CN117050077A

CN117050077A - Polymorphic substance of chloroindole hydrazide, preparation method and preparation processing technology of polymorphic substance

Info

Publication number: CN117050077A
Application number: CN202210486636.6A
Authority: CN
Inventors: 向川; 贾奇; 孙传厚; 马淼; 张方贺; 成道泉; 刘海静; 周芙蓉; 李珂; 刘坤; 王祥传
Original assignee: Shandong Jingbo Agrochemical Technology Co ltd
Current assignee: Shandong Jingbo Agrochemical Technology Co ltd
Priority date: 2022-05-06
Filing date: 2022-05-06
Publication date: 2023-11-14
Also published as: WO2023213174A1

Abstract

The invention relates to a polymorphic substance of chloroindole hydrazide, a preparation method and a preparation processing technology thereof, and belongs to the technical field of pesticides. The invention provides multiple crystal forms of chloroindole hydrazide, a preparation method and a preparation processing technology thereof. The invention makes up that no report on the crystal form of the chloroindole hydrazide exists in the prior art, and provides guarantee for the development of the processing technology of the subsequent preparation.

Description

Polymorphic substance of chloroindole hydrazide, preparation method and preparation processing technology of polymorphic substance

Technical Field

The invention belongs to the technical field of pesticides, and particularly relates to a polymorphic substance of chloroindole hydrazide, a preparation method and a preparation processing technology thereof.

Background

The carboline alkaloid and the derivative thereof have wide biological activity and have the functions of antivirus, antibiosis and the like. The patent CN104744460B mentions that the compound can well inhibit tobacco mosaic virus, capsicum virus, rice virus, tomato virus, sweet potato virus, melon virus, maize dwarf mosaic virus and the like, and can effectively prevent and treat the virus diseases of various crops. Meanwhile, the compound has bactericidal activity on 14 pathogenic bacteria such as cucumber wilt, peanut brown spot, apple ring spot, tomato early blight, wheat gibberella, potato late blight, rape sclerotium, cucumber gray mold, rice sheath blight, phytophthora capsici, rice bakanae, wheat sheath blight, corn small spot and watermelon anthracnose. The compound also has the activity of killing myxomycetes, cotton bollworms, corn borers and culex spinosa.

The chemical name of the chloroindole hydrazide is as follows: (1S, 3S) -N' - (4-chlorobenzenemethylene) -1-methyl-2, 3,4, 9-tetrahydro-1H-pyrido [3,4-b ] indole-3-carboxamide having the structural formula:

the chloroindole hydrazide belongs to tetrahydrocarboline compounds, and a lot of patents are available at present on the aspects of crop antiviral diseases, analysis methods, preparation compositions and application thereof, but the preparation processing properties of the crystalline form and different crystalline forms are not disclosed.

Disclosure of Invention

Aiming at the problem that the related crystal forms of the chloroindole hydrazide are not disclosed in the prior art, the invention provides a polymorph of the chloroindole hydrazide, a preparation method and a preparation processing technology thereof, and aims to solve the problem.

In a first aspect, the present invention provides various crystalline forms of chloroindole hydrazide, wherein:

the crystalline form ix-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ angles: 9.1+ -0.1 °, 14.7+ -0.1 °, 22.5+ -0.1 °, 22.8+ -0.1 °, 23.5+ -0.1 °;

further, the crystalline form ix powder diffraction pattern has characteristic diffraction peaks at the following 2θ angles: 7.2±0.1°, 9.1±0.1°, 14.7±0.1°, 15.5±0.1°, 17.5±0.1°, 18.5±0.1°, 22.5±0.1°, 22.8±0.1°, 23.5±0.1°, 24.2±0.1°, 27.5±0.1°;

form ii X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ angles: 16.2+ -0.1 °, 16.9+ -0.1 °, 20.6+ -0.1 °, 23.2+ -0.1 °, 26.7+ -0.1 °;

further, the form ii X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ angles: 8.4+ -0.1 °, 11.6+ -0.1 °, 16.2+ -0.1 °, 16.9+ -0.1 °, 19.9+ -0.1 °, 20.6+ -0.1 °, 22.6+ -0.1 °, 23.2+ -0.1 °, 24.9+ -0.1 °, 26.7+ -0.1 °, 29.2+ -0.1 °;

the crystalline form iii X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ angles: 18.9±0.1°, 22.1±0.1°, 23.4±0.1°, 24.1±0.1°, 26.1±0.1°;

further, the crystalline form iii X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ angles: 9.3+ -0.1 °, 11.6+ -0.1 °, 14.5+ -0.1 °, 14.9+ -0.1 °, 16.2+ -0.1 °, 18.9+ -0.1 °, 19.1+ -0.1 °, 22.1+ -0.1 °, 23.4+ -0.1 °, 24.1+ -0.1 °, 26.1+ -0.1 °;

the crystalline form iv X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ angles: 9.0+ -0.1 °, 12.6+ -0.1 °, 14.7+ -0.1 °, 23.5+ -0.1 °, 24.2+ -0.1 °;

further, the crystalline form iv X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ angles: 7.2.+ -. 0.1 °, 8.1.+ -. 0.1 °, 9.0.+ -. 0.1 °, 12.1.+ -. 0.1 °, 12.6.+ -. 0.1 °, 14.7.+ -. 0.1 °, 15.5.+ -. 0.1 °, 17.5.+ -. 0.1 °, 18.5.+ -. 0.1 °, 22.4.+ -. 0.1 °, 23.5.+ -. 0.1 °, 24.2.+ -. 0.1 °;

form v X-ray powder diffraction patterns have characteristic diffraction peaks at the following 2θ angles: 19.3±0.1°, 19.6±0.1°, 24.9±0.1°, 26.2±0.1°;

further, the crystalline form v X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ angles: 7.9±0.1°, 14.8±0.1°, 15.0±0.1°, 16.2±0.1°, 18.9±0.1°, 19.2±0.1°, 19.3±0.1°, 19.6±0.1°, 23.4±0.1°, 24.1±0.1°, 24.9±0.1°, 26.2±0.1°, 29.3±0.1°;

the crystalline form vi X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ angles: 16.2+ -0.1 °, 16.9+ -0.1 °, 20.7+ -0.1 °, 23.2+ -0.1 °, 26.8+ -0.1 °, 29.3+ -0.1 °;

further, the crystalline form vi X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ angles: 8.4.+ -. 0.1 °, 11.6.+ -. 0.1 °, 16.2.+ -. 0.1 °, 16.9.+ -. 0.1 °, 17.0.+ -. 0.1 °, 19.9.+ -. 0.1 °, 20.7.+ -. 0.1 °, 22.6.+ -. 0.1 °, 23.2.+ -. 0.1 °, 25.0.+ -. 0.1 °, 26.8.+ -. 0.1 °, 27.3.+ -. 0.1 °, 29.3.+ -. 0.1 °;

the crystalline form vii X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ angles: 15.2 + -0.1 deg., 16.3 + -0.1 deg., 16.9 + -0.1 deg., 20.7 + -0.1 deg., 23.0 + -0.1 deg., 23.3 + -0.1 deg., 26.9 + -0.1 deg., 30.8 + -0.1 deg..

Further, the crystalline form vii X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ angles: 8.4.+ -. 0.1 °, 15.2.+ -. 0.1 °, 16.3.+ -. 0.1 °, 16.9.+ -. 0.1 °, 19.8.+ -. 0.1 °, 20.7.+ -. 0.1 °, 22.7.+ -. 0.1 °, 23.0.+ -. 0.1 °, 23.3.+ -. 0.1 °, 25.1.+ -. 0.1 °, 26.9.+ -. 0.1 °, 29.3.+ -. 0.1 °, 30.8.+ -. 0.1 °.

In a second aspect, the present invention provides a process for the preparation of multiple crystalline forms of chloroindole hydrazide, wherein:

the preparation method of the crystal form I comprises the following steps:

(1) And adding chloroindole hydrazide into the solvent A, heating, stirring and dissolving.

(2) Cooling the mixture obtained in the step (1) by 10-15 ℃, and filtering the mixture while the mixture is hot.

(3) Slowly cooling the filtrate obtained in the step (2) to 0-10 ℃, and preserving heat and stirring for 2-24 h.

(4) Separating out the solid precipitated in the step (3).

(5) Drying the solid of step (4) to obtain form I.

The solvent A is selected from one solvent or a plurality of mixed solvents of tetrahydrofuran, 2-methyltetrahydrofuran and tetrahydrofurfuryl alcohol, and the ratio of the volume (mL) to the mass (g) of the chloroindole hydrazide is 2-20:1.

The drying temperature is 40-80 ℃ and the drying time is 6-18 h.

The preparation method of the crystal form II comprises the following steps:

(1) The chloroindole hydrazide is added to solvent B and heated until the solid is completely dissolved.

(2) Slowly cooling the mixture in the step (1) to 0-10 ℃ and filtering.

(3) Slowly dripping a solvent C into the filtrate obtained in the step (2), and stirring for 2-24 h at a constant temperature.

(4) Separating out the solid precipitated in the step (3).

(5) Drying the solid in step (4) to obtain form ii.

The solvent is selected from N, N-dimethylformamide, N-dimethylacetamide, N-dimethylpropionamide, N-dimethylbutyramide, N-diethylformamide, N-diethylacetamide, N, one solvent or a plurality of mixed solvents of N-diethyl propionamide, N-dipropyl formamide and N, N-dipropyl acetamide, and the ratio of the volume (mL) to the mass (g) of the chloroindole hydrazide is 2-6:1.

The solvent C is selected from one of water, acetone, cyclohexanone, butanone, acetonitrile, propionitrile and butyronitrile, and the volume ratio of the solvent C to the solvent B is 3-12:1.

The drying temperature is 40-80 ℃ and the drying time is 6-18 h.

The preparation method of the crystal form III comprises the following steps:

(1) And adding chloroindole hydrazide into the solvent D, and heating to 80-120 ℃.

(2) Cooling the mixture in the step (1) to 10-30 ℃, filtering while the mixture is hot, and naturally cooling the filtrate to 20-40 ℃.

(3) Slowly dripping a solvent E into the filtrate obtained in the step (2), and stirring for 2-24 h at a constant temperature.

(4) Separating the solid produced in step (3).

(5) Drying the solid in step (4) to obtain form III.

The solvent D is one solvent or a plurality of mixed solvents selected from ethylene glycol and propylene glycol, and the ratio of the volume (mL) to the mass (g) of the chloroindole hydrazide is 2-8:1.

The solvent E is selected from one of water, acetone, cyclohexanone, butanone, methyl acetate, ethyl acetate, acetonitrile, propionitrile and butyronitrile, and the volume ratio of the solvent E to the solvent D is 4-20:1.

The drying temperature is 40-80 ℃ and the drying time is 6-18 h.

The preparation method of the crystal form IV comprises the following steps:

(1) Chloroindole hydrazide is added to solvent F and heated to reflux.

(2) And (3) cooling the mixture in the step (1) to 10-20 ℃ below the reflux temperature, and filtering while the mixture is hot.

(3) Slowly cooling the filtrate obtained in the step (2) to 0-20 ℃, and preserving heat and stirring for 2-24 h.

(4) Separating out the solid precipitated in the step (3).

(5) Drying the solid in the step (4) to obtain the crystal form IV.

The solvent F is one solvent or a mixed solvent of a plurality of solvents selected from 1, 4-dioxane and ethylene glycol dimethyl ether, and the ratio of the volume (mL) to the mass (g) of the chloroindole hydrazide is 4-10:1.

The drying temperature is 40-80 ℃ and the drying time is 6-18 h.

The preparation method of the crystal form V comprises the following steps:

(1) The chloroindole hydrazide is added into the solvent G, and heated for dissolution.

(2) Slowly cooling the mixture in the step (1) to 10-20 ℃ and filtering.

(3) Slowly dripping solvent H into the filtrate obtained in the step (2), and stirring for 2-24H at a constant temperature.

(4) Separating out the solid precipitated in the step (3).

(5) Drying the solid in step (4) to obtain form v.

The solvent G is one solvent or a mixed solvent of a plurality of solvents selected from N-methyl pyrrolidone and N-ethyl pyrrolidone, and the ratio of the volume (mL) to the mass (G) of the chloroindole hydrazide is 2-5:1.

The solvent H is selected from one of water, dichloromethane, chloroform, dichloroethane, acetone, cyclohexanone, butanone, methyl acetate, ethyl acetate, acetonitrile, propionitrile and butyronitrile, and the volume ratio of the solvent H to the solvent G is 3-10:1.

The drying temperature is 40-80 ℃ and the drying time is 6-18 h.

The preparation method of the crystal form VI comprises the following steps:

(1) Chloroindole hydrazide is added to solvent I and heated to reflux.

(2) Slowly cooling the solid-liquid mixture in the step (1) to 0-20 ℃, and preserving heat and stirring for 2-24 h.

(3) The solids of step (2) are separated.

(4) Drying the solid of step (3) to obtain form VI.

The solvent I is selected from one solvent or a plurality of mixed solvents of toluene, dimethylbenzene, ethylbenzene and chlorobenzene, and the ratio of the volume (mL) to the mass (g) of the chloroindole hydrazide is 3-15:1.

The drying temperature is 40-80 ℃ and the drying time is 6-18 h.

The preparation method of the crystal form VII comprises the following steps:

(1) Chloroindole hydrazide is added to solvent J and heated to reflux.

(2) Slowly cooling the solid-liquid mixture in the step (1) to 10-30 ℃, and preserving heat and stirring for 2-24 h.

(3) The solids of step (2) are separated.

(4) Drying the solid in the step (3) to obtain the crystal form VII.

The solvent J is one solvent or a mixed solvent of a plurality of solvents selected from methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol and tertiary butanol, and the ratio of the volume (mL) to the mass (g) of the chloroindole hydrazide is 3-16:1.

The drying temperature is 40-80 ℃ and the drying time is 6-18 h.

In a third aspect, the present invention provides a formulation comprising the crystalline form of chloroindole hydrazide described above, the method of preparation of the formulation being as follows:

grinding by adopting a wet grinding method, mixing the crystal form of the chloroindole hydrazide, an auxiliary agent and water, adding the mixture into a sand mill for sand grinding and dispersing, stopping grinding when the particle size D90=5.0 μm of the sampled and detected material, and filtering out grinding sand to obtain a sample.

The crystal forms of the chloroindole hydrazide are selected from a crystal form I, a crystal form II, a crystal form III, a crystal form IV, a crystal form V, a crystal form VI, a crystal form VII and an uncrystallized chloroindole hydrazide of the chloroindole hydrazide. The auxiliary agent is a macromolecular amphiphilic anionic nonionic surfactant compound SP-SC29 (Jiangsu qingyu chemical engineering Co., ltd.), a polycarboxylate dispersant SP-27001 (Jiangsu qingyu chemical engineering Co., ltd.), a low-foam wetting agent GY-W07 (Beijing Guangyuan Yinong chemical Co., ltd.), xanthan gum, glycol and an organosilicon defoamer XPJ284 (Jiangsu Siemens Yue defoamer Co., ltd.), wherein the mass ratio is: chloroindole hydrazide various crystalline compounds: and (2) a surfactant: polycarboxylate dispersants: low foam wetting agent: xanthan gum: ethylene glycol: silicone defoamer: water=200:60:40:20:3:80:4:2000.

In a fourth aspect, the crystalline form of chloroindole hydrazide described above is used for controlling viral diseases, pathogenic bacteria and insects in crops.

The virus diseases comprise tobacco mosaic virus, pepper virus, rice virus, tomato virus, sweet potato virus, melon virus and maize dwarf mosaic virus.

The pathogenic bacteria include cucumber wilt, peanut brown spot, apple ring spot, tomato early blight, wheat gibberella, potato late blight, rape sclerotium, cucumber gray mold, rice sheath blight, phytophthora capsici, rice bakanae, wheat sheath blight, corn small spot and watermelon anthracnose

The insects include armyworms, cotton bollworms, corn borers, and culex spinosa.

The beneficial effects of the invention are as follows:

the invention provides a plurality of crystal forms of chloroindole hydrazide, which makes up the blank of chloroindole hydrazide in the crystal form field, and the prepared chloroindole hydrazide crystal form has the advantages of good processability in the aspect of preparation processing, high grinding efficiency, good fluidity of the preparation, high suspension rate, low energy consumption in production and high production efficiency

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required to be used in the description of the embodiments or the prior art will be briefly described below, and it will be obvious to those skilled in the art that other drawings can be obtained from these drawings without inventive effort.

Figure 1 is an XRD pattern of the product prepared according to example 1 of the present invention.

Figure 2 is an XRD pattern of the product prepared according to example 5 of the present invention.

Figure 3 is an XRD pattern of the product of example 9 of the present invention.

Figure 4 is an XRD pattern for the product of example 12 of the present invention.

Figure 5 is an XRD pattern for the product of example 15 of the present invention.

Figure 6 is an XRD pattern for the product of example 18 of the present invention.

Figure 7 is an XRD pattern of the product of example 21 of the present invention.

FIG. 8 is an SEM image of the product of example 1 of the present invention.

FIG. 9 is an SEM image of the product of example 5 of the invention.

FIG. 10 is an SEM image of the product of example 9 of the invention.

FIG. 11 is an SEM image of the product of example 12 of the invention.

FIG. 12 is an SEM image of the product of example 15 of the invention.

FIG. 13 is an SEM image of the chloroindole hydrazide starting material used in examples 1 to 23 of the present invention.

Detailed Description

In order to make the technical solution of the present invention better understood by those skilled in the art, the technical solution of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the present invention without making any inventive effort, shall fall within the scope of the present invention.

The chloroindole hydrazide raw material used in the embodiment of the invention is prepared according to the preparation method described in patent CN104744460B, and the uncrystallized chloroindole hydrazide is directly synthesized to obtain a dry product, and is not subjected to further treatment.

The patent uses SmartLab (9 KW) X-ray diffractometer manufactured by Japanese Kabushiki Kaisha, uses a Cu target, and generates X-ray with wavelength of 0.15406nm, detection current of 150mA, detection voltage of 40KV, detection range of 2 theta of 3-75 degrees, detection step length of 0.02 degrees and scanning speed of 1 degree/min.

The ApreoSHiVac scanning electron microscope (ThermoFisher scientific/Czech factory) used in the patent has an operating voltage of 1.0KV, a current of 50pA and a magnification of 500 times to 10000 times.

The sand mill used in the patent is manufactured by Jiangyin Zhuo Ying dry engineering technology Co., ltd; BT-9300ST laser particle sizer, available from Baud instruments, dendong, inc.; an electrothermal constant temperature drying oven, shandong Boke biological industry Co., ltd.

Example 1

Preparation of form I

The non-crystallized chloroindole hydrazide (50 g) is added into tetrahydrofuran (500 mL), stirred and heated to reflux, and the temperature is kept for 1h under the reflux state; cooling to 10deg.C, and filtering while it is hot; slowly cooling the filtrate to 5 ℃, and preserving heat and stirring for 12 hours; filtration and drying of the filter cake at 40℃for 12h gave 43.2g of a white solid in 86.4% yield.

The sample obtained is the crystal form I of the chloroindole hydrazide, the XRD pattern of which is shown in figure 1, and the main data of the sample are shown in the following table 1:

TABLE 1 Crystal form I X-ray diffraction principal data

Sequence number	2θ	Height	I％
				1	7.194	10305	44.5
2	9.055	23026	99.4
				3	14.743	23173	100.0
4	15.539	7821	33.8
				5	17.494	7768	33.5
6	18.544	7490	32.3
				7	22.456	13306	57.4
8	22.803	14603	63.0
				9	23.534	13846	59.8
10	24.229	10198	44.0
				11	27.459	8094	34.9

Example 2

Preparation of form I

Chloroindole hydrazide (50 g) was added to 2-methyltetrahydrofuran (750 mL), stirred and heated to reflux, and incubated for 2h under reflux; cooling to 15 ℃, and filtering while the mixture is hot; slowly cooling the filtrate to 10 ℃, and preserving heat and stirring for 8 hours; filtration and drying of the filter cake at 50℃for 10h gave 39.7g of a white solid in 79.4% yield. The XRD pattern of the sample obtained in example 2 is identical to that of the sample of crystalline form i of chloroindole hydrazide obtained in example 1.

Example 3

Preparation of form I

The uncrystallized chloroindole hydrazide (50 g) was added to tetrahydrofurfuryl alcohol (400 mL), stirred and heated to 80℃for 1h; cooling to 15 ℃, and filtering while the mixture is hot; slowly cooling the filtrate to 10 ℃, and preserving heat and stirring for 12 hours; filtration and drying of the filter cake at 60℃for 12h gave 43.5g of a white solid in 87.0% yield. The XRD pattern of the sample obtained in example 3 is identical to that of the sample of crystalline form I of chloroindole hydrazide obtained in example 1.

Example 4

Preparation of form I

Evenly mixing tetrahydrofuran and 2-methyltetrahydrofuran according to the volume ratio of 1:1 to form a mixed solvent, adding 50g of uncrystallized chloroindole hydrazide into the mixed solvent (600 mL), stirring and heating to reflux, and preserving heat for 1h in the reflux state; cooling to 10deg.C, and filtering while it is hot; slowly cooling the filtrate to 5 ℃, and preserving heat and stirring for 10 hours; filtration and drying of the filter cake at 40℃for 10h gave 41.1g of a white solid in 82.2% yield. The XRD pattern of the sample obtained in example 4 is identical to that of the sample of crystalline form I of chloroindole hydrazide obtained in example 1.

Example 5

Preparation of form II

The uncrystallized chloroindole hydrazide (50 g) was added to N, N-dimethylformamide (150 mL), heated and stirred until the solid was completely dissolved, and incubated at this temperature for 1h; cooling to 5 ℃, and preserving heat for 2 hours; filtering, slowly adding dropwise water (750 mL) to the filtrate, and stirring while dropwise adding; continuously stirring for 4 hours after the dripping is completed; filtering, and drying the filter cake at 70 ℃ for 16h. 44.7g of pale yellow solid was obtained in 89.4% yield.

The sample obtained is the crystal form II of the chloroindole hydrazide, the XRD pattern of which is shown in figure 2, and the main data of the sample are shown in the following table 2:

TABLE 2 Crystal form II X-ray diffraction main data

Sequence number	2θ	Height	I％
				1	8.359	10916	22.2
2	11.594	11544	23.5
				3	16.184	49182	100.0
4	16.856	24912	50.7
				5	19.913	12049	24.5
6	20.610	30526	62.1
				7	22.566	10316	21.0
8	23.156	28429	57.8
				9	24.932	9205	18.7
10	26.736	36321	73.9
				11	29.244	16203	32.9

Example 6

Preparation of form II

The uncrystallized chloroindole hydrazide (50 g) was added to N, N-dimethylformamide (200 mL), heated and stirred until the solid was completely dissolved, and incubated at this temperature for 1h; cooling to 10 ℃, and preserving heat for 3 hours; filtering, slowly adding cyclohexanone (800 mL) dropwise to the filtrate, and stirring while adding dropwise; continuously stirring for 2 hours after the dripping is completed; filtering, and drying the filter cake at 70 ℃ for 16h. 42.2g of pale yellow solid was obtained in 84.4% yield. The XRD pattern of the sample obtained in example 6 is identical to that of the sample of form ii of the chloroindole hydrazide obtained in example 5.

Example 7

Preparation of form II

The uncrystallized chloroindole hydrazide (50 g) was added to N, N-diethylacetamide (250 mL) and heated with stirring until the solid was completely dissolved, and incubated at this temperature for 2h; cooling to 5 ℃, and preserving heat for 1h; filtering, slowly adding propionitrile (2000 mL) dropwise to the filtrate, and stirring while adding dropwise; continuously stirring for 8 hours after the dripping is completed; filtering, and drying the filter cake at 70 ℃ for 16h. 40.8g of a pale yellow solid was obtained in 81.6% yield. The XRD pattern of the sample obtained in example 7 is identical to that of the sample of form ii of the chloroindole hydrazide obtained in example 5.

Example 8

Preparation of form II

Uniformly mixing N, N-diethyl formamide and N, N-diethyl acetamide according to a volume ratio of 1:1 to form a mixed solvent, adding 50g of uncrystallized chloroindole hydrazide into the mixed solvent (250 mL), heating and stirring until the solid is completely dissolved, and preserving heat for 1h at the temperature; cooling to 10 ℃, and preserving heat for 1h; filtering, slowly adding acetonitrile (1250 mL) dropwise to the filtrate, and stirring while adding dropwise; continuously stirring for 10 hours after the dripping is completed; filtering, and drying the filter cake at 70 ℃ for 16h. 41.1g of pale yellow solid was obtained in 82.2% yield. The XRD pattern of the sample obtained in example 8 is identical to that of the sample of form ii of the chloroindole hydrazide obtained in example 5.

Example 9

Preparation of form III

The uncrystallized chloroindole hydrazide (50 g) was added to ethylene glycol (150 mL), stirred and heated to 100 ℃ and incubated at that temperature for 1h; cooling to 15deg.C, filtering, naturally cooling filtrate to 30deg.C, maintaining temperature, and stirring for 1 hr; filtering, slowly adding acetone (750 mL) dropwise to the filtrate, and stirring while adding dropwise; continuously stirring for 5 hours after the dripping is completed; filtering, and drying the filter cake at 70 ℃ for 14h. 36.2g of pale yellow solid was obtained in 72.4% yield.

The sample obtained is crystalline form iii of chloroindole hydrazide, whose XRD pattern is shown in figure 3, with the main data shown in table 3 below.

TABLE 3 Crystal form III X-ray diffraction principal data

Sequence number	2θ	Height	I％
				1	9.279	8479	13.9
2	11.607	13066	21.4
				3	14.527	11791	19.4
4	14.935	8705	14.3
				5	16.245	17443	28.6
6	18.872	55235	90.7
				7	19.096	17468	28.7
8	22.107	19741	32.4
				9	23.380	28256	46.4
10	24.142	53563	87.9
				11	26.148	60925	100.0

Example 10

Preparation of form III

The uncrystallized chloroindole hydrazide (50 g) was added to propylene glycol (200 mL), stirred and heated to 110 ℃ and incubated at that temperature for 1h; cooling to 20deg.C, filtering, naturally cooling filtrate to 25deg.C, and maintaining the temperature for 2 hr; filtering, slowly dripping butyronitrile (800 mL) into the filtrate, and stirring while dripping; continuously stirring for 12 hours after the dripping is completed; filtering, and drying the filter cake at 70 ℃ for 14h. 33.4g of pale yellow solid was obtained in 66.8% yield. The XRD pattern of the sample obtained in example 10 is consistent with the sample of crystalline form iii of chloroindole hydrazide obtained in example 9.

Example 11

Preparation of form III

Uniformly mixing ethylene glycol and propylene glycol according to the volume ratio of 1:1 to form a mixed solvent, adding uncrystallized chloroindole hydrazide (50 g) into the mixed solvent (250 mL), stirring and heating to 105 ℃, and preserving heat for 1h at the temperature; cooling to 25deg.C, filtering while hot, naturally cooling filtrate to 25deg.C, and maintaining the temperature for 3 hr; filtering, slowly adding ethyl acetate (500 mL) dropwise to the filtrate, and stirring while adding dropwise; continuously stirring for 8 hours after the dripping is completed; filtering, and drying the filter cake at 70 ℃ for 14h. 30.0g of pale yellow solid was obtained in 60.0% yield. The XRD pattern of the sample obtained in example 11 is consistent with the sample of crystalline form iii of chloroindole hydrazide obtained in example 9.

Example 12

Preparation of form IV

The uncrystallized chloroindole hydrazide (50 g) was added to 1, 4-dioxane (250 mL), stirred and heated to reflux, and incubated for 1h under reflux; cooling to 20 ℃, and filtering while the mixture is hot; slowly cooling the filtrate to 20 ℃, and preserving heat and stirring for 12 hours; the mixture was filtered, and the cake was dried at 50℃for 12 hours to give 36.7g of white flaky crystals in 73.4% yield.

The sample obtained is crystal form IV of chloroindole hydrazide, its XRD pattern is shown in figure 4, and its main data are shown in table 4 below.

TABLE 4 Crystal form IV X-ray diffraction principal data

Sequence number	2θ	Height	I％
				1	7.158	8349	43.3
2	8.052	7885	40.8
				3	9.022	12949	67.1
4	12.075	7148	37.0
				5	12.637	10520	54.5
6	14.706	15618	80.9
				7	15.501	7963	41.3
8	17.462	9611	49.8
				9	18.531	9947	51.5
10	22.397	9011	46.7
				11	23.506	19303	100.0
12	24.185	11791	61.1

Example 13

Preparation of form IV

Adding uncrystallized chloroindole hydrazide (50 g) into ethylene glycol dimethyl ether (300 mL), stirring and heating to reflux, and preserving heat for 1h under the reflux state; cooling to 15 ℃, and filtering while the mixture is hot; slowly cooling the filtrate to 10 ℃, and preserving heat and stirring for 15h; the mixture was filtered, and the cake was dried at 40℃for 12 hours to give 35.8g of white flaky crystals in a yield of 71.6%. The XRD pattern of the sample obtained in example 13 is identical to that of the sample of form iv of the chloroindole hydrazide obtained in example 12.

Example 14

Preparation of form IV

Uniformly mixing 1, 4-dioxane and ethylene glycol dimethyl ether according to a volume ratio of 1:1 to form a mixed solvent, adding 50g of uncrystallized chloroindole hydrazide into the mixed solvent (200 mL), stirring, heating to reflux, and preserving heat for 1h in a reflux state; cooling to 10deg.C, and filtering while it is hot; slowly cooling the filtrate to 10 ℃, preserving heat and stirring for 18h; filtration and drying of the filter cake at 40℃for 12h gave 38.7g of white flaky crystals in 77.4% yield. The XRD pattern of the sample obtained in example 14 is consistent with the sample of form iv of the chloroindole hydrazide obtained in example 12.

Example 15

Preparation of form V

An uncrystallized chloroindole hydrazide (60 g) was added to N-methylpyrrolidone (180 mL), heated and stirred until the solid was completely dissolved, and incubated at this temperature for 1h; naturally cooling to 10 ℃, and preserving heat for 1h. Filtering, dripping cyclohexanone (1440 mL) into the filtrate, and stirring for 10h after dripping; filtering, and drying the filter cake at 70 ℃ for 14h. 55.8g of pale yellow solid was obtained in 93.0% yield.

The sample obtained was chloroindole hydrazide form v, whose XRD pattern is shown in figure 5, and the main data are shown in table 5 below:

TABLE 5 form V X-ray diffraction main data

Sequence number	2θ	Height	I％
				1	7.937	8362	23.4
2	14.776	22322	62.4
				3	14.972	22667	63.4
4	16.228	8619	24.1
				5	18.878	18833	52.6
6	19.152	8525	23.8
				7	19.342	26995	75.5
8	19.642	34124	95.4
				9	23.417	8644	24.2
10	24.117	18943	53.0
				11	24.863	35772	100.0
12	26.161	24675	69.0
				13	29.303	9754	27.3

Example 16

Preparation of form V

An uncrystallized chloroindole hydrazide (60 g) was added to N-ethyl pyrrolidone (240 mL), heated and stirred until the solid was completely dissolved, and incubated at this temperature for 1h; naturally cooling to 15 ℃, and preserving heat for 2h. Filtering, dropwise adding dichloroethane (1200 mL) into the filtrate, and stirring for 8h after dropwise adding the dichloroethane; filtering, and drying the filter cake at 70 ℃ for 12 hours. 53.8g of a pale yellow solid was obtained in 89.7% yield. The XRD pattern of the sample obtained in example 16 is consistent with the sample of form v of the chloroindole hydrazide obtained in example 15.

Example 17

Preparation of form V

Uniformly mixing N-methyl pyrrolidone and N-ethyl pyrrolidone according to a volume ratio of 1:1 to form a mixed solvent, adding uncrystallized chloroindole hydrazide (60 g) into the mixed solvent (270 mL), heating and stirring until the solid is completely dissolved, and preserving heat for 1h at the temperature; naturally cooling to 20 ℃, and preserving heat for 3 hours. Filtering, dropwise adding methyl acetate (1080 mL) into the filtrate, and stirring for 6h after dropwise adding; filtering, and drying the filter cake at 70 ℃ for 12 hours. 52.5g of pale yellow solid was obtained in 87.5% yield. The XRD pattern of the sample obtained in example 17 is consistent with the sample of form v of the chloroindole hydrazide obtained in example 15.

Example 18

Preparation of Crystal form VI

The uncrystallized chloroindole hydrazide (50 g) was added to toluene (250 mL), stirred and heated to reflux and incubated for 2h; slowly cooling the reaction mixture to 10 ℃, and preserving heat and stirring for 6 hours; filtering, and drying the filter cake at 60 ℃ for 12 hours. 48.1g of yellow solid was obtained in 96.2% yield.

The sample obtained is crystalline form vi of chloroindole hydrazide, whose XRD pattern is shown in figure 6, with the main data shown in table 6 below.

TABLE 6X-ray diffraction main data for crystalline form VI

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Example 19

Preparation of Crystal form VI

The uncrystallized chloroindole hydrazide (50 g) was added to ethylbenzene (500 mL), stirred and heated to reflux and incubated for 1h; slowly cooling the reaction mixture to 15 ℃, and preserving heat and stirring for 10 hours; filtering, and drying the filter cake at 60 ℃ for 12 hours. 46.6g of yellow solid was obtained in 93.2% yield. The XRD pattern of the sample obtained in example 19 is consistent with the sample of crystalline form vi of chloroindole hydrazide obtained in example 18.

Example 20

Preparation of Crystal form VI

Mixing ethylbenzene and chlorobenzene uniformly according to a volume ratio of 1:1 to form a mixed solvent, adding uncrystallized chloroindole hydrazide (50 g) into the mixed solvent (600 mL), stirring, heating to reflux, and preserving heat for 3h; slowly cooling the reaction mixture to 5 ℃, and preserving heat and stirring for 12 hours; filtering, and drying the filter cake at 60 ℃ for 12 hours. 46.0g of yellow solid was obtained in 92.0% yield. The XRD pattern of the sample obtained in example 20 is consistent with the sample of crystalline form vi of chloroindole hydrazide obtained in example 18.

Example 21

Preparation of crystalline form VII

The uncrystallized chloroindole hydrazide (50 g) was added to methanol (200 mL), stirred and heated to reflux and incubated for 3h; slowly cooling the reaction mixture to 10 ℃, and preserving heat and stirring for 10 hours; filtering, and drying the filter cake at 40 ℃ for 12 hours. 47.1g of pale yellow solid was obtained in 94.2% yield.

The sample obtained was crystalline form vii of chloroindole hydrazide, whose XRD pattern is shown in figure 7, with the main data shown in table 7 below.

TABLE 7X-ray diffraction main data for form VII

Sequence number	2θ	Height	I％
				1	8.447	14326	26.2
2	15.234	43440	79.4
				3	16.260	54739	100.0
4	16.926	28122	51.4
				5	19.843	19193	35.1
6	20.723	37045	67.7
				7	22.669	11743	21.5
8	22.963	30162	55.1
				9	23.266	33201	60.7
10	25.055	10936	20.0
				11	26.861	47565	86.9
12	29.346	18867	34.5
				13	30.825	36108	66.0

Example 22

Preparation of crystalline form VII

The uncrystallized chloroindole hydrazide (50 g) was added to isopropanol (300 mL), stirred and heated to reflux, and incubated for 1h; slowly cooling the reaction mixture to 15 ℃, and preserving heat and stirring for 7h; filtering, and drying the filter cake at 50 ℃ for 12 hours. 46.3g of pale yellow solid was obtained in 92.6% yield. The XRD pattern of the sample obtained in example 22 is identical to that of the sample of crystalline form vii of chloroindole hydrazide obtained in example 21.

Example 23

Preparation of crystalline form VII

Uniformly mixing ethanol and n-propanol according to the volume ratio of 1:1 to form a mixed solvent, adding uncrystallized chloroindole hydrazide (50 g) into the mixed solvent (500 mL), stirring, heating to reflux, and preserving heat for 2h; slowly cooling the reaction mixture to 20 ℃, and preserving heat and stirring for 5 hours; filtering, and drying the filter cake at 50 ℃ for 14h. 45.2g of pale yellow solid was obtained in 90.2% yield. The XRD pattern of the sample obtained in example 23 is identical to that of the sample of crystalline form vii of chloroindole hydrazide obtained in example 21.

Formulation examples

The sources of the auxiliary agents used in examples 24 to 36 and comparative examples 1 to 3 of the present invention were:

macromolecular amphiphilic anionic-nonionic surfactant complex SP-SC29: jiangsu Optimu chemical engineering Co., ltd; polyester type macromolecular surfactant GY-D266: beijing Guangyuan Yinong; comb-type macromolecular surfactant SP-2728: jiangsu qingyu chemical industry;

polycarboxylate dispersant SP-27001: jiangsu Optimu chemical engineering Co., ltd; polycarboxylate dispersant GY-D09: beijing Guangyuan Yinong;

low foam wetting agent GY-W07: beijing Guangyuan Yinong chemical Limited liability company;

silicone defoamer XPJ284: jiangsu Saikan defoamer Co., ltd.

Example 24

10 parts of chloroindole hydrazide crystal form I, 3 parts of surfactant complex SP-SC29, 2 parts of dispersing agent SP-27001, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ and 100 parts of water.

Example 25

10 parts of chloroindole hydrazide crystal form II, 3 parts of surfactant complex SP-SC29, 2 parts of dispersing agent SP-27001, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ and 100 parts of water.

Example 26

10 parts of chloroindole hydrazide crystal form III, 3 parts of surfactant complex SP-SC29, 2 parts of dispersing agent SP-27001, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ and 100 parts of water.

Example 27

10 parts of chloroindole hydrazide crystal form IV, 3 parts of surfactant complex SP-SC29, 2 parts of dispersing agent SP-27001, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ and 100 parts of water.

Example 28

10 parts of chloroindole hydrazide crystal form V, 3 parts of surfactant complex SP-SC29, 2 parts of dispersing agent SP-27001, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ and 100 parts of water.

Example 29

10 parts of chloroindole hydrazide crystal form VI, 3 parts of surfactant complex SP-SC29, 2 parts of dispersing agent SP-27001, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ and 100 parts of water.

Example 30

10 parts of chloroindole hydrazide crystal form VII, 3 parts of surfactant complex SP-SC29, 2 parts of dispersing agent SP-27001, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ and 100 parts of water.

Example 31

10 parts of chloroindole hydrazide crystal form I, 3 parts of surfactant GY-D266, 2 parts of dispersing agent SP-27001, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ and 100 parts of water.

Example 32

10 parts of chloroindole hydrazide crystal form I, 3 parts of surfactant GY-D266, 2 parts of dispersing agent GY-D09, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ and 100 parts of water.

Example 33

10 parts of chloroindole hydrazide crystal form I, 3 parts of surfactant SP-2728, 2 parts of dispersing agent SP-27001, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of glycol, 0.2 part of organosilicon defoamer XPJ and 100 parts of water.

Example 34

100 parts of water are added into 10 parts of chloroindole hydrazide crystal form II, 3 parts of surfactant GY-D266, 2 parts of dispersing agent SP-27001, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ.

Example 35

10 parts of chloroindole hydrazide crystal form II, 3 parts of surfactant GY-D266, 2 parts of dispersing agent GY-D09, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ and 100 parts of water.

Example 36

100 parts of water, namely 10 parts of chloroindole hydrazide crystal form II, 3 parts of surfactant SP-2728, 2 parts of dispersing agent SP-27001, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ.

Comparative example 1

10 parts of uncrystallized chloroindole hydrazide, 3 parts of surfactant SP-2728, 2 parts of dispersing agent SP-27001, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ and 100 parts of water.

Comparative example 2

10 parts of uncrystallized chloroindole hydrazide, 3 parts of surfactant complex SP-SC29, 2 parts of dispersing agent SP-2728, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ and 100 parts of water.

Comparative example 3

10 parts of uncrystallized chloroindole hydrazide, 3 parts of surfactant complex SP-SC29, 2 parts of dispersing agent SP-27001, 1 part of wetting agent GY-W07, 0.15 part of xanthan gum, 4 parts of ethylene glycol, 0.2 part of organosilicon defoamer XPJ and 100 parts of water.

Test case

The method for evaluating the processability comprises the following steps:

the grinding time, when the particle size D90 of the sample is ground to 5 mu m, the time is recorded, and the raw medicine is easy to grind when the time is short, so that the grinding efficiency is high and the energy consumption is less;

observing the flowability, suspension rate and flocculation of the sanded sample after water addition;

detecting thermal storage stability, namely placing a sample in an ampoule bottle, sealing, and placing the sample in a constant temperature box at 54 ℃ for 14 days; taking out, cooling to room temperature, and detecting the suspension rate after heat storage and the flocculation phenomenon after water addition.

Note that: the suspension rate test was performed in accordance with CIPAC MT 184.

In the preparation processing examples, the processing of 10% chloroindole hydrazide suspending agent is taken as an example, and the processing verification of different crystal forms of the chloroindole hydrazide raw medicine is carried out, wherein all the examples adopt the same grinding process and process parameters.

After the preparation of the formulations of examples 24 to 36 and comparative examples 1 to 3 was completed, sample comparison and data detection were performed, as shown in table 8 below.

TABLE 8 data comparison results after grinding of examples and comparative examples

From Table 8 above, it can be seen that forms I-V do not undergo creaming during milling, whereas forms VI, VII and uncrystallized chloroindole hydrazide all undergo creaming. Wherein examples 25, 35 and 36 have the shortest time for grinding to a particle size d90=5 μm, and the suspension ratio reaches 98% to 99%, and no flocculation or coalescence phenomenon occurs.

The heat storage observations were made for 14 days for examples 24 to 28, and the specific results are shown in Table 9.

TABLE 9 thermal storage of samples for 14 days results

	Sample state	Microscopic examination phenomenon	Suspension rate/%
				Example 24	Layering-free and knot-free sole	No flocculation and no coalescence	96.5
Example 25	Layering-free and knot-free sole	No flocculation and no coalescence	98.5
				Example 26	Layering-free and knot-free sole	No flocculation and no coalescence	95
Example 27	Layering-free and knot-free sole	No flocculation and no coalescence	94.5
				Example 28	Layering-free and knot-free sole	No flocculation and no coalescence	95
Comparative example 1	Obvious bottoming phenomenon	Obvious flocculation and coalescence	70
				Comparative example 2	Obvious bottoming phenomenon	Obvious flocculation and coalescence	75

As can be seen from tables 8-9, the chloroindole hydrazide form II has the best processing performance; secondly, the crystal form I, the crystal form III, the crystal form V and the crystal form IV are adopted; the three samples of the uncrystallized chloroindole hydrazide, form vi and form vii were the worst to process.

Although the present invention has been described in detail by way of preferred embodiments with reference to the accompanying drawings, the present invention is not limited thereto. Various equivalent modifications and substitutions may be made in the embodiments of the present invention by those skilled in the art without departing from the spirit and scope of the present invention, and it is intended that all such modifications and substitutions be within the scope of the present invention/be within the scope of the present invention as defined by the appended claims. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims

1. Polymorphic form of chloroindole hydrazide, characterized in that the polymorphic form is form i, form ii, form iii, form iv, form v, form vi or form vii.

2. The polymorph of claim 1, wherein the crystalline form ix X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2Θ angles: 9.1+ -0.1 °, 14.7+ -0.1 °, 22.5+ -0.1 °, 22.8+ -0.1 °, 23.5+ -0.1 °;

the crystal form II X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2 theta angles: 16.2+ -0.1 °, 16.9+ -0.1 °, 20.6+ -0.1 °, 23.2+ -0.1 °, 26.7+ -0.1 °;

the crystalline form III X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2 theta angles: 18.9±0.1°, 22.1±0.1°, 23.4±0.1°, 24.1±0.1°, 26.1±0.1°;

the crystalline form v X-ray powder diffraction pattern has characteristic diffraction peaks at the following 2θ angles: 19.3±0.1°, 19.6±0.1°, 24.9±0.1°, 26.2±0.1°;

3. A process for the preparation of the polymorph of claim 1 or 2, wherein the crystalline form i is prepared by:

(1) Adding chloroindole hydrazide into the solvent A, heating, stirring and dissolving;

(2) Cooling the mixture in the step (1) to 10115 ℃, and filtering while the mixture is hot;

(3) Slowly cooling the filtrate in the step (2) to 0110 ℃, and preserving heat and stirring for 2124 hours;

(4) Separating out the precipitated solid in the step (3);

(5) Drying the solid in the step (4) to obtain a crystal form I;

the preparation method of the crystal form II comprises the following steps:

(1) Adding chloroindole hydrazide into the solvent B, and heating until the solid is completely dissolved;

(2) Slowly cooling the mixture in the step (1) to 0110 ℃ and filtering;

(3) Slowly dripping a solvent C into the filtrate obtained in the step (2), and stirring for 2124h at a constant temperature;

(4) Separating out the precipitated solid in the step (3);

(5) Drying the solid in the step (4) to obtain a crystal form II;

the preparation method of the crystal form III comprises the following steps:

(1) Adding chloroindole hydrazide into the solvent D, and heating to 801120 ℃;

(2) Cooling the mixture in the step (1) to 10130 ℃, filtering while the mixture is hot, and naturally cooling the filtrate to 20140 ℃;

(3) Slowly dripping a solvent E into the filtrate obtained in the step (2), and stirring for 2124h at a constant temperature;

(4) Separating the solid produced in step (3);

(5) Drying the solid in the step (4) to obtain a crystal form III;

the preparation method of the crystal form IV comprises the following steps:

(1) Adding chloroindole hydrazide into the solvent F, and heating to reflux;

(2) Cooling the mixture in the step (1) to 10120 ℃ below the reflux temperature, and filtering while the mixture is hot;

(3) Slowly cooling the filtrate in the step (2) to 0120 ℃, and preserving heat and stirring for 2124 hours;

(4) Separating out the precipitated solid in the step (3);

(5) Drying the solid in the step (4) to obtain a crystal form IV;

the preparation method of the crystal form V comprises the following steps:

(1) Adding chloroindole hydrazide into a solvent G, and heating to dissolve;

(2) Slowly cooling the mixture in the step (1) to 10120 ℃ and filtering;

(3) Slowly dripping a solvent H into the filtrate obtained in the step (2), and stirring for 2124H at a constant temperature;

(4) Separating out the precipitated solid in the step (3);

(5) Drying the solid in step (4) to obtain form v.

4. The process according to claim 3, wherein the solvent B comprises N, N-dimethylformamide, N-dimethylacetamide, N-dimethylpropionamide, N, at least one of N-dimethylbutyramide, N-diethylformamide, N-diethylacetamide, N-diethylpropionamide, N-dipropylcarboxamide, N-dipropylacetamide; the solvent C is at least one selected from water, acetone, cyclohexanone, butanone, acetonitrile, propionitrile and butyronitrile; the volume ratio of the solvent C to the solvent B is 3112:1.

5. A process according to claim 3, wherein the solvent a is selected from at least one of tetrahydrofuran, 2-methyltetrahydrofuran, tetrahydrofurfuryl alcohol.

6. A method according to claim 3, wherein the solvent D is selected from at least one of ethylene glycol and propylene glycol.

7. A pesticidal composition comprising the polymorph of claim 1 or 2.

8. A process for preparing a pesticidal composition according to claim 7, characterized by the following: grinding by adopting a wet grinding method, mixing the crystal form of the chloroindole hydrazide, an auxiliary agent and water, adding into a sand mill for sand grinding and dispersing, stopping grinding when the particle size D90=5.0 μm of the sampled and detected material is detected, and filtering out grinding sand to obtain the pesticide composition.

9. Use of the polymorphic form of chloroindole hydrazide according to claim 1 for controlling viral diseases, pathogenic bacteria and insects in crops.

10. The use of claim 9, wherein the viral disease comprises tobacco mosaic virus, pepper virus, rice virus, tomato virus, sweet potato virus, melon virus, and maize dwarf mosaic virus; the pathogenic bacteria comprise cucumber wilt, peanut brown spot, apple ring spot, tomato early blight, wheat gibberella, potato late blight, rape sclerotium, cucumber gray mold, rice sheath blight, phytophthora capsici, rice bakanae, wheat sheath blight, corn small spot and watermelon anthracnose; the insects include armyworms, cotton bollworms, corn borers, and culex spinosa.