JP7592608B2 - Fluorinating agent and method for producing fluorine-containing compound - Google Patents

Description

The present invention relates to a fluorinating agent that introduces fluorine atoms into organic compounds, and a method for producing fluorine-containing compounds obtained using the fluorinating agent.

Fluorine atoms have a high electronegativity and are as small as hydrogen atoms. This characteristic allows fluorine atoms to bond stably with many atoms, and organic compounds into which fluorine has been introduced tend to have improved heat resistance, chemical resistance, light resistance, water resistance, etc. compared to before the introduction of fluorine. In particular, carbon-fluorine bonds have a short bond distance, are rigid, and have low polarizability. Due to these characteristics of carbon-fluorine bonds, organic compounds into which carbon-fluorine bonds have been introduced have reduced reactivity and improved stability as compounds. Useful organic compounds can be synthesized by fluorinating organic compounds, so a variety of fluorinating agents have been developed.

An example of a fluorinating agent is N-fluorobenzenesulfonimide (NFSI). It has been reported that NFSI can introduce a fluorine atom to the carbon atom adjacent to the carbonyl group (Non-Patent Documents 1 and 2). When NFSI is used, not only monofluorinated compounds in which one fluorine atom is introduced to the carbon atom adjacent to the carbonyl group, but also difluorinated compounds in which two fluorine atoms are introduced are synthesized, and the selectivity of monofluorinated compounds is insufficient.

In addition, N-fluoro-o-benzenedisulfonimide (NFOBS) (Non-Patent Document 3) and iodotoluene difluoride (ITDF) (Non-Patent Document 4) have been reported as fluorinating agents that introduce fluorine atoms into carbon atoms other than the carbon atom bonded to the silyl ether group among the carbon atoms constituting the C=C bond of a silyl enol ether compound. However, NFOBS has problems in that the raw materials are difficult to obtain, and the specific fluorocarbon _CFCl3 must be used as a solvent during raw material synthesis, and when _CHCl3 is used as the solvent instead of _CFCl3 , _CFCl3 is generated.

Vaithiyanathan, et al., Chemistry A European Journal, 2017, vol.23, p.1268-1272. Stavber, et al., Advanced synthesis & catalysis, 2010, vol.352, p.2838-2846. Davis, et al., Journal of Organic Chemistry, 1995, vol.60, p.4730-4737. Sato, et al., Synthesis, 2005, vol.15, p.2602-2605.

The present invention aims to provide a fluorinating agent capable of selectively producing a monofluorinated product by synthesizing a monofluorinated product preferentially over a difluorinated product in a fluorination reaction of a silyl enol ether compound in which a fluorine atom is introduced into a carbon atom other than the carbon atom bonded to the silyl ether group among the carbon atoms constituting the C=C bond, and a method for producing a fluorine-containing compound using the fluorinating agent.

The present inventors have discovered that when a fluorinated amine compound protected with a carbonyl or oxycarbonyl group and an arylsulfonyl group is used as a fluorinating agent, a monofluorinated product in which only one fluorine atom is introduced to one of the carbon atoms constituting the C=C bond of a silyl enol ether compound is selectively produced rather than a difluorinated product in which two fluorine atoms are introduced to the same carbon atom, thereby completing the present invention.

That is, the present invention is as follows.
[1] A compound represented by the following general formula (A1):

In the formula, the groups have the following meanings.
R ¹ is a C _6-14 aryl group which may have a substituent;
^R2 is a _C1-30 alkyl group which may have a substituent (which may have 1 to 5 ether-bonded oxygen atoms between the carbon atoms), or an aromatic group which may have a substituent.

[2] R ¹ is a phenyl group optionally having 1 to 3 substituents,
The compound of the above [1], wherein R ² is a C _1-10 alkyl group which may have a substituent, a C _6-14 aryl group which may have a substituent, or a nitrogen-containing heteroaryl group which may have a substituent.
[3] R ¹ is a phenyl group optionally having 1 to 3 substituents selected from the group consisting of a C _1-6 alkyl group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a halogen atom, and a trihalomethyl group;
The compound of the above [1], wherein R ² is a C _1-6 alkyl group optionally having a substituent, a C _1-10 alkoxy group optionally having a substituent, or a C _6-14 aryl group optionally having a substituent.
[4] A fluorinating agent comprising any one of the compounds according to [1] to [3] above as an active ingredient.

[5] A method for producing a fluorine-containing compound, comprising introducing one fluorine atom into a substrate compound represented by the following general formula (A2) using a fluorinating agent containing any of the compounds [1] to [3] above as an active ingredient, to produce a fluorine-containing compound represented by the following general formula (A3) or (A4):

［６］ Ｒ^２４及びＲ^２５が、互いに連結して置換基を有していてもよい環を形成し、当該環が、インデン環、インダン環、ジヒドロナフタレン環、ジヒドロベンゾアンヌレン環、クロマン環、クロメン環、イソクロメン環、ジヒドロチオフェン環、ベンゾチオフェン環、ジヒドロベンゾチオフェン環、チオピラン環、ジヒドロチオピラン環、ベンゾチオピラン環、及びジヒドロベンゾチオピラン環からなる群から選ばれる一種である、前記［５］に記載のフッ素含有化合物の製造方法。
［７］ Ｒ^２４及びＲ^２５が、それぞれ独立して、置換基を有していてもよいＣ_１－３０アルキル基、置換基を有していてもよいＣ_６－１４アリール基、及び置換基を有していてもよい含窒素ヘテロアリール基からなる群から選ばれる一種である、前記［５］に記載のフッ素含有化合物の製造方法。
［８］ Ｒ^２４が置換基を有していてもよいＣ_１－３０アルコキシ基である、前記［５］に記載のフッ素含有化合物の製造方法。
［９］ 前記基質化合物に、１００℃以下の温度でフッ素原子を導入する、前記［５］～［８］のいずれかのフッ素含有化合物の製造方法。 In the formulae, the groups have the following meanings.
R ²¹ , R ²² , and R ²³ are each independently a C _1-4 alkyl group; R ²⁴ is a hydrogen atom, a C _1-30 aliphatic hydrocarbon group which may have a substituent (which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms), a C _1-30 alkoxy group which may have a substituent, or an aromatic group which may have a substituent; R ²⁵ is a hydrogen atom, a C _1-30 aliphatic hydrocarbon group which may have a substituent (which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms), or an aromatic group which may have a substituent; R ²⁴ and R ²⁵ may be linked together to form a ring.

[6] The method for producing a fluorine-containing compound according to [5] above, wherein R ²⁴ and R ²⁵ are linked to each other to form a ring which may have a substituent, and the ring is one selected from the group consisting of an indene ring, an indane ring, a dihydronaphthalene ring, a dihydrobenzoannulene ring, a chroman ring, a chromene ring, an isochromene ring, a dihydrothiophene ring, a benzothiophene ring, a dihydrobenzothiophene ring, a thiopyran ring, a dihydrothiopyran ring, a benzothiopyran ring, and a dihydrobenzothiopyran ring.
[7] The method for producing a fluorine-containing compound according to the above [5], wherein R ²⁴ and R ²⁵ are each independently one selected from the group consisting of an optionally substituted C _1-30 alkyl group, an optionally substituted C _6-14 aryl group, and an optionally substituted nitrogen-containing heteroaryl group.
[8] The method for producing a fluorine-containing compound according to the above [5], wherein R ²⁴ is a C _1-30 alkoxy group optionally having a substituent.
[9] The method for producing a fluorine-containing compound according to any one of [5] to [8], wherein fluorine atoms are introduced into the substrate compound at a temperature of 100° C. or lower.

The compound according to the present invention, like NFSI, can introduce fluorine atoms into a wide range of substrates having unsaturated bonds. In particular, the compound can selectively produce monofluorinated compounds by synthesizing monofluorinated compounds preferentially over difluorinated compounds in the fluorination reaction of silyl enol ether compounds. For this reason, the compound is very useful as a fluorinating agent for synthesizing monofluorinated compounds.

In the present invention and this specification, "C _p1-p2 " (p1 and p2 are positive integers satisfying p1<p2) means a group having a carbon number of p1 to p2.

In the present invention and this specification, an "ether-bonded oxygen atom" refers to an oxygen atom that connects carbon atoms, and does not include oxygen atoms in which oxygen atoms are connected in series. An alkyl group with carbon number Nc (Nc is an integer of 2 or more) may have a maximum of Nc-1 ether-bonded oxygen atoms.

In the present invention and this specification, a "C _6-14 aryl group" is an aromatic hydrocarbon group having 6 to 14 carbon atoms, with a C _6-12 aryl group being particularly preferred. Examples of the C _6-14 aryl group include a phenyl group, a naphthyl group, an anthryl group, and a 9-fluorenyl group, with a phenyl group being particularly preferred.

In the present invention and this specification, a "substituted C _6-14 aryl group" is a group in which one or more, preferably 1 to 3, of the hydrogen atoms bonded to the carbon atoms of a C _6-14 aryl group have been substituted with other functional groups. When a C 6-14 aryl group has two or more substituents, the substituents may be the same or different. Examples of the substituent include a C _1-6 alkyl group, a C _1-6 alkoxy group, a methylenedioxy group (-O-CH ₂ -O-), a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), a trihalomethyl group, a cyano group, and a nitro group. Examples of the "optionally substituted C _6-14 aryl group" include a phenyl group, a naphthyl group, an anthryl group, a 2-methylphenyl group, a 4-methylphenyl group, a 3,5-dimethylphenyl group, a 2,6-dimethylphenyl group, a 2,4-dimethylphenyl group, a 2-trifluoromethylphenyl group, a 4-trifluoromethylphenyl group, a 3,5-di(trifluoromethyl)phenyl group, a 2,6-di(trifluoromethyl)phenyl group, a 2,4-di(trifluoromethyl)phenyl group, a 2-methoxyphenyl group, a 4-methoxyphenyl group, a 2,4-dimethoxyphenyl group, a 3,5-dimethoxyphenyl group, a 3-chlorophenyl group, a 4-cyanophenyl group, a 4-nitrophenyl group, and a 1,3-benzodioxol-5-yl group.

In the present invention and the present specification, a "heteroaryl group" is a cyclic group having aromaticity, and the ring is composed of carbon atoms and atoms other than carbon atoms. The heteroaryl group may be a group containing a nitrogen atom (nitrogen-containing heteroaryl group), a group containing an oxygen atom (oxygen-containing heteroaryl group), or a group containing a sulfur atom (sulfur-containing heteroaryl group). In addition, the aromatic ring may contain two or more atoms other than carbon atoms. Examples of the heteroaryl group include a pyrrolyl group, an imidazolyl group, a pyrazolyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, an isothiazolyl group, a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, a furanyl group, a pyranyl group, and a thienyl group.

In the present invention and this specification, a "substituted heteroaryl group" is a group in which one or more, preferably 1 to 3, hydrogen atoms bonded to atoms constituting the aromatic ring of the heteroaryl group are substituted with other functional groups. When a heteroaryl group has two or more substituents, the substituents may be the same or different. Examples of the substituent include a C _1-6 alkyl group, a C _1-6 alkoxy group, a methylenedioxy group (-O-CH ₂ -O-), a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), a trihalomethyl group, a cyano group, and a nitro group.

In the present invention and this specification, the term "aromatic group" includes both an aryl group (aromatic hydrocarbon group) which may have a substituent, and a heteroaryl group (heterocyclic group) which may have a substituent.

In the present invention and this specification, a "C _1-30 alkyl group" is an alkyl group having 1 to 30 carbon atoms, which may be linear or branched. A "C _2-30 alkyl group" is an alkyl group having 2 to 30 carbon atoms, which may be linear or branched. Examples of _C1-30 alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl, heneicosyl, docosyl, tricosyl, tetracosyl, pentacosyl, hexacosyl, heptacosyl, octacosyl, nonacosyl, and triacontyl groups.

In the present invention and this specification, a "C _1-10 alkyl group" is an alkyl group having 1 to 10 carbon atoms, which may be linear or branched. A "C _2-10 alkyl group" is an alkyl group having 2 to 10 carbon atoms, which may be linear or branched. Examples of a C _1-10 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, a hexyl group, a heptyl group, an octyl group, a nonyl group, and a decyl group.

In the present invention and this specification, a "C _1-6 alkyl group" is an alkyl group having 1 to 6 carbon atoms, and may be linear or branched. Examples of C _1-6 alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, and hexyl groups.

In the present invention and this specification, a "C _1-4 alkyl group" is an alkyl group having 1 to 4 carbon atoms, which may be linear or branched. Examples of C _1-4 alkyl groups include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, and a tert-butyl group.

In the present invention and this specification, a " _C1-3 alkyl group" is an alkyl group having 1 to 3 carbon atoms, and may be linear or branched. Examples of _C1-3 alkyl groups include a methyl group, an ethyl group, a propyl group, and an isopropyl group.

In the present invention and this specification, a "substituted C _p1-p2 alkyl group" is a group in which one or more, preferably 1 to 3, hydrogen atoms bonded to a carbon atom of a C _{p1-p2 alkyl group are substituted with other functional groups. When the C p1-p2} alkyl group has two or more substituents, the substituents may be the same or different. Examples of the substituent include a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), a C _6-14 aryl group which may have a substituent, a cyano group, and a nitro group.

An example of a "substituted C _p1-p2 alkyl group" is, for example, a C _6-14 aryl-C _1-6 alkyl group. A "C _6-14 aryl-C _1-6 alkyl group" is a group in which one hydrogen atom bonded to a carbon atom of a C _1-6 alkyl group is substituted with a C _6-14 aryl group. Examples of the C _6-14 aryl group in a C 6-14 aryl-C _1-6 alkyl group include a phenyl group, a naphthyl group, an anthryl group, and a 9-fluorenyl group, and a phenyl group and a 9-fluorenyl group are particularly preferred. A C _1-6 alkyl group in a _{C 6-14} aryl-C _1-6 alkyl group is preferably a C _1-4 alkyl group. Examples of a C _6-14 aryl-C _1-6 alkyl group include a benzyl group, a diphenylmethyl group, a triphenylmethyl group, a 2-phenylethyl group, a 9-anthrylmethyl group, and a 9-fluorenylmethyl group.

In the present invention and this specification, the term "C _1-30 aliphatic hydrocarbon group" includes all of a C _1-30 alkyl group which may have a substituent, a C _2-30 alkenyl group which may have a substituent, and a C _2-30 alkynyl group which may have a substituent. The "C _1-30 aliphatic hydrocarbon group" may be a straight chain, a branched chain, or a cyclic group. Examples of C _2-30 alkenyl groups include groups in which at least one single bond between carbon atoms in the groups listed as C _2-30 alkyl groups is replaced with a double bond. Examples of C _2-30 alkynyl groups include groups in which at least one single bond between carbon atoms in the groups listed as C _2-30 alkyl groups is replaced with a triple bond. More specifically, examples of _C2-30 alkenyl groups include vinyl, propenyl, 2-propenyl, butenyl, 1-methylpropenyl, 2-methylpropenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, etc. Examples of _C2-30 alkynyl groups include ethynyl, propynyl, butynyl, 1-methylpropynyl, pentynyl, 2-methylbutynyl, hexynyl, heptynyl, octynyl, etc.

In the present invention and this specification, a "substituted C _p1-p2 aliphatic hydrocarbon group" is a group in which one or more, preferably 1 to 3, of the hydrogen atoms bonded to a carbon atom of the C _p1-p2 aliphatic hydrocarbon group have a substituent in another functional group. When the group has two or more substituents, the substituents may be the same or different. Examples of the substituent include a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), a C _6-14 aryl group which may have a substituent, a cyano group, and a nitro group.

In the present invention and this specification, the term "C _1-30 alkoxy group" refers to a group in which an oxygen atom is bonded to the bonding terminal of a linear or branched alkyl group having 1 to 30 carbon atoms. Examples of the linear or branched alkyl group having 1 to 30 carbon atoms in the C _1-30 alkoxy group include the same as the C _1-30 alkyl group described above.

In the present invention and this specification, the term " _C1-10 alkoxy group" refers to a group in which an oxygen atom is bonded to the bonding terminal of a linear or branched alkyl group having 1 to 10 carbon atoms. Examples of the linear or branched alkyl group having 1 to 10 carbon atoms in the _C1-10 alkoxy group include the same as the _C1-10 alkyl group described above.

In the present invention and this specification, the term " _C1-6 alkoxy group" refers to a group in which an oxygen atom is bonded to the bonding terminal of a linear or branched alkyl group having 1 to 6 carbon atoms. Examples of the linear or branched alkyl group having 1 to 6 carbon atoms in the _C1-6 alkoxy group include the same as the above-mentioned _C1-6 alkyl group. Examples of the _C1-6 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, etc.

In the present invention and this specification, a "substituted C _p1-p2 alkoxy group" is a group in which one or more, preferably 1 to 3, hydrogen atoms bonded to a carbon atom of a C _{p1-p2 alkoxy group are substituted with other functional groups. When the C p1-p2} alkoxy group has two or more substituents, the substituents may be the same or different. Examples of the substituent include a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), a C _6-14 aryl group which may have a substituent, a cyano group, and a nitro group.

Furthermore, hereinafter, "compound (n)" means a compound represented by formula (n).

Subsequent chemical reactions can be carried out in a solvent that is inert to the reaction, such as methanol, 1,4-dioxane, diethyl ether, tetrahydrofuran, dichloromethane, acetonitrile, benzene, toluene, N,N-dimethylformamide, and N,N-dimethylacetamide.

[Fluorinating Agent]
The compound according to the present invention is a compound represented by the following general formula (A1).

In general formula (A1), R ¹ is a C _6-14 aryl group which may have a substituent. As compound (A1), the optionally substituted C _6-14 aryl group in R ¹ is preferably a phenyl group optionally having 1 to 3 substituents, more preferably a phenyl group optionally having 1 to 3 substituents selected from the group consisting of a C _1-6 alkyl group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a halogen atom, and a trihalomethyl group, further preferably a phenyl group, a 4-methylphenyl group, a 3-methylphenyl group, a 2,6-dimethylphenyl group, a 3,4-dimethylphenyl group, a 4-trifluoromethyl group, a 3-trifluoromethyl group, a 2,6-di(trifluoromethyl)phenyl group, a 3,4-di(trifluoromethyl)phenyl group, a 4-methoxyphenyl group, a 3-methoxyphenyl group, a 2,4-dimethoxyphenyl group, a 3,4-dimethoxyphenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a 2,6-dichlorophenyl group, a 3,4-dichlorophenyl group, or a 4-nitrophenyl group, and particularly preferably a phenyl group.

In general formula (A1), R ² is a C _1-30 alkyl group which may have a substituent (which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms), or an aromatic group which may have a substituent.

When R ² is a C _1-30 alkyl group which may have a substituent, the alkyl group may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms. As the compound (A1), R ² is preferably a C _1-10 alkyl group which may have a substituent, more preferably a C 1-6 alkyl group which may have a substituent, even more preferably an unsubstituted C _1-6 alkyl group and a C _6-14 aryl-C _1-6 alkyl group, even more preferably 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 benzyl group, a _{diphenylmethyl} group, a triphenylmethyl group, a 2-phenylethyl group, a 9-anthrylmethyl group, and a 9-fluorenylmethyl group, and particularly preferably a tert-butyl group, a benzyl group, and a 2-phenylethyl group.

When R ² is an aromatic group which may have a substituent, the aromatic group may be an aryl group or a heteroaryl group. In the compound (A1), R ² is preferably a C _6-14 aryl group which may have a substituent, or a nitrogen-containing heteroaryl group which may have a substituent, more preferably a C _6-14 aryl group which may have a substituent, a C _1-6 alkyl group, a C More preferred is a phenyl group which may have 1 to 3 substituents selected from the group consisting of _{a 1-6} alkoxy group, a trifluoromethyl group, a halogen atom, a cyano group, and a nitro group, and examples thereof include a phenyl group, a 2-methylphenyl group, a 4-methylphenyl group, a 3,5-dimethylphenyl group, a 2,6-dimethylphenyl group, a 2,4-dimethylphenyl group, a 2-trifluoromethylphenyl group, a 3-trifluoromethylphenyl group, a 4-trifluoromethylphenyl group, a 3,5-di(trifluoromethyl)phenyl group, a 2,6-di(trifluoromethyl)phenyl group, a 2,4-di(trifluoromethyl)phenyl group, a 2-methoxyphenyl group, a 3-methoxyphenyl group, a 4-methoxyphenyl group, a 2,4-dimethoxyphenyl group, a 3,5-dimethoxyphenyl group, a 2,6-dimethoxyphenyl group, a 2-chlorophenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a 2,4-dichlorophenyl group, a ,5-dichlorophenyl group, 2,6-dichlorophenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2,4-difluorophenyl group, 3,5-difluorophenyl group, 2,6-difluorophenyl group, 4-cyanophenyl group, and 4-nitrophenyl group are even more preferred, and phenyl group, 2-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 3,5-di(trifluoromethyl)phenyl group, 2,6-di(trifluoromethyl)phenyl group, 2,4-di(trifluoromethyl)phenyl group, 2-chlorophenyl group, 4-chlorophenyl group, 3,5-dichlorophenyl group, 2,6-dichlorophenyl group, 2,4-dichlorophenyl group, 2-fluorophenyl group, 4-fluorophenyl group, 3,5-difluorophenyl group, 2,6-difluorophenyl group, 2,4-difluorophenyl group, and 4-cyanophenyl group are particularly preferred.

As compound (A1), preferred are compounds in which R ¹ is a phenyl group optionally having 1 to 3 substituents selected from the group consisting of a C _1-6 alkyl group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a halogen atom, and a trihalomethyl group, and R ² is a C _1-6 alkyl group optionally having a substituent, a C _1-10 alkoxy group optionally having a substituent, and a C _6-14 aryl group optionally having a substituent; R ¹ is a phenyl group, a 4-methylphenyl group, a 3-methylphenyl group, a 2,6-dimethylphenyl group, a 3,4-dimethylphenyl group, a 4-trifluoromethyl group, a 3-trifluoromethyl group, a 2,6-di(trifluoromethyl)phenyl group, a 3,4-di(trifluoromethyl)phenyl group, a 4-methoxyphenyl group, a 3-methoxyphenyl group, a 2,4-dimethoxyphenyl group, a 3,4-dimethoxyphenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a 2,6-dichlorophenyl group, a 3,4-dichlorophenyl group, and a 4-nitrophenyl group; More preferred are compounds in which R 1 is a phenyl group, ^{R 2} is a C _1-6 alkyl group having no substituent, a C _6-14 aryl-C _1-6 alkyl group, and a phenyl group optionally having 1 to 3 substituents selected from the group consisting of a C _1-6 alkyl group, a C _1-6 alkoxy group, a trifluoromethyl group, a halogen atom, a ^cyano group, and a nitro group, and More preferred are compounds in which ² is a tert-butyl group, a benzyl group, a 2-phenylethyl group, a phenyl group, a 2-trifluoromethylphenyl group, a 4-trifluoromethylphenyl group, a 3,5-di(trifluoromethyl)phenyl group, a 2,6-di(trifluoromethyl)phenyl group, a 2,4-di(trifluoromethyl)phenyl group, a 2-chlorophenyl group, a 4-chlorophenyl group, a 3,5-dichlorophenyl group, a 2,6-dichlorophenyl group, a 2,4-dichlorophenyl group, a 2-fluorophenyl group, a 4-fluorophenyl group, a 3,5-difluorophenyl group, a 2,6-difluorophenyl group, a 2,4-difluorophenyl group, and a 4-cyanophenyl group.

Compound (A1) can be synthesized, for example, by synthesizing a sulfonylcarbamic acid ester by a condensation reaction between a carboxylic acid such as a fatty acid or a benzoic acid derivative and a sulfonamide, substituting a hydrogen atom bonded to the nitrogen atom of the amino group with a lithium atom, and further substituting the lithium atom with a fluorine atom. In the following formula, ^R1 and ^R2 are the same as ^R1 and ^R2 in general formula (A1).

[Method of producing fluorine-containing compound]
Compound (A1) can be an active ingredient of a fluorinating agent in various reactions. Compound (A1) can fluorinate carbon atoms in various organic compounds, similar to NFSI. Examples of organic compounds that can be used as substrates include compounds having unsaturated bonds, such as alkenes, allyl compounds, alkynes, and aromatic compounds. The unsaturated bond may be a bond formed between carbon atoms, or may be a bond between a carbon atom and an atom other than a carbon atom.

Compound (A1) is particularly suitable as a fluorinating agent for silyl enol ether compounds. For example, by using compound (A1) as a fluorinating agent, one fluorine atom can be introduced into a substrate compound (silyl enol ether compound) represented by general formula (A2) to produce a fluorine-containing compound represented by general formula (A3) or (A4).

It is believed that compounds (A3) and (A4) can be easily interconverted.

For example, compound (A3) can be converted to compound (A4) by adding a desilylating agent. The desilylating agent can be, for example, the compound described in the section on Silyl Ethers on page 201 of "Greene's Protective Groups in Organic Synthesis, 5th Edition". Specific examples include inorganic acids such as hydrochloric acid and sulfuric acid, organic acids such as formic acid and acetic acid, inorganic fluoride salts such as cesium fluoride, organic fluoride salts such as tetrabutylammonium fluoride (TBAF), inorganic hydroxide compounds such as sodium hydroxide, and alkoxides such as sodium methoxide. As the desilylating agent, inorganic acids, organic acids, and organic fluoride salts are preferred, and tetrabutylammonium fluoride is particularly preferred.

Compound (A4) can be converted to compound (A3) by adding a silylating agent (R ²¹ R ²² R ²³ SiX: R ²¹ , R ²² , and R ²³ are the same as in general formula (A3), and X is a halogen atom) and a base. The silylating agent and base can be, for example, the compounds described in the section on Silyl Ethers on page 201 of "Greene's Protective Groups in Organic Synthesis, 5th Edition." Examples of the silylating agent include silane chlorides such as Me ₃ SiCl, Et ₃ SiCl, iPr ₃ SiCl, and t-BuMe ₂ SiCl. Examples of the base include organic bases such as triethylamine, pyridine, and imidazole. The silylating agent used in the conversion of compound (A4) to compound (A3) is preferably Me ₃ SiCl, and the base is preferably imidazole.

In general formula (A2), R ²¹ , R ²² and R ²³ are each independently a C _1-4 alkyl group. As compound (A2), a compound in which R ²¹ , R ²² and R ²³ are each independently a methyl group or an ethyl group is preferred, a compound in which R ²¹ , R ²² and R ²³ are all methyl groups or an ethyl group is more preferred, and a compound in which R ²¹ , R ²² and R ²³ are all methyl groups is particularly preferred, because the selectivity to monofluorinated compounds is high.

In general formula (A2), R ²⁴ is a hydrogen atom, a C _1-30 aliphatic hydrocarbon group which may have a substituent (which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms), a C _1-30 alkoxy group which may have a substituent, or an aromatic group which may have a substituent. In general formula (A2), R ²⁵ is a hydrogen atom, a C _1-30 aliphatic hydrocarbon group which may have a substituent (which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms), or an aromatic group which may have a substituent.

When R ²⁴ or R ²⁵ is a C _{1-30 aliphatic hydrocarbon group which may have a substituent, the aliphatic hydrocarbon group may have 1 to 5 ether-bonding oxygen atoms between carbon atoms. As the C 1-30 aliphatic} hydrocarbon group, a C _1-30 alkyl group which may have a substituent is preferable, a C 1-10 alkyl group which may have a substituent is more preferable, a C _1-6 alkyl group which may have a substituent is still more preferable, and a C _1-6 alkyl group which does not have a _substituent is particularly preferable.

When R ²⁴ or R ²⁵ is an aromatic group which may have a substituent, the aromatic group may be an aryl group or a heteroaryl group. The aromatic group is preferably a C _6-14 aryl group which may have a substituent, or a nitrogen-containing heteroaryl group which may have a substituent, more preferably a C _6-14 aryl group which may have a substituent, even more preferably a phenyl group which may have a substituent, and even more preferably a phenyl group which may have 1 to 3 substituents selected from the group consisting of a C _1-6 alkyl group, a C _1-6 alkoxy group, a trifluoromethyl group, a halogen atom, a cyano group, and a nitro group. Examples of the phenyl group which may have 1 to 3 substituents selected from the group consisting of a C _1-6 alkyl group, a C _1-6 alkoxy group, a trifluoromethyl group, a halogen atom, a cyano group, and a nitro group include the same groups as those exemplified for R ² .

When R ²⁴ is a C _1-30 alkoxy group which may have a substituent, the alkoxy group may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms. In the compound (A2), R ²⁴ is preferably a C _1-10 alkoxy group which may have a substituent, more preferably a C _1-6 alkoxy group which may have a substituent, even more preferably an unsubstituted C _1-6 alkoxy group, and even more preferably a methoxy group, an ethoxy group, a propoxy group, a butoxy group, a tert-butoxy group, a pentyloxy group, or a hexyloxy group.

The R ²⁴ and R ²⁵ may be linked together to form a ring. The ring formed by R ²⁴ and R ²⁵ is preferably a 5-membered ring, a 6-membered ring, or a 7-membered ring, and may be a ring condensed with an aromatic ring or a saturated ring. It may also be a hydrocarbon ring or a heterocyclic ring. Examples of the ring include an indene ring, an indane ring, a dihydronaphthalene ring, a dihydrobenzoannulene ring, a chroman ring, a chromene ring, an isochromene ring, a dihydrothiophene ring, a benzothiophene ring, a dihydrobenzothiophene ring, a thiopyran ring, a dihydrothiopyran ring, a benzothiopyran ring, and a dihydrobenzothiopyran ring.

The ring constituted by R ²⁴ and R ²⁵ may have a substituent. When it has two or more substituents, the substituents may be the same or different. Examples of the substituent include a C _1-6 alkyl group, a C _1-6 alkoxy group, a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), a trihalomethyl group, a C _6-14 aryl group which may have a substituent, a cyano group, and a nitro group.

The fluorination reaction of compound (A2) with compound (A1) can be carried out by incubating with fluorine gas at a temperature of 100°C or less in the presence of a desilylation agent. As the desilylation agent, a fluoride such as sodium fluoride can be used. The amount of compound (A1) is preferably 0.5 to 100 moles, more preferably 0.5 to 50 moles, and even more preferably 0.5 to 10 moles, per mole of compound (A2).

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

The NMR apparatus used in the analysis of the Examples and Comparative Examples was a JNM-ECS400 (400 MHz) manufactured by JEOL. In ¹ H NMR, tetramethylsilane was set to a reference value of 0 PPM, and in ¹⁹ F NMR, C ₆ F ₆ was set to a reference value of -162 PPM. For the HPLC (high performance liquid chromatograph), an LC-20 manufactured by Shimadzu Corporation was used. The unit of yield (%) described in the Examples is mol %.

[Example 1]
A compound represented by the general formula (A1) in which R ¹ is a phenyl group and R ² is a phenyl group substituted with two trifluoromethyl groups was synthesized.

Under a nitrogen atmosphere, a solution of benzoic acid derivative compound (1) (1.29 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (1.15 g), N,N-dimethyl-4-aminopyridine (0.73 g), and sulfonamide (compound (2): 0.86 g) dissolved in 0.2 M methylene chloride was stirred at room temperature for 12 hours. The mixture was then quenched with 1 M hydrochloric acid, separated, the aqueous phase was extracted twice with ethyl acetate, and all the organic phases were combined and dried over sodium sulfate. The solvent was then distilled off under reduced pressure, and silica gel column chromatography was performed using a hexane/ethyl acetate mixed solvent system to obtain the target compound (3-H) (1.21 g) as a white solid.

¹ H NMR (d ₆ -acetone): δ = 11.48 (s, 1H), 8.55 (s, 2H), 8.32 (s, 1H), 8.13-8.16 (d, 2H), 7.74-7.78 (t, 1H), 7.64-7.68 (t, 2H) ¹⁹ F NMR (d ₆ -acetone): δ = -63.40 (s, 6F).

The lithium salt of compound (3-H) was prepared. Specifically, a mixed solution of compound (3-H) (0.79 g) and lithium hydroxide monohydrate (0.08 g) in acetone/water was stirred at room temperature for 12 hours. The solvent was then distilled off under reduced pressure to directly obtain the lithium salt (3-Li) (0.79 g).

¹ H NMR (d ₆ -acetone): δ = 8.61 (s, 2H), 8.12 (s, 1H), 7.99-8.01 (d, 2H), 7.47-7.56 (m, 3H) ¹⁹ F NMR (d ₆ -acetone): δ = -63.20 (s, 6F).

Furthermore, compound (3-H) and its lithium salt, compound (3-Li), were fluorinated.

First, a solution of compound (3-H) (1.29 g) and sodium fluoride (0.42 g) in acetonitrile (120 g) was cooled to 0°C using an ice bath. A 2% by volume fluorine/nitrogen mixed gas was adjusted to 100 mL/min using a mass flow controller, and 1 equivalent of fluorine gas was introduced into the reaction vessel over 40 minutes. Next, the precipitate was filtered, and the solvent was distilled off under reduced pressure. The target product (4) (0.63 g) was obtained by silica gel column chromatography using a hexane/ethyl acetate mixed solvent system.

Instead of the above compound (3-H), its lithium salt, compound (3-Li), was used. Specifically, when a 2% fluorine/nitrogen mixed gas was passed through a solution of compound (3-Li) (0.86 g) and sodium fluoride (0.09 g) in acetonitrile (30 g) for 25 minutes, 0.30 g of compound (4) was obtained.

¹ H NMR (d ₆ -acetone): δ=8.51 (s, 3H), 7.95-8.01 (m, 3H), 7.79-7.83 (t, 2H) ¹⁹ F NMR (d ₆ -acetone): δ=−52.35 (s, 1F), −63.39 (s, 6F).

[Example 2]
The silyl enol ether compound (9) was fluorinated using the compound (4) as a fluorinating agent.

Under a nitrogen atmosphere, silyl enol ether compound (9) (16 mg) was added dropwise to a solution of compound (4) (37 mg) dissolved in 0.1 M methylene chloride. After stirring at 25° C. for 24 hours, the crude liquid was quantified by ¹⁹ F NMR, and it was confirmed that compound (10m) was produced in a yield of 83%. At this time, it was also confirmed that compound (10d) was produced in a yield of 2%.

¹⁹ F NMR (CDCl ₃ ) of compound (10m): δ=−191.16 (d, 1F). ¹⁹ F NMR (CDCl ₃ ) of compound (10d): δ=−112.09 (t, 2F).

[Comparative Example 1]
The silyl enol ether compound (9) was fluorinated using NFSI as a fluorinating agent.

The experiment was carried out under the same conditions as in Example 2, using NFSI (28 mg) instead of compound (4) as the fluorinating agent. As a result, it was confirmed that compound (10m) was produced at 7%, compound (10d) at 36%, and compound (11m) at 8%. From these results, it was found that by using compound (A1) as the fluorinating agent, difluoro compounds can be synthesized more selectively than monofluoro compounds.

¹⁹ F NMR (CDCl ₃ ) of compound (11m): δ=−129.08 (s, 1F).

[Example 3]
Compound (13) was synthesized in which R ¹ is a phenyl group and R ² is a heteroaryl group in general formula (A1).

A solution of compound (12-H) (0.56 g) and sodium fluoride (0.27 g) dissolved in acetonitrile (30 g) was cooled to 0° C. using an ice bath. A 2% by volume fluorine/nitrogen mixed gas was adjusted to 100 mL/min using a mass flow controller, and 1 equivalent of fluorine gas was introduced into the reaction vessel over 25 minutes. After completion of the reaction, the crude liquid was quantified by ¹⁹ F NMR, and it was confirmed that compound (13) was produced in a yield of 35%.

^19F NMR (neat): δ=-47.67 (s, 1F).

[Example 4]
Compound (15) was synthesized, in which R ¹ in general formula (A1) is a phenyl group and R ² is a heteroaryl group substituted with two chlorine atoms.

A solution of compound (14-H) (0.40 g) and sodium fluoride (0.16 g) dissolved in acetonitrile (30 g) was cooled to 0° C. using an ice bath. A 2% by volume fluorine/nitrogen mixed gas was adjusted to 100 mL/min using a mass flow controller, and 1 equivalent of fluorine gas was introduced into the reaction vessel over 14 minutes. After completion of the reaction, the crude liquid was quantified by ¹⁹ F NMR, and it was confirmed that compound (15) was produced in a yield of 34%.

^19F NMR (neat): δ=-51.34 (s, 1F).

[Example 5]
The fluorination of silyl enol ether was carried out using compound (4) as a fluorinating agent. As the silyl enol ether, ((6,7-dihydro-5H-benzo[7]annulen-9-yl)oxy)trimethylsilane, (E)-trimethyl((1-phenylprop-1-en-1-yl)oxy)silane, (E)-((1,2-diphenylvinyl)oxy)trimethylsilane, ((2H-chromen-4-yl)oxy)trimethylsilane, (E)-trimethyl((1-phenylbut-1-en-1-yl)oxy)silane, and (E)-((1-([1,1'-biphenyl]-4-yl)prop-1-en-1-yl)oxy)trimethylsilane were used. The reaction conditions were the same as those in Example 2, except that the synthesis reaction of (E)-((1,2-diphenylvinyl)oxy)trimethylsilane was carried out for 50 hours.

As a result, it was confirmed that 6-fluoro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one was produced in a yield of 90% from ((6,7-dihydro-5H-benzo[7]annulen-9-yl)oxy)trimethylsilane. In addition, the synthesis ratio of the monofluorinated product (6-fluoro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one) to the difluorinated product (6,6-difluoro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one) was monofluorinated product:difluorinated product=98:2.
It was confirmed that 2-fluoro-1-phenylpropan-1-one was produced in a yield of 87% from (E)-trimethyl((1-phenylprop-1-en-1-yl)oxy)silane. The synthesis ratio of the monofluorinated product (2-fluoro-1-phenylpropan-1-one) to the difluorinated product (2,2-difluoro-1-phenylpropan-1-one) was monofluorinated product:difluorinated product=98:2.
It was confirmed that 2-fluoro-1,2-diphenylethan-1-one was produced in a yield of 71% from (E)-((1,2-diphenylvinyl)oxy)trimethylsilane. The synthesis ratio of the monofluorinated product (2-fluoro-1,2-diphenylethan-1-one) to the difluorinated product (2,2-difluoro-1,2-diphenylethan-1-one) was monofluorinated product:difluorinated product=99:1.
It was confirmed that 3-fluorochroman-4-one was produced in a yield of 57% from ((2H-chromen-4-yl)oxy)trimethylsilane. The synthesis ratio of the monofluorinated product (3-fluorochroman-4-one) to the difluorinated product (3,3-difluorochroman-4-one) was monofluorinated product:difluorinated product=98:2.
It was confirmed that 2-fluoro-1-phenylbutan-1-one was produced in a yield of 83% from (E)-trimethyl((1-phenylbut-1-en-1-yl)oxy)silane. The synthesis ratio of the monofluorinated product (2-fluoro-1-phenylbutan-1-one) to the difluorinated product (2,2-difluoro-1-phenylbutan-1-one) was monofluorinated product:difluorinated product=99:1.
It was confirmed that 1-([1,1'-biphenyl]-4-yl)-2-fluoropropan-1-one was produced in a yield of 96% from (E)-((1-([1,1'-biphenyl]-4-yl)prop-1-en-1-yl)oxy)trimethylsilane. In addition, the synthesis ratio of the monofluorinated product (1-([1,1'-biphenyl]-4-yl)-2-fluoropropan-1-one) and the difluorinated product (1-([1,1'-biphenyl]-4-yl)-2,2-difluoropropan-1-one) was monofluorinated product:difluorinated product=99:1.

[Example 6]
The silyl enol ether compound (16) was fluorinated using the compound (4) as a fluorinating agent.

Under a nitrogen atmosphere, silyl enol ether compound (16) (22.2 mg: 0.10 mmol) was added dropwise to a solution of compound (4) (49.8 mg: 0.12 mmol) dissolved in 0.1 M methylene chloride (1 mL). After stirring at 25° C. for 42 hours, the crude liquid was quantified by ¹⁹ F NMR, and it was confirmed that compound (17) was produced in a yield of 45%. At this time, no difluoro form was detected.

[Example 7]
The silyl enol ether compound (9-2) was fluorinated using the compound (4) as a fluorinating agent.

Under a nitrogen atmosphere, silyl enol ether compound (9-2) (24 mg: 0.091 mmol) was added dropwise to a solution of compound (4) (45.3 mg: 0.11 mmol) dissolved in 0.1 M methylene chloride. The mixture was then stirred at 25° C. for 24 hours, and the crude liquid was quantitatively analyzed by ¹⁹ F NMR, confirming that compound (10m) was produced in a yield of 54%. At this time, it was also confirmed that compound (10d) was produced in a yield of 3%.

[Example 8]
Using compound (4) as a fluorinating agent, fluorination of silyl enol ether was carried out under the same conditions as in Example 7. The synthesized monofluorinated and difluorinated products were analyzed by ¹⁹ F NMR. For ¹⁹ F NMR, the reference value for 2,3,5,6-tetrafluoro-p-xylene was set at -147 PPM. ^{The 19} F NMR analysis values and synthesis ratios of the synthesized monofluorinated and difluorinated products are shown together with the reaction formula. From these results, it was found that by using compound (4) as a fluorinating agent, difluoro compounds can be synthesized more selectively from various substrates than monofluoro compounds.

[Example 9]
Using compound (4) as a fluorinating agent, fluorination of silyl enol ether compound (18) was carried out in the same manner as in Example 2. The synthesis ratio of the monofluorinated product and the difluorinated product synthesized is shown together with the reaction formula.

[Example 10]
In the synthesis of compound (4) from compound (3-Li), compound (19), which is a lithium salt, was used instead of compound (3-Li), and the same procedure as in Example 1 was followed to obtain compound (20), which is a fluorination agent, with a fluorination yield of 87% and an isolation yield by column chromatography of 51%. In the same manner, the lithium salt was changed to obtain corresponding fluorination agents (compounds (21) to (23)). The fluorination yields (values outside parentheses) and isolation yields by column chromatography (values in parentheses) of the obtained fluorination agents are shown together with the reaction formula. In addition, these fluorination agents were analyzed by NMR. ¹⁹ F NMR was performed in the same manner as in Example 8.

NMR analysis value of compound (20)
¹ H NMR (CDCl ₃ ): 7.98-8.00 (d, 2H), 7.85-7.87 (d, 2H), 7.77-7.82 (m, 3H), 7.61-7.65 (t, 2H) ¹⁹ F NMR (CDCl ₃ ): -49.35 (s, 1F), -63.26 (s, 3F)

NMR analysis value of compound (21)
¹ H NMR (d ₆ -acetone): 8.04 (d, 2H), 7.91 (t, 1H), 7.76 (t, 2H), 1.05 (s, 9H) ¹⁹ F NMR (d ₆ -acetone): -51.19 (s, 1F)

NMR analysis value of compound (22)
¹ H NMR (d ₆ -acetone): 7.96-8.01 (m, 3H), 7.79-7.83 (t, 2H), 7.50-7.59 (m, 3H) ¹⁹ F NMR (d ₆ -acetone): -51.85 (s, 1F), -108.98 (s, 2F)

NMR analysis value of compound (23)
¹ H NMR (d ₆ -acetone): 7.95-8.02 (m, 4H), 7.90-7.91 (m, 2H), 7.82-7.87 (t, 2H) ¹⁹ F NMR (d ₆ -acetone): -52.11 (s, 1F)

[Example 11]
Using compounds (20) to (23) as fluorinating agents, fluorination of silyl enol ether compound (9) was carried out in the same manner as in Example 2. The synthesis ratio of the monofluorinated product and the difluorinated product synthesized is shown together with the reaction formula. These results show that by using compounds (20) to (23) as fluorinating agents, difluoro compounds can be synthesized more selectively than monofluoro compounds.

The present invention provides a fluorinating agent capable of selectively synthesizing a monofluorinated compound in which one fluorine atom has been introduced into a carbon atom other than the carbon atom to which the silyl ether group is bonded, among the carbon atoms constituting the C=C bond of a silyl enol ether compound, and a method for producing a monofluorinated compound using the fluorinating agent. The fluorinating agent according to the present invention is particularly useful for the selective production of monofluorinated compounds, since it can preferentially synthesize monofluorinated compounds over difluorinated compounds in which two fluorine atoms have been introduced.

The entire contents of the specifications, claims, drawings and abstracts of Japanese Patent Application No. 2019-173543 filed on September 24, 2019, and Japanese Patent Application No. 2020-128667 filed on July 29, 2020 are hereby incorporated by reference as the disclosure of the specification of the present invention.

Claims (9)

A compound represented by the following general formula (A1):

In the formula, the groups have the following meanings.
R ¹ is a C _6-14 aryl group optionally having 1 to 3 substituents selected from the group consisting of a C _1-6 alkyl group, a C _1-6 alkoxy group, a halogen atom, and a trihalomethyl group;
^R2 is a _C1-30 alkyl group (which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms) which optionally has 1 to 3 _C6-14 aryl groups as substituents, or an aromatic group which may have 1 to 3 substituents selected from the group consisting of a _C1-6 alkyl group, a _C1-6 alkoxy group, a trifluoromethyl group, and a halogen atom. R ¹ is a phenyl group optionally having 1 to 3 substituents selected from the group consisting of a C _1-6 alkyl group, a C _1-6 alkoxy group, a halogen atom, and a trihalomethyl group;
R ² is a C _6-14 aryl group optionally having 1 to 3 substituents selected from the group consisting of a C _1-10 alkyl group optionally having 1 to 3 C _6-14 aryl groups as substituents, a C _1-6 alkyl group, a C _1-6 alkoxy group, a trifluoromethyl group, and a halogen atom, or a nitrogen-containing heteroaryl group optionally having 1 to 3 substituents selected from the group consisting of a C _1-6 alkyl group, a C _1-6 alkoxy group, a trifluoromethyl group, and a halogen atom;
The compound of claim 1. R ¹ is a phenyl group optionally having 1 to 3 substituents selected from the group consisting of a C _1-6 alkyl group, a C _1-6 alkoxy group, a halogen atom, and a trihalomethyl group;
The compound according to claim 1, wherein R ² is a C _{1-6 alkyl group optionally having 1 to 3 C 6-14 aryl} groups as substituents , or a C _6-14 aryl group optionally having 1 to 3 substituents selected from the group consisting of a C _1-6 alkyl group, a C _1-6 alkoxy group, a trifluoromethyl group, and a halogen atom. A fluorinating agent containing the compound according to any one of claims 1 to 3 as an active ingredient. A method for producing a fluorine-containing compound, comprising introducing one fluorine atom into a substrate compound represented by the following general formula (A2) using a fluorinating agent containing the compound according to any one of claims 1 to 3 as an active ingredient, to produce a fluorine-containing compound represented by the following general formula (A3) or (A4).

In the formulae, the groups have the following meanings.
R ²¹ , R ²² , and R ²³ are each independently a C _1-4 alkyl group; R ²⁴ is a hydrogen atom, an optionally substituted C _1-30 aliphatic hydrocarbon group (which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms), an optionally substituted C _1-30 alkoxy group, or an optionally substituted aromatic group; R ²⁵ is a hydrogen atom, an optionally substituted C _1-30 aliphatic hydrocarbon group (which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms), or an optionally substituted aromatic group; the optionally substituted C _1-30 aliphatic hydrocarbon group is a C 1-30 aliphatic hydrocarbon group (which may have 1 to 5 ether-bonding oxygen atoms between the carbon atoms) which may have 1 to 3 substituents selected from the group consisting of halogen atoms and C _6-14 aryl groups; the optionally substituted C _1-30 alkoxy group is a C _1-30 alkoxy group which may have 1 to 3 substituents selected from the group consisting of halogen atoms and C _6-14 aryl groups. the aromatic group which may have a substituent is an aromatic group which may have 1 to 3 substituents selected from the group consisting of a halogen atom and a ^C _6-14 aryl group; R ₂₄ and R ²⁵ may be linked to each other to form a ring. The method for producing a fluorine-containing compound according to claim 5, wherein R ²⁴ and R ²⁵ are linked to each other to form a ring which may have a substituent, and the ring is one selected from the group consisting of an indene ring, an indane ring, a dihydronaphthalene ring, a dihydrobenzoannulene ring, a chroman ring, a chromene ring, and an isochromene ring. The method for producing a fluorine-containing compound according _to claim 5, wherein R ²⁴ and R ²⁵ are each independently one selected from the group consisting of a C _1-30 alkyl group optionally having 1 to 3 substituents selected from the group consisting of a halogen atom and a C _6-14 aryl group, a C _6-14 aryl group optionally having 1 to 3 substituents selected from the group consisting of a halogen atom and a C _6-14 aryl group, and a nitrogen-containing heteroaryl group optionally having 1 to 3 substituents selected from the group consisting of a halogen atom and a C 6-14 aryl group. The method for producing a fluorine-containing compound according to claim 5, wherein R ²⁴ is a C _1-30 alkoxy group optionally having 1 to 3 substituents selected from the group consisting of a halogen atom and a C _6-14 aryl group. The method for producing a fluorine-containing compound according to any one of claims 5 to 8, wherein fluorine atoms are introduced into the substrate compound at a temperature of 100°C or less.