CN1898187B - Fluorinating agent and method for producing fluorine-containing compound using same - Google Patents

Abstract

A process for producing a fluorine-containing organic compound represented by the formula (7), which comprises reacting an organic compound represented by the formula (6) with a fluorinating agent represented by the formula (1);

in the formula (1), R¹And R³Each of which is the same or different and represents an alkyl group which may be substituted, R²、R⁴And R⁵Each of which is the same or different and represents a hydrogen atom or an alkyl group which may be substituted, and 0 < x.ltoreq.1, Y-represents a 1-valent anion other than a fluoride ion; R-Ln (6) formula (6) wherein R represents a substituted or unsubstituted saturated hydrocarbon group, or a substituted or unsubstituted aromatic group, L represents a leaving group, and n represents an integer of 1 or more; R-Fm (7) formula (7), wherein R is as defined above, and m represents an integer satisfying the inequality: m is more than or equal to 1 and less than or equal to n.

Description

Fluorinating agent and method for producing fluorine-containing compound using same

technical field

The present invention relates to a method for producing important fluorine-containing compounds such as various chemical products mainly including medical and agricultural chemical compounds and electronic materials and their synthetic intermediates, and a fluorinating agent.

Background technique

It is known to react potassium fluoride as a fluorinating agent with a compound that can undergo a nucleophilic substitution reaction such as a halogen compound or a sulfonate to replace a halogen atom or a sulfonyloxy group with a fluorine atom (for example, Patent Document 1. Patent Document 2, Non-Patent Document 1, Non-Patent Document 2, Non-Patent Document 3).

In addition, a method of using a quaternary ammonium fluoride as a fluorinating agent (for example, see Non-Patent Document 4), a method of using a quaternary ammonium fluoride and cesium fluoride in combination (for example, see Non-Patent Document 5), etc. are known. Furthermore, methods using quaternary ammonium difluoride or quaternary phosphine difluoride synthesized from hydrofluoric acid containing hydrogen fluoride, which is highly corrosive and toxic, are known (see Non-Patent Document 6, Patent Document 3, and Patent Document 4) wait.

Patent Document 1: International Laid-Open Patent No. WO02/092608

Patent Document 2: International Laid-Open Patent WO03/076366 Gazette

Patent Document 3: Japanese Patent Application Laid-Open No. 61-161224

Patent Document 4: Japanese Patent Application Laid-Open No. 4-124146

Non-Patent Document 1: J. Amer. Chem. Soc., 78, 6034 (1956)

Non-Patent Document 2: Chemistry Lett., 761 (1981)

Non-Patent Document 3: Synthsis, 920 (1987)

Non-Patent Document 4: J.Org.Chem., 49 , 3216 (1984)

Non-Patent Document 5: Synthetic Commun., 18 , 1661 (1988)

Non-Patent Document 6: Tetrahedron Lett., 28 , 4733 (1987)

In addition, it is known to react a methanol solution of the corresponding imidazolium carbonate with ammonium fluoride or react with potassium fluoride in an aqueous solvent to obtain 1-ethyl-3-methylimidazolium fluoride ( Referring to Non-Patent Document 8 and Patent Document 5), there is also known a method of reacting 1-ethyl-3-methylimidazolium chloride with hydrogen fluoride to obtain a hydrogen fluoride adduct (see Non-Patent Document 7). It is also known to produce a hydrate of 1-butyl-3-methylimidazolium fluoride by thermally decomposing 1-butyl-3-methylimidazolium fluoride hexafluorophosphate (see Non-Patent Document 9).

Patent Document 5: Japanese Patent Laid-Open No. 2003-335734

Non-Patent Document 7: J. Fluorine. Chem., 99 , 1 (1999)

Non-Patent Document 8: Electrochemical and Solid-State Letters, 5(6)A119-A121(2002)

Non-Patent Document 9: Green Chemistry, 2003, 5, 361-363

Contents of the invention

According to the invention of the present application, a fluorine-containing compound can be easily produced.

The first aspect of the present invention is a method for producing a fluorine-containing organic compound represented by formula (7), which is characterized in that an imidazolium salt represented by formula (1) is reacted with an organic compound represented by formula (6);

In formula (1), R ¹ and R ³ are each the same or different, representing an alkyl group that may be substituted,

R ² , R ⁴ and R ⁵ are each the same or different, and represent a hydrogen atom or an alkyl group that may be substituted,

and 0<x≤1,

Y ^- represents a monovalent anion other than fluoride ion;

R-Ln (6)

In formula (6), R represents a substituted or unsubstituted saturated hydrocarbon group, or represents a substituted or unsubstituted aromatic group, L represents a leaving group, and n represents an integer greater than or equal to 1;

R-Fm (7)

In formula (7), R is as above, and m represents an integer satisfying the inequality: 1≤m≤n.

The second aspect of the present invention relates to an anhydrous imidazolium salt represented by formula (1), which is represented by the following formula (1);

In formula (1), R ¹ and R ³ are each the same or different, representing an alkyl group that may be substituted,

R ² , R ⁴ and R ⁵ are each the same or different, represent a hydrogen atom or an alkyl group that may be substituted, and 0<x≤1,

Y ^- represents a monovalent anion other than fluoride ion;

However, when x=1, any one of R ¹ and R ³ represents a methyl group, except the case where the other represents an ethyl group.

The third aspect of the present invention relates to an imidazolium salt of formula (1), which is represented by the following formula (1);

In formula (1), R ¹ and R ³ are each the same or different, representing an alkyl group that may be substituted,

R ² , R ⁴ and R ⁵ are each the same or different, represent a hydrogen atom or an alkyl group that may be substituted, and 0<x<1,

Y ^- represents a monovalent anion other than a fluoride ion.

A fourth aspect of the present invention relates to a method for producing an imidazolium salt represented by formula (3), characterized in that an alkyl-substituted imidazolium chloride represented by formula (2) is reacted with silver fluoride;

In formula (2), R ¹ and R ³ are each the same or different and represent an alkyl group that may be substituted, and R ² , R ⁴ and R ⁵ are each the same or different and represent a hydrogen atom or an alkyl group that may be substituted,

In formula (3), R ¹ , R ² , R ³ , R ⁴ and R ⁵ represent the same meanings as above, and 0<x≦1.

The fifth aspect of the present invention relates to a method for producing an alkyl-substituted imidazolium salt containing fluoride ions represented by formula (5), which is characterized in that the imidazolium salt of formula (4) is reacted with potassium fluoride in methanol,

In formula (4), R ¹ and R ³ are each the same or different, representing an alkyl group that may be substituted,

R ² , R ⁴ and R ⁵ are each the same or different, and represent a hydrogen atom or an alkyl group that may be substituted,

Z ^- means chloride ion or bromide ion,

In formula (5), R ¹ , R ² , R ³ , R ⁴ , R ⁵ and Z have the same meanings as above, and 0<x≦1.

Detailed ways

First, the alkyl-substituted imidazolium salt containing a fluoride ion represented by formula (1) (hereinafter simply referred to as fluorinating agent (1)) will be described.

基等直链状、支链状或环状的C1-20的烷基。Examples of the alkyl group represented by R ¹ , R ² , R ³ , R ⁴ and R ⁵ include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl Base, tert-butyl, n-pentyl, hexyl, heptyl, octyl, nonyl, n-decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, Hexadecyl, Heptadecyl, Octadecyl, Nonadecyl, Eicosyl, Cyclopropyl, 2,2-Dimethylcyclopropyl, Cyclopentyl, Cyclohexyl,

straight-chain, branched-chain or cyclic C1-20 alkyl groups.

The alkyl group may be substituted with at least one substituent selected from the following substituent groups A to I.

A: C1-20 alkoxy and fluorine-substituted C1-20 alkoxy (for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy , sec-butoxy, tert-butoxy, trifluoromethoxy, etc.)

B: C6-20 substituted by C6-20 aryl (for example, phenyl) and alkyl (for example, C1-3 alkyl) and/or alkoxy (for example, C1-3 alkoxy) Aryl (specifically, 4-methylphenyl, 4-methoxyphenyl, etc.).

C: C6-20 aryloxy (for example, phenoxy, etc.), and alkyl (for example, C1-3 alkyl) and/or alkoxy (for example, C1-3 alkoxy) substituted C6-20 aryloxy group (for example, 2-methylphenoxy, 4-methylphenoxy, 4-methoxyphenoxy, 3-phenoxyphenoxy, etc.).

D: C7-20 aralkyloxy, and C7-20 aralkyl substituted by alkyl (for example, C1-3 alkyl) and/or alkoxy (for example, C1-3 alkoxy) oxybenzyloxy (for example, benzyloxy, 4-methylbenzyloxy, 4-methoxybenzyloxy, 3-phenoxybenzyloxy, etc.).

E: fluorine atom.

F: C2-20 alkylcarbonyl (for example, acetyl, ethylcarbonyl, etc.).

G: C7-20 arylcarbonyl (for example, benzoyl, etc.), and alkyl (for example, C1-3 alkyl) and/or alkoxy (for example, C1-3 alkoxy) substituted C7-20 arylcarbonyl (for example, benzoyl, 2-methylbenzoyl, 4-methylbenzoyl, 4-methoxybenzoyl, etc.).

H: C8-20 aralkylcarbonyl (for example, benzylcarbonyl, etc.), and alkyl (for example, C1-3 alkyl) and/or alkoxy (for example, C1-3 alkoxy) substitution C8-20 aralkylcarbonyl (for example, 4-methylbenzylcarbonyl, 4-methoxybenzylcarbonyl, etc.).

I: Carboxyl

Examples of substituted alkyl groups include, for example, fluoromethyl, trifluoromethyl, methoxymethyl, ethoxyethyl, methoxyethyl, benzyl, 4-fluorobenzyl, 4-methylbenzyl, phenoxymethyl, 2-oxopropyl, 2-oxobutyl, phenacyl, 2-carboxyethyl, etc.

Examples of Y ⁻ when 0<x<1 include halide ions other than fluoride ions such as chloride ions, bromide ions, and iodide ions; borate ions such as tetrafluoroborate anions; and hexafluorophosphate anions. Phosphate ion such as; antimonate ion such as hexafluoroantimonate anion; sulfonate ion such as trifluoromethanesulfonate anion; nitrate ion; carbonate ion such as carbonate ion and methyl carbonate ion; carboxylate ion such as acetate ion and trifluoroacetic acid ion ; Amide ions such as bis(trifluoromethylsulfonyl)amide anion, etc.

x can be selected arbitrarily within the range of 0<x≤1. If x is close to 0, the effect of fluorination decreases, and if x is close to 1, the melting point tends to rise. In order to efficiently perform fluorination at a lower temperature, the range of about 0.4 < x < 0.9 is preferable. .

As the fluorinating agent, when x=1, for example, 1,3-dimethylimidazolium fluoride, 1,2,3-trimethylimidazolium fluoride, 1,2,3-trimethylimidazolium fluoride, , 4-tetramethylimidazolium, 1,2,3,4,5-pentamethylimidazolium fluoride, 1-methyl-3-ethylimidazolium fluoride, 1,2-dimethylimidazolium fluoride -3-ethylimidazolium, 1,3-diethylimidazolium fluoride, 1-methyl-3-(n-propyl)imidazolium fluoride, 1-methyl-3-(n-butyl) fluoride ) imidazolium, 1,2-dimethyl-3-(n-butyl)imidazolium fluoride, 1-methyl-3-(n-pentyl)imidazolium fluoride, 1-methyl-3- (n-hexyl)imidazolium, 1-methyl-3-(n-octyl)imidazolium fluoride, 1,3-dimethyl-2-ethylimidazolium fluoride, 1,3-dimethyl fluoride -2-(n-propyl)imidazolium, 1,3-dimethyl-2-(n-butyl)imidazolium fluoride, 1-dodecyl-2-methyl-3-dodecane fluoride imidazolium fluoride, 1-dodecyl-2-methyl-3-benzyl imidazolium fluoride, 1-ethoxymethyl-3-methylimidazolium fluoride, 1-methyl-3- -Alkyl-substituted imidazolium fluorides such as (methoxyethoxymethyl)imidazolium and 1-trifluoromethyl-3-methylimidazolium fluoride.

In addition, as specific examples of the imidazolium salt when 0<x<1 in formula (1), for example, 1,3-dimethylimidazolium cation, 1,2,3-trimethylimidazolium Onium cation, 1,2,3,4-tetramethylimidazolium cation, 1,2,3,4,5-pentamethylimidazolium cation, 1-methyl-3-ethylimidazolium cation, 1, 2-Dimethyl-3-ethylimidazolium cation, 1,3-diethylimidazolium cation, 1-methyl-3-(n-propyl)imidazolium cation, 1-methyl-3-(n- Butyl) imidazolium cation, 1,2-dimethyl-3-(n-butyl) imidazolium cation, 1-methyl-3-(n-pentyl) imidazolium cation, 1-methyl-3-( n-hexyl)imidazolium cation, 1-methyl-3-(n-octyl)imidazolium fluoride, 1,3-dimethyl-2-ethylimidazolium cation, 1,3-dimethyl-2- (n-propyl) imidazolium cation, 1,3-dimethyl-2-(n-butyl) imidazolium cation, 1-dodecyl-2-methyl 3-dodecyl imidazolium cation, 1 -Ethoxymethyl-3-methylimidazolium cation, 1-methyl-3-(methoxyethoxymethyl)imidazolium cation, 1-trifluoromethyl-3-methylimidazolium cation , imidazolium cations such as 1-n-dodecyl-2-methyl-3-benzyl imidazolium cation, and imidazolium salts containing both fluoride ions and chloride ions, further examples of the above-mentioned imidazolium salts The chloride ions are respectively bromide ion, iodide ion, tetrafluoroborate anion, hexafluorophosphate anion, hexafluoroantimonate anion, trifluoromethanesulfonate anion, nitrate anion, carbonate anion, acetate anion, bis(trifluoro imidazolium salts substituted with methylsulfonyl)amide anions, etc.

In the imidazolium salt (1) as a fluorinating agent of the present invention, unless otherwise specified, those that form anhydrous salts or are inert to nucleophilic substitution fluorination reactions in water, polar solvents, or both, etc. are also included. The compound forms a complex with the imidazolium salt of the fluorinating agent (1).

The fluorinating agent (1) can be produced, for example, by salt exchange reaction between a fluoride such as silver fluoride and potassium fluoride and an imidazolium salt when 0≤x<1 in formula (1). In addition, for example, x can be adjusted to an arbitrary value by mixing an imidazolium salt when 0≦x<1 in formula (1) and an imidazolium fluoride salt when x=1.

The imidazolium fluoride (1) can be produced, for example, by a known method such as reaction of a substituted imidazolium compound and an alkyl chloride (for example, see Tetrahedron, 59 , 2253 (2003).).

Hereinafter, a method for producing imidazolium fluoride by a salt exchange reaction using silver fluoride and potassium fluoride will be described in detail.

First, the imidazolium salt of formula (3) containing chloride anion and fluoride anion is characterized by the interaction of imidazolium chloride and silver fluoride of formula (2) (hereinafter referred to as imidazolium salt for short). (3)) for explanation.

Silver fluoride includes monovalent and divalent silver fluoride, and either silver fluoride can be used, but monovalent silver fluoride is preferably used. In addition, as the monovalent silver fluoride, two types of silver (I) fluoride and silver fluoride can be mentioned, but in consideration of cost, it is preferable to use silver (I) fluoride.

The amount of silver fluoride used can be properly adjusted so that x reaches a desired value within the range of 0<x≤1 in formula (3). For example, when it is desired to obtain imidazolium fluoride with x = 1 as the imidazolium salt (3), the objective can be achieved if 1 mole or more of silver fluoride is used relative to 1 mole of imidazolium chloride (2). , usually in the range of 1 to 2 moles, preferably in the range of about 1.0 to 1.1 moles.

This reaction is usually carried out in the presence of an organic solvent, water or a mixed solvent thereof, and may be carried out without using a solvent.

Examples of organic solvents include ether solvents such as methyl tert-butyl ether and tetrahydrofuran; nitrile solvents such as acetonitrile and propionitrile; amide solvents such as dimethylformamide and dimethylacetamide; Sulfur-containing solvents such as sulfone, etc.

The amount of the solvent used is not particularly limited, but in consideration of volumetric efficiency, it is generally equal to or less than 100 parts by weight relative to 1 part by weight of the alkyl-substituted imidazolium chloride (2).

The reaction temperature is usually in the range of about -20°C to 200°C.

The order of mixing the reagents is not particularly limited. For example, silver fluoride may be added to a solution containing imidazolium chloride (2) at the reaction temperature, or vice versa. In addition, it is also possible to adjust the reaction temperature after mixing the two reagents and the solvent at the same time.

The present invention can be carried out under normal pressure conditions or under pressurized conditions.

After the reaction is completed, usually, since the silver chloride generated by ion exchange precipitates in the system, the precipitate is filtered or decanted, etc., and the precipitate is removed by a common method, and the resulting solution is concentrated. , the alkyl-substituted imidazolium salt (3) containing fluoride ion can be obtained. The obtained alkyl-substituted imidazolium salt (3) containing fluoride ion can be further purified by methods such as crystallization and column chromatography.

The end point of the reaction can be confirmed by, for example, a common analysis method such as ion chromatography, but when silver chloride precipitates, no increase in the precipitation is seen as the end point.

The imidazolium salt (5) can be obtained by interacting the imidazolium salt (4) and potassium fluoride in methanol.

Commercially available potassium fluoride can be used as it is, and its usage amount is not particularly limited, but usually about 0.4 to 2 moles relative to 1 mole of imidazolium salt (4), so that the object of the present invention can be achieved.

The methanol used in the present invention may contain a small amount of water or other organic solvents, and usually a solvent with a methanol content greater than or equal to 90% is used. Although the amount used is not particularly limited, it is usually about 100 parts by weight or less with respect to 1 part by weight of the imidazolium salt (4).

The reaction temperature is usually in the range of about -20°C to 200°C.

The value of x in the imidazolium salt (5) is in the range of 0 < x ≤ 1. Depending on the desired value of x, the amount of potassium fluoride and methanol used, the water content, and the reaction temperature, etc., can be appropriately selected for the reaction. .

The mixing order of the reaction reagents is not particularly limited. For example, potassium fluoride may be added to a solution containing the imidazolium salt (4) at the reaction temperature, or vice versa. In addition, it is also possible to adjust the reaction temperature after mixing the two reagents and the solvent at the same time.

The present invention can be carried out under normal pressure conditions or under pressurized conditions. In addition, progress of the reaction can be confirmed, for example, by common analytical methods such as ion chromatography, NMR, and IR.

After the reaction is finished, usually, since potassium chloride or potassium bromide generated by ion exchange is precipitated in the system, common methods such as filtration or decantation are used to remove the precipitate, and the resulting solution is concentrated. Thus, an alkyl-substituted imidazolium salt (5) can be obtained. During the concentration treatment, when potassium chloride or potassium bromide and remaining potassium fluoride precipitate, these inorganic salts can be removed by the above-mentioned usual method, and then the concentration treatment can be carried out again. The obtained imidazolium salt (5) can be further purified by methods such as crystallization and column chromatography, if necessary.

The method for producing the fluorine-containing organic compound represented by the formula (7) characterized by reacting with the organic compound of the formula (6) will be described;

R-Ln (6)

In formula (6), R represents a substituted or unsubstituted saturated hydrocarbon group, or represents a substituted or unsubstituted aromatic group, L represents a leaving group, and n represents an integer greater than or equal to 1 (typically 1, 2 or 3;

R-Fm (7)

In formula (7), R is as above, and m represents an integer satisfying 1≤m≤n.

Examples of saturated hydrocarbon groups represented by R include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, n-pentyl, hexyl, heptyl, octyl, Nonyl, n-decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl C1-20 alkyl group, eicosyl straight chain or branched C1-20.

The following substituents are mentioned as a substituent which substitutes a saturated hydrocarbon group.

For example, C5-20 aryl (for example, 2-pyridyl, phenyl, 1-naphthyl, 2-naphthyl, etc.) and alkyl (for example, C1-3 alkyl), alkoxy (for example, C1-3 alkoxy), alkoxyalkyl (for example, C1-3 alkyl substituted by C1-3 alkoxy), and C5-20 substituted by at least one of fluorine atoms Aryl (specifically, 4-methylphenyl, 4-methoxyphenyl, 3-phenoxyphenyl, 2,3,5,6-tetrafluorophenyl, 2,3,5,6 -Tetrafluoro-4-methylphenyl, 2,3,5,6-tetrafluoro-4-methoxyphenyl, 2,3,5,6 tetrafluoro-4-methoxymethylphenyl, etc. );

C1-20 alkoxy and fluorine-substituted C1-20 alkoxy (for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec butoxy, tert-butoxy, trifluoromethoxy, etc.);

C6-20 substituted by C6-20 aryloxy (for example, phenoxy, etc.) and alkyl (for example, C1-3 alkyl) and/or alkoxy (for example, C1-3 alkoxy) Aryloxy groups (for example, 2-methylphenoxy, 4-methylphenoxy, 4-methoxyphenoxy, 3-phenoxyphenoxy, etc.)

C7-20 aralkyloxy and is selected from alkyl (for example, C1-3 alkyl), alkoxy (for example, C1-3 alkoxy), alkoxyalkyl (for example, C1 -3 alkoxy substituted C1-3 alkyl), phenoxy and fluorine atom at least one substituted C7-20 aralkyloxy (for example, benzyloxy, 4-methylbenzyloxy Base, 4-methoxybenzyloxy, 3-phenoxybenzyloxy, 2,3,5,6-tetrafluorobenzyloxy, 2,3,5,6-tetrafluoro-4-methylbenzyl Oxygen, 2,3,5,6-tetrafluoro-4-methoxybenzyloxy, 2,3,5,6-tetrafluoro-4-methoxymethylbenzyloxy);

fluorine atom;

C2-20 alkylcarbonyl (for example, acetyl, ethylcarbonyl, etc.);

C7-20 substituted by C7-20 arylcarbonyl (for example, benzoyl, etc.) and alkyl (for example, C1-3 alkyl) and/or alkoxy (for example, C1-3 alkoxy) Arylcarbonyl (for example, benzoyl, 2-methylbenzoyl, 4-methylbenzoyl, 4-methoxybenzoyl, etc.);

C8-20 aralkylcarbonyl (for example, benzylcarbonyl) and alkyl (for example, C1-3 alkyl) and/or alkoxy (for example, C1-3 alkoxy) substituted C8-20 Aralkylcarbonyl (for example, 4-methylbenzylcarbonyl, 4-methoxybenzylcarbonyl, etc.); and carboxyl and the like.

Specific examples of substituted saturated hydrocarbon groups include, for example, fluoromethyl, trifluoromethyl, methoxymethyl, ethoxymethyl, methoxyethyl, tolyl, 4- Methoxytolyl (4-methoxytolyl), 3-phenoxytolyl, 2,3,5,6-tetrafluorotolyl, 2,3,5,6-tetrafluoro-p-xylyl, 2,3 , 5,6-tetrafluoro-4-methoxytolyl, 2,3,5,6-tetrafluoro-4-methoxymethyltolyl, 2-propylnaphthyl, methyl isobutyl ketone , phenacyl, 4-methylphenacyl, phenylacetyl, etc. The saturated hydrocarbon group which is a substituted or unsubstituted saturated hydrocarbon group is preferably a primary or secondary saturated hydrocarbon group, more preferably a primary saturated hydrocarbon group.

Examples of the aryl group represented by R include hydrocarbon-based aryl groups such as phenyl and naphthyl; and heteroaryl groups such as pyridine and quinoline.

Examples of the substituent for the substituted aromatic group include a sulfonamide group, a cyano group, and an amido group in addition to the substituents mentioned above for A to I or the substituent for the above-mentioned substituted saturated hydrocarbon group.

In addition, among these substituents, adjacent substituents may be bonded to each other to form a ring together with the bonded carbon atom. Among the substituents that can substitute for these aryl groups, electron-withdrawing substituents are preferable in consideration of reactivity, and examples of the electron-withdrawing substituents include fluorine atoms, alkylcarbonyl groups that may be substituted, and Substituted aralkylcarbonyl, arylcarbonyl which may be substituted, carboxyl, sulfonamide, cyano and the like.

Examples of substituted aromatic compounds include benzonitrile, terephthalonitrile, isophthalonitrile, phthalonitrile, fluorobenzene, 1,4-difluorobenzene, benzenesulfonamide, biphenyl, 2 -Phenylnaphthalene, diphenyl ether, 3-picoline, 4-phenylpyridine, benzophenone, 1,2-diphenylethanone, etc.

Examples of L include a chlorine atom, a bromine atom, an iodine atom, a nitro group, a sulfo group, an alkylsulfonyloxy group that may be substituted, an arylsulfonyloxy group that may be substituted, an alkyl group that may be substituted ylcarbonyloxy or arylcarbonyloxy which can be substituted, etc. When having a plurality of such substituents, these groups may be the same or different.

Examples of the alkylsulfonyloxy group which may be substituted include methanesulfonyloxy, ethanesulfonyloxy, trifluoromethanesulfonyloxy and the like.

Examples of the arylsulfonyloxy group which may be substituted include p-toluenesulfonyloxy, benzenesulfonyloxy, 1-naphthalenesulfonyloxy and the like.

Examples of the optionally substituted alkylcarbonyloxy group include trifluoroacetoxy, pentafluoroethylcarbonyloxy, etc.,

Examples of the arylcarbonyloxy group which may be substituted include tetrafluorobenzoyloxy, benzoyloxy and the like.

As the compound of formula (6), for example, 1-chlorobutane, 1-bromobutane, 1-iodobutane, 1-chloropentane, 1-bromopentane, 1-chloro-4-bromo Butane, 1-chlorohexane, 1-bromohexane, 1,6-dibromohexane, 1-chloroheptane, 1-bromoheptane, 2-chloroheptane, 2-bromoheptane, 1- Chloroctane, 1-bromooctane, 2-chlorooctane, 2-bromooctane, benzyl chloride, benzyl bromide, 4-methoxybenzyl chloride, 4-methoxybenzyl bromide 3,4,5-trifluorobenzyl bromide, n-butyl p-toluenesulfonate, n-butyl methanesulfonate, n-pentyl p-toluenesulfonate, n-pentyl methanesulfonate, n-hexyl p-toluenesulfonate Esters, n-hexyl methanesulfonate, n-heptyl p-toluenesulfonate, n-heptyl methanesulfonate, n-octyl p-toluenesulfonate, n-octyl methanesulfonate, n-butyl trifluoroacetate, n-tetrafluorobenzoic acid Butyl ester, n-octyl trifluoroacetate, 4-chloronitrobenzene, 4-bromonitrobenzene, 2-chloronitrobenzene, 2-bromonitrobenzene, 4-cyanochlorobenzene, 4-cyanobromide Benzene, 1-chloro-2,4-dinitrobenzene, tetrachloroterephthalonitrile, tetrachloroisophthalonitrile, tetrachlorophthalonitrile, 1,3-dichloro-4,6-dinitro Benzene, 2-chloroquinoline, 2-chloro-5-nitropyridine, 2-chloro-5-trifluoromethylpyridine, etc.

When using an organic compound with multiple substituents L, which may be different substituents, generally express the following reactivity, either only the most reactive substituent is replaced by a fluorine atom, or, depending on the reaction conditions, the same Or different multiple substituents are substituted by fluorine atoms.

When the optionally substituted aryl group represented by R is a hydrocarbon-based aryl group, usually, a substituent that accepts a nucleophilic substitution fluorination reaction and has an electron-withdrawing substituent at the para-position or the ortho-position is preferentially substituted with a fluorine atom. For example, in the reaction of 4-chloronitrobenzene, although both the chlorine atom and the nitro group are substituents that accept the nucleophilic substitution fluorination reaction, the chlorine atom with a more electro-absorbing nitro group at the para position is preferred Substituted by fluorine atoms, usually selectively generating 4-fluoronitrobenzene. It goes without saying that, for example, when using a large excess of the fluorinating agent (1) or the like, if the reaction conditions are appropriately selected, the nitro group can also be replaced by a fluorine atom to obtain p-difluorobenzene.

In addition, when R is a heteroaromatic compound that may be substituted, usually, the substituent at the 2-, 4-, or 6-position that undergoes a nucleophilic fluorination reaction is preferentially substituted with a fluorine atom for the heteroatom constituting the heteroaromatic ring. For example, for 2-chloro-3-nitropyridine, typically, the chloro group at the 2-position is substituted to yield 2-fluoro-3-nitropyridine. It goes without saying that, for example, when a large excess of the fluorinating agent (1) is used, if the reaction conditions are appropriately selected, the nitro group can also be replaced by a fluorine atom to obtain 2,3-difluoropyridine.

The amount of the fluorinating agent (1) used is generally 1 mole or more based on fluoride ions relative to 1 mole of the substituent to be substituted with a fluorine atom in the compound of formula (6). The upper limit is not particularly limited, but when there is only one substituent that undergoes a nucleophilic fluorination reaction, it is preferably in the range of about 1.5 to 5.0 moles in consideration of reaction efficiency. In addition, when there are a plurality of substituents that undergo nucleophilic fluorination reactions, based on the above-mentioned reactivity priorities, the substituents that are not expected to undergo fluorination reactions can be appropriately set within the range of not being substituted by fluorine atoms. quantity.

This reaction may be carried out in the presence of an organic solvent, water or a mixed solvent thereof, or may be carried out without a solvent.

As an organic solvent when carrying out using a solvent, for example, ether solvents such as methyl tert-butyl ether and tetrahydrofuran; Nitrile solvents such as acetonitrile and propionitrile; Aromatic hydrocarbon solvents such as toluene and xylene; Cyclohexane, n- Aliphatic hydrocarbon solvents such as heptane; amide solvents such as dimethylformamide and dimethylacetamide; sulfur-containing solvents such as sulfolane and dimethyl sulfoxide, etc.

When a solvent is used, the usage amount of the solvent is not limited, but in practice, it is generally equal to or less than 100 parts by weight relative to 1 part by weight of the fluorinating agent (1) in consideration of volumetric efficiency.

If the reaction temperature is too low, the reaction will be difficult to proceed, and if the reaction temperature is too high, side reactions such as decomposition of raw materials or products may proceed. In practice, the reaction temperature is usually in the range of -20°C to 200°C.

The order of mixing the reagents is not particularly limited. For example, the fluorinating agent (1) may be added to the organic compound of the formula (6) undergoing nucleophilic substitution fluorination reaction under the reaction temperature conditions, or vice versa. In addition, it is also possible to adjust the reaction temperature after mixing the two reagents at the same time.

The present invention can be carried out under normal pressure conditions or under pressurized conditions. In addition, progress of the reaction can be confirmed by common analysis methods such as gas chromatography, high performance liquid chromatography, thin layer chromatography, NMR, and IR.

After the reaction is completed, crystallization or distillation is performed, and if necessary, water and/or a water-insoluble organic solvent is added for extraction treatment, and the obtained organic layer is concentrated to obtain a fluorine-containing compound as a reaction product. The obtained fluorine-containing compounds can be further refined by methods such as distillation and column chromatography.

Among them, as the water-insoluble organic solvent, for example, aromatic hydrocarbon solvents such as toluene, xylene, and chlorobenzene; Aliphatic hydrocarbon solvents such as benzene, hexane, and heptane; Dichloromethane, dichloroethane, Halogenated hydrocarbon solvents such as chloroform; ether solvents such as ethyl ether, methyl tert-butyl ether, and tetrahydrofuran; ester solvents such as ethyl acetate, etc.

As the fluorine compound thus obtained, for example, 1-fluorobutane, 1-fluoropentane, 1,4-difluorobutane, 1-chloro-4-fluorobutane, 1-fluorohexane, 1 , 6-difluorohexane, 1-fluoroheptane, 2-fluoroheptane, 1-fluorooctane, 2-fluorooctane, fluorinated benzyl, fluorinated 4-methoxybenzyl, fluorinated 4 -Methylbenzyl, fluorinated 3,4,5-trifluorobenzyl, 4-fluoronitrobenzene, 2-fluoronitrobenzene, 4-cyanofluorobenzene, 1-fluoro-2,4-dinitrobenzene phenylbenzene, tetrafluoroterephthalonitrile, tetrafluoroisophthalonitrile, tetrafluorophthalonitrile, 1,3-difluoro-4,6-dinitrobenzene, 2-fluoroquinoline, 2-fluoro- 5-nitropyridine, 2-fluoro-5-trifluoromethylpyridine, etc.

After the reaction, the alkyl-substituted imidazolium cation can be recovered as a mixed alkyl-substituted imidazolium salt containing a substituent which undergoes a nucleophilic substitution fluorination reaction. The mixed alkyl-substituted imidazolium salt is recovered from the reaction liquid by filtration treatment, liquid separation treatment, etc., and the mixed alkyl-substituted imidazolium salt is ion-exchanged into fluoride ion again, thereby reusing it as the fluorinating agent (1).

Example

Although the present invention will be further described in detail below through examples, the present invention is not limited to these examples.

Example 1 (production example of fluorinating agent (1) (x=1))

22 g of 1-methyl-3-n-butylimidazolium chloride and 200 g of water were added and dissolved in a three-cornered flask. After adding and dissolving 16.1 g of silver (I) fluoride and 120 g of water into another three-cornered flask, two kinds of aqueous solutions were mixed at 25° C., and stirring was continued at this temperature for 30 minutes. The precipitated crystals after the reaction were filtered and washed with water. The obtained filtrate and washing liquid were combined and concentrated to obtain 24.5 g of 1-methyl-3-n-butylimidazolium fluoride dihydrate. Yield: 100%.

Elemental analysis values: C: 49.5, H: 9.9, N: 14.5, F: 9.2

Calculated values: C: 49.5, H: 9.9, N: 14.5, F: 9.8

1H-NMR (δppm, DMSO-d6, TMS reference): 0.90(t, 3H), 1.25(m, 2H), 1.72(m, 2H), 3.88(s, 3H), 4.19(t, 2H), 7.79 (d, 2H), 10.1 (bs, 1H)

Example 2 (production example of fluorinating agent (1) (x=1))

5 g of 1-methyl-3-n-hexylimidazolium chloride and 50 g of water were added and dissolved in a three-cornered flask. After adding and dissolving 3.1 g of silver (I) fluoride and 50 g of water in another three-cornered flask, the two aqueous solutions were mixed at 25° C., and stirring was continued at this temperature for 30 minutes. The precipitated crystals after the reaction were filtered and washed with water. The obtained filtrate and washing liquid were combined and concentrated to obtain 5.4 g of a colorless oil. Elemental analysis revealed that the obtained oil was dihydrate of 1-methyl-3-n-hexylimidazolium fluoride. Yield: 99%.

Elemental analysis values: C: 54.4, H: 11.0, N: 12.7, F: 8.3

Calculated values: C: 54.0, H: 10.4, N: 12.6, F: 8.5

1H-NMR (δppm, DMSO-d6, TMS reference): 0.90 (m, 3H), 1.29 (m, 6H), 1.78 (m, 2H), 3.89 (s, 3H), 4.18 (q, 2H), 7.82 (d, 2H), 10(bs, 1H)

Example 3 (production example of fluorinating agent (1) (x=1))

5.0 g of 1-methyl-3-n-octyl imidazolium chloride and 50 g of water were added and dissolved in a three-cornered flask. After adding and dissolving 2.74 g of silver (I) fluoride and 50 g of water in another three-corner flask, the two aqueous solutions were mixed at 25° C., and stirring was continued at this temperature for 30 minutes. The precipitated crystals after the reaction were filtered and washed with water. The obtained filtrate and washing liquid were combined and concentrated to obtain 5.8 g of a colorless oil. Elemental analysis revealed that the obtained oil was trihydrate of 1-methyl-3-n-octyl imidazolium fluoride. Yield: 100%.

Elemental analysis values: C: 53.6, H: 10.8, N: 10.1, F: 6.7

Calculated values: C: 53.6, H: 11.0, N: 10.4, F: 7.1

1H-NMR (δppm, DMSO-d6, TMS reference): 0.86(m, 3H), 1.20(m, 10H), 1.77(m, 2H), 3.89(s, 3H), 4.16(q, 2H), 7.80 (d, 2H), 10(bs, 1H)

Example 4 (production example of fluorinating agent (1) (x=0.475))

5.0 g of 1-methyl-3-n-butylimidazolium chloride and 50 g of water were added and dissolved in a three-cornered flask. After adding and dissolving 1.72 g of silver (I) fluoride and 30 g of water in another three-corner flask, two aqueous solutions were mixed at 25° C., and stirring was continued at this temperature for 30 minutes. The precipitated crystals after the reaction were filtered and washed with water. The obtained filtrate and washing liquid were combined and concentrated to obtain 5.8 g of a colorless oil. The oil is liquid at 0°C. By elemental analysis, the obtained oil was a dihydrate containing 47.5 mole % of fluoride ion, 52.5 mole % of mixed anion of chloride ion and salt of fluorinated 1-methyl-3-n-butylimidazolium cation . Yield: 100%.

Elemental analysis value: C: 48.2, H: 9.5, N: 14.1, F: 4.6, Cl: 9.5

Calculated: C: 47.4, H: 9.5, N: 13.8, F: 4.5, Cl: 9.2

1H-NMR (δppm, DMSO-d6, TMS reference): 0.88(t, 3H), 1.25(m, 2H), 1.78(m, 2H), 3.90(s, 3H), 4.19(t, 2H), 7.85 (d, 2H), 10(bs, 1H)

Example 5 (production example of fluorinating agent (1) (x=0.83))

5.0 g of 1-methyl-3-n-butylimidazolium chloride and 50 g of water were added and dissolved in a three-cornered flask. After adding and dissolving 3.0 g of silver (I) fluoride and 30 g of water in another three-cornered flask, the two aqueous solutions were mixed at 25° C., and stirring was continued at this temperature for 30 minutes. The precipitated crystals after the reaction were filtered and washed with water. The obtained filtrate and washing liquid were combined and concentrated to obtain 5.6 g of a colorless oil. The oil partially crystallized at room temperature. By elemental analysis, the obtained oil was a dihydrate containing 83 mol % of fluoride ion, 17 mol % of mixed anion of chloride ion and salt of fluorinated 1-methyl-3-n-butylimidazolium cation . Yield: 99%.

Elemental analysis value: C: 47.3, H: 9.8, N: 13.8, F: 8.1, Cl: 3.1

Calculated: C: 48.7, H: 9.7, N: 14.2, F: 8.0, Cl: 3.1

1H-NMR (δppm, DMSO-d6, TMS reference): 0.88(t, 3H), 1.20(m, 2H), 1.75(m, 2H), 3.88(s, 3H), 4.19(t, 2H), 7.85 (d, 2H), 9.85 (s, 1H)

Example 6 (production example of fluorinating agent (1) (x=0.61))

12.0 g of 1-methyl-3-(methoxyethoxymethyl)imidazolium chloride and 50 g of water were added and dissolved in a three-cornered flask. After adding and dissolving 5.33 g of silver (I) fluoride and 30 g of water in another three-corner flask, the two aqueous solutions were mixed at 25° C., and stirring was continued at this temperature for 30 minutes. The precipitated crystals after the reaction were filtered and washed with water. The obtained filtrate and washing liquid were combined and concentrated to obtain 12.6 g of a colorless oil. The oil partially crystallized at room temperature. By elemental analysis, the oil obtained was a mixed anion containing 61 mol % of fluoride ions, 39 mol % of chloride ions and fluorinated 1-methyl-3-(methoxyethoxymethyl)imidazolium 1.3 hydrate of the salt of the cation. Yield: 99%.

Elemental analysis values: C: 42.7, H: 8.0, N: 12.6, F: 5.8, Cl: 6.9

Calculated: C: 43.6, H: 8.0, N: 12.7, F: 5.3, Cl: 6.3

1H-NMR (δppm, DMSO-d6, TMS reference): 3.19(s, 3H), 3.44(m, 2H), 3.67(m, 2H), 3.97(s, 3H), 5.69(s, 2H), 7.95 (d, 2H), 10.1 (bs, 1H)

Example 7 (production example of fluorinating agent (1) (x=0.61))

1.75 g of 1-methyl-3-n-butylimidazolium chloride and 10 g of methanol (water content: 1% by weight) were added and dissolved in a three-cornered flask. 460 mg of potassium fluoride and 10 g of methanol (water content: 1% by weight) were added and dissolved in another three-cornered flask, and the two methanol solutions were mixed at 25° C., and stirring was continued at this temperature for 30 minutes. The precipitated crystals after the reaction were filtered, and washed with methanol (water content: 1% by weight). The resulting filtrate and washings were combined and concentrated. After removing the white powder precipitated from the concentrated oil by decantation, the white powder was washed with a small amount of methanol, the filtrate and the concentrated oil were combined, and concentrated again to obtain 2.10 g of a colorless oil. Crystallization occurs when the oil is left at room temperature. According to elemental analysis, the obtained oil is a salt containing 61 mol % of fluoride ions, 39 mol % of mixed anions of chloride ions and fluorinated 1-methyl-3-n-butylimidazolium cations, and contains 2 /3 moles of methanol and 4/3 moles of water.

Yield based on imidazolium cation: 100%.

Elemental analysis values: C: 48.5, H: 10.3, N: 13.7, F: 5.7, Cl: 6.7

Calculated: C: 49.5, H: 9.8, N: 13.3, F: 5.5, Cl: 6.6

1H-NMR (δppm, DMSO-d6, TMS standard): 0.90(t, 3H), 1.23(m, 2H), 1.78(m, 2H), 3.10(s, methyl of methanol), 3.90(s, 3H ), 4.22(t, 2H), 7.85(d, 2H), 8.5(bs, 1H)

Example 8 (production example of fluorinating agent (1) (x=0.47))

8.20 g of 1-methyl-3-n-butylimidazolium chloride and 50 g of methanol (water content: 1% by weight) were added and dissolved in a three-cornered flask. 1.4 g of potassium fluoride and 35 g of methanol (water content: 1% by weight) were added and dissolved in another three-cornered flask, and the two methanol solutions were mixed at 25° C., and stirring was continued at this temperature for 30 minutes. . The precipitated crystals after the reaction were filtered, and washed with methanol (water content: 1% by weight). The resulting filtrate and washings were combined and concentrated. After removing the white powder precipitated from the concentrated oil by decantation, the white powder was washed with a small amount of methanol, and the filtered washing liquid and the concentrated oil were combined and concentrated again to obtain 9.61 g of a colorless oil. Crystallization occurs when the oil is left at room temperature. By elemental analysis, the obtained oil was a salt containing 47 mol % of fluoride ions, 53 mol % of mixed anions of chloride ions and fluorinated 1-methyl-3-n-butylimidazolium cations, and contained 2 /3 moles of methanol and 1 mole of water.

Yield based on imidazolium cation: 100%.

Elemental analysis value: C: 49.5, H: 10.1, N: 14.0, F: 4.5, Cl: 9.6

Calculated: C: 50.4, H: 9.6, N: 13.6, F: 4.3, Cl: 9.1

1H-NMR (δppm, DMSO-d6, TMS standard): 0.90(t, 3H), 1.23(m, 2H), 1.78(m, 2H), 3.10(s, methyl of methanol), 3.90(s, 3H ), 4.21(t, 2H), 7.90(d, 2H), 8.5(bs, 1H)

(The following is the fluorination reaction using fluorinating agent (1))

Example 9

Into a 50 mL flask equipped with a reflux cooling tube, 500 mg of the fluorinating agent (1) synthesized in Example 1 and 171 mg of benzyl bromide were added, and stirred at 80° C. for 5 hours. After cooling to room temperature, 5 g of ethyl acetate was added, stirred and separated into two layers when left still. Analysis of the upper layer by gas chromatography (internal standard method) revealed that the main product was benzyl fluoride.

Yield: 95%.

Example 10

Except that 284 mg of n-octyl p-toluenesulfonate was used instead of 171 mg of benzyl bromide used in Example 9, and stirred at 150° C. for 3 hours, it was carried out in the same manner as in Example 9, and the main product was 1-fluoro octane.

Yield: 98%.

Example 11

Except that 193 mg of 1-bromooctane was used instead of 171 mg of benzyl bromide used in Example 9, and stirred at 100° C. for 3 hours, the same procedure was carried out as in Example 9, and the main product was 1-fluorooctane. alkyl.

Yield: 90%.

Example 12

Except that 158 mg of 4-chloronitrobenzene was used instead of 171 mg of benzyl bromide used in Example 9, and stirred at 150° C. for 3 hours, it was carried out in the same manner as in Example 9, and the main product was 4-fluoro Nitrobenzene.

Yield: 88%.

Example 13

Into a 50 mL flask equipped with a reflux cooling tube, 640 mg of the fluorinating agent (1) synthesized in Example 4 and 254 mg of benzyl chloride were added, and stirred at 80° C. for 3 hours. After cooling to room temperature, 5 g of ethyl acetate was added, stirred and separated into two layers when left still. Analysis of the upper layer by gas chromatography (internal standard method) revealed that the main product was benzyl fluoride.

Yield: 75% (based on benzyl chloride). 25% of benzyl chloride was recovered. The yield based on the fluoride ion of the fluorinating agent (1) was 100%.

Example 14

Into a 50 mL flask with a reflux cooling tube, 300 mg of the fluorinating agent (1) synthesized in Example 5, 127 mg of benzyl chloride and 500 mg of acetonitrile were added, and stirred at 80° C. for 3 hours. After cooling to room temperature, 5 g of ethyl acetate was added, stirred and separated into two layers when left still. Analysis of the upper layer by gas chromatography (internal standard method) revealed that the main product was benzyl fluoride.

Yield: 99% (based on benzyl chloride). 1% benzyl chloride was recovered. The yield based on the fluoride ion of the fluorinating agent (1) was 79%.

Example 15

Into a 50 mL flask equipped with a reflux cooling tube, 300 mg of the fluorinating agent (1) synthesized in Example 2 and 149 mg of 1-octyl chloride were added, and stirred at 100° C. for 4 hours. After cooling to room temperature, 5 g of ethyl acetate and 5 g of water were added, stirred and then separated into two layers after standing still. Analysis of the upper layer by gas chromatography (internal standard method) showed that the main product was 1-octyl fluoride.

Yield: 63% (based on 1-octyl chloride). 32% of 1-octyl chloride was recovered.

Example 16

Except using 320 mg of the fluorinating agent (1) synthesized by Example 3 to replace the fluorinating agent (1) synthesized by Example 2 in Example 15, it was implemented in the same manner as in Example 15 to obtain 1- Octyl Fluoride.

Yield: 64% (based on 1-octyl chloride). 32% of 1-octyl chloride was recovered.

Example 17

Into a 50 mL flask with a reflux cooling tube, 500 mg of the fluorinating agent (1) synthesized in Example 1, 236 mg of 2,6-dibromopyridine and 2 g of acetonitrile were added, and stirred at 80° C. for 3 hours. After cooling to room temperature, 5 g of ethyl acetate and 5 g of water were added, and the mixture was stirred. When left still, two layers were separated. Analysis of the upper layer by gas chromatography (internal standard method) revealed that the main product was 2-fluoro-6-bromopyridine.

Yield: 78% (based on 2,6-dibromopyridine). 20% of 2,6-dibromopyridine was recovered.

Example 18

Into a 50 mL flask equipped with a reflux cooling tube, 600 mg of the fluorinating agent (1) synthesized in Example 1 and 250 mg of benzyl chloride were added, and stirred at 80° C. for 3 hours. After cooling to room temperature, 5 g of n-hexane and 5 g of water were added, stirred and then separated into two layers after standing still. Analysis of the upper layer by gas chromatography (internal standard method) showed that the main product was benzyl fluoride.

Yield: 94% (based on benzyl chloride). 6% benzyl chloride was recovered.

Embodiment 19 (recycling of fluorinating agent (1))

To the aqueous layer obtained in Example 18, was added an aqueous solution obtained by dissolving 390 mg of silver fluoride in 5 g of water, stirred at 25°C for 2 hours, filtered off the precipitated crystals, and concentrated to obtain 605 mg of a pale yellow oil. . 250 mg of benzyl chloride was added to this oil, followed by stirring at 80°C for 3 hours. After cooling to room temperature, 5 g of n-hexane and 5 g of water were added, stirred and then separated into two layers after standing still. Analysis of the upper layer by gas chromatography (internal standard method) showed that the main product was benzyl fluoride.

Yield: 95% (based on benzyl chloride). 5% benzyl chloride was recovered.

Example 20

Into a 50 mL flask equipped with a reflux cooling tube, 430 mg of 1-methyl-3-n-butylimidazolium fluoride obtained in Example 7 and 127 mg of benzyl chloride were added, and stirred at 80° C. for 3 hours. After cooling to room temperature, 5 g of ethyl acetate was added, stirred and left to stand to separate into two layers. Analysis of the upper layer by gas chromatography (internal standard method) revealed that the main product was benzyl fluoride. Yield: 95%.

Example 21

In a three-cornered flask, 5.0 g of 1-methyl-3-n-butylimidazolium chloride and 50 g of methanol (water content: 1% by weight) were added and dissolved. After adding and dissolving 1.33 g of potassium fluoride and 33 g of methanol (water content: 1% by weight) in another three-cornered flask, two kinds of methanol solutions were mixed at 25° C., and stirring was continued at this temperature for 30 minutes. The precipitated crystals after the reaction were filtered, and washed with methanol (water content: 1% by weight). The resulting filtrate and washings were combined and concentrated. After removing the white powder precipitated from the concentrated oil by decantation, the white powder was washed with a small amount of methanol, and the filtered washing liquid and the concentrated oil were combined and concentrated again to obtain 4.76 g of a colorless oil.

Into a 50 mL flask equipped with a reflux cooling tube, 400 mg of the synthesized colorless oil (fluorinating agent (1)) and 284 mg of n-octyl p-toluenesulfonate were added, followed by stirring at 80° C. for 5 hours. After cooling to room temperature, 5 g of ethyl acetate was added, stirred and left to stand to separate into two layers. Analysis of the upper layer by gas chromatography (internal standard method) showed that the main product was n-octyl fluoride. Yield: 98%.

Industrial applicability

According to the present invention, aliphatic and aromatic fluorine-containing compounds can be efficiently and easily produced without using highly corrosive and toxic hydrogen fluoride or its salts. Further, since the fluorinating agent of the present invention itself has the properties of an ionic liquid, it is easy to recycle and reuse. In addition, by properly selecting x in formula (1), the melting point can be made less than or equal to room temperature, so that it can be used in a relatively wide range. The reaction and the like can be carried out under a wide range of temperature conditions, which is also advantageous in terms of industrial operation and environment.

Claims (12)

1. the manufacture method of the fluorine-containing organic compound shown in formula (7), it is characterized in that making the fluorinating agent shown in formula (1) react with the organic compound of formula (6);

In formula (1), R ¹ and R ³ are each the same or different, representing an alkyl group that is unsubstituted or substituted by at least one group selected from the following substituent groups A to I: A: C1-20 alkoxy and fluorine-substituted C1-20 alkoxy, B: C6-20 aryl and C6-20 aryl substituted by C1-3 alkyl and/or C1-3 alkoxy, C: C6-20 aryloxy and C6-20 aryloxy substituted by C1-3 alkyl and/or C1-3 alkoxy, D: C7-20 aralkyloxy and C7-20 aralkyloxy substituted by C1-3 alkyl and/or C1-3 alkoxy, E: fluorine atom, F: C2-20 alkylcarbonyl, G: C7-20 arylcarbonyl and C7-20 arylcarbonyl substituted by C1-3 alkyl and/or C1-3 alkoxy, H: C8-20 aralkylcarbonyl and C8-20 aralkylcarbonyl substituted by C1-3 alkyl and/or C1-3 alkoxy, I: carboxyl group; R ² , R ⁴ and R ⁵ are each the same or different, representing a hydrogen atom or an alkyl group that is unsubstituted or substituted by at least one group selected from substituent groups A to I; And 0<x≤1; Y ^- represents a monovalent anion other than fluoride ion; R-Ln (6) In formula (6), R represents a C1-20 alkyl group that is unsubstituted or substituted by at least one substituent selected from the following groups: C5-20 aryl, C5-20 aryl group substituted by at least one group selected from the group consisting of C1-3 alkyl, C1-3 alkoxy, C1-3 alkyl substituted by C1-3 alkoxy and fluorine atom, C1-20 alkoxy, C1-20 alkoxy substituted by fluorine atom, C6-20 aryloxy, C6-20 aryloxy substituted by C1-3 alkyl and/or C1-3 alkoxy, C7-20 aralkyloxy, C7-20 aralkyloxy substituted by at least one group selected from the group consisting of C1-3 alkyl, C1-3 alkoxy, C1-3 alkyl substituted by C1-3 alkoxy, phenoxy and fluorine atoms, fluorine atom, C2-20 alkylcarbonyl, C7-20 arylcarbonyl, C7-20 arylcarbonyl substituted by C1-3 alkyl and/or C1-3 alkoxy, C8-20Aralkylcarbonyl, and C8-20 aralkylcarbonyl substituted by C1-3 alkyl and/or C1-3 alkoxy; or unsubstituted or substituted aryl by at least one group selected from the following groups: Substituents as described above for C1-20 alkyl, The groups of the above-mentioned substituent groups A to I, Sulfonamide, Cyano and amido; L represents a leaving group; n represents an integer greater than or equal to 1; R-Fm (7) In the formula (7), R is as described above, and m represents an integer satisfying the inequality 1≤m≤n. 2. The production method according to claim 1, wherein said R is a C1-20 alkyl group which is unsubstituted or substituted by at least one substituent selected from the following group: C5-20 aryl, C5-20 aryl group substituted by at least one group selected from the group consisting of C1-3 alkyl, C1-3 alkoxy, C1-3 alkyl substituted by C1-3 alkoxy and fluorine atom, C1-20 alkoxy, C1-20 alkoxy substituted by fluorine atom, C6-20 aryloxy, C6-20 aryloxy substituted by C1-3 alkyl and/or C1-3 alkoxy, C7-20 aralkyloxy, C7-20 aralkyloxy substituted by at least one group selected from the group consisting of C1-3 alkyl, C1-3 alkoxy, C1-3 alkyl substituted by C1-3 alkoxy, phenoxy and fluorine atoms, fluorine atom, C2-20 alkylcarbonyl, C7-20 arylcarbonyl, C7-20 arylcarbonyl substituted by C1-3 alkyl and/or C1-3 alkoxy, C8-20Aralkylcarbonyl, and C8-20 aralkylcarbonyl substituted by C1-3 alkyl and/or C1-3 alkoxy. 3. The manufacturing method as claimed in claim 1, wherein, said R is an aryl group which is unsubstituted or substituted by at least one group selected from the following group: the substitution as described in claim 1 for C1-20 alkyl group, the group of substituent group A～I as described in claim 1, sulfonamide group, cyano group and amido group. 4. The manufacturing method as claimed in claim 1, 2 or 3, wherein said L is a chlorine atom, a bromine atom, an iodine atom, a nitro group, a sulfo group, a methanesulfonyloxy group, an ethanesulfonyloxy group, Trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, benzenesulfonyloxy, 1-naphthalenesulfonyloxy, trifluoroacetoxy, pentafluoroethylcarbonyloxy, tetrafluorobenzoyloxy or benzoyloxy. 5. The production method according to claim 1, wherein the fluorinating agent of formula (1) is an anhydrous salt. 6. The production method according to claim 1, wherein the fluorinating agent of formula (1) is a polar solvent, water or an adduct of both. 7. The manufacturing method according to any one of claims 1 to 6, wherein x=1. 8. The manufacturing method according to any one of claims 1 to 6, wherein 0<x<1. 9. The manufacturing method according to claim 8, wherein 0.4<x<0.9. 10. The manufacturing method according to claim 1 or 8, wherein the monovalent anion represented by Y- is a halide ion, a borate ion, a phosphoric acid ion, an antimonate ion, a sulfonic acid ion, a nitrate ion, a carbonate ion , Carboxylate ion or amide ion. 11. The production method according to claim 10, wherein Y ^- is Cl ^- or Br ^- . 12. The manufacturing method according to claim 1, wherein n represents 1, 2 or 3.