Method for producing difluorovinyl group-containing compound

Abstract

To provide a method for producing a difluorovinyl group-containing compound in a simple and high-yield process.SOLUTION: An organic zinc compound is reacted with a halogenated difluorovinyl compound in the presence of a palladium catalyst to efficiently produce a difluorovinyl group-containing compound.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a method for producing a difluorovinyl group-containing compound. Difluorovinyl group-containing compounds are industrially useful compounds not only as functional materials such as crosslinking agents for fluororubbers, electrolyte membranes for fuel cells, and chemically amplified resist materials, but also as intermediates in the production of pharmaceuticals and agricultural chemicals. [Background technology]

[0002] As a method for producing a difluorovinyl group-containing compound, the Wittig reaction using a fluorohalomethane is known (for example, Non-Patent Document 1). The method of Non-Patent Document 1 has problems in that one equivalent of an organic phosphorus compound is by-produced as a waste product, and the yield is only moderate.

[0003] On the other hand, as a method for producing a difluorovinyl group-containing compound, a method is known in which a difluorovinyl organometallic compound is prepared and cross-coupled in the presence of a catalytic amount of a transition metal catalyst (e.g., Non-Patent Document 2). The method of Non-Patent Document 2 has a problem in that it is difficult to prepare and handle the thermally unstable difluorovinyl organometallic compound.

[0004] As a cross-coupling method using a transition metal catalyst, CF2=CHBr, a method is known in which an alkyne is reacted in the presence of a palladium catalyst, a copper catalyst, bis(pinacolato)diboron, and a base (for example, Non-Patent Document 3).

[0005] Furthermore, Non-Patent Document 4 and Non-Patent Document 5 are known as examples of cross-coupling by transition metal catalyst using CF2=CHI. In Non-Patent Document 4, in the cross-coupling with a (fluorine-containing) vinyl organometallic compound, a highly toxic organotin compound is used, and there is a problem that the yield is high, but when an organozinc compound is used, the yield decreases. In Non-Patent Document 5, the substrate is limited to an alkyne compound, and there is a problem that the yield is only moderate. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] DJ Burton et.al., J.Fluoro.Chem.,1983,23,339-357. [Non-Patent Document 2] J.Ichikawa et.al., J.Fluoro.Chem.,2015,170,29-37. [Non-Patent Document 3] W.Xu et.al.,Org.Lett.,2022,24,5884-5889. [Non-Patent Document 4] D.Lentz et.al.,Chem.Asian J.,2008,3,719-731. [Non-Patent Document 5] J. Normant et.al., J. Organomet. Chem., 1987, 328, 1-13. Summary of the Invention [Problem to be solved by the invention]

[0007] Therefore, an object of the present invention is to provide a method for producing a difluorovinyl group-containing compound simply and in high yield. [Means for solving the problem]

[0008] The present inventors have intensively investigated methods for producing difluorovinyl group-containing compounds and have found that difluorovinyl group-containing compounds can be efficiently obtained by reacting an organic zinc compound with a halogenated difluorovinyl compound in the presence of a palladium catalyst, thereby completing the present invention.

[0009] That is, the present invention relates to the following. [1] The following general formula (1) Ar1-ZnX1(1) (In formula (1), Ar1 represents a monovalent group of a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted fused polycyclic aromatic group. When Ar1 is a group having a substituent, it has one or more substituents selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, an alkyl group having 1 to 10 carbon atoms, a fluoroalkyl group having 1 to 10 carbon atoms containing one or more fluorine atoms, an alkenyl group having 1 to 10 carbon atoms, an acyl group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, a nitro group, and a cyano group. X1 represents a chlorine atom, a bromine atom, or an iodine atom.) in the presence of a palladium catalyst or a palladium catalyst and a copper(I) salt, The following general formula (2) CF2=CHX2(2) (In formula (2), X2 represents a chlorine atom, a bromine atom, or an iodine atom.) The present invention is characterized in that the halogenated difluorovinyl compound represented by the formula: The following general formula (3) Ar1-CH=CF2(3) (In formula (3), Ar1 represents a monovalent group of a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted fused polycyclic aromatic group. When Ar1 is a group having a substituent, it has one or more substituents selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, an alkyl group having 1 to 10 carbon atoms, a fluoroalkyl group having 1 to 10 carbon atoms containing one or more fluorine atoms, an alkenyl group having 1 to 10 carbon atoms, an acyl group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, a nitro group, and a cyano group. X1 represents a chlorine atom, a bromine atom, or an iodine atom.) A method for producing a difluorovinyl group-containing compound represented by the formula: [2] The method according to item [1], wherein X2 in general formula (2) is a bromine atom. [3] The method according to item [1], wherein Ar1 in the general formula (1) is a substituent selected from the group consisting of a phenyl group, a naphthyl group, a thienyl group, a furanyl group and a pyridinyl group, which optionally have one or more substituents selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group having 1 to 10 carbon atoms, a fluoroalkyl group having 1 to 10 carbon atoms and containing one or more fluorine atoms, an alkenyl group having 1 to 10 carbon atoms, an acyl group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, a nitro group and a cyano group. [4] The method according to item [1], wherein Ar1 in general formula (1) is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group having 1 to 10 carbon atoms, a fluoroalkyl group having 1 to 10 carbon atoms containing one or more fluorine atoms, an alkenyl group having 1 to 10 carbon atoms, an acyl group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, a substituent selected from the group consisting of a phenyl group, a naphthyl group, a thienyl group, a furanyl group and a pyridinyl group, which may have one or more substituents selected from the group consisting of a nitro group and a cyano group, and X2 in general formula (2) is a bromine atom. [5] A solvent having an amide bond is used in the reaction, Ar1 in general formula (1) is a substituent selected from the group consisting of a phenyl group, a naphthyl group, a thienyl group, a furanyl group and a pyridinyl group, which optionally have one or more substituents selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group having 1 to 10 carbon atoms, a fluoroalkyl group having 1 to 10 carbon atoms containing one or more fluorine atoms, an alkenyl group having 1 to 10 carbon atoms, an acyl group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, a nitro group and a cyano group; In the general formula (2), X2 is a bromine atom. The palladium catalyst may be triphenylphosphine, tri(o-tolyl)-phosphine, tri(m-tolyl)-phosphine, tri(p-tolyl)-phosphine, tri(2-furyl)phosphine, tri(2-thienyl)phosphine, tris(o-anisyl)phosphine, tris(p-anisyl)phosphine, tris(2,6-dimethoxyphenyl)phosphine, tris(4-fluorophenyl)phosphine, tris(pentafluorophenyl)phosphine, tris[3,5-bis(trifluoromethyl)phenyl]phosphine, cyclohexyldiphenylphosphine, dicyclohexylphenylphosphine, di-tert-butylphenylphosphine, tributylphosphine, trihexylphosphine, tri-n-octylphosphine, tricyclopentylphosphine, tricyclohexylphosphine, tri-tert-butylphosphine, 1,2-bis(diphenylphosphino)ethane, 1, 3-Bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,5-bis(diphenylphosphino)pentane, 1,6-bis(diphenylphosphino)hexane, 1,2-bis(diphenylphosphino)benzene, (±)-2,2´-bis(diphenylphosphino)-1,1´-binaphthyl, 1,8-bis(diphenylphosphino)naphthalene, bis[2-(diphenylphosphino)phenyl]ether, 4, a palladium catalyst coordinated with a phosphine selected from the group consisting of 5-bis(diphenylphosphino)-9,9-dimethylxanthene, 1,1'-bis(diphenylphosphino)ferrocene, 1,1'-bis(di-tert-butylphosphino)ferrocene, 1,1'-bis(dicyclohexylphosphino)ferrocene, 1,4-bis(di-tert-butylphosphino)butane, and 1,4-bis(dicyclohexylphosphino)butane; The method described in item [1]. [6] A difluorovinyl group-containing compound represented by the following formula (a), (b), or (c): [ka] [ka] [ka] Effect of the Invention

[0010] According to the present invention, a difluorovinyl group-containing compound useful as a functional material or a pharmaceutical / agricultural intermediate can be produced simply and in high yield. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] One aspect of the present invention relates to a method for producing a difluorovinyl group-containing compound. The respective terms and details are explained below.

[0012] <Organic zinc compounds> In the process for producing a difluorovinyl group-containing compound of the present invention, the organozinc compound represented by the above general formula (1) is necessary for the reaction to proceed in a good yield. Here, in the general formula (1), Ar1 represents a monovalent group of a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted condensed polycyclic aromatic group. Further, the substituted or unsubstituted aromatic hydrocarbon group represented by Ar1 may be a phenyl group (benzene ring). Examples of the substituted or unsubstituted aromatic heterocyclic group represented by Ar1 include heteroatom-containing aromatic rings containing at least one nitrogen atom, oxygen atom, or sulfur atom on the aromatic ring, such as a furyl group (furan ring), a pyrrolyl group (pyrrole ring), a thienyl group (thiophene ring), an imidazolyl group (imidazole ring), an oxazolyl group (oxazole ring), a thiazolyl group (thiazole ring), a pyridinyl group (pyridine ring), a pyrimidinyl group (pyrimidine ring), a pyrazinyl group (pyrazine ring), a pyridazinyl group (pyridazine ring), a quinolyl group (quinoline ring), an isoquinolinyl group (isoquinoline ring), an indolinyl group (indole ring), a benzothienyl group (benzothiophene ring), a benzofuryl group (benzofuran ring), a purinyl group (purine ring), and a 1,10-phenanthrolinyl group (1,10-phenanthroline ring). Examples of the substituted or unsubstituted fused polycyclic aromatic group represented by Ar1 include a naphthyl group (naphthalene ring), an anthracenyl group (anthracene ring), a tetracenyl group (tetracene ring), a pentacenyl group (pentacene ring), a heptacenyl group (heptacene ring), a phenanthrenyl group (phenanthrene ring), a pyrenyl group (pyrene ring), a chrysenyl group (chrysene ring), a triphenylenyl group (triphenylene ring), a perylenyl group (perylene ring), a corannulenyl group (corannulene ring), and a coronenyl group (coronene ring).

[0013] In the production method of the present invention, the metal contained in the organometallic reagent is preferably zinc, because of its high yield and high reactivity in the reaction for producing a difluorovinyl group-containing compound, and its low environmental and toxic concerns. When the metal is lithium or magnesium, the activity of the reaction in the present invention is too high, and the metal may react with the halogenated difluorovinyl compound or undergo metal exchange, resulting in a decrease in yield. When the metal (or typical element) is tin, silicon, or boron, the activity of the organometallic reagent is too low, and the yield may decrease. In addition, cadmium, tin, and mercury are not preferred from the viewpoint of environmental toxicity. In the production method of the present invention, the organozinc compound used may be one that has been prepared in advance or one that has been purchased, or one that has been prepared just before the reaction may be used as it is.

[0014] The method for preparing the organozinc compound is not limited to the following example, but may be, for example, ·Reaction of organic halides with zinc A method in which an organic halide or a hydrocarbon compound is reacted with an organolithium reagent at low temperature, followed by reaction with a zinc salt A method in which an organic halide is reacted with magnesium to prepare a Grignard reagent, and then the reagent is reacted with a zinc salt. A method in which an organic halide is reacted with magnesium to prepare a Grignard reagent, which is then reacted with a zinc salt ·How to react commercially available Grignard reagents with zinc salts - Reacting an organic halide with a turbo Grignard reagent and then reacting with a zinc salt ·Methods of zinc exchange with organic halides and other organozinc compounds etc.

[0015] Zinc that can be used when preparing an organic zinc compound using zinc is not limited to the following examples, but examples include zinc powder and Rieke (registered trademark) zinc. Among them, zinc powder is preferred because it is readily available and inexpensive.

[0016] Zinc salts that can be used when preparing an organic zinc compound using a zinc salt are not limited to the following examples, but include, for example, zinc acetate (II), bis(trifluoromethanesulfonyl)imide zinc (II), zinc dodecanoate (II), zinc naphthenate (II), zinc trifluoromethanesulfonate (II), bis(2,4-pentanedionato) zinc (II), dichloro(N,N,N',N'-tetramethylenediamine) zinc (II), zinc fluoride (II), zinc chloride (II), commercially available zinc chloride (II) organic solvent solution, zinc bromide (II), and zinc iodide (II). Among these, zinc chloride or zinc bromide is preferred because of its good availability and low cost.

[0017] In the production method of the present invention, the organozinc compound used may coexist with an inorganic salt, such as magnesium fluoride, magnesium chloride, magnesium bromide, magnesium iodide, lithium fluoride, lithium chloride, lithium bromide, lithium iodide, zinc fluoride, zinc chloride, zinc bromide, and zinc iodide. In the production method of the present invention, the concentration of the organic zinc compound is not particularly limited, but is preferably 0.01M to 2.0M, more preferably 0.1M to 1.5M, and more preferably 0.3M to 1.0M. If the concentration is too low, the reaction rate may decrease and a long reaction time may be required. If the concentration is too high, the organic zinc compound may be deactivated, resulting in a decrease in yield, and a large amount of salt may be precipitated, making the reaction difficult.

[0018] <Palladium catalyst> In the production method of the present invention, the palladium catalyst functions as a catalyst for the reaction. During the reaction, the palladium catalyst is considered to exist as a palladium complex coordinated with a ligand. Examples of the ligand include, but are not limited to, triphenylphosphine, tri(o-tolyl)-phosphine, tri(m-tolyl)-phosphine, tri(p-tolyl)-phosphine, tri(2-furyl)phosphine, tri(2-thienyl)phosphine, tris(o-anisyl)phosphine, tris(p-anisyl)phosphine, tris(2,6-dimethoxyphenyl)phosphine, tris(4-fluorophenyl)phosphine, tris(pentafluorophenyl)phosphine, and tris[3,5-bis(trifluoromethyl)phenyl]phosphine. , cyclohexyldiphenylphosphine, dicyclohexylphenylphosphine, di-tert-butylphenylphosphine, tributylphosphine, trihexylphosphine, tri-n-octylphosphine, tricyclopentylphosphine, tricyclohexylphosphine, tri-tert-butylphosphine, 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,5-bis(diphenylphosphino)pentane, 1,6-bis(diphenylphosphine) (±)-2,2´-bis(diphenylphosphino)-1,1´-binaphthyl, 1,8-bis(diphenylphosphino)naphthalene, bis[2-(diphenylphosphino)phenyl]ether, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 1,1´-bis(diphenylphosphino)ferrocene, 1,1´-bis(di-tert-butylphosphino)ferrocene, 1,1´-bis(dicyclohexylphosphino)ferrocene, 1,4-bis(di-tert Phosphine ligands such as 1,4-bis(dicyclohexylphosphino)butane, 1,4-bis(dicyclohexylphosphino)butane, Buchwald ligands such as JohnPhos, tBuXphos, tert-ButylBrettPhos, CyJohnPhos, Xphos, BrettPhos, RuPhos, SPhos, MePhos, DavePhos, PhDave-Phos, 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, 1,3-bis(2,6-di-3-pentylphenyl)imidazol-2-ylidene, 1,3-bis(2,6-di-3-pentylphenyl)imidazol-2-ylidene, 1,Examples of NHC ligands include 3-dimesitylimidazol-2-ylidene and 1,3-bis(2,6-diisopropylphenyl)imidazolidine-2-ylidene. In view of good yield, triphenylphosphine, tri-tert-butylphosphine, 1,3-bis(diphenylphosphino)propane, 1,1'-bis(diphenylphosphino)ferrocene, 1,1'-bis(di-tert-butylphosphino)ferrocene, and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene are preferred, in view of good availability, 1,3-bis(diphenylphosphino)propane and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene are preferred, and among these, 1,3-bis(diphenylphosphino)propane is preferred because it is inexpensive and the reaction proceeds in good yield.

[0019] The method for preparing the palladium catalyst used in the production method of the present invention is not particularly limited, and a commercially available palladium complex having a ligand coordinated thereto may be used as is, or a palladium complex prepared by mixing a palladium compound and a ligand (or a salt thereof) before or during the reaction may be used. Examples of commercially available ligand-coordinated palladium complexes include, but are not limited to, tetrakis(triphenylphosphine)palladium(0), bis(tri-tert-butylphosphine)palladium(0), bis[1,2-bis(diphenylphosphino)ethane]palladium(0), bis(triphenylphosphine)palladium(II) diacetate, benzylbis(triphenylphosphine)palladium(II) chloride, bis(triphenylphosphine)palladium(II) dichloride, bis(tri-o-tolylphosphine)palladium(II) dichloride, bis(tricyclohexylphosphine)palladium(II) dichloride, [1,2-bis(diphenylphosphino)ethane]palladium(II) dichloride, and [1,3-bis(diphenylphosphino)propane]palladium(II) dichloride. do, [1,4-bis(diphenylphosphino)butane]palladium(II) dichloride, [4,5-bis(diphenylphosphino)-9,9-dimethylxanthene]palladium(II) dichloride, [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride, [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct, [1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II) dichloride, [1,3-bis(2,6-di-3-pentylphenyl)imidazol-2-ylidene](3-chloropyridyl)dichloropalladium(II), [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)dichloropalladium(II), and the like. In view of good availability, tetrakis(triphenylphosphine)palladium(0), bis(tri-tert-butylphosphine)palladium(0), [1,3-bis(diphenylphosphino)propane]palladium(II) dichloride, [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride, and [4,5-bis(diphenylphosphino)-9,9-dimethylxanthene]palladium(II) dichloride are preferred, and in view of good yield, [1,3-bis(diphenylphosphino)propane]palladium(II) dichloride and [4,5-bis(diphenylphosphino)-9,9-dimethylxanthene]palladium(II) dichloride are particularly preferred. Examples of palladium compounds include, but are not limited to, allylpalladium(II) chloride (dimer), palladium(II) trifluoroacetate, bis(acetonitrile)(II) dichloride, bis(benzonitrile)palladium(II) dichloride, bis(dibenzylideneacetone)palladium(0), tris(dibenzylideneacetone)palladium(0), tris(dibenzylideneacetone)palladium(0) chloroform adduct, and bis(ethylenediamine). Examples include palladium(II) dichloride, bis(2,4-pentanedionato)palladium(II), dichloro(1,5-cyclooctadiene)palladium(II), 2,5-norbornadienepalladium(II) dichloride, palladium(II)(π-cinnamyl)chloride(dimer), palladium(II) acetate, palladium(II) acetate(trimer), sodium tetrachloropalladate(II), palladium(II) chloride, palladium(II) bromide, etc. Among these, bis(dibenzylideneacetone)palladium(0) or palladium(II) acetate is preferred due to its good availability.

[0020] In the production method of the present invention, the method of adding the palladium catalyst to the reaction system is not particularly limited as long as it does not deviate from the object of the present invention, but examples of the addition include mixing the palladium catalyst with the organozinc compound in advance and carrying out the reaction, or carrying out the reaction while adding the palladium catalyst to the organozinc compound.

[0021] In the production method of the present invention, the amount of the ligand used is not particularly limited. However, in terms of good yield, in the case of a monodentate ligand, it is preferable to use 1.0 molar equivalent or more of the monodentate ligand relative to 1.0 molar equivalent of the palladium site, and it is more preferable to use 1.2 to 6.0 molar equivalents. In the case of a bidentate ligand, it is preferable to use 0.5 molar equivalents or more of the bidentate ligand per 1 molar equivalent of the palladium site, and more preferably 0.6 to 3.0 molar equivalents. When a palladium catalyst and a copper salt are coexisted, the ligand is also coordinated to the copper salt, so the preferred amount of the ligand to be used changes. In the case of a monodentate ligand, it is preferably used in an amount of (1.0+0.5Y) or more molar equivalents relative to 1.0 molar equivalent of palladium site and Y molar equivalent of copper site, and more preferably in an amount of (1.2+0.6Y) to (6.0+3.0Y) molar equivalents. In the case of a bidentate ligand, it is preferable to use (0.5+0.2Y) molar equivalents or more relative to 1.0 molar equivalent of palladium moiety and Y molar equivalent of copper moiety, and more preferably (0.6+0.3Y) to (3.0+1.5Y) molar equivalents. If the amount of ligand used is small, the palladium may aggregate and be deactivated, resulting in a decrease in yield. If the amount of ligand used is large, the transmetallation rate may decrease, making the substrate more susceptible to decomposition, resulting in a decrease in yield.

[0022] The amount of the palladium catalyst used in the production method of the present invention is not particularly limited, but in terms of good reaction rate and yield, it is preferable to use 0.00001 mol to 0.5 mol equivalent relative to 1 mol equivalent of the organozinc compound, more preferably 0.0001 mol to 0.1 mol equivalent, and more preferably 0.001 mol to 0.01 mol equivalent. If the amount of the palladium catalyst is too small, the reaction rate may be slow and a long reaction time may be required. If the amount of the palladium catalyst is too large, palladium may easily aggregate, resulting in a decrease in yield, and the organozinc compound may be consumed when reducing palladium (II) to palladium (0), resulting in a decrease in yield.

[0023] <Copper(I) salts> In the production method of the present invention, a copper(I) salt can be added as necessary to improve the yield.

[0024] In the production method of the present invention, the copper(I) salt contributes to the improvement of the yield as a catalyst. Although the detailed reaction mechanism is unknown, it is considered that the copper(I) salt promotes the transmetallation reaction to the palladium catalyst by recovering the excess ligand in the system, or promotes the transmetallation reaction by generating an organocopper reagent, thereby suppressing the decomposition of the CF2=CH group on the palladium complex, thereby contributing to the improvement of the yield.

[0025] In the production method of the present invention, examples of copper(I) salts that can be used include, but are not limited to, the following examples: [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](1,3-diphenyl-1,3-propanedionato)copper(I), borohydride bis(triphenylphosphine)copper(I), chloro[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]copper(I), chloro(1,3-dimesitylimidazol-2-ylidene)copper(I), copper acetate(I), copper cyanide(I), etc. ), copper thiocyanate (I), copper 2-thiophene carboxylate (I), copper 1,5-cyclooctadiene (hexafluoro-2,4-pentanedionato) (I), copper trifluoromethanesulfonate (I) benzene complex, copper tetrakis (acetonitrile) (I) hexafluorophosphate, copper tetrakis (acetonitrile) (I) tetrafluoroborate, copper trifluoromethanesulfonate (I), copper fluoride (I), copper chloride (I), copper bromide (I), copper iodide (I), etc. are included. Copper chloride (I), copper bromide (I), and copper iodide (I) are preferred because they are inexpensive and readily available, and copper iodide (I) is particularly preferred because it is easy to handle.

[0026] In the production method of the present invention, the method of adding the copper (I) salt is not particularly limited, but A mixture of palladium catalyst and copper(I) salt is mixed with an organozinc compound and reacted. A copper(I) salt is added to a mixture of a palladium catalyst and an organozinc compound to carry out the reaction. A palladium catalyst is added to a mixture of copper(I) salt and an organozinc compound to carry out the reaction. It can be added in the following manner.

[0027] In the production method of the present invention, the amount of copper (I) salt used is not particularly limited, but in terms of good reaction rate and yield, it is preferable to use 0.0001 mol to 1.0 mol equivalent relative to 1 mol equivalent of the organozinc compound, more preferably 0.001 mol to 0.1 mol equivalent, and more preferably 0.01 mol to 0.05 mol equivalent. If the amount of copper (I) salt is too small, the yield improvement effect may not be obtained. If the amount of copper (I) salt is too large, the post-reaction treatment may become complicated due to precipitation of the salt.

[0028] <Reaction> The production method of the present invention can be carried out in an organic solvent, and is not particularly limited as long as there is no risk of inhibiting the reaction.Specific examples of the organic solvent used include ether solvents such as tetrahydrofuran, diethyl ether, 2-methyltetrahydrofuran, cyclopentyl methyl ether, 1,4-dioxane, methyl-tert-butyl ether, and 1,2-dimethoxyethane, aliphatic hydrocarbon solvents such as hexane, pentane, and cyclohexane, aromatic hydrocarbon solvents such as benzene, toluene, and xylene, nitrile solvents such as acetonitrile and propionitrile, sulfoxide solvents such as dimethyl sulfoxide and diethyl sulfoxide, amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and 1,3-dimethyl-2-imidazolidinone, and halogen solvents such as dichloromethane and chloroform, and two or more of the above may be mixed and used. Among these solvents, a solvent having an amide bond is preferably used.Furthermore, in terms of excellent solubility of the organic zinc compound, tetrahydrofuran, diethyl ether, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and 1,3-dimethyl-2-imidazolidinone are preferred, among which tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone are more preferred in terms of excellent yield, and among which N,N-dimethylformamide is particularly preferred in terms of excellent yield.

[0029] The production method of the present invention is not particularly limited to the reaction temperature, and can be carried out at an appropriate temperature, for example, from 0°C to 200°C. From the viewpoint of good yield, 20°C to 150°C is preferred, and 40°C to 100°C is more preferred. If the temperature is too low, the reaction may take a long time. If the temperature is too high, the yield may decrease due to decomposition of the organozinc compound or decomposition of the CF2=CH group.

[0030] <Side reactions> Side reactions caused by organometallic reagents in the production method of the present invention include, but are not limited to, the following examples: an adduct produced by nucleophilic addition of an organometallic reagent to a halogenated difluorovinyl compound, an alkene produced by defluorination after the addition, or a compound produced by further reacting these with an organometallic reagent. In addition, decomposition to fluorinated acetylene caused by β-F elimination after metal exchange between an organometallic reagent and a halogenated difluorovinyl compound, and the production of an alkyne compound caused by nucleophilic addition of an organometallic reagent to fluorinated acetylene are also possible. Examples of side reactions occurring during the coupling reaction in the production method of the present invention include, but are not limited to, homo-coupling products of organozinc compounds that occur mainly when palladium(II) is reduced to palladium(0), protonated products of organozinc compounds, and homo-coupling products of halogenated difluorovinyl compounds (CF2=CH-CH=CF2) that occur due to reverse transmetallation.

[0031] <Refining> In the manufacturing method of the present invention, difluorovinyl group-containing compound can be purified by various methods known in the technical field of the present invention as necessary.The method of producing difluorovinyl group-containing compound is not particularly limited, but can include solvent extraction, column chromatography, preparative thin layer chromatography, preparative liquid chromatography, recrystallization, reprecipitation, sublimation, distillation, etc.In addition, it can be isolated by these methods as necessary. EXAMPLES

[0032] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples. The following instruments were used in the analysis.

[0033] Gas chromatography (GC): Shimadzu GC-2025 Gas chromatograph mass spectrometer (GC-MS): Shimadzu GCMS-QP2010Plus 1 HNMR and 19 FNMR: AVANCEII400 manufactured by Bruker

[0034] The concentration determination of the organozinc compound and the Grignard reagent was carried out by iodometric titration as described in the literature (A. Krasovskiy and P. Knochel, Synthesis, 2006, 5, 0890-0891).

[0035] [Reference example 1] Preparation of phenylzinc bromide In a nitrogen atmosphere, 20.35 g (equivalent to 20 mmol) of phenylmagnesium bromide solution (0.96 M, tetrahydrofuran solution, manufactured by Sigma-Aldrich) and 4.51 g (20 mmol) of zinc bromide (II) were added to a 50 mL vial and left to stand for one day to prepare a phenylzinc bromide suspension. Iodine titration revealed that the concentration of the organozinc compound was 0.95 M.

[0036] [Example 1] Synthesis of (2,2-difluorovinyl)benzene [ka] In a nitrogen atmosphere, 2.3 mg (0.01 mmol) of palladium acetate (II), 4.0 mg (0.02 mmol) of tri-tert-butylphosphine, 1 mL of N,N-dimethylformamide (DMF) previously degassed under reduced pressure using a vacuum pump, and a stirrer chip were placed in a 6 mL vial, and the mixture was stirred at room temperature for 10 minutes to prepare a palladium catalyst. Then, 1.05 mL of phenyl bromide zinc bromide suspension (1.0 mmol of phenyl bromide zinc bromide) prepared in the same manner as in Reference Example 1 was added, and the mixture was stirred at room temperature for 10 minutes. The cap of the vial was replaced with a septum, and the mixture was heated in a nitrogen atmosphere in an oil bath at 50°C, and at the same time, 1.0 mL of a DMF solution of CF2=CHBr with a concentration of 1.1 M (corresponding to CF2=CHBr 1.1 mmol) was dropped with a syringe over 1 hour, and then the septum was replaced with the cap again, and the reaction was carried out at 50°C for 3 hours. The weight of the reaction solution was measured, and a portion of the reaction solution was diluted with benzotrifluoride, an internal standard. 1 HNMR and 19 The reaction yield was determined by FNMR (solvent: CDCl3) and was found to be 78%. The results are shown in Table 1.

[0037] [Examples 2 to 4] Except for changing the amounts of palladium acetate and ligand added, the same procedure as in Example 1 was carried out. The results are shown in Table 1.

[0038] [Example 5] The same procedure as in Example 1 was repeated except that the reaction was carried out at room temperature and the amounts of palladium acetate and ligand added were changed. The results are shown in Table 1.

[0039] [Examples 6 to 10] Except for changing the type of ligand, the same procedure as in Example 1 was carried out. The results are shown in Table 1.

[0040] [Examples 11 to 13] The procedure was the same as in Example 1, except that a different solvent was used instead of DMF. The results are shown in Table 1.

[0041] [Example 14] The same procedure as in Example 1 was repeated except that the amount of zinc bromide (II) added was 0.33 molar equivalents relative to the amount of phenyl magnesium bromide. The results are shown in Table 1.

[0042] [Comparative Examples 1 and 2] The procedure was carried out in the same manner as in Example 1, except that 1.04 mL of a 0.96 M phenylmagnesium bromide solution (1.0 mmol of phenylmagnesium bromide) was used in the reaction and the solvent was changed. The results are shown in Table 1.

[0043] [Table 1]

[0044] From Examples 1 to 4, it is seen that the reaction proceeds when the amount of palladium catalyst is 0.0001 to 0.10 molar equivalents (0.01 to 10 mol%) relative to 1 molar equivalent of the organozinc compound, and that 0.001 to 0.01 molar equivalents (0.1 to 1 mol%) is particularly suitable. From Examples 1 and 5, it can be seen that the reaction at 50° C. gives a higher yield than the reaction at room temperature. It is evident from Example 1 and Examples 6 to 10 that the reaction proceeds with a yield of just under 50% using various phosphine ligands. It is seen from Example 1 and Examples 11 to 13 that the yield is improved in the presence of an amide solvent, and in particular, the yield is excellent in the presence of N,N-dimethylformamide. From Examples 1 and 14, it is clear that the yield is improved when 1 equivalent of zinc salt is added to the Grignard reagent. It is clear from Example 1, Comparative Example 1, and Comparative Example 2 that the organic zinc compound (phenyl zinc bromide bromide) is superior in yield to the Grignard reagent (phenyl magnesium bromide bromide).

[0045] [Examples 15 to 21] The same procedure as in Example 1 was repeated except that 3.8 mg (0.02 mmol) of copper (I) iodide was added together with palladium acetate and the ligand, and the amount of the ligand added and the ligand were changed. The results are shown in Table 2.

[0046] [Comparative Example 3] The same procedure as in Example 15 was repeated except that palladium acetate was not added. The results are shown in Table 2.

[0047] [Table 2]

[0048] From Examples 1, 6 to 10, and 15 to 21, it can be seen that while the yield was slightly less than 50% without copper(I) iodide, the addition of copper(I) iodide can increase the yield to 50% or more depending on the ligand. In particular, it can be seen that the yield is significantly increased when 1,3-bis(diphenylphosphino)propane is used as the ligand. From Example 15 and Comparative Example 3, it is understood that the cross-coupling reaction hardly proceeds with copper(I) iodide alone, and a palladium catalyst is necessary for the cross-coupling reaction.

[0049] [Example 22] The same procedure as in Example 17 was carried out except that 1.0 mL of a 1.1 M DMF solution of CF2=CHBr (corresponding to 1.1 mmol of CF2=CHBr) was added at room temperature, the vial was closed, and the reaction was carried out for 4 hours in an oil bath at 50°C. The reaction yield was 98%. The results are shown in Table 3.

[0050] The results of NMR analysis are shown below. 1 HNMR (CDCl3,400MHz): δ=7.35-7.31(m,4H),7.25-7.21(m,1H),5.36(dd,J=26.4,4.0Hz,1H). 19FNMR (CDCl3,376MHz): δ=-83.6(dd,J=32.7,26.7Hz,1F),-85.4(dd,J=33.1,3.8Hz,1F).

[0051] [Example 23] [ka] In a nitrogen atmosphere, 0.99g (41mmol) of magnesium powder, 1.25g (29mmol) of lithium chloride, 1 piece of iodine (~10mg), 15mL of tetrahydrofuran, and a stirrer chip were placed in a 100mL eggplant flask and stirred at room temperature for 30 minutes. A mixture of 5.61g (30mmol) of p-bromoanisole and 5mL of tetrahydrofuran was taken into a 10mL syringe and slowly dropped at room temperature over 1 hour, and the mixture was allowed to react at room temperature for 3 hours. The eggplant flask was washed with a small amount of tetrahydrofuran and the excess magnesium was removed by decantation to obtain a Grignard reagent. Then, 6.76g (30mmol) of zinc bromide was added in an ice bath, stirred, and left to stand for 1 day to obtain an organozinc compound. Iodine titration revealed that the organozinc compound concentration was 1.06M. The reaction was carried out in the same manner as in Example 22, except that 0.94 mL (1.0 mmol) of the organozinc compound was used. The reaction yield was 95%. The results are shown in Table 3.

[0052] The results of NMR analysis are shown below. 1 HNMR (CDCl3,400MHz): δ=7.26(d,J=8.8Hz,2H),6.88(d,J=8.8Hz,2H),5.28(dd,J=26.8,4.0Hz,1H),3.79(s,3H). 19 FNMR (CDCl3,376MHz): δ=-85.9(dd,J=38.0,27.1Hz,1F),-87.7(dd,J=38.0,3.8Hz,1F).

[0053] [Example 24] [ka] An organozinc compound was prepared in the same manner as in Example 23, except that 6.40 g (30 mmol) of p-tert-butylbromobenzene was used instead of p-bromoanisole. Iodometric titration revealed that the concentration of the organozinc compound was 0.98 M. The reaction was carried out in the same manner as in Example 22, except that 1.02 mL (1.0 mmol) of the organozinc compound was used. The reaction yield was 78%. The results are shown in Table 3.

[0054] The results of NMR analysis are shown below. 1 HNMR (CDCl3,400MHz): δ=7.36(d,J=8.4Hz,2H),7.27(d,J=8.4Hz,2H),5.31(dd,J=26.8,4.0Hz,1H),1.31(s,9H). 19 FNMR (CDCl3,376MHz): δ=-84.3(dd,J=34.6,26.9Hz,1F),-86.2(dd,J=34.6,3.8Hz,1F).

[0055] [Example 25] [ka] An organozinc compound was prepared in the same manner as in Example 23, except that 25 mL of tetrahydrofuran and 6.21 g (30 mmol) of 1-bromonaphthalene were used instead of p-bromoanisole. Iodometric titration revealed that the organozinc compound had a concentration of 0.64 M. The reaction was carried out in the same manner as in Example 22, except that 1.57 mL (1.0 mmol) of the organozinc compound was used and the reaction time was 16 hours. The reaction yield was 90%. The results are shown in Table 3.

[0056] The results of NMR analysis are shown below. 1 HNMR (CDCl3,400MHz): δ=7.96(d,J=7.6Hz,1H),7.89-7.79(m,3H),7.48-7.45(m,3H),5.96(dd,J=24.8,3.2Hz,1H). 19FNMR (CDCl3,376MHz): δ=-84.3(dd,J=30.3,3.2Hz,1F),-86.3(dd,J=30.1,24.8Hz,1F).

[0057] [Example 26] [ka] An organozinc compound was prepared in the same manner as in Example 23, except that 0.490 g (20 mmol) of magnesium powder, 0.62 g (15 mmol) of lithium chloride, 7.5 mL of tetrahydrofuran, and 3.18 g (15 mmol) of 3,4,5-trifluorobromobenzene were used instead of p-bromoanisole. Iodometric titration revealed that the organozinc compound had a concentration of 0.95 M. The reaction was carried out in the same manner as in Example 22, except that 1.05 mL (1.0 mmol) of the organozinc compound was used and the reaction time was 16 hours. The reaction yield was 92%. The results are shown in Table 3.

[0058] The results of NMR analysis are shown below. 1 HNMR (CDCl3,400MHz): δ=7.08(dd,J=9.2,6.4Hz,2H),5.49(dd,J=25.6,3.2Hz,1H). 19 FNMR (CDCl3,376MHz): δ=-81.5(t,J=26.3Hz,1F),-89.3(d,J=27.4Hz,1F),-135.5(dd,J=20.3,9.0Hz,2F),-163.4(m,1F). GC-MS: m / z (M)194(100%),(MF)175(10%),(M-HF)174(10%),(M-CF2)144(36%),(M-CF2H)143(52%),(M-CF3)125(53%),99(13%),75(29%),31(18%).

[0059] [Example 27] [ka] In a nitrogen atmosphere, 2.69 g (41 mmol) of zinc powder, 15 mL of N,N-dimethylformamide, 0.040 mL of chlorotrimethylsilane, and a stirrer tip were placed in a 100 mL eggplant flask, and the mixture was stirred at room temperature for 30 minutes under a nitrogen atmosphere. 9.89 g (40 mmol) of pentafluorophenyl bromide was dispensed into a 10 mL syringe, slowly dripped over 30 minutes at room temperature, and allowed to react for 4 hours at room temperature. The eggplant flask was washed with a small amount of N,N-dimethylformamide, while excess zinc powder was removed by celite filtration, to obtain an organic zinc compound. Iodine titration revealed that the concentration of the organic zinc compound was 1.31 M. The reaction was carried out in the same manner as in Example 22, except that 11.6 mg (0.02 mmol) of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene was used instead of 1,3-bis(diphenylphosphino)propane, 0.76 mL (1.0 mmol) of the organozinc compound was used, the reaction temperature was 90° C., and the reaction time was 18 hours. The reaction yield was 71%. The results are shown in Table 3.

[0060] The results of NMR analysis are shown below. 1 HNMR (CDCl3,400MHz): δ=5.36(d,J=25.6Hz,1H). 19 FNMR (CDCl3,376MHz): δ=-75.6(m,1F),-79.5(d,J=12.8Hz,1F),-139.9(t,J=23.5Hz,2F),-155.9(t,J=20.9Hz,1F),-163.3(m,2F).

[0061] [Example 28] The same procedure as in Example 27 was repeated except that the reaction temperature was 130° C. The reaction yield was 26%. The results are shown in Table 3.

[0062] [Example 29] The same procedure as in Example 27 was repeated except that 8.2 mg (0.02 mmol) of 1,3-bis(diphenylphosphino)propane was used instead of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and the reaction temperature was 130° C. The reaction yield was 8%. The results are shown in Table 3.

[0063] [Example 30] [ka] In a nitrogen atmosphere, 0.95g (39mmol) of magnesium powder, 4.25g (31mmol) of zinc chloride, 1 piece of iodine (~10mg), 15mL of tetrahydrofuran, and a stirrer chip were placed in a 100mL eggplant flask, and stirred at room temperature for 30 minutes under a nitrogen atmosphere. A mixture of 6.53g (31mmol) of 2-iodothiophene and 5mL of tetrahydrofuran was taken into a 10mL syringe, slowly dripped at room temperature over 1 hour, and reacted for 3 hours in an oil bath at 60°C. The eggplant flask was washed with a small amount of tetrahydrofuran, and the excess magnesium was decanted off while dissolving the salt, obtaining an organozinc compound. Iodine titration revealed that the organozinc compound had a concentration of 0.64M. The reaction was carried out in the same manner as in Example 22, except that 1.56 mL (1.0 mmol) of the organozinc compound was used and the reaction time was 24 hours. The reaction yield was 78%. The results are shown in Table 3.

[0064] The results of NMR analysis are shown below. 1 HNMR (CDCl3,400MHz): δ=7.29(d,J=5.2Hz,1H),7.03-7.00(m,1H),7.00-6.99(m,1H),5.68(dd,J=26.2,2.2Hz,1H). 19 FNMR(CDCl3,376MHz): δ=-82.3(dd,J=29.7,26.4Hz,1F),-89.3(dd,J=30.1,1.1Hz,1F).

[0065] [Example 31] [ka] An organozinc compound was prepared in the same manner as in Example 23, except that 0.325 g (13 mmol) of magnesium powder, 0.425 g (10 mmol) of lithium chloride, 5.0 mL of tetrahydrofuran, and 2.24 g (10 mmol) of 4-bromobenzotrifluoride and 2.28 g (10 mmol) of zinc bromide were used instead of p-bromoanisole. Iodometric titration revealed that the organozinc compound had a concentration of 0.76 M. The reaction was carried out in the same manner as in Example 22, except that 1.31 mL (1.0 mmol) of the organozinc compound was used and the reaction time was 20 hours. A portion of the reaction solution was diluted with hexafluorobenzene, an internal standard, and then eluted with 100 mL of ethyl acetate. 19 The reaction yield was determined by FNMR (solvent: CDCl3) and was found to be 94%. The results are shown in Table 3.

[0066] The results of NMR analysis are shown below. 1 HNMR (CDCl3,400MHz): δ=7.57(d,J=7.8Hz,2H),7.50(d,J=7.8Hz,2H),5.51(dd,J=26.0,3.6Hz,1H). 19 FNMR (CDCl3,376MHz): δ=-63.1(s,3F),-80.5(dd,J=26.3,26.3Hz,1F),-89.3(dd,J=26.7,3.4Hz,1F).

[0067] [Example 32] [ka] In a nitrogen atmosphere, 0.915g (14mmol) zinc powder, 5mL tetrahydrofuran, 0.425g (10mmol) lithium chloride, 0.020mL chlorotrimethylsilane, and a stirrer tip were placed in a 25mL eggplant flask, and stirred at room temperature for 30 minutes under a nitrogen atmosphere. A mixture of 3.17g (14mmol) 4-iodobenzonitrile and 5mL tetrahydrofuran was taken into a 10mL syringe, slowly dripped at room temperature over 30 minutes, and allowed to react at room temperature for 3 hours. The excess zinc powder was removed by celite filtration while washing the eggplant flask with a small amount of tetrahydrofuran, and an organic zinc compound was obtained. Iodine titration was performed, and the concentration of the organic zinc compound was 0.55M. The reaction was carried out in the same manner as in Example 22, except that 1.89 mL (1.0 mmol) of the organozinc compound was used and the reaction time was 20 hours. A portion of the reaction solution was diluted with hexafluorobenzene, an internal standard, and then eluted with 100 mL of ethyl acetate. 19 The reaction yield was determined by FNMR (solvent: CDCl3) and was found to be 69%. The results are shown in Table 3.

[0068] The results of NMR analysis are shown below. 1 HNMR (CDCl3,400MHz): δ=7.68(d,J=8.2Hz,2H),7.54(d,J=8.2Hz,2H),5.57(dd,J=26.0,3.6Hz,1H). 19 FNMR (CDCl3,376MHz): δ=-78.9(dd,J=26.0,23.9Hz,1F),-80.6(dd,J=23.9,3.6Hz,1F).

[0069] [Example 33] [ka] In a nitrogen atmosphere, 0.82g (13mmol) zinc powder, 7.5mL N,N-dimethylformamide, 0.010mL chlorotrimethylsilane, and a stirrer tip were placed in a 20mL eggplant flask, and the mixture was stirred at room temperature for 30 minutes under a nitrogen atmosphere. A solution of 3.18g (10mmol) of 1-bromo-3-chloro-4-iodobenzene dissolved in 2.5mL N,N-dimethylformamide was taken into a 10mL syringe, slowly dripped over 30 minutes at room temperature, and allowed to react for 3 hours at room temperature. The eggplant flask was washed with a small amount of N,N-dimethylformamide while excess zinc powder was removed by celite filtration, and an organic zinc compound was obtained. Iodine titration was performed, and the concentration of the organic zinc compound was 0.31M. The reaction was carried out in the same manner as in Example 22, except that 3.24 mL (1.0 mmol) of the organozinc compound was used, the reaction temperature was 60° C., and the reaction time was 16 hours. A portion of the reaction solution was diluted with hexafluorobenzene, an internal standard, and then diluted with 1.0 mL of hexane. 19 The reaction yield was determined by FNMR (solvent: CDCl3) and was found to be 49%. The results are shown in Table 3.

[0070] The results of NMR analysis are shown below. 1 HNMR (CDCl3,400MHz): δ=7.60(d,J=2.0Hz,1H),7.48(d,J=2.0Hz,1H),7.47(s,1H),5.69(dd,J=25.6,3.6Hz,1H). 19 FNMR(CDCl3,376MHz): δ=-81.4(dd,J=24.8,3.4Hz,1F),-82.1(dd,J=24.8,24.8Hz,1F). GC-MS: m / z (M)254(100%),(M)252(77%),(M)256(24%),(M-Br)217(10%),(M-Br)219(10%),(M-Br-Cl)138(40%),87(10%),69(10%).

[0071] [Example 34] [ka] In a nitrogen atmosphere, 0.98g (40mmol) of magnesium powder, 1.29g (30mmol) of lithium chloride, 4.10g (30mmol) of zinc chloride, 1 piece of iodine (~10mg), 15mL of tetrahydrofuran, and a stirrer chip were placed in a 50mL eggplant flask, and stirred at room temperature for 30 minutes under a nitrogen atmosphere. 2.91g (16mmol) of 4-bromostyrene was dispensed into a 10mL syringe and slowly dripped at room temperature over 30 minutes, and allowed to react at room temperature for 3 hours. The eggplant flask was washed with a small amount of tetrahydrofuran to remove excess magnesium, and an organozinc compound was obtained. Iodine titration revealed that the organozinc compound had a concentration of 0.50M. The reaction was carried out in the same manner as in Example 22, except that 2.00 mL (1.0 mmol) of the organozinc compound was used, the reaction temperature was 60° C., and the reaction time was 16 hours. A portion of the reaction solution was diluted with hexafluorobenzene, an internal standard, and then diluted with 1,000 mL of hexane. 19 The reaction yield was determined by FNMR (solvent: CDCl3) and was found to be 48%. The results are shown in Table 3.

[0072] The results of NMR analysis are shown below. 1 HNMR(CDCl3,400MHz):δ=7.43(d,J=8.4Hz,2H),7.31(d,J=8.4Hz,2H),6.71-6. 63(m,1H),5.77-5.72(m,1H),5.38(dd,J=26.8,4.0Hz,1H),5.27-5.20(m,1H). 19 FNMR (CDCl3,376MHz): δ=-83.2(dd,J=31.6,26.7Hz,1F),-85.2(dd,J=31.6,3.8Hz,1F). GC-MS: m / z (M) 166 (100%), (MH) 165 (13%), (M-CF2H) 115 (28%), 63 (10%).

[0073] [Example 35] [ka] In a nitrogen atmosphere, 0.278g (1.0mmol) of ethyl 2-iodobenzoate, 1mL of tetrahydrofuran, and a stirrer tip were placed in a 10mL test tube, and the mixture was stirred at 0°C for 10 minutes under a nitrogen atmosphere. 1.0mL of a tetrahydrofuran solution of isopropyl magnesium chloride-lithium chloride complex (turbo Grignard reagent, concentration 1.00M) was dispensed into a 1mL syringe and slowly dropped over 15 minutes, and then reacted at 0°C for 30 minutes. 0.158g (1.2mmol) of zinc chloride was added to the reactor, and the mixture was further reacted at 0°C for 1 hour to obtain an organozinc compound. The reaction was carried out in the same manner as in Example 22, except that the total amount of the organozinc compound (corresponding to 1.0 mmol) was used, the reaction temperature was 60° C., and the reaction time was 16 hours. A portion of the reaction solution was diluted with hexafluorobenzene, an internal standard, and then diluted with 1.0 mmol of hexane. 19 The reaction yield was determined by FNMR (solvent: CDCl3) and was found to be 49%. The results are shown in Table 3.

[0074] The results of NMR analysis are shown below. 1 HNMR(CDCl3,400MHz):δ=7.97-7.92(m,1H),7.57-7.53(m,1H),7.48-7.40(m,1H),7.38- 7.32(m,1H),6.33(dd,J=26.0,3.6Hz,1H),4.34(q,J=7.2Hz,2H),1.39(t,J=7.2Hz,3H). 19 FNMR (CDCl3,376MHz): δ=-84.1(dd,J=31.2,4.5Hz,1F),-85.7(dd,J=30.8,26.3Hz,1F).

[0075] [Table 3]

[0076] It is apparent from Examples 22 to 35 that a difluorovinyl group-containing compound can be synthesized in high reaction yield using an organozinc compound represented by the general formula (1). [Industrial Applicability]

[0077] The difluorovinyl group-containing compound obtained by the present invention is expected to be used as a crosslinking agent for fluororubber, an electrolyte membrane for fuel cells, a functional material such as a chemically amplified resist material, and also as an intermediate in the production of pharmaceuticals and agricultural chemicals.

Claims

1. The following general formula (1) Arr １ -ZhnX １ (1) (In formula (1), Ar １ represents a monovalent group of a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted condensed polycyclic aromatic group; Ar １ is a group having a substituent, it has one or more substituents selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, an alkyl group having 1 to 10 carbon atoms, a fluoroalkyl group having 1 to 10 carbon atoms and containing one or more fluorine atoms, an alkenyl group having 1 to 10 carbon atoms, an acyl group having 1 to 10 carbon atoms, a (alkoxy)carbonyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, a nitro group, and a cyano group; １ represents a chlorine atom, a bromine atom, or an iodine atom.) in the presence of a palladium catalyst or a palladium catalyst and a copper (I) salt, The following general formula (2) CF ２ =CHX ２ (2) (In formula (2), X ２ represents a chlorine atom, a bromine atom, or an iodine atom.) The present invention is characterized in that the halogenated difluorovinyl compound represented by the formula: The following general formula (3) Ar １ -CH=CF ２ (3) (In formula (3), Ar １ represents a monovalent group of a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted condensed polycyclic aromatic group; Ar １ is a group having a substituent, it has one or more substituents selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, an alkyl group having 1 to 10 carbon atoms, a fluoroalkyl group having 1 to 10 carbon atoms and containing one or more fluorine atoms, an alkenyl group having 1 to 10 carbon atoms, an acyl group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, a nitro group, and a cyano group; １ represents a chlorine atom, a bromine atom, or an iodine atom.) A method for producing a difluorovinyl group-containing compound represented by the formula:

2. X in formula (2) ２ The method according to claim 1 , wherein is a bromine atom.

3. Ar in the general formula (1) １ is a substituent selected from the group consisting of a phenyl group, a naphthyl group, a thienyl group, a furanyl group and a pyridinyl group, which optionally have one or more substituents selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group having 1 to 10 carbon atoms, a fluoroalkyl group having 1 to 10 carbon atoms which contains one or more fluorine atoms, an alkenyl group having 1 to 10 carbon atoms, an acyl group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, a nitro group and a cyano group.

4. Ar in general formula (1) １ is a substituent selected from the group consisting of a phenyl group, a naphthyl group, a thienyl group, a furanyl group, and a pyridinyl group, which may have one or more substituents selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group having 1 to 10 carbon atoms, a fluoroalkyl group having 1 to 10 carbon atoms containing one or more fluorine atoms, an alkenyl group having 1 to 10 carbon atoms, an acyl group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, a nitro group, and a cyano group, and X in general formula (2) ２ The method according to claim 1 , wherein is a bromine atom.

5. A solvent having an amide bond is used in the reaction, Ar in general formula (1) １ is a substituent selected from the group consisting of a phenyl group, a naphthyl group, a thienyl group, a furanyl group and a pyridinyl group, which optionally have one or more substituents selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an alkyl group having 1 to 10 carbon atoms, a fluoroalkyl group having 1 to 10 carbon atoms which contains one or more fluorine atoms, an alkenyl group having 1 to 10 carbon atoms, an acyl group having 1 to 10 carbon atoms, an alkoxycarbonyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, a nitro group and a cyano group; X in formula (2) ２ is a bromine atom, The palladium catalyst may be selected from the group consisting of triphenylphosphine, tri(o-tolyl)-phosphine, tri(m-tolyl)-phosphine, tri(p-tolyl)-phosphine, tri(2-furyl)phosphine, tri(2-thienyl)phosphine, tris(o-anisyl)phosphine, tris(p-anisyl)phosphine, tris(2,6-dimethoxyphenyl)phosphine, tris(4-fluorophenyl)phosphine, tris(pentafluorophenyl)phosphine, tris[3,5-bis(trifluoromethyl)phenyl]phosphine, cyclohexyldiphenylphosphine, dicyclohexylphenylphosphine, di-tert-butylphenylphosphine, tributylphosphine, trihexylphosphine, tri-n-octylphosphine, tricyclopentylphosphine, tricyclohexylphosphine, tri-tert-butylphosphine, 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)ethane, 1,4-bis(diphenylphosphino)ethane, 1,5-bis(diphenylphosphino)ethane, 1,6-bis(diphenylphosphino)ethane, 1,7-bis(diphenylphosphino)ethane, 1,8-bis(diphenylphosphino)ethane, 1,9-bis(diphenylphosphino)ethane, 1,10-bis(diphenylphosphino)ethane, 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)ethane, 1,4-bis(diphenylphosphino)ethane, 1,5-bis(diphenylphosphino)ethane, 1,6-bis(diphenylphosphino)ethane, 1,7-bis(diphenylphosphino)ethane, 1,8-bis(diphenylphosphino)ethane, 1,9-bis( 1,4-bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,5-bis(diphenylphosphino)pentane, 1,6-bis(diphenylphosphino)hexane, 1,2-bis(diphenylphosphino)benzene, (±)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, 1,8-bis(diphenylphosphino)naphthalene, bis[2-(diphenylphosphino)phenyl]ether, 4,5-bis(diphenylphosphino) 2. The method according to claim 1, wherein the palladium catalyst is coordinated with a phosphine selected from the group consisting of 1,1'-bis(diphenylphosphino)-9,9-dimethylxanthene, 1,1'-bis(diphenylphosphino)ferrocene, 1,1'-bis(di-tert-butylphosphino)ferrocene, 1,1'-bis(dicyclohexylphosphino)ferrocene, 1,4-bis(di-tert-butylphosphino)butane, and 1,4-bis(dicyclohexylphosphino)butane.

6. A difluorovinyl group-containing compound represented by the following formula (a), (b), or (c): 【Chemistry 16】 【Chemistry 17】 【Chemistry 18】

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