JP2001199925A - Method of manufacturing 3,3'-difluoro-4,4'-dimehoxy- benzophenoe - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method of manufacturing for 3,3'-difluoro-4,4-dimthoxy- benzophenoe on an industrial scale. SOLUTION: This method for manufacturing 3,3'-difluoro-4,4-dimthoxy- benzophenoe includes (1) a process reacting 2-fluoroanisole and carbon tetrachloride in the presence of an aluminum chloride, (2) a process adding water to a reaction mixture obtained in the process (1), and if required (3) a process adding dimethyl sulfate to a reaction mixture obtained in the process (2).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing 3,3'-difluoro-4,4'-dimethoxy-benzophenone.

[0002]

2. Description of the Related Art 3,3'-Difluoro-4,4'-dimethoxy-benzophenone is an important compound as an intermediate of a functional material. As a method for producing 3,3′-difluoro-4,4′-dimethoxy-benzophenone, 2-fluoroanisole and propionic acid chloride are reacted as a by-product in carbon disulfide using aluminum chloride. A method of oxidizing the obtained 1,1-di (3-fluoro-4-methoxyphenyl) propene with chromic acid,
Journal of Organic Chemistry, 19
Vol., Pp. 1562-1566 (1954). In this method, only a small amount of 1,1-di (3-fluoro-4-methoxyphenyl) is produced as a by-product.
It is hard to say that it is an industrial and economical production method because it uses propene as a raw material and uses chromic acid as an oxidizing agent.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide an industrial process for producing 3,3'-difluoro-4,4'-dimethoxy-benzophenone.

[0004]

Means for Solving the Problems The present inventor has proposed 3,3'-
As a result of intensive studies on the industrial and economical production method of difluoro-4,4'-dimethoxy-benzophenone,
When water is added to a mixture obtained by reacting 2-fluoro-anisole and carbon tetrachloride with aluminum chloride and hydrolyzed, 3,3′-difluoro-4,4′-dimethoxy-benzophenone is obtained in high yield. It was found that it can be obtained by. In addition, the present inventor has found that, after hydrolysis, 3,3′-difluoro-4,4′-dimethoxy-benzophenone can be obtained in a high yield when dimethyl sulfate is added to the reaction mixture and reacted. . The present invention has been completed based on these findings.

That is, the present invention provides the inventions described in the following items.

Item 13.3,3'-Difluoro-4,4'-
A method for producing dimethoxy-benzophenone, comprising:
(1) reacting 2-fluoro-anisole with carbon tetrachloride in the presence of aluminum chloride; and (2)
A production method comprising a step of adding water to the reaction mixture obtained in the step (1).

Item 23: 3,3'-difluoro-4,4'-
A method for producing dimethoxy-benzophenone, comprising:
(1) a step of reacting 2-fluoro-anisole with carbon tetrachloride in the presence of aluminum chloride, (2) a step of adding water to the reaction mixture obtained in the step (1), and a step (3) of the step (2) A) adding dimethyl sulfate to the reaction mixture obtained in the above).

Item 3 The method according to Item 1 or 2, wherein dichloromethane is used as a solvent in the step (1).

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION Step (1) The amounts of carbon tetrachloride and 2-fluoro-anisole used in step (1) can be appropriately set without any particular limitation. 2-
Fluoro-anisole about 1.5 to 3 mol, preferably about 1.5 to 2.5 mol, more preferably 1.8 to 3 mol.
It is about 2.2 mol.

[0010] The amount of aluminum chloride in the step (1) is not particularly limited, but is usually 2-
About 1 to 3 mol per 1 mol of fluoro-anisole,
Preferably it is about 1.5 to 2.5 mol, more preferably about 1.8 to 2.5 mol.

In the step (1), carbon disulfide; a chlorine-based solvent such as dichloromethane and tetrachloroethane;
Aromatic solvents such as nitrobenzene and benzonitrile can be used. Among them, chlorine solvents such as dichloromethane and tetrachloroethane are preferably used, and dichloromethane is particularly preferably used. Raw materials such as carbon tetrachloride and 2-fluoro-anisole can also be used as a solvent, but it is preferable to use a compound other than these as a solvent. The amount of the solvent is not particularly limited and can be appropriately set to an amount such that the reaction suitably proceeds, but is usually about 3 to 10 mL per 1 g of carbon tetrachloride.

The reaction temperature in the step (1) is not particularly limited as long as the reaction proceeds suitably, and can be appropriately set.
Degree, preferably about 0 to 50 ° C, more preferably about 5 to 30 ° C.

The reaction time is not particularly limited and can be appropriately set according to other conditions such as the reaction temperature, but is usually about 2 to 100 hours, preferably 5 to 6 hours.
It is about 0 hours.

Although the reaction pressure is not particularly limited, it is usually carried out at normal pressure.

In the step (1), for example, a predetermined amount of aluminum chloride and carbon tetrachloride are charged into a reaction vessel in a solvent, and a predetermined amount of 2-fluoro-anisole is added dropwise while stirring at a predetermined temperature. After completion of the dropwise addition, stirring can be continued at a predetermined temperature until the reaction is completed. Alternatively, the method can be carried out by charging a predetermined amount of a solvent, carbon tetrachloride, and 2-fluoro-anisole, then dividing the predetermined amount of aluminum chloride and charging the reaction container. It is preferable to add aluminum chloride in portions because the yield becomes higher. For example, after no more increase in the amount of reaction product in the reaction mixture is observed by gas chromatography analysis, the remaining aluminum chloride can be added.

By the reaction in the step (1), bis (3-fluoro-4-methoxy-phenyl) -dichloromethane,
Bis (3-fluoro-4-hydroxy-phenyl) -dichloromethane and (3-fluoro-4-methoxy-
Phenyl)-(3-fluoro-4-hydroxy-phenyl) -dichloromethane is obtained.

Step (2) In step (2), bis (3-fluoro-4-methoxy-phenyl) -dichloromethane, bis (3-fluoro-4-hydroxy-phenyl) -dichloromethane obtained in step (1) is used. , And (3-fluoro-4-methoxy-phenyl)-(3-fluoro-4-hydroxy-phenyl) -dichloromethane. The hydrolysis is
For example, after the completion of the reaction in step (1), the reaction can be carried out by adding water to the same reaction vessel.

The hydrolysis can be carried out usually at about 0 to 50 ° C., preferably at about 0 to 40 ° C. The amount of water to be added is preferably at least 10 mol, more preferably at least 20 mol, particularly preferably about 25 to 50 mol, per 1 mol of aluminum chloride used in the step (1).

The addition of water is usually carried out by dropping water over a sufficient period of time to prevent sudden generation of hydrogen chloride and rapid boiling of the solvent due to rapid hydrolysis of aluminum chloride. For example, it can be performed for about 1 to 3 hours. The reaction is usually performed at normal pressure.

By the hydrolysis in step (2), bis (3
-Fluoro-4-methoxy-phenyl) -dichloromethane, bis (3-fluoro-4-hydroxy-phenyl)
-Dichloromethane and the hydrolyzate of (3-fluoro-4-methoxy-phenyl)-(3-fluoro-4-hydroxy-phenyl) -dichloromethane, i.e. 3,
3′-Difluoro-4,4′-dimethoxy-benzophenone, 3,3′-difluoro-4,4′-dihydroxy-benzophenone, and 3,3′-difluoro-4-methoxy-4′-hydroxy-dibenzophenone Obtained respectively.

The hydrolyzate of bis (3-fluoro-4-methoxy-phenyl) -dichloromethane is the target compound, 3,3'-difluoro-4,4'-dimethoxy-benzophenone. After completion of the above step), the target compound can be recovered by separation or purification.

The recovery can be carried out according to a conventional method, for example, by separating the organic phase from water added for hydrolysis and then removing the solvent.

Further, in order to remove impurities including aluminum dissolved in the organic phase, the organic phase is washed with water,
It is also possible to wash with an alkali.

In order to further purify the collected solid target substance, it may be washed with an alcohol such as methanol or recrystallized using an appropriate solvent.

Alternatively, the reaction mixture obtained in the step (2) may be directly subjected to the step (3).

Step (3) The process of the present invention comprises the bis (3-fluoro-4-hydroxy-phenyl) -dichloromethane and (3-fluoro-4-methoxy-phenyl)-(3
-Fluoro-4-hydroxy-phenyl) -dichloromethane hydrolyzate, i.e. 3,3'-difluoro-4,
4'-dihydroxy-benzophenone and 3,3'-difluoro-4-methoxy-4'-hydroxy-benzophenone are reacted with dimethyl sulfate, and the hydroxy group is methylated to obtain the target compound 3,3'-difluoro-4,
A method for obtaining 4'-dimethoxy-benzophenone is also included.

In step (2), bis (3-fluoro-4-
Since the target compound 3,3'-difluoro-4,4'-dimethoxy-benzophenone is obtained from the hydrolyzate of (methoxy-phenyl) -dichloromethane, it is separated from the reaction mixture after step (2). After that,
3'-difluoro-4,4'-dihydroxy-benzophenone and 3,3'-difluoro-4-methoxy-4'-
Dimethyl sulfate may be added to the reaction mixture containing hydroxy-benzophenone. Alternatively, from the viewpoint of working efficiency, dimethyl sulfate may be added to the reaction mixture obtained in the step (2) containing 3,3′-difluoro-4,4′-dimethoxy-benzophenone as it is.

The reaction with dimethyl sulfate in step (3) is usually carried out in a solvent in the presence of an alkali.

The amount of dimethylsulfuric acid can be appropriately set, but when it is added to the reaction mixture obtained in the step (2) as it is, it is usually used per 1 mol of carbon tetrachloride used in the step (1). , About 1 to 5 mol, preferably about 1 to 3 mol.

As the solvent, alcohols such as methanol and ethanol are preferably used, and ethanol is particularly preferable.

The amount of the solvent is not particularly limited.
An amount that allows the reaction to proceed suitably can be appropriately set, but is usually about 5 to 15 mL per 1 g of carbon tetrachloride used in the step (1).

As the alkali, an aqueous solution of sodium hydroxide or potassium hydroxide is preferably used. The concentration of the aqueous alkali solution is not particularly limited, but is preferably 20 to 3
A concentration of about 0% is suitably used, and the amount of alkali in the aqueous solution may be about the same as the molar number of dimethyl sulfate used.

The reaction with dimethyl sulfate is usually carried out at 0 to 60 ° C.
Degree, preferably about 5 to 50 ° C., more preferably about 1 to 50 ° C.
It is performed at about 0 to 40 ° C., and may be externally cooled as necessary.

The reaction time with dimethylsulfuric acid is not particularly limited and can be appropriately set according to other conditions such as the reaction temperature, but is usually about 1 to 3 hours, preferably 1.5 to 1.5 hours. It takes about 2 hours. Also, the reaction is
It is usually performed at normal pressure.

In the step (3), a solid target product is precipitated during the reaction with dimethyl sulfate, so that the target product can be recovered by filtration after completion of the reaction. In order to further purify the collected solid target, it may be washed with an alcohol such as methanol, or may be recrystallized using an appropriate solvent.

[0036]

According to the present invention, 3,3'-difluoro-4,4'-dimethoxy-benzophenone can be produced by an industrially advantageous method.

[0037]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to the following examples.

Example 1 242 g (1.6 mol) of carbon tetrachloride and 420 g (3.2 mol) of aluminum chloride were placed in a flask, and 1350 m 2 of dichloromethane was added.
L, add 398 g of 2-fluoroanisole (3.2 mo) at an internal temperature of 40 ° C on an oil bath while stirring with a mechanical stirrer.
l) was added dropwise over 1 hour.

After stirring at an internal temperature of 40 ° C. for 14 hours, the mixture was allowed to cool,
After carefully adding 1500 mL of ice water over 2 hours and 30 minutes on an ice bath, the mixture was stirred on an oil bath at an internal temperature of 40 ° C. for 1 hour and allowed to cool.

The reaction mixture was diluted with 750 mL of dichloromethane, and the precipitate was collected by filtration and dissolved in acetone. On the other hand, the dichloromethane layer was separated from the filtrate, and the aqueous layer was extracted three times with 300 mL of dichloromethane.The dichloromethane layer and the acetone layer obtained from the precipitate were combined, and concentrated under reduced pressure to obtain 611 g of a dark red liquid. Obtained. This was dissolved in 745 mL of ethanol, and 628 g (5.0 mol) of dimethyl sulfate was added at an internal temperature of 30 ° C.
696 g (5.0 mol) of 8.6% sodium hydroxide was added dropwise over 1 hour and 30 minutes, and the mixture was stirred at that temperature for 2 hours. The precipitate was collected by filtration, washed once with 300 mL of water, five times with 300 mL of methanol, and dried to obtain 153 g (0.5 mol, yield 31%) of white crude crystals.

Example 2 In a flask were placed 16 g (0.11 mol) of carbon tetrachloride and 27 g (0.20 mol) of aluminum chloride, and 90 mL of dichloromethane was added.
On the oil bath while stirring with a mechanical stirrer.
At room temperature, 27 g (0.21 mol) of 2-fluoroanisole was added dropwise over 1 hour. After stirring at room temperature for 3 hours, the mixture was left for 60 hours.

On an ice bath, 100 mL of ice water was carefully added over 1 hour, and the mixture was stirred at room temperature for 1 hour. Dichloromethane 5
After dilution with 0 mL, the dichloromethane layer was separated. The aqueous layer was extracted twice with 20 mL of dichloromethane, and the dichloromethane layers were combined, washed twice with 50 mL of 5% sodium hydrogen carbonate and once with 50 mL of water, and dried over anhydrous magnesium sulfate. The anhydrous magnesium sulfate was filtered and concentrated to obtain 23 g of a dark red liquid.
This was washed twice with 40 mL of methanol and dried to obtain 3 g of crude pink crystals (0.01 mol, yield 9%).

Example 3 In a flask were placed 16 g (0.11 mol) of carbon tetrachloride and 27 g (0.20 mol) of aluminum chloride, and 90 mL of dichloromethane was added.
On the oil bath while stirring with a mechanical stirrer.
At room temperature, 27 g (0.21 mol) of 2-fluoroanisole was added dropwise over 1 hour. After stirring at room temperature for 29 hours, 14 g (0.10 mol) of aluminum chloride was added and the mixture was further stirred for 30 hours.

On an ice bath, 100 mL of ice water was carefully added over 1 hour, followed by stirring at room temperature for 1 hour. Dichloromethane 5
After dilution with 0 mL, the dichloromethane layer was separated. The aqueous layer was extracted twice with 20 mL of dichloromethane, and the dichloromethane layers were combined, washed twice with 50 mL of 5% sodium hydrogen carbonate and once with 50 mL of water, and dried over anhydrous magnesium sulfate. The anhydrous magnesium sulfate was filtered and concentrated to obtain 30 g of crude brown crystals.
This was washed four times with 50 mL of methanol and dried to obtain 16 g of crude pink crystals (0.06 mol, yield 55%).

Continued on the front page (72) Inventor Toshihiko Tajima 1-1, Nishi-Itsuya, Settsu-shi, Osaka Daikin Industries, Ltd. Yodogawa Works F-term (reference) 4H006 AA02 AC44 BA09 BA37 BB12 BB18 BB21 BC10 BC19 BC34 4H039 CA62 CD20 CG20

Claims (3)

[Claims] 1. A process for producing 3,3′-difluoro-4,4′-dimethoxy-benzophenone, wherein (1) 2
Reacting -fluoro-anisole with carbon tetrachloride in the presence of aluminum chloride; and (2) step (1)
A production method comprising a step of adding water to the reaction mixture obtained in the step. 2. A process for producing 3,3′-difluoro-4,4′-dimethoxy-benzophenone, wherein (1) 2
-Reacting fluoro-anisole with carbon tetrachloride in the presence of aluminum chloride, (2) adding water to the reaction mixture obtained in step (1), and (3) obtaining in step (2) A process comprising adding dimethyl sulfate to the reaction mixture obtained. 3. The method according to claim 1, wherein dichloromethane is used as a solvent in the step (1).