JP5109499B2 - Production method of halogen-substituted benzenedimethanol - Google Patents

Description

  The present invention relates to a method for producing a halogen-substituted benzene dimethanol.

  Halogen-substituted benzenedimethanol is an important compound as a raw material and intermediate for medicines and agricultural chemicals. In particular, 2,3,5,6-tetrafluorobenzenedimethanol is known to be useful as an intermediate for household insecticides (see, for example, Patent Document 1).

As a method for synthesizing such halogen-substituted benzenedimethanol, for example, a method of reducing a corresponding halogen-substituted terephthalic acid diester using a borohydride compound (for example, see Patent Document 2 and Patent Document 3) is known. However, all of these reactions are not always satisfactory in terms of yield.
Japanese Patent No. 2606892 Chinese Patent Publication No. 1458137 WO2005 / 035474

  Under such circumstances, the present inventor has intensively studied to develop an industrially advantageous method for producing halogen-substituted benzene dimethanol. As a result, the halogen-substituted terephthalic acid diester is mixed with a metal borohydride and an acid. As a result of the reaction, it was found that halogen-substituted benzenedimethanol can be produced with good yield, and the present invention has been achieved.

（式中、Ｒ^１およびＲ^２はそれぞれ同一または相異なって、置換されていてもよいアルキル基を表し、Ｘ^１〜Ｘ^４はそれぞれ同一または相異なって、水素原子またはハロゲン原子を表す。ただし、Ｘ^１〜Ｘ^４の少なくとも一つはハロゲン原子である。）
で示されるハロゲン置換テレフタル酸ジエステルを還元する式（２）

（式中、Ｘ^１〜Ｘ^４はそれぞれ上記と同じ意味を表す。）
で示されるハロゲン置換ベンゼンジメタノールの製造法であって、さらに水素化ホウ素金属に対して、プロトン基準で０．２〜３モル倍の酸を用い、かつ、反応混合物が、固相と均一な溶相とからなる二相混合物または均一な溶液である状態で還元を実施することを特徴とする式（２）で示されるハロゲン置換ベンゼンジメタノールの製造法を提供するものである。 That is, the present invention employs a metal borohydride in the presence of an ether solvent to formula (1)

(Wherein R ¹ and R ² are the same or different and each represents an optionally substituted alkyl group, and X ^{1 to} X ⁴ are the same or different and each represents a hydrogen atom or a halogen atom. , At least one of X ^{1 to} X ⁴ is a halogen atom.)
Formula (2) for reducing the halogen-substituted terephthalic acid diester represented by formula (2)

(Wherein X ^{1 to} X ⁴ each represent the same meaning as described above.)
Wherein the acid is used in an amount of 0.2 to 3 moles of the borohydride metal based on protons, and the reaction mixture is homogeneous with the solid phase. The present invention provides a process for producing a halogen-substituted benzenedimethanol represented by the formula (2), wherein the reduction is carried out in a state of a two-phase mixture comprising a solution phase or a homogeneous solution.

  INDUSTRIAL APPLICABILITY According to the present invention, it is industrially useful in that a halogen-substituted benzene dimethanol, which is important as an intermediate for medicines and agricultural chemicals, can be produced with high yield.

  Hereinafter, the present invention will be described in detail.

In the halogen-substituted terephthalic acid diester represented by the above formula (1) (hereinafter abbreviated as halogen-substituted terephthalic acid diester (1)), in the formula, R ¹ and R ² are the same or different and are substituted. Represents an alkyl group, and X ^{1 to} X ⁴ are the same or different and each represents a hydrogen atom or a halogen atom. However, at least one of X ^{1 to} X ⁴ is a halogen atom.

  Examples of the alkyl group include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, n-decyl group, and cyclopropyl. And linear, branched or cyclic alkyl groups having 1 to 20 carbon atoms such as 2,2-dimethylcyclopropyl group, cyclopentyl group, cyclohexyl group and menthyl group. Examples of the substituent that may be present on the alkyl group include a fluorine atom; a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, and a tert-butoxy group. Group, trifluoromethoxy group, benzyloxy group, 4-methylbenzyloxy group, 4-methoxybenzyloxy group, 3-phenoxybenzyloxy group and the like, optionally substituted alkoxy group having 1 to 20 carbon atoms; phenyl group An optionally substituted aryl group having 6 to 20 carbon atoms such as 4-methylphenyl group and 4-methoxyphenyl group; phenoxy group, 2-methylphenoxy group, 4-methylphenoxy group, 4-methoxyphenoxy group, An optionally substituted aryloxy group having 6 to 20 carbon atoms such as a 3-phenoxyphenoxy group; It is below. Specific examples of the alkyl group substituted with such a substituent include a fluoromethyl group, a trifluoromethyl group, a methoxymethyl group, an ethoxymethyl group, a methoxyethyl group, and a benzyl group.

Examples of the halogen atom represented by X ^{1 to} X ⁴ include a fluorine atom, a chlorine atom, and a bromine atom.

Examples of the halogen-substituted terephthalic acid diester (1) include dimethyl 2-fluoroterephthalate, dimethyl 2-chloroterephthalate, dimethyl 2,5-difluoroterephthalate, dimethyl 2,6-difluoroterephthalate, and 2,3-difluoro. Dimethyl terephthalate, dimethyl 2,5-dichloroterephthalate, dimethyl 2,6-dichloroterephthalate, dimethyl 2,3-dichloroterephthalate, dimethyl 2,3,5-trifluoroterephthalate, 2,3,5-trichloro Dimethyl terephthalate, dimethyl 2,3,5,6-tetrafluoroterephthalate, diethyl 2,3,5,6-tetrafluoroterephthalate, di (n-propyl) 2,3,5,6-tetrafluoroterephthalate 2,3,5,6-tetrafluoroterephthalic acid diiso Lopyl, 2,3,5,6-tetrafluoroterephthalic acid di (n-butyl), 2,3,5,6-tetrafluoroterephthalic acid di (tert-butyl), 2,3,5,6-tetrachloro Dimethyl terephthalate, diethyl 2,3,5,6-tetrachloroterephthalate, di (n-propyl) 2,3,5,6-tetrachloroterephthalate, diisopropyl 2,3,5,6-tetrachloroterephthalate 2,3,5,6-tetrachloroterephthalate di (n-butyl), 2,3,5,6-tetrachloroterephthalate di (tert-butyl), 2,3,5,6-tetrachloroterephthalate Examples include di (n-pentyl) acid, di (n-hexyl) 2,3,5,6-tetrachloroterephthalate, dimethyl 2,3,5-trifluoro-6-chloroterephthalate, and the like. Among them, wherein ^{R 1} and ^{R 2} are identical in (1), halogen-substituted terephthalic acid diester (1) is preferably an alkyl group having 1 to 6 carbon atoms.

  Such halogen-substituted terephthalic acid diester (1) can be produced, for example, according to a method of reacting a corresponding acid halide with an alcohol (for example, see Japanese Patent Publication No. 4-66220).

  Examples of the borohydride metal include borohydride alkali metal salts such as sodium borohydride, lithium borohydride, and potassium borohydride, and alkaline earth metal borohydrides such as calcium borohydride and magnesium borohydride. Examples include salt. From the viewpoint of availability, alkali metal borohydride is preferably used, and sodium borohydride is more preferable.

  Such a metal borohydride may be a commercially available one or may be prepared and used. For example, sodium borohydride can be readily prepared from borate esters and sodium hydride. Other metal borohydrides can be prepared by reaction of sodium borohydride with the corresponding metal halide. For example, calcium borohydride can be obtained by reaction of sodium borohydride and calcium chloride. When preparing and using a metal borohydride, what was prepared beforehand may be added in a reaction system, and it may prepare in a reaction system and may use it as it is.

  The amount of the metal borohydride used is usually 1 mol times or more with respect to the halogen-substituted terephthalic acid diester (1), and the object of the present invention can be achieved. In general, it is 3.5 mol times or less. Preferably it is the range of 1-2.5 mol times.

  In this reaction, acids such as mineral acids, carboxylic acids, and sulfonic acids are usually used as acids. Examples of the mineral acid include hydrochloric acid, sulfuric acid, phosphoric acid and the like, and hydrochloric acid and sulfuric acid are preferably used. Examples of the carboxylic acid include aliphatic carboxylic acids such as formic acid, acetic acid, trifluoroacetic acid, propionic acid, butanoic acid, and oxalic acid; aromatic carboxylic acids such as benzoic acid; Examples of the sulfonic acid include aliphatic sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, and trifluoromethanesulfonic acid; aromatic sulfonic acids such as benzenesulfonic acid and p-toluenesulfonic acid; These acids are usually commercially available, and may be used as they are, or may be used by mixing with water or a reaction solvent described later. The mineral acid is preferably used as an aqueous solution. The concentration of the aqueous solution of mineral acid is usually 10% by weight or more, and there is no particular upper limit, but it is preferably 20 to 90% by weight.

  The amount of the acid used is usually in the range of 0.2 to 3 mol times, preferably 0.2 to 2.5 mol times, based on proton, with respect to the metal borohydride.

  This reaction is carried out in the presence of an ether solvent. Examples of such ether solvents include diethyl ether, methyl tert-butyl ether, tetrahydrofuran, dioxane, diisopropyl ether, dimethoxyethane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, and the like. Preferred are tetrahydrofuran, ethylene glycol dimethyl ether, and diethylene glycol dimethyl ether, and tetrahydrofuran is more preferred. The amount of the ether solvent used is not particularly limited as long as the liquid phase becomes uniform in the reaction mixture during the reduction. However, in consideration of volumetric efficiency and the like, practically relative to the halogen-substituted terephthalic acid diester (1). And 100 weight times or less.

  Moreover, you may use simultaneously the organic solvent which does not inhibit reaction other than an ether solvent. Examples of the organic solvent include aromatic hydrocarbon solvents such as toluene, xylene and chlorobenzene; halogen solvents such as chloroform and dichloroethane; The amount used is not particularly limited as long as the liquid phase becomes uniform in the reaction mixture being reduced.

  In the present invention, that the liquid phase is uniform means that the liquid phase is not separated into two or more layers. Therefore, a two-phase mixture composed of a solid phase and a uniform liquid phase is a mixture composed of a solid phase and a liquid phase, and the liquid phase portion is not separated into two or more layers. .

  The reaction temperature is usually in the range of -20 to 120 ° C, preferably 10 to 70 ° C.

  This reaction is usually carried out by adding an acid to a mixture containing a halogen-substituted terephthalic acid diester (1), a metal borohydride and an ether solvent. Especially, the aspect which adds an acid gradually in the said mixture on reaction temperature conditions is preferable.

  This reaction is usually performed under normal pressure conditions, but may be performed under pressurized conditions. The progress of the reaction can be confirmed by ordinary analytical means such as gas chromatography or liquid chromatography.

  After completion of the reaction, usually a dilute aqueous solution of mineral acid such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid or water is added to the reaction solution, followed by neutralization, extraction, concentration, etc. as necessary. The halogen-substituted benzene dimethanol represented by the above formula (2) (hereinafter abbreviated as “halogen-substituted benzene dimethanol (2)”) can be isolated. The obtained halogen-substituted benzenedimethanol (2) may be further purified by ordinary purification means such as crystallization and column chromatography.

  Examples of the halogen-substituted benzene dimethanol (2) thus obtained include 2-fluoro-1,4-benzene dimethanol, 2-chloro-1,4-benzene dimethanol, and 2,5-difluoro-1,4-benzene. Dimethanol, 2,6-difluoro-1,4-benzenedimethanol, 2,3-difluoro-1,4-benzenedimethanol, 2,5-dichloro-1,4-benzenedimethanol, 2,6-dichloro -1,4-benzenedimethanol, 2,3-dichloro-1,4-benzenedimethanol, 2,3,5-trifluoro-1,4-benzenedimethanol, 2,3,5-trichloro-1, 4-benzenedimethanol, 2,3,5,6-tetrafluorobenzenedimethanol, 2,3,5,6-tetrachlorobenzenedimethanol, 2, , 5-trifluoro-6-chlorobenzene dimethanol, and the like.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited by these Examples.

Example 1
A 200 ml flask equipped with a reflux condenser was charged with 9.4 g of sodium borohydride and 100 g of tetrahydrofuran at room temperature, and then 28.5 g of dimethyl 2,3,5,6-tetrafluoroterephthalate was dissolved in 100 g of tetrahydrofuran. The liquid was added. The mixture was heated to 60 ° C., and while stirring at the same temperature, 26 g of 35% by weight hydrochloric acid was added dropwise over 5 hours, and the mixture was kept warm and stirred for 2 hours, and then cooled to room temperature. The liquid phase of the reaction mixture was uniform. When 120 g of 5 wt% hydrochloric acid was added to this reaction mixture and stirred and allowed to stand, it was separated into two layers, and the layers were separated to obtain an upper organic layer. 100 g of toluene was added to the organic layer, and after washing twice with 30 g of water, the solvent was distilled off to obtain 26.0 g of 2,3,5,6-tetrafluorobenzenedimethanol as white crystals. When analyzed by the liquid chromatography internal standard method, the purity of 2,3,5,6-tetrafluorobenzenedimethanol was 80%. Yield 92%.

Example 2
A 200 ml flask equipped with a reflux condenser was charged with 4.6 g of sodium borohydride and 50 g of tetrahydrofuran at room temperature, and then 14.7 g of dimethyl 2,3,5,6-tetrafluoroterephthalate was dissolved in 50 g of tetrahydrofuran. The liquid was added. The mixture was heated to 60 ° C., and 13 g of 45 wt% sulfuric acid aqueous solution was added dropwise over 5 hours while stirring at the same temperature. After 2 hours of incubation and stirring, the mixture was cooled to room temperature. The liquid phase of the reaction mixture was uniform. When 50 g of water was added to this reaction mixture and stirred and allowed to stand, it was separated into two layers, and thus separated to obtain an upper organic layer. 50 g of toluene was added to the organic layer, and after washing twice with 30 g of water, the solvent was distilled off to obtain 12.4 g of 2,3,5,6-tetrafluorobenzenedimethanol as white crystals. When analyzed by the liquid chromatography internal standard method, the purity of 2,3,5,6-tetrafluorobenzenedimethanol was 85.7%. Yield 92%.

Example 3
A 200 ml flask equipped with a reflux condenser was charged with 1.6 g of sodium borohydride and 30 g of tetrahydrofuran at room temperature, and then 5.1 g of dimethyl 2,3,5,6-tetrafluoroterephthalate was dissolved in 20 g of tetrahydrofuran. The liquid was added. While stirring this mixture at room temperature, a mixture of 4.4 g of 35% by weight hydrochloric acid and 6 g of tetrahydrofuran was added dropwise over 5 hours, and the mixture was kept warm and stirred for 2 hours. The temperature in the flask was in the range of 25-30 ° C. The liquid phase of the reaction mixture was uniform. When 30 g of 5 wt% hydrochloric acid was added to this reaction mixture and stirred and allowed to stand, it was separated into two layers, and the layers were separated to obtain an upper organic layer. 50 g of toluene was added to the organic layer, and after washing twice with 20 g of water, the solvent was distilled off to obtain 4.4 g of 2,3,5,6-tetrafluorobenzenedimethanol as white crystals. When analyzed by a liquid chromatography internal standard method, the purity of 2,3,5,6-tetrafluorobenzenedimethanol was 85.4%. Yield 93%.

Example 4
A 200 ml flask equipped with a reflux condenser was charged with 1.7 g of sodium borohydride and 30 g of tetrahydrofuran at room temperature, and then 5.3 g of dimethyl 2,3,5,6-tetrafluoroterephthalate was dissolved in 20 g of tetrahydrofuran. The liquid was added. The mixture was heated to 50 ° C. and stirred at the same temperature. A mixture of 10.2 g of 35% by weight hydrochloric acid and 10 g of tetrahydrofuran was added dropwise over 5 hours, and the mixture was kept warm and stirred for 2 hours. Until cooled. The liquid phase of the reaction mixture was uniform. When 30 g of 5 wt% hydrochloric acid was added to this reaction mixture and stirred and allowed to stand, it was separated into two layers, and the layers were separated to obtain an upper organic layer. 50 g of toluene was added to the organic layer, and after washing twice with 30 g of water, the solvent was distilled off to obtain 4.3 g of 2,3,5,6-tetrafluorobenzenedimethanol as white crystals. When analyzed by a liquid chromatography internal standard method, the purity of 2,3,5,6-tetrafluorobenzenedimethanol was 89%. Yield 91%.

Example 5
A 200 ml flask equipped with a reflux condenser was charged with 1.7 g of sodium borohydride and 30 g of tetrahydrofuran at room temperature, and then 5.3 g of dimethyl 2,3,5,6-tetrafluoroterephthalate was dissolved in 20 g of tetrahydrofuran. The liquid was added. The mixture was heated to 50 ° C., and then a mixture of 3 g of acetic acid and 10 g of tetrahydrofuran was added dropwise over 5 hours while stirring at the same temperature. After stirring and stirring for 2 hours, the mixture was cooled to room temperature. The liquid phase of the reaction mixture was uniform. When 30 g of 5 wt% hydrochloric acid was added to this reaction mixture and stirred and allowed to stand, it was separated into two layers, and the layers were separated to obtain an upper organic layer. 50 g of toluene was added to the organic layer, and after washing twice with 30 g of water, the solvent was distilled off to obtain 4.1 g of 2,3,5,6-tetrafluorobenzenedimethanol as white crystals. When analyzed by a liquid chromatography internal standard method, the purity of 2,3,5,6-tetrafluorobenzenedimethanol was 94%. Yield 92%.

Example 6
A 50 ml flask equipped with a reflux condenser was charged with 310 mg of sodium borohydride and 7 g of tetrahydrofuran at room temperature, and then 840 mg of dimethyl 2,3,5,6-tetrafluoroterephthalate was added. The mixture was heated to 60 ° C., and then stirred at the same temperature, a mixture of 35 wt% hydrochloric acid 200 mg and tetrahydrofuran 3 g was added dropwise over 30 minutes, and the mixture was kept warm and stirred for 1 hour, and then cooled to room temperature. . The liquid phase of the reaction mixture was uniform. When 4 g of 5 wt% hydrochloric acid was added to this reaction mixture and stirred and allowed to stand, it was separated into two layers, and the layers were separated to obtain an upper organic layer. When the organic layer was analyzed by a liquid chromatography internal standard method, the yield of 2,3,5,6-tetrafluorobenzenedimethanol was 87%.

Example 7
A 100 ml flask equipped with a reflux condenser was charged with 1.6 g of sodium borohydride and 30 g of tetrahydrofuran at room temperature, and then 5.1 g of dimethyl 2,3,5,6-tetrafluoroterephthalate was dissolved in 20 g of tetrahydrofuran. The liquid was added. While this mixture was stirred at 50 ° C., a mixture of 98% by weight sulfuric acid 2.1 g and tetrahydrofuran 10 g was added dropwise over 6 hours, and the mixture was kept warm and stirred for 2 hours. The temperature in the flask was in the range of 50 to 55 ° C. The liquid phase of the reaction mixture was uniform. When 30 g of 5 wt% hydrochloric acid was added to this reaction mixture and stirred and allowed to stand, it was separated into two layers, and the layers were separated to obtain an upper organic layer. 50 g of toluene was added to the organic layer, and after washing twice with 20 g of water, the solvent was distilled off to obtain 3.8 g of 2,3,5,6-tetrafluorobenzenedimethanol as white crystals. When analyzed by a liquid chromatography internal standard method, the purity of 2,3,5,6-tetrafluorobenzenedimethanol was 82.0%. Yield 77%.

Comparative Example 1
A 200 ml flask was charged with 310 mg of sodium borohydride and 5 g of tetrahydrofuran at room temperature, and then a solution of 1.0 g of dimethyl 2,3,5,6-tetrafluoroterephthalate dissolved in 5 g of tetrahydrofuran was added. The temperature was raised to 65 ° C. After incubating and stirring at the same temperature for 6 hours, the mixture was cooled to room temperature. The liquid phase of the reaction mixture was uniform. To this reaction mixture, 10 g of 10 wt% hydrochloric acid was added dropwise at 25 to 30 ° C. over 30 minutes, and the mixture was stirred at the same temperature for 1 hour, and then extracted twice with 20 g of ethyl acetate. The organic layers were combined and washed with 10 g of water to obtain a solution containing 2,3,5,6-tetrafluorobenzenedimethanol. When analyzed by liquid chromatography internal standard method, the yield of 2,3,5,6-tetrafluorobenzenedimethanol was 57%.

Comparative Example 2
A 100 ml flask equipped with a reflux condenser was charged with 1.6 g of sodium borohydride and 30 g of tetrahydrofuran at room temperature, and then 5.1 g of dimethyl 2,3,5,6-tetrafluoroterephthalate was dissolved in 20 g of tetrahydrofuran. The liquid was added. While stirring this mixed solution at 50 ° C., 30 g of 5 wt% hydrochloric acid was added dropwise over 5 hours. After the addition, the reaction mixture was a liquid phase separated into two layers. Furthermore, it was kept warm and stirred at the same temperature for 2 hours. When this reaction mixture was allowed to stand, it was separated into two layers, and thus liquid separation was performed to obtain an upper organic layer. 50 g of toluene was added to the organic layer, and after washing twice with 20 g of water, the solvent was distilled off to obtain 3.9 g of 2,3,5,6-tetrafluorobenzenedimethanol as pale yellow crystals. When analyzed by a liquid chromatography internal standard method, the purity of 2,3,5,6-tetrafluorobenzenedimethanol was 47.0%. Yield 45%.

Comparative Example 3
A 200 ml flask equipped with a reflux condenser was charged with 1.7 g of sodium borohydride and 30 g of tetrahydrofuran at room temperature, and then 5.3 g of dimethyl 2,3,5,6-tetrafluoroterephthalate was dissolved in 20 g of tetrahydrofuran. The liquid was added. While this mixture was stirred at room temperature, a mixture of 2.8 g of water and 6 g of tetrahydrofuran was added dropwise over 5 hours, and the mixture was kept warm and stirred for 2 hours. The temperature in the flask was in the range of 25-30 ° C. The liquid phase of the reaction mixture was uniform. When 30 g of 20 wt% hydrochloric acid was added to this reaction mixture and stirred and allowed to stand, it was separated into two layers, and the layers were separated to obtain an upper organic layer. 50 g of toluene was added to the organic layer, and after washing twice with 20 g of water, the solvent was distilled off to obtain 2.8 g of 2,3,5,6-tetrafluorobenzenedimethanol as white crystals. When analyzed by a liquid chromatography internal standard method, the purity of 2,3,5,6-tetrafluorobenzenedimethanol was 78.0%. Yield 52%.

Comparative Example 4
A 100 ml flask equipped with a reflux condenser was charged with 0.81 g of sodium borohydride and 15 g of tetrahydrofuran at room temperature, and 2.6 g of dimethyl 2,3,5,6-tetrafluoroterephthalate was dissolved in 10 g of tetrahydrofuran. The liquid was added. While this mixture was stirred at 50 ° C., a mixture of 200 mg of 35 wt% hydrochloric acid and 5 g of tetrahydrofuran was added dropwise over 5 hours. Furthermore, it was kept warm and stirred at the same temperature for 2 hours. The liquid phase of the reaction mixture was uniform. When 15 g of 5 wt% hydrochloric acid was added to this reaction mixture and stirred and allowed to stand, it was separated into two layers, and the layers were separated to obtain an upper organic layer. 20 g of toluene was added to the organic layer, and after washing twice with 10 g of water, the solvent was distilled off to obtain 1.9 g of 2,3,5,6-tetrafluorobenzenedimethanol as yellowish brown crystals. When analyzed by the liquid chromatography internal standard method, the purity of 2,3,5,6-tetrafluorobenzenedimethanol was 53%. Yield 49%.

Comparative Example 5
A 100 ml flask equipped with a reflux condenser was charged with 0.81 g of sodium borohydride and 15 g of tetrahydrofuran at room temperature, and 2.6 g of dimethyl 2,3,5,6-tetrafluoroterephthalate was dissolved in 10 g of tetrahydrofuran. The liquid was added. While this mixture was stirred at 50 ° C., a mixture of 4 g of 86 wt% sulfuric acid and 10 g of tetrahydrofuran was added dropwise over 5 hours. Furthermore, it was kept warm and stirred at the same temperature for 2 hours. The liquid phase of the reaction mixture was uniform. When 20 g of water was added to this reaction solution and stirred and allowed to stand, it was separated into two layers, and thus separated to obtain an upper organic layer. 20 g of toluene was added to the organic layer, and after washing twice with 10 g of water, the solvent was distilled off to obtain 1.9 g of 2,3,5,6-tetrafluorobenzenedimethanol as yellowish brown crystals. When analyzed by a liquid chromatography internal standard method, the purity of 2,3,5,6-tetrafluorobenzenedimethanol was 51%. Yield 47%.

Claims (10)

Formula (1) using metal borohydride in the presence of an ether solvent.

(Wherein R ¹ and R ² are the same or different and each represents an optionally substituted alkyl group, and X ^{1 to} X ⁴ are the same or different and each represents a hydrogen atom or a halogen atom. , At least one of X ^{1 to} X ⁴ is a halogen atom.)
Formula (2) for reducing the halogen-substituted terephthalic acid diester represented by formula (2)

(Wherein X ^{1 to} X ⁴ each represent the same meaning as described above.)
Wherein the acid is a mineral acid, a carboxylic acid or a sulfonic acid, using 0.2 to 3 moles of acid on the proton basis relative to the metal borohydride. And the reaction mixture is a homogeneous liquid phase, or a two-phase mixture composed of a solid phase and a homogeneous liquid phase, and the reduction is performed in any state. A method for producing a halogen-substituted benzenedimethanol represented by the formula (2). The method for producing a halogen-substituted benzene dimethanol according to claim 1, wherein X ^{1 to} X ⁴ are all fluorine atoms. The method for producing a halogen-substituted benzene dimethanol according to claim 1 or 2, wherein R ¹ and R ² are the same alkyl group having 1 to 6 carbon atoms. The production of the halogen-substituted benzene dimethanol according to any one of claims 1 to 3, wherein an acid is added to the mixture containing the halogen-substituted terephthalic acid diester represented by the formula (1) and the metal borohydride. Law. The amount of the metal borohydride used is 1 to 2.5 mole times the halogen-substituted terephthalic acid diester represented by the formula (1). Manufacturing method. The method for producing a halogen-substituted benzene dimethanol according to any one of claims 1 to 5, wherein the borohydride metal is an alkali metal borohydride. The method for producing a halogen-substituted benzene dimethanol according to claim 6, wherein the alkali metal borohydride is sodium borohydride. The method for producing a halogen-substituted benzene dimethanol according to any one of claims 1 to 7, wherein the acid is a mineral acid. The method for producing a halogen-substituted benzene dimethanol according to claim 8 , wherein the mineral acid is an aqueous solution. The method for producing a halogen-substituted benzene dimethanol according to any one of claims 1 to 9 , wherein the ether solvent is tetrahydrofuran, ethylene glycol dimethyl ether or diethylene glycol dimethyl ether.