JPH07242593A - Production of 2,3,4,5-tetrafluorobenzoic acid - Google Patents

Abstract

PURPOSE:To safely obtain the subject compound useful as an intermediate for medicines, especially antimicrobial agents by fluorinating benzoic acid esters, hydrolyzing and decarboxylating the fluorinated compound and further hydrolyzing the decarboxylated compound. CONSTITUTION:A 2,3,4,5-tetrahalogeno-6-haloformyl-benzoic acid ester of formula I (X<1> to X<5> each is a halogen and at least one of X<1> to X<5> is Cl, Br or I; R is monovalent organic group) is reacted with a fluorinating agent (e.g. potassium fluoride), as necessary, in the presence of a phase-transfer catalyst (e.g. tetrabutylphosphonium bromide) to provide a compound of formula II. Then, the compound of formula II is hydrolyzed and successively heated to 100-220 deg.C to afford a 2,3,4,5-tetrafluorobenzoic acid ester of formula III. The compound of formula III is hydrolyzed to provide the objective 2,3,4,5-tetrafluorobenzoic acid of formula IV. The compound is obtained in short processes from a readily available raw material.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel method for producing 2,3,4,5-tetrafluorobenzoic acid, which is useful as an intermediate for pharmaceuticals, especially antibacterial agents.

[0002]

2. Description of the Related Art As a method for obtaining 2,3,4,5-tetrafluorobenzoic acid, phthalonitrile is chlorinated to be converted into tetrachlorophthalonitrile, and then fluorination, hydrolysis and decarboxylation are carried out ( JP 61-8534
9), chlorination of tetrachlorophthalic anhydride,
Next, the obtained 3,3,4,5,6,7-hexachloro-1- [3H] -isobenzofuranone (perchlorophthalide) was fluorinated, and the obtained tetrafluorophthaloyl fluoride was hydrolyzed. Method of decomposing and decarboxylating
2-61948), tetrachlorophthalic anhydride is reacted with amines to obtain tetrachlorophthalimides, and further fluorinated, hydrolyzed, and decarboxylated (JP-A-63).
-258442, USP 5047553) and the like are known.

[0003]

In the method using phthalonitrile as a starting material, a gas phase chlorination reaction is necessary to obtain tetrachlorophthalonitrile. At this time, the product tetrachlorophthalonitrile is toxic. Is high and there is a problem in handling. Further, in the chlorination reaction, it is necessary to vaporize phthalonitrile having a high melting point, deactivation of the chlorination catalyst, and the like, there are many problems to be adopted as an industrial process. The method via perchlorophthalide has a low yield of fluorination reaction, and further produces hydrofluoric acid during hydrolysis,
There are problems such as corrosion of the reactor. In the method via tetrachlorophthalimides, the stability of the imide at high temperature during fluorination is poor and the yield is low.

[0004]

The present invention solves the above-mentioned drawbacks and provides an industrially advantageous method for producing 2,3,4,5-tetrafluorobenzoic acid.

That is, according to the present invention, 2,3,4,5-tetrahalogeno-6-haloformyl-benzoic acid ester represented by the general formula (1) is fluorinated to give 2,3,
4,5-tetrafluoro-6-fluoroformyl-benzoic acid ester was prepared, and the 2,3,4,5-tetrafluoro-ester was used.
The fluoroformyl group of 6-fluoroformyl-benzoic acid ester is hydrolyzed to form tetrafluorophthalic acid monoester, and the tetrafluorophthalic acid monoester is decarboxylated to give 2,3,4,5-tetrafluorobenzoic acid. Provided is a method for producing 2,3,4,5-tetrafluorobenzoic acid, which comprises acid ester and hydrolyzes the 2,3,4,5-tetrafluorobenzoic acid ester.

[0006]

[Chemical 3]

(However, in the general formula (1), X ¹
X ^{5 s} may be the same or different and each represents a halogen atom, and at least one represents a chlorine atom, a bromine atom or an iodine atom. R represents a monovalent organic group. )

The reaction process in the present invention can be represented by the following formula.

[0009]

[Chemical 4]

(However, in chemical formula 4, X ¹ , X ² , X
³ , X ⁴ , X ⁵ , and R have the same meanings as described above. )

In the following description, the "halogen atom" is a fluorine atom, a chlorine atom, a bromine atom or the like, and a chlorine atom is preferable. Further, the “haloformyl group” refers to a group in which a hydrogen atom of the formyl group is replaced with a halogen atom.

"Alkyl group" means a linear structure, a branched structure,
Alternatively, any or all of them may have a ring structure. The alkyl group preferably has 1 to 20 carbon atoms, particularly preferably 1 to 10 carbon atoms, and more preferably 1 to 6 carbon atoms.
Is. Preferable specific examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an isobutyl group, a t-butyl group, a pentyl group and a hexyl group.

The "fluoroalkyl group" means a group having a structure in which some or all of the hydrogen atoms of the above "alkyl group" are substituted with fluorine atoms. The fluoroalkyl group also preferably has 1 to 20 carbon atoms, particularly preferably 1 to 10 carbon atoms, and more preferably 1 to 6 carbon atoms. The fluoroalkyl group may contain a halogen atom other than a fluorine atom, for example, a chlorine atom or a bromine atom. The fluoroalkyl group is preferably a perfluoroalkyl group having a structure in which all the hydrogen atoms of the “alkyl group” are substituted with fluorine atoms, or a structure in which the perfluoroalkyl group is present at the terminal portion of the fluoroalkyl group. Examples of fluoroalkyl groups include trifluoromethyl group, 2,2,2-trifluoroethyl group, pentafluoroethyl group, heptafluoropropyl group, 1,1-difluoro-2,2,2-trichloroethyl group, 1,1-di (trifluoromethyl)
Examples thereof include a methyl group.

The "aryl group" means a monovalent aromatic hydrocarbon group, and has a substituent (eg, lower alkyl group, lower fluoroalkyl group, halogen atom, lower alkoxyl group,
Lower alkylamino group). The aryl group is preferably a phenyl group or a derivative thereof, and examples thereof include a phenyl group, a tolyl group, a p-halophenyl group (for example, p-chlorophenyl group, p-bromophenyl group, etc.), an alkoxyphenyl group (for example, methoxyphenyl group, ethoxy group). Phenyl group, etc.) and the like.

In the 2,3,4,5-tetrahalogeno-6-haloformyl-benzoic acid ester represented by the general formula (1), which is the starting material of the present invention, X ^{1 to} X ⁵ are the same. May be different from each other and each represent a halogen atom, and at least one represents a chlorine atom, a bromine atom, or an iodine atom. It is preferable that at least one of X ^{1 to} X ⁵ is a chlorine atom. X ^{1 to} X ⁵ are X ^{1 to} X
^{The case} where all of ⁴ are chlorine atoms and X ⁵ is a chlorine atom or a fluorine atom is particularly preferable. R represents a monovalent organic group. The monovalent organic group is not particularly limited, but from the viewpoint of easy availability, an alkyl group, a fluoroalkyl group, or an aryl group is preferable, and an alkyl group or a fluoroalkyl group is particularly preferable.

2, 3, 4, 5-represented by the general formula (1)
Preferred specific examples of the tetrahalogeno-6-haloformyl-benzoic acid ester include 2,3,4,5-tetrachloro-6-chloroformylbenzoic acid-methyl ester,
2,3,4,5-Tetrachloro-6-chloroformylbenzoic acid-ethyl ester, 2,3,4,5-tetrachloro-6-chloroformylbenzoic acid-isopropyl ester, 2,3,4,5- Tetrachloro-6-chloroformylbenzoic acid- (n-propyl) ester, 2,3,4,
5-Tetrachloro-6-chloroformylbenzoic acid- (n
-Butyl) ester, 2,3,4,5-tetrachloro-
6-chloroformylbenzoic acid- (2 ', 2', 2'-trifluoroethyl) ester, 2,3,4,5-tetrachloro-6-chloroformylbenzoic acid- (2 ', 2',
2'-trichloro-1 ', 1'-difluoroethyl) ester, 2,3,4,5-tetrachloro-6-chloroformylbenzoic acid- [1', 1'-di (trifluoromethyl) methyl] ester, 2,3,4,5-tetrachloro-6-fluoroformylbenzoic acid-methyl ester,
2,3,4,5-Tetrachloro-6-fluoroformylbenzoic acid-ethyl ester, 2,3,4,5-tetrachloro-6-fluoroformylbenzoic acid-isopropyl ester, 2,3,4,5- Tetrachloro-6-fluoroformylbenzoic acid-isopropyl ester, 2,3,
4,5-Tetrachloro-6-fluoroformylbenzoic acid-butyl ester, 2,3,4,5-tetrachloro-6
-Fluoroformylbenzoic acid- (2 ', 2', 2'-trifluoroethyl) ester, 2,3,4,5-tetrachloro-6-fluoroformylbenzoic acid- (2 ',
2 ', 2'-trichloro-1', 1'-difluoroethyl) ester, 2,3,4,5-tetrachloro-6-fluoroformylbenzoic acid- [1 ', 1'-di (trifluoromethyl) methyl ] Ester etc. are mentioned.

Any of the compounds represented by the above general formula (1) can be easily synthesized. For example, 2,3,4,5-tetrachloro-6-chloroformylbenzoic acid ester is
It can be synthesized by reacting industrially easily available tetrachlorophthalic anhydride with an alcohol to obtain a tetrachlorophthalic acid monoester, and further reacting it with a chlorinating agent.

When reacted with alcohols, inorganic acids such as hydrochloric acid, phosphoric acid and sulfuric acid, organic acids such as p-toluenesulfonic acid, acetic acid and trifluoroacetic acid, or sodium hydrogen carbonate, potassium hydrogen carbonate and sodium carbonate. Inorganic bases such as potassium carbonate, sodium hydroxide and potassium hydroxide, and organic bases such as triethylamine and tributylamine may be present. The reaction temperature is preferably about 30 to 220 ° C.

As the chlorinating agent, thionyl chloride,
Examples thereof include phosphorus pentachloride and phosphorus oxychloride. The reaction with the chlorinating agent can be carried out without solvent or in a solvent. The amount of the chlorinating agent used is preferably 0.01 to 10 moles, and more preferably 0.1 to 1 mole of tetrachlorophthalic anhydride.
It is 8 to 3 mol. Further, in the chlorination reaction, a catalyst such as KF, pyridine, triethylamine or tributylamine may be present. The amount of the catalyst is preferably about 0.01 to 8 mol, and preferably 0.8 to 5 mol, per 1 mol of tetrachlorophthalic acid monoester. The reaction temperature is preferably 10 ° C to 150 ° C, preferably 30 ° C to 100 ° C.
Is.

2,3,4,5-tetrachloro-6
-When synthesizing fluoroformyl benzoate, tetrachlorophthalic acid monoester is added to NaF, K
Alkali metal fluorides such as F, RbF and CsF, or
It is preferable to react a chlorinating agent such as thionyl chloride or oxalyl chloride in the presence of hydrofluoric acid.

2,3 represented by the above general formula (1)
The 4,5-tetrahalogeno-6-haloformyl-benzoic acid ester is converted into a 2,3,4,5-tetrafluoro-6-fluoroformyl-benzoic acid ester by a fluorination reaction. 2,3,4,5-tetrafluoro-6-
The fluoroformyl-benzoic acid ester has the general formula (2)
Is a compound represented by.

[0022]

[Chemical 5]

(However, in the general formula (2), R has the same meaning as above.)

The conditions of the fluorination reaction are not particularly limited, but it is preferable to carry out the reaction with a fluorinating agent. As the fluorinating agent, NaF, KF, RbF,
Alternatively, an alkali metal fluoride such as CsF is preferable, and spray-dried potassium fluoride is particularly preferable. The amount of the fluorinating agent is 0.1 based on 1 mol of 2,3,4,5-tetrahalogeno-6-haloformyl-benzoic acid ester.
It is preferably about 20 to 20 mol, and preferably 2 to 12 mol.

The above fluorination reaction can be carried out either in the absence of solvent or in the presence of a solvent, and is preferably carried out in the presence of a solvent. The solvent is preferably an aprotic solvent, particularly N, N-dimethylformamide,
N, N-dimethylacetamide, dimethyl sulfoxide, dimethyl sulfone, sulfolane, hexamethylphosphortriamide, N-methyl-2-pyrrolidone, 1, 3
-Dimethyl-2-imidazolidinone, acetonitrile,
Benzonitrile, dioxane, diglyme, tetraglyme and the like are preferable, more preferably sulfolane,
It is 1,3-dimethyl-2-imidazolidinone. The amount of aprotic solvent is 2,3,4,5-tetrahalogeno-
The amount is preferably about 0.5 to 10 parts by weight, preferably 1 to 5 parts by weight, based on 1 part by weight of 6-haloformyl-benzoic acid ester.

In addition, during the fluorination, a phase transfer catalyst may be present as a reaction accelerator. As the phase transfer catalyst, quaternary ammonium salt, pyridinium salt, quaternary phosphonium salt and the like are preferable, and quaternary phosphonium salt is particularly preferable. Examples of the quaternary ammonium salt include tetramethylammonium chloride and tetrabutylammonium bromide, and examples of the pyridinium salt include N-neopentyl-4-.
(N ', N'-Dimethylamino) -pyridinium chloride, N- (2-ethyl-hexyl) -4- (N', N '
As the quaternary phosphonium salt such as -dimethylamino) -pyridinium chloride, tetrabutylphosphonium bromide, tetraphenylphosphonium bromide and the like are preferable. The amount of the phase transfer catalyst is usually 2, 3,
The amount is preferably 0.01 to 10 parts by weight, and more preferably 0.05 to 5 parts by weight, relative to 1 part by weight of 4,5-tetrahalogeno-6-haloformyl-benzoate.

The reaction temperature for the fluorination reaction is 50 ° C. to 250 ° C.
C is good, preferably 100 to 230 ° C.

2, 3, represented by the above general formula (2)
The 4,5-tetrafluoro-6-fluoroformyl-benzoic acid ester is converted into a tetrafluorophthalic acid monoester by the hydrolysis reaction of the fluoroformyl group. The tetrafluorophthalic acid monoester is a compound represented by the general formula (3).

[0029]

[Chemical 6]

(However, in the general formula (3), R has the same meaning as described above.)

As a method of hydrolyzing the fluoroformyl group, a known method or a known method can be applied. Usually, it can be carried out by reacting in the presence of water. The amount of water is usually 0.01 to 100 mol, preferably 0.1 to 100 mol, per mol of 2,3,4,5-tetrafluoro-6-fluoroformyl-benzoic acid ester.
It is 1 to 10 mol. An acid or a base may be present in the hydrolysis reaction. As the acid, hydrochloric acid, phosphoric acid,
Sulfuric acid is preferred. As the base, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide and the like are preferable. The amount of acid or base is 1 mol of 2,3,4,5-tetrafluoro-6-fluoroformyl-benzoic acid ester,
About 0.01 to 10 mol is preferable, and 0.1 to 5 is preferable.
It is a mole.

The temperature of the above hydrolysis reaction is about 0 ° C. to room temperature, and usually room temperature is preferable. If the reaction temperature is too high,
Not only the hydrolysis reaction of the fluoroformyl group but also the hydrolysis reaction of the ester group may proceed, which is not preferable.

The tetrafluorophthalic acid monoester represented by the general formula (3) is decarboxylated to give
The 2,3,4,5-tetrafluorobenzoic acid ester represented by the general formula (4) is produced.

[0034]

[Chemical 7]

(However, in the general formula (4), R has the same meaning as above.)

The decarboxylation reaction can be carried out by heating without a solvent or in the presence of a solvent, and it is preferable to heat in the presence of a solvent. As the solvent, water, a protic organic solvent, an aprotic organic solvent, or an aprotic apolar organic solvent can be adopted. The protic organic solvent is preferably glycols such as ethylene glycol, the aprotic polar organic solvent is preferably dimethylacetamide, sulfolane or the like, and the aprotic nonpolar organic solvent is preferably toluene, xylene or the like.

A catalyst may be present in the decarboxylation reaction. As the catalyst, ammonia, or a tertiary amine such as triethylamine or tributylamine, or an alkali metal or alkaline earth metal hydroxide, fluoride, carbonate, bicarbonate, sulfate, or organic acid salt, or Acid catalysts such as sulfuric acid, hydrochloric acid and p-toluenesulfonic acid may be used. The amount of the catalyst used is preferably about 0.1 to 10 mol, and preferably 1 to 5 mol, per 1 mol of tetrafluorophthalic acid monoester.

The temperature of the decarboxylation reaction is preferably about 100 to 220 ° C., and can be appropriately changed depending on the presence or absence of a solvent or a catalyst and the type. The amount of the catalyst used is usually about 0.1 to 10 mol, preferably 1 to 5 mol, per 1 mol of tetrafluorophthalic acid monoester.

2, 3, represented by the above general formula (4)
Hydrolysis reaction of 4,5-tetrafluorobenzoic acid monoester produces 2,3,4,5-tetrafluorobenzoic acid.

The hydrolysis reaction can be carried out in the presence of water and an acid or base. As the acid, hydrochloric acid, phosphoric acid, sulfuric acid and the like are preferable. As the base, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide and the like are preferable. The reaction temperature is 30 to 220 ° C., which can be changed depending on the types and concentrations of the acid and alkali used.
The amount of the catalyst is preferably about 0.01 to 10 mol, and preferably 0.1 to 5 mol, per 1 mol of tetrafluorobenzoic acid monoester.

The above-mentioned hydrolysis, decarboxylation and hydrolysis reaction of the formyl group may be carried out in a single stage reaction.

[0042]

EXAMPLES Examples of the present invention will be described more specifically below.

Reference Example 1 A 500 cc glass reactor equipped with a reflux condenser and a stirrer was charged with 200 g (0.70 mol) of tetrachlorophthalic anhydride and 252 g (4.20 mol) of isopropanol. The mixture was heated to 84 ° C. and stirred for 3 hours. After that, isopropanol was distilled off under reduced pressure to obtain 238 g of tetrachlorophthalic acid monoisopropyl ester. The yield was 98.4%.

Reference Example 2 Tetrachlorophthalic acid monoisopropyl ester 40 synthesized in Reference Example 1 in a 200 cc glass reactor equipped with a reflux condenser and a stirrer.
g (0.116 mol), toluene 80 g, and pyridine 9.13 g (0.116 mol) were charged, and 20.6 g (0.173 mol) of thionyl chloride with vigorous stirring.
Was added dropwise over 30 minutes. Then, the reaction solution was stirred for 3 hours. After completion of the reaction, the precipitate was removed by filtration, and the low boiling point material in the filtrate was distilled off under reduced pressure to give 2, 3, 4,
31.6 g of 5-tetrachloro-6-chloroformylbenzoic acid-isopropyl ester was obtained. Yield 74.9%
Met.

Reference Example 3 Tetrachlorophthalic acid monoisopropyl ester 10 synthesized in Reference Example 1 in a 500 cc glass reactor equipped with a reflux condenser and a stirrer.
0 g (0.289 mol), spray-dried potassium fluoride 67.0 g (1.156 mol), and N, N-dimethylformamide 200 g were charged and thionyl chloride 68.8 g (0.578 mol) with vigorous stirring. 30
It was dripped over a period of minutes. Then, it heated up at 70 degreeC and stirred for 4 hours. After completion of the reaction, the precipitate was removed by filtration, and the low boiling point material in the filtrate was distilled off under reduced pressure to give 2, 3, 4,
92.8 g of 5-tetrachloro-6-fluoroformylbenzoic acid-isopropyl ester was obtained. Yield 92.3
%Met.

[Reference Example 4] In a 500 cc glass reactor equipped with a reflux condenser and a stirrer, 100 g (0.35 mol) of tetrachlorophthalic anhydride, 37.1 g (0.368 mol) of triethylamine, and toluene. 1
00 g was charged, and 77.0 g (0.77 mol) of 2,2,2-trifluoroethanol was added dropwise over 30 minutes. The mixture was then stirred for 12 hours. After completion of the reaction, toluene and 5% hydrochloric acid were added for extraction. By concentrating the organic layer, tetrachlorophthalic acid mono (2 ', 2', 2'-trifluoroethyl) ester 1
17.5 g was obtained. The yield was 87.0%.

[Reference Example 5] In a 200 cc glass reactor equipped with a reflux condenser and a stirrer, 40 g of tetrachlorophthalic acid mono (2 ', 2', 2'-trifluoroethyl) ester synthesized in Reference Example 4 was used. (0.104 mol), toluene 80 g, and pyridine 8.22 g.
(0.104 mol) was charged, and 18.6 g (0.156 mol) of thionyl chloride was added dropwise over 30 minutes with vigorous stirring. Then, the reaction solution was stirred for 6 hours. After the reaction was completed, the precipitate was removed by filtration. By distilling off the low-boiling substance of the filtrate under reduced pressure, 2,3,4,5-tetrachloro-6-chloroformylbenzoic acid- (2 ',
2 ', 2'-trifluoroethyl) ester 35.5 g
Got The yield was 84.0%.

Example 1 20 g of 2,3,4,5-tetrachloro-6-chloroformylbenzoic acid-isopropyl ester synthesized in Reference Example 2 was placed in a 100 cc glass reactor equipped with a reflux condenser and a stirrer. (0.054
9 mol), spray dried potassium fluoride 25.5 g
(0.439 mol) and 60 g of sulfolane were charged and reacted at 180 ° C. for 20 hours with vigorous stirring. After that, inorganic substances were removed by filtration and distillation separation was performed to obtain 8.2 g of 2,3,4,5-tetrafluoro-6-fluoroformylbenzoic acid-isopropyl ester. The yield was 53.0%.

Example 2 In a 100 cc glass reactor equipped with a reflux condenser and a stirrer, 10 g of 2,3,4,5-tetrachloro-6-chloroformylbenzoic acid-isopropyl ester synthesized in Reference Example 2 was used. (0.054
9 mol), spray dried potassium fluoride 25.5 g
(0.439 mol), 2 g of tetrabutylphosphonium bromide, and 60 g of sulfolane were charged and reacted at 140 ° C. for 6 hours while vigorously stirring. After that, the inorganic substances are removed by filtration, and the mixture is separated by distillation, and 2, 3, 4, 5
11.3 g of tetrafluoro-6-fluoroformylbenzoic acid-isopropyl ester were obtained. Yield 73.0
%Met.

Example 3 20 g of 2,3,4,5-tetrachloro-6-fluoroformylbenzoic acid-isopropyl ester synthesized in Reference Example 3 was placed in a 100 cc glass reactor equipped with a reflux condenser and a stirrer. (0.05
75 mol), spray dried potassium fluoride 26.7 g
(0.46 mol), 2 g of tetrabutylphosphonium bromide, and 60 g of sulfolane were charged and reacted at 140 ° C. for 5 hours with vigorous stirring. After that, the inorganic substances are removed by filtration, and the mixture is separated by distillation to obtain 2, 3, 4, 5-
12.5 g of tetrafluoro-6-fluoroformylbenzoic acid-isopropyl ester was obtained. Yield 82.3%
Met.

Example 4 In a 100 cc glass reactor equipped with a reflux condenser and a stirrer, 2,3,4,5-tetrachloro-6-chloroformylbenzoic acid- (2 'was synthesized in Reference Example 5. , 2 ', 2'-trifluoroethyl) ester 20 g (0.0494 mol), spray-dried potassium fluoride 22.9 g (0.395 mol), tetrabutylphosphonium bromide 2 g, and sulfolane 60 g were charged and stirred vigorously. While reacting at 140 ° C. for 4 hours. Then, the inorganic substances are removed by filtration, and the mixture is separated by distillation to give 12.6 g of 2,3,4,5-tetrafluoro-6-fluoroformylbenzoic acid- (2 ', 2', 2'-trifluoroethyl) ester. Obtained. Yield 7
It was 9.1%.

Example 5 In a 200 cc three-necked flask, 20 g (0.0714 mol) of 2,3,4,5-tetrafluoro-6-fluoroformylbenzoic acid-isopropyl ester synthesized in Example 2 and carbonic acid were added. Potassium hydrogen 8.
Charge 6 g (0.0857 mol) and 60 g of water,
The mixture was heated and stirred at 60 ° C. for 5 hours. After the completion of the reaction, the suspension was cooled to room temperature, and methylene chloride and 5% hydrochloric acid were added for extraction. The solvent of the extract was distilled off under reduced pressure to obtain 18.8 g of tetrafluorophthalic acid monoisopropyl ester. The yield was 94.0%.

Example 6 In a 200 cc three-necked flask, 50 g (0.179 mol) of tetrafluorophthalic acid monoisopropyl ester synthesized in Example 5 and 66.2 g (0. (358 mol)
Was charged and heated and stirred at 120 ° C. for 4 hours. 5% Hydrochloric acid and ether were added to this solution for extraction. The ether was distilled off to obtain 40.6 g of 2,3,4,5-tetrafluorobenzoic acid-isopropyl ester. The yield was 96.2%.

Example 7 In a 200 cc three-necked flask, 30 g (0.127 mol) of 2,3,4,5-tetrafluorobenzoic acid-isopropyl ester synthesized in Example 6 and a concentration of 70% by weight were used. Charge 100g of sulfuric acid,
The mixture was reacted at 140 ° C. for 10 hours with stirring. Next, 200 cc of water was added to these reaction liquids, the mixture was allowed to cool, and the white precipitate was filtered and separated from the aqueous medium. After that, dry it 2,
23.3 g of 3,4,5-tetrafluorobenzoic acid was obtained. The yield was 94.7%.

[0055]

According to the present invention, 2,3,4,5-tetrafluorobenzoic acid can be safely synthesized in high yield. The reaction route of the method of the present invention is a short stage, and
Since the raw materials are easily available, it is an industrially very advantageous method.

Claims (9)

[Claims] 1. A compound represented by the general formula (1): 2, 3, 4, 5-
Fluorination reaction of tetrahalogeno-6-haloformyl-benzoic acid ester is carried out to give 2,3,4,5-tetrafluoro-6-fluoroformyl-benzoic acid ester, and said 2,3,4,5-tetrafluoro-6 ester -Fluoroformyl-benzoic acid ester hydroformyl group is hydrolyzed to form tetrafluorophthalic acid monoester, and the tetrafluorophthalic acid monoester is decarboxylated to give 2,3,4,5-tetrafluorobenzoic acid. 2,3,4,5 by converting the 2,3,4,5-tetrafluorobenzoic acid ester into a hydrolysis reaction
Method for producing 4,5-tetrafluorobenzoic acid. [Chemical 1] (However, in the general formula (1), X ^{1 to} X ⁵ may be the same or different and each represents a halogen atom, and at least one represents a chlorine atom, a bromine atom, or an iodine atom. R represents a monovalent organic group.) 2. A compound represented by the general formula (1): 2, 3, 4, 5-
Fluorination reaction of tetrahalogeno-6-haloformyl-benzoic acid ester 2, 3, 4,
Process for producing 5-tetrafluoro-6-fluoroformyl-benzoic acid ester. [Chemical 2] (However, in the general formula (1), X ^{1 to} X ⁵ may be the same or different and each represents a halogen atom, and at least one represents a chlorine atom, a bromine atom, or an iodine atom. R represents a monovalent organic group.) 3. The method according to claim 1, wherein X ^{1 to} X ^{4 in} the general formula (1) are each a chlorine atom, and X ⁵ is a chlorine atom or a fluorine atom. 4. The method according to claim 1, wherein R in the general formula (1) is an alkyl group, a fluoroalkyl group, or an aryl group. 5. The method according to claim 1, wherein an alkali metal fluoride is used in the fluorination reaction. 6. The production method according to claim 1, wherein a phase transfer catalyst is present during the fluorination reaction. 7. The method according to claim 6, wherein the phase transfer catalyst is tetrabutylphosphonium bromide or tetraphenylphosphonium bromide. 8. The method according to claim 1, wherein the fluorination reaction is carried out in the presence of an aprotic solvent. 9. The aprotic solvent is sulfolane or 1,
The method according to claim 8, which is 3-dimethyl-2-imidazolidinone.