Process for producing an aryl compound containing a pentafluorosulfanyl group

Abstract

The present invention provides a production method or the like that enables efficient synthesis of a SF5 group-containing compound. The present invention pertains to a method for synthesizing a SF5 group-containing compound represented by general formula (1), by an oxidative fluorination reaction using an organic salt and a metal fluoride having a valence of two or more, from a thioaryl compound represented by general formula (2) [A1 represents an aryl group or a heteroaryl group, G1 represents –SH, -SCN, -SF3, -S-S-R1, -S-CO-R2, -S-R3, -SF2-R4, -S-Si-(R5)3, -S-PO-(R6)2, a (N-phthalimidyl)thio group, or a thianthrenium group, (R1 represents an aryl group or a heteroaryl group, R2 and R5 each represent an aryl group, a heteroaryl group, an alkyl group, or an alkenyl group, R3 and R4 each represent an alkyl group or an alkenyl group, R6 represents an aryl oxy group, a heteroaryl oxy group, an alkyl oxy group, or an alkenyl oxy group)].

Description

Technical Field

[0001] The present invention relates to a method for producing a pentafluorosulfanyl group-containing aryl compound in which a pentafluorosulfanyl group is introduced into an aryl group. This application claims priority based on Japanese Patent Application No. 2021-032818 filed in Japan on March 2, 2021, the content of which is incorporated herein by reference.

Background Art

[0002] The pentafluorosulfanyl (SF 5 ) group is considered to be a "super trifluoromethyl (CF 3 ) group" with excellent properties because it has a relatively small size, high electron-withdrawing property, excellent hydrolysis stability, and improved lipophilicity. On the other hand, the introduction of the SF 5 group into existing compounds is difficult. Therefore, despite its high attractiveness, the use of the SF 5 group in pharmaceutical and agricultural active ingredients, organic materials, etc. has not progressed easily.

[0003] Conventional methods for synthesizing compounds in which SF 5 is introduced into an aryl group such as a phenyl group have various drawbacks. For example, there is a method of directly fluorinating an aryldisulfide using fluorine gas (F 2 ) (Patent Document 1). In this method, when an electron-withdrawing group such as a nitro group is not introduced into the benzene ring in the aryldisulfide, the benzene ring is fluorinated. Also, in a method of fluorinating an aryldisulfide using chlorine gas (Cl 2 ) and potassium fluoride to obtain aryltetrafluorosulfanyl chloride (Ar-SF 4 Cl), and then fluorinating this with zinc fluoride (ZnF 2 ) or the like to obtain arylsulfapentafluoride (Ar-SF 5 ) (Patent Document 2), the benzene ring is not fluorinated even in the absence of a nitro group or the like, but there is a risk of the benzene ring being chlorinated. Silver(II) fluoride (AgF 2In the method using [a certain reagent], first, an aryl disulfide is fluorinated in a chlorofluorocarbon refrigerant to obtain an arylsulfatotrifluoride (Ar-SF 3 ), and then this is further heated to 130 °C to obtain Ar-SF 5 (Non-Patent Document 1). However, in this method, the yield is insufficient. In addition, there is a method (Non-Patent Document 2) of fluorinating an aryl disulfide using tetraalkylammonium chloride and xenon(II) fluoride (XeF 2 ) to synthesize Ar-SF 5 . However, in this method, Ar-SF 4 Cl is also co-produced, so it is necessary to separate Ar-SF 4 Cl.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Non-Patent Documents

[0005]

Non-Patent Document 1

Non-Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0006] An object of the present invention is to provide a novel production method capable of efficiently synthesizing a pentafluorosulfanyl group-containing aryl compound in which a pentafluorosulfanyl group is introduced into an aryl group. [Means for Solving the Problems]

[0007] The present inventors have found that a pentafluorosulfanyl group-containing aryl compound can be synthesized from a thioaryl compound in a single step by using silver(II) fluoride and a tetraalkylammonium halide as a fluorinating agent, and have completed the present invention.

[0008] That is, the present invention is as follows. [1] By an oxidative fluorination reaction using a metal fluoride having a valence of 2 or more and an organic salt containing a quaternary ammonium cation or a quaternary phosphonium cation, the following general formula (2)

[0009] [Chemical Formula]

[0010] [In the formula, A 1 is an aryl group which may have a substituent or a heteroaryl group which may have a substituent; -G 1 is -SH, -SCN, -SF 3 , -S-S-R 1 (R 1 is an aryl group which may have a substituent or a heteroaryl group which may have a substituent), -S-CO-R 2 (R 2 is an aryl group which may have a substituent, a heteroaryl group which may have a substituent, an alkyl group having 1 to 6 carbon atoms which may have a substituent, or an alkenyl group having 2 to 6 carbon atoms which may have a substituent), -S-R 3 (R 3 is an alkyl group having 1 to 6 carbon atoms which may have a substituent or an alkenyl group having 2 to 6 carbon atoms which may have a substituent), -SF 2 -R 4 (R 4 is an alkyl group having 1 to 6 carbon atoms which may have a substituent or an alkenyl group having 2 to 6 carbon atoms which may have a substituent), -S-Si-(R5 ) 3 (R 5 is an aryl group which may have a substituent, a heteroaryl group which may have a substituent, an alkyl group having 1 to 6 carbon atoms which may have a substituent, or an alkenyl group having 2 to 6 carbon atoms which may have a substituent, and a plurality of Rs 5 may be the same group as each other or different groups), -S-PO-(R 6 ) 2 (R 6 is an aryloxy group which may have a substituent, a heteroaryloxy group which may have a substituent, an alkyloxy group having 1 to 6 carbon atoms which may have a substituent, an alkenyloxy group having 2 to 6 carbon atoms which may have a substituent, an aryl group which may have a substituent, a heteroaryl group which may have a substituent, an alkyl group having 1 to 6 carbon atoms which may have a substituent, or an alkenyl group having 2 to 6 carbon atoms which may have a substituent, and a plurality of Rs 6 may be the same group as each other or different groups), a (N-phthalimidyl)thio group which may have a substituent, or a thianthrenium group which may have a substituent] From a thioaryl compound represented by the following general formula (1)

[0011]

Chemical formula

[0012] [In the formula, A 1 is the same as described above] synthesize a pentafluorosulfanyl group-containing aryl compound represented by A method for producing a pentafluorosulfanyl group-containing aryl compound. [2] The A 1 is An aryl group which may have one or more substituents selected from the group consisting of a halogen atom, an alkyl group, a fluorinated alkyl group, an alkenyl group, an aryl group, a heteroaryl group, an alkoxy group, a hydroxy group, a carboxy group, an acyl group, a cyano group, a formyl fluoride group, an amino group, and a nitro group, or, A heteroaryl group which may have one or more substituents selected from the group consisting of a halogen atom, an alkyl group, a fluorinated alkyl group, an alkenyl group, an aryl group, a heteroaryl group, an alkoxy group, a hydroxy group, a carboxy group, an acyl group, a formyl fluoride group, a cyano group, an amino group, and a nitro group, The method for producing a pentafluorosulfanyl group-containing aryl compound according to [1] above. [3] The method for producing a pentafluorosulfanyl group-containing aryl compound according to [1] or [2] above, wherein the oxidative fluorination reaction is carried out at -40 to 130 °C. [4] The method for producing a pentafluorosulfanyl group-containing aryl compound according to any one of [1] to [3] above, wherein the metal after the oxidative fluorination reaction is recovered. [5] Fluorinating the recovered metal to regenerate a metal fluoride of divalent or higher, The method for producing a pentafluorosulfanyl group-containing aryl compound according to [4] above, wherein the obtained metal fluoride of divalent or higher is used again in the oxidative fluorination reaction. [6] The method for producing a pentafluorosulfanyl group-containing aryl compound according to any one of [1] to [5] above, wherein the metal fluoride of divalent or higher is silver(II) fluoride. [7] The method for producing a pentafluorosulfanyl group-containing aryl compound according to any one of [1] to [6] above, wherein the organic salt is a tetraalkylammonium halide. [Effects of the Invention]

[0013] According to the method of the present invention, the oxidative fluorination of a thioaryl compound can be carried out in a single step, and a pentafluorosulfanyl group-containing aryl compound can be efficiently synthesized. [Modes for Carrying Out the Invention]

[0014] In the present invention and this specification, "C" p1-p2 "(where p1 and p2 are positive integers satisfying p1 < p2) means a group having p1 to p2 carbon atoms."

[0015] In the present invention and this specification, "C" 1-6 "alkyl group" is an alkyl group having 1 to 6 carbon atoms, which may be linear or branched. C 1-6 Examples of the C

[0016] In the present invention and this specification, "C" 1-6 "alkoxy group" refers to a group in which an oxygen atom is bonded to the bonding terminal of a C 1-6 alkyl group. The C 1-6 alkoxy group may be linear or branched. C 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, a hexyloxy group, and the like.

[0017] In the present invention and this specification, "C" 2-6 "alkenyl group" refers to a group in which at least one carbon-carbon bond of an alkyl group having 2 to 6 carbon atoms becomes an unsaturated bond. C 2-6 The alkenyl group may be linear or branched. C 2-6 Examples of the alkenyl group include a vinyl group, an allyl group, a butenyl group, a pentenyl group, a hexenyl group, and the like.

[0018] In the present invention and this specification, "C" 2-7 "acyl group" means that the hydrocarbon group portion excluding the carbonyl group from the acyl group is a C 1-6 alkyl group, C 2-6It refers to a group that is an alkenyl group, an aryl group of a 5-membered or 6-membered ring, or a heteroaryl group of a 5-membered or 6-membered ring. The hydrocarbon group portion of the acyl group may be linear or branched. C 2-7 Examples of the acyl group include a formyl group, an acetyl group, a propanoyl group, a propenoyl group, a benzoyl group, and the like.

[0019] In the present invention and this specification, the "halogen atom" refers to a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom. The "halogen atom other than a fluorine atom" refers to a chlorine atom, a bromine atom, or an iodine atom. As an example of the "halogen atom other than a fluorine atom", a chlorine atom or a bromine atom is preferable, and a chlorine atom is particularly preferable.

[0020] Also, hereinafter, "compound (n)" means a compound represented by formula (n).

[0021] <Oxidative fluorination reaction> The method for producing a pentafluorosulfanyl group-containing aryl compound (hereinafter sometimes referred to as "SF 5 -containing aryl compound") according to the present invention is to use a divalent or higher metal fluoride such as silver (II) fluoride (AgF 2 ), and an organic salt such as tetraalkylammonium halide (hereinafter sometimes referred to as "NR 11 4 X". X represents a halogen atom.) and the like, and fluorinate by an oxidative fluorination reaction. When only AgF 2 is used as the fluorinating agent, the sulfur atom bonded to the aryl group is fluorinated only up to the SF 3 group (Non-Patent Document 1). In contrast, in the present invention, by using a divalent or higher metal fluoride such as AgF 2 and an organic salt such as NR 11 4 X in combination, the SF 4 X group-containing aryl compound obtained during the reaction is reacted with AgF 2 and the like in the reaction system without isolation, and SF 4The Cl group can be fluorinated to the SF 5 group. That is, by using a divalent or higher metal fluoride such as AgF 2 in combination with an organic salt such as NR 11 4 X, the target SF 5 -containing aryl compound can be obtained from the thioaryl compound in a single step.

[0022] Specifically, the method for producing the SF 5 -containing aryl compound according to the present invention is to carry out an oxidative fluorination reaction using a divalent or higher metal fluoride such as AgF 2 in combination with an organic salt such as NR 11 4 X to synthesize the SF 5 -containing aryl compound represented by the following general formula (1) from the thioaryl compound represented by the following general formula (2). The chemical reaction formula when using AgF 2 and NR 11 4 X is shown below.

[0023]

Chemical formula

[0024] In the general formulas (2) and (1), A 1 is 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, a 9-fluorenyl group, etc., and a phenyl group is 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, an isothiazolyl group, etc.

[0025] The "aryl group which may be substituted" is a group in which one or more, preferably 1 to 3, of the hydrogen atoms bonded to the carbon atoms of the aryl group are substituted with other functional groups. Similarly, the "heteroaryl group which may be substituted" is a group in which one or more, preferably 1 to 3, of the hydrogen atoms bonded to the carbon atoms of the heteroaryl group are substituted with other functional groups. When having two or more substituents, the substituents may be of the same kind or different kinds from each other.

[0026] A 1 The aryl group and heteroaryl group of A may have one or more substituents in addition to the sulfur atom for the purpose of fluorination. Examples of the substituent include a halogen atom, an alkyl group, a fluorinated alkyl group, an alkenyl group, an alkoxy group, an aryl group, a heteroaryl group, an acyl group, a hydroxy group, a carboxy group, a cyano group, a formyl fluoride group (-C(=O)F), an amino group, and a nitro group. As the alkyl group, a C 1-6 alkyl group is preferred. As the alkenyl group, a C 2-6 alkyl group is preferred. As the alkoxy group, a C 1-6 alkoxy group is preferred. As the acyl group, a C 2-7 acyl group is preferred. As the fluorinated alkyl group, a group in which one or more hydrogen atoms of the C 1-6 alkyl group are substituted with fluorine atoms is preferred, and a perfluorinated C 1-6 alkyl group in which all hydrogen atoms are substituted with fluorine atoms is more preferred, and a trifluoromethyl group is particularly preferred. Examples of the aryl group and heteroaryl group include the aryl group and heteroaryl group of A 1 respectively, and a phenyl group or a pyridyl group is preferred.

[0027] A 1The substituents of the aryl group and heteroaryl group may be protected with a protecting group. As the protecting group, a group commonly used in organic synthesis can be appropriately used. For example, when the substituent is an amino group, the amino group can be substituted with two hydrogen atoms with a tert-butoxycarbonyl group, benzyloxycarbonyl group, 9-fluorenylmethyloxycarbonyl group, 2,2,2-trichloroethoxycarbonyl group, allyloxycarbonyl group, trifluoroacetyl group, phthaloyl group, p-toluenesulfonyl group, or 2-nitrobenzenesulfonyl group before being subjected to the oxidative fluorination reaction. Similarly, when the substituent is a carboxy group, the carboxy group can be substituted with a hydrogen atom with a benzyl group or tert-butyl group.

[0028] AgF as a fluorinating agent 2 A divalent or higher metal fluoride such as etc. and NR 11 4 In order to use in combination with an organic salt such as X, even when the electron density of the aryl ring is high, the oxidative fluorination reaction of the sulfur atom bonded to the carbon atom of the aryl ring proceeds. Also, even if an electron-withdrawing group such as a nitro group is not bonded to the aryl ring, halogenation of the carbon atom itself of the aryl ring is unlikely to occur. Therefore, among the aryl groups of the thioaryl compound (2), whether one or more carbon atoms other than the carbon atom bonded to the sulfur atom for the purpose of fluorination are substituted with an electron-withdrawing group or an electron-donating group, fluorination of the aryl ring is not caused, and the target SF 5 -containing aryl compound can be efficiently obtained. The same applies to the heteroaryl ring.

[0029] In the general formula (2), G 1 is any of the following groups. The black circle represents a bond.

[0030]

Chemical formula

[0031] R 1is an aryl group which may have a substituent or a heteroaryl group which may have a substituent. R 2 is an aryl group which may have a substituent, a heteroaryl group which may have a substituent, a C 1-6 alkyl group which may have a substituent, or a C 2-6 alkenyl group which may have a substituent. R 3 is a C 1-6 alkyl group which may have a substituent or a C 2-6 alkenyl group which may have a substituent. R 4 is a C 1-6 alkyl group which may have a substituent or a C 2-6 alkenyl group which may have a substituent. R 5 is an aryl group which may have a substituent, a heteroaryl group which may have a substituent, a C 1-6 alkyl group which may have a substituent, or a C 2-6 alkenyl group, and a plurality of R 5 may be the same group as each other or different groups. R 6 is an aryloxy group which may have a substituent, a heteroaryloxy group which may have a substituent, an alkyloxy group having 1 to 6 carbon atoms which may have a substituent, an alkenyloxy group having 2 to 6 carbon atoms which may have a substituent, an aryl group which may have a substituent, a heteroaryl group which may have a substituent, a C 1-6 alkyl group which may have a substituent, or a C 2-6 alkenyl group, and a plurality of R 6 may be the same group as each other or different groups.

[0032] R 1 、R 2 、R 5 、and R 6 Among them, as the aryl group which may have a substituent, A 1It can be a group similar to those exemplified. R 1 , R 2 , R 5 , and R 6 Among them, as the heteroaryl group which may have a substituent, it can be a group similar to those exemplified by A 1 It can be a group similar to those exemplified.

[0033] R 2 , R 3 , R 4 , R 5 , and R 6 Among them, the "optionally substituted C 1-6 alkyl group" is a group in which one or more, preferably 1 to 3, of the hydrogen atoms bonded to the carbon atoms of the C 1-6 alkyl group are substituted with other functional groups. Similarly, the "optionally substituted C 2-6 alkenyl group" is a group in which one or more, preferably 1 to 3, of the hydrogen atoms bonded to the carbon atoms of the C 2-6 alkenyl group are substituted with other functional groups. When having two or more substituents, the substituents may be the same or different from each other. Examples of the substituent 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, a cyano group, an amino group, and a nitro group. As the alkyl group, a C 1-6 alkyl group is preferred, as the alkenyl group, a C 2-6 alkyl group is preferred, as the alkoxy group, a C 1-6 alkoxy group is preferred, and as the acyl group, a C 2-7 acyl group is preferred.

[0034] R 6 Among them, as the optionally substituted aryloxy group, the aryl group moiety can be a group similar to those exemplified by A 1 as the optionally substituted aryl group. As R 6 , a phenyloxy group is preferred. R 6As the heteroaryloxy group which may have a substituent, the heteroaryl group moiety may be the same group as those exemplified as the heteroaryl group which may have a substituent A 1 can be a group. R 6 is preferably a pyridyloxy group. R 6 Among them, as the C 1-6 alkyloxy group which may have a substituent, the C 1-6 alkyl group moiety can be the same group as those exemplified as the C 1-6 alkyl group such as the above-mentioned R 2 etc. R 6 is preferably a methyloxy group. R 6 Among them, as the C 2-6 alkenyloxy group which may have a substituent, the C 2-6 alkenyl group moiety can be the same group as those exemplified as the C 2-6 alkenyl group such as the above-mentioned R 2 etc. R 6 is preferably a vinyloxy group.

[0035] G 1 When G is an (N-phthalimidyl)thio group, 1 to 3 hydrogen atoms in the benzene ring in the (N-phthalimidyl)thio group may be substituted with substituents. The substituent is not particularly limited as long as it does not inhibit the fluorination reaction, and for example, the substituents exemplified in the "C 2 alkyl group which may have a substituent" in R 1-6 etc. can be the same groups. The plurality of substituents may all be the same group or different groups. G 1 is preferably an unsubstituted (N-phthalimidyl)thio group.

[0036] G 1When it is a thianthrenium group, one or both of the two benzene rings in the thianthrenium group may have 1 to 4 hydrogen atoms substituted with substituents. The substituent is not particularly limited as long as it does not inhibit the fluorination reaction. For example, R 2 and the like, "optionally substituted C 1-6 alkyl group", and can be a group similar to the substituents listed therein. The plurality of substituents may all be the same group or different groups. G 1 is preferably an unsubstituted thianthrenium group or a thianthrenium group substituted with a halogen atom.

[0037] As the thioaryl compound (2), there may be a compound having a plurality of structures of G 1 bonded to A 1 in one molecule. For example, when A 1 is a biphenyl group, a compound having a structure in which G 1 is linked to both of the two benzene rings is also included in the thioaryl compound (2). Thus, when there are a plurality of G 1 groups bonded to an aryl ring or a heteroaryl ring in one molecule, all G 1 groups are converted to pentafluorosulfanyl groups by the oxidative fluorination reaction.

[0038]

Chemical formula

[0039] Specific examples of the thioaryl compound (2) include the following compounds. Compounds in which one or more substituents are introduced into the benzene ring in these compounds are also preferable as the thioaryl compound (2) used in the present invention. Examples of the substituent 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, a cyano group, an amino group, and a nitro group.

[0040]

Chemical formula

[0041] [Chemical formula]

[0042] Examples of the metal fluoride with a valence of 2 or more used as the fluorinating agent in the oxidative fluorination reaction include fluorides of the first transition element, the second transition element, or the third transition element. Specifically, as the fluorinating agent used in the present invention, metal fluorides with a valence of 2 or more of silver, niobium, manganese, cobalt, copper, hafnium, tantalum, or cerium are preferable, and AgF 2 , manganese(III) fluoride (MnF 3 ), cobalt(III) fluoride (CoF 3 ), copper(II) fluoride (CuF 2 ), niobium(V) fluoride (NbF 5 ), hafnium(V) fluoride (HfF 5 ), tantalum fluoride (TaF 5 ), cerium(IV) fluoride (CeF 4 )) and the like can be mentioned. As the metal fluoride with a valence of 2 or more used as the fluorinating agent in the present invention, AgF 2 is particularly preferable from the viewpoint of good reactivity.

[0043] The organic salt used as the fluorinating agent in the oxidative fluorination reaction may be an organic salt containing a quaternary ammonium cation or a quaternary phosphonium cation, and is not particularly limited. Examples of the organic salt include compounds represented by the following general formulas (s1) to (s7).

[0044] [Chemical formula]

[0045] In the general formulas (s1) to (s5), R 12 is a C 1-6 alkyl group or an aryl group. As the aryl group, the above-mentioned A 1It can be the same group as those exemplified above. A plurality of R in one molecule 12 may all be the same group or may be different groups from each other.

[0046] In general formulas (s6) to (s7), R 13 is a C 1-6 alkyl group, aryl group, C 1-6 alkoxy group, or C 1-6 alkylamino group. As the aryl group, it can be the same group as those exemplified above for A 1 . As the C 1-6 alkylamino group, as long as one or two hydrogen atoms of the amino group are substituted with a C 1-6 alkyl group, it is not particularly limited. Examples of the C 1-6 alkylamino group include a dimethylamino group. A plurality of R in one molecule 13 may all be the same group or may be different groups from each other.

[0047] In general formulas (s1) to (s7), X 1 is not particularly limited as long as it is a monovalent anion that forms a salt with a quaternary ammonium cation or a quaternary phosphonium cation. Examples of X 1- include iodide ion (I - ), bromide ion (Br - ), chloride ion (Cl - ), fluoride ion (F - ), hydrogen difluoride ion (HF 2 - ), tribromide ion (Br 3 - ), azide ion (N 3 - ), cyanide ion (CN - ), cyanate ion (OCN - ), etc.

[0048] As the organic salt used as the fluorinating agent in the oxidative fluorination reaction, in particular, tetraalkylammonium halide (NR 114 X) is preferred. NR used in the oxidative fluorination reaction 11 4 X may be any halide in which four alkyl groups are bonded to a nitrogen atom, and is not particularly limited. As the halide, a chloride or a bromide is preferred, and a chloride is particularly preferred. Further, the alkyl group bonded to the nitrogen atom may be linear or branched, and the four alkyl groups may all be the same group or may be different groups from each other. The alkyl group is preferably a C 1-6 alkyl group, more preferably a methyl group, an ethyl group, or a propyl group. Among them, NR 11 4 As X, N(Et) 4 Cl (tetraethylammonium chloride) (CAS No: 56-34-8) or N(Et) 4 Br (tetraethylammonium bromide) (CAS No: 71-91-0) is preferred, and N(Et) 4 Cl is more preferred.

[0049] The amount of the organic salt such as NR 11 4 X added to the reaction system may be a stoichiometric amount or more. From the viewpoints of reaction efficiency and cost, the amount of the organic salt such as NR 11 4 X used in the oxidative fluorination reaction is preferably 1 to 10 equivalents, more preferably 1 to 6 equivalents, of the thioaryl compound (2).

[0050] The amount of the metal fluoride having a valence of 2 or more such as AgF 2 added to the reaction system is not particularly limited, but from the viewpoint of reaction efficiency, 5 equivalents or more, more preferably 8 equivalents or more, further preferably 10 equivalents or more of the thioaryl compound (2) is preferred. Also, from the viewpoint of cost, the amount of the metal fluoride having a valence of 2 or more such as AgF 2 used in the oxidative fluorination reaction is preferably 100 equivalents or less, more preferably 50 equivalents or less, further preferably 30 equivalents or less, and even more preferably 20 equivalents or less of the thioaryl compound (2).

[0051] The oxidative fluorination reaction can be carried out in a solvent inert to the reaction. The inert solvent is not particularly limited, but an aprotic polar solvent is preferred. Examples of the aprotic polar solvent include acetonitrile (MeCN), N,N'-dimethylformamide (DMF), N,N-dimethylacetamide, dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), dichloromethane (DCM), diethyl ether, and the like. The solvent used in the reaction may be a mixed solvent of two or more solvents.

[0052] In the oxidative fluorination reaction, a reaction solution obtained by mixing a thioaryl compound (2) and an organic salt such as NR 11 4 X and a metal fluoride of divalent or higher such as AgF 2 is reacted at an appropriate temperature and time. The oxidative fluorination 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, and it can be carried out at -40 to 130 °C, preferably at 0 to 80 °C, and can also be carried out at room temperature (0 to 30 °C). For example, by reacting the oxidative fluorination reaction at room temperature for less than 1 hour, the target SF 5 -containing aryl compound (1) can be obtained in an essentially quantitative yield.

[0053] In the oxidative fluorination reaction, a metal fluoride of divalent or higher such as AgF 2 is defluorinated to generate a metal such as Ag. By recovering the metal such as Ag generated by the reaction and fluorinating it, a metal fluoride of divalent or higher such as AgF 2 can be regenerated. The regenerated metal fluoride of divalent or higher such as AgF 2 can be used again in the oxidative fluorination reaction. The fluorination of a metal such as Ag can be carried out by a conventional method such as heating in fluorine gas.

[0054] The oxidative fluorination reaction is a single step under relatively mild reaction conditions, with a high yield, and SF 5The aryl compound (1) can be synthesized in one pot. Also, in the oxidative fluorination reaction, partial fluorides such as aryl compounds containing an SF 4 Cl group are hardly ever produced. Therefore, there is also an advantage that it is not necessary to isolate the target SF 4 from the reaction product and purify the aryl compound (1) containing an SF 5 group.

[0055] <Thiolation reaction of aryl> As the thioaryl compound (2), a commercially available compound may be used, or a compound synthesized by reacting a compound represented by the following general formula (3) with a compound represented by the following general formula (4) may be used. When the thioaryl compound (2) synthesized by the thiolation reaction of aryl is used in the oxidative fluorination reaction, the thiolation reaction of aryl and the subsequent oxidative fluorination reaction can also be carried out in one pot.

[0056]

Chemical formula

[0057] In general formula (3), A 1 is the same as described above. Also, G 2 is a halogen atom, a hydroxy group, or an amino group. In general formula (4), G 3 is a group obtained by removing the sulfur atom from which the bond is drawn from the above G 2 .

[0058] The thiolation reaction of aryl can be carried out in a solvent inert to the reaction at a temperature at which the reaction solvent is liquid. As the inert solvent, the same solvents as those that can be used in the oxidative fluorination reaction can be used.

Examples

[0059] Hereinafter, the present invention will be described by way of examples, but the present invention is not limited to these examples.

[0060] The NMR instrument used for the analysis of the examples and comparative examples was JNM-ECZ400S (400 MHz) manufactured by JEOL Ltd., 1 In 1H NMR, tetramethylsilane was set at 0 ppm, 19 In 19F NMR, C 6 F 6 was used as a reference value of -162 ppm. Also, the NMR yield of the SF 5 -containing aryl compound was determined by adding 1,4-bis(trifluoromethyl)benzene (BTB) or 1,4-difluorobenzene (DFB) (0.5 or 1 equivalent relative to the generated SF 5 -containing aryl compound) to the reaction mixture as an internal standard, filtering through a PTFE syringe filter, administering it into an NMR tube, and based on the integrated values of the 19F NMR signals of the SF 5 group and the CF 3 group respectively. 19 It was determined by the integrated value of each

[0061] [Example 1] The pentafluorosulfanylation of aryl disulfide was carried out as follows. First, in a glove box filled with argon, NEt 4 Cl (2 equivalents, 0.2 mmol), aryl disulfide (1 equivalent, 0.1 mmol), and a magnetic stirrer bar were placed in a glass vial, and further MeCN (1 mL) was added, and the reaction mixture was stirred until all the compounds were dissolved (usually for 2 minutes). Subsequently, while vigorously stirring the reaction mixture at room temperature, AgF 2 (16 equivalents, 1.6 mmol) was added all at once, and the vial was closed with a screw cap. Within about 1 minute after closing the cap, the initially black suspension changed to orange with a red-violet organic layer. Stirring was continued as it was until the organic layer became colorless and the oxidative fluorination reaction was completed (usually from 2 to 4 hours). The NMR yield of the obtained SF 5 -containing aryl compound was determined by adding 1,4-bis(trifluoromethyl)benzene (3 μL, 0.02 mmol) to the reaction mixture as an internal standard.

[0062] <Synthesis of Phenylsulfapentafluoride> Using phenyl disulfide (21.8 mg, 0.1 mmol) as the aryl disulfide, the above synthesis reaction was carried out, and phenylsulfapentafluoride was obtained in an NMR yield of >95%.

[0063]

Chemical formula

[0064] 1 H NMR (500 MHz, CD 3 CN, 298 K, δ): 8.02 - 7.94 (m, 2H), 7.82 - 7.62 (m, 3H). 19 F { 1 H} NMR (471 MHz, CD 3 CN, 298 K, δ): 85.38 (p, J = 147.7 Hz, 1F), 62.82 (d, J = 147.7 Hz, 4F).

[0065] <Synthesis of 4-Methoxyphenylsulfapentafluoride> Using 4-methoxyphenyl disulfide (55.7 mg, 0.2 mmol) as the aryl disulfide, the above synthesis reaction was carried out, and 4-methoxyphenylsulfapentafluoride was obtained in an NMR yield of >95%.

[0066]

Chemical formula

[0067] 1 H NMR (400 MHz, CD 3 CN, 298 K, δ): 7.92 (d, J = 9.3 Hz, 2H), 7.19 (d, J = 9.0 Hz, 2H), 4.01 (s, 3H). 19 F { 1 H} NMR (376 MHz, CD 3CN, 298 K, δ): 86.63 (p, J = 148 Hz, 1F), 64.13 (d, J = 148.0 Hz, 4F).

[0068] <Synthesis of 4-Nitrophenylsulfapentafluoride> Using 4-nitrophenyldisulfide (61.7 mg, 0.2 mmol) as the aryl disulfide, the above synthesis reaction was carried out to obtain 4-nitrophenylsulfapentafluoride in an NMR yield of >95%.

[0069]

Chemical Structure

[0070] 1 H NMR (400 MHz, CD 3 CN, 298 K, δ): 8.61 - 8.39 (m, 2H), 8.32 - 8.11 (m, 2H). 19 F { 1 H} NMR (376 MHz, CD 3 CN, 298 K, δ): 81.61 (p, J = 148.6 Hz, 1F), 62.26 (d, J = 148.6 Hz, 4F).

[0071] <Synthesis of 4-Chlorophenylsulfapentafluoride> Using 4-chlorophenyldisulfide (57.4 mg, 0.2 mmol) as the aryl disulfide, the above synthesis reaction was carried out to obtain 4-chlorophenylsulfapentafluoride in an NMR yield of >95%.

[0072]

Chemical Structure

[0073] 1 H NMR (400 MHz, CD 3CN, 298 K, δ): 7.98 (d, J = 9.0 Hz, 1H), 7.73 (d, J = 8.4 Hz, 1H). 19 F { 1 H} NMR (376 MHz, CD 3 CN, 298 K, δ): 83.37 (p, J = 149.1 Hz, 1F), 62.39 (d, J = 149.1 Hz, 4F).

[0074] <Synthesis of 2-Pyridinylsulfapentafluoride> Using 2-pyridyldisulfide (44.1 mg, 0.2 mmol) as the aryl disulfide, the above synthesis reaction was carried out to obtain 2-pyridinylsulfapentafluoride in an NMR yield of >95%.

[0075]

Chemical Structure

[0076] 1 H NMR (400 MHz, CD 3 CN, 298 K, δ): 8.80 - 8.69 (m, 1H), 8.24 (t, J = 7.9 Hz, 1H), 8.03 (d, J = 8.3 Hz, 1H), 7.86 - 7.76 (m, 1H). 19 F { 1 H} NMR (376 MHz, CD 3 CN, 298 K, δ): 78.56 (p, J = 147.4 Hz, 1F), 51.16 (d, J = 147.4 Hz).

[0077] <Synthesis of 4-Methylphenylsulfapentafluoride> Using 4-methyldiphenyl disulfide (24.4 mg, 0.1 mmol) as the aryl disulfide, the above synthesis reaction was carried out and reacted for 4 hours to obtain 4-methylphenylsulfapentafluoride in an NMR yield of 95%.

[0078]

Chem.

[0079] 1 H NMR (400 MHz, CD 3 CN) δ 7.73 - 7.64 (m, 2H), 7.34 (d, J = 8.1 Hz, 2H), 2.38 (s, 3H). 13 C NMR (101 MHz, CD 3 CN) δ 152.1 (d, J = 15.3 Hz), 144.3 - 143.9 (m), 130.6 (s), 126.7 (p, 3 J CF = 4.7 Hz), 21.2 (s). 19 F NMR (376 MHz, CD 3 CN) δ 85.4 (p, 2 J FF,ax = 147.8 Hz, 1F, SF), 62.6 (d, 2 J FF,eq = 147.8 Hz, 4F, SF 4 ).

[0080] <Synthesis of N,N-Bis(tert-butoxycarbonyl)-4-aminophenylsulfapentafluoride> Using N,N-bis(tert-butoxycarbonyl)-4-aminophenyl disulfide (65.0 mg, 0.1 mmol) as the aryl disulfide, the above synthesis reaction was carried out and reacted for 4 hours to obtain N,N-bis(tert-butoxycarbonyl)-4-aminophenylsulfapentafluoride in an NMR yield of 88%.

[0081]

Chem.

[0082] 1 H NMR (400 MHz, CD3 CN) 7.86 - 7.81 (m, 2H), 7.37 (d, J = 9.0 Hz, 2H), 1.40 (s, 18H). 13 C NMR (101 MHz, CD 3 CN) δ 152.9 - 152.4 (m), 152.1 (s), 144.0 - 143.7 (m), 129.6 (s), 127.5 (p, 3 J CF = 4.7 Hz), 84.1 (s), 28.0 (s). 19 F NMR (376 MHz, CD 3 CN) δ 84.1 (p, 2 J FF,ax = 148.2 Hz, 1F, SF), 62.6 (d, 2 J FF,eq = 147.9 Hz, 4F, SF 4 ).

[0083] [Example 2] The pentafluorosulfanylation of free thiophenol was carried out as follows. First, in a glove box filled with argon, NEt 4 Cl (2 - 3 equivalents, 0.4 - 0.6 mmol), thiophenol (1 equivalent, 0.2 mmol), and a magnetic stir bar were placed in a glass vial, and further MeCN (1 mL) was added. The reaction mixture was stirred until all the compounds were dissolved (usually for 2 minutes). Subsequently, while vigorously stirring the reaction mixture at room temperature, AgF 2 (10 equivalents, 2 mmol) was added all at once, and the vial was closed with a screw cap. Within about 1 minute after closing the cap, the initially black suspension turned orange with a red - purple organic layer. Stirring was continued until the organic layer became colorless and the oxidative fluorination reaction was complete (usually from 4 hours to 36 hours). The resulting SF 5The NMR yield of the aryl compound was determined by adding 1,4-bis(trifluoromethyl)benzene (3 μL, 0.02 mmol) to the reaction mixture as an internal standard. The results are shown in Table 1.

[0084] [Example 3] The pentafluorosulfanylation of (hetero)aryl thiocyanate can be carried out, for example, by the following method. First, in a glove box filled with argon, add NEt 4 Cl (66.3 mg, 0.4 mmol, 2 equivalents), the corresponding (hetero)aryl thiocyanate (0.2 mmol), MeCN (1 mL), and a magnetic stir bar to a PFA vial. Subsequently, add AgF 2 (292 mg, 2.0 mmol, 10 equivalents) to the stirred reaction solution in the vial at room temperature and close the vial with a screw cap. Within about 1 minute after closing the cap, the reaction solution, which was initially a black suspension, changes, and an orange precipitate with a red-violet organic layer is formed. Stir the reaction solution for 24 hours to react.

[0085] Among (hetero)aryl thiocyanates, the pentafluorosulfanylation of phenyl thiocyanate (phenyl thiocyanate) was carried out as follows. First, in a glove box filled with argon, add NEt 4 Cl (2 - 3 equivalents, 0.4 - 0.6 mmol), phenyl thiocyanate (1 equivalent, 0.2 mmol), and a magnetic stir bar to a glass vial, and further add MeCN (1 mL). Stir the reaction mixture until all the compounds are dissolved (usually for 2 minutes). Subsequently, while vigorously stirring the reaction mixture at room temperature, add AgF 2 (12 equivalents, 2.4 mmol) all at once and close the vial with a screw cap. Within about 1 minute after closing the cap, the initially black suspension changed to orange with a red-violet organic layer. Stirring was continued until the organic layer became colorless and the oxidative fluorination reaction was completed (usually 30 minutes to 1 hour). The obtained SF 5The NMR yield of the aryl compound was determined by adding 1,4-bis(trifluoromethyl)benzene (3 μL, 0.02 mmol) to the reaction mixture as an internal standard. The results are shown in Table 1.

[0086] [Example 4] The pentafluorosulfanylation of benzoyl-protected thiophenol (phenylthiol benzoate) was carried out as follows. First, in a glove box filled with argon, NEt 4 Cl (1 - 2 equivalents, 0.1 - 0.2 mmol), benzoylthiophenol (1 equivalent, 0.2 mmol), and a magnetic stirrer bar were placed in a glass vial, and further MeCN (1 mL) was added, and the reaction mixture was stirred until all the compounds were dissolved (usually for 2 minutes). Subsequently, while vigorously stirring the reaction mixture at room temperature, AgF 2 (10 equivalents, 2 mmol) was added all at once, and the vial was closed with a screw cap. Within about 1 minute after closing the cap, the initially black suspension changed to orange with a reddish-purple organic layer. Stirring was continued until the organic layer became colorless and the oxidative fluorination reaction was complete (usually from 2 hours to 24 hours). The obtained SF 5 The NMR yield of the aryl compound was determined by adding 1,4-bis(trifluoromethyl)benzene (3 μL, 0.02 mmol) to the reaction mixture as an internal standard. The results are shown in Table 1.

[0087] [Table 1]

[0088] [Example 5] The synthesis of aryl pentafluorosulfanyl compounds from benzenediazonium salts was carried out using copper-catalyzed Sandmeyer coupling / oxidative fluorination.

[0089] (1) Synthesis of tetraethylammonium thiobenzoate

[0090] [Chemistry]

[0091] In a reaction vessel, under a nitrogen atmosphere, potassium thiobenzoate (891 mg, 5.05 mmol) and tetraethylammonium chloride (818 mg, 4.95 mmol) were dissolved in dry MeOH (5 mL) and stirred at room temperature for 1 hour. After removing the KCl precipitate by filtration through a syringe filter, the solvent was further evaporated in vacuo. Subsequently, the reaction vessel was transferred to a glove box and the solid in the reaction vessel was dissolved in MeCN (10 mL). The resulting solution was filtered through a syringe filter and then concentrated in vacuo to obtain the product as a yellow solid (1.28 g, 96% yield).

[0092] 1 H NMR (500 MHz, d 3 -MeCN) δ 8.18 - 8.07 (m, 2H), 7.31 - 7.19 (m, 3H), 3.16 (q, J = 7.3 Hz, 8H), 1.19 (tt, J = 7.3 Hz, 1.8 Hz, 12H).

[0093] (2) Synthesis of (phen)CuSCOPh

[0094] [Chemistry]

[0095] Copper(I) bromide dimethyl sulfide complex (205 mg, 1 mmol) and tetraethylammonium thiobenzoate (295 mg, 1.1 mmol) were dissolved in MeCN (5 mL). The resulting yellow solution was filtered through a syringe filter and diluted with MeCN (5 mL). Then, 1,10-phenanthroline (198 mg, 1.1 mmol) was added little by little as a solid to the solution to obtain a red precipitate. The obtained red precipitate was filtered off, and MeCN and Et 2The product was isolated as a red powder by washing with O and subsequently drying under vacuum (360 mg, 95% yield).

[0096] (3) Copper-catalyzed Sandmeyer coupling / oxidative fluorination reaction

[0097] [Chemical formula]

[0098] In a dry box filled with argon, a glass vial was charged with (phen)CuSCOPh (3.8 mg, 0.01 mmol), potassium thiobenzoate (45.8 mg, 0.26 mmol), and a magnetic stir bar, and further MeCN (0.5 mL) was added. The mixture was stirred at room temperature. With stirring for approximately 2 minutes, a red solution containing undissolved potassium thiobenzoate was obtained. Subsequently, 4-methoxybenzenediazonium tetrafluoroborate (44.4 mg, 0.2 mmol) dissolved in MeCN (0.5 mL) was added dropwise to the red solution at room temperature using a syringe. During the dropwise addition, visible nitrogen gas formation occurred. The syringe was washed with 0.25 mL of MeCN, and the washings were also added to the reaction mixture. The reaction mixture was stirred at room temperature for 1 hour, 1,4-bis(trifluoromethyl)benzene (31 μL, 0.2 mmol) was added as an internal standard, and then filtered through a syringe filter. The syringe was washed with 0.25 mL of MeCN. Tetraethylammonium chloride (106 mg, 1.2 mmol) was added to the reaction mixture and dissolved (with stirring for about 2 minutes). Subsequently, silver(II) fluoride (525 mg, 3.6 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature overnight. The NMR yield (78%) of pentafluorosulfuranyl arene (where "2") was determined by 19 FNMR spectroscopy.

[0099] 1 H NMR (400 MHz, d 3-MeCN) δ 7.92 (d, J = 9.3 Hz, 2H), 7.19 (d, J = 9.0 Hz, 2H), 4.01 (s, 3H). 19 F {1H} NMR (376 MHz, d 3 -MeCN) δ 86.63 (p, J = 148 Hz, 1F), 64.13 (d, J = 148.0 Hz, 4F).

[0100] [Example 6] (Hetero)arylthiol pentafluorothiolation can be carried out, for example, by the following method. First, in a glove box filled with argon, add NEt to a PFA vial 4 Cl (66.3 mg, 0.4 mmol, 2 eq), the corresponding (hetero)arylthiol (0.2 mmol), MeCN (1 mL), and a magnetic stirrer bar. Subsequently, add AgF 2 (292 mg, 2.0 mmol, 10 eq) to the stirred reaction solution in the vial at room temperature, and close the vial with a screw cap. Within about 1 minute after closing the cap, the reaction solution, which was initially a black suspension, changes, and an orange precipitate with a red-violet organic layer is formed. Stir the reaction solution for 4 - 36 hours to react.

[0101] [Synthesis of 4-methoxyphenylsulfapentafluoride] Using 4-methoxythiophenol (25 μL, 0.2 mmol) as the (hetero)arylthiol, the above synthesis reaction was carried out and reacted for 36 hours to obtain 4-methoxyphenylsulfapentafluoride in a 42% NMR yield.

[0102] [Synthesis of 4-nitrophenylsulfapentafluoride] Using 4-nitrophenylthiol (30.6 mg, 0.1 mmol) as the (hetero)arylthiol, the above synthesis reaction was carried out and reacted for 4 hours to obtain 4-nitrophenylsulfapentafluoride in a 99% NMR yield.

[0103] <Synthesis of 4-Bromophenylsulfapentafluoride> (Hetero)arylthiol was used as 4-bromophenylthiol (37.8 mg, 0.2 mmol) to conduct the above synthesis reaction, and the reaction was carried out for 36 hours to obtain 4-bromophenylsulfapentafluoride in a 98% NMR yield.

[0104]

Chemical Structure

[0105] 1 H NMR (500 MHz, CD 3 CN) δ 7.78 -7.65 (m, 4H). 13 C NMR (126 MHz, CD 3 CN) δ 154.0 - 152.6 (m), 133.4 (s), 128.8 (p, 3 J CF = 4.7 Hz), 127.2 - 127.1 (m). 19 F NMR (471 MHz, CD 3 CN) δ 83.5 (p, 2 J FF,ax = 147.9 Hz, 1F, SF), 62.5 (d, 2 J FF,eq = 147.9 Hz, 4F, SF 4 ).

[0106] <Synthesis of 4-(Trifluoromethyl)phenylsulfapentafluoride> (Hetero)arylthiol was used as 4-(trifluoromethyl)phenylthiol (24 μL, 0.2 mmol) to conduct the above synthesis reaction, and the reaction was carried out for 36 hours to obtain 4-(trifluoromethyl)phenylsulfapentafluoride in a 99% NMR yield. As an internal standard, 1,4-difluorobenzene (DFB) (10 μL, 0.1 mmol) was used.

[0107] [Chemical formula]

[0108] 1 H NMR (500 MHz, CD 3 CN) δ 8.03 (d, J = 8.6 Hz, 2H), 7.89 (d, J = 8.4 Hz, 2H). 13 C NMR (126 MHz, CD 3 CN) δ 156.9 (t, 2 J CF = 17.9 Hz), 134.2 (q, 2 J CF = 33.8 Hz), 128.1 (p, 3 J CF = 4.8 Hz), 127.6 (q, 3 J CF = 3.8 Hz), 124.4 (q, 1 J CF = 272.0 Hz). 19 F NMR (471 MHz, CD 3 CN) δ 82.2 (p, 2 J FF,ax = 148.3 Hz, 1F, SF), 61.7 (d, 2 J FF,eq = 148.0 Hz, 4F, SF 4 ), -63.7 (s, 3F, CF 3 ).

[0109] <Synthesis of 3,5-Bis(trifluoromethyl)phenylsulfapentafluoride> (Hetero)arylthiol such as 3,5-bis(trifluoromethyl)phenylthiol (34 μL, 0.2 mmol) was used for the above synthesis reaction and reacted for 36 hours to obtain 3,5-bis(trifluoromethyl)phenylsulfapentafluoride in 99% NMR yield. 1,4-Difluorobenzene (10 μL, 0.1 mmol) was used as an internal standard.

[0110] [Chemical formula]

[0111] 1 H NMR (500 MHz, CD 3 CN) δ 8.40 (s, 2H), 8.28 (s, 1H). 13 C NMR (126 MHz, CD 3 CN) δ 155.1 - 154.5 (m), 133.3 (q, 2 J CF = 34.6 Hz), 128.2 (q, 3 J CF = 4.1 Hz), 127.7 (p, 3 J CF = 4.0 Hz), 123.66 (q, 1 J CF = 272.7 Hz). 19 F NMR (471 MHz, CD 3 CN) δ 80.0 (p, 2 J FF,ax = 149.9 Hz, 1F, SF), 62.3 (d, 2 J FF,eq = 149.9 Hz, 4F, SF 4 ), -63.4 (s, 6F, CF 3 ).

[0112] [Synthesis of 4-(Pentafluorothio)benzoyl Fluoride] Using 4-mercaptobenzoyl chloride (32.1 mg, 0.2 mmol) as the (hetero)arylthiol, the above synthesis reaction was carried out and reacted for 36 hours to obtain 4-(pentafluorothio)benzoyl fluoride in a 91% NMR yield.

[0113] [Chemical formula]

[0114] 1 H NMR (500 MHz, CD 3 CN) δ 8.24 - 8.17 (m, 2H), 8.07 - 8.01 (m, 2H). 19 F NMR (471 MHz, CD 3 CN) δ 81.6 (p, 2 J FF,ax = 148.3 Hz, 1F, SF), 61.5 (d, 2 J FF,eq = 148.5 Hz, 4F, SF 4 ), 19.1 (s, 1F, COF).

[0115] <Synthesis of 4,4'-Bis(pentafluorosulfanyl)-1,1'-biphenyl> (Hetero)arylthiol 4,4'-biphenyldithiol (43.7 mg, 0.2 mmol) was used, and the synthesis reaction was carried out with NEt 4 Cl (132 mg, 0.8 mmol, 4 equivalents), AgF 2 (584 mg, 4 mmol, 20 equivalents) for 36 hours. Then, the reaction mixture was filtered, and the residue was washed with MeCN. The filtrate combined with the washing solution was concentrated in vacuo, and the crude product was purified by column chromatography (hexane) to obtain 4,4'-bis(pentafluorosulfanyl)-1,1'-biphenyl as a colorless solid (46 mg, yield 57%).

[0116] [Chemical Structure]

[0117] 1 H NMR (400 MHz, benzene-d 6 ) δ 7.50 - 7.33 (m, 4H), 6.85 (d, J = 8.8 Hz, 4H). 13 C NMR (101 MHz, benzene-d 6 ) δ 153.8 (p, 2J CF = 17.5 Hz), 142.2 (s), 127.6 (s), 126.7 (p, 3 J CF = 4.6 Hz). 19 F NMR (376 MHz, benzene-d 6 ) δ 84.9 (p, 2 J FF,ax = 152.4 Hz, 1F, SF), 63.3 (d, 2 J FF,eq = 152.4 Hz, 4F, SF 4 ).

[0118] [Example 7] (Hetero)aryl thiol benzoate (benzoyl protected form of (hetero)aryl thiol) can be pentafluorosulfanylated, for example, by the following method. First, in a glove box filled with argon, add NEt 4 Cl (33.1 mg, 0.2 mmol, 1 equiv), the corresponding (hetero)aryl thiol benzoate (0.2 mmol), MeCN (1 mL), and a magnetic stirrer bar to a PFA vial. Subsequently, add AgF 2 (292 mg, 2.0 mmol, 10 equiv) to the stirred reaction solution in the vial at room temperature and close the vial with a screw cap. Within about 1 minute after closing the cap, the reaction solution, which was initially a black suspension, changes and an orange precipitate with a red-violet organic layer is formed. Stir the reaction solution for 2 - 24 hours to effect the reaction.

[0119] [Synthesis of 4-methoxyphenylsulfapentafluoride] Using 4-methoxyphenylthiobenzoate (49.2 mg, 0.2 mmol) as the (hetero)aryl thiol benzoate, the above synthesis reaction was carried out and reacted for 2 hours to obtain 4-methoxyphenylsulfapentafluoride in a 76% NMR yield.

[0120] [Example 8] (Hetero)arylthiol tritrate can be pentafluorosulfanylated, for example, by the following method. First, place the corresponding (hetero)arylthiol tritrate (0.2 mmol), MeCN (1 mL), and a magnetic stir bar in a PFA vial inside a glove box filled with argon. Subsequently, AgF 2 (175 mg, 1.2 mmol, 12 equivalents) is added to the stirred reaction solution in the vial at room temperature, and the mixture is further stirred for 1 hour. Subsequently, NEt 4 Cl (16.7 mg, 0.1 mmol, 1 equivalent) is added, and the vial is closed with a screw cap. The reaction solution is stirred for 2 - 24 hours to effect the reaction.

[0121] <Synthesis of 4 - Methoxyphenylsulfapentafluoride> Using (4 - methoxyphenyl)(trityl)sulfane (38.4 mg, 0.1 mmol) as the (hetero)arylthiol tritrate, the above - mentioned synthesis reaction was carried out and reacted for 2 hours to obtain 4 - methoxyphenylsulfapentafluoride in an NMR yield of 88%.

Industrial Applicability

[0122] The present invention provides a production method capable of synthesizing an SF 5 -containing aryl compound in a single step under relatively mild conditions. Further, in the oxidative fluorination reaction according to the present invention, since an SF 5 group can be introduced into various aryl compounds, the present invention is useful for introducing an SF 5 group into pharmaceutical and agricultural active ingredients, organic materials, etc.

Claims

1. By an oxidative fluorination reaction using a metal fluoride of divalent or higher and an organic salt containing a quaternary ammonium cation or a quaternary phosphonium cation, the following general formula (2) 【Chemical Formula 1】 [In the formula, A １ is an aryl group which may have a substituent or a heteroaryl group which may have a substituent; -G １ is -SH, -SCN, -SF ３ , -S-S-R １ (R １ is an aryl group which may have a substituent or a heteroaryl group which may have a substituent), -S-CO-R ２ (R ２ is an aryl group which may have a substituent, a heteroaryl group which may have a substituent, an alkyl group having 1 to 6 carbon atoms which may have a substituent, or an alkenyl group having 2 to 6 carbon atoms which may have a substituent), -S-R ３ (R ３ is an alkyl group having 1 to 6 carbon atoms which may have a substituent or an alkenyl group having 2 to 6 carbon atoms which may have a substituent), -SF ２ -R ４ (R ４ is an alkyl group having 1 to 6 carbon atoms which may have a substituent or an alkenyl group having 2 to 6 carbon atoms which may have a substituent), -S-Si-(R ５ ) ３ (R ５ is an aryl group which may have a substituent, a heteroaryl group which may have a substituent, an alkyl group having 1 to 6 carbon atoms which may have a substituent, or an alkenyl group having 2 to 6 carbon atoms which may have a substituent, and a plurality of R ５ may be the same group as each other or different groups), -S-PO-(R ６ ) ２ (R ６ is an aryloxy group which may have a substituent, a heteroaryloxy group which may have a substituent, an alkyloxy group having 1 to 6 carbon atoms which may have a substituent, an alkenyloxy group having 2 to 6 carbon atoms which may have a substituent, an aryl group which may have a substituent, a heteroaryl group which may have a substituent, an alkyl group having 1 to 6 carbon atoms which may have a substituent, or an alkenyl group having 2 to 6 carbon atoms which may have a substituent, and a plurality of R ６ may be the same group or different groups from each other), a (N-phthalimidyl) thio group which may have a substituent, or a thianthrenium group which may have a substituent], from a thioaryl compound represented by the following general formula (1) 【Chemical 2】 [wherein, A １ is the same as described above] To synthesize a pentafluorosulfanyl group-containing aryl compound represented by The metal fluoride of divalent or higher is silver (II) fluoride, The organic salt is a tetraalkylammonium halide in which four alkyl groups having 1 to 6 carbon atoms are bonded to a nitrogen atom, The tetraalkylammonium halide is tetraalkylammonium chloride or tetraalkylammonium bromide, The four alkyl groups bonded to the nitrogen atom of the tetraalkylammonium halide may all be the same group or may be different groups from each other, A method for producing a pentafluorosulfanyl group-containing aryl compound.

2. The said A １ is An aryl group which may have one or more substituents selected from the group consisting of a halogen atom, an alkyl group, a fluorinated alkyl group, an alkenyl group, an aryl group, a heteroaryl group, an alkoxy group, a hydroxy group, a carboxy group, an acyl group, a cyano group, a formyl fluoride group, an amino group, and a nitro group, or A heteroaryl group which may have one or more substituents selected from the group consisting of a halogen atom, an alkyl group, a fluorinated alkyl group, an alkenyl group, an aryl group, a heteroaryl group, an alkoxy group, a hydroxy group, a carboxy group, an acyl group, a formyl fluoride group, a cyano group, an amino group, and a nitro group, The method for producing a pentafluorosulfanyl group-containing aryl compound according to Claim 1.

3. The oxidative fluorination reaction is carried out at -40 to 130 °C. The method for producing a pentafluorosulfanyl group-containing aryl compound according to Claim 1 or 2.

4. Recovering the metal after the oxidative fluorination reaction. The method for producing a pentafluorosulfanyl group-containing aryl compound according to any one of Claims 1 to 3.

5. Fluorinating the recovered metal to regenerate a metal fluoride of divalent or higher, The method for producing a pentafluorosulfanyl group-containing aryl compound according to Claim 4, wherein the obtained metal fluoride of divalent or higher is used again in the oxidative fluorination reaction.

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