JP6830051B2 - Method for producing high-purity trifluoromethyl group-substituted aromatic ketone - Google Patents

Description

The present invention relates to a method for producing a high-purity trifluoromethyl group-substituted aromatic ketone. In particular, the present invention relates to a method for producing an industrially excellent high-purity trifluoromethyl group-substituted aromatic ketone.

Trifluoromethyl group-substituted aromatic ketones are useful compounds such as fine chemicals, raw materials for medical and agricultural chemicals, raw materials for resins and plastics, electronic information materials, and optical materials. Trifluoromethyl group-substituted aromatic ketones are useful in a wide range of industrial applications. In particular, as a raw material for medical and agricultural chemicals, the purity of a trifluoromethyl group-substituted aromatic ketone is required to be extremely high, exceeding 99%.

Patent Document 1 describes, as a method for producing a trifluoromethyl group-substituted aromatic ketone, a halogen-substituted benzotrifluoride compound is reacted with a magnesium metal, converted into a Grignard reagent, and the Grignard reagent is reacted with an acid anhydride. , Hydrolyze with an aqueous hydrogen chloride solution and obtain trifluoromethyl group-substituted aromatic ketone by distillation from the crude solution.

However, in Patent Document 1, the obtained trifluoromethyl group-substituted aromatic ketone was not obtained with a purity exceeding 99%, and the distillation yield was as low as 66 to 72%. When producing a trifluoromethyl group-substituted aromatic ketone, fatty acid halogenated butyl ester and fatty acid trifluoromethylphenyl ester are by-produced as impurities. Since these impurities have a boiling point close to that of the target trifluoromethyl group-substituted aromatic ketone, it is difficult to separate by distillation, which makes it difficult to obtain a high-purity target product. Further, when the fatty acid halogenated butyl ester and the fatty acid trifluoromethylphenyl ester are removed by distillation to obtain a high-purity target product, the distillation loss of the target product becomes large and the distillation yield is greatly reduced.

Therefore, in order to obtain a high-yield and high-purity target product, a method of reducing the fatty acid halogenated butyl ester and the fatty acid trifluoromethylphenyl ester before distillation has been desired.

International Publication 2016/043079

An object of the present invention is to provide a method for producing a high-purity trifluoromethyl group-substituted aromatic ketone in a high yield.

（但し、Ｘは、ＣｌまたはＢｒである。）
マグネシウム金属と反応させて、グリニャール試薬に転化し、該グリニャール試薬を酸無水物と反応させた後、酸を含む水溶液で加水分解処理して、下記一般式（２）で示されるトリフルオロメチル基置換芳香族ケトンを生成させた後、

（但し、ｎは、１〜４の整数である。）
前記反応の副生成物を、塩基を含む水溶液を用いて、相関移動触媒を共存させ、塩基性条件下で加水分解処理することを特徴とする。 The method for producing a high-purity trifluoromethyl group-substituted aromatic ketone of the present invention uses a halogen-substituted benzotrifluoride compound represented by the following general formula (1).

(However, X is Cl or Br.)
It is reacted with a magnesium metal to be converted into a Grignard reagent, the Grignard reagent is reacted with an acid anhydride, and then hydrolyzed with an aqueous solution containing an acid to carry out a trifluoromethyl group represented by the following general formula (2). After generating the substituted aromatic ketone

(However, n is an integer of 1 to 4.)
The by-products of the reaction, with an aqueous solution containing a base, it is allowed to coexist phase transfer catalyst, characterized by hydrolysis under basic conditions.

The method for producing a high-purity trifluoromethyl group-substituted aromatic ketone of the present invention rapidly removes fatty acid halogenated butyl ester and fatty acid trifluoromethylphenyl ester, which are impurities that are difficult to distill and separate from trifluoromethyl group-substituted aromatic ketone. It can be hydrolyzed under basic conditions and the degradation products can be transferred to the aqueous phase and removed. By distilling the decomposed oil phase, a high-purity trifluoromethyl group-substituted aromatic ketone can be obtained with a high distillation yield, which is an industrially excellent production method.

The trifluoromethyl group-substituted aromatic ketone produced by the method for producing a high-purity trifluoromethyl group-substituted aromatic ketone of the present invention is used as a fine chemical, a raw material for medical and agricultural chemicals, a resin / plastic raw material, an electronic information material, an optical material, and the like. be able to.

（但し、Ｘは、ＣｌまたはＢｒである。） Details of the present invention will be described below.
The method for producing a high-purity trifluoromethyl group-substituted aromatic ketone of the present invention uses a halogen-substituted benzotrifluoride compound represented by the following general formula (1) as a starting substrate.

(However, X is Cl or Br.)

Specific examples of the halogen-substituted benzotrifluoride compound include o-chlorobenzotrifluoride, o-bromobenzotrifluoride, m-chlorobenzotrifluoride, m-bromobenzotrifluoride, p-chlorobenzotrifluoride, and p-bromo. It is a benzotrifluoride. Preferred are o-chlorobenzotrifluoride and o-bromobenzotrifluoride.

In the present invention, the halogen atom of the halogen-substituted benzotrifluoride compound is reacted with a magnesium metal to convert it into a Grignard reagent. A known conversion reaction can be used for the conversion reaction to the Grignard reagent.

In the present invention, the magnesium metal used is preferably in the form of powder or shavings.

In the present invention, the amount of the magnesium metal used is preferably 0.8 to 3 mol times that of the raw material halogen-substituted benzotrifluoride compound.

In the present invention, it is preferable to add iodine, bromine, or an inexpensive compound containing these in order to remove the surface oxide film of the magnesium metal and enhance the reactivity. Preferable examples of such compounds include methyl iodide, methyl bromide, ethyl iodide, ethyl bromide and the like.

In the present invention, the reaction of conversion to Grignard reagent is carried out in a dehydrated system. Therefore, in the reaction, a solvent dehydrated in advance may be used, or before the reaction, an inexpensive Grignard reagent may be added to the solvent to remove water contained in the solvent.

As the solvent used in the production of the Grignard reagent of the present invention, a solvent capable of efficiently advancing the reaction is used. The solvent used in the production of Grignard reagents is tetrahydrofuran.

The amount of the solvent used is preferably determined according to the solubility of the halogen-substituted benzotrifluoride compound or the Grignard reagent, the concentration of the slurry, or the properties of the reaction solution. The amount of the solvent used is preferably 1 to 100 mol times the amount of the halogen-substituted benzotrifluoride compound. If it is 1 mol times or less, the yield of Grignard reagent may be low, and if it is 100 mol times or more, the productivity may be deteriorated, which may be an uneconomical process.

In the production of the Grignard reagent of the present invention, it is preferable that LiCl (lithium chloride) coexists when the halogen-substituted benzotrifluoride compound represented by the general formula (1) is reacted with a magnesium metal and converted into a Grignard reagent. This is because the coexistence of LiCl causes the Grignard reagent to be produced rapidly, and the subsequent reaction with the acid anhydride occurs in a high yield.

In the present invention, the amount of LiCl used is preferably 0.01 to 3 mol times that of the halogen-substituted benzotrifluoride compound. More preferably, the amount is 0.05 to 1 molar times. When the amount of LiCl is 0.01 to 3 mol times that of the halogen-substituted benzotrifluoride compound, the Grignard reagent is produced more rapidly and LiCl is completely dissolved in the reaction system.

Specific examples of the acid anhydride to be reacted with the Grignard reagent in the production method of the present invention include acetic anhydride, propionic anhydride, butyric anhydride, and valeric anhydride. The acid anhydride to be reacted with the Grignard reagent in the production method of the present invention is preferably acetic anhydride, propionic anhydride, or butyric anhydride.

The amount of the acid anhydride used is preferably 0.5 to 10 mol times, more preferably 1 mol to 5 mol times, with respect to 1 mol of the halogen-substituted benzotrifluoride compound. If the amount is less than 0.5 mol times, the unreacted Grignard reagent may remain, the yield may decrease, and the isolation and purification of the target product may be burdensome. If the amount is more than 10 molar times, unreacted acid anhydride may remain and productivity may be deteriorated, which may increase the load on separation of unreacted acid anhydride and trifluoromethyl group-substituted aromatic ketone. is there.

In the present invention, a solvent may be used for the reaction between the Grignard reagent and the acid anhydride. The solvent is preferably a solvent that does not inhibit the reaction and can proceed efficiently. Specific examples of the solvent include diethyl ether, diisopropyl ether, tetrahydrofuran, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, 1,3-dioxane, 1,4-dioxane, cyclopropylmethyl ether. , Methyl-tertiary butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, benzene, toluene, xylene and the like. Of these, tetrahydrofuran, 1,3-dioxane, cyclopropylmethyl ether, benzene, toluene and xylene are preferable. It is mesitylene.

The amount of the solvent used is preferably 0.05 to 50 times by weight with respect to the Grignard reagent. If the amount of the solvent used is 0.05 times by weight or less, it is difficult to remove the heat of reaction, and the reaction may run out of control. If it is 50 times or more by weight, productivity may be poor.

As a method for reacting a Grignard reagent with an acid anhydride, a solution containing an acid anhydride may be put into a Grignard reagent solution, or a Grignard reagent solution may be put into a solution containing an acid anhydride. In order to prevent sudden exothermic reaction and reaction runaway, the solution to be added is added while controlling the temperature in the reaction system so that it is within the set range, such as continuously or dividedly added over time. It is preferable to adjust the speed. The time required for charging is preferably 0.5 to 6 hours.

In the production method of the present invention, the reaction temperature of the Grignard reagent and the acid anhydride is preferably 0 to 100 ° C, more preferably 10 to 50 ° C. If the reaction temperature is lower than 0 ° C, the reaction hardly proceeds, and even if the reaction proceeds, it may be stopped in the middle, and if it exceeds 100 ° C, the Grignard reagent is thermally decomposed before the reaction. Is not preferable.

In the production method of the present invention, the reaction time of the Grignard reagent and the acid anhydride is usually 0.5 to 40 hours at 0 to 100 ° C. after mixing the entire amount of the Grignard reagent solution and the solution containing the acid anhydride.

In the production method of the present invention, after the reaction between the Grignard reagent and the acid anhydride is completed, a salt composed of a trifluoromethyl group-substituted aromatic ketone and magnesium halide is formed. Therefore, this is prepared with an aqueous solution containing an acid. Hydrolysis gives a trifluoromethyl group-substituted aromatic ketone. Preferably, an aqueous solution containing an acid composed of a mineral acid such as hydrochloric acid, nitric acid, or sulfuric acid is added to the reaction termination solution, and a salt composed of a trifluoromethyl group-substituted aromatic ketone and magnesium halide is hydrolyzed to produce a halogen. A method of obtaining an oil phase containing a trifluoromethyl group-substituted aromatic ketone after removing magnesium oxide into the aqueous phase is preferable.

The amount of acid used is preferably 0.1 to 2.0 mol times the amount of the magnesium metal used. If the amount of acid is less than 0.1 molar times, a salt consisting of a trifluoromethyl group-substituted aromatic ketone and magnesium halide may remain. If an excess amount of acid exceeding 2.0 mol times is used, the base will be consumed by the remaining acid during subsequent hydrolysis under basic conditions, so an excess amount of base is required. turn into. The concentration of the aqueous acid solution is preferably 5 to 35% by weight.

After the hydrolysis treatment with an acid, the underlying aqueous phase is removed to obtain an oil phase containing a trifluoromethyl group-substituted aromatic ketone. After that, it is preferable to remove the remaining acidic water by washing with water.

（但し、ＸはＣｌまたはＢｒ、ｎは１〜４の整数である。）

（但し、ｎは１〜４の整数である。） Subsequently, the obtained oil phase containing a trifluoromethyl group-substituted aromatic ketone is hydrolyzed under basic conditions using an aqueous solution containing a base. As a result, the fatty acid halogenated butyl ester and the fatty acid trifluoromethylphenyl ester, which are difficult to separate from the target trifluoromethyl group-substituted aromatic ketone, are decomposed and removed. The fatty acid halogenated butyl ester and the fatty acid trifluoromethylphenyl ester are by-products represented by the following general formulas (3) and (4).

(However, X is Cl or Br, and n is an integer of 1 to 4.)

(However, n is an integer of 1 to 4.)

Fatty acids, butyl alcohol halides and trifluoromethylphenol, which are decomposition products of these substances, are mainly extracted and removed on the aqueous phase side. Some impurities other than the fatty acid halogenated butyl ester and the fatty acid trifluoromethylphenyl ester remaining in the oil phase have significantly different physical properties from the trifluoromethyl group-substituted aromatic ketone, and thus can be easily separated.

The bases used in the present invention are inorganic bases such as lithium hydrogen carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, lithium carbonate, sodium carbonate, potassium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium methoxyd, sodium methoxy. Do, potassium methoxydo, lithium ethoxydo, sodium ethoxydo, potassium ethoxydo, lithium propoxide, sodium propoxide, potassium propoxide, lithium butoxide, sodium butoxide, alkali metal alkoxides such as potassium butoxide and the like can be mentioned. Among them, inorganic bases of lithium hydroxide, sodium hydroxide and potassium hydroxide are more preferable.

The amount of the base used may be 1.1 mol times or more with respect to the acid anhydride used, and usually 1.2 to 5.0 mol times is preferably used.

When the oil phase containing a trifluoromethyl group-substituted aromatic ketone is hydrolyzed under basic conditions using an aqueous solution containing a base, it is preferably carried out in the presence of a phase transfer catalyst. By adding and coexisting with a phase transfer catalyst, hydrolysis of the fatty acid halogenated butyl ester and fatty acid trifluoromethylphenyl ester, which are impurities, is promoted.

In the present invention, examples of the phase transfer catalyst include quaternary ammonium salts and quaternary phosphonium salts. Examples of the quaternary ammonium salt include tetramethylammonium, trimethyl-ethylammonium, dimethyldiethylammonium, triethyl-methylammonium, tripropyl-methylammonium, tributyl-methylammonium, trioctyl-methylammonium, tetraethylammonium, trimethyl-propylammonium, Trimethylphenylammonium, benzyltrimethylammonium, benzyltriethylammonium, diallyldimethylammonium, n-octyltrimethylammonium, stearyltrimethylammonium, cetyldimethylethylammonium, tetrapropylammonium, tetran-butylammonium, β-methylcholine, phenyltrimethylammonium, etc. Bromide, chloride, ammonium salt, ammonium hydrogensulfate, hydroxide and the like can be mentioned. Particularly preferred are trioctyl-methylammonium, tetraethylammonium, benzyltrimethylammonium, benzyltriethylammonium, tetran-butylammonium bromide, chloride, hydrogen sulfate and hydroxide.

As the quaternary phosphonium salt, tetramethylphosphonium, trimethyl-ethylphosphonium, dimethyldiethylphosphonium, triethyl-methylphosphonium, tripropyl-methylphosphonium, tributyl-methylphosphonium, trioctyl-methylphosphonium, tetraethylphosphonium, trimethyl-propylphosphonium. , Trimethylphenylphosphonium, benzyltrimethylphosphonium, diallyldimethylphosphonium, n-octyltrimethylphosphonium, stearyltrimethylphosphonium, cetyldimethylethylphosphonium, tetrapropylphosphonium, tetran-butylphosphonium, phenyltrimethylphosphonium, methyltriphenylphosphonium, ethyltriphenyl Examples thereof include bromide salts such as phosphonium and tetraphenylphosphonium, chloride salts, iodide salts, hydrogen sulfate salts and hydroxides.

The amount of the phase transfer catalyst used may be 0.001 mol times or more with respect to the trifluoromethyl group-substituted aromatic ketone, and usually 0.01 to 1.0 mol times is preferably used.

In hydrolysis with an aqueous solution containing a base, the base may be simply added to the obtained oil phase, or a new solvent may be added and used. As the solvent to be added, a hydrocarbon solvent is preferable, and for example, hexane, 2-methylpentane, 2,2-dimethylbutane, 2,3-dimethylbutane, heptane, octane, isooctane, nonane, trimethylhexane, decane, dodecane, etc. Examples thereof include benzene, toluene, xylene, ethylbenzene, cumene, mesitylene, cyclohexylbenzene, diethylbenzene, cyclopentane, methylcyclopentane, cyclohexane, methylcyclohexane and ethylcyclohexane.

The amount of the solvent used may be preferably 0.05 L or more with respect to 1 mol of the trifluoromethyl group-substituted aromatic ketone, and more preferably 0.1 L to 10 L.

In the present invention, the treatment temperature for hydrolysis with a base is preferably 10 to 100 ° C, particularly preferably 20 to 70 ° C.

The treatment time is usually within 24 hours, but it is preferable to follow the reduction status of the fatty acid halogenated butyl ester and the fatty acid trifluoromethylphenyl ester and set the time point at which the impurities are almost eliminated as the end point of the treatment.

（但し、ｎは、１〜４の整数である。） The trifluoromethyl group-substituted aromatic ketone produced in the production method of the present invention is represented by the following formula (2).

(However, n is an integer of 1 to 4.)

The high-purity trifluoromethyl group-substituted aromatic ketone produced in the production method of the present invention is 2'-trifluoromethylacetophenone, 2'-trifluoromethylpropiophenone, 2'-trifluoromethylbutyrophenone, 2'. -Trifluoromethylvalerophenone, 3'-trifluoromethylacetophenone, 3'-trifluoromethylpropiophenone, 3'-trifluoromethylbutyrophenone, 3'-trifluoromethylvalerophenone, 4'-trifluoromethylacetophenone, 4'-trifluoromethylpropiophenone, 4'-trifluoromethylbutyrophenone, 4'-trifluoromethylvalerophenone. Preferably, it is 2'-trifluoromethylacetophenone, 2'-trifluoromethylpropiophenone, and 2'-trifluoromethylbutyrophenone.

As a method for isolating the desired trifluoromethyl group-substituted aromatic ketone from the reaction solution of the present invention, a distillation method is preferably used. For example, simple distillation, rectification, vacuum distillation, atmospheric distillation are preferable, and vacuum distillation is more preferable. The purity of the trifluoromethyl group-substituted aromatic ketone obtained by the production method of the present invention is preferably 99.0% or more, more preferably 99.2% or more and 100.0% or less, still more preferably 99.5%. It is preferable that it is 100.0% or more and 100.0% or less.

Since the high-purity trifluoromethyl group-substituted aromatic ketone obtained by the production method of the present invention is a compound useful in a wide range of fields, it is of great significance to efficiently obtain it industrially.

Hereinafter, the present invention will be described in more detail with reference to Examples. The manufacturer grades of the reagents used here are all equivalent to the first grade level or higher.

The purity of the trifluoromethyl group-substituted aromatic ketone and the content of the fatty acid halogenated butyl ester and the fatty acid trifluoromethylphenyl ester (% of the trifluoromethyl group-substituted aromatic ketone standard) are determined by the gas chromatography (GC) method. It can be obtained as% of the area in the measurement. The analysis conditions of the GC method are shown below.

1. 1. Measurement conditions of GC method Detector: FID
Column: TC-17, 0.32 mmφ x 60 m, 0.25 μm (manufactured by J & W)
Column temperature: 50 ° C (hold for 3.0 minutes) → (10 ° C / min) → 250 ° C (hold for 3.0 minutes)
Injection port temperature: 250 ° C
Detector temperature: 250 ° C
Total flow rate: 62.6 mL / min (He 141.9 kPa)
Split ratio: 1/20
Sample injection volume: 1.0 μL
2. 2. Sample 0.2 g of the sample is weighed in a 10 ml volumetric flask using an electronic precision balance. Acetone was added to this, and the scalpel-up solution was used as a sample solution.

[Example 1]
75.0 g of tetrahydrofuran (1.04 mol; manufactured by nacalai tesque), 5.1 g of magnesium powder (0.208 mol; manufactured by Chuo Kosan Co., Ltd.), 2.5 g of LiCl (0.08 mol; manufactured by nacalai tesque) with a thermometer The mixture was placed in a four-necked flask (capacity: 200 ml), and the system was stirred while substituting nitrogen. To this, 0.5 g of a 1 mol / L ethylmagnesium bromide THF solution (manufactured by Tokyo Kasei Co., Ltd.) was added to remove water in the system. Subsequently, 0.44 g (0.004 mol; manufactured by Wako Pure Chemical Industries, Ltd.) of ethyl bromide was added. After stirring for a while, it was confirmed that heat generation occurred. Next, while maintaining the reaction solution temperature at 45 to 50 ° C., 36.1 g (0.2 mol; manufactured by Wako Pure Chemical Industries, Ltd.) of o-chlorobenzotrifluoride was gradually added dropwise. After completion of the dropping, the mixture was aged with stirring at 45 ° C. for 5 hours. After aging, 10.8 g of toluene was added and diluted to obtain a Grignard reagent solution.

Next, 4 9.8 g of acetic anhydride (0.19 mol; manufactured by Wako Pure Chemical Industries, Ltd.) and 43.3 g of toluene (1.2 weight times / o-chlorobenzotrifluoride: manufactured by Wako Pure Chemical Industries, Ltd.) with a thermometer. It was put into a mouth flask (capacity 200 ml), and the inside of the system was stirred in a water bath while substituting with nitrogen. The Grignard reagent solution was added dropwise thereto while controlling the reaction solution temperature to be 20 to 30 ° C. After the whole amount of the Grignard reagent solution was added dropwise, the mixture was stirred at 25 ° C. for 2 hours.

After completion of stirring, the reaction solution was cooled to room temperature, and 57.8 g of a 13 wt% hydrogen chloride aqueous solution was gradually added dropwise in a water bath. Hydrolysis was completed by stirring for 1 hour after the dropping. After hydrolysis, stirring was stopped and the aqueous phase was removed by static separation. The obtained oil phase was washed with 18.6 g of 5 wt% saline solution to remove the aqueous phase.

To this oil phase, 42.3 g of a 27.5 wt% NaOH aqueous solution and 1.67 g of tetran-butylammonium bromide were added, and hydrolysis treatment was carried out at a liquid temperature of 50 ° C. under basic conditions for 3 hours. After the hydrolysis treatment, stirring was stopped and the aqueous phase was removed by a static liquid separation. The obtained oil phase was washed twice with 18.6 g of 5 wt% saline solution, and the aqueous phase was removed to obtain an oil phase containing 2'-trifluoromethylacetophenone. The contents of the impurities chlorobutyl ester acetate and trifluoromethyl phenyl ester acetate contained in this oil phase were 0.1% and 0.1%, respectively, with respect to the contained 2'-trifluoromethylacetophenone.

After concentrating this oil phase, it was distilled under reduced pressure (vacuum degree 0.4 to 1.3 kPa, distillation temperature 95 to 100 ° C.), and as a result, the total yield was 82.7% (based on raw material o-chlorobenzotrifluoride). A 2'-trifluoromethylacetophenone with a GC purity of 99.2% was obtained. The contents of chlorobutyl acetate ester and trifluoromethylphenyl ester acetate as impurities were 0.1% or less.

[Example 2]
In Example 1, the reaction was carried out in the same manner as in Example 1 except that 19.8 g (0.19 mol) of acetic anhydride was changed to 25.2 g (0.19 mol; manufactured by Wako Pure Chemical Industries, Ltd.) of propionic anhydride. After the hydrolysis treatment under basic conditions, the content of the impurities propionic acid chlorobutyl ester and propionic acid trifluoromethylphenyl ester contained in the oil phase was changed to 2'-trifluoromethylpropiophenone contained. On the other hand, it was 0.2% and 0.1%, respectively.

The obtained oil phase was distilled under reduced pressure (vacuum degree 0.4 to 1.3 kPa, distillation temperature 105-110 ° C.), and as a result, the total yield was 84.5% (based on raw material o-chlorobenzotrifluoride), and GC. A 2'-trifluoromethylpropiophenone with a purity of 99.6% was obtained. The contents of propionic acid chlorobutyl ester and propionic acid trifluoromethylphenyl ester as impurities were 0.1% or less.

[Comparative Example 1]
In Example 1, an oil phase was obtained without performing hydrolysis treatment under basic conditions. The contents of the impurities chlorobutyl ester acetate and trifluoromethylphenyl acetate acetate contained in this oil phase were 2.5% and 1.2%, respectively, with respect to the contained 2'-trifluoromethylacetophenone. As a result of vacuum distillation (vacuum degree 0.4 to 1.3 kPa, distillation temperature 95 to 100 ° C.), the total yield was 62.5% (based on raw material o-chlorobenzotrifluoride), and the GC purity was 97.2. % 2'-Trifluoromethylacetophenone was obtained. As impurities, the content of chlorobutyl acetate ester 1.2% and trifluoromethyl phenyl ester acetate was 0.7%.

[Comparative Example 2]
In Example 2, an oil phase was obtained without performing hydrolysis treatment under basic conditions. The contents of the impurities propionic acid chlorobutyl ester and propionic acid trifluoromethylphenyl ester contained in this oil phase are 3.1% and 1.4%, respectively, with respect to the contained 2'-trifluoromethylpropiophenone. Met. This was distilled under reduced pressure (vacuum degree 0.4 to 1.3 kPa, distillation temperature 105-110 ° C.), resulting in a total yield of 68.2% (based on raw material o-chlorobenzotrifluoride) and a GC purity of 96.8. % 2'-Trifluoromethylpropiophenone was obtained. As impurities, the content of propionic acid chlorobutyl ester 1.5% and propionic acid trifluoromethylphenyl ester was 0.9%.

[ Reference example 3]
In Example 1, the reaction was carried out in the same manner as in Example 1 except that the hydrolysis treatment was carried out without adding tetra n-butylammonium promid. The contents of impurities chlorobutyl ester acetate and trifluoromethyl phenyl ester acetate contained in the oil phase were 0.5% and 0.3%, respectively, with respect to the contained 2'-trifluoromethylacetophenone. When the hydrolysis treatment time was further extended and carried out for 10 hours, the values were 0.3% and 0.2%, respectively.

[ Reference example 4]
In Example 2, the reaction was carried out in the same manner as in Example 2 except that the hydrolysis treatment was carried out without adding tetra n-butylammonium promid. The impurities contained in the oil phase, propionic acid chlorobutyl ester and propionic acid trifluoromethylphenyl ester, were 0.4% and 0.2%, respectively, with respect to the contained 2'-trifluoromethylpropiophenone. there were. When the hydrolysis treatment time was further extended and carried out for 10 hours, the values were 0.3% and 0.1%, respectively.

In the method for producing a high-purity trifluoromethyl group-substituted aromatic ketone of the present invention, a Grignard reagent is produced as an intermediate, the Grignard reagent is reacted with an acid anhydride, and then hydrolyzed with an aqueous solution containing an acid. A high-purity trifluoromethyl group-substituted aromatic ketone is produced by separating and removing the aqueous phase and then hydrolyzing the oil phase with an aqueous solution containing a base under basic conditions to separate and remove the aqueous phase. can do. The method for producing a high-purity trifluoromethyl group-substituted aromatic ketone of the present invention is an industrially excellent production method.

The high-purity trifluoromethyl group-substituted aromatic ketone produced by the method for producing a trifluoromethyl group-substituted aromatic ketone of the present invention is used as a fine chemical, a medical and agricultural chemical raw material, a resin / plastic raw material, an electronic information material, an optical material, and the like. be able to.

Claims (5)

A halogen-substituted benzotrifluoride compound represented by the following general formula (1)

(However, X is Cl or Br.)
It is reacted with a magnesium metal to be converted into a Grignard reagent, the Grignard reagent is reacted with an acid anhydride, and then hydrolyzed with an aqueous solution containing an acid to carry out a trifluoromethyl group represented by the following general formula (2). After generating the substituted aromatic ketone

(However, n is an integer of 1 to 4.)
The by-products of the reaction, with an aqueous solution containing a base, are allowed to coexist phase transfer catalyst, high purity method for producing a trifluoromethyl-substituted aromatic ketones that hydrolysis under basic conditions. The method for producing a high-purity trifluoromethyl group-substituted aromatic ketone according to claim 1, wherein the phase transfer catalyst is a tetra-n-butylammonium salt . The method for producing a high-purity trifluoromethyl group-substituted aromatic ketone according to claim 1 or 2, wherein the acid anhydride is acetic anhydride, propionic anhydride or butyric anhydride. The high-purity trifluoromethyl group-substituted aromatic ketone according to any one of claims 1 to 3, wherein the trifluoromethyl group-substituted aromatic ketone is trifluoromethylacetophenone, trifluoromethylpropiophenone, or trifluoromethylbutyrophenone. Manufacturing method. The method for producing a high-purity trifluoromethyl group-substituted aromatic ketone according to any one of claims 1 to 4, which is carried out at a treatment temperature of 40 to 100 ° C. when hydrolyzing with an aqueous solution containing a base.