Crystal form of bicyclopyrone as well as preparation method and application thereof

Abstract

The invention relates to the technical field of pesticide crystal form molecules, and discloses a bicyclopyrone crystal form as well as a preparation method and application thereof. The bicyclopyrone crystal form has characteristic peaks at 6.77 + / -0.2 degrees, 13.60 + / -0.2 degrees, 20.46 + / -0.2 degrees, 21.98 + / -0.2 degrees, 23.10 + / -0.2 degrees and 23.50 + / -0.2 degrees in an X-ray powder diffraction pattern represented by 2 theta measured by Cu-K alpha radiation at 25 DEG C. The bicyclopyrone crystal form provided by the invention is greatly improved in the aspects of hygroscopicity, caking resistance and the like. The bicyclopyrone crystal form is simple in preparation process, the problems that in the prior art, a purified product is high in impurity content and poor in purification effect are solved, and the obtained crystal is regular in crystal form and uniform in particle size, has definite crystallographic main parameters and exact atomic space position and is suitable for large-scale application and popularization.

Description

Technical Field

[0001] This invention relates to the field of pesticide crystal molecular technology, specifically to a flupyradifon crystal form, its preparation method, and its uses. Background Technology

[0002] Bicyclopyrone, chemical name (1RS,5SR)-4-hydroxy-3-{2-[(2-methoxyethoxy)methyl]-6-(trifluoromethyl)-3-pyridylcarbonyl}bicyclo[3.2.1]oct-3-en-2-one, CAS number 352010-68-5, molecular formula C 19 H 20 F3NO5, with a relative molecular mass of 399.36, has the following structure:

[0003]

[0004] Flupyridaben is a novel broad-spectrum insecticide and acaricide developed by Syngenta. It belongs to the class of p-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors and has a unique mechanism of action. As a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, it inhibits the biosynthesis of carotenoids, causing whitening symptoms in plant meristems and ultimately leading to plant death. It has a highly effective control effect on broadleaf weeds and grass weeds (such as barnyard grass, crabgrass, and velvetleaf) in cornfields and has high crop safety, making it one of the important tools for modern farmland weed management.

[0005] In 2015, flupyrazole was the first herbicide to be registered and marketed in the United States by the EPA. Its four-component compound formulation, Acuron (flupyrazole + nifedipine + metolachlor + atrazine), was launched in the US market for use in corn and sugarcane fields. Acuron has three different mechanisms of action and can control more than 70 annual weeds in corn fields, including giant ragweed, ragweed, horsetail, kochia, long-awned amaranth, and resistant weeds. In recent years, Syngenta has been promoting and marketing flupyrazole formulations globally. It is now registered and marketed in the United States, Canada, Argentina, Uruguay, Australia, and other countries, and its application has expanded from corn to sugarcane, barley, wheat, genetically modified corn, and turf.

[0006] In pesticide research, polymorphism plays an irreplaceable role in pesticide development. Crystal form is one of the important factors affecting the chemical properties of pesticides; therefore, studying the polymorphism of pesticides is of great significance for producing highly effective, low-toxicity, and stable pesticides. Currently, the environmental impact of pesticides is receiving increasing attention. With the continuous increase in environmental protection pressure and the strengthening of regulations in various regions, the development of more efficient, green, and environmentally friendly pesticides has become a current research hotspot. Finding superior pesticide crystal forms plays a crucial role in improving efficacy, increasing utilization rates, reducing usage, and minimizing adverse environmental impacts.

[0007] Furthermore, superior pesticide crystal forms can enhance both efficacy and formulation performance and stability. Improved efficacy reduces pesticide usage and environmental exposure, minimizing ecosystem impact and preventing the development of resistance; it also reduces pesticide production and associated chemical waste. Improved formulation processing performance increases production efficiency, lowers costs, extends pesticide shelf life, and facilitates storage and transportation.

[0008] Given the increasing emphasis on environmental protection and corporate interests, research on polymorphs of pesticides should and will receive increasing attention. For example, the organic herbicide cyclopyrflufen, while possessing good biological activity, has poor water solubility. Salt formation reactions of cyclopyrflufen can improve its water solubility; for instance, the reaction of cyclopyrflufen with dimethylamine aqueous solution yields the highly soluble dimethylamine salt of cyclopyrflufen. Existing technology has studied two polymorphs of DDT. By exposing fruit flies to slides of the two DDT polymorphs and recording their activity time, comparisons showed that polymorph II was more lethal. Bixaflufenican achieves its weeding effect by inhibiting HPPD activity. Among the five polymorphs prepared, studies have shown that polymorph B of bixaflufenican has good stability and significantly better weed control effect on wheat fields than polymorph A.

[0009] Currently, there are no reports on the polymorphism of flupyradifurone, and the research and development of superior flupyradifurone polymorphs is of great significance. Summary of the Invention

[0010] The purpose of this invention is to overcome the problems existing in the prior art and to provide a flupyradifurone crystal form, its preparation method, and its uses.

[0011] To achieve the above objectives, the first aspect of the present invention provides a flupyradifurone crystal form, wherein the X-ray powder diffraction pattern of the flupyradifurone crystal form, measured using Cu-Kα radiation at 25°C and expressed in 2θ, has characteristic peaks at 6.77±0.2°, 13.60±0.2°, 20.46±0.2°, 21.98±0.2°, 23.10±0.2°, and 23.50±0.2°.

[0012] A second aspect of the present invention provides a method for preparing the fluopyram crystal form according to the first aspect, wherein the method includes the following steps:

[0013] (1) In the presence of an organic solvent and a catalyst, 4-oxobicyclo[3.2.1]oct-2-en-2-yl-2-(2-methoxyethoxymethyl)-6-trifluoromethyl nicotinate reacts with a base to obtain a reaction solution;

[0014] (2) Using water as the base solvent, the reaction solution and hydrochloric acid solution obtained in step (1) are simultaneously added to water, and then crystallization, filtration, washing and drying are carried out to obtain flupyradifurone crystal form.

[0015] The third aspect of the present invention provides a flupyradifurone crystal form obtained according to the preparation method described in the second aspect.

[0016] A fourth aspect of the present invention provides a herbicidal compound composition, wherein the flupyradifon crystal form described in the first or third aspect is included as an active ingredient and an agrochemically acceptable formulation adjuvant.

[0017] The fifth aspect of the present invention provides the use of the flupyrazole crystal form according to the first or third aspect or the herbicidal compound composition according to the fourth aspect in controlling weeds.

[0018] The beneficial technical effects achieved by the present invention through the above technical solution are as follows:

[0019] (1) The flupyradifon crystal form provided by this invention has achieved significant improvements in hygroscopicity and anti-caking properties. In particular, it overcomes the problem of easy caking during the storage and transportation of existing flupyradifon solid technical materials. The flupyradifon crystal form of this application has excellent anti-caking properties. The preparation process of the flupyradifon crystal form is simple, overcoming the problems of high impurity content and poor purification effect of existing purification products. The resulting crystals have regular crystal forms, uniform particle size, clear crystallographic parameters, and precise atomic spatial positions, making them suitable for large-scale application.

[0020] (2) The preparation of the corresponding formulation has a good weed control effect, and the formulation has good stability after accelerated testing. Attached Figure Description

[0021] Figure 1 This is the X-ray powder diffraction pattern of flupyradifon crystal form of the present invention;

[0022] Figure 2 This is the ORTEP diagram of the flupyradifurone crystal form of the present invention;

[0023] Figure 3 This is a packing diagram of the crystal forms of flupyradifon of the present invention;

[0024] Figure 4 This is a differential scanning calorimetry (DSC) curve of flupyradifurone crystal form according to the present invention;

[0025] Figure 5 This is the thermogravimetric analysis (TGA) diagram of the flupyradifurone crystal form of the present invention. Detailed Implementation

[0026] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0027] The first aspect of the present invention provides a flupyradifurone crystal form, wherein the X-ray powder diffraction pattern of the flupyradifurone crystal form, measured by Cu-Kα radiation at 25°C and expressed in 2θ, has characteristic peaks at 6.77±0.2°, 13.60±0.2°, 20.46±0.2°, 21.98±0.2°, 23.10±0.2°, and 23.50±0.2°.

[0028] In some embodiments of the present invention, the X-ray powder diffraction pattern of the flupyradifurone crystal form, measured using Cu-Kα radiation at 25°C and expressed as 2θ, has characteristic peaks at 6.77±0.2°, 12.39±0.2°, 13.60±0.2°, 18.19±0.2°, 20.46±0.2°, 21.98±0.2°, 23.10±0.2°, and 23.50±0.2°.

[0029] In some embodiments of the present invention, the X-ray powder diffraction pattern of the flupyradifon crystal form, measured using Cu-Kα radiation at 25°C and expressed as 2θ, has characteristic peaks at 6.77±0.2°, 12.39±0.2°, 13.60±0.2°, 14.90±0.2°, 15.52±0.2°, 18.19±0.2°, 18.94±0.2°, 20.46±0.2°, 21.98±0.2°, 23.10±0.2°, 23.50±0.2°, 24.20±0.2°, 26.56±0.2°, 27.41±0.2°, and 27.86±0.2°.

[0030] In some embodiments of the present invention, the flupyradifon crystal form has the following characteristics: Figure 1 The X-ray powder diffraction pattern shown is shown.

[0031] In some embodiments of the present invention, the crystallographic parameters of the flupyradifon crystal form are as follows: the flupyradifon crystal form is monoclinic with space group P1 21 / n1; the unit cell parameters are: α = 90°, β = 95.841(5)°, γ = 90°, cell volume Z = 4.

[0032] In some embodiments of the present invention, the flupyradifon crystal form exhibits a differential scanning calorimetry curve with an endothermic peak at 63.36°C.

[0033] In some embodiments of the present invention, the flupyradifon crystal form has the following characteristics: Figure 4 The differential scanning calorimetry curve shown is shown.

[0034] A second aspect of the present invention provides a method for preparing the fluopyram crystal form according to the first aspect, wherein the method includes the following steps:

[0035] (1) In the presence of an organic solvent and a catalyst, 4-oxobicyclo[3.2.1]oct-2-en-2-yl-2-(2-methoxyethoxymethyl)-6-trifluoromethyl nicotinate reacts with a base to obtain a reaction solution;

[0036] (2) Using water as the base solvent, the reaction solution and hydrochloric acid solution obtained in step (1) are simultaneously added to water, and then crystallization, filtration, washing and drying are carried out to obtain flupyradifurone crystal form.

[0037] In some embodiments of the present invention, the organic solvent in step (1) is selected from at least one of toluene, acetonitrile, DCM and DMF, preferably toluene.

[0038] In some embodiments of the present invention, the catalyst in step (1) is selected from at least one of acetone cyanohydrin and sodium cyanate, preferably acetone cyanohydrin.

[0039] In some embodiments of the present invention, the base in step (1) is selected from at least one of triethylamine, N,N-diisopropylethylamine, 2,2,6,6-tetramethylpiperidine and N-methylmorpholine, preferably triethylamine.

[0040] In some embodiments of the present invention, the molar ratio of 4-oxobicyclo[3.2.1]oct-2-en-2-yl-2-(2-methoxyethoxymethyl)-6-trifluoromethylnicotinate, base, and catalyst in step (1) is 1:1-3:0.05-0.5, preferably 1:2:0.1.

[0041] In some embodiments of the present invention, the molar volume ratio of 4-oxobicyclo[3.2.1]oct-2-en-2-yl-2-(2-methoxyethoxymethyl)-6-trifluoromethylnicotinate to the organic solvent in step (1) is 1:1-5, preferably 1:3; wherein the volume of the organic solvent is in liters.

[0042] In some embodiments of the present invention, the reaction conditions in step (1) include: stirring; time is 20 h.

[0043] In some embodiments of the present invention, the volume ratio of water in step (2) to organic solvent in step (1) is 1:1-2.

[0044] In some embodiments of the present invention, the concentration of the hydrochloric acid solution in step (2) is 5-10%, and the volume ratio of the hydrochloric acid solution to the reaction solution obtained in step (1) is 1:1.

[0045] In some embodiments of the present invention, the crystallization conditions include: stirring; time is 1 hour.

[0046] The third aspect of the present invention provides a flupyradifurone crystal form obtained according to the preparation method described in the second aspect.

[0047] A fourth aspect of the present invention provides a herbicidal compound composition, wherein the flupyradifon crystal form described in the first or third aspect is included as an active ingredient and an agrochemically acceptable adjuvant.

[0048] In some embodiments of the present invention, the additive is selected from at least one of solvents, solid diluents, emulsifiers, wetting agents, dispersants, antifreeze agents, defoamers, and thickeners.

[0049] In some embodiments of the present invention, the selected solvents include, but are not limited to, polar solvents: water, N,N-dimethylamide, dimethyl sulfoxide, N-alkylpyrrolidone, methanol, ethanol, ethylene glycol, isopropanol, ethylene glycol butyl ether, propylene glycol methyl ether, etc.; aromatic solvent oil series: toluene, xylene, solvent oil, No. 150 solvent oil, No. 180 solvent oil, No. 200 solvent oil, etc.; vegetable oils: castor oil, linseed oil, sesame oil, corn oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil, and their corresponding methylated vegetable oils, etc.; ketones: cyclopentanone, cyclohexanone, cyclooctanone, 2-heptanone, isophorone, and 4-hydroxy-4-methyl-2-pentanone, etc.; acetate esters: methyl acetate, ethyl acetate, propyl acetate, sec-butyl acetate, isoamyl acetate, hexyl acetate, heptaethyl acetate, and octyl acetate, etc.; and other types such as: decanoamide, cyclohexanol, decanol, benzyl alcohol, and tetrahydrofurfuryl alcohol, etc.

[0050] In some embodiments of the present invention, the selected solid diluent may be water-soluble or water-insoluble. Water-soluble solid diluents include, but are not limited to: salts, such as alkali metal phosphates (sodium dihydrogen phosphate), alkaline earth metal phosphates, sulfates of sodium, potassium, magnesium, and zinc, sodium chloride and potassium chloride, sodium acetate, sodium carbonate, and sodium benzoate, as well as sugars and sugar derivatives, such as sorbitol, lactose, sucrose, mannitol, corn starch, etc. Water-insoluble solid diluents include, but are not limited to: clay, calcium carbonate, diatomaceous earth, silica, calcium silicate, bentonite, magnesium aluminum silicate, and kaolin, etc.

[0051] In some embodiments of the present invention, the wetting agent includes, but is not limited to: alkyl sulfosuccinate, laurate, alkyl sulfate, phosphate ester, ethoxyfluorinated alcohol, ethoxylated silicone, alkylphenol ethoxylate, benzene sulfonate, alkyl-substituted benzene sulfonate, alkyl α-olefin sulfonate, naphthalene sulfonate, alkyl-substituted alkali metal salt of naphthalene sulfonate, alkali metal salt of naphthalene sulfonate and condensate of alkyl-substituted naphthalene sulfonate with formaldehyde, and ethoxylated alcohol.

[0052] In some embodiments of the present invention, the dispersant includes, but is not limited to: sodium, calcium and ammonium salts of lignin sulfonic acid; sodium and ammonium salts of maleic anhydride copolymers; sodium salts of condensed phenol sulfonic acid; naphthalene sulfonate-formaldehyde condensates; phosphate ester dispersants, polycarboxylate dispersants, etc.

[0053] In some embodiments of the present invention, the thickeners include, but are not limited to: guar gum, pectin, xanthan gum, alginate, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, and magnesium aluminum silicate, etc.; the synthesized thickeners include derivatives of the aforementioned types, and also include polyvinyl alcohol, polyacrylamide, polyvinylpyrrolidone, various polyethers and their copolymers, as well as polyacrylic acid and their salts.

[0054] In specific implementation, other formulation components well known to those skilled in the art may be used in this invention, such as dyes, defoamers, and desiccants.

[0055] In some embodiments of the present invention, the composition further includes other active ingredients and / or safety agents.

[0056] In some embodiments of the present invention, the dosage form of the composition is selected from one of the following: aqueous suspension, aqueous emulsion, dispersible oil suspension, emulsifiable concentrate, microemulsion, granules, suspension emulsion, water-dispersible granules, and wettable powder.

[0057] The fifth aspect of this invention provides the use of the flupyridine crystal form according to the first or third aspect, or the herbicidal compound composition according to the fourth aspect, in controlling weeds. A herbicidally effective amount of the flupyridine crystal form or the herbicidal compound composition can be applied to crops or weedy areas.

[0058] The present invention will be described in detail below through embodiments.

[0059] Unless otherwise specified in the following examples and comparative examples, all conditions were performed under standard conditions or conditions recommended by the manufacturer. Reagents or instruments used, unless otherwise specified, are all commercially available products.

[0060] Materials used in the experiment: 4-oxobicyclo[3.2.1]oct-2-en-2-yl-2-(2-methoxyethoxymethyl)-6-trifluoromethyl nicotinate (CAS: 380355-62-4) can be prepared according to existing technology disclosures (such as patent WO2001094339) or purchased. Other materials whose source and specifications are not specified are commercially available analytical grade or chemically pure.

[0061] Example 1

[0062] 1) Add 0.1 mol of 4-oxobicyclo[3.2.1]oct-2-en-2-yl-2-(2-methoxyethoxymethyl)-6-trifluoromethyl nicotinate, 0.2 mol of triethylamine, and 0.01 mol of acetone cyanohydrin to toluene (300 mL), stir and react for 20 hours to obtain the reaction solution;

[0063] 2) Take 1000mL of three-necked flask and add deionized water (150mL) as the base solvent. Place the reaction solution obtained in step (1) and 8% hydrochloric acid solution (300mL) into two dropping funnels respectively. While stirring, add the reaction solution and hydrochloric acid solution dropwise to the three-necked flask. After the addition is completed, continue stirring to allow crystallization to occur for 1 hour. After crystallization is complete, filter, wash and dry to obtain flupyradifurone crystals with a purity of 99.4%.

[0064] Example 2

[0065] 1) Add 0.1 mol of 4-oxobicyclo[3.2.1]oct-2-en-2-yl-2-(2-methoxyethoxymethyl)-6-trifluoromethyl nicotinate, N,N-diisopropylethylamine (0.1 mol), and 0.005 mol of acetone cyanohydrin to acetonitrile (100 mL), stir and react for 20 hours to obtain the reaction solution;

[0066] 2) Take 1000mL of three-necked flask and add deionized water (150mL) as the base solvent. Place the reaction solution obtained in step (1) and 10% hydrochloric acid solution (100mL) into two dropping funnels respectively. While stirring, add the reaction solution and hydrochloric acid solution dropwise to the three-necked flask. After the addition is completed, continue stirring to allow crystallization to occur for 1 hour. After crystallization is complete, filter, wash and dry to obtain flupyradifurone crystals with a purity of 98.7%.

[0067] Example 3

[0068] 1) Add 0.1 mol of 4-oxobicyclo[3.2.1]oct-2-en-2-yl-2-(2-methoxyethoxymethyl)-6-trifluoromethyl nicotinate, 0.3 mol of triethylamine, and 0.05 mol of sodium cyanate to DMF (500 mL), stir and react for 20 hours to obtain the reaction solution;

[0069] 2) Take 2000mL of three-necked flask and add deionized water (250mL) as the base solvent. Place the reaction solution obtained in step (1) and 5% hydrochloric acid solution (500mL) into two dropping funnels respectively. While stirring, add the reaction solution and hydrochloric acid solution dropwise to the three-necked flask. After the addition is completed, continue stirring to allow crystallization to occur for 1 hour. After crystallization is complete, filter, wash and dry to obtain flupyradifurone crystals with a purity of 99.2%.

[0070] Example 4

[0071] 1) Add 0.1 mol of 4-oxobicyclo[3.2.1]oct-2-en-2-yl-2-(2-methoxyethoxymethyl)-6-trifluoromethyl nicotinate, 0.2 mol of N-methylmorpholine, and 0.05 mol of acetone cyanohydrin to toluene (300 mL), stir and react for 20 hours to obtain the reaction solution;

[0072] 2) Take 1000mL of three-necked flask and add deionized water (150mL) as the base solvent. Place the reaction solution obtained in step (1) and 8% hydrochloric acid solution (300mL) into two dropping funnels respectively. While stirring, add the reaction solution and hydrochloric acid solution dropwise to the three-necked flask. After the addition is completed, continue stirring to allow crystallization to occur for 1 hour. After crystallization is complete, filter, wash and dry to obtain flupyradifurone crystals with a purity of 98.5%.

[0073] Comparative Example 1

[0074] Flupyridaben solid was prepared according to Example H3 of patent CN1824662B. The specific steps are as follows:

[0075] 2-(2-methoxyethoxymethyl)-6-trifluoromethylnicotinic acid (2.49 g) was added to a mixed solution of 20 mL dichloromethane and 2 mL oxalyl chloride, and 0.01 mL DMF was added dropwise. After no gas was generated, the temperature was controlled at 0-5 °C, and triethylamine (2.79 mL), dimethylaminopyridine (0.122 g) and bicyclo[3.2.1]octane-2,4-dione (1.52 g) were added, and the temperature was controlled at 22 °C. After reacting for 3 hours, the mixture was extracted with 2N hydrochloric acid. The dichloromethane phase was separated, washed with water, extracted with 10% sodium bicarbonate aqueous solution, dried with sodium sulfate, and concentrated to obtain an oily substance. The oily substance and triethylamine (2.79 mL) were added to 40 mL of acetonitrile, and the temperature was controlled at 22 °C. Acetone cyanohydrin (0.092 mL) was added, and the reaction was carried out at controlled temperature for 18 hours. The mixture was poured into a water / 2N hydrochloric acid mixture and extracted with ethyl acetate. The ethyl acetate phase was washed with water and concentrated sodium chloride solution, dried with sodium sulfate, filtered, and concentrated. The concentrate was washed with n-hexane, filtered, and dried to obtain flupyradifurone as a white solid with a purity of 93.23% and a melting point of 55.2-55.8 °C.

[0076] Test Example 1: Characterization of Flupyradifon Crystal Form

[0077] (1) The X-ray powder diffraction testing instrument and testing conditions involved in this invention are as follows: X-ray powder diffractometer: PANalytical EMPYREA; Cu-Kα; sample stage: flat plate; incident light path: BBHD; diffraction light path: PLXCEL; voltage 45kV, current 40mA; divergence slit: 1 / 4; anti-scattering slit: 1; Solar slit: 0.04rad; step size: 0.5s; scanning range: 3-50°. The characteristic peaks in the corresponding X-ray powder diffraction pattern (Cu-Kα) are detailed in [reference needed]. Figure 1 And Table 1.

[0078] Table 1. PXRD peaks of flupyradifon crystal form

[0079]

[0080]

[0081] (2) X-ray single-crystal diffraction analysis was performed on the flupyradifurone crystal form prepared in this invention. The X-ray single-crystal diffraction instrument and testing conditions involved in this invention were: Rigaku XtaLAB Synergy X-ray single-crystal diffractometer, testing temperature 293(2) K, Cu-Kα radiation, data were collected in ω-scan mode and Lp correction was performed. The structure was resolved by direct method, all non-hydrogen atoms were identified by difference Fourier method, and hydrogen atoms on all carbon and nitrogen were obtained by theoretical hydrogenation. The structure was refined by least squares method.

[0082] The crystallographic parameters obtained from testing and analysis of the flupyradifon crystal form prepared in this invention are: monoclinic crystal system, space group P1 21 / n1; cell parameters are: α = 90°, β = 95.841(5)°, γ = 90°, cell volume Z = 4.

[0083] Table 2. Main crystallographic parameters of flupyradifon crystal forms

[0084]

[0085] (3) TGA / DSC thermal analysis tester and test conditions in this invention: TGA / DSC thermal analyzer: METTLERTOLEDO TGA / DSC3+; dynamic temperature range: 30-300℃; heating rate: 10℃ / min; program segment gas N2; gas flow rate: 50mL / min; crucible: aluminum crucible 40μL.

[0086] The DSC test results of the flupyradifon crystal form prepared in this invention are as follows: Figure 4 As shown, the DSC detection result has an endothermic peak, with a peak temperature of 63.36℃.

[0087] The flupyradifon crystal forms prepared in Examples 1-4 of this invention all have the same X-ray powder diffraction pattern, crystallographic parameters, differential scanning calorimetry (DSC) curve, and thermogravimetric analysis (TGA) curve.

[0088] Figure 2 This is the ORTEP diagram of the flupyradifurone crystal form of the present invention; Figure 3 This is a packing diagram of the crystal form of flupyradifurone according to the present invention. Figure 2 and 3 This is the structure after single-crystal diffraction testing; conventional software analysis will not require further explanation.

[0089] Test Example 2: Flupyridamole Crystal Form Performance Test

[0090] (1) Hygroscopicity test:

[0091] Three groups of 10 mg samples prepared in Example 1 and Comparative Example 1 were taken respectively and subjected to a hygroscopic weight gain experiment at 25°C and 90% relative humidity (after equilibration). The hygroscopicity of each sample was tested using a dynamic moisture adsorption (DVS) instrument and the average value was taken. The experimental results are shown in Table 3.

[0092] Table 3. Hygroscopicity Test Results

[0093] sample Average weight gain Example 1 0.1％ Comparative Example 1 0.72％

[0094] The results show that the flupyradifon crystal obtained in Example 1 of this invention has almost no moisture absorption and good stability, making it suitable for long-term storage; Examples 1-4 have similar moisture absorption test results, and the solid obtained in Comparative Example 1 has poorer moisture absorption than that in Example 1.

[0095] (2) Agglomeration performance test

[0096] Sample pretreatment: The samples prepared according to Example 1 and Comparative Example 1 were placed in a drying oven at 40°C for 24 hours and then cooled to room temperature before being passed through a 20-mesh sieve. 20g of the sieved sample was then evenly spread into the sample container and the surface was leveled.

[0097] Pressure application: Gently place the pressure block on the sample surface, ensuring full contact between the pressure block and the sample. Place a 25kg weight on top of the pressure block, and transfer the sample and container to a constant temperature and humidity chamber for 24h, 48h, and 72h respectively.

[0098] Agglomeration test: Separate agglomerated and unagglomerated raw material particles by sieving, and calculate the proportion of agglomerated mass to total mass; After pressure test, gently pour the raw material sample into a sieve and manually sieve for 2 minutes (amplitude ≤ 5cm, avoid forcefully breaking the agglomerated particles). After sieving, weigh the remaining agglomerated particles on the sieve.

[0099]

[0100] Table 4. Data on the clumping rate of flupyradifon samples.

[0101] sample 24 hours 48 hours 72 hours Example 1 2.3％ 4.6％ 8.2％ Comparative Example 1 12.4％ 22.8％ 31.7％

[0102] According to the agglomeration rate test data in Table 4, the flupyradifurone crystal form of this application has significantly improved anti-agglomeration performance compared with Comparative Example 1.

[0103] Test Example 3

[0104] Using the flupyridine crystal form prepared in Example 1 and the flupyridine solid prepared in Comparative Example 1 as active ingredients, 10% flupyridine water-dispersible granule samples were prepared (representing Application Example 1 and Application Comparative Example 1, respectively, with the specific formulation being 10% flupyridine, 4% sodium styrene-acrylic acid copolymer, 10% sodium lignin sulfonate, 4% polymer of olefin and butadiene anhydride, 3% disodium ethylenediaminetetraacetate, 30% ammonium sulfate, 15% corn starch, and kaolin to make up to 100%), and the formulation stability and efficacy were compared.

[0105] The suspension rate of different water qualities (C water: hardness 500 mg / L, pH = 7.0-8.0; 3WHO water: hardness 1026 mg / L, pH = 6.0-7.0) was tested according to CIPAC MT184; the sieving (wet sieving test) was tested according to CIPAC MT185; the persistent foaming property was tested according to CIPAC MT47.3; and the thermal storage stability was determined according to the requirements of solid dosage forms in GB / T 19136.

[0106] Disintegration is expressed by measuring the disintegration time. Generally, less than 3 minutes is considered acceptable. The test method is as follows: at 25℃, add 0.5g of sample particles to a 100mL stoppered graduated cylinder (22.5cm high, 28mm inner diameter) containing 90mL of distilled water. Clamp the middle of the graduated cylinder and rotate it uniformly around the center at a speed of 8r / min until the sample completely disintegrates in the water. Record the time. This time is the disintegration time.

[0107] (1) Comparison of formulation stability:

[0108] Table 5. Stability test results of flupyradifon sample formulations

[0109]

[0110] The experimental results in the table above show that the formulation stability of the flupyradifurone crystal form prepared in Example 1 is better than that of the flupyradifurone solid prepared in Comparative Example 1. It can be stored stably at room temperature without affecting further processing and use.

[0111] (2) Comparison of drug efficacy

[0112] The experiment was conducted in a greenhouse in May 2023. Seeds of four weed species—barberry, foxtail, velvetleaf, and amaranth—weeds were sown in 9cm diameter plastic pots, 20 seeds per pot, covered with 1-2mm of soil, and placed in enamel trays. Water was gradually seeped into the pots using a bottom-drip irrigation method. After the water reached the soil surface, the pots were moved to a glass greenhouse for cultivation. The cultivation conditions were natural light, day / night temperature of 35℃ / 25℃, and relative humidity of 80%. At the start of the experiment, each pot was thinned to 15 seedlings. The application time for the grass weeds barberry and foxtail was the 2-leaf-1-heart stage, while the application time for the broadleaf weeds velvetleaf and amaranth was the 2-true-leaf stage. An ASS-4 automatic control spraying system was used, with an actual spraying area of ​​1.1m². 2 Dilute with 50mL of water, equivalent to a water consumption of 450L / hm. 2 The spraying pressure was 0.35 MPa, using a fan-shaped nozzle, and the flow rate was 800 mL / min. Applications were made sequentially from low to high doses, with each concentration treatment repeated four times, one pot constituting one replicate. Weed symptoms were observed at 3, 7, 15, and 20 days after application. Twenty days after application, the fresh weight of the above-ground portion of the weeds in each treatment was weighed, and the fresh weight inhibition rate was calculated.

[0113] Fresh weight inhibition rate = (fresh weight of blank control weeds - fresh weight of herbicide-treated weeds) / fresh weight of blank control weeds × 100%.

[0114] Table 6. Results of efficacy tests on flupyradifon samples

[0115]

[0116] As can be seen from the results in Table 6, the flupyridine formulation prepared using the flupyridine crystal form of Example 1 has a better control effect on both broadleaf weeds and grass weeds, which is better than the formulation prepared using the flupyridine solid form of Comparative Example 1.

[0117] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A flupyradifon crystal form, characterized in that, The X-ray powder diffraction pattern of the flupyradifon crystal form, measured using Cu-Kα radiation at 25°C and expressed as 2θ, has characteristic peaks at 6.77±0.2°, 13.60±0.2°, 20.46±0.2°, 21.98±0.2°, 23.10±0.2°, and 23.50±0.2°.

2. The flupyradifon crystal form according to claim 1, wherein, The X-ray powder diffraction pattern of the flupyradifon crystal form, measured by Cu-Kα radiation at 25°C and expressed as 2θ, shows characteristic peaks at 6.77±0.2°, 12.39±0.2°, 13.60±0.2°, 18.19±0.2°, 20.46±0.2°, 21.98±0.2°, 23.10±0.2°, and 23.50±0.2°. Preferably, the X-ray powder diffraction pattern of the flupyradifon crystal form, measured using Cu-Kα radiation at 25°C and expressed as 2θ, has characteristic peaks at 6.77±0.2°, 12.39±0.2°, 13.60±0.2°, 14.90±0.2°, 15.52±0.2°, 18.19±0.2°, 18.94±0.2°, 20.46±0.2°, 21.98±0.2°, 23.10±0.2°, 23.50±0.2°, 24.20±0.2°, 26.56±0.2°, 27.41±0.2°, and 27.86±0.2°. Preferably, the flupyradifon crystal form has an X-ray powder diffraction pattern as shown in Figure 1.

3. The fluopyram crystal form according to claim 1 or 2, wherein, The fluopyram crystal form is monoclinic, with space group P1 21 / n1; the unit cell parameters are: α = 90°, β = 95.841(5)°, γ = 90°, cell volume Z = 4.

4. The flupyradifon crystal form according to any one of claims 1-3, wherein, The flupyradifon crystal form is shown in the differential scanning calorimetry curve with an endothermic peak at 63.36℃. Preferably, the flupyradifon crystal form has a differential scanning calorimetry curve as shown in Figure 4.

5. A method for preparing the flupyradifon crystal form according to any one of claims 1-4, characterized in that, The method includes the following steps: (1) In the presence of an organic solvent and a catalyst, 4-oxobicyclo[3.2.1]oct-2-en-2-yl-2-(2-methoxyethoxymethyl)-6-trifluoromethyl nicotinate reacts with a base to obtain a reaction solution; (2) Using water as the base solvent, the reaction solution and hydrochloric acid solution obtained in step (1) are simultaneously added to water, and then crystallization, filtration, washing and drying are carried out to obtain flupyradifurone crystal form.

6. The preparation method according to claim 5, characterized in that, The organic solvent mentioned in step (1) is selected from at least one of toluene, acetonitrile, DCM and DMF, preferably toluene; Preferably, the catalyst in step (1) is selected from at least one of acetone cyanohydrin and sodium cyanate, and is preferably acetone cyanohydrin; Preferably, the base in step (1) is selected from at least one of triethylamine, N,N-diisopropylethylamine, 2,2,6,6-tetramethylpiperidine and N-methylmorpholine, and is preferably triethylamine; Preferably, the 4-oxobicyclo[ in step (1)] 3.2.1] The molar ratio of oct-2-en-2-yl-2-(2-methoxyethoxymethyl)-6-trifluoromethyl nicotinate, base, and catalyst is 1:1-3:0.05-0.5, preferably 1:2:0.1; Preferably, the 4-oxobicyclo[ in step (1)] 3.2.1] The molar volume ratio of oct-2-en-2-yl-2-(2-methoxyethoxymethyl)-6-trifluoromethyl nicotinate to the organic solvent is 1:1-5, preferably 1:3; wherein the volume of the organic solvent is in liters (L); Preferably, the reaction conditions in step (1) include: stirring; time is 20 h; Preferably, the volume ratio of water in step (2) to organic solvent in step (1) is 1:1-2; Preferably, the concentration of the hydrochloric acid solution in step (2) is 5-10%, and the volume ratio of the hydrochloric acid solution to the reaction solution obtained in step (1) is 1:1; Preferably, the crystallization conditions include: stirring; time is 1 hour.

7. The fluopyram crystal form obtained by the preparation method according to claim 5 or 6.

8. A herbicidal compound composition, characterized in that, The flupyridone crystal form, as described in any one of claims 1-4 and 7, is used as an active ingredient and an agrochemically acceptable adjuvant.

9. The herbicidal compound composition according to claim 8, wherein, The additive is selected from at least one of solvents, solid diluents, emulsifiers, wetting agents, dispersants, antifreeze agents, defoamers, and thickeners; Preferably, the composition further includes other active ingredients and / or safety agents.

10. Use of the flupyradifon crystal form according to any one of claims 1-4 and 7, or the herbicidal compound composition according to claim 8 or 9, in the control of weeds.

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