severe form of the disease. On the backdrop that dihydrobenzofurans have previously shown antileishmanial activity, we present here the synthesis of a set of seventy trans-2-phenyl-2,3-dihydrobenzofurans and evaluation of their in vitro activity against Leishmania donovani as well as a discussion of structure-activity relationships. Compounds 8m-o and 8r displayed the highest potency (IC50 4.6). Nonetheless, structural optimization as further requirement was inferred from the high clearance of the most potent compound (8m) observed during determination in vitro of its metabolic stability. On the other hand, chiral separation of 8m and subsequent biological evaluation of its enantiomers demonstrated no effect of chirality on activity and cytotoxicity. Holistic analysis of in silico ADME-like properties and ligand efficiency metrics by a simple scoring function estimating druglikeness highlighted compounds 16c, 18 and 23 as promising candidates for further development. Overall, the potential of trans-2-phenyl-2,3-dihydrobenzofurans as leishmanicidal agents was confirmed.
- Bernal, Freddy A.,Gerhards, Marcel,Kaiser, Marcel,Wünsch, Bernhard,Schmidt, Thomas J.
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- A convenient and efficient H2SO4-promoted regioselective monobromination of phenol derivatives using N-bromosuccinimide
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A convenient, rapid H2SO4-promoted regioselective monobromination reaction with N-bromosuccinimide was developed. The desired para-monobrominated or ortho-monobrominated products of phenol derivatives were obtained in good to excellent yields with high selectivity. Regioselective chlorination and iodination were also achieved in the presence of H2SO4 using N-chlorosuccinimide and N-iodosuccinimide, respectively.
- Wu, Yong-Qi,Lu, Hai-Jia,Zhao, Wen-Ting,Zhao, Hong-Yi,Lin, Zi-Yun,Zhang, Dong-Feng,Huang, Hai-Hong
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supporting information
p. 813 - 822
(2020/02/15)
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- Bioinspired catalysis and bromoperoxidase like activity of a multistimuli-responsive supramolecular metallogel: Supramolecular assembly triggered by pi-pi stacking and hydrogen bonding interactions
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We report the synthesis and characterization of a new self-assembled VO2-L metallogel. Gel formation was investigated by dissolving VO2-L in various solvents and it was found that water/methanol (1?:?9 (v/v) ratio) induces gel formation. The single crystal X-ray structure of the VO2-L metallogel exhibits C-H?O and N-H?O hydrogen bonding interactions and pi-pi stacking. The VO2-L xerogel obtained after removing the solvents was found to exhibit outstanding performance in catalysis. Bromoperoxidase-like activity of the VO2-L metallogel was also reported. The present catalytic studies are simple and proceed under mild conditions.
- Kurbah, Sunshine Dominic,Lal, Ram A.
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p. 5410 - 5418
(2020/04/17)
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- Stepwise mechanism for the bromination of arenes by a hypervalent iodine reagent
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A mild, metal-free bromination method of arenes has been developed using the combination of bis(trifluoroacetoxy)iodobencene and trimethylsilyl bromide. In situ-formed dibromo(phenyl)-λ3-iodane (PhIBr2) is proposed as the reactive intermediate. This methodology using PIFA/TMSBr has been applied with success to a great number of substrates (25 examples). The treatment of mono-substituted activated arenes led to para-brominated products (2u-z) in excellent 83-96% yields. Density functional theory calculations indicate a stepwise mechanism involving a double bromine addition followed by a type II dyotropic reaction with concomitant re-aromatization of the six-membered ring.
- Arrieta, Ana,Cossío, Fernando P.,Granados, Albert,Shafir, Alexandr,Vallribera, Adelina
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p. 2142 - 2150
(2020/03/11)
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- 1,8-NAPHTHYRIDINONE COMPOUNDS AND USES THEREOF
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1,8-naphthyridinone compounds as modulators of an adenosine receptor are provided. The compounds may find use as therapeutic agents for the treatment of diseases mediated through a G-protein-coupled receptor signaling pathway and may find particular use in oncology.
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-
Paragraph 0350-0352
(2019/02/05)
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- Iodine(III)-Catalyzed Electrophilic Nitration of Phenols via Non-Br?nsted Acidic NO2+ Generation
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The first catalytic procedure for the electrophilic nitration of phenols was developed using iodosylbenzene as an organocatalyst based on iodine(III) and aluminum nitrate as a nitro group source. This atom-economic protocol occurs under mild, non-Br?nsted acidic and open-flask reaction conditions with a broad functional-group tolerance including several heterocycles. Density functional theory (DFT) calculations at the (SMD:MeCN)Mo8-HX/(LANLo8+f,6-311+G) level indicated that the reaction proceeds through a cationic pathway that efficiently generates the NO2+ ion, which is the nitrating species under neutral conditions.
- Juárez-Ornelas, Kevin A.,Jiménez-Halla, J. Oscar C.,Kato, Terumasa,Solorio-Alvarado, César R.,Maruoka, Keiji
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supporting information
p. 1315 - 1319
(2019/03/07)
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- Kinetics and mechanism of trichloroisocyanuric acid/NaNO2-triggered nitration of aromatic compounds under acid-free and Vilsmeier-Haack conditions
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Kinetics and mechanism of nitration of aromatic compounds using trichloroisocyanuric acid (TCCA)/NaNO2, TCCA-N,N-dimethyl formamide (TCCA-DMF)/NaNO2, and TCCA-N,N-dimethyl acetamide (TCCA-DMA)/NaNO2 under acid-free and Vilsmeier-Haack conditions. Reactions followed second-order kinetics with a first-order dependence on [Phenol] and [Nitrating agent] ([TCCA], [(TCCA-DMF)], or [(TCCA-DMA)] >> [NaNO2]). Reaction rates accelerated with the introduction of electron-donating groups and retarded with electron-withdrawing groups, but did not fit well into the Hammett's theory of linear free energy relationship or its modified forms like Brown-Okamoto or Yukawa-Tsuno equations. Rate data were analyzed by Charton's multiple linear regression analysis. Isokinetic temperature (β) values, obtained from Exner's theory for different protocols, are 403.7?K (TCCA-NaNO2), 365.8?K (TCCA-DMF)/NaNO2, and 358?K (TCCA-DMA)/NaNO2. These values are far above the experimental temperature range (303-323?K), indicating that the enthalpy factors are probably more important in controlling the reaction.
- Bhooshan,Rajanna,Govardhan,Venkanna,Satish Kumar
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p. 445 - 462
(2019/04/10)
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- Copper-mediated nitrosation: 2-nitrosophenolato complexes and their use in the synthesis of heterocycles
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A simple protocol yielding ortho-substituted nitrosophenols from phenols is demonstrated, in the form of copper(II) bis(nitrosophenolato) complexes. The developed methodology was applied to a range of substrates, confirming the role of the copper in both the formation and protection of the challenging 1, 2-substitution pattern. Using polymer supported thiourea, the Cu could be stripped from the complexes and thus enabled the isolation or identification of the uncoordinated ligands and their decomposition products, in yields generally low in line with the intrinsic high reactivity of 2-nitrosophenols. The product complexes are useful intermediates as demonstrated in revisiting a formal [4 + 2] cycloaddition with dimethylacetylene dicarboxylate to synthesise bicyclic products in variable yields, revealing the product has a novel structure different from those previously reported in the literature.
- Nicholls, Alexander J.,Batsanov, Andrei S.,Baxendale, Ian R.
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- Nitration method for aryl phenol or aryl ether derivative
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The invention relates to a nitration method for an aryl phenol or aryl ether derivative. The method comprises the steps of stirring an aryl phenol or aryl ether compound, nitrate, trimethylchlorosilane (TMSCl) and a copper salt in an acetonitrile solution in air at room temperature, simultaneously, monitoring extent of reaction through a TLC dot plate, removing a solvent from a mixture by a rotaryevaporator after a substrate is consumed completely, and carrying out purification through a silica-gel column, thereby obtaining a nitroolefin derivative. Meanwhile, the selective mono-nitration orbis-nitration of the substrate can be achieved through controlling equivalent weight of the nitrate. Compared with the prior art, the nitration method disclosed by the invention has the advantages that the consumption of strong-acid substances is avoided, the reaction conditions are mild, the yield is high, the applicable range of the substrate is wide, reaction activity is free of obvious attenuation after an amplified reaction, and an excellent yield is still obtained, so that the method has an obvious industrial application value.
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Paragraph 0050-0055; 0059-0061
(2020/01/03)
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- HETEROCYCLIC COMPOUNDS AS ADENOSINE ANTAGONISTS
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Aminopyrazine compounds as modulators of an adenosine receptor are provided. The compounds may find use as therapeutic agents for the treatment of diseases mediated through a G-protein-coupled receptor signaling pathway and may find particular use in oncology.
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Paragraph 0389; 0390
(2019/02/05)
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- 5 - Pyridyl -2 - amino - benzo [d] oxazole derivative and its preparation and use (by machine translation)
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The present invention discloses the general formula (I) indicated by the 5 - pyridyl - 2 - amino - benzo [d] oxazole derivative or its pharmaceutically acceptable salt, its preparation method, pharmaceutical composition and use: According to the compounds of this invention can be used for preparing the treatment of cervical cancer, breast cancer, stomach cancer, liver cancer, renal carcinomas of the drug. (by machine translation)
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Paragraph 0053-0056
(2018/05/16)
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- Sodium perborate/NaNO2/KHSO4-triggered synthesis and kinetics of nitration of aromatic compounds
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Sodium perborate (SPB) was used as efficient green catalyst for NaNO2/KHSO4-mediated nitration of aromatic compounds in aqueous acetonitrile medium. Synthesis of nitroaromatic compounds was achieved under both conventional and solvent-free microwave conditions. Reaction times were comparatively shorter in the microwave-assisted than conventional reaction. The reaction kinetics for nitration of phenols in aqueous bisulfate and acetonitrile medium indicated first-order dependence on [Phenol], [NaNO2], and [SPB]. Reaction rates accelerated with introduction of electron-donating groups but retarded with electron-withdrawing groups. Kinetic results did not fit well quantitatively with Hammett’s equation. Observed deviations from linearity were addressed in terms of exalted Hammett’s constants (σˉ or σeff), para resonance interaction energy (ΔΔGp) parameter, and Yukawa–Tsuno parameter (r). This term provides a measure of the extent of resonance stabilization for a reactive structure that builds up charge (positive) in its transition state. The observed negative entropy of activation (?ΔS#) suggests greater solvation and/or cyclic transition state before yielding products.
- Rajanna,Muppidi, Suresh,Pasnoori, Srinivas,Saiprakash
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p. 6023 - 6038
(2018/09/21)
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- A fluorine scan of a tubulin polymerization inhibitor isocombretastatin A-4: Design, synthesis, molecular modelling, and biological evaluation
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A novel series of tubulin polymerization inhibitors, based on fluorinated derivatives of isocombretastatin A-4 was synthesized with the goal of evaluating the effect of these compounds on the proliferative activity. The introduction of fluorine atom was performed on the phenyl ring or at the linker between the two aromatic rings. The modification of isoCA-4 by introduction of difluoromethoxy group at the para-position (3i) and substitution of the two protons of the linker by two fluorine atoms (3m), produced the most active compounds in the series, with IC50 values of 0.15–2.2 nM (3i) and 0.1–2 nM (3m) respectively, against a panel of six cancer cell lines. Compounds 3i and 3m had greater antiproliferative activity in comparison with references CA-4 or isoCA-4, the presence of fluorine group leads to a significant enhancement of the antiproliferative activity. Molecular docking studies indicated that compounds 3i and 3m occupy the colchicine binding site of tubulin. Evaluation of cytotoxicity in Human noncancer cells indicated that the compounds 3i and 3m were practically ineffective in quiescent peripheral blood lymphocytes, and may have a selective antiproliferative activity against cancer cells. Analyses of cell cycle distribution, and morphological microtubules organization showed that compound 3m induced G2/M phase arrest and, dramatically disrupted the microtubule network.
- Naret, Timothée,Bignon, Jér?me,Bernadat, Guillaume,Benchekroun, Mohamed,Levaique, Helene,Lenoir, Christine,Dubois, Joelle,Pruvost, Alain,Saller, Fran?ois,Borgel, Delphine,Manoury, Boris,Leblais, Veronique,Darrigrand, Romain,Apcher, Sébastien,Brion, Jean-Daniel,Schmitt, Etienne,Leroux, Frédéric R.,Alami, Mouad,Hamze, Abdallah
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p. 473 - 490
(2017/12/07)
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- 1,1,2,2-Tetrahydroperoxy-1,2-Diphenylethane: An efficient and high oxygen content oxidant in various oxidative reactions
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Several oxidative approaches namely thiocyanation of aromatic compounds, epoxidation of alkenes, amidation of aromatic aldehydes, epoxidation of α β-unsaturated ketones, oxidation of sulfides to sulfoxides and sulfones, bayer-villeger reaction, bromination and iodation of aniline and phenol derivatives oxidative esterification, oxidation of pyridines and oxidation of secondary, allylic and benzyllic alcohols were carried out using 1,1,2,2-Tetrahydroperoxy-1,2-Diphenylethane as the potential solid oxidant which can be stored for several months without any loss in its activity. All of the procedures were accomplished via mild reaction conditions and the products were afforded in high yields and short reaction times.
- Khosravi, Kaveh,Naserifar, Shirin
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supporting information
p. 6584 - 6592
(2018/10/05)
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- Polymer-anchored [Fe(III)Azo] complex: An efficient reusable catalyst for oxidative bromination and multi-components reaction for the synthesis of spiropiperidine derivatives
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A heterogeneous catalyst was prepared by attaching Fe(III) into organically modified chloromethylated polytstyrene and characterized by AAS, IR, PXRD, TG-DTA, UV–Vis, and SEM studies. In presence of H2O2 and KBr as bromine source, the catalyst showed remarkably high conversion with para-selectivity towards the oxidative bromination reaction in acetic acid medium. The catalyst was also very active and highly efficient for the production of spiropiperidine derivatives through multi-component reaction in isopropyl alcohol at room temperature. The catalyst was not leached during the catalytic reactions, moreover, after five cycles the catalytic activity and selectivity of the catalyst were not decreased very significantly.
- Khatun, Resmin,Biswas, Surajit,Ghosh, Swarbhanu,Islam, Sk. Manirul
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-
- Highly efficient protocol for the aromatic compounds nitration catalyzed by magnetically recyclable core/shell nanocomposite
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An efficient protocol for the nitration of aromatic compounds in the presence of a catalytic amount of sulfuric acid-functionalized silica-based magnetic core/shell nanocomposite was reported. The designed products were obtained in high yields in relatively short reaction times at room temperature under solvent-free conditions. The nanocatalyst was simply recovered from the reaction mixture by using an external magnet and efficiently reused for several times. The characterization of particle size, morphology and elemental analysis of the nanocatalyst were provided by scanning electron microscopy, transmission electron microscopy and energy-dispersive X-ray spectroscopy analyses, respectively.
- Maleki, Ali,Aghaei, Morteza,Paydar, Reza
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p. 485 - 490
(2017/01/10)
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- Potassium Periodate/NaNO2/KHSO4-Mediated Nitration of Aromatic Compounds and Kinetic Study of Nitration of Phenols in Aqueous Acetonitrile
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Synthesis and kinetics of potassium periodate(KIO4)/NaNO2/KHSO4)-initiated nitration of aromatic compounds have been studied in aqueous acetonitrile medium. Synthesis of nitroaromatic compounds is achieved under conventional and solvent-free microwave conditions. Reaction times in microwave-assisted reaction are comparatively less than in conventional reaction. The reaction kinetics for the nitration of phenols in aqueous bisulfate and acetonitrile medium indicated first-order dependence on [phenol], [NaNO2], and [KIO4]. An increase in [KHSO4] accelerated the rate of nitration under otherwise similar conditions. The rate of nitration increased in the solvent of high dielectric media (solvents with high dielectric constant (D)). Observed results were in accordance with Amis and Kirkwood plots [log k′ vs. (1/D) and [(D ? 1)/(2D + 1)]. These observations probably indicate the participation of anionic species and molecular or (dipolar) species in the rate-determining step. In addition, the plots of (log k′) versus volume% of organic solvent were also linear, which probably indicate the importance of both electrostatic and nonelectrostatic forces, solvent–solute interactions during nitration of phenols. Reaction rates accelerated with the introduction of electron-donating groups and retarded with electron-withdrawing groups, but results could not be quantitatively correlated with Hammett's equation and depicted deviations from linearity. These deviations could probably be attributed to cumulative effects arising inductive, resonance, and steric effects. Leffler's plot (ΔH# vs. ΔS#) was found linear indicating the compensation (cumulative) effect of both enthalpy and entropy parameters in controlling the mechanism of nitration.
- Sriram, Y. Hemanth,Fatima, Touheeth,Rajanna,Kumar, M. Satish,Raju, R. Madhusudan
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supporting information
p. 622 - 632
(2017/06/30)
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- Prussian Blue/NaNO2 as an Efficient Reagent for the Nitration of Phenols in Aqueous Bisulfate and Acetonitrile Medium: Synthetic and Kinetic Study
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The reaction kinetics of Prussian blue (PB)/NaNO2 initiated for the nitration of phenols by in aqueous bisulfate and acetonitrile medium indicated first-order dependence on [phenol], [NaNO2], and [PB]. An increase in [KHSO4] accelerated the rate of nitration under otherwise similar conditions. The rate of nitration was faster in the solvent of higher dielectric constant (D). Observed results were in accordance with Amis and Kirkwood plots [log k′ vs. (1/D) and [(D ? 1)/(2D + 1)]. These findings together with the linearity of plots, log k′ versus (vol% of acetonitrile (ACN)) and mole fraction of (nx) ACN, probably indicate the importance of both eloctrostatic and nonelctrostatic forces, solvent–solute interactions during nitration of phenols. Reaction rates accelerated with the introduction of electron-donating groups and retarded with electron-withdrawing groups, which are interpreted by Hammett's theory of linear free energy relationship. Hammett's reaction constant (ρ) is a fairly large negative (ρ 0) value, indicating attack of an electrophile on the aromatic ring. Furthermore, an increase in temperature decreased the reaction constant (ρ) values. This trend was useful in obtaining isokinetic temperature (β) from Exner's plot of ρ versus 1/T. Observed β value (337.8 K) is above the experimental temperature range (303–323 K), indicating that the enthalpy factors are probably more important in controlling the reaction.
- Srinivas, Pasnoori,Suresh, Muppidi,Rajanna,Krishnaiah
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supporting information
p. 209 - 218
(2017/02/05)
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- A ortho-nitro phenol and its derivative synthesis method (by machine translation)
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The invention relates to a method for the synthesis of organic compounds, in the existing technology of O-nitrophenol strong acid used in the synthesis process of the serious problem of environmental pollution and the synthesis step longer more complicated problem, the invention provides a ortho-nitro phenol and synthetic method of derivative thereof, proceeding by the phenol compound, synthesis of 2 - (phenoxy) pyridine, the obtained product, catalyst, tert-butyl nitrite, organic solvent and adding sealing in the pressure containers, in oil bath heating 50 - 100 °C, reaction 10 - 30 hours, to obtain 2 - (2 - nitrobenzene) ethoxy pyridine; re-processing by the ortho-nitro phenol and its derivatives; the method is simple, high-efficiency. (by machine translation)
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- Room-Temperature, Water-Promoted, Radical-Coupling Reactions of Phenols with tert -Butyl Nitrite
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A radical-radical cross-coupling reaction of phenols with tert -butyl nitrite has been developed with the use of water as an additive. This method allows the construction of C-N bonds under an air atmosphere at room temperature, providing the ortho -nitrated phenol derivative in moderate to good yields.
- Wei, Wen-Ting,Zhu, Wen-Ming,Liang, Weida,Wu, Yi,Huang, Hui-Yan,Huang, Yi-Ling,Luo, Junfei,Liang, Hongze
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supporting information
p. 2153 - 2156
(2017/09/26)
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- Nitration of arenes by 1-sulfopyridinium nitrate as an ionic liquid and reagent by in situ generation of NO2
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1-Sulfopyridinium nitrate was synthesized as a potent nitrating agent for the nitration of arenes without the need for any co-catalysts. A variety of nitro compounds were synthesized and fully characterized by IR, 1H NMR, 13C NMR, thermal gravimetric analysis (TGA), differential thermal gravimetry (DTG), CHN analysis and mass spectroscopy. Mechanistically, in situ generated nitrogen dioxide as a radical from the reagent is proposed for the presented nitration protocol.
- Moosavi-Zare, Ahmad Reza,Zolfigol, Mohammad Ali,Zarei, Mahmoud,Noroozizadeh, Ehsan,Beyzavi, M. Hassan
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p. 89572 - 89577
(2016/10/03)
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- Tertiary Butyl Nitrite Triggered Nitration of Phenols: Solvent- and Structure-Dependent Kinetic Study
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Nitration of phenols with tertiary butyl nitrite (TBN) obeyed second-order kinetics with a first-order dependence on [TBN] and [phenol] under acid-free conditions. Reaction rates were significantly altered by a change in the dielectric constant and other physical properties of solvent. The rate of nitration increased with an increase in temperature (303-323 K) in different solvent media (acetonitrile, dichloroethane, CCl4, dimethyl formamide (DMF), and toluene). The rates of nitration (log k) could not fit into either Amis or Kirkwood plots [log k' vs. (1/D) or [(D - 1)/(2D + 1)], but the trends were better explained by the basic form of multivariate linear solvent energy relationships (MLSER) suggested by the Koppel and Palm approach on the one hand and the Kamlet and Taft approach on the other hand. These observations probably substantiate that cumulative contributions of basic solvent parameters (equilibrium as well as frictional solvent effects) and solvent-solute interactions for solvation of transition state during nitration of phenols. Reaction rates accelerated with the introduction of electron-donating groups and retarded with electron-withdrawing groups. Accordingly, the reactivity of structurally different phenols was found to follow the following sequence: p-OH > p-MeO > p-Me > H > m-Me > p-Cl > p-Br > m-Cl > p-NO2 > m-OH. The results are interpreted by Hammett's theory of linear free energy relationship. The reaction constant (Hammett's ρ) is a measure of the sensitivity of the reaction toward the electronic effects of the substituent. The rho (ρ) values obtained from the present experiments are fairly large negative values (ρ CH3) versus σ? or, Es or combined Taft's relationship. However, Charton's MLRA of the log k with polar, resonance, steric, hydrophobicity, and molar refractivity showing a very good linear relationship was obtained. It is of interest to note that when log kexp values are correlated with log kcal a perfect linearity is obtained with a correlation coefficient of unity, indicating the consonance between experimental and calculated rate constants in the present work.
- Kumar, M. Satish,Rajanna,Venkateswarlu,Rao, K. Lakshman
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supporting information
p. 171 - 196
(2016/04/09)
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- An ortho-nitro phenol synthetic method of compound
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The invention relates to a synthesis method of o-nitrophenol compounds, solving the problems that production hazards are easily caused due to the release of a large deal of heat during the synthesis of o-nitrophenol and the severe environment pollution caused due to the generation of a large deal of waste gas and acid in the process in the prior art. The invention provides the synthesis method of the o-nitrophenol compounds, which comprises the steps: synthesizing 2-(phenoxy)pyridine from phenol compounds; and then sequentially adding 2-(phenoxy)pyridine and a catalyst, a nitrating reagent, an oxidant and an organic solvent into a sealed pressure container, heating and reacting for 10-50 hours in an oil bath of which the temperature is 80 DEG C-130 DEG C to obtain 2-(2-nitrophenyl)oxy pyridine; and finally treating to obtain o-nitrophenol. The synthesis method is simple, convenient and efficient.
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- The synthesis of 1,2-ethanediylbis(triphenylphosphonium) ditribromide as a new brominating agent in the presence of solvents and under solvent-free conditions
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Abstract: 1,2-Ethanediylbis(triphenylphosphonium) ditribromide was quantitatively prepared and used for the bromination of anilines and phenols in the presence of a mixed solvent system (DCM/MeOH 2:1) and also under solvent-free conditions. This new ionic liquid has advantages over similar brominating agents in terms of short reaction time, simple workup, regioselectivity and high yields. Single-crystal X-ray analysis of title salt revealed that the bistriphenylphosphonium cation is organized around an inversion center located at the center of the –CH2–CH2– bridge and the two triphenylphosphine segments are anti with respect to one another. All the tribromide anions adopt a linear geometry with different Br–Br–Br bond angles for each anion. Graphical Abstract: [Figure not available: see fulltext.]
- Salmasi, Reihaneh,Gholizadeh, Mostafa,Salimi, Alireza,Garrison, Jered C.
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p. 2019 - 2028
(2016/09/16)
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- Improved Protocol for Mononitration of Phenols with Bismuth(III) and Iron(III) Nitrates
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A simple and efficient multigram procedure was developed for the selective mononitration of various activated phenols. The reaction proceeded smoothly with 0.5 equivalents of Bi(NO3)3 · 5H2O or Fe(NO3)3 · 9H2O in acetone at ambient temperature or at reflux. The desired products were isolated in 62-93% total yield and essentially no overnitrated compounds were detected.
- W?sińska, Ma?gorzata,Korczewska, Anna,Giurg, Miros?aw,Skarzewski, Jacek
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supporting information
p. 143 - 150
(2015/10/20)
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- N-methyl-2-chloropyridinium iodide/NaNO2/Wet SiO2: Neutral reagent system for the nitration of activated aromatic compounds under very mild conditions
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Mononitration of activated aromatic compounds using N-methyl-2-chloro-pyridinium iodide (Mukaiyama reagent)/NaNO2/wet SiO2 reagent system under neutral, very mild and environmentally safer reaction condition has been developed. Various structurally diverse aromatic rings are subjected in this condition and the corresponding nitro-aromatic compounds are prepared in moderately high yields.
- Azadi, Roya,Nazari-Far, Zahra
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p. 136 - 140
(2015/06/22)
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- Enhanced treatment regimens using mTor inhibitors
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The present invention provides for methods and pharmaceutical compositions comprising inhibitors of mTorC1 and/or mTorC2. In some aspects, the invention provides for treatment regimens resulting in enhanced treatment efficacy and better tolerability.
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Page/Page column 114
(2015/11/27)
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- Vanadium pentoxide as a catalyst for regioselective nitration of organic compounds under conventional and nonconventional conditions
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Vanadium pentoxide is used as an efficient catalyst for regioselective nitration of aromatic compounds under conventional and nonconventional conditions such as ultrasonically assisted (USAR) and microwave-assisted reactions (MWAR). The reactions underwent smoothly and afforded good yields of products with high regioselectivity. Observed longer reaction times (about 8 h) in V2O5 catalyzed reactions reduced to (0.5/30 min) under sonication and (90 s) in the case of MWAR. When ortho position is blocked, para derivatives are obtained as end products while ortho nitro products are obtained when para position is blocked.
- Venkatesham,Reddy, K. Rajendar,Rajanna,Veerasomaiah
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p. 921 - 926
(2014/04/03)
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- Microwave assisted synthesis of nitro phenols from the reaction of phenols with urea nitrate under acid-free conditions
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Urea nitrate was found to be an inexpensive, acid-free, and safe nitrating agent that provides mononitration of phenols and substituted phenols in excellent yields with exclusive ortho-selectivity under microwave irradiation. Microwave assisted reactions reduced the reaction times substantially and enhanced the product yields from good to excellent within shorter reaction times.
- Verma, Sanny,Pandita, Sangeeta,Jain, Suman L.
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p. 1320 - 1322
(2014/03/21)
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- A practical nickel-catalyzed reductive alkylation of amidophenyl bromides
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A modified Weix's reductive coupling for alkylation of amidoaryl bromides based on Ni(COD)2 precatalyst and 2,2′-dipyridyl ligand was developed. This reaction is reliable for amidophenyl bromides and gives yields up to 87%, and is potentially useful in the synthesis of amidophenyl-containing molecules.
- Liu, Xuge,Yang, Zhilin,Li, Ya-Min,Yang, Fan,Feng, Liang,Wang, Nengzhong,Ma, Debiao,Chang, Kwen-Jen,Shen, Yuehai
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p. 9522 - 9529
(2015/03/04)
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- COMBINATION OF KINASE INHIBITORS AND USES THEREOF
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The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase a and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth. The present invention also provides a pharmaceutical kit effective for treating a disease condition associated with PI3 -kinase α and/or mTOR in a subject.
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Paragraph 00502
(2014/10/04)
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- COMBINATION PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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The present invention provides for methods and pharmaceutical compositions for treating proliferative disorders. In one aspect, the method comprises administration of two cell-cycle suppressors having a synergistic effect. In another aspect, two cell-cycle suppressors having a synergistic effect are provided in a pharmaceutical composition.
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Paragraph 0485
(2014/12/09)
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- Palladium-catalyzed aromatic C-H bond nitration using removable directing groups: Regiospecific synthesis of substituted o -nitrophenols from related phenols
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A general and regiospecific transformation of substituted phenols into the related o-nitrophenols has been achieved via a three-step process involving the palladium-catalyzed chelation-assisted ortho-C-H bond nitration as the key step. In the process, 2-pyridinyloxy groups act as removable directing groups for the palladium-catalyzed ortho-nitration of substituted 2-phenoxypridines, and they can be readily removed in the subsequent conversion of the resulting 2-(2-nitrophenoxy)pyridines into 2-nitrophenols.
- Zhang, Wei,Zhang, Jian,Ren, Shaobo,Liu, Yunkui
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p. 11508 - 11516
(2015/01/09)
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- A new oxidovanadium(IV) complex containing an O, N-bidentate Schiff base ligand: Synthesis, characterization, crystal structure determination, thermal study and catalytic activity for an oxidative bromination reaction
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A new oxidovanadium(IV) schiff base complex (1) containing an ethyl bromide pendant group was synthesized by the reaction of the related bidentate O, N-Schiff base ligand and VO(acac)2 in a 2:1 ratio in methanol, under reflux conditions. The Schiff base ligand and its vanadyl Schiff base complex were characterized by 1H NMR and FT-IR spectra, and CHN analysis. The crystal structure of 1 was also determined by single crystal X-ray analysis. The vanadium center in this structure has a distorted tetragonal pyramidal N2O3 coordination sphere. The Schiff base ligand HL acts as a bidentate ligand by coordinating via the nitrogen atom of the imine group and the oxygen atom of the phenolic group, thereby forming a six-membered chelating ring. There are some non-classical inter- and intra-molecular hydrogen bonds of the type C-Ha?O and C-Ha?Br in 1. The catalytic activity of 1 was studied for the oxidative bromination of 2-nitrophenol as a model substrate. Different reaction parameters were studied in this reaction and the oxidative bromination of some organic compounds by a catalytic amount of 1 showed that it was an effective and selective catalyst under optimal conditions. Thermogravimeric analysis of 1 showed that it decomposed in two stages. In addition, complex 1 thermally decomposed in air at 660 C and the XRD pattern of the obtained solid showed the formation of V2O5 nanoparticles with an average size of 57 nm.
- Grivani, Gholamhossein,Tahmasebi, Vida,Khalaji, Aliakbar Dehno
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p. 144 - 150
(2013/12/04)
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- Synthesis, characterization, crystal structure, catalytic activity in oxidative bromination, and thermal study of a new oxidovanadium Schiff base complex containing O, N-bidentate Schiff base ligand
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A new oxidovanadium(IV) Schiff base complex, VOL2 (1), HL = 2-{(E)-[2-(bromoethyl)imino]methyl}-6-methoxy phenol, containing ethyl bromide pendant group was synthesized by direct reaction of HL and VO(acac)2 in the ratio of 2: 1 in methanol at reflux. The Schiff base ligand and its vanadyl complex were characterized by FT-IR spectra and CHN analysis. Additionally, the Schiff base ligand has been characterized by 1H NMR spectroscopy. The crystal structure of 1 was also determined by single-crystal X-ray analysis, showing the distorted square-pyramidal N2O3 coordination around vanadium(IV). The catalytic activity of 1 was studied in the oxidative bromination of 2-nitrophenol as a model substrate, and different reaction parameters were investigated. The oxidative bromination of some organic compounds in the presence of 1 in optimal conditions showed that it was an effective and selective catalyst in those optimal conditions. Thermogravimetric analysis of 1 showed that it decomposed in two stages. 1 was thermally decomposed in air at 660 °C, and the XRD pattern of the obtained solid showed the formation of the V2O5 nanoparticles with average size of 34 nm.
- Grivani, Gholamhossein,Tahmasebi, Vida,Khalaji, Aliakbar Dehno,Eigner, Václav,Du?ek, Michal
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p. 3664 - 3677
(2015/10/19)
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- Oxalylchloride/DMF as an efficient reagent for nitration of aromatic compounds and nitro decarboxylation of cinnamic acids in presence of KNO 3 or NaNO2 under conventional and nonconventional conditions
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Nitration of aromatic compounds and cinnamic acids with oxalylchloride/DMF afforded the corresponding nitro derivatives in the presence of KNO3 or NaNO2 under conventional and nonconventional (ultrasonic and microwave) conditions. The present methodology offers several benefits such as excellent yields, simple work-up procedure, and short reaction times. The yields obtained under present methodology are comparable with those obtained from (POCl3/DMF/KNO3 or NaNO2) and (SOCl 2/DMF/KNO3 or NaNO2) systems followed by shorter reaction times. The reaction times of sonication and microwave conditions are very shorter than those of the conventional conditions.
- Kumar, M. Satish,Reddy, K. Rajendar,Rajanna,Venkanna,Krishnaiah
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p. 977 - 983
(2013/06/05)
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- Ultrasonic and microwave-assisted synthesis of β-nitro styrenes and nitro phenols with tertiary butyl nitrite under acid-free conditions
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Tertiary butyl nitrite (TBN) is an acid-free and safe nitrating agent that provides preferentially β-nitrostyrenes with cinnamic acids and corresponding nitro derivatives with phenols in good yields under classical conditions. However, ultrasonic and microwave-assisted reactions reduced the reaction times substantially and enhanced the yields from good to excellent. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
- Kumar, M. Satish,Rajanna,Reddy, K. Rajendar,Venkateswarlu,Venkanna
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supporting information
p. 2672 - 2677
(2013/07/26)
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- Mass spectra of halogenostyrylbenzoxazoles
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Several series of styrylbenzoxazoles of general formula XC 6H3(NCO)CHCHC6H4Y [X = F, Cl or Br; Y = H, F, Cl, Br, CH3 or CH3O] have been investigated by positive ion electrospray and electron ionization mass spectrometry. These compounds, many of which are biologically active or have pharmaceutical potential, show in their electrospray spectra strong peaks for MH+ ions, which undergo relatively little fragmentation. The electron ionization spectra are extremely clean, being dominated by the loss of an atom or radical, Y, from the ortho position of the pendant ring, by a rearrangement that may be interpreted as a proximity effect. The resultant [M-Y]+ ions are exceptionally stable and rarely undergo further fragmentation. The analytical value of this proximity effect, which is analogous to intramolecular aromatic substitution, in revealing the presence of a substituent in the pendant ring and determining its position, is emphasized. Elimination of a species (including H or F) derived from an ortho substituent in the pendant ring occurs even when apparently more favourable alternative fragmentation is possible by direct cleavage of the CX bond (X = Cl or Br) in the benzoxazole ring.
- Ayrton, Stephen T.,Panova, Jekaterina,Michalik, Adam R.,Martin, William H.C.,Gallagher, Richard T.,Bowen, Richard D.
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p. 120 - 131
(2013/07/27)
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- Fast and efficient bromination of aromatic compounds with ammonium bromide and Oxone
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A highly efficient, rapid and regioselective protocol was developed for the ring bromination of aromatic compounds under mild conditions with ammonium bromide as a source of bromine source and Oxone (potassium peroxysulfate) as an oxidant. No metal catalyst or acidic additive is required. A variety of aromatic compounds, including methoxy, hydroxy, amino, and alkyl arenes, reacted smoothly to give the corresponding monobrominated products in good to excellent yields in very short reaction times. Moreover, dibromination of deactivated anilines to give the corresponding dibromides proceeded in high yields. Interestingly, 1-(2-naphthyl)ethanone provided a ring-brominated product. Georg Thieme Verlag Stuttgart . New York.
- Naresh, Mameda,Arun Kumar, Macharla,Mahender Reddy, Marri,Swamy, Peraka,Nanubolu, Jagadeesh Babu,Narender, Nama
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p. 1497 - 1504
(2013/06/27)
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- Poly(4-vinylpyridinium bromochromate): An efficient reagent for bromination of aromatic compounds
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A simple and efficient method for the bromination of various aromatic compounds by using poly(4-vinylpyridinium bromochromate) is reported. This method has several advantages such as good selectivity between ortho and para positions of aromatic compounds, simple workup, short reaction times, and high yields of the products.
- Albadi, Jalal,Tajik, Hassan,Keshavarz, Mosadegh,Abedini, Masoumeh
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p. 179 - 181
(2013/07/27)
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- Design of ionic liquid 3-methyl-1-sulfonic acid imidazolium nitrate as reagent for the nitration of aromatic compounds by in situ generation of NO 2 in acidic media
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3-Methyl-1-sulfonic acid imidazolium nitrate ([Msim]NO3) as a new Bronsted acidic ionic liquid and nitrating agent was prepared and used for the efficient nitration of aromatic compounds (even aniline derivatives). The dramatic effect of this reagent by in situ generation of nitrogen dioxide as a radical on aromatic compounds to give nitroarenes has been studied.
- Zolfigol, Mohammad A.,Khazaei, Ardeshir,Moosavi-Zare, Ahmad R.,Zare, Abdolkarim,Kruger, Hendrik G.,Asgari, Zhila,Khakyzadeh, Vahid,Kazem-Rostami, Masoud
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experimental part
p. 3640 - 3645
(2012/06/15)
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- Aromatic nitration under neutral conditions using N-bromosuccinimide/ silver(I) nitrate
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The use of N-bromosuccinimide and silver nitrate as a convenient reagent system for the nitration of aromatic compounds under neutral and environmentally safer reaction conditions is described.
- Nowrouzi, Najmeh,Mehranpour, Abdol Mohammad,Bashiri, Elham,Shayan, Zohre
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experimental part
p. 4841 - 4842
(2012/09/22)
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- A new method for the mononitration of phenol derivatives by poly(4-vinylpyridinium nitrate) and silica sulfuric acid under mild conditions
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This procedure works efficiently for high selective mono nitration of phenol and substituted phenol to corresponding nitro compounds in moderate to high yield using poly(4-vinylpyridinium nitrate) and silica sulfuric acid in dichloromethane at room temperature.
- Goudarziafshar, Hamid
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experimental part
p. 458 - 461
(2012/06/18)
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- Synthesis and in vitro antimycobacterial and isocitrate lyase inhibition properties of novel 2-methoxy-2′-hydroxybenzanilides, their thioxo analogues and benzoxazoles
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A new series of 2-methoxy-2′-hydroxybenzanilide derivatives and their thioxo analogues have been synthesised and characterised by IR, NMR and elemental analysis. These compounds were investigated for their in vitro antimycobacterial activities against Mycobacterium tuberculosis 331/88, Mycobacterium avium 330/88, Mycobacterium kansasii 235/80, clinically isolated M. kansasii 6509/96 and the ability to act as in vitro isocitrate lyase inhibitors. The best ICL inhibitors were two compounds from the thiobenzanilide group (8f, 8m), which exhibited an inhibition potential that was equal to the standard compound, 3-nitropropionic acid. In addition, the best antimycobacterial properties were exhibited by benzanilide derivatives 6h, 6k and 6l with 5-Cl and 4′ or 5′ Cl/Br substitution. For all the thiobenzanilide derivatives tested, two conformers were observed in the NMR spectra, which is most likely due to the hindered rotation of the C-N bond.
- Kozic, Ján,Novotná, Eva,Volková, Marie,Stola?íková, Ji?ina,Trejtnar, Franti?ek,Wsól, Vladimír,Vin?ová, Jarmila
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p. 108 - 119
(2013/01/15)
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- Heteropolyacids as an efficient and reusable catalytic system for the regiospecific nitration of phenols with metal nitrates
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Highly regiospecific mononitration of phenols and substituted phenols is accomplished employing a metal nitrate and a catalytic amount of heteropolyacid in acetonitrile. An xclusive ortho-selectivity was observed with excellent yields. A variety of metal nitrates were used to obtain o-nitrophenols exclusively in good to excellent yields. The use of heteropolyacid is key for the selectivity observed.
- Baghernejad, Bita,Heravi, Majid M.,Oskooie, Hossein A.,Bamoharram, Fatemeh F.
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experimental part
p. 145 - 152
(2012/04/18)
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- Green, mild and efficient bromination of aromatic compounds by HBr promoted by trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane in water as a solvent
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A combination of HBr and trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane as a new and powerful oxidant was found effective for facile bromination of different aromatic compounds at room temperature in water as a green solvent. Mild reaction conditions, high selectivity and yield, high reaction rate and non-toxicity are some of the major advantages of this synthetic protocol.
- Khosravi, Kaveh,Kazemi, Samira
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experimental part
p. 387 - 390
(2012/05/20)
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- Regioselective bromination and iodination of aromatic substrates promoted by trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane
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Selective and efficient bromination and iodination of aromatic compounds by ammonium bromide and ammonium iodide, respectively, under promotion of trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane have been explored. Mild reaction conditions, high selectivity and yield, and high reaction rate are some of the major advantages of this synthetic method.
- Azarifar, Davood,Khosravi, Kaveh,Najminejad, Zohreh,Soleimani, Khadijeh
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experimental part
p. 321 - 326
(2012/08/14)
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- A mild procedure for the preparation of o-nitrophenols by nitro urea or ammonium nitrate in the presence of silica sulfuric acid (SiO 2-OSO3H)
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A mixture of ammonium nitrate or nitro urea and silica sulfuric acid was found to be efficient and environmentally friendly nitrating media for the preparation of orto-nitro phenols in dichloromethane at room temperature. A mixture of ammonium nitrate or nitro urea and silica sulfuric acid was found to be efficient and environmentally friendly nitrating media for the preparation of orto-nitro phenols in dichloromethane at room temperature.
- Ghorbani-Choghamarani, Arash,Nikoorazm, Mohsen,Goudarziafshar, Hamid,Naserifar, Zahra,Zamani, Parisa
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experimental part
p. 731 - 734
(2011/11/12)
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