1068-55-9Relevant articles and documents
Absolute kinetic rate constants and activation energies for the formation of Grignard reagents
Beals, Bridget J.,Bello, Zainab I.,Cuddihy, Kathleen P.,Healy, Ethan M.,Koon-Church, Stephanie E.,Owens, Jane M.,Teerlinck, Cynthia E.,Bowyer, Walter J.
, p. 498 - 503 (2002)
This paper reports the first absolute rate constants for the formation of Grignard reagents from magnesium metal and organohalides. The theory that allows calculation of heterogeneous rate constants from the rate of growth of individual pits is described. By monitoring the reaction of individual reactive sites on the magnesium surface using photomicrography, it is possible to determine the rate of reaction and the active surface area; rate constants then are calculated from those data. Rate constants are on the order of 10-4 cm/s and vary relatively little between various organohalides. By measuring rate constants over a range of temperatures, Arrhenius parameters are determined for the reaction. The magnitudes of the enthalpic and entropic barriers are not consistent with electron transfer as the rate-limiting step. Rather, the data suggest that the rate-limiting step is reaction of the organohalide at the magnesium surface with partial insertion of a magnesium atom into the carbon-halide bond in the transition state.
Association and Dissociation of Grignard Reagents RMgCl and Their Turbo Variant RMgC?LiCl
Schnegelsberg, Christoph,Bachmann, Sebastian,Kolter, Marlene,Auth, Thomas,John, Michael,Stalke, Dietmar,Koszinowski, Konrad
, p. 7752 - 7762 (2016)
Grignard reagents RMgCl and their so-called turbo variant, the highly reactive RMgC?LiCl, are of exceptional synthetic utility. Nevertheless, it is still not fully understood which species these compounds form in solution and, in particular, in which way LiCl exerts its reactivity-enhancing effect. A combination of electrospray-ionization mass spectrometry, electrical conductivity measurements, NMR spectroscopy (including diffusion-ordered spectroscopy), and quantum chemical calculations is used to analyze solutions of RMgCl (R=Me, Et, Bu, Hex, Oct, Dec, iPr, tBu, Ph) in tetrahydrofuran and other ethereal solvents in the absence and presence of stoichiometric amounts of LiCl. In tetrahydrofuran, RMgCl forms mononuclear species, which are converted into trinuclear anions as a result of the concentration increase experienced during the electrospray process. These trinuclear anions are theoretically predicted to adopt open cubic geometries, which remarkably resemble structural motifs previously found in the solid state. The molecular constituents of RMgCl and RMgC?LiCl are interrelated via Schlenk equilibria and fast intermolecular exchange processes. A small portion of the Grignard reagent also forms anionic ate complexes in solution. The abundance of these more electron-rich and hence supposedly more nucleophilic ate complexes strongly increases upon the addition of LiCl, thus rationalizing its beneficial effect on the reactivity of Grignard reagents.
Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides
Adamo, Andrea,Berton, Mateo,McQuade, D. Tyler,Sheehan, Kevin
supporting information, p. 1343 - 1356 (2020/07/10)
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.
Scalable Continuous Synthesis of Grignard Reagents from in Situ-Activated Magnesium Metal
Deitmann, Eva,G?ssl, Lars,Hofmann, Christian,L?b, Patrick,Menges-Flanagan, Gabriele
, p. 315 - 321 (2020/03/10)
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.
Ledipasvir key intermediate and preparation method thereof
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Paragraph 0040-0043; 0065; 0086, (2018/04/26)
The invention discloses a ledipasvir key intermediate LD-J, a structure of the ledipasvir key intermediate LD-J and a preparation method of the ledipasvir key intermediate LD-J. The preparation methodcomprises the following steps: (A1) preparing LD-G; (A2) preparing LD-H; (A3) preparing LD-I; (A4) preparing a Grignard reagent; and (A5) preparing LD-J. The ledipasvir key intermediate LD-J and thepreparation method thereof have the advantages that the process is mature and stable, the product is stable in quality, the production process is safe and reliable, and the preparation method is suitable for industrial production.
CYCLOPROPENES-GENERATING DEVICES TO CONTROL RIPENING PROCESSES OF AGRICULTURAL PRODUCTS
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Page/Page column 6-7, (2012/06/01)
Provided is a device for generation of cyclopropene compounds which is capable of achieving direct in situ preparation and application of cyclopropene compounds inhibiting the action of ethylene which accelerates the ripening process of plants, the device comprising a first storage part for storing precursors of cyclopropene compounds (“cyclopropene precursors”), a second storage part for storing reaction reagents which convert cyclopropene precursors into cyclopropene derivatives via chemical reaction, and a spray part for spraying the cyclopropene derivatives produced by the chemical reaction between the cyclopropene precursors and the reaction reagents.
ANTIBACTERIAL FLUOROQUINOLONE ANALOGS
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Page/Page column 267-268, (2010/01/29)
Compounds having antibacterial activity are disclosed. The compunds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein A, B, D, E, G, R1, R2, R3, R4, R5, R6 and R7 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
SALTS OF 2-FLUORO-N-METHYL-4-[7-(QUINOLIN-6-YL-METHYL)-IMIDAZO[1,2-b][1,2,4]TRIAZIN-2-YL]BENZAMIDE AND PROCESSES RELATED TO PREPARING THE SAME
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Page/Page column 25; 26, (2009/12/05)
The present invention is directed to dihydrochloric acid and dibenzenesulfonic acid salts of the c-Met kinase inhibitor 2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)-imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide, and pharmaceutical compositions thereof, useful in the treatment of cancer and other diseases related to the dysregulation of kinase pathways. The present invention further relates to processes and intermediates for preparing 2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide, and salts thereof.
BACTERICIDE COMPOSITION AND METHOD OF CONTROLLING PLANT DISEASE
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Page/Page column 19, (2008/06/13)
It is to provide a fungicidal composition having stable and high fungicidal effects against cultivated crops infected with plant diseases resulting from plant diseases. A fungicidal composition containing as active ingredients (a) a benzoylpyridine derivative represented by the formula (I) or its salt: (wherein X is a halogen atom, a nitro group, a substitutable hydrocarbon group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group, a hydroxyl group, a substitutable alkylthio group, a cyano group, a carboxyl group which may be esterified or amidated, or a substitutable amino group, n is 1, 2, 3 or 4; R1 is a substitutable alkyl group, R2' is a substitutable alkyl group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group or a hydroxyl group, p is 1, 2 or 3, and R2" is a substitutable alkoxy group or a hydroxyl group, provided that at least two of R2' and R2" may form a condensed ring containing an oxygen atom) and (b) at least one another fungicide.
Production processes for triorganomonoalkoxysilanes and triorganomonochlorosilanes
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Page/Page column 21; 22; 23; 24; 25; 27; 28; 29; 30, (2008/06/13)
A silane containing a bulky hydrocarbon group or groups R therein and having the formula (III) [in-line-formulae]R3-(x+y)(R1)x(R2)ySi(OR3) [/in-line-formulae] can be produced by reacting a silane of the formula (I) [in-line-formulae](R1)x(R2) ySiCl3-(x+y)(OR3) [/in-line-formulae] with a Grignard reagent of the formula (II) [in-line-formulae]RMgX [/in-line-formulae] Further, a tri-organo-chlorosilane of the formula (XIIa) [in-line-formulae](R1)(R2)(R3)SiCl [/in-line-formulae] can be produced by reacting a tri-organo-silane of the formula (XIa) [in-line-formulae](R1)(R2)(R3)SiZ1 [/in-line-formulae] with hydrochloric acid. Furthermore, a tri-organo-monoalkoxysilane of the formula (XXIII) [in-line-formulae]R3-(x+y)(R1)x(R2)ySi(OR3) [/in-line-formulae] can be produced when a silane of the formula (XXI) [in-line-formulae](R1)x(R2)ySiCl4-(x+y) [/in-line-formulae] is reacted with a Grignard reagent of the formula (XXII) [in-line-formulae]RMgX [/in-line-formulae] with addition of and reaction with an alcohol or an epoxy compound during the reaction.
