JPH04230344A - 3-substituted 2,4,5-trifluorobenzoic acid and production thereof - Google Patents

Abstract

PURPOSE:To provide the title new compound useful as an intermediate for pesticides or fluorine-contg. medicines such as fluoroquinoline-based antifungal agents. CONSTITUTION:The objective compound of formula I (R<1> and R<2> are such that one or both of them is phenyl, the other being H; part or the whole of the H atoms in these groups may be substituted by halogen, 1-8C alkoxy, CN and/or NO2), for example, 3-benzoxy-2,4,5-trifluorobenzoic acid. The present compound can be obtained by the following process: 3-hydroxy-2,4,5-trifluorobenzoic acid as raw material is reacted with an alkylating agent having in the molecule aryl group into a compound of formula II followed by saponification; alternatively, said raw material is esterified into a compound of formula III (R<4> is 1-8C alkyl, phenyl or benzyl), which is then reacted with the above-mentioned alkylating agent into a compound of formula IV followed by saponification.

Description

Detailed Description of the Invention [0001] [Industrial Application Field] The present invention relates to 3-substituted-2, Regarding 4,5-trifluorobenzoic acid, also 3-substituted-2,4,5
-Regarding a method for producing trifluorobenzoic acid. [Prior Art] Regarding the 3-substituted-2,4,5-trifluorobenzoic acid of the present invention, there is no description found in chemical abstracts, etc., and as far as the inventors know, Since no description is found in any other literature, the compound is considered to be a new substance. [0003] The present inventors have conducted intensive research in order to synthesize 3-substituted-2,4,5-trifluorobenzoic acid, which is extremely useful as an intermediate raw material for various substances as described above. As a result, 3-hydroxy-2,4,5-trifluorobenzoic acid was treated with benzyl bromide, etc. in the presence of an alkaline metal salt such as potassium carbonate in an aprotic polar solvent such as dimethylformamide. By reacting with 3-benzyloxy-2,4,5-trifluorobenzoic acid benzyl ester, this is saponified to obtain 3-benzyloxy-2,4,5- which is the object of the present invention. They discovered that trifluorobenzoic acid could be obtained, and as a result of further research, they completed the present invention. [Means for Solving the Problems] The present invention provides a novel compound, 3-substituted-2,4,5-trifluorobenzoic acid represented by the following general formula (1): (However, at least one of R1, R2 and R3 is a phenyl group, and the other two each independently represent a phenyl group or a hydrogen atom. All may be substituted with a halogen atom, an alkoxy group having 1 to 8 carbon atoms, a nitrile group and/or a nitro group.)
Regarding, 3-hydroxy-2,4,5-trifluorobenzoic acid is reacted with an alkylating agent having an aryl group in the molecule to form 3-aralkyloxy-2,4,5 of the following general formula -A method for producing 3-substituted-2,4,5-trifluorobenzoic acid represented by the above general formula (2), which is characterized by preparing an aralkyl ester of -trifluorobenzoic acid and then saponifying the same. ##STR6## (However, R1, R2 and R3 are the same as in the case of general formula (2).) Furthermore, 3-hydroxy-2
, 4,5-trifluorobenzoic acid is esterified to give 3-hydroxy-2,4,5-trifluorobenzoic acid ester of the following general formula (1), which is then reacted with an alkylating agent having an aryl group in the molecule. The 3-substituted-2,4, The present invention relates to a method for producing 5-trifluorobenzoic acid. [0010] [0010] (However, R4 represents an alkyl group having 1 to 8 carbon atoms, a phenyl group or a benzyl group) [0012] [0013] (However, R1, R2 and R3 is the same as in the case of the general formula (2), and R4 is the same as in the case of the general formula (2).) The present invention will be explained in detail below. of the present invention,
A new compound represented by the above general formula (1), 3-substituted-2,4
,5-trifluorobenzoic acid can be produced in two ways. The first method is to use 3-hydroxy-2,4,
5-trifluorobenzoic acid is reacted with an alkylating agent having an aryl group in the molecule to obtain 3-aralkyloxy-2,4,5-trifluorobenzoic acid aralkyl ester of the general formula (1), and then this is This is a saponification method. In the second method, 3-hydroxy-2,
4,5-trifluorobenzoic acid is esterified to give 3-hydroxy-2,4,5-trifluorobenzoic acid ester of the general formula (1), which is then reacted with an alkylating agent having an aryl group in the molecule. This is a method in which the 3-aralkyloxy-2,4,5-trifluorobenzoic acid ester of the general formula (1) is obtained by saponification. The method for producing 3-hydroxy-2,4,5-trifluorobenzoic acid used as the starting material in these first and second methods is not particularly limited; Examples include the methods described in Japanese Patent Application No. 63-264439 and Japanese Patent Application Laid-Open No. 1-6235, and further examples include the method proposed in Japanese Patent Application No. 2-27465. <First method> In the first method according to the present invention, reaction with an alkylating agent having an aryl group in the molecule (hereinafter sometimes referred to as alkylation reaction)
There are two methods: reacting with a halide alkylating agent in the presence of an alkaline metal salt in an aprotic polar organic solvent, and reacting with a halide alkylating agent in an aprotic organic solvent such as ether.
There are two methods: a method of reacting with a diazomethane alkylating agent; (1-1) Alkylation reaction using a halide alkylating agent When potassium carbonate is used as the alkaline metal salt, this reaction is thought to proceed according to the following reaction formula (2). [0020] [0021] (However, R1, R2 and R3 are the same as in the case of general formula (2), and X represents a halogen atom) 0
The halide alkylating agent used in this reaction has an aryl group in its molecule, and is a substituent of 3-substituted-2,4,5-trifluorobenzoic acid, which is the object compound of the present invention. It can be selected as appropriate depending on the type. Examples of such alkylating agents include bromophenylmethane, chlorophenylmethane, iodophenylmethane, bromo-p-methoxyphenylmethane, chloro-p-methoxyphenylmethane, iodo-p
-methoxyphenylmethane, bromodiphenylmethane,
Chlorodiphenylmethane, iododiphenylmethane, etc. can be used. The amount of the halide alkylating agent used is about 2 to 20 mol, and 2 to 10 mol, per 1 mol of 3-hydroxy-2,4,5-trifluorobenzoic acid as the starting material. It is preferable that The solvent used is an aprotic polar organic solvent, such as dimethylsulfoxide, diphenylsulfone, dimethylsulfone, sulfolane, N,N-dimethylformamide,
Examples include N,N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, hexamethylphosphoric triamide, dialkyl ether of glycolic acid, and quinoline. Among these, sulfolane and N,N-dimethylformamide are preferably used from the viewpoint of good reactivity when used in the method of the present invention. These aprotic polar organic solvents can be used alone or in a mixture of two or more. Additionally, the aprotic polar organic solvent may generally contain 10% by weight or less, preferably 5% by weight or less of water. The amount of the aprotic polar organic solvent used is generally 100 to 3000 parts by weight per 100 parts by weight of the starting material 3-hydroxy-2,4,5-trifluorobenzoic acid.
Parts by weight, preferably 200 to 1000 parts by weight. [0028] Preferred examples of the alkaline metal salts that can be used in this reaction include alkali metal carbonates such as potassium carbonate, sodium carbonate, and lithium carbonate. The amount of the alkaline metal salt used is about 1 to 20 moles, and about 2 to 20 moles per mole of 3-hydroxy-2,4,5-trifluorobenzoic acid as the starting material.
Preferably it is 10 mol. [0029] This reaction can usually be carried out under atmospheric pressure, the reaction temperature is generally about 20 to 140°C, preferably 50 to 100°C, and the reaction time is about 1 to 12 hours. After the reaction is completed, the reaction solution is preferably heated to 0 to 4
After cooling to 0° C., a precipitate mainly consisting of excess alkaline metal salt and by-produced alkali metal halide is removed by filtration. The filtrate thus obtained is an aqueous solution of 3-aralkyloxy-2,4,5-trifluorobenzoic acid aralkyl ester in an aprotic polar organic solvent,
From this, for example, after distilling off the solvent under conditions such as reduced pressure, add an organic solvent such as ethyl ether, i-propyl ether, or ethyl acetate and water, mix well, and separate the organic layer to be separated and concentrate. By drying, the desired 3-aralkyloxy-2,4,5-trifluorobenzoic acid aralkyl ester can be isolated. (1-2) Alkylation reaction using a diazomethane alkylating agent This reaction is preferably used when attempting to synthesize a relatively small amount of the target compound in high yield, and is generally expressed by the following reaction formula (1).
It is thought that the process will proceed according to the following. ##STR10## (However, R1 and R2 are the same as in the case of general formula (2).) Examples of the diazomethane alkylating agent used in this reaction include phenyldiazomethane and diphenyldiazomethane. I can do it. The amount of the diazomethane alkylating agent used is about 2 to 4 moles per mole of 3-hydroxy-2,4,5-trifluorobenzoic acid as the starting material.
The amount is preferably 2.0 to 2.5 moles. Solvents that can be used are, for example, aprotic organic solvents such as ethyl ether. The amount of the organic solvent used is generally 100 to 5 parts by weight per 100 parts by weight of the starting material 3-hydroxy-2,4,5-trifluorobenzoic acid.
000 parts by weight, preferably 200 to 2000 parts by weight. The reaction temperature is generally about 0 to 60°C, preferably 10 to 30°C, and the reaction time is about 0.5 to 2 hours. After completion of the reaction, the solvent is distilled off from the reaction solution containing the produced 3-aralkyloxy-2,4,5-trifluorobenzoic acid aralkyl ester under conditions such as reduced pressure, and the above-mentioned halide is then removed. The desired 3-aralkyloxy-2,4,5-trifluorobenzoic acid aralkyl ester can be isolated in the same manner as when using the alkylating agent. According to the first method of the present invention, 3 of the general formula (2) obtained by these two types of alkylation reactions
-Aralkyloxy-2,4,5-trifluorobenzoic acid aralkyl ester is saponified to give the object compound of the present invention, 3-substituted-2,4,5-2,4,5 of the general formula (1).
-trifluorobenzoic acid. (1-3) Saponification reaction This reaction involves converting the 3-aralkyloxy-2,4,5-trifluorobenzoic acid aralkyl ester of the general formula (1) obtained by the alkylation reaction to the ester and the target compound. The reaction is carried out in an aqueous solution containing a water-soluble organic solvent inert to 3-substituted-2,4,5-trifluorobenzoic acid in the presence of an alkaline compound. As such alkaline compounds, it is preferable to use alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide. The amount of the alkali metal hydroxide used is about 1 to 20 mol, preferably 1 to 5 mol, per 1 mol of 3-aralkyloxy-2,4,5-trifluorobenzoic acid aralkyl ester. preferable. [0042] The water-soluble organic solvents suitable for this reaction include, for example, dietherized products of ethylene glycol and aliphatic monohydric alcohols having 1 to 2 carbon atoms, such as ethylene glycol dimethyl ether and ethylene glycol diethyl ether; , dietherized products of diethylene glycol and aliphatic monohydric alcohols having 1 to 2 carbon atoms, such as diethylene glycol dimethyl ether and diethylene glycol diethyl ether; for example, cyclic ethers such as tetrahydrofuran, 1,3-dioxane, and 1,4-dioxane; can be mentioned. The amount of the water-soluble organic solvent used is 100% of 3-aralkyloxy-2,4,5-trifluorobenzoic acid.
It is generally 100 to 5000 parts by weight, preferably 200 to 2000 parts by weight. The reaction temperature is generally about 20 to 150°C, preferably 40 to 100°C, and the reaction time is about 1 to 12 hours. After completion of the reaction, the solvent is distilled off from the reaction solution containing the produced 3-aralkyloxy-2,4,5-trifluorobenzoate under conditions such as reduced pressure, and the obtained crystals are dissolved in water. Then, the target compound of the present invention is obtained by dissolving the crystals of 3-aralkyloxy-2,4,5-trifluorobenzoic acid using an appropriate acid such as sulfuric acid, separating by filtration, and drying. 3-aralkyloxy-2,4,5-trifluorobenzoic acid can be isolated. <Second method> The second method for producing 3-aralkyloxy-2,4,5-trifluorobenzoic acid, which is the target compound of the present invention, is a method for producing 3-hydroxy-2,4-trifluorobenzoic acid.
, 5-trifluorobenzoic acid is esterified to give 3-hydroxy-2,4,5-trifluorobenzoic acid ester of the general formula (1), and then this is reacted with an alkylating agent having an aryl group in the molecule. , 3- of the above general formula (■)
This is a method in which the aralkyloxy-2,4,5-trifluorobenzoic acid ester is prepared and then saponified. (2-1) Esterification reaction This reaction is
The starting material, 3-hydroxy-2,4,5-trifluorobenzoic acid, is reacted with various alcohols in the presence of a catalytic acid such as sulfuric acid to form 3-hydroxy-2.
, 4,5-trifluorobenzoic acid ester. Examples of the above-mentioned alcohols used in this reaction include methyl alcohol, ethyl alcohol, n- or i-propyl alcohol, n-, i-
, 1-8 carbon atoms such as t- or 2-butyl alcohol
Examples include aliphatic monohydric alcohols; phenol; benzyl alcohol; and the like. The amount of these alcohols used is based on the starting material 3-hydroxy-2,4,5-trifluorobenzoic acid 1
The amount is about 200 to 5000 parts by weight, preferably 300 to 2000 parts by weight. [0050] As the acid that serves as a catalyst for the esterification reaction,
In addition to sulfuric acid, examples include organic or inorganic acids such as hydrochloric acid and para-toluenesulfonic acid. The amount of such catalytic acid used is about 0.01 to 1 mol, and 0.05 to 0.5 mol, per 1 mol of starting material 3-hydroxy-2,4,5-trifluorobenzoic acid. It is preferable that The reaction temperature is generally about 20 to 200°C, preferably 50 to 150°C, and the reaction time is about 1 to 24 hours. After the completion of the reaction, the produced 3-hydroxy-2
, 4,5-trifluorobenzoic acid ester is distilled off under conditions such as reduced pressure to remove the solvent mainly composed of alcohols, and the resulting residue contains ethyl ether and i-propyl ether. , add an organic solvent such as ethyl acetate and water, mix well, separate the organic layer,
By concentrating and drying, the desired 3-hydroxy-
The 2,4,5-trifluorobenzoic acid ester can be isolated. (2-2) Alkylation reaction In the alkylation reaction of this second method, there are two methods similar to the alkylation reaction in the first method.
The 3-aralkyloxy-2,4,5-trifluorobenzoic acid ester can be isolated by reaction using a halide alkylating agent or a diazomethane alkylating agent under substantially similar conditions. These reactions are considered to follow the following reaction formulas (1) and (2). [Chemical Formula 11] [0055] (However, R1, R2 and R3 are the same as in the case of the general formula (■), and R4 is the same as in the case of the general formula (■).) [Chemical 12] (However, R1 and R2 are the same as in the case of the general formula (2), and R4 is the same as in the case of the general formula (2).) In the method using a halide alkylating agent, the The amount of the alkylating agent used is 1 to 10 mol, preferably about 1 to 5 mol, per 1 mol of 3-hydroxy-2,4,5-trifluorobenzoic acid ester. As in the method using a halide alkylating agent in method 1, an aprotic polar organic solvent is used, and the amount used is 3-hydroxy-2,4,5-trifluorobenzoic acid ester 100
It is generally 100 to 3000 parts by weight, preferably about 200 to 1000 parts by weight. In the method using a diazomethane alkylating agent, the amount of the alkylating agent used is 1 to 2 mol per 1 mol of 3-hydroxy-2,4,5-trifluorobenzoic acid ester. , preferably 1.0 to 1.
As in the first method using a diazomethane alkylating agent, the solvent used is an aprotic organic solvent such as ether, and the amount used is 3-hydroxy-2, Generally 100 to 100 parts by weight of 4,5-trifluorobenzoic acid ester
The amount is preferably about 5000 parts by weight, preferably about 200 to 2000 parts by weight. The thus obtained 3-aralkyloxy-
2,4,5-trifluorobenzoic acid ester is saponified and isolated in the same manner as in the first method,
3-aralkyloxy-2, which is the object compound of the present invention,
4,5-trifluorobenzoic acid can be produced. EXAMPLES The present invention will be explained in more detail with reference to Examples below. Example 1 (1) Synthesis of benzyl 3-benzoxy-2,4,5-trifluorobenzoate 3-hydroxy-2,4 was placed in a four-necked flask equipped with a stirrer, a thermometer, and a reflux condenser. , 5-trifluorobenzoic acid 5.00 g (about 26 mmol), bromophenylmethane 19.7 g (about 115 mmol) and potassium carbonate 15.9 g (about 115 mmol) in 50 ml (about 47 mmol)
．． 2g) in dimethylformamide (DMF) at 80°C.
, the reaction was allowed to proceed with stirring for 6 hours. After the reaction was completed, the mixture was allowed to cool to room temperature, the precipitated crystals were filtered off, and DMF was distilled off from the resulting filtrate under reduced pressure. Approximately 50 ml of deionized water and approximately 50 ml of ethyl ether were added to the resulting residue, mixed well, and then allowed to stand for liquid separation to separate the ether layer. The resulting ether solution was diluted with deionized water for approximately 50 min.
ml of water twice, dehydrated using anhydrous magnesium sulfate, and then distilled off the ether under reduced pressure. The resulting crude crystals were subjected to column chromatography [Column: Wako Gel C-
300 (trade name), manufactured by Wako Pure Chemical Industries, Ltd., developing solvent: hexane/ethyl acetate = 12/1] to obtain crystals of benzyl 3-benzoxy-2,4,5-trifluorobenzoate 5. 71g (about 15.3 mmol; yield 58.9%)
I got it. The physical properties of the obtained benzyl 3-benzoxy-2,4,5-trifluorobenzoate are shown in Table 1 below. [Table 1] (2) Synthesis of 3-benzoxy-2,4,5-trifluorobenzoic acid In the same apparatus as in (1) of Example 1, 3-benzoxy-2
, 0.745 g of benzyl 4,5-trifluorobenzoate
(approximately 2 mmol), 0.960 g (approximately 6 mmol) of 25% concentration sodium hydroxide aqueous solution, 6 ml of deionized water
and 6 ml (about 6.2 g) of 1,4-dioxane were charged, and the reaction was carried out at 80° C. for 6 hours. After the reaction was completed, the solvent was distilled off under reduced pressure, and 5 ml of deionized water was added to the obtained white crystals to dissolve them. Next, a 20% by weight aqueous sulfuric acid solution was added dropwise to this aqueous solution to adjust the pH to 1, and the precipitated white crystals were filtered off and dried to obtain 0.502 g (approx. .78 mmol; yield 88.
9%). The physical properties of the obtained 3-benzoxy-2,4,5-trifluorobenzoic acid are shown in Table 2 below. Example 2 (1) Synthesis of methyl 3-hydroxy-2,4,5-trifluorobenzoate In an apparatus similar to that used in Example 1 (1), 3-hydroxy-2,4,5-methyl trifluorobenzoate was prepared. Hydroxy-2,4,5-trifluorobenzoic acid 50.0g (
(approximately 260 mmol), 220 ml (approximately 173 g) of methyl alcohol, and 20 ml (approximately 37 g) of 98% concentrated sulfuric acid.
was charged and heated with stirring for 10 hours to react under reflux. After the reaction was completed, methyl alcohol was distilled off under reduced pressure, and about 100 ml of ethyl ether and about 100 ml of deionized water were added to the residue, which was thoroughly stirred and then allowed to stand for liquid separation to separate the ether layer. The obtained ether solution was washed twice with about 70 ml of deionized water, then dehydrated with anhydrous calcium chloride, the ether was distilled off under reduced pressure, and the obtained pale yellow crystals were dried and 46.2 g (about 224 mmol; yield about 86.1%) of methyl -hydroxy-2,4,5-trifluorobenzoate was obtained. The physical properties of the obtained methyl 3-hydroxy-2,4,5-trifluorobenzoate were as shown in Table 3 below. [Table 3] (2) Synthesis of methyl 3-benzoxy-2,4,5-trifluorobenzoate In an apparatus similar to that used in (1) of Example 1, 3-hydroxy-2 , methyl 4,5-trifluorobenzoate 10.
0g (approximately 48.5 mmol), bromophenylmethane 1
2.44 g (about 72.8 mmol) and 1 potassium carbonate
0.05 g (about 72.8 mmol) in 60 ml (about 57 mmol)
g) was reacted in DMF at 80° C. for 4 hours with stirring. After the reaction was completed, the reaction mixture was allowed to cool to room temperature, precipitated crystals were filtered off, and DMF was distilled off from the resulting filtrate under reduced pressure. Approximately 40 ml of deionized water and approximately 40 ml of ethyl ether were added to the resulting residue, mixed well, and then allowed to stand for liquid separation, and the ether layer was separated. The obtained ether solution was washed twice with about 40 ml of deionized water, dehydrated using anhydrous magnesium sulfate, and then the ether was distilled off under reduced pressure. -300, developing solvent: hexane/ethyl acetate = 10/1) to obtain oily 3
-Methyl benzoxy-2,4,5-trifluorobenzoate 13.9 g (approximately 47.0 mmol; yield 96.7%)
I got it. The physical properties of the obtained methyl 3-benzoxy-2,4,5-trifluorobenzoate are shown in Table 4 below. (3) Synthesis of 3-benzoxy-2,4,5-trifluorobenzoic acid Into the same apparatus as used in (1) of Example 1, 3-benzoxy-2, Methyl 4,5-trifluorobenzoate 0.5
93 g (approx. 2 mmol), 0.960 g (approx. 6 mmol) of a 25% strength by weight aqueous sodium hydroxide solution, 6 ml of deionized water and 6 ml (approx. 6.2 g) of 1,4-dioxane.
was charged, and the reaction was carried out at 80°C for 6 hours. [0080] The same procedure as in (2) of Example 1 was carried out to obtain 0.511 g of white crystals of 3-benzoxy-2,4,5-trifluorobenzoic acid (approximately 1.81
mmol; yield 90.5%). The physical properties of the obtained 3-benzoxy-2,4,5-trifluorobenzoic acid were the same as in Example 1. Example 3 (1) Synthesis of methyl 3-p-benzoxy-2,4,5-trifluorobenzoate In an apparatus similar to that used in Example 1 (1), (1) of Example 2 was added. 5.0 g (approximately 24.3 mmol) of methyl 3-hydroxy-2,4,5-trifluorobenzoate obtained in
, 5.70 g (approximately 36.4 mmol) of chloro-p-methoxyphenylmethane and 5.03 g (approximately 3 mmol) of potassium carbonate.
6.4 mmol) was reacted in 30 ml (approximately 28 g) of DMF at 80°C for 4 hours with stirring.
) to obtain an oily substance. Next, this oily substance was purified by column chromatography (column: Wakogel C-300, developing solvent: hexane/ethyl acetate = 5/1) to obtain an oily 3-
Methyl p-methoxybenzoxy-2,4,5-trifluorobenzoate 6.32 g (about 19.4 mmol; yield 7
9.9%). Obtained 3-p-methoxybenzoxy-2
The physical properties of methyl 4,5-trifluorobenzoate are shown in Table 5 below. [Table 5] (2) 3-p-methoxybenzoxy-2
, 4,5-Trifluorobenzoic acid Into the same apparatus as used in Example 1 (1), 1.31 g of methyl 3-p-methoxybenzoxy-2,4,5-trifluorobenzoate (approx. 4.02 mmol), 25% by weight
1.92 g (approx. 12 mmol) of concentrated aqueous sodium hydroxide solution, 12 ml of deionized water and 1 ml of 1,4-dioxane
2 ml (approximately 12.4 g) was charged and the reaction was carried out at 80°C for 6 hours. [0085] The same treatment as in Example 1 (2) was carried out to obtain the target compound, 3-p-methoxybenzoxy-2,
1.12 g of milky white crystals of 4,5-trifluorobenzoic acid
(about 3.58 mmol; yield 89.0%) was obtained. Obtained 3-p-methoxybenzoxy-2
, 4,5-trifluorobenzoic acid was as shown in Table 6 below. Example 4 (1) Synthesis of methyl 3-diphenylmethoxy-2,4,5-trifluorobenzoate In the same apparatus as used in Example 1 (1), the procedure was carried out. 5.0 g (about 24.3 mmol) of methyl 3-hydroxy-2,4,5-trifluorobenzoate obtained in Example 2 (1)
, 8.99 g (about 36.4 mmol) of bromodiphenylmethane and 5.03 g (about 36.4 mmol) of potassium carbonate were reacted in 30 ml (about 28 g) of DMF at 80° C. for 4 hours with stirring. [0089] The crude crystals obtained by the same treatment as in Example 2 (2) were subjected to column chromatography (column:
Purified with Wakogel C-300, developing solvent: hexane/ethyl acetate = 5/1) to give 3-diphenylmethoxy-2
, Milky white crystals of methyl 4,5-trifluorobenzoate 7
．． 58 g (approximately 20.4 mmol; yield 84.0%) was obtained. Obtained 3-diphenylmethoxy-2,4
The physical properties of methyl 5-trifluorobenzoate are shown in Table 7 below.
It was as follows. [Table 7] (2) 3-diphenylmethoxy-2,4
, 5-trifluorobenzoic acid Into the same apparatus as used in Example 1 (1), 1.50 g (about 4.03 mmol) of methyl 3-diphenylmethoxy-2,4,5-trifluorobenzoate was added. , 1.92 g (approximately 12 mmol) of 25% by weight aqueous sodium hydroxide solution
, 8 ml deionized water and 22 ml 1,4-dioxane (
About 22.7 g) was charged, and the reaction was carried out at 80°C for 6 hours. [0093] The same treatment as in Example 1 (2) was carried out to obtain the target compound, 3-diphenylmethoxy-2,4,
1.10 g (about 3.07 mmol; yield 76.2%) of milky white crystals of 5-trifluorobenzoic acid was obtained. Obtained 3-diphenylmethoxy-2,4
, 5-trifluorobenzoic acid were as shown in Table 8 below. [Table 8] Example 5 (1) Synthesis of methyl 3-diphenylmethoxy-2,4,5-trifluorobenzoate In the same apparatus as used in Example 1 (1), a procedure was carried out. 5.0 g (about 24.3 mmol) of methyl 3-hydroxy-2,4,5-trifluorobenzoate obtained in Example 2 (1)
and 30 ml (approximately 21.4 g) of ethyl ether, stirred and dissolved at room temperature (approximately 25°C), and added with diphenyldiazomethane (for example, synthesized according to the method described in JP-A-59-170146). An ethyl ether solution having a concentration of 0 mmol/l was slowly added dropwise, and the dropwise addition was stopped when the colorless reaction solution turned pale purple, and stirring was continued for 1 hour at room temperature. The diphenyldiazomethane solution used was approximately 13 ml (approximately 26 mmol)
Met. After the reaction is complete, add about 25 ml of deionized water to the reaction solution.
After washing twice with 8.48 g (approximately 22.8 mmol; yield 94%) of milky white crystals of methyl-2,4,5-trifluorobenzoate were obtained. Obtained 3-diphenylmethoxy-2,4
The physical properties of methyl 5-trifluorobenzoate are shown in Example 4.
It was the same as (1). In addition, the obtained methyl 3-diphenylmethoxy-2,4,5-trifluorobenzoate was reacted in the same manner as in Example 4 (1) to form 3-diphenylmethoxy-2,4,5-trifluorobenzoate. Obtained acid. Obtained 3-diphenylmethoxy-2,4
, 5-trifluorobenzoic acid are as shown in Example 4 (1
) was similar. Effects of the Invention The fluoroquinoline compound of the present invention synthesized using 3-substituted-2,4,5-trifluorobenzoic acid as an intermediate raw material has an aralkyl substituent at the 8-position of this compound. The oxy group leaves under relatively mild conditions, and by appropriately selecting the type of aralkyloxy group, it can be released under various conditions, so it can be used in an extremely wide range of applications as an excellent antibacterial agent. can. Thus, the 3-substituted-2,4,
5-Trifluorobenzoic acid is an extremely useful compound as an intermediate raw material for fluoroquinoline antibacterial agents.

Claims (3)

[Claims] [Claim 1] 3-substituted-2 represented by the following general formula (■)
,4,5-trifluorobenzoic acid. [Formula 1] (However, at least one of R1, R2 and R3 is a phenyl group, and the other two each independently represent a phenyl group or a hydrogen atom. Note that part of the hydrogen atoms in these groups Or all halogen atoms, carbon atoms 1 to 8
may be substituted with an alkoxy group, nitrile group and/or nitro group. ) 2. 3-hydroxy-2,4,5-trifluorobenzoic acid is reacted with an alkylating agent having an aryl group in the molecule to produce 3-aralkyloxy-2,4, A method for producing 3-substituted-2,4,5-trifluorobenzoic acid represented by the general formula (2) above, which comprises preparing an aralkyl ester of 5-trifluorobenzoic acid and then saponifying the same. [Chemical formula 2] (However, R1, R2 and R3 are the same as in the case of general formula (2).) Claim 3: 3-hydroxy-2,4,5-trifluorobenzoic acid is esterified into a 3-hydroxy-2,4,5-trifluorobenzoic acid ester of the following general formula is reacted with an alkylating agent having an aryl group to form a 3-aralkyloxy-2,4,5-trifluorobenzoic acid ester of the following general formula (1), which is then saponified. A method for producing 3-substituted-2,4,5-trifluorobenzoic acid. [Formula 3] (However, R4 represents an alkyl group having 1 to 8 carbon atoms, a phenyl group, or a benzyl group) [Formula 4] (However, R1, R2, and R3 are the same as in the case of general formula (2). (R4 is the same as in the case of general formula (■).)