A method for synthesizing 2,4-difluoronitrobenzene

Abstract

The present invention relates to the technical field of chemical synthesis, and provides a method for synthesizing 2,4-difluoronitrobenzene, which includes the following steps: under the action of a catalyst, 2,4-dichloronitrobenzene and a fluorinating agent are subjected to a fluorination reaction to obtain 2,4-difluoronitrobenzene; the catalyst includes tetrabutylammonium bromide and tetrabutylammonium chloride, and the mass ratio of tetrabutylammonium bromide to tetrabutylammonium chloride is 1:5 to 5:1. Through the above technical solution, the problems of low yield and low purity in the synthesis of 2,4-difluoronitrobenzene in the related art are solved.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and specifically, to a method for synthesizing 2,4-difluoronitrobenzene. Background Art

[0002] 2,4-Difluoronitrobenzene is an important organic compound. In the chemical industry, 2,4-difluoronitrobenzene has a wide range of applications. In the pharmaceutical industry, it is a key intermediate for synthesizing many drugs and plays a crucial role in the research and development of antibiotics and anticancer drugs. In the pesticide field, it can be used to manufacture specific pesticides, which helps to increase crop yields and resist pests. At the same time, it also has important application value in dye synthesis and other aspects. However, there are still some problems with the current synthesis methods of 2,4-difluoronitrobenzene. Low yield and low purity are the main bottlenecks restricting its large-scale application. Traditional synthesis methods often have disadvantages such as harsh reaction conditions, many side reactions, and difficult separation and purification. This not only increases production costs but also affects the quality and performance of the product. Therefore, developing a synthesis method for 2,4-difluoronitrobenzene with high yield and high purity has important practical significance and application value. Summary of the Invention

[0003] The present invention provides a method for synthesizing 2,4-difluoronitrobenzene, which solves the problems of low yield and low purity in the synthesis of 2,4-difluoronitrobenzene in the related art.

[0004] The technical solution of the present invention is as follows: The present invention provides a method for synthesizing 2,4-difluoronitrobenzene, comprising the following steps: Under the action of a catalyst, 2,4-dichloronitrobenzene and a fluorinating agent are subjected to a fluorination reaction to obtain 2,4-difluoronitrobenzene;

[0005] The catalyst includes tetrabutylammonium bromide and tetrabutylammonium chloride, and the mass ratio of tetrabutylammonium bromide to tetrabutylammonium chloride is 1:5 to 5:1.

[0006] As a further technical solution, the mass ratio of tetrabutylammonium bromide to tetrabutylammonium chloride is 1:2 to 3.

[0007] As a further technical solution, the fluorinating agent includes one or more of potassium fluoride, sodium fluoride, and cesium fluoride.

[0008] As a further technical solution, the temperature of the fluorination reaction is 160 to 180 °C, and the time of the fluorination reaction is 15 to 25 hours.

[0009] As a further technical solution, after the fluorination reaction, post-treatment is also included. The post-treatment is specifically as follows: The reaction solution is washed with water, dehydrated, and rectified to obtain 2,4-difluoronitrobenzene finished product;

[0010] The water washing is carried out in two steps, and the time for each step of water washing is 2 to 4 hours.

[0011] As a further technical solution, the vacuum degree for dehydration is -0.085 to -0.095 MPa, and the dehydration time is 3 to 5 hours.

[0012] As a further technical solution, the temperature for rectification is 82 to 90 °C, the bottom temperature of the tower is 110 to 130 °C, the pressure inside the tower is -0.095 to -0.01 MPa, and the rectification time is 16 to 20 hours.

[0013] As a further technical solution, the molar ratio of the 2,4-dichloronitrobenzene to the fluorinating agent is 1:2 to 3.

[0014] As a further technical solution, the catalyst further includes a crown ether catalyst, and the mass ratio of the crown ether catalyst to the fluorinating agent is 2 to 3:250.

[0015] In the present invention, a crown ether catalyst is also added, which can not only selectively form complexes with metal cations to reduce the occurrence of other side reactions, but also make fluoride ions dissociate and activate better, helping to improve the conversion rate of reactants within the same time, and thus improving the yield and purity of 2,4-difluoronitrobenzene.

[0016] As a further technical solution, the crown ether catalyst includes one or more of 18-crown-6, dicyclohexano-18-crown-6, and dibenzo-18-crown-6.

[0017] The working principle and beneficial effects of the present invention are as follows:

[0018] In the present invention, tetrabutylammonium bromide and tetrabutylammonium chloride are used as catalysts simultaneously, and the mass ratio of the two is limited to exert their synergistic effect, increase the contact opportunity between fluoride ions and the substrate, adjust the reaction activity of the substrate, guide the reaction to proceed along the expected path, reduce the occurrence of side reactions, accelerate the rate of the fluorination reaction, and improve the yield and purity of 2,4-difluoronitrobenzene. Specific Embodiments

[0019] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without making creative efforts fall within the scope of the present invention.

[0020] Example 1

[0021] A method for synthesizing 2,4-difluoronitrobenzene includes the following steps:

[0022] Fluorination: Weigh 2540 kg (13.23 mol) of 2,4-dichloronitrobenzene and put it into a metering tank. Pump it into the fluorination synthesis reactor through a closed pipeline. Then start stirring and heat up to 80 °C. After the temperature reaches 80 °C, manually place the packaging barrel into the feeding area. After aligning the opening of the packaging barrel with the feeding port of the synthesis reactor using equipment control, open the valve of the reactor feeding port and add 1695 kg (29.17 mol) of potassium fluoride and 56 kg of catalyst. Start the heating system and keep the temperature at 160 °C for 15 hours for the fluorination synthesis reaction. Cool down to 120 °C to obtain the crude product. Among them, the 56 kg of catalyst consists of tetrabutylammonium bromide and tetrabutylammonium chloride with a mass ratio of 1:1.

[0023] First water washing: Remotely open the valve of the synthesis reactor. The synthesis reaction solution flows into the water washing receiving tank with about 4000 kg of existing water (reclaimed water) by gravity due to the height difference. Start the stirring system, stir for 30 minutes, let it stand for 30 minutes, and separate the liquid. The upper layer is the aqueous phase, and the lower layer is the organic phase. The lower organic phase enters the secondary water washing reactor through a closed pipeline, and the upper aqueous phase is pumped into the first water washing distillation kettle through a closed pipeline. The time for the first water washing is 2 hours.

[0024] Second water washing: Pump about 1460 kg of recycled distilled water into the organic phase in the secondary water washing reactor. Start the stirring system, stir for 30 minutes, let it stand for 30 minutes, and separate the liquid. The upper layer is the aqueous phase, and the lower layer is the organic phase. The organic phase is pumped into the dehydration kettle through a pipeline for water removal, and the upper aqueous phase is pumped into the first water washing kettle through a closed pipeline for reuse in the first water washing process. The time for the second water washing process is 2 hours.

[0025] Dehydration: The organic phase completes the dehydration process in the dehydration kettle. First, evacuate to a vacuum degree below -0.085 MPa in the kettle, and then start the steam heating system for distillation dehydration. The time for the dehydration process is 3 hours, and the distillation temperature is maintained at 100 °C. After dehydration, start the cooling system to cool down to 60 °C (cooling method: circulating water). After dehydration, the qualified product enters the rectification tower for rectification.

[0026] Rectification: Control the rectification temperature with the top temperature of the tower at 82 °C, the bottom temperature of the tower at 110 °C, and the pressure inside the tower at -0.095 MPa. The product obtained by rectification is sent to the product tank through a closed pipeline, and the residue in the rectification kettle is disposed of as hazardous waste. The rectification process rectifies 3 batches of crude products together, and the total time for the rectification process is 16 hours, thus obtaining 2,4-difluoronitrobenzene.

[0027] Example 2

[0028] A method for synthesizing 2,4-difluoronitrobenzene, comprising the following steps:

[0029] Fluorination: Weigh 2540 kg (13.23 mol) of 2,4-dichloronitrobenzene and put it into a metering tank. Pump it into the fluorination synthesis kettle through a closed pipeline. Then start stirring and heat up to 80 °C. After the temperature reaches 80 °C, manually place the packaging barrel into the feeding area. Then, using equipment control, align the mouth of the packaging barrel with the feeding port of the synthesis kettle, and open the valve of the reaction kettle feeding port to add 1695 kg (29.17 mol) of potassium fluoride and 56 kg of catalyst. Start the heating system, heat up to 170 °C and keep the reaction for 20 hours to carry out the fluorination synthesis reaction. Cool down to 120 °C to obtain the crude product; among them, 56 kg of catalyst is composed of tetrabutylammonium bromide and tetrabutylammonium chloride with a mass ratio of 1:1.

[0030] First water washing: Remotely open the valve of the synthesis kettle. The synthesis reaction liquid flows into the water washing receiving kettle with about 4000 kg of existing water (reclaimed water) by gravity due to the height difference. Start the stirring system, stir for 30 minutes, let it stand for 30 minutes, and separate the liquid. The upper layer is the aqueous phase, and the lower layer is the organic phase. The lower-layer organic phase enters the secondary water washing kettle through a closed pipeline, and the upper-layer aqueous phase is pumped into the first water washing distillation kettle through a closed pipeline. The time for the first water washing is 3 hours.

[0031] Second water washing: Pump about 1460 kg of recycled distilled water into the organic phase in the secondary water washing kettle. Start the stirring system, stir for 30 minutes, let it stand for 30 minutes, and separate the liquid. The upper layer is the aqueous phase, and the lower layer is the organic phase. The organic phase is pumped into the dehydration kettle through a pipeline for water removal, and the upper-layer aqueous phase is pumped into the first water washing kettle through a closed pipeline for reuse in the first water washing process. The time for the second water washing process is 3 hours.

[0032] Dehydration: The organic phase completes the dehydration process in the dehydration kettle. First, start the vacuum until the vacuum in the kettle reaches below -0.09 MPa, and then start the steam heating system for distillation dehydration. The time for the dehydration process is 4 hours, and the distillation temperature is maintained at 100 °C. After dehydration is completed, start the cooling system to cool down to 60 °C (cooling method: circulating water). After dehydration is completed, the qualified product enters the rectification tower for rectification.

[0033] Rectification: Control the rectification temperature. The temperature at the top of the tower is 86 °C, the temperature at the bottom of the tower is 120 °C, and the pressure inside the tower is -0.098 MPa. The product obtained by rectification is sent to the product tank through a closed pipeline, and the residue in the rectification kettle is disposed of as hazardous waste; the rectification process rectifies 3 batches of crude products together, and the total time for the rectification process is 18 hours, thus obtaining 2,4-difluoronitrobenzene.

[0034] Example 3

[0035] A method for synthesizing 2,4-difluoronitrobenzene, comprising the following steps:

[0036] Fluorination: Weigh 2540 kg (13.23 mol) of 2,4-dichloronitrobenzene and put it into the metering tank. Pump it into the fluorination synthesis kettle through a closed pipeline. Then start stirring and heat up to 80 °C. After the temperature reaches 80 °C, manually place the packaging barrel into the feeding area. Then, use the equipment to align the opening of the packaging barrel with the feeding port of the synthesis kettle, and open the valve of the reaction kettle feeding port to add 1695 kg (29.17 mol) of potassium fluoride and 56 kg of catalyst. Start the heating system and heat up to 180 °C, then keep the temperature for reaction for 25 hours to carry out the fluorination synthesis reaction. Cool down to 120 °C to obtain the crude product; among them, the 56 kg catalyst is composed of tetrabutylammonium bromide and tetrabutylammonium chloride with a mass ratio of 1:1.

[0037] First water washing: Remotely open the valve of the synthesis kettle, and the synthesis reaction liquid flows into the water washing receiving kettle with about 4000 kg of existing water (reclaimed water) by gravity due to the height difference. Start the stirring system, stir for 30 minutes, let it stand for 30 minutes, and separate the liquid. The upper layer is the aqueous phase, and the lower layer is the organic phase. The lower organic phase enters the secondary water washing kettle through a closed pipeline, and the upper aqueous phase is pumped into the first water washing distillation kettle through a closed pipeline. The time for the first water washing is 4 hours.

[0038] Second water washing: Pump about 1460 kg of recycled distilled water into the organic phase in the secondary water washing kettle. Start the stirring system, stir for 30 minutes, let it stand for 30 minutes, and separate the liquid. The upper layer is the aqueous phase, and the lower layer is the organic phase. The organic phase is pumped into the dehydration kettle through a pipeline for water removal, and the upper aqueous phase is pumped into the first water washing kettle through a closed pipeline for reuse in the first water washing process. The time for the second water washing process is 4 hours.

[0039] Dehydration: The organic phase completes the dehydration process in the dehydration kettle. First, start the vacuum until the vacuum degree in the kettle is below -0.095 MPa, and then start the steam heating system for distillation dehydration. The time for the dehydration process is 5 hours, and the distillation temperature is maintained at 100 °C. After dehydration, start the cooling system to cool down to 60 °C (cooling method: circulating water). After dehydration, the qualified product enters the rectification tower for rectification.

[0040] Rectification: Control the rectification temperature, with the top temperature of the tower at 90 °C, the bottom temperature of the tower at 130 °C, and the pressure inside the tower at -0.01 MPa. The product obtained by rectification is sent to the product tank through a closed pipeline, and the residue in the rectification kettle is disposed of as hazardous waste; in the rectification process, 3 batches of crude products are rectified together, and the total time for the rectification process is 20 hours, thus obtaining 2,4-difluoronitrobenzene.

[0041] Example 4

[0042] Compared with Example 2, the difference in Example 4 is that the catalyst is composed of tetrabutylammonium bromide and tetrabutylammonium chloride with a mass ratio of 1:2.

[0043] Example 5

[0044] Compared with Example 2, Example 5 is different in that the catalyst is composed of tetrabutylammonium bromide and tetrabutylammonium chloride with a mass ratio of 1:3.

[0045] Example 6

[0046] Compared with Example 2, Example 6 is different in that the catalyst is composed of tetrabutylammonium bromide and tetrabutylammonium chloride with a mass ratio of 1:4.

[0047] Example 7

[0048] Compared with Example 5, Example 7 is different in that the preparation method of the crude product obtained by fluorination includes the following steps: Weigh 2540 kg of 2,4-dichloronitrobenzene and put it into a metering tank, pump it into the fluorination synthesis kettle through a closed pipeline, then start stirring and heat up to 80 °C. After the temperature reaches 80 °C, put the packaging barrel into the feeding area manually. Then, use the equipment to control the packaging barrel mouth to align with the feeding port of the synthesis kettle, and then open the valve of the reaction kettle feeding port to add 1695 kg of potassium fluoride, 56 kg of catalyst, and 6.78 kg of crown ether catalyst 18-crown-6. Start the heating system, heat up to 180 °C and keep the temperature for 25 hours for fluorination synthesis reaction, and cool down to 120 °C to obtain the crude product; among them, 56 kg of the catalyst is composed of tetrabutylammonium bromide and tetrabutylammonium chloride with a mass ratio of 1:1.

[0049] Example 8

[0050] Compared with Example 7, Example 8 is different in that the addition amount of crown ether catalyst 18-crown-6 is 13.56 kg.

[0051] Example 9

[0052] Compared with Example 7, Example 9 is different in that the addition amount of crown ether catalyst 18-crown-6 is 20.34 kg.

[0053] Example 10

[0054] Compared with Example 7, Example 10 is different in that the addition amount of crown ether catalyst 18-crown-6 is 27.12 kg.

[0055] Comparative Example 1

[0056] Compared with Example 2, Comparative Example 1 is different in that 56 kg of the catalyst is tetrabutylammonium bromide.

[0057] Comparative Example 2

[0058] Compared with Example 2, Comparative Example 2 is different in that 56 kg of the catalyst is tetrabutylammonium chloride.

[0059] The test results are shown in the following table:

[0060] Table 1 Purity and Yield of 2,4-Difluoronitrobenzene Prepared in Examples 1-10 and Comparative Examples 1-2

[0061]

[0062] Note: In the above table, the purity of 2,4-difluoronitrobenzene was determined by high performance liquid chromatography. The yield calculation formula is: (actual yield / theoretical yield) × 100%, and the theoretical yield was calculated based on 2,4-dichloronitrobenzene.

[0063] Compared with Example 2, tetrabutylammonium bromide was only added as a catalyst in Comparative Example 1, and tetrabutylammonium chloride was only added as a catalyst in Comparative Example 2. As a result, the yield and purity of Example 2 were higher than those of Comparative Examples 1 and 2, indicating that tetrabutylammonium bromide and tetrabutylammonium chloride played a synergistic role and could improve the yield and purity of 2,4-difluoronitrobenzene. Compared with Example 2, different mass ratios of tetrabutylammonium bromide and tetrabutylammonium chloride were added in Examples 4-6. As a result, the yields and purities of Examples 4 and 5 were higher than those of Examples 2 and 6, indicating that when the mass ratio of tetrabutylammonium bromide to tetrabutylammonium chloride was 1:2-3, the yield and purity of the obtained 2,4-difluoronitrobenzene were higher.

[0064] Compared with Example 5, 18-crown-6, a crown ether catalyst, was added in Examples 7-10. As a result, the yields and purities of Examples 7-10 were higher than those of Example 5, indicating that the addition of the crown ether catalyst 18-crown-6 could improve the yield and purity of 2,4-difluoronitrobenzene. In Examples 7-10, different mass ratios of the crown ether catalyst to the fluorinating agent were added. As a result, the yields and purities of Examples 8 and 9 were higher than those of Examples 7 and 10, indicating that when the mass ratio of the crown ether catalyst to the fluorinating agent was 2-3:250, the yield and purity of the obtained 2,4-difluoronitrobenzene were higher.

[0065] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for synthesizing 2,4-difluoronitrobenzene, characterized in that, It includes the following steps: Under the action of a catalyst, 2,4-dichloronitrobenzene and a fluorinating agent are subjected to a fluorination reaction to obtain 2,4-difluoronitrobenzene; The catalyst is tetrabutylammonium bromide, tetrabutylammonium chloride and a crown ether catalyst, and the mass ratio of the tetrabutylammonium bromide to the tetrabutylammonium chloride is 1:2 to 3; The mass ratio of the crown ether catalyst to the fluorinating agent is 2 to 3:

250.

2. The synthesis method of 2,4-difluoronitrobenzene according to claim 1, characterized in that, The fluorinating agent is one or more of potassium fluoride, sodium fluoride, and cesium fluoride.

3. The synthesis method of 2,4-difluoronitrobenzene according to claim 1, characterized in that, The temperature of the fluorination reaction is 160 to 180 °C, and the time of the fluorination reaction is 15 to 25 hours.

4. The synthesis method of 2,4-difluoronitrobenzene according to claim 1, characterized in that, After the fluorination reaction, it also includes post-treatment. The post-treatment is specifically: The reaction solution is washed with water, dehydrated, and rectified to obtain a finished product of 2,4-difluoronitrobenzene; The water washing is carried out in two steps, and the time for both steps of water washing is 2 to 4 hours.

5. The synthesis method of 2,4-difluoronitrobenzene according to claim 4, characterized in that, The vacuum degree of the dehydration is -0.085 to -0.095 MPa, and the time of the dehydration is 3 to 5 hours.

6. The synthesis method of 2,4-difluoronitrobenzene according to claim 4, wherein The temperature of the rectification is 82 to 90 °C, the bottom temperature is 110 to 130 °C, the pressure inside the tower is -0.095 to -0.01 MPa, and the time of the rectification is 16 to 20 hours.

7. The synthesis method of 2,4-difluoronitrobenzene according to claim 1, characterized in that, The molar ratio of the 2,4-dichloronitrobenzene to the fluorinating agent is 1:2 to 3.

8. The synthesis method of 2,4-difluoronitrobenzene according to claim 1, characterized in that, The crown ether catalyst is one or more of 18-crown-6, dicyclohexano-18-crown-6, and dibenzo-18-crown-6.

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