Polymorph of fluxapyroxad, preparation method therefor, and application thereof

Abstract

Disclosed are a polymorph of fluxapyroxad, a preparation method therefor, and an application thereof. The polymorph is a polymorph of a compound as shown in formula I, and the polymorph is a metastable polymorph. The polymorph of the present invention is a fluxapyroxad polymorph formed by means of induction in the presence of an organic acid, is suitable for preparing a pesticide composition for inhibiting harmful microorganisms, and has a better control effect against most diseases caused by ascomycetes, basidiomycetes, deuteromycetes, and other Eumycota, including brown leaf spot, sheath blight, botrytis cinerea, snow mold and the like.

Description

A polymorph of flupyraclostrobin, its preparation method and application Technical Field

[0001] The present invention belongs to the field of pesticide chemistry, and in particular relates to a polymorph of fluopyraclostrobin and a preparation method and application thereof. Background Art

[0002] Fluxapyroxad, whose chemical name is 3-(difluoromethyl)-1-methyl-N-(3',4',5'-trifluorobiphenyl-2-yl)pyrazole-4-carboxamide, has a structural formula as shown in Formula (I).

[0003] The pure product appears as a white crystalline powder with a melting point of 157°C and a water solubility of 3.44 mg / L at a pH of 7. This compound, a carboxamide fungicide developed by BASF, acts on succinate dehydrogenase in the mitochondrial respiratory chain, hindering energy metabolism and inhibiting the growth of pathogens, thereby achieving disease control. It is highly effective against most diseases caused by fungi such as Ascomycetes, Basidiomycetes, and Deuteromycetes, including brown spot, sheath blight, gray mold, and snow mold leaf blight.

[0004] The same compound may have different solubility, stability, fluidity, and compressibility depending on the crystal form. These physical and chemical properties may have a certain impact on the application of the compound. The preparation method of the original compound in patent CN101743225A produces crystal forms named Form A and Form B. Form A is generally a transparent block crystal, and Form B is a slightly yellow needle-shaped crystal. However, the configuration stability and phase transition stability of Form A are uncontrolled, and Form B has low solubility. Solid-state chemistry research on flupyraclostrobin is needed to improve its water solubility and other physical and chemical properties.

[0005] Therefore, there is an urgent need in the art to develop polymorphs of the compound of formula I, which require simple preparation methods, good thermal stability, low hygroscopicity, high solubility, and scalable production. Summary of the Invention

[0006] The present invention aims to provide a polymorph of a compound of formula I having a simple preparation method, good thermal stability, low hygroscopicity, high solubility, and scalable production, and specifically relates to a polymorph of flupyraclostrobin, a preparation method thereof, and an application thereof.

[0007] In a first aspect of the present invention, a polymorph of a compound represented by Formula I is provided, wherein the polymorph is a metastable crystalline form;

[0008] In another preferred embodiment, the polymorph is a metastable crystalline form selected from the group consisting of polymorph 3, polymorph 4, and polymorph 5;

[0009] Wherein, the X-ray powder diffraction pattern of the polymorph 3 includes 3 or more 2θ values ​​selected from the following group: 10.0±0.2°, 14.6±0.2°, 17.1±0.2°, 19.6±0.2°, 20.3±0.2°, 21.6±0.2°;

[0010] The X-ray powder diffraction pattern of the polymorph 4 includes 3 or more 2θ values ​​selected from the group consisting of 8.6±0.2°, 9.1±0.2°, 11.9±0.2°, 17.3±0.2°, 18.2±0.2°, and 24.5±0.2°;

[0011] The X-ray powder diffraction pattern of the polymorph 5 includes 3 or more 2θ values ​​selected from the following group: 7.9±0.2°, 12.0±0.2°, 14.8±0.2°, 17.4±0.2°, 18.7±0.2°, and 25.4±0.2°.

[0012] In another preferred embodiment, the polymorph is a metastable crystalline form selected from the group consisting of polymorph 3, polymorph 4, and polymorph 5;

[0013] Wherein, the X-ray powder diffraction pattern of the polymorph 3 includes 6 or more 2θ values ​​selected from the following group: 9.7±0.2°, 10.0±0.2°, 13.1±0.2°, 14.6±0.2°, 17.1±0.2°, 17.7±0.2°, 19.6±0.2°, 20.3±0.2°, 21.6±0.2°, 23.2±0.2°, 24.6±0.2°, 26.1±0.2°, 26.6±0.2°, 27.3±0.2°, 30.6±0.2°, 31.0±0.2°, 34.8±0.2°, 36.0±0.2°, 39.4±0.2°, 40.0±0.2°, 40.6±0.2°;

[0014] The X-ray powder diffraction pattern of the polymorph 4 includes 6 or more 2θ values ​​selected from the group consisting of 8.6±0.2°, 9.1±0.2°, 11.9±0.2°, 13.7±0.2°, 14.9±0.2°, 15.3±0.2°, 16.6±0.2°, 17.3±0.2°, 18.2±0.2°, 18.8±0.2° , 21.4±0.2°, 22.4±0.2°, 22.8±0.2°, 23.7±0.2°, 24.5±0.2°, 25.5±0.2°, 27.3±0.2°, 27.8±0.2°, 29.4±0.2°, 32.1±0.2°, 36.4±0.2°, 38.9±0.2°, 40.1±0.2°;

[0015] The X-ray powder diffraction pattern of the polymorph 5 includes 6 or more 2θ values ​​selected from the group consisting of: 7.9±0.2°, 9.4±0.2°, 10.2±0.2°, 12.0±0.2°, 14.8±0.2°, 16.4±0.2°, 17.4±0.2°, 18.7±0.2°, 20.1±0.2°, 22.1±0.2° , 22.8±0.2°, 24.3±0.2°, 25.4±0.2°, 26.0±0.2°, 27.3±0.2°, 29.4±0.2°, 30.0±0.2°, 30.9±0.2°, 31.8±0.2°, 34.8±0.2°, 38.8±0.2°, 40.1±0.2°, 41.2±0.2°.

[0016] In another preferred embodiment, the polymorph is a metastable crystalline form selected from the group consisting of polymorph 3, polymorph 4, and polymorph 5;

[0017] The X-ray powder diffraction pattern of the polymorph 3 is substantially as shown in FIG1 ;

[0018] The X-ray powder diffraction pattern of the polymorph 4 is substantially as shown in FIG2 ;

[0019] The X-ray powder diffraction pattern of the polymorph 5 is substantially as shown in FIG3 .

[0020] In another preferred embodiment, the polymorph is a metastable crystalline form selected from the group consisting of polymorph 3, polymorph 4, and polymorph 5;

[0021] The DSC graph of the polymorph 3 has an endothermic peak in the range of 130-150°C, a crystal transformation peak at 150°C, and a second endothermic peak in the range of 150°C-163°C;

[0022] The DSC graph of the polymorph 4 has an endothermic peak at 126-141°C, a crystal transformation peak at 141°C, and a second endothermic peak at 141°C-155°C;

[0023] The DSC graph of the polymorph 5 has an endothermic peak at 60-89°C and a second endothermic peak at 107-120°C.

[0024] In another preferred embodiment, the polymorph is a metastable crystalline form selected from the group consisting of polymorph 3, polymorph 4, and polymorph 5;

[0025] The DSC diagram of the polymorph 3 is substantially as shown in FIG4 ;

[0026] The DSC diagram of the polymorph 4 is substantially as represented in FIG5 ;

[0027] The DSC diagram of the polymorph 5 is substantially as shown in FIG6 .

[0028] In another preferred embodiment, the X-ray powder diffraction pattern of the polymorph 3 has a diffraction angle 2θ value of 9.7±0.2°, 10.0±0.2°, 10.9±0.2°, 11.2±0.2°, 13.1±0.2°, 14.6±0.2°, 17.1±0.2°, 17.7±0.2°, 19.6±0.2°, 20.3±0.2°, 21.6±0.2°, 22.1±0.2°, 22.7±0.2°, 23.2±0. There are characteristic peaks at 2°, 23.7±0.2°, 24.6±0.2°, 26.1±0.2°, 26.6±0.2°, 27.3±0.2°, 29.7±0.2°, 30.6±0.2°, 31.1±0.2°, 34.8±0.2°, 36.0±0.2°, 36.9±0.2°, 39.5±0.2°, 40.0±0.2°, 40.6±0.2°, 41.1±0.2°, and 44.2±0.2°.

[0029] In another preferred embodiment, the X-ray powder diffraction pattern of the polymorph 4 has a diffraction angle 2θ value of 6.2±0.2°, 8.6±0.2°, 9.1±0.2°, 9.3±0.2°, 10.0±0.2°, 11.9±0.2°, 13.1±0.2°, 13.7±0.2°, 14.9±0.2°, 15.3±0.2°, 16.1±0.2°, 16.6±0.2°, 16.9±0.2°, 17.3±0.2°, 18.2±0.2°, 18.8±0.2°, 20.3±0.2°, 20.5±0.2°, 21.0±0.2°, 21.4±0.2°, 22.4±0.2° There are characteristic peaks at 22.8±0.2°, 23.4±0.2°, 23.7±0.2°, 24.0±0.2°, 24.5±0.2°, 24.8±0.2°, 25.2±0.2°, 25.5±0.2°, 26.0±0.2°, 26.7±0.2°, 27.3±0.2°, 27.8±0.2°, 28.8±0.2°, 29.4±0.2°, 30.0±0.2°, 31.9±0.2°, 32.1±0.2°, 33.4±0.2°, 34.2±0.2°, 34.9±0.2°, 36.4±0.2°, 36.9±0.2°, and 38.9±0.2°.

[0030] In another preferred embodiment, the diffraction angle 2θ value of the X-ray powder diffraction pattern of the polymorph 5 is 7.9±0.2°, 8.4±0.2°, 8.9±0.2°, 9.4±0.2°, 10.2±0.2°, 11.3±0.2°, 12.0±0.2°, 14.6±0.2°, 14.8±0.2°, 16.0±0.2°, 16.4±0.2°, 17.4±0.2°, 18.2±0.2°, 18.7±0.2°, 19.6±0.2°, 20.1±0.2°, 21.6±0.2°, 22.1±0.2°, 22.8±0.2° There are characteristic peaks at 23.3±0.2°, 24.3±0.2°, 24.9±0.2°, 25.4±0.2°, 26.1±0.2°, 26.6±0.2°, 27.3±0.2°, 27.9±0.2°, 28.7±0.2°, 29.4±0.2°, 30.0±0.2°, 31.0±0.2°, 31.8±0.2°, 33.0±0.2°, 33.3±0.2°, 34.8±0.2°, 35.6±0.2°, 36.5±0.2°, 36.8±0.2°, 38.1±0.2°, and 38.9±0.2°.

[0031] In a second aspect of the present invention, there is provided a pesticide composition comprising:

[0032] (a) the polymorph as described in the first aspect, and

[0033] (b) a pesticide-acceptable carrier.

[0034] In another preferred embodiment, the pesticide composition further comprises an active substance selected from the group consisting of insecticides, baits, bactericides, acaricides, nematicides, fungicides, plant growth regulators, plant disease resistance activators, or combinations thereof.

[0035] In a third aspect of the present invention, a method for preparing the polymorph described in the first aspect is provided, the method comprising step (i):

[0036] (i-1) providing a first mixed solution, wherein the first mixed solution is obtained by dissolving the compound represented by formula (I), an organic acid, and a solvent;

[0037] (i-2) suspending the first mixed solution of step (i-1), centrifuging, volatilizing the supernatant, and vacuum drying to obtain the polymorph; or

[0038] comprising step (ii):

[0039] (ii-1) providing a second mixed solution, wherein the second mixed solution is obtained by dissolving the compound represented by formula (I), an organic acid, and a solvent;

[0040] (ii-2) volatilizing the second mixed solution from step (ii-1) and vacuum drying to obtain the polymorph;

[0041] Wherein, the organic acid is selected from the group consisting of 2,6-dihydroxybenzoic acid, 1-hydroxy-2-naphthoic acid, 3-nitrobenzoic acid, p-hydroxybenzoic acid, D-isoascorbic acid, γ-aminobutyric acid, 3-furoic acid, maleic acid, and itaconic acid;

[0042] The solvent is selected from the group consisting of dichloromethane, 1,2-dichloroethane, n-butanol, isopropanol, acetone, tetrahydrofuran (THF), 1,4-dioxane, benzyl ether, ethyl formate, methanol, acetonitrile, N,N-dimethylformamide (DMF), and N,N-dimethyl sulfoxide (DMSO), preferably methanol or acetonitrile.

[0043] In another preferred embodiment, the molar ratio of the compound represented by formula (I) to the organic acid in step (i-1) is 0.3-3:1.

[0044] In another preferred embodiment, the molar volume ratio of the compound represented by formula (I) and the organic acid to the solvent in step (i-1) is 0.2-1.5 mol / l, preferably 0.3-1.4 mol / l, and more preferably 0.3-1.2 mol / l.

[0045] In another preferred embodiment, the molar ratio of the compound represented by formula (I) to the organic acid in step (ii-1) is 0.3-3:1.

[0046] In another preferred embodiment, the molar volume ratio of the compound represented by formula (I) and the organic acid to the solvent in step (ii-1) is 0.5-1.5 mol / l, preferably 0.6-1.2 mol / l.

[0047] In another preferred embodiment, the compound of formula (I) in the method is crystalline form B.

[0048] In a fourth aspect of the present invention, there is provided a use of the polymorph described in the first aspect or the pesticide composition described in the second aspect for preparing a formulation for preventing or controlling diseases.

[0049] In another preferred embodiment, the disease is a plant disease selected from the group consisting of gray mold, rust, powdery mildew, sheath blight, or a combination thereof.

[0050] In the fifth aspect of the present invention, there is provided a use of the polymorph described in the first aspect or the pesticide composition described in the second aspect for preparing a formulation for inhibiting harmful microorganisms in agriculture, forestry or horticulture.

[0051] In another preferred embodiment, the harmful microorganisms are selected from the following groups: Ascomycetes, Basidiomycetes, Rust Fungi, Deuteromycetes or Oomycetes.

[0052] In another preferred embodiment, the prevention or control is the prevention or control of harmful microorganisms in agriculture, forestry or horticulture.

[0053] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features described in detail below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be listed here one by one. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] FIG1 shows the XRPD pattern of Flupyraclostrobin Form 3.

[0055] FIG2 shows the XRPD pattern of Flupyraclostrobin Form 4.

[0056] FIG3 shows the XRPD pattern of Flupyraclostrobin Form 5.

[0057] FIG4 shows the DSC spectrum of Flupyraclostrobin Form 3.

[0058] FIG5 shows the DSC spectrum of Flupyraclostrobin Form 4.

[0059] FIG6 shows the DSC spectrum of Flupyraclostrobin Form 5.

[0060] FIG7 shows the TGA spectrum of Flupyraclostrobin Form 3.

[0061] FIG8 shows the TGA spectrum of Flupyraclostrobin Form 4.

[0062] FIG9 shows the TGA spectrum of Flupyraclostrobin Form 5.

[0063] FIG10 shows the NMR spectrum of Flupyraclostrobin Form 3.

[0064] FIG11 shows a single crystal X-ray diffraction structure of Flupyraclostrobin Form 4.

[0065] FIG12 shows a single crystal X-ray diffraction structure diagram of Flupyraclostrobin Form 5.

[0066] FIG13 shows the XRPD pattern of the five-day high temperature stability of Flupyraclostrobin Form 3.

[0067] FIG14 shows the XRPD pattern of the high temperature stability of Flupyraclostrobin Form 3 for ten days.

[0068] FIG15 shows the XRPD pattern of Flupyraclostrobin Form 3 for five-day high humidity stability.

[0069] FIG16 shows the XRPD pattern of the ten-day high humidity stability of Flupyraclostrobin Form 3.

[0070] FIG17 shows the five-day light stability XRPD pattern of Flupyraclostrobin Form 3.

[0071] FIG18 shows the XRPD pattern of the ten-day light stability of Fluopyraclostrobin Form 3.

[0072] FIG19 shows the XRPD pattern of the five-day high temperature stability of Flupyraclostrobin Form 4.

[0073] FIG20 shows the XRPD pattern of the high temperature stability of Flupyraclostrobin Form 4 for ten days.

[0074] FIG21 shows the XRPD pattern of Flupyraclostrobin Form 4 for five-day high humidity stability.

[0075] FIG22 shows the XRPD pattern of Flupyraclostrobin Form 4 for ten-day high humidity stability.

[0076] FIG23 shows the five-day light stability XRPD pattern of Flupyraclostrobin Form 4.

[0077] FIG24 shows the XRPD pattern of the ten-day light stability of Flupyraclostrobin Form 4.

[0078] FIG25 shows the five-day high temperature stability XRPD pattern of Flupyraclostrobin Form 5.

[0079] FIG26 shows the XRPD pattern of the ten-day high temperature stability of Flupyraclostrobin Form 5.

[0080] FIG27 shows the XRPD pattern of Flupyraclostrobin Form 5 for five-day high humidity stability.

[0081] FIG28 shows the XRPD pattern of Flupyraclostrobin Form 5 for ten-day high humidity stability.

[0082] FIG29 shows the five-day light stability XRPD pattern of Flupyraclostrobin Form 5.

[0083] FIG30 shows the XRPD pattern of the ten-day light stability of Fluopyraclostrobin Form 5.

[0084] FIG31 shows a single crystal X-ray diffraction structure diagram of Flupyraclostrobin Form 3. DETAILED DESCRIPTION

[0085] Through extensive and in-depth research, the inventors unexpectedly discovered, for the first time, a polymorph of fluopyrab, using induced crystallization technology, as well as its preparation method and application. This polymorph exhibits superior solubility to fluopyrab Form B. It is suitable for use in preparing pesticide compositions for inhibiting harmful microorganisms, and exhibits superior efficacy against most diseases caused by fungi such as Ascomycetes, Basidiomycetes, and Deuteromycetes, including brown spot, sheath blight, gray mold, and snow mold leaf blight. Based on this, the inventors completed the present invention.

[0086] Terminology

[0087] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0088] As used herein, when used in reference to a specific recited value, the term "about" means that the value may vary by no more than 1% from the recited value. For example, as used herein, the expression "about 100" includes all values ​​between 99 and 101 (e.g., 99.1, 99.2, 99.3, 99.4, etc.).

[0089] As used herein, the terms "comprising" or "including" may be open, semi-closed, or closed. In other words, the terms also include "consisting essentially of" or "consisting of."

[0090] As used herein, the term "n or more 2θ values ​​selected from the following group" refers to n and any positive integer greater than n (e.g., n, n+1, ...), wherein the upper limit Nup is the number of all 2θ peaks in the group. For example, "3 or more" includes not only 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, ..., each positive integer of the upper limit Nup, but also includes ranges such as "4 or more," "5 or more," and "6 or more."

[0091] In another preferred embodiment, the 2θ value of the X-ray powder diffraction pattern of the polymorph has a deviation of ±0.5°, preferably a deviation of ±0.3°, and more preferably a deviation of ±0.1°.

[0092] Compounds of formula I

[0093] Flupyraclostrobin (Formula I), chemically known as 3-(difluoromethyl)-1-methyl-N-(3',4',5'-trifluorobiphenyl-2-yl)pyrazole-4-carboxamide, is a carboxamide fungicide developed by BASF. It acts on succinate dehydrogenase in the mitochondrial respiratory chain, hindering energy metabolism and inhibiting the growth of pathogens, thereby achieving the purpose of disease prevention. It is highly effective against most diseases caused by fungi such as Ascomycetes, Basidiomycetes, and Deuteromycetes, including brown spot, sheath blight, gray mold, and snow mold leaf blight.

[0094] polymorphs

[0095] Solids exist in either amorphous or crystalline forms. In the case of crystalline forms, the molecules are positioned within a three-dimensional lattice. When a compound crystallizes from a solution or slurry, it can crystallize in different spatial arrangements (a property known as "polymorphism"), forming crystals with different crystalline forms, which are known as "polymorphs." Different polymorphs of a given substance can differ from one another in one or more physical properties, such as solubility and dissolution rate, true specific gravity, crystal shape, packing pattern, flowability, and / or solid-state stability.

[0096] crystallization

[0097] Production-scale crystallization can be accomplished by manipulating the solution so that the solubility limit of the compound of interest is exceeded. This can be accomplished in a variety of ways, for example, by dissolving the compound at a relatively high temperature and then cooling the solution to below the saturation limit. Alternatively, the liquid volume can be reduced by boiling, atmospheric evaporation, vacuum drying, or other methods. The solubility of the compound of interest can be reduced by adding an antisolvent or a solvent or mixture of such solvents in which the compound has a low solubility. There are also novel crystallization methods that can induce the growth of polymorphs by adding additives or polymers.

[0098] Induced crystallization technology

[0099] Induced crystallization technology is a technique that uses external regulatory means to control seed formation, crystal growth, and crystal shape. The inducing media mainly include solvents and additives. Additives can be selected based on functional group interaction strategies or specific additives based on structural similarity. The introduction of additives can form potential interactions with solute molecules, adjust the solution environment, and thus change crystallization conditions, allowing metastable crystals to grow smoothly. Induced crystallization technology has broad application prospects in the field of pharmaceutical preparation and provides new research ideas and technical means for exploring crystal growth mechanisms and morphological control.

[0100] Solvates

[0101] When a compound or drug molecule comes into contact with a solvent, external and internal factors inevitably cause the solvent to form a co-crystal with the compound, leaving it trapped in the solid. The resulting crystallization of the compound and the solvent is called a solvate. Solvents that readily form solvates with organic compounds include water, methanol, benzene, ethanol, ethers, aromatic hydrocarbons, and heterocyclic aromatic hydrocarbons.

[0102] Hydrates are a special type of solvate. In the pharmaceutical industry, hydrates are worthy of separate discussion due to their special properties, whether in the synthesis of raw materials, drug formulation, drug storage, or drug activity evaluation.

[0103] In the present invention, the crystal of the compound represented by formula (I) may be a non-solvate or a solvate.

[0104] Pesticide composition

[0105] The "active ingredient" or "active compound" in the pesticide composition of the present invention refers to the compound of formula (I) of the present invention, especially the compound of formula (I) in the crystalline form of the present invention.

[0106] The "active ingredients" or "active compounds" and pesticide compositions of the present invention can be used to prevent or control diseases; or to inhibit harmful microorganisms in agriculture, forestry or horticulture.

[0107] Differential scanning calorimetry

[0108] Differential Scanning Calorimetry (DSC), also known as differential scanning calorimetry (DSC), is a technique that measures the relationship between the energy difference between a test substance and a reference substance and temperature during heating. The position, shape, and number of peaks on a DSC spectrum correlate with the properties of the substance and can therefore be used to qualitatively identify it. This method is commonly used in the field to measure various parameters, including phase transition temperature, glass transition temperature, and heat of reaction.

[0109] Preparation method

[0110] When preparing the fluopyraclostrobin polymorph, the present invention adopts an induced crystallization technology strategy, introduces an organic acid as an additive, and uses a solvent volatilization method or a grinding method.

[0111] use

[0112] The present invention provides uses of crystal forms 3, 4 and 5 and pesticide compositions thereof. The crystal forms are highly effective and broad-spectrum, and have excellent preventive effects on most diseases such as brown spot, sheath blight, gray mold, and snow mold leaf blight caused by fungi such as Ascomycetes, Basidiomycetes, and Deuteromycetes.

[0113] Compared with the prior art, the present invention has the following beneficial effects:

[0114] (1) The crystalline forms 3, 4 and 5 of the compound of formula I of the present invention have good solubility and are superior to the existing fluopyraclostrobin crystalline form B in terms of solubility.

[0115] (2) The preparation methods of the compound of formula I, Form 3, Form 4 and Form 5, are novel and suitable for further study of the induced crystallization mechanism.

[0116] (3) The crystalline forms 3, 4 and 5 of the compound of formula I of the present invention can be used to prevent or control diseases; or to inhibit harmful microorganisms in agriculture, forestry or horticulture.

[0117] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present invention only and are not intended to limit the scope of the invention. The experimental methods in the following examples, for which specific conditions are not specified, are generally based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are by weight.

[0118] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those familiar to those skilled in the art. Furthermore, any methods and materials similar or equivalent to those described herein can be applied to the methods of the present invention. The preferred embodiments and materials described herein are for illustrative purposes only.

[0119] Unless otherwise specified, the experimental materials and reagents used in the following examples can be obtained from commercial sources. Normal temperature or room temperature refers to 4°C-25°C, preferably 15-25°C.

[0120] Test method:

[0121] XRD (X-ray powder diffraction) method: Instrument model: Rigaku Ultima IV, target: Cu-Kα (40 kV, 40 mA), using a D / tex Ultra detector at room temperature. The scanning range is from 3° to 45° in the 2θ interval, and the scanning speed is 20° / min.

[0122] The measurement differences associated with such X-ray powder diffraction analysis results are caused by a variety of factors including: (a) errors in sample preparation (e.g., sample height), (b) instrument errors, (c) calibration differences, (d) operator errors (including errors that occur when determining peak positions), and (e) the properties of the material (e.g., preferred orientation errors). Calibration errors and sample height errors often result in displacements of all peaks in the same direction. When a flat support is used, small differences in sample height will result in large displacements of XRD peak positions. Systematic studies have shown that a sample height difference of 1 mm can result in peak displacements of up to 1° in 2θ. These displacements can be identified from the X-ray diffraction pattern and can be eliminated by compensating for the displacements (applying a system calibration factor to all peak position values) or recalibrating the instrument. As described above, by applying a system calibration factor to make the peak positions consistent, measurement errors from different instruments can be corrected.

[0123] TGA (thermogravimetric analysis) method: Instrument model: TA Q500 thermogravimetric analyzer, using N2 atmosphere, and a heating rate of 10°C / min.

[0124] DSC (Differential Scanning Calorimetry) Method: Instrument model: TA Q2000 differential scanning calorimeter, using N2 atmosphere, heating rate of 10°C / min.

[0125] Single crystal X-ray diffraction (SCXRPD) method: Instrument model: Bruker D8 QUEST single crystal diffractometer, test method: Cu-Kα ray The data were integrated and simplified using APEX3, and the crystal structure was refined using the SHELXL program in Olex2 software. The XRPD patterns and single crystal structure of the simulated single crystal were obtained using Mercury 4.3 software.

[0126] Example 1: Preparation of Form A

[0127] The preparation method of Form A is similar to the preparation method of CN101743225A, which is similar to Example 7, in which Form A is obtained by rapid rotary evaporation under reduced pressure. 50 mg of the compound of Formula I was dissolved in 3.0 ml of dichloromethane and rapidly rotary evaporated at 50°C. Powder X-ray diffraction (PXRD) analysis confirmed that the crystalline sample was Form A.

[0128] Example 2: Preparation of Form B

[0129] The preparation method of Form B is similar to Example 3 in reference patent CN101743225A. The preparation method of Form B is obtained by crystallization from a solvent by solvent evaporation at room temperature. 20 mg of the compound of Formula I is dissolved in a solvent and evaporated at room temperature to obtain a crystalline powder. The solvent can be methanol, methyl tert-butyl ether, ethylene glycol dimethyl ether, n-propanol, isopropanol, dichloromethane, 1,2-dichloroethane, tetrahydrofuran, acetone and acetonitrile. After all solvents are evaporated, the crystalline sample is analyzed by powder X-ray diffraction (PXRD) to be Form B.

[0130] Example 3: Preparation of Form 3

[0131] 3.1 Approximately 3 mmol of the compound of formula I and 1 mmol of 3-nitrobenzoic acid were weighed into a container in a molar ratio of 3:1. 3.0 mL of anhydrous methanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 3.

[0132] 3.2 About 1 mmol of the compound of formula I and 1 mmol of 3-nitrobenzoic acid were weighed into a container in a molar ratio of 1:1. 1.5 mL of anhydrous methanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 3.

[0133] 3.3 About 1 mmol of the compound of formula I and 3 mmol of 3-nitrobenzoic acid were weighed into a container in a molar ratio of 1:3. 3.0 mL of anhydrous methanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 3.

[0134] 3.4 About 3 mmol of the compound of formula I and 1 mmol of 3-furoic acid were weighed into a container in a molar ratio of 3:1. 3.0 mL of anhydrous methanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Fluopyraclostrobin Form 3.

[0135] 3.5 About 1 mmol of the compound of formula I and 1 mmol of 3-furoic acid were weighed into a container in a molar ratio of 1:1. 1.5 mL of anhydrous methanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Fluopyraclostrobin Form 3.

[0136] 3.6 About 1 mmol of the compound of formula I and 3 mmol of 3-furoic acid were weighed into a container in a molar ratio of 1:3. 3.0 mL of anhydrous methanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Fluopyraclostrobin Form 3.

[0137] 3.7 About 3 mmol of the compound of formula I and 1 mmol of itaconic acid were weighed into a container in a molar ratio of 3:1. 3.0 mL of anhydrous ethanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 3.

[0138] 3.8 About 1 mmol of the compound of formula I and 1 mmol of itaconic acid were weighed in a molar ratio of 1:1 into a container, 1.5 mL of anhydrous ethanol was added to dissolve the solution, filtered, and evaporated at room temperature to obtain Flupyraclostrobin Form 3.

[0139] 3.9 About 1 mmol of the compound of Formula I and 3 mmol of itaconic acid were weighed into a container in a molar ratio of 1:3. 3.0 mL of anhydrous ethanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 3.

[0140] 3.10 Approximately 3 mmol of the compound of Formula I and 1 mmol of 3-nitrobenzoic acid were weighed into a container in a molar ratio of 3:1. 3.0 mL of acetonitrile was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 3.

[0141] 3.11 About 1 mmol of the compound of formula I and 1 mmol of 3-nitrobenzoic acid were weighed in a molar ratio of 1:1 into a container, 1.5 mL of acetonitrile was added to dissolve the mixture, filtered, and evaporated at room temperature to obtain Flupyraclostrobin Form 3.

[0142] 3.12 Approximately 1 mmol of the compound of Formula I and 3 mmol of 3-nitrobenzoic acid were weighed in a molar ratio of 1:3 into a container. 3.0 mL of acetonitrile was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 3.

[0143] 3.13 Approximately 3 mmol of the compound of Formula I and 1 mmol of p-hydroxybenzoic acid were weighed into a container in a molar ratio of 3:1. 3.0 mL of acetonitrile was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 3.

[0144] 3.14 About 1 mmol of the compound of formula I and 1 mmol of p-hydroxybenzoic acid were weighed in a molar ratio of 1:1 into a container, 1.5 mL of acetonitrile was added to dissolve the mixture, filtered, and evaporated at room temperature to obtain Flupyraclostrobin Form 3.

[0145] 3.15 Approximately 1 mmol of the compound of Formula I and 3 mmol of p-hydroxybenzoic acid were weighed into a container in a molar ratio of 1:3. 3.0 mL of acetonitrile was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 3.

[0146] The XRD pattern of the obtained crystal form 3 is shown in Figure 1, and the diffraction angle data are basically shown in Table 1 below.

[0147] Table 1 XRD data of Form 3

[0148] In addition, the single crystal X-ray diffraction (SXRD) structure of Form 3 was obtained, as shown in FIG31 , and its parameters are basically as shown in Table 2 below:

[0149] Table 2 Single crystal X-ray diffraction parameters of Form 3

[0150] The DSC spectrum of Form 3 is basically as shown in Figure 4. The endothermic peak corresponds to the melting decomposition process, with an endothermic peak in the range of 130 to 150°C and a second endothermic peak in the range of 150 to 163°C.

[0151] The TGA spectrum of Form 3 is basically as shown in Figure 7, and there is basically no weight loss before decomposition.

[0152] The NMR spectrum of Form 3 is basically as shown in Figure 10, proving that its component is flupyraclostrobin.

[0153] Example 4: Preparation of Form 4

[0154] 4.1 About 3 mmol of the compound of formula I and 1 mmol of 2,6-dinitrobenzoic acid were weighed into a container in a molar ratio of 3:1. 3.0 mL of anhydrous methanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 4.

[0155] 4.2 About 1 mmol of the compound of formula I and 1 mmol of 2,6-dinitrobenzoic acid were weighed into a container in a molar ratio of 1:1. 1.5 mL of anhydrous methanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 4.

[0156] 4.3 About 1 mmol of the compound of formula I and 3 mmol of 2,6-dinitrobenzoic acid were weighed into a container in a molar ratio of 1:3. 3.0 mL of anhydrous methanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 4.

[0157] 4.4 About 3 mmol of the compound of formula I and 1 mmol of p-nitrobenzoic acid were weighed into a container in a molar ratio of 3:1. 3.0 mL of anhydrous methanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 4.

[0158] 4.5 About 1 mmol of the compound of formula I and 1 mmol of p-nitrobenzoic acid were weighed into a container in a molar ratio of 1:1. 1.5 mL of anhydrous methanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 4.

[0159] 4.6 About 1 mmol of the compound of formula I and 3 mmol of p-nitrobenzoic acid were weighed into a container in a molar ratio of 1:3. 3.0 mL of anhydrous methanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 4.

[0160] 4.7 About 3 mmol of the compound of formula I and 1 mmol of D-isoascorbic acid were weighed into a container in a molar ratio of 3:1. 3.0 mL of anhydrous ethanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 4.

[0161] 4.8 About 1 mmol of the compound of formula I and 1 mmol of D-isoascorbic acid were weighed in a molar ratio of 1:1 into a container, 1.5 mL of anhydrous ethanol was added to dissolve the mixture, filtered, and evaporated at room temperature to obtain Flupyraclostrobin Form 4.

[0162] 4.9 About 1 mmol of the compound of formula I and 3 mmol of D-isoascorbic acid were weighed into a container in a molar ratio of 1:3. 3.0 mL of anhydrous ethanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 4.

[0163] 4.10 Approximately 3 mmol of the compound of formula I and 1 mmol of maleic acid were weighed into a container in a molar ratio of 3:1. 3.0 mL of anhydrous ethanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 4.

[0164] 4.11 About 1 mmol of the compound of formula I and 1 mmol of maleic acid were weighed in a molar ratio of 1:1 into a container, 1.5 mL of anhydrous ethanol was added to dissolve the mixture, filtered, and evaporated at room temperature to obtain Flupyraclostrobin Form 4.

[0165] 4.12 About 1 mmol of the compound of formula I and 3 mmol of maleic acid were weighed in a molar ratio of 1:3 into a container. 3.0 mL of anhydrous ethanol was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 4.

[0166] The XRD pattern of the obtained crystal form 4 is shown in Figure 2, and the diffraction angle data are basically shown in Table 3 below.

[0167] Table 3 XRD data of Form 4

[0168] The DSC spectrum of Form 4 is basically as shown in Figure 5. The endothermic peak corresponds to the melting decomposition process, with an endothermic peak in the range of 126 to 141°C and a second endothermic peak in the range of 141 to 155°C.

[0169] The TGA spectrum of Form 4 is basically as shown in Figure 8, and there is basically no weight loss before decomposition.

[0170] In addition, the single crystal X-ray diffraction (SXRD) structure of Form 4 in Example 4 was obtained, as shown in FIG11 , and its parameters are basically as shown in Table 4 below:

[0171] Table 4 Single crystal X-ray diffraction parameters of Form 4

[0172] Example 5: Preparation of Form 5

[0173] 5.1 About 3 mmol of the compound of formula I and 1 mmol of 2,6-dihydroxybenzoic acid were weighed into a container in a molar ratio of 3:1. 3.0 mL of acetonitrile was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Fluopyraclostrobin Form 5.

[0174] 5.2 About 1 mmol of the compound of formula I and 1 mmol of 2,6-dihydroxybenzoic acid were weighed into a container in a molar ratio of 1:1. 1.5 mL of acetonitrile was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 5.

[0175] 5.3 About 1 mmol of the compound of formula I and 3 mmol of 2,6-dihydroxybenzoic acid were weighed into a container in a molar ratio of 1:3. 3.0 mL of acetonitrile was added to dissolve the mixture. The mixture was filtered and evaporated at room temperature to obtain Flupyraclostrobin Form 5.

[0176] 5.4 Approximately 3 mmol of the compound of formula I and 1 mmol of γ-aminobutyric acid were weighed into a container in a molar ratio of 3:1, and 3.0 mL of acetonitrile was added to dissolve the mixture. The mixture was suspended for 24 h and centrifuged. The supernatant was evaporated at room temperature to obtain Fluopyraclostrobin Form 5.

[0177] 5.5 About 1 mmol of the compound of formula I and 1 mmol of γ-aminobutyric acid were weighed into a container in a molar ratio of 1:1, and 2.0 mL of acetonitrile was added to dissolve the mixture. The mixture was suspended for 24 h and centrifuged. The supernatant was evaporated at room temperature to obtain Flupyraclostrobin Form 5.

[0178] 5.6 About 1 mmol of the compound of formula I and 3 mol of γ-aminobutyric acid were weighed into a container in a molar ratio of 1:3, and 3.0 mL of acetonitrile was added for dissolution. The mixture was suspended for 24 h and centrifuged. The supernatant was evaporated at room temperature to obtain Flupyraclostrobin Form 5.

[0179] The XRD pattern of the obtained crystal form 5 is shown in Figure 3, and the diffraction angle data are basically shown in Table 5 below.

[0180] Table 5 XRD data of Form 5

[0181] The DSC spectrum of Form 5 is basically as shown in Figure 6. The endothermic peak corresponds to the melting decomposition process, with an endothermic peak in the range of 60-89°C and a second endothermic peak in the range of 107°C to 120°C.

[0182] The TGA spectrum of Form 5 is substantially as shown in FIG9 , with weight loss of acetonitrile solvent before decomposition.

[0183] In addition, the single crystal X-ray diffraction (SXRD) structure of Form 5 in Example 5 was obtained, as shown in FIG12 , and its parameters are basically as shown in Table 6 below:

[0184] Table 6 Single crystal X-ray diffraction parameters of Form 5

[0185] Example 6: Stability Study of Flupyraclostrobin Crystal Form 3

[0186] 6.1 High temperature stability

[0187] Flupyraclostrobin Form 3 samples from Example 3 were placed in an oven at 60±2°C. After 5 and 10 days, the samples were removed and analyzed by XRPD to examine the temperature stability of the samples. As shown in Figures 13 and 14 , the results demonstrate that Form 3 samples are stable under these conditions.

[0188] 6.2 High humidity stability

[0189] Flupyraclostrobin Form 3 samples from Example 3 were placed in a humidity environment of 90±5%. After 5 and 10 days, the samples were removed and analyzed by XRPD to examine the humidity stability of the samples. As shown in Figures 15 and 16 , the results demonstrate that Form 3 samples are stable under these conditions.

[0190] 6.3 Light stability

[0191] Flupyraclostrobin Form 3 samples from Example 3 were placed under a light intensity of 4500±500 lux. After 5 and 10 days, the samples were removed and analyzed by XRPD to examine the crystal stability of the samples under light exposure. As shown in Figures 17 and 18, the results indicate that Form 3 samples are stable under these conditions.

[0192] Example 7: Stability Study of Flupyraclostrobin Crystal Form 4

[0193] 7.1 High temperature stability

[0194] Flupyraclostrobin Form 4 samples from Example 4 were placed in an oven at 60±2°C. After 5 and 10 days, the samples were removed and analyzed by XRPD to examine the temperature stability of the samples. As shown in Figures 19 and 20, the results indicate that Form 4 samples exhibited poor stability under these conditions.

[0195] 7.2 High humidity stability

[0196] Flupyraclostrobin Form 4 samples from Example 4 were placed in a humidity environment of 90±5%. After 5 and 10 days, the samples were removed and analyzed by XRPD to examine the stability of the sample's crystal form in response to humidity. As shown in Figures 21 and 22 , the results indicate that Form 4 samples exhibited poor stability under these conditions.

[0197] 7.3 Light stability

[0198] Flupyraclostrobin Form 4 samples from Example 4 were placed under a light intensity of 4500±500 lux. After 5 and 10 days, the samples were removed and subjected to XRPD analysis to investigate the stability of the crystal form under light exposure. As shown in Figures 23 and 24, the results indicate that Form 4 samples exhibited poor stability under these conditions.

[0199] Example 8: Stability Study of Flupyraclostrobin Crystal Form 5

[0200] 6.1 High temperature stability

[0201] Flupyraclostrobin Form 5 samples from Example 5 were placed in an oven at 60±2°C. After 5 and 10 days, the samples were removed and analyzed by XRPD to examine the temperature stability of the samples. As shown in Figures 25 and 26 , the results indicate that Form 5 samples exhibited poor stability under these conditions.

[0202] 6.2 High humidity stability

[0203] Flupyraclostrobin Form 5 samples from Example 5 were placed in a humidity environment of 90±5%. After 5 and 10 days, the samples were removed and analyzed by XRPD to examine the stability of the crystal form under humidity. As shown in Figures 27 and 28, the results indicate that Form 5 samples were poorly stable under these conditions.

[0204] 6.3 Light stability

[0205] Flupyraclostrobin Form 5 samples from Example 5 were placed under a light intensity of 4500±500 lux. After 5 and 10 days, the samples were removed and analyzed by XRPD to examine the crystal stability of the samples under light exposure. As shown in Figures 29 and 30, the results indicate that Form 5 samples are stable under these conditions.

[0206] Example 9: Solubility comparison of polymorphs

[0207] The solubility of the polymorphs was studied using the equilibrium method. Excess amounts of Form A, Form B, Form 3, Form 4, and Form 5 were weighed and suspended in water and methanol. After shaking for 24 hours, the solubility was measured using UPLC. The test results are shown in Table 7 below. It can be concluded that Forms 3, Form 4, and Form 5 have greater solubility in methanol than Forms A and B.

[0208] Table 7 Solubility of Flupyraclostrobin Polymorphs (25°C)

[0209] All documents mentioned in this application are incorporated herein by reference, just as if each document were incorporated herein by reference individually. It should also be understood that after reading the above teachings of the present invention, those skilled in the art may make various changes or modifications to the present invention, and that such equivalents also fall within the scope of the claims appended hereto.

Claims

1. A polymorph of the compound represented by formula I, characterized in that: The polymorph is a metastable crystalline form; 2. The polymorph according to claim 1, wherein The polymorph is a metastable crystalline form selected from the group consisting of polymorph 3, polymorph 4, and polymorph 5; Wherein, the X-ray powder diffraction pattern of the polymorph 3 includes 3 or more 2θ values ​​selected from the following group: 10.0±0.2°, 14.6±0.2°, 17.1±0.2°, 19.6±0.2°, 20.3±0.2°, 21.6±0.2°; The X-ray powder diffraction pattern of the polymorph 4 includes 3 or more 2θ values ​​selected from the group consisting of 8.6±0.2°, 9.1±0.2°, 11.9±0.2°, 17.3±0.2°, 18.2±0.2°, and 24.5±0.2°; The X-ray powder diffraction pattern of the polymorph 5 includes 3 or more 2θ values ​​selected from the following group: 7.9±0.2°, 12.0±0.2°, 14.8±0.2°, 17.4±0.2°, 18.7±0.2°, and 25.4±0.2°.

3. The polymorph according to claim 1, wherein The polymorph is a metastable crystalline form selected from the group consisting of polymorph 3, polymorph 4, and polymorph 5; Wherein, the X-ray powder diffraction pattern of the polymorph 3 includes 6 or more 2θ values ​​selected from the following group: 9.7±0.2°, 10.0±0.2°, 13.1±0.2°, 14.6±0.2°, 17.1±0.2°, 17.7±0.2°, 19.6±0.2°, 20.3±0.2°, 21.6±0.2°, 23.2±0.2°, 24.6±0.2°, 26.1±0.2°, 26.6±0.2°, 27.3±0.2°, 30.6±0.2°, 31.0±0.2°, 34.8±0.2°, 36.0±0.2°, 39.4±0.2°, 40.0±0.2°, 40.6±0.2°; The X-ray powder diffraction pattern of the polymorph 4 includes 6 or more 2θ values ​​selected from the group consisting of 8.6±0.2°, 9.1±0.2°, 11.9±0.2°, 13.7±0.2°, 14.9±0.2°, 15.3±0.2°, 16.6±0.2°, 17.3±0.2°, 18.2±0.2°, 18.8±0.2° , 21.4±0.2°, 22.4±0.2°, 22.8±0.2°, 23.7±0.2°, 24.5±0.2°, 25.5±0.2°, 27.3±0.2°, 27.8±0.2°, 29.4±0.2°, 32.1±0.2°, 36.4±0.2°, 38.9±0.2°, 40.1±0.2°; The X-ray powder diffraction pattern of the polymorph 5 includes 6 or more 2θ values ​​selected from the group consisting of: 7.9±0.2°, 9.4±0.2°, 10.2±0.2°, 12.0±0.2°, 14.8±0.2°, 16.4±0.2°, 17.4±0.2°, 18.7±0.2°, 20.1±0.2°, 22.1±0.2° , 22.8±0.2°, 24.3±0.2°, 25.4±0.2°, 26.0±0.2°, 27.3±0.2°, 29.4±0.2°, 30.0±0.2°, 30.9±0.2°, 31.8±0.2°, 34.8±0.2°, 38.8±0.2°, 40.1±0.2°, 41.2±0.2°.

4. The polymorph according to claim 1, wherein The polymorph is a metastable crystalline form selected from the group consisting of polymorph 3, polymorph 4, and polymorph 5; The X-ray powder diffraction pattern of the polymorph 3 is substantially as shown in FIG1 ; The X-ray powder diffraction pattern of the polymorph 4 is substantially as shown in FIG2 ; The X-ray powder diffraction pattern of the polymorph 5 is substantially as shown in FIG3 .

5. The polymorph according to claim 1, wherein The polymorph is a metastable crystalline form selected from the group consisting of polymorph 3, polymorph 4, and polymorph 5; The DSC graph of the polymorph 3 has an endothermic peak in the range of 130-150°C, a crystal transformation peak at 150°C, and a second endothermic peak in the range of 150°C-163°C; The DSC graph of the polymorph 4 has an endothermic peak at 126-141°C, a crystal transformation peak at 141°C, and a second endothermic peak at 141°C-155°C; The DSC graph of the polymorph 5 has an endothermic peak at 60-89°C and a second endothermic peak at 107-120°C.

6. The polymorph according to claim 1, wherein The polymorph is a metastable crystalline form selected from the group consisting of polymorph 3, polymorph 4, and polymorph 5; The DSC diagram of the polymorph 3 is substantially as shown in FIG4 ; The DSC diagram of the polymorph 4 is substantially as represented in FIG5 ; The DSC diagram of the polymorph 5 is substantially as shown in FIG6 .

7. A pesticide composition, characterized in that The composition comprises: (a) the polymorph according to any one of claims 1 to 6, and (b) a pesticide-acceptable carrier.

8. A method for preparing the polymorph according to claim 1, characterized in that: The method comprises the steps of (i): (i-1) providing a first mixed solution, wherein the first mixed solution is obtained by dissolving the compound represented by formula (I), an organic acid, and a solvent; (i-2) suspending the first mixed solution of step (i-1), centrifuging, volatilizing the supernatant, and vacuum drying to obtain the polymorph; or comprising step (ii): (ii-1) providing a second mixed solution, wherein the second mixed solution is obtained by dissolving the compound represented by formula (I), an organic acid, and a solvent; (ii-2) volatilizing the second mixed solution from step (ii-1) and vacuum drying to obtain the polymorph; Wherein, the organic acid is selected from the group consisting of 2,6-dihydroxybenzoic acid, 1-hydroxy-2-naphthoic acid, 3-nitrobenzoic acid, p-hydroxybenzoic acid, D-isoascorbic acid, γ-aminobutyric acid, 3-furoic acid, maleic acid, and itaconic acid; The solvent is selected from the following group: dichloromethane, 1,2-dichloroethane, n-butanol, isopropanol, acetone, tetrahydrofuran (THF), 1,4-dioxane, dibenzyl ether, ethyl formate, methanol, acetonitrile, N,N-dimethylformamide (DMF), N,N-dimethyl sulfoxide (DMSO).

9. Use of the polymorph according to claim 1 or the pesticide composition according to claim 7, characterized in that: Used to prepare preparations for preventing or controlling diseases.

10. Use of the polymorph according to claim 1 or the pesticide composition according to claim 7, characterized in that: Used to prepare preparations for inhibiting harmful microorganisms in agriculture, forestry or horticulture.

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