cas 95-52-3, 2-Fluorotoluene | Articles data

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Full continuous flow synthesis process of fluorine-containing aromatic hydrocarbon compounds
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.
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Paragraph 0095-0108

(2021/04/07)

Catalytic Hydrogenolysis of Aryl C-F Bonds Using a Bimetallic Rhodium-Indium Complex
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.
Moore, James T.,Lu, Connie C.
supporting information
p. 11641 - 11646
(2020/07/27)

Fluorination of arylboronic esters enabled by bismuth redox catalysis
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.
Planas, Oriol,Wang, Feng,Leutzsch, Markus,Cornella, Josep
p. 313 - 317
(2020/01/28)

Mechanochemical Activation of Zinc and Application to Negishi Cross-Coupling
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.
Cao, Qun,Howard, Joseph L.,Wheatley, Emilie,Browne, Duncan L.
supporting information
p. 11339 - 11343
(2018/08/28)

Expanding the Balz–Schiemann Reaction: Organotrifluoroborates Serve as Competent Sources of Fluoride Ion for Fluoro-Dediazoniation
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.
Mohy El Dine, Tharwat,Sadek, Omar,Gras, Emmanuel,Perrin, David M.
supporting information
p. 14933 - 14937
(2018/09/25)

Crystal Structures of Diaryliodonium Fluorides and Their Implications for Fluorination Mechanisms
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.
Lee, Yong-Sok,Chun, Joong-Hyun,Hodo??ek, Milan,Pike, Victor W.
p. 4353 - 4363
(2017/04/03)

Preparation method of o-fluorotobuene
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.
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Paragraph 0016-0020; 0021-0025; 0026-0030

(2018/09/21)

Reactions of aromatic compounds with xenon difluoride
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.
Bardin,Adonin, N. Yu.
p. 1400 - 1407
(2016/11/29)

Copper-Mediated Oxidative Fluorination of Aryl Stannanes with Fluoride
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.
Gamache, Raymond F.,Waldmann, Christopher,Murphy, Jennifer M.
supporting information
p. 4522 - 4525
(2016/09/28)

Synthetic method for flurazepam drug intermediate o-fluorotoluene
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.
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Paragraph 0008; 0018-0020

(2017/03/17)

Fluorination of aromatic compounds with xenon difluoride in the presence of boron trifluoride etherate
Fluorination of benzene with the XeF2 - BF3?Et2O system in acetonitrile at low temperatures affords fluorobenzene in 18% yield, the conversion of benzene being 92%. The rest products are di-, tri-, tetra-, and polyphenyls with different fluorination pattern. Toluene and chloro- and bromobenzenes are fluorinated predominantly at the ortho and para positions. Fluorination of 4-nitroanisole affords 2-fluoro-4-nitroanisole in 73% yield.
Fedorov,Zubarev,Mortikov, V. Yu.,Rodinovskaya,Shestopalov
p. 1049 - 1052
(2016/02/09)

Synthesis of aryl fluorides from potassium aryltrifluoroborates and selectfluor mediated by iron(III) chloride
The synthesis of fluorinated arenes by the iron-mediated fluorination of potassium aryltrifluoroborates with Selectfluor and potassium fluoride is described. The fluorination reaction uses commercially available reagents and without requiring the addition
Dubbaka, Srinivas Reddy,Gadde, Satyanarayana,Narreddula, Venkateswara Reddy
p. 854 - 860
(2015/03/14)

FLUORINATION OF ARYL COMPOUNDS
The invention provides compositions and methods of using the compositions in fluorinating aryl precursors containing a leaving group replaceable by a fluorine atom. The compositions include a metal ion source, a electrophilic fluorine source, a base, and a compound, which is an aryl precursor of the aryl fluoride, and which has a leaving group replaceable by the fluorine atom. Exemplary methods of the invention make use of such compositions and methods to prepare an aryl fluoride compound. In an exemplary embodiment, the electrophilic fluorine source is a source of 18F.
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Paragraph 00117; 00118-00121; 00123

(2014/07/22)

Silver-mediated fluorination of potassium aryltrifluoroborates with Selectfluor Dedicated to Professor Andrea Vasella on the occasion of his 71st birthday
A simple and practical procedure for the silver-mediated fluorination of aryl- and heteroaryltrifluoroborates with electrophilic fluorine from Selectfluor and LiOH·H2O is presented. The reaction procedure is simple and easy to set up, the process produces fluorinated arenes and heteroarenes in good to excellent yields and a wide range of electronically and structurally diverse substrates are tolerated.
Dubbaka, Srinivas Reddy,Narreddula, Venkateswara Reddy,Gadde, Satyanarayana,Mathew, Thresen
p. 9676 - 9681
(2015/01/08)

Direct fluorination of cyclic carbonates and closo-K2[B 12H12] in a slug-flow ministructured reactor
A novel minireactor for direct fluorination of organic and inorganic substances was tested. The reactor consists of nickel-coated copper blocks with mechanically machined 1 mm channels and is equipped with an active cooling system. The direct fluorination of ethylene carbonate and propylene carbonate is described. For the fluorinated propylene carbonate, the NMR data of various fluorinated isomers were determined. The Gibbs reaction energies for the direct fluorination of ethylene and propylene carbonate were calculated at the reliable G3 level of theory. The excellent decomposition stability of the cyclic carbonates against high fluorine and HF concentrations also qualifies them as good solvents for direct fluorination processes, especially for ionic substrates. In this respect, the direct fluorination of the inorganic salt closo-K2[B12H12] in cyclic carbonates is presented.
Hill, Mathias,Baron, Patrick,Cobry, Keith,Goll, Sascha K.,Lang, Philipp,Knapp, Carsten,Scherer, Harald,Woias, Peter,Zhang, Pengcheng,Krossing, Ingo
p. 292 - 301
(2013/08/23)

Mild copper-mediated fluorination of aryl stannanes and aryl trifluoroborates
This communication describes a mild copper-mediated fluorination of aryl stannanes and aryl trifluoroborates with N-fluoro-2,4,6-trimethylpyridinium triflate. This protocol demonstrates broad substrate scope and functional group tolerance, and does not require the use of any noble metal additives. The reaction is proposed to proceed via an arylcopper(III) fluoride intermediate.
Ye, Yingda,Sanford, Melanie S.
supporting information
p. 4648 - 4651
(2013/05/09)

Cu(OTf)2-mediated fluorination of aryltrifluoroborates with potassium fluoride
This Communication describes the Cu(OTf)2-mediated fluorination of aryltrifluoroborates with KF. The reaction proceeds under mild conditions (at 60 C over 20 h) and shows a broad substrate scope and functional group tolerance. The Cu is proposed to play two separate roles in this transformation: (1) as a mediator for the aryl-F coupling and (2) as an oxidant for accessing a proposed CuIII(aryl)(F) intermediate.
Ye, Yingda,Schimler, Sydonie D.,Hanley, Patrick S.,Sanford, Melanie S.
supporting information
p. 16292 - 16295
(2013/12/04)

Copper-mediated fluorination of arylboronate esters. Identification of a Copper(III) fluoride complex
A method for the direct conversion of arylboronate esters to aryl fluorides under mild conditions with readily available reagents is reported. Tandem reactions have also been developed for the fluorination of arenes and aryl bromides through arylboronate ester intermediates. Mechanistic studies suggest that this fluorination reaction occurs through facile oxidation of Cu(I) to Cu(III), followed by rate-limiting transmetalation of a bound arylboronate to Cu(III). Fast C-F reductive elimination is proposed to occur from an aryl-copper(III)-fluoride complex. Cu(III) intermediates have been generated independently and identified by NMR spectroscopy and ESI-MS.
Fier, Patrick S.,Luo, Jingwei,Hartwig, John F.
supporting information
p. 2552 - 2559
(2013/03/29)

Continuous flow reactor for Balz-Schiemann reaction: A new procedure for the preparation of aromatic fluorides
A facile and highly efficient procedure for the preparation of aromatic fluorides by Balz-Schiemann reaction via two continuous flow reactors has been set up. The continuous diazotization reactor was run at about 25 °C with residence times of 10-20 s, and the continuous fluorodediazoniation reactor was performed with a residence time of 1 min in high yields. The reaction times can be greatly reduced by increasing temperature and thereby taking advantage of superior mass and heat transfer of a continuous flow system.
Yu, Zhi-Qun,Lv, Yan-Wen,Yu, Chuan-Ming,Su, Wei-Ke
p. 1261 - 1263
(2013/03/14)

A convenient synthesis of N,N-bis(trifluoromethyl)anilines
A convenient synthesis of N,N-bis(trifluoromethyl)anilines by means of dediazotation reactions of previously unknown aryldiazoniumbis(trifluoromethyl) imides in the presence of CuI salts are described. Properties and applications of N,N-bis(trifluoromethyl)anilines in syntheses of aromatic compounds containing the (CF3)2N group are presented.
Hirschberg,Ignat'Ev,Wenda,Frohn,Willner
body text
p. 176 - 182
(2012/03/27)

Synthesis of 1H-indazole: A combination of experimental and theoretical studies
A new practical synthesis of 1H-indazole is presented. A previous mechanism for the cyclization step is proved to be nonfeasible and a hydrogen bond propelled mechanism is proposed. The new mechanism is suitable for similar cyclization, and a new reaction is predicted. Springer Science+Business Media B.V. 2012.
Chen, Xinzhi,Zhou, Shaodong,Qian, Chao,He, Chaohong
p. 1619 - 1628
(2012/10/30)

Copper-mediated fluorination of aryl iodides
The synthesis of aryl fluorides has been studied intensively because of the importance of aryl fluorides in pharmaceuticals, agrochemicals, and materials. The stability, reactivity, and biological properties of aryl fluorides can be distinct from those of the corresponding arenes. Methods for the synthesis of aryl fluorides, however, are limited. We report the conversion of a diverse set of aryl iodides to the corresponding aryl fluorides. This reaction occurs with a cationic copper reagent and silver fluoride. Preliminary results suggest this reaction is enabled by a facile reductive elimination from a cationic arylcopper(III) fluoride.
Fier, Patrick S.,Hartwig, John F.
supporting information; experimental part
p. 10795 - 10798
(2012/08/07)

FLUORINATION OF ORGANIC COMPOUNDS
Methods for fluorinating organic compounds are described herein.
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Page/Page column 25

(2012/11/06)

Mechanistic and computational studies of oxidatively-induced Aryl-CF 3 bond-formation at Pd: Rational design of room temperature aryl trifluoromethylation
This article describes the rational design of first generation systems for oxidatively induced Aryl-CF3 bond-forming reductive elimination from PdII. Treatment of (dtbpy)PdII(Aryl)(CF3) (dtbpy = di-tert-butylbipyridine) with NFTPT (N-fluoro-1,3,5-trimethylpyridinium triflate) afforded the isolable PdIV intermediate (dtbpy)Pd IV(Aryl)(CF3)(F)(OTf). Thermolysis of this complex at 80 °C resulted in Aryl-CF3 bond-formation. Detailed experimental and computational mechanistic studies have been conducted to gain insights into the key reductive elimination step. Reductive elimination from this PdIV species proceeds via pre-equilibrium dissociation of TfO- followed by Aryl-CF3 coupling. DFT calculations reveal that the transition state for Aryl-CF3 bond formation involves the CF3 acting as an electrophile with the Aryl ligand serving as a nucleophilic coupling partner. These mechanistic considerations along with DFT calculations have facilitated the design of a second generation system utilizing the tmeda (N,N,N′,N′-tetramethylethylenediamine) ligand in place of dtbpy. The tmeda complexes undergo oxidative trifluoromethylation at room temperature.
Ball, Nicholas D.,Gary, J. Brannon,Ye, Yingda,Sanford, Melanie S.
supporting information; experimental part
p. 7577 - 7584
(2011/06/25)

Deoxyfluorination of phenols
An operationally simple ipso fluorination of phenols with a new deoxyfluorination reagent is presented.
Tang, Pingping,Wang, Weike,Ritter, Tobias
supporting information; experimental part
p. 11482 - 11484
(2011/10/02)

Process for the Synthesis of Highly Active Binary Metal Fluoride as a Fluorinating Agent for Aromatics
The subject invention relates to a process for the synthesis of highly active binary metal fluoride system for the fluorination of aromatic compounds. Fluorinated aromatic compounds are valuable synthons for the chemical synthesis of pharmaceutical drugs and novel polymers. Fluorobenzene is used to control carbon content in steel manufacturing, is an intermediate for pharmaceuticals, pesticides and other organic compounds. Fluorobenzene is typically produced by the reaction of aniline and sodium nitrite in the presence of hydrogen fluoride. The present invention relates to a process for the synthesis of highly active binary metal fluoride system consists of copper (II) fluoride and aluminum (III) fluoride for the fluorination of aromatic compounds in gas phase and recycling of the reagent, in situ, using O2 and HF.
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Page/Page column 6-7

(2010/02/17)

Efficient synthesis of aryl fluorides
Chemical Equation Presented Creating C-F bonds: A novel electrophilic fluorination of aryl and heteroaryl Crignard reagents has been discovered and was used for the efficient synthesis of various aryl fluoride derivatives (see picture; THF = tetrahydrofuran).
Anbarasan, Pazhamalai,Neumann, Helfried,Beller, Matthias
experimental part
p. 2219 - 2222
(2010/06/17)

Formation of arf from lpdar(f): catalytic conversion of aryl triflates to aryl fluorides
Despite increasing pharmaceutical importance, fluorinated aromatic organic molecules remain difficult to synthesize. Present methods require either harsh reaction conditions or highly specialized reagents, making the preparation of complex fluoroarenes ch
Watson, Donald A.,Su, Mingjuan,Teverovskiy, Georgiy,Zhang, Yong,Garcia-Fortanet, Jorge,Kinzel, Tom,Buchwaldf, Stephen L.
scheme or table
p. 1661 - 1664
(2010/06/16)

PROCESS FOR THE PREPARATION OF PHARMACEUTICAL INTERMEDIATES
The invention relates to a process for the preparation of cyclopropyl benzyl ketone compounds of formula (II) wherein R1 represents fluorine or chlorine atom or C1-4 alkoxy group, by the reaction of a Grignard reagent, obtained from the reaction of compound of formula (V), wherein X represents chlorine or fluorine atom, with the compound of formula (IV), wherein R2 represents C1-4 alkyl group, having a straight or branched chain. The process can be applied preferably on industrial scale. Compound of formula (II), wherein R represents a fluorine atom in position 2 is an intermediate of the preparation process of prasugrel, which is a platelet inhibitor used in the therapy.
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Page/Page column 14

(2009/07/03)

Method for separating substances
An objective of the present invention is to provide electrophoretic separation methods and devices that enable the various features of a substrate surface that comes in contact with an electrophoresis medium to be controlled. The present invention provides methods for electrophoresing substances, which comprises the steps of: (a) adding a substance to be analyzed to an electrophoresis medium retained in a substrate, whose surface that has come in contact with the electrophoresis medium has been coated with a polymer membrane; and (b) adding electrophoretic pressure to the electrophoresis medium. For example, the use of a plasma-polymerized membrane allows the formation of a membrane with homogeneous quality and thickness on the surface of an arbitrary shape. In addition, desired characteristics can be conferred on the surface through selection of monomeric substances. Protein adsorption onto micro-chips can be effectively prevented as well.
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(2008/06/13)

New practical synthesis of indazoles via condensation of o-fluorobenzaldehydes and their O-methyloximes with hydrazine
The reaction of o-fluorobenzaldehydes and their O-methyloximes with hydrazine has been developed as a new practical synthesis of indazoles. Utilization of the methyloxime derivatives of benzaldehydes (in the form of the major E-isomers) in this condensation effectively eliminated a competitive Wolf-Kishner reduction to fluorotoluenes, which was observed in the direct preparations of indazoles from aldehydes. Reaction of Z-isomers of methyloximes with hydrazine resulted in the formation of 3-aminoindazoles via a benzonitrile intermediate.
Lukin, Kirill,Hsu, Margaret C.,Fernando, Dilinie,Leanna, M. Robert
p. 8166 - 8172
(2007/10/03)

Oxidative fluorination of aromatic derivatives by copper (II) fluoride and silver (I) fluoride
The subject invention provides methods of fluorinating an aromatic or chloroaromatic compound comprising combining an aromatic compound, a chloroaromatic compound, a mixture of aromatic compounds, a mixture of chloroaromatic compounds, or a mixture of chloroaromatic and aromatic compounds and a fluorinating composition comprising at least one active fluorinating agent selected from the group consisting of CuF2, AgF, HgF2, TeF4, MnF4, FeF3, and CoF2-4 and at least one support selected from the group consisting of activated carbon, ZnF2, CaF2, MgF2, AIF3, and combinations of activated carbon, ZnF2, CaF2, MgF2, or AlF3.
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Page/Page column 5

(2008/06/13)

Microwave fluorination: A novel, rapid approach to fluorination with Selectfluor
Fluorination of electron rich aromatic systems with electrophilic fluorination reagents such as Selectfluor and Accufluor is a well-established process. Herein we report results from investigations into the use of such procedures to perform rapid, small-scale fluorinations under microwave irradiation. We have investigated the transformation with a range of different substrates and discuss the effects of two key factors, namely reaction time and choice of fluorination reagent. The use of Selectfluor in acetonitrile at 150°C with microwave heating for 10 min affords products in comparable yields to those obtained by prolonged heating in acetonitrile at its reflux temperature.
Bluck, Gavin W.,Carter, Neil B.,Smith, Stephen C.,Turnbull, Michael D.
p. 1873 - 1877
(2007/10/03)

Flash vacuum pyrolysis over magnesium. Part 1 - Pyrolysis of benzylic, other aryl/alkyl and aliphatic halides
Flash vacuum pyrolysis over a bed of freshly sublimed magnesium on glass wool results in efficient coupling of benzyl halides to give the corresponding bibenzyls. Where an ortho halogen substituent is present further dehalogenation gives some dihydroanthracene and anthracene. Efficient coupling is also observed for halomethylnaphthalenes and halodiphenylmethanes while chlorotriphenylmethane gives 4,4′-bis(diphenylmethyl)biphenyl. By using α,α′-dihalo-o-xylenes, benzocyclobutenes are obtained in good yield, while the isomeric α,α′-dihalo-p-xylenes give a range of high thermal stability polymers by polymerisation of the initially formed p-xylylenes. Other haloalkylbenzenes undergo largely dehydrohalogenation where this is possible, in some cases resulting in cyclisation. Deoxygenation is also observed with haloalkyl phenyl ketones to give phenylalkynes as well as other products. With simple alkyl halides there is efficient elimination of HCl or HBr to give alkenes. For aliphatic dihalides this also occurs to give dienes but there is also cyclisation to give cycloalkanes and dehalogenation with hydrogen atom transfer to give alkenes in some cases. For 5-bromopent-1-ene the products are those expected from a radical pathway but for 6-bromohex-1-ene they are clearly not. For 2,2-dichloropropane and 1,1-dichloropropane elimination of HCl occurs but for 1,1-dichlorobutane, -pentane and -hexane partial hydrolysis followed by elimination of HCl gives E, E-, E,Z- and Z,Z- isomers of the dialk-1-enyl ethers and fully assigned 13C NMR data are presented for these. With 6-chlorohex-1-yne and 7-chlorohept-1-yne there is cyclisation to give methylenecycloalkanes and -cycloalkynes. The behaviour of 1,2-dibromocyclohexane and 1,2-dichlorocyclooctane under these conditions is also examined. Various pieces of evidence are presented that suggest that these processes do not involve generation of free gas-phase radicals but rather surface-adsorbed organometallic species.
Aitken, R. Alan,Hodgson, Philip K.G.,Morrison, John J.,Oyewale, Adebayo O.
p. 402 - 415
(2007/10/03)

Preparation process of fluorine substituted aromatic compound
A preparation process of a fluorine substituted aromatic compound comprising reacting an alkali metal or alkali earth metal salt of an aromatic compound having a hydroxy group with an organic fluorinating agent is disclosed. As a representative fluorinating agent, a bis-dialkylamino-difluoromethane compound, for example, 2,2′-difluoro-1,3-dimethylimidazolidine, is exemplified. According to the process, an industrially useful fluorinated aromatic compound, for example, a fluorobenzene, a fluorine substituted benzophenone, a fluorine substituted diarylsulfone can be prepared with ease in economy without specific equipment.
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(2008/06/13)

Fluorodediazoniation in ionic liquid solvents: New life for the Balz-Schiemann reaction
Drawbacks associated with the classic Balz-Schiemann reaction are eliminated in a series of examples by conducting fluorodediazoniation in ionic liquid solvents, thus opening up a new horizon for a much in demand process.
Laali, Kenneth K.,Gettwert, Volker J.
p. 31 - 34
(2007/10/03)

Direct fluorination of toluene using elemental fluorine in gas/liquid microreactors
Direct fluorination of toluene, pure or dissolved in either acetonitrile or methanol, using elemental fluorine was investigated in gas/liquid microreactors, namely a falling film microreactor and a micro bubble column. The experiments included measurements at high substrate concentrations and at high fluorine contents diluted in a nitrogen carrier gas, e.g. up to 50vol.% fluorine. Results obtained were compared to the performance of a laboratory bubble column which served as a technological benchmark. Due to the formation of liquid layers of only a few tens of micrometers thickness, the microreactors provide very large interfacial areas, e.g. up to 40,000m2/m3. These values exceed by far those of the laboratory bubble column as well as all other devices applied in practice. The potential for enhancing mass and heat transfer was verified by several experiments resulting in an increase in conversion and selectivity for the microreactors compared to the laboratory benchmark. For the falling film microreactor, yields of up to 28% of monofluorinated ortho and para products for a degree of toluene conversion of 76% were obtained. These values are of the same order as described for the industrially applied Schiemann process. Space-time yields of the microreactors, when referred to the reaction channel volume, were orders of magnitude higher than those of the laboratory bubble column. Taking into account the construction material needed, the corresponding figures of merit, for an idealized geometry as well as the existing total reactor geometry, still indicate technological and economic benefits. A variation of operating conditions for the direct fluorination revealed that conversion can be increased in the microreactors by using higher fluorine-to-toluene ratios and reaction temperatures. The choice of solvent is also essential, with acetonitrile yielding much better results than methanol.
J?hnisch,Baerns,Hessel,Ehrfeld,Haverkamp,L?we,Wille,Guber
p. 117 - 128
(2007/10/03)

Electrophilic fluorination of aromatics with selectfluor and trifluoromethanesulfonic acid 1
1-(chloromethyl)-4-fluoro-1,4-diazabicyclo[2.2.2]octane bis (tetrafluoroborate) [Selectfluor F-TEDA-BF4 (TEDA = triethylenediamine)] in the presence of trifluoromethanesulfonic acid has been found to be a very effective reagent system for the direct electrophilic fluorination of a wide variety of aromatic compounds under mild reaction conditions to the corresponding fluoroaromatics in good to excellent yields.
Shamma, Tatyana,Buchholz, Herwig,Prakash, G. K. Surya,Olah, George A.
p. 207 - 210
(2007/10/03)

The synthesis of [18F]fluoroarenes from the reaction of cyclotron-produced [18F]fluoride ion with diaryliodonium salts
Diaryliodonium salts have been shown to react with fluoride ion at 80°C in acetonitrile to generate aryl fluorides. The regioselectivity is controlled electronically and by the bulk of the ortho-substituents on the rings, with the latter the dominant factor such that electron-rich rings can be fluorinated. ortho-Substituted aryl fluorides can be selectively produced from unsymmetrical diaryliodonium salts. The process has been used to synthesise [18F] labelled aromatics by the use of cyclotron generated [18F]fluoride ion.
Shah, Aneela,Pike, Victor W.,Widdowson, David A.
p. 2043 - 2046
(2007/10/03)

Deaminative Fluorination of Anilines with Silicon Tetrafluoride: Utility of Silicon Tetrafluoride as a Fluorine Source
Application of silicon tetrafluoride to deaminative fluorination of anilines as a fluorine source is investigated. A diazotization of anilines proceeds with silicon tetrafluoride and tbutyl nitrite under mild condition and the following fluorodediazoniation affords fluoroarenes in good yields.
Tamura, Masanori,Shibakami, Motonari,Sekiya, Akira
p. 725 - 727
(2007/10/03)

Dehalogenation of organic halides by flash vacuum pyrolysis over magnesium: A versatile synthetic method
Flash vacuum pyrolysis over magnesium at 600°C results in efficient dehalogenation of a variety of organic halides and provides a preparatively useful method for C-C bond formation and other reactions.
Aitken, R. Alan,Hodgson, Philip K. G.,Oyewale, Adebayo O.,Morrison, John J.
p. 1163 - 1164
(2007/10/03)

Hydrogen atom attack on fluorotoluenes: Rates of fluorine displacement
Rates of hydrogen atom attack on o-fluorotoluene (o-FTOL) and m-fluorotoluene (m-FTOL) at temperatures of 988-1144 K and pressures of 2-2.5 bar have been determined in a single-pulse shock tube study. Hydrogen atoms, generated from the decomposition of hexamethylethane, were allowed to react with the substrates and the characteristic products observed. Rate constants for two reaction channels, displacement of fluorine or methyl, were determined relative to displacement of methyl from 1,3,5-trimethylbenzene (135TMB). Evidence is presented that abstraction of F is unimportant over the studied temperature range. With k(H + 135TMB → m-xylene + CH3) = 6.7 × 1013 exp(-3255/T) cm3 mol-1s-1, the following rate expressions have been derived: k(H + o-FTOL → C6H5CH3 + F) = 8.38 × 1013 exp(-6041/T) cm3 mol-1s-1; (1012-1142 K) k(H + o-FTOL → C6H5F + CH3) = 2.37 × 1013 exp(-2938/T) cm3 mol-1s-1; (988-1142 K) k(H + m-FTOL → C6H5CH3 + F) = 1.33 × 1014 exp(-6810/T) cm3 mol-1s-1; (1046-1144 K) k-(H + m-FTOL → C6H5F + CH3) = 2.04 × 1013 exp(-3104/T) cm3 mol-1s-1; (1008-1144 K) Uncertainties in the relative rate constants are estimated to be factors of about 1.1, while the above absolute values have estimated expanded uncertainties of about a factor of 1.4 in rate, 10 kJ mol-1 in the activation energy, and a factor of 3 in the A-factor. The present data are compared with relevant literature data. From our data and the thermochemistry, a model of the elementary steps comprising displacement of F is developed. On the basis of the model fit to our data, rate constants for the addition of atomic fluorine to toluene at 1100 K are derived. Rate expressions for fluorination reactions of toluene are also determined. The significance of the present results is discussed in the context of the formation of fluorinated byproducts in high-temperature systems.
Manion, Jeffrey A.,Tsang, Wing
p. 263 - 273
(2007/10/03)

Facile preparation of aromatic fluorides by deaminative fluorination of aminoarenes using hydrogen fluoride combined with bases
One-pot deaminative fluorination of aminoarenes including heteroaromatics, namely, diazotization of aminoarenes followed by in situ fluoro-dediazoniation of the corresponding diazonium ions, was successfully accomplished to produce fluoroarenes in high yields by using hydrogen fluoride combined with base solutions. The diazotization stage has been found to play the most important part in yielding fluoroarenes effectively. It was greatly influenced by the composition of the HF solution and enhanced by employing appropriate amounts of bases such as pyridine under carefully controlled conditions. The fluoro-dediazoniation stage was effectively accelerated photochemically to afford fluoroarenes having polar substituents such as hydroxyl, nitro and so on in high yields.
Yoneda,Fukuhara
p. 23 - 36
(2007/10/02)

Deaminative fluorination of anilines using potassium hydrogen fluoride and silicon tetrafluoride
It has been found that the combination of potassium hydrogen fluoride and silicon tetrafluoride works as an efficient fluorinating agent for the deaminative fluorination of anilines. A one-pot diazotization of anilines followed by fluoro-dediazoniation proceeds with this combination of the reagents and t-butyl nitrite to afford fluoroarenes.
Tamura, Masanori,Shibakami, Motonari,Kurosawa, Shigeru,Arimura, Takashi,Sekiya, Akira
p. 95 - 96
(2007/10/03)

Direct Formation of (Haloaryl)copper Nucleophiles from Haloiodobenzenes and Active Copper
(o-Halophenyl)-, (m-halophenyl)-, and (p-halophenyl)copper reagents have been formed in moderate to high yields at room temperature from active copper and the corresponding haloiodobenzenes.These reagents have been cross-coupled with a variety of alkyl and acyl halides to produce the respective haloarenes and haloaryl ketones.Remarkably, (o-fluorophenyl)- and (o-chlorophenyl)copper are produced in good yields by this procedure without undergoing elimination to form benzyne making this approach a convenient method for generating o-halophenyl nucleophiles.
Ebert, Greg W.,Pfennig, Deborah R.,Suchan, Scott D.,Donovan, Thomas A.,Aouad, Emmanuel,et al.
p. 2361 - 2364
(2007/10/02)

Liquid-phase fluorination of aromatic compounds by elemental fluorine
The fluorination of aromatic compounds (benzene, toluene, phenol and benzoic acid) by elemental fluorine diluted with nitrogen has been investigated in various solvents (Freon 11, chloroform, methanol, trifluoroacetic acid, 2,2,2-trifluoroethanol, water) in order to define the influence of the experimental conditions on the reaction.Experiments have been carried out by varying the temperature, the substrate concentration in solution, the molar ratio of fluorine to substrate, and the concentration of fluorine in the fluorine/nitrogen mixture.In all cases, the effects on the yield of fluorinated products were studied.Monofluorinated compounds were mainly found in the reaction mixture, the isomers formed being in accord with the mechanism for electrophilic substitution.The highest yield of monofluorinated products was obtained with polar solvents and the following order was found: CFCl3 CHCl3 CH3OH CF3CH2OH CF3COOH.Interesting results were also found using particular additives (for instance, KOH or C4F9SO3Na in methanol) or water as the solvent.A direct relationship was observed between the yield of monofluorinated compounds and the molar ratio of fluorine to substrate, which has to be less than one in order to obtain high yields.In contrast, low selectivity, expressed as the yield ratio of ortho to para (or meta) isomers, was found. - Keywords: Fluorination; Aromatic compounds; Elemental fluorine; Isomer formation; Solvent effects; Additive effects
Conte, L.,Gambaretto, G. P.,Napoli, M.,Fraccaro, C.,Legnaro, E.
p. 175 - 180
(2007/10/02)

Remarkably stable ortho-halophenylcopper reagents
We wish to report the generation of remarkably stable o-halophenlycopper reagents at room temperature by the direct oxidative addition of activated copper to o-flouro-and o-choloriodobenzene. The reagents will undergo substitution reactions with suitable organic halides at 25°C.
Ebert, Greg W.,Pfennig, Deborah R.,Suchan, Scott D.,Donovan Jr., Thomas A.
p. 2279 - 2282
(2007/10/02)

Aryl fluoride syntheses involving reactions of aryllead triacetates with boron trifluoride-diethyl ether complex
Aryllead(IV) triacetates react at room temperature with BF3.Et2O to give the corresponding aryl fluoride in moderate to good yields; triarylboroxines, electron rich aryltrimethylsilanes and some arenes, which yield aryllead triacetates in acid catalysed reactions with lead tetraacetate, are converted directly into aryl fluorides when stirred with lead tetraacetate in BF3.Et2O. An investigation of the mechanism of the fluoro-deplumbation reaction indicates that it probably proceeds by acid catalysed heterolytic cleavage of the C-Pb bond to produce an aryl cation.
De Meio,Morgan,Pinhey
p. 8129 - 8138
(2007/10/02)

Site-Selective Fluorination of Organic Compounds Using 1-Alkyl-4-fluoro-1,4-diazabicyclooctane Salts (Selectfluor Reagents)
The new "N-F"-type electrophilic reagent family of 1-alkyl-4-fluoro-1,4-diazabicyclooctane salts (derived from elemental fluorine (F2) and 1-alkyl-1,4-diazabicyclooctane salts) has been found to be very effective for the fluorination of a wide variety of organic substrates.These include steroidal enol acetates and silyl enol ethers, phenyl-substituted olefins, sulfides bearing α-H atoms, certain carbanions, and mildly activated aromatic compounds.The products were obtained with good yields and regioselectivity under very mild reaction conditions.
Lal, G. Sankar
p. 2791 - 2796
(2007/10/02)

Facile conversion of arenediazonium salts to the corresponding fluoroarenes using boron trifluoride diethyl ether complex
The conversion of various arenediazonium salts 1 to the corresponding fluoroarenes 2 has been achieved in good yields under mild conditions in boron trifluoride diethyl ether complex.
Shinhama,Aki,Furuta,Minamikawa
p. 1577 - 1582
(2007/10/02)