Crystal form b of benzoxazine compound, and preparation method therefor and use thereof

Abstract

Disclosed in the present invention are a crystal form B of a benzoxazine compound, a preparation method therefor and a use thereof. The crystal form B is a crystal form B of compound (I), and an X-ray powder diffraction pattern of the crystal form B has characteristic absorption peaks at reflection angles 2θ of 5.6±0.2°, 8.9±0.2°, 12.8±0.2°, 13.8±0.2°, 14.5±0.2°, and 17.6±0.2°. The crystal form B of the compound of formula (I) of the present invention is a thermodynamically more stable crystal form, which can be stored simply and conveniently at room temperature, is easy for industrial large-scale production, and facilitates subsequent processing and application of products.

Description

A benzoxazine compound, crystal form B, preparation method and application Technical Field

[0001] This invention belongs to the field of agrochemicals, specifically relating to a benzoxazine compound, crystal form B, its preparation method, and its application. Background Technology

[0002] Compound 3-(7-fluoro-3-oxo-4-(prop-2-yn-1-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazinyl)-1-methyl-6-(trifluoromethyl)pyrimidine-2,4(1H,3H)-dione (i.e., Formula I below) and its herbicidal activity have been reported in US Patent US5084084A. Its structure is similar to the commercial herbicide propyzamide, belonging to the protoporphyrinogen oxidase inhibitor class. It enhances cell membrane lipid peroxidation by inducing the accumulation of protoporphyrin, inhibiting plant photosynthesis, and causing rapid leaf drying and death. It exhibits high efficiency, low toxicity, and broad-spectrum activity. Its chemical structural formula is as follows:

[0003] Whether in pharmaceuticals or pesticides, the active ingredients (collectively known as technical grade pesticides) are what truly exert their effects. Technical grade pesticides generally cannot be used directly; a stable and high-quality formulation is crucial for maximizing efficacy. For industrial-scale technical grade pesticide production and formulation development, understanding the possible states of the technical grade pesticide is often essential, such as its polymorphs (also called crystal forms) or solvates. This understanding is often decisive. A technical grade pesticide can exist in different crystal forms or in an amorphous form. Different states can lead to different effects and benefits, for example, differences in the following properties: solubility, vapor pressure, dissolution rate, thermal stability, stability during grinding, suspension stability, optical and mechanical properties, hygroscopicity, crystal form and size, flowability, filterability, density, melting point, decomposition stability, color, chemical reactivity, or biological activity.

[0004] Laboratory findings revealed that the compound of formula I, as provided in patent US5084084A, exists in an oily form, exhibiting several problems including low grinding efficiency, low suspension rate, and substandard dilution stability. In particular, oily pesticides typically possess high volatility and persistence, increasing the risk to non-target organisms and posing a potential pollution hazard to the environment, especially groundwater. In terms of application, oily pesticides may require additional equipment and can become viscous and difficult to handle at low temperatures, causing inconvenience during processing. Furthermore, the preparation of formulations may encounter several challenges. First, these substances often have low solubility in water, limiting their application in water-based formulations; second, they may affect the physical stability of the formulation, such as causing stratification or precipitation, especially noticeable with temperature changes. Summary of the Invention

[0005] The purpose of this invention is to solve the technical problems of existing oily Formula I technical materials and formulations, such as storage instability, aggregation after storage, and inability to prepare suitable compositions or formulations. Based on the prior art, this invention provides a new crystal form of Formula I compound, its preparation method, and its uses.

[0006] After studying the technical grade I compound prepared by patent US5084084A, the inventors discovered numerous technical problems in its later processing, and its physical properties and herbicidal activity were unsatisfactory. Through extensive experimental verification, they surprisingly found that, through a suitable method, previously unknown crystalline, stable variants could be obtained while simultaneously improving the purity of the compound I, without exhibiting the oily characteristics of Formula I. These variants are also described below as crystal form B. The method for preparing crystal form B provided by this invention is simple to operate, has low economic cost, produces high-purity products with good crystal stability, and is easily suitable for large-scale industrial production.

[0007] The objective of this invention can be achieved through the following measures:

[0008] A crystal form of compound I, specifically crystal form B, exhibits characteristic absorption peaks at reflection angles 2θ of 5.6±0.2°, 8.9±0.2°, 12.8±0.2°, 13.8±0.2°, 14.5±0.2°, and 17.6±0.2° in its X-ray powder diffraction pattern. Compound I possesses the following chemical structure:

[0009] In one embodiment, the crystal form B of compound I of the present invention has the following single-crystal unit cell parameters: crystal system Monoclinic, space group P21 / c. α=90°, β=101.573(10)°, γ=90°.; volume

[0010] In a preferred embodiment, the X-ray powder diffraction pattern of crystal form B of compound I of the present invention further exhibits characteristic absorption peaks at reflection angle 2θ at 11.3±0.2°, 13.3±0.2°, 15.4±0.2°, 17.9±0.2°, 18.2±0.2°, 19.4±0.2°, 19.5±0.2°, 21.6±0.2°, 22.7±0.2°, 24.1±0.2°, and 25.0±0.2°.

[0011] In a preferred embodiment, the X-ray powder diffraction pattern of crystal form B of compound I of the present invention has characteristic absorption peaks at reflection angles 2θ at 5.6±0.1°, 8.9±0.1°, 11.3±0.1°, 12.8±0.1°, 13.3±0.1°, 13.8±0.1°, 14.5±0.1°, 15.4±0.1°, 17.6±0.1°, 17.9±0.1°, 18.2±0.1°, 19.4±0.1°, 19.5±0.1°, 21.6±0.1°, 22.7±0.1°, 24.1±0.1°, and 25.0±0.1°.

[0012] In a preferred embodiment, the X-ray powder diffraction pattern of crystal form B of compound I of the present invention has characteristic absorption peaks at reflection angles 2θ at 5.6, 8.9, 11.3, 12.8, 13.3, 13.8, 14.5, 15.4, 17.6, 17.9, 18.2, 19.4, 19.5, 20.8, 21.6, 22.7, 23.7, 24.1, 25.0, 25.8, 26.7, and 27.0.

[0013] In a preferred embodiment, crystal form B of compound I of the present invention exhibits the following reflections in X-ray powder diffraction patterns and Cu-K radiation at 25°C, with 2-Theta values ​​of 5.6, 8.9, 11.3, 12.8, 13.3, 13.8, 14.5, 14.9, 15.4, 17.6, 17.9, 18.2, 19.4, 19.5, 20.4, 20.8, 21.6, 21.8, 22.7, 23.3, 23.5, 23.7, 24.1, 24.8, and 25°C. 0, 25.8, 26.7, 27.0, 27.7, 27.9, 28.5, 29.2, 29.6, 29.8, 30.2, 30.8, 31.0, 31.9, 32.7, 32.8, 33.4, 33.9, 34.0, 34.9, 35.1, 35.4, 35.6, 36.6, 37.9, 39.1, 39.6, 40.2, 41.1, 41.6, 42.1, 42.4, 43.0, 43.5, 44.2, 44.4.

[0014] In a preferred embodiment, the X-ray powder diffraction pattern of crystal form B of compound I of the present invention is basically as shown in Figure 1.

[0015] In a preferred embodiment, the DSC spectrum of crystal form B of compound I of the present invention has an endothermic peak at 194–210 °C.

[0016] In a preferred embodiment, the DSC spectrum of crystal form B of compound I of the present invention is shown in Figure 3, which has an endothermic peak at 202.67℃.

[0017] In a preferred embodiment, the compound I of the present invention, crystal form B, has a UV spectrum that is essentially as shown in Figure 4.

[0018] In one embodiment, the infrared spectrum of compound I, crystal form B of the present invention, displays at least the following bands (in cm⁻¹). -1 The peak values ​​(recorded) are: 3313.8, 3064.5, 1700.8, 1517.4, 1380.3, 1166.0, and 1035.5. In a preferred embodiment, crystal form B has the infrared spectrum shown in Figure 5.

[0019] The single-crystal data of this invention can be acquired on a single-crystal X-ray diffractometer (Bruker D8 VENTURE) and performed in accordance with the general rules of JY / T 0588-2020 for the determination of crystal and molecular structure of small molecule compounds by four-circle single-crystal X-ray diffractometer.

[0020] This invention provides a method for preparing crystal form B of compound I, comprising steps S1, S2, or S3:

[0021] S1) Under ultrasonic conditions, solvent is added dropwise to the raw material compound I oily drug until it is dissolved. The solution is then placed in a stable environment for crystallization, with or without filtration. The solvent is selected from methyl acetate, propylene oxide, or a mixture of propylene oxide and water.

[0022] S2) The raw material compound I, in oil form, is dissolved in a solvent under boiling conditions until the solution is clear. The solution is then cooled to crystallize, with or without filtration. The solvent is selected from propylene oxide, methyl acetate, 2-butanone, or acetone.

[0023] S3) After dissolving the oily raw material compound I in a good solvent, the antisolvent is slowly added to precipitate the solid. The solid is collected and dried. The good solvent is selected from methyl acetate or tetrahydrofuran, and the antisolvent is selected from petroleum ether, n-hexane, n-octane or n-heptane.

[0024] This invention discloses a pesticide formulation comprising an effective dose of crystalline form B of compound I. The pesticide formulation herein includes, but is not limited to, solid or liquid formulations such as emulsifiable concentrates, soluble liquids, dispersible liquids, microemulsions, suspension emulsions, water-in-oil emulsions, aqueous suspensions, oil-dispersible suspensions, wettable powders, and water-dispersible granules. In a preferred embodiment, suspension concentrates (SC), wettable powders, or water-dispersible granules (WG) may be used. Excipients used in the formulation include, but are not limited to, dispersants, wetting agents, thickeners, antifreeze agents, fillers, and dispersion media.

[0025] The crystal form B of compound I provided by this invention can be used in the preparation of pesticide herbicides, or in the preparation of formulations for controlling unwanted plants.

[0026] The beneficial effects of this invention are:

[0027] 1. The compound I crystal form B discovered in this invention is a more thermodynamically stable crystal. It can be easily and conveniently stored at room temperature, making it easy for large-scale industrial production and facilitating further processing and application of the product;

[0028] 2. The method of the present invention has low overall energy consumption, the purified mother liquor can be reused multiple times, produces less waste, and has low production cost;

[0029] 3. Compound I, crystal form B, can be prepared into various dosage forms such as dispersible oil suspensions. For the same particle size target, compared to the technical grade I prepared according to patent US5084084A, its grinding time can be reduced by 50%, significantly saving production energy and facilitating processing. The dispersible oil suspension prepared using crystal form B has low viscosity, good dispersion in water, no flocculation, and better efficacy.

[0030] 4. The compound I crystal form B provided by this invention can be conveniently and directly used in agrochemical formulations, especially greener and more environmentally friendly solid formulations, such as suspension concentrates, water-dispersible granules, wettable powders, etc., which significantly improve the herbicidal activity against weeds. Attached Figure Description

[0031] Figure 1 is the X-ray powder diffraction pattern of crystal form B of compound I of the present invention;

[0032] Figure 2 is a single-crystal diffraction pattern of crystal form B of compound I of the present invention;

[0033] Figure 3 is the DSC spectrum of crystal form B of compound I of the present invention;

[0034] Figure 4 is the ultraviolet spectrum of crystal form B of compound I of the present invention;

[0035] Figure 5 is the infrared spectrum of crystal form B of compound I of the present invention;

[0036] Figure 6 is the XRD pattern of the volatilized crystalline powder of compound I, crystal form B of the present invention;

[0037] Figure 7 is the XRD pattern of the crystalline form B of compound I of the present invention, which is a volatile crystallized powder of propylene oxide-water.

[0038] Figure 8 is the XRD pattern of acetone recrystallization (rapid cooling) of compound I, crystal form B, of the present invention.

[0039] Figure 9 is the XRD pattern of compound I, crystal form B, methyl acetate-antisolvent n-octane powder of the present invention;

[0040] Figure 10 is the XRD pattern of n-heptane powder with liquid-phase diffusion of compound I of the present invention, crystal form B tetrahydrofuran;

[0041] Figure 11 is a comparison chart of the test results of compound I of the present invention in crystal form B and various samples.

[0042] Figure 12 is the single-crystal diffraction pattern of compound I, crystal form C;

[0043] Figure 13 is the powder XRD pattern of compound I, crystal form C. Detailed Implementation

[0044] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims.

[0045] The compounds represented by Formula I in this invention may also be referred to simply as Formula I compounds, Compound I, or Formula (I) compounds.

[0046] Example 1: Preparation of crystal form B of compound I

[0047] Preparation of single crystals of compound I crystal form B: Using the oily drug of compound I as raw material, about 30 mg was weighed and methyl acetate was added dropwise under ultrasonic conditions until it reached a clear state. After filtration, the filtered solution was placed in a stable environment for single crystal culture. After 7 days, samples were taken for single crystal testing.

[0048] The X-ray powder diffraction pattern of single crystal of compound I, crystal form B, is shown in Figure 1, and the single crystal diffraction pattern of crystal form B is shown in Figure 2. Specific single crystal data are shown in Table 1.

[0049] Table 1 - Powder XRD data of single crystal samples of crystal type B

[0050] The following reflections are observed in X-ray powder diffraction patterns and Cu-K radiation at 25 °C, denoted as 2-Theta values: 5.6±0.2°, 8.9±0.2°, 12.8±0.2°, 13.8±0.2°, 14.5±0.2°, and 17.6±0.2°.

[0051] More specifically, the B crystal form of compound I exhibits the following reflectances in X-ray powder diffraction patterns and Cu-K radiation at 25 °C, with 2-Theta values ​​of 5.6, 8.9, 11.3, 12.8, 13.3, 13.8, 14.5, 14.9, 15.4, 17.6, 17.9, 18.2, 19.4, 19.5, 20.4, 20.8, 21.6, 21.8, 22.7, 23.3, 23.5, 23.7, 24.1, 24.8, and 25.0. 25.8, 26.7, 27.0, 27.7, 27.9, 28.5, 29.2, 29.6, 29.8, 30.2, 30.8, 31.0, 31.9, 32.7, 32.8, 33.4, 33.9, 34.0, 34.9, 35.1, 35.4, 35.6, 36.6, 37.9, 39.1, 39.6, 40.2, 41.1, 41.6, 42.1, 42.4, 43.0, 43.5, 44.2, 44.4.

[0052] Table 2 and Figure 2 show the single crystal data for crystal form B.

[0053] Example 2: XRD of volatile crystallized B-type powder

[0054] Using compound I (oil-like drug substance) as raw material, the preparation method is as follows: Weigh approximately 30 mg of the drug substance sample, and under ultrasonic conditions, add solvent (propylene oxide) dropwise until a clear solution is reached. For slightly soluble solutions, add up to 10 ml, but in principle, do not exceed 20 ml. Filter the solution and place it in a stable environment for evaporation and crystallization. The XRD pattern of the volatile propylene oxide sample powder is shown in Figure 6.

[0055] Example 3: XRD analysis of A-type powder obtained by evaporation and crystallization with a water-mixed solvent.

[0056] Using the oily active ingredient of compound I as raw material, the preparation method is as follows: Weigh approximately 30 mg of the active ingredient sample, and under ultrasonic conditions, add a mixed solvent (V... 环氧丙烷 V 水 =95:5) until a clear solution is reached; alternatively, if slightly soluble, direct filtration can be performed, and the filtered solution can be placed in a stable environment for volatilization and crystallization. The XRD patterns of the propylene oxide and water volatilization sample powder are shown in Figure 7.

[0057] Example 4: XRD of recrystallized B-type powder (slow cooling)

[0058] Using the oily active ingredient of compound I as raw material, the preparation method is as follows: Weigh approximately 200 mg of the active ingredient sample, use p-acetone as the recrystallization solvent, set the temperature 5°C above its boiling point, add the solvent at the set temperature and continuously stir to promote dissolution until clear, without filtration, then turn off the heating device and transfer it to a room temperature environment for cooling and crystallization.

[0059] The XRD pattern of acetone recrystallized powder under slow cooling is shown in Figure 8.

[0060] Example 5: XRD of B-type powder using anti-solvent method

[0061] Methyl acetate as a solvent can yield crystal form B under the conditions of the antisolvent n-octane.

[0062] Using the oily active ingredient of compound I as raw material, the preparation method is as follows: weigh about 50 mg of the active ingredient sample, add an appropriate volume of good solvent (methyl acetate) to completely dissolve it, and then add the anti-solvent (n-octane) dropwise to allow sufficient solid to precipitate. Stir at room temperature, and collect the wet solid by centrifugation. Then, further dry under reduced pressure (40°C) overnight, and then determine the powder XRD of the dried solid.

[0063] The XRD pattern of n-octane powder, the antisolvent of methyl acetate, is shown in Figure 9.

[0064] Example 6: Liquid-phase diffusion A-type powder XRD

[0065] Toluene, a solvent, can be used to obtain crystal form A under liquid-phase diffusion conditions.

[0066] Using the oily active ingredient of compound I as raw material, the preparation method is as follows: Take an appropriate amount of active ingredient sample, prepare 3.0 ml of saturated tetrahydrofuran solution, add 2.5 ml of the saturated solution to a long test tube, dilute the remaining 0.5 ml with solvent to 1 ml as a buffer solution, add it along the wall of the cup to the test tube, and then slowly add 8 ml of unsuitable solvent (n-heptane), seal and store in a stable environment, and wait for diffusion crystallization.

[0067] The XRD pattern of tetrahydrofuran-liquid-diffusion-n-heptane powder is shown in Figure 10.

[0068] Example 7: Comparison of powder XRD overlay images

[0069] The XRD patterns of the powders in Examples 2-6 above were compared with Figure 1. It was determined that all crystals belonged to the B crystal form.

[0070] The results are shown in Figure 11.

[0071] Example 8, Ultraviolet UV

[0072] The crystal form of compound B of formula I obtained in Example 1 was subjected to ultraviolet (UV) testing, and the results are shown in Figure 4.

[0073] Table 3. Ultraviolet Data of Crystal Form B

[0074] Example 9, Infrared IR

[0075] The crystal form of compound B of formula I obtained in Example 1 was subjected to infrared IR testing, and the results are shown in Figure 5.

[0076] The following bands are shown in the infrared spectrum of B crystal form (in cm⁻¹). -1 (Peak values ​​recorded): 441.6, 477.5, 497.4, 528.3, 549.1, 565.1, 584.6, 612.0, 633.7, 659.4, 687.4, 709.6, 736.1, 759.1, 786.5, 828.5, 880.2, 911.3, 930.7, 1008.8, 1035. 5, 1064.5, 1083.2, 1166.0, 1220.3, 1273.3, 1295.4, 1380.3, 1406.0, 1422.1, 1457.6, 1517.4, 1615.6, 1700.8, 1728.6, 2978.5, 3064.5, 3079.8, 3313.8, 3409.0.

[0077] The infrared spectrum of B crystal form shows at least the following bands (in cm⁻¹). -1 (Peak values ​​recorded): 3313.8, 3064.5, 1700.8, 1517.4, 1380.3, 1166.0, 1035.5.

[0078] Example 10: Differential Scanning Calorimetry (DSC)

[0079] The crystal form of compound B of formula I obtained in Example 1 was subjected to DSC testing, and the results are shown in Figure 3.

[0080] The DSC test temperature of crystal form B sample is 50-250℃, the melting point is 194-210℃, and the temperature of the highest change is 202.67℃.

[0081] Example 11: Preparation and XRD of Crystal Form C

[0082] Weigh approximately 30 mg of the oily raw material sample of compound I. Under ultrasonic conditions, add the solvent 1,4-dioxane dropwise until a clear solution is reached. Filter the solution and place it in a stable environment for evaporation and crystallization to obtain a solvate of 1,4-dioxane, named crystal form C.

[0083] Single-crystal diffraction tests were performed on the C-type sample to obtain its unit cell parameters: crystal system Monoclinic, space group P21 / c; α=90°, β=95.239(2)°, γ=90°.Volume Its single-crystal diffraction pattern is shown in Figure 12.

[0084] Table 4. Single Crystal Data for Crystal Form C

[0085] The X-ray powder diffraction pattern of this crystal form C was determined using a Cu-K radiation diffractometer, and is shown in Figure 13.

[0086] Example 12, Stability of Crystal Form C

[0087] The C sample of the compound is in a good crystallization state.

[0088] Stability tests, conducted at 45℃ and 75% RH, showed that XRD data of crystalline C powder exhibited a transformation phenomenon, gradually transforming into crystalline B. Simultaneously, differential scanning calorimetry (DSC) analysis of the melting point of crystalline C revealed a distinct transformation peak at approximately 161℃.

[0089] In addition, according to the preliminary compilation and reference of the list of carcinogens published by the International Agency for Research on Cancer of the World Health Organization, 1,4-dioxane is listed as a Group 2B carcinogen.

[0090] Example 13, 5% aqueous suspension

[0091] A 5% aqueous suspension was prepared using the oily active ingredient of compound I and the crystal form B of compound I prepared by the method in Example 1, respectively; specific preparation method:

[0092] Weigh all raw materials according to the formula, place all raw materials except xanthan gum in the material tank, and shear them for 2 minutes using a shearing machine. After the raw materials and adjuvants are fully mixed and homogeneous, use a vertical sand mill at 1800 rpm to grind until the particle size D90 < 1 micrometer. Add 2% xanthan gum solution and stir at high speed for 10 minutes until the xanthan gum is fully mixed and swollen to obtain a 5% water suspension.

[0093] Table 5. Formulation of 5% Formula (I) Compound Aqueous Suspension

[0094] Table 6. Comparison of particle size at different grinding times Note: The value of D50 indicates that 50% of the suspension particles are smaller than this value; similarly, D90 and D98 indicate that 90% and 98% of the suspension particles are smaller than this value, respectively.

[0095] The table uses Duncan's new multiple range method in SPSS software for one-way ANOVA. Lowercase letters indicate that the differences in the data in the same column are significant (P<0.05), and uppercase letters indicate that the differences in the data in the same column are extremely significant (P<0.01).

[0096] According to the laser particle size analyzer results, under the same grinding time, the particle size of crystalline form B was consistently smaller. Crystalline form B exhibits superior grinding efficiency compared to the oily active ingredient. For example, after 2 hours of grinding, the D90 of the suspension prepared from crystalline form B reached 2.1134 micrometers, meeting product specifications; while the suspension prepared from the active ingredient required a D90 of 2.7087 micrometers after 4 hours of grinding to meet product specifications. This indicates that under the same grinding conditions, crystalline form B is easier to grind and has higher grinding efficiency. Furthermore, crystalline form B is more sensitive to grinding time, especially after prolonged grinding (4 hours), showing significant differences in its D50, D90, and D98. In actual large-scale production, improved grinding efficiency leads to energy conservation and reduced consumption, thereby lowering production costs. This suggests that crystalline form B has higher market value.

[0097] The results of stability tests on the technical grade and formulations of different crystal forms after two weeks of storage at 40°C, 54°C and 70°C are shown in Table 7.

[0098] Table 7. Stability of different crystalline forms of active pharmaceutical ingredients and formulations under different temperature conditions.

[0099] As shown in the table above, the decomposition rate of compound B (formula I) is no different from that of the original drug under 40°C heat storage. However, differences in decomposition rates are observed at 54°C and 70°C, with a highly significant difference at 70°C. The results of heat storage of suspensions prepared from the two original drugs under different temperature conditions also show significant differences, with the differences becoming more pronounced as the temperature increases. In the industry, two weeks of heat storage at 54°C typically represents two years of storage at room temperature. Therefore, the table shows that the stability of the B crystal form is significantly higher than that of the original drug. The 70°C experiment was conducted to simulate the stability of goods passing through the equator in a container. The data indicates that the higher the temperature, the higher the decomposition rate of the original drug. The B crystal form is more stable, has a longer shelf life, and shows great application potential.

[0100] Example 14: Dispersible oil suspension

[0101] Dispersible oil suspensions were prepared using the oily active ingredient of compound I and the crystal form B of compound I prepared by the method of Example 1, respectively.

[0102] Table 8: Formulations of 5% Formula (I) Compound Dispersible Oil Suspension

[0103] Specific preparation method: Weigh each raw material according to the formula and place it in the material tank. Stir for 3 minutes using a high shear dispersion emulsifier. After the original drug, adjuvants and solvent are fully mixed, use a vertical sand mill at 1800 rpm to grind until the particle size D90 < 3 micrometers to obtain a 5% dispersible oil suspension.

[0104] Table 9. Comparison of particle size at different grinding times

[0105] Comparison of grinding efficiency of dispersible oil suspensions of different forms of compound I: The D50, D90 and D98 of suspensions prepared from different forms of compound I showed significant differences; compared with the grinding particle size of water suspensions, oil suspensions were more difficult to grind, but the B crystal form still showed a certain grinding advantage over the original drug.

[0106] Example 15: Wettable Powder

[0107] Cocoa wet powders were prepared using the oily technical grade of compound I and the crystal form B of compound I prepared by the method of Example 1, respectively.

[0108] Table 10. Formulation of 10% Formula I compound wettable powder

[0109] Specific preparation method: Weigh each raw material according to the formula and place them in an air jet mill. After pulverization, a 10% wettable powder is obtained.

[0110] Table 11. Test Results of 10% Wettable Powder Product Indicators

[0111] As can be seen from the table above, under the same adjuvant system, the suspension rate of the wettable powder prepared by crystal form B is 94.3%, and 94.1% after two weeks of heat storage at 54 degrees Celsius; while the suspension rate of the powder prepared by the technical grade is 89.4%, and 87.8% after heat storage. The higher suspension rate of the wettable powder prepared by crystal form B indicates that crystal form B is easier to pulverize, thereby increasing the suspension rate and achieving energy saving and consumption reduction during large-scale production.

[0112] Example 16, Water-dispersible granules

[0113] Cocoa wet powders were prepared using the oily technical grade of compound I and the crystal form B of compound I prepared by the method of Example 1, respectively.

[0114] Table 12. Formulation of 10% Formula I compound in water-dispersible granules

[0115] Specific preparation method: Weigh each raw material according to the formula and place it in an air jet mill. After grinding, add water and knead, extrude and granulate, dry and sieve in sequence to obtain 10% water-dispersible granules.

[0116] Table 13. Test Results of Product Indicators for 10% Water Dispersible Granules

[0117] As can be seen from the table above, under the same adjuvant system, the suspension rate of water-dispersible granules prepared by crystal form B is 96.4%, and 96.3% after two weeks of heat storage at 54 degrees Celsius; while the suspension rate of the original drug is 89.3%, and 89.1% after heat storage. The higher suspension rate of water-dispersible granules prepared by crystal form B indicates that crystal form B is easier to pulverize, thereby increasing the suspension rate and achieving energy saving and consumption reduction during large-scale production.

[0118] Example 17, Bioassay

[0119] The tested weeds were: goosegrass and crabgrass.

[0120] Test reagents: The following dosage forms (D90<3) were prepared according to the methods of Examples 14 and 15: 5% crystal form B dispersible oil suspension, 5% oily dispersible oil suspension, 10% crystal form B wettable powder and 10% oily wettable powder.

[0121] Experimental Method: Foliar spraying (NY / T 1155.4-2006) was used. A measured amount of soil was filled to 3 / 4 of the height of 11cm and diameter pots. The test targets (goosegrass and crabgrass) were sown on the soil surface, covered with about 1cm of fine soil, and then placed in a greenhouse for cultivation. Foliar spraying was performed when the weeds had 4-5 leaves. Different dosage gradients of the pesticides were set up. The dosages of the four pesticides were 30g.ai / ha, 22.5g.ai / ha, 15g.ai / ha, 11.25g.ai / ha, 7.5g.ai / ha, and 3.75g.ai / ha, respectively. Each treatment was replicated 4 times, with a control treatment without pesticides. After treatment, the test materials were placed in a greenhouse for cultivation, and the growth of the weeds was observed regularly.

[0122] Investigation method: Visually observe the damage symptoms and growth inhibition of the target after the experimental treatment. Weigh the fresh weight of the aboveground parts 21 days after the application of the pesticide and calculate the fresh weight inhibition rate.

[0123] Fresh weight inhibition rate (%) = (Control fresh weight - Treatment fresh weight) / Control fresh weight × 100%

[0124] Data analysis: The logarithmic value of the pesticide dosage and the probability value of the inhibition rate of weed fresh weight were regressed using DPS statistical software. The correlation coefficient, GR50, and GR95 were calculated, and the results are listed in Table 14.

[0125] Table 14. Results of the control efficacy of crystal form B and oily compounds against goosegrass and crabgrass.

[0126] As shown in Table 14, regression analysis results for all formulations showed a significant linear correlation (correlation coefficient ≥ 0.96) between pesticide dosage and weed growth inhibition rate, indicating the good reliability of the experimental data. Notably, the 5% crystalline B oil suspension had the lowest GR50 and GR95 values ​​against *Eleusine indica* and *Digitaria sanguinalis*, significantly better than other formulations, indicating the highest herbicidal activity. In contrast, the oil-based formulations (5% oil-based suspension and 10% oil-based wettable powder) had significantly higher GR50 and GR95 values ​​than the crystalline B formulation, indicating a significantly reduced control effect against *Eleusine indica* and *Digitaria sanguinalis*. Therefore, the experimental data in this embodiment clearly confirm that the crystalline B formulation of Formula I has a significant advantage in herbicidal activity compared to the oil-based formulation.

[0127] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications may still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions may be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A crystal form of compound I, characterized in that... It is crystal form B of compound I, and its X-ray powder diffraction pattern shows characteristic absorption peaks at reflection angles 2θ of 5.6±0.2°, 8.9±0.2°, 12.8±0.2°, 13.8±0.2°, 14.5±0.2°, and 17.6±0.2°. Compound I has the following chemical structure:

2. The crystal form according to claim 1, characterized in that... The single-crystal unit cell parameters of crystal form B are: crystal system Monoclinic, space group P21 / c; α=90°, β=101.573(10)°, γ=90°.; volume 3. The crystal form according to claim 1, characterized in that... The X-ray powder diffraction pattern shows characteristic absorption peaks at reflection angles 2θ at 11.3±0.2°, 13.3±0.2°, 15.4±0.2°, 17.9±0.2°, 18.2±0.2°, 19.4±0.2°, 19.5±0.2°, 21.6±0.2°, 22.7±0.2°, 24.1±0.2°, and 25.0±0.2°.

4. The crystal form according to claim 1, characterized in that... The X-ray powder diffraction pattern shows characteristic absorption peaks at reflection angles 2θ at 5.6, 8.9, 11.3, 12.8, 13.3, 13.8, 14.5, 15.4, 17.6, 17.9, 18.2, 19.4, 19.5, 20.8, 21.6, 22.7, 23.7, 24.1, 25.0, 25.8, 26.7, and 27.

0.

5. The crystal form according to claim 1, characterized in that... Its X-ray powder diffraction pattern is basically shown in Figure 1.

6. The crystal form according to claim 1, characterized in that... The DSC spectrum of crystal form B shows an endothermic peak in the range of 194–210 °C; the infrared spectrum of crystal form B shows at least the following bands (in cm⁻¹). -1 (Peak values ​​recorded): 3313.8, 3064.5, 1700.8, 1517.4, 1380.3, 1166.0, 1035.

5.

7. The crystal form according to claim 6, characterized in that... The DSC spectrum of crystal form B is shown in Figure 3, which shows an endothermic peak at 202.67℃. Alternatively, crystal form B has a UV spectrum as shown in Figure 4, or an infrared spectrum as shown in Figure 5.

8. A method for preparing the crystal form according to claim 1, characterized in that... Including steps S1, S2, or S3: S1) Under ultrasonic conditions, solvent is added dropwise to the raw material compound I oily drug until it is dissolved. The solution is then placed in a stable environment for crystallization, with or without filtration. The solvent is selected from methyl acetate, propylene oxide, or a propylene oxide-water mixture. S2) The raw material compound I, in oil form, is dissolved in a solvent under boiling conditions until the solution is clear. The solution is then cooled to crystallize, with or without filtration. The solvent is selected from propylene oxide, methyl acetate, 2-butanone, or acetone. S3) After dissolving the oily raw material compound I in a good solvent, the antisolvent is slowly added to precipitate the solid. The solid is collected and dried. The good solvent is selected from methyl acetate or tetrahydrofuran, and the antisolvent is selected from petroleum ether, n-hexane, n-octane or n-heptane.

9. A pesticide formulation, characterized in that... It contains an effective dose of crystal form B of compound I.

10. The pesticide formulation according to claim 9, characterized in that... The formulation includes aqueous suspensions, dispersible oil suspensions, wettable powders, or water-dispersible granules.

11. Use of crystal form B of compound I according to claim 1 in the preparation of formulations for controlling unwanted plants.

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