Polymorphic substance of parazaloquinazafop-p-ethyl as well as preparation method and application of polymorphic substance

Abstract

The invention relates to a crystal form of a compound, in particular to a polymorphic substance of pyrazol-quinclorac-ethyl as well as a preparation method and application of the polymorphic substance of pyrazol-quinclorac-ethyl. The polymorphic substances of the pyrazol-quinclorac ester are white powder, have different molecular accumulation modes microcosmically, and can be divided into multiple crystal forms, and the X-ray powder diffraction pattern of each crystal form is shown in the specification. The invention discloses that each crystal form of pyrazol-quinclorac ester has excellent biological activity and dissolving property.

Description

Technical Field

[0001] The invention relates to a compound crystal form, in particular to a polymorph of quinclorac-butyl and a preparation method and application thereof. Background Art

[0002] 4-HPPD is widely present in aerobic organisms and is mainly involved in the metabolism of tyrosine in organisms. In plants, the metabolite of tyrosine, p-hydroxyphenylpyruvate, generates homogentisic acid under the action of 4-HPPD, which is further converted into the synthesis of plastoquinone and tocopherol, hindering plant photosynthesis, causing the plant to develop albinism symptoms and die. Herbicides targeting 4-HPPD have the characteristics of high efficiency, low toxicity, environmental friendliness, and good safety for subsequent crops. Therefore, 4-HPPD herbicides are a class of herbicides with great research value and development prospects. Mesotrione is a well-known herbicide based on 4-HPPD. Currently, three crystal forms (crystal form I, crystal form II, and crystal form III) have been reported. Among them, crystal form I is relatively stable and suitable for production. However, in the actual production process of crystal form I, it is often accompanied by the production of crystal form II. Crystal form II is a fine needle-shaped metastable crystal form that will clog the filter and make it difficult to filter. At the same time, the thermodynamic instability of crystal form II may lead to instability problems during the storage of the formulation or when the product is applied on site. WO 2007 / 083242 and WO 2006 / 021743 disclose a method for selectively controlling the crystallization of thermodynamically stable crystal form I or kinetically stable crystal form II mesotrione from a mesotrione aqueous solution. In addition, WO2011016018A1 discloses crystal form III with reduced phytotoxicity. Currently, mesotrione still has the problem of low stability. It will degrade at a temperature exceeding 60°C, and heat sources and direct sunlight should be avoided as much as possible during storage.

[0003] At the same time, pyraclostrobin (Formula I compound) is also a kind of 4-HPPD herbicide. Pyraclostrobin (Formula I compound), chemical name is 4-3-(3-chlorophenyl)-1,5-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-carbonyl)-1,3-dimethylpyrazole-5-diethylcarbamate, which is a 4-HPPD herbicide independently developed in my country. A large number of experiments have shown that it has excellent control effects on resistant barnyard grass, lycopodiella, foxtail grass, crabgrass and other grass weeds. There is no report on the crystal form of this substance. The compound has poor water solubility (less than 1ppm), and the dosage used for controlling barnyard grass is relatively large (10-20g / mu).

[0004] Summary of the invention

[0005] In order to overcome the shortcomings of the prior art, an object of the present invention is to provide a polymorph of pyraclostrobin, which has a clear crystal form and the number of crystal waters, exact main crystallographic parameters and atomic spatial positions; another object of the present invention is to provide a method for preparing the polymorph of pyraclostrobin; and a further object of the present invention is to provide the use of the polymorph of pyraclostrobin in the preparation of a herbicide.

[0006] To achieve the above purpose, the present invention adopts the following technical solution:

[0007] A polymorph of quinoline-butyl, wherein the polymorphs of quinoline-butyl are all white powders. Microscopically, they have different crystal stacking modes and can be divided into crystal form I, crystal form II, crystal form III, crystal form IV, crystal form V, crystal form VI, and crystal form VII. The X-ray powder diffraction pattern of each crystal form is as follows, and the X-ray powder diffraction pattern of the crystal form I is selected from the following 2θ values ​​with diffraction peaks:

[0008] 10.5±0.2°, 11.7±0.2°, 12.6±0.2°, 13.7±0.2°, 21.0±0.2°, 21.7±0.2°, 24.0±0.2°; 12.2±0.2°, 16.3±0.2°, 21.6±0.2°, 23.5±0.2°, 13.7±0.2°, 24.0±0.2°, 30.9±0.2° ; 9.3±0.2°, 11.4±0.2°, 16.3±0.2°, 19.9±0.2°, 21.3±0.2°, 22.3±0.2°, 25.2±0.2°; 9.3±0.2°, 10.3±0.2°, 13.3±0.2°, 17.6±0.2°, 21.3±0.2°, 25.8±0.2°, 32.1±0.2°;

[0009] The X-ray powder diffraction spectrum of the crystalline form II has diffraction peaks at the following 2θ values: 11.0±0.2°, 11.5±0.2°, 16.0±0.2°, 16.9±0.2°, 21.1±0.2°, 26.4±0.2°, 27.3±0.2°; 12.2±0.2°, 16.3±0.2°, 21.6±0.2°, 23.5±0.2°, 17.1±0.2°, 21. 1±0.2°, 30.9±0.2°; 9.3±0.2°, 11.4±0.2°, 16.3±0.2°, 19.9±0.2°, 21.3±0.2°, 22.3±0.2°, 25.2±0.2°; 9.3±0.2°, 10.3±0.2°, 11.8±0.2°, 17.6±0.2°, 21.3±0.2°, 25.8±0.2°, 32.1±0.2°;

[0010] The X-ray powder diffraction spectrum of the crystalline form III has diffraction peaks selected from the following 2θ values:

[0011] 6.5±0.2°, 10.9±0.2°, 12.7±0.2°, 17.1±0.2°, 21.1±0.2°, 23.8±0.2°, 27.5±0.2°; 12.2±0.2°, 16.3±0.2°, 21.6±0.2°, 23.5±0.2°, 17.1±0.2°, 21.1±0.2°, 30.9±0.2° ; 9.3±0.2°, 11.4±0.2°, 16.3±0.2°, 19.9±0.2°, 21.3±0.2°, 22.3±0.2°, 25.2±0.2°; 9.3±0.2°, 10.3±0.2°, 11.8±0.2°, 17.6±0.2°, 21.3±0.2°, 25.8±0.2°, 32.1±0.2°;

[0012] The X-ray powder diffraction spectrum of the crystalline form IV has diffraction peaks selected from the following 2θ values:

[0013] 6.5±0.2°, 11.6±0.2°, 13.1±0.2°, 15.4±0.2°, 16.0±0.2°, 21.4±0.2°, 25.4±0.2°; 9.3±0.2°, 20.3±0.2°, 21.4±0.2°, 15.4±0.2°, 21.3±0.2°, 22.3±0.2°, 25.2±0.2°; 9.3±0.2°, 11.6±0.2°, 13.3±0.2°, 17.6±0.2°, 21.6±0.2°, 21.6±0.2°, 25.8±0.2°;

[0014] The X-ray powder diffraction spectrum of the crystalline form V has diffraction peaks selected from the following 2θ values:

[0015] 6.4±0.2°, 11.7±0.2°, 12.8±0.2°, 13.6±0.2°, 14.6±0.2°, 25.7±0.2°, 27.2±0.2°; 12.2±0.2°, 16.3±0.2°, 21.6±0.2°, 23.5±0.2°, 13.7±0.2°, 24.0±0.2°, 30.9±0.2° ; 9.3±0.2°, 11.4±0.2°, 12.8±0.2°, 13.6±0.2°, 21.3±0.2°, 22.3±0.2°, 25.2±0.2°; 5.4±0.2°, 11.7±0.2°, 13.3±0.2°, 17.6±0.2°, 21.3±0.2°, 25.8±0.2°, 32.1±0.2°;

[0016] The crystal form VI is amorphous, and its X-ray powder diffraction spectrum shows a mantou peak at (3-35°);

[0017] The X-ray powder diffraction spectrum of the crystalline form VII has diffraction peaks selected from the following 2θ values:

[0018] 10.5±0.2°, 11.2±0.2°, 13.6±0.2°, 16.5±0.2°, 17.6±0.2°, 21.1±0.2°, 24.5±0.2°; 13.1±0.2°, 16.5±0.2°, 21.6±0.2°, 23.5±0.2°, 13.7±0.2°, 24.5±0.2°, 30.9±0.2° ; 9..3±0.2°, 11.4±0.2°, 12.8±0.2°, 17.0±0.2°, 21.3±0.2°, 22.3±0.2°, 25.2±0.2°; 5.4±0.2°, 11.2±0.2°, 13.3±0.2°, 17.6±0.2°, 21.3±0.2°, 26.7±0.2°, 32.1±0.2°.

[0019] The specific structural formula of each crystalline form of pyraclostrobin is The unit cell parameters of the crystal form I are:

[0020]

[0021] Space group: P-1

[0022] The unit cell parameters of the Form II are as follows

[0023]

[0024] Space group: P-1;

[0025] The unit cell parameters of the Form III

[0026]

[0027] Space group: P2 1 / n;

[0028] The crystal form IV unit cell parameters

[0029]

[0030] Space group: P-1;

[0031] The unit cell parameters of the crystalline form VII (hydrate)

[0032]

[0033] Space group: P-1.

[0034] A method for preparing the polymorph of pyraclostrobin, comprising adding 50-1000 mg of pyraclostrobin (compound of formula I) into 2 ml of solvent at 5-100° C., mixing and drying to obtain corresponding crystalline pyraclostrobin; the solvent is one or more of methanol, ethyl acetate, acetonitrile, tetrahydrofuran, acetone, dioxane, chloroform, N,N-dimethylformamide, methyl tert-butyl ether, ether, n-hexane, cyclohexane, isopropanol, toluene, methyl oleate, and dichloromethane.

[0035] When the solvent is one or more of methanol, ethyl acetate, acetonitrile, tetrahydrofuran, acetone, dioxane, chloroform, and N,N-dimethylformamide, crystalline form I of quinoxaline can be obtained;

[0036] When the solvent is one or more of methyl tert-butyl ether, ethyl ether, n-hexane, cyclohexane, isopropanol, toluene, and methyl oleate, pyraclostrobin in crystal form II can be obtained;

[0037] When the solvent is dichloromethane, pyraclostrobin of crystal form V can be obtained.

[0038] A method for preparing the polymorph of quinclorac, comprising adding a solvent to 500 mg of quinclorac (compound of formula I) to completely dissolve it, filtering, stirring at room temperature, adding water to the solution until a solid precipitates, and then filtering and drying to obtain the crystalline form VII of quinclorac.

[0039] The solvent is one or more of acetonitrile, butanone and chloroform.

[0040] A method for preparing a polymorph of quinclorac-butyl is disclosed, wherein quinclorac-butyl (compound of formula I) is heated to 50-300° C., then cooled to below 200° C., and the corresponding crystal form of quinclorac-butyl is obtained by standing and crystallizing.

[0041] Generally speaking, a relatively fast heating rate (greater than 5°C / min (generally not exceeding 30°C / min)) will yield Form III, and a relatively slow heating rate (5°C / min) will generally yield Form IV.

[0042] A method for preparing the polymorph of quinclorac-butyl is provided, wherein quinclorac-butyl (compound of formula I) is heated to 50-300° C., then cooled to room temperature, and allowed to stand to obtain the crystalline form VI of quinclorac-butyl.

[0043] An application of the polymorphs of quinclorac-butyl, and an application of each crystalline form of quinclorac-butyl in the preparation of herbicides.

[0044] The advantages of the present invention are:

[0045] The invention provides 7 polymorphs of pyraclostrobin (crystal form I, crystal form II, crystal form III, crystal form IV, crystal form V, crystal form VI and crystal form VII (hydrate)), the preparation method of each crystal form is simple, the obtained crystal forms, crystal form I, crystal form II, crystal form III, crystal form IV and crystal form VII (hydrate) have clear crystal forms and the number of crystal waters, clear main crystallographic parameters and exact atomic spatial positions, and are suitable for large-scale promotion and application.

[0046] The polymorphs of pyraclostrobin of the present invention have excellent biological activity. Compared with crystal form I, the solubility of other crystal forms is improved, and thus the herbicidal activity thereof can be further improved, wherein the herbicidal activity of crystal forms II and VII is more prominent, and the obtained crystal forms are suitable for large-scale promotion and application. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Figure 1 The X-ray powder diffraction pattern (PXRD) of pyraclostrobin crystalline form I provided in an embodiment of the present invention.

[0048] Figure 2 This is a single crystal structure diagram of pyraclostrobin crystal form I provided in an embodiment of the present invention.

[0049] Figure 3 The differential scanning calorimetry (DSC) diagram of the pyraclostrobin crystalline form I provided in an embodiment of the present invention.

[0050] Figure 4 This is a thermogravimetric analysis (TG) diagram of pyraclostrobin crystal form I provided in an embodiment of the present invention.

[0051] Figure 5 The X-ray powder diffraction pattern (PXRD) of pyraclostrobin crystalline form II provided in an embodiment of the present invention.

[0052] Figure 6 This is a single crystal structure diagram of pyraclostrobin crystal form II provided in an embodiment of the present invention.

[0053] Figure 7 The differential scanning calorimetry (DSC) diagram of the pyraclostrobin crystal form II provided in an embodiment of the present invention.

[0054] Figure 8 This is a thermogravimetric analysis (TG) diagram of pyraclostrobin crystalline form II provided in an embodiment of the present invention.

[0055] Fig. 9 The X-ray powder diffraction pattern (PXRD) of pyraclostrobin crystalline form III provided in an embodiment of the present invention.

[0056] Fig.10This is a single crystal structure diagram of pyraclostrobin crystal form III provided in an embodiment of the present invention.

[0057] Fig.11 The X-ray powder diffraction pattern (PXRD) of pyraclostrobin crystal form IV provided in an embodiment of the present invention.

[0058] Fig.12 This is a single crystal structure diagram of pyraclostrobin crystal form IV provided in an embodiment of the present invention.

[0059] Fig.13 The X-ray powder diffraction pattern (PXRD) of pyraclostrobin crystal form V provided in an embodiment of the present invention.

[0060] Fig.14 The differential scanning calorimetry (DSC) diagram of the pyraclostrobin crystal form V provided in an embodiment of the present invention.

[0061] Fig.15 This is a thermogravimetric analysis (TG) diagram of pyraclostrobin crystal form V provided in an embodiment of the present invention.

[0062] Fig.16 The X-ray powder diffraction pattern (PXRD) of pyraclostrobin crystal form VI provided in an embodiment of the present invention.

[0063] Fig.17 The differential scanning calorimetry (DSC) diagram of the pyraclostrobin crystal form provided in the embodiments of the present invention is shown.

[0064] Fig.18 The X-ray powder diffraction pattern (PXRD) of the pyraclostrobin crystal form VII (hydrate) provided in an embodiment of the present invention.

[0065] Fig.19 This is a single crystal structure diagram of the pyraclostrobin crystal form VII (hydrate) provided in an embodiment of the present invention.

[0066] Fig. 20 The differential scanning calorimetry (DSC) diagram of the pyraclostrobin crystal form VII (hydrate) provided in an embodiment of the present invention.

[0067] Fig.21 This is a thermogravimetric analysis (TG) diagram of the pyraclostrobin crystal form VII (hydrate) provided in an embodiment of the present invention.

[0068] Fig. 22 This is an X-ray powder diffraction pattern (PXRD) of the stability test of the pyraclostrobin crystal form I at 50°C provided in an embodiment of the present invention.

[0069] Fig.23This is an X-ray powder diffraction pattern (PXRD) of the stability test of the pyraclostrobin crystal form II at 50°C provided in an embodiment of the present invention.

[0070] Fig.24 This is an X-ray powder diffraction pattern (PXRD) of the stability test of the pyraclostrobin crystal form V at 50°C provided in an embodiment of the present invention.

[0071] Fig.25 This is an X-ray powder diffraction pattern (PXRD) of the stability test of the pyraclostrobin crystal form VI at 50°C provided in an embodiment of the present invention.

[0072] Fig.26 This is an X-ray powder diffraction pattern (PXRD) of the stability test of the pyraclostrobin crystal form VII at 50°C provided in an embodiment of the present invention.

[0073] Fig. 27 The X-ray powder diffraction pattern (PXRD) of the pyraclostrobin crystal form I provided in the embodiment of the present invention in a water suspension stability experiment at 25°C.

[0074] Fig.28 This is an X-ray powder diffraction pattern (PXRD) of the pyraclostrobin crystal form II provided in an embodiment of the present invention in a water suspension stability experiment at 25°C.

[0075] Fig.29 This is an X-ray powder diffraction pattern (PXRD) of the pyraclostrobin crystal form V provided in an embodiment of the present invention in a water suspension stability experiment at 25°C.

[0076] Fig.30 The X-ray powder diffraction pattern (PXRD) of the pyraclostrobin crystal form VI provided in the embodiment of the present invention in a water suspension stability experiment at 25°C.

[0077] Fig.31 The X-ray powder diffraction pattern (PXRD) of the pyraclostrobin crystal form VII provided in the embodiment of the present invention in a water suspension stability experiment at 25°C. DETAILED DESCRIPTION

[0078] The present invention is further described below by way of examples. It should be correctly understood that the examples of the present invention are only used to illustrate the present invention, rather than to limit the present invention, so simple improvements to the present invention based on the method of the present invention are within the scope of protection claimed by the present invention.

[0079] Materials used in the experiment: The compound of formula I used can be prepared as described in the Chinese patent specification of patent number ZL201910272386.4, or can be purchased commercially; other materials used in the experiment without indicating the source and specification are all commercially available analytical grade or chemically pure.

[0080] Example 1

[0081] Preparation of Form I:

[0082] 200 mg of pyraclostrobin (compound of formula I) is added to 2 ml of acetonitrile at 5-100° C., mixed and dried to obtain the crystal form of the compound of formula I, i.e., crystal form I;

[0083] The yield of the above-obtained crystal form I was 80% and the purity was 99% (PXRD spectrum confirmed the purity, powder diffractometer model and important parameters: Rigaku SmartLab, Cu-K target (tube pressure 40kV, tube flow 150mA)) (see Figure 1-4 ).

[0084] The X-ray powder diffraction pattern of the crystalline form I has diffraction peaks at the following 2θ values: 10.5±0.2°, 11.7±0.2°, 12.6±0.2°, 13.7±0.2°, 21.0±0.2°, 21.7±0.2°, 24.0±0.2°;

[0085] 12.2±0.2°, 16.3±0.2°, 21.6±0.2°, 23.5±0.2°, 13.7±0.2°, 24.0±0.2°, 30.9±0.2°;

[0086] 9.3±0.2°, 11.4±0.2°, 16.3±0.2°, 19.9±0.2°, 21.3±0.2°, 22.3±0.2°, 25.2±0.2°;

[0087] 9.3±0.2°, 10.3±0.2°, 13.3±0.2°, 17.6±0.2°, 21.3±0.2°, 25.8±0.2°, 32.1±0.2°;

[0088] Unit cell parameters:

[0089]

[0090] Space group: P-1.

[0091] Example 2

[0092] Acquisition of Form II:

[0093] 200 mg of pyraclostrobin (compound of formula I) is added to 2 ml of n-hexane at 5-100° C., mixed and dried to obtain the crystal form of the compound of formula I, i.e., crystal form II;

[0094] The yield of the above-obtained crystal form II is 90% and the purity is 99% (PXRD spectrum confirms the purity, powder diffractometer model and important parameters: Rigaku SmartLab, Cu-K target (tube pressure 40kV, tube flow 150mA)) (see Figure 5-8 ).

[0095] The X-ray powder diffraction pattern of the crystalline form II has diffraction peaks at the following 2θ values: 11.0±0.2°, 11.5±0.2°, 16.0±0.2°, 16.9±0.2°, 21.1±0.2°, 26.4±0.2°, 27.3±0.2°;

[0096] 12.2±0.2°, 16.3±0.2°, 21.6±0.2°, 23.5±0.2°, 17.1±0.2°, 21.1±0.2°, 30.9±0.2°;

[0097] 9.3±0.2°, 11.4±0.2°, 16.3±0.2°, 19.9±0.2°, 21.3±0.2°, 22.3±0.2°, 25.2±0.2°;

[0098] 9.3±0.2°, 10.3±0.2°, 11.8±0.2°, 17.6±0.2°, 21.3±0.2°, 25.8±0.2°, 32.1±0.2°;

[0099] Unit cell parameters

[0100]

[0101] Space group: P-1.

[0102] Example 3

[0103] Acquisition of Form III:

[0104] 5 mg of pyraclostrobin (compound of formula I) was heated to 210° C. at a rate greater than 5° C. / min (in this embodiment, the temperature was increased at a rate of 10° C. / min) and then cooled to 195° C. to obtain the compound crystal form III by standing and crystallizing;

[0105] The yield of the prepared form III was greater than 95%, and the purity was above 99% (the purity was confirmed by single crystal diffractometer, instrument model and important parameters: Rigaku 007Saturn 70 (Rigaku, Japan) instrument, Mo target Kα ray Collected at 113.15k) (see Figure 9-10 ).

[0106] The X-ray powder diffraction spectrum of the crystalline form III has diffraction peaks selected from the following 2θ values:

[0107] 6.5±0.2°, 10.9±0.2°, 12.7±0.2°, 17.1±0.2°, 21.1±0.2°, 23.8±0.2°, 27.5±0.2°;

[0108] 12.2±0.2°, 16.3±0.2°, 21.6±0.2°, 23.5±0.2°, 17.1±0.2°, 21.1±0.2°, 30.9±0.2°;

[0109] 9.3±0.2°, 11.4±0.2°, 16.3±0.2°, 19.9±0.2°, 21.3±0.2°, 22.3±0.2°, 25.2±0.2°;

[0110] 9.3±0.2°, 10.3±0.2°, 11.8±0.2°, 17.6±0.2°, 21.3±0.2°, 25.8±0.2°, 32.1±0.2°;

[0111] Unit cell parameters

[0112]

[0113] Space group: P2 1 / n.

[0114] Example 4

[0115] The preparation of Form IV is obtained by the following different methods:

[0116] 5 mg of pyraclostrobin (compound of formula I) was heated to 205° C. at a rate of 5° C. / min, and then cooled to 196° C., and crystallized by standing to obtain the compound crystal form IV;

[0117] The yield of the prepared crystal form IV is greater than 95%, and the purity is above 99% (the purity is confirmed by single crystal diffractometer, instrument model and important parameters: Rigaku 007Saturn 70 (Rigaku, Japan) instrument, Mo target Kα ray Collected at 113.15k) (see Figure 11-12 ).

[0118] The X-ray powder diffraction spectrum of the crystalline form IV has diffraction peaks selected from the following 2θ values:

[0119] 6.5±0.2°, 11.6±0.2°, 13.1±0.2°, 15.4±0.2°, 16.0±0.2°, 21.4±0.2°, 25.4±0.2°;

[0120] 9.3±0.2°, 20.3±0.2°, 21.4±0.2°, 15.4±0.2°, 21.3±0.2°, 22.3±0.2°, 25.2±0.2°;

[0121] 9.3±0.2°, 11.6±0.2°, 13.3±0.2°, 17.6±0.2°, 21.6±0.2°, 21.6±0.2°, 25.8±0.2°;

[0122] Unit cell parameters

[0123]

[0124] Space group: P-1.

[0125] Example 5

[0126] Obtaining Form V:

[0127] 1000 mg of pyraclostrobin (compound of formula I) is added to 2 ml of dichloromethane at 25° C., mixed and dried to obtain the crystal form of the compound of formula I, i.e., crystal form V;

[0128] The yield of the above-obtained crystal form V was 95% and the purity was 98% (PXRD spectrum confirmed the purity, powder diffractometer model and important parameters: Rigaku SmartLab, Cu-K target (tube pressure 40kV, tube flow 150mA)) (see Figure 13-15 ).

[0129] The X-ray powder diffraction spectrum of the crystalline form V has diffraction peaks selected from the following 2θ values:

[0130] 6.4±0.2°, 11.7±0.2°, 12.8±0.2°, 13.6±0.2°, 14.6±0.2°, 25.7±0.2°, 27.2±0.2°;

[0131] 12.2±0.2°, 16.3±0.2°, 21.6±0.2°, 23.5±0.2°, 13.7±0.2°, 24.0±0.2°, 30.9±0.2°;

[0132] 9.3±0.2°, 11.4±0.2°, 12.8±0.2°, 13.6±0.2°, 21.3±0.2°, 22.3±0.2°, 25.2±0.2°;

[0133] 1.4±0.2°, 11.7±0.2°, 13.3±0.2°, 17.6±0.2°, 21.3±0.2°, 25.8±0.2°, 32.1±0.2°;

[0134] Example 6

[0135] Obtaining Form VI:

[0136] 5 mg of quinoxaline (compound of formula I) was heated to 230° C., then cooled to 25° C., and allowed to stand to obtain the compound crystal form VI.

[0137] The yield of the prepared crystal form VI is greater than 98%, and the purity is above 99% (PXRD spectrum confirms the purity, powder diffractometer model and important parameters: Rigaku SmartLab, Cu-K target (tube pressure 40kV, tube flow 150mA)) (see Figure 16-17 ).

[0138] The crystal form VI is amorphous, and its X-ray powder diffraction pattern shows a mantou peak at (5-35°).

[0139] Example 7

[0140] Acquisition of Form VII (hydrate):

[0141] Add butanone to 500 mg of pyraclostrobin (compound of formula I) until it is completely dissolved, filter through an organic filter membrane, stir magnetically at 25° C., add water to the solution until solids precipitate, and then filter and dry to obtain the compound crystalline form VII;

[0142] The yield of the prepared form VII was 85% and the optical purity was 99% (PXRD spectrum confirmed the purity, powder diffractometer model and important parameters: Rigaku SmartLab, Cu-K target (tube pressure 40kV, tube flow 150mA)) (see Figure 18-21 ).

[0143] The X-ray powder diffraction pattern of the crystalline form VII has diffraction peaks at the following 2θ values: 10.5±0.2°, 11.2±0.2°, 13.6±0.2°, 16.5±0.2°, 17.6±0.2°, 21.1±0.2°, 24.5±0.2°;

[0144] 13.1±0.2°, 16.5±0.2°, 21.6±0.2°, 23.5±0.2°, 13.7±0.2°, 24.5±0.2°, 30.9±0.2°;

[0145] 9..3±0.2°, 11.4±0.2°, 12.8±0.2°, 17.0±0.2°, 21.3±0.2°, 22.3±0.2°, 25.2±0.2°;

[0146] 5.4±0.2°, 11.2±0.2°, 13.3±0.2°, 17.6±0.2°, 21.3±0.2°, 26.7±0.2°, 32.1±0.2°;

[0147] Unit cell parameters

[0148]

[0149] Space group: P-1.

[0150] Application Examples

[0151] Solubility test

[0152] 1) At 25°C, the solubility of the crystalline forms obtained in the above examples in water was tested (see the table below). The results showed that the solubility of crystalline forms II and V was significantly better than that of crystalline form I.

[0153]

[0154] 2) Accelerated stability test:

[0155] Take appropriate amount of the crystalline powder obtained in the above embodiment to be tested and put them into respective sample bottles, seal them and place them in a constant temperature box at 50±2℃ for 90 days. Take samples from the constant temperature box on the 10th day, 30th day and 90th day respectively, cool them to room temperature and test their PXRD. The PXRD spectrum ( Figure 22-26 ) to determine the storage and crystal transformation of each crystal form. The test results show that, except for the amorphous form (VI), several other solid forms including the hydrate (crystal form VII) can stably exist within the maximum test period (3 months). The detailed results are as follows:

[0156]

[0157] 3) Suspension stability test in water: At 25°C, the crystalline powder obtained in the above example was placed in a glass sample bottle filled with 10 mL of high-purity water, sealed after adding a magnetic rod, and stirred at 300 rpm. Samples were taken with a pipette at 8 h, 24 h, 48 h, and 168 h, and the PXRD was directly tested after filtration. The PXRD spectrum ( Figure 27-31 ) Comparison and judgment of the suspension stability test of each crystal form in water. Crystal form V was sampled after one week and found to have transformed into a hydrate (crystal form VII). The amorphous form (crystal form VI) first transformed into crystal form II after 8 hours, and then transformed into a hydrate (crystal form VII) after one week. The detailed results are as follows:

[0158]

[0159] Indoor herbicidal activity test:

[0160] In this experiment, barnyard grass was selected as the test weed. The test material cultivation, pesticide preparation and treatment were carried out in accordance with the national agricultural industry standard - Pesticide Indoor Bioassay Test Standard Herbicide Part 4: Activity Assay Test Stem Leaf Spray Method (N / Y1155.4-2006).

[0161] Investigation method 1: Each crystal form is configured with a series of concentration gradient suspensions. After 21 days of indoor test treatment, the growth status of the tested barnyard grass is observed and recorded, and the fresh weight of the aboveground part is weighed. The fresh weight control effect E (%) of each crystal form is calculated and compared. E = (CT) / C * 100, where E is the fresh weight control effect, C is the fresh weight of the aboveground part of the control barnyard grass, and T is the fresh weight of the aboveground part of the treated barnyard grass. The logarithm of the dosage of the drug and the probability value of the control effect are regressed using DPS or SPSS standard statistical software to calculate the ED of each crystal form. 98 (98% effective drug dose) and 95% confidence interval. The statistical analysis of the test results is as follows:

[0162]

[0163] Investigation method 2: After 21 days of treatment with 1.25g / mu suspension concentrate, the growth status of the test barnyard grass was observed and recorded, and the fresh weight of the aboveground part was weighed. The fresh weight protective effect E(%) of each crystal form was calculated and compared, E=(CT) / C*100, where E is the fresh weight protective effect, C is the fresh weight of the aboveground part of the control barnyard grass, and T is the fresh weight of the aboveground part of the treated barnyard grass.

[0164] Grading evaluation of herbicidal activity:

[0165] Grade A - extremely active, with a protection rate of 90-100%;

[0166] Grade B - high activity, protection efficiency is 80-90%;

[0167] Grade C - high activity, with a protection rate of 70-80%;

[0168] Grade D - medium activity, protection efficiency is 50-70%;

[0169] Grade E - low activity, protection efficiency is 10-50%;

[0170] Class F - almost inactive, protection efficiency is 0-10%;

[0171] Results of indoor herbicidal activity tests of various crystal forms (1.25 g / mu suspension):

[0172] Crystal name Crystalline Form I Crystal form II Crystalline Form VII (hydrate) Rating C A A

[0173] The above barnyard grass activity test results show that under the experimental conditions, the three crystal forms involved in the present invention have great differences in weed control effects, and crystal forms II and VII have significantly better weed control effects than the currently commercially available crystal form I.

[0174] Field trials

[0175] Crop test: Three rice varieties (three leaves and one heart, namely, Gujing, Zhongxianghuangzhan and Xiuzhan 15), three barnyard grass varieties, and one Leptochloa chinensis variety were tested.

[0176] Weed test method: 20m 2 For one plot, each treatment was repeated 3 times. The rice was sprayed on the stems and leaves 12 days after direct seeding. Water was applied 48 hours after spraying and the water was retained for 5-7 days.

[0177] 20 days after the treatment, the treated area and the control area were observed and the weed control efficacy and crop safety were statistically analyzed by visual inspection in the same survey method as in Test Example 1.

[0178] Experimental location: Sanya, Hainan

[0179] The results are listed in Table 9.

[0180] Table 9: Field herbicidal activity test results of compound 2

[0181]

[0182] The above results show that the effect of the crystal forms involved in the field experiment on barnyard grass is consistent with the indoor results, and has an outstanding weed control effect on weeds, while having good safety for wheat. At the same time, crystal forms II and VII have significantly better weed control effects than the currently commercially available crystal form I.

Claims

1. A polymorph of quinazolam, characterized in that: The polymorphs of pyraclostrobin are all white powders. Microscopically, they have different molecular stacking modes and can be divided into Form I, Form II, Form III, Form IV, Form V, Form VI, and Form VII. The X-ray powder diffraction patterns of each form are as follows: The X-ray powder diffraction spectrum of the crystalline form I has diffraction peaks selected from the following 2θ values: 10.5±0.2°、11.7±0.2°、12.6±0.2°、13.7±0.2°、21.0±0.2°、21.7±0.2°、24.0±0.2°； 12.2±0.2°、16.3±0.2°、21.6±0.2°、23.5±0.2°、13.7±0.2°、24.0±0.2°、30.9±0.2°； 9.3±0.2°、11.4±0.2°、16.3±0.2°、19.9±0.2°、21.3±0.2°、22.3±0.2°、25.2±0.2°； 9.3±0.2°、10.3±0.2°、13.3±0.2°、17.6±0.2°、21.3±0.2°、25.8±0.2°、32.1±0.2°； The X-ray powder diffraction spectrum of the crystal form II has diffraction peaks selected from the following 2θ values: 11.0±0.2°、11.5±0.2°、16.0±0.2°、16.9±0.2°、21.1±0.2°、26.4±0.2°、27.3±0.2°； 12.2±0.2°、16.3±0.2°、21.6±0.2°、23.5±0.2°、17.1±0.2°、21.1±0.2°、30.9±0.2°； 9.3±0.2°、11.4±0.2°、16.3±0.2°、19.9±0.2°、21.3±0.2°、22.3±0.2°、25.2±0.2°； 9.3±0.2°、10.3±0.2°、11.8±0.2°、17.6±0.2°、21.3±0.2°、25.8±0.2°、32.1±0.2°； The X-ray powder diffraction spectrum of the crystalline form III has diffraction peaks selected from the following 2θ values: 6.5±0.2°、10.9±0.2°、12.7±0.2°、17.1±0.2°、21.1±0.2°、23.8±0.2°、27.5±0.2°； 12.2±0.2°、16.3±0.2°、21.6±0.2°、23.5±0.2°、17.1±0.2°、21.1±0.2°、30.9±0.2°； 9.3±0.2°、11.4±0.2°、16.3±0.2°、19.9±0.2°、21.3±0.2°、22.3±0.2°、25.2±0.2°； 9.3±0.2°、10.3±0.2°、11.8±0.2°、17.6±0.2°、21.3±0.2°、25.8±0.2°、32.1±0.2°； The X-ray powder diffraction spectrum of the crystalline form IV has diffraction peaks selected from the following 2θ values: 6.5±0.2°、11.6±0.2°、13.1±0.2°、15.4±0.2°、16.0±0.2°、21.4±0.2°、25.4±0.2°； 9.3±0.2°、20.3±0.2°、21.4±0.2°、15.4±0.2°、21.3±0.2°、22.3±0.2°、25.2±0.2°； 9.3±0.2°、11.6±0.2°、13.3±0.2°、17.6±0.2°、21.6±0.2°、21.6±0.2°、25.8±0.2°； The X-ray powder diffraction spectrum of the crystalline form V has diffraction peaks selected from the following 2θ values: 6.4±0.2°、11.7±0.2°、12.8±0.2°、13.6±0.2°、14.6±0.2°、25.7±0.2°、27.2±0.2°； 12.2±0.2°、16.3±0.2°、21.6±0.2°、23.5±0.2°、13.7±0.2°、24.0±0.2°、30.9±0.2°； 9.3±0.2°、11.4±0.2°、12.8±0.2°、13.6±0.2°、21.3±0.2°、22.3±0.2°、25.2±0.2°； 5.4±0.2°、11.7±0.2°、13.3±0.2°、17.6±0.2°、21.3±0.2°、25.8±0.2°、32.1±0.2°； The crystal form VI is amorphous, and its X-ray powder diffraction spectrum shows a mantou peak at (3-35°); The X-ray powder diffraction spectrum of the crystalline form VII has diffraction peaks selected from the following 2θ values: 10.5±0.2°、11.2±0.2°、13.6±0.2°、16.5±0.2°、17.6±0.2°、21.1±0.2°、24.5±0.2°； 13.1±0.2°、16.5±0.2°、21.6±0.2°、23.5±0.2°、13.7±0.2°、24.5±0.2°、30.9±0.2°； 9..3±0.2°、11.4±0.2°、12.8±0.2°、17.0±0.2°、21.3±0.2°、22.3±0.2°、25.2±0.2°； 5.4±0.2°、11.2±0.2°、13.3±0.2°、17.6±0.2°、21.3±0.2°、26.7±0.2°、32.1±0.2°。 2. The polymorph of quinazolam according to claim 1, characterized in that: The specific structural formula of each crystalline form of pyraclostrobin is The unit cell parameters of the crystal form I are: Space group: P-1 The unit cell parameters of the Form II are as follows Space group: P-1; The unit cell parameters of the Form III Space group: P21 / n; The crystal form IV unit cell parameters Space group: P-1; The unit cell parameters of the crystalline form VII (hydrate) Space group: P-1.

3. A method for preparing the polymorph of quinpyraclostrobin according to claim 1, characterized in that: The pyraclostrobin (compound of formula I) is added into a solvent at 5-100° C., mixed and dried to obtain the corresponding crystalline pyraclostrobin; the solvent is one or more of methanol, ethyl acetate, acetonitrile, tetrahydrofuran, acetone, dioxane, chloroform, N,N-dimethylformamide, methyl tert-butyl ether, ethyl ether, n-hexane, cyclohexane, isopropanol, toluene, methyl oleate and dichloromethane.

4. The method for preparing the polymorph of quinpyraclostrobin according to claim 3, characterized in that: When the solvent is one or more of methanol, ethyl acetate, acetonitrile, tetrahydrofuran, acetone, dioxane, chloroform, and N,N-dimethylformamide, crystalline form I of quinoxaline can be obtained; When the solvent is one or more of methyl tert-butyl ether, ethyl ether, n-hexane, cyclohexane, isopropanol, toluene, and methyl oleate, pyraclostrobin in crystal form II can be obtained; When the solvent is dichloromethane, pyraclostrobin of crystal form V can be obtained.

5. A method for preparing the polymorph of quinpyraclostrobin according to claim 1, characterized in that: A solvent is added to quinclorac (compound of formula I) to completely dissolve it, and the mixture is stirred at room temperature and water is added to the solution until a solid precipitates, which is then filtered and dried to obtain the crystalline form VII quinclorac.

6. The method for preparing the polymorph of quinpyraclostrobin according to claim 5, characterized in that: The solvent is one or more of acetonitrile, butanone and chloroform.

7. A method for preparing the polymorph of quinpyraclostrobin according to claim 1, characterized in that: The temperature of quinoxaline (compound of formula I) is raised to 50-300° C., and then cooled to below 200° C. and allowed to stand for crystallization to obtain quinoxaline of the corresponding crystal form (crystal form III or crystal form IV).

8. A method for preparing the polymorph of quinpyraclostrobin according to claim 1, characterized in that: The pyraclostrobin (compound of formula I) is heated to 50-300° C., then cooled to room temperature, and allowed to stand to obtain the crystalline form VI of pyraclostrobin.

9. An application of the polymorph of quinazolam according to claim 1, characterized in that: The invention relates to the application of various crystal forms of quinclorac-butyl in the preparation of herbicides.

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