CN111747899A - Azoxystrobin channel solvate, eutectic and preparation method thereof - Google Patents

Azoxystrobin channel solvate, eutectic and preparation method thereof Download PDF

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CN111747899A
CN111747899A CN201910241780.1A CN201910241780A CN111747899A CN 111747899 A CN111747899 A CN 111747899A CN 201910241780 A CN201910241780 A CN 201910241780A CN 111747899 A CN111747899 A CN 111747899A
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徐晓勇
任国宾
李忠
齐明辉
石志萍
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East China University of Science and Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • 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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/36—Oxygen or sulfur atoms
    • C07D207/40—2,5-Pyrrolidine-diones
    • C07D207/404—2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
    • 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

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Abstract

The invention provides an azoxystrobin channel solvate, an eutectic and a preparation method thereof. In particular, the invention relates to a channel type solvate and a eutectic crystal of (E) -methyl 2- {2- [6- (2-cyanophenoxy) pyrimidin-4-yloxy ] phenyl } -3-methoxyacrylate, and a preparation method and application thereof.

Description

Azoxystrobin channel solvate, eutectic and preparation method thereof
Technical Field
The invention belongs to the field of pesticide chemistry, and particularly relates to an azoxystrobin channel solvate, an eutectic, and applications and preparation methods thereof.
Background
Figure BDA0002009132820000011
Azoxystrobin (a compound of formula I) with the chemical name of (E) -2- {2- [6- (2-cyanophenoxy) pyrimidin-4-yloxy ] phenyl } -3-methoxy methyl acrylate and the common name of Azoxystrobin (Azoxystrobin) is known, and the compound is a beta methoxy acrylate bactericide, can inhibit the mitochondrial respiration of pathogenic fungi and destroy the energy synthesis of pathogenic bacteria as a systemic broad-spectrum bactericide, and has triple effects of protecting, treating and eradicating pathogenic fungi. Has good control effect on four plant pathogenic fungi, namely ascomycete (such as powdery mildew), basidiomycete (such as rust disease), fungi imperfecti (such as rice blast) and oomycete (such as downy mildew).
The solubility of the same compound may differ from one compound to another in different crystal forms, and the stability, flowability, compressibility and bioavailability of the compound may also differ from one compound to another. These physical and chemical properties have a certain influence on the application of the compound. According to the preparation method in the original compound patent CN101522639A, the prepared crystal form is named as crystal form I, and the crystal form I has the conditions of low solubility and instability.
Therefore, there is a need in the art to develop other crystal forms of the compound of formula I, which require simple preparation method, good photo-thermal stability, low hygroscopicity, high solubility, and large-scale production.
Disclosure of Invention
The invention aims to provide a polymorphic substance or a eutectic crystal of an azoxystrobin solvate and a preparation method thereof.
In a first aspect of the invention, there is provided a solvate of a compound of formula I,
Figure BDA0002009132820000012
the solvent in the solvate is selected from the group consisting of: dimethyl succinate, thiophene, ethylene glycol diethyl ether, or combinations thereof.
In another preferred embodiment, the solvate is a channel-type solvate.
In another preferred embodiment, the solvent molecule suitable for the channel has a volume of 90-109 cm3Or in the range of 40-64 cm3Between the mol.
In another preferred embodiment, the solvate is formed by a compound of formula I and dimethyl succinate, and the molar ratio of the compound of formula I to the dimethyl succinate solvent in the solvate is (1.8-2.2):1, preferably 2: 1.
In another preferred embodiment, the solvate is a solvate of the compound of formula I and thiophene, wherein the molar ratio of the compound of formula I to the thiophene solvent is (0.8-1.2):1, preferably 1: 1.
In another preferred embodiment, the solvate is formed by the compound of formula I and ethylene glycol diethyl ether, and the molar ratio of the compound of formula I to the ethylene glycol diethyl ether solvent in the solvate is (1.8-2.2):1, preferably 2: 1.
In another preferred embodiment, the solvate is crystalline or amorphous, preferably crystalline.
In another preferred embodiment, the solvate is selected from the group consisting of: form III, form IV, form V, or a combination thereof.
In another preferred embodiment, the form iii has an X-ray powder diffraction pattern comprising 3 or more 2 θ values selected from the group consisting of: 7.7 +/-0.2 degrees, 8.4 +/-0.2 degrees, 14.2 +/-0.2 degrees, 18.3 +/-0.2 degrees, 18.9 +/-0.2 degrees, 20.4 +/-0.2 degrees, 21.4 +/-0.2 degrees and 22.0 +/-0.2 degrees.
In another preferred embodiment, the form iii has an X-ray powder diffraction pattern comprising 3 or more 2 θ values selected from the group consisting of: 7.4 +/-0.2 °, 7.7 +/-0.2 °, 8.4 +/-0.2 °, 12.0 +/-0.2 °, 13.4 +/-0.2 °, 14.2 +/-0.2 °, 14.9 +/-0.2 °, 15.7 +/-0.2 °, 16.8 +/-0.2 °, 18.3 +/-0.2 °, 18.9 +/-0.2 °, 20.4 +/-0.2 °, 21.4 +/-0.2 °, 22.0 +/-0.2 °, 23.0 +/-0.2 °, 23.4 +/-0.2 °, 23.8 +/-0.2 °, 23.9 +/-0.2 °, 24.7 +/-0.2 °, 25.4 +/-0.2 °, 26.7 +/-0.2 °, 27.0 +/-0.2 °, 27.5 +/-0.2 °, 28.6 +/-0.2 °, 31.3 +/-0.2 °, 31.7 +/-0.2 °, 35.8 +/-0.2 °, 37.3 ± 0.2 °, 39.0.2 °, 39.3 +/-0.2 ° and 39.2 °.
In another preferred embodiment, the X-ray powder diffraction pattern of form iii comprises 5 or more 2 θ values selected from the group consisting of: 7.4 +/-0.2 °, 7.7 +/-0.2 °, 8.4 +/-0.2 °, 12.0 +/-0.2 °, 13.4 +/-0.2 °, 14.2 +/-0.2 °, 14.9 +/-0.2 °, 15.7 +/-0.2 °, 16.8 +/-0.2 °, 18.3 +/-0.2 °, 18.9 +/-0.2 °, 20.4 +/-0.2 °, 21.4 +/-0.2 °, 22.0 +/-0.2 °, 23.0 +/-0.2 °, 23.4 +/-0.2 °, 23.8 +/-0.2 °, 23.9 +/-0.2 °, 24.7 +/-0.2 °, 25.4 +/-0.2 °, 26.7 +/-0.2 °, 27.0 +/-0.2 °, 27.5 +/-0.2 °, 28.6 +/-0.2 °, 31.3 +/-0.2 °, 31.7 +/-0.2 °, 35.8 +/-0.2 °, 37.3 ± 0.2 °, 39.0.2 °, 39.3 +/-0.2 ° and 39.2 °.
In another preferred embodiment, the X-ray powder diffraction pattern of form iii comprises 10 or more 2 θ values selected from the group consisting of: 7.4 +/-0.2 °, 7.7 +/-0.2 °, 8.4 +/-0.2 °, 12.0 +/-0.2 °, 13.4 +/-0.2 °, 14.2 +/-0.2 °, 14.9 +/-0.2 °, 15.7 +/-0.2 °, 16.8 +/-0.2 °, 18.3 +/-0.2 °, 18.9 +/-0.2 °, 20.4 +/-0.2 °, 21.4 +/-0.2 °, 22.0 +/-0.2 °, 23.0 +/-0.2 °, 23.4 +/-0.2 °, 23.8 +/-0.2 °, 23.9 +/-0.2 °, 24.7 +/-0.2 °, 25.4 +/-0.2 °, 26.7 +/-0.2 °, 27.0 +/-0.2 °, 27.5 +/-0.2 °, 28.6 +/-0.2 °, 31.3 +/-0.2 °, 31.7 +/-0.2 °, 35.8 +/-0.2 °, 37.3 ± 0.2 °, 39.0.2 °, 39.3 +/-0.2 ° and 39.2 °.
In another preferred embodiment, the X-ray powder diffraction pattern of said form iii may further comprise 1 or more 2 θ values selected from the group consisting of: 12.4 +/-0.2 degrees, 13.8 +/-0.2 degrees, 14.7 +/-0.2 degrees, 18.5 +/-0.2 degrees, 19.3 +/-0.2 degrees, 26.1 +/-0.2 degrees, 37.7 +/-0.2 degrees, 38.8 +/-0.2 degrees, 42.7 +/-0.2 degrees and 43.6 +/-0.2 degrees.
In another preferred embodiment, said crystalline form iii has a value selected from the group consisting of the 2 θ (°) values shown in table 1.
In another preferred embodiment, the form iii has an X-ray powder diffraction pattern substantially as characterized in figure 1.
In another preferred embodiment, the TGA profile of form iii is substantially as characterized in figure 3.
In another preferred embodiment, the DSC chart of the crystal form III has endothermic peaks in the range of 62-88 ℃ and 100-125 ℃.
In another preferred embodiment, the DSC profile of form iii is substantially as characterized in figure 2.
In another preferred embodiment, the purity of the crystal form III is more than 95%.
In another preferred embodiment, the X-ray powder diffraction pattern of form iv comprises 3 or more than 32 θ values selected from the group consisting of: 7.6 + -0.2 deg., 8.7 + -0.2 deg., 18.3 + -0.2 deg., 20.6 + -0.2 deg., 21.7 + -0.2 deg., 22.5 + -0.2 deg., 24.0 + -0.2 deg., and 26.6 + -0.2 deg..
In another preferred embodiment, the X-ray powder diffraction pattern of form iv comprises 3 or more than 32 θ values selected from the group consisting of: 7.6 +/-0.2 degrees, 8.7 +/-0.2 degrees, 13.4 +/-0.2 degrees, 14.6 +/-0.2 degrees, 15.5 +/-0.2 degrees, 16.4 +/-0.2 degrees, 17.4 +/-0.2 degrees, 18.3 +/-0.2 degrees, 18.7 +/-0.2 degrees, 19.3 +/-0.2 degrees, 20.6 +/-0.2 degrees, 21.7 +/-0.2 degrees, 22.5 +/-0.2 degrees, 24.0 +/-0.2 degrees, 24.4 +/-0.2 degrees, 26.6 +/-0.2 degrees, 28.4 +/-0.2 degrees, 29.0 +/-0.2 degrees, 30.5 +/-0.2 degrees, 33.9 +/-0.2 degrees, 36.9 +/-0.2 degrees and 38.2 +/-0.2 degrees.
In another preferred embodiment, the X-ray powder diffraction pattern of said form iv comprises 5 or more 2 θ values selected from the group consisting of: 7.6 +/-0.2 degrees, 8.7 +/-0.2 degrees, 13.4 +/-0.2 degrees, 14.6 +/-0.2 degrees, 15.5 +/-0.2 degrees, 16.4 +/-0.2 degrees, 17.4 +/-0.2 degrees, 18.3 +/-0.2 degrees, 18.7 +/-0.2 degrees, 19.3 +/-0.2 degrees, 20.6 +/-0.2 degrees, 21.7 +/-0.2 degrees, 22.5 +/-0.2 degrees, 24.0 +/-0.2 degrees, 24.4 +/-0.2 degrees, 26.6 +/-0.2 degrees, 28.4 +/-0.2 degrees, 29.0 +/-0.2 degrees, 30.5 +/-0.2 degrees, 33.9 +/-0.2 degrees, 36.9 +/-0.2 degrees and 38.2 +/-0.2 degrees.
In another preferred embodiment, the X-ray powder diffraction pattern of said form iv comprises 10 or more than 10 2 θ values selected from the group consisting of: 7.6 +/-0.2 degrees, 8.7 +/-0.2 degrees, 13.4 +/-0.2 degrees, 14.6 +/-0.2 degrees, 15.5 +/-0.2 degrees, 16.4 +/-0.2 degrees, 17.4 +/-0.2 degrees, 18.3 +/-0.2 degrees, 18.7 +/-0.2 degrees, 19.3 +/-0.2 degrees, 20.6 +/-0.2 degrees, 21.7 +/-0.2 degrees, 22.5 +/-0.2 degrees, 24.0 +/-0.2 degrees, 24.4 +/-0.2 degrees, 26.6 +/-0.2 degrees, 28.4 +/-0.2 degrees, 29.0 +/-0.2 degrees, 30.5 +/-0.2 degrees, 33.9 +/-0.2 degrees, 36.9 +/-0.2 degrees and 38.2 +/-0.2 degrees.
In another preferred embodiment, the X-ray powder diffraction pattern of said form iv may further comprise 1 or more than 12 θ values selected from the group consisting of: 11.8 +/-0.2 degrees, 22.9 +/-0.2 degrees, 23.7 +/-0.2 degrees, 25.4 +/-0.2 degrees, 27.5 +/-0.2 degrees, 29.4 +/-0.2 degrees, 31.1 +/-0.2 degrees, 32.2 +/-0.2 degrees, 40.75 +/-0.2 degrees, 41.4 +/-0.2 degrees and 43.9 +/-0.2 degrees.
In another preferred embodiment, said crystalline form iv has a value selected from the group consisting of the values of 2 θ (°) shown in table 4.
In another preferred embodiment, the form iv has an X-ray powder diffraction pattern substantially as characterized in fig. 10.
In another preferred embodiment, the TGA profile of form iv is substantially as characterized in figure 12.
In another preferred embodiment, the DSC chart of the crystal form IV has endothermic peaks in the ranges of 77-100 ℃ and 106-123 ℃.
In another preferred embodiment, the DSC profile of form iv is substantially as characterized in figure 11.
In another preferred embodiment, the purity of the crystal form IV is more than 95%.
In another preferred embodiment, the form v has an X-ray powder diffraction pattern comprising 3 or more 2 Θ values selected from the group consisting of: 7.7 +/-0.2 degrees, 8.5 +/-0.2 degrees, 14.5 +/-0.2 degrees, 21.5 +/-0.2 degrees, 22.5 +/-0.2 degrees, 23.0 +/-0.2 degrees, 24.5 +/-0.2 degrees and 29.0 +/-0.2 degrees.
In another preferred embodiment, the form v has an X-ray powder diffraction pattern comprising 3 or more 2 Θ values selected from the group consisting of: 7.7 +/-0.2 degrees, 8.5 +/-0.2 degrees, 13.9 +/-0.2 degrees, 14.5 +/-0.2 degrees, 17.8 +/-0.2 degrees, 18.3 +/-0.2 degrees, 19.1 +/-0.2 degrees, 20.5 +/-0.2 degrees, 21.5 +/-0.2 degrees, 22.5 +/-0.2 degrees, 23.0 +/-0.2 degrees, 24.5 +/-0.2 degrees, 26.4 +/-0.2 degrees, 27.0 +/-0.2 degrees, 29.0 +/-0.2 degrees, 30.8 +/-0.2 degrees, 36.3 +/-0.2 degrees and 38.7 +/-0.2 degrees.
In another preferred embodiment, the form v has an X-ray powder diffraction pattern comprising 5 or more 2 Θ values selected from the group consisting of: 7.7 +/-0.2 degrees, 8.5 +/-0.2 degrees, 13.9 +/-0.2 degrees, 14.5 +/-0.2 degrees, 17.8 +/-0.2 degrees, 18.3 +/-0.2 degrees, 19.1 +/-0.2 degrees, 20.5 +/-0.2 degrees, 21.5 +/-0.2 degrees, 22.5 +/-0.2 degrees, 23.0 +/-0.2 degrees, 24.5 +/-0.2 degrees, 26.4 +/-0.2 degrees, 27.0 +/-0.2 degrees, 29.0 +/-0.2 degrees, 30.8 +/-0.2 degrees, 36.3 +/-0.2 degrees and 38.7 +/-0.2 degrees.
In another preferred embodiment, the form v has an X-ray powder diffraction pattern comprising 10 or more 2 Θ values selected from the group consisting of: 7.7 +/-0.2 degrees, 8.5 +/-0.2 degrees, 13.9 +/-0.2 degrees, 14.5 +/-0.2 degrees, 17.8 +/-0.2 degrees, 18.3 +/-0.2 degrees, 19.1 +/-0.2 degrees, 20.5 +/-0.2 degrees, 21.5 +/-0.2 degrees, 22.5 +/-0.2 degrees, 23.0 +/-0.2 degrees, 24.5 +/-0.2 degrees, 26.4 +/-0.2 degrees, 27.0 +/-0.2 degrees, 29.0 +/-0.2 degrees, 30.8 +/-0.2 degrees, 36.3 +/-0.2 degrees and 38.7 +/-0.2 degrees.
In another preferred embodiment, the X-ray powder diffraction pattern of form v may further comprise 1 or more 2 θ values selected from the group consisting of: 10.9 +/-0.2 degrees, 13.4 +/-0.2 degrees, 15.3 +/-0.2 degrees, 15.9 +/-0.2 degrees, 17.1 +/-0.2 degrees, 24.0 +/-0.2 degrees, 28.1 +/-0.2 degrees, 31.3 +/-0.2 degrees, 41.4 +/-0.2 degrees and 41.9 +/-0.2 degrees.
In another preferred embodiment, said form v has a value selected from the group consisting of the 2 θ (°) values shown in table 5.
In another preferred embodiment, the form v has an X-ray powder diffraction pattern substantially as characterized in figure 13.
In another preferred embodiment, the TGA profile of form v is substantially as characterized in figure 15.
In another preferred embodiment, the DSC chart of the crystal form V has an endothermic peak within the range of 106-127 ℃.
In another preferred embodiment, the DSC profile of form v is substantially as characterized in figure 14.
In another preferred embodiment, the purity of form v is greater than 95%.
In a second aspect of the invention, there is provided a co-crystal of a compound of formula I and a succinimide,
Figure BDA0002009132820000041
in another preferred embodiment, the co-crystal is formed by the compound of the formula I and the succinimide in a molar ratio of 1:0.8-1.2 (preferably 1: 1).
In another preferred embodiment, the co-crystal is form ix.
In another preferred embodiment, the X-ray powder diffraction pattern of form ix comprises 3 or more than 32 θ values selected from the group consisting of: 14.1 +/-0.2 degrees, 15.7 +/-0.2 degrees, 16.6 +/-0.2 degrees, 17.1 +/-0.2 degrees, 20.3 +/-0.2 degrees, 21.8 +/-0.2 degrees, 23.6 +/-0.2 degrees and 29.0 +/-0.2 degrees.
In another preferred embodiment, the X-ray powder diffraction pattern of form ix comprises 3 or more than 32 θ values selected from the group consisting of: 7.4 +/-0.2 °, 10.2 +/-0.2 °, 10.7 +/-0.2 °, 11.7 +/-0.2 °, 13.1 +/-0.2 °, 14.1 +/-0.2 °, 15.7 +/-0.2 °, 16.6 +/-0.2 °, 17.1 +/-0.2 °, 17.4 +/-0.2 °, 18.4 +/-0.2 °, 19.6 +/-0.2 °, 20.3 +/-0.2 °, 21.2 +/-0.2 °, 21.8 +/-0.2 °, 23.6 +/-0.2 °, 24.3 +/-0.2 °, 24.9 +/-0.2 °, 25.8 +/-0.2 °, 26.3 +/-0.2 °, 26.7 +/-0.2 °, 27.2 +/-0.2 °, 28.0 +/-0 °, 29.0 +/-0.2 °, 31.0 +/-0.2 °, 36.8 +/-0.2 ° and 37.4 +/-0.2 °.
In another preferred embodiment, said form ix has an X-ray powder diffraction pattern comprising 5 or more 2 Θ values selected from the group consisting of: 7.4 +/-0.2 °, 10.2 +/-0.2 °, 10.7 +/-0.2 °, 11.7 +/-0.2 °, 13.1 +/-0.2 °, 14.1 +/-0.2 °, 15.7 +/-0.2 °, 16.6 +/-0.2 °, 17.1 +/-0.2 °, 17.4 +/-0.2 °, 18.4 +/-0.2 °, 19.6 +/-0.2 °, 20.3 +/-0.2 °, 21.2 +/-0.2 °, 21.8 +/-0.2 °, 23.6 +/-0.2 °, 24.3 +/-0.2 °, 24.9 +/-0.2 °, 25.8 +/-0.2 °, 26.3 +/-0.2 °, 26.7 +/-0.2 °, 27.2 +/-0.2 °, 28.0 +/-0 °, 29.0 +/-0.2 °, 31.0 +/-0.2 °, 36.8 +/-0.2 ° and 37.4 +/-0.2 °.
In another preferred embodiment, the X-ray powder diffraction pattern of form ix comprises 10 or more 2 θ values selected from the group consisting of: 7.4 +/-0.2 °, 10.2 +/-0.2 °, 10.7 +/-0.2 °, 11.7 +/-0.2 °, 13.1 +/-0.2 °, 14.1 +/-0.2 °, 15.7 +/-0.2 °, 16.6 +/-0.2 °, 17.1 +/-0.2 °, 17.4 +/-0.2 °, 18.4 +/-0.2 °, 19.6 +/-0.2 °, 20.3 +/-0.2 °, 21.2 +/-0.2 °, 21.8 +/-0.2 °, 23.6 +/-0.2 °, 24.3 +/-0.2 °, 24.9 +/-0.2 °, 25.8 +/-0.2 °, 26.3 +/-0.2 °, 26.7 +/-0.2 °, 27.2 +/-0.2 °, 28.0 +/-0 °, 29.0 +/-0.2 °, 31.0 +/-0.2 °, 36.8 +/-0.2 ° and 37.4 +/-0.2 °.
In another preferred embodiment, the X-ray powder diffraction pattern of form ix may further comprise 1 or more 2 θ values selected from the group consisting of: 10.7 +/-0.2 degrees, 14.9 +/-0.2 degrees, 15.3 +/-0.2 degrees, 23.9 +/-0.2 degrees, 25.4 +/-0.2 degrees, 30.3 +/-0.2 degrees, 31.3 +/-0.2 degrees, 34.1 +/-0.2 degrees, 38.4 +/-0.2 degrees, 38.8 +/-0.2 degrees and 41.5 +/-0.2 degrees.
In another preferred embodiment, said crystalline form ix has a value selected from the group consisting of 2 θ (°) values set forth in table 6.
In another preferred embodiment, the form IX has an X-ray powder diffraction pattern substantially as characterized in FIG. 16.
In another preferred embodiment, the TGA profile of form IX is substantially as characterized in FIG. 18.
In another preferred example, the DSC chart of the crystal form IX has an endothermic peak within the range of 79-113 ℃.
In another preferred embodiment, the DSC diagram of form ix is substantially as characterized in figure 17.
In another preferred embodiment, the purity of crystal form ix is greater than 95%.
In a third aspect of the present invention, there is provided a pesticidal composition comprising: (a) a solvate according to the first aspect of the invention and/or a co-crystal according to the second aspect of the invention, and (b) an agriculturally pharmaceutically acceptable carrier.
In a fourth aspect of the invention, there is provided a process for preparing form iii according to the first aspect of the invention, comprising the steps of:
(i) providing a first solution of a compound of formula I in dimethyl succinate;
(ii) and volatilizing the first solution or mixing the first solution with an anti-solvent and crystallizing to obtain the crystal form III.
In another preferred embodiment, the antisolvent is selected from the group consisting of: n-hexane, cyclohexane, n-heptane, water, or combinations thereof.
In another preferred example, the method comprises the steps of:
(i) providing a first solution of a compound of formula I in dimethyl succinate;
(ii) volatilizing the first solution to obtain form iii according to the first aspect of the invention.
In another preferred example, the method comprises the steps of:
(i) providing a first solution of a compound of formula I in dimethyl succinate;
(ii) and adding n-hexane into the first solution to form a second solution, and carrying out crystallization treatment on the second solution to obtain the crystal form III of the first aspect of the invention.
In a fifth aspect, the present invention provides a process for preparing form iv according to the first aspect of the present invention, comprising the steps of:
(i) providing a first solution of a compound of formula I in thiophene;
(ii) and volatilizing the first solution or mixing the first solution with an anti-solvent and crystallizing to obtain the crystal form IV.
In another preferred embodiment, the antisolvent is selected from the group consisting of: n-hexane, cyclohexane, n-heptane, water, or combinations thereof.
In another preferred example, the method comprises the steps of:
(i) providing a first solution of a compound of formula I in a thiophene solvent;
(ii) volatilizing the first solution to obtain the crystalline form IV of the first aspect of the invention.
In another preferred example, the method comprises the steps of:
(i) providing a first solution of a compound of formula I in a thiophene solvent;
(ii) and adding n-hexane into the first solution to form a second solution, and carrying out crystallization treatment on the second solution to obtain the crystal form IV of the first aspect of the invention.
In a sixth aspect of the present invention, a process for preparing crystalline form viii according to the first aspect of the present invention comprises the steps of:
(i) providing a first solution of a compound of formula I in ethylene glycol diethyl ether;
(ii) and mixing the first solution with an anti-solvent to form a second solution, and carrying out crystallization treatment on the second solution to obtain the crystal form V of the first aspect of the invention.
In another preferred embodiment, the antisolvent is selected from the group consisting of: n-hexane, cyclohexane, n-heptane, water, or combinations thereof.
In another preferred example, the method comprises the steps of:
(i) providing a first solution of a compound of formula I in diethylglycol diethyl ether;
(ii) and adding n-hexane into the first solution to form a second solution, and carrying out crystallization treatment on the second solution to obtain the crystal form V of the first aspect of the invention.
In a seventh aspect of the invention, a process for preparing crystalline form IX according to the second aspect of the invention comprises the steps of:
(i) providing a first solution of a compound of formula I and succinimide in dichloromethane;
(ii) and carrying out quick rotary evaporation treatment on the first solution to obtain the crystal form IX of the second aspect of the invention.
In another preferred embodiment, the rapid rotary evaporation treatment comprises the step of obtaining the crystal form IX in the second aspect of the invention after rotary evaporation at a rotation speed of 120-140 rmp/min and a water bath temperature of 10 +/-5 ℃.
In an eighth aspect of the invention, there is provided a use of the solvate according to the first aspect of the invention and the co-crystal according to the second aspect or the pesticidal composition according to the third aspect of the invention for preventing or controlling diseases; or for inhibiting harmful microorganisms in agriculture, forestry or horticulture.
In another preferred example, the prevention or control is prevention or control of diseases in agriculture, forestry or horticulture.
In another preferred embodiment, the disease is selected from the group consisting of plant diseases: downy mildew, powdery mildew, anthracnose, leaf spot, or combinations thereof.
In another preferred embodiment, the harmful microorganism is selected from the group consisting of: ascomycetes, basidiomycetes, deuteromycetes, and oomycetes, or combinations thereof.
In another preferred embodiment, the preventing, controlling or inhibiting is in vitro preventing, controlling or inhibiting.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Drawings
Figure 1 shows an XRPD pattern of azoxystrobin form iii.
Figure 2 shows a DSC diagram of azoxystrobin form iii.
Figure 3 shows a TGA diagram of azoxystrobin form iii.
Figure 4 shows a perspective view of the crystalline form iii molecule.
Fig. 5 shows a projection of the crystalline form iii cell packing.
Figure 6 shows a five day high humidity stability XRPD pattern of form iii.
Figure 7 shows a ten day high humidity stability XRPD pattern of form iii.
Figure 8 shows an XRPD pattern of five day light stability of form iii.
Figure 9 shows a ten day photostability XRPD pattern for form iii.
Figure 10 shows an XRPD pattern of azoxystrobin form iv.
Figure 11 shows a DSC diagram of azoxystrobin form iv.
Figure 12 shows a TGA plot of azoxystrobin form iv.
Figure 13 shows an XRPD pattern of azoxystrobin form v.
Figure 14 shows a DSC diagram of azoxystrobin form v.
Figure 15 shows a TGA plot of azoxystrobin form v.
FIG. 16 shows an XRPD pattern of azoxystrobin form IX.
FIG. 17 shows a DSC of azoxystrobin form IX.
FIG. 18 shows a TGA diagram of azoxystrobin crystalline form IX.
FIG. 19 shows a crystal form IX five day high temperature stability XRPD pattern.
FIG. 20 shows a crystal form IX ten day high temperature stability XRPD pattern.
Figure 21 shows a crystal form ix XRPD pattern for five days high humidity stability.
Figure 22 shows a crystal form ix ten day high humidity stability XRPD pattern.
Figure 23 shows a crystal form ix five day light stability XRPD pattern.
Figure 24 shows a crystal form ix ten day light stability XRPD pattern.
Detailed Description
The present inventors have unexpectedly found, through extensive and intensive studies, novel solvates and co-crystals of azoxystrobin and a method for preparing the same for the first time. The 3 solvates (crystal forms III-V) and the eutectic crystal (crystal form IX) have high purity, good thermal stability and non-hygroscopicity, and are superior to the existing azoxystrobin in solubility. The pesticide composition is suitable for preparing pesticide compositions for inhibiting harmful microorganisms, so that the pesticide composition has better control effect on most diseases such as downy mildew, powdery mildew, anthracnose, leaf spot and the like caused by four main diseases such as ascomycetes, basidiomycetes, deuteromycetes and oomycetes. In addition, the preparation method of the solvate is simple and is suitable for large-scale industrial production. On this basis, the inventors have completed the present invention.
Description of the terms
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
As used herein, the term "about" when used in reference to a specifically recited value means that the value may vary by no more than 1% from the recited value. For example, as used herein, the expression "about 100" includes 99 and 101 and all values in between (e.g., 99.1, 99.2, 99.3, 99.4, etc.).
As used herein, the term "comprising" or "includes" can be open, semi-closed, and closed. In other words, the term also includes "consisting essentially of …," or "consisting of ….
As used herein, the term "n or more than n 2 θ values selected from the group" is meant to include n as well as any positive integer greater than n (e.g., n +1, ….), where the upper bound Nup is the number of all 2 θ peaks in the group. For example, "1 or more" includes not only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, …, each positive integer of upper limit Nup, but also ranges of "2 or more", "3 or more", "4 or more", "5 or more", "6 or more", "7 or more", "8 or more", "9 or more", "10 or more", and the like. For example, "3 or more" includes not only 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, …, each positive integer of the upper limit Nup, but also ranges such as "4 or more", "5 or more", "6 or more", "7 or more", "8 or more", "9 or more", "10 or more", and the like.
A compound of formula I
Figure BDA0002009132820000071
Azoxystrobin (compound of formula I) with chemical name (E) -2- {2- [6- (2-cyanophenoxy) pyrimidin-4-yloxy ] phenyl } -3-methoxyacrylate methyl ester. The compound is a brand-new beta methoxy acrylate fungicide, can inhibit the mitochondrial respiration of pathogenic fungi and destroy the energy synthesis of pathogenic bacteria, and has triple effects of protection, treatment and eradication. Has good control effect on most diseases such as downy mildew, powdery mildew, anthracnose, leaf spot and the like caused by four main diseases such as ascomycetes, basidiomycetes, deuteromycetes and oomycetes.
Polymorphic substance
The solid is present either in amorphous or crystalline form. In the case of crystalline forms, the molecules are positioned within three-dimensional lattice sites. When a compound crystallizes from a solution or slurry, it can crystallize in different spatial lattice arrangements (this property is known as "polymorphism"), forming crystals with different crystalline forms, each of which is known as a "polymorph". Different polymorphs of a given substance may differ from each other in one or more physical properties such as solubility and dissolution rate, true specific gravity, crystal form, packing pattern, flowability, and/or solid state stability.
Crystallization of
Production scale crystallization can be accomplished by manipulating the solution such that the solubility limit of the compound of interest is exceeded. This can be accomplished by a variety of methods, for example, dissolving the compound at relatively high temperatures and then cooling the solution below the saturation limit. Or by boiling, atmospheric evaporation, vacuum drying, or by some other method to reduce the liquid volume. The solubility of the compound of interest may be reduced by adding an anti-solvent or a solvent in which the compound has low solubility or a mixture of such solvents. Another alternative is to adjust the pH to reduce solubility. For a detailed description of the Crystallization see crystallation, third edition, J W Mullins, Butterworth-Heineman Ltd.,1993, ISBN 0750611294.
If salt formation is desired to occur simultaneously with crystallization, addition of an appropriate acid or base may result in direct crystallization of the desired salt if the salt is less soluble in the reaction medium than the starting material. Also, in media where the final desired form is less soluble than the reactants, completion of the synthesis reaction can result in direct crystallization of the final product.
Optimization of crystallization may include seeding the crystallization medium with crystals of the desired form. In addition, many crystallization methods use a combination of the above strategies. One example is to dissolve the compound of interest in a solvent at elevated temperature, followed by the addition of an appropriate volume of anti-solvent in a controlled manner so that the system is just below the saturation level. At this point, seeds of the desired form may be added (and the integrity of the seeds maintained) and the system cooled to complete crystallization.
Solvates
In the process of contacting a compound or a drug molecule with a solvent molecule, the solvent molecule and the compound molecule form eutectic crystals and remain in the solid substance due to external condition and internal condition factors, which is difficult to avoid. The material formed after crystallization of the compound with a solvent is known as a solvate or solvate (solvate). The solvent which is easily solvated with organic compounds is selected from water, methanol, benzene, ethanol, ether, aromatic hydrocarbon, heterocyclic aromatic hydrocarbon, etc.
Hydrates are a particular solvate. In the pharmaceutical industry, hydrates have separately discussed value for their specificity, whether in the synthesis of drug substances, pharmaceutical formulations, drug storage, and evaluation of drug activity.
In the invention, the crystal forms III-V of the compound shown in the formula I are channel type solvates.
In another preferred embodiment, the solvent in the solvate is selected from the group consisting of: dimethyl succinate, thiophene, ethylene glycol diethyl ether, or combinations thereof.
Eutectic type substance
Pharmaceutical co-crystals are crystals of the Active Pharmaceutical Ingredient (API) and the co-crystal former (CCF) bound by hydrogen bonds or other non-covalent bonds, wherein the API and CCF are both solid in pure form at room temperature. The CCF in the pharmaceutical co-crystals may include physiologically acceptable acid, base, and non-ionic molecules such as food additives, preservatives, pharmaceutical excipients, vitamins, minerals, amino acids and other active molecules, and even other APIs, which may be bound to the API in the same lattice by hydrogen bonding, pi-pi stacking, van der waals forces and other non-covalent bonds. Chemically, the API molecule is not changed, so the original drug effect is kept, the solubility, bioavailability, stability and other aspects of the eutectic drug are greatly improved, and the eutectic drug has a very positive effect on the development of some oral pharmaceutical preparations.
As used herein, "co-crystal" and "co-crystal" are used interchangeably and refer to co-crystal IX formed from methyl (E) -2- {2- [6- (2-cyanophenoxy) pyrimidin-4-yloxy ] phenyl } -3-methoxyacrylate and succinimide according to the second aspect of the present invention.
Pesticide composition
The "active ingredient" or "active compound" in the pesticidal composition according to the present invention refers to the compound of formula I according to the present invention, especially the compound of formula I in the crystalline form according to the present invention.
The "active ingredient" or "active compound" and the pesticidal composition of the present invention can be used for preventing or controlling diseases; or for inhibiting harmful microorganisms in agriculture, forestry or horticulture.
Differential scanning calorimetry analysis
Also known as differential thermal scanning analysis (DSC), is a technique for measuring the relationship between the energy difference between a measured substance and a reference substance and the temperature during heating. The position, shape and number of peaks on a DSC spectrum are related to the nature of the substance and can be used qualitatively to identify the substance. The method is commonly used in the field to detect various parameters such as phase transition temperature, glass transition temperature, reaction heat and the like of a substance.
Preparation method
When the azoxystrobin crystal form V is prepared, a method which is easy to realize rapid mass industrial production and is used for elution is adopted; the method for preparing the azoxystrobin crystal forms III and IV uses a volatilization or elution method, and the two methods are simple, convenient and feasible and are easy for industrial production.
Use of
The invention provides a solvate of azoxystrobin and application of a pesticide composition thereof, wherein the solvate has high efficiency and broad spectrum, and has good control effect on most diseases such as downy mildew, powdery mildew, anthracnose, leaf spot and the like caused by four major pathogenic fungi of ascomycetes, basidiomycetes, deuteromycetes and oomycetes.
The main advantages of the invention
(1) The compound solvate and the eutectic crystal of the formula I have good thermal stability and non-hygroscopicity, are superior to the prior azoxystrobin original drug crystal form I in solubility, can greatly improve bioavailability, and are very suitable for synthetic drugs.
(2) The preparation method of the solvate and the eutectic of the compound of the formula I has the advantages of simple and easy operation, low cost, high purity of the prepared crystal and less solvent residue, and is suitable for drug research and development and large-scale industrial production.
(3) The solvates and co-crystals of the compounds of formula I of the present invention can be used for the prevention or control of diseases; or for inhibiting harmful microorganisms in agriculture, forestry or horticulture.
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out under conventional conditions or conditions recommended by the manufacturers. Unless otherwise indicated, percentages and parts are by weight. The test materials and reagents used in the following examples are commercially available without specific reference. The normal temperature or room temperature is 4-25 deg.C, preferably 15-25 deg.C.
The test method comprises the following steps:
XRD (X-ray powder diffraction) method: the instrument comprises the following steps: rigaku Ultima IV powder diffractometer, target: Cu-K α (40kV, 40mA), performed at room temperature using a D/tex Ultra detector. The scan range is from 3 ° to 45 ° in the 2 θ interval, and the scan speed is 20 °/min.
The differences in measurements associated with such X-ray powder diffraction analysis results arise from a number of factors including: (a) errors in sample preparation (e.g., sample height), (b) instrument errors, (c) calibration differences, (d) operator errors (including errors in determining peak position), and (e) properties of the substance (e.g., preferred orientation errors). Calibration errors and sample height errors often result in a shift of all peaks in the same direction. When using a flat holder, small differences in sample height will result in large shifts in XRD peak positions. Systematic studies show that sample height differences of 1mm can result in peak shifts of 2 θ up to 1 °. These shifts can be identified from the X-ray diffraction patterns and can be eliminated by compensating for them (using the system calibration factor for all peak position values) or recalibrating the instrument. As described above, measurement errors from different instruments can be corrected by applying a system calibration factor to make the peak positions consistent.
TGA (thermogravimetric analysis) method: the instrument model is as follows: TA Q500 thermogravimetric analyzer using N2The temperature rise rate is 10 ℃/min under the atmosphere.
DSC (differential scanning calorimetry) method: the instrument model is as follows: TA Q2000 differential scanning calorimeter using N2The temperature rise rate is 10 ℃/min under the atmosphere.
Example 1 preparation of form I
The preparation method of the crystal form I refers to the preparation method in patent CN 101522639A.
Example 2 preparation of azoxystrobin Crystal form III
Weighing 50mg of raw materials into a container, adding 0.5ml of dimethyl succinate for dissolving, volatilizing at normal temperature, and drying the solid in vacuum to obtain azoxystrobin crystal form III (yield is 97%).
50mg of the raw material was weighed into a container, 0.5ml of dimethyl succinate was added to dissolve, 2.5ml of cyclohexane was added, filtration was performed, and the solid was vacuum dried to obtain azoxystrobin crystal form III (yield 95%).
Weighing 50mg of raw materials into a container, adding 0.5ml of dimethyl succinate solution, adding 2.5ml of n-hexane, filtering, and carrying out vacuum drying on the solid to obtain azoxystrobin crystal form III (yield 95%).
Weighing 50mg of raw materials into a container, adding 0.5ml of dimethyl succinate solution, adding 2.5ml of n-heptane, filtering, and drying the solid in vacuum to obtain azoxystrobin crystal form III (yield 95%).
Weighing 50mg of raw materials into a container, adding 0.5ml of dimethyl succinate for dissolving, adding 2.5ml of water, filtering, and drying the solid in vacuum to obtain the azoxystrobin crystal form III (yield 95%).
The XRD pattern of the obtained azoxystrobin crystal form III is basically shown in figure 1, and the diffraction angle data are basically shown in the following table 1.
Table 1 XRD data for form iii
Figure BDA0002009132820000101
Figure BDA0002009132820000111
The DSC chart of the crystal form III is shown in figure 2, wherein the endothermic peak corresponds to the solvent loss process and has an endothermic peak within the range of 90-110 ℃.
The TGA profile of form iii is shown in fig. 3, which shows that there is substantially no weight loss before decomposition.
In addition, a single crystal X-ray diffraction (SXRD) structure of form iii in example 2 was obtained as shown in fig. 4 and 5, with the parameters shown in table 2 below.
TABLE 2 Single Crystal X-ray diffraction parameters of form III
Figure BDA0002009132820000121
Example 3 stability study of azoxystrobin form III
Azoxystrobin form III in example 2 was placed under high humidity (RH 92.5%), illumination (4500lx + -500 lx) conditions and after 5 and 10 days the samples were taken for XRPD testing to investigate form III stability. As shown in fig. 6, 7, 8 and 9, the results indicate that the sample of form iii was stable under these conditions.
Example 4 comparison of the solubilities of form I and form III
Weighing excessive crystal form I and crystal form III, suspending the excessive crystal form I and crystal form III in ethanol, and testing the solubility by using UPLC after shaking for 24 hours, wherein the test results are shown in the following table 3:
TABLE 3 solubilities of form III and form I
Crystal form Solubility (mg/ml)
Crystal form I 14.18
Crystal form III 18.33
It can be seen from table 3 that the solubility of form iii in ethanol is greater than that of form i, about 1.3 times that of form i.
Example 5 preparation of azoxystrobin crystalline form IV
Weighing 50mg of raw materials into a container, adding 0.5ml of thiophene solvent, volatilizing at normal temperature, and drying the solid in vacuum to obtain azoxystrobin crystal form IV (yield is 97%).
Weighing 50mg of raw materials into a container, adding 0.5ml of thiophene solvent, adding 2.5ml of cyclohexane, filtering, and drying the solid in vacuum to obtain azoxystrobin crystal form IV (yield is 93%).
Weighing 50mg of raw materials into a container, adding 0.5ml of thiophene solvent, adding 2.5ml of n-hexane, filtering, and drying the solid in vacuum to obtain the azoxystrobin crystal form IV (yield is 93%).
Weighing 50mg of raw materials into a container, adding 0.5ml of thiophene solvent, adding 2.5ml of n-heptane, filtering, and drying the solid in vacuum to obtain azoxystrobin crystal form IV (yield is 93%).
The XRD pattern of the obtained azoxystrobin crystal form IV is basically shown in figure 10, and the diffraction angle data are basically shown in the following table 4.
TABLE 4 XRD data for form IV
Figure BDA0002009132820000131
Figure BDA0002009132820000141
The DSC chart of the crystal form IV is shown in figure 11, wherein an endothermic peak corresponds to a solvent loss process and has an endothermic peak within the temperature range of 106-123 ℃.
The TGA profile of form IV is shown in FIG. 12, which shows that there is substantially no weight loss prior to decomposition.
The stability and the solubility of the prepared crystal form IV are inspected, and the result shows that the crystal form IV has good stability and solubility, lower hygroscopicity and high bioavailability.
Example 6 preparation of azoxystrobin crystalline form V
Weighing 50mg of raw materials into a container, adding 1.75ml of ethylene glycol diethyl ether to dissolve the raw materials, adding 9ml of n-hexane, filtering, and drying the solid in vacuum to obtain azoxystrobin crystal form V (yield 82%).
The XRD pattern of the obtained azoxystrobin crystal form V is basically shown in figure 13, and the diffraction angle data are basically shown in the following table 5.
TABLE 5 XRD data for form V
Figure BDA0002009132820000142
Figure BDA0002009132820000151
The DSC chart of the crystal form V is shown in figure 14, wherein the first endothermic peak corresponds to the solvent loss process, the second endothermic peak corresponds to the melting decomposition process, and the endothermic peak is arranged in the range of 109-125 ℃.
The TGA profile of form v is shown in fig. 15, which shows that there is substantially no weight loss before decomposition.
The stability and the solubility of the prepared crystal form V are inspected, and the result shows that the crystal form V has good stability and solubility, lower hygroscopicity and high bioavailability.
Example 7 preparation of Crystal form IX azoxystrobin
80.6mg of raw material and 19.8mg of succinimide are weighed in a container, a proper amount of dichloromethane is added for dissolving, then quick rotary evaporation is carried out, and the solid is dried in vacuum to obtain the azoxystrobin crystal form IX (yield is 97%).
The XRD pattern of the obtained crystal form IX azoxystrobin is basically shown in figure 16, and the data of diffraction angles are basically shown in the following table 6.
TABLE 6 XRD data for crystalline form IX
Figure BDA0002009132820000152
Figure BDA0002009132820000161
The DSC chart of crystal form IX is shown in FIG. 17, wherein the endothermic peak corresponds to the melting decomposition process and has an endothermic peak in the range of 79 to 113 ℃.
The TGA profile of form IX is shown in FIG. 18, which shows essentially no weight loss prior to decomposition.
Example 8 stability study of Crystal form IX azoxystrobin
The azoxystrobin crystal form IX sample in example 11 was placed under conditions of high temperature (60. + -. 2 ℃), high humidity (RH 92.5%), illumination (4500 lx. + -. 500lx), and after 5 days and 10 days, the sample was taken out for XRPD test to examine the crystal form stability of the sample against temperature, humidity and light. As shown in fig. 19, 20, 21, 22, 23 and 24, the results indicate that the sample of crystal form ix is stable under the conditions of high temperature, high humidity and light.
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims (10)

1. A solvate or co-crystal of a compound of formula I,
Figure FDA0002009132810000011
the solvent in the solvate is selected from the group consisting of: dimethyl succinate, thiophene, ethylene glycol diethyl ether, or a combination thereof, preferably, the solvate is selected from the group consisting of: form III, form IV, form V, or a combination thereof;
the co-crystal is formed by the compound shown in the formula I and succinimide.
2. The solvate or co-crystal of claim 1, wherein the solvate is form iii having a characteristic selected from the group consisting of:
(1) the X-ray powder diffraction pattern of form iii comprises 3 or more 2 Θ values selected from the group consisting of: 7.4 +/-0.2 °, 7.7 +/-0.2 °, 8.4 +/-0.2 °, 12.0 +/-0.2 °, 13.4 +/-0.2 °, 14.2 +/-0.2 °, 14.9 +/-0.2 °, 15.7 +/-0.2 °, 16.8 +/-0.2 °, 18.3 +/-0.2 °, 18.9 +/-0.2 °, 20.4 +/-0.2 °, 21.4 +/-0.2 °, 22.0 +/-0.2 °, 23.0 +/-0.2 °, 23.4 +/-0.2 °, 23.8 +/-0.2 °, 23.9 +/-0.2 °, 24.7 +/-0.2 °, 25.4 +/-0.2 °, 26.7 +/-0.2 °, 27.0 +/-0.2 °, 27.5 +/-0.2 °, 28.6 +/-0.2 °, 31.3 +/-0.2 °, 31.7 +/-0.2 °, 35.8 +/-0.2 °, 37.3.0.3 ± 0.2 °, and 30.3 +/-0.3 °; and/or
(2) The X-ray powder diffraction pattern of the crystal form III is basically characterized as shown in figure 1; and/or
(3) The TGA profile of form iii is substantially as characterized in figure 3; and/or
(4) The DSC chart of the crystal form III has an endothermic peak within the range of 90-110 ℃; and/or
(5) The DSC profile of form iii is substantially as characterized in figure 2; and/or
(6) The purity of the crystal form III is more than 95%.
3. The solvate or co-crystal of claim 1, wherein the solvate is form iv having a characteristic selected from the group consisting of:
(1) the X-ray powder diffraction pattern of the crystal form IV comprises 3 or more than 32 theta values selected from the following groups: 7.6 +/-0.2 °, 8.7 +/-0.2 °, 13.4 +/-0.2 °, 14.6 +/-0.2 °, 15.5 +/-0.2 °, 16.4 +/-0.2 °, 17.4 +/-0.2 °, 18.3 +/-0.2 °, 18.7 +/-0.2 °, 19.3 +/-0.2 °, 20.6 +/-0.2 °, 21.7 +/-0.2 °, 22.5 +/-0.2 °, 24.0 +/-0.2 °, 24.4 +/-0.2 °, 26.6 +/-0.2 °, 28.4 +/-0.2 °, 29.0 +/-0.2 °, 30.5 +/-0.2 °, 33.9 +/-0.2 °, 36.9 +/-0.2 ° and 38.2 +/-0.2 °; and/or
(2) The X-ray powder diffraction pattern of the crystal form IV is basically characterized as shown in figure 10; and/or
(3) The TGA profile of form iv is substantially as characterized in figure 12; and/or
(4) The DSC chart of the crystal form IV has an endothermic peak within the range of 106-123 ℃; and/or
(5) The DSC profile of form iv is substantially as characterized in figure 11; and/or
(6) The purity of the crystal form IV is more than 95%.
4. The solvate or co-crystal of claim 1, wherein the solvate is form v, having a characteristic selected from the group consisting of:
(1) the form v has an X-ray powder diffraction pattern comprising 3 or more 2 Θ values selected from the group consisting of: 7.7 +/-0.2 °, 8.5 +/-0.2 °, 13.9 +/-0.2 °, 14.5 +/-0.2 °, 17.8 +/-0.2 °, 18.3 +/-0.2 °, 19.1 +/-0.2 °, 20.5 +/-0.2 °, 21.5 +/-0.2 °, 22.5 +/-0.2 °, 23.0 +/-0.2 °, 24.5 +/-0.2 °, 26.4 +/-0.2 °, 27.0 +/-0.2 °, 29.0 +/-0.2 °, 30.8 +/-0.2 °, 36.3 +/-0.2 °, 38.7 +/-0.2 °; and/or
(2) The form v has an X-ray powder diffraction pattern substantially as characterized in figure 13; and/or
(3) The TGA profile of form v is substantially as characterized in figure 15; and/or
(4) The DSC chart of the crystal form V has endothermic peaks within the range of 65-87 ℃ and 109-125 ℃; and/or
(5) The DSC profile of form v is substantially as characterized in figure 14; and/or
(6) The purity of the crystal form V is more than 95%.
5. The solvate or co-crystal of claim 1, wherein the co-crystal is form IX having characteristics selected from the group consisting of:
(1) the X-ray powder diffraction pattern of the crystal form IX comprises 3 or more than 32 theta values selected from the following groups: 7.4 +/-0.2 °, 10.2 +/-0.2 °, 10.7 +/-0.2 °, 13.1 +/-0.2 °, 14.1 +/-0.2 °, 15.7 +/-0.2 °, 16.6 +/-0.2 °, 17.1 +/-0.2 °, 17.4 +/-0.2 °, 18.4 +/-0.2 °, 19.6 +/-0.2 °, 20.3 +/-0.2 °, 21.2 +/-0.2 °, 21.8 +/-0.2 °, 23.6 +/-0.2 °, 23.9 +/-0.2 °, 24.9 +/-0.2 °, 25.4 +/-0.2 °, 25.8 +/-0.2 °, 26.3 +/-0.2 °, 26.7 +/-0.2 °, 27.2 +/-0.2 °, 28.0 +/-0 °, 36.8 +/-0.2 °, 37.4 +/-0.2 °; and/or
(2) An X-ray powder diffraction pattern of said crystalline form IX substantially as characterized in FIG. 16; and/or
(3) The TGA diagram of crystalline form IX is substantially as characterized in FIG. 18; and/or
(4) The DSC chart of the crystal form IX has an endothermic peak within the range of 79-113 ℃; and/or
(5) A DSC diagram of said crystalline form ix substantially as characterized in figure 17; and/or
(6) The purity of the crystal form IX is more than 95%.
6. A pesticidal composition, characterized in that the composition comprises:
(a) the solvate or co-crystal of any one of claims 1 to 5, and (b) an agriculturally acceptable carrier.
7. A process for preparing the solvate of claim 2, wherein the solvate is form iii, comprising the steps of:
(i) providing a first solution of a compound of formula I in dimethyl succinate; and
(ii) volatilizing the first solution or mixing the first solution with an anti-solvent and crystallizing to obtain the crystal form III;
and/or
A process for preparing the solvate of claim 3 as form iv comprising the steps of:
(i) providing a first solution of a compound of formula I in thiophene; and
(ii) volatilizing the first solution or mixing the first solution with an anti-solvent and crystallizing to obtain the crystal form IV;
and/or
A method of preparing the solvate of claim 4 in form v comprising the steps of:
(i) providing a first solution of a compound of formula I in ethylene glycol diethyl ether; and
(ii) mixing the first solution with an anti-solvent to form a second solution, and carrying out crystallization treatment on the second solution to obtain the crystal form V as claimed in claim 1.
8. The method of claim 7, wherein the anti-solvent is selected from the group consisting of: water, n-hexane, cyclohexane, n-heptane, or combinations thereof.
9. A method of preparing the co-crystal of claim 5, comprising the steps of:
(i) providing a first solution of a compound of formula I and succinimide in dichloromethane; and
(ii) subjecting the solution to a rapid rotary evaporation treatment to obtain a co-crystal of claim 5, form IX.
10. Use of the solvate or co-crystal according to any one of claims 1 to 5 or the pesticidal composition according to claim 6 for preventing or controlling diseases; or for inhibiting harmful microorganisms in agriculture, forestry or horticulture.
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