The invention discloses a method for continuously synthesizing 3apos by using a continuous flow reactor. , 5apos; method for preparing 2, 2, 2-trifluoroacetophenone

Abstract

The invention provides a method for continuously synthesizing 3 ', 5'-dichloro-2, 2, 2-trifluoroacetophenone by using a continuous flow reactor, and relates to the technical field of pesticides, the continuous flow reactor is one or a combination of more of a tubular reactor, a microreactor, a fixed bed reactor or a fluidized bed reactor, and the continuous flow reactor is one or a combination of more of the tubular reactor, the microreactor, the fixed bed reactor and the fluidized bed reactor. The continuous flow reactor is provided with an efficient mixing and heat transfer device, the device can ensure uniform mixing and rapid heat transfer of reactants, raw materials and reagents are continuously input through one or more inlets of the continuous flow reactor, and continuous reaction is carried out under the conditions of set temperature, pressure and flow speed in the reactor; key parameters in the reaction process are monitored in real time, the continuous flow reactor is adopted, continuous production of the 3 ', 5'-dichloro-2, 2, 2-trifluoroacetophenone is achieved, compared with a traditional batch reactor, the production efficiency is greatly improved, the continuous flow reactor has excellent mass and heat transfer performance, reaction conditions can be rapidly met, and the continuous flow reactor can be used for continuous production of the 3 ', 5'-dichloro-2, 2, 2-trifluoroacetophenone. Therefore, the reaction speed is accelerated and the production period is shortened.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticides, and more specifically, particularly relates to a method for continuously synthesizing 3',5'-dichloro-2,2,2-trifluoroacetophenone by using a continuous flow reactor. Background Art

[0002] 3′,5′-Dichloro-2,2,2-trifluoroacetophenone is an organic compound with a special chemical structure and properties. Due to its unique physical and chemical properties, it has broad application prospects in many fields such as pesticides, medicines, dyes and materials science. This compound is usually used as an intermediate for the synthesis of other high-value chemicals. Especially in the field of pesticides, it can be used as a key raw material for the synthesis of high-efficiency, low-toxic and environmentally friendly pesticides, which is of great significance for improving agricultural production efficiency and ensuring the safety of agricultural products.

[0003] The invention patent with the patent publication number WO2022061917 discloses a method for synthesizing 3,5-dichloro-2,2,2-trifluoroacetophenone. The method first reacts 1,3,5-trichlorobenzene or 3,5-dichloro-1-bromobenzene with magnesium to form a Grignard reagent, and then reacts with a trifluoroacetyl reagent for nucleophilic addition reaction. The target product is obtained after acid treatment. This process shows a specific chemical transformation path. However, the process may be limited to the batch production mode, resulting in relatively low production efficiency, room for improvement in raw material utilization, and more manual operations, which may affect the stability and consistency of product quality. In contrast, the continuous flow process can overcome these limitations, significantly improve production efficiency by realizing continuous input of raw materials and continuous output of products, and precisely control the reaction conditions to ensure stable product quality and high purity. In addition, the continuous flow process can also optimize the use of resources and energy, reduce waste, and reduce dependence on manual operations, thereby improving overall production efficiency and sustainability. Therefore, although the process provided by the patent has its own unique features, the continuous flow process shows more obvious advantages in improving production efficiency, product quality and resource utilization efficiency.

[0004] Traditionally, the synthesis of 3′,5′-dichloro-2,2,2-trifluoroacetophenone is mostly carried out using a batch reactor, which has problems such as low production efficiency, long reaction time, high energy consumption, and difficulty in controlling product purity. With the rapid development of the chemical industry and the continuous advancement of continuous production technology, continuous flow reactors have gradually become a research hotspot in the field of organic synthesis due to their advantages such as high efficiency, flexibility, and easy scale-up.

[0005] The continuous flow reactor is a new type of reactor that can achieve continuous feeding of reactants and continuous discharge of products. It has excellent mass and heat transfer performance and can accurately control the reaction conditions, thereby improving the selectivity and yield of the reaction. At the same time, the continuous flow reactor can also achieve automatic control and remote monitoring, reduce operating difficulty and labor costs, and improve production safety.

[0006] However, the application of continuous flow reactors in the synthesis of 3′,5′-dichloro-2,2,2-trifluoroacetophenone still faces some challenges, such as precise control of reaction conditions, suppression of by-products during the reaction, etc. Therefore, the development of an efficient, stable and controllable continuous flow synthesis method is of great significance for the industrial production of 3′,5′-dichloro-2,2,2-trifluoroacetophenone. Summary of the invention

[0007] In order to solve the above technical problems, the present invention provides a method for continuously synthesizing 3′,5′-dichloro-2,2,2-trifluoroacetophenone using a continuous flow reactor to solve the above problems.

[0008] A method for continuously synthesizing 3',5'-dichloro-2,2,2-trifluoroacetophenone using a continuous flow reactor, wherein the continuous flow reactor is one or more combinations of a tubular reactor, a microreactor, a fixed bed reactor or a fluidized bed reactor, and the continuous flow reactor is equipped with an efficient mixing and heat transfer device, which can ensure uniform mixing of reactants and rapid heat transfer.

[0009] Preferably, raw materials and reagents are continuously input through one or more inlets of the continuous flow reactor, and continuous reaction is carried out under the temperature, pressure and flow rate conditions set in the reactor. The key parameters in the reaction process are monitored in real time and adjusted in real time by means of automatic adjustment systems, heating / cooling systems, etc. to ensure the stability and controllability of the reaction process, wherein the key parameters include reactant concentration, reaction temperature, pressure and flow rate. The reaction temperature of the continuous flow reaction is 0-45°C. Within this temperature range, the reaction can be effectively promoted and the selectivity and yield of the product can be guaranteed. The preferred reaction temperature of the continuous flow reaction is 20-45°C. For example, the specific reaction temperature can be 0°C, 10°C, 25°C, 35°C, 45°C. At these preferred temperatures, the reaction efficiency and product quality are better.

[0010] Preferably, the reaction time of the reaction liquid in the continuous flow reactor is 5-45min. By controlling the reaction time, the reaction process and product distribution can be accurately controlled. The preferred reaction time of the reaction liquid in the continuous flow reactor is 10-30min. For example, the specific reaction time can be 10min, 15min, 20min, 25min, 30min. Within these preferred times, higher quality products can be obtained. The solvent is selected from a system formed by tetrahydrofuran, toluene, petroleum ether, n-heptane, methyl tert-butyl ether, n-hexane, etc. The system can be any one of the above compounds, or a homogeneous system formed by any number of them. By selecting a specific solvent system, the reaction environment can be optimized and the reaction effect can be improved.

[0011] Preferably, the system formed by toluene, petroleum ether, n-heptane, methyl tert-butyl ether, n-hexane, etc., the system can be any one of the above compounds, or a homogeneous system formed by any number of them. By real-time monitoring of the reactant concentration and the product generation amount, the input rate of the raw materials and reagents is adjusted. After the reaction is completed, the product is treated by a specific separation and purification process to obtain high-purity 3',5'-dichloro-2,2,2-trifluoroacetophenone.

[0012] Compared with the prior art, the present invention has the following beneficial effects:

[0013] 1. Significantly improved production efficiency

[0014] Continuous production: The present invention adopts a continuous flow reactor to achieve the continuous production of 3′,5′-dichloro-2,2,2-trifluoroacetophenone. Compared with the traditional batch reactor, the production efficiency is greatly improved.

[0015] Fast reaction speed: The continuous flow reactor has excellent mass transfer and heat transfer performance, and can quickly reach the reaction conditions, thereby accelerating the reaction speed and shortening the production cycle.

[0016] 2. Product purity and yield improvement

[0017] Precise control of reaction conditions: Continuous flow reactors can precisely control the feed rate of reactants, reaction temperature, pressure and catalyst dosage, thereby optimizing reaction conditions and improving product purity and yield.

[0018] Reducing the generation of by-products: By precisely controlling the reaction process, the present invention effectively inhibits the generation of by-products and further improves the purity of the product.

[0019] 3. Easy to operate and easy to enlarge

[0020] Automatic control: The continuous flow reactor can realize automatic control and remote monitoring, which reduces the operation difficulty and labor cost and improves production safety.

[0021] Easy to scale up: The design of the continuous flow reactor makes it easy to scale up from laboratory scale to industrial scale, providing convenience for industrial production.

[0022] 4. Significant economic benefits

[0023] Reduction of production cost: Due to the improvement of production efficiency and the reduction of by-products, the production cost of the present invention is significantly reduced.

[0024] Improve market competitiveness: The efficient and stable continuous production method gives the present invention a significant advantage in market competition and can bring higher economic benefits to the enterprise.

[0025] 5. Enhanced environmental friendliness

[0026] Reduced energy consumption and emissions: The high efficiency of the continuous flow reactor reduces energy consumption and emissions during the reaction process, which is in line with the development concept of green chemistry.

[0027] Easy to handle waste: Due to the high purity of the product and the small amount of by-products, the difficulty of waste treatment is reduced, which is beneficial to environmental protection.

[0028] In summary, the method for continuously synthesizing 3′,5′-dichloro-2,2,2-trifluoroacetophenone using a continuous flow reactor of the present invention has achieved remarkable technical progress in production efficiency, product purity and yield, ease of operation, economic benefit and environmental friendliness. These advances not only solve the problems existing in traditional synthesis methods, but also provide a new and efficient solution for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 is a GC chart of the 3′,5′-dichloro-2,2,2-trifluoroacetophenone product of the present invention;

[0030] Figure 2 It is a data parameter diagram of the 3′,5′-dichloro-2,2,2-trifluoroacetophenone product of the present invention. DETAILED DESCRIPTION

[0031] The following embodiments of the present invention are described in further detail in conjunction with the accompanying drawings and examples. The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention.

[0032] See also Figure 1-Figure 2The present invention provides a method for continuously synthesizing 3′,5′-dichloro-2,2,2-trifluoroacetophenone by using a continuous flow reactor. The continuous flow reactor is a combination of one or more of a tubular reactor, a microreactor, a fixed bed reactor or a fluidized bed reactor. The continuous flow reactor is equipped with an efficient mixing and heat transfer device, which can ensure uniform mixing of reactants and rapid heat transfer.

[0033] Raw materials and reagents are continuously input through one or more inlets of the continuous flow reactor, and continuous reaction is carried out under the temperature, pressure and flow rate conditions set in the reactor. Key parameters in the reaction process are monitored in real time and adjusted in real time by means of automatic adjustment systems, heating / cooling systems, etc. to ensure the stability and controllability of the reaction process. Key parameters include reactant concentration, reaction temperature, pressure and flow rate. The reaction temperature of the continuous flow reaction is 0-45°C. Within this temperature range, the reaction can be effectively promoted and the selectivity and yield of the product can be guaranteed. The preferred reaction temperature of the continuous flow reaction is 20-45°C. For example, the specific reaction temperature can be 0°C, 10°C, 25°C, 35°C, 45°C. At these preferred temperatures, the reaction efficiency and product quality are better.

[0034] The reaction time of the reaction liquid in the continuous flow reactor is 5-45min. By controlling the reaction time, the reaction process and product distribution can be accurately controlled. The preferred reaction time of the reaction liquid in the continuous flow reactor is 10-30min. For example, the specific reaction time can be 10min, 15min, 20min, 25min, 30min. Within these preferred times, higher quality products can be obtained. The solvent is selected from a system formed by tetrahydrofuran, toluene, petroleum ether, n-heptane, methyl tert-butyl ether, n-hexane, etc. The system can be any one of the above compounds, or a homogeneous system formed by any number of them. By selecting a specific solvent system, the reaction environment can be optimized and the reaction effect can be improved.

[0035] A system formed by toluene, petroleum ether, n-heptane, methyl tert-butyl ether, n-hexane, etc. The system can be any one of the above compounds, or a homogeneous system formed by any number of them. By real-time monitoring of the reactant concentration and the product generation amount, the input speed of the raw materials and reagents is adjusted. After the reaction is completed, the product is treated with a specific separation and purification process to obtain high-purity 3',5'-dichloro-2,2,2-trifluoroacetophenone.

[0036] The raw materials and reagents of the present invention are continuously input through one or more inlets of the continuous flow reactor, and a continuous reaction is carried out under the temperature, pressure and flow rate conditions set in the reactor. Key parameters are monitored in real time and adjusted in real time by means of an automatic adjustment system, a heating / cooling system, etc., to ensure the stability and controllability of the reaction process.

[0037] The reaction temperature of the continuous flow reaction is 0 to 45°C, preferably 20 to 45°C. For example, the reaction temperature may be 0°C, 10°C, 25°C, 35°C, 45°C, etc.

[0038] The reaction time of the reaction liquid in the continuous flow reactor is 5 to 45 minutes, preferably 10 to 30 minutes. For example, the reaction time may be 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, etc.

[0039] The solvent is selected from tetrahydrofuran, toluene, petroleum ether, n-heptane, methyl tert-butyl ether, n-hexane, etc. The system formed can be any one of the above compounds, or a homogeneous system formed by any number of them.

[0040] The present invention is described in detail below with reference to specific embodiments / comparative examples:

[0041] The following realizes continuous and screens the reaction conditions:

[0042] Experimental preparation: First rinse the reactor with 1000ml of water, then rinse it twice with tetrahydrofuran, and dry it at 100℃. Purge the reactor with nitrogen to remove moisture and air, fill the reactor with nitrogen, and carry out the following reactions under nitrogen protection;

[0043] Ingredients: Add 400 ml of tetrahydrofuran to a conical flask with a magnetic stirrer and start stirring, then add 200 g of 3,5-dichlorobromobenzene and dissolve it completely, then add an appropriate initiator (iodine) and dissolve it for later use. Fill the reactor packing column with magnesium chips.

[0044] Example 1: The pre-configured solution was stably injected into the continuous flow reactor through an efficient plunger pump to ensure precise control of the reaction conditions. During the reaction, the temperature was strictly controlled at 25°C and the flow rate was accurately set to 8 mL / min. The solution reacted evenly in the reactor for 10 minutes, and the reaction solution that flowed out entered a three-necked bottle pre-filled with a mixture of tetrahydrofuran and trifluoroacetyl dimethylamine for reaction for 30 minutes, and the central control GC: 67.36%.

[0045] Example 2: Under the same experimental conditions as Example 1, only the reaction temperature was changed. The reaction temperature was raised to 35°C, and other conditions remained unchanged: the flow rate was still 8 mL / min. Similarly, the solution was uniformly reacted in the reactor for 10 minutes, and the reaction solution that flowed out entered a three-necked flask pre-filled with a mixture of tetrahydrofuran and trifluoroacetyl dimethylamine to react for 30 minutes, and the central control GC: 86.64%.

[0046] Example 3: Under the same experimental conditions as Example 1, only the reaction temperature was changed. The reaction temperature was raised to 45°C, and other conditions remained unchanged: the flow rate was still 8 mL / min. Similarly, the solution was uniformly reacted in the reactor for 10 minutes, and the reaction solution that flowed out entered a three-necked flask pre-filled with a mixture of tetrahydrofuran and trifluoroacetyl dimethylamine to react for 30 minutes, and the central control GC: 99.64%.

[0047] Example 4: Under the same experimental conditions as Example 1, 3,5-dichlorobromobenzene was replaced with 1,3,5-trichlorobenzene. The reaction temperature was set to 45°C and the flow rate was 8 mL / min. Similarly, the solution was uniformly reacted in the reactor for 10 minutes, and the reaction solution that flowed out entered a three-necked flask pre-filled with a mixture of tetrahydrofuran and trifluoroacetyl dimethylamine for reaction for 30 minutes. The central control GC was 89.36%.

[0048] Comparative Example 1: Weigh 7.2g magnesium chips (0.3mol) and add them to the reaction bottle, add 60mL tetrahydrofuran (solvent 1), stir at room temperature, evenly, and obtain mixed system I; weigh 67.2g 3,5-dichlorobromobenzene (0.3mol), dissolve it in 70mL tetrahydrofuran, and obtain mixed system II; add 0.1g iodine as an initiator to the mixed system I in the reaction bottle, and exotherm is obvious. Slowly add the mixed system II to the mixed system I, and continue to react for 2h to obtain the mixed system III, which contains 1,3-dichlorobenzene-5-magnesium bromide. Control the temperature at 0℃, slowly add the mixed system III to the tetrahydrofuran solution (40mL) of 46.6g trifluoroacetyl dimethylamine (0.33mol), and continue to stir for 1h after the addition is complete. The GC is controlled at 61%.

[0049] The embodiments of the present invention are given for the purpose of illustration and description, and are not intended to be exhaustive or to limit the invention to the disclosed forms. Many modifications and variations will be apparent to those of ordinary skill in the art. The embodiments are selected and described in order to better illustrate the principles and practical applications of the present invention and to enable those of ordinary skill in the art to understand the present invention and thereby design various embodiments with various modifications suitable for specific uses.

Claims

1. A method for continuously synthesizing 3',5'-dichloro-2,2,2-trifluoroacetophenone using a continuous flow reactor, characterized in that: The continuous flow reactor is one or more combinations of a tubular reactor, a microreactor, a fixed bed reactor or a fluidized bed reactor. The continuous flow reactor is equipped with an efficient mixing and heat transfer device, which can ensure uniform mixing of reactants and rapid heat transfer.

2. A method for continuously synthesizing 3',5'-dichloro-2,2,2-trifluoroacetophenone using a continuous flow reactor as claimed in claim 1, characterized in that: Raw materials and reagents are continuously input through one or more inlets of the continuous flow reactor, and continuous reactions are carried out under the temperature, pressure and flow rate conditions set in the reactor. Key parameters in the reaction process are monitored in real time and adjusted in real time through automatic adjustment systems, heating / cooling systems, etc. to ensure the stability and controllability of the reaction process, where key parameters include reactant concentration, reaction temperature, pressure and flow rate.

3. A method for continuously synthesizing 3',5'-dichloro-2,2,2-trifluoroacetophenone using a continuous flow reactor as claimed in claim 2, characterized in that: The reaction temperature of the continuous flow reaction is 0-45°C. Within this temperature range, the reaction can be effectively promoted and the selectivity and yield of the product can be guaranteed.

4. A method for continuously synthesizing 3',5'-dichloro-2,2,2-trifluoroacetophenone using a continuous flow reactor as claimed in claim 3, characterized in that: The preferred reaction temperature of the continuous flow reaction is 20-45°C. For example, the specific reaction temperature may be 0°C, 10°C, 25°C, 35°C, or 45°C. At these preferred temperatures, the reaction efficiency and product quality are better.

5. A method for continuously synthesizing 3',5'-dichloro-2,2,2-trifluoroacetophenone using a continuous flow reactor as claimed in claim 4, characterized in that: The reaction time of the reaction liquid in the continuous flow reactor is 5-45 minutes. By controlling the reaction time, the reaction process and product distribution can be precisely regulated.

6. A method for continuously synthesizing 3',5'-dichloro-2,2,2-trifluoroacetophenone using a continuous flow reactor as claimed in claim 5, characterized in that: The preferred reaction time of the reaction solution in the continuous flow reactor is 10-30 min. For example, the specific reaction time can be 10 min, 15 min, 20 min, 25 min, 30 min. Within these preferred times, higher quality products can be obtained.

7. A method for continuously synthesizing 3',5'-dichloro-2,2,2-trifluoroacetophenone using a continuous flow reactor as claimed in claim 6, characterized in that: The solvent is selected from a system formed by tetrahydrofuran, toluene, petroleum ether, n-heptane, methyl tert-butyl ether, n-hexane, etc. The system can be any one of the above compounds, or a homogeneous system formed by any number of them. By selecting a specific solvent system, the reaction environment can be optimized and the reaction effect can be improved.

8. A method for continuously synthesizing 3',5'-dichloro-2,2,2-trifluoroacetophenone using a continuous flow reactor as claimed in claim 7, characterized in that: The system formed by toluene, petroleum ether, n-heptane, methyl tert-butyl ether, n-hexane, etc., the system can be any one of the above compounds, or a homogeneous system formed by any number of them.

9. A method for continuously synthesizing 3',5'-dichloro-2,2,2-trifluoroacetophenone using a continuous flow reactor as claimed in claim 8, characterized in that: By real-time monitoring of reactant concentrations and product generation, the input rates of raw materials and reagents can be adjusted.

10. A method for continuously synthesizing 3',5'-dichloro-2,2,2-trifluoroacetophenone using a continuous flow reactor as claimed in claim 9, characterized in that: After the reaction is completed, the product is treated by a specific separation and purification process to obtain high-purity 3',5'-dichloro-2,2,2-trifluoroacetophenone.

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