A polymorph of fluoxastrobin and a preparation method and application thereof

Abstract

The application discloses a polymorph of fluoxastrobin and a preparation method and application thereof. The polymorph is a polymorph of a compound shown in formula I, and the polymorph is a metastable crystal form. The polymorph of the application is induced to form in the presence of an organic acid, and is suitable for preparing a pesticide composition for inhibiting harmful microorganisms, and has a better prevention effect on most diseases caused by Ascomycota, Basidiomycota, Deuteromycota and other fungal domains, such as brown spot, sheath blight, gray mold, snow mold and the like.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of pesticide chemistry, and particularly relates to a polymorph of fluxapyroxad and a preparation method and application thereof. BACKGROUND

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

[0003]

[0004] The pure product is white crystal powder, the melting point is 157 DEG C, and the water solubility is 3.44 mg / L at PH value of 7. The compound is a carboxamide fungicide developed by BASF company, which hinders the metabolism of energy by acting on succinate dehydrogenase in mitochondrial respiratory chain, and then inhibits the growth of pathogenic bacteria, so that the purpose of preventing and treating diseases is achieved. Most of the diseases caused by ascomycetes, basidiomycetes, deuteromycetes and other fungal phyla such as brown spot, sheath blight, gray mold, snow mold and the like have good control effect.

[0005] For the same compound, the solubility may also be different, and in addition, the stability, fluidity, compressibility may also be different. And these physicochemical properties will have a certain influence on the application of the compound. The preparation method of the original compound in patent CN101743225A, the prepared crystal form is named as crystal form A and crystal form B, the crystal form A is generally transparent block crystal, and the crystal B is yellowish needle-like crystal. However, the configuration stability and phase transition stability of the crystal form A are not controlled, the solubility of the crystal form B is low, and the solid state chemical research of fluxapyroxad is needed to improve the water solubility and other physicochemical properties.

[0006] Therefore, the field of the art needs to develop the polymorph of the compound of formula I, and the preparation method is simple, the thermal stability is good, the hygroscopicity is low, the solubility is high, and the production can be scaled up. SUMMARY

[0007] The purpose of the present application is to provide a polymorph of the compound of formula I, which has the advantages of simple preparation method, good thermal stability, low hygroscopicity, high solubility and scalable production, and particularly relates to a polymorph of fluxapyroxad and a preparation method and application thereof.

[0008] In the first aspect of the present application, a polymorph of the compound shown in formula I is provided, and the polymorph is a metastable crystal form.

[0009]

[0010] In another preferred embodiment, the polymorph is a metastable polymorph selected from the group consisting of polymorph 3, polymorph 4, polymorph 5;

[0011] wherein the X-ray powder diffraction pattern of the polymorph 3 comprises 3 or more 2Θ values selected from the group consisting of 10.0±0.2°, 14.6±0.2°, 17.1±0.2°, 19.6±0.2°, 20.3±0.2°, 21.6±0.2°;

[0012] the X-ray powder diffraction pattern of the polymorph 4 comprises 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°, 24.5±0.2°;

[0013] the X-ray powder diffraction pattern of the polymorph 5 comprises 3 or more 2Θ values selected from the group consisting of 7.9±0.2°, 12.0±0.2°, 14.8±0.2°, 17.4±0.2°, 18.7±0.2°, 25.4±0.2°.

[0014] In another preferred embodiment, the polymorph is a metastable polymorph selected from the group consisting of polymorph 3, polymorph 4, polymorph 5;

[0015] wherein the X-ray powder diffraction pattern of the polymorph 3 comprises 6 or more 2Θ values selected from the group consisting of 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°;

[0016] the X-ray powder diffraction pattern of said polymorph Form 4 comprises 6 or more 2theta 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°;

[0017] the X-ray powder diffraction pattern of said polymorph Form 5 comprises 6 or more 2theta 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°.

[0018] In another preferred embodiment, said polymorph is a metastable polymorph selected from the group consisting of polymorph Form 3, polymorph Form 4, polymorph Form 5;

[0019] the X-ray powder diffraction pattern of said polymorph Form 3 is substantially as characterized by Figure 1 ;

[0020] the X-ray powder diffraction pattern of said polymorph Form 4 is substantially as characterized by Figure 2 ;

[0021] the X-ray powder diffraction pattern of said polymorph Form 5 is substantially as characterized by Figure 3 .

[0022] In another preferred embodiment, said polymorph is a metastable polymorph selected from the group consisting of polymorph Form 3, polymorph Form 4, polymorph Form 5;

[0023] the DSC pattern of said polymorph Form 3 has an endothermic peak in the range of 130 to 150 °C, a crystallization peak at 150 °C, and a second endothermic peak in the range of 150 °C to 163 °C;

[0024] The DSC pattern of said polymorph 4 has an endothermic peak at 126-141 °C, a crystallization peak at 141 °C, and a second endothermic peak at 141 °C-155 °C.

[0025] The DSC pattern of said polymorph 5 has an endothermic peak at 60-89 °C, and a second endothermic peak at 107 °C-120 °C.

[0026] In another preferred embodiment, said polymorph is a metastable polymorph selected from the group consisting of polymorph 3, polymorph 4, polymorph 5;

[0027] The DSC pattern of said polymorph 3 is substantially as characterized by Figure 4 ;

[0028] The DSC pattern of said polymorph 4 is substantially as characterized by Figure 5 ;

[0029] The DSC pattern of said polymorph 5 is substantially as characterized by Figure 6 .

[0030] In another preferred embodiment, said polymorph 3 has an X-ray powder diffraction pattern with diffraction angle 2 theta values at 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±0.2°, 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°, 44.2±0.2°.

[0031] In another preferred embodiment, the polymorph Form 4 has an X-ray powder diffraction pattern with peaks at diffraction angles 2Q values 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°, 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°, 38.9 ± 0.2°.

[0032] In another preferred embodiment, the polymorph Form 5 has an X-ray powder diffraction pattern with peaks at diffraction angles 2Q values of 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°, 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°, 38.9 ± 0.2°.

[0033] In a second aspect of the application, there is provided a pesticidal composition comprising:

[0034] (a) the polymorph of the first aspect, and

[0035] (b) a pesticidally acceptable carrier.

[0036] In another preferred embodiment, the pesticidal composition further comprises an active substance selected from the group consisting of an insecticide, a bait, a fungicide, a miticide, a nematicide, a fungicide, a plant growth regulator, a plant disease activator, or a combination thereof.

[0037] In a third aspect of the present application, there is provided a method for preparing the polymorph of the first aspect, the method comprising the step of (i):

[0038] (i-1) providing a first mixture, the first mixture being obtained by dissolving a compound of formula (I), an organic acid and a solvent;

[0039] (i-2) suspending the first mixture of step (i-1), centrifuging, volatilizing the supernatant, and vacuum drying to obtain the polymorph; or

[0040] comprising the step of (ii):

[0041] (ii-1) providing a second mixture, the second mixture being obtained by dissolving a compound of formula (I), an organic acid and a solvent;

[0042] (ii-2) volatilizing the second mixture of step (ii-1), and vacuum drying to obtain the polymorph;

[0043] 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-erythorbic acid, gamma-aminobutyric acid, 3-furoic acid, maleic acid, itaconic acid;

[0044] the solvent is selected from the group consisting of dichloromethane, 1,2-dichloroethane, n-butanol, isopropyl alcohol, acetone, tetrahydrofuran (THF), 1,4-dioxane, benzyl ether, ethyl formate, methanol, acetonitrile, N,N-dimethylformamide (DMF), N,N-dimethyl sulfoxide (DMSO), preferably methanol, acetonitrile.

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

[0046] In another preferred embodiment, the molar volume ratio of the compound of 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, more preferably 0.3-1.2 mol / l.

[0047] In another preferred embodiment, the molar ratio of the compound of formula (I) to the organic acid in step (ii-1) is 0.3-3:1.

[0048] In another preferred embodiment, the molar volume ratio of the compound of 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.

[0049] In another preferred embodiment, the compound of formula (I) in the process is in crystalline Form B.

[0050] In a fourth aspect of the present application, there is provided the use of the polymorph of the first aspect or the pesticidal composition of the second aspect for the preparation of a preparation for preventing or controlling a disease.

[0051] 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.

[0052] In a fifth aspect of the present application, there is provided the use of the polymorph of the first aspect or the pesticidal composition of the second aspect for the preparation of a preparation for inhibiting a harmful microorganism in agriculture, forestry or horticulture.

[0053] In another preferred embodiment, the harmful microorganism is selected from the group consisting of Ascomycetes, Basidiomycetes, Pucciniomycetes, Deuteromycetes or Oomycetes.

[0054] In another preferred embodiment, the preventing or controlling is preventing or controlling a harmful microorganism in agriculture, forestry or horticulture.

[0055] It should be understood that, within the scope of the present application, each of the technical features of the present application described above and each of the technical features specifically described hereinafter (e.g. in the examples) can be combined with each other to form a new or preferred technical solution. Due to the limited space, they are not listed one by one here. BRIEF DESCRIPTION OF DRAWINGS

[0056] Figure 1 XRPD pattern of fluoxastrobin Form 3 is shown.

[0057] Figure 2 XRPD pattern of fluoxastrobin Form 4 is shown.

[0058] Figure 3 XRPD pattern of fluoxastrobin Form 5 is shown.

[0059] Figure 4 DSC pattern of fluoxastrobin Form 3 is shown.

[0060] Figure 5 DSC pattern of fluoxastrobin Form 4 is shown.

[0061] Figure 6 A DSC pattern of fl uazinamid crystal form 5 is shown.

[0062] Figure 7 A TGA pattern of fl uazinamid crystal form 3 is shown.

[0063] Figure 8 A TGA pattern of fl uazinamid crystal form 4 is shown.

[0064] Figure 9 A TGA pattern of fl uazinamid crystal form 5 is shown.

[0065] Figure 10 A NMR pattern of fl uazinamid crystal form 3 is shown.

[0066] Figure 11 A single crystal X-ray diffraction structure of fl uazinamid crystal form 4 is shown.

[0067] Figure 12 A single crystal X-ray diffraction structure of fl uazinamid crystal form 5 is shown.

[0068] Figure 13 A five-day high temperature stability XRPD pattern of fl uazinamid crystal form 3 is shown.

[0069] Figure 14 A ten-day high temperature stability XRPD pattern of fl uazinamid crystal form 3 is shown.

[0070] Figure 15 A five-day high humidity stability XRPD pattern of fl uazinamid crystal form 3 is shown.

[0071] Figure 16 A ten-day high humidity stability XRPD pattern of fl uazinamid crystal form 3 is shown.

[0072] Figure 17 A five-day light stability XRPD pattern of fl uazinamid crystal form 3 is shown.

[0073] Figure 18 A ten-day light stability XRPD pattern of fl uazinamid crystal form 3 is shown.

[0074] Figure 19 A five-day high temperature stability XRPD pattern of fl uazinamid crystal form 4 is shown.

[0075] Figure 20 A ten-day high temperature stability XRPD pattern of fl uazinamid crystal form 4 is shown.

[0076] Figure 21 A five-day high humidity stability XRPD pattern of fl uazinamid crystal form 4 is shown.

[0077] Figure 22 Fluoxastrobin crystalline form 4 ten day high humidity stability XRPD pattern is shown.

[0078] Figure 23 Fluoxastrobin crystalline form 4 five day light stability XRPD pattern is shown.

[0079] Figure 24 Fluoxastrobin crystalline form 4 ten day light stability XRPD pattern is shown.

[0080] Figure 25 Fluoxastrobin crystalline form 5 five day high temperature stability XRPD pattern is shown.

[0081] Figure 26 Fluoxastrobin crystalline form 5 ten day high temperature stability XRPD pattern is shown.

[0082] Figure 27 Fluoxastrobin crystalline form 5 five day high humidity stability XRPD pattern is shown.

[0083] Figure 28 Fluoxastrobin crystalline form 5 ten day high humidity stability XRPD pattern is shown.

[0084] Figure 29 Fluoxastrobin crystalline form 5 five day light stability XRPD pattern is shown.

[0085] Figure 30 Fluoxastrobin crystalline form 5 ten day light stability XRPD pattern is shown. DETAILED DESCRIPTION

[0086] The present inventors, through extensive and in-depth research, for the first time unexpectedly discovered polymorphs of fluoxastrobin, and a preparation method and application thereof by inducing crystallization technology. The solubility of the polymorphs is superior to that of fluoxastrobin crystalline form B. The polymorphs are suitable for preparing a pesticide composition for inhibiting harmful microorganisms, and have better prevention effects on most diseases caused by Ascomycota, Basidiomycota, Deuteromycota and the like, such as brown spot, sheath blight, gray mold, snow mold leaf blight and the like. On this basis, the present inventors completed the present application.

[0087] Explanation of terms

[0088] Unless otherwise defined, 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 application belongs.

[0089] As used herein, the term "about," when used in reference to a particular recited numerical value, means that the value can vary from the recited value by not more than 1%. 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.).

[0090] As used herein, the terms "containing" or "including" can be open, semi-closed and closed. In other words, the terms also include "consisting essentially of or "consisting of.

[0091] As used herein, the term "n or more 2-theta values selected from the group consisting of" means any positive integer n and greater (e.g., n, n+1,...) up to the number of 2-theta peaks in the group, Nup. For example, "3 or more" includes each positive integer up to Nup, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and so on, as well as ranges such as "4 or more," "5 or more," "6 or more," and so on.

[0092] In another preferred embodiment, the X-ray powder diffraction pattern of the polymorph has a 2-theta value that is within ±0.5°, preferably within ±0.3°, more preferably within ±0.1°.

[0093] Compound of formula I

[0094]

[0095] Fluoxastrobin (compound of formula I), chemical name 3-(difluoromethyl)-1-methyl-N-(3',4',5'-trifluorobiphenyl-2-yl)pyrazole-4-carboxamide. This compound is a carboxamide fungicide developed by BASF, which acts on succinate dehydrogenase in the mitochondrial respiratory chain, hinders the metabolism of energy, and then inhibits the growth of pathogenic fungi, so as to achieve the purpose of preventing and treating diseases. It has good effect on most diseases caused by Ascomycetes, Basidiomycetes, Deuteromycetes and other fungal phyla, such as brown spot, sheath blight, gray mold, snow mold and so on.

[0096] Polymorph

[0097] A solid exists either in amorphous form or in crystalline form. In the case of crystalline form, the molecules are positioned within a three-dimensional lattice site. When a compound crystallizes out of solution or slurry, it can crystallize in different space lattices (this property is known as "polymorphism") to form crystals having different crystalline forms, which are known as "polymorphs". Different polymorphs of a given substance can differ from each other in one or more physical properties (such as solubility and dissolution rate, true specific gravity, crystal shape, packing, flow properties, and / or solid state stability).

[0098] Crystallization

[0099] ​Crystallization at production scale can be accomplished by manipulating the solution so that the solubility limit of the compound of interest is exceeded. This can be done by a variety of methods, for example, dissolving the compound at a relatively high temperature and then cooling the solution below the solubility limit. Alternatively, the volume of liquid can be reduced by boiling, evaporation at atmospheric pressure, drying under vacuum or by some other method. The solubility of the compound of interest can be reduced by adding an antisolvent or a solvent in which the compound has a low solubility or a mixture of such solvents. There are also new crystallization techniques that can induce the growth of polymorphs by the addition of additives or polymers.

[0100] Induced crystallization techniques

[0101] Induced crystallization techniques are techniques that control the formation of seeds, the growth of crystals and the shape of crystals by external means, the induced media mainly include solvents, additives, etc. Additives can be selected by functional group interaction strategy, and special additives can also be selected by structural similarity. The introduction of additives can form potential interactions with solute molecules, adjust the solution environment and change the crystallization conditions, so that metastable crystals can grow smoothly. Induced crystallization techniques have wide application prospects in the field of drug preparation, and provide new research ideas and technical means for exploring the mechanism of crystal growth and morphology control.

[0102] Solvate

[0103] During the contact between the compound or drug molecules and the solvent molecules, it is difficult to avoid the situation that the solvent molecules and the compound molecules form a co-crystal and remain in the solid material due to external and internal conditions. The material formed after the compound and the solvent are crystallized is called a solvate. The types of solvents that are easy to form solvates with organic compounds are water, methanol, benzene, ethanol, ether, aromatic hydrocarbons, heterocyclic aromatic hydrocarbons, etc.

[0104] Hydrate is a special solvate. In the pharmaceutical industry, whether in the synthesis of bulk drugs, drug preparation, drug storage and drug activity evaluation, hydrates have a separate discussion value due to their special nature.

[0105] In the present application, the crystal of the compound represented by formula (I) can be a non-solvate or a solvate.

[0106] Pesticide composition

[0107] The "active ingredient" or "active compound" in the pesticide composition described in the present application refers to the compound of formula (I) described in the present application, especially the compound of formula (I) in the crystal form of the present application.

[0108] The "active ingredient" or "active compound" and the pesticidal composition of the present application can be used for preventing or controlling diseases; or for inhibiting harmful microorganisms in agriculture, forestry or horticulture.

[0109] Differential scanning calorimetry analysis

[0110] Differential scanning calorimetry analysis, also known as "differential calorimetry scanning analysis" (DSC), is a technique for measuring the relationship between the energy difference between a measured substance and a reference substance and the temperature during heating. The peak position, shape and peak number on the DSC spectrum are related to the properties of the substance, so it can be used qualitatively to identify the substance. The method is commonly used in the art to detect various parameters such as phase transition temperature, glass transition temperature and reaction heat of the substance.

[0111] Preparation method

[0112] In the preparation of the polymorphs of fluazinam, the present application adopts the strategy of induced crystallization technology, and uses solvent evaporation method or grinding method by introducing organic acid as an additive.

[0113] Use

[0114] The present application provides the use of crystal form 3, crystal form 4 and crystal form 5 and the pesticidal composition thereof, which has high efficiency and broad spectrum against most diseases caused by fungi in Ascomycota, Basidiomycota, Deuteromycota and other fungal phyla, such as brown spot, sheath blight, gray mold, snow mold and so on.

[0115] Compared with the prior art, the present application has the following beneficial effects:

[0116] (1) The crystal form 3, crystal form 4 and crystal form 5 of the compound of formula I of the present application have good solubility, which is superior to the existing fluazinam crystal form B in solubility.

[0117] (2) The preparation method of the crystal form 3, crystal form 4 and crystal form 5 of the compound of formula I of the present application is novel, and is suitable for further research on the induced crystallization mechanism.

[0118] (3) The crystal form 3, crystal form 4 and crystal form 5 of the compound of formula I of the present application can be used for preventing or controlling diseases; or for inhibiting harmful microorganisms in agriculture, forestry or horticulture.

[0119] The present application will be further described in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present application and not to limit the scope of the present application. The experimental methods in the following examples are not specified, which are usually carried out according to the conventional conditions, or according to the conditions recommended by the manufacturer. Unless otherwise specified, percentages and parts are by weight.

[0120] Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this application belongs. Also, any method and material similar or equivalent to those described herein can be used in the practice of the present application. The methods and materials described herein are illustrative only and not intended to be limiting.

[0121] The experimental materials and reagents used in the following examples were obtained from commercial sources unless otherwise indicated. Room temperature or ambient temperature means 4°C to 25°C, preferably 15 to 25°C.

[0122] Test Methods:

[0123] XRD (X-ray powder diffraction) method: Instrument model: Rigaku Ultima IV, Target: Cu-Ka (40 kV, 40 mA), using D / tex Ultra detector at room temperature. Scan range from 3° to 45° in 2Q interval, scan speed 20° / min.

[0124] Measurement differences associated with such X-ray powder diffraction analysis results arise from 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 arise when determining peak positions), and (e) properties of the material (e.g., preferred orientation errors). Calibration errors and sample height errors often result in shifts of all peaks in the same direction. Small differences in sample height when using a flat holder will result in large shifts in XRD peak positions. Systematic studies have shown that a 1 mm difference in sample height can result in peak shifts of up to 1° in 2Q. These shifts can be identified from the X-ray diffraction pattern and can be eliminated by either compensating for the shifts (using a systematic calibration factor for all peak position values) or recalibrating the instrument. As noted above, measurement errors from different instruments can be corrected by applying a systematic calibration factor to bring the peak positions into agreement.

[0125] TGA (Thermogravimetric Analysis) method: Instrument model: TA Q500 Thermogravimetric Analyzer, using N2 atmosphere, heating rate 10 °C / min.

[0126] DSC (Differential Scanning Calorimetry) method: Instrument model: TA Q2000 Differential Scanning Calorimeter, using N2 atmosphere, heating rate 10 °C / min.

[0127] Single Crystal X-ray Diffraction (SCXRPD) method: Instrument model: Bruker D8 QUEST Single Crystal Diffractometer, test method: Cu-Ka radiation APEX3 was used to integrate and simplify the data and the crystal structure was refined in the Olex2 software via the SHELXL program. The simulated XRPD pattern of the single crystal and the single crystal structure diagram were performed in the Mercury 4.3 software.

[0128] Example 1: Preparation of Form A

[0129] The preparation method of Form A was similar to the preparation method of Form A in the patent CN101743225A by rapid rotary evaporation under reduced pressure. 50 mg of the compound of Formula I was dissolved in 3.0 mL of dichloromethane, and rapid rotary evaporation was carried out at 50°C. The crystalline sample was analyzed by powder X-ray diffraction (PXRD) to be Form A.

[0130] Example 2: Preparation of Form B

[0131] The preparation method of Form B was similar to Example 3 in the patent CN101743225A. The preparation method of Form B was crystallized from the solvent by solvent evaporation at room temperature. 20 mg of the compound of Formula I was dissolved in a solvent, and the crystalline powder was obtained by evaporation at room temperature. 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 the solvents were evaporated, the crystalline sample was analyzed by powder X-ray diffraction (PXRD) to be Form B.

[0132] Example 3: Preparation of Form 3

[0133] 3.1 About 3 mmol of the compound of Formula I and 1 mmol of 3-nitrobenzoic acid were weighed in a container at a molar ratio of 3:1, 3.0 mL of anhydrous methanol was added, filtered, and evaporated at room temperature to obtain flubendiamide Form 3.

[0134] 3.2 About 1 mmol of the compound of Formula I and 1 mmol of 3-nitrobenzoic acid were weighed in a container at a molar ratio of 1:1, 1.5 mL of anhydrous methanol was added, filtered, and evaporated at room temperature to obtain flubendiamide Form 3.

[0135] 3.3 About 1 mmol of the compound of Formula I and 3 mmol of 3-nitrobenzoic acid were weighed in a container at a molar ratio of 1:3, 3.0 mL of anhydrous methanol was added, filtered, and evaporated at room temperature to obtain flubendiamide Form 3.

[0136] 3.4 About 3 mmol of the compound of Formula I and 1 mmol of 3-furoic acid were weighed in a container at a molar ratio of 3:1, 3.0 mL of anhydrous methanol was added, filtered, and evaporated at room temperature to obtain flubendiamide Form 3.

[0137] 3.5 About 1 mmol of the compound of formula I and 1 mmol of 3-furoic acid were weighed in a container in a molar ratio of 1 : 1, 1.5 mL of anhydrous methanol was added, filtered, and volatilized at room temperature to obtain Form 3 of fluoxymoxystrobin crystals.

[0138] 3.6 About 1 mmol of the compound of formula I and 3 mmol of 3-furoic acid were weighed in a container in a molar ratio of 1 : 3, 3.0 mL of anhydrous methanol was added, filtered, and volatilized at room temperature to obtain Form 3 of fluoxymoxystrobin crystals.

[0139] 3.7 About 3 mmol of the compound of formula I and 1 mmol of itaconic acid were weighed in a container in a molar ratio of 3: 1, 3.0 mL of anhydrous ethanol was added, filtered, and volatilized at room temperature to obtain Form 3 of fluoxymoxystrobin crystals.

[0140] 3.8 About 1 mmol of the compound of formula I and 1 mmol of itaconic acid were weighed in a container in a molar ratio of 1 : 1, 1.5 mL of anhydrous ethanol was added, filtered, and volatilized at room temperature to obtain Form 3 of fluoxymoxystrobin crystals.

[0141] 3.9 About 1 mmol of the compound of formula I and 3 mmol of itaconic acid were weighed in a container in a molar ratio of 1 : 3, 3.0 mL of anhydrous ethanol was added, filtered, and volatilized at room temperature to obtain Form 3 of fluoxymoxystrobin crystals.

[0142] 3.10 About 3 mmol of the compound of formula I and 1 mmol of 3-nitrobenzoic acid were weighed in a container in a molar ratio of 3: 1, 3.0 mL of acetonitrile was added, filtered, and volatilized at room temperature to obtain Form 3 of fluoxymoxystrobin crystals.

[0143] 3.11 About 1 mmol of the compound of formula I and 1 mmol of 3-nitrobenzoic acid were weighed in a container in a molar ratio of 1 : 1, 1.5 mL of acetonitrile was added, filtered, and volatilized at room temperature to obtain Form 3 of fluoxymoxystrobin crystals.

[0144] 3.12 About 1 mmol of the compound of formula I and 3 mmol of 3-nitrobenzoic acid were weighed in a container in a molar ratio of 1 : 3, 3.0 mL of acetonitrile was added, filtered, and volatilized at room temperature to obtain Form 3 of fluoxymoxystrobin crystals.

[0145] 3.13 About 3 mmol of the compound of formula I and 1 mmol of p-hydroxybenzoic acid were weighed in a container in a molar ratio of 3: 1, 3.0 mL of acetonitrile was added, filtered, and volatilized at room temperature to obtain Form 3 of fluoxymoxystrobin crystals.

[0146] 3.14 About 1 mmol of the compound of formula I and 1 mmol of p-hydroxybenzoic acid were weighed in a container in a molar ratio of 1 : 1, 1.5 mL of acetonitrile was added, filtered, and volatilized at room temperature to obtain Form 3 of fluoxymoxystrobin crystals.

[0147] 3.15 Weigh approximately 1 mmol of compound I and 3 mmol of p-hydroxybenzoic acid into a container at a molar ratio of 1:3, add 3.0 mL of acetonitrile to dissolve, filter, and evaporate at room temperature to obtain fluopyram crystal form 3.

[0148] The XRD pattern of the obtained crystal form 3 is shown in the figure. Figure 1 The basic diffraction angle data are shown in Table 1 below.

[0149] Table 1. XRD data for crystal form 3

[0150]

[0151]

[0152] The DSC spectrum of crystal form 3 is basically as follows Figure 4 As shown, the endothermic peak corresponds to the melting and decomposition process, with an endothermic peak in the range of 130 to 150℃ and a second endothermic peak in the range of 150℃ to 163℃.

[0153] The TGA spectrum of crystal form 3 is basically as follows Figure 7 As shown, there is essentially no weight loss before decomposition.

[0154] The NMR spectrum of crystal form 3 is basically as follows Figure 10 As shown, this proves that its component is fluopyram.

[0155] Example 4: Preparation of crystal form 4

[0156] 4.1 Weigh approximately 3 mmol of compound I and 1 mmol of 2,6-dinitrobenzoic acid into a container at a molar ratio of 3:1, add 3.0 mL of anhydrous methanol to dissolve, filter, and evaporate at room temperature to obtain fluopyram crystal form 4.

[0157] 4.2 Weigh approximately 1 mmol of compound I and 1 mmol of 2,6-dinitrobenzoic acid into a container at a molar ratio of 1:1, add 1.5 mL of anhydrous methanol to dissolve, filter, and evaporate at room temperature to obtain fluopyram crystal form 4.

[0158] 4.3 Weigh approximately 1 mmol of compound I and 3 mmol of 2,6-dinitrobenzoic acid into a container at a molar ratio of 1:3, add 3.0 mL of anhydrous methanol to dissolve, filter, and evaporate at room temperature to obtain fluopyram crystal form 4.

[0159] 4.4 Weigh approximately 3 mmol of compound I and 1 mmol of p-nitrobenzoic acid into a container at a molar ratio of 3:1, add 3.0 mL of anhydrous methanol to dissolve, filter, and evaporate at room temperature to obtain fluopyram crystal form 4.

[0160] 4.5 About 1 mmol of the compound of formula I and 1 mmol of p-nitrobenzoic acid were weighed in a container according to a molar ratio of 1:1, dissolved in 1.5 mL of anhydrous methanol, filtered, and volatilized at room temperature to obtain fl uazinam crystal form 4.

[0161] 4.6 About 1 mmol of the compound of formula I and 3 mmol of p-nitrobenzoic acid were weighed in a container according to a molar ratio of 1:3, dissolved in 3.0 mL of anhydrous methanol, filtered, and volatilized at room temperature to obtain fl uazinam crystal form 4.

[0162] 4.7 About 3 mmol of the compound of formula I and 1 mmol of D-isoascorbic acid were weighed in a container according to a molar ratio of 3:1, dissolved in 3.0 mL of anhydrous ethanol, filtered, and volatilized at room temperature to obtain fl uazinam crystal form 4.

[0163] 4.8 About 1 mmol of the compound of formula I and 1 mmol of D-isoascorbic acid were weighed in a container according to a molar ratio of 1:1, dissolved in 1.5 mL of anhydrous ethanol, filtered, and volatilized at room temperature to obtain fl uazinam crystal form 4.

[0164] 4.9 About 1 mmol of the compound of formula I and 3 mmol of D-isoascorbic acid were weighed in a container according to a molar ratio of 1:3, dissolved in 3.0 mL of anhydrous ethanol, filtered, and volatilized at room temperature to obtain fl uazinam crystal form 4.

[0165] 4.10 About 3 mmol of the compound of formula I and 1 mmol of maleic acid were weighed in a container according to a molar ratio of 3:1, dissolved in 3.0 mL of anhydrous ethanol, filtered, and volatilized at room temperature to obtain fl uazinam crystal form 4.

[0166] 4.11 About 1 mmol of the compound of formula I and 1 mmol of maleic acid were weighed in a container according to a molar ratio of 1:1, dissolved in 1.5 mL of anhydrous ethanol, filtered, and volatilized at room temperature to obtain fl uazinam crystal form 4.

[0167] 4.12 About 1 mmol of the compound of formula I and 3 mmol of maleic acid were weighed in a container according to a molar ratio of 1:3, dissolved in 3.0 mL of anhydrous ethanol, filtered, and volatilized at room temperature to obtain fl uazinam crystal form 4.

[0168] The XRD pattern of the obtained crystal form 4 is shown in Figure 2 , and the diffraction angle data are substantially as shown in Table 2 below.

[0169] Table 2 XRD data of crystal form 4

[0170]

[0171]

[0172] The DSC pattern of crystal form 4 is substantially as shown in Figure 5As shown, the endothermic peak corresponds to the melting and decomposition process, having an endothermic peak in the range of 126-141 °C and a second endothermic peak in the range of 141 °C-155 °C.

[0173] The TGA pattern of Form 4 is substantially as shown in Figure 8 As shown, there is substantially no weight loss before decomposition.

[0174] In addition, the single crystal X-ray diffraction (SXRD) structure of Form 4 in Example 4 was also obtained, as shown in Figure 11 The parameters thereof are substantially as shown in Table 3 below:

[0175] Table 3 Single crystal X-ray diffraction parameters of Form 4

[0176]

[0177]

[0178] Example 5: Preparation of Form 5

[0179] 5.1 About 3 mmol of the compound of Formula I and 1 mmol of 2,6-dihydroxybenzoic acid were weighed in a container according to a molar ratio of 3:1, 3.0 mL of acetonitrile was added to dissolve, filtered, and volatilized at room temperature to obtain the fl uazinam crystal Form 5.

[0180] 5.2 About 1 mmol of the compound of Formula I and 1 mmol of 2,6-dihydroxybenzoic acid were weighed in a container according to a molar ratio of 1:1, 1.5 mL of acetonitrile was added to dissolve, filtered, and volatilized at room temperature to obtain the fl uazinam crystal Form 5.

[0181] 5.3 About 1 mmol of the compound of Formula I and 3 mmol of 2,6-dihydroxybenzoic acid were weighed in a container according to a molar ratio of 1:3, 3.0 mL of acetonitrile was added to dissolve, filtered, and volatilized at room temperature to obtain the fl uazinam crystal Form 5.

[0182] 5.4 About 3 mmol of the compound of Formula I and 1 mmol of γ-aminobutyric acid were weighed in a container according to a molar ratio of 3:1, 3.0 mL of acetonitrile was added to dissolve, suspended for 24 h, and the supernatant was volatilized at room temperature after centrifugation to obtain the fl uazinam crystal Form 5.

[0183] 5.5 About 1 mmol of the compound of Formula I and 1 mmol of γ-aminobutyric acid were weighed in a container according to a molar ratio of 1:1, 2.0 mL of acetonitrile was added to dissolve, suspended for 24 h, and the supernatant was volatilized at room temperature after centrifugation to obtain the fl uazinam crystal Form 5.

[0184] 5.6 About 1 mmol of the compound of Formula I and 3 mmol of γ-aminobutyric acid were weighed in a container according to a molar ratio of 1:3, 3.0 mL of acetonitrile was added to dissolve, suspended for 24 h, and the supernatant was volatilized at room temperature after centrifugation to obtain the fl uazinam crystal Form 5.

[0185] The XRD pattern of the obtained crystal form 5 is shown in Figure 3 , and the diffraction angle data are substantially as shown in Table 4 below.

[0186] Table 4 XRD data of crystal form 5

[0187]

[0188]

[0189] The DSC pattern of crystal form 5 is substantially as shown in Figure 6 , and the endothermic peak corresponds to the melting and decomposition process, having an endothermic peak in the range of 60-89°C, and a second endothermic peak in the range of 107-120°C.

[0190] The TGA pattern of crystal form 5 is substantially as shown in Figure 9 , and there is a weight loss of acetonitrile solvent before decomposition.

[0191] In addition, the single crystal X-ray diffraction (SXRD) structure of crystal form 5 in Example 5 is also obtained, as shown in Figure 12 , and the parameters are substantially as shown in Table 5 below:

[0192] Table 5 Single crystal X-ray diffraction parameters of crystal form 5

[0193]

[0194]

[0195] Example 6: Stability investigation of fluoxastrobin crystal form 3

[0196] 6.1 High temperature stability

[0197] The fluoxastrobin crystal form 3 sample in Example 3 was placed in an oven at 60±2°C, and after 5 days and 10 days, the sample was taken out for XRPD test to investigate the crystal form stability of the sample to temperature. As shown in Figure 13 , Figure 14 , the results showed that the crystal form 3 sample was stable under this condition.

[0198] 6.2 High humidity stability

[0199] The fluoxastrobin crystal form 3 sample in Example 3 was placed in a 90±5% humidity condition, and after 5 days and 10 days, the sample was taken out for XRPD test to investigate the crystal form stability of the sample to humidity. As shown in Figure 15 , Figure 16 , the results showed that the crystal form 3 sample was stable under this condition.

[0200] 6.3 Light stability

[0201] The fluazuronamide Form 3 sample in Example 3 was placed under 4500±500 lux light intensity, and after 5 days and 10 days, the sample was taken out for XRPD test to investigate the crystal form stability of the sample to light. As shown in Figure 17 , Figure 18 indicated, the results showed that the Form 3 sample was stable under this condition.

[0202] Example 7: Stability investigation of fluazuronamide Form 4

[0203] 7.1 High temperature stability

[0204] The fluazuronamide Form 4 sample in Example 4 was placed in a 60±2°C oven, and after 5 days and 10 days, the sample was taken out for XRPD test to investigate the crystal form stability of the sample to temperature. As shown in Figure 19 , Figure 20 indicated, the results showed that the Form 4 sample had poor stability under this condition.

[0205] 7.2 High humidity stability

[0206] The fluazuronamide Form 4 sample in Example 4 was placed under 90±5% humidity, and after 5 days and 10 days, the sample was taken out for XRPD test to investigate the crystal form stability of the sample to humidity. As shown in Figure 21 , Figure 22 indicated, the results showed that the Form 4 sample had poor stability under this condition.

[0207] 7.3 Light stability

[0208] The fluazuronamide Form 4 sample in Example 4 was placed under 4500±500 lux light intensity, and after 5 days and 10 days, the sample was taken out for XRPD test to investigate the crystal form stability of the sample to light. As shown in Figure 23 , Figure 24 indicated, the results showed that the Form 4 sample had poor stability under this condition.

[0209] Example 8: Stability investigation of fluazuronamide Form 5

[0210] 6.1 High temperature stability

[0211] The fluazuronamide Form 5 sample in Example 5 was placed in a 60±2°C oven, and after 5 days and 10 days, the sample was taken out for XRPD test to investigate the crystal form stability of the sample to temperature. As shown in Figure 25 , Figure 26 indicated, the results showed that the Form 5 sample had poor stability under this condition.

[0212] 6.2 High humidity stability

[0213] The fluazuron crystal form 5 sample in Example 5 was placed under 90±5% humidity condition, and after 5 days and 10 days, the sample was taken out for XRPD test to investigate the crystal form stability of the sample to humidity. As shown in Figure 27 , Figure 28 indicated, the results showed that the sample of crystal form 5 was not stable under this condition.

[0214] 6.3 Light stability

[0215] The fluazuron crystal form 5 sample in Example 5 was placed under 4500±500 lux light intensity, and after 5 days and 10 days, the sample was taken out for XRPD test to investigate the crystal form stability of the sample to light. As shown in Figure 29 , Figure 30 indicated, the results showed that the sample of crystal form 5 was stable under this condition.

[0216] Example 9: Comparison of solubility of polymorphs

[0217] The solubility of polymorphs was studied using the equilibrium method. Excess crystal form A, crystal form B, crystal form 3, crystal form 4 and crystal form 5 were suspended in water and methanol, and after shaking for 24 h, the solubility was tested using UPLC, and the test results are shown in Table 6 below, from which it can be concluded that the solubility of crystal form 3, crystal form 4 and crystal form 5 in methanol is greater than that of crystal form A and crystal form B.

[0218] Table 6 Solubility of fluazuron polymorphs (25℃)

[0219] Crystal form Solubility (mg / ml) Crystal form A 22.9 Crystal form B 27.6 Crystal form 3 47.0 Crystal form 4 46.3 Crystal form 5 50.9

[0220] All documents referred to in this disclosure are incorporated by reference herein as if each were individually incorporated by reference. In addition, it is to be understood that various alterations and modifications will become apparent to the skilled artisan after reviewing the above teachings of the present application and that the present application should be limited only by the scope of the claims presented below.

Claims

1. A crystalline form of the compound shown in Formula I, characterized in that, The crystalline form is a metastable polymorph 3, and the X-ray powder diffraction pattern of the polymorph 3 includes the following 2θ values: 10.0±0.2°, 14.6±0.2°, 17.1±0.2°, 19.6±0.2°, 20.3±0.2°, and 21.6±0.2°.

2. The crystalline form of claim 1, characterized by, The X-ray powder diffraction pattern of the polymorph 3 shows diffraction angle 2θ values ​​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±0.2°, and 2... Characteristic peaks are observed at 3.7±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°.

3. The crystalline form as described in claim 1, characterized in that, The X-ray powder diffraction pattern of the polymorph 3 includes the following 2θ values: 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°, and 40.6±0.2°.

4. The crystalline form of claim 1, characterized by, The X-ray powder diffraction pattern of the polymorph 3 is basically characterized as shown in Figure 1.

5. The crystalline form as described in claim 1, characterized in that, The DSC pattern of the polymorph 3 has an endothermic peak in the range of 130 to 150°C, a crystallization peak at 150°C, and a second endothermic peak in the range of 150°C to 163°C.

6. The crystalline form as described in claim 1, characterized in that, The DSC diagram of polymorph 3 is basically represented as shown in Figure 4.

7. A pesticidal composition, characterized by, The composition comprises: (a) the crystalline form as described in any one of claims 1-6, and (b) A pesticide-acceptable carrier.

8. A process for preparing the crystalline form of claim 1, characterized in that, The method includes step (i): (i-1) Provide a first mixture, which is obtained by dissolving the compound of formula (I), an organic acid and a solvent; (i-2) Suspension step (i-1): The first mixture is centrifuged, the supernatant is evaporated, and vacuum dried to obtain the crystalline product; or Including step (ii): (ii-1) A second mixture is provided, which is obtained by dissolving the compound of formula (I), an organic acid and a solvent; (ii-2) volatilizing the second mixed solution of step (ii-1) to obtain the crystal form; 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-erythorbic acid, γ-aminobutyric acid, 3-furoic acid, maleic acid, itaconic acid; the solvent is selected from the group consisting of dichloromethane, 1,2-dichloroethane, n-butanol, isopropyl alcohol, acetone, tetrahydrofuran (THF), 1,4-dioxane, benzyl ether, ethyl formate, methanol, acetonitrile, N,N-dimethylformamide (DMF), N,N-dimethyl sulfoxide (DMSO); the crystal form is polymorph 3; the X-ray powder diffraction pattern of the polymorph 3 includes the 2θ values of 10.0±0.2°, 14.6±0.2°, 17.1±0.2°, 19.6±0.2°, 20.3±0.2°, 21.6±0.2°.

9. The production method according to claim 8, wherein The molar ratio of the compound of formula (I) to the organic acid in step (i-1) is 0.3-3:

1.

10. The production method according to claim 8, wherein The molar volume ratio of the compound of formula (I) and the organic acid to the solvent in step (i-1) is 0.2-1.5 mol / l.

11. The production method according to claim 8, wherein The molar ratio of the compound of formula (I) to the organic acid in step (ii-1) is 0.3-3:

1.

12. The production method according to claim 8, wherein The molar volume ratio of the compound of formula (I) and the organic acid to the solvent in step (ii-1) is 0.5-1.5 mol / l.

13. The production method according to claim 8, wherein The compound of formula (I) in the method is crystal form B.

14. Use of the crystalline form of claim 1 or the pesticidal composition of claim 7, characterized in that, A preparation for preventing or controlling a disease.

15. Use of the crystalline form of claim 1 or the pesticidal composition of claim 7, characterized in that, A preparation for inhibiting harmful microorganisms in agriculture, forestry or horticulture.

Images