- Generation of alkyl radicals from alkylsilyl peroxides and their applications to C-N or C-O bond formations
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This article describes a novel method for the generation of alkyl radicals from alkylsilyl peroxides and their applications to the Cu-catalyzed mono-N-alkylation of amides or arylamines, and to the O-alkylation of carboxylic acids. The use of alkylsilyl peroxides as alkyl radical sources includes the following synthetic advantages: i) various alkylsilyl peroxides can be readily synthesized from the corresponding alcohols and be stored at bench, and ii) a variety of alkyl radicals can be generated efficiently under mild conditions.
- Sakurai, Shunya,Kato, Terumasa,Sakamoto, Ryu,Maruoka, Keiji
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p. 172 - 179
(2018/12/11)
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- Structure-Guided Modification of Heterocyclic Antagonists of the P2Y14 Receptor
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The P2Y14 receptor (P2Y14R) mediates inflammatory activity by activating neutrophil motility, but few classes of antagonists are known. We have explored the structure-activity relationship of a 3-(4-phenyl-1H-1,2,3-triazol-1-yl)-5-(aryl)benzoic acid antagonist scaffold, assisted by docking and molecular dynamics (MD) simulation at a P2Y14R homology model. A computational pipeline using the High Throughput MD Python environment guided the analogue design. Selection of candidates was based upon ligand-protein shape and complementarity and the persistence of ligand-protein interactions over time. Predictions of a favorable substitution of a 5-phenyl group with thiophene and an insertion of a three-methylene spacer between the 5-aromatic and alkyl amino moieties were largely consistent with empirical results. The substitution of a key carboxylate group on the core phenyl ring with tetrazole or truncation of the 5-aryl group reduced affinity. The most potent antagonists, using a fluorescent assay, were a primary 3-aminopropyl congener 20 (MRS4458) and phenyl p-carboxamide 30 (MRS4478).
- Yu, Jinha,Ciancetta, Antonella,Dudas, Steven,Duca, Sierra,Lottermoser, Justine,Jacobson, Kenneth A.
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supporting information
p. 4860 - 4882
(2018/06/20)
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- Visible-Light-Driven Oxidation of N -Alkylamides to Imides Using Oxone/H 2 O and Catalytic KBr
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Imides are prepared conveniently by visible-light-driven oxidations of various N -alkylamides under mild conditions. The majority of the reactions proceed efficiently by using Oxone as the oxidant in the presence of a catalytic amount of KBr in H 2 O/CH 2 Cl 2 under irradiation by an 8 W white LED at room temperature. Experimental studies suggest that an imine, obtained from the substrate amide via a radical process, is the key intermediate.
- Mei, Chong,Hu, Yixin,Lu, Wenjun
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supporting information
p. 2999 - 3005
(2018/05/25)
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- Bis(trialkylsilyl) peroxides as alkylating agents in the copper-catalyzed selective mono-: N -alkylation of primary amides
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The copper-catalyzed selective mono-N-alkylation of primary amides with bis(trialkylsilyl) peroxides as alkylating agents was reported. The results of a mechanistic study suggest that this reaction should proceed via a free radical process that includes the generation of alkyl radicals from bis(trialkylsilyl) peroxides.
- Sakamoto, Ryu,Sakurai, Shunya,Maruoka, Keiji
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supporting information
p. 6484 - 6487
(2017/07/10)
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- Alkylsilyl Peroxides as Alkylating Agents in the Copper-Catalyzed Selective Mono-N-Alkylation of Primary Amides and Arylamines
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The copper-catalyzed selective mono-N-alkylation of primary amides or arylamines using alkylsilyl peroxides as alkylating agents is reported. The reaction proceeds under mild reaction conditions and exhibits a broad substrate scope with respect to the alkylsilyl peroxides, as well as to the primary amides and arylamines. Mechanistic studies suggest that the present reaction should proceed through a free-radical process that includes alkyl radicals generated from the alkylsilyl peroxides.
- Sakamoto, Ryu,Sakurai, Shunya,Maruoka, Keiji
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supporting information
p. 9030 - 9033
(2017/07/11)
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- Tandem oxidative amidation of benzyl alcohols with amine hydrochloride salts catalysed by iron nitrate
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A tandem process for the oxidative amidation of benzyl alcohols with amine hydrochloride salts has been developed using inexpensive Fe(NO3) 3 as the catalyst, air and aqueous t-butyl hydroperoxide as oxidants. A wide range of benzamides have been synthesized under mild conditions. This greener amide formation method provides an economical and practical assess to benzamides from readily available and inexpensive starting materials.
- Ghosh, Subhash Chandra,Ngiam, Joyce S.Y.,Seayad, Abdul M.,Tuan, Dang Thanh,Johannes, Charles W.,Chen, Anqi
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p. 4922 - 4925
(2013/09/02)
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- The conversion of aryl and heteroaryl methylketones to the corresponding secondary or tertiary amides
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Secondary or tertiary amides have been prepared directly from aryl, heteroaryl methyl ketones using an iodineamine-NaOH system which afforded the expected products in good yields in an aqueous medium. The present method has the advantages of using inexpensive reagents, mild reaction condition and ease of manipulation.
- Ding, Jiaoyang,Cao, Liping,Wang, Jungang,Xue, Weijian,Zhu, Yanping,Wu, Anxin
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experimental part
p. 298 - 301
(2011/10/02)
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- IMPROVED METHOD FOR THE PRODUCTION OF N-SUBSTITUTED AMIDES FROM NITRILES
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An improved method for the production of N-substituted amides of formula RCONHR1 (I) wherein R represents an optionally monosubstituted or polysubstituted C1-C20-alkyl-, C5 -C20-aryl- or C5-C20--heterocyclic radical and R1 represents an optionally monosubstituted or polysubstituted C1-C20-alkyl- or C5-C20-aryl radical from corresponding nitriles of formula RCN (II) wherein R1 is defined as above, wherein a nitril of formula (II) is reacted in polyphosphoric acid with an alcohol of formula R10H (III) wherein R1 is as defined above, in the presence of a compound from the group consisting of phosphorpentoxide, phosphoroxychloride, sulfurylchloride, dialkylcarbonate and dialkylsulfate at a temperature of 80 -190 °C to form the corresponding N-substituted amide.
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Page/Page column 8
(2010/02/06)
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- Noncovalent interactions between tetrazole and an N,N′-diethyl-substituted benzamidine
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Amidines have long been known to form strong noncovalent complexes with carboxylates and phosphates. However, their interaction with tetrazoles, which are acidic heterocycles and important bioisosteric replacements for carboxylic acids in medicinal chemistry, has remained unexplored so far. The binding of a tetrazole to an N,N′-diethyl-substituted benzamidine has been studied for the first time by X-ray crystallography, solution NMR methods, and electrospray mass spectrometry. The amidinium group of model complex 3 was found to prefer an E,Z configuration in the crystal. Benzamidinium and tetrazolate groups alternate along an infinite chain of hydrogen bonds and salt bridges between the amidine-NH groups and the two tetrazole-N atoms next to the ring carbon. In solution, a 1:1 complex was evident from Job's method of continuous variation, and an association constant of 4.0 × 103 ± 1.6 × 103 M-1 (in CDCl3/CD3CN, 6:1) could be determined by 1H NMR dilution experiments. Tetrazolate was not only found to be a weaker ligand than carboxylates but, surprisingly, the: binding mode also changed with concentration in neat CDCl3. At low concentrations, the amidine group in complex 3 adapted an E,E configuration as it does in a related carboxylic acid complex 4. With increasing concentration, the E,Z isomer starts to predominate. A free activation enthalpy Δ298? of 64 ± 1 kJ mol-1 for the E,E to E,Z isomerization was determined by line shape analysis at different magnetic fields. Binding strength was further probed in a competition experiment between a bisamidine, a carboxylate, and a tetrazolate by electrospray mass spectrometry.
- Peters,Froehlich,Boyd,Kraft
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p. 3291 - 3298
(2007/10/03)
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- Does Formal Intramolecular Transfer of an Acidic Deuterium to a Site of Halogen-Lithium Exchange Show That Lithium-Halogen Exchange Is Faster than Loss of the Acidic Deuterium? Evidence in Favor of an Alternative Mechanism
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Reactions in which there is formal intramolecular transfer of an acidic deuterium to a site of halogen-lithium exchange could be interpreted to show that initial halogen-lithium exchange occurs faster than loss of the acidic deuterium.However studies of the competition between halogen-metal-deuterium exchange and deuterium loss for N-deuterio-N-alkyl-o, -m, and -p-halobenzimides are not consistent with that mechanism.We suggest an alternative in which initial loss of the acidic deuterium is followed by halogen-lithium exchange to give a dilithiated intermediate.Deuterium transfer to the site of halogen-lithium exchange then occurs by reaction of the dilithiated species intermolecularly with unreacted N-deuteriated amide.The halogen-lithium exchange is faster than complete mixing of the reactants and can occur either in an initially formed deprotonated complex or in a transient high local concentration of organolithium reagent.Evidence for both possibilities is provided.Two reactions from the literature in which halogen-lithium exchange appears to be faster than transfer of an acidic hydrogen have been reinvestigated and found to be interpretable in terms of similar sequences.
- Beak, Peter,Musick, Timothy J.,Chen, Chin-wen
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p. 3538 - 3542
(2007/10/02)
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