CN114213402A - Metastable-state and stable-state crystal forms of xaflufen-ethyl, preparation method and application - Google Patents
Metastable-state and stable-state crystal forms of xaflufen-ethyl, preparation method and application Download PDFInfo
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- 239000013078 crystal Substances 0.000 title claims abstract description 215
- 238000002360 preparation method Methods 0.000 title claims abstract description 33
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- 238000003756 stirring Methods 0.000 claims abstract description 24
- 239000005605 Pyraflufen-ethyl Substances 0.000 claims abstract description 21
- 238000002156 mixing Methods 0.000 claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 14
- APTZNLHMIGJTEW-UHFFFAOYSA-N pyraflufen-ethyl Chemical group C1=C(Cl)C(OCC(=O)OCC)=CC(C=2C(=C(OC(F)F)N(C)N=2)Cl)=C1F APTZNLHMIGJTEW-UHFFFAOYSA-N 0.000 claims abstract description 14
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- YXIIPOGUBVYZIW-UHFFFAOYSA-N pyraflufen Chemical compound ClC1=C(OC(F)F)N(C)N=C1C1=CC(OCC(O)=O)=C(Cl)C=C1F YXIIPOGUBVYZIW-UHFFFAOYSA-N 0.000 description 2
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- AIAYSXFWIUNXRC-PHIMTYICSA-N (1r,5s)-3-[hydroxy-[2-(2-methoxyethoxymethyl)-6-(trifluoromethyl)pyridin-3-yl]methylidene]bicyclo[3.2.1]octane-2,4-dione Chemical compound COCCOCC1=NC(C(F)(F)F)=CC=C1C(O)=C1C(=O)[C@@H](C2)CC[C@@H]2C1=O AIAYSXFWIUNXRC-PHIMTYICSA-N 0.000 description 1
- XMTQQYYKAHVGBJ-UHFFFAOYSA-N 3-(3,4-DICHLOROPHENYL)-1,1-DIMETHYLUREA Chemical compound CN(C)C(=O)NC1=CC=C(Cl)C(Cl)=C1 XMTQQYYKAHVGBJ-UHFFFAOYSA-N 0.000 description 1
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- GVGUFUZHNYFZLC-UHFFFAOYSA-N dodecyl benzenesulfonate;sodium Chemical compound [Na].CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 GVGUFUZHNYFZLC-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
-
- 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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- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Dentistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Plant Pathology (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Agronomy & Crop Science (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The invention provides a metastable state and stable state crystal form of pyraflufen-ethyl, a preparation method and application thereof, comprising the following steps of stirring and heating pyraflufen-ethyl in a first compound solvent to completely dissolve solids, cooling and crystallizing, filtering and drying to obtain white fine needle-shaped crystals, namely a metastable state fine needle-shaped crystal form A; and step two, mixing the metastable state fine needle crystal form A and a second compound solvent in a pressure kettle, pressurizing in an inert gas atmosphere, preserving heat and pressure, keeping the reaction kettle sealed for reaction, cooling and crystallizing, decompressing, filtering and drying to obtain a semitransparent columnar crystal B, namely a stable state columnar crystal B. The crystal form B treated by high temperature, high pressure and high degree of over saturation is a stable crystal form, so that the stability is better, the hygroscopicity is lower, the storage is convenient, the solid preparations such as wettable powder, water dispersible granules and the like of single dosage forms or compound dosage forms prepared by the crystal form B have good stability and drug effect, and the solid preparations have strong practical value for industrial production, popularization and application of the xaflufen.
Description
Technical Field
The invention belongs to the technical field of pesticides, relates to pyraflufen-ethyl, and particularly relates to a stable-state crystal form of pyraflufen-ethyl, a preparation method and application thereof.
Background
Sulfonyl pyrazoxazole (WO2002/062770) is a pre-emergence soil treatment agent developed by Nippon combinatorical Chemicals and industrially produced in combination with Nippon fomentata chemical company, and belongs to a super-long chain fatty acid elongation synthase inhibitor herbicide, and has a chemical name of [3- [ (5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl) -methylxanthoyl ] -4, 5-dihydro-5, 5-dimethyl-1, 2-oxazole ], and a structure represented by formula 1. The action mechanism is that the meristem and the coleoptile of the weed seedling are damaged by inhibiting the super-long chain fatty acid to prolong the synthetase VLCFAE, and the weeding composition has the advantages of high activity, small dosage, wide weed control spectrum, good safety and the like.
Sulfonepyrazazole was registered in 2011 in australia, 2012 in the united states and canada. Technical material registration (PD20190017 and PD20190059) is carried out by Shanghai Mass Chemicals Co., Ltd in 2019 in 1 month in China. It is protected by the domestic synthetic patent (CN1257895C) by 2022. The domestic related patent applications mostly relate to the composition and application of the sulfuryl pyraflufen-ethyl and other raw medicines, such as granted patents CN109588416A, CN109730080A and CN106070244A, which respectively adopt diuron, formamidosulfuron, bicyclopyrone and sulfuryl pyraflufen-ethyl to be combined for use. Patents CN111393427A and CN111574511A optimize the synthesis process of sulfuryl pyrazoxazole and apply for protection. Although the sultopyrazole has the performance advantages and market advantages, the crystal form of the sultopyrazole is not subjected to comprehensive and deep expansibility research.
The crystal forms of the original drugs are converted and preferentially screened, so that an ideal crystal form product which is excellent in performance and suitable for market popularization can be obtained. The chemical substance is influenced by various factors during crystallization, the bonding mode in molecules or between molecules is generally changed, so that the arrangement mode of molecules or atoms in lattice space is changed to form different crystal forms, and the specific method is suitable for the nucleation and growth of a specific crystal form. Applying different conditions during the crystallization of the material, such as cooling, volatilization, pressurization of the solution, melting due to heating of the material, sublimation, etc., are commonly used crystal transformation methods. The solution crystallization method is the most common crystal form conversion method at present because of the advantages of easy generation of polymorphic substances, mild temperature conditions, simple and convenient operation, easy market popularization and the like. The crystal form difference generally has great influence on the physicochemical property and the drug effect of the original drug, different crystal forms of the same material generally have obvious difference in the aspects of stability, solubility, melting point, dissolution speed and the like, stable crystal molecules are compactly and regularly stacked, the thermal entropy is small, the melting point is high, and the chemical stability is high, so that the crystal form difference has important significance on the safe transportation and storage of the original drug and is beneficial to the popularization and application of products. On the contrary, the original drug in the metastable crystal form or amorphous form is easily converted into other polymorphic forms under the conventional conditions, so that the properties of the product are unpredictably and uncontrollably changed, and even the phenomena of agglomeration, moisture absorption, deterioration and the like are generated, which is very unfavorable for the popularization and application of the product.
According to the disclosed method for preparing the sulfone pyraflufen-ethyl, after the reaction, a method of adding water or poor solvent into a reaction system is mostly adopted to separate out the solid of the sulfone pyraflufen-ethyl from the system, and because the system contains impurities and the amount and the temperature of the added water or the poor solvent have no specific process, the purity of the separated white solid is not high enough, the appearance is powdery and has no specific crystal form. In addition, the fine powder is so shaped that it tends to clog the funnel during filtration, resulting in a time-consuming filtration step. In addition, the water-soluble organic silicon dioxide is easy to aggregate into blocks in the drying process, the drying effect is uneven, and the drying efficiency is influenced. The water is easy to adhere to the inner wall of the vessel during storage and has the phenomenon of moisture absorption. Although the traditional solvent recrystallization method has a certain effect on improving the purity, the method generally comprises the steps of sequentially adding a good solvent and a poor solvent for dissolution and crystallization, the solvent amount and the heating temperature are continuously adjusted depending on the phenomenon of material dissolution, the crystallization process is not fixed, the variety of the precipitated crystal form is large in fluctuation, most of the crystal forms are mixed crystal forms, and the quality control and the dosage form design of the product are not facilitated. Therefore, the method has important significance in the aspects of improving the product purity, optimizing the production process and the storage stability, enriching the preparation types and the like by carrying out crystal form variant conversion on the sulfonepyrafluzole to obtain a stable crystal form.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide a metastable-state and stable-state crystal form of the sulfuryl pyraflufen, a preparation method and application thereof, and solve the technical problem that the stable single crystal form of titanium is difficult to obtain in the prior art.
In order to solve the technical problems, the invention adopts the following technical scheme:
a preparation method of a stable-state crystal form of sultoprazole comprises the following steps:
stirring and heating the sulfuryl pyraflufen in a first compound solvent to completely dissolve a solid, cooling and crystallizing, and filtering and drying to obtain a white fine needle crystal which is a metastable fine needle crystal form A;
mixing the metastable state fine needle crystal form A and a second compound solvent in a pressure kettle, pressurizing in an inert gas atmosphere, preserving heat and pressure, keeping the reaction kettle sealed for reaction, cooling and crystallizing, decompressing, filtering and drying to obtain a semitransparent columnar crystal B, namely a stable state columnar crystal B;
the first compound solvent and the second compound solvent are both formed by combining a solvent I and a solvent II according to the volume ratio of 1: 5-5: 1, wherein:
the solvent I is one or more mixed solvents selected from ketones, esters, halogenated alkanes and ethers;
the solvent II is one or more mixed solvents selected from water, alcohols, alkanes and aromatics.
The invention also has the following technical characteristics:
preferably, the solvent I is one or more mixed solvents selected from butanone, n-butyl acetate, chloroform and tetrahydrofuran; the solvent II is one or more mixed solvents selected from methanol or methanol/water combination, n-heptane and toluene.
Further preferably, the first compound solvent is a mixed solvent of butanone and methanol/water, and the volume ratio of the butanone to the methanol/water is (2.8-3) to (0.7: 0.3); the second compound solvent is a mixed solvent of n-butyl acetate and n-heptane, and the volume ratio of the n-butyl acetate to the n-heptane is (1.5-3): 1.
More specifically, the method comprises the steps of:
mixing the pyraflufen-ethyl and a compound solvent according to the mass-volume ratio of 10-200 g/L, stirring and heating the pyraflufen-ethyl in the compound solvent at the heating temperature of 30-110 ℃ for 10-30 minutes to completely dissolve solids, cooling to 25-0 ℃ for crystallization, wherein the crystallization time is 1-48 hours, and filtering and drying to obtain white fine needle crystals, namely the metastable fine needle crystal form A;
and secondly, mixing the metastable state fine needle crystal form A and a compound solvent in a mass-to-volume ratio of 20-350 g/L in a pressure kettle, pressurizing to 0.5-3 MPa in an inert gas atmosphere, heating the mixture in the pressure kettle at 50-150 ℃ for 0.5-2.5 hours, keeping the reaction kettle sealed, cooling the mixture to 25-0 ℃ for crystallization, wherein the crystallization time is 1-72 hours, and filtering and drying the mixture after pressure relief to obtain a semitransparent columnar crystal B, namely a stable state columnar crystal B.
The invention also discloses a stable-state crystal form of the sulfone pyraflufen, which is prepared by the preparation method of the stable-state crystal form of the sulfone pyraflufen, namely the stable-state columnar crystal form B.
The molecular formula of the stable-state crystal form of the sulfonepyraflufen is C12H14F5N3O4S, the stable-state crystal form of the sulfonepyrazoxazole has the following bond length and bond angle:
the invention also protects the application of the stable-state crystal form of the sultopyrazole in herbicides.
The invention also provides a preparation method of the metastable crystal form of the sulfuryl pyraflufen, which is the same as the step I. Thus obtaining the metastable fine needle crystal form A.
The invention also protects the application of the metastable state crystal form of the sultopyrazole prepared by the preparation method of the metastable state crystal form of the sultopyrazole in herbicides.
Compared with the prior art, the invention has the following technical effects:
the invention overcomes the defects of unstable process, poor crystal form unicity and the like of the traditional solvent recrystallization method, and fixes the solvent composition by preferably mixing two or more solvents into a compound solvent with a specific proportion, wherein the white fine needle-shaped crystal form A is obtained by simply heating up, dissolving and cooling down crystallization processes of a certain amount of the pyraflufen-ethyl in the compound solvent under normal pressure, and the frequent adjustment of the solvent ratio and the heating temperature in the heating process of the traditional recrystallization method is avoided; the crystal form B is obtained by carrying out crystal transformation treatment on the crystal form A by using a compound solvent under the conditions of pressurizing and heating and increasing supersaturation degree to obtain a semitransparent columnar crystal form B.
Compared with the white powdery solid separated out from the reaction solution in the preparation process, the two crystal forms have high purity, good dispersibility, single and definite crystal form and realize the conversion of two specific crystal form variants, wherein the crystal form B treated by high temperature, high pressure and high degree of supersaturation is a stable crystal form, so that the stability is better, the hygroscopicity is lower, the storage is convenient, the solid preparations such as wettable powder, water dispersible granules and the like of a single dosage form or a compound dosage form prepared from the crystal form B have good stability and good drug effect, and have strong practical value for industrial production, popularization and application of the pyraflufen-ethyl.
The single dosage form and the compound dosage form prepared by the crystal form B of the sulpirazole have good overall control effect on field weeds, wherein the compound dosage form combined with isoproturon obtains the overall control effect of synergistic interaction, and the water dispersible granules also obtain the best overall control effect.
Drawings
Figure 1 is an X-ray powder diffraction pattern of form a.
Figure 2 is an X-ray powder diffraction pattern of form B.
Figure 3 is an X-ray powder diffraction contrast diagram of form a and form B.
Fig. 4 is a single crystal X-ray diffraction pattern of form B.
Fig. 5 is a schematic diagram of a single crystal X-ray diffraction unit cell structure of form B.
Figure 6 is a thermogravimetric analysis of form a and form B.
Fig. 7 is an infrared spectrum of form a and form B.
Fig. 8 is a partial enlarged view of the infrared spectrum of form a and form B.
Figure 9 is a nuclear magnetic resonance hydrogen spectrum of form a in deuterated chloroform.
Figure 10 is a nuclear magnetic resonance hydrogen spectrum of form B in deuterated chloroform.
The present invention will be explained in further detail with reference to examples.
Detailed Description
It is to be noted that all the raw materials in the present invention, unless otherwise specified, may be those known in the art.
The technical conception of the invention is as follows: firstly, preferably preparing a compound solvent according to the properties of the solvent and solute, then stirring and heating the solid comprising the pyraflufen-ethyl and the compound solvent in a certain mass-volume ratio under normal pressure, and cooling and crystallizing after dissolving; under the pressurizing condition, the mass ratio of the single-crystal-form sultopyrazole to the compound solvent is increased, cooling and crystallization are carried out under certain pressure after heating for certain time, products with different appearances are obtained under the action of multiple crystal transformation factors of high pressure, temperature and supersaturation degree, and the fact that the crystal form of the sultopyrazole is converted and changed from a metastable state to a stable state is confirmed through X-ray powder diffraction analysis, single-crystal X-ray structural analysis, infrared spectrum analysis and thermal analysis.
In the present invention, the starting material of the sulfoxaflor is selected from amorphous type, a mixture containing amorphous type of sulfoxaflor or non-single crystal type of sulfoxaflor.
In the invention, the oxazole is in a metastable fine needle-like crystal form A, namely a crystal form A; and (3) stable columnar crystal form B, namely the crystal form B.
The present invention is not limited to the following embodiments, and all equivalent changes based on the technical solutions of the present invention fall within the protection scope of the present invention.
Comparative example 1:
adding 20g of powdery non-single crystal form xaflufen-ethyl into a 250mL three-neck round-bottom flask containing 100mL of butanone, installing a reflux condenser tube, then violently stirring (800 revolutions per minute) at 80 ℃ by using magnetons until the solution is clear, gradually adding a mixed solution of methanol and water (0.7:0.3) until the solution is turbid, dropwise adding a few drops of butanone, continuously heating and stirring, just recovering the clear solution to obtain a heat supersaturated solution. And (3) cooling the supersaturated solution under the condition of stirring, cooling to room temperature for about 1 hour, gradually separating out a white solid, continuing the recrystallization process for 6 hours, and filtering and drying to obtain 18.2g of a mixed solid containing white powder and fine needles, wherein the content of liquid chromatography is 98.0%, the yield is 89%, and the mixed solid is an unspecified single crystal form.
Comparative example 2:
adding 29.7g of the crystal form A of the sulfonepyrazoxazole into a 500mL pressure kettle containing 110mL of n-butyl acetate/n-heptane (1.8:1) compound solvent, replacing air in the kettle with nitrogen for 3 times, sealing the kettle, continuously filling nitrogen until the pressure reaches 2.4MPa, keeping the state for 20 hours under the condition of no stirring and room temperature, decompressing, filtering and drying to obtain a mixture containing a small amount of columnar white fine needle-shaped solid 28.2g, the liquid chromatogram content is 96.8%, the yield is 92%, and the mixture is a mixture of incompletely dissolved raw materials and partially crystallized products.
Comparative example 3:
adding 20g of powdery non-single crystal type sulfoxaflor into a 250mL three-mouth round-bottom flask containing 110mL of acetone/(methanol/water) ═ 2.9 (0.7:0.3) compound solvent, installing a return pipe, violently stirring with magnetons at 56 ℃ (800 rpm) for 20 minutes until the solution is clear, stopping heating, cooling to about 3 ℃ by using an ice water bath, separating out less white solid, continuously stirring for 12 hours, filtering and crystallizing to obtain 11.6g of a small amount of white fine needle-shaped crystals, wherein the liquid chromatogram content is 99.4%, the yield is 58%, and part of the sulfoxaflor cannot be separated out.
Comparative example 4:
adding 29.7g of powdery non-single crystal type sulfonepyrazoxazole into a 500mL pressure kettle containing a compound solvent with the volume ratio of 110mL of n-butyl acetate to n-heptane being 1.8:1, replacing air in the kettle with nitrogen for 3 times, sealing the kettle, continuously filling nitrogen until the pressure reaches 2.1MPa, heating to 120 ℃ under the condition of no stirring, at the moment, keeping the pressure to 2.4MPa, keeping the state for 2 hours, and stopping heating. And naturally cooling the pressure kettle to about 25 ℃, continuing the state for 18 hours to perform crystallization, decompressing, filtering and drying to obtain 27.8g of a solid containing a small amount of columnar crystals and the balance of white powder to fine needle shape, wherein the content of liquid chromatogram is 99.2 percent, the yield is 93 percent, and the obtained sulfonepyrazoxazole has a complex crystal form state and is a non-specific single crystal form.
Example 1:
the embodiment provides a preparation method of a stable-state crystal form of sultopyrazole, which is characterized by comprising the following steps of:
adding 20g of powdery non-single crystal form xaflufen-ethyl into a 250mL three-neck round-bottom flask containing a compound solvent with the volume ratio of 110mL butanone/(methanol/water) being 2.9 (0.7:0.3), installing a return pipe, vigorously stirring with a magneton at 65 ℃ for 20 minutes (800 revolutions per minute) until the solution is clear, stopping heating, naturally cooling to about 25 ℃, gradually precipitating a white solid, continuously stirring at room temperature for 6 hours, filtering and crystallizing to obtain 17.8g of white fine needle crystals, the content of liquid chromatogram is 99.0%, the yield is 89%, the melting point is tested to be 134.2 ℃, the crystals are tested to be specific crystal forms by an X-ray powder diffraction method, and the crystals are called as crystal forms A as shown in figure 1. The thermogravimetric analysis is shown in fig. 6, the fourier transform infrared spectrum is shown in fig. 7 and 8, and the nuclear magnetic resonance hydrogen spectrum is shown in fig. 9.
Adding 29.7g of the crystal form A of the sulfoxaflor into a 500mL pressure kettle containing a compound solvent with the volume ratio of 110mL of n-butyl acetate to n-heptane being 1.8:1, replacing air in the kettle with nitrogen for 3 times, sealing the kettle, continuously filling nitrogen until the pressure reaches 2.1MPa, heating to 120 ℃ under the condition of no stirring, at the moment, keeping the pressure to reach 2.4MPa, and stopping heating after the state is maintained for 2 hours. The autoclave is naturally cooled to about 25 ℃ and is kept in the state for 18 hours for crystallization, pressure is released, then the obtained product is filtered and dried to obtain 27.8g of semitransparent columnar crystal, the content of liquid chromatogram is 99.2 percent, the yield is 93 percent, the melting point of the semitransparent columnar crystal is tested to be 131.7 ℃, and the semitransparent columnar crystal is tested to be a specific single crystal form by an X-ray powder diffraction method, as shown in figure 2, the crystal form B is called as a crystal form B. The single crystal X-ray diffraction structure analysis is shown in fig. 4 and 5, the thermogravimetric analysis is shown in fig. 6, the fourier transform infrared spectrum is shown in fig. 7 and 8, and the nuclear magnetic resonance hydrogen spectrum is shown in fig. 10.
Characterization and performance testing:
an X-ray powder diffraction pattern of the crystal form A is shown in figure 1, and the 2 theta value has characteristic peaks at 5.0 degrees +/-0.2 degrees, 10.0 degrees +/-0.2 degrees, 15.0 degrees +/-0.2 degrees, 20.0 degrees +/-0.2 degrees, 22.0 degrees +/-0.2 degrees, 22.8 degrees +/-0.2 degrees, 25.2 degrees +/-0.2 degrees, 30.2 degrees +/-0.2 degrees and 31.6 degrees +/-0.2 degrees.
An X-ray powder diffraction pattern of the stable crystal form B is shown in figure 2, and the 2 theta value has characteristic peaks at 5.1 +/-0.2 degrees, 7.6 +/-0.2 degrees, 10.0 +/-0.2 degrees, 11.2 +/-0.2 degrees, 15.0 +/-0.2 degrees, 17.8 +/-0.2 degrees, 20.0 +/-0.2 degrees, 22.4 +/-0.2 degrees, 25.6 +/-0.2 degrees, 27.0 +/-0.2 degrees, 28.4 +/-0.2 degrees, 30.2 +/-0.2 degrees, 31.6 +/-0.2 degrees, 32.4 +/-0.2 degrees, 34.6 +/-0.2 degrees and 35.6 +/-0.2 degrees.
Figure 3 is an X-ray powder diffraction contrast diagram of form a and form B.
As shown in fig. 4, the crystal structure of the crystal form B was analyzed by single crystal X-ray diffraction, and important parameters for clearly characterizing the crystal structure of the crystal form B, that is, the stable state crystal form of xaflufen had the following bond lengths and bond angles:
as shown in fig. 5, the crystal structure parameters obtained from the crystal structure and unit cell of form B are:
two crystals of different appearances were tested by thermogravimetric analysis (fig. 6), form a being heated to 298 deg.f℃With a weight loss of about 7% during the preceding temperature rise, 298℃The weight loss then increases with increasing temperature. Heating the crystal form B to 302℃A weight loss of about 3% with a temperature rise, 302℃The weight loss then increases with increasing temperature. The accelerated heat loss onset temperature of form B is higher than that of form a. And below the initial temperature of accelerated heat loss, the mass loss of the crystal form B at the same heating temperature is less than that of the crystal form A, the crystal form B is a stable crystal form, and the crystal form A is a metastable crystal form.
Fourier transform infrared spectroscopy (FT-IR) is adopted to test two crystals with different appearances (figure 7 and figure 8), and the infrared characteristic peak of the crystal form A and the infrared characteristic peak of the crystal form B have the wave number of 440cm-1、708cm-1、768cm-1、906cm-1、924cm-1、1033cm-1、1301cm-1、1376cm-1、1382cm-1、1462cm-1、1580cm-1、2952cm-1、3078cm-1、3400cm-1The peak shape and the peak intensity are different, which shows the bonding mode in the two crystal formsChanges are made.
By NMR1HNMR) the solutions of the two crystal forms were subjected to structural characterization (fig. 9, fig. 10), and it can be seen that the two have the same structure in the deuterated chloroform solution. Hydrogen spectroscopy was as follows, form a solution:1H NMR(CDCl3500MHz) delta (ppm) 6.62-6.90(t,1H),4.53(s,2H),3.81(s,3H),3.03(s,2H),1.45(s, 6H). Form B solution:1H NMR(CDCl3500MHz) delta (ppm) 6.69-6.97(t,1H),4.60(s,2H),3.88(s,3H),3.10(s,2H),1.52(s, 6H). The crystal form characteristics of the crystal form A and the crystal form B disappear in a solution state, the structures of the crystal form A and the crystal form B are the same, and the nuclear magnetic hydrogen spectrum does not contain other miscellaneous peaks, so that the crystal form A and the crystal form B obtained by the two methods are high-purity products.
The melting points of the two crystal forms are tested by a melting point instrument in an indoor environment, and the melting point of the crystal form A is 131.7℃Form B has a melting point of 134.2℃And the melting point of the crystal form B is high.
The stability and the hygroscopicity of the crystal form A and the crystal form B are tested, and the appearance, the crystal form and the quality of the crystal form B have no obvious change within a certain temperature and humidity range.
The crystal form B and the crystal form A are provided with single dosage forms of wettable powder and water dispersible granules, and the wettable powder and the water dispersible granules are combined with isoproturon to form compound dosage forms of wettable powder and water dispersible granules, and the dosage forms, particularly the dosage forms based on the crystal form B, show good stability under the environments of normal temperature, low temperature and high temperature. The dosage forms based on the crystal form B are subjected to field efficacy tests, and the whole control effects of the dosage forms on eleusine indica, crabgrass, barnyard grass, green bristlegrass, chenopodium album, amaranthus retroflexus and the like are all over 91 percent and are maximally over 94 percent by adopting a pre-emergence soil spray treatment method, so that the weed control effect is good.
Example 2:
the embodiment provides a preparation method of a stable-state crystal form of sultopyrazole, which is characterized by comprising the following steps of:
22g of powdery non-single crystal form xaflufen-ethyl is added into a 250mL three-neck round bottom flask containing 110mL of butanone/n-heptane (3.2:1) compound solvent, a return pipe is installed, magnetons are vigorously stirred (800 revolutions per minute) for 30 minutes at the temperature of 98 ℃ until the solution is clear, heating is stopped, cooling is carried out to room temperature, white solid is gradually separated out, stirring is continuously carried out for 8 hours, and filtering crystallization is carried out to obtain 18.4g of white fine needle-shaped crystals, the liquid chromatogram content is 99.1%, the yield is 83%, and the crystal form is characterized to be the same as that of example 1 and is crystal form A.
Adding 31.9g of the crystal form A of the sulfonepyrazoxazole into a 500mL pressure kettle containing 110mL of tetrahydrofuran/toluene (3:1) compound solvent, replacing air in the kettle with nitrogen for 3 times, sealing the kettle, continuously filling nitrogen until the pressure reaches 1.8MPa, raising the temperature to 120 ℃ under the condition of no stirring, keeping the pressure at 2.3MPa, keeping the state for 2 hours, and stopping heating. Naturally cooling the pressure kettle to 25 ℃, transferring the pressure kettle into a low-temperature bath tank at 0 ℃ for heat preservation, continuing the state for 12 hours to perform crystallization, decompressing, filtering and drying to obtain 28.6g of semitransparent columnar crystals, wherein the content of liquid chromatogram is 99.1%, the yield is 89%, and the crystal form is represented as the crystal form B in the same way as in example 2.
Example 3:
the embodiment provides a preparation method of a stable-state crystal form of sultopyrazole, which is characterized by comprising the following steps of:
19.8g of powdery non-single crystal type sulfonepyrazoxazole is added into a 250mL three-mouth round-bottom flask containing 110mL of chloroform/methanol (1.8:1) compound solvent, a return pipe is installed, magnetons are stirred vigorously (800 revolutions per minute) for 30 minutes at the temperature of 65 ℃ until the solution is clear, heating is stopped, cooling is carried out to room temperature, white solid is gradually separated out, stirring is carried out continuously for 20 hours, and filtration and crystallization are carried out to obtain 17.4g of white fine needle-shaped crystals, the liquid chromatogram content is 99.2%, the yield is 87%, and the crystal form is characterized to be the same as that of example 1 and is crystal form A.
30.9g of the crystal form A of the sulfonepyrazoxazole is added into a 500mL pressure kettle containing 110mL of trichloromethane/toluene (1.8:1) compound solvent, the air in the kettle is replaced by nitrogen for 3 times, the kettle is sealed, then the nitrogen is continuously filled until the pressure reaches 1.8MPa, the temperature is raised to 100 ℃ under the condition of no stirring, the pressure reaches 2.2MPa at the moment, the state is maintained for 2 hours, and the heating is stopped. And naturally cooling the pressure kettle to 25 ℃, transferring the pressure kettle into a low-temperature bath tank at 0 ℃ for heat preservation, continuing the state for 12 hours to perform crystallization, decompressing, filtering and drying to obtain 27.7g of semitransparent columnar crystals, wherein the content of liquid chromatogram is 99.2%, the yield is 89%, and the crystal form is represented as the crystal form B in the same way as in example 2.
Example 4:
the embodiment provides a preparation method of a stable-state crystal form of sultopyrazole, which is characterized by comprising the following steps of:
adding 20g of powdery non-single crystal type sulfonepyrazoxazole into a 250mL three-neck round-bottom flask containing 110mL of tetrahydrofuran/toluene/methanol (1.9:0.3:0.7) compound solvent, installing a reflux pipe, violently stirring (800 revolutions per minute) for 20 minutes at the temperature of 66 ℃ until the solution is clear, stopping heating, cooling to about 5 ℃ by using an ice water bath, gradually separating out a white solid, continuously stirring for 6 hours, filtering and crystallizing to obtain 17.1g of white fine needle-shaped crystals, wherein the content of liquid chromatogram is 99.2 percent, the yield is 85 percent, and the crystal form is characterized to be the same as that of example 1 and is crystal form A.
Adding 29.7g of the crystal form A of the sulfonepyrazoxazole into a 500mL pressure kettle containing 110mL of tetrahydrofuran/trichloromethane/n-heptane (1:0.5:1) compound solvent, replacing the air in the kettle with nitrogen for 3 times, sealing the kettle, continuously filling nitrogen until the pressure reaches 2.0MPa, heating to 110 ℃ under the condition of no stirring, at the moment, keeping the pressure to reach 2.4MPa, and stopping heating after the state is maintained for 2 hours. The autoclave is naturally cooled to about 25 ℃ and kept in the state for 18 hours to perform crystallization, and after pressure relief, filtration and drying are performed to obtain 24.2g of semitransparent columnar crystals, the content of liquid chromatogram is 99.3%, the yield is 81%, and the crystal form is represented as the crystal form B in the same way as in example 2.
Example 5:
this example shows the use of a stable crystalline form of xaflufen for herbicides. Wherein, the crystal form A and the crystal form B are both the crystal form A and the crystal form B prepared in the example 1.
Firstly, crystal form stability experiment:
the experimental method comprises the following steps: storing the solid of the crystal form A and the solid of the crystal form B of the sulfoxaflor at different temperatures for 14 days, and retesting the change condition of the crystal forms.
Experimental data:
and (4) experimental conclusion: the crystal form B of the sulpyrazox is stable, and the obvious crystal transformation phenomenon does not occur in the conventional storage; the crystal form A is relatively stable, and a certain amount of amorphous transformation phenomenon occurs at higher temperature.
II, crystal form hygroscopicity experiment:
the experimental method comprises the following steps: taking 100 g of the topramezone A and B solid respectively, storing for 7 days under different humidity, and retesting the quality and appearance change conditions.
Experimental data:
and (4) experimental conclusion: the crystal form B of the sulpyrazox has no obvious hygroscopicity within a set humidity and temperature range; the crystal form A has no obvious hygroscopicity in a lower humidity and temperature range, but shows a slight moisture absorption hardening phenomenon when the humidity and the temperature are increased to a higher level.
Thirdly, formulation and field efficacy experiment:
the first experiment and the second experiment show that the crystal form B of the sulfoxaflor has obvious advantages in the aspects of crystal structure and storage stability and also has obvious advantages in the aspect of configuration of solid dosage forms.
The obtained sulfonepyrazoxazole crystal form B can be used alone or compounded with other herbicides to be used as an effective active ingredient, and then is prepared into an adaptive dosage form together with an agriculturally commonly acceptable auxiliary agent, wherein the preferable dosage form is wettable powder, water dispersible granules and the like.
1. The formula of the 30% sulfonepyrazoxazole wettable powder is as follows:
| material(s) | Percent by mass (%) |
| Crystal form B/crystal form A of |
40 |
| |
10 |
| Sodium dodecyl benzene sulfonate | 9 |
| |
6 |
| |
10 |
| Diatomite | Make up to 100 |
The preparation method of the preparation comprises the following steps: and (2) uniformly mixing the materials in a mixer, crushing the materials by using an airflow crusher, further mixing the materials in the mixer, and drying the materials by using a 600-mesh standard sieve to obtain the sulfuryl pyraflufen-ethyl wettable powder.
The physical and chemical properties of the obtained wettable powder product are tested, the content is tested after the product is placed in a sealing way for 14 days at room temperature, the content is tested after the product is placed in a sealing way for 7 days at 0 ℃ in cold storage, and the content is tested after the product is placed in a sealing way for 14 days at 54 ℃ in hot storage, so that the stability is good, the use requirements can be met, and the results are shown in the following table:
2. the formulation of a 40% sulfonepyrazofen/isoproturon (20:20) wettable powder is as follows:
the preparation method of the preparation comprises the following steps: and uniformly mixing the materials in a mixer, crushing the materials by using a jet mill, further mixing the materials in the mixer, and drying the materials by using a 600-mesh standard sieve to obtain the sulfuryl pyraflufen/isoproturon wettable powder.
The physical and chemical properties of the obtained compounded wettable powder product are tested, the content is tested after the compounded wettable powder product is placed in a sealing way for 14 days at room temperature, the content is tested after the compounded wettable powder product is placed in a sealing way for 7 days at 0 ℃ in cold storage, and the content is tested after the compounded wettable powder product is placed in a sealing way for 14 days at 54 ℃ in hot storage, so that the stability is good, the use requirements can be met, and the results are shown in the following table:
3. the formula of the 30% sulfonepyrazoxazole water dispersible granule is as follows:
| material(s) | Percent by mass (%) |
| Crystal form B/crystal form A of |
30 |
| Lignosulfonic |
15 |
| |
15 |
| Polydimethylsiloxane | 0.5 |
| Kaolin clay | Make up to 100 |
The preparation method of the preparation comprises the following steps: and uniformly mixing the materials in a mixer, crushing the materials by using an air flow crusher, further mixing the materials in the mixer, adding the materials into a kneader after passing through a 600-mesh standard sieve, kneading the materials into a plastic material, adding the plastic material into an extrusion granulator, carrying out extrusion granulation, and drying to obtain the water dispersible granules of the pyraflufen-ethyl.
The physicochemical properties of the obtained water dispersible granule product are tested, the content is tested after the water dispersible granule product is placed in a sealing way for 14 days at room temperature, the content is tested after the water dispersible granule product is placed in a sealing way for 7 days at 0 ℃ in cold storage, and the content is tested after the water dispersible granule product is placed in a sealing way for 14 days at 54 ℃ in hot storage, so that the stability is good, the use requirements can be met, and the results are shown in the following table:
4. the formula of the 40% sulfonepyrazofen/isoproturon (20:20) water dispersible granule is as follows:
| material(s) | Percent by mass (%) |
| Crystal form B/crystal form A of |
20 |
| |
20 |
| Tea seed cake powder | 7 |
| |
5 |
| |
5 |
| Disodium hydrogen phosphate | 4 |
| Bentonite clay | Make up to 100 |
The preparation method of the preparation comprises the following steps: and uniformly mixing the materials in a mixer, crushing the materials by using an air flow crusher, further mixing the materials in the mixer, adding the materials into a kneader after passing through a 600-mesh standard sieve, kneading the materials into a plastic material, adding the plastic material into an extrusion granulator, extruding and granulating the plastic material, and drying the plastic material to obtain the water dispersible granule containing the pyriflufen/isoproturon.
The physicochemical properties of the obtained water dispersible granule product were tested, the content was tested after being placed in a sealed manner at room temperature for 14 days at room temperature, the content was tested after being placed in a sealed manner at 0 ℃ for 7 days in cold storage, and the content was tested after being placed in a sealed manner at 54 ℃ for 14 days in hot storage, so that the stability was good, the use requirements could be met, and particularly the preparation obtained from the crystal form B was better, and the results are shown in the following table:
5. test of field weed efficacy
And performing a field weed efficacy test on the crystal form B preparation with good stability.
The weeds generated in the field of the selected test field mainly comprise eleusine indica, crabgrass, barnyard grass, green bristlegrass, chenopodium album, amaranthus retroflexus and the like.
The test method comprises the following steps: the soil is treated by manual spraying before weed germination, the water adding amount is 40 kg/mu, the area of a cell is 50 square meters, the treatment is repeated for 4 times, and the control effect is investigated 45 days after the application. Wherein the weed control effect (%) (the number of weed plants in the clear water control area-the number of weed plants in the medicament treatment area)/the number of weed plants in the clear water control area. The control effect results are as follows:
| group of embodiments | Dosage forms | Amount (ga.i./ha) | Overall control Effect (%) |
| 40% Sulfoxaden | Wettable powder | 180 | 91.2 |
| 50% Sulfuron pyrazofen + isoproturon (20+30) | Wettable powder | 225 | 93.3 |
| 30% Sulfoxaden | Water |
200 | 91.9 |
| 40% Sulfuron pyrazofen + isoproturon (20+20) | Water dispersible granule | 225 | 94.2 |
The result of a pharmacodynamic test shows that the single dosage form and the compound dosage form prepared from the crystal form B of the sulpirazole have good overall control effect on field weeds, wherein the compound dosage form combined with isoproturon obtains the overall control effect of synergistic interaction, and the water dispersible granules also obtain the optimal overall control effect.
The application examples are only used for illustrating the practical application value of the stable crystal form of the sulpirazole, and the protection scope of the invention cannot be limited by the application examples. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.
Claims (10)
1. A preparation method of a stable-state crystal form of sultoprazole is characterized by comprising the following steps:
stirring and heating the sulfuryl pyraflufen in a first compound solvent to completely dissolve a solid, cooling and crystallizing, and filtering and drying to obtain a white fine needle crystal which is a metastable fine needle crystal form A;
mixing the metastable state fine needle crystal form A and a second compound solvent in a pressure kettle, pressurizing in an inert gas atmosphere, preserving heat and pressure, keeping the reaction kettle sealed for reaction, cooling and crystallizing, decompressing, filtering and drying to obtain a semitransparent columnar crystal B, namely a stable state columnar crystal B;
the first compound solvent and the second compound solvent are both formed by combining a solvent I and a solvent II according to the volume ratio of 1: 5-5: 1, wherein:
the solvent I is one or more mixed solvents selected from ketones, esters, halogenated alkanes and ethers;
the solvent II is one or more mixed solvents selected from water, alcohols, alkanes and aromatics.
2. The method for preparing the stable-state crystal form of the sulfone pyraflufen-ethyl as claimed in claim 1, wherein the solvent I is one or more mixed solvents selected from butanone, n-butyl acetate, trichloromethane and tetrahydrofuran; the solvent II is one or more mixed solvents selected from methanol or methanol/water combination, n-heptane and toluene.
3. The preparation method of the stable-state crystal form of the sulfone pyraflufen-ethyl as claimed in claim 2, characterized in that the first compound solvent is a mixed solvent of butanone and methanol/water, and the volume ratio of the butanone to the methanol/water is (2.8-3): (0.7: 0.3); the second compound solvent is a mixed solvent of n-butyl acetate and n-heptane, and the volume ratio of the n-butyl acetate to the n-heptane is (1.5-3): 1.
4. A process for the preparation of a steady state crystalline form of sulfonepyrazoxazole as claimed in claim 1 which comprises the steps of:
mixing the pyraflufen-ethyl and a first compound solvent according to the mass-volume ratio of 10-200 g/L, stirring and heating the pyraflufen-ethyl in the compound solvent at the heating temperature of 30-110 ℃ for 10-30 minutes to completely dissolve solids, cooling to 25-0 ℃ for crystallization, wherein the crystallization time is 1-48 hours, and filtering and drying to obtain white fine needle crystals, namely the metastable fine needle crystal form A;
and secondly, mixing the metastable state fine needle crystal form A and a second compound solvent in a mass-to-volume ratio of 20-350 g/L in a pressure kettle, pressurizing to 0.5-3 MPa in an inert gas atmosphere, heating to 50-150 ℃ in the pressure kettle for 0.5-2.5 hours, keeping the reaction kettle sealed, cooling to 25-0 ℃ for crystallization, wherein the crystallization time is 1-72 hours, and filtering and drying after pressure relief to obtain a semitransparent columnar crystal B, namely a stable state columnar crystal B.
5. A stable-state crystal form of sulfuryl pyrazole, which is characterized by being prepared by the preparation method of the stable-state crystal form of the sulfuryl pyrazole as claimed in any one of claims 1 to 4.
6. The stable crystalline form of sulfonepyrafluzole of claim 5, wherein the stable crystalline form of sulfonepyrafluzole has the formula C12H14F5N3O4S, the stable-state crystal form of the sulfonepyrazoxazole has the following bond length and bond angle:
7. the stable-state crystal form of the xaflufen-ethyl is characterized in that the molecular formula of the stable-state crystal form of the xaflufen-ethyl is C12H14F5N3O4S, the stable-state crystal form of the sulfonepyrazoxazole has the following bond length and bond angle:
8. use of the steady state crystalline form of sulfonepyrazoxazole as claimed in any of claims 6 to 7 for herbicides.
9. A preparation method of a metastable crystal form of sulfonepyrazoxazole, which is characterized by comprising the following steps: mixing the pyraflufen-ethyl and a first compound solvent according to the mass-to-volume ratio of 10-200 g/L, stirring and heating the pyraflufen-ethyl in the compound solvent at the heating temperature of 30-110 ℃ for 10-30 minutes to completely dissolve solids, cooling to 25-0 ℃ for crystallization, wherein the crystallization time is 1-48 hours, and filtering and drying to obtain white fine needle crystals, namely the metastable fine needle crystal form A;
the first compound solvent and the second compound solvent are both formed by combining a solvent I and a solvent II according to the volume ratio of 1: 5-5: 1, wherein:
the solvent I is one or more mixed solvents selected from ketones, esters, halogenated alkanes and ethers;
the solvent II is one or more mixed solvents selected from water, alcohols, alkanes and aromatics.
10. The use of the metastable crystal form of sulfonepyrazoxazole prepared by the process for preparing the metastable crystal form of sulfonepyrazoxazole as claimed in claim 9 in herbicides.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114989157A (en) * | 2022-06-28 | 2022-09-02 | 安徽久易农业股份有限公司 | Crystal form A of pyraflufen-ethyl and preparation method and application thereof |
| CN119899181A (en) * | 2025-02-13 | 2025-04-29 | 鹤壁市宝瑞德化工有限公司 | A crystal form of sulfonepyraclostrobin and preparation method thereof |
| CN120441564A (en) * | 2025-06-26 | 2025-08-08 | 济南大学 | Crystal form of dihydroisoxazole compound, preparation method and application thereof |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1678588A (en) * | 2002-08-01 | 2005-10-05 | 庵原化学工业株式会社 | Pyrazole derivatives and production methods thereof |
| CN102666502A (en) * | 2009-11-26 | 2012-09-12 | 巴斯夫欧洲公司 | Method for producing 5,5-disubstituted 4,5-dihydroisoxazol-3-thiocarboxamidine salts |
| CN111393427A (en) * | 2020-04-30 | 2020-07-10 | 安徽久易农业股份有限公司 | Synthetic method of sulfuryl pyraflufen |
| CN112969697A (en) * | 2019-10-31 | 2021-06-15 | 组合化学工业株式会社 | Process for producing herbicide and intermediate thereof |
| WO2021144796A1 (en) * | 2020-01-15 | 2021-07-22 | Adama Agan Ltd. | Solid state form of pyroxasulfone |
| CN113754647A (en) * | 2020-06-02 | 2021-12-07 | 山东润博生物科技有限公司 | Synthesis method of sulfuryl pyraflufen-ethyl and intermediate thereof |
| CN113754648A (en) * | 2020-06-02 | 2021-12-07 | 山东润博生物科技有限公司 | Preparation method of xaflufen and intermediate thereof |
| CN113831333A (en) * | 2021-10-14 | 2021-12-24 | 大连九信精细化工有限公司 | Synthetic method of sulfuryl pyraflufen |
-
2021
- 2021-12-01 CN CN202111451046.1A patent/CN114213402A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1678588A (en) * | 2002-08-01 | 2005-10-05 | 庵原化学工业株式会社 | Pyrazole derivatives and production methods thereof |
| CN102666502A (en) * | 2009-11-26 | 2012-09-12 | 巴斯夫欧洲公司 | Method for producing 5,5-disubstituted 4,5-dihydroisoxazol-3-thiocarboxamidine salts |
| CN112969697A (en) * | 2019-10-31 | 2021-06-15 | 组合化学工业株式会社 | Process for producing herbicide and intermediate thereof |
| WO2021144796A1 (en) * | 2020-01-15 | 2021-07-22 | Adama Agan Ltd. | Solid state form of pyroxasulfone |
| CN111393427A (en) * | 2020-04-30 | 2020-07-10 | 安徽久易农业股份有限公司 | Synthetic method of sulfuryl pyraflufen |
| CN113754647A (en) * | 2020-06-02 | 2021-12-07 | 山东润博生物科技有限公司 | Synthesis method of sulfuryl pyraflufen-ethyl and intermediate thereof |
| CN113754648A (en) * | 2020-06-02 | 2021-12-07 | 山东润博生物科技有限公司 | Preparation method of xaflufen and intermediate thereof |
| CN113831333A (en) * | 2021-10-14 | 2021-12-24 | 大连九信精细化工有限公司 | Synthetic method of sulfuryl pyraflufen |
Non-Patent Citations (2)
| Title |
|---|
| ""砜吡草唑"", 《农药科学与管理》, vol. 40, no. 12, pages 50 - 51 * |
| 沈运河等: ""砜吡草唑的合成工艺研究"", 《世界农药》, vol. 42, no. 9, pages 40 - 43 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114989157A (en) * | 2022-06-28 | 2022-09-02 | 安徽久易农业股份有限公司 | Crystal form A of pyraflufen-ethyl and preparation method and application thereof |
| WO2024001401A1 (en) * | 2022-06-28 | 2024-01-04 | 安徽久易农业股份有限公司 | Crystal form a of pyroxasulfone, and preparation method therefor and use thereof |
| CN119899181A (en) * | 2025-02-13 | 2025-04-29 | 鹤壁市宝瑞德化工有限公司 | A crystal form of sulfonepyraclostrobin and preparation method thereof |
| CN120441564A (en) * | 2025-06-26 | 2025-08-08 | 济南大学 | Crystal form of dihydroisoxazole compound, preparation method and application thereof |
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