JP2000327629A - Phenylacetic acid derivative, benzonitrile derivative and production thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel compound that is useful as medicines, antimicrobial agents, agrochemicals or their intermediates. SOLUTION: This compound is represented by formula I (X1-X4 are each H, a halogen or the like), typically 2-(4-carboxy-2,3-difluorophenyl)acetic acid. The compound of formula I is prepared by allowing an acid catalyst (for example, sulfuric acid) to act on a benzonitrile derivative of formula II [R1 and R2 are each cyano group, COOR3 (R3 is an alkyl group)], for example, 2-(4- cyano-2,3-difluorophenyl)malonic dimethyl ester in an amount of the catalyst of 0.01-50 moles per mole of the benzonitrile derivative in a solvent at 0-300 deg.C. The benzonitrile derivative is obtained by reaction of a compound of formula III (for example, pentafluorobenzo-nitrile) with a compound of the formula: R2-CH2R1 (for example, malonic dimethyl ester) in the presence of a basic compound, for example, an alkali metal hydroxide (potassium carbonate) at 0-200 deg.C.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a phenylacetic acid derivative, a benzonitrile derivative and a method for producing the same, and more particularly to a novel compound represented by 2- (4-carboxy-2,3,5,6-tetrafluorophenyl) acetic acid. Phenylacetic acid derivatives, diethyl 2- (4-cyano-2,3,5,6-tetrafluorophenyl) malonate, 2- (4-cyano-2,3,5,6-tetrafluorophenyl) acetic acid, etc. The present invention relates to a typical novel benzonitrile derivative and a method for producing these compounds.

[0002]

2. Description of the Related Art Compounds represented by the following general formulas (1), (2) and (3) can be used as pharmaceuticals, antibacterial agents, pesticides, etc. or as pharmaceuticals, antibacterial agents, pesticides, etc. from their structures. It is expected to be used as an intermediate or the like. These compounds are new substances that are not yet known.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a novel chemical substance and a method for producing the same.

[0004]

The present invention provides a compound represented by the following general formula (1):

[0005]

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(Wherein X ^{1 to} X ⁴ are each independently a hydrogen atom, a halogen atom, an alkyl group or an alkoxyl group).

Further, the present invention provides a compound represented by the following general formula (2):

[0008]

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Wherein X ^{1 to} X ⁴ are each independently a hydrogen atom, a halogen atom, an alkyl group or an alkoxyl group, and R ^{1 to} R ² are each independently a cyano group or a C
A benzonitrile derivative (A) represented by OOR ³ (where R ³ is an alkyl group).

Further, the present invention provides a compound represented by the following general formula (4):

[0011]

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Wherein X ^{1 to} X ⁴ are the same as described above, and a compound represented by the general formula (5):

[0013]

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Wherein the compound represented by the formula ( ¹ ) wherein R ^{1 and} R ² are the same as described above, is reacted in the presence of a basic compound. It is a manufacturing method of (A).

Further, the present invention provides a method for producing a phenylacetic acid derivative of the above general formula (1), wherein the benzonitrile derivative (A) of the above general formula (2) is reacted in the presence of an acid catalyst. is there.

Further, the present invention provides a compound represented by the following general formula (3):

[0017]

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(Wherein X ^{1 to} X ⁴ are the same as described above), which is a benzonitrile derivative (B).

Further, the present invention is characterized in that the benzonitrile derivative (A) represented by the general formula (2) is reacted in the presence of an acid catalyst, It is a manufacturing method of B).

The present invention also provides a method for producing a phenylacetic acid derivative of the above general formula (1), wherein the benzonitrile derivative (B) of the above general formula (2) is reacted in the presence of an acid catalyst. is there.

Further, the present invention provides a reaction between the compound represented by the general formula (4) and the compound represented by the general formula (5) in the presence of a basic compound, A method for producing a phenylacetic acid derivative represented by the above general formula (1), which comprises producing a benzonitrile derivative (A) and then reacting the benzonitrile derivative (A) in the presence of an acid catalyst.

Further, the present invention provides a method of reacting a compound represented by the general formula (4) with a compound represented by the general formula (5) in the presence of a basic compound, A method for producing a benzonitrile derivative (B) of the above general formula (3), which comprises producing the benzonitrile derivative (A) and then reacting the benzonitrile derivative (A) in the presence of an acid catalyst. .

[0023]

BEST MODE FOR CARRYING OUT THE INVENTION The phenylacetic acid derivative of the present invention is represented by the general formula (1). In the general formula (1), X ^{1 to} X ⁴ each independently represent a hydrogen atom, a halogen atom, It is an alkyl group or an alkoxyl group. As the halogen atom, a fluorine atom is preferable. The alkyl group and the alkoxyl group each have 1 to 1 carbon atoms.
6 alkyl groups (e.g., methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group and t-butyl group), and alkoxyl groups having 1 to 6 carbon atoms (e.g., methoxy group, Ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy and t-butoxy) are preferred. Among them, a compound in which at least one of X ^{1 to} X ⁴ is a fluorine atom is preferable. Representative examples of the phenylacetic acid derivative represented by the general formula (1) are as follows.

2- (4-carboxy-2,3-difluorophenyl) acetic acid 2- (4-carboxy-2,5-difluorophenyl)
Acetic acid 2- (4-carboxy-2,6-difluorophenyl)
Acetic acid 2- (4-carboxy-2,3,5-trifluorophenyl) acetic acid 2- (4-carboxy-2,3,6-trifluorophenyl) acetic acid 2- (4-carboxy-3-methyl-2, acetic acid 5,6-trifluorophenyl) acetic acid 2- (4-carboxy-3-methoxy-2,5,6-trifluorophenyl) acetic acid 2- (4-carboxy-2,3,5,6-tetrafluorophenyl) The benzonitrile acetate derivative (A) is represented by the general formula (2). In the general formula (2), X ^{1 to} X ⁴ are as defined above, and R ¹ and R ² are each independently And a cyano group or COOR ³ (where R ³ is an alkyl group)
It is. As the alkyl group, an alkyl group having 1 to 6 carbon atoms, particularly an alkyl group having 1 to 4 carbon atoms is preferable. Above all, R ¹ , R ²
Are both COOR ³ or a cyano group.

Representative examples of the benzonitrile derivative (A) represented by the general formula (2) are as follows.

Dimethyl 2- (4-cyano-2,3-difluorophenyl) malonate Diethyl 2- (4-cyano-2,3-difluorophenyl) malonate 2- (4-cyano-2,3-difluorophenyl) ) Dipropyl malonate 2- (4-cyano-2,3-difluorophenyl) diisopropyl malonate 2- (4-cyano-2,3-difluorophenyl) dibutyl malonate 2- (4-cyano-2,3-difluoro Diisobutyl phenyl) malonate Di-tert-butyl 2- (4-cyano-2,3-difluorophenyl) malonate Dimethyl 2- (4-cyano-2,5-difluorophenyl) malonate 2- (4-cyano-2) Dimethyl 2,6-difluorophenyl) malonate Dimethyl 2- (4-cyano-2,3,5-trifluorophenyl) malonate 2- ( Dimethyl 4-cyano-2,3,6-trifluorophenyl) malonate Dimethyl 2- (4-cyano-3-methyl-2,5,6-trifluorophenyl) malonate 2- (4-cyano-3- Dimethyl methoxy-2,5,6-trifluorophenyl) malonate Dimethyl 2- (4-cyano-2,3,5,6-tetrafluorophenyl) malonate 2- (4-cyano-2,3,5) Diethyl 6-tetrafluorophenyl) malonate Dipropyl 2- (4-cyano-2,3,5,6-tetrafluorophenyl) malonate 2- (4-cyano-2,3,5,6-tetrafluorophenyl) Diisopropyl malonate 2- (4-cyano-2,3,5,6-tetrafluorophenyl) dibutyl malonate 2- (4-cyano-2,3,5,6-tetrafluorophenyl) Diisobutyl lonate 2-tert-butyl 2- (4-cyano-2,3,5,6-tetrafluorophenyl) malonate The benzonitrile derivative (A) represented by the general formula (2) is represented by the general formula (4) ) And a compound represented by the general formula (5) in the presence of a basic compound.

In the compound represented by the general formula (4) as a starting material, X ^{1 to} X ⁴ each independently represent a hydrogen atom,
It is a halogen atom, an alkyl group or an alkoxyl group. As the halogen atom, a fluorine atom is preferable. Moreover, as an alkyl group and an alkoxyl group, a C1-C6 alkyl group (for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, and t-butyl group) is respectively used. And an alkoxyl group having 1 to 6 carbon atoms (e.g., methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy and t-butoxy). Among them, a compound in which at least one of X ^{1 to} X ⁴ is a fluorine atom is preferable.

Representative examples of the compound of the general formula (4) are as follows.

2,3,4-trifluorobenzonitrile 2,4,5-trifluorobenzonitrile 3,4,5-trifluorobenzonitrile 2,3,4,5-tetrafluorobenzonitrile 2,3,4 2,6-tetrafluorobenzonitrile 2-methyl-3,4,5,6-tetrafluorobenzonitrile 2-methoxy-3,4,5,6-tetrafluorobenzonitrile pentafluorobenzonitrile Benzonitrile is preferably used.

In the compound represented by the general formula (5), which is another starting material, R ^{1 to} R ² are each independently a cyano (CN) group or COOR ³ (where R ³ is an alkyl group) There is). The alkyl group has 1 carbon atom.
To 6, particularly preferably an alkyl group having 1 to 4 carbon atoms.

Representative examples of the compound of the general formula (5) include
Dimethyl malonate, diethyl malonate, di-n-propyl malonate, diisopropyl malonate, di-n-butyl malonate, diisobutyl malonate, di-t-butyl malonate, malononitrile, methyl cyanoacetate, Examples include ethyl cyanoacetate. Of these, malonic acid dimethyl ester and malonic acid diethyl ester are preferably used.

The compound represented by the general formula (4) and the compound represented by the general formula (5) are reacted in the presence of a basic compound to give a benzonitrile derivative represented by the general formula (2) (A ) To manufacture. Examples of the basic compound include an alkali metal hydride, an alkaline earth metal hydride, an alkali metal carbonate, an alkaline earth metal carbonate, an alkali metal alcoholate, an alkaline earth metal alcoholate, an amine, At least one selected from cyclic amines and pyridines can be used.

Representative examples of the basic compound include sodium hydride, potassium hydride, calcium hydride, sodium carbonate, potassium carbonate, calcium carbonate, magnesium carbonate, sodium methylate, sodium ethylate, sodium propylate, and sodium isopropylate. , Sodium butyrate, sodium isobutyrate, sodium t-butyrate, potassium methylate,
Potassium ethylate, potassium propylate, potassium isopropylate, potassium butylate, potassium isobutylate, potassium t-butylate, magnesium methylate, magnesium ethylate, magnesium propylate, magnesium isopropylate, magnesium butylate, magnesium isobutyrate , Magnesium t-butyrate, calcium methylate, calcium ethylate, calcium propylate, calcium isopropylate, calcium butyrate, calcium isobutyrate, calcium t-butyrate, trimethylamine, triethylamine, 1-methylpyrrolidine,
-Methylpiperidine, 1,4-dimethylpiperazine, 4
-(Dimethylamino) pyridine, 1,8-diazabicyclo [5.4.0] undecene, 1,4-diazabicyclo [2.2.2] octane, and the like. Of these, potassium carbonate, sodium carbonate, sodium hydride, calcium hydride, sodium methylate,
Sodium ethylate, sodium t-butylate, potassium methylate, potassium ethylate and potassium t-butylate are preferably used.

Although the mechanism of the above reaction is not necessarily clear, for example, when diethyl malonate is used as the compound represented by the general formula (5) and potassium carbonate is used as the basic compound, potassium is converted to the methylene group of diethyl malonate. And further substituted with a fluorine atom (para position) of the compound of the general formula (4) to obtain potassium fluoride (K
It is thought that the substitution reaction proceeds while leaving as F). Note that the present invention is not limited by such theoretical considerations.

The amount of the basic compound to be used is generally 0.1 to 10 mol, preferably 0.5 to 1.5 mol, per 1 mol of the compound represented by the general formula (4). In the absence of a basic compound, the reaction does not proceed, and even if 10 mol or more is used, no further improvement in yield or the like corresponding thereto can be obtained.

The above reaction is usually performed in an organic solvent. As the organic solvent, any organic solvent can be used, and among them, an aprotic polar organic solvent is preferably used.
Typical examples are N, N-dimethylformamide,
N, N-dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide, tetrahydrofuran, dioxane, tetramethylurea and the like can be mentioned.
When an alcoholate is used as the basic compound, an alcohol solvent is preferably used. Representative examples include methanol, ethanol, propanol, isopropanol, butanol, isobutanol, t-butanol, ethylene glycol and the like.

The reaction temperature is usually from 0 to 200 ° C.
Preferably it is 20-100 degreeC. If the temperature exceeds 200 ° C., decomposition may occur.

With respect to the ratio of the compound represented by the general formula (4) and the compound represented by the general formula (5), the two are usually reacted in an equimolar amount. May be changed.

After completion of the reaction, aging is performed if necessary. After the completion of the reaction or aging, the reaction solution is cooled to separate out by-products such as potassium fluoride by-produced by the reaction, and these separated products are separated by filtration. The benzonitrile derivative (A) represented by the general formula (2) is contained in the filtrate.
This filtrate may be subjected to the next reaction as it is, or may be collected from the filtrate, purified as necessary, and then subjected to the next reaction.

The method of recovering and purifying the benzonitrile derivative (A) represented by the general formula (2) from the filtrate is not particularly limited. For example, the filtrate is concentrated as it is, or the content is dissolved. The resulting water-insoluble solvent is added, washed with an acidic aqueous solution composed of an acid such as hydrochloric acid, dried if necessary, and then concentrated. Of course, the purity of the compound can be increased by recrystallization.

The phenylacetic acid derivative represented by the general formula (1) can be obtained by reacting the benzonitrile derivative (A) represented by the general formula (2) in the presence of an acid catalyst. By this reaction, the cyano group and -CHR < ¹ > R < ² > of the benzonitrile derivative (A) represented by the general formula (2) are hydrolyzed and decarboxylated, and COOH and CH2, respectively.
Converted to ₂ COOH. As the acid catalyst, an acid catalyst generally used for the above-mentioned hydrolysis / decarboxylation reaction can be used, and typical examples thereof include sulfuric acid,
Examples thereof include hydrochloric acid, nitric acid, formic acid, acetic acid, methanesulfonic acid, and p-toluenesulfonic acid. These can be used alone or in combination of two or more.
Of these, sulfuric acid is preferably used.

The amount of the acid catalyst used is usually 1 mole of the benzonitrile derivative (A) represented by the general formula (2).
It is 0.01 to 50 mol, preferably 0.1 to 20 mol.

The above reaction is usually carried out in water and / or an organic solvent. Representative examples of the organic solvent include N, N-dimethylformamide, N, N-dimethylacetamide,
Examples thereof include N-methylpyrrolidone, dimethylsulfoxide, tetrahydrofuran, dioxane, tetramethylurea and the like.

The reaction temperature is usually from 0 to 300 ° C.
Preferably it is 50-200 degreeC. After completion of the reaction, aging is performed if necessary. When the reaction solvent is water after completion of the reaction or aging, for example, the target substance is deposited by cooling the reaction solution, and then recovered by filtration. The obtained compound may be washed and purified with water or the like, if necessary. Alternatively, the target substance may be extracted by adding a water-insoluble solvent to the reaction solution, and the extract may be washed with water as necessary, dried, and then concentrated. When the reaction solvent is an organic solvent, it may be washed with water if necessary, dried, and then concentrated.

The phenylacetic acid derivative represented by the general formula (1) of the present invention can be obtained by reacting the benzonitrile derivative (B) represented by the general formula (3) in the presence of an acid catalyst.

The benzonitrile derivative (B) is represented by the general formula (3). In the general formula (3), X ^{1 to} X ⁴ have the same meanings as described above.

Representative examples of the benzonitrile derivative (B) represented by the general formula (3) are as follows.

2- (4-cyano-2,3-difluorophenyl) acetic acid 2- (4-cyano-2,5-difluorophenyl) acetic acid 2- (4-cyano-2,6-difluorophenyl) acetic acid 2- (4-cyano-2,3,5-trifluorophenyl) acetic acid 2- (4-cyano-2,3,6-trifluorophenyl) acetic acid 2- (4-cyano-3-methyl-2,5,6 -(Trifluorophenyl) acetic acid 2- (4-cyano-3-methoxy-2,5,6-trifluorophenyl) acetic acid 2- (4-cyano-2,3,5,6-tetrafluorophenyl) acetic acid general formula Benzonitrile derivative (B) represented by (3)
Is obtained by reacting the benzonitrile derivative (A) represented by the general formula (2) in the presence of an acid catalyst. By this reaction, -CHR ¹ R ² of the benzonitrile derivative (A) represented by the general formula (2) is hydrolyzed and decarboxylated to form CH 2.
Converted to ₂ COOH. As the acid catalyst, an acid catalyst generally used for the above-mentioned hydrolysis / decarboxylation reaction can be used, and typical examples thereof include sulfuric acid,
Examples include hydrochloric acid, nitric acid, formic acid, acetic acid, methanesulfonic acid, p-toluenesulfonic acid and the like. These can be used alone or in combination of two or more.
Of these, hydrochloric acid is preferably used.

The amount of the acid catalyst used is usually 1 mole of the benzonitrile derivative (A) represented by the general formula (2).
It is 0.01 to 50 mol, preferably 0.1 to 20 mol.

The above reaction is usually carried out in water and / or an organic solvent. Representative examples of the organic solvent include N, N-dimethylformamide, N, N-dimethylacetamide,
Examples thereof include N-methylpyrrolidone, dimethylsulfoxide, tetrahydrofuran, dioxane, tetramethylurea and the like.

The reaction temperature is usually from 0 to 300 ° C.,
Preferably it is 50-200 degreeC. After completion of the reaction, aging is performed if necessary. When the reaction solvent is water after completion of the reaction or aging, for example, the target substance is deposited by cooling the reaction solution, and then recovered by filtration. The obtained compound may be washed and purified with water or the like, if necessary. Alternatively, the target substance may be extracted by adding a water-insoluble solvent to the reaction solution, and the extract may be washed with water as necessary, dried, and then concentrated. When the reaction solvent is an organic solvent, it may be washed with water if necessary, dried, and then concentrated.

Next, a method for producing the phenylacetic acid derivative represented by the general formula (1) from the benzonitrile derivative (B) represented by the general formula (3) will be described.

The phenylacetic acid derivative represented by the general formula (1) can be obtained by reacting the benzonitrile derivative (B) represented by the general formula (3) in the presence of an acid catalyst. By this reaction, the cyano group of the benzonitrile derivative (B) represented by the general formula (3) is hydrolyzed, and
Converted to OH. As the acid catalyst, an acid catalyst generally used for the above-mentioned hydrolysis reaction can be used, and typical examples thereof include sulfuric acid, hydrochloric acid, nitric acid, formic acid, acetic acid, methanesulfonic acid, and p-toluene. Sulfonic acid and the like can be mentioned. These can be used alone or in combination of two or more. Of these,
Sulfuric acid is preferably used.

The amount of the acid catalyst used is usually 1 mole of the benzonitrile derivative (B) represented by the general formula (3).
It is 0.01 to 50 mol, preferably 0.1 to 20 mol.

The above reaction is usually carried out in water and / or an organic solvent. Representative examples of the organic solvent include N, N-dimethylformamide, N, N-dimethylacetamide,
Examples thereof include N-methylpyrrolidone, dimethylsulfoxide, tetrahydrofuran, dioxane, tetramethylurea and the like.

The reaction temperature is usually from 0 to 300 ° C.
Preferably it is 50-200 degreeC. After completion of the reaction, aging is performed if necessary. When the reaction solvent is water after completion of the reaction or aging, for example, the target substance is deposited by cooling the reaction solution, and then recovered by filtration. The obtained compound may be washed and purified with water or the like, if necessary. Alternatively, the target substance may be extracted by adding a water-insoluble solvent to the reaction solution, and the extract may be washed with water as necessary, dried, and then concentrated. When the reaction solvent is an organic solvent, it may be washed with water if necessary, dried, and then concentrated.

Phenylacetic acid derivatives and benzonitrile derivatives (A) represented by the general formulas (1), (2) and (3)
And the benzonitrile derivative (B) are useful as pharmaceuticals, antibacterial agents and the like, or intermediates thereof.

[0058]

According to the method of the present invention, general formula (1):
The phenylacetic acid derivative, benzonitrile derivative (A) and benzonitrile derivative (B) represented by (2) and (3) can be produced in a high yield by a simple method.

[0059]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples.

Example 1 <Production of Benzonitrile Derivative (A)> In a four-necked flask sufficiently purged with nitrogen, 19.559 g of pentafluorobenzonitrile as fluorobenzonitrile was charged, and 100 ml of dimethylformamide was added and dissolved. . Further, 16.221 g of diethyl malonate and 27.595 g of potassium carbonate as a basic compound were charged. The mixture was heated to 62 ° C. with stirring and reacted for 4 hours.

After completion of the reaction, the reaction solution was allowed to cool, and the precipitated crystals were filtered. 1N-hydrochloric acid was added to the filtrate, and extracted with ether. The extract was washed with water, further washed with saturated saline, and dried over sodium sulfate. After the sodium sulfate was filtered off, the filtrate was concentrated to obtain 33.424 g of an oily substance. This crystal
^When analyzed by ¹⁹ F-NMR, 2- (4-cyano-
Diethyl 2,3,5,6-tetrafluorophenyl) malonate was included at a purity of 91.4%.

¹ H-NMR (CDCl ₃ ): 1.29 (6
H, t), 4.29 (4H, q), 5.03 (1H,
s) ¹⁹ F-NMR (CDCl ₃ ) (standard substance: trifluoroacetic acid): −60.8 (2F, m), −56.1 (2F,
m) M / e = 333 Example 2 <Production of phenylacetic acid derivative from benzonitrile derivative (A)>
29.805 g of diethyl (4-cyano-2,3,5,6-tetrafluorophenyl) malonate and 215.46 g of a 68% aqueous sulfuric acid solution were charged. The mixture is stirred 1
The mixture was heated to 10 ° C. and reacted for 8 hours.

After completion of the reaction, the reaction solution was allowed to cool, water was added, and the mixture was extracted with diethyl ether. A saturated aqueous sodium hydrogen carbonate solution was added to the extract to perform extraction. The aqueous layer was made acidic with 1N hydrochloric acid and extracted with diethyl ether. The extract was dried over sodium sulfate. After the sodium sulfate was filtered off, the filtrate was concentrated to obtain 13.711 g of crystals. This crystal was converted to ¹⁹ F-NM
When analyzed by R, 2- (4-carboxy-2,3,
5,6-Tetrafluorophenyl) acetic acid was contained at 98.3% purity.

¹ H-NMR (acetone-d6): 3.9
3 (2H, s), 8.9 (2H, b) ¹⁹ F-NMR (acetone-d6): -67.7 (2F,
m), -66.8 (2F, m) Example 3 <Production of benzonitrile derivative (B) from benzonitrile derivative (A)> In a three-necked flask, the 2- (4-) obtained in Example 1 was placed. Diethyl cyano-2,3,5,6-tetrafluorophenyl) malonate 20.176 g, acetic acid 2
4.466 g and 27.810 g of hydrochloric acid were charged. The mixture was heated to 109 ° C. with stirring, and reacted for 3.5 hours while distilling off the solvent.

After the completion of the reaction, the reaction solution was allowed to cool, water was added, and the mixture was extracted with diisopropyl ether. The extract was washed with water and dried over sodium sulfate. The sodium sulfate was filtered off, and the filtrate was concentrated to obtain crystals. Hexane was added to these crystals,
After suction filtration, the cake was dried under reduced pressure.
0.499 g was obtained. When the crystals were analyzed by ¹⁹ F-NMR, 2- (4-cyano-2,3,5,6-tetrafluorophenyl) acetic acid was obtained with a purity of 94.1%.

¹ H-NMR (acetone-d6): 3.9
9 (2H, s), 8.4-11 (1H, b) 19 F-NMR ( acetone -d6): - 65.5 (2F,
m), -60.5 (2F, m) M / e = 233 Example 4 <Production of phenylacetic acid derivative from benzonitrile derivative (B)> In a three-necked flask, 2- (4-cyano-2,
(3,5,6-tetrafluorophenyl) acetic acid 2.150
g of 15.63 g of a 63% aqueous sulfuric acid solution. The mixture was heated to 120 ° C. with stirring and reacted for 4 hours.

After completion of the reaction, the reaction solution was allowed to cool, water was added, and the mixture was extracted with diethyl ether. The extract was dried over sodium sulfate. The sodium sulfate was filtered off, and the filtrate was concentrated to obtain 2.245 g of crystals. When the crystals were analyzed by ¹⁹ F-NMR, 2- (4-carboxy-2,3,5,6-tetrafluorophenyl) acetic acid was obtained with a purity of 99%.

¹ H-NMR (acetone-d6): 3.9
3 (2H, s), 8.9 (2H, b) ¹⁹ F-NMR (acetone-d6): -67.7 (2F,
m), -66.8 (2F, m)

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07C 255/54 C07C 255/54 255/57 255/57 // C07B 61/00 300 C07B 61/00 300

Claims (9)

[Claims] 1. General formula (1): (Wherein, X ^{1 to} X ⁴ are each independently a hydrogen atom, a halogen atom, an alkyl group or an alkoxyl group). 2. General formula (2): (Wherein, X ¹ to X ⁴ are each independently a hydrogen atom, a halogen atom, an alkyl group or an alkoxyl group, R ¹
To R ² are each independently a cyano group or a COOR ³ (where R ³ is an alkyl group), a benzonitrile derivative (A). 3. A compound of the general formula (4): Wherein X ^{1 to} X ⁴ are each independently a hydrogen atom, a halogen atom, an alkyl group or an alkoxyl group, and a compound represented by the general formula (5): (Wherein R ^{1 and} R ² are each independently a cyano group or a C
3. The process for producing a benzonitrile derivative (A) according to claim 2, wherein a compound represented by OOR ³ (where R ³ is an alkyl group) is reacted in the presence of a basic compound. Method. 4. The benzonitrile derivative (A) according to claim 2.
Is reacted in the presence of an acid catalyst. 5. A compound of the general formula (3): (Wherein X ^{1 to} X ⁴ are each independently a hydrogen atom, a halogen atom, an alkyl group or an alkoxyl group) (B). 6. The benzonitrile derivative (A) according to claim 2.
Is reacted in the presence of an acid catalyst to produce the benzonitrile derivative (B). 7. The benzonitrile derivative (B) according to claim 5.
Is reacted in the presence of an acid catalyst. 8. A compound of the general formula (4): (Wherein X ^{1 to} X ⁴ are each independently a hydrogen atom, a halogen atom, an alkyl group or an alkoxyl group) and a compound represented by the general formula (5): (Wherein R ^{1 and} R ² are each independently a cyano group or a C
Reacting with a compound represented by OOR ³ (where R ³ is an alkyl group) in the presence of a basic compound to produce the benzonitrile derivative (A) of claim 2; The method for producing a phenylacetic acid derivative according to claim 1, wherein the benzonitrile derivative (A) is reacted in the presence of an acid catalyst. 9. A compound of the general formula (4): Wherein X ^{1 to} X ⁴ are each independently a hydrogen atom, a halogen atom, an alkyl group or an alkoxyl group, and a compound represented by the general formula (5): (Wherein R ^{1 and} R ² are each independently a cyano group or a C
Reacting with a compound represented by OOR ³ (where R ³ is an alkyl group) in the presence of a basic compound to produce the benzonitrile derivative (A) of claim 2; The method for producing a benzonitrile derivative (B) according to claim 5, wherein the benzonitrile derivative (A) is reacted in the presence of an acid catalyst.