- Stable and reusable nanoscale Fe2O3-catalyzed aerobic oxidation process for the selective synthesis of nitriles and primary amides
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The sustainable introduction of nitrogen moieties in the form of nitrile or amide groups in functionalized molecules is of fundamental interest because nitrogen-containing motifs are found in a large number of life science molecules, natural products and materials. Hence, the synthesis and functionalization of nitriles and amides from easily available starting materials using cost-effective catalysts and green reagents is highly desired. In this regard, herein we report the nanoscale iron oxide-catalyzed environmentally benign synthesis of nitriles and primary amides from aldehydes and aqueous ammonia in the presence of 1 bar O2 or air. Under mild reaction conditions, this iron-catalyzed aerobic oxidation process proceeds to synthesise functionalized and structurally diverse aromatic, aliphatic and heterocyclic nitriles. Additionally, applying this iron-based protocol, primary amides have also been prepared in a water medium.
- Murugesan, Kathiravan,Senthamarai, Thirusangumurugan,Sohail, Manzar,Sharif, Muhammad,Kalevaru, Narayana V.,Jagadeesh, Rajenahally V.
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supporting information
p. 266 - 273
(2018/01/12)
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- A Homogeneous Method for the Conveniently Scalable Palladium- and Nickel-Catalyzed Cyanation of Aryl Halides
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Homogeneous conditions for the palladium-catalyzed cyanation of aryl halides were developed. This new system features a broad scope of aryl chlorides and bromides, uses 2-propanol or 1-butanol as solvent, and is readily scalable. The same conditions can also provide simple benzonitriles using the recently developed (TMEDA)NiCl(o-tolyl) precatalyst in conjunction with 1,1′-bis(diphenylphosphino)ferrocene (dppf) as a ligand.
- Burg, Finn,Egger, Julian,Deutsch, Johannes,Guimond, Nicolas
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p. 1540 - 1545
(2016/08/30)
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- Green halogenation of aromatic heterocycles using ammonium halide and hydrogen peroxide in acetic acid solvent
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The green generation of X+ (X = Br, I) using hydrogen peroxide in aqueous acetic acid allows access to aromatic heterocyclic halides in yields and purities comparable to syntheses employing N-bromosuccinimide. In activated and unsubstituted thiophene rings, regioselectivity is quantitative for positions α to the sulfur; pyrroles also give quantitative reactions, at least initially. Deactivated rings, including furans and thiazoles, as well as thiophenes with strongly electron-withdrawing groups showed little to no reactivity under the conditions investigated. The reaction shows remarkable functional group tolerance (to alcohol, nitro, alkyl, halo, and carbonyl groups), as shown through reaction with substituted phenols. In all bromination reactions, reaction yields and regiochemistry were very similar to reactions involving N-bromosuccinimide in tetrahydrofuran solvent.
- D'Aleo, Danielle N.,Allard, Sheena R.,Foglia, Cassandra C.,Parent, Shawna L.M.,Rohr, David J.,Gottardo, Christine,MacKinnon, Craig D.
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p. 679 - 683
(2013/08/23)
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- Cyclopropenone-catalyzed direct conversion of aldoximes and primary amides into nitriles
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Efficient conversion of aldoximes and primary amides into nitriles by employing cyclopropenone as an organocatalyst is reported. The reaction proceeds smoothly under mild conditions with 5 mol-% catalyst loading to afford nitriles in excellent yields (78-94 %) in a single operation. This method is equally applicable to both aldoximes and primary amides bearing aromatic, heterocyclic, and aliphatic moieties. The convenient and catalytic procedure widens the scope of the utilization of cyclopropenones in organic synthesis. Cyclopropenone- catalyzed conversion of aldoximes and primary amides into nitriles in a one-pot procedure is described. The reaction proceeds smoothly under mild conditions with low catalyst loading. The convenient and catalytic procedure widens the scope of the utilization of cyclopropenones in organic synthesis.
- Rai, Ankita,Yadav, Lal Dhar S.
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p. 1889 - 1893
(2013/05/08)
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- Cyanation of aryl bromides with K4[Fe(CN)6] catalyzed by dichloro[bis{1-(dicyclohexylphosphanyl)piperidine}]palladium, a molecular source of nanoparticles, and the reactions involved in the catalyst-deactivation processes
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Dichloro[bis{1-(dicyclohexylphosphanyl)piperidine}]palladium [(P{(NC 5H10)(C6H11)2}) 2PdCl2] (1) is a highly active and generally applicable C-C cross-coupling catalyst. Apart from its high catalytic activity in Suzuki, Heck, and Negishi reactions, compound 1 also efficiently converted various electronically activated, nonactivated, and deactivated aryl bromides, which may contain fluoride atoms, trifluoromethane groups, nitriles, acetals, ketones, aldehydes, ethers, esters, amides, as well as heterocyclic aryl bromides, such as pyridines and their derivatives, or thiophenes into their respective aromatic nitriles with K4[Fe(CN)6] as a cyanating agent within 24 h in NMP at 140 °C in the presence of only 0.05 mol % catalyst. Catalyst-deactivation processes showed that excess cyanide efficiently affected the molecular mechanisms as well as inhibited the catalysis when nanoparticles were involved, owing to the formation of inactive cyanide complexes, such as [Pd(CN)4]2-, [(CN)3Pd(H)]2-, and [(CN)3Pd(Ar)]2-. Thus, the choice of cyanating agent is crucial for the success of the reaction because there is a sharp balance between the rate of cyanide production, efficient product formation, and catalyst poisoning. For example, whereas no product formation was obtained when cyanation reactions were examined with Zn(CN)2 as the cyanating agent, aromatic nitriles were smoothly formed when hexacyanoferrate(II) was used instead. The reason for this striking difference in reactivity was due to the higher stability of hexacyanoferrate(II), which led to a lower rate of cyanide production, and hence, prevented catalyst-deactivation processes. This pathway was confirmed by the colorimetric detection of cyanides: whereas the conversion of β-solvato-α-cyanocobyrinic acid heptamethyl ester into dicyanocobyrinic acid heptamethyl ester indicated that the cyanide production of Zn(CN)2 proceeded at 25 °C in NMP, reaction temperatures of >100 °C were required for cyanide production with K4[Fe(CN) 6]. Mechanistic investigations demonstrate that palladium nanoparticles were the catalytically active form of compound 1. A balancing act: Compound 1 (see scheme) is a highly active cyanation catalyst. Furthermore, a sharp balance between the rates of cyanide generation, efficient product formation, and catalyst deactivation owing to excess cyanide was observed in deactivation processes. Copyright
- Gerber, Roman,Oberholzer, Miriam,Frech, Christian M.
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supporting information; experimental part
p. 2978 - 2986
(2012/04/04)
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- ANTIMICROBIAL/ADJUVANT COMPOUNDS AND METHODS
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Among other things, in general, antimicrobial and/or adjuvant compounds are provided according to Formula la: (Ia) in which E and R1-11 have the meanings described herein; and prodrugs and pharmaceutically acceptable salts thereof. Other formulae and methods of use are also provided.
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Page/Page column 66; 67
(2012/09/21)
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- Development of Pd/C-catalyzed cyanation of Aryl halides
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A practical method for palladium-catalyzed cyanation of aryl halides using Pd/C is described. The new method can be applied to a variety of aryl bromide and active aryl chloride substrates to effect efficient conversions. The process features many advantages over existing cyanation conditions and the practical utility of the process has been demonstrated on scale.
- Yu, Hannah,Richey, Rachel N.,Miller, William D.,Xu, Jiansheng,May, Scott A.
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supporting information; experimental part
p. 665 - 668
(2011/03/19)
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- Straightforward conversion of arene carboxylic acids into aryl nitriles by palladium-catalyzed decarboxylative cyanation reaction
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A one-pot procedure to convert aromatic carboxylic acids into aromatic nitriles is described. The methodology is based on a palladium(II)-catalyzed decarboxylative cyanation reaction using cyanohydrins as soluble cyanide sources. The described reaction worked on a panel of substrates and is additionally of particular interest for the straightforward preparation of 13C- or 14C-labeled compounds.
- Ouchaou, Kahina,Georgin, Dominique,Taran, Frédéric
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experimental part
p. 2083 - 2086
(2010/10/03)
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- Hypervalent iodine(III): selective and efficient single-electron-transfer (SET) oxidizing agent
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In 1994, we first determined the single-electron-transfer (SET) oxidation ability of phenyliodine(III) bis(trifluoroacetate) (PIFA) toward phenyl ethers, affording the corresponding aromatic cation radicals. Since then, hypervalent iodine(III) has been utilized as a selective and efficient SET oxidizing agent that enables a variety of direct C-H functionalizations of aromatic rings in electron-rich arenes under mild conditions. We have now extended the original method to work in a series of heteroaromatic compounds such as thiophenes, pyrroles, and indoles. The investigations and results obtained since the start of this century are summarized in this article.
- Dohi, Toshifumi,Ito, Motoki,Yamaoka, Nobutaka,Morimoto, Koji,Fujioka, Hiromichi,Kita, Yasuyuki
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experimental part
p. 10797 - 10815
(2010/03/01)
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- Direct cyanation of heteroaromatic compounds mediated by hypervalent iodine(III) reagents: In situ generation of PhI(III)-CN species and their cyano transfer
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Hypervalent iodine(III) reagents mediate the direct cyanating reaction of a wide range of electron-rich heteroaromatic compounds such as pyrroles 1, thiophenes 3, and indoles 5 under mild conditions (ambient temperature), without the need for any prefunctionalization. Commercially available trimethylsilylcyanide is usable as a stable and effective cyanide source, and the reaction proceeds in a homogeneous system. The N-substituent of pyrroles is crucial to avoid the undesired oxidative bipyrrole coupling process, and thus a cyano group was introduced selectively at the 2-position of N-tosylpyrroles 1 in good yields using the combination of phenyliodine bis(trifluoroacetate) (PIFA), TMSCN, and BF3·Et2O at room temperature. In the reaction mechanism, cation radical intermediates of heteroaromatic compounds are involved as a result of single electron oxidation, and the key to successful transformations seems to depend on the oxidation potential of the substrates used. Thus, the reaction was also successfully extended to other heteroaromatic compounds having oxidation potentials similar to that of N-tosylpyrroles such as thiophenes 3 and indoles 5. However, regioisomeric mixtures of the products derived from the reaction at the 2- and 3-positions were obtained in the case of N-tosylindole 5a. Further investigation performed in our laboratory provided insights into the real active iodine(III) species during the reaction; the reaction is induced by an active hypervalent iodine(III) species having a cyano ligand in situ generated by ligand exchange reaction at the iodine(III) center between trifluoroacetoxy group in PIFA and TMSCN, and effective cyanide introduction into heteroaromatic compounds is achieved by means of the high cyano transfer ability of the hypervalent iodine(III)-cyano intermediates. In fact, the reaction of N-tosylpyrrole 1a with a hypervalent iodine(III)-cyano compound (e.g., (dicyano)iodobenzene 8), in the absence of TMSCN, took place to afford the 2-cyanated product 2a in good yield, and an effective preparation of the intermediates is of importance for successful transformation. 1,3,5,7-Tetrakis[4-{bis(trifluoroacetoxy)-iodo}phenyl]adamantane 12, a recyclable hypervalent iodine(III) reagent, was also comparable in the cyanating reactions as a valuable alternative to PIFA, affording a high yield of the heteroaromatic cyanide by facilitating isolation of the cyanated products with a simple workup. Accordingly, after preparing the active hypervalent iodine(III)-CN species by premixing of a recyclable reagent 12, TMSCN, and BF3· Et2U for 30 min in dichloromethane, reaction of a variety of pyrroles 1 and thiophenes 3 provided the desired cyanated products 2 and 4 in high yields. The iodine compound 13, recovered by filtration after replacement of the reaction solvent to MeOH, could be reused without any loss of activity (the oxidant 12 can be obtained nearly quantitatively by reoxidation of 13 using m-CPBA).
- Dohi, Toshifumi,Morimoto, Koji,Takenaga, Naoko,Goto, Akihiro,Maruyama, Akinobu,Kiyono, Yorito,Tohma, Hirofumi,Kita, Yasuyuki
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p. 109 - 116
(2007/10/03)
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- Mild and general methods for the palladium-catalyzed cyanation of aryl and heteroaryl chlorides
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New methods for the palladium-catalyzed cyanation of aryl and heteroaryl chlorides have been developed, featuring sterically demanding, electron-rich phosphines. Highly challenging electron-rich aryl chlorides, in addition to electron-neutral and electron-deficient substrates, as well as nitrogen- and sulfur-containing heteroaryl chlorides can all undergo efficient cyanation under relatively mild conditions using readily available materials. In terms of substrate scope and temperature, these methods compare very favorably with the state-of-the-art cyanations of aryl chlorides.
- Littke, Adam,Soumeillant, Maxime,Kaltenbach III, Robert F.,Cherney, Robert J.,Tarby, Christine M.,Kiau, Susanne
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p. 1711 - 1714
(2008/02/02)
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- A facile and clean direct cyanation of heteroaromatic compounds using a recyclable hypervalent iodine(III) reagent
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The facile and clean direct cyanating reaction of pyrroles and thiophenes has been achieved using a recyclable hypervalent iodine(III) reagent 1b by a simple solid-liquid separation of the products and the reagent.
- Dohi, Toshifumi,Morimoto, Koji,Takenaga, Naoko,Maruyama, Akinobu,Kita, Yasuyuki
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p. 1608 - 1610
(2007/10/03)
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- Novel and direct oxidative cyanation reactions of heteroaromatic compounds mediated by a hypervalent iodine(III) reagent
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(Chemical Equation Presented) The hypervalent iodine(III) reagent phenyliodine bis(trifluoroacetate) (PIFA) mediates the selective cyanation reactions of a wide range of electron-rich heteroaromatic compounds such as pyrroles, thiophenes, and indoles unde
- Dohi, Toshifumi,Morimoto, Koji,Kiyono, Yorito,Tohma, Hirofumi,Kita, Yasuyuki
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p. 537 - 540
(2007/10/03)
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- FUROISOQUINOLINE DERIVATIVES, PROCESS FOR PRODUCING THE SAME AND USE THEREOF
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A compound having a partial structure represented by Formula: or a salt thereof has an excellent phosphodiesterase (PDE) IV-inhibiting effect, and is useful as a prophylactic or therapeutic agent against inflammatory diseases, for example, bronchial asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, autoimmune disease, diabetes and the like.
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- Selective cyclooxygenase-2 inhibitors: Heteroaryl modified 1,2-diarylimidazoles are potent, orally active antiinflammatory agents
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A series of heteroaryl modified 1,2-diarylimidazoles has been synthesized and found to be potent and highly selective (1000-9000-fold) inhibitors of the human COX-2.3-Pyridyl derived COX-2 selective inhibitor (25) exhibited excellent activity in acute (carrageenan induced paw edema, ED50 = 5.4 mg/kg) and chronic (adjuvant induced arthritis, ED50 = 0.25 mg/kg) models of inflammation. The relatively long half-life of 25 in rat and dog prompted investigation of the pyridyl and other heteroaromatic systems containing potential metabolic functionalities. A number of substituted pyridyl and thiazole containing compounds (e.g., 44, 46, 54, 76, and 78) demonstrated excellent oral activity in every efficacy model evaluated. Several orally active diarylimidazoles exhibited desirable pharmacokinetics profiles and showed no GI toxicity in the rat up to 100 mg/kg in both acute and chronic models. The paper describes facile and practical syntheses of the targeted diarylimidazoles. The structure-activity relationships and antiinflammatory properties of a series of diarylimidazoles are discussed.
- Khanna,Yu,Huff,Weier,Xu,Koszyk,Collins,Cogburn,Isakson,Koboldt,Masferrer,Perkins,Seibert,Veenhuizen,Yuan,Yang,Zhang
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p. 3168 - 3185
(2007/10/03)
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- A New Synthesis of Benzothiophenes and Benzothiophenes by Annulation of Disubstituted Thiophenes
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Nine newly prepared ortho-disubtituted thiophenes (1-5) react with Michael acceptors to form benzo- and benzothiophenes.This novel annulation process is specifically suited to form benzothiophenes with substituents in the benzene moiety.Substitution
- Terpstra, Jan W.,Leusen, Albert M. van
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p. 230 - 238
(2007/10/02)
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