CN117050077A - Polymorphic substance of chloroindole hydrazide, preparation method and preparation processing technology of polymorphic substance - Google Patents
Polymorphic substance of chloroindole hydrazide, preparation method and preparation processing technology of polymorphic substance Download PDFInfo
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- CN117050077A CN117050077A CN202210486636.6A CN202210486636A CN117050077A CN 117050077 A CN117050077 A CN 117050077A CN 202210486636 A CN202210486636 A CN 202210486636A CN 117050077 A CN117050077 A CN 117050077A
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- chloroindole
- hydrazide
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- HBZHNVUMFPGVHW-UHFFFAOYSA-N 2-chloro-1h-indole Chemical compound C1=CC=C2NC(Cl)=CC2=C1 HBZHNVUMFPGVHW-UHFFFAOYSA-N 0.000 title claims abstract description 114
- 238000002360 preparation method Methods 0.000 title claims abstract description 57
- 238000012545 processing Methods 0.000 title abstract description 13
- 239000000126 substance Substances 0.000 title abstract description 9
- 238000005516 engineering process Methods 0.000 title abstract description 7
- 239000013078 crystal Substances 0.000 claims abstract description 65
- 239000000575 pesticide Substances 0.000 claims abstract description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 64
- 238000003756 stirring Methods 0.000 claims description 54
- 238000001914 filtration Methods 0.000 claims description 53
- 239000007787 solid Substances 0.000 claims description 53
- 238000001816 cooling Methods 0.000 claims description 52
- 239000002904 solvent Substances 0.000 claims description 50
- 238000001035 drying Methods 0.000 claims description 48
- 239000000203 mixture Substances 0.000 claims description 34
- 239000000706 filtrate Substances 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- 238000010992 reflux Methods 0.000 claims description 24
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 19
- 241000700605 Viruses Species 0.000 claims description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 238000010438 heat treatment Methods 0.000 claims description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- 238000000227 grinding Methods 0.000 claims description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 240000007594 Oryza sativa Species 0.000 claims description 9
- 235000007164 Oryza sativa Nutrition 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 9
- 235000009566 rice Nutrition 0.000 claims description 9
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 239000004576 sand Substances 0.000 claims description 7
- 240000008067 Cucumis sativus Species 0.000 claims description 6
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 claims description 6
- 235000007688 Lycopersicon esculentum Nutrition 0.000 claims description 6
- 240000003768 Solanum lycopersicum Species 0.000 claims description 6
- 235000021307 Triticum Nutrition 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 6
- 244000052616 bacterial pathogen Species 0.000 claims description 5
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000002245 particle Substances 0.000 claims description 5
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 4
- 241000238631 Hexapoda Species 0.000 claims description 4
- 239000012752 auxiliary agent Substances 0.000 claims description 4
- AJFDBNQQDYLMJN-UHFFFAOYSA-N n,n-diethylacetamide Chemical compound CCN(CC)C(C)=O AJFDBNQQDYLMJN-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 235000017060 Arachis glabrata Nutrition 0.000 claims description 3
- 244000105624 Arachis hypogaea Species 0.000 claims description 3
- 235000010777 Arachis hypogaea Nutrition 0.000 claims description 3
- 235000018262 Arachis monticola Nutrition 0.000 claims description 3
- 235000002566 Capsicum Nutrition 0.000 claims description 3
- 244000241235 Citrullus lanatus Species 0.000 claims description 3
- 235000012828 Citrullus lanatus var citroides Nutrition 0.000 claims description 3
- 241000219112 Cucumis Species 0.000 claims description 3
- 235000015510 Cucumis melo subsp melo Nutrition 0.000 claims description 3
- 241000256054 Culex <genus> Species 0.000 claims description 3
- 241000223218 Fusarium Species 0.000 claims description 3
- 241000255967 Helicoverpa zea Species 0.000 claims description 3
- 244000017020 Ipomoea batatas Species 0.000 claims description 3
- 235000002678 Ipomoea batatas Nutrition 0.000 claims description 3
- 241000723994 Maize dwarf mosaic virus Species 0.000 claims description 3
- 241000346285 Ostrinia furnacalis Species 0.000 claims description 3
- 241000233616 Phytophthora capsici Species 0.000 claims description 3
- 241000233622 Phytophthora infestans Species 0.000 claims description 3
- 241001558929 Sclerotium <basidiomycota> Species 0.000 claims description 3
- 241000723873 Tobacco mosaic virus Species 0.000 claims description 3
- 240000008042 Zea mays Species 0.000 claims description 3
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 claims description 3
- 235000002017 Zea mays subsp mays Nutrition 0.000 claims description 3
- 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 claims description 3
- FJJCIZWZNKZHII-UHFFFAOYSA-N [4,6-bis(cyanoamino)-1,3,5-triazin-2-yl]cyanamide Chemical compound N#CNC1=NC(NC#N)=NC(NC#N)=N1 FJJCIZWZNKZHII-UHFFFAOYSA-N 0.000 claims description 3
- 235000005822 corn Nutrition 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 235000020232 peanut Nutrition 0.000 claims description 3
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 claims description 3
- 230000003612 virological effect Effects 0.000 claims description 3
- 241001477931 Mythimna unipuncta Species 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- 239000006002 Pepper Substances 0.000 claims description 2
- 235000016761 Piper aduncum Nutrition 0.000 claims description 2
- 235000017804 Piper guineense Nutrition 0.000 claims description 2
- 244000203593 Piper nigrum Species 0.000 claims description 2
- 235000008184 Piper nigrum Nutrition 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 102220042174 rs141655687 Human genes 0.000 claims description 2
- 238000001238 wet grinding Methods 0.000 claims description 2
- 244000098338 Triticum aestivum Species 0.000 claims 2
- 230000000361 pesticidal effect Effects 0.000 claims 2
- 229940016681 dipropylacetamide Drugs 0.000 claims 1
- 238000002441 X-ray diffraction Methods 0.000 description 35
- 239000012065 filter cake Substances 0.000 description 21
- 239000012046 mixed solvent Substances 0.000 description 21
- 239000002270 dispersing agent Substances 0.000 description 20
- 239000013530 defoamer Substances 0.000 description 19
- 239000004094 surface-active agent Substances 0.000 description 19
- 239000000080 wetting agent Substances 0.000 description 19
- 229920001285 xanthan gum Polymers 0.000 description 18
- 239000000230 xanthan gum Substances 0.000 description 18
- 229940082509 xanthan gum Drugs 0.000 description 18
- 235000010493 xanthan gum Nutrition 0.000 description 18
- 239000000047 product Substances 0.000 description 13
- 238000005189 flocculation Methods 0.000 description 10
- 230000016615 flocculation Effects 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 238000004581 coalescence Methods 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 8
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000001878 scanning electron micrograph Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 241000209140 Triticum Species 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 229920005646 polycarboxylate Polymers 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- ZFPGARUNNKGOBB-UHFFFAOYSA-N 1-Ethyl-2-pyrrolidinone Chemical compound CCN1CCCC1=O ZFPGARUNNKGOBB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- 238000005338 heat storage Methods 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 240000008574 Capsicum frutescens Species 0.000 description 1
- 240000000425 Chaenomeles speciosa Species 0.000 description 1
- 235000005078 Chaenomeles speciosa Nutrition 0.000 description 1
- 241001467460 Myxogastria Species 0.000 description 1
- SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000001390 capsicum minimum Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- IFTIBNDWGNYRLS-UHFFFAOYSA-N n,n-dipropylacetamide Chemical compound CCCN(C(C)=O)CCC IFTIBNDWGNYRLS-UHFFFAOYSA-N 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P3/00—Fungicides
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P7/00—Arthropodicides
- A01P7/04—Insecticides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Environmental Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Health & Medical Sciences (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Insects & Arthropods (AREA)
- Indole Compounds (AREA)
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
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 (10)
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 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 °;
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°;
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 °;
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..
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.
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