CN106866533B - Pyraclostrobin crystal form and preparation method - Google Patents
Pyraclostrobin crystal form and preparation method Download PDFInfo
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- 239000013078 crystal Substances 0.000 title claims abstract description 84
- 239000005869 Pyraclostrobin Substances 0.000 title claims abstract description 60
- HZRSNVGNWUDEFX-UHFFFAOYSA-N pyraclostrobin Chemical compound COC(=O)N(OC)C1=CC=CC=C1COC1=NN(C=2C=CC(Cl)=CC=2)C=C1 HZRSNVGNWUDEFX-UHFFFAOYSA-N 0.000 title claims abstract description 60
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 238000001816 cooling Methods 0.000 claims abstract description 24
- 238000002425 crystallisation Methods 0.000 claims abstract description 16
- 230000008025 crystallization Effects 0.000 claims abstract description 15
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 239000000463 material Substances 0.000 claims abstract description 6
- 239000002002 slurry Substances 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 22
- 239000002904 solvent Substances 0.000 claims description 22
- 238000001704 evaporation Methods 0.000 claims description 17
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 12
- 238000005406 washing Methods 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- 230000008020 evaporation Effects 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 3
- 239000012043 crude product Substances 0.000 claims description 2
- 239000002245 particle Substances 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- 238000001228 spectrum Methods 0.000 claims description 2
- 238000004128 high performance liquid chromatography Methods 0.000 abstract description 8
- 238000005054 agglomeration Methods 0.000 abstract 1
- 230000002776 aggregation Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 22
- 238000000113 differential scanning calorimetry Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 238000002441 X-ray diffraction Methods 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 239000000575 pesticide Substances 0.000 description 5
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 3
- 230000008821 health effect Effects 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 230000006911 nucleation Effects 0.000 description 3
- 238000010899 nucleation Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 102100025287 Cytochrome b Human genes 0.000 description 2
- 108010075028 Cytochromes b Proteins 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000000417 fungicide Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- PLAZTCDQAHEYBI-UHFFFAOYSA-N 2-nitrotoluene Chemical compound CC1=CC=CC=C1[N+]([O-])=O PLAZTCDQAHEYBI-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- 230000002407 ATP formation Effects 0.000 description 1
- 102000019265 Cytochrome c1 Human genes 0.000 description 1
- 108010007528 Cytochromes c1 Proteins 0.000 description 1
- 229930182692 Strobilurin Natural products 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 239000012296 anti-solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004581 coalescence Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- IAGUPODHENSJEZ-UHFFFAOYSA-N methyl n-phenylcarbamate Chemical compound COC(=O)NC1=CC=CC=C1 IAGUPODHENSJEZ-UHFFFAOYSA-N 0.000 description 1
- BSDQITJYKQHXQR-UHFFFAOYSA-N methyl prop-2-eneperoxoate Chemical compound COOC(=O)C=C BSDQITJYKQHXQR-UHFFFAOYSA-N 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 230000003032 phytopathogenic effect Effects 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000004546 suspension concentrate Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
- C07D231/22—One oxygen atom attached in position 3 or 5 with aryl radicals attached to ring nitrogen atoms
-
- 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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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及吡唑醚菌酯晶型及制备方法，以X射线粉末衍射2θ表示在9.3±0.1、14.5±0.1、14.7±0.1、15.0±0.1、18.0±0.1、18.4±0.1、18.7±0.1、22.2±0.1、22.6±0.1、24.8±0.1、25.8±0.1度处有特征峰。将吡唑醚菌酯粗品溶于有机溶剂中，初始溶液浓度0.001～0.1g/mL，在30～50℃条件下蒸发结晶，一段时间后进行冷却结晶，将物料继续降温至‑5～5℃，晶浆经过滤、洗涤、干燥，得到所述的吡唑醚菌酯晶型。收率为92％～95％，HPLC检测纯度为99.9％，产品稳定性好。晶体呈白色，棒状，表面光洁且边缘规则，产品无聚结。
The invention relates to a pyraclostrobin crystal form and a preparation method, which are represented by X-ray powder diffraction 2θ at 9.3±0.1, 14.5±0.1, 14.7±0.1, 15.0±0.1, 18.0±0.1, 18.4±0.1, 18.7±0.1, There are characteristic peaks at 22.2±0.1, 22.6±0.1, 24.8±0.1, 25.8±0.1 degrees. Dissolve the crude pyraclostrobin in an organic solvent, the initial solution concentration is 0.001～0.1g/mL, evaporate and crystallize under the condition of 30～50 ℃, carry out cooling crystallization after a period of time, and continue to cool down the material to ‑5～5 ℃ , the crystal slurry is filtered, washed and dried to obtain the pyraclostrobin crystal form. The yield is 92% to 95%, the purity detected by HPLC is 99.9%, and the product has good stability. The crystals are white, rod-shaped, with a smooth surface and regular edges, and the product has no agglomeration.
Description
Technical Field
The invention belongs to the technical field of medical crystallization, and particularly relates to a pyraclostrobin crystal form and a preparation method thereof.
Background
Pyraclostrobin (pyraclostatin), also known as Pyraclostrobin, N-methoxy-N-2- [ l- (4-chlorophenyl) -3-pyrazolyloxymethyl]Phenyl carbamic acid methyl ester of formula C19H18ClN3O4Molecular weight is 387.82, and chemical structural formula is:
pyraclostrobin is a Strobilurin fungicide that was first developed and synthesized by BASF corporation, germany, for controlling phytopathogenic fungi. It achieves the bactericidal effect by inhibiting the respiration of the mitochondria of fungi. Acting on the Qo-center of cytochrome b blocks the transfer of electrons from cytochrome b to cytochrome c1, thereby preventing the production of ATP. The low degree, high efficiency and broad spectrum of pyraclostrobin are not available for other classes of fungicides. The worldwide sales in 2011 reaches $ 7.9 million, and is the second place in the methoxy acrylate bactericide market. In 2004-2013, the composite annual growth rate is as high as 13.61%, which is more than twice of the composite annual growth rate of 6.51% in the global crop pesticide market.
Pyraclostrobin was used as a seed treatment agent by monsanto in 2009 with consent from basf. 31 months and 3 years in 2013, the 250g/L pyraclostrobin EC obtains formal registration of 'plant health effect' on corn in China. Pyraclostrobin not only has broad-spectrum bactericidal activity, but also is a plant health care product, is the first product registered for plant health action by the United states environmental protection agency, European Union and China, is a model of a new concept of 'treating diseases and strengthening bodies without diseases', and is about to become a hotspot and focus of scientific research and market attention.
At present, pyraclostrobin is obtained by taking o-nitrotoluene as an initial raw material and performing condensation reaction with 1- (4-halogenated phenyl) -3-pyrazole alcohol by a condensation method or a post-condensation method. Because the product directly obtained in the last stage is a brownish red oily substance, the market pyraclostrobin with stable property can be obtained only by further crystallization process.
Patent CN 101203136a discloses four crystal forms of pyraclostrobin. The pyraclostrobin crystal IV is prepared by taking a mixture of a completely water-soluble organic solvent and water as a solvent for cooling crystallization or taking water as an anti-solvent for elution crystallization, and becomes the most stable crystal form of pyraclostrobin. Form I is typically prepared by cooling a melt of pyraclostrobin with a purity of at least 95%. The preparation method of the crystal form II is similar to that of the crystal form IV, but the duration of the crystallization process is shorter than that of the crystal form IV. Form III, however, is prepared by maintaining the melt at room temperature for a longer period of time, similar to the preparation of form I. The patent also proposes the use of form II or form IV in combination with a suitable liquid phase and a carrier for the preparation of aqueous suspension concentrates for crop protection. In patent CN 1025955879B, pyraclostrobin and 4-hydroxybenzoic acid are prepared into a crystalline complex (the molar ratio is 2: 1-1: 1), and compared with the single pesticide, the melting point is remarkably improved, so that the preparation method is more beneficial to the production of suspension concentrates, emulsion concentrates and granular preparations. The patent CN 104365590A discloses a method for continuously preparing pyraclostrobin suspending agent, and the obtained product has high raw material utilization rate, good performance and low cost.
In conclusion, pyraclostrobin has attracted extensive attention and application due to its excellent bactericidal activity and plant growth promoting health effect. In the developed crystal forms, the crystal form I and the crystal form III both use a melt crystallization method, and are not suitable for industrial production due to long production period of melt crystallization, difficult control of operation conditions and low crystallinity of the obtained crystals; the crystal form II is a metastable state of the crystal form IV, the instability of the crystal form II also determines that the crystal form II is not suitable for large-scale industrial production, and the product of the crystal form IV is often accompanied with the existence of the crystal form II, so that the purity is reduced. And in terms of the crystal form obtained at present, the granularity is often small, the fluidity is poor, and the processing of pesticide preparations is not facilitated.
Therefore, the pyraclostrobin crystal form which is unique in crystal form, good in stability, high in crystallinity, large in particle size, good in fluidity and good in water solubility needs to be invented, and the preparation period is shortened, so that the pyraclostrobin crystal form can be better applied to industrial production.
Disclosure of Invention
The invention discloses a new pyraclostrobin crystal form and a preparation method thereof, the prepared pyraclostrobin crystal form is unique, the stability and the water solubility are good, the crystallinity is high, the granularity is large, the fluidity is good, the preparation period is short, and the crystal form can be applied to preparation of a preparation agent in pesticide production.
The invention discloses a new pyraclostrobin crystal form, wherein an X-ray powder diffraction pattern of the new pyraclostrobin crystal form has characteristic peaks at diffraction angles 2 theta of 9.3 +/-0.1, 14.5 +/-0.1, 14.7 +/-0.1, 15.0 +/-0.1, 18.0 +/-0.1, 18.4 +/-0.1, 18.7 +/-0.1, 22.2 +/-0.1, 22.6 +/-0.1, 24.8 +/-0.1 and 25.8 +/-0.1 degrees, which are shown in figure 1.
The X-ray powder diffraction pattern of the new pyraclostrobin crystal form has characteristic peaks at 9.48 +/-0.01, 6.09 +/-0.01, 6.01 +/-0.01, 5.90 +/-0.01, 4.92 +/-0.01, 4.82 +/-0.01, 4.74 +/-0.01, 4.00 +/-0.01, 3.93 +/-0.01, 3.59 +/-0.01 and 3.45 +/-0.01 by the interplanar spacing d.
The pyraclostrobin crystal has a characteristic endothermic peak at 64.3 +/-3 ℃ in a Differential Scanning Calorimetry (DSC) spectrum, is the melting point of the crystal, and is shown in figure 2.
The preparation method of the new pyraclostrobin crystal form comprises the following steps of: dissolving pyraclostrobin in an organic solvent to form a clear solution, wherein the concentration of the solution is 0.001-0.1 g/mL, evaporating and crystallizing at 30-50 ℃, stopping evaporation until the residual volume of the solution is 50-80% of the initial volume of the solution, then cooling and crystallizing, cooling the material to-5 ℃, maintaining for 0.5-2 hr, filtering, washing and drying crystal slurry to obtain the pyraclostrobin crystal form.
The organic solvent is selected from A solvent or the mixed solvent of A solvent and B solvent. Wherein the A-type solvent is one or a mixture of cyclohexane, n-hexane and n-octane; the B solvent is selected from one of methanol, ethanol, n-propanol, isopropanol, acetonitrile, acetic acid, acetone, dichloromethane, methyl tert-butyl ether or ethyl acetate, and in the mixed solvent of the A solvent and the B solvent, the volume fraction of the A solvent is more than or equal to 50%.
In the method, the seed crystal is added when the solution is evaporated until the residual volume of the solution is 85-95% of the initial volume of the solution, and the addition amount of the seed crystal is 5-10% of the mass of the initial pyraclostrobin.
In the method, the operation time of evaporation crystallization is 2-6 hr.
In the method, the cooling rate of the cooling crystallization is 5-10 min/DEG C.
The washing liquid is selected from a solvent A used for crystallization, water or a mixture thereof.
The drying is carried out at 10-40 ℃ for 2-8 hr.
The pyraclostrobin crude product is dissolved in an organic solvent, and then is subjected to evaporative crystallization to saturate the solution, so that crystals are separated out, and the solubility of the product in the solvent can be further reduced by cooling crystallization, and the yield of the product is increased. Product nucleation growth is formed by evaporation of the solvent and a decrease in temperature. The driving force for nucleation and growth of crystals is the degree of supersaturation (Δ c ═ c-c)*Concentration-equilibrium concentration or solubility) resulting from evaporation of the solvent and reduction of temperature. The faster the evaporation or cooling rate, the faster the supersaturation increases, the easy explosion to form nuclei or oil, the product viscosity is larger,drying is difficult and the crystal purity is poor. According to the change rule of the solubility curve, the supersaturation degree is always in a uniform level, and a physical and chemical stable environment which is favorable for crystallization nucleation and growth is created, so that high process yield and good stability are ensured.
Compared with other crystal form processes, the method has the advantages of high crystal purity, mild conditions, good repeatability and short operation period. The yield of the crystallization process is 92-95%, and the purity of the product is 99.9% by HPLC detection. The crystal is white and rod-shaped, the surface is smooth and the edge is regular, the product has no coalescence, and the granularity is 150-200 mu m, as shown in figure 3. The solubility of the pyraclostrobin crystal in water at 20 ℃ is 0.000212g/100ml of water, the crystal form IV is 0.000198g/100ml of water, and the solubility is improved by 7.07%. The crystal has unique crystal form, good stability and water solubility, high crystallinity, large granularity, good fluidity and short preparation period.
The following table compares the four crystal forms in patent CN 101203136a with the crystal form in the present invention.
The XRD pattern is expressed in the interplanar spacing d. The data of the XRD pattern expressed in diffraction angle 2 θ is converted into data expressed in interplanar spacing d according to the bragg equation n λ 2dsin θ.
As can be seen from the table, the XRD diffraction peak of the new crystal form obtained by the evaporation and cooling method is obviously different from that of the developed four crystal forms; the melting point of the new crystal form is between that of the crystal form III and that of the crystal form IV; the solubility of the new crystal form in water at 20 ℃ is 0.000212g/100ml of water, the solubility of the new crystal form IV is 0.000198g/100ml of water, the solubility is improved by 7.07 percent, and the bioavailability of the medicine can be effectively enhanced.
The pyraclostrobin is easy to hydrolyze and photolyze, so the stability of the pyraclostrobin crystal form is inspected, and the pyraclostrobin crystal form product is respectively placed at 25 ℃ and RH 75%; accelerated tests are carried out under the conditions of 30 ℃, RH 75% and 40 ℃ and RH 75%, samples are respectively taken in 1, 2, 3 and 6 months, and changes in aspects of appearance color, product purity, crystal transformation and the like are inspected. The specific XRD pattern is shown in figure 4, and the results in the following table show that the crystal form of the pyraclostrobin is not transformed.
The accelerated test in the table shows that the pyraclostrobin crystal prepared by the invention has no change in appearance, color and crystal form under the accelerated condition. Both figure 4 and the above table show the good stability of the product of the invention.
The pyraclostrobin crystal obtained by the invention has the advantages of unique crystal form, good stability and water solubility, high crystallinity, large granularity, good fluidity and short preparation period, and can be used for preparing pesticide preparations.
Drawings
FIG. 1 is an X-ray diffraction pattern of the pyraclostrobin crystal form of the present invention.
FIG. 2 is a differential scanning calorimetry DSC chart of the pyraclostrobin crystal form of the present invention.
FIG. 3 is a microscope photograph of pyraclostrobin crystal form of the present invention.
FIG. 4 is a comparison of stability test patterns of pyraclostrobin crystal form of the present invention, wherein the XRD patterns are from bottom to top for 0 day, 30 days, 60 days, 90 days and 180 days.
Detailed Description
The following are specific embodiment examples of the crystal form of pyraclostrobin.
Example 1
Weighing 2g pyraclostrobin, adding 200ml cyclohexane, dissolving at 50 deg.C, evaporating at 50 deg.C for 4hr until the residual volume of the solution is 60% of the initial volume of the solution, cooling to 5 deg.C at a cooling rate of 8 min/deg.C, and maintaining at 5 deg.C for 1 hr; filtering, washing, and drying at 10 deg.C for 3hr to obtain 1.85g solid; the yield is 92.5%, the purity is 99.9% by HPLC, the powder X-ray diffraction pattern of the product is consistent with that of figure 1, and the DSC pattern is shown in figure 2.
Example 2
Weighing 0.2g pyraclostrobin, adding 200ml n-hexane, dissolving at 45 deg.C, evaporating at 45 deg.C for 3hr until the residual volume of the solution is 50% of the initial volume of the solution, cooling to 0 deg.C at a cooling rate of 5 min/deg.C, and maintaining at 0 deg.C for 1 hr; filtering, washing, and drying at 40 deg.C for 2hr to obtain 0.186g solid; the yield was 93%, and the purity by HPLC was 99.9%. The powder X-ray diffraction pattern of the product has characteristic peaks at 9.34, 14.56, 14.74, 15.02, 18.04, 18.42, 18.64, 22.40, 22.64, 24.80 and 25.84 degrees, and DSC shows that the melting point is 64.2 ℃.
Example 3
Weighing 200g pyraclostrobin, adding 2023ml n-hexane and 453ml dichloromethane, dissolving at 30 deg.C, evaporating at 30 deg.C for 6hr until the residual volume is 80% of the initial volume of the solution, cooling to-5 deg.C at cooling rate of 10 min/deg.C, and maintaining at-5 deg.C for 2 hr; filtering, washing, and drying at 30 deg.C for 8hr to obtain 189.2g solid; the yield was 94.6% and the purity was 99.9% by HPLC. The powder X-ray diffraction pattern of the product has characteristic peaks at 9.30, 14.52, 14.70, 14.98, 18.00, 18.38, 18.60, 22.36, 22.60, 24.76 and 25.80 degrees, and DSC shows that the melting point is 64.6 ℃.
Example 4
Weighing 0.2g pyraclostrobin, adding 200ml n-hexane, dissolving at 45 deg.C, evaporating at 45 deg.C until the residual volume of the solution is 95% of the initial volume of the solution, adding 0.02g seed crystal, continuing to evaporate at 45 deg.C for 1.5hr until the residual volume of the solution is 60% of the initial volume of the solution, cooling the material to-5 deg.C at a cooling rate of 6 min/deg.C, and maintaining at-5 deg.C for 1 hr; filtering, washing, and drying at 30 deg.C for 2hr to obtain 0.204g solid; the yield is 92.7%, the purity is 99.9% by HPLC detection, the powder X-ray diffraction pattern of the product has characteristic peaks at 9.22, 14.44, 14.62, 14.90, 17.92, 18.30, 18.62, 22.10, 22.52, 24.70 and 25.72 degrees, and the DSC shows that the melting point is 64.5 ℃.
Example 5
Weighing 30g pyraclostrobin, adding 900ml n-hexane and 400ml ethanol, dissolving at 45 deg.C, evaporating at 45 deg.C until the residual volume of the solution is 85% of the initial volume of the solution, adding 1.5g seed crystal, continuing to evaporate at 45 deg.C for 4hr until the residual volume of the solution is 60% of the initial volume of the solution, cooling the material to-5 deg.C at a cooling rate of 5 min/deg.C, and maintaining at-5 deg.C for 1.5 hr; filtering, washing, and drying at 40 deg.C for 4hr to obtain 29.01g solid; the yield is 92.1%, the purity is 99.9% by HPLC detection, the powder X-ray diffraction pattern of the product has characteristic peaks at 9.32, 14.54, 14.72, 15.00, 18.02, 18.40, 18.72, 22.20, 22.62, 24.80 and 25.82 degrees, and the DSC shows that the melting point is 64.5 ℃.
Example 6
Weighing 1.2g pyraclostrobin, adding 100ml n-hexane and 100ml cyclohexane, dissolving at 50 deg.C, evaporating at 50 deg.C until the residual volume of the solution is 90% of the initial volume of the solution, adding 0.1g seed crystal, continuing to evaporate at 50 deg.C for 1.5hr until the residual volume of the solution is 50% of the initial volume of the solution, cooling the material to-5 deg.C at a cooling rate of 6 min/deg.C, and maintaining at-5 deg.C for 1.5 hr; filtering, washing, and drying at 30 deg.C for 1.5hr to obtain 1.21g solid; the yield is 93.3%, the purity is 99.9% by HPLC detection, the powder X-ray diffraction pattern of the product has characteristic peaks at 9.31, 14.51, 14.71, 15.01, 18.01, 18.41, 18.71, 22.21, 22.61, 24.81 and 25.81 degrees, and the DSC shows that the melting point is 64.3 ℃.
The invention discloses and provides a new pyraclostrobin crystal form and a preparation method thereof, and can be realized by appropriately changing links such as raw materials, process parameters and the like by referring to the content. While the methods and products of the present invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and products described herein may be made and equivalents employed to practice the techniques of the present invention without departing from the spirit and scope of the invention. It is expressly intended that all such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and content of the invention.
Claims (8)
1. A crystal form of pyraclostrobin is characterized in that an X-ray powder diffraction pattern expressed by 2 theta has characteristic peaks at 9.3 +/-0.1, 14.5 +/-0.1, 14.7 +/-0.1, 15.0 +/-0.1, 18.0 +/-0.1, 18.4 +/-0.1, 18.7 +/-0.1, 22.2 +/-0.1, 22.6 +/-0.1, 24.8 +/-0.1 and 25.8 +/-0.1 degrees, and an XRD characteristic peak of the crystal is shown as figure 1; the DSC spectrum has a characteristic endothermic peak at 64.3 +/-3 ℃; the crystal is rod-shaped, and the particle size is 150-200 μm.
2. The preparation method of the pyraclostrobin crystal form as claimed in claim 1, characterized by dissolving pyraclostrobin in an organic solvent to form a clear solution, evaporating and crystallizing at 30-50 ℃, stopping evaporation until the residual volume of the solution is 50% -80% of the initial volume of the solution, then cooling and crystallizing, cooling the material to-5 ℃, maintaining for 0.5-2 hours, filtering, washing and drying the crystal slurry to obtain the pyraclostrobin crystal form;
the organic solvent is selected from a solvent A or a mixed solvent of the solvent A and the solvent B; wherein the A-type solvent is one or a mixture of cyclohexane, n-hexane and n-octane; the B solvent is selected from one of methanol, ethanol, normal propyl alcohol, isopropanol, acetonitrile, acetic acid, acetone, dichloromethane, methyl tertiary butyl ether or ethyl acetate, and in the mixed solvent of the A solvent and the B solvent, the volume fraction of the A solvent is more than or equal to 50 percent;
and adding seed crystals when the solution is evaporated until the residual volume is 85-95% of the initial volume, wherein the addition amount of the seed crystals is 5-10% of the mass of the initial pyraclostrobin.
3. The method as claimed in claim 2, wherein the initial concentration of the pyraclostrobin crude product solution is 0.001-0.1 g/mL.
4. The method according to claim 2, wherein the evaporation temperature is in the range of 30 to 50 ℃ and the evaporation time is 2 to 6 hours.
5. The method of claim 2, wherein the temperature reduction rate is 5 to 10min/° C.
6. The process of claim 2, wherein the washing solution is selected from the group consisting of a group A solvent used for crystallization, water, and a mixture thereof.
7. The method according to claim 2, wherein the drying temperature is 10 to 40 ℃.
8. The method according to claim 2, wherein the drying time is 2 to 8 hours.
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| CN106008347A (en) * | 2016-05-13 | 2016-10-12 | 安徽广信农化股份有限公司 | Synthesis technology of pyraclostrobin |
| CN106008349A (en) * | 2016-07-02 | 2016-10-12 | 安徽广信农化股份有限公司 | Crystallization treating technology for pyraclostrobin |
| CN106243040A (en) * | 2016-07-28 | 2016-12-21 | 山东康乔生物科技有限公司 | A kind of pyraclostrobin novel crystal forms V and preparation method thereof |
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| CN101203136A (en) * | 2005-06-20 | 2008-06-18 | 巴斯福股份公司 | Crystalline modifications to pyraclostrobin |
| CN106008347A (en) * | 2016-05-13 | 2016-10-12 | 安徽广信农化股份有限公司 | Synthesis technology of pyraclostrobin |
| CN106008349A (en) * | 2016-07-02 | 2016-10-12 | 安徽广信农化股份有限公司 | Crystallization treating technology for pyraclostrobin |
| CN106243040A (en) * | 2016-07-28 | 2016-12-21 | 山东康乔生物科技有限公司 | A kind of pyraclostrobin novel crystal forms V and preparation method thereof |
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