Method for producing aryl compounds having fluoroalkyl groups

Abstract

This invention provides a method for producing aryl compounds having a fluoroalkyl group under milder conditions, using an easily handled and inexpensive cobalt compound as a catalyst. [Solution] A method for producing an aryl compound having a fluoroalkyl group represented by the following general formula (3) is used, characterized by reacting an aryl compound with a halogenated fluoroalkyl compound in the presence of a cobalt compound, a phosphine ligand, and a metal reducing agent. JPEG2026141856000022.jpg36170

Description

[Technical Field]

[0001] This disclosure relates to a method for producing aryl compounds having a fluoroalkyl group using a cobalt catalyst. [Background technology]

[0002] Aromatic compounds having perfluoroalkyl groups are compounds that are expected to have applications such as surface treatment agents, polymer materials, or proton exchange membranes for fuel cells. Known methods for synthesizing aromatic compounds having perfluoroalkyl groups include a method in which an aromatic compound is reacted with a perfluorocarboxylic acid anhydride and a urea-hydrogen peroxide complex by heating in the presence of a copper catalyst (Patent Document 1), a method in which a perfluoroalkylcarboxylic acid anhydride is reacted with an aromatic compound such as anilines in the presence of a nickel catalyst (Non-Patent Document 1), or a method in which an aromatic compound is reacted with a perfluoroalkyl iodide by heating in the presence of copper powder (Non-Patent Document 2). Conventional methods for producing aryl compounds containing fluoroalkyl groups have several problems, including the need for large excess amounts of fluoroalkylating reagents (6 to 10 equivalents), the requirement for high temperatures (80 to 160°C) for the reaction, the long reaction time (10 to 180 hours), the need to use urea-hydrogen peroxide complexes that are harmful to humans, the need to use nickel complexes that are difficult to handle, or the use of explosive perfluoroalkyl carboxylic acid anhydrides, which poses risks for large-scale synthesis. [Prior art documents] [Patent Documents]

[0003] [Patent Document 1] Re-tabled publication No. 2017 / 104589 [Non-patent literature]

[0004] [Non-Patent Document 1] Journal of Fluorine Chemistry, Vol. 39, pp. 87-98, 1988. [Non-Patent Document 2] Tetrahedron, Volume 25, pages 5921-5940, 1969 [Summary of the Invention] [Problem to be Solved by the Invention]

[0005] An object of the present invention is to provide a method for producing an aryl compound having a fluoroalkyl group, which is a target product, under milder conditions, using a cobalt compound that is easy to handle and inexpensive as a catalyst. [Means for Solving the Problem]

[0006] As a result of intensive studies conducted by the present inventor to solve the above problems, the inventor found that the above problems can be solved by subjecting a fluoroalkyl iodide and an aryl compound to a coupling reaction in the presence of a cobalt compound, a ligand and a metal reducing agent, and thus completed the present invention.

[0007] That is, the present disclosure includes the following embodiments. [1] General formula (1) [Chemical Formula] (wherein, R represents an alkyl group having 1 to 6 carbon atoms, an alkyloxy group having 1 to 4 carbon atoms, a haloalkyl group having 1 to 4 carbon atoms, an aromatic ring group, a boryl group or a halogen atom, and may be the same or different and may be substituted, n represents an integer of 0 to 4, A represents an amino group or a hydroxyl group.) an aryl compound represented by general formula (2) [Chemical Formula] (wherein, Rf represents a fluoroalkyl group having 1 to 10 carbon atoms; X represents a bromine atom, a chlorine atom or an iodine atom.) a halogenated fluoroalkyl compound represented by, The reaction is carried out in the presence of a cobalt compound, a phosphine ligand, and a metal reducing agent. General formula (3) [ka] A method for producing an aryl compound having a fluoroalkyl group represented by the formula (wherein R, n, A, and Rf are as defined above; m is 1 or 2; however, n+m is an integer from 1 to 5). [2] The manufacturing method according to [1], wherein X is an iodine atom. [3] The manufacturing method according to either item [1] or [2], wherein the metal reducing agent is zinc. [4] The cobalt compounds include cobalt(III) fluoride, cobalt(II) chloride, cobalt(II) bromide, cobalt(II) iodide, cobalt(II) carbonate, cobalt(II) acetate, cobalt(II) oxalate, cobalt(II) benzoate, cobalt(II) citrate, cobalt(II) phosphate, cobalt(III) acetylacetonate, cobalt(II) isopropoxide, cobalt(II) thiocyanate, tris(2,2,6,6-tetramethyl-3,5-heptanedionate)cobalt(III) tricarbonylnitrosylcobalt, hexafluoro A method for producing the product according to either one of the following: [1] or [2], wherein the compound is one or more compounds selected from the group consisting of bis(cyclopentadienyl)cobalt phosphate, cobalt(II) hydroxide, cobalt(II) silide, cobalt(II) stearate, hexaamminecobalt(III) chloride, bis(pentamethylcyclopentadienyl)cobalt hexafluorophosphate, cobalt(II) sulfide, cyclopentadienylcobalt dicarbonyl, sarcomine, tetracobalt dodecacarbonyl, phthalocyanine cobalt(II), and ammonium cobalt(II) phosphate. [5] The method for producing a cobalt compound according to either [1] or [2], wherein the cobalt compound is cobalt(II) bromide or cobalt(III) acetylacetonate. [6] The manufacturing method according to either [1] or [2], wherein the phosphine ligand is a bidentate phosphine ligand. [7] The method for producing a product according to either one of the following items [1] or [2], wherein the phosphine ligand is 1,2-bis(diphenylphosphino)ethane (dppe), 1,2-bis(diphenylphosphino)benzene, or cis-1,2-bis(diphenylphosphino)ethylene. [8] A manufacturing method according to either item [1] or [2], characterized in that the reaction temperature is in the range of 20 to 40°C. [Effects of the Invention]

[0008] According to one aspect of this disclosure, a method for producing fluorine-containing compounds by fluoroalkylating various aryl compounds under mild conditions can be provided. [Modes for carrying out the invention]

[0009] The present invention will be described in detail below. <Method for producing aryl compounds containing fluoroalkyl groups> A method for producing an aryl compound having a fluoroalkyl group represented by general formula (3) according to one aspect of this disclosure (hereinafter also referred to as the "production method") will be described below. The production method is as shown in the reaction formula below. [ka] (In the formula, R, A, Rf, and X, n, and m have the same meanings as above.)

[0010] This manufacturing method involves reacting a halogenated fluoroalkyl compound (2) with an aryl compound represented by general formula (1) in the presence of a cobalt compound, a phosphine ligand, and a metal reducing agent to obtain an aryl compound having a fluoroalkyl group represented by general formula (3).

[0011] An example of the aryl compound represented by general formula (1) used in this manufacturing method will be explained below. The aryl compounds represented by formula (1) can be produced, for example, by a reduction reaction of nitrobenzenes (e.g., Organic Reactactions, Vol. 2, pp. 428-431, 1944) or by a hydrolysis reaction of diazonium salts (e.g., Journal of Organic Chemistry, Vol. 42, pp. 2053-2058, 1977). Commercial products may also be used. Specifically, examples include compounds with aromatic rings such as anthracene, phenanthrene, tetracene, chrysene, pyrene, benzo[a]anthracene, pentacene, picene, and triphenylene rings in their skeletons, with benzene and naphthalene rings being preferred among these.

[0012] In the aryl compound represented by general formula (1) used in this manufacturing method, the alkyl group having 1 to 6 carbon atoms represented by the substituent R may be linear, branched, or cyclic alkyl groups. Examples include methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopropyl, and cyclohexyl groups. Examples of alkyloxy groups with 1 to 4 carbon atoms represented by R include methoxy, ethoxy, propyloxy, isopropyloxy, butyloxy, and t-butyloxy groups. The haloalkyl group having 1 to 4 carbon atoms represented by R may be linear, branched, or cyclic, and examples include fluoromethyl group, difluoromethyl group, trifluoromethyl group, 2,2,2-trifluoroethyl group, 2,2,3,3,3-pentafluoropropyl group, 2,2,3,3,4,4,4-heptafluorobutyl group, perfluorocyclopropyl group, and perfluorocyclobutyl group. Examples of aromatic ring groups represented by R include benzene rings, naphthalene rings, anthracene rings, phenanthrene rings, tetracene rings, chrysene rings, pyrene rings, benzo[a]anthracene rings, pentacene rings, picene rings, and triphenylene rings. Among these, benzene rings and naphthalene rings are preferred, with benzene rings being even more preferred. Examples of boryl groups represented by R include dialkoxyboryl groups such as dimethoxyboryl, diisopropoxyboryl, and dibutoxyboryl; and cyclic boryl groups such as pinacolateboryl, 1,3,2-dioxaborinan-2-yl, and 5,5-dimethyl-1,3,2-dioxaborinan-2-yl. Examples of halogen atoms represented by R include fluorine, chlorine, bromine, and iodine atoms.

[0013] Examples of the halogenated fluoroalkyl compounds (2) used in this manufacturing method will be explained below. The halogenated fluoroalkyl compounds represented by formula (2) can be produced, for example, by a reaction using a trihaloacetate and an elemental halogen (e.g., Journal of the American Chemical Society, Vol. 72, pp. 3806-3807, 1950). Commercially available products may also be used. The fluoroalkyl group having 1 to 10 carbon atoms represented by Rf may be linear, branched, or cyclic. Examples include trifluoromethyl, pentafluoroethyl, heptafluoropropyl, heptafluoroisopropyl, nonafluorobutyl, sec-nonafluorobutyl, tert-nonafluorobutyl, undecafluoropentyl, and tridecafluorohexyl groups. As the halogen atom represented by X, iodine is preferred because it yields particularly excellent yields of aryl compounds having a fluoroalkyl group.

[0014] The cobalt compounds used in this manufacturing method are not particularly limited, but include cobalt(III) fluoride, cobalt(II) chloride, cobalt(II) bromide, cobalt(II) iodide, cobalt(II) carbonate, cobalt(II) acetate, cobalt(II) oxalate, cobalt(II) benzoate, cobalt(II) citrate, cobalt(II) phosphate, cobalt(III) acetylacetonate, cobalt(II) isopropoxide, cobalt(II) thiocyanate, and tris(2,2,6,6-tetramethyl-3,5-heptanedionate)cobalt(II) I) Examples of cobalt compounds include tricarbonylnitrosylcobalt, bis(cyclopentadienyl)cobalt hexafluorophosphate, cobalt(II) hydroxide, cobalt(II) silicide, cobalt(II) stearate, hexaamminecobalt(III) chloride, bis(pentamethylcyclopentadienyl)cobalt hexafluorophosphate, cobalt(II) sulfide, cyclopentadienylcobaltdicarbonyl, sarcomine, tetracobaltdodecacarbonyl, phthalocyaninecobalt(II), and ammoniumcobalt(II) phosphate. Cobalt(II) bromide or cobalt(III) acetylacetonate are preferred because they yield particularly good yields of aryl compounds having fluoroalkyl groups.

[0015] The ligands used in this manufacturing method are not particularly limited, but examples of monodentate ligands include trialkylphosphines such as trimethylphosphine, tricycloalkylphosphines such as tricyclohexylphosphine (PCy3), triphenylphosphine, tri(4-fluorophenyl)phosphine, tri(2-tolyl)phosphine, tri(3-tolyl)phosphine, tri(4-tolyl)phosphine, tris[4-(trifluoromethyl)phenyl]phosphine, and tris(4-anisyl)phosphine. Examples of triarylphosphines such as tris(2,4-xylyl)phosphine, tris(3,5-xylyl)phosphine, and tri(2,4,6-trimethoxyphenyl)phosphine, and triheteroarylphosphines such as tris-2-furanylphosphine, are examples of bidentate ligands such as bisdiphenylphosphinomethane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp), and 1,4-bis(diphenylphosphino) 1,5-Bis(diphenylphosphino)pentane (dppb), 1,6-Bis(diphenylphosphino)hexane (dpphe), 1,2-Bis(diphenylphosphino)benzene, cis-1,2-Bis(diphenylphosphino)ethylene, 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene, 2,2'-Bis(diphenylphosphino)-1,1'-Binaphthyl (BINAP), 1,1'-Bis(diphenylphosphino)ferrocene, 1,4-Bis Examples of tridentate ligands include (bis(3,5-dimethylphenyl)phosphino)butane and 1,4-bis(bis(3,5-di-t-butylphenyl)phosphino)butane. Examples of tridentate ligands include bis(2-diphenylphosphinoethyl)phenylphosphine, 1,1,1-tris(diphenylphosphinomethyl)ethane, and 1,1,1-tris(bis(3,5-dimethylphenyl)phosphinomethyl)ethane. Examples of tetradentate ligands include tris(2-diphenylphosphinoethyl)phosphine.Because it yields particularly good yields of aryl compounds having fluoroalkyl groups, 1,2-bis(diphenylphosphino)ethane, 1,2-bis(diphenylphosphino)benzene, and cis-1,2-bis(diphenylphosphino)ethylene are preferred as ligands, with 1,2-bis(diphenylphosphino)ethane being the most preferred.

[0016] There are no particular restrictions on the molar ratio of the halogenated fluoroalkyl compound (2) and the aryl compound (1) in this manufacturing method, but it is desirable to use 2 to 3 molar equivalents of the aryl compound (1) for every 1 molar equivalent of the halogenated fluoroalkyl compound (2) in order to obtain a good yield.

[0017] There are no particular restrictions on the amount of cobalt compound used in this manufacturing method. Generally, it is preferable to use 0.01 to 0.2 molar equivalents per molar equivalent of the fluoroalkyl halogenated compound, and more preferably 0.01 to 0.05 molar equivalents. There are no particular restrictions on the molar ratio of cobalt catalyst to ligand used in this manufacturing method, but it is preferable that the ratio of cobalt compound to ligand is in the range of 1:1 to 1:10, and more preferably in the range of 1:1 to 1:2.

[0018] Examples of metal reducing agents used in this manufacturing method include zinc, manganese, copper, iron, magnesium, and aluminum. The form of the metal is not particularly limited, but powder form is preferred. Zinc is preferred because it yields particularly good yields of aryl compounds containing fluoroalkyl groups.

[0019] There are no particular restrictions on the type of solvent that can be used in this manufacturing method, as long as it does not inhibit the reaction. Examples of usable solvents include haloalkanes such as dichloromethane, chloroform, tetrachloromethane, 1,2-dichloroethane, and 1,1,2,2-tetrachloroethane; ethers such as diisopropyl ether, dibutyl ether, CPME, THF, 2-methyltetrahydrofuran, 1,4-dioxane, and dimethoxyethane; carbonate esters such as ethylene carbonate, propylene carbonate, dimethyl carbonate, diethyl carbonate, ethyl methyl carbonate, and 4-fluoroethylene carbonate; esters such as ethyl acetate, butyl acetate, methyl propionate, ethyl propionate, methyl butyrate, and γ-lactone; amides such as DMF, DMAc, and NMP; ureas such as TMU and DMPU; acetonitrile; and acetone. One of these solvents can be used alone, or multiple solvents can be mixed in any ratio. DMF, methanol, or acetonitrile are preferred as solvents because they yield particularly good yields of aryl compounds having fluoroalkyl groups.

[0020] There are no particular restrictions on the reaction temperature of this manufacturing method. For example, it can be carried out at a temperature appropriately selected within the range of -78°C to 150°C. A range of 20°C to 40°C is preferred for good yield. There are no particular restrictions on the reaction time in this manufacturing method. For example, the reaction time can be appropriately selected from the range of 10 minutes to 100 hours. A range of 1 hour to 24 hours is preferred for good yield.

[0021] In this manufacturing method, it is preferable to carry out the process in an inert gas atmosphere because it yields excellent results. Specific examples of the inert gas include helium, neon, argon, krypton, xenon, and nitrogen gas. Nitrogen gas or argon gas are preferred because they are inexpensive.

[0022] A typical embodiment of this manufacturing method involves mixing a cobalt compound, a ligand, a metal reducing agent, and an aryl compound (1) in a reaction vessel, then adding a halogenated fluoroalkyl compound (2) and mixing to carry out the reaction.

[0023] After the reaction is complete, the aryl compound having a fluoroalkyl group produced can be purified by appropriately selecting and using a general purification method used by those skilled in the art for purifying aryl compounds. Specific purification methods include filtration, extraction, centrifugation, washing, crystallization, column chromatography, and preparative liquid chromatography. [Examples]

[0024] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0025] 1 A Bruker ASCEND (400 MHz; manufactured by BRUKER) was used to measure the H-NMR spectrum. 1 The 1H-NMR spectrum was measured using deuterated chloroform (CDCl3) as the measurement solvent and tetramethylsilane (TMS) as the internal standard. 19 The 1F-NMR spectrum was measured using deuterated chloroform (CDCl3) as the measurement solvent and pentafluorobenzene (C6F6) as the internal standard.

[0026] Unless otherwise specified, reaction products were identified using a gas chromatography-mass spectrometer (GC-MS). The measurement conditions were as follows: Shimadzu GC-2030, electron electrophoresis (EI), split injection method, DB-5MS UI column (length: 30m, inner diameter: 0.250mm, film thickness: 0.25μm), helium carrier gas 100kPa, injection volume 1.0μL, and heating conditions: held at 80°C for 2 minutes, then heated to 180°C at 20°C / min, and held at 180°C for 8 minutes.

[0027] Example 1 [ka] Under an argon atmosphere, p-toluidine (129 mg, 1.80 mmol), perfluorohexyl iodide (268.0 mg, 0.60 mmol), cobalt(II) acetylacetonate (8.0 mg, 0.03 mmol), 1,2-bis(diphenylphosphin)ethane (12 mg, 0.03 mmol), zinc powder (47 mg, 0.72 mmol), and acetonitrile (0.50 mL) were added and the mixture was stirred at 24°C for 2 hours. Ethyl acetate was added to the reaction mixture, and the residue was removed by Celite filtration. The filtrate was concentrated under reduced pressure. The crude product obtained was purified by silica gel column chromatography (n-hexane / ethyl acetate) to obtain the target compound (4-methyl-2-(perfluorohexyl)aniline) (241 mg, 95%).

[0028] 4-Methyl-2-(perfluorohexyl)aniline: 1 H NMR (400MHz, CDCl3): δ7.10(brs,2H),6.63(d,J=8.8Hz,1H),4.07(brs,2H),2.25(s,3H). 19 FNMR(377MHz,CDCl3):δ-81.2(t,J=9.8Hz,3F),-108.8(t,J=15.1Hz,2F),-122.1-122.2(m,2F),-123.1(s,2F),-126.4 7-126.54(m,2F).IR(KBr)3527,3422,1633,1511,1360,1192,1041,1118,1036,870,818,739,698,650,571,534,464cm -1 .

[0029] Example 2 [ka] Under an argon atmosphere, p-toluidine (129 mg, 1.20 mmol), perfluoropentyliodide (238.0 mg, 0.6 mmol), cobalt(II) acetylacetonate (8.0 mg, 0.03 mmol), 1,2-bis(diphenylphosphino)ethane (12 mg, 0.03 mmol), zinc powder (47 mg, 0.72 mmol), and acetonitrile (0.50 mL) were added, and the mixture was stirred at 24°C for 2 hours. Ethyl acetate was added to the reaction mixture, the mixture was filtered through Celite to remove residues, and the filtrate was concentrated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (normal hexane / ethyl acetate) to give the target compound (4-methyl-2-(perfluoropentyl)aniline) (259 mg, 69%).

[0030] 4-Methyl-2-(perfluorohexyl)aniline: 1 1H NMR (400 MHz, CDCl3): δ 7.10 (brs, 2H), 6.63 (d, J=8.8 Hz, 1H), 4.07 (brs, 2H), 2.54 (s, 3H). 19 19F NMR (377 MHz, CDCl3): δ -81.2 (t, J=9.4 Hz, 3F), -108.8 (t, J=15.1 Hz, 2F), -122.4 (s, 2F), -122.9-123.0 (m, 2F), -126.5-126.6 (m, 2F). IR (KBr) 3526, 3422, 1633, 1511, 1356, 1230, 1192, 1137, 1100, 880, 820, 140, 697, 643, 570, 533, 463 cm -1 .

[0031] Example 3 [Chemical Formula] Under an argon atmosphere, p-toluidine (129 mg, 1.20 mmol), perflubutyl iodide (208 mg, 0.60 mmol), cobalt(II) acetylacetonate (8.0 mg, 0.03 mmol), 1,2-bis(diphenylphosphin)ethane (12 mg, 0.03 mmol), zinc powder (47 mg, 0.72 mmol), and acetonitrile (0.50 mL) were added and the mixture was stirred at 24°C for 2 hours. Ethyl acetate was added to the reaction mixture, and the residue was removed by Celite filtration. The filtrate was concentrated under reduced pressure. The crude product obtained was purified by silica gel column chromatography (n-hexane / ethyl acetate) to obtain the target compound (4-methyl-2-(perfluorobutyl)aniline) (184 mg, 94%).

[0032] 4-Methyl-2-(perfluorobutyl)aniline: 1 H NMR (400MHz, CDCl3): δ7.10(d,J=7.2Hz,2H),6.63(d,J=8.8Hz,1H),4.06(brs,2H),2.25(s,3H). 19 F NMR (377MHz, CDCl3): δ-81.4(tJ=9.8Hz,3F),-109.0(tJ=13.6Hz,3F)-123.1(tJ=2.6Hz,3F),-126.2-126. 3(m,2F).IR(KBr)3525,3413,1720,1631,1512,1349,1201,1128,1020,891,814,741,689,626,537,461cm -1 .

[0033] Example 4 [ka] Under an argon atmosphere, p-toluidine (129 mg, 1.20 mmol), perfluoropropyl iodide (200 mg, 0.60 mmol), cobalt(II) acetylacetonate (8.0 mg, 0.03 mmol), 1,2-bis(diphenylphosphin)ethane (12 mg, 0.03 mmol), zinc powder (47 mg, 0.72 mmol), and acetonitrile (0.50 mL) were added and the mixture was stirred at 24°C for 2 hours. Ethyl acetate was added to the reaction mixture, and the residue was removed by Celite filtration. The filtrate was concentrated under reduced pressure. The crude product obtained was purified by silica gel column chromatography (n-hexane / ethyl acetate) to obtain the target compound (4-methyl-2-(perfluoropropyl)aniline) (145 mg, 88%).

[0034] 4-Methyl-2-(perfluoropropyl)aniline: 1 H NMR (400MHz, CDCl3): δ7.10(d,J=6.4Hz,2H),6.63(d,J=8.8Hz,1H),4.07(brs,2H),2.25(s,3H). 19 F NMR(377MHz,CDCl3):δ-80.6(t,J=9.4Hz,3F),-109.6-109.7(m,2F),-126.7(s,2F).IR(KBr)35 24,3418,1719,1633,1510,1422,1345,1208,1178,1107,929,839,818,745,679,592,529,465cm -1 .

[0035] Example 5 [ka] Under an argon atmosphere, p-toluidine (129 mg, 1.20 mmol), perfluoroisopropyl iodide (200 mg, 0.60 mmol), cobalt(II) acetylacetonate (8.0 mg, 0.03 mmol), 1,2-bis(diphenylphosphin)ethane (12 mg, 0.03 mmol), zinc powder (47 mg, 0.72 mmol), and acetonitrile (0.50 mL) were added and the mixture was stirred at 24°C for 2 hours. Ethyl acetate was added to the reaction mixture, and the residue was removed by Celite filtration. The filtrate was concentrated under reduced pressure. The crude product obtained was purified by silica gel column chromatography (n-hexane / ethyl acetate) to obtain the target compound (4-methyl-2-(perfluoroisopropyl)aniline) (164 mg, 99%).

[0036] 4-Methyl-2-(perfluoroisopropyl)aniline: 1 H NMR (400MHz, CDCl3): δ7.09(d,J=7.2Hz,2H),6.66(d,J=8.4Hz,1H),4.17(brs,2H),2.27(s,3H). 19 F NMR(377MHz,CDCl3):δ-75.0(s,6F),-181.8(s,1F).IR(KBr)3533,3420,1726,1 631,1513,1319,1276,1216,1169,1104,968,850,816,744,706,674,540,464cm -1 .

[0037] Example 6 [ka] Under an argon atmosphere, 4-n-butylaniline (179 mg, 1.20 mmol), perfluorobutyliodide (208 mg, 0.60 mmol), cobalt(II) acetylacetonate (8.0 mg, 0.03 mmol), 1,2-bis(diphenylphosphin)ethane (12 mg, 0.03 mmol), zinc powder (47 mg, 0.72 mmol), and acetonitrile (0.50 mL) were added and the mixture was stirred at 24°C for 2 hours. Ethyl acetate was added to the reaction mixture, and the residue was removed by Celite filtration. The filtrate was concentrated under reduced pressure. The crude product obtained was purified by silica gel column chromatography (n-hexane / ethyl acetate) to obtain the target compound (4-butyl-2-(perfluorobutyl)aniline) (95 mg, 43%).

[0038] 4-Butyl-2-(perfluorobutyl)aniline: 1 H NMR(400MHz, CDCl3): δ7.14(d,J=9.6Hz,2H),6.68(d,J=8.0Hz,1H),4.11(brs,2H ),2.54(t,J=8.0Hz,2H),1.60-1.53(m,2H),1.40-1.31(m,2H),0.99-0.92(m,3H). 19 F NMR(377MHz,CDCl3):δ-81.4(t,J=9.8Hz,3F),-109.3(t,J=12.4Hz,2F),-123.1-123.2(m,2F),-126.3(t,J=14.0Hz,2 F).IR(KBr)3523,3422,2960,2932,2863,1631,1510,1431,1349,1229,1200,1129,1012,892,813,743,692,752,462cm -1 .

[0039] Example 7 [ka] Under an argon atmosphere, 3,4-dimethoxyaniline (184 mg, 1.20 mmol), perfluorobutyl iodide (208 mg, 0.60 mmol), cobalt(II) acetylacetonate (8.0 mg, 0.03 mmol), 1,2-bis(diphenylphosphin)ethane (12 mg, 0.03 mmol), zinc powder (47 mg, 0.72 mmol), and acetonitrile (0.50 mL) were added and the mixture was stirred at 24°C for 2 hours. Ethyl acetate was added to the reaction mixture, and the residue was removed by Celite filtration. The filtrate was concentrated under reduced pressure. The crude product obtained was purified by silica gel column chromatography (n-hexane / ethyl acetate) to obtain the target compound (4,5-dimethoxy-2-(perfluorobutyl)aniline) (106 mg, 47%).

[0040] 4,5-Dimethoxy-2-(perfluorobutyl)aniline: 1 H NMR (400MHz, CDCl3): δ6.75(s,1H),6.23(s,1H),4.00(brs,2H),3.87(s,3H),3.82(s,3H). 19 F NMR(377MHz,CDCl3):δ-81.4(t,J=9.4Hz,3F),-108.0(t,J=12.4Hz,2F),-123.2(t,J=6.8Hz,2F),-126.2-126.3(m,2H).IR(KBr)351 0,3372,3247,2933,2850,1669,1519,1455,1415,1387,1350,1230,1205,1160,1128,1092,1017,981,864,790,737,661,585,533cm -1 .

[0041] Example 8 [ka] Under an argon atmosphere, 1-naphthaleneamine (184 mg, 1.20 mmol), perfluorobutyl iodide (208 mg, 0.60 mmol), cobalt(II) acetylacetonate (8.0 mg, 0.03 mmol), 1,2-bis(diphenylphosphin)ethane (12 mg, 0.03 mmol), zinc powder (47 mg, 0.72 mmol), and acetonitrile (0.50 mL) were added and the mixture was stirred at 24°C for 2 hours. Ethyl acetate was added to the reaction mixture, and the residue was removed by Celite filtration. The filtrate was concentrated under reduced pressure. The crude product obtained was purified by silica gel column chromatography (n-hexane / ethyl acetate) to obtain the target compound (1-amino-2-(perfluorobutyl)naphthalene) (105 mg, 48%).

[0042] 1-Amino-2-(perfluorobutyl)naphthalene: 1 H NMR (400MHz, CDCl3): δ7.88(d,J=8.0Hz,1H),7.80-7.78(m,1H),7.59-7.50(m,2H),7.34(d,J=8.8Hz,1H),7.27(d,J=8.8Hz,1H),4.93(brs,2H). 19 F NMR(377MHz,CDCl3):δ-81.3(t,J=9.8Hz,3F),-107.8(t,J=13.9Hz,2F),-123.1(d,J=8.3Hz,2F),-126.2(t,J=16.2H z,2H).IR(KBr)3533,3438,3069,2925,2852,1628,1573,1513,1435,1348,1194,1127,858,786,726,662,569,532cm -1 .

[0043] Example 9 [ka] Under an argon atmosphere, 4-aminophenylboronic acid pinacol ester (263 mg, 1.20 mmol), perfluorobutyl iodide (208 mg, 0.60 mmol), cobalt(II) acetylacetonate (8.0 mg, 0.03 mmol), 1,2-bis(diphenylphosphin)ethane (12 mg, 0.03 mmol), zinc powder (47 mg, 0.72 mmol), and acetonitrile (0.50 mL) were added and the mixture was stirred at 24°C for 2 hours. Ethyl acetate was added to the reaction mixture, and the mixture was filtered by Celite filtration to remove the residue. The filtrate was concentrated under reduced pressure. The crude product obtained was purified by silica gel column chromatography (n-hexane / ethyl acetate) to obtain the target compound (4-butyl-2-(perfluorobutyl)aniline) (81 mg, 31%).

[0044] 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(perfluorobutyl)aniline: 1 H NMR (400MHz, CDCl3): δ7.77(s,1H),7.71(d,J=8.0Hz,1H),6.67(d,J=8.0Hz,1H),4.42( brs,2H),1.32(s,12H).19FNMR(377MHz,CDCl3):δ-81.4(t,J=9.4Hz,3F),-109.0(t,J= 13.9Hz,2F),-123.0(d,J=6.8Hz,2F),-126.3(t,J=13.6Hz,2H).IR(KBr)3406,3987,16 13,1564,1362,1315,1228,1128,1020,961,886,850,812,741,661,614,535,448cm-1.

[0045] Example 10 [ka] Under an argon atmosphere, aniline (168 mg, 1.80 mmol), perfluorobutyl iodide (208 mg, 0.60 mmol), cobalt(II) acetylacetonate (8.0 mg, 0.03 mmol), 1,2-bis(diphenylphosphin)ethane (12 mg, 0.03 mmol), zinc powder (47 mg, 0.72 mmol), and acetonitrile (0.50 mL) were added, and the mixture was stirred at 24°C for 2 hours. After the reaction was complete, the target product was identified by GC-MS measurement of the reaction mixture. Ethyl acetate was added to the reaction mixture, and the residue was removed by Celite filtration. The filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (n-hexane / ethyl acetate) to obtain the target compounds (2-(perfluorobutyl)aniline (82 mg, 26%), 2-(perfluorobutyl)aniline (71 mg, 23%), 2,4-bis(perfluorobutyl)aniline) (2%).

[0046] 2-(perfluorobutyl)aniline (82 mg, 26%): 19 1F NMR (377MHz, CDCl3): δ-80.9 (t, J=9.4Hz, 3F), -108.7 (t, J=13.6Hz, 2F), -122.8 (d, J=6.8Hz, 2F), -125.8-125.9 (m, 2F).; 4-(perfluorobutyl)aniline (71mg, 23%): 19 F NMR (377MHz, CDCl3): -81.0 (t, J=9.4Hz, 3F), -109.5 (t, J=13.6Hz, 2F), -122.8 (q, J=9.4Hz, 2F), -125.5 (q, J=10.9Hz, 2H).; 2,4-Bis(perfluorobutyl)aniline (2%): GCMS (EI): m / z: calcd for C 14 H5F 18 N[M]529.

[0047] Example 13 [ka] Under an argon atmosphere, 4-methoxyphenol (224 mg, 1.80 mmol), perfluorobutyl iodide (208 mg, 0.60 mmol), cobalt(II) acetylacetonate (8.0 mg, 0.03 mmol), 1,2-bis(diphenylphosphin)ethane (12 mg, 0.03 mmol), zinc powder (47 mg, 0.72 mmol), and acetonitrile (0.50 mL) were added, and the mixture was stirred at 24°C for 2 hours. After the reaction was complete, the target product was identified by GC-MS analysis of the reaction mixture, and the yield was calculated by gas chromatography (32%).

[0048] 4-Methoxy-2-(perfluorobutyl)phenol:GCMS(EI):m / z:calcd for C 11 H7F9O2[M]342.

[0049] Example 14 [ka] Under an argon atmosphere, 4-ethylphenol (220 mg, 0.60 mmol), perfluorobutyl iodide (208 mg, 0.60 mmol), cobalt(II) acetylacetonate (8.0 mg, 0.03 mmol), 1,2-bis(diphenylphosphin)ethane (12 mg, 0.03 mmol), zinc powder (47 mg, 0.72 mmol), and acetonitrile (0.50 mL) were added and stirred at 24°C for 2 hours. After the reaction was complete, the target product was identified by GC-MS analysis of the reaction mixture, and the yield was calculated by gas chromatography (19%).

[0050] 4-Ethyl-2-(perfluorobutyl)phenol:GCMS(EI):m / z:calcd for C 12 H9F9O[M]340.

[0051] Example 15 [ka] Under an argon atmosphere, 4-isopropylphenol (245 mg, 1.80 mmol), perfluorobutyl iodide (208 mg, 0.60 mmol), cobalt(II) acetylacetonate (8.0 mg, 0.03 mmol), 1,2-bis(diphenylphosphin)ethane (12 mg, 0.03 mmol), zinc powder (47 mg, 0.72 mmol), and acetonitrile (0.50 mL) were added and stirred at 24°C for 2 hours. After the reaction was complete, the target product was identified by GC-MS analysis of the reaction mixture, and the yield was calculated by gas chromatography (36%).

[0052] 4-Isopropyl-2-(perfluorobutyl)phenol:GCMS(EI):m / z:calcd for C 13 H 11 F9O[M]354.

[0053] Example 16 [ka] Under an argon atmosphere, 4-cyclohexylphenol (317 mg, 1.80 mmol), perfluorobutyl iodide (208 mg, 0.60 mmol), cobalt(II) acetylacetonate (8.0 mg, 0.03 mmol), 1,2-bis(diphenylphosphin)ethane (12 mg, 0.03 mmol), zinc powder (47 mg, 0.72 mmol), and acetonitrile (0.50 mL) were added, and the mixture was stirred at 24°C for 2 hours. After the reaction was complete, the target product was identified by GC-MS analysis of the reaction mixture, and the yield was calculated by gas chromatography (44%).

[0054] 4-Cyclohexyl-2-(perfluorobutyl)phenol:GCMS(EI):m / z:calcd for C 16 H 15 F9O[M]394.

Claims

1. General formula (1) 【Chemistry 1】 (In the formula, R represents an alkyl group having 1 to 6 carbon atoms, an alkyloxy group having 1 to 4 carbon atoms, a haloalkyl group having 1 to 4 carbon atoms, an aromatic ring group, a boryl group, or a halogen atom, and may be substituted in the same or different ways. n represents an integer between 0 and 4. A represents an amino group or a hydroxyl group. An aryl compound represented by, General formula (2) 【Chemistry 2】 A halogenated fluoroalkyl compound represented by (wherein Rf represents a fluoroalkyl group having 1 to 10 carbon atoms, and X represents a bromine atom, a chlorine atom, or an iodine atom) is reacted in the presence of a cobalt compound, a phosphine ligand, and a metal reducing agent, resulting in general formula (3). 【Transformation 3】 A method for producing an aryl compound having a fluoroalkyl group represented by the formula (wherein R, n, A, and Rf are as defined above; m is 1 or 2; however, n + m is an integer from 1 to 5).

2. The manufacturing method according to claim 1, wherein X is an iodine atom.

3. The manufacturing method according to claim 1 or 2, wherein the metal reducing agent is zinc.

4. The aforementioned cobalt compounds include cobalt(III) fluoride, cobalt(II) chloride, cobalt(II) bromide, cobalt(II) iodide, cobalt(II) carbonate, cobalt(II) acetate, cobalt(II) oxalate, cobalt(II) benzoate, cobalt(II) citrate, cobalt(II) phosphate, cobalt(III) acetylacetonate, cobalt(II) isopropoxide, cobalt(II) thiocyanate, tris(2,2,6,6-tetramethyl-3,5-heptanedionate)cobalt(III) tricarbonylnitrosylcobalt, and hexafluorophosphate. A method for producing a product according to claim 1 or 2, wherein the compound is one or more compounds selected from the group consisting of bis(cyclopentadienyl)cobalt, cobalt(II) hydroxide, cobalt(II) silide, cobalt(II) stearate, hexaamminecobalt(III) chloride, bis(pentamethylcyclopentadienyl)cobalt hexafluorophosphate, cobalt(II) sulfide, cyclopentadienylcobaltdicarbonyl, sarcomine, tetracobaltdodecacarbonyl, phthalocyaninecobalt(II), and ammoniumcobalt(II).

5. The method for producing a product according to any one of claims 1 or 2, wherein the cobalt compound is cobalt(II) bromide or cobalt(III) acetylacetonate.

6. The manufacturing method according to claim 1 or 2, wherein the phosphine ligand is a bidentate phosphine ligand.

7. The method for producing a product according to any one of claims 1 or 2, wherein the phosphine ligand is 1,2-bis(diphenylphosphino)ethane (dppe), 1,2-bis(diphenylphosphino)benzene, or cis-1,2-bis(diphenylphosphino)ethylene.

8. A manufacturing method according to any one of claims 1 or 2, characterized in that the reaction temperature is in the range of 20 to 40°C.

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