- Application of copper(II)-mediated radical cross-dehydrogenative coupling to prepare spirocyclic oxindoles and to a formal total synthesis of Satavaptan
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Application of radical cross-dehydrogenative coupling (CDC) procedures to prepare a range of novel spirocyclic oxindoles and to a formal total synthesis of the vasopressin V2 receptor antagonist Satavaptan is reported. The key step involves a c
- Hurst, Timothy E.,Gorman, Ryan,Drouhin, Pauline,Taylor, Richard J.K.
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- Electrochemical Carboxylation of Ketones RCOCH2R' Coupled with CO2 Reduction by 2+
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Electrochemical carboxylation of PhCOCH3 and C6H10(O) coupled with CO2 reduction by 2+ was carried out in CO2-saturated dry CH3CN.CO2 ligated on the ruthenium atom is reduced to HCOO- or CO upon the electrochemical reduction of the complex, where PhCOCH3 and C6H10(O) function as a proton source, and the resultant carbanions react with CO2 to afford the corresponding ketoacids, catalytically.
- Tanaka, Koji,Miyamoto, Hajime,Tanaka, Toshio
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- Mechanism of the Carboxylation of Cyclohexanone with Carbon Dioxide Catalyzed by 1,8-Diazabicycloundec-7-ene
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The dependence of the rate of carboxylation upon the concentration of the reactant was investigated in dimethyl sulfoxide.The reaction rate depended upon the concentration of cyclohexanone and 1,8-diazabicycloundec-7-ene(DBU) in the first order, re
- Mori, Hisakazu
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- Ethyl cyclohexanone-2-carboxylate in aqueous micellar solutions. 2: Enol nitrosation in anionic and cationic micelles
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Micellar-mediated rates of both the ester hydrolysis and enol nitrosation reactions of ethyl cyclohexanone-2-carboxylate, ECHC, were measured in aqueous acid media. In equal acid concentration, the enol nitrosation reaction rate is more than 10 times faster than the ester hydrolysis reaction rate; this fact makes possible the separate (independent) study of both reactions undergone by ECHC. Anionic micelles of sodium dodecyl sulfate, SDS, inhibit the ester hydrolysis; by contrast, the nitrosation reaction goes through maxima as the [SDS] increases above the critical micelle concentration. A similar pattern of behavior is observed in the study of the effect of anionic micelles of hydrogen dodecyl sulfate, HDS, on the rates of the two reactions: the first-order rate constant (ko) of the ester hydrolysis goes through minima as [HDS] increases, even though the rates are actually affected very little by HDS addition; in sharp contrast, the overall rate constant of the nitrosation reaction is enhanced by HDS addition and levels off at high surfactant concentration. The values of the rate constant at high surfactant concentration is more than 6 times that determined in the absence of HDS. Despite the different micellar effects observed in the two reactions occurring in the same substrate, experimental data fit the pseudophase ion exchange (PPIE) model and predict similar values for the second-order rate constant of each reaction in the different types of micelles of a given counterion. The implications of these findings for the reactivity in micelles are discussed. Cationic micelles inhibit the nitrosation reaction throughout the surfactant concentration range; although the reaction at the micellar phase is not negligible, the physicochemical properties of this reaction region account for the lower reactivity in this medium. Experimental data are quantitatively explained by means of the pseudophase model, and kinetic rate constants or equilibrium constants appearing in the proposed reaction scheme are reported.
- Iglesias, Emilia
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- Ethyl cyclohexanone-2-carboxylate in aqueous micellar solutions. 1: Ester hydrolysis in cationic and nonionic micelles
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Hydrolysis rates for the ester of ethyl cyclohexanone-2-carboxylate (ECHC) were measured in aqueous dioxane mixtures and in aqueous micellar solutions of cationic, nonionic, and mixed cationic-nonionic detergents. The following cationic surfactants were used: dodecyltrimethylammonium bromide (DTABr), tetradecyltrimethylammonium bromide (TTABr), tetradecyltrimethylammonium chloride (TTACl), tetradecyltrimethylammonium acetate (TTAAc), and cetyltrimethylammonium bromide (CTABr). Poly(ethylene oxide)-9-dodecyl ether (C12E9) and poly(ethylene oxide)-20-cetyl ether (C16E20) were used as the nonionic surfactants. The kinetic profiles of the reactions were investigated as a function of surfactant concentration. In aqueous strong mineral acid (HCl or HBr) solutions of the cationic surfactants DTABr, TTABr, TTACl, and CTABr, the reaction was greatly inhibited at surfactant concentrations above the critical micelle concentration; the same behavior was observed for the influence of the nonionic surfactants and for the mixed surfactants DTABr + C12E9 analyzed in an equimolar mixture of both surfactants. Micellar effects were analyzed by means of the pseudophase model. When the hydrolysis reaction was studied in aqueous buffered solutions of acetic acid-acetate, the shape of the observed rate constant versus surfactant concentration (of TTACl and TTABr) profiles depended on surfactant concentration. At low surfactant concentration, first-order rate constants pass through maxima with increasing surfactant concentration followed by a gradual but steady decrease in the rate as the surfactant concentration increases further. By contrast, the first-order rate constant increases throughout the whole concentration range of TTAAc used. Micellar effects observed for the reaction in aqueous buffered solutions were analyzed qualitatively or quantitatively by means of the pseudophase ion exchange (PPIE) model. In every experimental situation, the reaction at the micellar interface is not negligible; however, the second-order rate constant in this region is lower than that measured in water.
- Iglesias, Emilia
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- Enantioselective Synthesis of Medium-Sized-Ring Lactones via Iridium-Catalyzed Z-Retentive Asymmetric Allylic Substitution Reaction
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Medium-sized rings are important structural units, but their synthesis, especially in a highly enantioselective manner, has been a great challenge. Herein we report an enantioselective synthesis of medium-sized-ring lactones by an iridium-catalyzed Z-retentive asymmetric allylic substitution reaction. The reaction features mild conditions and a broad substrate scope. Various eight- to 11-membered-ring lactones can be afforded in moderate to excellent yields (up to 88%) and excellent enantioselectivity (up to 99% ee). The utilization of both Z-allyl precursors and an Ir catalyst is critical for the medium-sized-ring formation.
- Ding, Lu,Song, Hao,Zheng, Chao,You, Shu-Li
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supporting information
p. 4770 - 4775
(2022/03/27)
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- Design, synthesis, and molecular simulation studies of N-phenyltetrahydroquinazolinones as protoporphyrinogen IX oxidase inhibitors
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Discovering new protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors is a promising direction for agrochemical research. Herein, we reported the discovery and in silico structure-guided optimization of N-phenyltetrahydroquinazolinones 1 and 2 as new PP
- Liang, Lu,Yu, Shuyi,Li, Qian,Wang, Xia,Wang, Dawei,Xi, Zhen
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- Amide derivative, preparation method of amide derivative, and application of amide derivative to pharmacy
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The invention provides an amide derivative, a preparation method of the amide derivative, and application of the amide derivative to pharmacy. The amide derivative compound is selected from one of the following structures. The compound can be used for preparing medicines in the fields of local anaesthesia or analgesia. (The formulas are as shown in the description).
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Paragraph 0250-0253
(2017/08/30)
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- Substrate scope in the copper-mediated construction of bis-oxindoles via a double C-H/Ar-H coupling process
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Abstract The synthesis of bis-oxindoles via the copper(II)-mediated double cyclisation of linear bis-anilides is described. Cu(OAc)2·H2O was identified as an efficient and inexpensive catalyst for this process. In contrast to previous methods, which rely on the synthesis of the central core from existing oxindole building blocks, this new approach focusses on concurrent formation of both oxindole rings from a simple linear precursor, allowing the formation of bis-oxindoles containing a diverse range of cyclic and acyclic linkers using a single synthetic method.
- Drouhin, Pauline,Hurst, Timothy E.,Whitwood, Adrian C.,Taylor, Richard J.K.
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supporting information
p. 7124 - 7136
(2015/03/30)
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- Copper-mediated construction of spirocyclic bis-oxindoles via a double C-H, Ar-H coupling process
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A double C-H, Ar-H coupling process for the conversion of bis-anilides into spirocyclic bis-oxindoles, enabling the concomitant formation of two all-carbon quaternary centers at oxindole 3-positions in a diastereoselective manner, is described. The optimum cyclization conditions utilize stoichiometric Cu(OAc)2·H2O/KOtBu in DMF at 110 °C and have been applied to prepare a range of structurally diverse bis-spirooxindoles in fair to good yields (28-77%); the method has also been extended to prepare bis-oxindoles linked by a functionalized acyclic carbon chain.
- Drouhin, Pauline,Hurst, Timothy E.,Whitwood, Adrian C.,Taylor, Richard J.K.
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supporting information
p. 4900 - 4903
(2015/04/27)
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- Discovery of a novel chemotype of tyrosine kinase inhibitors by fragment-based docking and molecular dynamics
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We have discovered a novel chemical class of inhibitors of the EphB4 tyrosine kinase by fragment-based high-throughput docking followed by explicit solvent molecular dynamics simulations for assessment of the binding mode. The synthesis of a single derivative (compound 7) of the hit identified in silico has resulted in an improvement of the inhibitory potency in an enzymatic assay from 8.4 μM to 160 nM and a ligand efficiency of 0.39 kcal/mol per non-hydrogen atom. Such remarkable improvement in affinity is due to an additional hydroxyl group involved in two favorable (buried) hydrogen bonds as predicted by molecular dynamics and validated by the crystal structure of the complex with EphA3 solved at 1.7 a resolution.
- Zhao, Hongtao,Dong, Jing,Lafleur, Karine,Nevado, Cristina,Caflisch, Amedeo
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supporting information
p. 834 - 838
(2013/01/15)
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- Ambient carboxylation on a supported reversible CO2 carrier: Ketone to β-keto ester
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A reversible CO2 carrier (RCC) has been developed to perform carboxylation of ketone to β-ketoester under ambient CO2 pressure and temperature. RCC has been synthesized by immobilizing 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) on methylhydrosiloxane support and reacting with CO2 with 100% degree of functionalisation. RCC is found to be recyclable and shows retention of activity in 5 recycles. CO2 absorption under ambient temperature and desorption at 120°C renders the material suitable for carrying out carboxylation reactions at 25°C with excellent yields. The yield of the reaction can reach up to 100% with TON 200 in 4 h. The extent of the reaction primarily depends upon enol content of the substrate. β-Ketoacid produced during the reaction can be isolated and converted to its corresponding methyl ester derivative by reacting with methyl iodide.
- Beckman, Eric J.,Munshi, Pradip
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experimental part
p. 376 - 383
(2011/04/17)
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- SELECTIVE ANDROGEN RECEPTOR MODULATORS
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This invention provides compounds of Formula (I), (Ia), (Ib), (Ic), (II), (IIa) or (III) and or salts thereof, pharmaceutical compositions comprising a compound of Formula (I), (Ia), (Ib), (Ic), (II), (IIa) or (III) and a pharmaceutically acceptable excipient, methods of modulating the androgen receptor, methods of treating diseases beneficially treated by an androgen receptor modulator (e.g., sarcopenia, prostate cancer, contraception, type II diabetes related disorders or diseases, anemia, depression, and renal disease) and processes for making compounds of Formula (I), (Ia), (Ib), (Ic), (II), (IIa) or (III) and intermediates useful in the preparation of same.
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Page/Page column 78; 95
(2011/09/14)
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- The 2-oxocyclohexanecarboxylic acid keto-enol system in aqueous solution
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Flash photolysis of 2-diazocycloheptane-1,3-dione or 2,2-dimethyl-5,6,7,8-tetrahydrobenzo-4H-1,3-dioxin-4-one in aqueous solution produced 2-oxocyclohexylideneketene, which underwent hydration to the enol of 2-oxocyclohexanecarboxylic acid, and the enol then isomerized to the keto form of the acid. Isomerization of the enol to keto forms was also observed using solid enol, a substance heretofore commonly believed to be the keto acid. Rates of ketonization were measured in perchloric acid, sodium hydroxide, and buffer solutions, and a ketonization rate profile was constructed. Rates of enolization of the keto acid were also measured using bromine to scavenge the enol as it formed. Rates of enolization and ketonization were then combined to provide the keto - enol equilibrium constant pKE = 1.27. This and some of the other results obtained are different from the corresponding quantities for the 2-oxocyclopentanecarboxylic acid keto - enol system. These differences are discussed.
- Chang,Kresge,Nikolaev,Popik
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p. 6478 - 6484
(2007/10/03)
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- New electrochemical carboxylation of vinyl triflates. Synthesis of β-keto carboxylic acids
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Electrochemical reduction of alicyclic vinyl triflates (1a-1e) in a DMF solution containing 0.1 M Bu4NBF4 under an atmospheric pressure of carbon dioxide with a platinum cathode and a magnesium anode resulted in the cleavage of an ox
- Kamekawa, Hisato,Senboku, Hisanori,Tokuda, Masao
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p. 1591 - 1594
(2007/10/03)
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- Synthesis of 1,2,4-triazole-fused heterocycles by tandem appel dehydration/thermal rearrangement methodology
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The reaction of α-substituted benzophenone 1-acetamidoethylidenehydrazones 6b,c and 13a-d with a mixture of triphenylphosphine, carbon tetrachloride, and triethylamine in dichloromethane (Appel's condition) provides a general route to a variety of 1,2,4-triazole-fused heterocycles such as compounds 9-11, 16a-d, 17b-d, and 18 via the thermal rearrangement of the expected amino ketenimine intermediates.
- Lee, Kee-Jung,Kim, Seong Heon,Kwon, Jong Hyuk
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p. 1461 - 1466
(2007/10/03)
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- Oxidative decarboxylation of cyclohexane monocarboxylic acid as a degenerate branching chain reaction II. Mechanism
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Based on the experimental results obtained studying the oxidative decarboxylation of cyclohexane monocarboxylic acid and published earlier, a mechanism is suggested, according to which in the thermal oxidation two main chain carrier radicals exist: tertiary and secondary peroxy radicals yielding cyclohexanone as well as hydroxy and keto acids in parallel reaction sequences. Carbon dioxide is formed in both pathways independently. The corresponding hydroperoxide molecules, formed during oxidation, decompose partly into radicals and partly into molecules resulting in degenerate branching and chemiluminescence phenomena, respectively. The rate determining termination is the cross combination process between secondary and tertiary peroxy radicals. The combinatorial generation of the mechanism of the thermal process and its reduction enabled the construction of the sequence network of the formation of products indicating that the primary attack of the hydrogen abstraction (secondary or tertiary) determines the product distribution.
- Heberger,Keszler,Vidoczy,Gal,Cotarca,Delogu
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p. 1303 - 1307
(2007/10/02)
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- Carboxylation of Active Methylene Compounds Using Anilide, Potassium Carbonate, and Carbon Dioxide
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Active methylene compounds were effectively carboxylated with carbon dioxide in the presence of anilide (acetanilide or formanilide) and potassium carbonate at 20-40 deg C for 0.5-10 h.In the carboxylation of fluorene, a high yield (48percent) was obtained at 20 deg C for 4 h.The yield of carboxylic acid using 2,6-dimethylacetanilide was 8.9percent, and smaller than 26.6percent when using acetanilide at 20 deg C for 2 h, indicating the interference of a methyl group for the carboxylation.
- Chiba, Koji,Tagaya, Hideyuki,Karasu, Masa,Ishizuka, Masahiko,Sugo, Toshiyuki
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p. 452 - 454
(2007/10/02)
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- The Carboxylation of Active Methylene Compounds with Carbon Dioxide in the Presence of Diphenylcarbodiimide and Potassium Carbonate
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Active methylene compounds were effectively carboxylated with carbon dioxide in the presence of diphenylcarbodiimide (DPC) as a biotin model and potassium carbonate.Fluorene was carboxylated even under a nitrogen atmosphere in the presence of DPC, indicating that a carbonate ion was the carbon source.The reaction occured even in the presence of water.It was considered that reaction intermediates are stable to water and that the concentration of the carbonate ion is important for carboxylation.
- Chiba, Koji,Tagaya, Hideyuki,Karasu, Masa,Ono, Tsuyoyuki,Hashimoto, Kazumi,Moriwaki, Yasusi
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p. 966 - 970
(2007/10/02)
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- The Carboxylation of Active Methylene Compounds with Diphenylcarbodiimide and Potassium Carbonate
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Active methylene compounds were carboxylated by employing the reagent system, diphenylcarbodiimide and potassium carbonate, in dimethyl sulfoxide at room temperature and atmospheric pressure.The reaction proceeded even in the absence of carbon dioxide, but the carboxylation easily proceeded in carbon dioxide atmosphere.
- Chiba, Koji,Tagaya, Hideyuki,Karasu, Masa,Ono, Tsuyoyuki,Kugiya, Masashi
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- Carboxylation of Ketones Using Triethylamine and Magnesium Halides
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Procedures for the carboxylation of ketones with carbon dioxide at atmospheric pressure in the presence of magnesium halides and triethylamine are described.A variety of ketones are converted to the corresponding β-keto acids in satisfactory yields by using magnesium chloride-sodium iodide mixtures in acetonitrile.This carboxylation reaction exhibits little regioselectivity with 2-butanone.
- Tirpak, Robin E.,Olsen, Richard, S.,Rathke, Michael W.
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p. 4877 - 4879
(2007/10/02)
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- Synthesis of 1,3-dioxin-4-one Derivatives
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A facile and general synthesis of 2,2-dimethyl-1,3-dioxin-4-one derivatives (1) is reported.Treatment of β-keto acids with a mixture of isopropenyl acetate and conc. sulfuric acid gave 2,2-dimethyl-1,3-dioxin-4-ones (1).Similar treatment of tert-butyl esters of β-keto acids also gave 1.KEYWORDS - 2,2-dimethyl-1,3-dioxin-4-one derivative; diketene-acetone adduct; diketene; acylketene; β-keto acid; β-keto ester
- Sato, Masayuki,Ogasawara, Hiromichi,Oi, Keiichi,Kato, Tetsuzo
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p. 1896 - 1901
(2007/10/02)
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- The Function of Magnesium(II) N,N'-Dicyclohexylamidinide Complexes as a Carbon Dioxide Carrier
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It is found that magnesium(II) N,N'-dicyclohexylamidinide complexes are useful reagents for the fixation of carbon dioxide and the transfer of the captured carbon dioxide moiety to active methylene compounds.
- Matsumura, Noboru,Ohba, Takayuki,Inoue, Hiroo
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p. 3949 - 3950
(2007/10/02)
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- α-Carboxylation reaction of carbonyl compounds with bromomagnesium ureide-carbon dioxide adducts
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Bromomagnesium ureide-carbon dioxide adducts, models of the carboxylated biotin complex, undergo caboxylation of a variety of carbonyl compounds in good yield.
- Sakurai, Hideki,Shirahata, Akihiko,Hosomi, Akira
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p. 1967 - 1970
(2007/10/02)
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- Process for carboxylating organic substrates with carbon dioxide in hydrocarbon solvents
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Carboxylable substrates i.e., ketones, esters, nitroparaffins and nitriles, containing activated hydrogen atoms are carboxylated by reaction with alkaline phenates and CO2 in at least one hydrocarbon solvent selected from aliphatic, alicyclic, aromatic and alkyl-aromatic hydrocarbon solvents.
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