Synthesis method of 2, 4-difluoronitrobenzene

Abstract

The invention relates to the technical field of chemical synthesis, and provides a synthesis method of 2, 4-difluoronitrobenzene, which comprises the following steps: under the action of a catalyst, carrying out fluorination reaction on 2, 4-dichloronitrobenzene and a fluorinating agent to obtain 2, 4-difluoronitrobenzene; the catalyst comprises tetrabutylammonium bromide and tetrabutylammonium chloride, and the mass ratio of the tetrabutylammonium bromide to the tetrabutylammonium chloride is (1: 5)-(5: 1). According to the technical scheme, the problems of low yield and low purity during synthesis of 2, 4-difluoronitrobenzene in related technologies are solved.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and in particular 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 the synthesis of many drugs and plays a vital role in the research and development of antibiotics and anticancer drugs. In the field of pesticides, 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. However, there are still some problems with the current synthesis method of 2,4-difluoronitrobenzene. Low yield and low purity are the main bottlenecks restricting its large-scale application. Traditional synthesis methods often have the disadvantages of harsh reaction conditions, many side reactions, and difficult separation and purification. This not only increases the production cost, but also affects the quality and performance of the product. Therefore, the development of a high-yield, high-purity synthesis method of 2,4-difluoronitrobenzene has important practical significance and application value. Summary of the invention

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

[0004] The technical scheme 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 undergo a fluorination reaction to obtain 2,4-difluoronitrobenzene; The catalyst comprises tetrabutylammonium bromide and tetrabutylammonium chloride, and the mass ratio of the tetrabutylammonium bromide to the tetrabutylammonium chloride is 1:5-5:1.

[0005] As a further technical solution, the mass ratio of the tetrabutylammonium bromide to the tetrabutylammonium chloride is 1:2-3.

[0006] As a further technical solution, the fluorinating agent includes one or more of potassium fluoride, sodium fluoride, and cesium fluoride.

[0007] As a further technical solution, the temperature of the fluorination reaction is 160-180° C., and the time of the fluorination reaction is 15-25 hours.

[0008] As a further technical solution, after the fluorination reaction, post-treatment is also included, and the post-treatment is specifically: washing, dehydrating and distilling the reaction liquid to obtain a 2,4-difluoronitrobenzene finished product; The water washing is carried out in two steps, and the time of the two steps of water washing is 2 to 4 hours.

[0009] As a further technical solution, the vacuum degree of dehydration is -0.085~-0.095MPa, and the dehydration time is 3~5 hours.

[0010] As a further technical solution, the distillation temperature is 82-90°C, the tower bottom temperature is 110-130°C, the pressure in the tower is -0.095-0.01MPa, and the distillation time is 16-20 hours.

[0011] As a further technical solution, the molar ratio of the 2,4-dichloronitrobenzene to the fluorinating agent is 1:2-3.

[0012] As a further technical solution, the catalyst also includes a crown ether catalyst, and the mass ratio of the crown ether catalyst to the fluorinating agent is 2~3:250.

[0013] In the present invention, a crown ether catalyst is added, which can not only selectively form a complex with a metal cation to reduce the occurrence of other side reactions, but also enable the fluoride ions to be better dissociated and activated, which helps to increase the conversion rate of the reactants within the same time, thereby increasing the yield and purity of 2,4-difluoronitrobenzene.

[0014] As a further technical solution, the crown ether catalyst includes one or more of 18-crown-6, dicyclohexane-18-crown-6, and dibenzo-18-crown-6.

[0015] The working principle and beneficial effects of the present invention are: In the present invention, tetrabutylammonium bromide and tetrabutylammonium chloride are used as catalysts at the same time, the mass ratio of the two is limited, the synergistic effect of the two is brought into play, the contact opportunity between fluoride ions and substrates is increased, the reaction activity of the substrate is adjusted, the reaction is guided to proceed along the expected path, the occurrence of side reactions is reduced, the rate of fluorination reaction is accelerated, and the yield and purity of 2,4-difluoronitrobenzene are improved. DETAILED DESCRIPTION

[0016] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0017] Example 1 A method for synthesizing 2,4-difluoronitrobenzene comprises the following steps: Fluorination: weigh 2540kg (13.23mol) of 2,4-dichloronitrobenzene and put it into a metering tank, pump it into the fluorination synthesis reactor through a closed pipe, then start stirring and heat it to 80°C. After the temperature reaches 80°C, manually put the packaging barrel into the feeding area, and then use the equipment to control the packaging barrel mouth to align with the synthesis reactor feeding port, open the reactor feeding port valve, add 1695kg (29.17mol) of potassium fluoride and 56kg of catalyst, start the heating system, heat it to 160°C, and then keep it warm for 15 hours to react, perform fluorination synthesis reaction, and cool it to 120°C to obtain a crude product; wherein 56kg of catalyst is composed of tetrabutylammonium bromide and tetrabutylammonium chloride in a mass ratio of 1:1; First water washing: remotely open the synthesis kettle valve, and the synthesis reaction liquid flows into the water washing receiving kettle with about 4000 kg of water (recycled water) by gravity through the height difference. Turn on the stirring system, stir for 30 minutes, let it stand for 30 minutes, separate the liquids, the upper layer is the water phase, and the lower layer is the organic phase. The lower organic phase enters the secondary water washing kettle through a closed pipe, and the upper water phase is pumped into the primary water washing distillation kettle through a closed pipe. The first water washing time is 2 hours; Second water washing: pump about 1460 kg of recycled distilled water into the organic phase in the secondary water washing kettle, turn on the stirring system, stir for 30 minutes, let stand for 30 minutes, separate the liquids, the upper layer is the water phase, the lower layer is the organic phase, the organic phase is pumped into the dehydration kettle through the pipeline to remove water, the upper water phase is pumped into the primary water washing kettle through the closed pipeline for reuse in the primary water washing process, the secondary water washing process time is 2 hours; Dehydration: The organic phase completes the dehydration process in the dehydration kettle. First, the vacuum is turned on until the vacuum in the kettle reaches a vacuum degree below -0.085MPa, and then the steam heating system is turned on for distillation and dehydration. The dehydration process takes 3 hours, and the distillation temperature is maintained at 100°C. After the dehydration is completed, the cooling system is turned on to cool down to 60°C (cooling method: circulating water). After the dehydration is completed, the qualified products enter the distillation tower for distillation; Distillation: The distillation temperature controls the top temperature of the tower to 82°C, the bottom temperature to 110°C, and the pressure in the tower to -0.095MPa. The product obtained by distillation is sent to the product tank through a closed pipeline, and the residue in the distillation kettle is disposed of as hazardous waste. The distillation process distills 3 batches of crude products together. The total distillation process takes 16 hours to obtain 2,4-difluoronitrobenzene.

[0018] Example 2 A method for synthesizing 2,4-difluoronitrobenzene comprises the following steps: Fluorination: weigh 2540kg (13.23mol) of 2,4-dichloronitrobenzene and put it into a metering tank, pump it into the fluorination synthesis reactor through a closed pipe, then start stirring and heat it to 80°C. After the temperature reaches 80°C, manually put the packaging barrel into the feeding area, and then use the equipment to control the packaging barrel mouth to align with the synthesis reactor feeding port, open the reactor feeding port valve, add 1695kg (29.17mol) of potassium fluoride and 56kg of catalyst, start the heating system, heat it to 170°C and then keep it warm for 20 hours, carry out fluorination synthesis reaction, and cool it to 120°C to obtain a crude product; wherein 56kg of catalyst is composed of tetrabutylammonium bromide and tetrabutylammonium chloride in a mass ratio of 1:1; First water washing: remotely open the synthesis kettle valve, and the synthesis reaction liquid flows into the water washing receiving kettle with about 4000 kg of water (recycled water) by gravity through the height difference. Turn on the stirring system, stir for 30 minutes, let it stand for 30 minutes, separate the liquids, the upper layer is the water phase, and the lower layer is the organic phase. The lower organic phase enters the secondary water washing kettle through a closed pipe, and the upper water phase is pumped into the primary water washing distillation kettle through a closed pipe. The first water washing time is 3 hours; Second water washing: pump about 1460 kg of recycled distilled water into the organic phase in the secondary water washing kettle, turn on the stirring system, stir for 30 minutes, let stand for 30 minutes, separate the liquids, the upper layer is the water phase, the lower layer is the organic phase, the organic phase is pumped into the dehydration kettle through the pipeline to remove water, the upper water phase is pumped into the primary water washing kettle through the closed pipeline for reuse in the primary water washing process, the secondary water washing process time is 3 hours; Dehydration: The organic phase completes the dehydration process in the dehydration kettle. First, the vacuum is turned on until the vacuum in the kettle reaches a vacuum degree below -0.09MPa, and then the steam heating system is turned on for distillation and dehydration. The dehydration process takes 4 hours, and the distillation temperature is maintained at 100°C. After the dehydration is completed, the cooling system is turned on to cool down to 60°C (cooling method: circulating water). After the dehydration is completed, the qualified products enter the distillation tower for distillation; Distillation: The distillation temperature controls the top temperature of the tower to 86°C, the bottom temperature to 120°C, and the pressure in the tower to -0.098MPa. The product obtained by distillation is sent to the product tank through a closed pipeline, and the residue in the distillation kettle is disposed of as hazardous waste. The distillation process distills 3 batches of crude products together. The total distillation process takes 18 hours to obtain 2,4-difluoronitrobenzene.

[0019] Example 3 A method for synthesizing 2,4-difluoronitrobenzene comprises the following steps: Fluorination: weigh 2540kg (13.23mol) of 2,4-dichloronitrobenzene and put it into a metering tank, pump it into the fluorination synthesis reactor through a closed pipe, then start stirring and heat it to 80°C. After the temperature reaches 80°C, manually put the packaging barrel into the feeding area, and then use the equipment to control the packaging barrel mouth to align with the synthesis reactor feeding port, open the reactor feeding port valve, add 1695kg (29.17mol) of potassium fluoride and 56kg of catalyst, start the heating system, heat it to 180°C, and then keep it warm for 25 hours to react, perform fluorination synthesis reaction, and cool it to 120°C to obtain a crude product; wherein 56kg of catalyst is composed of tetrabutylammonium bromide and tetrabutylammonium chloride in a mass ratio of 1:1; First water washing: remotely open the synthesis kettle valve, and the synthesis reaction liquid flows into the water washing receiving kettle with about 4000kg of water (recycled water) by gravity through the height difference. Turn on the stirring system, stir for 30 minutes, let it stand for 30 minutes, separate the liquids, the upper layer is the water phase, and the lower layer is the organic phase. The lower organic phase enters the secondary water washing kettle through a closed pipe, and the upper water phase is pumped into the primary water washing distillation kettle through a closed pipe. The first water washing time is 4 hours; Second water washing: pump about 1460 kg of recycled distilled water into the organic phase in the secondary water washing kettle, turn on the stirring system, stir for 30 minutes, let stand for 30 minutes, separate the liquids, the upper layer is the water phase, the lower layer is the organic phase, the organic phase is pumped into the dehydration kettle through the pipeline to remove water, the upper water phase is pumped into the primary water washing kettle through the closed pipeline for reuse in the primary water washing process, the secondary water washing process time is 4 hours; Dehydration: The organic phase completes the dehydration process in the dehydration kettle. First, the vacuum is turned on until the vacuum in the kettle reaches a vacuum degree below -0.095MPa, and then the steam heating system is turned on for distillation and dehydration. The dehydration process takes 5 hours, and the distillation temperature is maintained at 100°C. After the dehydration is completed, the cooling system is turned on to cool down to 60°C (cooling method: circulating water). After the dehydration is completed, the qualified products enter the distillation tower for distillation; Distillation: The distillation temperature controls the top temperature of the tower to 90°C, the bottom temperature to 130°C, and the pressure in the tower to -0.01MPa. The product obtained by distillation is sent to the product tank through a closed pipeline, and the residue in the distillation kettle is disposed of as hazardous waste. The distillation process distills 3 batches of crude products together. The total distillation process takes 20 hours to obtain 2,4-difluoronitrobenzene.

[0020] Example 4 Compared with Example 2, the difference of Example 4 is that the catalyst consists of tetrabutylammonium bromide and tetrabutylammonium chloride in a mass ratio of 1:2.

[0021] Example 5 Compared with Example 2, the difference of Example 5 is that the catalyst consists of tetrabutylammonium bromide and tetrabutylammonium chloride in a mass ratio of 1:3.

[0022] Example 6 Compared with Example 2, the difference of Example 6 is that the catalyst consists of tetrabutylammonium bromide and tetrabutylammonium chloride in a mass ratio of 1:4.

[0023] Example 7 Compared with Example 5, the difference of Example 7 is that the preparation method of the crude product obtained by fluorination comprises the following steps: weighing 2540 kg of 2,4-dichloronitrobenzene and putting it into a metering tank, pumping it into the fluorination synthesis kettle through a closed pipe, and then starting stirring and heating it to 80°C. After the temperature reaches 80°C, manually putting the packaging barrel into the feeding area, and then aligning the mouth of the packaging barrel with the feeding port of the synthesis kettle by equipment control, opening the valve of the reactor feeding port, adding 1695 kg of potassium fluoride, 56 kg of catalyst, and 6.78 kg of crown ether catalyst 18-crown-6, starting the heating system, heating to 180°C and then keeping the temperature for reaction for 25 hours, carrying out fluorination synthesis reaction, and cooling to 120°C to obtain a crude product; wherein 56 kg of catalyst is composed of tetrabutylammonium bromide and tetrabutylammonium chloride in a mass ratio of 1:1.

[0024] Example 8 Compared with Example 7, the difference in Example 8 is that the added amount of the crown ether catalyst 18-crown-6 is 13.56 kg.

[0025] Example 9 Compared with Example 7, the difference in Example 9 is that the added amount of the crown ether catalyst 18-crown-6 is 20.34 kg.

[0026] Example 10 Compared with Example 7, the difference in Example 10 is that the added amount of the crown ether catalyst 18-crown-6 is 27.12 kg.

[0027] Comparative Example 1 Compared with Example 2, the difference in Comparative Example 1 is that 56 kg of the catalyst is tetrabutylammonium bromide.

[0028] Comparative Example 2 Compared with Example 2, the difference of Comparative Example 2 is that 56 kg of the catalyst is tetrabutylammonium chloride.

[0029] The test results are shown in the following table: Table 1 Purity and yield of 2,4-difluoronitrobenzene obtained in Examples 1 to 10 and Comparative Examples 1 to 2

[0030] Note: In the above table, the purity of 2,4-difluoronitrobenzene was determined by high performance liquid chromatography, and the yield was calculated as follows: (actual yield / theoretical yield) × 100%. The theoretical yield was calculated based on 2,4-dichloronitrobenzene.

[0031] Compared with Example 2, Comparative Example 1 only adds tetrabutylammonium bromide as a catalyst, and Comparative Example 2 only adds tetrabutylammonium chloride as a catalyst. As a result, the yield and purity of Example 2 are higher than those of Comparative Examples 1 and 2, indicating that tetrabutylammonium bromide and tetrabutylammonium chloride play a synergistic role and can improve the yield and purity of 2,4-difluoronitrobenzene. Compared with Example 2, Examples 4 to 6 add tetrabutylammonium bromide and tetrabutylammonium chloride in different mass ratios. As a result, the yield and purity of Examples 4 and 5 are higher than those of Examples 2 and 6, indicating that when the mass ratio of tetrabutylammonium bromide to tetrabutylammonium chloride is 1:2~3, the yield and purity of the obtained 2,4-difluoronitrobenzene are higher.

[0032] Compared with Example 5, Examples 7 to 10 added a crown ether catalyst 18-crown-6, and the yield and purity of Examples 7 to 10 were higher than those of Example 5, indicating that the addition of the crown ether catalyst 18-crown-6 can improve the yield and purity of 2,4-difluoronitrobenzene. In Examples 7 to 10, different mass ratios of crown ether catalyst and fluorinating agent were added, and the yield and purity 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 to 3:250, the yield and purity of the obtained 2,4-difluoronitrobenzene were higher.

[0033] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing 2,4-difluoronitrobenzene, characterized in that: The method comprises 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 comprises tetrabutylammonium bromide and tetrabutylammonium chloride, and the mass ratio of the tetrabutylammonium bromide to the tetrabutylammonium chloride is 1:5-5:

1.

2. A method for synthesizing 2,4-difluoronitrobenzene according to claim 1, characterized in that: The mass ratio of the tetrabutylammonium bromide to the tetrabutylammonium chloride is 1:2-3.

3. A method for synthesizing 2,4-difluoronitrobenzene according to claim 1, characterized in that: The fluorinating agent includes one or more of potassium fluoride, sodium fluoride, and cesium fluoride.

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

5. A method for synthesizing 2,4-difluoronitrobenzene according to claim 1, characterized in that: After the fluorination reaction, post-treatment is also included, and the post-treatment specifically comprises: washing, dehydrating and distilling the reaction liquid to obtain a 2,4-difluoronitrobenzene finished product; The water washing is carried out in two steps, and the time of the two steps of water washing is 2 to 4 hours.

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

7. A method for synthesizing 2,4-difluoronitrobenzene according to claim 5, characterized in that: The distillation temperature is 82-90° C., the tower bottom temperature is 110-130° C., the tower internal pressure is -0.095-0.01 MPa, and the distillation time is 16-20 hours.

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

9. A method for synthesizing 2,4-difluoronitrobenzene according to claim 1, characterized in that: The catalyst also includes a crown ether catalyst, and the mass ratio of the crown ether catalyst to the fluorinating agent is 2-3:

250.

10. The method for synthesizing 2,4-difluoronitrobenzene according to claim 9, characterized in that: The crown ether catalyst includes one or more of 18-crown-6, dicyclohexane-18-crown-6, and dibenzo-18-crown-6.

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