- Degradation of ibuprofen by hydrodynamic cavitation: Reaction pathways and effect of operational parameters
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Ibuprofen (IBP) is an anti-inflammatory drug whose residues can be found worldwide in natural water bodies resulting in harmful effects to aquatic species even at low concentrations. This paper deals with the degradation of IBP in water by hydrodynamic cavitation in a convergent-divergent nozzle. Over 60% of ibuprofen was degraded in 60 min with an electrical energy per order (EEO) of 10.77 kWh m-3 at an initial concentration of 200 μg L-1 and a relative inlet pressure pin = 0.35 MPa. Five intermediates generated from different hydroxylation reactions were identified; the potential mechanisms of degradation were sketched and discussed. The reaction pathways recognized are in line with the relevant literature, both experimental and theoretical. By varying the pressure upstream the constriction, different degradation rates were observed. This effect was discussed according to a numerical simulation of the hydroxyl radical production identifying a clear correspondence between the maximum kinetic constant kOH and the maximum calculated OH production. Furthermore, in the investigated experimental conditions, the pH parameter was found not to affect the extent of degradation; this peculiar feature agrees with a recently published kinetic insight and has been explained in the light of the intermediates of the different reaction pathways.
- Musmarra, Dino,Prisciandaro, Marina,Capocelli, Mauro,Karatza, Despina,Iovino, Pasquale,Canzano, Silvana,Lancia, Amedeo
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Read Online
- Abiotic degradation and environmental toxicity of ibuprofen: Roles of mineral particles and solar radiation
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The growing medical and personal needs of human populations have escalated release of pharmaceuticals and personal care products into our natural environment. This work investigates abiotic degradation pathways of a particular PPCP, ibuprofen, in the presence of a major mineral component of soil (kaolinite clay), as well as the health effects of the primary compound and its degradation products. Results from these studies showed that the rate and extent of ibuprofen degradation is greatly influenced by the presence of clay particles and solar radiation. In the absence of solar radiation, the dominant reaction mechanism was observed to be the adsorption of ibuprofen onto clay surface where surface silanol groups play a key role. In contrast, under solar radiation and in the presence of clay particles, ibuprofen breaks down to several fractions. The decay rates were at least 6-fold higher for irradiated samples compared to those of dark conditions. Toxicity of primary ibuprofen and its secondary residues were tested on three microorganisms: Bacillus megaterium, Pseudoaltermonas atlantica; and algae from the Chlorella genus. The results from the biological assays show that primary PPCP is more toxic than the mixture of secondary products. Overall, however, biological assays carried out using only 4-acetylbenzoic acid, the most abundant secondary product, show a higher toxic effect on algae compared to its parent compound.
- Rubasinghege, Gayan,Gurung, Rubi,Rijal, Hom,Maldonado-Torres, Sabino,Chan, Andrew,Acharya, Shishir,Rogelj, Snezna,Piyasena, Menake
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Read Online
- Silicon nanowires as photoelectrodes for carbon dioxide fixation
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Lights on: When illuminated, p-type Si nanowires donate photogenerated electrons to aromatic ketones, producing reactive radicals that can harvest CO2 to yield α-hydroxy acids (see scheme). The reaction scheme closely resembles that of natural photosynthesis and gives up to 98 % yield and selectivity. Products obtained by this reaction include important precursors for nonsteroidal anti-inflammatory drugs, such as ibuprofen and naproxen. Copyright
- Liu, Rui,Yuan, Guangbi,Joe, Candice L.,Lightburn, Thomas E.,Tan, Kian L.,Wang, Dunwei
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Read Online
- CONTINUOUS FLOW SYNTHESIS OF IBUPROFEN
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This disclosure generally relates to methods of making ibuprofen, naproxen, and derivatives thereof. This disclosure also generally relates to compounds made by the disclosed methods. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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Paragraph 0018; 0024; 0379
(2021/04/23)
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- Oxidative Cleavage of Alkenes by O2with a Non-Heme Manganese Catalyst
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The oxidative cleavage of C═C double bonds with molecular oxygen to produce carbonyl compounds is an important transformation in chemical and pharmaceutical synthesis. In nature, enzymes containing the first-row transition metals, particularly heme and non-heme iron-dependent enzymes, readily activate O2 and oxidatively cleave C═C bonds with exquisite precision under ambient conditions. The reaction remains challenging for synthetic chemists, however. There are only a small number of known synthetic metal catalysts that allow for the oxidative cleavage of alkenes at an atmospheric pressure of O2, with very few known to catalyze the cleavage of nonactivated alkenes. In this work, we describe a light-driven, Mn-catalyzed protocol for the selective oxidation of alkenes to carbonyls under 1 atm of O2. For the first time, aromatic as well as various nonactivated aliphatic alkenes could be oxidized to afford ketones and aldehydes under clean, mild conditions with a first row, biorelevant metal catalyst. Moreover, the protocol shows a very good functional group tolerance. Mechanistic investigation suggests that Mn-oxo species, including an asymmetric, mixed-valent bis(μ-oxo)-Mn(III,IV) complex, are involved in the oxidation, and the solvent methanol participates in O2 activation that leads to the formation of the oxo species.
- Bennett, Elliot L.,Brookfield, Adam,Guan, Renpeng,Huang, Zhiliang,Mcinnes, Eric J. L.,Robertson, Craig M.,Shanmugam, Muralidharan,Xiao, Jianliang
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supporting information
p. 10005 - 10013
(2021/07/19)
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- FeCl3-catalyzed oxidative decarboxylation of aryl/heteroaryl acetic acids: Preparation of selected API impurities
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There is an ever-increasing demand for impurity compounds for use in impurity profiling as regulatory agencies seek information during registration. Herein, we report the FeCl3-catalyzed oxidative decarboxylation of aryl- and heteroaryl acetic acids to the corresponding carbonyl compounds. A variety of useful aldehydes and ketones were prepared in a simple one-pot transformation by employing an environmentally benign, low-cost, and readily available iron salt. The utility of this method has been demonstrated by preparing five valuable API impurities including a multi-gram-scale synthesis of ketorolac impurity B for the first time. This journal is
- Gangadurai, Chinnakuzhanthai,Illa, Giri Teja,Reddy, D. Srinivasa
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p. 8459 - 8466
(2020/11/05)
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- Visible-light-promoted oxidative decarboxylation of arylacetic acids in air: Metal-free synthesis of aldehydes and ketones at room temperature
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A metal-free photocatalytic oxidative decarboxylation reaction at room temperature was developed for the synthesis of aromatic aldehydes and ketones from the corresponding arylacetic acids. The reaction was realized under blue-light irradiation by adding 1 molpercent of 4CzIPN as photocatalyst and air as oxidant. This reaction represents a novel decarboxylation of a sp3-hybridized carboxylic acids without traditional heating, additional oxidants, and metal reagents under mild conditions.
- He, Shuaiqi,Chen, Xiaolan,Zeng, Fanlin,Lu, Peipei,Peng, Yuyu,Qu, Lingbo,Yu, Bing
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supporting information
p. 1863 - 1867
(2020/01/03)
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- Preparation method of aryl propionic acid compound
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The invention provides a preparation method of an aryl propionic acid compound, wherein the preparation method comprises the following steps: carrying out acetylation reaction on substituted aryl benzene to obtain aryl acetophenone; carrying out hydrogenation reduction reaction on alpha-substituted aryl ethyl ketone to obtain alpha-substituted aryl ethanol; and in an acidic solution, introducing carbon monoxide gas into the alpha-substituted aryl ethanol, and carrying out a carbonylation reaction under the co-catalytic action of a main catalyst and a cocatalyst to obtain the aryl propionic acid compound, wherein the cocatalyst has the following structural formula described in the specification, R1 is one of hydrogen and a substituted carboxylic acid group, and R2 is one of hydrogen, halogen, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C3-C12 naphthenic base, substituted carbonyl containing C6-C24 aryl or substitutedaryl, substituted carbonyl containing C3-C12 heterocyclic radical or substituted heterocyclic radical, phenyl, substituted phenyl, naphthyl and substituted naphthyl.
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Paragraph 0087-0090
(2020/10/04)
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- Selective C-C bond cleavage of amides fused to 8-aminoquinoline controlled by a catalyst and an oxidant
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Herein, copper-catalyzed direct C-C bond cleavage of amides fused to 8-aminoquinoline as a directing group to form urea in the presence of amines and dioxygen is reported. Compared to the previous C-H aminations of amides via C-H activation, this reaction presents a catalyst and oxidant controlled C-C bond cleavage strategy that enables amidation through a radical process. CuBr/Ag2CO3/O2 shows the best catalytic result at 150 °C. A series of aryl and alkyl amides were compatible with this transformation. Notably, this method provided access to cyclohexanone, one of the most important industrial materials. The pathway of this reaction was investigated.
- Li, Sen,Jie, Kun,Yan, Wenjie,Pan, Qingjun,Zhang, Min,Wang, Yufeng,Fu, Zhengjiang,Guo, Shengmei,Cai, Hu
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supporting information
p. 13820 - 13823
(2020/11/18)
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- Hydroxylamine promoted Fe(III)/Fe(II) cycle on ilmenite surface to enhance persulfate catalytic activation and aqueous pharmaceutical ibuprofen degradation
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This study demonstrates a new system for the degradation of emerging pharmaceutical contaminants (e.g., ibuprofen) in water by coupling the naturally occurring ilmenite with hydroxylamine (HA) and persulfate (PS). Ilmenite was able to activate persulfate to generate sulfate radicals (SO4?·) and hydroxyl radicals (HO·). The radical generation was greatly improved by adding small amount of hydroxylamine into the solution, due to the efficient Fe(III)/Fe(II) cycle on the ilmenite surface promoted by HA, which was confirmed by X-ray photoelectron spectroscopy and electron paramagnetic resonance (EPR) spectroscopy analysis. SO4?· and HO· contributed comparably to ibuprofen degradation, which was verified by the radical scavenging tests. The degradation was enhanced with increasing ilmenite, PS and HA dosages, but the HA exhibited strong scavenging effect at its high concentrations. The ilmenite/PS/HA process worked well in the real treated wastewater, because the surface-controlled radical generation was less affected by the water matrix. However, the formation of bromate in the bromide-containing water by this process should be concerned. Ibuprofen was partially mineralized, and the degradation products were identified by ESI-tqMS. A radical-induced degradation pathway was proposed based on the product identification. This work provides the mechanistic insights on persulfate activation based on the surface-controlled catalytic processes. It also offers a new strategy to degrade emerging contaminants in water and sheds light on the environmental functions of natural minerals.
- Yin, Ran,Hu, Lingling,Xia, Dehua,Yang, Jingling,He, Chun,Liao, Yuhong,Zhang, Qing,He, Jia
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p. 294 - 302
(2019/05/10)
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- Enantiocomplementary decarboxylative hydroxylation combining photocatalysis and whole-cell biocatalysis in a one-pot cascade process
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Designing a green, highly efficient and stereoselective catalytic system to generate valuable enantioenriched products is a long-standing goal in green chemistry. Here, we report a one-pot cascade combining photocatalysts with (R)- or (S)-selective ketoreductases for the decarboxylative carbonylation of carboxylic acids and the subsequent bioreduction to generate valuable chiral alcohols. Using this approach, various chiral alcohols with complementary (R)- or (S)-configurations were prepared with good yields (up to 93%) and excellent stereoselectivity (up to 99% ee). Such a photochemo-enzymatic one-pot whole-cell process combines the advantages of both photocatalysts and enzyme catalysts and provides a mild, green, metal-free and highly stereoselective alternative in asymmetric decarboxylative hydroxylation reactions.
- Xu, Jian,Arkin, Mamatjan,Peng, Yongzhen,Xu, Weihua,Yu, Huilei,Lin, Xianfu,Wu, Qi
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supporting information
p. 1907 - 1911
(2019/04/27)
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- Photocarboxylation of Benzylic C-H Bonds
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The carboxylation of sp3-hybridized C-H bonds with CO2 is a challenging transformation. Herein, we report a visible-light-mediated carboxylation of benzylic C-H bonds with CO2 into 2-arylpropionic acids under metal-free conditions. Photo-oxidized triisopropylsilanethiol was used as the hydrogen atom transfer catalyst to afford a benzylic radical that accepts an electron from the reduced form of 2,3,4,6-tetra(9H-carbazol-9-yl)-5-(1-phenylethyl)benzonitrile generated in situ. The resulting benzylic carbanion reacts with CO2 to generate the corresponding carboxylic acid after protonation. The reaction proceeded without the addition of any sacrificial electron donor, electron acceptor or stoichiometric additives. Moderate to good yields of the desired products were obtained in a broad substrate scope. Several drugs were successfully synthesized using the novel strategy.
- Meng, Qing-Yuan,Schirmer, Tobias E.,Berger, Anna Lucia,Donabauer, Karsten,K?nig, Burkhard
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supporting information
p. 11393 - 11397
(2019/08/20)
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- METHODS OF ACYLATION WITH AN IONIC LIQUID CATALYZING MEDIUM
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Described herein are methods of acylating an aryl substrate comprising combining a substituted aryl substrate with an acylating agent in the presence of a catalyzing medium, thereby acylating the substituted aryl substrate in the para position, wherein the catalyzing medium is an ionic liquid comprising at least one cation and at least one metal halide anion.
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Paragraph 0107
(2018/07/05)
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- Hydrogen bond donor solvents enabled metal and halogen-free Friedel–Crafts acylations with virtually no waste stream
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We have developed a metal and halogen-free Friedel–Crafts acylation protocol with virtually no waste stream generation. We propose a hydrogen bonding donor solvent will form a hydrogen bonding network and may provide significant rate enhancement for Friedel–Crafts reactions. Trifluoroacetic acid is one of the strongest H-bond donor solvents, which is also volatile and can be easily recovered by distillation without need for reaction workup. Our protocol is a ‘green’ Friedel–Crafts acylation process: 1) the catalyst can be recovered and reused; 2) using halogen free starting material (carboxylic acids anhydride or carboxylic acids); 3) no need for aqueous reaction work-up; 4) minimum or no waste steam generation.
- Liu, Guangchang,Xu, Bo
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supporting information
p. 869 - 872
(2018/02/09)
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- Oxidative decarboxylation of arylacetic acids in water: One-pot transition-metal-free synthesis of aldehydes and ketones
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One-pot transition-metal-free synthesis of aromatic aldehydes and ketones via oxidative decarboxylation of arylacetic acids in water is developed. Protocol relies on the direct decarboxylation of sp3-hybridized carbon in water without any over oxidation into carboxylic acids with minimal waste. Reaction mechanism is investigated and application of this protocol is demonstrated on a gram scale.
- Mete, Trimbak B.,Khopade, Tushar M.,Bhat, Ramakrishna G.
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supporting information
p. 2822 - 2825
(2017/06/27)
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- A 4 - isobutyl phenyl ketone compounds (by machine translation)
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The invention discloses a 4 - isobutyl phenyl ketone compounds, the compound structure is as follows: said compound 4 - isobutyl-benzene as the starting material, substituted sulfonic acid and substituted sulfonate as the catalyst, the reaction with the acyl chloride, the following reaction: the application of this method to synthesize 4 - isobutyl phenyl ketone compound, simple and convenient operation, mild reaction conditions, environment-friendly, and has excellent industrial prospect. (by machine translation)
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Paragraph 0021; 0022; 0029; 0030; 0033; 0034; 0039-0048
(2017/08/25)
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- Study on the design, synthesis and structure-activity relationships of new thiosemicarbazone compounds as tyrosinase inhibitors
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52 Structure-based thiosemicarbazone compounds bearing various substituted-lipophilic part, including substituted-benzaldehyde, substituted-phenylalkan-1-one and their biphenyl-type thiosemicarbazone analogs, were designed, synthesized and evaluated as new tyrosinase inhibitors. The results demonstrated that 22 compounds have potent inhibitory activities against tyrosinase with the IC50 value of lower than 1.0 μM. On the basis of the obtained experimental data, the structure-activity relationships (SARs) were rationally derived. Besides, the inhibition mechanism and the inhibitory kinetics of selected compounds 3d and 6e were investigated, revealing that such type of compounds were belonged to the reversible and competitive tyrosinase inhibitors. To verify the safety of these developed thiosemicarbazone compounds, four randomly selected compounds 3d, 4e, 6a and 9a were also tested in 293T cell line for the evaluation of the cytotoxicity. Interestingly, all these compounds almost did not perform any toxicity to 293T cells even at a high concentration of 1000 μmol/L. Taken together, these results suggested that such compounds could serve as the highly efficient and more safe candidates for the treatment of tyrosinase-related disorders.
- Song, Senchuan,You, Ao,Chen, Zhiyong,Zhu, Guoxun,Wen, Huan,Song, Huacan,Yi, Wei
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p. 815 - 825
(2017/09/05)
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- Phenol Derivatives as Coupling Partners with Alkylsilicates in Photoredox/Nickel Dual Catalysis
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Photoredox/nickel dual catalysis via single electron transmetalation allows coupling of Csp3-Csp2 hybridized centers under mild conditions. A procedure for the coupling of electron-deficient aryl triflates, -tosylates, and -mesylates with alkylbis(catecholato)silicates is presented. This method represents the first example of the use of phenol derivatives as electrophilic coupling partners in photoredox/nickel dual catalysis.
- Patel, Niki R.,Molander, Gary A.
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supporting information
p. 7271 - 7275
(2016/08/30)
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- Thioetherification via Photoredox/Nickel Dual Catalysis
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Hypervalent alkylsilicates represent new and readily accessible precursors for the generation of alkyl radicals under photoredox conditions. Alkyl radicals generated from such silicates serve as effective hydrogen atom abstractors from thiols, furnishing thiyl radicals. The reactive sulfur species generated in this manner can be funneled into a nickel-mediated cross-coupling cycle employing aromatic bromides to furnish thioethers. The serendipitous discovery of this reaction and its utilization for the thioetherification of various aryl and heteroaryl bromides with a diverse array of thiols is described. The S-H selective H atom abstraction event enables a wide range of functional groups, including those bearing protic moieties, to be tolerated. (Chemical Equation Presented).
- Jouffroy, Matthieu,Kelly, Christopher B.,Molander, Gary A.
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supporting information
p. 876 - 879
(2016/03/04)
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- Investigations in sono-enzymatic degradation of ibuprofen
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The drug ibuprofen (IBP) appears frequently in the wastewater discharge from pharmaceutical industries. This paper reports studies in degradation of IBP employing hybrid technique of sono-enzymatic treatment. This paper also establishes synergy between individual mechanisms of enzyme and sonolysis for IBP degradation by identification of degradation intermediates, and Arrhenius & thermodynamic analysis of the experimental data. Positive synergy between sonolysis and enzyme treatment is attributed to formation of hydrophilic intermediates during degradation. These intermediates form due to hydroxylation and oxidation reactions induced by radicals formed during transient cavitation. Activation energy and enthalpy change in sono-enzymatic treatment are lower as compared to enzyme treatment, while frequency factor and entropy change are higher as compared to sonolysis. Degradation of IBP in sono-enzymatic treatment is revealed to be comparable with other hybrid techniques like photo-Fenton, sono-photocatalysis, and sono-Fenton.
- Chakma, Sankar,Moholkar, Vijayanand S.
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p. 485 - 494
(2015/11/24)
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- Simultaneous identification of Fenton degradation by-products of diclofenac, ibuprofen and ketoprofen in aquatic media by comprehensive two-dimensional gas chromatography coupled with mass spectrometry
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Diclofenac, ibuprofen and ketoprofen are anti-inflammatory drugs intensively used both in human and animal treatment. Due to their high stability these compounds are partially removed by wastewater treatment plants and from this reason the development of some alternative treatments such as advanced oxidative processes are necessary. The main problems in the optimization of an advanced oxidative process rise from the difficulties which appear in the identification of degradation by-products necessary for the establishment of degradation pathway. In this paper a developed method for the simultaneous identification of Fenton degradation by-products of the three above mentioned pharmaceuticals is presented. The obtained results show the comprehensive two-dimensional gas chromatography coupled with mass spectrometry as a proper method for the analysis of the complex mixture of compounds resulted from the Fenton degradation process. Moreover, some compounds never mentioned in the scientific literature were identified. (Chemical Equation Presented).
- Beldean-Galea, Mihail Simion,Coman, Virginia,Copaciu, Florina,Thiébaut, Didier,Vial, Jér?me
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p. 1021 - 1027
(2015/07/15)
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- Iron-catalyzed hydromagnesiation: Synthesis and characterization of benzylic grignard reagent intermediate and application in the synthesis of ibuprofen
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Iron-catalyzed hydromagnesiation of styrene derivatives using ethylmagnesium bromide has been investigated for the synthesis of benzylic Grignard reagents. The benzylic Grignard reagent formed in the reaction was observed directly and its conformation in solution characterized by multinuclear and variable-temperature NMR spectroscopy. The Grignard reagent could be stored for at least 2 weeks without significant loss in activity. Hydromagnesiation of styrene in tetrahydrofuran gave a mixture of monoalkyl- and dialkylmagnesium species, (1-phenylethyl)magnesium bromide (2; RMgBr) and bis(1-phenylethyl)magnesium (3; R2Mg), with the equilibrium between these species lying in favor of the dialkylmagnesium species. The thermodynamic parameters of alkyl exchange for the reaction MgBr2 + R2Mg (3) 2RMgBr (2) were quantified, with the enthalpy and entropy of formation of 2 from MgBr2 and 3 calculated as 32 ± 7 and 0.10 ± 0.03 kJ mol-1, respectively. This methodology was applied, on a 10 mmol scale, as the key step in the synthesis of ibuprofen, using sequential iron-catalyzed alkyl-aryl and aryl-vinyl cross-coupling reactions to give 4-isobutylstyrene, which following hydromagnesiation and reaction with CO2 gave ibuprofen. Each step proceeded in excellent yield, at temperatures between 0 °C and room temperature, at atmospheric pressure. Inexpensive, nontoxic, and air- and moisture-stable iron(III) acetylacetonate was used as the precatalyst in each step in combination with inexpensive amine ligands.
- Greenhalgh, Mark D.,Kolodziej, Adam,Sinclair, Fern,Thomas, Stephen P.
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supporting information
p. 5811 - 5819
(2015/02/19)
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- Manganese terpyridine artificial metalloenzymes for benzylic oxygenation and olefin epoxidation
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New catalysts for non-directed hydrocarbon functionalization have great potential in organic synthesis. We hypothesized that incorporating a Mn-terpyridine cofactor into a protein scaffold would lead to artificial metalloenzymes (ArMs) in which the selectivity of the Mn cofactor could be controlled by the protein scaffold. We designed and synthesized a maleimide-substituted Mn-terpyridine cofactor and demonstrated that this cofactor could be incorporated into two different scaffold proteins to generate the desired ArMs. The structure and reactivity of one of these ArMs was explored, and the broad oxygenation capability of the Mn-terpyridine catalyst was maintained, providing a robust platform for optimization of ArMs for selective hydrocarbon functionalization.
- Zhang, Chen,Srivastava, Poonam,Ellis-Guardiola, Ken,Lewis, Jared C.
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supporting information
p. 4245 - 4249
(2014/06/09)
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- Aldehydes and ketones formation: Copper-catalyzed aerobic oxidative decarboxylation of phenylacetic acids and α-hydroxyphenylacetic acids
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Aromatic aldehydes or ketones from copper catalyzed aerobic oxidative decarboxylation of phenylacetic acids and α-hydroxyphenylacetic acids have been synthesized. This reaction combined decarboxylation, dioxygen activation, and C-H bond oxidation steps in a one-pot protocol with molecular oxygen as the sole terminal oxidant. This reaction represents a novel decarboxylation of an sp3-hybridized carbon and the use of a benzylic carboxylic acid as a source of carbonyl compounds.
- Feng, Qiang,Song, Qiuling
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p. 1867 - 1871
(2014/03/21)
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- Identification of novel benzimidazole derivatives as inhibitors of leukotriene biosynthesis by virtual screening targeting 5-lipoxygenase- activating protein (FLAP)
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Pharmacological suppression of leukotriene biosynthesis by 5-lipoxygenase (5-LO)-activating protein (FLAP) inhibitors is a promising strategy to intervene with inflammatory, allergic and cardiovascular diseases. Virtual screening targeting FLAP based on a combined ligand- and structure-based pharmacophore model led to the identification of 1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl) ethyl)-1H-benzimidazole (7) as developable candidate. Compound 7 potently suppressed leukotriene formation in intact neutrophils (IC50 = 0.31 μM) but essentially failed to directly inhibit 5-LO suggesting that interaction with FLAP causes inhibition of leukotriene synthesis. For structural optimization, a series of 46 benzimidazole-based derivatives of 7 were synthesized leading to more potent analogues (70-72, 82) with IC50 = 0.12-0.19 μM in intact neutrophils. Together, our results disclose the benzimidazole scaffold bearing an ibuprofen fingerprint as a new chemotype for further development of anti-leukotriene agents.
- Banoglu, Erden,Caliskan, Burcu,Luderer, Susann,Eren, Goekcen,Oezkan, Yagmur,Altenhofen, Wolfram,Weinigel, Christina,Barz, Dagmar,Gerstmeier, Jana,Pergola, Carlo,Werz, Oliver
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supporting information; experimental part
p. 3728 - 3741
(2012/08/28)
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- Efficient and selective oxidative decarboxylation of arylcarboxylic acids into the corresponding aldehydes and ketones using K5Co IIIW12O40 as a green oxidant under microwave and conventional heating
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The oxidative decarboxylation of various α-aryl- and α, α-arylcarboxylic acids having electron-donating and electronwithdrawing groups by using a stoichiometric amount of potassium 12-tungstocobaltate(III), K5CoIIIW12O40, in 50% aqueous acetonitrile solution resulted in the corresponding aldehydes and ketones in high yields within short reaction times under microwave irradiation. This transformation was also carried out under the conventional heating conditions which produced the corresponding aldehydes and ketones in relatively longer reaction times. The arylacetic acids with electron-withdrawing substituents required longer reaction times and produced lower yields. In contrast to arylacetic esters which were inert toward decarboxylation, the sodium arylacetates were decarboxylated in shorter times with yields better than those of the parent acids.
- Farhadi,Ansari
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experimental part
p. 470 - 476
(2012/06/18)
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- Chemoenzymatic synthesis of (2S)-2-arylpropanols through a dynamic kinetic resolution of 2-arylpropanals with alcohol dehydrogenases
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We applied Horse Liver Alcohol Dehydrogenase (HLADH) to the enantioselective synthesis of six (2S)-2-arylpropanols, useful intermediates in the synthesis of Profens. The influence of substrate structure and reaction conditions on yields and enantioselectivity were investigated. The high yields and high enantioselectivity towards the (S)-enantiomer obtained in the bioreduction of 2-arylpropionic aldehydes, clearly indicate the achievement of a DKR process through a combination of an enzyme-catalyzed kinetic reduction with a chemical base-catalyzed racemization of the unreacted aldehydes. The racemization step is represented by the keto-enol equilibrium of the aldehyde and can be controlled by modulating pH and reaction conditions.
- Galletti, Paola,Emer, Enrico,Gucciardo, Gabriele,Quintavalla, Arianna,Pori, Matteo,Giacomini, Daria
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experimental part
p. 4117 - 4123
(2010/10/03)
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- One-step oxidation of 2-arylpropanols to 2-arylpropionic acids: Improving sustainability in the synthesis of profens
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Three oxidation procedures were evaluated for the synthesis of optically pure 2-arylpropionic acids. Efficient, mild, and eco-friendly conditions were obtained with the system comprising TEMPO, NaClO, and NaClO2. Thus a series of profens were obtained in good to excellent yields. Georg Thieme Verlag Stuttgart New York.
- Galletti, Paola,Pori, Matteo,Giacomini, Daria
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experimental part
p. 2644 - 2648
(2010/11/18)
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- Polystyrene-bound Mn(T4PyP): A highly efficient and reusable catalyst for biomimetic oxidative decarboxylation of carboxylic acids with sodium periodate
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In this report, highly efficient oxidative decarboxylation of carboxylic acids with sodium periodate catalyzed by a supported manganese(III) porphyrin is described. In the presence of manganese(III) tetra(4-pyridyl)porphyrin supported on cross-linked chloromethylated polystyrene, [Mn(T4PyP)-CMP], as catalyst, carboxylic acids were converted to their corresponding carbonyl compounds via oxidative decarboxylation with sodium periodate using imidazole as axial ligand. The oxidation of anti-inflammatory drugs such Indomethacin and Ibuprofen was carried out successfully and the decarboxylated products were obtained. This catalyst can be reused several times without loss of its catalytic activity in the oxidation reactions.
- Moghadam, Majid,Tangestaninejad, Shahram,Mirkhani, Valiollah,Mohammadpoor-baltork, Iraj,Sirjanian, Narges,Parand, Somayeh
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experimental part
p. 3394 - 3398
(2009/09/08)
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- Facile one-pot preparation of 2-arylpropionic and arylacetic acids from cyanohydrins by treatment with aqueous HI
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A novel one-pot two-step procedure has been developed to synthesize highly substituted 2-arylpropionic and arylacetic acids, by treatment with aqueous HI, from cyanohydrins. The hydrogenolytic reduction of α-hydroxy-2-arylpropionic acids was the key step of the process and the optimization of the reaction conditions led to identify aqueous HI as an appropriate and selective reagent for the reductive deoxygenation of cyanohydrins. The synthetic route described a general and efficient strategy for the preparation of large libraries of phenylacetic and phenylpropionic acids derivatives.
- Aramini, Andrea,Sablone, Manolo R.,Bianchini, Gianluca,Amore, Alessia,Fanì, Michela,Perrone, Plinio,Dolce, Alberto,Allegretti, Marcello
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experimental part
p. 2015 - 2021
(2009/07/04)
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- NOVEL PROTEIN TYROSINE PHOSPHATASE - IB INHIBITORS
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The present invention relates to the novel compounds of the general formula (I), wherein the symbols are same as described in specification, their pharmaceutically acceptable salts, their tautomeric forms, their stereoisomers, pharmaceutical compositions containing them, to process and intermediates for the preparation of the above said compounds, having the utility of these compounds in medicine and to methods for their therapeutic use, and their use in the treatment of diabetes and related diseases.
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Page/Page column 55
(2009/10/22)
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- Expedient method for oxidation of alcohol by hydrogen peroxide in the presence of amberlite IRA 400 resin (basic) as phase-transfer catalyst
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Amberlite IRA 400 (strongly basic), a classical polymer imparts phase-transfer catalysis in the oxidation of primary and secondary alcohols by hydrogen peroxide to give excellent yields of the corresponding carbonyl compounds or carboxylic acids in acetonitrile solvent at reflux temperature in 4-6 h. The catalytic system is inert to other susceptible oxidation sites such as carbon-carbon double bonds. Copyright Taylor & Francis Group, LLC.
- Bhati, Nishi,Sarma, Kuladip,Goswami, Amrit
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p. 1416 - 1424
(2008/09/20)
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- Oxidative conversion of α,α-disubstituted acetamides to corresponding one-carbon-shorter ketones using hypervalent iodine (λ5) reagents in combination with tetraethylammonium bromide
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(Chemical Equation Presented) α,α-Disubstituted acetamides undergo oxidative dehomologation to give one-carbon-shorter ketones when reacted with a hypervalent iodine (λ5) reagent in combination with tetraethylammonium bromide (TEAB) in various solvents. In further studies, one such combination of a hypervalent iodine (λ5) reagent, o-iodoxybenzoic acid, and TEAB has been established as a new, mild, efficient, and general method for the transformation.
- Bellale, Eknath V.,Bhalerao, Dinesh S.,Akamanchi, Krishnacharya G.
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supporting information; experimental part
p. 9473 - 9475
(2009/04/06)
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- High turnover remote catalytic oxygenation of alkyl groups: How steric exclusion of unbound substrate contributes to high molecular recognition selectivity
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H-bonding mediated molecular recognition between substrate and ligand -COOH groups orients the substrate so that remote, catalyzed oxygenation of an alkyl C-H bond by a Mn-oxo active site can occur with very high (>98%) regio- and stereoselectivity. This paper identifies steric exclusion - exclusion of non H-bonded substrate molecules from the active site - as one requirement for high selectivity, along with the entropic advantage of intramolecularity. If unbound substrate molecules were able to reach the active site, they would react unselectively, degrading the observed selectivity. Both of the faces of the catalyst are blocked by two ligand molecules each with a -COOH group. The acid p-tBuC6H4COOH binds to the ligand -COOH recognition site but is not oxidized and merely blocks approach of the substrate therefore acting as an effective inhibitor for ibuprofen oxidation in both free acid and ibuprofen ester form. Dixon plots show that inhibition is competitive for the free acid ibuprofen substrate, no doubt because this substrate can compete with the inhibitor for binding to the recognition site. In contrast, inhibition is uncompetitive for the ibuprofen-ester substrate, consistent with this ester substrate no longer being able to bind to the recognition site. Inhibition can be reversed with MeCOOH, an acid that can competitively bind to the recognition site but, being sterically small, no longer blocks access to the active site.
- Das, Siddhartha,Brudvig, Gary W.,Crabtree, Robert H.
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p. 1628 - 1637
(2008/09/18)
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- PROCESS FOR PRODUCING HIGH PURITY KETONES BY FRIEDEL-CRAFTS ACYLATION AT LOW TEMPERATURE
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The present invention relates to improved conditions for the Friedel-Crafts acylation of alkylbenzenes and to application of these improved conditions to the synthesis of para-isobutyl acetophenone and ibuprofen. The reaction conditions include operating the reaction at a temperature below 0°C and typically below -10° C.
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Page/Page column 9-11
(2008/06/13)
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- Photolytic decarboxylation of α-arylcarboxylic acids mediated by HgF2 under a dioxygen atmosphere
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Mercuric fluoride (HgF2), as a light-sensitive inorganic compound, in the presence of dioxygen is able to convert various α-aryl- and α,α-diarylcarboxylic acids into the corresponding aldehydes and ketones selectively under photoirradiation via trapping of the benzylic radical by O2.
- Farhadi, Saeid,Zaringhadam, Parisa,Sahamieh, Reza Zarei
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p. 1965 - 1968
(2007/10/03)
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- Transition-metal- and organic-solvent-free: A highly efficient anaerobic process for selective oxidation of alcohols to aldehydes and ketones in water
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A new system, I2-KI-K2CO3-H2O, selectively oxidized alcohols to aldehydes and ketones under anaerobic condition in water at 90°C with excellent yields. The process is green, mild and inexpensive. The Royal Society of Chemistry 2005.
- Gogoi, Pranjal,Konwar, Dilip
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p. 3473 - 3475
(2007/10/03)
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- Surfactant/I2/water: An efficient system for deprotection of oximes and imines to carbonyls under neutral conditions in water
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(Chemical Equation Presented) I2/surfactant/water system deprotecting oximes and imines to the corresponding carbonyl compounds under neutral conditions in water at 25-40°C with very high to excellent yields.
- Gogoi, Pranjal,Hazarika, Parasa,Konwar, Dilip
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p. 1934 - 1936
(2007/10/03)
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- Enantioselective synthesis of (S)-α-arylpropionic acids via Pd-catalyzed kinetic resolution of benzylic alcohols
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A convenient synthetic route for the synthesis of three (S)-α-propionic acids, (5)-naproxen (90% ee), (S)-ibuprofen (82% ee) and (5)-phenylpropionic acid (92% ee) is described. Pd-catalyzed oxidative kinetic resolution of the corresponding benzylic alcohols is used as a key step to introduce stereogenicity into the molecule.
- Thakur, Vinay V.,Sudalai
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p. 557 - 562
(2007/10/03)
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- CATALYSED ACYLATION OF ALKYLATED BENZENE DERIVATIVES
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The present invention relates to an improved zeolite based catalytic process for the preparation of acylated aromatic ethers and more particularly, the invention relates to eco-friendly catalysed acylation of isobutylbenzene for the preparation of acylated aromatic compound, namely p-isobutylacetopenone.
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Page/Page column 9-10
(2010/02/11)
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- DMSO/N2H4·H2O/I2/H 2O/CH3CN: A new system for selective oxidation of alcohols in hydrated media
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A new alternative system for the oxidation of secondary alcohols to ketones with DMSO/N2H4·H2O/I2/H 2O/CH3CN in hydrated media has been developed. The system also selectively oxidizes the secondary alcoholic groups to the corresponding ketones in the presence of primary alcoholic groups present within the same molecule in moderate to very good yields at reflux temperature.
- Gogoi, Pranjal,Sarmah, Gautam Kumar,Konwar, Dilip
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p. 5153 - 5154
(2007/10/03)
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- Rapid and efficient oxidative decarboxylation of carboxylic acids with sodium periodate catalyzed by manganese (III) Schiff base complexes
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Rapid and efficient oxidative decarboxylatoin of α-aryl carboxylic acids was observed. In the chemical system containing Mn(III)-salophen complex as catalyst, carboxylic acids are converted efficiently to the corresponding carbonyl derivatives with sodium periodate. The ability of various Schiff base complexes in the oxidative decarboxylation of carboxylic acids was also investigated.
- Mirkhani, Valiollah,Tangestaninejad, Shahram,Moghadam, Majid,Moghbel, Maryam
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p. 903 - 906
(2007/10/03)
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- Sulfonic acids, their derivatives and pharmaceutical compositions containing them
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Selected sulfonic acids, their derivatives and pharmaceutical compositions containing such compounds are useful in inhibiting the chemotactic activation of neutrophils (PMN leukocytes) induced by the interaction of Interleukin-8 (IL-8) with CXCR1 and CXCR2 membrane receptors. The compounds are used for the prevention and treatment of pathologies deriving from said activation. Notably, the selected sulfonic acids and their derivativas are devoid of cyclo-oxygenase inhibition activity and are particularly useful in the treatment of neutrofil-dependent pathologies such as psoriasis, ulcerative colitis, melanoma, chronic obstructive pulmonary disease (COPD), bullous pemphigoid, rheumatoid arthritis, idiopathic fibrosis, glomerulonephritis and in the prevention and treatment of damages caused by ischemia and reperfusion.
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- Tetraphosphine/palladium catalysed Suzuki cross-coupling reactions of aryl halides with alkylboronic acids
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Through the use of [PdCl(C3H5)]2/cis,cis, cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as a catalyst, a range of aryl bromides and chlorides undergoes Suzuki cross-coupling with alkylboronic acids in good yields. Several alkyl substituents such as ethyl, n-butyl, n-octyl, isobutyl or 2,2-dimethylpropyl on the alkylboronic acids have been successfully used. The functional group tolerance on the aryl halide is remarkable; substituents such as fluoro, methyl, methoxy, acetyl, formyl, benzoyl, nitro or nitrile are tolerated. Furthermore, this catalyst can be used at low loading, even for reactions of sterically hindered aryl bromides.
- Kondolff, Isabelle,Doucet, Henri,Santelli, Maurice
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p. 3813 - 3818
(2007/10/03)
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- Efficient oxidative decarboxylation of carboxylic acids with sodium periodate catalyzed by supported manganese (III) porphyrin
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Oxidative decarboxylation of carboxylic acids by a supported manganese (III) porphyrin was investigated. In the chemical system using 5,10,15,20-tetrakis(4-aminophenyl)porphyrinatomanganese (III) chloride supported on crosslinked chloromethylated polystyrene, [Mn(H 2NTPP)-CMP], as catalyst, carboxylic acids are converted to the corresponding carbonyl compounds via oxidative decarboxylation with sodium periodate.
- Mirkhani, Valiollah,Tangestaninejad, Shahram,Moghadam, Majid,Karimian, Zohreh
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p. 3433 - 3435
(2007/10/03)
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- Efficient aromatic acylation using catalytic ytterbium(III) bis(trifluoromethylsulfonyl)amide activated by lithium perchlorate in nitromethane
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Various aromatic ketones were prepared in good to high yields by acylation using ytterbium bis(trifluoromethylsulfonyl) amide as catalyst in 4M lithium perchlorate in nitromethane.
- Nie, Jin,Gong, Yanwei,Zhang, Zhengbo,Liu, Wenming
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p. 708 - 709
(2007/10/03)
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- 4-(Benzoylindolizinyl)butyric acids; novel nonsteroidal inhibitors of steroid 5α-reductase. III
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A novel series of indolizinebutyric acids with various benzoyl substituents was synthesized to develop nonsteroidal inhibitors of steroid 5α-reductase, and the structure-activity relationships in this series were studied. We previously reported the structure-activity relationships in a series of indolebutyric acids as well as the discovery of the novel nonsteroidal 5α-reductase inhibitor, FK143. We have now made other modifications to this compound to improve in vivo inhibitory activity. By altering the heterocyclic nucleus and changing the benzoyl substituent we have succeeded in identifying the strongly active compound, FK687, (S)-4-[1-[4-[[1-(4-isobutylphenyl)butyl]oxy]benzoyl]indolizin-3-yllbutyric acid, which displays strong in vitro inhibitory activity against the human enzyme and in vivo inhibitory activity against the castrated young rat model. This compound should be a useful agent for the treatment of benign prostatic hyperplasia.
- Sawada,Okada,Kuroda,Watanabe,Sawada,Tanaka
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p. 799 - 813
(2007/10/03)
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- Synthesis and carbonylation of aryl acetylenes
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Several substituted aryl acetylenes have been prepared from acetophenones using the Vilsmeier reaction. Carbonylation of aryl acetylenes to produce aryl acrylic acids has been studied as a potential route to optically pure anti-inflammatory drugs such as ibuprofen and naproxen.
- Kotha,Tafesh,Davenport,Ortiz
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p. 1166 - 1169
(2007/10/03)
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- Biomimetic oxidation of ibuprofen with hydrogen peroxide catalysed by Horseradish peroxidase (HRP) and 5,10,15,20- tetrakis-(2',6'-dichloro-3'- sulphonatophenyl)porphyrinatoiron(III) and manganese(III) hydrates in AOT reverse micelles
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The oxidation of ibuprofen with H2O2 catalysed by Horseradish peroxidase (HRP), Cl8TPPS4Fe(III)(OH2)2 and Cl8TPPS4Mn(III)(OH2)2 in AOT reverse micelles gives 2-(4'-isobutyl-phenyl)ethanol (5) and p-isobutyl acetophenone (6) in moderate yields. The reaction of ibuprofen (2) with H2O2 catalysed by HRP form carbon radicals by the oxidative decarboxylation, which on reaction with molecular oxygen to form hydroperoxy intermediate, responsible for the formation of the products 5 and 6. The yields of different oxidation products depend on the pH, the water to surfactant ratio (Wo), concentration of Cl8TPPS4Fe(III)(OH2)2 and Cl8TPPS4Mn(III)(OH2)2 and amount of molecular oxygen present in AOT reverse micelles. The formation of 2-(4'-isobutyl phenyl)ethanol (5) may be explained by the hydrogen abstraction from ibuprofen by high valent oxo- manganese(IV) radical cation, followed by decarboxylation and subsequent recombination of either free hydroxy radical or hydroxy iron(III)/manganese(III) porphyrins. The over-oxidation of 5 with high valent oxo-manganese, Mn(IV)radical cation intermediate form 6 in AOT reverse micelles by abstraction and recombination mechanism. (C) 1999 Elsevier Science Ltd.
- Chauhan,Sahoo
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p. 2629 - 2634
(2007/10/03)
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- Performances of homogeneous charge transfer catalysts in the electrocarboxylation of benzyl halides
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The electrocarboxylation of benzyl halides to the corresponding carboxylic acids performed by homogeneous charge transfer catalysts is reported here. The performances of selected ester derivatives of benzoic acid and of the three isomers of benzenedicarboxylic acid as catalysts are evaluated on the basis of the faradaic efficiency of the carboxylation and of the decomposition rate of the catalyst. The standard redox potentials of catalysts are related to the selectivity of the process. Rates of catalyst decomposition appear to be dependent on the molar ratio [halide]/[catalyst] and on the cathode material.
- Scialdone, Onofrio,Filardo, Giuseppe,Galia, Alessandro,Mantione, Davide,Silvestri, Giuseppe
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p. 800 - 806
(2007/10/03)
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