- Catalytic Activation of Unstrained C(Aryl)-C(Alkyl) Bonds in 2,2′-Methylenediphenols
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Catalytic activation of unstrained and nonpolar C-C bonds remains a largely unmet challenge. Here, we describe our detailed efforts in developing a rhodium-catalyzed hydrogenolysis of unstrained C(aryl)-C(alkyl) bonds in 2,2′-methylenediphenols aided by removable directing groups. Good yields of the monophenol products are obtained with tolerating a wide range of functional groups. In addition, the reaction is scalable, and the catalyst loading can be reduced to as low as 0.5 mol %. Moreover, this method proves to be effective to cleave C(aryl)-C(alkyl) linkages in both models of phenolic resins and commercial novolacs resins. Finally, detailed experimental and computational mechanistic studies show that with C-H activation being a competitive but reversible off-cycle reaction, this transformation goes through a directed C(aryl)-C(alkyl) oxidative addition pathway.
- Dong, Guangbin,Ratchford, Benjamin L.,Xue, Yibin,Zhang, Rui,Zhu, Jun
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p. 3242 - 3249
(2022/02/23)
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- Electrophotocatalytic C?H Heterofunctionalization of Arenes
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The electrophotocatalytic heterofunctionalization of arenes is described. Using 2,3-dichloro-5,6-dicyanoquinone (DDQ) under a mild electrochemical potential with visible-light irradiation, arenes undergo oxidant-free hydroxylation, alkoxylation, and amination with high chemoselectivity. In addition to batch reactions, an electrophotocatalytic recirculating flow process is demonstrated, enabling the conversion of benzene to phenol on a gram scale.
- Huang, He,Lambert, Tristan H.
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supporting information
p. 11163 - 11167
(2021/04/19)
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- New procedure for the highly regioselective aerobic bromination of aromatic compounds using copper-based nanocatalyst
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A new procedure for the highly regioselective aerobic bromination of aromatic compounds in the presence of copper-based nanoparticles (CuO/ZnO nanocatalyst) under reflux condition is described. Mechanistic parameters are discussed and the plausible mechanism is proposed. Recyclability of the CuO/ZnO nanocatalyst has also been explored upon aerobic bromination of aromatic compounds.
- Albadi, Jalal,Jalali, Mehdi
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p. 234 - 239
(2020/02/29)
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- Regioselective monobromination of phenols with KBr and ZnAl–BrO3?–layered double hydroxides
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The regioselective mono-bromination of phenols has been successfully developed with KBr and ZnAl–BrO3?–layered double hydroxides (abbreviated as ZnAl–BrO3?–LDHs) as brominating reagents. The para site is much favorable and the ortho site takes the priority if para site is occupied. This reaction featured with excellent regioselectivity, cheap brominating reagents, mild reaction condition, high atom economy, broad substrate scope, and provided an efficient method to synthesize bromophenols.
- Wang, Ligeng,Feng, Chun,Zhang, Yan,Hu, Jun
-
supporting information
(2020/02/22)
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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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- Novel pleconaril derivatives: Influence of substituents in the isoxazole and phenyl rings on the antiviral activity against enteroviruses
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Today, there are no medicines to treat enterovirus and rhinovirus infections. In the present study, a series of novel pleconaril derivatives with substitutions in the isoxazole and phenyl rings was synthesized and evaluated for their antiviral activity against a panel of pleconaril-sensitive and -resistant enteroviruses. Studies of the structure-activity relationship demonstrate the crucial role of the N,N-dimethylcarbamoyl group in the isoxazole ring for antiviral activity against pleconaril-resistant viruses. In addition, one or two substituents in the phenyl ring directly impact on the spectrum of antienteroviral activity. The 3-(3-methyl-4-(3-(3-N,N-dimethylcarbamoyl-isoxazol-5-yl)propoxy)phenyl)-5-trifluoromethyl-1,2,4-oxadiazole 10g was among the compounds exhibiting the strongest activity against pleconaril-resistant as well as pleconaril-susceptible enteroviruses with IC50 values from 0.02 to 5.25 μM in this series. Compound 10g demonstrated markedly less CYP3A4 induction than pleconaril, was non-mutagenic, and was bioavailable after intragastric administration in mice. These results highlight compound 10g as a promising potential candidate as a broad spectrum enterovirus and rhinovirus inhibitor for further preclinical investigations.
- Egorova, Anna,Ekins, Sean,Jahn, Birgit,Kazakova, Elena,Makarov, Vadim,Schmidtke, Michaela
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- Catalytic activation of unstrained C(aryl)–C(aryl) bonds in 2,2′-biphenols
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Transition metal catalysis has emerged as an important means for C–C activation that allows mild and selective transformations. However, the current scope of C–C bonds that can be activated is primarily restricted to either highly strained systems or more polarized C–C bonds. In contrast, the catalytic activation of non-polar and unstrained C–C moieties remains an unmet challenge. Here we report a general approach for the catalytic activation of the unstrained C(aryl)–C(aryl) bonds in 2,2′-biphenols. The key is to utilize the phenol moiety as a handle to install phosphinites as a recyclable directing group. Using hydrogen gas as the reductant, monophenols are obtained with a low catalyst loading and high functional group tolerance. This approach is also applied to the synthesis of 2,3,4-trisubstituted phenols. A further mechanistic study suggests that the C–C activation step is mediated by a rhodium(i) monohydride species. Finally, a preliminary study on breaking the inert biphenolic moieties in lignin models is illustrated.
- Zhu, Jun,Wang, Jianchun,Dong, Guangbin
-
-
- Synthesis method of 3,6-dichlorosalicylic acid
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The invention provides a synthesis method of 3,6-dichlorosalicylic acid. The synthesis method comprises the following steps: S1, brominating o-cresol to obtain 2-methyl-4-bromophenol; S2, chlorinating2-methyl-4-bromophenol to obtain 2-methyl-3,6-dichloro-4-bromophenol; S3, oxidizing 2-methyl-3,6-dichloro-4-bromophenol to obtain 3,6-dichloro-4-bromosalicylic acid; S4, debrominating 3,6-dichloro-4-bromosalicylic acid to obtain 3,6-dichlorosalicylic acid. In the synthesis route, the raw materials are easily available and the comprehensive cost is low. The preparation process comprises directional bromination and directional chlorination, selectivity is high, product quality is stable, and total yield is high. Besides, the preparation process of 3,6-dichlorosalicylic acid is simple, and industrial implementation is facilitated.
- -
-
Paragraph 0043; 0044; 0048; 0049
(2019/06/05)
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- Regioselective bromination of arenes mediated by triphosgene-oxidized bromide
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This article first time describes triphosgene (BTC) as an oxidant while the non-toxic and easy-to-handle potassium bromide (KBr) as the source of bromine to the bromination reaction of aromatic substrates. The novel brominating protocol gives excellent para-regioselectivity of the alkoxyl/hydroxyl arenes and high yield, offering good potential of commercial scale applications. The mechanism of “Triphosgene oxidize bromide” was proposed.
- Xu, Yingzhou,Hu, Dufen,Zheng, Hui,Mei, David,Gao, Zhaobo
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supporting information
(2019/08/30)
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- Directed Structural Transformations of Coordination Polymers Supported Single-Site Cu(II) Catalysts to Control the Site Selectivity of C-H Halogenation
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A main difficulty in C-H bond functionalization is to undertake the catalyst control accurately where the reaction takes place. In this work, to achieve highly effective and regioselective single-site catalysts, a three-dimensional (3D) rhombus-like framework of {[Mn(Hidbt)DMF]·H2O}n (1) [H3idbt = 5,5′-(1H-imidazole-4,5-diyl)-bis(2H-tetrazole)] containing coordinated DMF molecules was constructed. For the dissolution-recrystallization structural transformation process, attractive structural transformations proceeded from 1 to a new crystalline species formulated as {[Mn3(idbt)2(H2O)2]·3H2O}n (2) with a 3D windowlike architecture, and then the Mn ions in 2 could be exchanged with Cu ions through cation exchange in a single-crystal to single-crystal fashion to produce the Cu-exchanged product {[Mn2Cu(idbt)2(H2O)2]·3H2O}n (2a), which had a windowlike framework like that of 2. Furthermore, 2 and 2a were used as heterogeneous catalysts for the regioselective C-H halogenation of phenols with N-halosuccinimides (NCS and NBS) to produce the site selective single monohalogenated products. It was found that the catalytic activity and site selectivity of 2a were much higher than those of 2, because the unique structural features of 2a with the uniformly dispersed CuII active centers served as a single-site catalyst with a site-isolated and well-defined platform to promote the C-H halogenation reaction in regiocontrol and guide an orientation that favored the para selectivity during the reaction process.
- Huang, Chao,Zhu, Kaifang,Zhang, Yingying,Shao, Zhichao,Wang, Dandan,Mi, Liwei,Hou, Hongwei
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supporting information
p. 12933 - 12942
(2019/10/11)
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- Mild and Regioselective Bromination of Phenols with TMSBr
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In this work, an unexpected promoting effect of by-product thioether was observed, leading to a mild and regioselective bromination of phenols with TMSBr. This method can tolerate a series of functional groups such as the reactive methoxyl, amide, fluoro, chloro, bromo, aldehyde, ketone and ester groups, and has the potential to recycle the by-product thioether and isolate the desired product under column chromatography-free conditions. Mechanism studies revealed that O–H···S hydrogen bond may be formed between phenol and by-product thioether. Possibly owing to the steric hindrance effect from by-product thioether, the electrophilic bromination at para-position of phenols is much favorable.
- Ma, Xiantao,Yu, Jing,Jiang, Mengyuan,Wang, Mengyu,Tang, Lin,Wei, Mengmeng,Zhou, Qiuju
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supporting information
p. 4593 - 4596
(2019/07/05)
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- A phenol compound high regioselective bromination method
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The invention discloses a phenol compound high regioselective bromination of the method, the method to trimethyl silane as brominating agent, in order to aryl sulfoxide as activator, with the phenol compound in the 0 - 50 °C lower, in a solvent, the reaction is stirred under an atmosphere of nitrogen at 1 - 12 hours, to realize the phenol compound high regioselective bromination, filtered, extraction columns chromatography separation to obtain the bromo phenol compound. This invention adopts the aryl sulfoxide as activator, sulfoxide substituted Kiev, on the one hand so that the phenol compound bromo the higher selectivity of the reaction region, and when the phenol compound hydroxy alignment not substituted basetime, regional selective para - bromo product, when the phenol compound hydroxy position there is substituted basetime, selective ortho - bromo product obtained; on the other hand if it through the filter, the extraction can be realized at the same time the isolation and purification of the recycling of the by-product, compared with column chromatography, reduces the separation and purification cost.
- -
-
Paragraph 0022; 0023; 0024
(2019/06/05)
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- Green synthesis of bromo organic molecules and investigations on their antibacterial properties: An experimental and computational approach
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A simple, environmentally benign methodology has been developed to synthesize some bromoorganic compounds which have potential as antimicrobial agents. The required compounds were obtained through microwave (MW) irradiation, on-water reactions and using cetyltrimethylammonium tribromide (CTMATB) as the bromine source. The high yield of the product could be achieved within short reaction times, thus representing the main attribute of the present synthetic approach. The compounds were evaluated for in vitro antibacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Bacillus subtilis. Further, in silico studies were carried out to elucidate the interactions of the compounds with the bacterial proteins.
- Longkumer, Naruti,Richa, Kikoleho,Karmaker, Rituparna,Kuotsu, Visekhonuo,Supong, Aola,Jamir, Latonglila,Bharali, Pranjal,Sinha, Upasana Bora
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p. 276 - 283
(2019/07/12)
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- A selective PPAR δ agonist GW501516 preparation method
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The invention discloses a selective PPAR δ agonist GW501516 preparation method, which belongs to the technical field of synthesis of pharmaceutical intermediates. In order to O-methyl phenol as raw materials, and the iodine/potassium bromide through the o
- -
-
Paragraph 0033-0035
(2019/07/01)
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- o-xylylene bis(triethyl ammonium tribromide) as a mild and recyclable reagent for rapid and regioselective bromination of anilines and phenols
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Background: o-Xylylene bis(triethyl ammonium tribromide) (OXBTEATB) as a recyclable and high bromine containing di-(tribromide) reagent has been employed for the bromination of various organic substrates such as phenol and aniline or its derivatives. This catalyst can be recovered and reused several times. Methods: Aryl bromides shown in Table 1, were easily produced from bromination of aromatic compounds by OXBTEATB. This high-yield process lets the reagents to be recycled and reused. Results: As shown in Table 1, substituted anilines, phenols and β-naphthol were found to be the most reactive and immediately converted to the corresponding mono-brominated products by OXBTEATB. Conclusion: OXBTEATB can be considered a solidified bromine. This novel reagent has variable solubility in different polar protic and aprotic solvents but insoluble in non-polar aprotic solvent. Subsequently, OXBTEATB can be recognized as a more useful brominating and regioselective catalyst than the liquid bromine.
- Hemati, Roya,Shahvelayati, Ashraf S.,Yadollahzadeh, Khadijeh
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p. 682 - 687
(2018/07/14)
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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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- Ultrasonically assisted halogenation of aromatic compounds using isoquinolinium bound hypervalent chromium and tetrabutylammonium halides in PEG-600 solutions under acid free and solvent-free conditions
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Isoquinolinium bound Cr(VI) reagents like isoquinolinium dichromate (IQDC) and isoquinolinium chlorochromate (IQCC) have been successfully accomplished as efficient reagents for oxidative halogenation of aromatic compounds using tetrabutylammonium halide (TBAX) as halogenating agents in aqueous polyethylene glycol (PEG-600) under acid free conditions. Tetrabutylammonium bromide (TBAB) has been used for bromination and tetrabutylammonium iodide (TBAI) for iodination. The halogenation reactions that occurred smoothly in 2 to 7 h under conventional conditions are accelerated magnificently under sonication with few minutes (25 to 70 min) of reaction time and fairly good yields. The reactions occurred at moderate temperature under mild and environmentally safe conditions with simple work up.
- Sambashiva Rao,Ramesh, Kola,Rajanna,Chakrvarthi
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p. 1892 - 1896
(2018/07/10)
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- Examination of Selectivity in the Oxidation of ortho- and meta-Disubstituted Benzenes by CYP102A1 (P450 Bm3) Variants
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Cytochrome P450 CYP102A1 (P450 Bm3) variants were used to investigate the products arising from the P450 catalysed oxidation of a range of disubstituted benzenes. The variants used all generated increased levels of metabolites compared to the wild-type enzyme. With ortho-halotoluenes up to six different metabolites could be identified whereas the oxidation of 2-methoxytoluene generated only two aromatic oxidation products. Addition of an ethyl group markedly shifted the selectivity for oxidation to the more reactive benzylic position. Epoxidation of an alkene was also preferred to aromatic oxidation in 2-methylstyrene. Significant minor products arising from the migration of one substituent to a different position on the benzene ring were formed during certain P450-catalysed substrate turnovers. For example, 2-bromo-6-methylphenol was formed from the turnover of 2-bromotoluene and the dearomatisation product 6-ethyl-6-methylcyclohex-2,4-dienone was generated from the oxidation of 2-ethyltoluene. The RLYF/A330P variant altered the product distribution enabling the generation of certain metabolites in higher quantities. Using this variant produced 4-methyl-2-ethylphenol from 3-ethyltoluene with ≥90 % selectivity and with a biocatalytic activity suitable for scale-up of the reaction.
- Munday, Samuel D.,Dezvarei, Shaghayegh,Lau, Ian C.-K.,Bell, Stephen G.
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p. 2512 - 2522
(2017/07/12)
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- Regioselective monobromination of aromatics via a halogen bond acceptor-donor interaction of catalytic thioamide and N-bromosuccinimide
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Regioselective monobromination of various aromatics was achieved at room temperature using N-bromosuccinimide and 5 mol% of thioamides in acetonitrile. With thiourea as catalyst, activated aromatics, such as anisole, acetanilide, benzamide and phenol analogues containing electron donating or withdrawing groups, were brominated with high regioselectivity. Room temperature brominations of weakly activated aromatics and deactivated 9-fluorenone were accomplished by 5 mol% thioacetamide, higher substrates concentrations and longer reaction times. A backbonding of the bromine lone pairs with the π*of C[dbnd]S group and a halogen bond between the halogen bond donor bromine and the halogen bond acceptor sulfur of the thioamide are thought to be the principal interactions and cause of N-bromosuccinimide activation.
- Bovonsombat, Pakorn,Teecomegaet, Pattaradra,Kulvaranon, Panisanun,Pandey, Aditi,Chobtumskul, Kittithorn,Tungsirisurp, Sireethorn,Sophanpanichkul, Punyanuch,Losuwanakul, Satreerat,Soimaneewan, Dechathon,Kanjanwongpaisan, Patcharida,Siricharoensang, Pornpawit,Choosakoonkriang, Sirirat
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p. 6564 - 6572
(2017/10/17)
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- Ti-Catalyzed Synthesis of Exocyclic Allenes on Oxygen Heterocycles
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A general method for the straightforward synthesis of exocyclic allenes on five-, six-, seven-, and eight-membered oxygen heterocycles is described. A Barbier-type titanocene(III)-catalyzed cyclization of propargyl halides with a pendant carbonyl group is
- Padial, Natalia M.,Hernández-Cervantes, Carmen,Mu?oz-Bascón, Juan,Roldán-Molina, Esther,García-Martínez, Mireya,Ruiz-Muelle, Ana Belén,Rosales, Antonio,álvarez-Corral, Míriam,Mu?oz-Dorado, Manuel,Rodríguez-García, Ignacio,Oltra, J. Enrique
-
supporting information
p. 639 - 645
(2017/02/05)
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- The Catalyst-Controlled Regiodivergent Chlorination of Phenols
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Different catalysts are demonstrated to overcome or augment a substrate's innate regioselectivity. Nagasawa's bis-thiourea catalyst was found to overcome the innate para-selectivity of electrophilic phenol chlorination, yielding ortho-chlorinated phenols that are not readily obtainable via canonical electrophilic chlorinations. Conversely, a phosphine sulfide derived from 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) was found to enhance the innate para-preference of phenol chlorination.
- Maddox, Sean M.,Dinh, Andrew N.,Armenta, Felipe,Um, Joann,Gustafson, Jeffrey L.
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supporting information
p. 5476 - 5479
(2016/11/17)
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- Vanadium bromoperoxidase (VBrPO) mimics: Synthesis, structure and a comparative account of the catalytic activity of newly synthesized oxidovanadium and oxido-peroxidovanadium complexes
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The bioinspired catalytic activities of two newly synthesised vanadium(iv)dioxido (complex 1) and vanadium(v) oxido-peroxido (complex 2) complexes with the neutral tridentate benzimidazole ligand, 2,6-di-(1H-benzo[d]imidazol-2-yl)pyridine (Byim) have been established. The bromoperoxidase activities of these complexes have been established through the activation of C-H bonds of substrates like phenol, o-cresol and p-cresol. The products, characterized by GC analysis shows that good conversions have been achieved. Considering the catalytic efficiency of the complexes, complex 2, with one in-built peroxido group is found to be more potent than complex 1. The catalytic cycles of both the complexes have been established from experimental results.
- Palmajumder, Eshita,Patra, Swarup,Drew, Michael G. B.,Mukherjea, Kalyan K.
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p. 8696 - 8703
(2016/10/13)
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- Accelerated Discovery in Photocatalysis using a Mechanism-Based Screening Method
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Herein, we report a conceptually novel mechanism-based screening approach to accelerate discovery in photocatalysis. In contrast to most screening methods, which consider reactions as discrete entities, this approach instead focuses on a single constituent mechanistic step of a catalytic reaction. Using luminescence spectroscopy to investigate the key quenching step in photocatalytic reactions, an initial screen of 100 compounds led to the discovery of two promising substrate classes. Moreover, a second, more focused screen provided mechanistic insights useful in developing proof-of-concept reactions. Overall, this fast and straightforward approach both facilitated the discovery and aided the development of new light-promoted reactions and suggests that mechanism-based screening strategies could become useful tools in the hunt for new reactivity. Enlightened! A mechanism-based screening approach can accelerate discovery in photocatalysis. It focuses on a single mechanistic step of a reaction class: the quenching step central to photocatalytic transformations. Luminescence spectroscopy was used to screen 100 compounds, identifying two promising substrate classes. A second, more-focused screen provided mechanistic insights for developing proof-of-concept reactions.
- Hopkinson, Matthew N.,Gómez-Suárez, Adrián,Teders, Michael,Sahoo, Basudev,Glorius, Frank
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supporting information
p. 4361 - 4366
(2016/04/05)
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- Isoquinolinium Dichromate and Chlorochromate as Efficient Catalysts for Oxidative Halogenation of Aromatic Compounds under Acid-Free Conditions
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Isoquinolinium dichromate and isoquinolinium chlorochromate were found as efficient catalysts to trigger oxidative bromination and iodination of aromatic hydrocarbons with KBr/KI and KHSO4 under acid-free conditions. Reaction times reduced highly significantly under sonication, followed by corresponding mono bromo derivatives in very good yield with high regioselectivity.
- Rao, A. Sambashiva,Rajanna,Reddy, K. Rajendar,Kulkarni, Subhash
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p. 832 - 837
(2016/02/12)
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- A Metal-Free and Ionic Liquid-Catalyzed Aerobic Oxidative Bromination in Water
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A metal-free aerobic oxidative bromination of aromatic compounds in water has been developed. Hydrobromic acid is used as a bromine source and 2-methylpyridinium nitrate ionic liquid is used as a recyclable catalyst. Water is used as the reaction mediate. This is the first report of aerobic oxidative bromination using only catalytic amount of metal-free catalyst. This system shows not only high bromine atom economy, but also high bromination selectivity. The possible mechanism and the role of the catalyst in this system have also been discussed.
- Wang, Jian,Chen, Shu-Bin,Wang, Shu-Guang,Li, Jing-Hua
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p. 513 - 517
(2015/03/30)
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- Efficient and Practical Oxidative Bromination and Iodination of Arenes and Heteroarenes with DMSO and Hydrogen Halide: A Mild Protocol for Late-Stage Functionalization
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An efficient and practical system for inexpensive bromination and iodination of arenes as well as heteroarenes by using readily available dimethyl sulfoxide (DMSO) and HX (X = Br, I) reagents is reported. This mild oxidative system demonstrates a versatile protocol for the synthesis of aryl halides. HX (X = Br, I) are employed as halogenating reagents when combined with DMSO which participates in the present chemistry as a mild and inexpensive oxidant. This oxidative system is amenable to late-stage bromination of natural products. The kilogram-scale experiment (>95% yield) shows great potential for industrial application.
- Song, Song,Sun, Xiang,Li, Xinwei,Yuan, Yizhi,Jiao, Ning
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supporting information
p. 2886 - 2889
(2015/06/30)
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- Synthesis of deuterated benzopyran derivatives as selective COX-2 inhibitors with improved pharmacokinetic properties
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We designed a series of specifically deuterated benzopyran analogues as new COX-2 inhibitors with the aim of improving their pharmacokinetic properties. As expected, the deuterated compounds retained potency and selectivity for COX-2. The new molecules possess improved pharmacokinetic profiles in rats compared to their nondeuterated congeners. Most importantly, the new compounds showed pharmacodynamic efficacy in several murine models of inflammation and pain. The benzopyran derivatives were separated into their enantiomers, and the activity was found to reside with the S-isomers. To streamline the synthesis of the desired S-isomers, an organocatalytic asymmetric domino oxa-Michael/aldol condensation reaction was developed for their preparation.
- Zhang, Yanmei,Tortorella, Micky D.,Wang, Yican,Liu, Jianqi,Tu, Zhengchao,Liu, Xiaorong,Bai, Yang,Wen, Dingsheng,Lu, Xin,Lu, Yongzhi,Talley, John J.
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p. 1162 - 1166
(2014/12/10)
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- Preparation of carbazole and dibenzofuran derivatives by selective bromination on aromatic rings or benzylic groups with N-bromosuccinimide
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N-Bromosuccinimide (NBS), a bromine source, has been used to study the bromination of toluidine and cresols systematically to clarify the underlying mechanism and the orientation effect. It has been found that bromination of toluidine and cresols which possess electron-donating NH2/OH with NBS gives electrophilic aromatic substitution products quickly instead of the desired benzylic bromination products. In contrast, when the electronic effect of the substituted groups is reversed, only the benzylic bromination products are gained. Based on this methodology, several potential AChE inhibitors, such as 2-methoxy-5-(benzylamino)methyl-dibenzofuran, 3-bromo-2-methoxy-5-methyl-9H- carbazole, 3,6-dibromo-2-methoxy-5-methyl-9H-carbazole, and 5-(bromomethyl)-2- methoxy-9H-(phenylsulfonyl)-carbazole have been synthesized.
- Fang, Lei,Zhang, Haun,Fang, Xubin,Gou, Shaohua,Cheng, Lin
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p. 635 - 641
(2014/06/23)
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- BIARYL DERIVATIVES AS GPR120 AGONISTS
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The present invention relates to biaryl derivatives of Formula 1, a method for preparing the same, a pharmaceutical composition comprising the same and use thereof. The biaryl derivatives of Formula 1 according to the present invention promote GLP-1 formation in the gastrointestinal tract and improve insulin resistance in the liver or in muscle due to anti-inflammatory action in macrophages, lipocytes, etc., and can accordingly be effectively used for preventing or treating diabetes, complications of diabetes, obesity, non-alcoholic fatty liver, steatohepatitis, osteoporosis or inflammation.
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Paragraph 528; 529; 530
(2015/01/16)
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- ORGANIC COMPOUNDS
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Novel benzofuran derivatives are disclosed. The derivatives have S1P1 receptor activity and/or disease modifying activity and find use in the treatment of conditions or diseases associated with the immune, vascular and nervous systems in animals and/or humans
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Page/Page column 50
(2014/05/24)
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- Synthesis, structural characterization, VHPO mimicking peroxidative bromination and DNA nuclease activity of oxovanadium(v) complexes
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The two novel oxovanadium(v) complexes [VO(PyDC)(BHA)] (1) [PyDC = pyridine-2,6-dicarboxylate, BHA = benzohydroxamate] and [VO(PyDC)(BPHA)] (2) [BPHA = benzophenyl hydroxamate] were synthesized by successive addition of a methanolic solution of H2PyDC and the corresponding hydroxamic acid ligand to the aqueous solution of ammonium metavanadate (NH4VO 3). The hydroxamic acid ligands were characterized by elemental analysis, IR, UV-vis and NMR studies whereas the complexes were characterized by IR, UV-vis, CHN, molar conductance, magnetic moment, mass and NMR spectroscopic methods. The structures of the complexes were determined by single crystal X-ray crystallography. The structures of both complexes reveal that vanadium(v) has distorted octahedral geometry. The bromoperoxidase activities of these complexes have been demonstrated through the activation of C-H bonds of phenol, o-cresol and p-cresol. The catalytic products have been characterized by GC-MS analysis which shows that good conversions have been achieved. So far as the catalytic efficiency of the complexes are concerned complex 2 is found to be superior to complex 1. Both the complexes were tested for DNA nuclease activity with pUC19 plasmid DNA. The results show that both of them exhibited nuclease activity against pUC19 circular plasmid DNA. The complexes produced both nicked coils and linear forms. In this case also it is observed that complex 2 shows better nuclease activity than complex 1.
- Patra, Swarup,Chatterjee, Suparna,Si, Tapan Kr.,Mukherjea, Kalyan K.
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p. 13425 - 13435
(2013/09/23)
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- Vanadate-dependent bromoperoxidases from Ascophyllum nodosum in the synthesis of brominated phenols and pyrroles
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Bromoperoxidases from the brown alga Ascophyllum nodosum, abbreviated as VBrPO(AnI) and VBrPO(AnII), show 41% sequence homology and differ by a factor of two in the percentage of α-helical secondary structures. Protein monomers organize into homodimers for VBrPO(AnI) and hexamers for VBrPO(AnII). Bromoperoxidase II binds hydrogen peroxide and bromide by approximately one order of magnitude stronger than VBrPO(AnI). In oxidation catalysis, bromoperoxidases I and II turn over hydrogen peroxide and bromide similarly fast, yielding in morpholine-4-ethanesulfonic acid (MES)-buffered aqueous tert-butanol (pH 6.2) molecular bromine as reagent for electrophilic hydrocarbon bromination. Alternative compounds, such as tribromide and hypobromous acid are not sufficiently electrophilic for being directly involved in carbon-bromine bond formation. A decrease in electrophilicity from bromine via hypobromous acid to tribromide correlates in a frontier molecular orbital (FMO) analysis with larger energy gaps between the π-type HOMO of, for example, an alkene and the σ*Br,X-type LUMO of the bromination reagent. By using this approach, the reactivity of substrates and selectivity for carbon-bromine bond formation in reactions mediated by vanadate-dependent bromoperoxidases become predictable, as exemplified by the synthesis of bromopyrroles occurring naturally in marine sponges of the genera Agelas, Acanthella, and Axinella. The Royal Society of Chemistry.
- Wischang, Diana,Radlow, Madlen,Hartung, Jens
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p. 11926 - 11940
(2013/09/02)
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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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- Synthesis and antioxidant activity of 5-hydroxycoumarans,c 6-hydroxychromanes and sulfur-containing derivatives on their base
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A synthesis of 5-hydroxycoumarans, 6-hydroxychromanes and their dodecylthiomethyl- substituted derivatives was accomplished based on methylphenols through the intermediate preparation of 2-allyl-4-alkoxyphenols. The sulfur-containing compounds synthesized
- Yagunov,Khol'shin,Kandalintseva,Prosenko
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p. 1395 - 1400
(2014/05/06)
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- Enthalpy-entropy compensation combined with cohesive free-energy densities for tuning the melting temperatures of cyanobiphenyl derivatives
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This work illustrates how minor structural perturbations produced by methylation of 4′-(dodecyloxy)-4-cyanobiphenyl leads to enthalpy-entropy compensation for their melting processes, a trend which can be analyzed within the frame of a simple intermolecular cohesive model. The transformation of the melting thermodynamic parameters collected at variable temperatures into cohesive free-energy densities expressed at a common reference temperature results in a novel linear correlation, from which melting temperatures can be simply predicted from molecular volumes. In tune with temperature! The transformation of the melting thermodynamic parameters into cohesive free-energy densities (CFED) for 4′-(n-oxy)-i′-methyl-j-methyl-4-cyanobiphenyl (CnLi′,j) provides a novel linear correlation for predicting melting temperatures in a simple way. Copyright
- Dutronc, Thibault,Terazzi, Emmanuel,Guenee, Laure,Buchwalder, Kerry-Lee,Spoerri, Aurore,Emery, Daniel,Mareda, Jiri,Floquet, Sebastien,Piguet, Claude
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supporting information
p. 8447 - 8456
(2013/07/19)
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- Structure-activity relationships of bisphenol a analogs at estrogen receptors (ERs): Discovery of an ERα-selective antagonist
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Our multi-template approach for drug discovery, focusing on protein targets with similar fold structures, has yielded lead compounds for various targets. We have also shown that a diphenylmethane skeleton can serve as a surrogate for a steroid skeleton. H
- Maruyama, Keisuke,Nakamura, Masaharu,Tomoshige, Shusuke,Sugita, Kazuyuki,Makishima, Makoto,Hashimoto, Yuichi,Ishikawa, Minoru
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p. 4031 - 4036
(2013/07/19)
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- PROCESS FOR PRODUCTION OF OXIDATION REACTION PRODUCT OF AROMATIC COMPOUND
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The present invention provides a process for producing an oxidation reaction product of an aromatic compound, having excellent environmental load reduction performance, cost reduction performance, etc. Provided is a process for producing an oxidation reaction product of a raw material aromatic compound by reacting the raw material aromatic compound with an oxidizing agent. The process further uses an electron donor-acceptor linked molecule. The process includes the step of: reacting the electron donor-acceptor linked molecule in an electron-transfer state, the oxidizing agent, and the raw material aromatic compound, thereby generating an oxidation reaction product resulting from oxidation of the raw material aromatic compound.
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Page/Page column 20
(2012/07/14)
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- Selectivity enhancement of aromatic halogenation reactions at the micellar interface: Effect of highly ionic media
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Halogenation (iodination and bromination) of various aromatic compounds has been studied in micellar media in order to observe the effect on regioselectivity and conversion of the reaction. The addition of surfactant causes a change in the chemical shifts of the aromatic proton resonance of phenol which proves the orientation of the aromatic compound on the micellar surface. However, increase in ionic strength of the reaction media affects the selectivity of reaction by disturbing this spatial orientation of the aromatic compound in the micelle. Selectivity towards particular isomers is dependent on the concentration of the surfactant. In bromination of chlorobenzene (deactivated aromatic compound) enhancement in selectivity and conversion towards the para isomer has been observed.
- Samant, Bhupesh S.,Bhagwat, Sunil S.
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scheme or table
p. 1039 - 1044
(2012/10/18)
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- Bromination of phenols in bromoperoxidase-catalyzed oxidations
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Phenol and ortho-substituted derivatives furnish products of selective para-bromination, if treated with sodium bromide, hydrogen peroxide, and the vanadate(V)-dependent bromoperoxidase I from the brown alga Ascophyllum nodosum. Relative rates of bromination in morpholine-4-ethane sulfonic acid (MES)-buffered aqueous tert-butanol (pH 6.2) increase by a factor 32, as the ortho-substituent in a phenol changes from F via Cl, OCH3, C(CH 3)3, and H to CH3. The polar effect in phenol bromination by the enzymatic method, according to a Hammett-correlation (ρ=-3), compares to reactivity of molecular bromine under identical conditions (ρ=-2). Hypobromous acid is not able to electrophilically substitute bromine for hydrogen at pH 6.2 in aqueous tert-butanol. The tribromide anion behaves in MES-buffered aqueous tert-butanol as electrophile (ρ~-3), showing a similar polar effect in phenol bromination as molecular bromine.
- Wischang, Diana,Hartung, Jens
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supporting information
p. 9456 - 9463
(2012/11/07)
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- Molecular cloning, structure, and reactivity of the second bromoperoxidase from Ascophyllum nodosum
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The sequence of bromoperoxidase II from the brown alga Ascophyllum nodosum was determined from a full length cloned cDNA, obtained from a tandem mass spectrometry RT-PCR-approach. The clone encodes a protein composed of 641 amino-acids, which provides a mature 67.4 kDa-bromoperoxidase II-protein (620 amino-acids). Based on 43% sequence homology with the previously characterized bromoperoxidase I from A. nodosum, a tertiary structure was modeled for the bromoperoxidase II. The structural model was refined on the basis of results from gel filtration and vanadate-binding studies, showing that the bromoperoxidase II is a hexameric metalloprotein, which binds 0.5 equivalents of vanadate as cofactor per 67.4 kDa-subunit, for catalyzing oxidation of bromide by hydrogen peroxide in a bi-bi-ping-pong mechanism (kcat = 153 s-1, 22 °C, pH 5.9). Bromide thereby is converted into a bromoelectrophile of reactivity similar to molecular bromine, based on competition kinetic data on phenol bromination and correlation analysis. Reactivity provided by the bromoperoxidase II mimics biosynthesis of methyl 4-bromopyrrole-2-carboxylate, a natural product isolated from the marine sponge Axinella tenuidigitata.
- Wischang, Diana,Radlow, Madlen,Schulz, Heiko,Vilter, Hans,Viehweger, Lutz,Altmeyer, Matthias O.,Kegler, Carsten,Herrmann, Jennifer,Mueller, Rolf,Gaillard, Fanny,Delage, Ludovic,Leblanc, Catherine,Hartung, Jens
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supporting information
p. 25 - 34
(2012/11/13)
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- Cu-Mn spinel oxide catalyzed regioselective halogenation of phenols and N-heteroarenes
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A novel simple, mild chemo- and regioselective method has been developed for the halogenation of phenols using Cu-Mn spinel oxide as a catalyst and N-halosuccinimide as halogenating agent. In the presence of Cu-Mn spinel oxide B, both electron-withdrawing and electron-donating groups bearing phenols gave monohalogenated products in good to excellent yields with highest para-selectivity. The para-substituted phenol gave monohalogenated product with good yield and ortho-selectivity. N-Heteroarenes such as indoles and imidazoles also gave monohalogenated products with high selectivity. Unlike the copper-catalyzed halogenation, the present method works well with electron-withdrawing group bearing phenols and gives comparatively better yields and selectivity. The Cu-Mn spinel catalyst is robust and reused three times under optimized conditions without any loss in catalytic activity. Nonphenolics did not undergo this transformation.
- Singh, Parvinder Pal,Thatikonda, Thanusha,Kumar, K. A. Aravinda,Sawant, Sanghapal D.,Singh, Baldev,Sharma, Amit Kumar,Sharma,Singh, Deepika,Vishwakarma, Ram A.
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scheme or table
p. 5823 - 5828
(2012/09/05)
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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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- 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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- Synthesis of substituted asymmetrical biphenyl amino esters as alpha helix mimetics
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As part of our ongoing project to develop new molecular probes for estrogen receptor-alpha, we are exploring the utility of internally-substituted asymmetric biphenyls as a proteomimetic scaffold. In this study, we describe synthetic methods for preparing
- Williams, Anna B.,Hanson, Robert N.
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experimental part
p. 5406 - 5414
(2012/09/08)
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- PAI-1 INHIBITOR
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The compound represented by the following formula (I) and the like have PAI-1 inhibition activity; wherein: R1 represents a C6-10 aryl group which may be substituted or the like; T represents a single bond or the like; m represents 0
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Page/Page column 271
(2011/02/17)
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- Simple and improved regioselective brominations of aromatic compounds using N-benzyl-N,N-dimethylanilinium peroxodisulfate in the presence of potassium bromide under mild reactions conditions
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A simple, efficient, and mild method for the selective bromination of some activated aromatic compounds using N-benzyl-N,N-dimethylanilinium peroxodisulfate in the presence of potassium bromide in non-aqueous solution is reported. The results obtained revealed good to excellent selectivity between the ortho and para positions of phenols and methoxyarenes.
- Ghasemnejad-Bosra, Hassan,Ramzanian-Lehmali, Farhad,Jafari, Somaye
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experimental part
p. 685 - 692
(2012/01/16)
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- Aerobic oxybromination of phenols catalyzed by sodium nitrite under mild conditions
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An efficient catalytic system for oxybromination of phenols under mild conditions has been developed, which utilizes sodium nitrite as the catalyst, dioxygen or air as the terminal oxidant, aqueous hydrobromic acid or molecular bromine as the bromine resource. From both the atom-economic and environmental points of view, the developed protocol is expected to provide a valuable synthetic method for practical applications in laboratory or industry. Georg Thieme Verlag Stuttgart - New York.
- Xu, Li,Wang, Yong,Wen, Xin,Ding, Chengrong,Zhang, Guofu,Liang, Xinmiao
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supporting information; experimental part
p. 2265 - 2269
(2011/10/31)
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- Regioselective and high-yielding bromination of phenols and anilins using N-bromosaccharin and amberlyst-15
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A regioselective and facile conversion method for bromination of anilines and phenols using N-bromosaccharine in the presence of a catalytic amount of Amberlyst-15 lead to enhancement of the reaction rate and yielded brominated products in good to excellent yields and short reaction times.
- Baharfar,Alinezhad,Azimi,Salehian
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experimental part
p. 863 - 865
(2012/04/23)
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- Regioselective bromination of organic substrates by LDH-CO3 2--Br- promoted by V2O5-H 2O2
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An efficient, fast, simple, mild, and selective monobromination of aromatic compounds, with high para-selectivity, is reported. The catalytic system is readily prepared from a Mg-Al-layered double hydroxide-CO3 2--Br- (LDH-CO32--Br-) as the source of bromide, V2O5 as a promoter and hydrogen peroxide as the oxidant. The use of hydrogen peroxide as a synthetically useful oxidizing agent is reported for generating electrophilic bromine in situ from easily available KBr as a bromine source, to brominate electron rich aromatic compounds, employing LDH-CO32--Br3- as the phase-transfer catalyst. The phase-transfer catalyst leads to nearly complete bromination in 3 h at room temperature with high selectivity. The reaction rate of p-bromoanisole and p-bromotoluene formation by LDH-CO 32--Br3- in a triphasic system was studied. The heterogeneity of the reaction system facilitates the recovery and recycling of the catalyst, and the reagent components are environmentally acceptable. The catalyst, LDH-CO32--Br3 -, and its precursors, LDH-CO32--Br- and LDH-CO32-, were characterized by powder XRD, FT-IR and UV-vis spectroscopy.
- Ghiaci,Sedaghat,Ranjbari,Gil
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experimental part
p. 18 - 26
(2011/01/05)
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- An efficient regioselective NBS aromatic bromination in the presence of an ionic liquid
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A simple, efficient, and rapid method was developed for high-yielding regioselective monobromination of activated aromatic compounds using NBS in combination with ionic liquid 1-butyl-1-methylimidazolium bromide ([Bmim]Br) or dioxane. The ionic liquid is recyclable and can be reused with minimal loss in the catalytic efficiency if the ionic liquid is rapidly microwaved prior to reactions.
- Pingali, Subramanya R.K.,Madhav, Monika,Jursic, Branko S.
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experimental part
p. 1383 - 1385
(2010/04/25)
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