Polymorph a of benzoxazine compound, and preparation method therefor and use thereof

Abstract

A polymorph A of a benzoxazine compound, and a preparation method therefor and the use thereof. The polymorph is polymorph A of compound I. In the X-ray powder diffraction pattern thereof, the 2θ diffraction angle has characteristic absorption peaks at 7.0±0.2°, 10.5±0.2°, 12.0±0.2°, 12.6±0.2°, 16.5±0.2° and 20.2±0.2°. The polymorph A of the compound of formula I is a thermodynamically more stable crystal, which can be simply and conveniently stored at room temperature, is easy for industrial large-scale production, and facilitates further processing and application of the product.

Description

A crystalline form A of a benzoxazine compound, its preparation method and application Technical Field

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

[0002] The 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 (Formula I), its preparation method, 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 Formula I technical grade pesticide prepared according to patent US5084084A exists as an oily substance. The following problems arise during formulation processing: First, the technical grade pesticide exists in oily form, resulting in high viscosity. This makes it difficult to effectively reduce particle size using conventional methods during preparation, thus affecting the uniformity and efficacy of the final product. Second, the suspension rate is low: oily technical grade pesticides are generally not easily dispersed or suspended in water, which can lead to the active ingredient settling easily during application, reducing the effective concentration and affecting the control effect. Third, dilution stability is inadequate: when the technical grade pesticide is diluted, stratification and precipitation may occur. This means that in practical applications, the active ingredient of the pesticide may not be evenly distributed in the target area, reducing the pesticide's activity and safety. 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 using 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, using a suitable method, it was possible to improve the purity of the Formula I compound while simultaneously obtaining previously unknown crystalline, stable variants that did not exhibit the oily characteristics of Formula I. These variants are also described below as crystal form A. The preparation method provided by this invention is simple to operate, has low economic cost, produces high-purity products with good crystal stability, and is easier 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 A, exhibits characteristic absorption peaks at reflection angles 2θ of 7.0±0.2°, 10.5±0.2°, 12.0±0.2°, 12.6±0.2°, 16.5±0.2°, and 20.2±0.2° in its X-ray powder diffraction pattern. Compound I possesses the following chemical structure:

[0009] In a preferred embodiment, the X-ray powder diffraction pattern of crystal form A of compound I further exhibits characteristic absorption peaks at reflection angles 2θ at 14.0±0.2°, 18.1±0.2°, 19.3±0.2°, 21.0±0.2°, 22.5±0.2°, 23.9±0.2°, 25.0±0.2°, 26.6±0.2°, and 27.3±0.2°.

[0010] In one embodiment, the X-ray powder diffraction pattern of crystal form A of compound I exhibits characteristic absorption peaks at reflection angles 2θ of 7.0±0.1°, 10.5±0.1°, 12.0±0.1°, 12.6±0.1°, 16.5±0.1°, and 20.2±0.1°, or further, it exhibits characteristic absorption peaks at 14.0±0.1°, 18.1±0.1°, 19.3±0.1°, 21.0±0.1°, 22.5±0.1°, 23.9±0.1°, 25.0±0.1°, 26.6±0.1°, and 27.3±0.1°.

[0011] In a preferred embodiment, the X-ray powder diffraction pattern of compound I crystal form A has characteristic absorption peaks at reflection angles 2θ of 7.0, 10.5, 12.0, 12.6, 16.5, and 20.2°, or further, it has characteristic absorption peaks at 14.0, 18.1, 19.3, 21.0, 22.5, 23.9, 25.0, 26.6, and 27.3°.

[0012] In a more preferred embodiment, the X-ray powder diffraction pattern of crystal form A of compound I has characteristic absorption peaks at reflection angles 2θ at 7.020, 10.498, 12.022, 12.637, 14.061, 16.521, 18.103, 19.319, 20.182, 21.082, 22.521, 23.918, 25.058, 26.640, and 27.338.

[0013] In a preferred embodiment, the X-ray powder diffraction pattern of crystal form A of compound I is basically as shown in Figure 1.

[0014] In a preferred embodiment, the single-crystal unit cell parameters of compound I crystal form A are Monoclinic crystal system and space group P21 / n; α=90°, β=95.139(2)°, γ=90°.; volume

[0015] The DSC spectrum of compound I, crystal form A of the present invention, shows an endothermic peak at 194–208 °C.

[0016] In a preferred embodiment, the DSC spectrum of crystal form A of compound I of the present invention is shown in Figure 12, which has an endothermic peak at 201.61℃.

[0017] The compound I of this invention, crystal form A, has a basic ultraviolet spectrum as shown in Figure 10.

[0018] The compound I of the present invention, crystal form A, has an infrared spectrum as shown in Figure 11.

[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 A of compound I, including the step of treating the crude oily technical product of compound I with various organic solvents.

[0021] This invention discloses a method for preparing crystal form A of compound I, which includes steps S1, S2, or S3:

[0022] S1) Under ultrasonic conditions, solvent is added dropwise to the raw material compound I oily drug until it is dissolved. The solution is placed in a stable environment for crystallization, with or without filtration. The solvent is selected from methyl tert-butyl ether, acetone, acetonitrile, N,N-dimethylformamide, o-xylene, toluene or a methanol-water mixture.

[0023] 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 methanol, isopropanol, xylene, p-ethylbenzene, or ethyl acetate.

[0024] 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 1,2-dichloroethane or toluene, and the antisolvent is selected from petroleum ether, n-hexane, n-octane, n-pentane or n-heptane.

[0025] This invention discloses a pesticide formulation comprising an effective dose of crystalline form A 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.

[0026] The crystal form A 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.

[0027] The beneficial effects of this invention are:

[0028] 1. The crystal form A of the compound of formula I discovered in this invention is a more thermodynamically stable crystal. It can be easily and conveniently stored at room temperature, making it easy to mass-produce in the industrial sector and facilitating further processing and application of the product.

[0029] 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;

[0030] 3. Compound I, crystal form A, can be prepared into various dosage forms, including dispersible oil suspensions. For the same particle size target, compared to the technical grade I prepared according to patent US5084084A, the grinding time is reduced by 50%, significantly saving production energy and facilitating processing. The dispersible oil suspension prepared using crystal form A has low viscosity, good dispersion in water, no flocculation, and better efficacy.

[0031] 4. The compound I crystal form A 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

[0032] Figure 1 is the X-ray powder diffraction pattern of crystal form A of compound I of the present invention;

[0033] Figure 2 is the XRD pattern of toluene volatilized crystal powder of compound I, crystal form A;

[0034] Figure 3 is the XRD pattern of methanol-water volatile crystallization powder of compound I, crystal form A;

[0035] Figure 4 shows the XRD pattern of xylene recrystallized (slowly cooled) compound I crystal form A.

[0036] Figure 5 is the powder XRD pattern of ethylbenzene recrystallization (rapid) of compound I crystal form A;

[0037] Figure 6 is the XRD pattern of n-octane powder, the antisolvent of compound I (crystal form A);

[0038] Figure 7 is the XRD pattern of toluene-n-pentane gas-phase diffusion n-octane powder of compound I crystal form A;

[0039] Figure 8 is the XRD pattern of toluene-n-heptane liquid-phase diffusion n-octane powder of compound I crystal form A;

[0040] Figure 9 shows a comparison between the crystal form A of compound I and the test images of various samples;

[0041] Figure 10 shows the UV spectra of crystal form A of compound I;

[0042] Figure 11 is the infrared test pattern of crystal form A of compound I;

[0043] Figure 12 shows the DSC test results for crystal form A of compound I;

[0044] Figure 13 is the single-crystal diffraction pattern of compound I, crystal form A;

[0045] Figure 14 is the single-crystal diffraction pattern of compound I, crystal form C;

[0046] Figure 15 shows the powder XRD pattern of compound I, crystal form C. Detailed Implementation

[0047] 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.

[0048] 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.

[0049] Example 1: Preparation of Crystal Form A of Compound I

[0050] Using the oily active ingredient of compound I as raw material, about 30 mg was weighed and added dropwise with o-xylene as solvent under ultrasonic conditions until it was dissolved. After filtration, the filtered solution was placed in a stable environment for single crystal culture. After 2 days, the crystal form was sampled and single crystal test was performed.

[0051] The X-ray powder diffraction pattern of compound I, crystal form A, was determined using a Cu-K radiation diffractometer, and is shown in Figure 1.

[0052] In Figure 1, the specific single-crystal data are shown in Table 1.

[0053] Table 1 and Figure 1 show the powder XRD data for single crystal A.

[0054] The following 15 characteristic peaks were selected as the main peaks in the XRD data: 7.020, 10.498, 12.022, 12.637, 14.061, 16.521, 18.103, 19.319, 20.182, 21.082, 22.521, 23.918, 25.058, 26.640, and 27.338.

[0055] Single-crystal X-ray diffraction measurements were performed on crystal form A of compound I, and its single-crystal diffraction pattern is shown in Figure 13. The unit cell parameters of crystal form A are: crystal system Monoclinic, space group P21 / n; α=90°, β=95.139(2)°, γ=90°.; volume

[0056] Table 2 and Figure 13 show the single crystal data for crystal form A.

[0057] Example 2: XRD of volatile crystallized A-type powder

[0058] Using compound I oily drug substance as raw material and toluene as solvent, the preparation method is as follows: weigh about 30 mg of the drug substance sample, add 20 ml of solvent under ultrasonic conditions, and filter the solution. Place the filtered solution in a stable environment for volatilization and crystallization.

[0059] XRD patterns of solid powder were determined, and the XRD patterns of toluene volatile sample powder were obtained. The results are shown in Figure 2.

[0060] Example 3: XRD analysis of A-type powder obtained by evaporation and crystallization with a water-mixed solvent.

[0061] A crystal form sample can be obtained by adding 5% water to the solvent methanol and allowing it to evaporate at room temperature.

[0062] 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... 甲醇 V 水 =95:5) until a clear solution is reached; or if slightly soluble, directly filter the solution and place the filtered solution in a stable environment for volatilization and crystallization.

[0063] XRD analysis of solid powder was performed to obtain the XRD pattern of methanol-water volatile sample powder, and the results are shown in Figure 3.

[0064] Example 4: XRD of recrystallized A-type powder (slow cooling)

[0065] The solvent p-xylene can be used to obtain crystal form A sample under slow cooling conditions during recrystallization.

[0066] Using the oily active ingredient of compound I as raw material, the preparation method is as follows: Weigh about 200 mg of the active ingredient sample, use p-xylene as the recrystallization solvent, set the temperature 5°C above its boiling point, add the solvent at the set temperature and stir continuously to promote dissolution until it is clear. No filtration is required. Then turn off the heating device and transfer it to a room temperature environment for cooling and crystallization.

[0067] XRD patterns of the solid powder were determined, and the XRD patterns of the p-xylene recrystallized powder under slow cooling were obtained. The results are shown in Figure 4.

[0068] Example 5: XRD of recrystallized A-type powder (rapid cooling)

[0069] Solvent-based ethylbenzene can be used to obtain crystal form A sample under rapid cooling conditions during recrystallization.

[0070] Using the oily active ingredient of compound I as raw material, the preparation method is as follows: Weigh about 200 mg of the active ingredient sample, use p-ethylbenzene as the recrystallization solvent, set the temperature 5°C higher than its boiling point, add the solvent at the set temperature and stir continuously to promote dissolution until it is clear, then add 10% more solvent, no filtration is required, then turn off the heating device and transfer it to an ice-water bath for cooling and crystallization.

[0071] XRD patterns of solid powder were determined, and the XRD patterns of p-ethylbenzene recrystallized under rapid cooling were obtained. The results are shown in Figure 5.

[0072] Example 6: XRD of A-type powder using antisolvent method

[0073] The solvent 1,2-dichloroethane, under the condition of the antisolvent n-octane, can yield crystal form A sample.

[0074] 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 (1,2-dichloroethane) to completely dissolve it, and then add the antisolvent (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.

[0075] The XRD pattern of 1,2-dichloroethane antisolvent n-octane powder was obtained, and the results are shown in Figure 6.

[0076] Example 7: XRD of vapor-phase diffusion A-type powder

[0077] Toluene, a solvent, can be used to obtain crystal form A under gas-phase diffusion conditions.

[0078] Using the oily active ingredient of compound I as raw material, the preparation method is as follows: Weigh approximately 100 mg of the active ingredient sample and add it to a 4 mL glass vial. Add an appropriate volume of good solvent (toluene) to completely dissolve the sample. Add an appropriate amount of antisolvent (n-pentane) to a 40 mL bottle. Place the open 4 mL glass vial containing the clear solution into the 40 mL bottle, seal the 40 mL bottle, and place it in a fume hood. After solid precipitation, collect the solid and dry it under reduced pressure (40 °C) overnight. Then, determine the XRD pattern of the dried solid powder.

[0079] The XRD pattern of toluene-gas phase diffusion-n-pentane powder was obtained, and the results are shown in Figure 7.

[0080] Example 8: Liquid-phase diffusion A-type powder XRD

[0081] Toluene, a solvent, can be used to obtain crystal form A under liquid-phase diffusion conditions.

[0082] Using the oily active ingredient of compound I as raw material, the preparation method is as follows: Take an appropriate amount of the active ingredient sample, prepare 3.0 ml of saturated toluene 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.

[0083] XRD patterns of solid powder were determined, and the XRD patterns of toluene-liquid-diffusion-n-heptane powder were obtained. The results are shown in Figure 8.

[0084] Example 9: Comparison of powder XRD overlay images

[0085] The XRD patterns of the powders in Examples 2-8 above were compared with Figure 1. It was determined that all crystals belonged to the A crystal form.

[0086] The results are shown in Figure 9.

[0087] Example 10, Ultraviolet UV

[0088] The crystal form of compound A of formula I obtained in Example 1 was subjected to ultraviolet (UV) testing, and the results are shown in Figure 10.

[0089] Table 3. Ultraviolet Data Table for Crystal Form A

[0090] Example 11, Infrared IR

[0091] The crystal form of compound A of formula I obtained in Example 1 was subjected to infrared IR testing, and the results are shown in Figure 11.

[0092] Example 12: Differential Scanner (DSC)

[0093] The crystal form of compound A of formula I obtained in Example 1 was subjected to DSC testing, and the results are shown in Figure 12.

[0094] The DSC test temperature for crystal form A sample ranged from 50 to 250℃, with the highest temperature variation being 201.61℃.

[0095] Example 13: Preparation and XRD of Crystal Form C

[0096] 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.

[0097] 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 14.

[0098] Table 4. Single Crystal Data for Crystal Form C

[0099] The X-ray powder diffraction pattern of this crystal form C was determined using a Cu-K radiation diffractometer, and is shown in Figure 15.

[0100] Example 14, Stability of Crystal Form C

[0101] The C sample of the compound is in a good crystallization state.

[0102] Stability tests, conducted at 45℃ and 75% RH, revealed XRD patterns in crystalline C powder, indicating a crystal transformation phenomenon. Furthermore, differential scanning calorimetry (DSC) analysis of the melting point of crystalline C showed a distinct crystal transformation peak at approximately 161℃.

[0103] 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.

[0104] Example 15, 5% aqueous suspension

[0105] A 5% aqueous suspension was prepared using the oily active ingredient of compound I and crystal form A of compound I prepared by the method in Example 1, respectively; specific preparation method:

[0106] Weigh each raw material according to the following formula. Place all raw materials except xanthan gum in a material tank and shear them for 2 minutes using a shearing machine. After the raw material 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.

[0107] Table 5. Formulation of 5% Formula I compound aqueous suspension

[0108] Table 6. Comparison of particle size at different grinding times

[0109] 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.

[0110] 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).

[0111] According to the laser particle size analyzer results, under the same grinding time, the particle size of crystal form A was consistently smaller. Crystal form A exhibited better grinding efficiency than the oily active ingredient. For example, after 2 hours of grinding, the D90 of the suspension prepared from crystal form A reached 1.8973 micrometers, meeting the product specifications; while the suspension prepared from the active ingredient required a D90 of 2.7087 micrometers after 4 hours of grinding to meet the product specifications. This indicates that under the same grinding conditions, crystal form A is easier to grind and has higher grinding efficiency. Furthermore, crystal form A is more sensitive to grinding time, especially after prolonged grinding (4 hours), showing significant differences in its D50, D90, and D98.

[0112] In actual large-scale production, improved grinding efficiency leads to energy conservation and reduced consumption, thereby lowering production costs. This indicates that crystal form A has a higher market value.

[0113] The stability test results of different forms of Formula I compounds and formulations after storage at 40°C, 54°C and 70°C for two weeks are shown in Table 7:

[0114] Table 7. Stability of different form I compounds and formulations under different temperature conditions

[0115] As shown in the table above, there was no significant difference in the decomposition rate of compound A (crystal form) and the oily technical grade at 40°C. However, differences in the decomposition rates of crystal form A and the oily technical grade were observed at 54°C and 70°C, with the difference being particularly significant at 70°C. The results of heat storage of suspensions prepared from the two forms of compound I at different temperatures also showed significant differences, with the differences becoming more pronounced as the temperature increased.

[0116] In the industry, two weeks of heat storage at 54 degrees Celsius typically represents two years of storage at room temperature. Therefore, as shown in the table above, the stability of crystal form A is significantly improved compared to the oily form. The 70-degree Celsius experiment was conducted to simulate the stability of goods passing the equator in a container. Data indicates that the higher the temperature, the higher the decomposition rate of the oily form. Crystal form A is more stable, has a longer shelf life, and shows great application potential.

[0117] Example 16: Dispersible oil suspension

[0118] Dispersible oil suspensions were prepared using the oily active ingredient of compound I and the crystal form A of compound I prepared by the method of Example 1, respectively.

[0119] Table 8. Formulation of 5% Formula I compound dispersible oil suspension

[0120] 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.

[0121] Table 9. Comparison of particle size at different grinding times

[0122] The results of the grinding efficiency comparison of dispersible oil suspensions of different forms of Formula I compounds showed that the D50, D90 and D98 of the suspensions prepared from different forms of Formula I compounds all showed significant differences. Compared with the grinding particle size of water suspensions, oil suspensions were more difficult to grind, but the A crystal form still showed a certain grinding advantage over the oily active ingredient.

[0123] Example 17: Wettable Powder

[0124] Wettable powders were prepared using the oily active ingredient of compound I and the crystal form A of compound I prepared by the method of Example 1, respectively.

[0125] Table 10. Formulation of 10% Formula I compound wettable powder

[0126] 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.

[0127] Table 11. Test Results of 10% Wettable Powder Product Indicators

[0128] As can be seen from the table above, under the same adjuvant system, the suspension rate of the wettable powder prepared by crystal form A is 95.6%, and 95.4% after two weeks of heat storage at 54 degrees Celsius; while the suspension rate of the oily active ingredient is 89.4%, and 87.8% after heat storage. The higher suspension rate of the wettable powder prepared by crystal form A indicates that crystal form A is easier to pulverize, thereby increasing the suspension rate and achieving energy saving and consumption reduction during large-scale production.

[0129] Example 18, Water-dispersible granules

[0130] Water-dispersible granules were prepared using the oily active ingredient of compound I and the crystal form A of compound I prepared by the method of Example 1, respectively.

[0131] Table 12. Formulation of 10% Formula I compound in water-dispersible granules

[0132] 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.

[0133] Table 13. Test Results of Product Indicators for 10% Water Dispersible Granules

[0134] As can be seen from the table above, under the same adjuvant system, the suspension rate of water-dispersible granules prepared by crystal form A is 97.5%, and 97.3% after two weeks of heat storage at 54 degrees Celsius; while the suspension rate of the oily active ingredient is 89.3%, and 89.1% after heat storage. The higher suspension rate of water-dispersible granules prepared by crystal form A indicates that crystal form A is easier to pulverize, thereby increasing the suspension rate and achieving energy saving and consumption reduction during large-scale production.

[0135] Example 19, Bioassay

[0136] The tested weeds were: goosegrass and crabgrass.

[0137] Test reagents: The following dosage forms (D90<3) were prepared according to the methods of Examples 16 and 17: 5% crystal form A dispersible oil suspension, 5% oily dispersible oil suspension, 10% crystal form A wettable powder and 10% oily wettable powder.

[0138] 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.

[0139] 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.

[0140] Fresh weight inhibition rate (%) = (Control fresh weight - Treatment fresh weight) / Control fresh weight × 100%

[0141] Data analysis: DPS statistical software was used to analyze the data based on the dosage of the pesticide and the inhibition rate of fresh weight of weeds, and the linear regression equation, correlation coefficient, GR50 and GR95 values ​​were obtained. The results are shown in Table 14.

[0142] Table 14. Control efficacy of crystal form A and oily compounds against goosegrass and crabgrass.

[0143] 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 A oil suspension concentrate exhibited the lowest GR50 and GR95 values ​​against *Eleusine indica* and *Digitaria sanguinalis*, significantly superior to other formulations, indicating the highest herbicidal activity. In contrast, the oil-based formulations (5% oil-based suspension concentrate and 10% oil-based wettable powder) showed significantly higher GR50 and GR95 values ​​than the crystalline formulations, indicating a significantly reduced control effect against *Eleusine indica* and *Digitaria sanguinalis*. Therefore, the experimental data in this embodiment clearly confirm that the crystalline A formulation of Formula I has a significant advantage in herbicidal activity compared to the oil-based formulation.

[0144] 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 A of compound I, and its X-ray powder diffraction pattern shows characteristic absorption peaks at reflection angles 2θ of 7.0±0.2°, 10.5±0.2°, 12.0±0.2°, 12.6±0.2°, 16.5±0.2°, and 20.2±0.2°; compound I has the following chemical structure:

2. The crystal form according to claim 1, characterized in that... The X-ray powder diffraction pattern shows characteristic absorption peaks at reflection angles 2θ of 14.0±0.2°, 18.1±0.2°, 19.3±0.2°, 21.0±0.2°, 22.5±0.2°, 23.9±0.2°, 25.0±0.2°, 26.6±0.2°, and 27.3±0.2°.

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 7.020, 10.498, 12.022, 12.637, 14.061, 16.521, 18.103, 19.319, 20.182, 21.082, 22.521, 23.918, 25.058, 26.640, and 27.

338.

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

5. The crystal form according to claim 1, characterized in that... Its single-crystal unit cell parameters are: crystal system Monoclinic, space group P21 / n; α=90°, β=95.139(2)°, γ=90°; volume 6. The crystal form according to claim 1, characterized in that... The DSC spectrum of crystal form A shows an endothermic peak in the range of 194–208 °C.

7. The crystal form according to claim 5, characterized in that... The DSC spectrum of crystal form A is shown in Figure 12, with an endothermic peak at 201.61℃.

8. The crystal form according to claim 1, characterized in that... Crystal form A has a basic ultraviolet spectrum as shown in Figure 10 or a basic infrared spectrum as shown in Figure 11.

9. 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 placed in a stable environment for crystallization, with or without filtration. The solvent is selected from methyl tert-butyl ether, acetone, acetonitrile, N,N-dimethylformamide, o-xylene, toluene or a methanol-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 methanol, isopropanol, xylene, p-ethylbenzene, or ethyl acetate. 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 1,2-dichloroethane or toluene, and the antisolvent is selected from petroleum ether, n-hexane, n-octane, n-pentane or n-heptane.

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

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

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

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