JPS59139329A - Preparation of 4-fluorobenzotrifluoride - Google Patents

Abstract

PURPOSE:To provide the titled substance in high yield, by the thermal reaction of a 4-halogenobenzotrifluoride with KF in DMSO and/or dimethylsulfone solvent, keeping the reaction system in anhydrous state and distilling out the product from the system. CONSTITUTION:The compound of formula II is prepared by reacting the compound of formula I (X is Cl or Br; Y is Cl) with KF under heating in DMSO and/or dimethylsulfone solvent keeping the reaction system in anhydrous state and distilling out the produced compound of formula II from the system. The amount of KF and the solvent are 2-4mol. and 4-8mol. per 1mol. of the compound of formula I , and the reaction temperature is selected to 170-240 deg.C. USE:Raw material of pharmaceuticals and agricultural chemicals.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 4-fluorohenecytrifluoride, and more specifically, 4-halogenohenecytrifluoride is reacted with potassium fluoride, and the halogen at the 4-position is replaced with a fluorine atom. Concerning an improved manufacturing method.

4-Fluorohenecytrifluorides are substances useful as raw materials for medicines and agricultural chemicals.

The simplest method for producing 4-fluorobencytrifluorides is the halogen substitution of 4-chlorobencytrifluoride or 4-bromobencytrifluoride with potassium fluoride, which is industrially difficult in view of the availability of raw materials. It is also considered an advantageous method. In this specification, pensitrifluorides refer to general formulas (1) and (I
t) where Y is a hydrogen atom or C/! It refers to something that has an atom, and its R form is 3,4-dichlorohenzo)')
7 Jl/olide, 3-chloro-4-bromo-hencytrifluoride, parachlorhencytrifluoride, para-bromohencytrifluoride, and the like.

In general, a method for substituting a halogenated benzene with an electron-withdrawing group at the ortho or rose position with potassium fluoride is to use a polar aprotic acid such as dimethylsulfoxide, dimethylformamide, N-methylpyrrolidone, dimethylsulfone, etc. 150-300' in a substantially anhydrous state with sufficiently dried potassium fluoride powder in a solvent.
The desired fluoro compound may be obtained in a yield of 50 to 70% by heating to c. However, in the case of 4-halogenohene trifluoride in the present invention, fluorination is not necessarily easy as described below.

For example, 3,4-dichlorohendztrifluoride (hereinafter abbreviated as DCBT) is mixed with 2 times the mole of potassium fluoride in 1.5 times the amount of dimethyl sulfoxide (hereinafter abbreviated as DMSO) and 210 When reacting at °C, the reaction proceeds extremely slowly, reaching a yield of 10% after 18 hours and 14% after 25 hours, but it reaches 13% after 54 hours, and the yield peaks out. It will decrease slightly. When three times the amount of DMSO is used, the production rate of the target product becomes extremely high,
The yield becomes 8% after 5 hours, 16% after 9 hours, and 27% after 18 hours, but decreases to 20% after 34 hours. When 6 times the amount of DMSO is used, the reaction rate increases further, reaching a yield of 15% after 5 hours and a maximum yield of 26% after 9 hours, but thereafter the yield decreases rapidly with the passage of time. result.

In view of this current situation, the present inventors have conducted intensive studies with the aim of significantly improving the yield of 4-fluorobensitrifluorides, and as a result, have developed an innovative method for carrying out this reaction extremely advantageously. I was able to find out.

According to the present invention, 4-halogenobencytrifluorides represented by the general formula (1) (wherein, X represents a C1 or Br atom, and Y represents a hydrogen atom or a C1 atom) are heated with potassium fluoride. When reacting to produce 4-fluorobensitrifluorides represented by general formula (It) (wherein Y is as defined above), using dimethyl sulfoxide and/or dimethyl sulfone as a solvent, Provided is a method characterized in that the reaction is carried out while keeping the reaction system substantially anhydrous and distilling off the produced 4-fluorobensitrifluoride from the system.

The conditions for effectively carrying out the method of the present invention include approximately 1.2 to 6 moles of sufficiently dried potassium fluoride per 1 mole of 4-halogenobencitrifluoride as a raw material;
Preferably, 2 to 4 mol of DMSO and/or dimethylsulfone (D
MS C2) is used in an amount of 2 to 12 times, preferably 4 to 8 times. The reaction temperature range is 150 to 270"C, preferably 170 to 240"C.In the present invention, the most important method is to further treat the 4-
The process is carried out while quickly distilling off fluorobensitrifluoride (4FBTF) from the reaction system. When the reaction is carried out near atmospheric pressure, for example, the boiling point of DCBT is 173°C, the boiling point of DMSO (7) is 183°C, the boiling point of the product 4FBTF is 134°C, and the reaction is carried out using a fractionator tube. It is carried out in a reactor, for example at about 180'c. The temperature at the top of the fractionating tube is adjusted to approximately 150"C. If necessary, the reaction may be carried out under slightly reduced pressure or slightly increased pressure to effectively distill the desired product out of the reaction system. You can also do that.

In a representative example, 80% DCBT conversion, 3-
Chlor-4-fluoro-hensitrifluoride (CF
-BTF) yield of 74% and selectivity of 92%.

Unreacted DCBT can be recovered and reused, for example, by fractional distillation, if necessary.

Next, in order to effectively implement the present invention, the influence of water in the reaction solution will be explained. First, regarding potassium fluoride,
For example, it is preferable to use a commercially available spray-dried potassium fluoride (Arita Chemical Industry ■, Powder KF) that is dried at 200°C under reduced pressure and has a moisture content of 0.1% or less. In addition, the water content in the reaction solution is 0.05% or less,
Preferably, it is substantially anhydrous. For this purpose, for example, the reaction according to the present invention may be carried out by adding benzene, toluene, etc. to the raw materials and solvent in advance and dehydrating them by azeotropic distillation to make the reaction solution substantially anhydrous, or alternatively, the starting materials, products, solvent, etc. Aromatic isocyanates that can be fractionally distilled, such as tolylene diisocyanate, 1,5-naphthalene diisocyanate, and diphenylmethane diisocyanate, can be added in small amounts to the reaction solution to maximize the effect. I can do it. The amount added is preferably 0.1 to 5% based on the reaction solution. Another effect of adding aromatic diisocyanate is that the decomposition or side reactions of DMSO are suppressed, and the odor (dimethyl sulfide) of the produced 4-fluorohenecytrifluoride is significantly reduced.

The method of the present invention can be carried out either batchwise or continuously. Alternatively, the reaction may be carried out using a plurality of reactors, and a fractionating column may be provided in a specified reactor. The reaction time varies depending on the reaction temperature, but is preferably about 5 to 24 hours. The target substance produced, 4-fluoropene citrifluoride, can be used as it is as a raw material for agricultural chemicals or medicines, but if necessary, it can be used after further purification by precision distillation. As a fluorinating agent, potassium fluoride can be used alone, but other alkali metal fluorides or alkaline earth metal fluorides, such as potassium fluoride,
It may be used in combination with sodium fluoride, cesium fluoride, calcium fluoride, etc. Preferred solvents used in the method of the present invention include DMSO and DMSO2. The use of other aprotic polar solvents, which are generally used when fluorinating halogenated benzenes having electron-withdrawing groups in the ortho or para positions, gives unfavorable results.

Next, the present invention will be explained in more detail with reference to Examples and Reference Examples.

Reference Example 1 29 g of potassium fluoride (0
,5mol), DCBT54g (0.25mol)
) 320 g of DSM0 and 2 g of 2,4-1-lylene diisocyanate were charged. A calcium chloride tube was connected to the top of the reflux condenser. The reaction flask was placed in a 210°C oil bath and reacted for 5 hours.

After the reaction was completed, it was cooled, the contents were poured into 500 g of ice water, and extracted three times with 300 m6 of dichloromethane. The extracts were combined, dehydrated by adding calcium chloride particles, and dichloromethane was distilled off under closed pressure. The residue was rectified to a boiling point of 13
7.9 g of CF-BTF fraction with a temperature of 2 to 134°C was obtained (
yield 16%).

Furthermore, analysis of the distillation residue revealed that DCBT was 29.7 g (5
5%) remained.

Reference Example 2 When the reaction of Reference Example 1 was carried out in the same manner without 2,4-tolylene diisocyanate, 5.5 g of CF-BTF (
Yield 1.1%) was obtained, and 29.6 g (5
It was confirmed that 5%) remained unreacted.

Reference Example 3 In the reaction of Reference Example 1, potassium fluoride was heated to 200°C in advance.
When dried under reduced pressure with Sanryu Hg and cooled, 8.5 g (17% yield) of CF'-BTF was obtained, with 36.2 g (67%) of unreacted DcBT remaining. This was confirmed.

Reference example 4 Stirring device 1. 6゜mj2 equipped with reflux condenser and temperature needle
2.9 g of potassium fluoride (50 m
mol), DCBT5.4 g (25 mmol),
32g DMSO & 0.2g tolylene diisocyanate
was loaded. The reaction was carried out under reflux in an oil bath (210°C) using a reflux condenser equipped with a calcium chloride tube. During the progress of the reaction, the reaction solution was sampled and analyzed for CF-BTF by gas chromatography.The results are shown in the following table.

Below margin yield (%) 11kLDCBT KF DMSo
5 hours 9 hours 16 hours 1 5.4g 2.
9g 8g 3 5 3*(25mmol>
(50 mmol) 2 16'8 16 27 3 32152616 4 1.7 32 16 24 13 (29 m
mo ri5 〃2.9 4815 10 4 (50 mmol
) *10% after 18 hours, 14% after 25 hours, 1 after 54 hours
3% Reference Example 5 The same apparatus and method as in Reference Example 4 were used, but the type of solvent was changed, and a heating reaction was carried out in an oil bath (210°C) for 5 hours.

The final product was converted into CF-BT by gas chromatography.
The results of the analysis of F were as shown in the following table.

隘DCBT KF Solvent Yield (%) 1 5.4g 2.1g DMSO
32g 17 (3.8 mmol) 2〃〃NHP〃5 3〃DMF〃0 4〃DGM〃0 5〃 Dimethylsulfur 0 fluorane〃 6〃 Dimethylsulfonone
〃34 *A white gel-like substance adhered to the cooling part of the reflux condenser.

NMP: N-methylpyrrolidone (boiling point 202°C) DMF
Nidimethylformamide (boiling point 153°C) Dimethylsulforane (boiling point 281°C) Dimethylsulfone (
Boiling point 238°C) DGM Nidiethylene glycol dimethyl ether (boiling point 162°C) Example 1 Potassium fluoride 58 g (1 mol ), DCBTl 08 g
(0.5 mol), 640 g of DMSO with a water content of 0.05% or less, and 2 g of 2.4-1-lylene diisocyanate were charged. The reaction flask was placed in an oil bath, stirred to slowly reflux, and reacted for 20 hours. The reaction was carried out while extracting a fraction having a boiling point of 150'C or less at the top of the distillation column.

81 g of distillate was washed with water and extracted with dichloromethane, the dichloromethane extract was dried with calcium chloride particles, the dichloromethane was evaporated, and the residue was analyzed by gas chromatography. 77 g (78%) of CI'-BTF was obtained. Unreacted DCBT was 15 g (14%).

Note that the weight ratio of DMSO and DCBT is 6.

Example 2 51! equipped with a stirring device and packed distillation device! In a pressure-resistant reactor, 4.51 g of parachlorhencytrifluoride and 2.9 g of potassium fluoride, which had been sufficiently dried in the same manner as in Reference Example 3, were placed in a pressure-resistant reactor.
kg and DMS025kg with a moisture content of 0.03% or less
I prepared it. The reaction system has a pressure retention valve of 4 kg/cl.
The reaction was carried out in an oil bath (215 to 220°C) while maintaining the temperature. From the top of the distillation tower boiling point 145℃ / 4 kg /
The reaction was carried out for 24 hours while distilling the fraction below CD.

3.6 kg of distillate was obtained, and as a result of analysis by gas chromatography, the purity of 4-fluorogen trifluoride was 97.2%. Note that the weight ratio of DMSO and parachlorhencytrifluoride was 5.6.

Example 3 Using the same equipment and method as in Example 1, 3-chloro-4
-bromopene citrifluoride 129g (0.5m
ol) was allowed to react for 24 hours, and 85 g of a distillate having a boiling point of 150° C. or lower was obtained from the top of the distillation column. As a result of the analysis, it was confirmed that 81 g (82%) of CF-BTF was obtained, and 11.6 g (9%) of unreacted raw material was obtained.
) remained in the reaction flask. In addition, DMSO and 3
The weight ratio of -chloro-4-brombene trifluoride is 5.

Example 4 Into a 400 mβ reaction flask equipped with a stirrer and a packed precision distillation column, 17.4 g (0.3 mol) of potassium fluoride, which had been dried by heating under reduced pressure in the same manner as in Reference Example 3, was added to DC.
BT32.4g (0.15mol), moisture content 0.
0.05% or less dimethyl sulfone and 0.6 g of 1.8-nac diisocyanate were charged. The reaction flask was heated in an oil bath (210°C), and the reaction was carried out for 8 hours while extracting the fraction having a boiling point of 140 to 146°C at the top of the distillation column.

In this way, 24.6 g of distillate was obtained. Analysis by gas chromatography revealed that CF-BTF22
．． It contained 5g. Note that the weight ratio of dimethylsulfone and DCBT was 5.9.

Procedural amendment (voluntary) March 9, 1980 Kazuo Wakasugi, Commissioner of the Patent Office1, Indication of the case 1988 Patent Application No. 139172, Title of the invention 4 - Process for producing fluoropene citrifluorides 3 , Relationship with the case of the person making the amendment Patent applicant name (003) Asahi Kasei Kogyo Co., Ltd. 4, Agent (3 others) 5. Subject of amendment 1) Specification Q [Claims j column 2] " on the statement
"Detailed Description of the Invention" Column 6 Contents of Amendment 1) The scope of claims is amended as shown in the attached sheet.

2Xl) Lines 4-5 of Specification 3R [, parachlorobencitrifluoride, parabrompencitrifluoride” are deleted.

(2) Correct the phrase ``Y indicates a hydrogen atom and a Ct atom'' to ``i'Y indicates a Ct atom'' in lines 5 to 6 of the same 5th text.

(3) Delete the entire text of page 15, lines 1 to 15, "Implementation ff1J2."

(4) 15th member TMI 6th line “Example 3” is changed to “Example 2”
Correct to J.

(5) Correct the 7th line of the 16th motor vehicle, ``Actual mga 4'', to ``1 Example 3''.

7. List of Attached Documents Amended Claims] General 2. Claims ■ General formula (II (wherein, In producing 4-fluoropene citrifluorides represented by the general formula OD (wherein Y is as defined above), one reaction system is prepared using dimethyl sulfoxide and/or dimethyl sulfone as a catalyst. A patent characterized in that the reaction is carried out while keeping the system substantially anhydrous and distilling the generated 4-fluoropene citrifluoride out of the system.

Claims (1)

[Scope of Claims] (2) 4-halogenobencytrifluorides represented by the general formula (+) (wherein, X represents a CX or Br atom, and Y represents a hydrogen atom or a Cβ atom) are converted into potassium fluoride. In producing 4-fluoropene citrifluoride 'W4 represented by general formula (II) (wherein Y is as defined above) by heating reaction with
It is characterized by using dimethyl sulfoxide and/or dimethyl sulfone as a solvent, keeping the reaction system substantially anhydrous, and carrying out the reaction while distilling the produced 4-fluorobencytrifluoride out of the system. Method.