CN108840893A - A kind of novel crystal forms of emamectin-benzoate and preparation method thereof - Google Patents
A kind of novel crystal forms of emamectin-benzoate and preparation method thereof Download PDFInfo
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- CN108840893A CN108840893A CN201810706993.2A CN201810706993A CN108840893A CN 108840893 A CN108840893 A CN 108840893A CN 201810706993 A CN201810706993 A CN 201810706993A CN 108840893 A CN108840893 A CN 108840893A
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- benzoate
- crystal forms
- emamectin
- novel crystal
- butanone
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- 239000013078 crystal Substances 0.000 title claims abstract description 83
- CXEGAUYXQAKHKJ-NSBHKLITSA-N emamectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](NC)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 CXEGAUYXQAKHKJ-NSBHKLITSA-N 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 14
- 229910017488 Cu K Inorganic materials 0.000 claims abstract description 3
- 229910017541 Cu-K Inorganic materials 0.000 claims abstract description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 72
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 52
- 235000019441 ethanol Nutrition 0.000 claims description 25
- 239000011259 mixed solution Substances 0.000 claims description 15
- 239000007864 aqueous solution Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 12
- 239000004519 grease Substances 0.000 claims description 11
- 239000000725 suspension Substances 0.000 claims description 11
- 238000005352 clarification Methods 0.000 claims description 10
- 239000000706 filtrate Substances 0.000 claims description 10
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 10
- 229940011051 isopropyl acetate Drugs 0.000 claims description 10
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 10
- 238000002604 ultrasonography Methods 0.000 claims description 10
- 229920002518 Polyallylamine hydrochloride Polymers 0.000 claims description 9
- 238000001914 filtration Methods 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 6
- 239000012065 filter cake Substances 0.000 claims description 5
- 238000002390 rotary evaporation Methods 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims 2
- 238000012360 testing method Methods 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 238000012512 characterization method Methods 0.000 description 5
- 238000013112 stability test Methods 0.000 description 4
- 239000005660 Abamectin Substances 0.000 description 3
- 229940078916 carbamide peroxide Drugs 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- -1 polypropylene Polymers 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000255777 Lepidoptera Species 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 230000000895 acaricidal effect Effects 0.000 description 1
- 239000000642 acaricide Substances 0.000 description 1
- 238000012271 agricultural production Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- RRZXIRBKKLTSOM-XPNPUAGNSA-N avermectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 RRZXIRBKKLTSOM-XPNPUAGNSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000000003 thermogravimetry coupled to Fourier transform infrared spectroscopy Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
-
- 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)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses novel crystal forms of a kind of emamectin-benzoate and preparation method thereof, are radiated using Cu-K α, which has following characteristics peak with the X-ray powder diffraction figure that 2 θ angles indicate：4.6 ± 0.2 °, 5.8 ± 0.2 °, 9.3 ± 0.2 °, 14.2 ± 0.2 °, 15.7 ± 0.2 ° and 22.6 ± 0.2 °, have the advantages that improve stability.
Description
Technical field
The present invention relates to novel crystal forms of a kind of emamectin-benzoate and preparation method thereof.
Background technique
Emamectin-benzoate (abbreviation emamectin benzoate) new and effective is killed by one kind that avermectin synthesizes
Worm acaricide especially has high bioactivity to lepidoptera pest, has the characteristics that toxicity is low, remains less, is nuisanceless, thus
It is widely used in agricultural production.
Known emamectin-benzoate exists with many polymorphics.US6486195 discloses methylamino AVM hereinafter
Four kinds of polymorphics of rhzomorph benzoate, wherein crystal form B (semihydrate) is the most stable crystal form of the prior art.To methylamino Ah
The crystal form research for tieing up rhzomorph benzoate is still worth with certain production application.
Summary of the invention
The first object of the present invention is to provide a kind of novel crystal forms of emamectin-benzoate, has to improve and stablize
The advantages of property.
Above-mentioned technical purpose of the invention technical scheme is that：
A kind of novel crystal forms of emamectin-benzoate, are radiated using Cu-K α, and the novel crystal forms are with 2 θ angle tables
The X-ray powder diffraction figure shown has following characteristics peak：4.6±0.2°,5.8±0.2°,9.3±0.2°,14.2±0.2°,
15.7 ± 0.2 ° and 22.6 ± 0.2 °.
Further preferably：The novel crystal forms have following characteristics peak with the X-ray powder diffraction figure that 2 θ angles indicate：
4.6±0.2°、5.8±0.2°、7.3±0.2°、9.3±0.2°、10.9±0.2°、14.2±0.2°、15.7±0.2°、18.0
± 0.2 °, 22.6 ± 0.2 ° and 30.2 ± 0.2 °.
Further preferably：The X-ray powder diffraction figure that the novel crystal forms are indicated with 2 θ angles have following characteristics peak and
Its relative intensity：
The second object of the present invention is to provide a kind of preparation method of the novel crystal forms of emamectin-benzoate.
Above-mentioned technical purpose of the invention technical scheme is that：
A kind of preparation method of the novel crystal forms of emamectin-benzoate, includes the following steps：
It takes purity to be higher than 97% emamectin-benzoate, isopropyl acetate is added, ultrasound makes its dissolved clarification, uses
0.22 μm of organic filter film filtering, takes filtrate concentrated by rotary evaporation at 30~32 DEG C to obtain grease；By mass, methylamino AVM hereinafter
The amount ratio 1: 15~18 of rhzomorph benzoate and isopropyl acetate；
The aqueous solution for preparing butanone saturation, is put into the crystal seed of novel crystal forms, is dispersed with stirring at 15~35 DEG C, obtains suspension,
It grease is put into suspension and is stirred to react 2~r for 24 hours, filters to take filter cake and dry 1~2hr at 40~45 DEG C, i.e.,
?；By mass, the aqueous solution, crystal seed of butanone saturation and the amount ratio of grease are 2~3: 0.05~0.08: 1.
Further preferably：The crystal seed of the novel crystal forms is prepared by the following method：
The mass ratio of the mixed solution of preparation butanone and ethyl alcohol, butanone and ethyl alcohol is 1: 0.25~0.40；Purity is taken to be higher than
The mixed solution for having prepared butanone and ethyl alcohol is added in 97% emamectin-benzoate, and ultrasound makes its dissolved clarification, uses
0.22 μm of organic filter film filtering, puts the filtrate into open vial, polyallylamine hydrochloride is put into, at 4~6 DEG C
Volatilize 12~16hr, obtains solid, at 40~45 DEG C dry 1~2hr to get；
By mass, the mixed solution of butanone and ethyl alcohol, emamectin-benzoate and polyallylamine hydrochloride
Amount ratio 2~3: 1: 0.03~0.04.
In conclusion the invention has the advantages that：
1, the novel crystal forms of the application 25 DEG C of driers or 60 DEG C of convection ovens or 40 DEG C/75%RH environment or 40 DEG C/
The most stable crystal form B of shelf-stability and the prior art under carbamide peroxide environment is suitable；
2, stability and the prior art that the novel crystal forms of the application are placed for a long time at 25 DEG C/60%RH, 40 DEG C/75%RH
Most stable crystal form B it is suitable；
3, ethyl alcohol of the mixture of the novel crystal forms of the application and the most stable crystal form B of the prior art at 10,25 and 40 DEG C, second
Alcohol solution (ethyl alcohol and water volume ratio 1: 1), water suspension in do competition experiments, the stability of the novel crystal forms of the application is better than
Existing crystal form B, medication are safer.
Detailed description of the invention
Fig. 1 is the XRPD map of the novel crystal forms of the application.
Specific embodiment
Below in conjunction with attached drawing, invention is further described in detail.
This specific embodiment is only explanation of the invention, is not limitation of the present invention, those skilled in the art
Member can according to need the modification that not creative contribution is made to the present embodiment after reading this specification, but as long as at this
All by the protection of Patent Law in the protection scope of invention.
Detecting instrument and method：Instrument used in X-ray powder diffraction (XPRD) is Bruker D8Advance
Diffractometer uses copper target wavelength for the K α X-ray of 1.54nm, under the operating condition of 40kV and 40mA, θ -2 θ
Angular instrument, Mo monochromator, Lynxeye detector.Instrument was detected using preceding with diamond dust.Acquisition software is Diffrac
Plus XRD Commander.Sample is tested at room temperature, and the sample that needs are detected is placed on phosphatization silicon on piece.Inspection in detail
Survey condition is as follows, angular range：3-40 ° of 2 θ, step-length：0.02 ° of 2 θ, speed：0.2s. step -1.Unless stated otherwise, sample is being examined
It is not ground before surveying.
Embodiment 1：A kind of novel crystal forms of emamectin-benzoate, are prepared by the following method：Prepare fourth
The mass ratio of the mixed solution of ketone and ethyl alcohol, butanone and ethyl alcohol is 1: 0.25；Taking purity is 99.0% emamectin benzoate
The mixed solution for having prepared butanone and ethyl alcohol is added in benzoate, and ultrasound makes its dissolved clarification, is filtered with 0.22 μm of organic filter film,
It puts the filtrate into open vial, is put into polyallylamine hydrochloride, volatilize 16hr at 4 DEG C, solid is obtained, in 40 DEG C
Lower dry 2.0hr to get；By mass, the mixed solution of butanone and ethyl alcohol, emamectin-benzoate and polypropylene
The amount ratio 2.0: 1: 0.03 of amine hydrochlorate.
Its XRPD map is as shown in Figure 1, be novel crystal forms；Moisture measurement is that (TG-FTIR combination test is also one to monohydrate
Hydrate).
Embodiment 2：A kind of novel crystal forms of emamectin-benzoate, are prepared by the following method：Prepare fourth
The mass ratio of the mixed solution of ketone and ethyl alcohol, butanone and ethyl alcohol is 1: 0.33；Taking purity is 98.1% emamectin benzoate
The mixed solution for having prepared butanone and ethyl alcohol is added in benzoate, and ultrasound makes its dissolved clarification, is filtered with 0.22 μm of organic filter film,
It puts the filtrate into open vial, is put into polyallylamine hydrochloride, volatilize 14hr at 5 DEG C, solid is obtained, in 42 DEG C
Lower dry 1.5hr is obtained and the consistent novel crystal forms of Fig. 1；By mass, the mixed solution of butanone and ethyl alcohol, methylamino Avermectin
The amount ratio 2.5: 1: 0.04 of plain benzoate and polyallylamine hydrochloride.
Embodiment 3：A kind of novel crystal forms of emamectin-benzoate, are prepared by the following method：Prepare fourth
The mass ratio of the mixed solution of ketone and ethyl alcohol, butanone and ethyl alcohol is 1: 0.40；Taking purity is 97.2% emamectin benzoate
The mixed solution for having prepared butanone and ethyl alcohol is added in benzoate, and ultrasound makes its dissolved clarification, is filtered with 0.22 μm of organic filter film,
It puts the filtrate into open vial, is put into polyallylamine hydrochloride, volatilize 12hr at 6 DEG C, solid is obtained, in 45 DEG C
Lower dry 1.0hr is obtained and the consistent novel crystal forms of Fig. 1；By mass, the mixed solution of butanone and ethyl alcohol, methylamino Avermectin
The amount ratio 3.0: 1: 0.04 of plain benzoate and polyallylamine hydrochloride.
Embodiment 4：A kind of novel crystal forms of emamectin-benzoate, are prepared by the following method：
Taking purity is 99.0% emamectin-benzoate, and isopropyl acetate is added, and ultrasound makes its dissolved clarification, is used
0.22 μm of organic filter film filtering, takes filtrate concentrated by rotary evaporation at 30 DEG C to obtain grease；By mass, emamectin benzoate
The amount ratio 1: 15 of benzoate and isopropyl acetate；
The aqueous solution for preparing butanone saturation, is put into the crystal seed of novel crystal forms, is dispersed with stirring at 15 DEG C, obtains suspension, will be oily
Shape object is put into suspension and is stirred to react r for 24 hours, filters to take filter cake and dries 2.0hr at 40 DEG C to get purity is
99.60%；By mass, the aqueous solution, crystal seed of butanone saturation and the amount ratio of grease are 2.0: 0.05: 1.
The aqueous solution of butanone saturation, referring to that butanone has been saturated in water cannot dissolve in again, be prepared by the following method：Dividing
Water and butanone are put into liquid funnel, shaking sufficiently, after placing layering, takes lower layer.
Embodiment 5：A kind of novel crystal forms of emamectin-benzoate, are prepared by the following method：
Taking purity is 98.1% emamectin-benzoate, and isopropyl acetate is added, and ultrasound makes its dissolved clarification, is used
0.22 μm of organic filter film filtering, takes filtrate concentrated by rotary evaporation at 32 DEG C to obtain grease；By mass, emamectin benzoate
The amount ratio 1: 16 of benzoate and isopropyl acetate；
The aqueous solution for preparing butanone saturation, is put into the crystal seed of novel crystal forms, is dispersed with stirring at 25 DEG C, obtains suspension, will be oily
Shape object is put into suspension and is stirred to react 10hr, filters to take filter cake and dries 1.5hr at 42 DEG C to get purity is
99.58%；By mass, the aqueous solution, crystal seed of butanone saturation and the amount ratio of grease are 2.5: 0.06: 1.
The aqueous solution of butanone saturation, referring to that butanone has been saturated in water cannot dissolve in again, be prepared by the following method：Dividing
Water and butanone are put into liquid funnel, shaking sufficiently, after placing layering, takes lower layer.
Embodiment 6：A kind of novel crystal forms of emamectin-benzoate, are prepared by the following method：
Taking purity is 97.2% emamectin-benzoate, and isopropyl acetate is added, and ultrasound makes its dissolved clarification, is used
0.22 μm of organic filter film filtering, takes filtrate concentrated by rotary evaporation at 32 DEG C to obtain grease；By mass, emamectin benzoate
The amount ratio 1: 18 of benzoate and isopropyl acetate；
The aqueous solution for preparing butanone saturation, is put into the crystal seed of novel crystal forms, is dispersed with stirring at 35 DEG C, obtains suspension, will be oily
Shape object is put into suspension and is stirred to react 2hr, filters to take filter cake and dries 1.0hr at 45 DEG C to get purity is
99.57%；By mass, the aqueous solution, crystal seed of butanone saturation and the amount ratio of grease are 3.0: 0.08: 1.
The aqueous solution of butanone saturation, referring to that butanone has been saturated in water cannot dissolve in again, be prepared by the following method：Dividing
Water and butanone are put into liquid funnel, shaking sufficiently, after placing layering, takes lower layer.
Performance characterization
1, stability test
Taking commercially available purity is that (test through XRPD is existing most stable crystalline substance to 99.51% emamectin-benzoate
Type B) it is control group, the novel crystal forms for being 99.60% using the application preparation purity are tested as test group.
Test content is：20mg sample is respectively taken to be placed in 20ml vial, opening is placed in 25 DEG C of driers or 60 respectively
DEG C convection oven or 40 DEG C/75%RH environment or 40 DEG C/carbamide peroxide environment lower 10 days, in placing front and back, to carry out HPLC pure
Degree characterization and XRPD crystal form characterization.It parallel test 5 times, is averaged.
Test result is as shown in table 1.Table 1 is shown：The novel crystal forms of the application and the most stable crystal form B of the prior art are at 25 DEG C
Drier or 60 DEG C of convection ovens or the lower 10 days purity variation of 40 DEG C/75%RH environment or 40 DEG C/carbamide peroxide environment
It is negligible, and crystal form remains unchanged, the novel crystal forms of the application stability under test conditions and the prior art it is most steady
The stability for determining crystal form B is suitable.
1 stability test of table (is placed 10 days)
2, long term stability tests
Taking commercially available purity is that (test through XRPD is existing most stable crystalline substance to 99.51% emamectin-benzoate
Type B) it is control group, the novel crystal forms for being 99.60% using the application preparation purity are tested as test group.
Test content is：Respectively take 20mg sample to be placed in 20ml vial, respectively opening be placed in 25 DEG C/60%RH or
60,180 days under 40 DEG C/75%RH environment, HPLC purity characterization and XRPD crystal form characterization are carried out in placing front and back.Parallel test 5
It is secondary, it is averaged.
Test result is as shown in table 2.Table 2 is shown：The novel crystal forms of the application and the most stable crystal form B of the prior art are 25
DEG C/60%RH under place 60,180 days purity variation it is negligible, and crystal form remains unchanged；The novel crystal forms of the application and existing
The purity for having the most stable crystal form B of technology to place 180 days at 40 DEG C/75%RH is slightly decreased, but crystal form remains unchanged；This Shen
The stability of the most stable crystal form B of the stability under test conditions of novel crystal forms please and the prior art is suitable.
2 long term stability tests of table
3, competition test
Taking commercially available purity is that (test through XRPD is existing most stable crystalline substance to 99.51% emamectin-benzoate
Type B) and the application prepare the novel crystal forms (temporarily with crystal form VI name) that purity is 99.60%, in mass ratio 1: 1 mixing is matched respectively
The suspension of ethyl alcohol, ethanol water (ethyl alcohol and water volume ratio 1: 1), water is made, tests it after stirring 12hr, 48hr and 10d
Crystal form, whipping temp have 10,25 and 40 DEG C.It parallel test 5 times, is averaged.
Test result is as shown in table 3.Table 3 is shown：Ethyl alcohol, the ethyl alcohol of crystal form B and crystal form VI mixture at 10,25 and 40 DEG C
Aqueous solution (ethyl alcohol and water volume ratio 1: 1), water suspension in do competition experiments, be crystal form VI to stablize, illustrate testing
Under the conditions of crystal form VI stability be better than existing crystal form B.
The competition test of table 3
The specific implementation of the invention is not to be limited to these illustrations for the above content, and technology belonging to the present invention is led
For the those of ordinary skill in domain, without departing from the inventive concept of the premise, a number of simple deductions or replacements can also be made,
It all shall be regarded as belonging to present invention scope of patent protection determined by the appended claims.
Claims (5)
1. a kind of novel crystal forms of emamectin-benzoate, which is characterized in that radiated using Cu-K α, the novel crystal forms
There is following characteristics peak with the X-ray powder diffraction figure that 2 θ angles indicate：4.6±0.2°,5.8±0.2°,9.3±0.2°,
14.2 ± 0.2 °, 15.7 ± 0.2 ° and 22.6 ± 0.2 °.
2. novel crystal forms according to claim 1, which is characterized in that the X-ray powder that the novel crystal forms are indicated with 2 θ angles
Diffraction pattern has following characteristics peak：4.6±0.2°,5.8±0.2°,7.3±0.2°,9.3±0.2°,10.9±0.2°,14.2
± 0.2 °, 15.7 ± 0.2 °, 18.0 ± 0.2 °, 22.6 ± 0.2 ° and 30.2 ± 0.2 °.
3. novel crystal forms according to claim 2, which is characterized in that the X-ray powder that the novel crystal forms are indicated with 2 θ angles
Diffraction pattern has following characteristics peak and its relative intensity：
4. a kind of preparation method of the novel crystal forms of emamectin-benzoate as described in any one of claims 1-3,
It is characterized by comprising the following steps：
It takes purity to be higher than 97% emamectin-benzoate, isopropyl acetate is added, ultrasound makes its dissolved clarification, with 0.22
The filtering of μm organic filter film, takes filtrate concentrated by rotary evaporation at 30~32 DEG C to obtain grease；By mass, emamectin benzoate
The amount ratio 1: 15~18 of benzoate and isopropyl acetate；
The aqueous solution for preparing butanone saturation, is put into the crystal seed of novel crystal forms, is dispersed with stirring at 15~35 DEG C, obtains suspension, will be oily
Shape object be put into suspension and is stirred to react 2~r for 24 hours, filter to take filter cake and at 40~45 DEG C dry 1~2hr to get；It presses
Quality meter, the amount ratio of aqueous solution, crystal seed and grease that butanone is saturated are 2~3: 0.05~0.08: 1.
5. the preparation method according to claim 4, which is characterized in that the crystal seed of the novel crystal forms is made by the following method
It is standby：
The mass ratio of the mixed solution of preparation butanone and ethyl alcohol, butanone and ethyl alcohol is 1: 0.25~0.40；Purity is taken to be higher than 97%
Emamectin-benzoate, be added and prepared the mixed solution of butanone and ethyl alcohol, ultrasound makes its dissolved clarification, with 0.22 μm
The filtering of organic filter film, puts the filtrate into open vial, is put into polyallylamine hydrochloride, volatilizees 12 at 4~6 DEG C
~16hr, obtains solid, at 40~45 DEG C dry 1~2hr to get；
By mass, the use of the mixed solution of butanone and ethyl alcohol, emamectin-benzoate and polyallylamine hydrochloride
Measure ratio 2~3: 1: 0.03~0.04.
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| CN113912659A (en) * | 2021-12-01 | 2022-01-11 | 河北威远生物化工有限公司 | Emamectin benzoate crystal and amorphous crystal of emamectin B2a and preparation method thereof |
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