JP3533126B2 - Method for producing fluorine-substituted aromatic compound - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a fluorine-substituted aromatic compound. More particularly, it relates to a method for producing substituted fluorobenzenes, fluorine-substituted benzophenones and fluorine-substituted diaryl sulfones by fluorinating an alkali metal or alkaline earth metal salt of a corresponding hydroxy-containing aromatic compound.

[0002]

2. Description of the Related Art Fluorine-substituted aromatic compounds have specific properties derived from fluorine and are industrially useful compounds. For example, substituted fluorobenzenes are used as raw materials and intermediates for physiologically active substances and functional materials such as medical and agricultural chemicals, and also have applications in a wide range of fields such as refrigerants, raw materials for resins, and lubricating oils. There is. Fluorine-substituted benzophenone is also commonly used as a raw material for polyether polyketones, including polyether ether ketone, which is a super engineering plastic that also has excellent heat resistance, electrical insulation, slidability, and chemical resistance. Has been done. In addition, it is also a compound useful for agricultural and medicinal purposes such as being used as a flame retardant, an analgesic, an antiplatelet agent, an antithrombotic agent or the like or an intermediate thereof. Further, fluorine-substituted diaryl sulfones are generally used as a raw material for polyether sulfones and polysulfones, which are engineering plastics excellent in heat resistance, electric insulation, slidability and chemical resistance. Further, it is a useful compound that is indispensable in industry, such as being used as a raw material for functional materials such as organic EL materials and as an intermediate for agricultural drugs such as anticancer agents and immunodeficiency suppressants.

The methods for producing these compounds have been studied so far, and the following methods are known. As a method for producing a substituted fluorobenzene, a method in which fluorobenzenes already containing fluorine are reacted as a raw material to induce a desired product, and a method in which a desired product is synthesized by a fluorine substitution reaction of benzenes having various functional groups It is roughly divided into. In the former method, the raw materials are often expensive. On the other hand, according to the latter method, the target substituted fluorobenzenes can be produced using inexpensive raw materials, and there has been a demand for a fluorination reaction technique that enables a desired substitution reaction. Further, the following method has been known as a method for producing a fluorine-substituted benzophenone. EP
69598, EP 178184, EP 14729
9, JP-A-61-211146 discloses a method by Friedel-Crafts reaction from fluorobenzene and p-fluorobenzoyl chloride. Further, JP-A-58-126829 discloses a production method using 1,1-bis (4-fluorophenyl) -2,2-dichloroethylene as a raw material, and JP-A-57-154139 discloses 1, 1-bis (4-fluorophenyl) -2,
Manufacturing method using 2-trichloroethanol as a raw material, AU 5
33574, JP-A-57-169441,
A production method using 4,4′-dichlorobenzophenone as a raw material is shown. These methods are based on the reaction of a raw material containing fluorine or other halogen atom,
A great deal of labor is required at the stage of raw material synthesis.

As a method for fluorinating a functional group on an aromatic ring, the Baltz-Sieman reaction for displacing an amino group is known, and as described in JP-A-54-132558, fluorine-substituted. It is also used in the production of benzophenone. In this method, a large excess of hydrogen fluoride is used to replace the amino group with fluorine. Further, conventionally, as a method for producing a fluorine-substituted diaryl sulfone, a method using a fluorinated aromatic compound such as fluorobenzene as a starting material has been described in J. Am. Chem. Soc., 6
2,511940) and JP-A-58-206552.
Method for reacting with chlorosulfonic acid or fluorosulfonic acid described in JP-A-1-250342, EP
147298, a method of reacting with boron trifluoride and concentrated sulfuric acid in the presence of hydrogen fluoride, J. Am.
Chem. Soc., 70, 654 (1948) and Japanese Chemical Journal No. 76 (1955) pp. 775-8, a method of reacting with aryl sulfonic acid chlorides is known. Further, a method by an oxidation reaction of 4,4′-difluorodiphenyl sulfide and 4,4′-difluorodiphenyl sulfoxide is described in J. Am. Ch.
em.Soc., 70, 1564 (1948) and Acta.
Chim.hug., 4, 111 (1954) and the like. These are all disadvantageous as an industrial production method because they use expensive fluorinated aromatics as raw materials.

On the other hand, as the fluorinating agent used in the fluorination reaction, there are fluorine, hydrogen fluoride, sulfur tetrafluoride, diethylaminosulfur trifluoride and the like. These conventional fluorinating agents are toxic and corrosive. However, it was difficult to handle due to the danger of explosion during the reaction, and therefore special equipment and techniques were required. For example, as a fluorinating agent effective for a direct conversion reaction of a hydroxy group to a fluorine group, sulfur tetrafluoride (SF4) or diethylaminosulfur trifluoride (DAST) is typical,
SF4 is highly toxic and its handling is a problem. On the other hand, DAST is known as a useful fluorinating agent for efficiently fluorinating not only hydroxy groups but also oxygen-containing compounds such as ketones and carboxylic acids under mild conditions (US Pat. No. 3,976,691). However, the production method of DAST is a method of reacting highly dangerous SF4 and diethylaminotrimethylsilane at a low temperature of -78 ° C to -60 ° C, and a special production facility is required. Regarding safety, there is a report that there was an explosion in the production and use of DAST [J. Fl
uorine Chem. , 42, 137 (198
9)]. As in this example, conventionally, fluorine gas, hydrogen fluoride, sulfur tetrafluoride gas, etc. have been used as a fluorination agent for producing a fluorine compound. These fluorinated agents have problems such as being difficult to handle due to toxicity, corrosiveness, and risk of explosion during reaction, and requiring special equipment and techniques. Then, in order to solve these problems, various fluorinated reagents are being developed in recent years. As described above, as a hydroxy group fluorinating agent, industrially usable fluorinating agent is still sufficiently developed in view of its production method, reaction selectivity and yield, and economical efficiency. Is hard to say. However, a safe, stable and economical method for producing a fluorine-substituted benzophenone using a fluorinating agent has not been found yet.

As a method other than these, diaryl sulfones having halogens other than fluorine or a nitro group as a substituent in an aprotic polar solvent in the presence of special ammonium salts or organometallic complexes at a temperature of 200 ° C. or higher. The method of reacting with KF is WO8704148-87.
No. 04150, JP-A-2-273626, etc., but these methods are industrially disadvantageous because of severe reaction conditions. J. Fluorine Chem., 70 (2),
201 (1995), etc., describes a method of reacting 4,4′-dinitrodiphenyl sulfone with tetramethylammonium fluoride in an aprotic polar solvent under relatively mild conditions. Methylammonium fluoride is difficult to produce, and it is an expensive fluorinating agent, so it cannot be said to be an industrially excellent production method. Under these circumstances, it has been desired to develop a production method of fluorine-substituted diaryl sulfones which can be easily implemented economically and industrially.

[0007]

SUMMARY OF THE INVENTION An object of the present invention is to provide an economical and industrial method for producing a fluorine-substituted aromatic compound. Another problem is to obtain a substituted fluorobenzene from an aromatic compound having a hydroxy group such as hydroxybenzenes, benzophenones having a hydroxy group or diaryl sulfones having a hydroxy group,
It is an object of the present invention to provide a method for efficiently producing useful fluorine-substituted aromatic compounds such as fluorine-substituted benzophenones and fluorine-substituted diallyl sulfones.

[0008]

Means for Solving the Problems As a result of intensive studies to solve these problems, the present inventors have found that the alkali metal or alkaline earth metal salt of an aromatic compound having a hydroxy group can be used as a raw material. It was found that the reaction yield was improved by reacting with an agent, and by this method, an industrially useful fluorine-substituted aromatic compound, in particular, substituted fluorobenzene, fluorine-substituted benzophenone or fluorine-substituted diallyl sulfone was economically produced. The inventors have found that they can be produced industrially and industrially, and have completed the present invention.

Further, in this manufacturing method, particularly as the fluorinating agent, the compound represented by the general formula (5)

[Chemical 14] (In the formula, R ₂ , R ₃ , R ₄ , and R ₅ represent an alkyl group or an aryl group having 1 to 6 carbon atoms, and may be the same or different. Also, R ₂ and R ₃ Alternatively, R ₄ and R ₅ may combine to form a nitrogen atom, or a ring containing a nitrogen atom and another heterocycle, and R ₂ and R ₄ may combine to form a nitrogen atom, or a nitrogen atom and another heterocycle. It may form a ring containing a hetero atom, X ₁ is a fluorine atom, X ₂ is a fluorine atom or a chlorine atom, and X ₁ and X ₂ are covalently bonded to a carbon atom, but only X ₁ is present. Bis-dialkylamino-difluoromethane compound represented by the formula (1) may be covalently bonded to X _{2 and} may be present in the form of a counter ion.) Is excellent as a novel fluorination agent for a hydroxy group-containing aromatic compound. , And from the production of this compound to its use in fluorination reactions. Without the need for special equipment or technology,
It was found that it is extremely safe and easy, and that it is economical because it can be recovered as the original raw material, such as tetraalkylurea, after use in the fluorination reaction and reused again as the fluorination reagent. It was

That is, the method of the present invention comprises (1) the general formula (1)

[Chemical 15] [In the formula, M represents an alkali metal or alkaline earth metal atom, a and b are integers from 1 to 5 and may be the same or different, and a + b ≦ 6, and X ₁ is the following (a): ,
A monovalent group selected from the group consisting of (b) and (c) is shown. (a) Alkyl group, alkoxy group, aryl group, aryloxy group, nitro group, cyano group, halogen atom, acyl group, perhalogenated alkyl group, perhalogenated alkoxy group, alkylsulfonyl group, arylsulfonyl group, alkyl sulfoxide A monovalent group selected from the group consisting of a group, an aryl sulfoxide group, an alkyl sulfide group and an aryl sulfide group,

(B) Formula (2)

[Chemical 16] (In the formula, Y ₁ is a sulfonyl group, a sulfoxide group, a sulfide group, an ether group, a carbonyl group, or 2 having 1 to 3 carbon atoms.
A divalent group selected from a valent alkenyl group, a C1-C3 perfluoroalkenyl group, and a direct bond,
X ₂ represents a monovalent group selected from the group consisting of the monovalent group represented by X ₁ and a salt of an alkali metal or an alkaline earth metal having a hydroxyl group, and c represents an integer of 1 to 5. ), And (c) Formula (3)

[Chemical 17] (In the formula, Y ₁ is the same as in the case of the formula (2), and R represents a perhalogenated alkyl group.) Represents a monovalent group. ] The compound represented by the formula and an organic fluorinating agent are reacted, and the general formula (4)

[Chemical 18] (In the formula, a, b and X ₁ are the same as in the general formula (1).) A method for producing a fluorine-substituted aromatic compound.

2. The compound represented by the general formula (1) is
General formula (1-1):

[Chemical 19] (In the formula, M represents an alkali metal or alkaline earth metal atom, c is an integer from 1 to 5, and R ₁ is an alkyl group, an alkoxy group, an aryl group, an aryloxy group,
Nitro group, cyano group, halogen atom, acyl group, perhalogenated alkyl group, perhalogenated alkoxy group, alkylsulfonyl group, arylsulfonyl group, alkyl sulfoxide group, aryl sulfoxide group, alkyl sulfide group, aryl sulfide group) 1. The method according to the above 1, which is a phenolate represented by:

3. The fluorine-substituted aromatic compound represented by the general formula (4) has the general formula (4-1):

[Chemical 20] (In the formula, b is an integer from 1 to 5, and R ₁ is an alkyl group, an alkoxy group, an aryl group, an aryloxy group,
Nitro group, cyano group, halogen atom, acyl group, perhalogenated alkyl group, perhalogenated alkoxy group, alkylsulfonyl group, arylsulfonyl group, alkyl sulfoxide group, aryl sulfoxide group, alkyl sulfide group, aryl sulfide group) 1. The method according to the above 1, which is a substituted fluorobenzene represented by

4. The compound represented by the general formula (1) is
General formula (1-2):

[Chemical 21] (In the formula, e and f are integers of 0 to 5 and may be the same or different. However, when e = 0, f is 1
This is the above, and when f = 0, e is 1 or more. M represents an alkali metal or alkaline earth metal atom. ) The production method of 1, wherein the hydroxybenzophenone is an alkali metal salt or an alkaline earth metal salt thereof.

5. The fluorine-substituted aromatic compound represented by the general formula (4) has the general formula (4-2):

[Chemical formula 22] (In the formula, g and h represent 0 or 1, and are not 0 at the same time. E and f represent 0 or 1, and are not 1. at the same time, and e is 0 or 1 when g is 0; g is 1
When, it is 0. Furthermore, f is 0 or 1 when h is 0.
And when h is 1, it is 0. The manufacturing method of said 1 which is a fluorine-substituted benzophenone represented by these.

6. The compound represented by the general formula (1) is
4,4′-dihydroxybenzophenone, wherein the fluorine-substituted aromatic compound represented by the general formula (4) is
6. The production method of 5, which is 4′-difluorobenzophenone.

7. The compound represented by the general formula (1) is
4,4′-dihydroxybenzophenone, wherein the fluorine-substituted aromatic compound represented by the general formula (4) is 4-
6. The production method of 5, which is hydroxy-4′-fluorobenzophenone.

8. The compound represented by the general formula (1) is
General formula (1-3):

[Chemical formula 23] (In the formula, e, f and M are the same as those in the case of the general formula (1-2)) The production method of the above 1, which is an alkali metal or alkaline earth metal salt of a hydroxydiaryl sulfone.

9. The fluorine-substituted aromatic compound represented by the general formula (4) has the general formula (4-3):

[Chemical formula 24] (In the formula, g and h represent 0 or 1, and are not 0 at the same time. E and f represent 0 or 1, and are not 1. at the same time, and e is 0 or 1 when g is 0; g is 1
When, it is 0. Furthermore, f is 0 or 1 when h is 0.
And when h is 1, it is 0. The manufacturing method of said 1 which is a fluorine-substituted diaryl sulfone represented by these.

10. The compound represented by the general formula (1) is 4,4′-dihydroxydiphenylsulfone, and the fluorine-substituted aromatic compound represented by the general formula (4) is 4,4′-difluorodiphenylsulfone. Production method.

11. The compound represented by the general formula (1) is 4,4′-dihydroxydiphenylsulfone, and the fluorine-substituted aromatic compound represented by the general formula (4) is 4-hydroxy-4′-fluorodiphenylsulfone. 9. The manufacturing method of 9.

12. The organic fluorinating agent has the general formula (5):

[Chemical 25] (In the formula, R ₂ , R ₃ , R ₄ , and R ₅ represent an alkyl group or an aryl group having 1 to 6 carbon atoms, and may be the same or different. R ₂ , R ₃ Alternatively, R ₄ and R ₅ may combine to form a nitrogen atom, or a ring containing a nitrogen atom and another heterocycle, and R ₂ and R ₄ may combine to form a nitrogen atom, or a nitrogen atom and another heterocycle. It may form a ring containing a hetero atom, X ₁ is a fluorine atom, X ₂ is a fluorine atom or a chlorine atom, and X ₁ and X ₂ are covalently bonded to a carbon atom, but only X ₁ is present. May be present in the form of a counter ion, and X ₂ may be present in the form of a counter ion).
Manufacturing method.

13. The organic fluorinating agent is represented by the general formula (5-
1):

[Chemical formula 26] (1) The production method according to the above (1), which is a compound represented by the formula (wherein R ₂ , R ₃ , R ₄ and R ₅ are the same as in the case of the general formula (5)).

14. The organic fluorinating agent is represented by the general formula (5-
2):

[Chemical 27] 2,2-difluoro-1,3-dimethyl- represented by
The method for producing 1 to 11, which is imidazolidine.

The present invention uses an alkali metal or alkaline earth metal salt of an aromatic compound having a hydroxy group as a raw material, and uses a fluorinating agent to produce a fluorine-substituted aromatic compound in a safe, stable and economical industrial manner. A manufacturing method is provided. Among them, by using a bis-dialkylamino-difluoromethane compound as a fluorination reaction agent, no special equipment is required, and easily and economically, substituted fluorobenzenes, fluorine-substituted benzophenones and fluorine-substituted diarylsulfones can be prepared. Such fluorine-substituted aromatic compounds can be produced.

[0026]

BEST MODE FOR CARRYING OUT THE INVENTION The alkali metal or alkaline earth metal salt of an aromatic compound having a hydroxy group used in the present invention is represented by the general formula (1):

[Chemical 28] Is an alkali metal or alkaline earth metal salt of a compound having a hydroxy group represented by: That is, in the general formula (1), M represents an alkali metal or alkaline earth metal atom. a and b are integers from 1 to 5, which may be the same or different, and a + b ≦ 6.

X ₁ represents a monovalent group selected from the group consisting of the following (a), (b) and (c). (a) Alkyl group, alkoxy group, aryl group, aryloxy group, nitro group, cyano group, halogen atom, acyl group, perhalogenated alkyl group, perhalogenated alkoxy group, alkylsulfonyl group, arylsulfonyl group, alkyl sulfoxide A monovalent group selected from the group consisting of a group, an aryl sulfoxide group, an alkyl sulfide group and an aryl sulfide group, (b) Formula (2)

[Chemical 29] (In the formula, Y ₁ is a sulfonyl group, a sulfoxide group, a sulfide group, an ether group, a carbonyl group, or 2 having 1 to 3 carbon atoms.
A divalent group selected from a valent alkenyl group, a C1-C3 perfluoroalkenyl group, and a direct bond,
X ₂ represents a monovalent group selected from the group consisting of the monovalent group represented by X ₁ above and an alkali metal or alkaline earth metal salt of a hydroxyl group, and c represents an integer of 1 to 5. ), And (c) Formula (3)

[Chemical 30] (In the formula, Y ₁ is the same as in the case of the formula (2), and R represents a perhalogenated alkyl group.) Represents a monovalent group. In addition, in the above (a), the arylsulfonyl group, the aryl sulfoxide group, and the aryl sulfide group are an aryl sulfonyl group, an aryl sulfoxide group, and an aryl sulfide group which do not have a substituent.

In the compound represented by the general formula (1), M represents an alkali metal atom or an alkaline earth metal atom, for example, sodium atom, potassium atom, lithium atom,
A calcium atom, preferably a sodium atom,
It is a potassium atom. These salts can be easily prepared by subjecting a compound having a corresponding hydroxy group to salt formation dehydration with, for example, sodium hydroxide or potassium hydroxide.

Specific examples of the aromatic compound corresponding to the alkali metal or alkaline earth metal salt of the aromatic group-containing aromatic compound represented by the general formula (1) include the following compounds. (A) In formula (1), X ₁ is a substituent of group (a); 2-methylphenol, 3-methylphenol, 4-methylphenol, 2-ethylphenol, 3
-Ethylphenol, 4-ethylphenol, 2,3-
Dimethylphenol, 2,4-dimethylphenol,
2,5-dimethylphenol, 2,6-dimethylphenol, 3,4-dimethylphenol, 3,5-dimethylphenol, 2-methoxyphenol, 3-methoxyphenol, 4-methoxyphenol, 2-ethoxyphenol, 3- Ethoxyphenol, 4-ethoxyphenol, 2,3-dimethoxyphenol, 2,6-dimethoxyphenol, 3,4-dimethoxyphenol, 3,
5-dimethoxyphenol, 2-hydroxybiphenyl, 3-hydroxybiphenyl, 4-hydroxybiphenyl, 2,6-diphenylphenol, 4-phenoxyphenol, 2-nitrophenol, 3-nitrophenol, 4-nitrophenol, 2,4 -Dinitrophenol, 2,5-dinitrophenol, 2,4,6-trinitrophenol, 2-cyanophenol, 3-cyanophenol, 4-cyanophenol, 2-chlorophenol, 3-chlorophenol, 4-chlorophenol ,
2,4-dichlorophenol, 2,5-dichlorophenol, 2,6-dichlorophenol, 3,4-dichlorophenol, 3,5-dichlorophenol, 2,4,6
-Trichlorophenol, 2,4,5-trichlorophenol, pentachlorophenol, 2-fluorophenol, 3-fluorophenol, 4-fluorophenol, 2,4-difluorophenol, 2,5-difluorophenol, 2,6- Difluorophenol, 3,4
-Difluorophenol, 3,5-difluorophenol, 2,4,6-trifluorophenol, 2,4,5
-Trifluorophenol, pentafluorophenol, 2-bromophenol, 3-bromophenol, 4
-Bromophenol, 2,4-dibromophenol,
2,5-dibromophenol, 2,6-dibromophenol, 3,4-dibromophenol, 3,5-dibromophenol, 2,4,6-tribromophenol, 2,
4,5-tribromophenol, pentabromophenol, 2-hydroxybenzaldehyde, 3-hydroxybenzaldehyde, 4-hydroxybenzaldehyde,
2-hydroxyacetophenone, 3-hydroxyacetophenone, 4-hydroxyacetophenone, 2-hydroxybenzophenone, 3-hydroxybenzophenone,
4-hydroxybenzophenone, 2-trifluoromethylphenol, 3-trifluoromethylphenol, 4
-Trifluoromethylphenol, 2-trichloromethylphenol, 3-trichloromethylphenol, 4-
Trichloromethylphenol, 2-trifluoromethoxyphenol, 3-trifluoromethoxyphenol,
4-trifluoromethoxyphenol, 2-trichloromethoxyphenol, 3-trichloromethoxyphenol, 4-trichloromethoxyphenol, 2-hydroxyphenylmethylsulfone, 3-hydroxyphenylmethylsulfone, 4-hydroxyphenylmethylsulfone, 2-hydroxydiphenyl Sulfone, 4-hydroxydiphenyl sulfone, 4-hydroxyphenylmethyl sulfoxide, 4-hydroxydiphenyl sulfoxide, 4-hydroxyphenylmethyl sulfide, 4-hydroxydiphenyl sulfide,

(B) In the general formula (1), X ₁ is a substituent of the group (b); 2,2'-dihydroxydiphenyl sulfone, 2,3'-dihydroxydiphenyl sulfone, 2,4'-dihydroxy. Diphenyl sulfone,
3,3'-dihydroxydiphenyl sulfone, 3,4 '
-Dihydroxydiphenyl sulfone, 4,4'-dihydroxydiphenyl sulfone, 4-methyl-4'-hydroxydiphenyl sulfone, 4-methoxy-4'-hydroxydiphenyl sulfone, 4-phenyl-4'-hydroxydiphenyl sulfone, 4-nitro -4'-hydroxydiphenyl sulfone, 4-cyano-4'-hydroxydiphenyl sulfone, 4-chloro-4'-hydroxydiphenyl sulfone, 4-bromo-4'-hydroxydiphenyl sulfone, 4-acetyl-4'-hydroxydiphenyl Sulfone, 4-benzoyl-4'-hydroxydiphenyl sulfone, 4-trifluoromethyl-4'-hydroxydiphenyl sulfone, 4-trichloromethyl-
4'-hydroxydiphenyl sulfone, 4-trifluoromethoxy-4'-hydroxydiphenyl sulfone, 4
-Trichloromethoxy-4'-hydroxydiphenyl sulfone, 4-methylsulfonyl-4'-hydroxydiphenyl sulfone, 4-phenylsulfonyl-4'-hydroxydiphenyl sulfone, 2,2'-dihydroxydiphenyl sulfoxide, 2,3'-dihydroxy Diphenyl sulfoxide, 2,4'-dihydroxydiphenyl sulfoxide, 3,3'-dihydroxydiphenyl sulfoxide, 3,4'-dihydroxydiphenyl sulfoxide, 4,4'-dihydroxydiphenyl sulfoxide, 4-methyl-4'-hydroxydiphenyl sulfoxide, 4-methoxy-4'-hydroxydiphenyl sulfoxide, 4-phenyl-4'-hydroxydiphenyl sulfoxide, 4-nitro-4'-hydroxydiphenyl sulfoxide, 4-cyano-4'-hi Roxydiphenyl sulfoxide, 4-chloro-4′-hydroxydiphenyl sulfoxide, 4-bromo-4′-hydroxydiphenyl sulfoxide, 4-acetyl-4′-hydroxydiphenyl sulfoxide, 4-benzoyl-4′-hydroxydiphenyl sulfoxide, 4- Trifluoromethyl-4'-hydroxydiphenyl sulfoxide, 4-
Trichloromethyl-4'-hydroxydiphenyl sulfoxide, 4-trifluoromethoxy-4'-hydroxydiphenyl sulfoxide, 4-trichloromethoxy-
4'-hydroxydiphenyl sulfoxide 2,2'-
Dihydroxydiphenyl sulfide, 2,3'-dihydroxydiphenyl sulfide, 2,4'-dihydroxydiphenyl sulfide, 3,3'-dihydroxydiphenyl sulfide, 3,4'-dihydroxydiphenyl sulfide, 4,4'-dihydroxydiphenyl sulfide, 4 -Methyl-4'-hydroxydiphenyl sulfide, 4-methoxy-4'-hydroxydiphenyl sulfide, 4-phenyl-4'-hydroxydiphenyl sulfide, 4-nitro-4'-hydroxydiphenyl sulfide, 4-cyano-4'- Hydroxydiphenyl sulfide, 4-chloro-4'-hydroxydiphenyl sulfide, 4-bromo-4'-hydroxydiphenyl sulfide, 4-acetyl-4'-hydroxydiphenyl sulfide, 4-benzoyl-4'-hi B carboxymethyl diphenyl sulfide, 4-trifluoromethyl-4'-hydroxydiphenyl sulfide, 4-trichloromethyl -
4'-hydroxydiphenyl sulfide, 4-trifluoromethoxy-4'-hydroxydiphenyl sulfide, 4-trichloromethoxy-4'-hydroxydiphenyl sulfide, 2,2'-dihydroxydiphenyl ether, 2,3'-dihydroxydiphenyl ether,
2,4'-dihydroxydiphenyl ether, 3,3 '
-Dihydroxydiphenyl ether, 3,4'-dihydroxydiphenyl ether, 4,4'-dihydroxydiphenyl ether, 4-methyl-4'-hydroxydiphenyl ether, 4-methoxy-4'-hydroxydiphenyl ether, 4-phenyl-4'-hydroxydiphenyl ether, 4-nitro-4'-hydroxydiphenyl ether, 4-cyano-4'-hydroxydiphenyl ether, 4-chloro-4'-hydroxydiphenyl ether, 4-bromo-4'-hydroxydiphenyl ether, 4-acetyl-4'-hydroxydiphenyl ether, 4-benzoyl-4'-hydroxydiphenyl ether, 4-trifluoromethyl-4'-hydroxydiphenyl ether, 4-trichloromethyl-4'-hydroxydiphenyl ether, 4-to Lifluoromethoxy-4'-hydroxydiphenyl ether, 4-trichloromethoxy-4'-hydroxydiphenyl ether,
4-methylsulfonyl-4'-hydroxydiphenyl ether, 4-phenylsulfonyl-4'-hydroxydiphenyl ether 2,2'-dihydroxybenzophenone, 2,3'-dihydroxybenzophenone, 2,
4'-dihydroxybenzophenone, 3,3'-dihydroxybenzophenone, 3,4'-dihydroxybenzophenone, 4,4'-dihydroxybenzophenone, 4
-Methyl-4'-hydroxybenzophenone, 4-methoxy-4'-hydroxybenzophenone, 4-phenyl-4'-hydroxybenzophenone, 4-nitro-4 '
-Hydroxybenzophenone, 4-cyano-4'-hydroxybenzophenone, 4-chloro-4'-hydroxybenzophenone, 4-bromo-4'-hydroxybenzophenone, 4-acetyl-4'-hydroxybenzophenone, 4-benzoyl-4 ' -Hydroxybenzophenone, 4-trifluoromethyl-4'-hydroxybenzophenone, 4-trichloromethyl-4'-hydroxybenzophenone, 4-trifluoromethoxy-4'-hydroxybenzophenone, 4-trichloromethoxy-4 '
-Hydroxybenzophenone, 4-methylsulfonyl-
4'-hydroxybenzophenone, 4-phenylsulfonyl-4'-hydroxybenzophenone, 2,2'-dihydroxydiphenylmethane, 2,3'-dihydroxydiphenylmethane, 2,4'-dihydroxydiphenylmethane, 3,3'-dihydroxydiphenylmethane,
3,4'-dihydroxydiphenylmethane, 4,4'-
Dihydroxydiphenylmethane, 4-methyl-4'-hydroxydiphenylmethane, 4-methoxy-4'-hydroxydiphenylmethane, 4-phenyl-4'-hydroxydiphenylmethane, 4-nitro-4'-hydroxydiphenylmethane, 4-cyano-4'- Hydroxydiphenylmethane, 4-chloro-4'-hydroxydiphenylmethane, 4-bromo-4'-hydroxydiphenylmethane, 4-acetyl-4'-hydroxydiphenylmethane, 4-benzoyl-4'-hydroxydiphenylmethane, 4-trifluoromethyl-4 '-Hydroxydiphenylmethane, 4-trichloromethyl-4'-hydroxydiphenylmethane, 4-trifluoromethoxy-4'-
Hydroxydiphenylmethane, 4-trichloromethoxy-4'-hydroxydiphenylmethane, 4-methylsulfonyl-4'-hydroxydiphenylmethane, 4-phenylsulfonyl-4'-hydroxydiphenylmethane,
2,2-bis (2-hydroxyphenyl) propane, 2
-(2-hydroxyphenyl) -2- (3-hydroxyphenyl) propane, 2- (2-hydroxyphenyl)
-2- (4-hydroxyphenyl) propane, 2,2-
Bis (3-hydroxyphenyl) propane, 2- (3-
Hydroxyphenyl) -2- (4-hydroxyphenyl) propane, 2,2-bis (4-hydroxyphenyl) propane, 2- (4-methylphenyl) -2- (4
-Hydroxyphenyl) propane, 2- (4-methoxyphenyl) -2- (4-hydroxyphenyl) propane, 2- (4-phenylphenyl) -2- (4-hydroxyphenyl) propane, 2- (4-nitro) Phenyl)
-2- (4-hydroxyphenyl) propane, 2- (4
-Cyanophenyl) -2- (4-hydroxyphenyl)
Propane, 2- (4-chlorophenyl) -2- (4-hydroxyphenyl) propane, 2- (4-acetylphenyl) -2- (4-hydroxyphenyl) propane, 2
-(4-benzoylphenyl) -2- (4-hydroxyphenyl) propane, 2- (4-trifluoromethylphenyl) -2- (4-hydroxyphenyl) propane,
2- (4-trichloromethylphenyl) -2- (4-hydroxyphenyl) propane, 2- (4-trifluoromethoxyphenyl) -2- (4-hydroxyphenyl)
Propane, 2- (4-trichloromethoxyphenyl)-
2- (4-hydroxyphenyl) propane, 2- (4-
Methylsulfonylphenyl) -2- (4-hydroxyphenyl) propane, 2- (4-phenylsulfonylphenyl) -2- (4-hydroxyphenyl) propane,
2,2-bis (2-hydroxyphenyl) -1,1,
1,3,3,3-hexafluoropropane, 2- (2-
Hydroxyphenyl) -2- (3-hydroxyphenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (2-hydroxyphenyl) -2- (4-hydroxyphenyl) -1,1 , 1,3,3,3-hexafluoropropane, 2,2-bis (3-hydroxyphenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (3-hydroxyphenyl)- 2- (4-hydroxyphenyl) -1,1,1,3,3,3-hexafluoropropane, 2,2-bis (4-hydroxyphenyl) -1,1,1,3,3,3-hexa Fluoropropane, 2- (4-methylphenyl) -2- (4-hydroxyphenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (4-methoxyphenyl) -2- (4
-Hydroxyphenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (4-phenylphenyl)
-2- (4-hydroxyphenyl) -1,1,1,3
3,3-hexafluoropropane, 2- (4-nitrophenyl) -2- (4-hydroxyphenyl) -1,1,
1,3,3,3-hexafluoropropane, 2- (4-
Cyanophenyl) -2- (4-hydroxyphenyl)-
1,1,1,3,3,3-hexafluoropropane, 2
-(4-chlorophenyl) -2- (4-hydroxyphenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (4-acetylphenyl) -2- (4-hydroxyphenyl)- 1,1,1,3,3,3-hexafluoropropane, 2- (4-benzoylphenyl) -2
-(4-hydroxyphenyl) -1,1,1,3,3,
3-hexafluoropropane, 2- (4-trifluoromethylphenyl) -2- (4-hydroxyphenyl)-
1,1,1,3,3,3-hexafluoropropane, 2
-(4-Trichloromethylphenyl) -2- (4-hydroxyphenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (4-trifluoromethoxyphenyl) -2- (4- Hydroxyphenyl) -1,1,
1,3,3,3-hexafluoropropane, 2- (4-
Trichloromethoxyphenyl) -2- (4-hydroxyphenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (4-methylsulfonylphenyl) -2
-(4-hydroxyphenyl) -1,1,1,3,3,
3-hexafluoropropane, 2- (4-phenylsulfonylphenyl) -2- (4-hydroxyphenyl)-
1,1,1,3,3,3-hexafluoropropane,
2,2'-dihydroxybiphenyl, 2,3'-dihydroxybiphenyl, 2,4'-dihydroxybiphenyl, 3,3'-dihydroxybiphenyl, 3,4'-dihydroxybiphenyl, 4,4'-dihydroxybiphenyl, 4- Methyl-4'-hydroxybiphenyl, 4-
Methoxy-4'-hydroxybiphenyl, 4-phenyl-4'-hydroxybiphenyl, 4-nitro-4'-hydroxybiphenyl, 4-cyano-4'-hydroxybiphenyl, 4-chloro-4'-hydroxybiphenyl,
4-bromo-4'-hydroxybiphenyl, 4-acetyl-4'-hydroxybiphenyl, 4-benzoyl-
4'-hydroxybiphenyl, 4-trifluoromethyl-4'-hydroxybiphenyl, 4-trichloromethyl-4'-hydroxybiphenyl, 4-trifluoromethoxy-4'-hydroxybiphenyl, 4-trichloromethoxy-4'-hydroxy Biphenyl, 4-methylsulfonyl-4'-hydroxybiphenyl, 4-phenylsulfonyl-4'-hydroxybiphenyl,

(C) In the general formula (1), X ₁ is a substituent of group (c); 2-hydroxyphenyltrifluoromethylsulfone, 3-hydroxyphenyltrifluoromethylsulfone, 4-hydroxyphenyltrifluoro. Methyl sulfone, 2-hydroxyphenyl trichloromethyl sulfone, 3-hydroxyphenyl trichloromethyl sulfone, 4-hydroxyphenyl trichloromethyl sulfone, 4-hydroxyphenyl trifluoromethyl sulfoxide, 4-hydroxyphenyl trichloromethyl sulfoxide, 4-hydroxyphenyl trifluoro Methyl sulfide, 4-hydroxyphenyl trichloromethyl sulfide, 2-hydroxyphenyl trifluoromethyl ketone, 3-hydroxyphenyl trifluoromethyl ketone , 4-hydroxyphenyltrifluoromethylketone, 2-hydroxyphenyltrichloromethylketone, 3-hydroxyphenyltrichloromethylketone, alkali metal or alkaline earth metal salts of compounds having various hydroxy groups such as 4-hydroxyphenyltrichloromethylketone However, the present invention is not limited to these exemplified compounds.

Of these compounds, the general formula (1-1):

[Chemical 31] (In the formula, M, R ₁ and c are the same as described above.) An alkali metal salt or alkaline earth metal salt of substituted hydroxybenzene represented by the general formula (1-2):

[Chemical 32] (In the formula, e and f are integers of 0 to 5 and may be the same or different numbers. However, when e = 0, f is 1 or more and when f = 0. , E is 1 or more, and M is an alkali metal or alkaline earth metal atom of hydroxybenzophenone represented by an alkali metal or alkaline earth metal atom), or a general formula (1
-3):

[Chemical 33] [In the formula, e, f and M are the same as in the case of the general formula (1-2)], and are alkali metal or alkaline earth metal salts of hydroxydiaryl sulfones.

The alkali metal or alkaline earth metal salt of the compound having a hydroxy group represented by the general formula (1) used in the present invention is a compound having a corresponding hydroxy group and an alkali metal or alkaline earth metal base. (Hereinafter, abbreviated as a base). The reaction can be carried out in an aqueous solution, and then a solvent that does not react with a substrate such as benzene, toluene, xylene, etc. is added, heated, and water is distilled off to take out.

Specific examples of the organic fluorinating agent used in the present invention include N, N-diethyl (1,1,2-trifluoro-2-chloroethyl) amine, N, N-diethyl (1,1,1)
Fluoroalkylamine reagents such as 2,3,3,3, -hexafluoroethyl) amine, 1-dimethylamino-1
-Fluoroenamine type fluorinating agents such as fluoro-2-methylpropene and 1-diethylamino-1-fluoro-2-methylpropene, fluorophenylphosphoranes such as triphenylphosphine difluoride and phenylphosphine tetrafluoride, diethylamino Sulfur trifluoride,

Or general formula (5):

[Chemical 34] (In the formula, R ₂ , R ₃ , R ₄ , and R ₅ represent an alkyl group or an aryl group having 1 to 6 carbon atoms, and may be the same or different. R ₂ , R ₃ Alternatively, R ₄ and R ₅ may combine to form a nitrogen atom, or a ring containing a nitrogen atom and another heterocycle, and R ₂ and R ₄ may combine to form a nitrogen atom, or a nitrogen atom and another heterocycle. It may form a ring containing a hetero atom, X ₁ is a fluorine atom, X ₂ is a fluorine atom or a chlorine atom, and X ₁ and X ₂ are covalently bonded to a carbon atom, but only X ₁ is present. Is a covalent bond and X ₂ may be present in the form of a counter ion).

Preferably, the general formula (5-1):

[Chemical 35] (In the formula, R ₂ , R ₃ , R ₄ and R ₅ are the same as those in the general formula (5)), more preferably the compound represented by the general formula (5-2):

[Chemical 36] Is 1,3-dimethyl-imidazolidine.

In the general formula (5), the substituent represented by R _{2 to} R ₅ is an alkyl group or an aryl group having 1 to 6 carbon atoms. For example, methyl group, ethyl group, n-propyl group, i
-Propyl group, n-butyl group, n-pentyl group, n-hexyl group, and phenyl group. R ₂ in the formula
And R ₄ may be bonded to form a 5-membered ring or a 6-membered ring, or R ₂ and R ₃ , R ₄ and R ₅ are bonded to each other, and the number of carbon atoms bonded to each N atom is 3 5 to 5 heterocyclic compounds may be constituted.

Among the compounds represented by the general formula (5), specific examples include bis-dimethylamino-difluoromethane,
Bis-diethylamino-difluoromethane, bis-dipropylamino-difluoromethane, bis-di-i-propylamino-difluoromethane, bis-di-n-butylamino-difluoromethane, bis-di-i-butylamino-difluoro Methane, bis-di-t-butylamino-
Difluoromethane, bis-di-n-pentylamino-difluoromethane, bis-di-n-hexylamino-difluoromethane, 2,2-difluoro-1,3-dimethyl-imidazolidine, 2,2-difluoro-1- Ethyl-
3-methyl-imidazolidine, 2,2-difluoro-
1,3-diethyl-imidazolidine, 2,2-difluoro-1,3-di-n-propyl-imidazolidine, 2,
2-difluoro-1,3-di-i-propyl-imidazolidine, 2,2-difluoro-1,3-di-n-butyl-imidazolidine, N, N-dimethyl-N'-methyl-
N'-phenyl-difluoromethane, bis-piperidyl-difluoromethane and the like can be mentioned, but the present invention is not limited to the examples shown here.

R ₂ and R ₃ , R ₄ and R ₅ are bonded to each other to contain a nitrogen atom, preferably having 3 to 5 carbon atoms.
Examples of the hetero ring formed include a pyrrolidine ring and a piperidine ring. Furthermore, as an example of a ring in which R ₂ and R ₄ are bonded to each other to form a hetero 5-membered ring or a 6-membered ring containing two nitrogen atoms, an imidazolidine ring,
Examples thereof include an imidazolidinone ring, a pyrimidine ring, and a pyrimidinone ring.

The production of these compounds can be carried out according to the general formula (6)

[Chemical 37] (In the formula, R ₂ , R ₃ , R ₄ , and R ₅ represent an alkyl or aryl group having 1 to 6 carbon atoms and may be the same or different. R ₂ and R ₃ , and R ₄ and R ₅ may combine to form a nitrogen atom or a ring containing a nitrogen atom and another hetero atom, or R ₂ and R ₄ may combine to form a nitrogen atom, or a nitrogen atom and another hetero atom. May also form a ring containing) tetraalkyl-
Chloroform amidinium chloride and an alkali metal salt of fluorine, for example, cesium fluoride, rubidium fluoride, potassium fluoride, sodium fluoride and the like can be used, but fluorine is preferable because of its economical efficiency and reaction efficiency. By subjecting the spray-dried potassium fluoride for chemical reaction to a halogen exchange reaction in a solvent, it can be obtained safely and easily.

In the case of producing a compound in which the counter ion is chlorine in the general formula (5), the amount of the alkali metal salt of fluorine used in the halogen exchange reaction is based on the compound represented by the general formula (6). It is usually 1-fold mole or more, preferably 1-1.5-fold mole. If it is less than 1-fold mol, unexchanged chloride may remain and may be insufficient. If it exceeds 1.5 times, the amount of difluoro compound produced tends to increase. However, even if difluoro compounds are mixed, there is no problem in the production of substituted fluorobenzenes. The reaction solvent is not particularly limited as long as it is a solvent that does not react with the compound represented by the general formula (5) and the compound represented by the general formula (6).
Preferably acetonitrile, dimethylformamide,
1,3-dimethyl-2-imidazolidinone, dichloromethane, ethylene dichloride and the like. Although the amount of the solvent is not particularly limited, it is usually 1 to 10 times by weight based on the reaction substrate in view of reaction efficiency and operability.
The reaction temperature is not particularly limited, but is usually -20 ° C to 150 ° C, preferably 0 ° C from the viewpoint of reaction rate and stability of the product.
Is in the range of -100 ° C.

In the production of the compound represented by the general formula (5), the halogen exchange reaction can be carried out in the presence of a phase transfer catalyst such as a quaternary alkyl ammonium salt or a quaternary alkyl phosphonium salt. The obtained general formula (5)
The compound represented by can be used in the next synthetic reaction of the fluorine-substituted compound as the halogen exchange reaction liquid. Further, the inorganic salt can be used after being filtered off from the reaction solution, or the inorganic salt can be used after being filtered off and then isolated by distillation or crystallization. The compound represented by the general formula (6) used as a raw material for producing the compound represented by the general formula (5) includes tetraalkylurea, tetraalkylthiourea, 1,3-dialkylimidazolidinone, 1,3- It can be produced by chlorinating dialkylimidazolidine-2-thione or the like with a chlorinating agent such as phosgene or thionyl chloride. For example, 2-chloro-
1,3-Dimethylimidazolinium chloride can be easily produced by the method described in JP-B-59-25375. In the production of the present invention, the amount of the alkali metal salt of fluorine used in the halogen exchange reaction is 2 equivalents or more, preferably 2 to 5 equivalents based on tetraalkyl-chloroformamidinium chloride. If it is less than 2 equivalents, unexchanged chloride remains and is insufficient, and if it is used in excess of 5 equivalents, the reaction results are not significantly improved.

The fluorination reaction of the alkali metal or alkaline earth metal salt of the compound having a hydroxy group represented by the general formula (1) using the above fluorinating agent will be described in detail below. The fluorinating agent is the above-mentioned fluorinating agent, preferably bis-dialkylamino-difluoromethane represented by the general formula (5), more preferably the general formula (5).
-1) represented by bis-dialkylamino-difluoromethane, more preferably 2,2-difluoro-1,3-dimethyl-imidazolidine represented by the general formula (5-1). The amount of the fluorinating agent used is represented by the general formula (1)
With respect to the functional group of the compound having a hydroxy group represented by (-OM in formula (1)), the amount is preferably 1 equivalent or more, and 1 to 10 equivalents is particularly preferable. If it is less than 1 equivalent, unreacted hydroxy groups remain, so if desired,
Only when the amount used is adjusted to obtain a compound having a hydroxy group and a fluorine group.

The reaction solvent is not particularly limited as long as it does not react with a fluorinating agent, an alkali metal or alkaline earth metal salt of a compound having a hydroxy group, and a fluorine-substituted aromatic compound as a reaction product. Preferred are acetonitrile, dichloromethane, chloroform, ethylene dichloride, N-methylpyrrolidinone, dimethylformamide, 1,3-dimethyl-2-imidazolidinone and the like. The reaction temperature is preferably 0 ° C to 200 ° C, particularly preferably 40 ° C to 150 ° C. If the temperature is lower than 0 ° C, the reaction rate becomes slow and the operation becomes complicated. When it exceeds 200 ° C, the stability of the fluorinating agent is lowered. The fluorine-substituted aromatic compound produced by the reaction can be easily taken out from the reaction mixture by concentration or extraction operation. When bis-dialkylamino-difluoromethane is used as the fluorinating agent, it can be recovered as tetraalkylurea, 1,3-dialkylimidazolidinone or the like after the reaction. The recovered compound is chlorinated by the above-mentioned method to give a compound of the general formula (6)
Chloroform amidinium chloride represented by
Furthermore, it can be used again as a compound represented by the general formula (5) by performing a halogen exchange reaction between the compound represented by the general formula (6) and an alkali metal salt of fluorine.

In the method of the present invention, when the aromatic compound having a hydroxy group is, for example, a disodium salt or a dipotassium salt of 4,4'-dihydroxybenzophenone or 4,4'-dihydroxydiphenylsulfone, it is applicable. Although 4,4'-difluorobenzophenone or 4,4'-difluorodiphenyl sulfone is obtained as a product, it is preferable to use the fluorinating agent in an excess of 2 to 10 equivalents in order to increase the selectivity. When the fluorinating agent is bis-dialkylamino-difluoromethane, it is more preferable to add 4'-dihydroxybenzophenone or 4,4'-dihydroxydiphenyl sulfone disodium salt or dipotassium salt dropwise thereto.

By the method of the present invention described above, the following fluorine-substituted aromatic compounds of the general formula (4) corresponding to the general formula (1) can be obtained. (D) In the general formula (1), X ₁ is a substituent of the group (a), the fluorine-substituted aromatic compound of the general formula (4) corresponding to the compound having a hydroxy group; 2-methylfluorobenzene, 3 -Methylfluorobenzene, 4-methylfluorobenzene, 2-ethylfluorobenzene, 3-ethylfluorobenzene, 4-ethylfluorobenzene,
2,3-dimethylfluorobenzene, 2,4-dimethylfluorobenzene, 2,5-dimethylfluorobenzene, 2,6-dimethylfluorobenzene, 3,4-dimethylfluorobenzene, 3,5-dimethylfluorobenzene, 2- Methoxyfluorobenzene, 3-methoxyfluorobenzene, 4-methoxyfluorobenzene, 2-
Ethoxyfluorobenzene, 3-ethoxyfluorobenzene, 4-ethoxyfluorobenzene, 2,3-dimethoxyfluorobenzene, 2,6-dimethoxyfluorobenzene, 3,4-dimethoxyfluorobenzene, 3,5
-Dimethoxyfluorobenzene, 2-fluorobiphenyl, 3-fluorobiphenyl, 4-fluorobiphenyl, 2,6-diphenylfluorobenzene, 4-phenoxyfluorobenzene, 2-nitrofluorobenzene,
3-nitrofluorobenzene, 4-nitrofluorobenzene, 2,4-dinitrofluorobenzene, 2,5-dinitrofluorobenzene, 2,4,6-trinitrofluorobenzene, 2-cyanofluorobenzene, 3-cyanofluorobenzene , 4-cyanofluorobenzene, 2
-Chlorofluorobenzene, 3-chlorofluorobenzene, 4-chlorofluorobenzene, 2,4-dichlorofluorobenzene, 2,5-dichlorofluorobenzene,
2,6-dichlorofluorobenzene, 3,4-dichlorofluorobenzene, 3,5-dichlorofluorobenzene, 2,4,6-trichlorofluorobenzene, 2,
4,5-Trichlorofluorobenzene, pentachlorofluorobenzene, 1,2-difluorobenzene, 1,3
-Difluorobenzene, 1,4-difluorobenzene,
1,2,4-trifluorobenzene, 1,2,5-trifluorofluorobenzene, 1,2,6-trifluorofluorobenzene, 1,3,4-trifluorobenzene, 1,3,5-trifluoro Benzene, 1, 2, 4,
6-tetrafluorobenzene, 1,2,4,5-tetrafluorobenzene, hexafluorobenzene, 2-bromofluorobenzene, 3-bromofluorobenzene, 4
-Bromofluorobenzene, 2,4-dibromofluorobenzene, 2,5-dibromofluorobenzene, 2,6
-Dibromofluorobenzene, 3,4-dibromofluorobenzene, 3,5-dibromofluorobenzene, 2,
4,6-tribromofluorobenzene, 2,4,5-tribromofluorobenzene, pentabromofluorobenzene, 2-fluorobenzaldehyde, 3-fluorobenzaldehyde, 4-fluorobenzaldehyde, 2-
Fluoroacetophenone, 3-fluoroacetophenone, 4-fluoroacetophenone, 2-fluorobenzophenone, 3-fluorobenzophenone, 4-fluorobenzophenone, 2-trifluoromethylfluorobenzene, 3-trifluoromethylfluorobenzene, 4-
Trifluoromethylfluorobenzene, 2-trichloromethylfluorobenzene, 3-trichloromethylfluorobenzene, 4-trichloromethylfluorobenzene,
2-trifluoromethoxyfluorobenzene, 3-trifluoromethoxyfluorobenzene, 4-trifluoromethoxyfluorobenzene, 2-trichloromethoxyfluorobenzene, 3-trichloromethoxyfluorobenzene, 4-trichloromethoxyfluorobenzene, 2-
Fluorophenylmethyl sulfone, 3-fluorophenylmethyl sulfone, 4-fluorophenylmethyl sulfone, 2-fluorodiphenyl sulfone, 4-fluorodiphenyl sulfone, 4-fluorophenylmethyl sulfoxide, 4-fluorodiphenyl sulfoxide, 4-fluorophenylmethyl sulfide , 4-fluorodiphenyl sulfide,

(E) A fluorine-substituted aromatic compound of the general formula (4) corresponding to a compound having a hydroxy group, wherein X ₁ in the general formula (1) is a substituent of the group (b);
2,2'-dihydroxydiphenyl sulfone, 2,2 '
-Difluorodiphenyl sulfone, 2,3'-difluorodiphenyl sulfone, 2,4'-difluorodiphenyl sulfone, 3,3'-difluorodiphenyl sulfone, 3,4'-difluorodiphenyl sulfone, 4,
4'-difluorodiphenyl sulfone, 4-methyl-
4'-fluorodiphenyl sulfone, 4-methoxy-
4'-fluorodiphenyl sulfone, 4-phenyl-
4'-fluorodiphenyl sulfone, 4-nitro-4 '
-Fluorodiphenyl sulfone, 4-cyano-4'-fluorodiphenyl sulfone, 4-chloro-4'-fluorodiphenyl sulfone, 4-bromo-4'-fluorodiphenyl sulfone, 4-acetyl-4'-fluorodiphenyl sulfone, 4 -Benzoyl-4'-fluorodiphenyl sulfone, 4-trifluoromethyl-4'-fluorodiphenyl sulfone, 4-trichloromethyl-4 '
-Fluorodiphenyl sulfone, 4-trifluoromethoxy-4'-fluorodiphenyl sulfone, 4-trichloromethoxy-4'-fluorodiphenyl sulfone, 4
-Methylsulfonyl-4'-fluorodiphenyl sulfone, 4-phenylsulfonyl-4'-fluorodiphenyl sulfone, 2,2'-difluorodiphenyl sulfoxide, 2,3'-difluorodiphenyl sulfoxide,
2,4'-difluorodiphenyl sulfoxide, 3,
3'-difluorodiphenyl sulfoxide, 3,4'-
Difluorodiphenyl sulfoxide, 4,4'-difluorodiphenyl sulfoxide, 4-methyl-4'-fluorodiphenyl sulfoxide, 4-methoxy-4'-fluorodiphenyl sulfoxide, 4-phenyl-4'-
Fluorodiphenyl sulfoxide, 4-nitro-4'-
Fluorodiphenyl sulfoxide, 4-cyano-4'-
Fluorodiphenyl sulfoxide, 4-chloro-4'-
Fluorodiphenyl sulfoxide, 4-bromo-4'-
Fluorodiphenyl sulfoxide, 4-acetyl-4 '
-Fluorodiphenyl sulfoxide, 4-benzoyl-
4'-fluorodiphenyl sulfoxide, 4-trifluoromethyl-4'-fluorodiphenyl sulfoxide,
4-trichloromethyl-4'-fluorodiphenyl sulfoxide, 4-trifluoromethoxy-4'-fluorodiphenyl sulfoxide, 4-trichloromethoxy-
4'-fluorodiphenyl sulfoxide, 2,2'-difluorodiphenyl sulfide, 2,3'-difluorodiphenyl sulfide, 2,4'-difluorodiphenyl sulfide, 3,3'-difluorodiphenyl sulfide, 3,4'-difluorodiphenyl Sulfide,
4,4'-difluorodiphenyl sulfide, 4-methyl-4'-fluorodiphenyl sulfide, 4-methoxy-4'-fluorodiphenyl sulfide, 4-phenyl-4'-fluorodiphenyl sulfide, 4-nitro-4'-fluoro Diphenyl sulfide, 4-cyano-
4'-fluorodiphenyl sulfide, 4-chloro-
4'-fluorodiphenyl sulfide, 4-bromo-
4'-fluorodiphenyl sulfide, 4-acetyl-
4'-fluorodiphenyl sulfide, 4-benzoyl-4'-fluorodiphenyl sulfide, 4-trifluoromethyl-4'-fluorodiphenyl sulfide, 4
-Trichloromethyl-4'-fluorodiphenyl sulfide, 4-trifluoromethoxy-4'-fluorodiphenyl sulfide, 4-trichloromethoxy-4'-fluorodiphenyl sulfide, 2,2'-difluorodiphenyl ether, 2,3'-difluoro Diphenyl ether, 2,4'-difluorodiphenyl ether,
3,3'-difluorodiphenyl ether, 3,4'-
Difluorodiphenyl ether, 4,4'-difluorodiphenyl ether, 4-methyl-4'-fluorodiphenyl ether, 4-methoxy-4'-fluorodiphenyl ether, 4-phenyl-4'-fluorodiphenyl ether, 4-nitro-4'-fluorodiphenyl ether , 4-cyano-4'-fluorodiphenyl ether, 4-chloro-4'-fluorodiphenyl ether,
4-bromo-4'-fluorodiphenyl ether, 4-
Acetyl-4'-fluorodiphenyl ether, 4-benzoyl-4'-fluorodiphenyl ether, 4-trifluoromethyl-4'-fluorodiphenyl ether, 4-trichloromethyl-4'-fluorodiphenyl ether, 4-trifluoromethoxy-4'- Fluorodiphenyl ether, 4-trichloromethoxy-4'-
Fluorodiphenyl ether, 4-methylsulfonyl-
4'-fluorodiphenyl ether, 4-phenylsulfonyl-4'-fluorodiphenyl ether, 2,2 '
-Difluorobenzophenone, 2,3'-difluorobenzophenone, 2,4'-difluorobenzophenone,
3,3'-difluorobenzophenone, 3,4'-difluorobenzophenone, 4,4'-difluorobenzophenone, 4-methyl-4'-fluorobenzophenone,
4-methoxy-4'-fluorobenzophenone, 4-phenyl-4'-fluorobenzophenone, 4-nitro-
4'-fluorobenzophenone, 4-cyano-4'-fluorobenzophenone, 4-chloro-4'-fluorobenzophenone, 4-bromo-4'-fluorobenzophenone, 4-acetyl-4'-fluorobenzophenone,
4-benzoyl-4'-fluorobenzophenone, 4-
Trifluoromethyl-4′-fluorobenzophenone,
4-trichloromethyl-4'-fluorobenzophenone, 4-trifluoromethoxy-4'-fluorobenzophenone, 4-trichloromethoxy-4'-fluorobenzophenone, 4-methylsulfonyl-4'-fluorobenzophenone, 4-phenylsulfonyl- 4'-fluorobenzophenone, 2,2'-difluorodiphenylmethane, 2,4'-difluorodiphenylmethane, 3,
3'-difluorodiphenylmethane, 3,4'-difluorodiphenylmethane, 4,4'-difluorodiphenylmethane, 4-methyl-4'-fluorodiphenylmethane, 4-methoxy-4'-fluorodiphenylmethane,
4-phenyl-4'-fluorodiphenylmethane, 4-
Nitro-4'-fluorodiphenylmethane, 4-cyano-4'-fluorodiphenylmethane, 4-chloro-4 '
-Fluorodiphenylmethane, 4-bromo-4'-fluorodiphenylmethane, 4-acetyl-4'-fluorodiphenylmethane, 4-benzoyl-4'-fluorodiphenylmethane, 4-trifluoromethyl-4'-fluorodiphenylmethane, 4-trichloromethyl -4'-
Fluorodiphenylmethane, 4-trifluoromethoxy-4'-fluorodiphenylmethane, 4-trichloromethoxy-4'-fluorodiphenylmethane, 4-methylsulfonyl-4'-fluorodiphenylmethane, 4-phenylsulfonyl-4'-fluorodiphenylmethane,
2,2-bis (2-fluorophenyl) propane, 2-
(2-Fluorophenyl) -2- (3-fluorophenyl) propane, 2- (2-fluorophenyl) -2-
(4-fluorophenyl) propane, 2,2-bis (3
-Fluorophenyl) propane, 2- (3-fluorophenyl) -2- (4-fluorophenyl) propane,
2,2-bis (4-fluorophenyl) propane, 2-
(4-Methylphenyl) -2- (4-fluorophenyl) propane, 2- (4-methoxyphenyl) -2-
(4-fluorophenyl) propane, 2- (4-phenylphenyl) -2- (4-fluorophenyl) propane, 2- (4-nitrophenyl) -2- (4-fluorophenyl) propane, 2- (4 -Cyanophenyl) -2
-(4-fluorophenyl) propane, 2- (4-chlorophenyl) -2- (4-fluorophenyl) propane, 2- (4-acetylphenyl) -2- (4-fluorophenyl) propane, 2- (4 -Benzoylphenyl) -2- (4-fluorophenyl) propane, 2-
(4-trifluoromethylphenyl) -2- (4-fluorophenyl) propane, 2- (4-trichloromethylphenyl) -2- (4-fluorophenyl) propane,
2- (4-trifluoromethoxyphenyl) -2- (4
-Fluorophenyl) propane, 2- (4-trichloromethoxyphenyl) -2- (4-fluorophenyl) propane, 2- (4-methylsulfonylphenyl) -2-
(4-Fluorophenyl) propane, 2- (4-phenylsulfonylphenyl) -2- (4-fluorophenyl) propane, 2,2-bis (2-fluorophenyl)
-1,1,1,3,3,3-hexafluoropropane,
2- (2-fluorophenyl) -2- (3-fluorophenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (2-fluorophenyl) -2- (4-fluorophenyl) ) -1,1,1,3,3,3-hexafluoropropane, 2,2-bis (3-fluorophenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (3 -Fluorophenyl) -2- (4-fluorophenyl) -1,1,1,3,3,3-hexafluoropropane, 2,2-bis (4-fluorophenyl)-
1,1,1,3,3,3-hexafluoropropane, 2
-(4-Methylphenyl) -2- (4-fluorophenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (4-methoxyphenyl) -2- (4-fluorophenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (4-phenylphenyl) -2- (4
-Fluorophenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (4-nitrophenyl) -2
-(4-fluorophenyl) -1,1,1,3,3,3
-Hexafluoropropane, 2- (4-cyanophenyl) -2- (4-fluorophenyl) -1,1,1,
3,3,3-hexafluoropropane, 2- (4-chlorophenyl) -2- (4-fluorophenyl) -1,
1,1,3,3,3-hexafluoropropane, 2-
(4-Acetylphenyl) -2- (4-fluorophenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (4-benzoylphenyl) -2- (4-fluorophenyl)- 1,1,1,3,3,3-hexafluoropropane, 2- (4-trifluoromethylphenyl) -2- (4-fluorophenyl) -1,1,1,
3,3,3-hexafluoropropane, 2- (4-trichloromethylphenyl) -2- (4-fluorophenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (4- Trifluoromethoxyphenyl) -2-
(4-fluorophenyl) -1,1,1,3,3,3-
Hexafluoropropane, 2- (4-trichloromethoxyphenyl) -2- (4-fluorophenyl) -1,
1,1,3,3,3-hexafluoropropane, 2-
(4-Methylsulfonylphenyl) -2- (4-fluorophenyl) -1,1,1,3,3,3-hexafluoropropane, 2- (4-phenylsulfonylphenyl)
-2- (4-fluorophenyl) -1,1,1,3
3,3-hexafluoropropane,

(F) A fluorine-substituted aromatic compound of the general formula (4) corresponding to a compound having a hydroxy group, wherein X ₁ is a substituent of the group (c) in the general formula (1);
2'-difluorobiphenyl, 2,3'-difluorobiphenyl, 2,4'-difluorobiphenyl, 3,3 '
-Difluorobiphenyl, 3,4'-difluorobiphenyl, 4,4'-difluorobiphenyl, 4-methyl-
4'-fluorobiphenyl, 4-methoxy-4'-fluorobiphenyl, 4-phenyl-4'-fluorobiphenyl, 4-nitro-4'-fluorobiphenyl, 4-cyano-4'-fluorobiphenyl, 4-chloro- 4'-
Fluorobiphenyl, 4-bromo-4'-fluorobiphenyl, 4-acetyl-4'-fluorobiphenyl, 4
-Benzoyl-4'-fluorobiphenyl, 4-trifluoromethyl-4'-fluorobiphenyl, 4-trichloromethyl-4'-fluorobiphenyl, 4-trifluoromethoxy-4'-fluorobiphenyl, 4-trichloromethoxy-4 '-Fluorobiphenyl, 4-methylsulfonyl-4'-fluorobiphenyl, 4-phenylsulfonyl-4'-fluorobiphenyl, 2-fluorophenyltrifluoromethylsulfone, 3-fluorophenyltrifluoromethylsulfone, 4-fluorophenyltriphenyl Fluoromethyl sulfone, 2-fluorophenyl trichloromethyl sulfone, 3-fluorophenyl trichloromethyl sulfone, 4-fluorophenyl trichloromethyl sulfone, 4-fluorophenyl trifluoromethyl sulfoxide, 4- Fluorophenyl trichloromethyl sulfoxide, 4-fluorophenyl trifluoromethyl sulfide, 4-fluorophenyl trichloromethyl sulfide, 2-fluorophenyl trifluoromethyl ketone, 3-fluorophenyl trifluoromethyl ketone, 4-fluorophenyl trifluoromethyl ketone, 2-fluorophenyl trichloromethyl ketone, 3-fluorophenyl trichloromethyl ketone, 4
-Fluorophenyl trichloromethyl ketone and the like can be mentioned.

[0049]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.
In addition, 2,2-difluoro-1,3-dimethylimidazolidine (hereinafter referred to as DFI) in the acetonitrile solution in Synthesis Example 1 was used.
The concentration will be abbreviated as follows. DFI is reacted with aniline to derivatize it and then subjected to high performance liquid chromatography (hereinafter referred to as HP).
(Abbreviated as LC). The concentration of fluorine ion (hereinafter abbreviated as F ⁻ ) was measured by absorptiometry using a lanthanum-alizarin complexone reagent.

Synthesis Example 1 Synthesis of 2,2-difluoro-1,3-dimethylimidazolidine (DFI) 2-chloro-1,3-dimethylimidazolinium = 80.0 g (0.452 mol) of chloride and spray 105.1g (1.810mo) of dry potassium fluoride
1) and 320 ml of acetonitrile were charged into a 500 ml four-neck reaction flask and reacted at 80 ° C. for 17 hours under a nitrogen atmosphere. The reaction solution was cooled to 25 ° C., and then inorganic salts were separated from the reaction solution to obtain 414.2 g of an acetonitrile solution of DFI (MW136.14). The DFI concentration in the solution was 11.4 wt% and the yield was 77%. The reaction liquid was distilled under reduced pressure to obtain 32 g of DFI (purity: 97.8%). The physical property values are as follows. Boiling point 47.0 ° C / 37mm
Hg, EIMS: 136 (M ⁺ ), 117 (M ⁺ -
F ⁺ ), IR (neat) cm ⁻¹ : 1486, 138
5,1295,1242,1085,966, F analysis:
Calculated value 27.9%, Found value 27.7%, ¹ H-NM
R (δ ppm, CDCl ₃ , TMS standard): 2.52
_{(S, 6H, -CH 3 ×} 2), 3. O5 (s, 4H,-
CH ₂ CH ₂ —), ¹³ C-NMR (δ ppm, CDCl
₃ , -45 ° C, CDCl ₃ standard): 31.4 (s, -C
_{H 3 × 2), 47.6 (} s, -CH 2 CH 2 -), 12
8.5 (t, J = 230Hz, = CF 2), 19 F-N
MR (δppm, CDCl ₃ , -45 ° C, CFCl ₃ standard): -70.9 (s, = CF ₂ ).

Synthesis Example 2 Synthesis of potassium salt of p-nitrophenol In a 500 ml four-necked flask equipped with a Dean-Stuck tube, 27.8 g of p-nitrophenol (0.2 mo) was obtained.
1) and 12.5 wt% potassium hydroxide aqueous solution 82.5 g
(0.2 mol) and charged at 30 ° C. under nitrogen atmosphere for 3
The reaction was allowed for 0 minutes. Then, add 300 g of toluene,
The mixture was heated under a nitrogen atmosphere, and water-toluene distilled out was separated in a Dean-Stuck tube to reflux only toluene. Then, from the time when the internal temperature reaches 110 ° C, 2
Hold the time and continue processing. The toluene slurry of potassium salt of p-nitrophenol obtained was filtered,
C. and was dried at 5.33 kPa (40 mmHg) for 4 hours to obtain 34.4 g of potassium salt of p-nitrophenol. Yield 97%.

Synthesis Example 3 Synthesis of dipotassium salt of 4,4'-dihydroxybenzophenone In a 1000 ml four-necked flask equipped with a Dean-Stuck tube, 42.8 g of dihydroxybenzophenone (0.
2 mol) and 13.6 wt% potassium hydroxide aqueous solution 16
Charge 5 g (0.4 mol) and under a nitrogen atmosphere at 30 ° C.
And reacted for 30 minutes. Thereafter, 500 g of toluene was charged and heated under a nitrogen atmosphere, and water-toluene distilled was separated in a Dean-Stuck tube to reflux only toluene. Then, the treatment was continued for 2 hours after the internal temperature reached 110 ° C. The obtained toluene slurry of the dipotassium salt of 4,4′-dihydroxybenzophenone was filtered to obtain 160 ° C. and 5.33 kPa (40 mmH).
g) and dried for 4 hours to obtain 56.9 g of a dipotassium salt of 4,4'-dihydroxybenzophenone. Yield 98
%.

Synthesis Example 4 Synthesis of dipotassium salt of 4,4'-dihydroxydiphenyl sulfone 4,5 'in a 500 ml four-necked flask equipped with a stirrer, a thermometer, a Dean-Stak tube with a cooling tube, and a 100 ml dropping funnel. -Dihydroxydiphenyl sulfone 3
0.0 g (0.12 mol), 1,3-dimethyl-2-
Imidazolidinone 200.9 g and p-xylene 9
6.7g was prepared and heated at 115 ° C under a nitrogen atmosphere.
20.7 wt% potassium hydroxide aqueous solution 50.7
g (0.24 mol) was added dropwise from the dropping funnel over one and a half hours. During that time, water-p-xylene distilled out was separated in a Deanstadt tube to reflux only p-xylene. Then, when the internal temperature reached 160 ° C., heating was stopped and cooling was performed. The obtained slurry solution of the dipotassium salt of 4,4′-dihydroxydiphenyl sulfone was filtered and washed with toluene, and then 120 ° C. and 5.33 kPa (4
After drying at 0 mmHg) for 8 hours, 160 ° C.,
It was dried at 5.33 kPa (40 mmHg) for 5 hours to obtain 35.8 g of a dipotassium salt of 4,4′-dihydroxydiphenylsulfone. Yield 92%.

Example 1 1.10 g of potassium salt of p-nitrophenol was placed in a 50 ml flask equipped with a stirrer and a condenser.
Charge (6.2 mmol) and 40 g of acetonitrile,
Next, 6.34 g (46.6 mmol) of DFI was charged and heated to reflux (84 ° C.) under a nitrogen atmosphere.
The treatment was continued for 8 hours. After the treatment, the reaction mass was subjected to GC-MS analysis to confirm the production of p-nitrofluorobenzene. Further, the reaction yield was 93.6% by GC analysis.

Example 2 In a 50 ml flask equipped with a stir bar and a condenser, 1.10 g of potassium salt of p-nitrophenol was added.
Charge (6.2 mmol) and 40 g of acetonitrile,
Then, 0.86 g (6.3 mmol) of DFI was charged and heated to reflux (84 ° C.) 5 under a nitrogen atmosphere.
Time processing continued. After the treatment, the reaction mass was subjected to GC-MS analysis to confirm the production of p-nitrofluorobenzene. The reaction yield was 50.8% according to GC analysis.

Example 3 1.54 g (5.00 mmol) of dipotassium salt of 4,4'-dihydroxybenzophenone and 4.08 of DFI
g (30.00 mmol) and 40 ml of acetonitrile were placed in a reaction vessel and reacted at 80 ° C. for 8 hours under a nitrogen atmosphere. After completion of the reaction, generation of 4,4′-difluorobenzophenone (parent ion; 218, base peak; 123) was confirmed by GC-MS measurement of the reaction solution. or,
The reaction yield was 50% from the GC analysis value.

Example 4 0.31 g (1.07 mmol) of dipotassium salt of 4,4'-dihydroxybenzophenone and 0.29 of DFI.
g (2.14 mmol) and 30 ml of nitrobenzene were placed in a reaction vessel and reacted at 120 ° C. for 4 hours under a nitrogen atmosphere. After completion of the reaction, generation of 4,4′-difluorobenzophenone (parent ion; 218, base peak; 123) was confirmed by GC-MS measurement of the reaction solution. or,
The reaction yield was 45% from the GC analysis value.

Comparative Example 1 4,4'-dihydroxybenzophenone 1.07 g
(5.00 mmol) and DFI 4.08 g (30.0
(0 mmol) and 50 ml of acetonitrile were placed in a reaction vessel and reacted at 84 ° C. for 4 hours under a nitrogen atmosphere. After completion of the reaction, generation of 4,4′-difluorobenzophenone (parent ion; 218, base peak; 123) was confirmed by GC-MS measurement of the reaction solution. The reaction yield was 20% from the GC analysis value.

Example 5 1.18 g (4.12 mmol) of monopotassium salt of 4,4'-dihydroxydiphenyl sulfone and DFI
2.33 g (17.09 mmol) and acetonitrile 1
0 ml was placed in a reaction vessel and reacted at 84 ° C. for 16 hours under a nitrogen atmosphere. After completion of the reaction, excess DFI was hydrolyzed with aqueous NaOH, acidified with aqueous hydrochloric acid, and extracted with ether to separate the components obtained by thin-layer chromatography to give 4-fluoro-4′-hydroxy. Generation of diphenyl sulfone (EI-MASS measurement, molecular ion peak; 252) was confirmed. The reaction yield was 64% from the HPLC analysis value.

Example 6 2.82 g (8.64 mmol) of dipotassium salt of 4,4'-dihydroxydiphenyl sulfone and DFI 7.
01 g (51.49 mmol) and 20 m of acetonitrile
1 was placed in a reaction vessel and reacted at 84 ° C. for 10 hours under a nitrogen atmosphere. After the completion of the reaction, excess DFI was hydrolyzed with aqueous NaOH, acidified with aqueous hydrochloric acid, and extracted with ether to separate the components obtained by thin layer chromatography to obtain 4,4'-difluorodiphenyl sulfone. Generation (EI-MASS measurement molecular ion peak; 2
54) was confirmed. The reaction yield was 44% from the HPLC analysis value.

Example 7 19.75 g (145.07 mmol) of DFI and 30 ml of acetonitrile were placed in a reaction vessel and under a nitrogen atmosphere.
After heating to ℃, 4.91 g (15.04 mmo) of dipotassium salt of 4,4′-dihydroxydiphenyl sulfone.
A slurry solution of 1) and 60 ml of acetonitrile was added dropwise over 9 hours. Then, the mixture was reacted at the same temperature for 5 hours. From the HPLC analysis value, the reaction yield of 4,4′-difluorodiphenyl sulfone was 70%.

Comparative Example 2 1.04 g of 4,4'-dihydroxydiphenyl sulfone
(4.32 mmol) and DFI 1.28 g (9.38)
(mmol) and 10 ml of acetonitrile were placed in a reaction vessel and reacted at 84 ° C. for 6 hours under a nitrogen atmosphere. HPLC
From the analysis value, the reaction yield of 4,4′-difluorodiphenyl sulfone was 7%.

[0063]

INDUSTRIAL APPLICABILITY The present invention uses an alkali metal salt or an alkaline earth metal salt of an aromatic compound having a hydroxy group as a raw material and uses a fluorinating agent to prepare a fluorine-substituted aromatic compound in a safe, stable and economical manner. It is an industrial production method, uses a bis-dialkylamino-difluoromethane compound as a fluorination reaction reagent, does not require special equipment, and can be easily and economically substituted fluorobenzenes, fluorine-substituted benzophenones and fluorine-substituted compounds. Fluorine-substituted aromatic compounds such as diaryl sulfones can be prepared.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁷ identification code FI C07C 315/04 C07C 315/04 317/14 317/14 (72) Inventor Junko Naruse 30 Asamu-cho, Omuta-shi, Fukuoka Mitsuika Gaku Co., Ltd. (72) Inventor Hidetoshi Hayashi 30 Asamu-cho, Omuta-shi, Fukuoka Mitsui Kagaku Co., Ltd. (72) Inventor Hideaki Oikawa 30 Asakuta-cho, Omuta-shi, Fukuoka Mitsui Kagaku Co., Ltd. (72 ) Inventor Teruyuki Nagata 580-32 Takuji Nagaura, Sodegaura City, Chiba Prefecture Mitsui Chemicals, Inc. (56) Reference JP 2000-38370 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07B 39/00 C07C 45/63 C07C 49/813 C07C 201/12 C07C 205/12 C07C 315/04 C07C 317/14 C07C 17/16 C07D 233/02

Claims (14)

(57) [Claims] 1. A compound represented by the general formula (1): [In the formula, M represents an alkali metal or alkaline earth metal atom, a and b are integers from 1 to 5 and may be the same or different, and a + b ≦ 6, and X ₁ is the following (a): ,
A monovalent group selected from the group consisting of (b) and (c) is shown. (a) Alkyl group, alkoxy group, aryl group, aryloxy group, nitro group, cyano group, halogen atom, acyl group, perhalogenated alkyl group, perhalogenated alkoxy group, alkylsulfonyl group, arylsulfonyl group, alkyl sulfoxide A monovalent group selected from the group consisting of a group, an aryl sulfoxide group, an alkyl sulfide group and an aryl sulfide group, (b) a compound represented by the formula (2): (In the formula, Y ₁ is a sulfonyl group, a sulfoxide group, a sulfide group, an ether group, a carbonyl group, or 2 having 1 to 3 carbon atoms.
A divalent group selected from a valent alkenyl group, a C1-C3 perfluoroalkenyl group, and a direct bond,
X ₂ represents a monovalent group selected from the group consisting of the monovalent group represented by X ₁ and a salt of an alkali metal or an alkaline earth metal having a hydroxyl group, and c represents an integer of 1 to 5. ), And (c) Formula (3) (In the formula, Y ₁ is the same as in the case of the formula (2), and R represents a perhalogenated alkyl group.) Represents a monovalent group. ] A compound represented by the general formula (4): (In the formula, a, b and X ₁ are the same as in the general formula (1).) A method for producing a fluorine-substituted aromatic compound. 2. A compound represented by the general formula (1) has the general formula (1-1): (In the formula, M represents an alkali metal or alkaline earth metal atom, c is an integer from 1 to 5, and R ₁ is an alkyl group, an alkoxy group, an aryl group, an aryloxy group,
Nitro group, cyano group, halogen atom, acyl group, perhalogenated alkyl group, perhalogenated alkoxy group, alkylsulfonyl group, arylsulfonyl group, alkyl sulfoxide group, aryl sulfoxide group, alkyl sulfide group, aryl sulfide group) The method according to claim 1, which is a phenolate represented by: 3. A fluorine-substituted aromatic compound represented by the general formula (4) has the general formula (4-1): (In the formula, b is an integer from 1 to 5, and R ₁ is an alkyl group, an alkoxy group, an aryl group, an aryloxy group,
Nitro group, cyano group, halogen atom, acyl group, perhalogenated alkyl group, perhalogenated alkoxy group, alkylsulfonyl group, arylsulfonyl group, alkyl sulfoxide group, aryl sulfoxide group, alkyl sulfide group, aryl sulfide group) The method according to claim 1, which is a substituted fluorobenzene represented by: 4. A compound represented by the general formula (1) is represented by the general formula (1-2): (In the formula, e and f are integers of 0 to 5 and may be the same or different. However, when e = 0, f is 1
This is the above, and when f = 0, e is 1 or more. M represents an alkali metal or alkaline earth metal atom. The method according to claim 1, which is an alkali metal or alkaline earth metal salt of hydroxybenzophenone represented by the formula (1). 5. A fluorine-substituted aromatic compound represented by the general formula (4) has the general formula (4-2): (In the formula, g and h represent 0 or 1, and are not 0 at the same time. E and f represent 0 or 1, and are not 1. at the same time, and e is 0 or 1 when g is 0; g is 1
When, it is 0. Furthermore, f is 0 or 1 when h is 0.
And when h is 1, it is 0. The production method according to claim 1, which is a fluorine-substituted benzophenone represented by 6. A compound represented by the general formula (1) is 4,
4′-dihydroxybenzophenone, the fluorine-substituted aromatic compound represented by the general formula (4) is 4,
The production method according to claim 5, which is 4'-difluorobenzophenone. 7. A compound represented by the general formula (1) is 4,
The production method according to claim 5, which is 4'-dihydroxybenzophenone, and the fluorine-substituted aromatic compound represented by the general formula (4) is 4-hydroxy-4'-fluorobenzophenone. 8. A compound represented by the general formula (1) has the general formula (1-3): The method according to claim 1, which is an alkali metal or alkaline earth metal salt of a hydroxydiaryl sulfone represented by the formula (wherein e, f and M are the same as in the case of the general formula (1-2)). .. 9. A fluorine-substituted aromatic compound represented by the general formula (4) has the general formula (4-3): (In the formula, g and h represent 0 or 1, and are not 0 at the same time. E and f represent 0 or 1, and are not 1. at the same time, and e is 0 or 1 when g is 0; g is 1
When, it is 0. Furthermore, f is 0 or 1 when h is 0.
And when h is 1, it is 0. The production method according to claim 1, which is a fluorine-substituted diaryl sulfone represented by the formula (1). 10. A compound represented by the general formula (1):
4,4′-dihydroxydiphenyl sulfone, which is a fluorine-substituted aromatic compound represented by the general formula (4),
The method according to claim 9, which is 4,4'-difluorodiphenyl sulfone. 11. A compound represented by the general formula (1):
4,4′-dihydroxydiphenyl sulfone, wherein the fluorine-substituted aromatic compound represented by the general formula (4) is 4
The method according to claim 9, which is -hydroxy-4'-fluorodiphenyl sulfone. 12. The organic fluorinating agent is represented by the general formula (5): (In the formula, R ₂ , R ₃ , R ₄ , and R ₅ represent an alkyl group or an aryl group having 1 to 6 carbon atoms, and may be the same or different. R ₂ , R ₃ Alternatively, R ₄ and R ₅ may combine to form a nitrogen atom, or a ring containing a nitrogen atom and another heterocycle, and R ₂ and R ₄ may combine to form a nitrogen atom, or a nitrogen atom and another heterocycle. It may form a ring containing a hetero atom, X ₁ is a fluorine atom, X ₂ is a fluorine atom or a chlorine atom, and X ₁ and X ₂ are covalently bonded to a carbon atom, but only X ₁ is present. May be present covalently and X ₂ may be present in the form of a counter ion). 13. The organic fluorinating agent is represented by the general formula (5-1): The production method according to claim 1, wherein the compound is a compound represented by the formula (wherein R ₂ , R ₃ , R ₄ and R ₅ are the same as in the case of the general formula (5)). 14. The organic fluorinating agent is represented by the general formula (5-2): 2,2-difluoro-1,3-dimethyl- represented by
It is imidazolidine, The manufacturing method of Claims 1-11.