Preparation method of pyraclostrobin crystal form II

Abstract

The invention relates to a preparation method of a pyraclostrobin crystal form II, which is characterized by comprising the following steps: A, adding a pyraclostrobin solid into tert-butyl alcohol, and stirring under the condition of controlling the temperature to be 40-60 DEG C until the pyraclostrobin solid is completely dissolved; b, cooling to 20-30 DEG C, and stirring until crystals are separated out; c, continuously cooling to 0-15 DEG C to grow the crystal; and D, filtering and drying.

Description

Technical Field

[0001] The invention relates to a method for preparing pyraclostrobin crystal form II. Background Art

[0002] Pyraclostrobin, also known as pyraclostrobin, is a broad-spectrum fungicide of the methoxyacrylate type with a pyrazole structure discovered by BASF in Germany in 1993. Pyraclostrobin is a mitochondrial respiration inhibitor that inhibits mitochondrial respiration by blocking the electron transfer between cytochrome b and c1, making it impossible for mitochondria to produce and provide the energy (ATP) required for normal cell metabolism, ultimately leading to cell death. It has protective and therapeutic effects, systemic conductivity, and resistance to rain erosion. It has a long lasting effect and a wide range of applications. Different crystal forms of pyraclostrobin have different application ranges in the field of formulations. Pyraclostrobin crystal form II can be used to prepare aqueous suspension concentrates.

[0003] Chinese patent application CN110590672A discloses a method for preparing pyraclostrobin crystal form II, which uses isopropanol or a mixture of isopropyl ether and ethanol as a solvent, heats and stirs at 50°C or 80°C for 2 hours, then filters while hot, and cools the filtrate to room temperature and stands for 3-4 days. This method requires natural cooling to room temperature and maintains for 3-4 days to obtain crystals. On the one hand, the production efficiency is low, and on the other hand, natural cooling is greatly affected by the environment, and different weather or seasons may affect the experiment.

[0004] Chinese patent CN101203136B also discloses a method for preparing pyraclostrobin crystal form II, which heats 100g of isopropanol to 60°C, adds 15g of pyraclostrobin under stirring and stirs the mixture until all substances are dissolved, then cools the mixture to 20°C and stirs for another 4h, then cools the mixture to 10°C and stirs for another 1h, immediately separates the crystals and dries them under reduced pressure and ambient temperature for 16h. This method roughly describes the preparation process, does not specifically describe conditions such as the cooling rate, and this method uses a large amount of solvent and has a low yield. Summary of the invention

[0005] In view of the above problems, the present invention aims to provide a new method for preparing pyraclostrobin crystal form II. The method of the present invention uses less solvent and is simple to operate. The prepared pyraclostrobin crystal form II has high purity and yield, high stability, regular crystal habit, no agglomeration phenomenon, no solvent residue in the crystal product, larger particle size, and more uniform particle size distribution.

[0006] Specifically, the present invention relates to:

[0007] (1) A method for preparing pyraclostrobin crystal form II, characterized in that it comprises the following steps:

[0008] A. Add pyraclostrobin solid into tert-butyl alcohol and stir until completely dissolved at a temperature of 40-60°C;

[0009] B. Cool down to 20-30°C and stir until crystals precipitate;

[0010] C. Continue to cool down to 0-15℃ for crystal growth;

[0011] D. Filter and dry.

[0012] (2) The preparation method according to the above (1), wherein the mass ratio of tert-butyl alcohol to pyraclostrobin solid in step A is (3-10):1, preferably (3-6):1.

[0013] (3) According to the preparation method described in (1) or (2) above, the temperature in step A is controlled at 45 to 55°C.

[0014] (4) The preparation method according to any one of (1) to (3) above, wherein the temperature in step B is lowered to 20-25°C.

[0015] (5) The preparation method according to any one of (1) to (4) above, wherein the cooling rate in step B is 2 to 3 min / °C.

[0016] (6) The preparation method according to any one of (1) to (5) above, wherein the stirring time in step B is 1 to 6 hours, preferably 1 to 4 hours.

[0017] (7) The preparation method according to any one of (1) to (6) above, wherein a dissolving agent or seed crystals are preferably added in step B to promote crystallization. In terms of mass ratio, the amount of the dissolving agent is preferably 10 to 50% of the amount of tert-butyl alcohol, and the amount of the seed crystals is preferably 0.5 to 1% of the amount of pyraclostrobin solid feed.

[0018] (8) The preparation method according to (7) above, wherein the solvent in step B is water, cyclohexane, n-hexane, or heptane, preferably water.

[0019] (9) The preparation method according to any one of (1) to (8) above, wherein in step C, the temperature is further lowered to 5-10°C and the crystal is grown for 0.5-1 hour.

[0020] (10) The preparation method according to any one of (1) to (9) above, wherein the drying temperature in step D is 30 to 40°C, and the drying time is 2 to 8 hours, preferably 2 to 4 hours. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is the X-ray powder diffraction spectrum of pyraclostrobin Form II prepared in Example 1 of the present application.

[0022] Figure 2 This is the DSC curve of pyraclostrobin Form II prepared in Example 1 of the present application.

[0023] Figure 3 This is a comparison of the stability test spectra of pyraclostrobin Form II prepared in Example 1 of the present application, which, from bottom to top, are the X-ray powder diffraction spectra of 0 days, 30 days, 60 days, and 90 days.

[0024] Figure 4 This is the X-ray powder diffraction spectrum of the product of Comparative Example 3 of the present application.

[0025] Figure 5 Schematic diagram of the particle size distribution of pyraclostrobin Form II prepared in Example 1 of the present application and the product of Comparative Example 1.

[0026] Figure 6 This is a scanning electron microscope photograph of the pyraclostrobin crystal form II prepared in Example 1 of the present application.

[0027] Figure 7 This is a scanning electron microscope photograph of the product of Comparative Example 1 of the present application.

[0028] Figure 8 This is the gas phase spectrum of pyraclostrobin Form II prepared in Example 1 of the present application.

[0029] Fig. 9 This is the gas phase spectrum of the product of comparative example 1 of this application.

[0030] Fig.10 This is the gas phase spectrum of tert-butyl alcohol and isopropanol determined by the internal standard method.

[0031] Fig.11 This is a photo of the oil separation of Comparative Example 7 of this application. DETAILED DESCRIPTION

[0032] The present invention provides a method for preparing pyraclostrobin crystal form II, which comprises the following steps:

[0033] A. Add pyraclostrobin solid into tert-butyl alcohol and stir until completely dissolved at a temperature of 40-60°C;

[0034] B. Cool down to 20-30°C and stir until crystals precipitate;

[0035] C. Continue to cool down to 0-15℃ for crystal growth;

[0036] D. Filter and dry.

[0037] In step A, tert-butyl alcohol is used as a single solvent, which is simple to operate and easy to control.

[0038] In some specific embodiments, the mass ratio of tert-butanol to pyraclostrobin solid in step A is (3-10): 1, preferably (3-6): 1. If the amount of tert-butanol is too little, the pyraclostrobin solid is not easy to dissolve, and the subsequent cooling process system is prone to oil precipitation due to high supersaturation, thereby affecting the purity and yield of the crystal form; if the amount of tert-butanol is too much, it will cause waste and reduce production capacity.

[0039] By using tert-butyl alcohol as solvent, on the one hand, less solvent is used to produce the same output of pyraclostrobin Form II, which is in line with the low-carbon and environmentally friendly production concept; on the other hand, the production capacity per unit equipment volume is greater than that of other containers, that is, the equipment volume required to produce the same output of pyraclostrobin Form II per unit time is smaller.

[0040] In some specific embodiments, the temperature control temperature in step A is 40-60° C., preferably 45-55° C. Low temperature will lead to insufficient dissolution of pyraclostrobin solid; high temperature will lead to a prolonged subsequent cooling and crystallization operation time, reducing production efficiency.

[0041] In some specific embodiments, the temperature is lowered to 20-30°C, preferably 20-25°C in step B. When the temperature is lowered to above 30°C, crystals are not easily precipitated, and the operation time is prolonged; when the temperature is lowered to below 20°C, oil will precipitate from the system, affecting the purity of the crystal form. Lowering the temperature to the above range can effectively avoid pyraclostrobin from not precipitating crystals and precipitating oil from pyraclostrobin.

[0042] In some specific embodiments, the cooling rate in step B is 2-3 min / ° C. Cooling too fast will affect the quality and yield of the crystals; cooling too slowly will result in low production efficiency.

[0043] In some specific embodiments, a dissolving agent may be added in step B to promote crystallization. The dissolving agent may be water, cyclohexane, n-hexane, or heptane, preferably water. By mass ratio, the amount of the dissolving agent is preferably 10 to 50% of the amount of the organic solvent. Excessive use of the dissolving agent may, on the one hand, cause a drastic change in the supersaturation of the system, resulting in rapid growth of the crystals, oil precipitation, and affect the quality of the crystals, and on the other hand, may also affect the recovery of the solvent.

[0044] In some specific embodiments, seed crystals may be added in step B to promote crystallization. In terms of mass ratio, the preferred amount of seed crystals is 0.5-1% of the amount of pyraclostrobin solid feed. Too little seed crystal addition will result in slow crystal growth; too much seed crystal addition will affect the purity and quality of the crystal.

[0045] In some specific embodiments, the stirring time in step B is 1 to 6 hours, preferably 1 to 4 hours. Too long a stirring time will reduce production efficiency and may cause crystal transformation of Form II; too short a stirring time will cause oil precipitation in the system.

[0046] In some specific embodiments, step C continues to cool to 0-15°C, preferably 5-10°C, and grows the crystal for 0.5-1 hour. The second cooling and growing helps to improve the yield.

[0047] By controlling the temperature of two step-by-step cooling processes, oil precipitation in the system is avoided, and the system can be crystallized smoothly.

[0048] In some specific embodiments, the drying temperature in step D is 30-40° C., and the drying time is 2-8 hours, preferably 2-4 hours.

[0049] Example

[0050] The present invention is further described in detail below in conjunction with specific embodiments, but the present invention is not limited to these specific embodiments, and any modifications or changes within the scope of the present invention fall within the scope of this application.

[0051] In the following examples, the conditions for high performance liquid chromatography analysis are as follows: the instrument is Agilent 1100LC liquid chromatograph, UV detector. The chromatographic column is Kromasil 100-5-C18, 4.6×250 mm. The mobile phase is acetonitrile: water (adjusted with formic acid to pH=3.7-4.1)=80:20, the column temperature is 30°C, the flow rate is 1.0 mL / min, and the wavelength is 260 nm.

[0052] Example 1

[0053] Take 20g of pyraclostrobin raw material into a four-necked bottle, add 80g of tert-butanol, control the temperature at 50°C, and stir for 0.5 hour until it is completely dissolved; control the stirring speed at 200r / min to cool down, first reduce the system temperature to 20°C at a cooling rate of 2-3min / °C, use a constant pressure dropping funnel to add 30g of deionized water, stir for 1h, then continue to cool to 5°C, and grow crystals for 1 hour; filter; place in a 40°C oven and dry for 2 hours to obtain 18.7g of white crystals, with a yield of 93.5% and a purity of 99%.

[0054] The X-ray powder diffraction (XRD) pattern was determined under the following conditions. Figure 1 shown.

[0055] Scanning 2θ range: 2.0~50.0°, step: 0.02° / sec, Cu (40kv, 100mA).

[0056] The 2θ values ​​of the XRD characteristic peaks of the white crystals are: 9.34°±0.2, 11.66°±0.2, 14.16°±0.2, 14.56°±0.2, 14.78°±0.2, 15.84°±0.2, 16.90°±0.2, 18.04°±0.2, 18.44°±0.2, 18.76°±0.2, 19.54°±0.2, 19.98°±0.2, 20.86°±0.2, 22.26°±0.2, 22.70°±0.2, 23.46°±0.2, 24.78°±0.2, 25.10°±0.2, 25.88°±0.2, 26.58°±0.2, and 30.50°±0.2.

[0057] The interplanar spacing d value of the XRD characteristic peak of white crystals is:

[0058] The above d value is compared with the d value of pyraclostrobin crystalline form II described in paragraphs

[0080] -

[0090] of CN101203136B, respectively.

[0059] The white crystals were confirmed to be pyraclostrobin crystal form II.

[0060] The measurement conditions of differential scanning calorimeter (DSC) are as follows, and the results are as follows Figure 2 shown.

[0061] Heating range: 30-110℃; heating rate: 5℃ / min.

[0062] Example 2

[0063] Take 20g of pyraclostrobin raw material into a four-necked bottle, add 80g of tert-butanol, control the temperature at 45°C, stir for 0.5 hour until completely dissolved; control the stirring speed at 200r / min to cool down, first cool the system to 25°C at a cooling rate of 2-3min / °C, stir for 4h, then continue to cool to 5°C, and grow crystals for 1 hour; filter; place in an oven at 40°C and dry for 2 hours to obtain 18.3g of white pyraclostrobin crystal form II product, with a yield of 91.5% and a purity of 99%.

[0064] Example 3

[0065] Take 38.7g of pyraclostrobin raw material into a four-necked bottle, add 154.8g of tert-butanol, control the temperature at 50°C, and stir for 0.5 hour until it is completely dissolved; control the stirring speed at 200r / min to cool down, first cool the system to 25°C at a cooling rate of 2-3min / °C, add 0.387g of pyraclostrobin crystal form II seeds, stir for 1 hour, then continue to cool to 5°C, and grow crystals for 1 hour; filter, place in a 40°C oven and dry for 2 hours to obtain 36.5g of white pyraclostrobin crystal form II product, with a yield of 94.3% and a purity of 99%.

[0066] Comparative Example 1 Crystallization by isopropanol

[0067] According to the description of Example 4 in CN101203136B, the preparation was carried out as follows: 100 g of isopropanol was heated to 60° C., and then 15 g of pyraclostrobin was added under stirring and the mixture was stirred until all substances were dissolved; the mixture was cooled to 20° C. and stirred for 4 hours, and then the mixture was cooled to 10° C. and stirred for another hour; the crystals were immediately separated and dried at a reduced pressure ambient temperature for 16 hours to obtain 10.8 g of a white solid with a yield of 72% and a purity of 99%.

[0068] Comparative Example 2 Crystallization by isopropanol

[0069] According to the description of Example 1 in CN110590672A, the following preparation was performed: 38.7 g of pyraclostrobin crystal form IV raw material was taken into a round-bottom flask, 300 ml of isopropanol was added, and the mixture was heated in a water bath at 80° C. with stirring for 2 hours, filtered while hot, and the filtrate was cooled to room temperature and allowed to stand for 3 days, and then the precipitated solid phase was collected to obtain 29.7 g of pyraclostrobin crystal form II product with a yield of 76.7% and a purity of 98%.

[0070] Example 4: Stability of the crystal form

[0071] The product of Example 1 was placed at room temperature for 0 days, 30 days, 60 days and 90 days respectively, and the XRD of the product was detected in the same way as in Example 1 to examine the stability of Form II. The results are as follows: Figure 3 shown.

[0072] according to Figure 3 The XRD patterns shown in the figure are the XRD patterns of the target product pyraclostrobin crystalline form II obtained by the present invention after being placed at room temperature for 0 days, 30 days, 60 days and 90 days respectively. Figure 1 Similarly, no crystal transformation occurred during storage, so pyraclostrobin crystal form II has good stability.

[0073] Example 5 Crystalline particle size study

[0074] The particle size of the product of Example 1 and the product of Comparative Example 1 were measured using a Master size 3000 Malvern particle size analyzer. The particle size distribution diagram is shown in Figure 5 The data of main particle size and diameter distance are shown in Table 1.

[0075] Table 1

[0076] sample Main particle size / um Diameter Comparative Example 1 19.277 11.228 Example 1 270.821 1.757

[0077] According to the data in Table 1, the target product pyraclostrobin crystal form II obtained in the present invention has a larger particle size and a more uniform particle size distribution than the crystal obtained in Comparative Example 1.

[0078] Example 6: Appearance of the Crystalline Form

[0079] The appearance of the product of Example 1 and the product of Comparative Example 1 were examined using a scanning electron microscope (SEM). The results of the product of Example 1 are as follows: Figure 6 As shown, the results of the comparative example 1 product are as follows Figure 7 shown.

[0080] according to Figure 6 and Figure 7 It can be seen from the scanning electron microscope photos shown that the target product pyraclostrobin crystal form II obtained by the present invention has a more regular crystal habit than the crystal of comparative example 1, and there is no agglomeration phenomenon.

[0081] Example 7 Investigation of Residual Solvent in Crystalline Forms

[0082] The conditions for gas chromatography analysis were as follows: Agilent 6890 gas phase; PEG-20M chromatographic column; column temperature 55°C, heating to 200°C at a rate of 11.5°C / min; vaporization chamber: 200°C; detector: 200°C.

[0083] The solvent residues of the product of Example 1 and the product of Comparative Example 1 were detected by gas chromatograph. The results of the product of Example 1 are as follows: Figure 8 As shown, the results of the comparative example 1 product are as follows Fig. 9 The gas phase peak positions of tert-butyl alcohol and isopropanol were determined by the internal standard method. The results are shown in Fig.10 shown.

[0084] After analysis, the peak at 11.05 is N,N-dimethylformamide, the solvent used to dissolve the product during injection; the peak at 7.24 is toluene, the internal standard; the peak at 5.40 is isopropanol; and the peak at 5.03 is tert-butanol.

[0085] according to Figure 8 and Fig. 9It can be seen from the gas phase spectrum shown that the target product pyraclostrobin crystal form II obtained in Example 1 of the present invention has no residual tert-butyl alcohol, while the pyraclostrobin crystal form II obtained in Comparative Example 1 has residual isopropanol.

[0086] Comparative Example 3: Effect of Cooling Temperature on Crystal Form

[0087] 20 g of pyraclostrobin raw material was placed in a four-necked bottle, 80 g of tert-butyl alcohol was added, the temperature was controlled at 45 ° C, and the mixture was stirred for 0.5 hours until it was completely dissolved; the stirring speed was controlled at 200 r / min and the temperature was lowered to 15 ° C. Oil was observed to come out from the bottom of the bottle. After being kept at this temperature for a period of time, the oil solidified and crystals were precipitated on the oil; after filtering and drying to obtain white crystals, XRD was detected in the same way as in Example 1. The results were as follows: Figure 4 shown.

[0088] The 2θ values ​​of the XRD characteristic peaks of the white crystals are: 14.736°±0.2, 18.580°±0.2, 22.178°±0.2, 14.557°±0.2, 24.982°±0.2, and 29.687°±0.2.

[0089] The interplanar spacing d value of the XRD characteristic peak of white crystals is:

[0090] The above d value was compared with the d value of pyraclostrobin crystal form IV recorded in paragraphs

[0008] to

[0012] of CN101203136B, and all of them overlapped, confirming that the white crystals were pyraclostrobin crystal form IV.

[0091] The temperature was lowered to 10°C, and other conditions were the same as those in Comparative Example 3. XRD was detected in the same manner as in Example 1, and the obtained crystals were found to be Form IV after comparison.

[0092] The temperature was lowered to 5°C, and other conditions were the same as those in Comparative Example 3. XRD was detected in the same manner as in Example 1, and the obtained crystals were found to be Form IV after comparison.

[0093] Comparative Example 4 Investigating the Effect of a Single Organic Solvent on Crystalline Form

[0094] Take 20g of pyraclostrobin raw material into a four-necked bottle, add 80g of methanol, control the temperature at 45°C, stir for 0.5 hour until completely dissolved; control the stirring speed at 200r / min to cool down, first reduce the system temperature to 25°C at a cooling rate of 2-3min / °C, stir for 4h, then cool to 5°C, grow the crystal for 1h and then filter; place in an oven at 40°C and dry for 2 hours to obtain crystals, detect XRD in the same way as in Example 1, and the obtained crystals are found to be form IV after comparison.

[0095] The solvent was replaced with ethanol, and the other conditions were the same as those in Comparative Example 4. XRD was detected in the same manner as in Example 1, and the obtained crystals were found to be Form IV after comparison.

[0096] The solvent was replaced with n-propanol, and the other conditions were the same as those in Comparative Example 4. XRD was detected in the same manner as in Example 1, and the obtained crystals were found to be Form IV after comparison.

[0097] The solvent was replaced with dichloromethane, and the other conditions were the same as those in Comparative Example 4. XRD was detected in the same manner as in Example 1, and the obtained crystals were found to be Form IV after comparison.

[0098] The solvent was replaced with ethyl acetate, and other conditions were the same as those in Comparative Example 4. XRD was detected in the same manner as in Example 1, and the obtained crystals were found to be Form IV after comparison.

[0099] The solvent was replaced with anisole, and other conditions were the same as those in Comparative Example 4. XRD was detected in the same manner as in Example 1, and the obtained crystals were found to be Form IV after comparison.

[0100] The solvent was replaced with acetone, and the other conditions were the same as those in Comparative Example 4. XRD was detected in the same manner as in Example 1, and the obtained crystals were found to be Form IV after comparison.

[0101] Comparative Example 5 Investigating the Effects of Common Solvent and Solvent Water on Crystalline Form

[0102] Take 80g of dichloromethane and 20g of pyraclostrobin and dissolve them completely at room temperature, control the stirring speed at 200r / min, cool down to 20°C, add 30g of deionized water, stir for 1h, then continue to cool to 5°C, grow crystals for 1h and filter. Dry in an oven at 40°C for 2 hours to obtain crystals, detect XRD in the same way as in Example 1, and the obtained crystals are found to be crystal form IV after comparison.

[0103] The solvent was replaced with ethyl acetate, and other conditions were the same as those in Comparative Example 5. XRD was detected in the same manner as in Example 1, and the obtained crystals were found to be Form IV after comparison.

[0104] The solvent was replaced with anisole, and other conditions were the same as those in Comparative Example 5. XRD was detected in the same manner as in Example 1, and the obtained crystals were found to be Form IV after comparison.

[0105] The solvent was replaced with acetone, and the other conditions were the same as those in Comparative Example 5. XRD was detected in the same manner as in Example 1, and the obtained crystals were found to be Form IV after comparison.

[0106] The solvent was replaced with methanol, and the other conditions were the same as those in Comparative Example 5. XRD was detected in the same manner as in Example 1, and the obtained crystals were found to be Form IV after comparison.

[0107] The solvent was replaced with ethanol, and the other conditions were the same as those in Comparative Example 5. XRD was detected in the same manner as in Example 1, and the obtained crystals were found to be Form IV after comparison.

[0108] The solvent was replaced with n-propanol, and other conditions were the same as those in Comparative Example 5. XRD was detected in the same manner as in Example 1, and the obtained crystals were found to be Form IV after comparison.

[0109] Comparative Example 6 Investigating the Effect of the Amount of Tert-Butanol and Pyraclostrobin and Temperature

[0110] 5 g of pyraclostrobin and 25 g of tert-butanol were stirred at 30°C. After 2 hours of stirring, the mixture still could not be dissolved. When the temperature was raised to 45°C, the pyraclostrobin was completely dissolved within 0.5 hour.

[0111] 5 g of pyraclostrobin and 10 g of tert-butyl alcohol were stirred at 50° C. The pyraclostrobin was difficult to stir and did not dissolve easily.

[0112] Comparative Example 7 Investigating the Effect of the Amount of Solvent Water on the Crystalline Form

[0113] Take 20g of pyraclostrobin raw material in a four-necked bottle, add 80g of tert-butyl alcohol, control the temperature at 50℃, stir for 0.5 hours until completely dissolved; control the stirring speed at 200r / min to cool down, first cool the system temperature to 20℃ at a cooling rate of 2-3min / ℃, use a constant pressure dropping funnel to add 100g of deionized water, stir for 1h, and find that oil comes out from the bottom of the bottle, which is not conducive to obtaining crystals. The oil separation photo is as follows Fig.11 shown.

Claims

1. A method for preparing pyraclostrobin crystal form II, characterized in that: The following steps are involved: A. Add pyraclostrobin solid into tert-butyl alcohol and stir until completely dissolved at a temperature of 40-60°C; B. Cool down to 20-30°C and stir until crystals precipitate; C. Continue to cool down to 0-15℃ for crystal growth; D. Filter and dry.

2. The preparation method according to claim 1, wherein the mass ratio of tert-butyl alcohol to pyraclostrobin solid in step A is (3-10):1, preferably (3-6):

1.

3. The preparation method according to claim 1 or 2, wherein the temperature in step A is controlled at 45-55°C.

4. The preparation method according to any one of claims 1 to 3, wherein the temperature in step B is lowered to 20-25°C.

5. The preparation method according to any one of claims 1 to 4, wherein the cooling rate in step B is 2 to 3 min / °C.

6. The preparation method according to any one of claims 1 to 5, wherein the stirring time in step B is 1 to 6 hours, preferably 1 to 4 hours.

7. The preparation method according to any one of claims 1 to 6, wherein in step B, a dissolving agent or a seed crystal is preferably added to promote crystallization, and the amount of the dissolving agent is preferably 10-50% of the amount of tert-butyl alcohol, and the amount of the seed crystal is 0.5-1% of the amount of pyraclostrobin solid feed.

8. The preparation method according to claim 7, wherein the solvent in step B is water, cyclohexane, n-hexane, heptane, preferably water.

9. The preparation method according to any one of claims 1 to 8, wherein in step C, the temperature is further lowered to 5-10°C; and the crystal is grown for 0.5-1 hour.

10. The preparation method according to any one of claims 1 to 9, wherein the drying temperature in step D is 30-40°C, and the drying time is 2-8 hours, preferably 2-4 hours.

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