WO2024119657A1 - Supported zinc trifluoroacetate, preparation method and use - Google Patents
Supported zinc trifluoroacetate, preparation method and use Download PDFInfo
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- WO2024119657A1 WO2024119657A1 PCT/CN2023/081797 CN2023081797W WO2024119657A1 WO 2024119657 A1 WO2024119657 A1 WO 2024119657A1 CN 2023081797 W CN2023081797 W CN 2023081797W WO 2024119657 A1 WO2024119657 A1 WO 2024119657A1
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- Prior art keywords
- zinc trifluoroacetate
- supported
- supported zinc
- catalyst
- trifluoroacetate
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- VCQWRGCXUWPSGY-UHFFFAOYSA-L zinc;2,2,2-trifluoroacetate Chemical compound [Zn+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F VCQWRGCXUWPSGY-UHFFFAOYSA-L 0.000 title claims abstract description 71
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 239000003054 catalyst Substances 0.000 claims abstract description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 32
- 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 claims abstract description 28
- 239000011347 resin Substances 0.000 claims abstract description 23
- 229920005989 resin Polymers 0.000 claims abstract description 23
- 239000004005 microsphere Substances 0.000 claims abstract description 20
- 229920003053 polystyrene-divinylbenzene Polymers 0.000 claims abstract description 17
- 239000007787 solid Substances 0.000 claims abstract description 15
- 238000010992 reflux Methods 0.000 claims abstract description 8
- 239000000203 mixture Substances 0.000 claims abstract description 7
- CHRJZRDFSQHIFI-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;styrene Chemical compound C=CC1=CC=CC=C1.C=CC1=CC=CC=C1C=C CHRJZRDFSQHIFI-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 238000005406 washing Methods 0.000 claims abstract description 6
- 238000001035 drying Methods 0.000 claims abstract description 3
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 26
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 14
- 229940011051 isopropyl acetate Drugs 0.000 claims description 14
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- 238000007254 oxidation reaction Methods 0.000 claims description 12
- 239000000047 product Substances 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- 239000000543 intermediate Substances 0.000 claims description 11
- ZSMNRKGGHXLZEC-UHFFFAOYSA-N n,n-bis(trimethylsilyl)methanamine Chemical group C[Si](C)(C)N(C)[Si](C)(C)C ZSMNRKGGHXLZEC-UHFFFAOYSA-N 0.000 claims description 11
- 239000005660 Abamectin Substances 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- 238000005576 amination reaction Methods 0.000 claims description 9
- 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 claims description 9
- 230000003647 oxidation Effects 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- XBWIAVHZEWSRJI-UHFFFAOYSA-N Cl.Cl.OP(O)(=O)OC1=CC=CC=C1 Chemical compound Cl.Cl.OP(O)(=O)OC1=CC=CC=C1 XBWIAVHZEWSRJI-UHFFFAOYSA-N 0.000 claims description 5
- 238000001308 synthesis method Methods 0.000 claims description 5
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 4
- 239000007810 chemical reaction solvent Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- CAEWJEXPFKNBQL-UHFFFAOYSA-N prop-2-enyl carbonochloridate Chemical compound ClC(=O)OCC=C CAEWJEXPFKNBQL-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 238000013517 stratification Methods 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000001816 cooling Methods 0.000 abstract description 3
- 238000005303 weighing Methods 0.000 abstract description 3
- 238000011084 recovery Methods 0.000 abstract description 2
- 238000000967 suction filtration Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- 230000007547 defect Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.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 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/06—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing polymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/50—Catalysts, in general, characterised by their form or physical properties characterised by their shape or configuration
- B01J35/51—Spheres
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Definitions
- the invention relates to the technical field of emamectin benzoate preparation, and in particular to supported zinc trifluoroacetate, a preparation method and application thereof.
- Emamectin benzoate full name avermectin benzoate, is a new type of highly effective semi-synthetic antibiotic insecticide synthesized from the fermentation product avermectin B. It has the characteristics of ultra-high efficiency, low toxicity (the preparation is nearly non-toxic), low residue, and pollution-free biological pesticides.
- Emamectin benzoate mainly includes B1 emamectin benzoate and B2 emamectin benzoate, which are widely used in the prevention and control of various pests on crops such as vegetables, fruit trees, and cotton. Among them, B2 emamectin benzoate can also be used for the prevention and control of underground nematodes.
- amination reaction (or imidization reaction) is an indispensable step.
- the amination reaction for synthesizing emamectin benzoate usually uses heptamethyldisilazane as an amination reagent and zinc trifluoroacetate as a reaction catalyst.
- the problem is that the catalyst is expensive and cannot be recycled, which makes the preparation cost of emamectin benzoate high and the economic benefit is not significant.
- the purpose of the present invention is to overcome the defects of the prior art and provide a supported zinc trifluoroacetate, a preparation method and an application thereof.
- the catalyst recovery process is simple and convenient, and the catalyst can be recycled for multiple times, thereby greatly reducing the synthesis cost of emamectin benzoate.
- a supported zinc trifluoroacetate, using styrene divinylbenzene resin microspheres to support the zinc trifluoroacetate; the styrene divinylbenzene resin microspheres supported zinc trifluoroacetate are prepared from the following raw materials in parts by weight:
- Polystyrene divinylbenzene resin microspheres 9-11 parts.
- a method for preparing the supported zinc trifluoroacetate comprises the following steps:
- the amount of ethanol added is: polystyrene divinylbenzene resin microspheres and ethanol are added in a mass volume ratio of 1g:10-30mL.
- the drying is carried out in a vacuum drying oven at 40° C. for 5 hours.
- the invention discloses an application of the supported zinc trifluoroacetate or the supported zinc trifluoroacetate prepared by the preparation method in preparing an emamectin benzoate intermediate, wherein the emamectin benzoate intermediate is 5-allylformyl-4"-methyleneaminoavermectin, and the supported zinc trifluoroacetate is used as a catalyst in a C-4 imidization reaction.
- the imidization agent is heptamethyldisilazane.
- the synthesis method of the 5-allylformyl-4"-methyleneaminoavermectin comprises the following steps:
- Imidization reaction add isopropyl acetate as a reaction solvent to the oxidation product 5-allylformyl-4"-carbonylavermectin, and simultaneously add aminating reagent heptamethyldisilazane and the supported zinc trifluoroacetate, stir and heat to 73-77°C, keep the temperature for reaction for about 3.0h, cool and filter, collect the filtrate and the catalyst solid; then combine the filtrate and the washing liquid to obtain a 5-allylformyl-4"-methyleneaminoavermectin solution.
- the mass ratio of the 5-allylformyl-4"-carbonylavermectin, isopropyl acetate, amination reagent heptamethyldisilazane, and supported zinc trifluoroacetate catalyst is 1:3:0.28-0.38:0.3;
- the collected catalyst-supported zinc trifluoroacetate is washed with isopropyl acetate to recover the catalyst; preferably, when washing the catalyst, the mass volume ratio of the catalyst to isopropyl acetate is 1:2.
- the synthesis method of the oxidation product 5-allylformyl-4"-carbonylavermectin comprises:
- Step a protection reaction: dissolve avermectin in dichloromethane and cool to -20°C, add allyl chloroformate and stir for 1 hour, cool to -30°C, add tetramethylethylenediamine dropwise, and keep warm for 0.5 hour;
- Step b oxidation reaction: dimethyl sulfoxide was added to the reaction solution after the protection reaction, and then phenyl phosphate dichloride was added dropwise, and the mixture was stirred at -20°C for 1 hour, and then post-treated. The reaction was terminated by acid, and the pH value was adjusted to 7.5 by alkali. The mixture was allowed to stand for stratification, dried, and desolvated to obtain solid 5-allylformyl-4"-carbonylavermectin.
- the invention prepares a supported zinc trifluoroacetate catalyst by loading zinc trifluoroacetate with polystyrene divinylbenzene resin microspheres.
- the supported zinc trifluoroacetate catalyst not only has high catalytic activity, but also can be reused within a certain range of times and is easy to recycle, thereby improving the use efficiency of the catalyst, reducing the defects of high production cost and more generation of three wastes caused by traditional catalysts, and improving economic benefits.
- the synthesis method of 5-allylformyl-4"-carbonyl-avermectin B used comprises the following steps:
- a supported zinc trifluoroacetate is prepared by the following method:
- Step 1 Weigh 1.0 g of polystyrene divinylbenzene resin microspheres into a 100 mL flask, add 10 mL of ethanol, and stir. 0.2 g of zinc trifluoroacetate solid was added, heated to reflux for 11 h, cooled and filtered, the solid was washed with ethanol several times, and dried in a vacuum oven at 40° C. for 5 h to obtain a polystyrene divinylbenzene resin microsphere-supported zinc trifluoroacetate catalyst, and the content of zinc trifluoroacetate in the supported catalyst was determined. The content of zinc trifluoroacetate in the catalyst prepared in this example was 18% based on the weight of the polystyrene divinylbenzene resin microspheres.
- a supported zinc trifluoroacetate is prepared by the following method:
- Step 1 Weigh 0.9g of polystyrene divinylbenzene resin microspheres, add 20mL of ethanol into a 100mL flask, stir, add 0.15g of zinc trifluoroacetate solid, heat and reflux for 10h, cool and filter, wash the solid with ethanol several times, dry in a vacuum oven at 40°C for 5h, obtain a polystyrene divinylbenzene resin microsphere-supported zinc trifluoroacetate catalyst, and determine the content of zinc trifluoroacetate in the supported catalyst. Based on the weight of the polystyrene divinylbenzene resin microspheres, the content of zinc trifluoroacetate in the catalyst prepared in this embodiment is 15%.
- a supported zinc trifluoroacetate is prepared by the following method:
- Step 1 Weigh 1.1g of polystyrene divinylbenzene resin microspheres, add 30mL of ethanol to a 100mL flask, stir, add 0.25g of zinc trifluoroacetate solid, heat to reflux for 13h, cool and filter, wash the solid with ethanol several times, dry in a vacuum oven at 40°C for 5h, obtain a polystyrene divinylbenzene resin microsphere-supported zinc trifluoroacetate catalyst, and determine the content of zinc trifluoroacetate in the supported catalyst. Based on the weight of the polystyrene divinylbenzene resin microspheres, the content of zinc trifluoroacetate in the catalyst prepared in this embodiment is 22%.
- a method for synthesizing emamectin benzoate B1, comprising:
- the mass ratio of 5-allylformyl-4"-carbonylavermectin B1, isopropyl acetate, aminating agent heptamethyldisilazane, and zinc trifluoroacetate 1:3:0.28:0.3
- the oxidation product 5-allylformyl-4"-carbonylavermectin B1 is added to a three-necked flask, and then isopropyl acetate is added as a reaction solvent, and at the same time, the aminating agent heptamethyldisilazane and the supported zinc trifluoroacetate (catalyst, calculated as zinc trifluoroacetate) prepared in Example 1 are added, and the temperature is raised to 75°C with stirring, and the reaction is kept warm for about 3.0h.
- the volume ratio is 1:2.5:0.004:0.08:0.115.
- the 5-allylformyl-4"-methyleneaminoavermectin B1 solution obtained in step 1 is cooled to about -5°C, methanol is added, and catalyst B tetrakis(triphenylphosphine)palladium is added.
- Sodium borohydride is slowly added under stirring. After the addition is completed, it is stirred at 0-5°C for 1h. The residue of the amination product is detected to be less than 0.5, which is qualified.
- the pH is adjusted to weak alkalinity, the layers are allowed to stand, the liquids are separated, and the extraction is performed. Benzoic acid is added and stirred to completely dissolve it, the solvent is removed, and the crude emamectin benzoate is obtained.
- the test was carried out at three dosage levels of 125g, 50g and 100g of avermectin oxidation product 5-allylformyl-4"-carbonylavermectin B.
- the results are shown in Table 1.
- the test was conducted at the dosage level of 125 g of avermectin oxidation product 5-allylformyl-4"-carbonylavermectin B1.
- the method of Example 5 was used to synthesize emamectin benzoate B1 multiple times. Except for the first synthesis, the supported zinc trifluoroacetate catalyst was a newly prepared catalyst. In the remaining synthesis reactions, the supported zinc trifluoroacetate catalyst recovered in the previous synthesis was used for amination reaction.
- Table 2 The results are shown in Table 2:
- a method for synthesizing emamectin benzoate comprises the following steps:
- the test was carried out at three dosage levels of 125g, 50g and 100g of avermectin oxidation product 5-allylformyl-4"-carbonylavermectin B.
- the results are shown in Table 3.
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Abstract
The present invention relates to supported zinc trifluoroacetate, a preparation method and the use. Zinc trifluoroacetate supported by styrene-divinylbenzene resin microspheres is used as the supported zinc trifluoroacetate. The preparation method for zinc trifluoroacetate supported by styrene-divinylbenzene resin microspheres comprises the following steps: weighing raw materials in parts by weight, placing polystyrene-divinylbenzene resin microspheres into a flask, then sequentially adding ethanol and zinc trifluoroacetate thereto, heating and refluxing the mixture for 10-12 h, subjecting the mixture to cooling and suction filtration, collecting solids, then washing the mixture with ethanol multiple times, and drying same to obtain the supported zinc trifluoroacetate. When the supported zinc trifluoroacetate of the present invention is used as a catalyst, the recovery process is simple and convenient, and the supported zinc trifluoroacetate can be recycled multiple times, such that the synthesis cost of emamectin benzoate is greatly reduced.
Description
本发明涉及甲维盐制备技术领域，具体涉及一种负载型三氟乙酸锌、制备方法及应用。The invention relates to the technical field of emamectin benzoate preparation, and in particular to supported zinc trifluoroacetate, a preparation method and application thereof.
甲维盐，全称甲氨基阿维菌素苯甲酸盐，是从发酵产品阿维菌素B开始合成的一种新型高效半合成抗生素杀虫剂，具有超高效、低毒(制剂近无毒)、低残留、无公害等生物农药的特点。甲维盐主要包括B1甲维盐和B2甲维盐，广泛用于蔬菜、果树、棉花等农作物上的多种害虫的防治，其中，B2甲维盐还可应用于对地下线虫的防治。Emamectin benzoate, full name avermectin benzoate, is a new type of highly effective semi-synthetic antibiotic insecticide synthesized from the fermentation product avermectin B. It has the characteristics of ultra-high efficiency, low toxicity (the preparation is nearly non-toxic), low residue, and pollution-free biological pesticides. Emamectin benzoate mainly includes B1 emamectin benzoate and B2 emamectin benzoate, which are widely used in the prevention and control of various pests on crops such as vegetables, fruit trees, and cotton. Among them, B2 emamectin benzoate can also be used for the prevention and control of underground nematodes.
在甲维盐的合成过程中，胺化反应(或称亚胺化反应)是其必不可少的一个环节，目前合成甲维盐的胺化反应通常是以七甲基二硅氮烷为胺化试剂，三氟乙酸锌为反应催化剂，其存在的问题是，催化剂价格较贵，且无法回收再利用，使得甲维盐的制备成本偏高，经济效益不显著。In the synthesis process of emamectin benzoate, amination reaction (or imidization reaction) is an indispensable step. At present, the amination reaction for synthesizing emamectin benzoate usually uses heptamethyldisilazane as an amination reagent and zinc trifluoroacetate as a reaction catalyst. The problem is that the catalyst is expensive and cannot be recycled, which makes the preparation cost of emamectin benzoate high and the economic benefit is not significant.
发明内容Summary of the invention
本发明的目的在于克服现有技术的缺陷，提供一种负载型三氟乙酸锌、制备方法及应用，其催化剂回收工艺简便，能够多次循环利用，极大的降低甲维盐的合成成本。The purpose of the present invention is to overcome the defects of the prior art and provide a supported zinc trifluoroacetate, a preparation method and an application thereof. The catalyst recovery process is simple and convenient, and the catalyst can be recycled for multiple times, thereby greatly reducing the synthesis cost of emamectin benzoate.
为了实现上述目的，本发明采取的技术方案如下：In order to achieve the above object, the technical solution adopted by the present invention is as follows:
技术方案一：Technical solution 1:
一种负载型三氟乙酸锌，采用苯乙烯二乙烯苯树脂微球负载三氟乙酸锌；所述苯乙烯二乙烯苯树脂微球负载三氟乙酸锌由包括以下重量份的各原料制备而成：A supported zinc trifluoroacetate, using styrene divinylbenzene resin microspheres to support the zinc trifluoroacetate; the styrene divinylbenzene resin microspheres supported zinc trifluoroacetate are prepared from the following raw materials in parts by weight:
三氟乙酸锌： 1.5-2.5份；Zinc trifluoroacetate: 1.5-2.5 parts;
聚苯乙烯二乙烯苯树脂微球： 9-11份。Polystyrene divinylbenzene resin microspheres: 9-11 parts.
技术方案二：Technical solution 2:
一种所述负载型三氟乙酸锌的制备方法，包括如下步骤：A method for preparing the supported zinc trifluoroacetate comprises the following steps:
按重量份称取各原料，然后向聚苯乙烯二乙烯苯树脂微球中依次加入乙醇和三氟乙酸锌，加热回流10-12h，降温抽滤，收集固体，然后用乙醇洗涤后，干燥即得负载型三氟乙酸锌。Weigh each raw material by weight, then add ethanol and zinc trifluoroacetate to the polystyrene divinylbenzene resin microspheres in sequence, heat and reflux for 10-12 hours, cool and filter, collect the solid, then wash with ethanol and dry to obtain the supported zinc trifluoroacetate.
进一步的，所述加热回流前，乙醇的加入量为：按聚苯乙烯二乙烯苯树脂微球与乙醇质量体积比1g:10-30mL加入。Furthermore, before the heating and reflux, the amount of ethanol added is: polystyrene divinylbenzene resin microspheres and ethanol are added in a mass volume ratio of 1g:10-30mL.
进一步的，所述干燥采用真空干燥箱于40℃干燥5h。
Furthermore, the drying is carried out in a vacuum drying oven at 40° C. for 5 hours.
技术方案三：Technical solution three:
一种所述负载型三氟乙酸锌或所述的制备方法制得的负载型三氟乙酸锌在制备甲维盐中间体中的应用，所述甲维盐中间体为5-甲酸烯丙酯基-4"-亚甲氨基阿维菌素，所述负载型三氟乙酸锌作为C-4亚胺化反应中的催化剂。The invention discloses an application of the supported zinc trifluoroacetate or the supported zinc trifluoroacetate prepared by the preparation method in preparing an emamectin benzoate intermediate, wherein the emamectin benzoate intermediate is 5-allylformyl-4"-methyleneaminoavermectin, and the supported zinc trifluoroacetate is used as a catalyst in a C-4 imidization reaction.
进一步的，所述亚胺化试剂采用七甲基二硅氮烷。Furthermore, the imidization agent is heptamethyldisilazane.
进一步的，所述5-甲酸烯丙酯基-4"-亚甲氨基阿维菌素的合成方法，包括如下步骤：Further, the synthesis method of the 5-allylformyl-4"-methyleneaminoavermectin comprises the following steps:
亚胺化反应：向氧化产物5-甲酸烯丙酯基-4"-羰基阿维菌素中加入乙酸异丙酯作为反应溶剂，同时加入胺化试剂七甲基二硅氮烷和所述的负载型三氟乙酸锌，搅拌升温至73-77℃，保温反应约3.0h，降温过滤，收集滤液和催化剂固体；然后合并滤液与洗涤液，得5-甲酸烯丙酯基-4"-亚甲氨基阿维菌素溶液。Imidization reaction: add isopropyl acetate as a reaction solvent to the oxidation product 5-allylformyl-4"-carbonylavermectin, and simultaneously add aminating reagent heptamethyldisilazane and the supported zinc trifluoroacetate, stir and heat to 73-77°C, keep the temperature for reaction for about 3.0h, cool and filter, collect the filtrate and the catalyst solid; then combine the filtrate and the washing liquid to obtain a 5-allylformyl-4"-methyleneaminoavermectin solution.
进一步的，在亚胺化反应中，所述5-甲酸烯丙酯基-4"-羰基阿维菌素、乙酸异丙酯、胺化试剂七甲基二硅氮烷、负载型三氟乙酸锌催化剂的质量比为1:3:0.28-0.38:0.3；Further, in the imidization reaction, the mass ratio of the 5-allylformyl-4"-carbonylavermectin, isopropyl acetate, amination reagent heptamethyldisilazane, and supported zinc trifluoroacetate catalyst is 1:3:0.28-0.38:0.3;
进一步的，用乙酸异丙酯洗涤收集的催化剂负载型三氟乙酸锌，进行催化剂的回收；优选的在洗涤催化剂时，催化剂与乙酸异丙酯的质量体积比为1:2。Furthermore, the collected catalyst-supported zinc trifluoroacetate is washed with isopropyl acetate to recover the catalyst; preferably, when washing the catalyst, the mass volume ratio of the catalyst to isopropyl acetate is 1:2.
进一步的，所述氧化产物5-甲酸烯丙酯基-4"-羰基阿维菌素的合成方法，包括：Furthermore, the synthesis method of the oxidation product 5-allylformyl-4"-carbonylavermectin comprises:
步骤a、保护反应：将阿维菌素溶解于二氯甲烷中降温至-20℃，加入氯甲酸烯丙酯搅拌1h，降温至-30℃，滴加四甲基乙二胺，保温0.5h；Step a, protection reaction: dissolve avermectin in dichloromethane and cool to -20°C, add allyl chloroformate and stir for 1 hour, cool to -30°C, add tetramethylethylenediamine dropwise, and keep warm for 0.5 hour;
步骤b、氧化反应：向完成保护反应的反应液中加入二甲亚砜，然后滴加磷酸苯酯二酰氯，-20℃保温搅拌1h，进行后处理，酸终止反应，碱调节pH值为7.5，静置分层，干燥、脱溶得固体5-甲酸烯丙酯基-4"-羰基阿维菌素。Step b, oxidation reaction: dimethyl sulfoxide was added to the reaction solution after the protection reaction, and then phenyl phosphate dichloride was added dropwise, and the mixture was stirred at -20°C for 1 hour, and then post-treated. The reaction was terminated by acid, and the pH value was adjusted to 7.5 by alkali. The mixture was allowed to stand for stratification, dried, and desolvated to obtain solid 5-allylformyl-4"-carbonylavermectin.
在本发明甲维盐的合成路线如下：
The synthetic route of emamectin benzoate of the present invention is as follows:
The synthetic route of emamectin benzoate of the present invention is as follows:
其中，式1-7中，
Among them, in formula 1-7,
Among them, in formula 1-7,
与现有技术相比，本发明所取得的有益效果如下：Compared with the prior art, the beneficial effects achieved by the present invention are as follows:
本发明通过将三氟乙酸锌采用聚苯乙烯二乙烯苯树脂微球进行负载制备成负载型三氟乙酸锌催化剂，其不仅具有较高的催化活性，还可以在一定次数范围内重复利用，且便于回收，提高了催化剂的使用效率，降低由传统催化剂引起的生产成本较高，三废的产生较多的缺陷，提高了经济效益。The invention prepares a supported zinc trifluoroacetate catalyst by loading zinc trifluoroacetate with polystyrene divinylbenzene resin microspheres. The supported zinc trifluoroacetate catalyst not only has high catalytic activity, but also can be reused within a certain range of times and is easy to recycle, thereby improving the use efficiency of the catalyst, reducing the defects of high production cost and more generation of three wastes caused by traditional catalysts, and improving economic benefits.
以下结合实施例对本发明进行进一步详细的叙述。The present invention is further described in detail below with reference to the embodiments.
在本发明中，所用5-甲酸烯丙酯基-4"-羰基-阿维菌素B的合成方法，包括以下步骤：In the present invention, the synthesis method of 5-allylformyl-4"-carbonyl-avermectin B used comprises the following steps:
步骤a、保护反应：Step a, protection reaction:
按阿维菌素、氯甲酸烯丙酯、四甲基乙二胺质量比为1:0.15:0.3称取各原料后，首先将阿维菌素(B1含量为95％以上)溶解于二氯甲烷中降温至-20℃，加入氯甲酸烯丙酯搅拌1h，降温至-30℃，滴加四甲基乙二胺，保温0.5h，液相检测，合格，进行下一步，After weighing each raw material according to the mass ratio of avermectin, allyl chloroformate and tetramethylethylenediamine of 1:0.15:0.3, first dissolve avermectin (B1 content is more than 95%) in dichloromethane and cool to -20°C, add allyl chloroformate and stir for 1h, cool to -30°C, add tetramethylethylenediamine dropwise, keep warm for 0.5h, liquid phase detection, qualified, proceed to the next step,
步骤b、氧化反应：Step b, oxidation reaction:
按阿维菌素B1与磷酸苯酯二酰氯质量比4:1称取磷酸苯酯二酰氯后，首先向完成保护反应的反应液中加入二甲亚砜，然后滴加磷酸苯酯二酰氯，-20℃保温搅拌1h，进行后处理，酸终止反应，碱调节pH值为7.5，静置分层，干燥、脱溶得固体5-甲酸烯丙酯基-4"-羰基阿维菌素B1。After weighing phenyl phosphate dichloride in a mass ratio of avermectin B1 to phenyl phosphate dichloride of 4:1, dimethyl sulfoxide was first added to the reaction solution in which the protection reaction was completed, and then phenyl phosphate dichloride was added dropwise. The reaction was stirred at -20°C for 1 hour, and post-treatment was performed. The reaction was terminated with acid, and the pH value was adjusted to 7.5 with alkali. The reaction was allowed to stand for stratification, and then dried and desolventized to obtain solid 5-allylformyl-4"-carbonylavermectin B1.
实施例1Example 1
一种负载型三氟乙酸锌，由如下方法制备而成：A supported zinc trifluoroacetate is prepared by the following method:
步骤1：称取1.0g聚苯乙烯二乙烯苯树脂微球于100mL烧瓶中加入10mL乙醇，搅拌，
加入0.2g三氟乙酸锌固体，加热回流11h，降温抽滤，乙醇多次洗涤固体，40℃真空干燥箱干燥5h，得聚苯乙烯二乙烯苯树脂微球负载三氟乙酸锌催化剂，测定负载型催化剂中三氟乙酸锌含量。以聚苯乙烯二乙烯苯树脂微球重量计，本实施例制备的催化中三氟乙酸锌的含量为18％。Step 1: Weigh 1.0 g of polystyrene divinylbenzene resin microspheres into a 100 mL flask, add 10 mL of ethanol, and stir. 0.2 g of zinc trifluoroacetate solid was added, heated to reflux for 11 h, cooled and filtered, the solid was washed with ethanol several times, and dried in a vacuum oven at 40° C. for 5 h to obtain a polystyrene divinylbenzene resin microsphere-supported zinc trifluoroacetate catalyst, and the content of zinc trifluoroacetate in the supported catalyst was determined. The content of zinc trifluoroacetate in the catalyst prepared in this example was 18% based on the weight of the polystyrene divinylbenzene resin microspheres.
实施例2Example 2
一种负载型三氟乙酸锌，由如下方法制备而成：A supported zinc trifluoroacetate is prepared by the following method:
步骤1：称取0.9g聚苯乙烯二乙烯苯树脂微球于100mL烧瓶中加入20mL乙醇，搅拌，加入0.15g三氟乙酸锌固体，加热回流10h，降温抽滤，乙醇多次洗涤固体，40℃真空干燥箱干燥5h，得聚苯乙烯二乙烯苯树脂微球负载三氟乙酸锌催化剂，测定负载型催化剂中三氟乙酸锌含量。以聚苯乙烯二乙烯苯树脂微球重量计，本实施例制备的催化中三氟乙酸锌的含量为15％。Step 1: Weigh 0.9g of polystyrene divinylbenzene resin microspheres, add 20mL of ethanol into a 100mL flask, stir, add 0.15g of zinc trifluoroacetate solid, heat and reflux for 10h, cool and filter, wash the solid with ethanol several times, dry in a vacuum oven at 40°C for 5h, obtain a polystyrene divinylbenzene resin microsphere-supported zinc trifluoroacetate catalyst, and determine the content of zinc trifluoroacetate in the supported catalyst. Based on the weight of the polystyrene divinylbenzene resin microspheres, the content of zinc trifluoroacetate in the catalyst prepared in this embodiment is 15%.
实施例3Example 3
一种负载型三氟乙酸锌，由如下方法制备而成：A supported zinc trifluoroacetate is prepared by the following method:
步骤1：称取1.1g聚苯乙烯二乙烯苯树脂微球于100mL烧瓶中加入30mL乙醇，搅拌，加入0.25g三氟乙酸锌固体，加热回流13h，降温抽滤，乙醇多次洗涤固体，40℃真空干燥箱干燥5h，得聚苯乙烯二乙烯苯树脂微球负载三氟乙酸锌催化剂，测定负载型催化剂中三氟乙酸锌含量。以聚苯乙烯二乙烯苯树脂微球重量计，本实施例制备的催化中三氟乙酸锌的含量为22％。Step 1: Weigh 1.1g of polystyrene divinylbenzene resin microspheres, add 30mL of ethanol to a 100mL flask, stir, add 0.25g of zinc trifluoroacetate solid, heat to reflux for 13h, cool and filter, wash the solid with ethanol several times, dry in a vacuum oven at 40°C for 5h, obtain a polystyrene divinylbenzene resin microsphere-supported zinc trifluoroacetate catalyst, and determine the content of zinc trifluoroacetate in the supported catalyst. Based on the weight of the polystyrene divinylbenzene resin microspheres, the content of zinc trifluoroacetate in the catalyst prepared in this embodiment is 22%.
实施例4Example 4
一种甲维盐B1的合成方法，包括：A method for synthesizing emamectin benzoate B1, comprising:
步骤1、亚胺化反应：Step 1, imidization reaction:
按5-甲酸烯丙酯基-4"-羰基阿维菌素B1、乙酸异丙酯、胺化试剂七甲基二硅氮烷、三氟乙酸锌的质量比为1:3:0.28:0.3，将氧化产物5-甲酸烯丙酯基-4"-羰基阿维菌素B1加入三口烧瓶中，然后加入乙酸异丙酯作为反应溶剂，同时加入胺化试剂七甲基二硅氮烷和实施例1制备的负载型三氟乙酸锌(催化剂,以三氟乙酸锌计)，搅拌升温至75℃，保温反应约3.0h，降温至室温后过滤，收集滤液和催化剂固体，然后按催化剂与乙酸异丙酯质量体积比1g：2mL，用乙酸异丙酯洗涤催化剂后，合并滤液与洗涤液，即得甲维盐中间体5-甲酸烯丙酯基-4"-亚甲氨基阿维菌素B1溶液；同时回收负载型三氟乙酸锌催化剂；According to the mass ratio of 5-allylformyl-4"-carbonylavermectin B1, isopropyl acetate, aminating agent heptamethyldisilazane, and zinc trifluoroacetate of 1:3:0.28:0.3, the oxidation product 5-allylformyl-4"-carbonylavermectin B1 is added to a three-necked flask, and then isopropyl acetate is added as a reaction solvent, and at the same time, the aminating agent heptamethyldisilazane and the supported zinc trifluoroacetate (catalyst, calculated as zinc trifluoroacetate) prepared in Example 1 are added, and the temperature is raised to 75°C with stirring, and the reaction is kept warm for about 3.0h. After cooling to room temperature, the filtrate and the catalyst solid are collected, and then the catalyst is washed with isopropyl acetate at a mass volume ratio of the catalyst to isopropyl acetate of 1g:2mL, and the filtrate and the washing liquid are combined to obtain a solution of 5-allylformyl-4"-methyleneaminoavermectin B1 as an emamectin benzoate intermediate; and the supported zinc trifluoroacetate catalyst is recovered at the same time;
步骤2、还原、脱保护反应：Step 2, reduction and deprotection reaction:
按5-甲酸烯丙酯基-4"-亚甲氨基阿维菌素B1、甲醇、催化剂B、硼氢化钠、苯甲酸质量
体积比1:2.5:0.004:0.08:0.115，将步骤1得到的5-甲酸烯丙酯基-4"-亚甲氨基阿维菌素B1溶液降温至-5℃左右，加入甲醇，加入催化剂B四(三苯基膦)钯，搅拌条件下缓慢加入硼氢化钠，加入完毕后，于0-5℃搅拌1h，检测胺化产物残留＜0.5，合格，调节pH至弱碱性，静置分层，分液，萃取，加入苯甲酸搅拌使其完全溶解，脱溶，烘干，即得甲维盐粗品。According to the mass of 5-allylformyl-4"-methyleneaminoavermectin B1, methanol, catalyst B, sodium borohydride, and benzoic acid The volume ratio is 1:2.5:0.004:0.08:0.115. The 5-allylformyl-4"-methyleneaminoavermectin B1 solution obtained in step 1 is cooled to about -5°C, methanol is added, and catalyst B tetrakis(triphenylphosphine)palladium is added. Sodium borohydride is slowly added under stirring. After the addition is completed, it is stirred at 0-5°C for 1h. The residue of the amination product is detected to be less than 0.5, which is qualified. The pH is adjusted to weak alkalinity, the layers are allowed to stand, the liquids are separated, and the extraction is performed. Benzoic acid is added and stirred to completely dissolve it, the solvent is removed, and the crude emamectin benzoate is obtained.
按照上述方法，在阿维菌素氧化产物5-甲酸烯丙酯基-4"-羰基阿维菌素B125g、50g和100g三个用量水平上进行试验，结果见表1；According to the above method, the test was carried out at three dosage levels of 125g, 50g and 100g of avermectin oxidation product 5-allylformyl-4"-carbonylavermectin B. The results are shown in Table 1.
表1
Table 1
Table 1
实施例5Example 5
在阿维菌素氧化产物5-甲酸烯丙酯基-4"-羰基阿维菌素B125g用量水平上进行试验，采用实施例5的方法进行多次甲维盐B1的合成，除第一次合成时，负载型三氟乙酸锌催化剂采用新制备的催化剂外，其余次合成反应，均采用上一次回收的负载型三氟乙酸锌催化剂进行胺化反应，结果见表2：The test was conducted at the dosage level of 125 g of avermectin oxidation product 5-allylformyl-4"-carbonylavermectin B1. The method of Example 5 was used to synthesize emamectin benzoate B1 multiple times. Except for the first synthesis, the supported zinc trifluoroacetate catalyst was a newly prepared catalyst. In the remaining synthesis reactions, the supported zinc trifluoroacetate catalyst recovered in the previous synthesis was used for amination reaction. The results are shown in Table 2:
表2
Table 2
Table 2
对比例1Comparative Example 1
一种甲维盐的合成方法，包括如下步骤：A method for synthesizing emamectin benzoate comprises the following steps:
步骤1、胺化反应：Step 1, amination reaction:
按5-甲酸烯丙酯基-4"-羰基-阿维菌素B1、乙酸异丙酯、胺化试剂七甲基二硅氮烷、三氟乙酸锌的质量比为1:3:0.32:0.3，将氧化产物5-甲酸烯丙酯基-4"-羰基阿维菌素B1加入三口烧瓶中，然后再加入乙酸异丙酯作为反应溶剂，同时加入氨化试剂七甲基二硅氮烷与催化剂三氟乙酸锌，搅拌升温到73-77℃，保温反应约3.5h，即得甲维盐中间体5-甲酸烯丙酯基-4"-亚甲氨基阿维菌素B1溶液；According to the mass ratio of 5-allylformyl-4"-carbonyl-avermectin B1, isopropyl acetate, aminating agent heptamethyldisilazane and zinc trifluoroacetate of 1:3:0.32:0.3, the oxidation product 5-allylformyl-4"-carbonylavermectin B1 is added into a three-necked flask, and then isopropyl acetate is added as a reaction solvent, and the aminating agent heptamethyldisilazane and the catalyst zinc trifluoroacetate are added at the same time, and the temperature is raised to 73-77° C. with stirring, and the reaction is kept at this temperature for about 3.5 hours to obtain the emamectin benzoate intermediate 5-allylformyl-4"-methyleneaminoavermectin B1 solution;
步骤2、还原、脱保护反应：Step 2, reduction and deprotection reaction:
按5-甲酸烯丙酯基-4"-亚甲氨基阿维菌素B1、甲醇、催化剂B、硼氢化钠质量比1:2.5:0.004:0.08:0.115；将步骤1得到的5-甲酸烯丙酯基-4"-亚甲氨基阿维菌素B1溶液降温至-5℃左右后，加入甲醇和催化剂B四(三苯基膦)钯，搅拌条件下缓慢加入硼氢化钠，加入完毕后，于0-5℃搅拌1h，检测胺化产物残留＜0.5，合格，调节pH至弱碱性，静置分层，分液，萃取，加入苯甲酸搅拌使其完全溶解，脱溶，烘干，即得甲维盐B1粗品。According to the mass ratio of 5-allylformyl-4"-methyleneaminoavermectin B1, methanol, catalyst B, and sodium borohydride of 1:2.5:0.004:0.08:0.115; after cooling the 5-allylformyl-4"-methyleneaminoavermectin B1 solution obtained in step 1 to about -5°C, methanol and catalyst B tetrakis(triphenylphosphine)palladium are added, and sodium borohydride is slowly added under stirring. After the addition is completed, it is stirred at 0-5°C for 1h, and the residue of the amination product is detected to be less than 0.5, which is qualified, and the pH is adjusted to weak alkalinity, and the layers are allowed to stand, separated, extracted, benzoic acid is added and stirred to completely dissolve it, desolventized, and dried to obtain a crude product of emamectin benzoate B1.
按照上述方法，在阿维菌素氧化产物5-甲酸烯丙酯基-4"-羰基阿维菌素B125g、50g和100g三个用量水平上进行试验，结果见表3；According to the above method, the test was carried out at three dosage levels of 125g, 50g and 100g of avermectin oxidation product 5-allylformyl-4"-carbonylavermectin B. The results are shown in Table 3.
表3
table 3
table 3
以上所述实施方式仅为本发明的优选实施例，而并非本发明可行实施的穷举。对于本领域一般技术人员而言，在不背离本发明原理和精神的前提下对其所作出的任何显而易见的改动，都应当被认为包含在本发明的权利要求保护范围之内。
The above-described embodiments are only preferred embodiments of the present invention, and are not exhaustive of the feasible implementations of the present invention. For those skilled in the art, any obvious changes made thereto without departing from the principles and spirit of the present invention should be considered to be included in the scope of protection of the claims of the present invention.
Claims (10)
- 一种负载型三氟乙酸锌，其特征在于，采用苯乙烯二乙烯苯树脂微球负载三氟乙酸锌；所述苯乙烯二乙烯苯树脂微球负载三氟乙酸锌由包括以下重量份的各原料制备而成：
三氟乙酸锌： 1.5-2.5份；
聚苯乙烯二乙烯苯树脂微球： 9-11份。A supported zinc trifluoroacetate, characterized in that the zinc trifluoroacetate is supported by styrene divinylbenzene resin microspheres; the styrene divinylbenzene resin microspheres supported zinc trifluoroacetate are prepared from the following raw materials in parts by weight:
Zinc trifluoroacetate: 1.5-2.5 parts;
Polystyrene divinylbenzene resin microspheres: 9-11 parts. - 一种如权利要求1所述负载型三氟乙酸锌的制备方法，其特征在于，包括如下步骤：A method for preparing supported zinc trifluoroacetate as claimed in claim 1, characterized in that it comprises the following steps:按重量份称取各原料，然后向聚苯乙烯二乙烯苯树脂微球中依次加入乙醇和三氟乙酸锌，加热回流10-12h，降温抽滤，收集固体，然后用乙醇洗涤后，干燥即得负载型三氟乙酸锌。Weigh each raw material by weight, then add ethanol and zinc trifluoroacetate to the polystyrene divinylbenzene resin microspheres in sequence, heat and reflux for 10-12 hours, cool and filter, collect the solid, then wash with ethanol and dry to obtain the supported zinc trifluoroacetate.
- 根据权利要求2所述的一种负载型三氟乙酸锌催化剂的制备方法，其特征在于，The method for preparing a supported zinc trifluoroacetate catalyst according to claim 2, characterized in that:所述加热回流前，乙醇的加入量为：按聚苯乙烯二乙烯苯树脂微球与乙醇质量体积比1g:10-30mL加入。Before the heating and reflux, the amount of ethanol added is: the mass volume ratio of polystyrene divinylbenzene resin microspheres to ethanol is 1g:10-30mL.
- 根据权利要求2所述的一种负载型三氟乙酸锌的制备方法，其特征在于，The method for preparing a supported zinc trifluoroacetate according to claim 2, characterized in that:所述干燥采用真空干燥箱于40℃干燥5h。The drying was carried out in a vacuum drying oven at 40° C. for 5 h.
- 一种如权利要求1所述负载型三氟乙酸锌或权利要求2-3任一项所述的制备方法制得的负载型三氟乙酸锌在制备甲维盐中间体中的应用，所述甲维盐中间体为5-甲酸烯丙酯基-4"-亚甲氨基阿维菌素，其特征在于所述负载型三氟乙酸锌作为C-4亚胺化反应中的催化剂。A use of the supported zinc trifluoroacetate as claimed in claim 1 or the supported zinc trifluoroacetate prepared by the preparation method according to any one of claims 2 to 3 in the preparation of an emamectin benzoate intermediate, wherein the emamectin benzoate intermediate is 5-allylformyl-4"-methyleneaminoavermectin, characterized in that the supported zinc trifluoroacetate is used as a catalyst in a C-4 imidization reaction.
- 根据权利要求5所述一种负载型三氟乙酸锌在制备甲维盐中间体中的应用，其特征在于，所述亚胺化试剂采用七甲基二硅氮烷。The use of a supported zinc trifluoroacetate in the preparation of an emamectin benzoate intermediate according to claim 5, characterized in that the imidization reagent is heptamethyldisilazane.
- 根据权利要求5所述负载型三氟乙酸锌在制备甲维盐中间体中的应用，其特征在于，所述5-甲酸烯丙酯基-4"-亚甲氨基阿维菌素的合成方法，包括如下步骤：The use of supported zinc trifluoroacetate in the preparation of emamectin benzoate intermediates according to claim 5, characterized in that the synthesis method of 5-allylformyl-4"-methyleneaminoavermectin comprises the following steps:亚胺化反应：向氧化产物5-甲酸烯丙酯基-4"-羰基阿维菌素中加入乙酸异丙酯作为反应溶剂，同时加入胺化试剂七甲基二硅氮烷和所述的负载型三氟乙酸锌，搅拌升温至73-77℃，保温反应约3.0h，降温过滤，收集滤液和催化剂固体；然后合并滤液与洗涤液，得5-甲酸烯丙酯基-4"-亚甲氨基阿维菌素溶液。Imidization reaction: add isopropyl acetate as a reaction solvent to the oxidation product 5-allylformyl-4"-carbonylavermectin, and simultaneously add aminating reagent heptamethyldisilazane and the supported zinc trifluoroacetate, stir and heat to 73-77°C, keep the temperature for reaction for about 3.0h, cool and filter, collect the filtrate and the catalyst solid; then combine the filtrate and the washing liquid to obtain a 5-allylformyl-4"-methyleneaminoavermectin solution.
- 根据权利要求7所述一种负载型三氟乙酸锌在制备甲维盐中间体中的应用，其特征在于，The use of a supported zinc trifluoroacetate in the preparation of an emamectin benzoate intermediate according to claim 7, characterized in that:在亚胺化反应中，所述5-甲酸烯丙酯基-4"-羰基阿维菌素、乙酸异丙酯、胺化试剂七甲基二硅氮烷、负载型三氟乙酸锌催化剂的质量比为1:3:0.28-0.38:0.3。In the imidization reaction, the mass ratio of the 5-allylformyl-4"-carbonylavermectin, isopropyl acetate, amination reagent heptamethyldisilazane, and supported zinc trifluoroacetate catalyst is 1:3:0.28-0.38:0.3.
- 根据权利要求7所述一种负载型三氟乙酸锌在制备甲维盐中间体中的应用，其特征在于，用乙酸异丙酯洗涤收集的催化剂负载型三氟乙酸锌，进行催化剂的回收；优选的在洗涤催化剂时，催化剂与乙酸异丙酯的质量体积比为1:2。 The use of a supported zinc trifluoroacetate in the preparation of an emamectin benzoate intermediate according to claim 7, characterized in that the collected catalyst-supported zinc trifluoroacetate is washed with isopropyl acetate to recover the catalyst; preferably, when washing the catalyst, the mass volume ratio of the catalyst to isopropyl acetate is 1:2.
- 根据权利要求5所述负载型三氟乙酸锌在制备甲维盐中间体中的应用，其特征在于，The use of supported zinc trifluoroacetate in the preparation of an emamectin benzoate intermediate according to claim 5, characterized in that:所述氧化产物5-甲酸烯丙酯基-4"-羰基阿维菌素的合成方法，包括：The synthesis method of the oxidation product 5-allylformyl-4"-carbonylavermectin comprises:步骤a、保护反应：将阿维菌素溶解于二氯甲烷中降温至-20℃，加入氯甲酸烯丙酯搅拌1h，降温至-30℃，滴加四甲基乙二胺，保温0.5h；Step a, protection reaction: dissolve avermectin in dichloromethane and cool to -20°C, add allyl chloroformate and stir for 1 hour, cool to -30°C, add tetramethylethylenediamine dropwise, and keep warm for 0.5 hour;步骤b、氧化反应：向完成保护反应的反应液中加入二甲亚砜，然后滴加磷酸苯酯二酰氯，-20℃保温搅拌1h，进行后处理，酸终止反应，碱调节pH值为7.5，静置分层，干燥、脱溶得固体5-甲酸烯丙酯基-4"-羰基阿维菌素。 Step b, oxidation reaction: dimethyl sulfoxide was added to the reaction solution after the protection reaction, and then phenyl phosphate dichloride was added dropwise, and the mixture was stirred at -20°C for 1 hour, and then post-treated. The reaction was terminated by acid, and the pH value was adjusted to 7.5 by alkali. The mixture was allowed to stand for stratification, dried, and desolvated to obtain solid 5-allylformyl-4"-carbonylavermectin.
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| CN106279319A (en) * | 2016-08-15 | 2017-01-04 | 曹正祥 | A kind of synthesis technique of acaricide emamectin benzoate |
| US20200283360A1 (en) * | 2019-03-04 | 2020-09-10 | Honeywell International Inc. | Processes for producing trifluoroiodomethane using metal trifluoroacetates |
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