A preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine

Abstract

The present application relates to the technical field of pesticide fungicides and insecticides, and more specifically, to a preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine. A preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine, comprising the following steps: S1, 2-aminomethyl-3-chloro-5-trifluoromethylpyridine reacts with sodium nitrite, and dichloromethane is extracted to obtain a dichloromethane phase; S2, a halogenating agent is slowly added dropwise to the dichloromethane phase to obtain a crude product of 2-chloromethyl-3-chloro-5-trifluoromethylpyridine; S3, nitromethane, solvent one, alkali and 2-chloromethyl-3-chloro-5-trifluoromethylpyridine crude product react to obtain an intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine; S4, intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine, Raney nickel and solvent two react, filter, suck and dry to obtain 2-aminoethyl-3-chloro-5-trifluoromethylpyridine. The preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine of the present application has the advantages of low cost and high yield.

Description

Technical Field

[0001] The present application relates to the technical field of pesticides, fungicides and insecticides, and more specifically, to a preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine. Background Art

[0002] Fluopyram is a new type of organic fungicide with high efficiency and low toxicity. It is mainly used for the prevention and control of bacterial diseases and pests of crops, and can effectively control a variety of pests and bacterial diseases. Compared with traditional pesticides, fluopyram is less toxic, less polluting to the environment, and less harmful to human health. Therefore, it has been widely used in agricultural production.

[0003] 3-Chloro-2-aminoethyl-5-trifluoromethylpyridine is an important intermediate for the synthesis of fluopyram. At present, the main synthetic route of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine is: ;

[0004] The above method requires the use of expensive methyl cyanoacetate as a raw material, and the reduction of the cyano group requires the use of expensive metal palladium, which is relatively costly. At the same time, the decarboxylation reaction process requires a high temperature reaction. Therefore, a new preparation method is urgently needed to obtain 3-chloro-2-aminoethyl-5-trifluoromethylpyridine. Summary of the invention

[0005] In order to improve the defects of the current process for preparing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine, such as high process cost and complicated reaction conditions, the present application provides a process for preparing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine.

[0006] The present application provides a preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine, which adopts the following technical scheme:

[0007] A preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine comprises the following steps:

[0008] S1. Under acidic conditions, slowly drop sodium nitrite into 2-aminomethyl-3-chloro-5-trifluoromethylpyridine, then react at a temperature of 0-5°C for 20-40 minutes, and then extract and separate the liquid with dichloromethane to obtain a dichloromethane phase;

[0009] S2, controlling the temperature at 20-25°C, then slowly adding the halogenating agent to the dichloromethane phase, and after the raw material disappears by GC detection, evaporating the solvent to obtain a crude product of 2-chloromethyl-3-chloro-5-trifluoromethylpyridine;

[0010] S3, mixing nitromethane, solvent one and a base to obtain a substrate; dissolving the crude 2-chloromethyl-3-chloro-5-trifluoromethylpyridine with solvent one, and then slowly dropping it into the substrate at a dropping temperature of 0-5°C. After the dropping is completed, keeping the temperature at 0-5°C for 0.5-1.5h, and then washing and filtering the product to obtain an intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine;

[0011] S4, adding the intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine and Raney nickel to the solvent 2, and then filling the nitrogen pressure to 0.2-0.4MPa, replacing three times; then replacing with hydrogen three times; then controlling the reaction temperature to 30-35°C, the hydrogen filling pressure to 0.4-0.6Mpa, reacting for 6-8h, and then filtering the Raney nickel and evaporating the solvent under reduced pressure, washing with water, filtering and drying to obtain 2-aminoethyl-3-chloro-5-trifluoromethylpyridine;

[0012] The above reaction formula is: ;

[0013] -X in the above formula III is a halogen atom: one of fluorine, chlorine, bromine and iodine;

[0014] The reaction process from formula III to formula IV is alkaline, using sodium hydroxide or potassium hydroxide, and the solvent can be any polar solvent such as DMF, DMSO, 1,4-dioxane, acetonitrile, etc.

[0015] In the above preparation process, expensive methyl cyanoacetate and metal palladium are omitted, which effectively reduces the cost without affecting the normal output of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine.

[0016] Preferably, in the acidic environment S1, the added acid is one of hydrochloric acid and sulfuric acid.

[0017] Preferably, in S2, the halogenating agent is one or more of thionyl chloride, phosphorus tribromide, and phosphorus trichloride.

[0018] Preferably, in S3, the base is one of sodium hydroxide and potassium hydroxide, and the solvent one is one of DMF and acetonitrile.

[0019] Preferably, in S4, the second solvent is one of methanol and 1,4-dioxane.

[0020] Preferably, in the acidic environment of S1, the added acid is 36.5% hydrochloric acid; in S2, the halogenating agent is thionyl chloride; in S3, the base is sodium hydroxide, and the first solvent is DMF; in S4, the second solvent is 1,4-dioxane.

[0021] Preferably, the preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine comprises the following steps:

[0022] S1. First, 21 g of 2-aminomethyl-3-chloro-5-trifluoromethylpyridine, 30 g of 36.5% hydrochloric acid and 30 parts of water were mixed, and then 16.56 g of 50% sodium nitrite aqueous solution was slowly added dropwise, and then reacted at a temperature of 0-5° C. for 20-40 min. The product conversion rate was 93% when detected by GC, and then the liquid was extracted with 100 ml of dichloromethane to obtain a dichloromethane phase;

[0023] S2, the temperature was controlled at 20-25°C, and then 14.28 g of thionyl chloride was slowly added dropwise to the dichloromethane phase. After the raw material disappeared during GC detection, the solvent was evaporated to obtain 22.9 g of crude 2-chloromethyl-3-chloro-5-trifluoromethylpyridine, with an external standard content of 92.1%;

[0024] S3, 6.1g nitromethane, 12ml DMF and 4g sodium hydroxide were mixed to obtain a substrate; 2-chloromethyl-3-chloro-5-trifluoromethylpyridine crude product was dissolved in 40ml DMF, and then slowly added to the substrate at a temperature of 0-5°C. After the addition was completed, the temperature was kept at 0-5°C for 0.5-1.5h, and then the product was washed and filtered to obtain 22g of the intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine, with a content of 98.1%;

[0025] S4. Add the intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine and 0.5g of Raney nickel to 220ml of 1,4-dioxane, then fill with nitrogen pressure to 0.2-0.4MPa, and replace three times; then replace with hydrogen three times; then control the reaction temperature to 30-35°C, the hydrogen filling pressure to 0.4-0.6Mpa, react for 6-8h, and after GC detection of the complete reaction of the raw materials and the intermediates, release the pressure and filter out the catalyst; then evaporate the solvent under reduced pressure, add 100g of water for washing, then filter with suction, and dry the filter cake at 60°C to obtain 18.71g of 2-aminoethyl-3-chloro-5-trifluoromethylpyridine, with an external standard content of 98.5% and a yield of 83.5%.

[0026] When S1 is in an acidic environment, the added acid is 36.5% hydrochloric acid; in S2, the halogenating agent is thionyl chloride; in S3, the base is sodium hydroxide, and the solvent one is DMF; in S4, the solvent two is 1,4-dioxane, and when the raw materials are added in the above amounts, the prepared 2-aminoethyl-3-chloro-5-trifluoromethylpyridine will have a better yield.

[0027] Preferably, the S4 operation is carried out using a high-pressure reactor, which includes a detachably connected reaction part and a filtration part, the reaction part and the filtration part are interconnected through a valve, and both the reaction part and the filtration part are provided with a heater; a filter screen is mounted at the bottom of the reaction part, and Raney nickel is mounted on the filter screen; a stirring assembly is installed on the top of the reaction part, and the stirring assembly includes a driving motor, a stirring rod and a stirring paddle, the driving motor is fixedly connected to the top of the reaction part, the stirring rod is fixedly connected to the output end of the driving motor, the stirring rod passes through the filter screen, and the stirring paddle is fixedly connected to the stirring rod.

[0028] After the reaction is completed, the filter automatically separates the catalyst from the reaction liquid, thereby eliminating the filtering operation. At the same time, since the stirring rod passes through the filter, the stirring paddle can stir the reaction liquid in all directions, and the filter will not affect the operation of the stirring component.

[0029] Preferably, the reaction part is provided with a nitrogen pipe, a hydrogen pipe, a pressure relief pipe, a plugging member and a control member, the nitrogen pipe, the hydrogen pipe and the pressure relief pipe are arranged in parallel, the nitrogen pipe, the hydrogen pipe and the pressure relief pipe are all penetrated by the plugging member, the plugging member is used to connect or plug the nitrogen pipe, the hydrogen pipe and the pressure relief pipe, and the control member is used to control the operation of the plugging member;

[0030] The control component includes a base, a nitrogen block, a hydrogen block and a pressure relief block. A nitrogen cavity, a hydrogen cavity and a pressure relief cavity are provided in the base. The nitrogen cavity is connected to the nitrogen pipe, the hydrogen cavity is connected to the hydrogen pipe, and the pressure relief cavity is connected to the pressure relief cavity.

[0031] The nitrogen block slides back and forth in the nitrogen cavity, the nitrogen block blocks or opens the nitrogen pipe, the lower end of the nitrogen block is fixedly connected to a nitrogen shaft, and the nitrogen shaft passes through the nitrogen cavity; the hydrogen block slides back and forth in the hydrogen cavity, the hydrogen block blocks or opens the hydrogen pipe, the lower end of the hydrogen block is fixedly connected to a hydrogen shaft, and the hydrogen shaft passes through the hydrogen cavity; the pressure relief block slides back and forth in the pressure relief cavity, the pressure relief block blocks or opens the pressure relief pipe, the lower end of the pressure relief block is fixedly connected to a pressure relief shaft, and the pressure relief shaft passes through the pressure relief cavity;

[0032] The control component includes a nitrogen control cylinder, a hydrogen control cylinder and a pressure relief control cylinder. The output end of the nitrogen control cylinder is fixedly connected with a nitrogen trapezoidal block, and the inclined surface of the nitrogen trapezoidal block is always in contact with the lower end of the nitrogen shaft; the output end of the hydrogen control cylinder is fixedly connected with a hydrogen trapezoidal block, and the inclined surface of the hydrogen trapezoidal block is always in contact with the lower end of the hydrogen shaft; the output end of the pressure relief control cylinder is fixedly connected with a pressure relief trapezoidal block, and the inclined surface of the pressure relief trapezoidal block is always in contact with the lower end of the pressure relief shaft.

[0033] When the reaction part needs to be filled with nitrogen, the nitrogen control cylinder drives the nitrogen trapezoidal block to move, so that the nitrogen trapezoidal block drives the nitrogen shaft to move upward through the inclined surface, and the upward movement of the nitrogen shaft drives the nitrogen block to move upward, thereby releasing the nitrogen block from blocking the nitrogen pipe, thereby realizing the nitrogen filling operation. After the nitrogen filling is completed, the nitrogen control cylinder is reset, and the nitrogen block blocks the nitrogen pipe again. The hydrogen filling and pressure relief operations are the same as the nitrogen filling operations.

[0034] Preferably, a filter plate is provided in the middle of the suction filtration part, the filter plate is used to support the suction filter paper, and a suction filtration funnel is provided at the bottom of the suction filtration part.

[0035] In summary, this application has the following beneficial effects:

[0036] 1. The preparation process of the present application eliminates the expensive methyl cyanoacetate and metal palladium, effectively reducing the cost without affecting the normal output of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine.

[0037] 2. When the acid added in S1 is 36.5% hydrochloric acid; in S2, the halogenating agent is thionyl chloride; in S3, the base is sodium hydroxide, and the solvent one is DMF; in S4, the solvent two is 1,4-dioxane, and the raw materials are added in the above amounts, the prepared 2-aminoethyl-3-chloro-5-trifluoromethylpyridine will have a better yield.

[0038] 3. After the reaction is completed, the filter automatically separates the catalyst from the reaction liquid, thereby eliminating the filtering operation. At the same time, since the stirring rod passes through the filter, the stirring paddle can stir the reaction liquid in all directions, and the filter will not affect the operation of the stirring component.

[0039] 4. When the reaction part needs to be filled with nitrogen, the nitrogen control cylinder drives the nitrogen trapezoidal block to move, so that the nitrogen trapezoidal block drives the nitrogen shaft to move upward through the inclined surface, and the upward movement of the nitrogen shaft drives the nitrogen block to move upward, thereby releasing the nitrogen block from blocking the nitrogen pipe, thereby realizing the nitrogen filling operation. After the nitrogen filling is completed, the nitrogen control cylinder is reset, and the nitrogen block blocks the nitrogen pipe again. The hydrogen filling and pressure relief operations are the same as the nitrogen filling operations. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 It is a structural schematic diagram of a high-pressure reactor;

[0041] Figure 2 is along Figure 1 Sectional view along line AA;

[0042] Figure 3 It is a schematic diagram of the structure of the blocking component and the control component;

[0043] Figure 4 It is an exploded diagram of the blocking parts and control parts.

[0044] 1. Reaction unit; 2. Filtration unit; 3. Heater; 11. Stirring assembly; 12. Filter screen; 13. Nitrogen pipe; 14. Hydrogen pipe; 15. Pressure relief pipe; 16. Sealing piece; 17. Control piece; 21. Filter plate; 22. Filtration funnel; 111. Driving motor; 112. Stirring rod; 113. Stirring paddle; 161. Base; 162. Nitrogen block; 163. Hydrogen block; 164. Pressure relief block; 165. Nitrogen shaft; 166. Hydrogen shaft; 167. Pressure relief shaft; 171. Nitrogen control cylinder; 172. Hydrogen control cylinder; 173. Pressure relief control cylinder; 174. Nitrogen trapezoidal block; 175. Hydrogen trapezoidal block; 176. Pressure relief trapezoidal block; 1611. Nitrogen cavity; 1612. Hydrogen cavity; 1613. Pressure relief cavity. DETAILED DESCRIPTION

[0045] The following is combined with Figure 1-4 The present application is further described in detail with Examples 1-3.

[0046] raw material

[0047] 2-Aminomethyl-3-chloro-5-trifluoromethylpyridine CAS: 175277-74-4; Hydrochloric acid CAS: 7647-01-0; Sulfuric acid CAS: 7664-93-9; Sodium nitrite CAS: 7632-00-0; Dichloromethane CAS: 75-09-2; Sulfur oxide CAS: 7719-09-7; Phosphorus tribromide CAS: 7789-60-8; Nitromethane CAS: 75-52-5; DMF CAS: 68-12-2; Acetonitrile CAS: 75-05-8; Potassium hydroxide CAS: 1310-58-3; Sodium hydroxide CAS: 1310-73-2; Methanol CAS: 67-56-1; 1,4-Dioxane CAS: 123-91-1; Raney nickel CAS: 7440-02-0.

[0048] Example

[0049] Example 1

[0050] A preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine comprises the following steps:

[0051] S1. In a 250ml four-necked flask, add 21g (0.1mol) of 2-aminomethyl-3-chloro-5-trifluoromethylpyridine, 30g (0.3mol, 300mol%) of 36.5% hydrochloric acid, and 30g of water, control the temperature in the range of 0-5°C, and dropwise add 27.6g (0.12mol, 120mol%) of 30% sodium nitrite aqueous solution. After the dropwise addition is completed, react for 30min in the range of 0-5°C; the product conversion rate is 90% when detected by GC, and then extract the liquid with 100ml of dichloromethane to obtain a dichloromethane phase;

[0052] S2. The temperature was controlled within the range of 20-25°C, and then 14.28 g (0.12 mol) of thionyl chloride was slowly added dropwise to the extracted dichloromethane phase. After the raw material disappeared during GC detection, the solvent was evaporated to obtain 22.8 g of crude 2-chloromethyl-3-chloro-5-trifluoromethylpyridine, with an external standard content of 89.7%;

[0053] S3, add nitromethane 6.1g (0.1mol), DMF 12ml, potassium hydroxide 5.6g (0.1mol) into a 250ml reaction bottle, then pass 22.8g of the crude 2-chloromethyl-3-chloro-5-trifluoromethylpyridine from the previous step through 40ml of DMF solution, control the temperature to 0-5℃, and slowly add it dropwise into the reaction bottle. After the addition is complete, keep the temperature at 0-5℃ for 1h, then wash the product with 100ml of water, and filter it to obtain 20.57g of the intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine, with a content of 98%;

[0054] S4, in a 500ml autoclave, add 20.57g of the intermediate 3-chloro-2-nitroethyl-5-trifluoromethyl pyridine in the previous step and 200ml of methanol, then add 1g of Raney nickel, fill the nitrogen pressure to 0.3MPa, replace three times, and then replace with hydrogen three times; then control the reaction temperature to be within the range of 30-35°C, the hydrogen filling pressure is 0.5Mpa, react for 5h, and after GC detection of the complete reaction of the raw materials and the intermediates, release the pressure, filter out the catalyst Raney nickel, then evaporate the solvent under reduced pressure, add 100g of water for washing, then filter with suction, and dry the filter cake at 60°C to obtain 17.47g of 3-chloro-2-aminoethyl-5-trifluoromethyl pyridine, with an external content of 98.9%. Calculated based on the initial raw material 2-aminomethyl-3-chloro-5-trifluoromethyl pyridine, the total yield is 78%.

[0055] Example 2

[0056] A preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine comprises the following steps:

[0057] S1. In a 250ml four-necked flask, add 21g (0.1mol) of 2-aminomethyl-3-chloro-5-trifluoromethylpyridine, 30g (0.3mol, 300mol%) of 36.5% hydrochloric acid, and 30g of water. Control the temperature in the range of 0-5°C, and dropwise add 16.56gg (0.12mol, 120mol%) of 50% sodium nitrite aqueous solution. After the dropwise addition is completed, react for 30min in the range of 0-5°C. The product conversion rate is 93% when detected by GC. Then, extract and separate the liquid with 100ml of dichloromethane to obtain a dichloromethane phase.

[0058] S2. The temperature was controlled within the range of 20-25°C, and then 14.28 g (0.12 mol) of thionyl chloride was slowly added dropwise to the extracted dichloromethane phase. After the raw material disappeared during GC detection, the solvent was evaporated to obtain 22.8 g of crude 2-chloromethyl-3-chloro-5-trifluoromethylpyridine, with an external standard content of 92.1%;

[0059] S3, add nitromethane 6.1g (0.1mol), DMF 12ml, sodium hydroxide 4g (0.1mol) into a 100ml reaction bottle, then pass 22.8g of the crude 2-chloromethyl-3-chloro-5-trifluoromethylpyridine from the previous step through 40ml of DMF solution, control the temperature to 0-5℃, and slowly add it dropwise into the reaction bottle. After the addition is complete, keep the temperature at 0-5℃ for 1h, then wash the product with 100ml of water, and filter it to obtain 20.57g of the intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine, with a content of 98.1%;

[0060] S4. In a 500 ml high-pressure reactor, add 20.57 g of the intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine from the previous step and 220 ml of 1,4-dioxane, then add 0.5 g of Raney nickel, fill the nitrogen pressure to 0.3 MPa, replace three times, and then replace with hydrogen three times; then control the reaction temperature to be within the range of 30-35°C, the hydrogen filling pressure is 0.5 MPa, react for 7 hours, and after GC detection of the complete reaction of the raw materials and the intermediates, release the pressure, filter out the catalyst Raney nickel, then evaporate the solvent under reduced pressure, add 100 g of water for washing, and then filter with suction. The filter cake is dried at 60°C to obtain 18.71 g of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine, with an external standard content of 98.5%. Calculated based on the initial raw material 2-aminomethyl-3-chloro-5-trifluoromethylpyridine, the total yield is 83.5%.

[0061] Example 3

[0062] A preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine comprises the following steps:

[0063] S1. In a 500ml four-necked flask, add 21g (0.1mol) of 2-aminomethyl-3-chloro-5-trifluoromethylpyridine, 98g (0.3mol, 300mol%) of 30% sulfuric acid, and 98g of water. Control the temperature in the range of 0-5°C, and dropwise add 16.56g (0.12mol, 120mol%) of 50% sodium nitrite aqueous solution. After the dropwise addition is completed, react for 30min in the range of 0-5°C. The product conversion rate is 92.6% when detected by GC. Then, extract the liquid with 100ml of dichloromethane to obtain a dichloromethane phase.

[0064] S2, the temperature was controlled within the range of 20-25°C, and then 32.48 g (0.12 mol) of phosphorus tribromide was slowly added dropwise to the extracted dichloromethane phase. After the raw material disappeared during GC detection, the reaction solution was added to 100 ml of ice water, and then separated. The separated oil phase was washed with 50 ml of water, separated, and the solvent was evaporated to obtain 26.5 g of crude 2-chloromethyl-3-chloro-5-trifluoromethylpyridine, with an external standard content of 90.3%;

[0065] S3, add nitromethane 6.1g (0.1mol), acetonitrile 30ml, potassium hydroxide 5.6g (0.1mol) into a 250ml reaction bottle, then pass 22.8g of the crude 2-chloromethyl-3-chloro-5-trifluoromethylpyridine from the previous step through 100ml of acetonitrile solution, control the temperature to 20-25℃, and slowly add it dropwise into the reaction bottle. After the addition is complete, keep the temperature at 20-25℃ for 2h, then wash the product with 500ml of water, and filter it to obtain 21.1g of the intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine, with a content of 98.5%;

[0066] S4. In a 500ml autoclave, 21.1g of the intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine in the previous step and 200ml of methanol were added, followed by 0.5g of Raney nickel. The nitrogen pressure was inflated to 0.3MPa, replaced three times, and then replaced three times with hydrogen; the reaction temperature was then controlled within the range of 30-35°C, the hydrogen inflation pressure was 0.5Mpa, the reaction was performed for 7h, and after GC detection of the complete reaction of the raw materials and the intermediates, the pressure was released, the catalyst Raney nickel was filtered out, the solvent was evaporated under reduced pressure, 100g of water was added for washing, and then suction filtered, the filter cake was dried at 60°C to obtain 18.30g of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine, with an external standard content of 98.6%, and the total yield was 81.7% calculated based on the initial raw material 2-aminomethyl-3-chloro-5-trifluoromethylpyridine.

[0067] The reaction formula of above-mentioned embodiment 1-3 is:

[0068]

[0069] -X in the above formula III is a halogen atom: one of fluorine, chlorine, bromine and iodine;

[0070] The reaction process from formula III to formula IV is carried out under alkaline conditions, using sodium hydroxide or potassium hydroxide, and the solvent is any one of DMF, DMSO, 1,4-dioxane, and acetonitrile.

[0071] In addition, the S4 operation in the above-mentioned Examples 1-3 was carried out in a high-pressure reactor.

[0072] Reference Figure 1 and Figure 2 The high-pressure reactor comprises a reaction part 1 and a suction filtration part 2 which are connected by threads. The reaction part 1 and the suction filtration part 2 are connected to each other through a valve, and a heater 3 is provided in both the reaction part 1 and the suction filtration part 2. A filter plate 21 is fixedly connected to the middle of the suction filtration part 2, and the filter plate 21 is used to set up the suction filter paper, and a suction filtration funnel 22 is fixedly connected to the bottom of the suction filtration part 2.

[0073] Reference Figure 2 and Figure 3 A stirring assembly 11 is installed on the top of the reaction part 1. The stirring assembly 11 includes a driving motor 111, a stirring rod 112 and a stirring paddle 113. The driving motor 111 is fixedly connected to the top of the reaction part 1, the stirring rod 112 is fixedly connected to the output end of the driving motor 111, the stirring rod 112 is inserted into the reaction part 1, and the stirring paddle 113 is connected to the stirring rod 112. A filter screen 12 is set in the middle of the reaction part 1, and Raney nickel is set on the filter screen 12. The filter screen 12 is fixedly connected to the stirring rod 112, and the filter screen 12 and the stirring paddle 113 are staggered.

[0074] Reference Figure 3 and Figure 4 The outer peripheral surface of the reaction part 1 is fixedly connected with a nitrogen pipe 13, a hydrogen pipe 14, a pressure relief pipe 15, a plugging piece 16 and a control piece 17. The nitrogen pipe 13, the hydrogen pipe 14 and the pressure relief pipe 15 are arranged in parallel. The nitrogen pipe 13, the hydrogen pipe 14 and the pressure relief pipe 15 are all penetrated by the plugging piece 16. The nitrogen pipe 13, the hydrogen pipe 14 and the pressure relief pipe 15 are all installed with pressure sensors. The plugging piece 16 is used to connect or plug the nitrogen pipe 13, the hydrogen pipe 14 or the pressure relief pipe 15, and the control piece 17 is used to control the operation of the plugging piece 16.

[0075] The sealing member 16 includes a base 161, a nitrogen block 162, a hydrogen block 163 and a pressure relief block 164. A nitrogen chamber 1611, a hydrogen chamber 1612 and a pressure relief chamber 1613 are provided in the base 161. The nitrogen chamber 1611 is interconnected with the nitrogen pipe 13, the hydrogen chamber 1612 is interconnected with the hydrogen pipe 14, and the pressure relief chamber 1613 is interconnected with the pressure relief pipe 15.

[0076] The nitrogen block 162 slides back and forth in the nitrogen chamber 1611, and the nitrogen block 162 blocks or opens the nitrogen pipe 13. The lower end of the nitrogen block 162 is fixedly connected with a nitrogen shaft 165, and the nitrogen shaft 165 passes through the nitrogen chamber 1611; the hydrogen block 163 slides back and forth in the hydrogen chamber 1612, and the hydrogen block 163 blocks or opens the hydrogen pipe 14. The lower end of the hydrogen block 163 is fixedly connected with a hydrogen shaft 166, and the hydrogen shaft 166 passes through the hydrogen chamber 1612; the pressure relief block 164 slides back and forth in the pressure relief chamber 1613, and the pressure relief block 164 blocks or opens the pressure relief pipe 15. The lower end of the pressure relief block 164 is fixedly connected with a pressure relief shaft 167, and the pressure relief shaft 167 passes through the pressure relief chamber 1613.

[0077] The control component 17 includes a nitrogen control cylinder 171, a hydrogen control cylinder 172 and a pressure relief control cylinder 173. The output end of the nitrogen control cylinder 171 is fixedly connected with a nitrogen trapezoidal block 174, and the inclined surface of the nitrogen trapezoidal block 174 always abuts against the lower end of the nitrogen shaft 165; the output end of the hydrogen control cylinder 172 is fixedly connected with a hydrogen trapezoidal block 175, and the inclined surface of the hydrogen trapezoidal block 175 always abuts against the lower end of the hydrogen shaft 166; the output end of the pressure relief control cylinder 173 is fixedly connected with a pressure relief trapezoidal block 176, and the inclined surface of the pressure relief trapezoidal block 176 always abuts against the lower end of the pressure relief shaft 167.

[0078] When the reaction part 1 needs to be filled with nitrogen, the nitrogen control cylinder 171 drives the nitrogen trapezoidal block 174 to move, thereby prompting the nitrogen trapezoidal block 174 to drive the nitrogen shaft 165 to move upward through the inclined surface, and the upward movement of the nitrogen shaft 165 drives the nitrogen block 162 to move upward, thereby releasing the blockage of the nitrogen block 162 on the nitrogen pipe 13, thereby realizing the nitrogen filling operation. After the nitrogen filling is completed, the nitrogen control cylinder 171 is reset, and the nitrogen block 162 blocks the nitrogen pipe 13 again. The hydrogen filling and pressure relief operations are the same as the nitrogen filling operation.

[0079] It should be noted that, in this embodiment, the above-mentioned fixed connection can be selected according to actual conditions using conventional fixed connection methods such as welding, threaded connection, and bolted connection.

[0080] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed, but such modifications are protected by the patent law as long as they are within the scope of the claims of the present application.

[0081] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed, but such modifications are protected by the patent law as long as they are within the scope of the claims of the present application.

Claims

1. A process for preparing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine, characterized in that: The following steps are involved: S1. Under acidic conditions, slowly add sodium nitrite to 2-aminomethyl-3-chloro-5-trifluoromethylpyridine, then react at a temperature of 0-5°C for 20-40 minutes, and then extract and separate the liquid with dichloromethane to obtain a dichloromethane phase; in the acidic conditions, the added acid is one of hydrochloric acid and sulfuric acid. S2, controlling the temperature at 20-25°C, then slowly adding the halogenating agent to the dichloromethane phase, and after the raw material disappears by GC detection, evaporating the solvent to obtain a crude product of 2-chloromethyl-3-chloro-5-trifluoromethylpyridine; S3, mixing nitromethane, solvent one and a base to obtain a substrate; dissolving the crude 2-chloromethyl-3-chloro-5-trifluoromethylpyridine with solvent one, and then slowly dropping it into the substrate at a dropping temperature of 0-5°C. After the dropping is completed, keeping the temperature at 0-5°C for 0.5-1.5h, and then washing and filtering the product to obtain an intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine; S4, adding the intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine and Raney nickel to the solvent 2, and then filling the nitrogen pressure to 0.2-0.4MPa, replacing three times; then replacing with hydrogen three times; then controlling the reaction temperature to 30-35°C, the hydrogen filling pressure to 0.4-0.6Mpa, reacting for 6-8h, and then filtering the Raney nickel and evaporating the solvent under reduced pressure, washing with water, filtering and drying to obtain 2-aminoethyl-3-chloro-5-trifluoromethylpyridine; The above reaction formula is: ； -X in the above formula III is a halogen atom: chlorine; The reaction process from formula III to formula IV is carried out under alkaline conditions, using sodium hydroxide or potassium hydroxide, and the solvent is any one of DMF, DMSO, 1,4-dioxane, and acetonitrile.

2. The preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 1, characterized in that: In S2, the halogenating agent is one or more of thionyl chloride and phosphorus trichloride.

3. The preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 1, characterized in that: In S3, the base is one of sodium hydroxide and potassium hydroxide, and the solvent 1 is one of DMF and acetonitrile.

4. The preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 1, characterized in that: In S4, the second solvent is one of methanol and 1,4-dioxane.

5. The preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 1, characterized in that: In the acidic conditions of S1, the added acid is 36.5% hydrochloric acid; in S2, the halogenating agent is thionyl chloride; in S3, the base is sodium hydroxide and the solvent one is DMF; in S4, the solvent two is 1,4-dioxane.

6. The process for preparing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 5, characterized in that: The following steps are involved: S1. First, 21 g of 2-aminomethyl-3-chloro-5-trifluoromethylpyridine, 30 g of 36.5% hydrochloric acid and 30 parts of water were mixed, and then 16.56 g of 50% sodium nitrite aqueous solution was slowly added dropwise, and then reacted at a temperature of 0-5° C. for 20-40 min. The product conversion rate was 93% when detected by GC, and then the liquid was extracted with 100 ml of dichloromethane to obtain a dichloromethane phase; S2, the temperature was controlled at 20-25°C, and then 14.28 g of thionyl chloride was slowly added dropwise to the dichloromethane phase. After the raw material disappeared during GC detection, the solvent was evaporated to obtain 22.9 g of crude 2-chloromethyl-3-chloro-5-trifluoromethylpyridine, with an external standard content of 92.1%; S3, 6.1g nitromethane, 12ml DMF and 4g sodium hydroxide were mixed to obtain a substrate; 2-chloromethyl-3-chloro-5-trifluoromethylpyridine crude product was dissolved in 40ml DMF, and then slowly added to the substrate at a temperature of 0-5°C. After the addition was completed, the temperature was kept at 0-5°C for 0.5-1.5h, and then the product was washed and filtered to obtain 22g of the intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine, with a content of 98.1%; S4. Add the intermediate 3-chloro-2-nitroethyl-5-trifluoromethylpyridine and 0.5g of Raney nickel to 220ml of 1,4-dioxane, then fill with nitrogen pressure to 0.2-0.4MPa, and replace three times; then replace with hydrogen three times; then control the reaction temperature to 30-35°C, the hydrogen filling pressure to 0.4-0.6Mpa, react for 6-8h, and after GC detection of the complete reaction of the raw materials and the intermediates, release the pressure and filter out the catalyst; then evaporate the solvent under reduced pressure, add 100g of water for washing, then filter with suction, and dry the filter cake at 60°C to obtain 18.71g of 2-aminoethyl-3-chloro-5-trifluoromethylpyridine, with an external standard content of 98.5% and a yield of 83.5%.

7. The preparation process of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 1, characterized in that: The S4 operation is carried out using a high-pressure reactor, the high-pressure reactor comprising a detachably connected reaction part (1) and a suction filtration part (2), the reaction part (1) and the suction filtration part (2) being interconnected via a valve, and the reaction part (1) and the suction filtration part (2) are both provided with a heater (3); A filter screen (12) is mounted at the bottom of the reaction part (1), and Raney nickel is mounted on the filter screen (12). A stirring assembly (11) is installed at the top of the reaction part (1), and the stirring assembly (11) comprises a driving motor (111), a stirring rod (112) and a stirring paddle (113). The driving motor (111) is fixedly connected to the top of the reaction part (1), and the stirring rod (112) is fixedly connected to the output end of the driving motor (111). The stirring rod (112) passes through the filter screen (12), and the stirring paddle (113) is fixedly connected to the stirring rod (112).

8. The process for preparing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 7, characterized in that: The reaction part (1) is provided with a nitrogen pipe (13), a hydrogen pipe (14), a pressure relief pipe (15), a plugging component (16) and a control component (17); the nitrogen pipe (13), the hydrogen pipe (14) and the pressure relief pipe (15) are arranged in parallel; the nitrogen pipe (13), the hydrogen pipe (14) and the pressure relief pipe (15) are all penetrated by the plugging component (16); the plugging component (16) is used to connect or plug the nitrogen pipe (13), the hydrogen pipe (14) and the pressure relief pipe (15); and the control component (17) is used to control the operation of the plugging component (16); The blocking member (16) comprises a base (161), a nitrogen block (162), a hydrogen block (163) and a pressure relief block (164); a nitrogen cavity (1611), a hydrogen cavity (1612) and a pressure relief cavity (1613) are provided in the base (161); the nitrogen cavity (1611) and the nitrogen pipe (13) are in communication with each other; the hydrogen cavity (1612) and the hydrogen pipe (14) are in communication with each other; and the pressure relief cavity (1613) and the pressure relief cavity (1613) are in communication with each other; The nitrogen block (162) slides back and forth in the nitrogen cavity (1611), and the nitrogen block (162) blocks or opens the nitrogen pipe (13); the lower end of the nitrogen block (162) is fixedly connected to a nitrogen shaft (165), and the nitrogen shaft (165) passes through the nitrogen cavity (1611); the hydrogen block (163) slides back and forth in the hydrogen cavity (1612), and the hydrogen block (163) blocks or opens the hydrogen pipe (14). The pressure relief block (164) is opened, the lower end of the hydrogen block (163) is fixedly connected to a hydrogen shaft (166), and the hydrogen shaft (166) passes through the hydrogen cavity (1612); the pressure relief block (164) slides back and forth in the pressure relief cavity (1613), the pressure relief block (164) blocks or opens the pressure relief pipe (15), the lower end of the pressure relief block (164) is fixedly connected to a pressure relief shaft (167), and the pressure relief shaft (167) passes through the pressure relief cavity (1613); The control component (17) comprises a nitrogen control cylinder (171), a hydrogen control cylinder (172) and a pressure relief control cylinder (173); the output end of the nitrogen control cylinder (171) is fixedly connected to a nitrogen trapezoidal block (174), and the inclined surface of the nitrogen trapezoidal block (174) always abuts against the lower end of the nitrogen shaft (165); the output end of the hydrogen control cylinder (172) is fixedly connected to a hydrogen trapezoidal block (175), and the inclined surface of the hydrogen trapezoidal block (175) always abuts against the lower end of the hydrogen shaft (166); the output end of the pressure relief control cylinder (173) is fixedly connected to a pressure relief trapezoidal block (176), and the inclined surface of the pressure relief trapezoidal block (176) always abuts against the lower end of the pressure relief shaft (167).

9. The process for preparing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 7, characterized in that: A filter plate (21) is provided in the middle of the suction filtration part (2), and the filter plate (21) is used to support the suction filter paper. A suction filtration funnel (22) is provided at the bottom of the suction filtration part (2).

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