- Highly variable Zr-CH2-Ph bond angles in tetrabenzylzirconium: Analysis of benzyl ligand coordination modes
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Analysis of a monoclinic modification of Zr(CH2Ph)4 by single-crystal X-ray diffraction reveals that the bond angles Zr-CH 2-Ph in this compound span a range of 25.1° , which is much larger than previously observed for the orthorhombic form (12.1°). In accord with this large range, density functional theory calculations demonstrate that little energy is required to perturb the Zr-CH2-Ph bond angles in this compound. Furthermore, density functional theory calculations on Me 3ZrCH2Ph indicate that bending of the Zr-CH2-Ph moiety in the monobenzyl compound is also facile, thereby demonstrating that a benzyl ligand attached to zirconium is intrinsically flexible, such that its bending does not require a buffering effect involving another benzyl ligand.
- Rong, Yi,Al-Harbi, Ahmed,Parkin, Gerard
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Read Online
- Polymer supporeted 'Magnesium(anthracene)': Effective in Forming Benzylic Grignard Reagents (via Electron Transfer Reactions)
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A polymer supported 'magnesium(anthracene)' (4) has been prepared from the reaction in tetrahydrofuran (thf) of (1) with polystyrene bearing -9-CH2SiMe2(C14H9) groups (3); the green paramagnetic solid, containing dianion radical anion anthracene sites, yields Grignard reagents (>90percent) with benzylic halides in thf via electron transfer reactions, as does the model compound for the dianion sites, viz. (thf)2> (6).
- Harvey, Stephen,Raston, Colin L.
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Read Online
- Scalable Continuous Synthesis of Grignard Reagents from in Situ-Activated Magnesium Metal
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The continuous synthesis of Grignard reagents has been investigated under continuous processing conditions using Mg turnings at variable liquid throughputs and concentrations. A novel process window easily accessible through continuous processing was employed, namely, using a large molar access of Mg turnings within the reactor and achieving Mg activation by mechanical means. A laboratory and a 10-fold-increased pilot-scale reactor setup were built and evaluated, including integrated inline analytics via ATR-IR measurements. The main goal of this work was to explore the full potential of classic Grignard reagent formation through the use of scalable flow chemistry and to allow for fast and safe process optimization. It was found that on both the laboratory and pilot scales, full conversion of the employed halides could be achieved with a single passage through the reactor. Furthermore, Grignard reagent yields of 89-100% were reached on the laboratory scale.
- Deitmann, Eva,G?ssl, Lars,Hofmann, Christian,L?b, Patrick,Menges-Flanagan, Gabriele
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p. 315 - 321
(2020/03/10)
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- Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides
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Magnesium organometallic reagents occupy a central position in organic synthesis. The freshness of these compounds is the key for achieving a high conversion and reproducible results. Common methods for the synthesis of Grignard reagents from metallic magnesium present safety issues and exhibit a batch-to-batch variability. Tubular reactors of solid reagents combined with solution-phase reagents enable the continuous-flow preparation of organomagnesium reagents. The use of stratified packed-bed columns of magnesium metal and lithium chloride for the synthesis of highly concentrated turbo Grignards is reported. A low-cost pod-style synthesizer prototype, which incorporates single-use prepacked perfluorinated cartridges and bags of reagents for the automated on-demand lab-scale synthesis of carbon, nitrogen, and oxygen turbo magnesium bases is presented. This concept will provide access to fresh organomagnesium reagents on a discovery scale and will do so independent from the operator’s experience in flow and/or organometallic chemistry.
- Adamo, Andrea,Berton, Mateo,McQuade, D. Tyler,Sheehan, Kevin
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supporting information
p. 1343 - 1356
(2020/07/10)
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- Redox-Active Ligand-Assisted Two-Electron Oxidative Addition to Gallium(II)
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The reaction of digallane (dpp-bian)Ga?Ga(dpp-bian) (2) (dpp-bian=1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene) with allyl chloride (AllCl) proceeded by a two-electron oxidative addition to afford paramagnetic complexes (dpp-bian)Ga(η1-All)Cl (3) and (dpp-bian)(Cl)Ga?Ga(Cl)(dpp-bian) (4). Treatment of complex 4 with pyridine induced an intramolecular redox process, which resulted in the diamagnetic complex (dpp-bian)Ga(Py)Cl (5). In reaction with allyl bromide, complex 2 gave metal- and ligand-centered addition products (dpp-bian)Ga(η1-All)Br (6) and (dpp-bian-All)(Br)Ga?Ga(Br)(dpp-bian-All) (7). The reaction of digallane 2 with Ph3SnNCO afforded (dpp-bian)Ga(SnPh3)2 (8) and (dpp-bian)(NCO)Ga?Ga(NCO)(dpp-bian) (9). Treatment of GaCl3 with (dpp-bian)Na in diethyl ether resulted in the formation of (dpp-bian)GaCl2 (10). Diorganylgallium derivatives (dpp-bian)GaR2 (R=Ph, 11; tBu, 14; Me, 15; Bn, 16) and (dpp-bian)Ga(η1-All)R (R=nBu, 12; Cp, 13) were synthesized from complexes 3, 10, Bn2GaCl, or tBu2GaCl by salt metathesis. The salt elimination reaction between (dpp-bian)GaI2 (17) and tBuLi was accompanied by reduction of both the metal and the dpp-bian ligand, which resulted in digallane 2 as the final product. Similarly, the reaction of complex 10 with MentMgCl (Ment=menthyl) proceeded with reduction of the dpp-bian ligand to give the diamagnetic complex [(dpp-bian)GaCl2][Mg2Cl3(THF)6] (18). Compounds 11, 12, 13, 15, and 16 were thermally robust, whereas compound 14 decomposed when heated at reflux in toluene to give complex (dpp-bian-tBu)GatBu2 (19). Both complexes 7 and 19 contain R-substituted dpp-bian ligand: in the former compound the allyl group was attached to the imino-carbon atom, whereas in complex 19, the tBu group was situated on the naphthalene ring. Crystal structures of complexes 3, 8, 9, 10, 13, 14, 18, and 19 were determined by single-crystal X-ray analysis. The presence of dpp-bian radical anions in 3, 6, 8, and 10–16 was determined by ESR spectroscopy.
- Fedushkin, Igor L.,Dodonov, Vladimir A.,Skatova, Alexandra A.,Sokolov, Vladimir G.,Piskunov, Alexander V.,Fukin, Georgii K.
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p. 1877 - 1889
(2018/01/27)
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- Regioselective 1,4-conjugate addition of grignard reagents to nitrodienes in the presence of catalytic amounts of Zn(II) salts
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Grignard reagents undergo facile regioselective 1,4-conjugate addition to nitrodienes in the presence of catalytic amounts of Zn(II) salts with excellent yields. A wide range of ligands such as alkyl, aryl, heteroaryl, allyl, vinyl, 1-alkynyl, and alkoxy ligands were transferred, while a thiolate ligand afforded 1,6-regioselectivity. The reactions were successfully carried out on δ-alkyl- or aryl-substituted α,β,γ,δ-diunsaturated nitrodiene substrates. Regioselectivity is minimally influenced by temperature or choice of solvent.
- Dhakal, Ramesh C.,Dieter, R. Karl
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supporting information
p. 1362 - 1365
(2014/04/03)
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- PROCESS FOR THE PREPARATION OF GRIGNARD COMPOUNDS
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The invention relates to a process for the preparation of Grignard compounds using a continuous method which involves the reaction of an organic halide dissolved in an organic solvent with metallic magnesium which, together with the activator solution in an organic solvent, fills the flow reactor or optionally a system of flow reactors, and subsequently, the resulting reaction mixture is fed into the terminal flow reactor containing metallic magnesium in order to achieve complete conversion of the organic halide, whereby preferably the organic solvent is re-circulated to flow reactors in a form of vapour.
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Page/Page column 8
(2010/11/03)
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- N-acyl sulfamic acid esters (or thioesters), N-acyl sulfonamides, and N-sulfonyl carbamic acid esters (or thioesters) as hypercholesterolemic agents
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The present invention is directed to compounds useful for the regulation of cholesterol of Formula I, methods for using them and pharmaceutical compositions thereof, STR1 wherein X and Y are oxygen, sulfur, or (CR'R")n wherein n is 1 to 4; R is hydrogen, alkyl, or benzyl; R1 and R2 are phenyl, substituted phenyl, naphthyl, substituted naphthyl, an aralkyl group, an alkyl chain, adamantyl, or a cycloalkyl group.
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- C-GLYCOSIDE ANALOGUES OF N-(4-HYDROXYPHENYL)RETINAMIDE-O-GLUCURONIDE
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The present invention provides breast cancer chemopreventive arylamide analogues of retinoic acid, more particularly C-glycoside analogues of N-(4-hydroxyphenyl)retinamide-O-glucuronide and N-glycoside analogue of retinoyl beta-glucuronide that resist both beta-glucuronidase mediated enzymatic hydrolysis as well as acid catalyzed hydrolysis. Specifically, the drugs include 4-(retinamido)phenyl-C-glucuronide; 4-(retinamido)phenyl-C-glucoside; 4-(retinamido)benzyl-C-xyloside; 4-(retinamido)benzyl-C-glucoside; 4-(retinamido)benzyl-C-glucuronide; 4-(retinamido)phenyl-C-xyloside, 1-(B-D-lucopyranosyl) retinamide and 1-(D-glucopyranosyluronosly) retinamide. The invention also relates to a method for making such drugs.
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- Mechanical Activation of Magnesium Turnings for the Preparation of Reactive Grignard Reagents
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Preactivation of magnesium by dry stirring in an inert atmosphere is highly beneficial for the clean synthesis of reactive allylic or benzylic organomagnesium chlorides.This procedure routinely produces 0.4 M solutions of the Grignard reagent in diethyl ether free from coupling products.The purity may be directly assayed by 13C spectroscopy.Using spin saturation transfer techniques, the rate constant for interconversion of the enantiomers of (1-phenyl-2-methylpropyl)magnesium chloride in Et2O at 25 deg C was shown to be -1.Electron microscopy has been used to define the surface changes occurring during the dry stirring of magnesium turnings.
- Baker, Karen V.,Brown, John M.,Hughes, Nigel,Skarnulis, A. Jerome,Sexton, Ann
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p. 698 - 703
(2007/10/02)
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- Use of Magnesium Anthracene * 3 THF in Synthesis: Generation of Grignard Compounds and Other Reactions with Organic Halides
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The course (a), (b), (c) (Scheme 1) of the reaction of magnesium anthracene * 3 THF (1) with organic halides (RX) is dependent on the nature of RX.With alkyl halides in THF 1 reacts as a nucleophile, whereby primary as well as secondary alkyl halides produce dialkyldihydroanthracenes (4-4'') and tertiary alkyl halides yield primarily monoalkyl-substituted dihydroanthracenes (2, 2').With bromo- and iodobenzene in THF 1 reacts predominantly as a radical with H atom abstraction from the solvent affording benzene and 9.The formation of Grignard compounds (5) and anthracene (6), originating from primary and secondary alkyl and aryl halides and 1 in toluene or ether at elevated temperatures, is not caused by the reaction of 1 but by the "active magnesium" (Mg*) formed by decomposition of 1 in these solvents.In contrast, allyl, propargyl, and benzyl halides react with 1 independently of the solvent under mild conditions to produce 5 and 6.Allyl- and the difficultly accessible allenylmagnesium chloride can be prepared in THF at -78 and 0 deg C, respectively, from the corresponding halides and ordinary Mg powder via catalytic amounts of 1.
- Bogdanovic, Borislav,Janke, Nikolaus,Kinzelmann, Hans-Georg
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p. 1507 - 1515
(2007/10/02)
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- Magnesium Adducts of Substituted Anthracenes - Preparation and Properties
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2-Methyl-, 1,4-dimethyl-, 9-methyl-, 9-ethyl-, 9,10-dimethyl-, and 9-phenylanthracene (1a-f) react with magnesium in THF at room temperature to afford the corresponding substituted magnesium anthracenes 2a-f. 9,10-Diphenylanthracene (1g), however, reacts with magnesium under the same conditions to produce the deep-blue magnesium bis(9,10-diphenylanthracenide) * 6 THF (4g).Upon heating to 60 deg C in THF, 4g reversibly dissociates to give magnesium 9,10-diphenylanthracene * 3 THF (2g) and 1g, while prolonged heating at 60 deg C causes decomposition of 2g to active magnesium (Mg*) and 1g.In THF 2a-c, e, and f exhibit temperature-dependent equilibria with 1a-c, e, and f and magnesium.Compared with magnesium anthracene * 3 THF (2), these equilibria are strongly shifted toward substituted anthracenes and magnesium, and only at 0 deg C high conversions are achieved.The magnesium exchange between 2 and the substituted anthracenes 1a, b, and f in THF has been experimentally verified. 2a, e, and f react with organic halides in the same way as 2, however, in the case of allyl, propargyl, and benzyl chloride the yields of Grignard compounds are lower than for 2; with bromobenzene, the tendency for the radical transfer reaction is stronger than for 2.Magnesium 9,10-dimethylanthracene (2e) reacts with ethyl acetate to give the bicyclic tertiary alcohol 9 by an intramolecular C-C coupling reaction.
- Bogdanovic, Borislav,Janke, Nikolaus,Kinzelmann, Hans-Georg,Seevogel, Klaus,Treber, Joachim
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p. 1529 - 1535
(2007/10/02)
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- Benzotriazol-1-ylmethylammonium Salts Synthesis and Reactivity
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Benzotriazol-1-ylmethylamines on treatment with alkylating agents afford benzotriazol-1-ylmethylammonium salts, also available from reactions of chloromethylbenzotriazole with tertiary amines.In deuterated solvents under basic conditions the methylene protons of these salts exchange with deuterium.At elevated temperatures, an alkyl group substituent migrated from the ammonium center to the benzotriazolyl N-3.Reactions of the salts with Grignard reagents afforded various products arising from substitution of the ammonium moiety and/or from attack on the benzotriazolyl N-3 or on the benzenoid ring.
- Katritzky, Alan R.,Hughes, Craig V.,Rachwal, Stanislaw
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p. 1579 - 1588
(2007/10/02)
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- GENERATION AND DIENOPHILIC REACTIVITY OF α-OXOSELENOALDEHYDES AND KETONES
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The reaction elemental selenium with sulfur ylides stabilized by electron-withdrawing substituent(s) affords a facile method for generation of functionalized selenocarbonyl compounds, which can be effectively trapped by Diels-Alder reaction with 1,3-dienes.
- Nakayama, Juzo,Akimoto, Keiichi,Niijima, Jun,Hoshino, Masamatsu
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p. 4423 - 4426
(2007/10/02)
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- Triazine derivatives, and pharmaceutical compositions comprising the same
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New triazine derivatives represented by the formula: STR1 wherein R1 is aryl, pyridyl, thienyl, 1,2,3,4-tetrahydroquinolyl or 1,3,4,5-tetrahydro-2H-1-benzazepinyl, optionally substituted with lower alkyl, lower alkoxy, halogen, nitro or oxo, R2 is hydrogen, lower alkyl or carbamoyl substituted with lower alkyl or ar(lower)alkyl, and Z is a group selected from STR2 and pharmaceutically acceptable salt thereof, processes for preparation thereof and pharmaceutical compositions comprising the same of antihypertensive and antithrombotic activity.
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- CYCLISATION DE DIARYLALCANES EN MILIEU SUPERACIDE: SYNTHESE DE CETONES TRICYCLIQUES A METHYLE ANGULAIRE ET MECANISME DE LEUR ISOMERISATION
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Cyclisation of redily available diaryl-1,2 ethanes 1-4 proceeds in SbF5-HF at 0oC to yield tricyclic phenantrenones 5,6,7 and 11 bearing an angular methyl group.This process implies the electrophilic attack of the more basic aromatic ring, reacting through its disprotonated form (on the oxygen and the meta carbon atom) on the second aromatic ring.Isomerization of these primary products may be observed (to give ketones 8,9,10 from 3 and 12 from 4) and it has been demonstrated by the use of specifically deuterated 3d that it involves stereospecific 1,2 hydride (or deuteride) shifts, without exchange.
- Berrier, C.,Jacquesy, J. C.,Gesson, J. P.,Renoux, A.
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p. 1983 - 1994
(2007/10/02)
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- Hydroxypropyl-triazole compounds, their production and their medicinal use
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The invention relates to hydroxypropyl-triazole compounds and methods for their preparation. Also included are compositions containing said hydroxypropyl-triazoles and methods for the use of the said active compounds and compositions, as antimycotic agents.
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- Mechanism of the Reaction between Benzylmagnesium Chloride and Carbonyl Compounds. A Detailed Study with Formaldehyde
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The reaction of benzylmagnesium chloride in THF with monomeric formaldehyde has been studied in detail.A mechanism is presented which accounts for the formation of the products, 2-phenylethanol, o-tolylcarbinol, and o-(2-hydroxyethyl)benzyl alcohol.A change in technique for Grignard titration and formaldehyde addition results in a much-improved mass balance than achieved previously.The decreased yield of the major product, o-tolylcarbinol, with increased reaction time is explained in terms of a hitherto unsuspected equilibrium influenced by the polymerization of monomeric formaldehyde.An intermediate organometallic species which could lead to some of the diol product, o-(2-hydroxyethyl)benzyl alcohol can be trapped as the trimethylsilyl derivative, but the quantity is insufficient to account for the amount of diol when an excess of formaldehyde is employed.An ene or Prins reaction is invoked for the formation of most of the diol.Deuterium tracer studies suggest competition between a proton abstraction pathway leading to the trimethylsilyl-trapped organometallic species and a base-catalyzed, stereospecific 1,3 hydrogen shift.
- Benkeser, Robert A.,Snyder, Dudley C.
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p. 1243 - 1249
(2007/10/02)
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