- An expeditious study of the nature of halogen(s) at α-positions in carbonyl compounds
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The detailed study, of the behaviour of di/tri halo carbonyls to act as the synthetic equivalents of corresponding mono α-halo carbonyls, is carried out.
- Ahluwalia,Mehta,Rawat
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Read Online
- One-Pot Transformation of Lignin and Lignin Model Compounds into Benzimidazoles
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It is a challenging task to simultaneously achieve selective depolymerization and valorization of lignin due to their complex structure and relatively stable bonds. We herein report an efficient depolymerization strategy that employs 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as oxidant/catalyst to selectively convert different oxidized lignin models to a wide variety of 2-phenylbenzimidazole-based compounds in up to 94 % yields, by reacting with o-phenylenediamines with varied substituents. This method could take full advantage of both Cβ and/or Cγ atom in lignin structure to furnish the desirable products instead of forming byproducts, thus exhibiting high atom economy. Furthermore, this strategy can effectively transform both the oxidized hardwood (birch) and softwood (pine) lignin into the corresponding degradation products in up to 45 wt% and 30 wt%, respectively. Through a “one-pot” process, we have successfully realized the oxidation/depolymerization/valorization of natural birch lignin at the same time and produced the benzimidazole derivatives in up to 67 wt% total yields.
- Guo, Tao,He, Jianghua,Liu, Tianwei,Zhang, Yuetao
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- Alkylation of monomeric, dimeric, and polymeric lignin models through carbon-hydrogen activation using Ru-catalyzed Murai reaction
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In this study, we have assessed directed carbon-hydrogen activation (CHA) for alkylation of monomeric, dimeric, and polymeric lignin models using Murai's catalyst [RuH2(CO)(PPh3)3]. Based on related work from our laboratory showing that isolated organosolv lignin bears benzylic directing groups ideal for CHA reactions, this approach could offer new methodology for the valorization of biorefinery lignin. Monomeric and dimeric models bearing a keto group at the benzylic position undergo Ru-catalyzed alkylation in good to excellent yield. Similarly, models bearing a benzylic OH group also undergo alkylation via a tandem oxidation/alkylation process enabled by the Ru catalyst. Polymeric models show low levels of functionalization as a result of the poor solubility of the starting polymer. With unsymmetrical models, functionalization occurs first at the least sterically hindered ortho-site, but a subsequent alkylation, leading to disubstituted products can occur at the more sterically hindered site, leading to hexasubstituted arenes. The reaction shows sensitivity to free phenolic OH groups, which appears to reduce the yield in some reactions, and is also a contributing factor to the low yields observed with polymeric lignin models. Combining CHA methodology with lignin isolation technology able to introduce appropriate directing groups for catalytic functionalization will form the basis for improved conversion of lignin to high value chemical products.
- Zuleta, Ernesto C.,Bozell, Joseph J.
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- Cleavage∕cross-coupling strategy for converting β-O-4 linkage lignin model compounds into high valued benzyl amines via dual C–O bond cleavage
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Lignin is the most recalcitrant of the three components of lignocellulosic biomass. The strength and stability of the linkages have long been a great challenge for the degradation and valorization of lignin biomass to obtain bio-fuels and commercial chemicals. Up to now, the selective cleavage of C–O linkages of lignin to afford chemicals contains only C, H and O atoms. Our group has developed a cleavage/cross-coupling strategy for converting 4-O-5 linkage lignin model compounds into high value-added compounds. Herein, we present a palladium-catalyzed cleavage/cross-coupling of the β-O-4 lignin model compounds with amines via dual C–O bond cleavage for the preparation of benzyl amine compounds and phenols.
- Jia, Le,Li, Chao-Jun,Zeng, Huiying
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- Synthesis and in vitro anti-Toxoplasma gondii activity of a new series of aryloxyacetophenone thiosemicarbazones
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Abstract: A new series of aryloxyacetophenone thiosemicarbazones 4a–q have been synthesized as anti-Toxoplasma gondii agents. All compounds showed significant inhibitory activity against T. gondii-infected cells (IC50 values 1.09–25.19?μg/mL). The 4-fluorophenoxy derivative (4l) was the most potent compound with the highest selectivity toward host cells (SI = 19), being better than standard drug pyrimethamine. SAR study indicated that the concurrence of proper substituents on both aryl ring of phenoxyacetophenone is important for potency and safety profile. Further in vitro experiments with the representative compounds 4l and 4p revealed that these compounds at the concentration of 5?μg/mL can significantly reduce the viability of T. gondii tachyzoites, as well as their infectivity rate and intracellular proliferation, comparable to those of pyrimethamine. Graphic abstract: [Figure not available: see fulltext.]
- Ansari, Mahsa,Montazeri, Mahbobeh,Daryani, Ahmad,Farshadfar, Kaveh,Emami, Saeed
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p. 1223 - 1234
(2019/09/09)
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- Sulfuryl Fluoride Mediated Synthesis of Amides and Amidines from Ketoximes via Beckmann Rearrangement
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A metal-free and redox-neutral method for Beckmann rearrangement employing inexpensive and readily available SO2F2 gas is described. The reported transformation proceeds at ambient temperature and is compatible with a wide range of sterically and electronically diverse aromatic, heteroaromatic, aliphatic and lignin-like oximes providing amides in good to excellent yields. The reaction proceeds through the formation of an imidoyl fluoride intermediate that can also be used for the synthesis of amidines.
- Gurjar, Jitendra,Fokin, Valery V.
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p. 10402 - 10405
(2020/07/25)
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- Multiple Mechanisms Mapped in Aryl Alkyl Ether Cleavage via Aqueous Electrocatalytic Hydrogenation over Skeletal Nickel
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We present here detailed mechanistic studies of electrocatalytic hydrogenation (ECH) in aqueous solution over skeletal nickel cathodes to probe the various paths of reductive catalytic C-O bond cleavage among functionalized aryl ethers relevant to energy science. Heterogeneous catalytic hydrogenolysis of aryl ethers is important both in hydrodeoxygenation of fossil fuels and in upgrading of lignin from biomass. The presence or absence of simple functionalities such as carbonyl, hydroxyl, methyl, or methoxyl groups is known to cause dramatic shifts in reactivity and cleavage selectivity between sp3 C-O and sp2 C-O bonds. Specifically, reported hydrogenolysis studies with Ni and other catalysts have hinted at different cleavage mechanisms for the C-O ether bonds in α-keto and α-hydroxy β-O-4 type aryl ether linkages of lignin. Our new rate, selectivity, and isotopic labeling results from ECH reactions confirm that these aryl ethers undergo C-O cleavage via distinct paths. For the simple 2-phenoxy-1-phenylethane or its alcohol congener, 2-phenoxy-1-phenylethanol, the benzylic site is activated via Ni C-H insertion, followed by beta elimination of the phenoxide leaving group. But in the case of the ketone, 2-phenoxyacetophenone, the polarized carbonyl πsystem apparently binds directly with the electron rich Ni cathode surface without breaking the aromaticity of the neighboring phenyl ring, leading to rapid cleavage. Substituent steric and electronic perturbations across a broad range of β-O-4 type ethers create a hierarchy of cleavage rates that supports these mechanistic ideas while offering guidance to allow rational design of the catalytic method. On the basis of the new insights, the usage of cosolvent acetone is shown to enable control of product selectivity.
- Hegg, Eric L.,Jackson, James E.,Klinger, Grace E.,Saffron, Christopher M.,Zhou, Yuting
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p. 4037 - 4050
(2020/03/10)
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- A multicentre synergistic polyoxometalate-based metal-organic framework for one-step selective oxidative cleavage of β-: O -4 lignin model compounds
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A novel mixed-valence polyoxovanadate-based copper-organic framework, [CuI(bbi)]2{[CuI(bbi)]2VIV2VV8O26}·2H2O (NENU-MV-5, bbi = 1,1′-(1,4-butanediyl)bis(imidazole)), was facilely synthesized from routine reagents under mild hydrothermal conditions. Using NENU-MV-5 as a heterogeneous catalyst without any co-catalyst, one-step oxidative cleavage of β-O-4 lignin into phenols and aromatic acids with high catalytic activity and selectivity was realized under an oxygen atmosphere. No obvious decrease in activity was observed after five cycles, which indicates the excellent stability and sustainability of NENU-MV-5. The perfect catalytic performance of NENU-MV-5 can be attributed to the multi-site synergistic effect of the mixed-valence VV-O-VIV sites on polyoxovanadate for the oxidation of β-O-4 alcohol to β-O-4 ketone and the Cu(i) sites on the framework for the rapid cleavage of the Cα-Cβ bond of β-O-4 ketone. This system represented the first co-catalyst-free example for the one-step selective degradation of lignin catalyzed by a well-defined crystalline catalyst with definite composition and structure in a single solvent.
- Tian, Hong-Rui,Liu, Yi-Wei,Zhang, Zhong,Liu, Shu-Mei,Dang, Tian-Yi,Li, Xiao-Hui,Sun, Xiu-Wei,Lu, Ying,Liu, Shu-Xia
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supporting information
p. 248 - 255
(2020/01/13)
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- Cobalt-Catalyzed Reductive C-O Bond Cleavage of Lignin β-O-4 Ketone Models via in Situ Generation of the Cobalt-Boryl Species
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An efficient and mild method for reductive C-O bond cleavage of lignin β-O-4 ketone models was developed to afford the corresponding ketones and phenols with PDI-CoCl2 as the precatalyst and diboron reagent as the reductant. The synthetic utility of the methodology was demonstrated by depolymerization of a polymeric model and gram-scale transformation. Mechanistic studies suggested that this transformation involves steps of carbonyl insertion, 1,2-Brook type rearrangement, β-oxygen elimination, and rate-limiting regeneration of the catalytic active Co-B species.
- Gao, Kecheng,Xu, Man,Cai, Cheng,Ding, Yanghao,Chen, Jianhui,Liu, Bosheng,Xia, Yuanzhi
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supporting information
p. 6055 - 6060
(2020/08/12)
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- Identification of a Novel Oxadiazole Inhibitor of Mammalian Target of Rapamycin
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We performed a biochemical screen against mTOR using in-house small molecule library. Two novel, structurally distinct hits were identified. Among them, a novel oxadiazole scaffold compound (2) suppressed the phosphorylation of both S6K1 and Akt1 in HeLa cells. Docking study suggested that 2 is ATP-competitive and shows a pi-pi interaction with Trp2239 and hydrogen bonds with Trp2239 and Thr2245. Through derivatization, a slightly more potent analogue (2a) was identified with IC50 of 9.6 μM. Our study provides a starting point for discovery of novel potent mTOR inhibitors.
- Lim, Sunwoo,Lee, Hyomin,Kim, Euijung,Hur, Wooyoung
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p. 296 - 303
(2020/02/04)
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- Lewis-acid-mediated intramolecular trifluoromethylthiolation of alkenes with phenols: Access to SCF3-containing chromane and dihydrobenzofuran compounds
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A Lewis-acid-mediated intramolecular trifluoromethylthiolation of alkenes with phenols that can offer direct access to SCF3-containing chromane and dihydrobenzofuran compounds was disclosed for the first time. Numerous SCF3-containing chromanes were obtai
- Song, Xu-Feng,Ding, Tong-Mei,Zhu, Deng,Huang, Jie,Chen, Zhi-Min
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supporting information
p. 7052 - 7056
(2020/09/15)
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- Visible-light-induced C-C bond cleavage of lignin model compounds with cyanobenziodoxolone
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The catalytic degradation of lignin to value-added chemicals has received considerable attention over the past decade. Photocatalysis provides promising approaches to enable previously inaccessible transformations. However, examples of the visible-light promoted degradation of lignin are still limited. In this work, the visible-light-induced selective C-C bond cleavage of β-O-4 lignin model compounds has been disclosed via β-scission of in situ generated alkoxy radical intermediates. With cyanobenziodoxolone as the oxidant, a variety of substrates could be transformed into aldehydes in moderate to good yields. In addition, unexpected acetal esters which could conveniently furnish formaldehyde and phenols by alcoholysis were observed.
- Zheng, Ming,Huang, Yan,Zhan, Le-Wu,Hou, Jing,Li, Bin-Dong
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supporting information
(2020/10/02)
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- Visible light induced redox neutral fragmentation of 1,2-diol derivatives
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A homogeneous, redox-neutral photo fragmentation of diol derivatives was developed. Under photo/hydrogen atom transfer (HAT) dual catalysis, diol derivatives such as lignin model compounds and diol monoesters undergo selective β C(sp3)-O bond cleavage to afford ketones, phenols and acids effectively.
- Chen, Kang,Schwarz, Johanna,Karl, Tobias A.,Chatterjee, Anamitra,K?nig, Burkhard
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p. 13144 - 13147
(2019/11/11)
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- Selective Cα Alcohol Oxidation of Lignin Substrates Featuring a β-O-4 Linkage by a Dinuclear Oxovanadium Catalyst via Two-Electron Redox Processes
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Developing highly efficient catalyst systems to transform lignin biomass into value-added chemical feedstocks is imperative for utilizing lignin as renewable alternatives to fossil fuels. Recently, the pre-activated strategy involving the selective oxidat
- Tsai, Yan-Ting,Chen, Chih-Yao,Hsieh, Yi-Ju,Tsai, Ming-Li
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p. 4637 - 4646
(2019/11/16)
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- Cleavage of lignin model compounds and ligninox using aqueous oxalic acid
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Aqueous oxalic acid cleaves oxidised β-O-4 lignin model compounds by two distinct mechanisms that are dependent on the presence of the hydroxymethyl substituent. Various β-O-4 phenoxyacetophenones that do not contain the hydroxymethyl substituent undergo oxidative cleavage upon exposure to aqueous oxalic acid in the presence of air, likely through concerted ring opening of a dioxetane intermediate to give the corresponding benzoic acid and phenyl formate. Importantly, detrimental side reactions arising from singlet oxygen and hydroperoxy radicals (from both O2 and oxalic acid) are minimal when the cleavage is run under air compared to neat oxygen. When oxidised β-O-4 lignin model compounds bearing the hydroxymethyl group are cleaved by aqueous oxalic acid, the resulting diketone and phenol products arise from a redox neutral cleavage that is analogous to the formic acid-sodium formate mediated lignin cleavage process reported by Stahl. Aqueous oxalic acid also cleaves lignin itself, with oxidised milled wood lignin (MWLox) from Pinus radiata giving a 14% yield of ethyl acetate soluble aromatics with good selectivity for vanillin. Aqueous oxalic acid appears to be a promising lignin cleavage system given the benign, bio-based reagents, absence of metals and organic solvents and a simple extraction procedure that enables oxalic acid recycling.
- Lindsay, Ashley C.,Kudo, Shinji,Sperry, Jonathan
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supporting information
p. 7408 - 7415
(2019/08/15)
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- Method for synthesizing β - O - 4 lignin dimers model compounds (by machine translation)
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The invention belongs to the field of biological chemical and biological-based material, and in particular relates to a synthetic β - O - 4 lignin dimers model compounds. The phenolic material with the alkali is dissolved in the acetone in magnetic stirring and mixing, [...] ketone material under protection of inert gas in the room temperature to 60 °C reaction 16 - 48 h, filtering the filtrate after reaction is rotary evaporated to obtain crude product, crude after excessive polar organic solvent, washing the collection after dissolving the organic phase, dried and filtered, concentrated in vacuo, re-crystallization, dried under vacuum to get β - O - 4 lignin dimers model compound. The invention synthetic method and the conventional method compared with the universality is relatively strong, mild reaction conditions, the operation is simple, one-step synthesis output is high, and high purity, can reach 98% or more. (by machine translation)
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Paragraph 0092-0097
(2019/01/08)
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- Acid promoted C-C bond oxidative cleavage of β-O-4 and β-1 lignin models to esters over a copper catalyst
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Depolymerisation of lignin to aromatics is a challenging task. We herein report that a Cu(OAc)2/BF3·OEt2 catalyst is effective in simultaneously cleaving C-C bonds in β-1 and β-O-4 ketones, yielding esters and phenols. In-depth studies show that C-H bond activation is the rate determining step for C-C bond cleavage. BF3·OEt2 promotes the reaction via activating the β-C-H bond. This study offers the potential to obtain aromatic esters from lignin.
- Wang,Li,Lu,Li,Zhang,Liu,Luo,Wang
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p. 702 - 706
(2017/08/15)
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- Self-hydrogen transfer hydrogenolysis of β-O-4 linkages in lignin catalyzed by MIL-100(Fe) supported Pd-Ni BMNPs
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A MIL-100(Fe) supported Pd-Ni BMNP catalyst has been fabricated, and the catalyst exhibits superior catalytic performance toward the intramolecular transfer hydrogenolysis of lignin model compounds and organosolv lignin. Alcoholic groups (CαH-OH) of lignin were exploited as the hydrogen source, and selective cleavage of β-O-4 linkages in lignin was realized without an extra hydrogen donor. This protocol was suitable for organosolv lignin as well as model compounds; several phenols and functionalized acetophenones were detected when extracted lignin was treated in our system. The catalyst exhibits outstanding catalytic stability during the reaction process, which can be ascribed to the porous structure and the strong water stability of MIL-100(Fe). The excellent catalytic performance of Pd1Ni4/MIL-100(Fe) highlights the "synergistic effect" between the BMNPs and the functional synergy between MNPs and MOFs, and our work shows the bright future of BMNPs and MOFs in the development of catalysts for sustainable chemistry.
- Zhang, Jia-Wei,Lu, Guo-Ping,Cai, Chun
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p. 4538 - 4543
(2017/10/13)
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- Cleavage of the lignin β-O-4 ether bond: Via a dehydroxylation-hydrogenation strategy over a NiMo sulfide catalyst
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The efficient cleavage of lignin β-O-4 ether bonds to produce aromatics is a challenging and attractive topic. Recently a growing number of studies have revealed that the initial oxidation of CαHOH to CαO can decrease the β-O-4 bond dissociation energy (BDE) from 274.0 kJ mol-1 to 227.8 kJ mol-1, and thus the β-O-4 bond is more readily cleaved in the subsequent transfer hydrogenation, or acidolysis. Here we show that the first reaction step, except in the above-mentioned pre-oxidation methods, can be a Cα-OH bond dehydroxylation to form a radical intermediate on the acid-redox site of a NiMo sulfide catalyst. The formation of a Cα radical greatly decreases the Cβ-OPh BDE from 274.0 kJ mol-1 to 66.9 kJ mol-1 thereby facilitating its cleavage to styrene, phenols and ethers with H2 and an alcohol solvent. This is supported by control experiments using several reaction intermediates as reactants, analysis of product generation and by radical trap with TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) as well as by density functional theory (DFT) calculations. The dehydroxylation-hydrogenation reaction is conducted under non-oxidative conditions, which are beneficial for stabilizing phenol products.
- Zhang, Chaofeng,Lu, Jianmin,Zhang, Xiaochen,Macarthur, Katherine,Heggen, Marc,Li, Hongji,Wang, Feng
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p. 6545 - 6555
(2018/06/06)
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- Facile and selective hydrogenolysis of β-O-4 linkages in lignin catalyzed by Pd-Ni bimetallic nanoparticles supported on ZrO2
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The β-O-4 linkage in lignin can be selectively cleaved by Pd-Ni bimetallic nanoparticles supported on ZrO2 using hydrogen gas as the hydrogen donor under ambient pressure and neutral conditions. Conspicuous enhancement in activity is observed compared with single nickel and palladium catalysts based on the results of experiments and characterization. Moreover, hydrogenation of the produced phenols is tuned by adjusting the amount of NaBH4. The catalyst can be reused over ten times in the model reaction and over five times in the hydrogenolysis of lignin without an obvious change in activity and selectivity.
- Zhang, Jia-Wei,Cai, Yao,Lu, Guo-Ping,Cai, Chun
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p. 6229 - 6235
(2016/12/03)
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- Aerobic Oxidation of Olefins and Lignin Model Compounds Using Photogenerated Phthalimide-N-oxyl Radical
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A metal-free protocol to generate phthalimide-N-oxyl (PINO) radicals from N-hydroxyphthalimide (NHPI) via a photoinduced proton-coupled electron transfer process is reported. Using donor-substituted aromatic ketones, such as 4,4′-bis(diphenylamino)benzophenone (DPA-BP), PINO radicals are efficiently produced and subsequently utilized to functionalize olefins to afford a new class of alkyl hydroperoxides. The DPA-BP/NHPI/O2 photocatalytic system exhibits high efficiency toward the aerobic oxidation of β-O-4 lignin models.
- Luo, Jian,Zhang, Jian
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p. 9131 - 9137
(2016/10/17)
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- Chemoselective oxidant-free dehydrogenation of alcohols in lignin using Cp?Ir catalysts
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A remarkably effective method of chemoselective dehydrogenation of alcohols in lignin has been developed with an iridium catalyst. An additional operation of Zn/NH4Cl via a two-step one pot process could further promote the cleavage of the C-O bond in β-O-4 units in lignin. And this reaction system was also applicable to native lignin as the molecular weight of native lignin decreased obviously as detected by gel permeation chromatography (GPC). Additionally, this is the first to date generation of the by-product H2 from native lignin and the by-product was straightforwardly captured by 1-decene. A probable mechanistic pathway was also proposed with the help of density functional theory (DFT) calculations.
- Zhu, Rui,Wang, Bing,Cui, Minshu,Deng, Jin,Li, Xinglong,Ma, Yingbo,Fu, Yao
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supporting information
p. 2029 - 2036
(2016/04/19)
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- Two-Step, Catalytic C-C Bond Oxidative Cleavage Process Converts Lignin Models and Extracts to Aromatic Acids
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We herein report a two-step strategy for oxidative cleavage of lignin C-C bond to aromatic acids and phenols with molecular oxygen as oxidant. In the first step, lignin β-O-4 alcohol was oxidized to β-O-4 ketone over a VOSO4/TEMPO [(2,2,6,6-tetramethylpiperidin-1-yl)oxyl)] catalyst. In the second step, the C-C bond of β-O-4 linkages was selectively cleaved to acids and phenols by oxidation over a Cu/1,10-phenanthroline catalyst. Computational investigations suggested a copper-oxo-bridged dimer was the catalytically active site for hydrogen-abstraction from Cβ-H bond, which was the rate-determining step for the C-C bond cleavage.
- Wang, Min,Lu, Jianmin,Zhang, Xiaochen,Li, Lihua,Li, Hongji,Luo, Nengchao,Wang, Feng
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p. 6086 - 6090
(2016/09/09)
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- Selective aerobic benzylic alcohol oxidation of lignin model compounds: Route to aryl ketones
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A mild and chemoselective oxidation of the α-alcohol in β-O-4'-ethanoaryl and β-O-4'-glycerolaryl ethers has been developed. The benzylic alcohols were selectively dehydrogenated to the corresponding ketones in 60-93-% yield. A one-pot selective route to aryl ethyl ketones was performed. The catalytic system comprises recyclable heterogeneous palladium, mild reaction conditions, green solvents, and oxygen in air as oxidant. Catalytic amounts of a coordinating polyol were found pivotal for an efficient aerobic oxidation. The ligninator: A mild and chemoselective oxidation of the α-alcohol in β-O-4' lignin model compounds is developed. The benzylic alcohols are selectively dehydrogenated to the corresponding ketones in 60-93-% yield. A one-pot selective route to aryl ethyl ketones is performed. The catalytic system comprises recyclable heterogeneous palladium, mild reaction conditions, green solvents, and oxygen in air as oxidant.
- Dawange, Monali,Galkin, Maxim V.,Samec, Joseph S. M.
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p. 401 - 404
(2015/03/04)
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- Structural design, synthesis and structure-activity relationships of thiazolidinones with enhanced anti-Trypanosoma cruzi activity
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Pharmacological treatment of Chagas disease is based on benznidazole, which displays poor efficacy when administered during the chronic phase of infection. Therefore, the development of new therapeutic options is needed. This study reports on the structural design and synthesis of a new class of anti-Trypanosoma cruzi thiazolidinones (4 a-p). (2-[2-Phenoxy-1-(4-bromophenyl) ethylidene)hydrazono]-5-ethylthiazolidin-4-one (4 h) and (2-[2-phenoxy-1-(4- phenylphenyl)ethylidene)hydrazono]-5-ethylthiazolidin-4-one (4 l) were the most potent compounds, resulting in reduced epimastigote proliferation and were toxic for trypomastigotes at concentrations below 10 μM, while they did not display host cell toxicity up to 200 μM. Thiazolidinone 4 h was able to reduce the in vitro parasite burden and the blood parasitemia in mice with similar potency to benznidazole. More importantly, T. cruzi infection reduction was achieved without exhibiting mouse toxicity. Regarding the molecular mechanism of action, these thiazolidinones did not inhibit cruzain activity, which is the major trypanosomal protease. However, investigating the cellular mechanism of action, thiazolidinones altered Golgi complex and endoplasmic reticulum (ER) morphology, produced atypical cytosolic vacuoles, as well as induced necrotic parasite death. This structural design employed for the new anti-T. cruzi thiazolidinones (4 a-p) led to the identification of compounds with enhanced potency and selectivity compared to first-generation thiazolidinones. These compounds did not inhibit cruzain activity, but exhibited strong antiparasitic activity by acting as parasiticidal agents and inducing a necrotic parasite cell death. Stop the cycle! The attachment of an aryl ring to the iminic carbon produced thiazolidinones that are conformationally more restricted than first-generation thiazolidinones. This enhanced the potency of antiparasitic thiazolidinones, as observed under treatment with compound 4 h where parasite development and invasion in host cells were substantially reduced. Copyright
- Moreira, Diogo Rodrigo Magalhaes,Lima Leite, Ana Cristina,Cardoso, Marcos Verissimo Oliveira,Srivastava, Rajendra Mohan,Hernandes, Marcelo Zaldini,Rabello, Marcelo Montenegro,Da Cruz, Luana Faria,Ferreira, Rafaela Salgado,De Simone, Carlos Alberto,Meira, Cassio Santana,Guimaraes, Elisalva Teixeira,Da Silva, Aline Caroline,Dos Santos, Thiago Andre Ramos,Pereira, Valeria Rego Alves,Pereira Soares, Milena Botelho
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p. 177 - 188
(2014/01/17)
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- Liquid chromatographic resolution of mexiletine and its analogs on crown ether-based chiral stationary phases
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Mexiletine, an effective class IB antiarrhythmic agent, and its analogs were resolved on three different crown ether-based chiral stationary phases (CSPs), one (CSP 1) of which is based on (+)-(18-crown-6)-2,3,11,12- tetracarboxylic acid and the other two (CSP 2 and CSP 3) are based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6. Mexiletine was resolved with a resolution (RS) of greater than 1.00 on CSP 1 and CSP 3 containing residual silanol group-protecting n-octyl groups on the silica surface, but with a resolution (RS) of less than 1.00 on CSP 2. The chromatographic behaviors for the resolution of mexiletine analogs containing a substituted phenyl group at the chiral center on the three CSPs were quite dependent on the phenoxy group of analytes. Namely, mexiletine analogs containing 2,6-dimethylphenoxy, 3,4-dimethylphenoxy, 3-methylphenoxy, 4-methylphenoxy, and a simple phenoxy group were resolved very well on the three CSPs even though the chiral recognition efficiencies vary with the CSPs. However, mexiletine analogs containing 2-methylphenoxy group were not resolved at all or only slightly resolved. Among the three CSPs, CSP 3 was found to show the highest chiral recognition efficiencies for the resolution of mexiletine and its analogs, especially in terms of resolution (RS). Chirality 26:272-278, 2014. 2014 Wiley Periodicals, Inc.
- Jin, Kab Bong,Kim, Hee Eun,Hyun, Myung Ho
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p. 272 - 278
(2014/05/06)
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- Catalytic C-O bond cleavage of 2-aryloxy-1-arylethanols and its application to the depolymerization of lignin-related polymers
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A ruthenium-catalyzed, redox neutral C-O bond cleavage of 2-aryloxy-1-arylethanols was developed that yields cleavage products in 62-98% isolated yield. This reaction is applicable to breaking the key ethereal bond found in lignin-related polymers. The bond transformation proceeds by a tandem dehydrogenation/reductive ether cleavage. Initial mechanistic investigations indicate that the ether cleavage is most likely an organometallic C-O activation. A catalytic depolymerization of a lignin-related polymer quantitatively yields the corresponding monomer with no added reagent.
- Nichols, Jason M.,Bishop, Lee M.,Bergman, Robert G.,Ellman, Jonathan A.
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supporting information; experimental part
p. 12554 - 12555
(2010/12/19)
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- Mechanistic insights into the rhodium-catalyzed intramolecular ketone hydroacylation
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[Rh((fl)-DTBM-SEGPHOS)]BF4 catalyzes the intramolecular hydroacylation of ketones to afford seven-membered lactones in large enantiomeric excess. Herein, we present a combined experimental and theoretical study to elucidate the mechanism and origin of selectivity in this C-H bond activation process. Evidence is presented for a mechanistic pathway involving three key steps: (1) rhodium(I) oxidative addition into the aldehyde C-H bond, (2) insertion of the ketone C=O double bond into the rhodium hydride, and (3) C-O bond-forming reductive elimination. Kinetic isotope effects and Hammett plot studies support that ketone insertion isthe turnover-limiting step. Detailed kinetic experiments were performed using both 1,3- bis(diphenylphosphino)propane (dppp) and (R)-DTBM-SEGPH OS as ligands. With dppp, the keto-aldehyde substrate assists in dissociating a dimeric precatalyst 8 and binds an active monomeric catalyst 9. With [Rh((R)-DTBM-SEGPHOS)]BF4, there is no induction period and both substrate and product inhibition are observed. In addition, competitive decarbonylation produces a catalytically inactive rhodium carbonyl species that accumulates over the course of the reaction. Both mechanisms were modeled with a kinetics simulation program, and the models were consistent with the experimental data. Density functional theory calculations were performed to understand more elusive details of this transformation. These simulations support that the ketone insertion step has the highest energy transition state and reveal an unexpected interactionbetween the carbonyl-oxygen lone pair and a Rh d-orbital in this transi tion state structure. Finally, a model based on the calculated transition-state geometry is proposed to rationalize the absolute sense of enantioinduction observed using (R)-DTBM-SEGPHOS as the chiral ligand.
- Shen, Zengming,Dornan, Peter K.,Khan, Hasan A.,Woo, Tom K.,Dong, Vy M.
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supporting information; experimental part
p. 1077 - 1091
(2009/06/28)
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- Biomimetic transfer hydrogenation of 2-alkoxy- and 2-aryloxyketones with iron-porphyrin catalysts
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In situ generated iron porphyrins are applied as homogeneous catalysts in the transfer hydrogenation of α-substituted ketones. Using 2-propanol as hydrogen donor various protected 1,2-hydroxyketones are reduced to the corresponding mono-substituted 1,2-di
- Enthaler, Stephan,Spilker, Bj?rn,Erre, Giulia,Junge, Kathrin,Tse, Man Kin,Beller, Matthias
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p. 3867 - 3876
(2008/09/20)
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- Transformation of aryl acyloin O-alkyl and O-phenyl derivatives to ketones
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The treatment of aryl acyloin (α-hydroxyketone) O-alkyl and O-phenyl derivatives with 2-3 equiv of Zn and 1-2 equiv of NH4Cl in ethanol, refluxing for 20-120 min, gave the corresponding ketones with excellent yields. Further, α,β-epoxy ketones can be efficiently transformed to β-hydroxy ketones, and 2,2-dialkoxy-1-phenyl ketone also can be dealkoxylated to 1-phenyl ketone. Copyright Taylor & Francis Group, LLC.
- Yao, Zhiyi,Ye, Deju,Liu, Hong,Chen, Kaixian,Jiang, Hualiang
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p. 149 - 156
(2007/10/03)
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- Generation and reactivity of ketyl radicals with lignin related structures. On the importance of the ketyl pathway in the photoyellowing of lignin containing pulps and papers
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(Chemical Equation Presented) Ketyl radicals with lignin related structures have been generated by means of radiation chemical and photochemical techniques. In the former studies ketyl radicals are produced by reaction of α-carbonyl-β-aryl ether lignin models with the solvated electron produced by pulse radiolysis of an aqueous solution at pH 6.0. The UV-vis spectra of ketyl radicals are characterized by three main absorption bands. The shape and position of these bands slightly change when the spectra are recorded in alkaline solution (pH 11.0) being now assigned to the ketyl radical anions and a pKa = 9.5 is determined for the 1-(3,4,5-trimethoxyphenyl)-2- phenoxyethanol-1-yl radical. Decay rates of ketyl radicals are found to be dose dependent and, at low doses, lie in the range (1.7-2.7) × 103 s-1. In the presence of oxygen a fast decay of the ketyl radicals is observed (k2 = 1.8-2.7 × 109 M-1 s -1) that is accompanied by the formation of stable products, i.e., the starting ketones. In the photochemical studies ketyl radicals have been produced by charge-transfer (CT) photoactivation of the electron donor-acceptor salts of methyl viologen (MV2+) with α-hydroxy-α- phenoxymethylaryl acetates. This process leads to the instantaneous formation of the reduced acceptor (methyl viologen radical cation, MV+?), as is clearly shown in a laser flash photolysis experiment by the two absorption bands centered at 390 and 605 nm, and an acyloxyl radical [ArC(CO 2?)(OH)CH2(OC6H5)], which undergoes a very fast decarboxylation with formation of the ketyl radicals. Steady-state photoirradiation of the CT ion pairs indicates that 1-aryl-2-phenoxyethanones are formed as primary photoproducts by oxidation of ketyl radicals by MV2+ (under argon) or by molecular oxygen. Small amounts of acetophenones are formed by further photolysis of 1-aryl-2-phenoxyethanones and not by β-fragmentation of the ketyl radicals. The high reactivity of ketyl radicals with oxygen coupled with the low rates of β-fragmentation of the same species have an important bearing in the context of the photoyellowing of lignin containing pulps and papers.
- Fabbri, Claudia,Bietti, Massimo,Lanzalunga, Osvaldo
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p. 2720 - 2728
(2007/10/03)
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- Three-step synthesis of an array of substituted benzofurans using polymer-supported reagents
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An efficient combinatorial route to substituted 3-phenyl-benzofurans, is achieved by the bromination of acetophenones to α-bromoacetophenones by polymer-supported pyridinium bromide perbromide (PSPBP). The subsequent clean substitution of the obtained bromides by phenols using 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD-P) and cyclodehydration of the resulting α-phenoxyacetophenones using Amberlyst 15, affords pure products without the need for any chromatographic purification step.
- Habermann, Joerg,Ley, Steven V.,Smits, Rene
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p. 2421 - 2423
(2007/10/03)
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- ONE ELECTRON OXIDATION OF BENZYL AND 2-PHENYLETHYL PHENYL ETHERS. THE FATE OF THE INTERMEDIATE RADICAL CATIONS
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The one electron oxidations of benzyl phenyl ether (1), 2-phenylethyl phenyl ether (2) and 2-(4-methoxyphenyl)ethyl phenyl ether (3) promoted (a) by cerium(IV) ammonium nitrate (CAN) in AcOH, (b) electrochemically in AcOH-MeCN/AcOK and (c) photochemically in MeCN, in the presence of 9,10-dicyanoanthracene (DCA), have been investigated.With 1 benzaldehyde forms, under all the reaction conditions, accompanied by products of acetoxylation at the phenoxy ring (conditions a and b) or by phenyl benzoate (condition c).The CAN-promoted and the electochemical oxidation of 2 exclusively lead to substitution at the phenoxy ring, whereas only side-chain attack at the benzylic carbon occurs in all of the reactions of 3, with formation of 4-methoxybenzaldehyde and products of side-chain oxidation.Phenyl 4-methoxybenzoate is also formed (conditions b and c).However, when the electrochemical oxidation is carried out in the absence of AcOK, only a product of intermolecular ring closure forms.These results allow one to draw some interesting conclusion on the competition between the various reaction pathways available to the cation radicals which are the first formed reaction intermediates in these one electron processes.
- Baciocchi, Enrico,Piermattei, Alessandro,Rol, Cesare,Ruzziconi, Renzo,Sebastiani, Giovanni Vittorio
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p. 7049 - 7062
(2007/10/02)
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- PHOTOCHEMISTRY OF α-PHENOXY-p-METHOXYACETOPHENONE
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The triplet state of the title compound decays by a competition of β-phenyl quenching and β-cleavage leading to CH3OC6H4COCH2. and phenoxyl radicals.The latter process occurs with a quantum yield of 0.020.
- Netto-Ferreira, J. C.,Scaiano, J. C.
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p. 443 - 446
(2007/10/02)
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