95-52-3Relevant academic research and scientific papers
Full continuous flow synthesis process of fluorine-containing aromatic hydrocarbon compounds
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Paragraph 0095-0108, (2021/04/07)
The invention provides a full continuous flow synthesis process of a fluorine-containing aromatic hydrocarbon compound, and belongs to the technical field of preparation of halogenated hydrocarbon carbocyclic organic compounds. Arylamine and hydrogen fluoride are pumped into a thermostat A and a thermostat B respectively and flow into a micro-channel reactor C for a salt forming reaction after constant temperature treatment, and a sulfuric acid solution of nitrosyl sulfuric acid is pumped into a thermostat D and flows into a micro-channel reactor E together with a salt forming product flowing out of the micro-channel reactor C for a diazotization reaction after constant temperature treatment. A product flows into a micro-channel reactor F to be subjected to a thermal decomposition reaction, is cooled by a cooler G and then enters a three-phase separator H to be continuously separated, nitrogen is discharged after being subjected to spraying deacidification, a fluorine-containing aromatic hydrocarbon crude product is subjected to continuous alkali washing, continuous drying and continuous rectification to obtain a fluorine-containing aromatic hydrocarbon finished product, and a hydrofluoric acid and sulfuric acid mixture is subjected to continuous distillation to obtain a product. The hydrogen fluoride and sulfuric acid are obtained. The full continuous flow synthesis process has the advantages of high reaction yield, excellent product quality, good production safety, less pollutant discharge and the like.
Catalytic Hydrogenolysis of Aryl C-F Bonds Using a Bimetallic Rhodium-Indium Complex
Moore, James T.,Lu, Connie C.
supporting information, p. 11641 - 11646 (2020/07/27)
A homogeneous rhodium-indium catalyst hydrodefluorinates substrates bearing strong aryl C-F bonds, including difluoro- and fluorobenzene, using 1 atm of H2, alkoxide bases, and moderate temperatures (70-90 °C). Characterization of catalytic intermediates establishes a formal Rh-I/RhI redox cycle. The Rh → In interaction is proposed to enable catalysis by stabilizing the reactive Rh-I species, which is responsible for cleaving the Ar-F bond and is ultimately regenerated using H2 and base.
Fluorination of arylboronic esters enabled by bismuth redox catalysis
Planas, Oriol,Wang, Feng,Leutzsch, Markus,Cornella, Josep
, p. 313 - 317 (2020/01/28)
Bismuth catalysis has traditionally relied on the Lewis acidic properties of the element in a fixed oxidation state. In this paper, we report a series of bismuth complexes that can undergo oxidative addition, reductive elimination, and transmetallation in a manner akin to transition metals. Rational ligand optimization featuring a sulfoximine moiety produced an active catalyst for the fluorination of aryl boronic esters through a bismuth (III)/bismuth (V) redox cycle. Crystallographic characterization of the different bismuth species involved, together with a mechanistic investigation of the carbonfluorine bond-forming event, identified the crucial features that were combined to implement the full catalytic cycle.
Expanding the Balz–Schiemann Reaction: Organotrifluoroborates Serve as Competent Sources of Fluoride Ion for Fluoro-Dediazoniation
Mohy El Dine, Tharwat,Sadek, Omar,Gras, Emmanuel,Perrin, David M.
supporting information, p. 14933 - 14937 (2018/09/25)
The Balz–Schiemann reaction endures as a method for the preparation of (hetero)aryl fluorides yet is eschewed due to the need for harsh conditions or high temperatures along with the need to isolate potentially explosive diazonium salts. In a departure from these conditions, we show that various organotrifluoroborates (RBF3?s) may serve as fluoride ion sources for solution-phase fluoro-dediazoniation in organic solvents under mild conditions. This methodology was successfully extended to a one-pot process obviating aryl diazonium salt isolation. Sterically hindered (hetero)anilines are fluorinated under unprecedentedly mild conditions in good-to-excellent yields. Taken together, this work expands the repertoire of RBF3?s to act as fluorine ion sources in an update to the classic Balz–Schiemann reaction.
Mechanochemical Activation of Zinc and Application to Negishi Cross-Coupling
Cao, Qun,Howard, Joseph L.,Wheatley, Emilie,Browne, Duncan L.
supporting information, p. 11339 - 11343 (2018/08/28)
A form independent activation of zinc, concomitant generation of organozinc species and engagement in a Negishi cross-coupling reaction via mechanochemical methods is reported. The reported method exhibits a broad substrate scope for both C(sp3)–C(sp2) and C(sp2)–C(sp2) couplings and is tolerant to many important functional groups. The method may offer broad reaching opportunities for the in situ generation organometallic compounds from base metals and their concomitant engagement in synthetic reactions via mechanochemical methods.
Preparation method of o-fluorotobuene
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Paragraph 0016-0020; 0021-0025; 0026-0030, (2018/09/21)
The invention discloses a preparation method of o-fluorotobuene. The method comprises the following steps: (1) acid formation reaction: adding an anhydrous hydrogen fluoride raw material into a reaction kettle and stirring; adding sodium nitrite into the reaction kettle, introducing frozen salt water to cool and carrying out reaction to obtain a nitrous acid; (2) diazotization reaction: adding o-toluidine into the reaction kettle containing the nitrous acid, stirring and carrying out the diazotization reaction; (3) thermal decomposition reaction: transferring diazonium liquid obtained in the step (2) into a tubular reactor; heating and carrying out the thermal decomposition reaction to obtain an o-fluorotobuene crude product; (4) post-treatment: carrying out washing and steam distillation on the o-fluorotobuene crude product obtained in the step (3), regulating a pH value, pressing into a rectifying tower for distillation to obtain the qualified o-fluorotobuene. The preparation method disclosed by the invention has the beneficial effects that energy consumption is low, continuous production is realized, the problems of long production period of fluorination reaction and low yield of products are solved, the occurrence of side reaction is reduced, and a good foundation is laid for preparing high-purity o-fluorotobuene.
Crystal Structures of Diaryliodonium Fluorides and Their Implications for Fluorination Mechanisms
Lee, Yong-Sok,Chun, Joong-Hyun,Hodo??ek, Milan,Pike, Victor W.
, p. 4353 - 4363 (2017/04/03)
The radiofluorination of diaryliodonium salts is of value for producing radiotracers for positron emission tomography. We report crystal structures for two diaryliodonium fluorides. Whereas diphenyliodonium fluoride (1 a) exists as a tetramer bridged by four fluoride ions, 2-methylphenyl(phenyl)iodonium fluoride (2 a) forms a fluoride-bridged dimer that is further halogen bonded to two other monomers. We discuss the topological relationships between the two and their implications for fluorination in solution. Both radiofluorination and NMR spectroscopy show that thermolysis of 2 a gives 2-fluorotoluene and fluorobenzene in a 2 to 1 ratio that is in good agreement with the ratio observed from the radiofluorination of 2-methylphenyl(phenyl)iodonium chloride (2 b). The constancy of the product ratio affirms that the fluorinations occur via the same two rapidly interconverting transition states whose energy difference dictates chemoselectivity. From quantum chemical studies with density functional theory we attribute the “ortho-effect” to the favorable electrostatic interaction between the incoming fluoride and the o-methyl in the transition state. By utilizing the crystal structures of 1 a and 2 a, the mechanisms of fluoroarene formation from diaryliodonium fluorides in their monomeric, homodimeric, heterodimeric, and tetrameric states were also investigated. We propose that oligomerization energy dictates whether the fluorination occurs through a monomeric or an oligomeric pathway.
Synthetic method for flurazepam drug intermediate o-fluorotoluene
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Paragraph 0008; 0018-0020, (2017/03/17)
The invention discloses a synthetic method for a flurazepam drug intermediate o-fluorotoluene. The method comprises the following steps: (i) in a reaction container equipped with a stirrer, a temperature meter and a drop funnel, adding 200-230ml of a strong phosphoric acid solution, cooling the solution to 15-20 DEG C, adding 1.2mol of o-toluidine, after o-toluidine is completely dissolved, cooling the solution to 5-9 DEG C, adding 1.2-1.25mol of potassium nitrite to be dissolved in the solution, controlling the reaction temperature to be 5-8 DEG C, measuring a reaction termination point by using potassium iodide test paper, and obtaining diazonium salt; and (ii) cooling 1.4mol of a sodium fluoride solution to 3-5 DEG C, adding a diazonium salt solution generated in the step (i), stirring for 6-9 minutes, performing suction filtration, washing a filter cake with a phosphoric acid solution, a washing solvent and a neutral solution in sequence, drying in vacuum to obtain fluorine-containing diazonium salt (3), heating the fluorine-containing diazonium salt to 90-98 DEG C for decomposing the fluorine-containing diazonium salt, collecting distillate, washing the distillate with a potassium carbonate solution and a salt solution in sequence, drying by a dehydrating agent, performing low-pressure distillation, and collecting cut fraction with the temperature of 103-110 DEG C to obtain a colorless liquid o-fluorotoluene.
Reactions of aromatic compounds with xenon difluoride
Bardin,Adonin, N. Yu.
, p. 1400 - 1407 (2016/11/29)
Reactions of substituted benzenes C6H5R (R = Me, F, Cl, Br, CF3, NO2) with xenon difluoride in the presence of boron trifluoride–diethyl ether complex in weakly acidic (1,1,1,3,3-pentafluorobutane) and weakly basic media (acetonitrile) have been studied. These reactions lead to the formation of fluorobenzene derivatives FC6H4R (isomer mixture) together with isomeric difluorobenzenes and fluorinated and non-fluorinated biphenyls. The results have been compared with previously reported data obtained in other solvents using other catalysts.
Copper-Mediated Oxidative Fluorination of Aryl Stannanes with Fluoride
Gamache, Raymond F.,Waldmann, Christopher,Murphy, Jennifer M.
supporting information, p. 4522 - 4525 (2016/09/28)
A regiospecific method for the oxidative fluorination of aryl stannanes using tetrabutylammonium triphenyldifluorosilicate (TBAT) and copper(II) triflate is described. This reaction is robust, uses readily available reagents, and proceeds via a stepwise protocol under mild conditions (60 °C, 3.2 h). Broad functional group tolerance, including arenes containing protic and nucleophilic groups, is demonstrated.
