925-90-6Relevant articles and documents
Synthesis and structures of titanium complexes bearing tetradentate tripodal [O2XC] ligands (X = C, P)
Nakanishi, Yusuke,Ishida, Yutaka,Kawaguchi, Hiroyuki
, p. 27 - 30 (2019)
We report the synthesis and structures of titanium complexes supported by tripodal mixed-donor [O2CC] and [O2PC] ligands. Stepwise cyclometallation of a chelating bis(phenoxide) complex led to tetradentate binding of the [O2CC] ligand to the titanium center. Phosphination of a Ti-C bond of the [O2CC] complex afforded the tripodal [O2PC] ligand.
4-Alkyl-3-azidomethyl-2-ethoxy-2,5-dihydro-5 H-1,2-oxaphosphole 2-Oxides: Synthesis and 1,3-Cycloaddition
Alekseychuk, Ekaterina P.,Anikina, Lada V.,Artyushin, Oleg I.,Brel, Valery K.
supporting information, (2021/11/04)
Starting from phosphorylated allenes, a three-steps synthesis of a new class of organic azides with a 1,2-oxaphospholene carbon skeleton has been developed. The series of obtained 4-alkyl-3-azidomethyl-2-ethoxy-2,5-dihydro-5H-1,2-oxaphosphole 2-oxides were utilized in the 1,3-cycloaddition with alkyl 2-[1-(propyn-2-yl)-1H-indol-3-yl]-2-oxoacetates for the synthesis of conjugates, which are potentially active cytostatics.
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.
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.
Ni-Catalyzed β-Alkylation of Cyclopropanol-Derived Homoenolates
Mills, L. Reginald,Zhou, Cuihan,Fung, Emily,Rousseaux, Sophie A. L.
supporting information, p. 8805 - 8809 (2019/11/03)
Metal homoenolates are valuable synthetic intermediates which provide access to β-functionalized ketones. In this report, we disclose a Ni-catalyzed β-alkylation reaction of cyclopropanol-derived homoenolates using redox-active N-hydroxyphthalimide (NHPI) esters as the alkylating reagents. The reaction is compatible with 1°, 2°, and 3° NHPI esters. Mechanistic studies imply radical activation of the NHPI ester and 2e β-carbon elimination occurring on the cyclopropanol.
Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of Macrophage Migration Inhibitory Factor
Trivedi-Parmar, Vinay,Robertson, Michael J.,Cisneros, José A.,Krimmer, Stefan G.,Jorgensen, William L.
supporting information, p. 1092 - 1097 (2018/04/30)
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is implicated in the regulation of inflammation, cell proliferation, and neurological disorders. MIF is also an enzyme that functions as a keto–enol tautomerase. Most potent MIF tautomerase inhibitors incorporate a phenol, which hydrogen bonds to Asn97 in the active site. Starting from a 113-μm docking hit, we report results of structure-based and computer-aided design that have provided substituted pyrazoles as phenol alternatives with potencies of 60–70 nm. Crystal structures of complexes of MIF with the pyrazoles highlight the contributions of hydrogen bonding with Lys32 and Asn97, and aryl–aryl interactions with Tyr36, Tyr95, and Phe113 to the binding.
Synthetic method for 3-methylpropiophenone
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Paragraph 0022; 0028; 0034; 0040; 0046, (2017/10/07)
The invention specifically relates to a synthetic method for 3-methylpropiophenone, belonging to the technical field of organic synthesis. The synthetic method comprises the following steps: (1) preparation of a Grignard reagent; (2) treatment of the Grignard reagent; (3) preparation of 3-methylphenylpropanol; and (4) (3) preparation of 3-methylpropiophenone. With such a technical scheme, the synthetic method can effectively overcome the disadvantages of difficulty in removal of solvents and low product yield in the prior art.
A Short Access to Symmetrically α,α-Disubstituted α-Amino Acids from Acyl Cyanohydrins
Boukattaya, Fatma,Caillé, Julien,Ammar, Houcine,Rouzier, Florian,Boeda, Fabien,Pearson-Long, Morwenna S. M.,Bertus, Philippe
, p. 906 - 916 (2016/03/12)
A straightforward synthesis of symmetrically α,α-disubstituted α-amino acids is presented. The key step of this process relies on the efficient double addition of Grignard reagents to acyl cyanohydrins to provide N-acyl amino alcohols selectively in good yields. The chemoselectivity of the reaction was modulated by the nature of the acyl moiety. Eleven amino acids were prepared, including the particularly simple divinylglycine, which is not easily accessible by using conventional methods.
Fluoro-ene reaction versus [2+2] cycloaddition in the thermal C 2-C6 cyclization of enyne-allenes: An experimental and theoretical investigation
Cinar, M. Emin,Vavilala, Chandrasekhar,Jaquet, Ralph,Bats, Jan W.,Schmittel, Michael
, p. 5166 - 5177 (2014/10/15)
A series of fluoroalkyl-substituted enyne-allenes have been synthesized by a new route with the aim of elucidating the possibility of a fluoro-ene reaction via an intermediate fulvenyl diradical generated in the thermal C 2-C6 (Schmittel) cyclization reaction. As a result of the strong C-F bond, fluorine atom transfer was not observed. Instead, 1H-cyclobuta[a]indenes were formed in good yields despite the high strain energy. DFT calculations at the B3LYP level of theory indicated that although the fluoro-ene reaction is the most exothermic reaction available, cyclobutene formation is kinetically favored over the [1,5]-fluorine shift by 5-15 kcal mol-1 in various model compounds. Copyright
PROCESS OF PREPARING GRIGNARD REAGENT
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Paragraph 0306-0313, (2014/05/25)
A novel process of preparing a Grignard reagent is disclosed. The process is effected by electrochemically reacting a Grignard precursor with an electrode which comprises a metal for forming the Grignard reagent, in the presence an electrolyte solution that comprises a room temperature ionic liquid (RTIL). Electrochemical cells and systems for performing the process, and uses thereof in various applications are also disclosed.
