Separation and purification method of pendimethalin
Through the combination of three-stage melt crystallization and molecular distillation, the safety, efficiency and purity problems in dimethyl-Wuling separation and purification are solved, and high purity preparation is achieved, energy consumption and operation complexity are reduced, and it is suitable for industrial production. .
Patent Information
- Application Number
- CN202411152429.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-21
- Publication Date
- 2024-12-31
AI Technical Summary
The existing separation and purification methods of dimethyl Wuling cannot take into account safety, efficiency and separation purity, and there are problems such as solvent residue, complex operation and high energy consumption.
The three-stage melt crystallization method combined with molecular distillation is used to achieve high-purity dimethyl-pure separation and purification through gradual cooling and sweating operations, the cooling rate and temperature are controlled to remove impurities, and molecular distillation is performed under vacuum conditions.
It realizes high-purity dimethyl purine preparation, reduces energy consumption and operational complexity, is suitable for industrial production, reduces solvent residues, and improves product stability and consistency.
Smart Images
Figure CN119219507A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of pendimethalin preparation, and in particular to a method for separating and purifying pendimethalin. Background Art
[0002] Dimethenamid-P, chemical name is 2-(2,4-dichlorophenoxy)-N,N-dimethylacetamide, molecular formula is C 13 H 19 N3O4 is a dinitroaniline herbicide that mainly inhibits the division of meristem cells. It does not affect the germination of weed seeds, but works after the young shoots, stems and roots absorb the agent during the germination of weed seeds. It is mainly suitable for corn, soybeans, cotton, vegetables and orchards to control annual grass and broad-leaved weeds such as crabgrass, foxtail grass, bluegrass, foxtail grass, goosegrass, gray lily, champignon intestine, nightshade, quinoa, amaranth, etc. It also has a strong inhibitory effect on the growth of dodder seedlings.
[0003] At present, the preparation process of pendimethalin mainly includes direct esterification, Grignard reaction, direct amination and continuous flow reaction. Many countries and regions have strict purity and impurity limit regulations for pesticide products (high-purity pendimethalin can reduce the impact on the environment and reduce the risk of residues). Therefore, in the actual production process, in order to ensure product quality, pendimethalin is usually required to be separated and purified to remove by-products and impurities. At present, the separation and purification methods of pendimethalin include solvent crystallization, chromatography column method, high performance liquid chromatography, extraction method and distillation method. Among them, the solvent crystallization method is simple to operate, but the purity improvement is limited. Multiple crystallizations are required to achieve the required purity. At the same time, the solvent has the problem of solvent residue; the column chromatography method has good separation effect, but the operation is complicated and time-consuming, and it is not suitable for large-scale production; the high performance liquid chromatography method has high equipment cost, complex operation and high maintenance cost; the extraction method is suitable for processing a large number of samples, but the use of extractants may have the problem of solvent residue; the distillation method is simple to operate and is suitable for removing volatile impurities, but the separation effect is poor for compounds with similar boiling points, and decomposition may occur at high temperatures. At present, the industry generally adopts the method of molecular distillation combined with rectification to purify pendimethalin, but the molecular distillation combined with rectification method has a large amount of residual in the kettle at the later stage of purification, and the distillation is dangerous and explosive, and the yield is low and the energy consumption is high. Therefore, it is urgent to develop a new, safe and efficient method for purifying pendimethalin. Summary of the invention
[0004] The present invention aims to provide a method for separating and purifying pendimethalin, so as to solve the problem that safety, high efficiency and separation purity cannot be taken into account when separating and purifying pendimethalin in the prior art.
[0005] To achieve the above-mentioned purpose, the present invention adopts the following technical scheme: a method for separating and purifying dimethoate, comprising the following steps: melting dimethoate and then performing tertiary melt crystallization, the sweating liquid of the primary crystallization is returned to the primary crystallization, and the mother liquor of the primary crystallization is sent to the secondary crystallization; the product obtained by the secondary crystallization is returned to the primary crystallization, the sweating liquid of the secondary crystallization is returned to the secondary crystallization, and the mother liquor of the secondary crystallization is sent to the tertiary crystallization; the product obtained by the tertiary crystallization is returned to the secondary crystallization, the sweating liquid of the tertiary crystallization is returned to the tertiary crystallization, the mother liquor of the tertiary crystallization is collected in multiple batches and then subjected to molecular distillation, and the product obtained by molecular distillation is returned to the tertiary crystallization.
[0006] Preferably, as an improvement, the cooling rate of the primary crystallization is 1-2°C / h.
[0007] Preferably, as an improvement, during the primary crystallization, the medium temperature is 49° C., the internal temperature is 51-53° C., and the crystallization time is 1-5 h.
[0008] Preferably, as an improvement, the sweating temperature of the primary crystallization is 51-59° C., and the sweating time is 5-10 h.
[0009] Preferably, as an improvement, the cooling rate of the secondary crystallization is 1-2°C / h.
[0010] Preferably, as an improvement, during the secondary crystallization, the medium temperature is 48°C, the internal temperature is 51-53°C, and the crystallization time is 1-5h.
[0011] Preferably, as an improvement, the sweating temperature of the secondary crystallization is 51-58° C., and the sweating time is 5-10 h.
[0012] Preferably, as an improvement, the cooling rate of the tertiary crystallization is 1-2°C / h.
[0013] Preferably, as an improvement, during the tertiary crystallization, crystallization is first performed at a medium temperature of 48°C, an internal temperature of 50.8°C, and a temperature difference of 1 to 2°C for 2.0 h; and then recrystallization is performed at a medium temperature of 47°C, an internal temperature of 49.5°C, and a temperature difference of 2 to 3°C for 1.0 h.
[0014] Preferably, as an improvement, the sweating temperature of the tertiary crystallization is 50-55.5°C, and the sweating time is 5-10 hours; the conditions for molecular distillation are: carried out at a temperature of 120-140°C and a pressure of 20-50Pa under vacuum.
[0015] The principle and advantages of this solution are: in actual application, the industry currently generally uses distillation or distillation coupled with molecular distillation to purify pendimethalin; in this technical solution, melt crystallization is used instead of distillation to purify pendimethalin. Melt crystallization refers to the partial crystallization achieved by gradually lowering the temperature of the initial mixed / impurity state material according to the difference in melting points of the materials to be processed. There is a concentration difference between the crystallized solid phase and the mother liquor, thereby achieving the purpose of separation and purification. The advantages of melt crystallization purification in this solution are:
[0016] 1. High purity: By precisely controlling the cooling rate and temperature, high-purity crystals can be effectively separated from the mixture. In the molten state, impurities are often not easy to form crystals, so they can be effectively removed.
[0017] 2. Easy operation: Compared with other separation technologies, melt crystallization is relatively simple to operate and easy to industrialize. It does not require complex equipment and excessive chemical reagents, which reduces the difficulty and cost of operation.
[0018] 3. Low energy consumption: Melt crystallization is usually carried out at a lower temperature, and compared with other methods that require high-temperature evaporation, the energy consumption is lower. For heat-sensitive substances, low-temperature operation can avoid the decomposition or denaturation of the substance. Existing high-purity chemicals are usually achieved through distillation. In addition to steam heating, the distillation process is often accompanied by high vacuum, which consumes very high energy. The heat of vaporization is 2 to 3 times the heat of melting. Therefore, the energy consumption of melt crystallization is only equivalent to 10 to 30% of distillation.
[0019] 4. Wide range of applications: Melt crystallization is applicable to many types of compounds, including organic compounds, inorganic compounds, etc. It is particularly suitable for processing substances that are solid at room temperature but can melt at lower temperatures.
[0020] 5. Easy to scale up production: The melt crystallization process is easy to scale up from small-scale experiments to industrial production. By optimizing parameters such as cooling rate and sweating rate, the growth of crystals can be effectively controlled.
[0021] 6. Controllable crystal form: By controlling the cooling conditions, the growth direction and shape of the crystal can be effectively controlled, thereby affecting the physical properties of the product. For some drugs, different crystal forms may have different bioavailability and stability.
[0022] 7. Environmentally friendly: A large amount of solvent is not required in the melt crystallization process, which reduces the impact on the environment. For solvents that need to be recycled and reused, melt crystallization can reduce the need for solvent treatment.
[0023] 8. Easy to automate: The melt crystallization process can be precisely controlled by an automated control system, improving production efficiency and consistency of product quality.
[0024] 9. Stable product quality: By optimizing process conditions, crystalline products with uniform particle size distribution and high purity can be obtained. This helps to improve product stability and consistency and meet strict regulatory requirements.
[0025] After the melt is crystallized, the crystals are precipitated on the wall of the crystallizer, and some impurities are also contained on the surface and inside of the crystals, so it is necessary to purify the crude crystals after crystallization. The present technical solution uses sweating operation to complete the further purification process, slowly raising the temperature of the crystals containing impurities to near the melting point (equilibrium temperature), and the local crystal layer containing more impurities has a lower melting point, which first melts and seeps out from the inside of the crystal. In this process, the inventors have found that the purity of the crystals after sweating is not only related to the heating temperature and heating rate, but also to the formation and growth process of the crystal layer. The faster the cooling rate and the lower the crystallization temperature, the thicker the crystal layer will be, and the more impurities will be. The better the effect of sweating purification. For layer crystallization, as the sweating time increases, the impurity inclusion body in the crystal layer has a low melting point, and will first melt and move in the direction of high temperature. The larger the volume of the inclusion body, the faster the movement speed. In addition, the movement speed of the inclusion body will also be affected by the crystal layer structure. The inventors have found that the inclusion body moves faster in the crystal layer formed at a slower cooling rate. In addition, during the technical research and development stage, the cooling rate and sweating rate of melt crystallization are one of the difficulties and key points of this technical solution, which will have a key impact on the purity and yield of the product, and there is a synergistic effect between melt crystallization and sweating, which influence each other. The inventors have obtained a better range of condition control by overall optimization of melt crystallization and sweating rate. In summary, the inventors have comprehensively optimized the temperature, heating rate, and cooling rate during crystallization and sweating, so as to achieve the purpose of efficiently purifying dimethoate. BRIEF DESCRIPTION OF THE DRAWINGS
[0026] Figure 1 It is a liquid chromatogram of the pendimethalin crystals in the embodiment of the present invention.
[0027] Figure 2 This is a picture of the pendimethalin product in the embodiment of the present invention.
[0028] Figure 3 The present invention is a flowchart of the purification process of pendimethalin according to an embodiment of the present invention. DETAILED DESCRIPTION
[0029] The following is further described in detail through specific implementations, but the implementation of the present invention is not limited thereto. Unless otherwise specified, the technical means used in the following implementations are conventional means well known to those skilled in the art; the experimental methods used are all conventional methods; the materials, reagents, etc. used can all be obtained from commercial channels.
[0030] Example 1
[0031] like Figure 3 As shown, a method for separating and purifying pendimethalin comprises the following steps:
[0032] Step 1: primary crystallization, the specific steps are as follows:
[0033] S1. Clean and dry the 5L plate crystallizer, connect the heating device, and heat it to 65℃ for preheating.
[0034] S2. Add pendimethalin raw material into the plate crystallizer.
[0035] S3. Start the plate crystallizer cooling circulation system, start cooling, and control the cooling rate in the kettle at about 1-2°C / h.
[0036] S4. When the medium temperature drops to 49°C and the temperature in the crystallizer drops to 51.3°C, crystallization begins.
[0037] S5. Maintain medium temperature at 49°C and internal temperature at 51-53°C for crystallization for 1.3 hours.
[0038] S6, after the heat preservation is finished, the crystallization mother liquor is released until almost no liquid flows out;
[0039] S7. Adjust the temperature of the crystallizer medium to heat up and sweat. The cooling medium temperature is controlled at about 50-57°C, the internal temperature is 51-59°C, and sweating is carried out for 7.1 hours.
[0040] S8. After sweating is completed, the temperature of the cooling medium is increased and controlled at 65-70°C. All the crystals in the kettle are melted and taken out, and the content of the taken out liquid is tested.
[0041] Step 2: Secondary crystallization, the specific steps are as follows:
[0042] S1. Clean and dry the 1L plate crystallizer, connect the heating device, and heat it to 65℃ for preheating.
[0043] S2. Add the primary crystallization mother liquor into the plate crystallizer at a temperature of 65-70°C.
[0044] S3. Start the plate crystallizer cooling circulation system, start cooling, and control the cooling rate in the kettle at about 1-2°C / h.
[0045] S4. When the medium temperature drops to 49°C and the temperature in the crystallizer drops to 51.3°C, crystallization begins.
[0046] S5. Maintain the medium temperature at 48°C, the internal temperature at 51-53°C, and the temperature difference at 2-3°C for crystallization for 1.5 hours.
[0047] S6. After the heat preservation is completed, the crystallization mother liquor is released until almost no liquid flows out.
[0048] S7. Adjust the temperature of the crystallizer medium to heat up and sweat. The cooling medium temperature is controlled at about 50-57°C, the internal temperature is 51-58°C, and sweating is carried out for 6.5 hours.
[0049] S8. After sweating is completed, the temperature of the cooling medium is increased and controlled at 65-70°C. All the crystals in the kettle are melted and taken out, and the content of the taken out liquid is tested.
[0050] Step 3: Tertiary crystallization, the specific steps are as follows:
[0051] S1. Clean and dry the 1L plate crystallizer, connect the heating device, and heat it to 65℃ for preheating.
[0052] S2. Add secondary crystallization mother liquor into the plate crystallizer at a temperature of 65-70°C.
[0053] S3. Start the plate crystallizer cooling circulation system, start cooling, and control the cooling rate in the kettle at about 1-2°C / h.
[0054] S4. When the medium temperature drops to 49°C and the temperature in the crystallizer drops to 51.3°C, start timing the crystallization.
[0055] S5. Maintain the medium temperature at 48°C and the internal temperature at 50.8°C, with a temperature difference of 1 to 2°C, and crystallize for 2.0 hours; then maintain the medium temperature at 47°C and the internal temperature at 49.5°C, with a temperature difference of 2 to 3°C, and crystallize for 1.0 hour, with a cumulative crystallization time of 3.0 hours.
[0056] S6. After the heat preservation is completed, the crystallization mother liquor is released until almost no liquid flows out.
[0057] S7. Adjust the temperature of the crystallizer medium to heat up and sweat. The cooling medium temperature is controlled at about 49-54.5°C, the internal temperature is 50-55.5°C, and sweating is carried out for 5.0 hours.
[0058] S8. After sweating is completed, the temperature of the cooling medium is increased and controlled at 65-70°C. All the crystals in the kettle are melted and taken out, and the content of the taken out liquid is tested.
[0059] Step 4: distillation of the tertiary crystallization mother liquor, the specific steps are as follows:
[0060] Collect multiple batches of tertiary crystallization mother liquor, carry out molecular distillation at 120-140°C and 20-50Pa vacuum to obtain fractions and still residues, respectively. The fractions are returned to the tertiary crystallization step to realize the circulation of the whole system, and the still residues are incinerated.
[0061] Experimental Example 1: Purity test of a single batch of products
[0062] ① Primary crystallization: purification from 96.89% to above 98.5%.
[0063] ② Secondary crystallization: Using the primary crystallization mother liquor as raw material, purify it from 93.92% to above 96.89%.
[0064] ③Third-stage crystallization: Using the second-stage crystallization mother liquor as raw material, purify it from 90.40% to above 93.92%.
[0065] ④ Molecular distillation: Use the tertiary crystallization mother liquor as raw material for distillation and purification to recover pendimethalin.
[0066] The main experimental data of each batch are summarized in the following table:
[0067] Table 1
[0068]
[0069] Experimental Example 2 Liquid Chromatography Detection
[0070] Pendimethalin crystalline product picture Figure 2 As shown, the pendimethalin crystalline product (the product obtained by primary crystallization) was subjected to liquid chromatography detection, and the results were as follows Figure 1 shown.
[0071] Comparative Example 1 The comparative examples all take primary crystallization as an example to illustrate the effects of cooling rate and sweating rate.
[0072] The difference between this comparative example and Example 1 is that the cooling rate of the melt crystallization in this comparative example is 0.5°C / h.
[0073] The results are shown in Table 2:
[0074] Table 2
[0075]
[0076] Comparative Example 2
[0077] The difference between this comparative example and Example 1 is that the cooling rate of the melt crystallization in this comparative example is 3°C / h. The results are shown in Table 3:
[0078] Table 3
[0079]
[0080] Comparative Example 3
[0081] The difference between this comparative example and Example 1 is that the sweating time in this comparative example is 3 hours. The results are shown in Table 4:
[0082] Table 4
[0083]
[0084] Comparative Example 4
[0085] The difference between this comparative example and Example 1 is that the sweating rate in this comparative example is 12h. The results are shown in Table 5:
[0086] Table 5
[0087]
[0088] The above is only an embodiment of the present invention, and the common knowledge such as the known specific technical solutions and / or characteristics in the solution is not described in detail here. It should be pointed out that for those skilled in the art, without departing from the technical solution of the present invention, several modifications and improvements can be made, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to interpret the content of the claims.
Claims
1. A method for separating and purifying pendimethalin, characterized in that: The steps include: melting pendimethalin and then performing tertiary melt crystallization, returning the primary crystallization sweating liquid to the primary crystallization, and sending the primary crystallization mother liquor to the secondary crystallization; The product obtained from the secondary crystallization is pumped back to the primary crystallization, the sweat liquid from the secondary crystallization is pumped back to the secondary crystallization, and the mother liquor from the secondary crystallization is sent to the tertiary crystallization; The product obtained from the tertiary crystallization is fed back to the secondary crystallization, the sweat liquid from the tertiary crystallization is fed back to the tertiary crystallization, the mother liquor from the tertiary crystallization is collected in multiple batches and then molecularly distilled, and the product obtained from the molecular distillation is fed back to the tertiary crystallization.
2. The method for separating and purifying pendimethalin according to claim 1, characterized in that: The cooling rate of the primary crystallization is 1-2°C / h.
3. The method for separating and purifying pendimethalin according to claim 2, characterized in that: During the primary crystallization, the medium temperature is 49° C., the internal temperature is 51-53° C., and the crystallization time is 1-5 hours.
4. The method for separating and purifying pendimethalin according to claim 3, characterized in that: The sweating temperature of the primary crystallization is 51-59° C., and the sweating time is 5-10 hours.
5. The method for separating and purifying pendimethalin according to claim 4, characterized in that: The cooling rate of the secondary crystallization is 1-2°C / h.
6. The method for separating and purifying pendimethalin according to claim 5, characterized in that: During the secondary crystallization, the medium temperature is 48° C., the internal temperature is 51-53° C., and the crystallization time is 1-5 hours.
7. The method for separating and purifying pendimethalin according to claim 6, characterized in that: The sweating temperature of the secondary crystallization is 51-58° C., and the sweating time is 5-10 hours.
8. The method for separating and purifying pendimethalin according to claim 7, characterized in that: The cooling rate of the tertiary crystallization is 1-2°C / h.
9. The method for separating and purifying pendimethalin according to claim 8, characterized in that: During the tertiary crystallization, crystallization is first performed at a medium temperature of 48°C, an internal temperature of 50.8°C, and a temperature difference of 1-2°C for 2.0 h; and then recrystallization is performed at a medium temperature of 47°C, an internal temperature of 49.5°C, and a temperature difference of 2-3°C for 1.0 h.
10. The method for separating and purifying pendimethalin according to claim 9, characterized in that: The sweating temperature of the tertiary crystallization is 50-55.5° C., and the sweating time is 5-10 hours; the conditions for molecular distillation are: carried out at a temperature of 120-140° C. and a pressure of 20-50 Pa in vacuum.