Method for producing tetrafluorosulfanyl group-containing aryl compounds

Abstract

The present invention provides a method for producing a tetrafluorosulfanyl group-containing aryl compound, wherein a tetrafluorosulfanyl group-containing aryl compound represented by general formula (1) is synthesized by carrying out a reaction in which a thioaryl compound represented by general formula (2) is added to an olefin compound represented by general formula (3) in the presence of a radical initiator. (In the formula, A1 represents an optionally substituted aryl group or an optionally substituted heteroaryl group; each of R1, R2, R3 and R4 independently represents a hydrogen atom, a fluorine atom or a chlorine atom; and two or more moieties among the R1, R2, R3 and R4 moieties are fluorine atoms.)

Description

[Technical Field]

[0001] The present invention relates to a method for producing a tetrafluorosulfanyl group-containing aryl compound in which a tetrafluorosulfanyl group is introduced into an aryl group. This application claims priority based on Japanese Patent Application No. 2021-154611 filed in Japan on September 22, 2021, Japanese Patent Application No. 2021-171007 filed in Japan on October 19, 2021, and Japanese Patent Application No. 2022-046766 filed in Japan on March 23, 2022, the contents of which are incorporated herein by reference. [Background technology]

[0002] Fluorine-containing compounds exhibit unique material properties and biological activity. For example, the introduction of fluorine atoms or trifluoromethyl groups into organic compounds improves metabolic stability and hydrophobicity. For this reason, the use of compounds containing fluorine atoms is particularly prominent in the development of pharmaceuticals and agricultural chemicals. In recent years, with a view to improving the functionality of fluorine-containing compounds, research has shifted to functional groups that have a greater effect on improving hydrophobicity. For example, sulfur-fluorine functional groups, which have a structure in which multiple fluorine atoms are bonded to hexavalent sulfur, have attracted attention as they confer higher hydrophobicity than the corresponding carbon-fluorine functional groups (Non-Patent Document 1).

[0003] On the other hand, it is difficult to introduce sulfur-fluorine functional groups into existing compounds. For this reason, despite their attractiveness, the use of sulfur-fluorine functional groups in active ingredients of pharmaceuticals and pesticides, organic materials, etc. has not progressed very much. Research that has progressed so far has focused on the use of pentafluoro-λ as a sulfur-fluorine functional group. 6 -sulfanyl (SF5) group. A practical method for synthesizing aromatic SF5 compounds is the introduction of chlorotetrafluoro-λ 6 A two-step synthesis using a -sulfanyl (SF4Cl) compound as an intermediate has been developed (Patent Document 1). In addition, aromatic SF4CF3 compounds have been synthesized and have been found to have greater hydrophobicity than aromatic SF5 compounds (Non-Patent Document 2). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2010 / 014665 [Non-patent literature]

[0005] [Non-Patent Document 1] Savoie and Welch, Chemical Reviews, 2015, vol.115, p.1130-1190. [Non-patent document 2] Kirsch and Hahn, Eur. J. Org. Chem. 2006, vol.2006(5), p.1125-1131. Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide a novel method for efficiently synthesizing a tetrafluorosulfanyl group-containing aryl compound in which a tetrafluorosulfanyl group is introduced into an aryl group. [Means for solving the problem]

[0007] The present inventors have discovered that a tetrafluorosulfanyl group-containing aryl compound can be synthesized in a single step by reacting an SF4Cl compound with a fluorine-substituted olefin in the presence of a radical initiator, and have thus completed the present invention.

[0008] That is, the present invention is as follows. [1] In the presence of a radical initiator, a compound represented by the following general formula (2)

[0009] [ka]

[0010] [In the formula, A 1 is an optionally substituted aryl group or an optionally substituted heteroaryl group. A thioaryl compound represented by the following general formula (3)

[0011] [ka]

[0012] [In the formula, R 1 , R 2 , R 3 , and R 4 are each independently a hydrogen atom, a fluorine atom, or a chlorine atom, provided that R 1 , R 2 , R 3 , and R 4 At least two of the atoms are fluorine atoms. and carrying out an addition reaction with an olefin compound represented by the following general formula (1):

[0013] [ka]

[0014] [In the formula, A 1 , R 1 , R 2 , R 3 , and R 4 is the same as above] synthesizing a tetrafluorosulfanyl group-containing aryl compound represented by the formula: A method for producing a tetrafluorosulfanyl group-containing aryl compound. [2] A. 1 is an aryl group optionally having one or more substituents selected from the group consisting of a halogen atom, an alkyl group, an alkenyl group, an aryl group, an alkoxy group, a hydroxy group, a carboxy group, an acyl group, a cyano group, an amino group, and a nitro group. [3] The method for producing the tetrafluorosulfanyl group-containing aryl compound according to [1] or [2], wherein the reaction is carried out at -40 to 130 °C. [4] The following general formula (1)

[0015] [Chemical formula]

[0016] [In the formula, A 1 is an aryl group which may have a substituent or a heteroaryl group which may have a substituent; R 1 , R 2 , R 3 , and R 4 are each independently a hydrogen atom, a fluorine atom, or a chlorine atom, and among R 1 , R 2 , R 3 , and R 4 , two or more are fluorine atoms.] The tetrafluorosulfanyl group-containing aryl compound represented by [Advantages of the Invention]

[0017] According to the method of the present invention, the addition reaction of the SF4Cl compound to the fluorine-substituted olefin can be carried out in a single step, and the tetrafluorosulfanyl group-containing aryl compound can be efficiently synthesized. [Embodiments for Carrying Out the Invention]

[0018] In the present invention and the specification of the present application, "C p1-p2 " (p1 and p2 are positive integers satisfying p1 < p2) means a group having a carbon number of p1 to p2.

[0019] In the present invention and the specification of the present application, "C 1-6 alkyl group" is an alkyl group having 1 to 6 carbon atoms, which may be linear or branched. C 1-6Examples of the alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a neopentyl group, a tert-pentyl group, and a hexyl group.

[0020] In the present invention and the present specification, "C 1-6 "Alkoxy group" means C 1-6 A group in which an oxygen atom is bonded to the bond terminal of an alkyl group. 1-6 The alkoxy group may be straight-chain or branched. 1-6 Examples of the alkoxy group include a methoxy group, an ethoxy group, a propoxy group, a butoxy group, a tert-butoxy group, a pentyloxy group, and a hexyloxy group.

[0021] In the present invention and the present specification, "C 2-6 The term "alkenyl group" refers to an alkyl group having 2 to 6 carbon atoms in which at least one carbon-carbon bond is unsaturated. 2-6 The alkenyl group may be a straight chain or a branched chain. 2-6 Examples of the alkenyl group include a vinyl group, an allyl group, a butenyl group, a pentenyl group, and a hexenyl group.

[0022] In the present invention and the present specification, "C 2-7 An "acyl group" is an acyl group in which the hydrocarbon group portion obtained by removing the carbonyl group is C 1-6 Alkyl group, C 2-6 The acyl group is an alkenyl group, a 5- or 6-membered aryl group, or a 5- or 6-membered heteroaryl group. The hydrocarbon portion of the acyl group may be either linear or branched. 2-7 Examples of the acyl group include a formyl group, an acetyl group, a propanoyl group, a propenoyl group, and a benzoyl group.

[0023] In the present invention and the present specification, the "halogen atom" means a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom. The "halogen atom other than fluorine atom" means a chlorine atom, a bromine atom, or an iodine atom. As an example of the "halogen atom other than fluorine atom", a chlorine atom or a bromine atom is preferable, and a chlorine atom is particularly preferable.

[0024] Also, hereinafter, "Compound (n)" means a compound represented by formula (n).

[0025] <Addition reaction of <SF4Cl compound> and fluorine-substituted olefin> The method for producing a tetrafluorosulfanyl group-containing aryl compound (hereinafter sometimes referred to as "SF4-containing aryl compound") according to the present invention adds a sulfur atom in the SF4Cl group in the SF4Cl group-containing aryl compound to a fluorine-substituted olefin. Specifically, in the presence of a radical initiator, a thioaryl compound represented by the following general formula (2) is added to an olefin compound represented by the following general formula (3). Thereby, a tetrafluorosulfanyl group-containing aryl compound (1) having higher hydrophobicity than the SF5-containing aryl compound is obtained.

[0026]

Chemical formula

[0027] In general formula (2) and general formula (1), A 1is an aryl group which may have a substituent or a heteroaryl group which may have a substituent. The aryl group is not particularly limited, and examples thereof include a phenyl group, a naphthyl group, an anthryl group, and a 9-fluorenyl group, with a phenyl group being particularly preferred. The heteroaryl group is not particularly limited, and examples thereof include a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, a pyrazolyl group, a quinolyl group, an isoquinolyl group, a pyrrolyl group, an imidazolyl group, an indolyl group, a furyl group, a benzofuryl group, a thienyl group, a benzothienyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, and an isothiazolyl group.

[0028] An "optionally substituted aryl group" is a group in which one or more, preferably 1 to 3, hydrogen atoms bonded to a carbon atom of an aryl group have been substituted with other functional groups. Similarly, an "optionally substituted heteroaryl group" is a group in which one or more, preferably 1 to 3, hydrogen atoms bonded to a carbon atom of a heteroaryl group have been substituted with other functional groups. When a heteroaryl group has two or more substituents, the substituents may be the same or different.

[0029] A 1 The aryl group and heteroaryl group may have one or more substituents in addition to the sulfur atom for fluorination. The substituents include a halogen atom, an alkyl group, an alkenyl group, an alkoxy group, an aryl group, an acyl group, a hydroxy group, a carboxy group, an alkyloxycarbonyl group, an aryloxycarbonyl group, a cyano group, an amino group, and a nitro group. The alkyl group may be C 1-6 Alkyl groups are preferred, and C 2-6 Alkyl groups are preferred, and C 1-6 Alkoxy groups are preferred, and C 2-7 An acyl group is preferred. As the alkyloxycarbonyl group, the alkyl group portion is C 1-6 The alkyl group is preferred, and the alkyl group moiety is C 1-3A group that is an alkyl group is more preferred. As the aryloxycarbonyl group, a group in which the aryl group moiety is a phenyl group is preferred.

[0030] In general formula (3), R 1 , R 2 , R 3 , and R 4 are each independently a hydrogen atom, a fluorine atom, or a chlorine atom, provided that R 1 , R 2 , R 3 , and R 4 At least two of these are fluorine atoms. Examples of compound (3) include CF2=CF2, CF2=CFCl, CF2=CHF, CF2=CCl2, CF2=CHCl, CF2=CH2, CFCl=CFCl, CFCl=CHF, and CHF=CHF.

[0031] The amount of thioaryl compound (2) added to the reaction system may be at least a stoichiometric amount. From the viewpoints of reaction efficiency and cost, the amount of thioaryl compound (2) used is preferably 1 to 10 equivalents, more preferably 1 to 6 equivalents, of olefin compound (3).

[0032] The addition reaction of the thioaryl compound (2) and the olefin compound (3) is carried out in the presence of a radical initiator. Conventionally known initiators can be used as the radical initiator. Specifically, for example, azo compounds or peroxide radical initiators can be used. The radical initiator used in the addition reaction of the thioaryl compound represented by general formula (2) and the olefin compound represented by general formula (3) preferably contains an azo compound.

[0033] Examples of the azo compound radical initiator include azobisisobutyronitrile (hereinafter also referred to as "AIBN"), 2,2'-azobis-2-methylbutyronitrile, 2,2'-azobis-2,4-dimethylvaleronitrile (ADVN), 2,2'-azobis-N-butyl-2-methylpropionamide, dimethyl-2,2'-azobis-2-methylpropionamide, 1,1'-azobis-cyclohexane-1-carbonitrile, etc. From the viewpoint of solubility in the reaction system, AIBN, 2,2'-azobis-2-methylbutyronitrile, and 2,2'-azobis-2,4-dimethylvaleronitrile are preferred.

[0034] Examples of peroxide radical initiators include benzoyl peroxide, t-butyl peroxide, acetyl peroxide, diisopropyl peroxydicarbonate, t-butyl peroxy-2-ethylhexanate, 2-hexyl-peroxy-2-ethylhexanate, 1,1,3,3-tetramethylbutylperoxy-2-ethylhexanoate, etc. Benzoyl peroxide, t-butyl peroxide, t-butyl peroxy-2-ethylhexanate, and 2-hexyl-peroxy-2-ethylhexanate are preferred because they allow for easy reaction control.

[0035] The addition reaction of thioaryl compound (2) and olefin compound (3) can be carried out in a solvent inert to the reaction. The inert solvent is not particularly limited, but aprotic polar solvents are preferred. Examples of aprotic polar solvents include acetonitrile (MeCN), N,N'-dimethylformamide (DMF), N,N-dimethylacetamide, dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), dichloromethane (DCM), 1,2-dichloroethane (DCE), and diethyl ether. The solvent used in the reaction may be a mixture of two or more solvents.

[0036] The addition reaction is carried out by mixing a thioaryl compound (2), an olefin compound (3), and a radical initiator in a reaction solvent, and reacting the resulting mixture at an appropriate temperature for an appropriate time. The addition reaction proceeds under mild conditions. For example, the reaction temperature is not particularly limited as long as the reaction solvent is in a liquid state. The reaction can be carried out at -40 to 130°C, preferably 0 to 80°C, more preferably 20 to 50°C, or even at room temperature (0 to 30°C). For example, the addition reaction can be carried out at 20 to 50°C for less than 3 hours to obtain the desired tetrafluorosulfanyl group-containing aryl compound (1) in essentially quantitative yield. [Example]

[0037] The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

[0038] The NMR apparatus used in the analyses of the Examples and Comparative Examples was a JNM-ECZ400S (400 MHz) manufactured by JEOL Ltd. 1 H NMR showed tetramethylsilane at 0 ppm, 19 For F NMR, C6F6 was used as the reference value at -162 PPM.

[0039] <Synthesis of tetrafluorosulfanyl group-containing aryl compounds> A tetrafluorosulfanyl group-containing aryl compound was synthesized according to the following synthesis procedure.

[0040] [ka]

[0041] A solution of compound (1) (0.20 mmol) and ADVN (10 mol%) in DCE (0.1 M) was stirred in a microwave vial (10 mL) under a nitrogen atmosphere and then cooled to 0 °C. Tetrafluoroethylene (TFE) was then bubbled into the solution (1.0 atm). After stirring on an oil bath at 40 °C for 72 h, the insoluble solid was removed by filtration, and the filtrate was evaporated under reduced pressure. The resulting crude product was purified by flash silica gel column chromatography (n-hexane / EtOAc = 9 / 1 (v / v)) to give the desired compound (2).

[0042] [Example 1] (2-chlorotetrafluoroethyltetrafluoro-λ 6 Synthesis of (-sulfanyl)benzene According to the procedure described above, (chlorotetrafluoro-λ 6 -sulfanyl)benzene to (2-chlorotetrafluoroethyltetrafluoro-λ 6 Purification by flash silica gel column chromatography (n-hexane / Et0Ac=9 / 1 (volume ratio)) gave (2-chlorotetrafluoroethyltetrafluoro-λ 6 -sulfanyl)benzene (0.024 g, 37% yield) was obtained as colorless crystals.

[0043] [ka]

[0044] 1 H NMR (400 MHz, CDCl3) δ 7.71-7.83 (m, 2H), 7.42-7.54 (m, 3H). 19 F NMR (376 MHz, CDCl3) δ 47.7 (m, 4F), -67.9 (t, J = 10.8 Hz, 2F), -90.8 (m, 2F).

[0045] [Example 2] 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6Synthesis of (-sulfanyl)nitrobenzene Following the procedure described above, 4-(chlorotetrafluoro-λ 6 -sulfanyl)nitrobenzene to 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Purification by flash silica gel column chromatography (n-hexane / Et0Ac=9 / 1 (volume ratio)) gave 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 -sulfanyl)nitrobenzene (0.040 g, 55% yield) was obtained as colorless crystals.

[0046] [ka]

[0047] 1 H NMR (400 MHz, CDCl3) δ 8.33 (d, J = 8.7 Hz, 2H), 8.00 (d, J = 9.2 Hz, 2H). 13 C NMR (100 MHz, CDCl3) δ 159.4 (quint, J C-F = 21.9 Hz), 149.2, 127.7 (quint, J C-F = 4.8 Hz), 124.2, 122.1 (tt, J C-F = 303.4, 35.6 Hz), 121.3 (ttquint, J C-F = 312.1, 37.6, 36.6 Hz). 19 F NMR (376 MHz, CDCl3) δ 48.0 (m, 4F), -68.1 (t, J = 10.7 Hz, 2F), -90.7 (m, 2F).

[0048] [Example 3] 3-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Synthesis of (-sulfanyl)nitrobenzene Following the procedure described above, 3-(chlorotetrafluoro-λ6 -sulfanyl)nitrobenzene to 3-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Purification by flash silica gel column chromatography (n-hexane / Et0Ac=9 / 1 (volume ratio)) gave 3-(2-chlorotetrafluoroethyltetrafluoro-λ 6 -sulfanyl)nitrobenzene (0.034 g, 46% yield) was obtained as a colorless liquid.

[0049] [ka]

[0050] 1 H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 8.41 (d, J = 8.2 Hz, 1H), 8.13 (d, J = 8.2 Hz, 1H), 7.71 (t, J = 8.2 Hz, 1H). 19 F NMR (376 MHz, CDCl3) δ 48.3 (m, 4F), -68.1 (t, J = 10.8 Hz, 2F), -90.6 (m, 2F).

[0051] [Example 4] 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Synthesis of (-sulfanyl)fluorobenzene Following the procedure described above, 4-(chlorotetrafluoro-λ 6 -sulfanyl)fluorobenzene to 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Purification by flash silica gel column chromatography (n-hexane / EtOAc = 9 / 1 (volume ratio)) gave 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 -sulfanyl)fluorobenzene (0.035 g, 51% yield) was obtained as a colorless liquid.

[0052] [ka]

[0053] 1 H NMR (400 MHz, CDCl3) δ 7.77-7.82 (m, 2H), 7.11-7.16 (m, 2H). 19 F NMR (376 MHz, CDCl3) δ 49.0 (m, 4F), -68.0 (t, J = 10.8 Hz, 2F), -90.7 (m, 2F).

[0054] [Example 5] 3-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Synthesis of (-sulfanyl)fluorobenzene Following the procedure described above, 3-(chlorotetrafluoro-λ 6 -sulfanyl)fluorobenzene to 3-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Purification by flash silica gel column chromatography (n-hexane / Et0Ac=9 / 1 (volume ratio)) gave 3-(2-chlorotetrafluoroethyltetrafluoro-λ 6 -sulfanyl)fluorobenzene (0.012 g, 18% yield) was obtained as a colorless liquid.

[0055] [ka]

[0056] 1 H NMR (400 MHz, CDCl3) δ 7.58-7.61 (m, 1H), 7.50-7.55 (m, 1H), 7.42-7.49 (m, 1H), 7.20-7.26 (m, 1H). 19 F NMR (376 MHz, CDCl3) δ 48.0 (m, 4F), -68.0 (t, J = 10.8 Hz, 2F), -90.8 (m, 2F).

[0057] [Example 6] 2-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Synthesis of (-sulfanyl)fluorobenzene Following the procedure described above, 2-(chlorotetrafluoro-λ 6 -sulfanyl)fluorobenzene to 2-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Purification by flash silica gel column chromatography (n-hexane / Et0Ac=9 / 1 (volume ratio)) gave 2-(2-chlorotetrafluoroethyltetrafluoro-λ 6 -sulfanyl)fluorobenzene (0.009 g, 13% yield) was obtained as a colorless liquid.

[0058] [ka]

[0059] 1 H NMR (400 MHz, CDCl3) δ 7.79 (m, 1H), 7.51 (m, 1H), 7.19-7.26 (m, 2H). 19 F NMR (376 MHz, CDCl3) δ 49.0 (m, 4F), -68.0 (t, J = 10.8 Hz, 2F), -90.7 (m, 2F).

[0060] [Example 7] 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Synthesis of (-sulfanyl)chlorobenzene Following the procedure described above, 4-(chlorotetrafluoro-λ 6 -sulfanyl)chlorobenzene to 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6Purification by flash silica gel column chromatography (n-hexane / Et0Ac=9 / 1 (volume ratio)) gave 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 -sulfanyl)chlorobenzene (0.035 g, 50% yield) was obtained as a colorless liquid.

[0061] [ka]

[0062] 1 H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 9.1 Hz, 2H), 7.43 (d, J = 9.1 Hz, 2H). 19 F NMR (376 MHz, CDCl3) δ 48.4 (m, 4F), -68.0 (t, J = 10.8 Hz, 2F), -90.7 (m, 2F).

[0063] [Example 8] 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Synthesis of (-sulfanyl)bromobenzene Following the procedure described above, 4-(chlorotetrafluoro-λ 6 -sulfanyl)bromobenzene to 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Purification by flash silica gel column chromatography (n-hexane / Et0Ac=9 / 1 (volume ratio)) gave 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 -sulfanyl)bromobenzene (0.019 g, 24% yield) was obtained as a colorless liquid.

[0064] [ka]

[0065] 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 9.1 Hz, 2H), 7.60 (d, J = 9.1 Hz, 2H). 19 F NMR (376 MHz, CDCl3) δ 48.3 (m, 4F), -68.0 (t, J = 10.8 Hz, 2F), -90.8 (m, 2F).

[0066] [Example 9] 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Synthesis of Ethyl (-sulfanyl)benzoate Following the procedure described above, 4-(chlorotetrafluoro-λ 6 -sulfanyl)benzoic acid ethyl ester to 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Purification by flash silica gel column chromatography (n-hexane / Et0Ac=9 / 1 (volume ratio)) gave 4-(2-chlorotetrafluoroethyltetrafluoro-λ)benzoic acid ethyl ester. 6 Ethyl (-sulfanyl)benzoate (0.038 g, 48% yield) was obtained as a colorless liquid.

[0067] [ka]

[0068] 1 H NMR (400 MHz, CDCl3) δ 8.12 (d, J = 8.7 Hz, 2H), 7.85 (d, J = 9.0 Hz, 2H), 4.42 (q, J = 7.0 Hz, 2H), 1.41 (d, J = 7.1 Hz, 3H). 19 F NMR (376 MHz, CDCl3) δ 47.6 (m, 4F), -68.0 (t, J = 10.8 Hz, 2F), -90.8 (m, 2F).

[0069] [Example 10] 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Synthesis of (-sulfanyl)tert-butylbenzene Following the procedure described above, 4-(chlorotetrafluoro-λ 6 -sulfanyl)tert-butylbenzene to 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Purification by flash silica gel column chromatography (n-hexane / EtOAc = 9 / 1 (volume ratio)) gave 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 -sulfanyl) tert-butylbenzene (0.014 g, 18% yield) was obtained as a colorless liquid.

[0070] [ka]

[0071] 1 H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 9.1 Hz, 2H), 7.45 (d, J = 7.8 Hz, 2H), 1.34 (s, 9H). 19 F NMR (376 MHz, CDCl3) δ48.2 (m, 4F), -67.9 (t, J = 10.8 Hz, 2F), -90.8 (m, 2F).

[0072] [Example 11] 2-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Synthesis of (-sulfanyl)-5-nitropyridine Following the procedure described above, 2-(chlorotetrafluoro-λ 6 -sulfanyl)-5-nitropyridine to 2-(2-chlorotetrafluoroethyltetrafluoro-λ 6-sulfanyl)-5-nitropyridine was obtained. Purification by flash silica gel column chromatography (n-hexane / Et0Ac=9 / 1 (volume ratio)) gave 2-(2-chlorotetrafluoroethyltetrafluoro-λ 6 -sulfanyl)-5-nitropyridine (0.024 g, 33% yield) was obtained as a colorless liquid.

[0073] [ka]

[0074] 1 H NMR (400 MHz, CDCl3) δ 9.39 (d, J = 2.7 Hz, 1H), 8.72 (m, 1H), 8.02 (d, J = 8.7 Hz, 1H). 19 F NMR (376 MHz, CDCl3) δ 38.5 (m, 4F), -68.3 (m, 2F), -91.2 (m, 2F).

[0075] [Synthesis Example 1] In a glass vial (15 mL) under a nitrogen atmosphere, 2-chlorotetrafluoroethyl tetrafluoro-λ 6 A mixture of (1,1,2,2-tetrafluoroethyltetrafluoro-λ-sulfanyl)benzene (0.07 mmol), AIBN (50 mol%), and tris(trimethylsilyl)silane (3.0 equivalents) was dissolved and stirred in an oil bath at 100° C. for 1 hour. The solvent was then evaporated under reduced pressure, and the resulting crude product was purified by flash silica gel column chromatography (n-hexane / EtOAc = 9 / 1 (volume ratio)) to give the desired (1,1,2,2-tetrafluoroethyltetrafluoro-λ-sulfanyl)benzene. 6 -sulfanyl)benzene (0.014 g, 40% yield) was obtained as a colorless liquid.

[0076] [ka]

[0077] 1 H NMR (400 MHz, CDCl3) δ 7.76-7.81 (m, 2H), 7.44-7.51 (m, 3H), 6.18 (m, 1H). 19 F NMR (376 MHz, CDCl3) δ 42.7 (m, 4F), -98.0 (m, 2F), -134.3 (m, 2F).

[0078] [Example 12] 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Synthesis of (-sulfanyl)aniline 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Iron (11 equivalents) and saturated aqueous ammonium chloride solution (5 mL) were added to a solution of (0.98 mmol)-sulfanyl)nitrobenzene in ethanol (20 mL) and stirred for 2 hours at 80 °C in an oil bath. The insoluble solid was then removed by filtration through Celite, and the filtrate was evaporated under reduced pressure. The resulting crude product was dissolved in ethyl acetate and washed with water. The aqueous layer was extracted twice with ethyl acetate, and the combined organic extracts were dried over sodium sulfate and the solvent was evaporated under reduced pressure. The resulting crude product was purified by flash silica gel column chromatography (n-hexane / EtOAc = 4 / 1 (v / v)) to give the desired 4-(2-chlorotetrafluoroethyltetrafluoro-λ). 6 -sulfanyl)aniline (0.311 g, 95% yield) was obtained as a pale yellow liquid.

[0079] [ka]

[0080] 1 H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.7 Hz, 2H), 6.58 (d, J = 9.1 Hz, 2H) , 3.97 (br, 2H) 19F NMR (376 MHz, CDCl3) δ 49.5 (m, 4F), -67.9 (t, J = 10.8 Hz, 2F), -90.7 (m, 2F).

[0081] [Example 13] A tetrafluorosulfanyl group-containing aryl compound was synthesized according to the following synthesis procedure.

[0082] [ka]

[0083] A solution of compound (1) and ADVN (10 mol%) in 0.25 M EtOAc was stirred in a microwave vial (25 mL) under a nitrogen atmosphere and then cooled to 0 °C. Tetrafluoroethylene (TFE) was then bubbled into the solution (1.0 atm). After stirring on an oil bath at 40 °C for 72 h, the insoluble solid was removed by filtration, and the filtrate was evaporated under reduced pressure. The resulting crude product was purified by flash silica gel column chromatography (n-hexane / EtOAc) to give the desired compound (2).

[0084] (1) Acetic acid 4-(2-chlorotetrafluoroethyl tetrafluoro-λ 6 Synthesis of (-sulfanyl)phenyl Acetic acid 4-(chlorotetrafluoro-λ) was prepared according to the procedure described above. 6 -sulfanyl)phenyl (0.6 mmol) to 4-(2-chlorotetrafluoroethyl tetrafluoro-λ acetate 6 Purification by flash silica gel column chromatography (n-hexane / Et0Ac=19 / 1 (volume ratio)) gave 4-(2-chlorotetrafluoroethyl tetrafluoro-λ)phenyl acetate. 6 -sulfanyl)phenyl (0.164 g, yield 72%) was obtained as colorless crystals.

[0085] [ka]

[0086] 1 H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 9.2 Hz, 2H), 7.19 (d, J = 8.7 Hz, 2H), 2.32 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ 49.2 (m, 4F), -67.4 (t, J = 11.6 Hz, 2F), -90.2 (m, 2F).

[0087] (2) 2-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Synthesis of (-sulfanyl)pyridine Following the procedure described above, 2-(chlorotetrafluoro-λ 6 -sulfanyl)pyridine (1.0 mmol) to 2-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Purification by flash silica gel column chromatography (n-hexane / Et0Ac=4 / 1 (volume ratio)) gave 2-(2-chlorotetrafluoroethyltetrafluoro-λ)pyridine. 6 -sulfanyl)pyridine (0.230 g, 72% yield) was obtained as a colorless liquid.

[0088] [ka]

[0089] 1 H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 4.1 Hz, 1H), 7.92 (t, J = 7.3 Hz, 1H), 7.77 (d, J = 8.2 Hz, 1H), 7.49 (dd, J = 7.3, 4.6 Hz, 1H). 19 F NMR (376 MHz, CDCl3) δ 38.0 (m, 4F), -67.5 (m, 2F), -90.7 (m, 2F).

[0090] (3) 2-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Synthesis of (-sulfanyl)pyrimidine Following the procedure described above, 2-(chlorotetrafluoro-λ 6 -sulfanyl)pyrimidine (0.5 mmol) to 2-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Purification by flash silica gel column chromatography (n-hexane / Et0Ac=1 / 1 (volume ratio)) gave 2-(2-chlorotetrafluoroethyltetrafluoro-λ)pyrimidine. 6 -sulfanyl)pyrimidine (0.129 g, 80% yield) was obtained as a colorless liquid.

[0091] [ka]

[0092] 1 H NMR (400 MHz, CDCl3) δ 8.93 (d, J = 4.6 Hz, 2H), 7.57 (t, J = 4.6 Hz, 1H). 19 F NMR (376 MHz, CDCl3) δ 33.7 (m, 4F), -67.5 (m, 2F), -91.1 (m, 2F).

[0093] (4) 1-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Synthesis of (-sulfanyl)-2,3,4,5,6-pentafluorobenzene Following the procedure described above, 1-(chlorotetrafluoro-λ 6 -sulfanyl)-2,3,4,5,6-pentafluorobenzene (0.5 mmol, cis:trans mixture = 2:3) to obtain 1-(2-chlorotetrafluoroethyltetrafluoro-λ 6-sulfanyl)-2,3,4,5,6-pentafluorobenzene was purified by flash silica gel column chromatography (n-hexane / Et0Ac=19 / 1 (volume ratio)) to give 1-(2-chlorotetrafluoroethyltetrafluoro-λ 6 -sulfanyl)-2,3,4,5,6-pentafluorobenzene (0.072 g, 58% yield) was obtained as a colorless liquid.

[0094] [ka]

[0095] 19 F NMR (376 MHz, CDCl3) δ 59.2 (m, 4F), -67.9 (t, J = 10.8 Hz, 2F), -91.4 (m, 2F), -132.4 (m, 2F), -146.8 (m, 1F), -159.0 (m, 2F).

[0096] [Example 14] A tetrafluorosulfanyl group-containing aryl compound was synthesized according to the following synthesis procedure.

[0097] [ka]

[0098] A solution of compound (1) and AIBN (10 mol%) in 0.25 M EtOAc was stirred in a microwave vial (25 mL) under a nitrogen atmosphere and then cooled to 0 °C. Tetrafluoroethylene (TFE) was then bubbled into the solution (1.0 atm). After stirring on an oil bath at 60 °C for 48 h, the insoluble solid was removed by filtration, and the filtrate was evaporated under reduced pressure. The resulting crude product was purified by flash silica gel column chromatography (n-hexane / EtOAc) to give the desired compound (2).

[0099] (1) 4-(2-chlorotetrafluoroethyltetrafluoro-λ6 Synthesis of (-sulfanyl)toluene Following the procedure described above, 4-(chlorotetrafluoro-λ 6 -sulfanyl)toluene (1.0 mmol) to 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 Purification by flash silica gel column chromatography (n-hexane / Et0Ac=19 / 1 (volume ratio)) gave 4-(2-chlorotetrafluoroethyltetrafluoro-λ)toluene. 6 -sulfanyl)toluene (0.225 g, 67% yield) was obtained as colorless crystals.

[0100] [ka]

[0101] 1 H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.7 Hz, 2H), 7.24 (d, J = 8.2 Hz, 2H), 2.40 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ 48.8 (m, 4F), -67.3 (t, J = 11.6Hz, 2F), -90.2 (m, 2F).

[0102] [Example 15] 2-Chlorotetrafluoroethyl tetrafluoro-λ in EtOAc (0.05M) 6 A solution of 1-sulfanylbenzene (0.20 mmol) and ADVN (10 mol%) was frozen in liquid nitrogen and degassed under reduced pressure. The solution was then stirred at 0°C and charged with tetrafluoroethylene (TFE) to 1.1 MPa. After stirring for 24 hours at 40°C in an oil bath, the desired compound (3) was obtained in a 42% yield by NMR. GC / MS analysis revealed that compound (3) satisfied the relationship 1≦n≦7.

[0103] [ka]

[0104] 19 F NMR (376 MHz, CDCl3) δ 48.3-47.3 (m, 4F), -67.9 - -67.3 (m, 2F), -90.5 - -90.2 (m, 2F), -121.5 - -118.4 (m, 4(n-1)F).

[0105] [Example 16] 3-(2-chlorotetrafluoroethyltetrafluoro-λ 6 To a solution of (2-sulfanyl)nitrobenzene (0.75 mmol) in ethanol (15 mL), iron (10 equivalents) and saturated aqueous ammonium chloride (3.7 mL) were added and the mixture was stirred in an oil bath at 80 °C for 2 hours. The insoluble solid was then removed by filtration through Celite, and the filtrate was evaporated under reduced pressure. The resulting crude product was dissolved in ethyl acetate and washed with water. The aqueous layer was extracted twice with ethyl acetate, and the combined organic extracts were dried over sodium sulfate and the solvent was evaporated under reduced pressure. The resulting crude product was purified by flash silica gel column chromatography (n-hexane / EtOAc = 4 / 1 (v / v)) to give the desired 3-(2-chlorotetrafluoroethyltetrafluoro-λ) compound. 6 -sulfanyl)aniline (0.209 g, 83% yield) was obtained as a pale yellow liquid.

[0106] [ka]

[0107] 1 H NMR (400 MHz, CDCl3) δ 7.20 (t, J = 7.8 Hz, 1H), 7.14 (d, J = 8.2 Hz, 1H), 7.07 (t, J = 2.0 Hz, 1H), 6.76 (d, J = 7.8 Hz, 1H), 3.84 (br, 2H). 19F NMR (376 MHz, CDCl3) δ 48.0 (m, 4F), -67.3 (t, J = 10.0 Hz, 2F), -90.3 (m, 2F).

[0108] [Example 17] 3-(2-chlorotetrafluoroethyl tetrafluoro-λ)-2-chloro-1,2-difluoro-2,3-dimethyl-2,4-dimethyl-1,2-difluoro ... 6 N,N-dimethyl-N'-[3-(1,1,2,2-tetrafluoroethyl)tetrafluoro-2-(2-methyl-2-methyl-1 ... 6 -sulfanyl)phenyl]urea (0.045 g, 30% yield) was obtained as a pale yellow liquid.

[0109] [ka]

[0110] 1 H NMR (400 MHz, CDCl3) δ 7.83 (m, 1H), 7.52 (m, 1H), 7.38 (m, 1H), 7.30 (m, 1H), 6.70 (br, 1H), 6.14 (m, 1H), 3.00 (s, 6H). 19F NMR (376 MHz, CDCl3) δ 43.4 (m, 4F), -97.5 (t, J = 10.0 Hz, 2F), -133.6 (d, J = 55.2 Hz, 2F).

[0111] [Example 18] 4-(2-chlorotetrafluoroethyltetrafluoro-λ 6 (2-sulfanyl)bromobenzene (0.50 mmol) was dissolved in dimethoxyethane (1.0 mL) along with tetrakis(triphenylphosphine)palladium(0) (3 mol%) and stirred for 10 min. A saturated ethanol solution of phenylboronic acid (1.1 equiv.) and a saturated aqueous solution of sodium carbonate (2.0 equiv.) were then added, followed by stirring in an oil bath at 80 °C for 18 h. The insoluble solid was then removed by filtration, and the filtrate was dissolved in ethyl acetate and washed three times with saturated aqueous sodium chloride. The resulting organic extract was dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The desired 4-(2-chlorotetrafluoroethyl tetrafluoro-λ) was obtained by flash silica gel column chromatography (n-hexane / EtOAc = 19 / 1 (v / v)). 6 -sulfanyl)biphenyl (0.182 g, 92% yield) was obtained as a colorless solid.

[0112] [ka]

[0113] 1 H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.2 Hz, 2H), 7.66 (d, J = 8.2 Hz, 2H), 7.60 (d, J = 8.2 Hz, 2H), 7.50 (t, J = 7.8 Hz, 2H), 7.44 (t, J = 7.8 Hz, 1H). 19 F NMR (376 MHz, CDCl3) δ 48.9 (m, 4F), -67.3 (t, J = 11.6 Hz, 2F), -90.1 (m, 2F). [Industrial Applicability]

[0114] The present invention provides a method for synthesizing SF4-containing aryl compounds in a single step under relatively mild conditions. This method is useful for introducing SF4 groups into active ingredients of pharmaceuticals and pesticides, organic materials, etc.

Claims

1. In the presence of a radical initiator, a compound represented by the following general formula (2) 【Chemical 1】 [In the formula, A １ represents an optionally substituted aryl group or an optionally substituted heteroaryl group. with a thioaryl compound represented by the following general formula (3): 【Chemistry 2】 [In the formula, R １ , R ２ , R ３ , and R ４ are each independently a hydrogen atom, a fluorine atom, or a chlorine atom. １ , R ２ , R ３ , and R ４ At least two of the groups are fluorine atoms. and carrying out an addition reaction with an olefin compound represented by the following general formula (1): 【Chemistry 3】 [In the formula, A １ , R １ , R ２ , R ３ , and R ４ is the same as above] synthesizing a tetrafluorosulfanyl group-containing aryl compound represented by the formula: A method for producing a tetrafluorosulfanyl group-containing aryl compound.

2. The above A １ is an aryl group optionally having one or more substituents selected from the group consisting of a halogen atom, an alkyl group, an alkenyl group, an aryl group, an alkoxy group, a hydroxy group, a carboxy group, an acyl group, a cyano group, an amino group, and a nitro group.

3. The method for producing a tetrafluorosulfanyl group-containing aryl compound according to claim 1 or 2, wherein the reaction is carried out at a temperature of from −40 to 130° C.

4. The following general formula (1) 【Chemistry 4】 [In the formula, A １ is an optionally substituted aryl group or an optionally substituted heteroaryl group; R １ , R ２ , R ３ , and R ４ are each independently a hydrogen atom, a fluorine atom, or a chlorine atom, and R １ , R ２ , R ３ , and R ４ At least two of the groups are fluorine atoms. A tetrafluorosulfanyl group-containing aryl compound represented by the formula:

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