- A NOVEL SYNTHESIS OF α,β-UNSATURATED NITRILES FROM AROMATIC KETONES VIA CYANOPHOSPHATES
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Reaction of aromatic ketones with diethyl phosphorocyanidate in the presence of lithium cyanide gave cyanophosphates, which were converted into α,β-unsaturated nitriles by treatment with boron trifluoride etherate in high yields.
- Harusawa, Shinya,Yoneda, Ryuji,Kurihara, Takushi,Hamada, Yasumasa,Shioiri, Takayuki
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- Synthesis, pharmacological activity and hydrolytic behavior of glyceride prodrugs of ibuprofen
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For reducing the gastrointestinal toxicity associated with ibuprofen its carboxylic group was condensed with the hydroxyl group of 1,2,3-trihydroxy propane 1,3-dipalmitate/stearate to give the ester prodrugs 3a and 3b. The release of ibuprofen from these prodrugs has been studied at pH 3, 4, 5 and 7.4 by HPLC using methanol and 0.05% phosphoric acid (80%) (70:30) as mobile phase. The prodrugs showed insignificant hydrolysis at pH 5 compared to pH 7.4 indicating that the prodrugs do not break in stomach but release ibuprofen at pH 7.4 in adequate amounts. In vivo hydrolysis studies in rats, the peak plasma concentration of ibuprofen was attained in 1.5:h in case of ibuprofen and in 2:h in prodrugs treated animals. The plasma concentration was found to be less at all times in animals treated with ibuprofen compared to the prodrugs treated animals. The maximum anti-inflammatory activity of ibuprofen was observed at 2 h whereas prodrugs showed maximum activity at 3 h and remained practically constant upto 8:h whereas a decrease in activity was observed with free ibuprofen. Further the prodrugs showed less gastric ulcers compared to ibuprofen. An average score of 0.16, 0.45, 0.97 and 0.20, 0.76, 1.02 of ulcers was observed with 3a and 3b compared to an average score of 0.75, 1.10, and 2.97 with ibuprofen. These prodrugs also showed significant protection against acetic acid induced writhings in rats. These finding suggested that both the prodrugs are better in action as compared to the parent drug and are advantageous in having less gastrointestinal side effects.
- Khan,Akhter, Mymoona
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- The continuous-flow synthesis of ibuprofen
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Let relief flow forth I A three-step, continuous-flow synthesis of ibuprofen was accomplished using a simplified microreactor. By designing a synthesis in which excess reagents and byproducts are compatible with downstream reactions, no intermediate purification or isolation steps are required.
- Bogdan, Andrew R.,Poe, Sarah L.,Kubis, Daniel C.,Broadwater, Steven J.,McQuade, D. Tyler
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- The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot
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An automated synthesis robot was constructed by modifying an open source 3D printing platform. The resulting automated system was used to 3D print reaction vessels (reactionware) of differing internal volumes using polypropylene feedstock via a fused deposition modeling 3D printing approach and subsequently make use of these fabricated vessels to synthesize the nonsteroidal antiinflammatory drug ibuprofen via a consecutive one-pot three-step approach. The synthesis of ibuprofen could be achieved on different scales simply by adjusting the parameters in the robot control software. The software for controlling the synthesis robot was written in the python programming language and hard-coded for the synthesis of ibuprofen by the method described, opening possibilities for the sharing of validated synthetic 'programs' which can run on similar low cost, user-constructed robotic platforms towards an 'open-source' regime in the area of chemical synthesis.
- Kitson, Philip J.,Glatzel, Stefan,Cronin, Leroy
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- Highly active supported palladium catalyst for the regioselective synthesis of 2-arylpropionic acids by carbonylation
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A catalyst system consisting of supported palladium in the presence of phosphine ligands, TsOH and LiCl catalyses the carbonylation of 1-arylethanols to 2-arylpropionic acids with significantly improved activity and regioselectivity; the catalyst can be recycled with no loss in activity and selectivity.
- Jayasree,Seayad,Chaudhari
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- Synthesis and hydrolytic behaviour of glycerol-1,2-diibuprofenate-3-nitrate, a putative pro-drug of ibuprofen and glycerol-1-nitrate
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Nitroxylated derivatives of non-steroidal anti-inflammatory drugs appear to offer protection against the gastrotoxicity normally associated with non-steroidal anti-inflammatory drugs, ostensibly via local production of nitric oxide. A diester of ibuprofen and glycerol-1-mononitrate has been prepared via the condensation of ibuprofen with 3-bromopropan-1,2-diol, followed by silver-(I)-nitrate-mediated nitroxylation. The release of ibuprofen from this diester has been studied in a simulated gastric fluid model with direct analysis by reverse-phase HPLC, using an acetonitrile-water (80 % :20 %) mobile phase containing trifluoroacetic acid (0.005%). n-Propyl ibuprofen was found to undergo pH-dependent hydrolysis, ranging from negligible hydrolysis at pH 5 to 52 % hydrolysis at pH 3, over a 2-h period in this model. The ibuprofen-glycerol mononitrate diester was subjected to the most vigorous model hydrolytic conditions and was found to undergo 50 % hydrolysis during the study period. This study shows that pro-drugs of ibuprofen and glycerol mononitrate can be obtained, and can undergo degradation to the parent drugs under conditions simulating those likely to be encountered in the stomach.
- Ingram,Moynihan,Powell,Rostron
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- Carbonylation of vinyl aromatics: Convenient regioselective synthesis of 2-arylpropanoic acids
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(equation presented) Various substituted and nonsubstituted 2-arylpropanoic acids have been synthesized in high turnovers with high regioselectivity by palladium-catalyzed carbonylation of vinyl aromatics. Both terminal and internal olefins are carbonylated, though hindered olefins are less reactive. In all the cases high yields and high selectivity are observed. Olefins with electron-withdrawing para substituents gave the highest regioselectivity in the formation of the corresponding 2-arylpropanoic acids.
- Seayad,Jayasree,Chaudhari
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- Separate mechanisms of ion oligomerization tune the physicochemical properties of n-butylammonium acetate: Cation-base clusters vs. Anion-acid dimers
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We investigated the ability of the ions comprising protic ionic liquids to strongly interact with their neutral acid and base forms through the characterization of n-butylammonium acetate ([C4NH3][OAc]) in the presence of excess n-butylamine (C4NH2) or excess acetic acid (HOAc). The conjugate and parent acid or base form new nonstoichiometric, noncovalently bound species (i.e., oligomeric ions) which change the physical and chemical properties of the resulting liquids, thus offering tunability. The effects of adding C4NH2 or HOAc to [C4NH3][OAc] on the resulting thermal and spectroscopic properties differ and suggest that C4NH2 interacts primarily with [C4NH3]+ to form 3-dimensional polymeric networks likely similar to those in H2O/[H3O]+, while HOAc interacts primarily with [OAc]- to form oligomeric ions (e.g., [H(OAc)2]-). The densities of the systems increased with the increase of acid content and reached a maximum when the acid molar fraction was 0.90, but decreased with increasing amine concentration. The viscosities decreased significantly with increasing acid or base concentration. The solvent properties of the mixtures were assessed by measuring the solubilities of benzene, ethyl acetate, diethyl ether, heptane, ibuprofen free acid, and lidocaine free base. The solubilities of the organic solutes and active pharmaceutical ingredients can be tuned with the concentration of acid or amine in the mixtures. In addition, crystallization of the active pharmaceutical ingredients can be induced with the modification of the composition of the mixtures. These observations support the usage of these mixtures for the synthesis and purification of acid or basic active pharmaceutical ingredients in the pharmaceutical industry.
- Berton, Paula,Kelley, Steven P.,Wang, Hui,Myerson, Allan S.,Rogers, Robin D.
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- NMR spectroscopic studies on the in vitro acyl glucuronide migration kinetics of ibuprofen ((±)-(R,S)-2-(4-isobutylphenyl) propanoic acid), its metabolites, and analogues
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Carboxylic acid-containing drugs are often metabolized to 1-β-O-acyl glucuronides (AGs). These can undergo an internal chemical rearrangement, and the resulting reactive positional isomers can bind to endogenous proteins, with clear potential for adverse effects. Additionally any 1-β-O-acyl- glucuronidated phase I metabolite of the drug can also show this propensity, and investigation of the adverse effect potential of a drug also needs to consider such metabolites. Here the transacylation of the common drug ibuprofen and two of its metabolites is investigated in vitro. 1-β-O-Acyl (S)-ibuprofen glucuronide was isolated from human urine and also synthesized by selective acylation. Urine was also used as a source of the (R)-ibuprofen, (S)-2-hydroxyibuprofen, and (S,S)-carboxy-ibuprofen AGs. The degradation rates (a combination of transacylation and hydrolysis) were measured using 1H NMR spectroscopy, and the measured decrease in the 1-β anomer over time was used to derive half-lives for the glucuronides. The biosynthetic and chemically synthesized (S)-ibuprofen AGs had half-lives of 3.68 and 3.76 h, respectively. (R)-Ibuprofen AG had a half-life of 1.79 h, a value approximately half that of the (S)-diastereoisomer, consistent with results from other 2-aryl propionic acid drug AGs. The 2-hydroxyibuprofen and carboxyibuprofen AGs gave half-lives of 5.03 and 4.80 h, considerably longer than that of either of the parent drug glucuronides. In addition, two (S)-ibuprofen glucuronides were synthesized with the glucuronide carboxyl function esterified with either ethyl or allyl groups. The (S)-ibuprofen AG ethyl ester and (S)-ibuprofen AG allyl esters were determined to have half-lives of 7.24 and 9.35 h, respectively. In order to construct useful structure-reactivity relationships, it is necessary to evaluate transacylation and hydrolysis separately, and here it is shown that the (R)- and (S)-ibuprofen AGs have different transacylation properties. The implications of these findings are discussed in terms of structure-activity relationships.
- Johnson, Caroline H.,Wilson, Ian D.,Harding, John R.,Stachulski, Andrew V.,Iddon, Lisa,Nicholson, Jeremy K.,Lindon, John C.
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- Expanding the substrate scope of enzymes: Combining mutations obtained by CASTing
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In a previous paper, the combinatorial active-site saturation test (CAST) was introduced as an effective strategy for the directed evolution of enzymes toward broader substrate acceptance. CASTing comprises the systematic design and screening of focused libraries around the complete binding pocket, but it is only the first step of an evolutionary process because only the initial libraries of mutants are considered. In the present study, a simple method is presented for further optimization of initial hits by combining the mutational changes obtained from two different libraries. Combined lipase mutants were screened for hydrolytic activity against six notoriously difficult substrates (bulky carboxylic acid esters) and improved mutants showing significantly higher activity were identified. The enantioselectivity of the mutants in the hydrolytic kinetic resolution of two substrates was also studied, with the best mutant-substrate combination resulting in a selectivity factor of E=49. Finally, the catalytic profile of the evolved mutants in the hydrolysis of simple nonbranched carboxylic acid esters, ranging from acetate to palmitate, was studied for theoretical reasons.
- Reetz, Manfred T.,Carballeira, Jose Daniel,Peyralans, Jerome,Hoebenreich, Horst,Maichele, Andrea,Vogel, Andreas
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- Room-temperature Pd-catalyzed methoxycarbonylation of terminal alkynes with high branched selectivity enabled by bisphosphine-picolinamide ligand
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We report the room-temperature Pd-catalyzed methoxy-carbonylation with high branched selectivity using a new class of bisphosphine-picolinamide ligands. Systematic optimization of ligand structures and reaction conditions revealed the significance of both
- Chen, Fen-Er,Ke, Miaolin,Liu, Ding,Ning, Yingtang,Ru, Tong
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p. 1041 - 1044
(2022/01/28)
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- The total synthesis of (-) -strempeliopine: Via palladium-catalyzed decarboxylative asymmetric allylic alkylation
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In the work reported herein, the concise and enantioselective total synthesis of the Schizozygine alkaloid (-)-strempeliopine was developed. This synthetic strategy featured the palladium-catalyzed decarboxylative asymmetric allylic alkylation of N-benzoy
- An, Yi,Chen, Fener,Li, Weijian,Li, Yaling,Tang, Pei,Wang, Zhenzhen,Wu, Mengjuan,Xue, Yansong
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p. 1402 - 1405
(2022/02/09)
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- Coupling of Reformatsky Reagents with Aryl Chlorides Enabled by Ylide-Functionalized Phosphine Ligands
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The coupling of aryl chlorides with Reformatsky reagents is a desirable strategy for the construction of α-aryl esters but has so far been substantially limited in the substrate scope due to many challenges posed by various possible side reactions. This limitation has now been overcome by the tailoring of ylide-functionalized phosphines to fit the requirements of Negishi couplings. Record-setting activities were achieved in palladium-catalyzed arylations of organozinc reagents with aryl electrophiles using a cyclohexyl-YPhos ligand bearing an ortho-tolyl-substituent in the backbone. This highly electron-rich, bulky ligand enables the use of aryl chlorides in room temperature couplings of Reformatsky reagents. The reaction scope covers diversely functionalized arylacetic and arylpropionic acid derivatives. Aryl bromides and chlorides can be converted selectively over triflate electrophiles, which permits consecutive coupling strategies.
- Hu, Zhiyong,Wei, Xiao-Jing,Handelmann, Jens,Seitz, Ann-Katrin,Rodstein, Ilja,Gessner, Viktoria H.,Goo?en, Lukas J.
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supporting information
p. 6778 - 6783
(2021/02/01)
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- Palladium-Catalyzed Distal m-C-H Functionalization of Arylacetic Acid Derivatives
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Herein, we present m-C-H olefination on derivatives of phenylacetic acids by tethering with a simple nitrile-based template through palladium catalysis. Notably, the versatility of the method is evaluated with a wide range of phenylacetic acid derivatives for obtaining the meta-olefination products in fair to excellent yields with outstanding selectivities under mild conditions. Significantly, the present strategy is successfully exemplified for the synthesis of drugs/natural product analogues (naproxen, ibuprofen, paracetamol, and cholesterol).
- Srinivas, Dasari,Satyanarayana, Gedu
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p. 7353 - 7358
(2021/10/01)
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- 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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- Cobalt-Catalyzed Deprotection of Allyl Carboxylic Esters Induced by Hydrogen Atom Transfer
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A brief, efficient method has been developed for the removal of the allyl protecting group from allyl carboxylic esters using a Co(II)/TBHP/(Me2SiH)2O catalytic system. This facile strategy displays excellent chemoselectivity, functional group tolerance, and high yields. This transformation probably occurs through the hydrogen atom transfer process, and a Co(III)-six-membered cyclic intermediate is recommended.
- Li, Nan,Gui, Yizhen,Chu, Mengqi,You, Mengdi,Qiu, Xiaohan,Liu, Hejia,Wang, Shiang,Deng, Meng,Ji, Baoming
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supporting information
p. 8460 - 8464
(2021/11/13)
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- Suppressing carboxylate nucleophilicity with inorganic salts enables selective electrocarboxylation without sacrificial anodes
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Although electrocarboxylation reactions use CO2as a renewable synthon and can incorporate renewable electricity as a driving force, the overall sustainability and practicality of this process is limited by the use of sacrificial anodes such as magnesium and aluminum. Replacing these anodes for the carboxylation of organic halides is not trivial because the cations produced from their oxidation inhibit a variety of undesired nucleophilic reactions that form esters, carbonates, and alcohols. Herein, a strategy to maintain selectivity without a sacrificial anode is developed by adding a salt with an inorganic cation that blocks nucleophilic reactions. Using anhydrous MgBr2as a low-cost, soluble source of Mg2+cations, carboxylation of a variety of aliphatic, benzylic, and aromatic halides was achieved with moderate to good (34-78%) yields without a sacrificial anode. Moreover, the yields from the sacrificial-anode-free process were often comparable or better than those from a traditional sacrificial-anode process. Examining a wide variety of substrates shows a correlation between known nucleophilic susceptibilities of carbon-halide bonds and selectivity loss in the absence of a Mg2+source. The carboxylate anion product was also discovered to mitigate cathodic passivation by insoluble carbonates produced as byproducts from concomitant CO2reduction to CO, although this protection can eventually become insufficient when sacrificial anodes are used. These results are a key step toward sustainable and practical carboxylation by providing an electrolyte design guideline to obviate the need for sacrificial anodes.
- Corbin, Nathan,Lazouski, Nikifar,Manthiram, Karthish,Steinberg, Katherine,Yang, Deng-Tao
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p. 12365 - 12376
(2021/10/08)
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- Desulfonylative Electrocarboxylation with Carbon Dioxide
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Electrocarboxylation of organic halides is one of the most investigated electrochemical approaches for converting thermodynamically inert carbon dioxide (CO2) into value-added carboxylic acids. By converting organic halides into their sulfone derivatives, we have developed a highly efficient electrochemical desulfonylative carboxylation protocol. Such a strategy takes advantage of CO2as the abundant C1 building block for the facile preparation of multifunctionalized carboxylic acids, including the nonsteroidal anti-inflammatory drug ibuprofen, under mild reaction conditions.
- Zhong, Jun-Song,Yang, Zi-Xin,Ding, Cheng-Lin,Huang, Ya-Feng,Zhao, Yi,Yan, Hong,Ye, Ke-Yin
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supporting information
p. 16162 - 16170
(2021/09/02)
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- PHOTOLYTIC COMPOUNDS AND TRIPLET-TRIPLET ANNIHILATION MEDIATED PHOTOLYSIS
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The invention provides novel photolytic compounds and prodrugs, nanoparticles and compositions thereof, and methods of conducting photolysis mediated by triplet-triplet annihilation.
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Paragraph 0026
(2021/04/17)
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- Mechanistic Investigation of the Nickel-Catalyzed Carbonylation of Alcohols
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The carbonylation of alcohols represents a straightforward and atom-efficient methodology for the preparation of carboxylic acids. It is desirable to perform these reactions under precious metal-free and low-pressure conditions, with regioselectivity control. In this work, we present a detailed mechanistic study of a catalytic system based on NiI2, which can carbonylate benzylic alcohols in a highly regioselective manner to the corresponding branched carboxylic acids, core motifs for nonsteroidal drugs. The combination of catalytic amounts of nickel and iodide is crucial for efficient catalytic and regioselective conversion. Quantum-chemical computations were used to evaluate the underlying mechanistic processes. They revealed that a combination of two mechanisms is responsible for the observed reactivity and that the oxidative addition of alkyl halides to the Ni(0) species follows a radical oxidation pathway via two one-electron steps.
- Comba, Peter,Ghosh, Tamal,Hashmi, A. Stephen K.,Krieg, Saskia,Menche, Maximilian,Paciello, Rocco,Rück, Katharina S. L.,Sabater, Sara,Sch?fer, Ansgar,Schaub, Thomas
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supporting information
(2020/03/19)
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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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Page/Page column 11-14
(2020/10/04)
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- Oxidation of Alkynyl Boronates to Carboxylic Acids, Esters, and Amides
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A general efficient protocol was developed for the synthesis of carboxylic acids, esters, and amides through oxidation of alkynyl boronates, generated directly from terminal alkynes. This protocol represents the first example of C(sp)?B bond oxidation. This approach displays a broad substrate scope, including aryl and alkyl alkynes, and exhibits excellent functional group tolerance. Water, primary and secondary alcohols, and amines are suitable nucleophiles for this transformation. Notably, amino acids and peptides can be used as nucleophiles, providing an efficient method for the synthesis and modification of peptides. The practicability of this methodology was further highlighted by the preparation of pharmaceutical molecules.
- Li, Chenchen,Li, Ruoling,Zhang, Bing,Zhao, Pei,Zhao, Wanxiang
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supporting information
p. 10913 - 10917
(2020/05/25)
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- Deoxygenative α-alkylation and α-arylation of 1,2-dicarbonyls
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Construction of C-C bonds at the α-carbon is a challenging but synthetically indispensable approach to α-branched carbonyl motifs that are widely represented among drugs, natural products, and synthetic intermediates. Here, we describe a simple approach to generation of boron enolates in the absence of strong bases that allows for introduction of both α-alkyl and α-aryl groups in a reaction of readily accessible 1,2-dicarbonyls and organoboranes. Obviation of unselective, strongly basic and nucleophilic reagents permits carrying out the reaction in the presence of electrophiles that intercept the intermediate boron enolates, resulting in two new α-C-C bonds in a tricomponent process. This journal is
- Arman, Hadi D.,Dang, Hang T.,Haug, Graham C.,Jin, Shengfei,Larionov, Oleg V.,Nguyen, Viet D.
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p. 9101 - 9108
(2020/09/17)
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- MIDA boronate allylation-synthesis of ibuprofen
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MIDA boronates are among the most useful reagents for the Suzuki-Miyaura reaction. This chemistry typically generates new bonds between two aromatic rings, thereby restricting access to important areas of chemical space. Here we demonstrate the coupling of MIDA boronates to allylic electrophiles, including a new synthesis of the well-known COX inhibitor ibuprofen. This journal is
- Brodie, Glen,France, David J.,Memarzadeh, Sarah,Phillips, David,Tang, Gi Lum
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p. 30624 - 30630
(2020/09/11)
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- Nickel-Catalyzed Cyanation of Aryl Halides and Hydrocyanation of Alkynes via C-CN Bond Cleavage and Cyano Transfer
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We report nickel-catalyzed cyanation and hydrocyanation methods to prepare aryl nitriles and vinyl nitriles from aryl halides and alkynes, respectively. Using inexpensive and nontoxic 4-cyanopyridine N-oxide as the cyano shuttle, the methods provide an efficient approach to prepare aryl cyanides and vinyl nitriles under mild and operationally simple reaction conditions with a broad range of functional group tolerances. In hydrocyanation of alkynes, the method demonstrated good regioselectivity, producing predominantly E- or Z-alkenyl nitriles in a controlled manner and exclusively Markovnikov vinyl nitriles when internal diaryl alkynes and terminal alkynes were applied as the substrates, respectively. The preliminary mechanistic investigation indicated that the C-CN bond cleavage process is promoted by oxidative addition to the nickel(I) complex in the cyanation of aryl halides, and further studies via a series of deuterium exchange experiments indicated that water serves as the hydrogen source for the hydrocyanation of alkynes.
- Chen, Hui,Sun, Shuhao,Liu, Yahu A.,Liao, Xuebin
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p. 1397 - 1405
(2020/02/04)
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- para-Selective arylation and alkenylation of monosubstituted arenes using thianthreneS-oxide as a transient mediator
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Using thianthreneS-oxide (TTSO) as a transient mediator,para-arylation and alkenylation of mono-substituted arenes have been demonstratedviaapara-selective thianthrenation/Pd-catalyzed thio-Suzuki-Miyaura coupling sequence under mild conditions. This reaction features a broad substrate scope, and functional group and heterocycle tolerance. The versatility of this approach was further demonstrated by late-stage functionalization of complex bioactive scaffolds, and direct synthesis of some pharmaceuticals, including Tetriprofen, Ibuprofen, Bifonazole, and LJ570.
- Chen, Xiao-Yue,Nie, Xiao-Xue,Wu, Yichen,Wang, Peng
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supporting information
p. 5058 - 5061
(2020/05/18)
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- Preparation method of para-substituted aryl compound
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The invention discloses a preparation method of a para-substituted aryl compound shown as a formula (I) which is described in the specfication. The preparation method is characterized by comprising the following step of: subjecting an aryl sulfonium salt shown as a formula (II) which is described in the specfication and boride to a coupling reaction in a solvent in an inert atmosphere under the action of alkali and a palladium catalyst to obtain the para-substituted aryl compound. According to the method, mono-substituted aromatic hydrocarbon is taken as a substrate, the aryl sulfonium salt isconstructed in situ, and the palladium catalyst catalyzes the aryl sulfonium salt constructed in situ to undergo the Suzuki-Miyaura coupling reaction, so a mono-substituted aromatic hydrocarbon para-arylation or alkenylation product is constructed quickly and efficiently. The method is mild in conditions, high in substrate universality and wide in tolerance of a heterocyclic coupling substrate.
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Paragraph 0501-0503l 0505
(2020/06/09)
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- Preparation method of organic carboxylic acid
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The invention discloses a preparation method of organic carboxylic acid. The preparation method comprises the following steps that catalysts, olefins, water and solvents are added into a reaction container; CO is introduced; heating reaction is performed; after the reaction completion, separation is performed to obtain organic carboxylic acid; the catalysts comprise transition metal catalysts, ligands and catalysis assistants; the catalysis assistants comprise Lewis acid salt. The preparation method has the advantages that the dependency on protonic acid in the prior art is avoided; the Lewisacid salt is used as the catalysis assistant, so that the corrosion of a reaction system on equipment can be effectively prevented; the requirements on equipment are lowered. The preparation method has excellent substrate practicability; the operation steps are simple and fast; the reaction conditions are mild and are easy to control; the raw materials are cheap and can be easily obtained; the product yield and the product purity are high; the preparation method is suitable for large-scale industrial production; the normal/iso ratio of reaction products can be regulated and controlled throughthe catalysis assistants; the defects of regulating and controlling the normal/iso ratio of the reaction products by traditional phosphine ligands are overcome; the reaction progress of the reaction is simplified; the cost is favorably reduced.
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Paragraph 0083-0085; 0089-0091
(2019/10/15)
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- From p-Xylene to Ibuprofen in Flow: Three-Step Synthesis by a Unified Sequence of Chemoselective C?H Metalations
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Ibuprofen was prepared from an inactive and inexpensive p-xylene by three-step flow functionalizations through chemoselective metalations of benzyl positions in sequence using an in situ generated LICKOR-type superbase. The flow approach in the microreactor facilitated the comprehensive exploration of over 100 conditions in the first-step reaction by varying concentrations, temperatures, solvents, and equivalents of reagents, enabling optimal conditions to be found with 95 % yield by significantly suppressing the formation of byproducts, followed by the second C?H metalation step in 95 % yield. Moreover, gram-scale synthesis of ibuprofen in the final step was achieved by biphasic flow reaction of solution-phase intermediate with CO2, isolating 2.3 g for 10 min of operation time.
- Lee, Hyune-Jea,Kim, Heejin,Kim, Dong-Pyo
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p. 11641 - 11645
(2019/08/30)
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- Preparation method of ibuprofen
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The invention discloses a preparation method of ibuprofen. According to the preparation method, isobutyl benzene is taken as the primary raw material and carries out Friedel-Crafts reactions with epoxy propane to obtain a key intermediate namely 2-(4-isobutylphenyl)propanol; the intermediate can be directly oxidized to prepare ibuprofen without separation, and the preparation method also comprisesa refining step. The preparation method has the advantages that no any heavy metal catalyst is used, the steps of the synthesis route are few, the raw materials are easily available, the operation issimple, the reaction conditions are mild, the preparation method is environmentally friendly, the cost is low, the atom utilization rate is high, and the preparation method is suitable for industrialproduction.
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Paragraph 0037-0045
(2019/08/30)
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- Palladium-Catalyzed α-Arylation of Carboxylic Acids and Secondary Amides via a Traceless Protecting Strategy
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A novel traceless protecting strategy is presented for the long-standing challenge of conducting the palladium-catalyzed α-arylation of carboxylic aids and secondary amides with aryl halides. Both of the presented coupling processes occur with a variety of carboxylic acids and amides and with a variety of aryl bromides containing a broad range of functional groups, including base-sensitive functionality like acyl, alkoxycarbonyl, nitro, cyano, and even hydroxyl groups. Five commercial drugs were prepared through this method in one step in 81-96% yield. Gram-scale synthesis of medication Naproxen and Flurbiprofen with low palladium loading further highlights the practical value of this method.
- He, Zhi-Tao,Hartwig, John F.
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supporting information
p. 11749 - 11753
(2019/08/26)
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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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p. 11393 - 11397
(2019/08/20)
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- Regioselectivity inversion tuned by iron(iii) salts in palladium-catalyzed carbonylations
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Impactful regioselectivity control is crucial for cost-effective chemical synthesis. By using cheap and abundant iron(iii) salts, the hydroxycarbonylations of both aromatic and aliphatic alkenes were significantly enhanced in both reactivity and selectivity (iso/n or n/iso up to >99:1). Moreover, Pd-catalyzed carbonylation selectivity can be switched from branched to linear by using different Fe(iii) salts. In addition, similar results were obtained for the carbonylation of secondary alcohols.
- Huang, Zijun,Cheng, Yazhe,Chen, Xipeng,Wang, Hui-Fang,Du, Chen-Xia,Li, Yuehui
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supporting information
p. 3967 - 3970
(2018/04/23)
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- Palladium-Catalyzed Regioselective Aerobic Allylic C?H Oxygenation: Direct Synthesis of α,β-Unsaturated Aldehydes and Allylic Alcohols
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A protocol for the synthesis of α,β-unsaturated aldehydes and allylic alcohols from simple allylic hydrocarbons with water via palladium-catalyzed functionalization of allylic C?H bonds was described. Molecular oxygen is utilized as the sole oxidant in this oxygenation of terminal alkenes. This protocol features good functional group compatibility, broad substrate scope, and high atom- and step-economy. Moreover, the synthetic utility of this method can be highlighted by its application to the synthesis of ibuprofen, which is a highly potent analgesic. (Figure presented.).
- Li, Chunsheng,Chen, Huoji,Li, Jianxiao,Li, Meng,Liao, Jianhua,Wu, Wanqing,Jiang, Huanfeng
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supporting information
p. 1600 - 1604
(2018/03/05)
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- Visible-Light-Driven External-Reductant-Free Cross-Electrophile Couplings of Tetraalkyl Ammonium Salts
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Cross-electrophile couplings between two electrophiles are powerful and economic methods to generate C-C bonds in the presence of stoichiometric external reductants. Herein, we report a novel strategy to realize the first external-reductant-free cross-electrophile coupling via visible-light photoredox catalysis. A variety of tetraalkyl ammonium salts, bearing primary, secondary, and tertiary C-N bonds, undergo selective couplings with aldehydes/ketone and CO2. Notably, the in situ generated byproduct, trimethylamine, is efficiently utilized as the electron donor. Moreover, this protocol exhibits mild reaction conditions, low catalyst loading, broad substrate scope, good functional group tolerance, and facile scalability. Mechanistic studies indicate that benzyl radicals and anions might be generated as the key intermediates via photocatalysis, providing a new direction for cross-electrophile couplings.
- Liao, Li-Li,Cao, Guang-Mei,Ye, Jian-Heng,Sun, Guo-Quan,Zhou, Wen-Jun,Gui, Yong-Yuan,Yan, Si-Shun,Shen, Guo,Yu, Da-Gang
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p. 17338 - 17342
(2019/01/04)
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- Ligand-Controlled Regioselective Hydrocarboxylation of Styrenes with CO2 by Combining Visible Light and Nickel Catalysis
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The ligand-controlled Markovnikov and anti-Markovnikov hydrocarboxylation of styrenes with atmospheric pressure of CO2 at room temperature using dual visible-light-nickel catalysis has been developed. In the presence of neocuproine as ligand, the Markovnikov product is obtained exclusively, while employing 1,4-bis(diphenylphosphino)butane (dppb) as the ligand favors the formation of the anti-Markovnikov product. A range of functional groups and electron-poor, -neutral, as well as electron-rich styrene derivatives are tolerated by the reaction, providing the desired products in moderate to good yields. Preliminary mechanistic investigations indicate the generation of a nickel hydride (H-NiII) intermediate, which subsequently adds irreversibly to styrenes.
- Meng, Qing-Yuan,Wang, Shun,Huff, Gregory S.,Konig, Burkhard
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supporting information
p. 3198 - 3201
(2018/03/13)
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- Synthetic method of fatty acid containing nitrogen heterocycle
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The invention discloses a synthetic method of fatty acid containing nitrogen heterocycle. The synthetic method comprises the following steps: (S1) adding a heterocyclic compound with substitution of chloromethyl groups, a catalyst and a solvent DMF into a reaction kettle; (S2) introducing carbon dioxide to lead the pressure in the kettle to be 2-4MPa, adjusting and reacting for 10-16 hours at thetemperature of 40-50 DEG C; (S3) adding diluted hydrochloric acid into the reaction kettle to carry out acidification, using ethyl acetate for extraction, combining organic phases, carrying out rotaryevaporation to remove liquid, and further carrying out vacuum drying, thus obtaining the fatty acid containing nitrogen heterocycle. The synthetic method disclosed by the invention has the beneficialeffects that a one-pot method is adopted, the raw materials are easy to obtain, price is low, aftertreatment of products is also simpler, the universality for a substrate is also very high, and the promotion and application are easy.
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Paragraph 0042
(2018/07/30)
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- Synthesis of Bicyclo[n.1.0]alkanes by a Cobalt-Catalyzed Multiple C(sp3)?H Activation Strategy
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A cobalt-catalyzed dual C(sp3)?H activation strategy has been developed and it provides a novel strategy for the synthesis of bicyclo[4.1.0]heptanes and bicyclo[3.1.0]hexanes. A key to the success of this reaction is the conformation-induced methylene C(sp3)?H activation of the resulting cobaltabicyclo[4.n.1] intermediate. In addition, the synthesis of bicyclo[3.1.0]hexane from pivalamide, by a triple C(sp3)?H activation, has also been demonstrated.
- Zhang, Zhuo-Zhuo,Han, Ye-Qiang,Zhan, Bei-Bei,Wang, Sai,Shi, Bing-Feng
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supporting information
p. 13145 - 13149
(2017/09/28)
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- Dissociative reactions of benzonorbornadienes with tetrazines: Scope of leaving groups and mechanistic insights
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Bioorthogonal dissociative reactions boast diverse potential applications in chemical biology and drug delivery. The reaction of benzonorbornadienes with tetrazines to release amines from carbamate leaving groups was recently introduced as a bioorthogonal bond-cleavage reaction. The present study aimed at investigating the scope of leaving groups that are compatible with benzonorbornadienes. Synthesis of several benzonorbornadienes with different releasable groups is reported, and the reaction of these molecules with tetrazine was found to be rapid and afforded high release yields. The tetrazine-induced release of molecules proceeds in a cascade of steps including inverse-electron demand cycloaddition and cycloreversion reactions that form unstable isoindoles/isobenzofuran intermediates and spontaneously eliminate a leaving group of interest. In the case of oxygen-bridged BNBDs at room temperature, we observed the formation of an unproductive byproduct.
- Xu,Galindo-Murillo,Cheatham,Franzini
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supporting information
p. 9855 - 9865
(2017/12/12)
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- A Ligand-Directed Catalytic Regioselective Hydrocarboxylation of Aryl Olefins with Pd and Formic Acid
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An effective Pd-catalyzed hydrocarboxylation of aryl olefins with Ac2O and formic acid is described. A variety of 2- and 3-arylpropanoic acids can be regioselectively formed by the judicious choice of ligand without the use of toxic CO gas.
- Liu, Wei,Ren, Wenlong,Li, Jingfu,Shi, Yuan,Chang, Wenju,Shi, Yian
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supporting information
p. 1748 - 1751
(2017/04/11)
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- Design and Synthesis of Novel Nonsteroidal Anti-Inflammatory Drugs and Carbonic Anhydrase Inhibitors Hybrids (NSAIDs-CAIs) for the Treatment of Rheumatoid Arthritis
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We report the synthesis of a series of hybrid compounds incorporating 6- and 7-substituted coumarins (carbonic anhydrase, CA inhibitors) derivatized with clinically used NSAIDs (indomethacin, sulindac, ketoprofen, ibuprofen, diclofenac, ketorolac, etc., cyclooxygenase inhibitors) as agents for the management of rheumatoid arthritis (RA). Most compounds were effective in inhibiting the RA overexpressed hCA IX and XII, with KI values in the low nanomolar-subnanomolar ranges. The antihyperalgesic activity of such compounds was assessed by means of the paw-pressure and incapacitance tests using an in vivo RA model. Among all tested compounds, the 7-coumarine hybrid with ibuprofen showed potent and persistent antihyperalgesic effect up to 60 min after administration.
- Bua, Silvia,Di Cesare Mannelli, Lorenzo,Vullo, Daniela,Ghelardini, Carla,Bartolucci, Gianluca,Scozzafava, Andrea,Supuran, Claudiu T.,Carta, Fabrizio
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p. 1159 - 1170
(2017/02/19)
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- Site-Selective Catalytic Carboxylation of Unsaturated Hydrocarbons with CO2 and Water
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A catalytic protocol that reliably predicts and controls the site-selective incorporation of CO2 to a wide range of unsaturated hydrocarbons utilizing water as formal hydride source is described. This platform unlocks an opportunity to catalytically repurpose three abundant, orthogonal feedstocks under mild conditions.
- Gaydou, Morgane,Moragas, Toni,Juliá-Hernández, Francisco,Martin, Ruben
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supporting information
p. 12161 - 12164
(2017/09/12)
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- 2-ARYL-ZINC-PROPIONATE CATALYST AND PREPARATION METHOD AND USE THEREOF
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The present invention belongs to the technical field of chemical catalysts, and particularly relates to a zinc 2-arylpropionate catalyst, a preparation method therefor and use thereof The structural formula of the zinc 2-arylpropionate catalyst of the present invention is one of the following structures. The catalyst can be used for homogeneous catalysis of a 1,2-aryl rearrangement reaction of α-haloarylketal, and especially for synthesis of high yield and environmentally friendly 2-arylpropanonic acid non-steroidal anti-inflammatory analgesic drugs, such as, ibuprofen, ketoprofen, loxoprofen, flurbiprofen, fenoprofen, or naproxen and the like.
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Paragraph 022
(2016/11/28)
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- Cp2TiCl2-Catalyzed Regioselective Hydrocarboxylation of Alkenes with CO2
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Cp2TiCl2-catalyzed regioselective hydrocarboxylation of alkenes with CO2 to give carboxylic acids in high yields has been developed in the presence of iPrMgCl. The reaction proceeds with a wide range of alkenes under mild conditions. Styrene and its derivatives can transform to α-aryl carboxylic acids, and aliphatic alkenes can transform to form alkanoic acids.
- Shao, Peng,Wang, Sheng,Chen, Chao,Xi, Chanjuan
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supporting information
p. 2050 - 2053
(2016/06/01)
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- METHOD FOR BIOCATALYTIC SYNTHESIS OF SUBSTITUTED OR UNSUBSTITUTED PHENYLACETIC ACIDS AND KETONES HAVING ENZYMES OF MICROBIAL STYRENE DEGRADATION
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The present invention relates to a method for the biocatalytic synthesis of substituted and unsubstituted phenylacetic acids and ketones from styrenes and bicyclic aromatic hydrocarbons using enzymes of microbial styrene degradation in a whole-cell sensor, as well as a kit for the biocatalytic synthesis of substituted and unsubstituted phenylacetic acids and ketones containing a whole-cell catalyst and the use of the method, wherein the method comprises the following steps: a) providing at least one type of whole-cell catalyst, containing genes which code for the enzymes of styrene degradation and are under the functional control of a regulatable promoter, in an aqueous component,b) activating the whole-cell catalyst with an inducer and/or an activator, leading to expression of the gene,c) bringing the activated whole-cell catalyst into contact with a substrate,d) isolating the reaction products produced, which are advantageously not further metabolized by the whole-cell cat and advantageously accumulate in the aqueous component.
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- A high-throughput screening method for determining the substrate scope of nitrilases
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Nitrile compounds are intermediates in the synthesis of pharmaceuticals such as atorvastatin. We have developed a chromogenic reagent to screen for nitrilase activity as an alternative to Nessler's reagent. It produces a semi-quantifiable blue colour and hydrolysis of 38 nitrile substrates by 23 nitrilases as cell-free extracts has been shown. This journal is
- Black, Gary W.,Brown, Nicola L.,Perry, Justin J. B.,Randall, P. David,Turnbull, Graeme,Zhang, Meng
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supporting information
p. 2660 - 2662
(2015/03/05)
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- Ionic fluids containing both strongly and weakly interacting ions of the same charge have unique ionic and chemical environments as a function of ion concentration
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Liquid multi-ion systems made by combining two or more salts can exhibit charge ordering and interactions not found in the parent salts, leading to new sets of properties. This is investigated herein by examining a liquid comprised of a single cation, 1-ethyl-3-methylimidazolium ([C2mim]+), and two anions with different properties, acetate ([OAc]-) and bis(trifluoromethylsulfonyl)imide ([NTf2]-). NMR and IR spectroscopy indicate that the electrostatic interactions are quite different from those in either [C2mim][OAc] or [C2mim][NTf2]. This is attributed to the ability of [OAc]- to form complexes with the [C2mim]+ ions at greater than 1:1 stoichiometries by drawing [C2mim]+ ions away from the less basic [NTf2]- ions. Solubility studies with molecular solvents (ethyl acetate, water) and pharmaceuticals (ibuprofen, diphenhydramine) show nonlinear trends as a function of ion content, which suggests that solubility can be tuned through changes in the ionic compositions.
- Wang, Hui,Kelley, Steven P.,Brantley, Jimmy W.,Chatel, Gregory,Shamshina, Julia,Pereira, Jorge F. B.,Debbeti, Varun,Myerson, Allan S.,Rogers, Robin D.
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p. 993 - 1002
(2015/04/14)
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- Laccase-Mediator System for Alcohol Oxidation to Carbonyls or Carboxylic Acids: Toward a Sustainable Synthesis of Profens
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By combining two green and efficient catalysts, such as the commercially available enzyme laccase from Trametes versicolor and the stable free radical 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), the oxidation in water of some primary alcohols to the corresponding carboxylic acids or aldehydes and of selected secondary alcohols to ketones can be accomplished. The range of applicability of bio-oxidation is widened by applying the optimized protocol to the oxidation of enantiomerically pure 2-arylpropanols (profenols) into the corresponding 2-arylpropionic acids (profens), in high yields and with complete retention of configuration.
- Galletti, Paola,Pori, Matteo,Funiciello, Federica,Soldati, Roberto,Ballardini, Alberto,Giacomini, Daria
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p. 2684 - 2689
(2016/12/23)
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- A chemoselective Reformatsky-Negishi approach to α-haloaryl esters
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A practical synthesis of α-haloaryl esters has been achieved via a chemoselective Negishi coupling of poly-halogenated aromatics and Reformatsky reagents in the presence of catalytic Pd(dba)2 and Xantphos. This chemistry tolerates a variety of aryl halides and was successfully applied to the synthesis of Ibuprofen. The α-haloaryl ester products, exemplified by ethyl 2-(4-bromo-2-chlorophenyl)acetate (3a), can be further functionalized via palladium or copper catalysis to afford an array of α-aryl esters.
- Wong, Brian,Linghu, Xin,Crawford, James J.,Drobnick, Joy,Lee, Wendy,Zhang, Haiming
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p. 1508 - 1515
(2014/02/14)
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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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- Synthesis and Pharmacological Evaluation of New Chemical Entities from Ibuprofen as Novel Analgesic Candidates
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Non-steroidal anti-inflammatory drugs (NSAIDs) are the first choice of drugs that are normally used for the treatment of pain and inflammation. Ibuprofen (I) and its analogues as the most widely used NSAIDs have been synthesized in recent years. In an effort to establish new candidates with improved analgesic properties, derivatives (II-VII) with substituted aromatic as well as aliphatic moieties were synthesized in this experiment and evaluated in formalin test with rats. The results were compared to ibuprofen and control groups. Findings indicated that derivatives with new alkylphenyl rings (VI and VII) had some similar or more analgesic activities relative to the control and ibuprofen groups, respectively; which could be justified as to more alkyl and phenyl groups instead of p-isobutylphenyl moiety in I.
- Ahmadi,Naderi,Daniali,Kazemi,Aazami,Alizadeh,Nahri-Niknafs
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p. 457 - 462
(2015/09/15)
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- PROCESS FOR SYNTHESIZING PHENYLACETIC ACID BY CARBONYLATION OF TOLUENE
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A production process for substituted phenylacetic acids or ester analogues thereof is disclosed. In this process toluene or toluene substituted with various substituents, an alcohol, an oxidant and carbon monoxide are used as raw materials to obtain compounds comprising structure of phenylacetic acid ester or analogues thereof by catalysis of the complex catalyst formed from transition metal and ligand, and such compounds are hydrolyzed to obtain various substituted phenylacetic acid based compounds. This type of compounds and their derivatives serve as important fine chemicals used widely in the industries of pharmaceuticals, pesticides, perfume and the like.
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Paragraph 0018; 0104; 0105
(2013/11/19)
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- Laboratory evolution of enantiocomplementary Candida antarctica lipase B mutants with broad substrate scope
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Candida antarctica lipase B (CALB) is a robust and easily expressed enzyme used widely in academic and industrial laboratories with many different kinds of applications. In fine chemicals production, examples include acylating kinetic resolution of racemic secondary alcohols and amines as well as desymmetrization of prochiral diols (or the reverse hydrolytic reactions). However, in the case of hydrolytic kinetic resolution of esters or esterifying kinetic resolution of acids in which chirality resides in the carboxylic acid part of the substrate, rate and stereoselectivity are generally poor. In the present study, directed evolution based on iterative saturation mutagenesis was applied to solve the latter problem. Mutants with highly improved activity and enantioselectivity relative to wild-type CALB were evolved for the hydrolytic kinetic resolution of p-nitrophenyl 2-phenylpropanoate, with the selectivity factor increasing from E = 1.2 (S) to E = 72 (S) or reverting to E = 42 (R) on an optional basis. Surprisingly, point mutations both in the acyl and alcohol pockets of CALB proved to be necessary. Some of the evolved CALB mutants are also efficient biocatalysts in the kinetic resolution of other chiral esters without performing new mutagenesis experiments. Another noteworthy result concerns the finding that enantiocomplementary CALB mutants for α-substituted carboxylic acid esters also show stereocomplementarity in the hydrolytic kinetic resolution of esters derived from chiral secondary alcohols. Insight into the source of stereoselectivity was gained by molecular dynamics simulations and docking experiments.
- Wu, Qi,Soni, Pankaj,Reetz, Manfred T.
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supporting information
p. 1872 - 1881
(2013/08/24)
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- The vehicle attitude angle estimating device and program
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PROBLEM TO BE SOLVED: To estimate an attitude angle with high precision even in the case of a road surface the vertical acceleration of which changes. SOLUTION: An acceleration state quantity saturating characteristic correction means 30 corrects vertical acceleration state quantity obtained by using the estimation value of a roll angle and the estimation value of a pitch angle so that the vertical acceleration state quantity is provided with saturating characteristics. A state quantity deviation low pass filter value calculation means 26 calculates the deviation of longitudinal acceleration state quantity, the deviation of lateral acceleration state quantity, and the deviation of vertical acceleration state quantity to which low pass filter processing has been performed based on: the low pass filter processing values of the longitudinal acceleration state quantity, the lateral acceleration state quantity, and the vertical acceleration state quantity, calculated by an attitude angle observer; and the longitudinal acceleration state quantity and the lateral acceleration state quantity obtained by using a sensor signal and the estimation value of the longitudinal body speed and the estimation value of the lateral body speed. An attitude angle estimation means 28 estimates a roll angle and a pitch angle by feeding back the deviation of the longitudinal acceleration state quantity, the deviation of the lateral acceleration state quantity, and the deviation of the vertical acceleration state quantity. COPYRIGHT: (C)2010,JPO&INPIT
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- Raney nickel-catalyzed hydrogenation of unsaturated carboxylic acids with sodium borohydride in water
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A mild, selective, and green method for the reduction of unsaturated carboxylic acids with sodium borohydride-Raney nickel (W6) system in water is reported. This method is practical and safe and avoids use of organic solvents. Taylor & Francis Group, LLC.
- Rao, Gopal Krishna,Gowda, Narendra B.,Ramakrishna, Ramesha A.
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experimental part
p. 893 - 904
(2012/02/01)
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- Iron(III) chloride-catalysed aerobic reduction of olefins using aqueous hydrazine at ambient temperature
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A chemoselective reduction of olefins and acetylenes is demonstrated by employing catalytic amounts of ferric chloride hexahydrate (FeCl 3·6 H2O) and aqueous hydrazine (NH 2NH2·H2O) as hydrogen source at room temperature. The reduction is chemoselective and tolerates a variety of reducible functional groups. Unlike other metal-catalysed reduction methods, the present method employs a minimum amount of aqueous hydrazine (1.5-2 equiv.). Also, the scope of this method is demonstrated in the synthesis of ibuprofen in aqueous medium. Copyright
- Lamani, Manjunath,Ravikumara, Guralamata S.,Prabhu, Kandikere Ramaiah
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supporting information; experimental part
p. 1437 - 1442
(2012/07/03)
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- Guanidine catalyzed aerobic reduction: A selective aerobic hydrogenation of olefins using aqueous hydrazine
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An efficient aerobic reduction of olefins, internal as well as terminal, is developed using guanidine as an organocatalyst. A remarkable chemoselectivity in reduction has been demonstrated in the presence of a variety of functional groups and protective groups and a selective reduction of a terminal olefin in the presence of an internal olefin is revealed.
- Lamani, Manjunath,Guralamata, Ravikumara Siddappa,Prabhu, Kandikere Ramaiah
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supporting information; experimental part
p. 6583 - 6585
(2012/07/14)
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- Unexpected extension of usage of PPh3/CBr4, a versatile reagent: Isomerization of aromatic allylic alcohols
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The PPh3/CBr4-catalyzed isomerization of 2-aromatic allylic alcohols into the corresponding saturated aldehydes or ketones has been achieved at room temperature in good to excellent yields under mild and metal-free conditions. This new methodology has been applied successfully to the synthesis of ibuprofen in four steps.
- Gong, Wanchun,Liu, Yun,Xue, Jijun,Xie, Zhixiang,Li, Ying
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supporting information
p. 1597 - 1599
(2013/02/23)
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