Preparation method of 2, 4 '-difluorobenzophenone

Abstract

The invention discloses a preparation method of 2, 4 '-difluorobenzophenone.The preparation method comprises the steps that fluorobenzene and o-fluorobenzyl chloride serve as raw materials, reaction is conducted under the action of a catalyst, and then reaction is conducted under the action of an oxidizing agent; wherein the catalyst is an MCM-22 molecular sieve loaded with metal La, and the preparation method specifically comprises the following steps: (1) mixing fluorobenzene and the catalyst, dropwise adding o-fluorobenzyl chloride into the mixture at the reaction temperature of-40-30 DEG C in a stirring state, controlling the reaction temperature to be unchanged in the dropwise adding process, and keeping the temperature and continuing to react for 2-10 hours after the dropwise adding is completed; and (2) dropwise adding an oxidant solution, carrying out a reflux reaction at 80-120 DEG C for 0.5-1 h, distilling to recover fluorobenzene, washing with water, carrying out suction filtration, drying, and recrystallizing to obtain the 2, 4 '-difluorobenzophenone.The preparation method provided by the invention is completed by adopting a one-pot two-step method, so that the equipment cost is saved, the operation is simple, and the control is easy.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing 2,4'-difluorobenzophenone. Background Technology

[0002] Pyrimethanil is a sterol demethylation inhibitor developed by ICI (now Astra Zeneca) in the UK in 1980. It has systemic, protective and eradicative effects and has good protective and curative effects on a variety of diseases caused by basidiomycetes and ascomycetes. It can effectively prevent and control powdery mildew, rust, smut and corn smut in wheat crops. It has been well received for its broad-spectrum fungicidal effect and effectiveness since it was launched on the market.

[0003] 2,4'-Difluorobenzophenone is the most typical intermediate in the synthesis of fenitrothion. To further expand the market for fenitrothion and reduce its price, it is essential to start with the intermediate 2,4'-difluorobenzophenone. Therefore, it is necessary to explore a green, environmentally friendly, mild, and efficient synthetic route for 2,4'-difluorobenzophenone.

[0004] Based on domestic and international literature and patent reports, the traditional synthetic route for the intermediate 2,4'-difluorobenzophenone uses fluorobenzene and o-fluorobenzoyl chloride as raw materials, and anhydrous aluminum trichloride as a catalyst, through Friedel-Crafts acylation. The reaction principle is as follows: However, this route has harsh reaction conditions, is highly dangerous, and has a relatively low yield, which greatly limits the large-scale industrial production of triazinon. In addition, the production process generates a large amount of wastewater, which does not comply with the national energy conservation and emission reduction policy.

[0005] Chinese patent (CN116891403A) reports a method for preparing 2,4'-difluorobenzophenone by first synthesizing 2-fluorodichlorotoluene or a mixture thereof via photochlorination using 2-fluorotoluene as the main raw material, followed by Friedel-Crafts reaction with fluorobenzene, and then hydrolysis and oxidation. The reaction principle is as follows: , , Although this method uses 2-fluorotoluene as the main raw material, which reduces the synthesis cost of 2,4'-difluorobenzophenone, the technical route requires a three-step reaction and uses chlorine as a raw material in the synthesis process, generating hydrogen chloride gas, which poses certain safety hazards and environmental pollution risks. Summary of the Invention

[0006] This invention provides a method for preparing 2,4'-difluorobenzophenone, which overcomes the shortcomings of existing technologies such as harsh reaction conditions, lack of environmental friendliness, and potential safety hazards.

[0007] A method for preparing 2,4'-difluorobenzophenone, wherein the preparation method uses fluorobenzene and o-fluorobenzyl chloride as raw materials, and first reacts them under the action of a catalyst, and then reacts them under the action of an oxidant; wherein the catalyst is a molecular sieve of MCM-22 supported on metal La, denoted as La / MCM-22.

[0008] Preferably, the preparation method is as follows: (1) Mix fluorobenzene with the catalyst, and add o-fluorobenzyl chloride dropwise at a reaction temperature of -40~30℃ and under stirring. During the dropwise addition, keep the reaction temperature constant. After the dropwise addition is completed, keep the temperature and continue the reaction for 2~10h. (2) Add an oxidizing agent solution to it, reflux at 80~120℃ for 0.5~1h, distill to recover fluorobenzene, wash with water, filter, dry, recrystallize to obtain 2,4'-difluorobenzophenone.

[0009] Preferably, the drying conditions are drying at 80-85°C for 18-20 hours, and the recrystallization is carried out using isopropanol.

[0010] Preferably, the molar ratio of o-fluorobenzyl chloride to fluorobenzene is 1:2~5, and the mass of the catalyst accounts for 2~10% of the mass of o-fluorobenzyl chloride.

[0011] Preferably, the concentration of the oxidant solution is 10-20 wt%, and the mass of the oxidant solution accounts for 13-28% of the mass of the o-fluorobenzyl chloride.

[0012] Preferably, the oxidant solution is an ethanol solution of tert-butyl hydroperoxide (TBHP) or m-chloroperoxybenzoic acid (m-CPBA).

[0013] Preferably, La accounts for 2-5% of the catalyst mass.

[0014] Preferably, the catalyst is prepared by the following method: under vacuum and stirring, a lanthanum nitrate solution is dropped into an MCM-22 molecular sieve, stirred for 30-35 min, then allowed to stand at room temperature for 12-13 h for equal volume impregnation, dried, and activated in a glow discharge device to obtain the catalyst.

[0015] Preferably, the activation conditions are as follows: the glow discharge device is evacuated and 20 mL / min of 10% H2 / Ar gas is introduced, the pressure inside the discharge tube is maintained at 100~150 Pa, and reduction is carried out at room temperature for 60 min.

[0016] Preferably, the drying conditions are as follows: drying at 100~110℃ for 6-12 hours.

[0017] The reaction mechanism of this invention is as follows: .

[0018] Advantages of this invention: (1) Although the preparation method provided by the present invention is divided into two steps, there is no need to change the reaction system. The two steps can be carried out in the same reaction system in sequence, that is, the "one pot two steps" method is adopted, which saves equipment costs and is simple to operate and easy to control. (2) The preparation method described in this invention has mild reaction conditions, no special requirements for reaction equipment, low emissions of waste, and minimal environmental pollution; (3) The catalyst used in this invention employs an equal-volume vacuum impregnation method, which can more efficiently load metallic La onto the surface or pores of the MCM-22 molecular sieve. The catalyst is reduced at room temperature using glow discharge plasma, which avoids the agglomeration of metallic La caused by traditional high-temperature calcination, thus affecting its acidity distribution. Due to its suitable acidity and pore structure, the catalyst has high catalytic activity and is easy to separate and can be repeatedly recycled, reducing production costs. Attached Figure Description

[0019] Figure 1 The XRD pattern of the catalyst described in this invention; Figure 2 The NH3-TPD spectrum of the catalyst described in this invention; Figure 3 This is a gas chromatographic analysis spectrum of the reaction results in Example 3. Detailed Implementation

[0020] Example 1 The catalyst is La / MCM-22, with La accounting for 5% of the catalyst mass. The catalyst is prepared as follows: Under vacuum and stirring, an aqueous solution of lanthanum nitrate is slowly added dropwise to MCM-22 molecular sieve, stirred for 30 min, and then allowed to stand at room temperature for 12 h for equal volume impregnation. After drying at 110℃ for 6 h, the sample is placed in a glow discharge device, evacuated and 10% H2 / Ar gas at 20 mL / min is introduced, and the pressure inside the discharge tube is maintained at 150 Pa. The sample is reduced at room temperature for 60 min for activation, thus obtaining the catalyst. The catalyst was subjected to XRD analysis, and the results are shown in the figure. Figure 1 .Depend on Figure 1 It can be seen that 2Θ shows obvious characteristic peaks of MCM-22 between 5-30°, and there are no other impurity phases, indicating that the crystal form was not affected during the preparation of the catalyst.

[0021] The catalyst was subjected to NH3-TPD analysis, and the results are shown in the figure. Figure 2 .Depend on Figure 2It can be seen that the catalyst exhibits two distinct NH3 desorption peaks near 253℃ and 455℃. The low-temperature desorption peak near 253℃ corresponds to NH3 desorption related to physical adsorption, which is associated with weak acid centers. The high-temperature desorption peak near 455℃ corresponds to NH3 desorption at the Brønsted acid centers of the molecular sieve, which is associated with strong acid centers.

[0022] Example 2 The catalyst is La / MCM-22, with La accounting for 2% of the catalyst mass. The catalyst is prepared as follows: Under vacuum and stirring, an aqueous solution of lanthanum nitrate is slowly added dropwise to MCM-22 molecular sieve, stirred for 35 min, and then allowed to stand at room temperature for 13 h for equal volume impregnation. After drying at 100℃ for 12 h, the sample is placed in a glow discharge device, evacuated, and 10% H2 / Ar gas at 20 mL / min is introduced. The pressure inside the discharge tube is maintained at 100 Pa, and the sample is reduced at room temperature for 60 min for activation to obtain the catalyst.

[0023] Example 3 A method for preparing 2,4'-difluorobenzophenone, the method being as follows: (1) Mix 461.66g (4.80mol) fluorobenzene with 18.25g of the La / MCM-22 catalyst described in Example 1, place in a constant temperature bath at -20℃, and slowly add 232.12g (1.6mol) o-fluorobenzyl chloride dropwise while stirring. During the dropwise addition, control the reaction temperature to be maintained at -20℃. After the dropwise addition is completed, continue the reaction at -20℃ for 8h. (2) 50.36 g of ethanol solution of 20 wt% m-chloroperoxybenzoic acid was added dropwise, and the mixture was refluxed at 100 °C for 0.5 h. The fluorobenzene was recovered by distillation, washed with water, filtered, dried at 80 °C for 18 h, and recrystallized with isopropanol to obtain 335.31 g of 2,4'-difluorobenzophenone. The raw material conversion rate was 100%, the product yield was 96.04%, and the product purity was 99.5%. The product was analyzed by gas chromatography, and the results are shown below. Figure 3 ;Depend on Figure 3 It can be seen that the raw materials are completely converted after the reaction, and the selectivity and yield of the product are both high.

[0024] Example 4 A method for preparing 2,4'-difluorobenzophenone, the method being as follows: (1) Mix 240.33g (2.5mol) fluorobenzene with 7.29g of the La / MCM-22 catalyst described in Example 1 and place it in a constant temperature water bath at 20℃. While stirring, slowly add 145.02g (1.00mol) o-fluorobenzyl chloride. During the addition, control the reaction temperature to be maintained at 20℃. After the addition is completed, continue the reaction at 20℃ for 3h. (2) 25.02 g of ethanol solution of 18 wt% m-chloroperoxybenzoic acid was added dropwise, and the mixture was refluxed at 90 °C for 0.8 h. Fluorobenzene was recovered by distillation, washed with water, filtered, dried at 80 °C for 18 h, and recrystallized with isopropanol to obtain 185.52 g of 2,4'-difluorobenzophenone. The raw material conversion rate was 100%, the product yield was 85.02%, and the product purity was 99.3%.

[0025] Example 5 A method for preparing 2,4'-difluorobenzophenone, the method being as follows: (1) Mix 230.66g (2.40mol) fluorobenzene with 2.55g of the La / MCM-22 catalyst described in Example 1 and place it in a constant temperature water bath at 10℃. While stirring, slowly add 115.62g (0.80mol) o-fluorobenzyl chloride. During the addition, control the reaction temperature to be maintained at 10℃. After the addition is completed, continue the reaction at 10℃ for 4h. (2) 50.52 g of 15 wt% tert-butyl hydroperoxide ethanol solution was added dropwise, and the mixture was refluxed at 100 °C for 0.6 h. Fluorobenzene was recovered by distillation, washed with water, filtered, dried at 80 °C for 18 h, and recrystallized with isopropanol to obtain 152.63 g of 2,4'-difluorobenzophenone. The raw material conversion rate was 100%, the product yield was 87.44%, and the product purity was 99.2%.

[0026] Example 6 A method for preparing 2,4'-difluorobenzophenone, the method being as follows: (1) Mix 288.54g (3.0mol) fluorobenzene with 11.75g ​​of the La / MCM-22 catalyst described in Example 1, place in an ice bath at 0°C, and slowly add 144.62g (1.00mol) o-fluorobenzyl chloride dropwise while stirring. During the dropwise addition, control the reaction temperature to be maintained at 0°C. After the dropwise addition is completed, continue the reaction at 0°C for 5h. (2) 30.22 g of ethanol solution of 20 wt% m-chloroperoxybenzoic acid was added dropwise, and the mixture was refluxed at 100 °C for 0.5 h. Fluorobenzene was recovered by distillation, washed with water, filtered, dried at 80 °C for 18 h, and recrystallized with isopropanol to obtain 205.36 g of 2,4'-difluorobenzophenone. The raw material conversion rate was 100%, the product yield was 94.11%, and the product purity was 99.5%.

[0027] Example 7 A method for preparing 2,4'-difluorobenzophenone, the method being as follows: (1) Mix 241.12g (2.51mol) fluorobenzene with 4.52g of the La / MCM-22 catalyst described in Example 1 and place it in a constant temperature bath at -30℃. While stirring, slowly add 146.35g (1.01mol) o-fluorobenzyl chloride. During the addition, control the reaction temperature to be maintained at -30℃. After the addition is completed, continue the reaction at -30℃ for 4h. (2) 40.26 g of 12 wt% tert-butyl hydroperoxide ethanol solution was added dropwise, and the mixture was refluxed at 100 °C for 0.5 h. Fluorobenzene was recovered by distillation, washed with water, filtered, dried at 80 °C for 18 h, and recrystallized with isopropanol to obtain 180.47 g of 2,4'-difluorobenzophenone. The raw material conversion rate was 87.69%, the product yield was 82.54%, and the product purity was 98.6%.

[0028] Example 8 A method for preparing 2,4'-difluorobenzophenone, the method being as follows: (1) Mix 192.22g (2.00mol) fluorobenzene with 14.45g of the La / MCM-22 catalyst described in Example 2 and place it in a constant temperature bath at 30°C. While stirring, slowly add 144.57g (1.00mol) o-fluorobenzyl chloride. During the addition, control the reaction temperature to be maintained at 30°C. After the addition is completed, continue the reaction at 30°C for 2 hours. (2) Add 40g of 10wt% tert-butyl hydroperoxide ethanol solution to it, reflux at 120℃ for 0.5h, distill to recover fluorobenzene, wash with water, filter, dry at 90℃ for 20h, recrystallize with isopropanol to obtain 179.31g of 2,4'-difluorobenzophenone, with a raw material conversion rate of 100%, a product yield of 82.68%, and a product purity of 98.8%.

[0029] Example 9 A method for preparing 2,4'-difluorobenzophenone, the method being as follows: (1) Mix 480.55g (5.00mol) fluorobenzene with 2.90g of the La / MCM-22 catalyst described in Example 1 and place it in a constant temperature bath at -40℃. While stirring, slowly add 144.57g (1.00mol) o-fluorobenzyl chloride. During the addition, control the reaction temperature to be maintained at -40℃. After the addition is completed, continue the reaction at -40℃ for 10h. (2) Add 30g of 15wt% tert-butyl hydroperoxide ethanol solution to it, reflux at 80℃ for 1h, distill to recover fluorobenzene, wash with water, filter, dry at 85℃ for 20h, recrystallize with isopropanol to obtain 196.95g of 2,4'-difluorobenzophenone, with a raw material conversion rate of 93.62%, a product yield of 90.82%, and a product purity of 99.3%.

Claims

1. A method for preparing 2,4'-difluorobenzophenone, characterized in that: The preparation method uses fluorobenzene and o-fluorobenzyl chloride as raw materials, and first reacts them under the action of a catalyst, and then reacts them under the action of an oxidant; wherein, the catalyst is MCM-22 molecular sieve supported on metal La.

2. The method for preparing 2,4'-difluorobenzophenone according to claim 1, characterized in that: The preparation method is as follows: (1) Mix fluorobenzene with the catalyst, and add o-fluorobenzyl chloride dropwise at a reaction temperature of -40~30℃ and under stirring. During the dropwise addition, keep the reaction temperature constant. After the dropwise addition is completed, keep the temperature and continue the reaction for 2~10h. (2) Add an oxidizing agent solution to it, reflux at 80~120℃ for 0.5~1h, distill to recover fluorobenzene, wash with water, filter, dry, recrystallize to obtain 2,4'-difluorobenzophenone.

3. The method for preparing 2,4'-difluorobenzophenone according to claim 2, characterized in that: The molar ratio of o-fluorobenzyl chloride to fluorobenzene is 1:2~5, and the mass of the catalyst accounts for 2~10% of the mass of o-fluorobenzyl chloride.

4. The method for preparing 2,4'-difluorobenzophenone according to claim 3, characterized in that: The concentration of the oxidant solution is 10-20 wt%, and the mass of the oxidant solution accounts for 13-28% of the mass of the o-fluorobenzyl chloride.

5. The method for preparing 2,4'-difluorobenzophenone according to claim 3, characterized in that: The oxidant solution is an ethanol solution of tert-butyl hydroperoxide or m-chloroperoxybenzoic acid.

6. The method for preparing 2,4'-difluorobenzophenone according to claim 1, characterized in that: In the catalyst, La accounts for 2-5% of the catalyst mass.

7. The method for preparing 2,4'-difluorobenzophenone according to claim 1, characterized in that: The catalyst was prepared by the following method: Lanthanum nitrate solution was dropped into MCM-22 molecular sieve under vacuum and stirring, stirred for 30-35 min, then allowed to stand at room temperature for 12-13 h for equal volume impregnation, dried, and activated in a glow discharge device to obtain the catalyst.

8. The method for preparing 2,4'-difluorobenzophenone according to claim 7, characterized in that: The activation conditions are as follows: the glow discharge device is evacuated and 20 mL / min of 10% H2 / Ar gas is introduced, the pressure inside the discharge tube is maintained at 100~150 Pa, and reduction is carried out at room temperature for 60 min.

9. The method for preparing 2,4'-difluorobenzophenone according to claim 7, characterized in that: The drying conditions are as follows: drying at 100~110℃ for 6-12 hours.

10. The method for preparing 2,4'-difluorobenzophenone according to claim 2, characterized in that: The drying conditions are drying at 80-85℃ for 18-20 hours, and the recrystallization is carried out using isopropanol.

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