CN108947914B - Azoxystrobin acetic acid solvate and preparation method thereof - Google Patents

Azoxystrobin acetic acid solvate and preparation method thereof Download PDF

Info

Publication number
CN108947914B
CN108947914B CN201810573514.4A CN201810573514A CN108947914B CN 108947914 B CN108947914 B CN 108947914B CN 201810573514 A CN201810573514 A CN 201810573514A CN 108947914 B CN108947914 B CN 108947914B
Authority
CN
China
Prior art keywords
azoxystrobin
acetic acid
degrees
solvate
raw material
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201810573514.4A
Other languages
Chinese (zh)
Other versions
CN108947914A (en
Inventor
龚俊波
杨海燕
刘裕
侯宝红
李鸣晨
贾丽娜
张诺阳
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tianjin University
Original Assignee
Tianjin University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Tianjin University filed Critical Tianjin University
Priority to CN201810573514.4A priority Critical patent/CN108947914B/en
Publication of CN108947914A publication Critical patent/CN108947914A/en
Application granted granted Critical
Publication of CN108947914B publication Critical patent/CN108947914B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention relates to an azoxystrobin acetic acid solvate and a preparation method thereof. The X-ray powder diffraction pattern has characteristic peaks at diffraction angles 2 theta of 7.40 +/-0.20 degrees, 8.28 +/-0.20 degrees, 13.26 +/-0.20 degrees, 14.07 +/-0.20 degrees, 14.52 +/-0.20 degrees, 18.08 +/-0.20 degrees, 18.42 +/-0.20 degrees, 18.86 +/-0.20 degrees, 20.46 +/-0.20 degrees, 21.18 +/-0.20 degrees, 22.14 +/-0.20 degrees, 22.68 +/-0.20 degrees, 24.46 +/-0.20 degrees, 26.88 +/-0.20 degrees, 28.60 +/-0.20 degrees and the like, wherein 7.40 +/-0.20 degrees is an initial peak, and the relative intensity of the characteristic peaks at 21.18 +/-0.20 degrees is 100 percent. The preparation method is a constant-temperature suspension crystal transformation method, is simple to operate, has good reproducibility, good product fluidity, is not easy to agglomerate, and is easy to industrialize.

Description

Azoxystrobin acetic acid solvate and preparation method thereof
Technical Field
The invention belongs to the field of pharmaceutical chemicals, and particularly relates to an azoxystrobin acetic acid solvate and a preparation method thereof.
Background
Polymorphism refers to the phenomenon of solid states with different physicochemical properties formed by solid substances in two or more different spatial arrangements. In the field of pharmaceutical research, polymorphs include multicomponent crystalline forms such as organic solvates, hydrates, and the like.
Drug polymorphism is a characteristic inherent in small organic molecule compounds and widely exists in the drug development process. Different crystal forms have different colors, melting points, solubilities, dissolution properties, reactivities, chemical stabilities, mechanical stabilities and the like, and the physical and chemical properties or the processability sometimes directly influence the safety and the effective performance of the medicine. Therefore, research and control of crystal forms become important research content in the process of drug development.
The crystal form research comprises two stages of crystal discovery and crystal form optimization, in the crystal discovery stage, various crystallization means are mainly adopted, such as crystallization methods of melt crystallization, solution volatilization, rapid cooling, a constant-temperature suspension method and the like, external factors influencing drug crystallization are changed by changing crystallization conditions, solvents, temperatures, speeds, suspension solvent ratios and the like, a high-throughput sample preparation platform is adopted, hundreds of crystallization tests are prepared simultaneously, and a trace sample preparation technology and an analysis test means are adopted to prepare and discover a new crystal form. In the crystal form optimization stage, new crystal form process amplification and preparation conditions are required to be searched, various solid characterization means such as X-ray diffraction, solid nuclear magnetic resonance, Raman spectroscopy, infrared spectroscopy and other means are adopted for crystal form crystal characterization, in addition, DSC, TG A, DVS, HPLC and the like are adopted for carrying out physical and chemical property research on the crystal form, the stability, the processability and the like of different crystal forms are compared for carrying out research, and finally, the most preferable solid form is selected for development.
China is a large country for using and producing pesticides, but the research attention on the crystallization process and the crystal property of the pesticides is far from enough, and Azoxystrobin (Azoxystrobin) with the name of 'King of fungicide' and the chemical name of 3- (E) -2- [2- [6- (2-cyanophenoxy) pyrimidin-4-yloxy group]-phenyl radical]-3-methoxy-acrylate of formula: c22H17N3O5The chemical structural formula is as follows:
Figure BDA0001686520960000021
the azoxystrobin is a strobilurin fungicide, has good activity on almost all fungal diseases, and can be used for gardening, agriculture (vegetables and fruits), lawn maintenance on courts and the like. The preparation is mainly suspending agent and water dispersant.
Chinese invention patents CN103012285ACN and 101621926a describe the preparation of azoxystrobin A, B crystalline form and amorphous form by characterizing the various crystalline forms using XRPD, DSC, TGA and IR, Raman. And 2 theta angle is used for representing the diffraction characteristic peak of X-ray powder with different crystal forms, so that the characteristic peak of the crystal form A is as follows: 6.25 +/-0.20 degrees, 11.0 +/-0.20 degrees, 13.8 +/-0.20 degrees, 14.4 +/-0.20 degrees, 17.65 +/-0.20 degrees, 19.05 +/-0.20 degrees, 26.4 +/-0.20 degrees and 28.5 +/-0.20 degrees. The DSC curve has an endothermic peak in the range of about 114 ℃ to 117 ℃. The crystal form A has small granularity, uneven granularity distribution and serious coalescence, is easy to contain impurities in the purification and separation process, and is difficult to filter. The characteristic peaks of the crystal form B are as follows: 7.5 +/-0.20 degrees, 11.75 +/-0.20 degrees, 13.20 +/-0.20 degrees, 14.15 +/-0.20 degrees, 17.1 +/-0.20 degrees, 19.65 +/-0.20 degrees and 23.6 +/-0.20 degrees; the DSC curve has an endothermic peak in the range of about 101 ℃ to 105 ℃. The form B has poor stability, and can be quickly converted into the stable form A in a solvent, so that the storage and the transportation are influenced. The amorphous form is extremely unstable, can be converted into the crystal form B at room temperature, cannot be stored and is difficult to apply in production. The commercial products are crystal forms B and A and a mixture, the agglomeration is serious, the fluidity is poor, the drying and filtering speed is slow, the crystal form transformation is easy to occur in grinding and a solvent, the stability is poor, and a plurality of problems are brought to later processing and preparation.
Disclosure of Invention
One of the objects of the present invention is: provides a novel azoxystrobin acetic acid solvate with high crystallinity and larger granularity, and solves the problems of small granularity and serious coalescence of azoxystrobin in the prior art.
The second purpose of the invention is: the preparation method of the azoxystrobin acetic acid solvate is simple and convenient to prepare, good in reproducibility and good in fluidity, is suitable for industrial production, solves the problems of difficult filtration, high cost and low efficiency in production, and fills up the technical blank.
In order to solve the technical problems, the invention is realized by the following technical scheme:
the azoxystrobin acetic acid solvate has characteristic peaks at the diffraction angles expressed by 2 theta angle of 7.40 +/-0.20 degrees, 8.28 +/-0.20 degrees, 13.26 +/-0.20 degrees, 14.07 +/-0.20 degrees, 14.52 +/-0.20 degrees, 18.08 +/-0.20 degrees, 18.42 +/-0.20 degrees, 18.86 +/-0.20 degrees, 20.46 +/-0.20 degrees, 21.18 +/-0.20 degrees, 22.14 +/-0.20 degrees, 22.68 +/-0.20 degrees, 24.46 +/-0.20 degrees, 26.88 +/-0.20 degrees, 28.60 +/-0.20 degrees and the like, wherein 7.40 +/-0.20 degrees is an initial peak, and the relative intensity of the characteristic peak at 21.18 +/-0.20 degrees is 100 percent.
The diffraction angle of X-ray powder diffraction of the azoxystrobin acetic acid solvate measured by Cu-Kalpha ray, which is expressed by 2 theta angle, has the characteristic peaks shown in the following table 1.
TABLE 1X-ray powder diffraction List of azoxystrobin acetic acid solvate
Figure BDA0001686520960000031
Figure BDA0001686520960000041
The azoxystrobin acetic acid solvate of the invention has a d-value as shown in the table
Figure BDA0001686520960000042
Preferably, the solvate form has characteristic peak intensities as shown in the above table.
The azoxystrobin acetic acid solvate is characterized in that an X-ray powder diffraction pattern of the crystal form is shown in figure 1.
The azoxystrobin acetic acid solvate is characterized in that the crystal form is a monoclinic system, and the space group is P21N, unit cell parameter of
Figure BDA0001686520960000043
Figure BDA0001686520960000044
α is 90.00 °; β 97.32(3) °; gamma 90 DEG, unit cell volume of
Figure BDA0001686520960000045
In the azoxystrobin acetic acid solvate, the molar ratio of azoxystrobin to acetic acid molecules is 1:1, and the molecular formula is C22H17N3O5·C2H4O2There was a weight loss of 13.0% ± 0.5% before heating to 100 ℃. Specific thermogravimetric analysis (TG A) such asAs shown in fig. 2.
The Differential Scanning Calorimetry (DSC) spectrum of the azoxystrobin acetic acid solvate has an endothermic peak at 78.9 +/-5 ℃ and a characteristic melting peak at 110.0 +/-5 ℃. As shown in particular in figure 3.
According to the invention, the azoxystrobin acetic acid solvate has an infrared spectrum at 3107, 3040, 1772, 1705, 1408, 1376, 1277, 947, 619, 510 and 477cm-1Etc. have characteristic peaks. As shown in particular in fig. 4.
The invention also provides a preparation method of the azoxystrobin acetic acid solvate, which is prepared by adopting a constant-temperature suspension crystal transformation method, the azoxystrobin is added into acetic acid, the mass ratio of the azoxystrobin to the solvent acetic acid is 1: 0.5-4, the constant-temperature suspension crystal transformation temperature is 20-60 ℃, the stirring is carried out for 2-6 h, a white solid is generated, a product is filtered while hot, and the azoxystrobin acetic acid solvate is obtained after drying.
The specific preparation of azoxystrobin acetic acid solvate is shown in the examples.
The third purpose of the invention is that: provides the application of the azoxystrobin acetic acid solvate in preparing a solvent-free azoxystrobin compound with good fluidity and larger granularity.
The azoxystrobin acetic acid solvate is used for preparing the azoxystrobin pure crystal compound which has good fluidity and larger granularity and does not contain solvent. The specific operation is that the azoxystrobin acetic acid solvate is dried under the conditions of 60-100 ℃ and 0.08-0.1 MPa to obtain the azoxystrobin pure crystal compound without solvent. The azoxystrobin solvate obtained by the method can keep the rod-shaped crystal morphology and the crystal granularity of the original azoxystrobin acetic acid solvate, and the azoxystrobin solvate is the crystal form A reported by the previous patent, so that the mobility of the azoxystrobin solvate is greatly improved compared with that of a product sold in the market, and the azoxystrobin solvate is not easy to agglomerate.
The method adopts a constant-temperature suspension crystallization method, and the selected solvent is three solvents, namely acetic acid, so that the method is low in toxicity to human bodies, safe and environment-friendly; compared with the elution crystallization process disclosed in patent CN101621926A, the method is simple and easy to operate, good in reproducibility and easy to control; compared with the method of reflux and quenching after melting described in patent CN101621926A, the method avoids high-temperature operation, is safer, and has mild crystallization conditions and lower energy consumption; the product obtained by the invention is a short rod-shaped crystal, has high crystallinity, complete crystal habit, smooth surface and no coalescence phenomenon, improves the filtering speed, reduces the operation difficulty in the production, storage and transportation processes, and has a scanning electron microscope picture shown in an attached figure 5 and a scanning electron microscope picture shown in an attached figure 6 for a product sold in the market. The product of the invention has the volume average particle size of 39 μm and the angle of repose of 26 degrees, while the product sold in the market has the volume average particle size of 22 μm and the angle of repose of 50 degrees, thereby greatly improving the particle size of the product, improving the fluidity of the product, being beneficial to storage and transportation, ensuring the good performance of the product, improving the industrial production efficiency, reducing the production cost, and promoting the production and development of pesticides to better serve the society. The product of the invention has good stability and is easy to store. The stability of the azoxystrobin acetic solvate is inspected, the azoxystrobin acetic solvate crystal form product is placed in a centrifugal tube, the centrifugal tube is sealed and placed in a dryer, the temperature is controlled at 25 ℃, the humidity is 75%, samples are taken at 14 days to carry out XRPD and TGA detection, and the comparison with the result of the day 0 is carried out, so that the result shows that the azoxystrobin acetic solvate crystal form is not transformed, and the stability is good.
The azoxystrobin acetic acid solvate is not reported, and the obtained crystal product has complete crystal habit, high crystallinity, uniform granularity and good fluidity; the preparation method adopts constant-temperature suspension and cooling crystallization, is simple and easy to implement, is easy to control the crystallization process, and has good reproducibility; and the desolvation of the azoxystrobin can be used for preparing the azoxystrobin pure crystal compound without the solvent, the operation is simple and convenient, and a novel, simple and economic method for preparing the azoxystrobin pure crystal compound without the solvent is provided. The product of the invention has the same sterilization effect principle as the A, B crystal form, inhibits mitochondrial respiration by hindering electron transfer among cytochromes, then controls and prevents fungi growing on agricultural and horticultural crops, plays the function of a bactericide, has no cross resistance with other existing bactericides, and has the characteristics of high efficiency, broad spectrum, protection, treatment, eradication, permeation, systemic activity and the like.
Drawings
FIG. 1 is an X-ray powder diffraction (XRPD) pattern of azoxystrobin acetic acid solvate provided by the present invention;
FIG. 2 is a thermogravimetric analysis (TG) plot of azoxystrobin acetic acid solvate provided by the present invention;
FIG. 3 is a Differential Scanning Calorimetry (DSC) plot of the azoxystrobin acetic acid solvate provided in the present invention;
FIG. 4 is an infrared spectrum (IR) plot of azoxystrobin acetic acid solvate provided by the present invention;
FIG. 5 is a Scanning Electron Microscope (SEM) image of azoxystrobin acetic acid solvate provided by the invention
FIG. 6 is a Scanning Electron Microscope (SEM) image of commercially available azoxystrobin
FIG. 7 is an XRPD pattern for azoxystrobin feedstock used in example 1 of the present invention
Figure 8 is an XRPD pattern of the azoxystrobin solventless compound prepared after desolvation of azoxystrobin acetic acid solvate in example 8 of the present invention.
Detailed Description
The present invention will be described in further detail below with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. Any modifications and variations made on the basis of the present invention are still within the scope of the present invention.
Example 1
At a constant temperature of 20 ℃, 20g of acetic acid is added into a crystallizer, and the mixture is stirred to keep a better mixing state of the system. And adding 5g of azoxystrobin raw material into a crystallizer, continuously stirring the solution for 2 hours after the raw material is added, filtering the solid, and drying to obtain the product. The product has an X-ray powder diffraction pattern as shown in fig. 1, and has characteristic peaks at 7.40 ± 0.20 °, 8.28 ± 0.20 °, 13.26 ± 0.20 °, 14.07 ± 0.20 °, 14.52 ± 0.20 °, 18.08 ± 0.20 °, 18.42 ± 0.20 °, 18.86 ± 0.20 °, 20.46 ± 0.20 °, 21.18 ± 0.20 °, 22.14 ± 0.20 °, 22.68 ± 0.20 °, 24.46 ± 0.20 °, 26.88 ± 0.20 °, 28.60 ± 0.20 °, etc., wherein 2 θ ═ 7.40 ± 0.20 ° is an initial peak, and the relative intensity of the characteristic peaks at 2 θ ═ 21.18 ± 0.20 ° is 100%. The TGA results are shown in FIG. 2, with a weight loss of 13.0% + -0.5% before heating to 100 ℃. The DSC result is shown in FIG. 3, which shows an endothermic peak at 78.9 + -5 deg.C and an endothermic peak at 110.0 + -5 deg.CCharacteristic melting peak. The IR results are shown in FIG. 4 at 3107, 3040, 1772, 1705, 1408, 1376, 1277, 947, 619, 510, 477cm-1Etc. have characteristic peaks. The SEM result is shown in FIG. 5, which shows a rod-like crystal habit with a smooth surface. Indicating that azoxystrobin acetic acid solvate was obtained. The volume average particle size is 40 μm, the angle of repose is 23 DEG, no coalescence is caused, and the fluidity is good. The azoxystrobin raw material crystal form XRPD is shown as a crystal form A in figure 7.
Example 2
At a constant temperature of 30 ℃, 25g of acetic acid is added into a crystallizer, and the mixture is stirred to keep a better mixing state of the system. And adding 6g of azoxystrobin raw material into a product forming device, continuously stirring the solution for 3 hours after the raw material is added, filtering the solid, and drying to obtain the product. The X-ray powder diffraction pattern of the product is shown in figure 1. The TGA and DSC curves are shown in figure 2 and figure 3. Its infrared spectrum (IR) is shown in FIG. 4. The crystal shape is rod-like as in fig. 5, and the surface is smooth. Indicating that azoxystrobin acetic acid solvate was obtained. The volume average particle size is 36 μm, the angle of repose is 24 degrees, no coalescence is caused, and the fluidity is good. The azoxystrobin raw material crystal form XRPD is shown as a crystal form A in figure 7.
Example 3
At a constant temperature of 35 ℃, 30g of acetic acid is added into a crystallizer, and the mixture is stirred to keep a better mixing state of the system. And adding 10g of azoxystrobin raw material into a crystallizer, continuously stirring the solution for 3.5h after the raw material is added, filtering the solid, and drying to obtain the product. The X-ray powder diffraction pattern of the product is shown in figure 1. The TGA and DSC curves are shown in figure 2 and figure 3. Its infrared spectrum (IR) is shown in FIG. 4. The crystal shape is rod-like as in fig. 5, and the surface is smooth. Indicating that azoxystrobin acetic acid solvate was obtained. The volume average particle size is 36 μm, the angle of repose is 22 degrees, no coalescence is caused, and the fluidity is good. The azoxystrobin raw material crystal form XRPD is shown as a crystal form A in figure 7.
Example 4
20g of acetic acid is added into a product forming device at a constant temperature of 40 ℃, and the mixture is stirred to keep the system in a better mixing state. And adding 8g of azoxystrobin raw material into a crystallizer, continuously stirring the solution for 4 hours after the raw material is added, filtering the solid, and drying to obtain the product. The X-ray powder diffraction pattern of the product is shown in figure 1. The TGA and DSC curves are shown in figure 2 and figure 3. Its infrared spectrum (IR) is shown in FIG. 4. The crystal shape is rod-like as in fig. 5, and the surface is smooth. Indicating that azoxystrobin acetic acid solvate was obtained. The volume average particle size is 39 μm, the angle of repose is 23 DEG, no coalescence is caused, and the fluidity is good. The azoxystrobin raw material crystal form XRPD is shown as a crystal form A in figure 7.
Example 5
At a constant temperature of 50 ℃, 20g of acetic acid is added into a crystallizer, and the mixture is stirred to keep a better mixing state of the system. And adding 10g of azoxystrobin raw material into a crystallizer, continuously stirring the solution for 3.5h after the raw material is added, filtering the solid, and drying to obtain the product. The X-ray powder diffraction pattern of the product is shown in figure 1. The TGA and DSC curves are shown in figure 2 and figure 3. Its infrared spectrum (IR) is shown in FIG. 4. The crystal shape is rod-like as in fig. 5, and the surface is smooth. Indicating that azoxystrobin acetic acid solvate was obtained. The volume average particle size is 41 μm, the angle of repose is 23 DEG, no coalescence is caused, and the fluidity is good. The azoxystrobin raw material crystal form XRPD is shown as a crystal form A in figure 7.
Example 6
20g of acetic acid is added into a product forming device at a constant temperature of 60 ℃, and the mixture is stirred to keep the system in a better mixing state. And adding 12g of azoxystrobin raw material into a crystallizer, continuously stirring the solution for 4 hours after the raw material is added, filtering the solid, and drying to obtain the product. The X-ray powder diffraction pattern of the product is shown in figure 1. The TGA and DSC curves are shown in figure 2 and figure 3. Its infrared spectrum (IR) is shown in FIG. 4. The crystal shape is rod-like as in fig. 5, and the surface is smooth. Indicating that azoxystrobin acetic acid solvate was obtained. The volume average particle size is 36 μm, the angle of repose is 24 degrees, no coalescence is caused, and the fluidity is good. The azoxystrobin raw material crystal form XRPD is shown as a crystal form A in figure 7.
Example 7
Taking 1.0g of the product in example 1, placing the product in a drying oven at 80 ℃, keeping the vacuum degree at about 0.09MPa, drying for 24h, wherein the XRPD pattern of the solid product analysis is as shown in figure 8, and is consistent with the XRPD pattern in figure 7, and the same peak spectrum position and shape exist, after TG thermogravimetric analysis, the dried sample has no weight loss before the decomposition temperature, which indicates that the azoxystrobin acetic acid solvate is converted into a solvent-free compound. The obtained azoxystrobin solvate-free compound can keep the rod-like crystal morphology and the crystal granularity of the original azoxystrobin acetic solvate crystal form, and compared with a commercially available product, the azoxystrobin solvate-free compound has greatly improved fluidity and is not easy to agglomerate.
Example 8
2.0g of the product in example 6 is placed in a drying oven at 90 ℃, the vacuum degree is kept at about 0.08MPa, the product is dried for 12 hours, the XRPD pattern of the solid product analysis is consistent with the XRPD pattern in figure 7, the same peak spectrum position and shape are obtained, after TG thermogravimetric analysis, the dried sample has no weight loss before the decomposition temperature, and the azoxystrobin acetic acid solvate is converted into a solvent-free compound. The obtained azoxystrobin solvate-free compound can keep the rod-like crystal morphology and the crystal granularity of the original azoxystrobin acetic solvate crystal form, and compared with a commercially available product, the azoxystrobin solvate-free compound has greatly improved fluidity and is not easy to agglomerate.
The azoxystrobin acetic acid solvate provided by the invention can be used for controlling and preventing fungi growing on agricultural and horticultural crops, has the same action mechanism as the reported A, B crystal form, and has a disclosed action, so the bactericidal action of the azoxystrobin acetic acid solvate is not repeated herein.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.

Claims (7)

1. An azoxystrobin acetic acid solvate, characterized in that the azoxystrobin acetic acid solvate has characteristic peaks at 2 theta angles expressed by X-ray powder diffraction at 7.40 + -0.20 °, 8.28 + -0.20 °, 13.26 + -0.20 °, 14.07 + -0.20 °, 14.52 + -0.20 °, 18.08 + -0.20 °, 18.42 + -0.20 °, 18.86 + -0.20 °, 20.46 + -0.20 °, 21.18 + -0.20 °, 22.14 + -0.20 °, 22.68 + -0.20 °, 24.46 + -0.20 °, 26.88 + -0.20 ° and 28.60 + -0.20 ° in its crystalline form measured using Cu-Kalpha radiation, wherein the relative intensity of the characteristic peaks at 21.18 + -0.20 ° is 100%;
the azoxystrobin acetic acid solvate is prepared by adopting a constant-temperature suspension crystal transformation method, and the specific preparation method comprises the following steps: adding an azoxystrobin raw material into acetic acid, wherein the mass ratio of the azoxystrobin raw material to acetic acid as a solvent is 1: 0.4-4, the constant-temperature suspension and crystal transition temperature is 20-60 ℃, stirring for 2-6 h to generate a white solid, filtering the product while the product is hot, and drying to obtain an azoxystrobin acetic acid solvate; the azoxystrobin raw material is of a crystal form A, and XRPD of the azoxystrobin raw material is shown in figure 7;
the molar ratio of azoxystrobin to acetic acid molecules in the solvate is 1:1, and the molecular formula is C22H17N3O5·C2H4O2There was a weight loss of 13.0% ± 0.5% before heating to 100 ℃.
2. The solvate according to claim 1, wherein the crystalline form of azoxystrobin acetic acid solvate is monoclinic and space group is P21N, unit cell parameter of
Figure FDA0003118066910000011
Figure FDA0003118066910000012
α is 90.00 °; β 97.32(3) °; gamma 90 DEG, unit cell volume of
Figure FDA0003118066910000013
3. The solvate of claim 1, wherein the azoxystrobin acetic acid solvate has a Differential Scanning Calorimetry (DSC) pattern with an endothermic peak at 78.9 ± 5 ℃ and a characteristic melting peak at 110.0 ± 5 ℃.
4. The solvate according to claim 1, wherein the azoxystrobin acetic acid solvate has an infrared spectrum at 3107, 3040, 1772, 1705, 1408, 1376, 1277, 947, 619, 510, 477cm-1Has characteristic peaks.
5. The preparation method of the azoxystrobin acetic acid solvate according to any one of claims 1 to 4, which is prepared by a constant-temperature suspension crystal transformation method, wherein the azoxystrobin raw material is added into acetic acid, the mass ratio of the azoxystrobin raw material to the acetic acid solvent is 1: 0.4-4, the constant-temperature suspension crystal transformation temperature is 20-60 ℃, the stirring is carried out for 2-6 h, a white solid is generated, the product is filtered while hot, and the azoxystrobin acetic acid solvate is obtained after drying; the azoxystrobin raw material is of a crystal form A, and XRPD of the azoxystrobin raw material is shown in figure 7.
6. Use of azoxystrobin acetic acid solvate according to claim 1 for the preparation of azoxystrobin solventless compounds.
7. The use as claimed in claim 6, wherein the process for the preparation of azoxystrobin solvent-free compounds is: drying the azoxystrobin acetic acid solvate of claim 1 at 60-100 ℃ and 0.08-0.1 MPa to obtain the azoxystrobin solvent-free compound.
CN201810573514.4A 2018-06-06 2018-06-06 Azoxystrobin acetic acid solvate and preparation method thereof Active CN108947914B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810573514.4A CN108947914B (en) 2018-06-06 2018-06-06 Azoxystrobin acetic acid solvate and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810573514.4A CN108947914B (en) 2018-06-06 2018-06-06 Azoxystrobin acetic acid solvate and preparation method thereof

Publications (2)

Publication Number Publication Date
CN108947914A CN108947914A (en) 2018-12-07
CN108947914B true CN108947914B (en) 2021-07-23

Family

ID=64493020

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810573514.4A Active CN108947914B (en) 2018-06-06 2018-06-06 Azoxystrobin acetic acid solvate and preparation method thereof

Country Status (1)

Country Link
CN (1) CN108947914B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111742927A (en) * 2019-03-27 2020-10-09 Upl有限公司 Azoxystrobin solvate and preparation method thereof
CN111747899A (en) * 2019-03-27 2020-10-09 华东理工大学 Azoxystrobin channel solvate, eutectic and preparation method thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101621926A (en) * 2007-02-01 2010-01-06 马克特辛姆化学工厂有限公司 Polymorphs of 3-(e)-2-{2-[6-(2-cyanophenoxy) pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate
CN109384728A (en) * 2017-08-07 2019-02-26 华东理工大学 Fluoxastrobin channel solvates and preparation method thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101621926A (en) * 2007-02-01 2010-01-06 马克特辛姆化学工厂有限公司 Polymorphs of 3-(e)-2-{2-[6-(2-cyanophenoxy) pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate
CN109384728A (en) * 2017-08-07 2019-02-26 华东理工大学 Fluoxastrobin channel solvates and preparation method thereof

Also Published As

Publication number Publication date
CN108947914A (en) 2018-12-07

Similar Documents

Publication Publication Date Title
US8258327B2 (en) Crystalline minocycline base and processes for its preparation
CN108947914B (en) Azoxystrobin acetic acid solvate and preparation method thereof
EP3184513B1 (en) Process for the preparation of crystalline hydrated form b of olaparib
WO2016107289A1 (en) Method for preparing sofosbuvir crystal form-6
CN106890996A (en) A kind of nano-silver thread and preparation method thereof
CN108947915B (en) Azoxystrobin acetone solvate and preparation method thereof
CN108675963B (en) Azoxystrobin 1,4 dioxane solvate and preparation method thereof
CN103755723B (en) A kind of preparation method of rifampicin I crystal form
CN111303098B (en) Sphaelactone dimethylamine fumarate crystal form E and preparation method thereof
CN107652199A (en) A kind of preparation method of crystal type N AAAs
US10196360B2 (en) Crystal forms of bedaquiline fumarate and preparation methods therefor
CN111303097B (en) Crystal form C of michelia lactone fumarate dimethylamine and preparation method thereof
CN106046086B (en) It is a kind of to prepare the unformed method of tylonolide
CN111748009B (en) Crystal form of emamectin benzoate and preparation method thereof
EP3372602B1 (en) Pyrroloquinoline quinone b crystal form and preparation method therefor
HU229071B1 (en) Crystal modification b of 8-cyano-1-cyclopropyl-7-(1s,6s-2,8-diazabicyclo[4.3.0]nonan-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid, process for its preparation and pharmaceutical compositions thereof
WO2021249395A1 (en) Solid state forms of cyantraniliprole
US20070167494A1 (en) Process for preparing a polymorph or rosiglitazone maleate
EA008055B1 (en) Crystal forms of olanzapine and processes for their preparation
CN106046084B (en) Tylonolide acetone solvent compound and preparation method
CN113861105B (en) Cocrystal of acetamiprid and organic acid as well as preparation method and application thereof
WO2021134943A1 (en) Flazasulfuron crystal form and preparation method therefor
KR20150079043A (en) Process for Preparation and Conversion of Taltirelin Crystalline Form α
CN107759670A (en) Crystallization of aerosporin 1, B2 or its mixture and preparation method thereof
JP7211612B2 (en) Crystal forms of tempvermectin B, methods for their preparation and uses thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant