CN111187204B - Acetamiprid eutectic crystal and preparation method and application thereof - Google Patents
Acetamiprid eutectic crystal and preparation method and application thereof Download PDFInfo
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- CN111187204B CN111187204B CN202010029719.3A CN202010029719A CN111187204B CN 111187204 B CN111187204 B CN 111187204B CN 202010029719 A CN202010029719 A CN 202010029719A CN 111187204 B CN111187204 B CN 111187204B
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- acetamiprid
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- eutectic
- oxalic acid
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- WCXDHFDTOYPNIE-RIYZIHGNSA-N (E)-acetamiprid Chemical compound N#C/N=C(\C)N(C)CC1=CC=C(Cl)N=C1 WCXDHFDTOYPNIE-RIYZIHGNSA-N 0.000 title claims abstract description 92
- 239000005875 Acetamiprid Substances 0.000 title claims abstract description 92
- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- 239000013078 crystal Substances 0.000 title claims abstract description 26
- 230000005496 eutectics Effects 0.000 title abstract description 46
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims abstract description 102
- 235000006408 oxalic acid Nutrition 0.000 claims abstract description 27
- 239000000203 mixture Substances 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 238000010438 heat treatment Methods 0.000 claims description 9
- 241000607479 Yersinia pestis Species 0.000 claims description 8
- 238000009472 formulation Methods 0.000 claims description 8
- 238000001228 spectrum Methods 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 25
- 238000002844 melting Methods 0.000 abstract description 20
- 230000008018 melting Effects 0.000 abstract description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract description 19
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 abstract description 12
- 150000001875 compounds Chemical class 0.000 abstract description 11
- 150000007524 organic acids Chemical class 0.000 abstract description 11
- 239000000575 pesticide Substances 0.000 abstract description 9
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 235000005985 organic acids Nutrition 0.000 abstract description 3
- 238000012360 testing method Methods 0.000 description 15
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 239000011248 coating agent Substances 0.000 description 9
- 238000000634 powder X-ray diffraction Methods 0.000 description 9
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 230000035784 germination Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 5
- 240000008042 Zea mays Species 0.000 description 4
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 4
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 4
- 235000005822 corn Nutrition 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000011812 mixed powder Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- PQUXFUBNSYCQAL-UHFFFAOYSA-N 1-(2,3-difluorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC(F)=C1F PQUXFUBNSYCQAL-UHFFFAOYSA-N 0.000 description 3
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- NVVZQXQBYZPMLJ-UHFFFAOYSA-N formaldehyde;naphthalene-1-sulfonic acid Chemical compound O=C.C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 NVVZQXQBYZPMLJ-UHFFFAOYSA-N 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 229920002545 silicone oil Polymers 0.000 description 3
- 229940047670 sodium acrylate Drugs 0.000 description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229910017488 Cu K Inorganic materials 0.000 description 2
- 229910017541 Cu-K Inorganic materials 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 239000005925 Pymetrozine Substances 0.000 description 2
- 239000012752 auxiliary agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- QHMTXANCGGJZRX-WUXMJOGZSA-N pymetrozine Chemical compound C1C(C)=NNC(=O)N1\N=C\C1=CC=CN=C1 QHMTXANCGGJZRX-WUXMJOGZSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 238000010008 shearing Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 230000001502 supplementing effect Effects 0.000 description 2
- 241001124076 Aphididae Species 0.000 description 1
- 235000009024 Ceanothus sanguineus Nutrition 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 0.000 description 1
- 229910002483 Cu Ka Inorganic materials 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000258937 Hemiptera Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000255777 Lepidoptera Species 0.000 description 1
- 240000003553 Leptospermum scoparium Species 0.000 description 1
- 235000015459 Lycium barbarum Nutrition 0.000 description 1
- JNGOGRQGYCFRHT-UHFFFAOYSA-N NC(=O)C1=CC=CN=C1.CC(=O)OCC[N+](C)(C)C Chemical compound NC(=O)C1=CC=CN=C1.CC(=O)OCC[N+](C)(C)C JNGOGRQGYCFRHT-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241001414989 Thysanoptera Species 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- -1 acetamiprid) Chemical compound 0.000 description 1
- 102000034337 acetylcholine receptors Human genes 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229910001566 austenite Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000011229 interlayer Substances 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000005232 molecular self-assembly Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000005070 ripening Effects 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 230000003335 steric effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/61—Halogen atoms or nitro radicals
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
- A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
- C07C53/08—Acetic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
- C07C55/02—Dicarboxylic acids
- C07C55/06—Oxalic acid
- C07C55/07—Salts thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
- C07C55/02—Dicarboxylic acids
- C07C55/08—Malonic acid
-
- 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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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Dentistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Plant Pathology (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Agronomy & Crop Science (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The invention relates to the field of compound crystal forms, in particular to an acetamiprid eutectic and a preparation method and application thereof, wherein the acetamiprid eutectic comprises the following components: acetamiprid (acetamiprid) and organic acids; wherein the molar ratio of the acetamiprid (acetamiprid) to the organic acid is 10; the invention also provides a preparation method and application of the acetamiprid eutectic. According to the technical scheme, organic acids such as acetic acid, oxalic acid or malonic acid are used as eutectic formers and form cocrystals with acetamiprid, and the acetamiprid eutectic crystal has the advantages of high melting point, high water solubility value and high water solubility rate, and is suitable for being applied to the production process of pesticide preparations.
Description
Technical Field
The invention belongs to the field of compound crystal forms, and particularly relates to an acetamiprid eutectic, and a preparation method and application of the eutectic.
Background
In the field of agricultural chemistry, different solid forms of compounds have different physicochemical properties, such as melting point, density, powder flowability and the like, which all affect the preparation process and quality of preparation products, and even affect the effects on crops and plant diseases and insect pests after application, so the selection of the solid form of the compound is one of the factors to be considered in the research of pesticide preparations. The solid form of the compound mainly comprises different crystal forms, salts, hydrates or solvates and eutectic crystals. A co-crystal, which generally refers to a crystal in which the active ingredient and the co-crystal former are bound by hydrogen bonds or other non-covalent bonds, is a multicomponent crystal. The eutectic is essentially a supramolecular self-assembly system, and is a balanced result of thermodynamics, kinetics and molecular recognition. During the process of molecular self-assembly, intermolecular interactions and steric effects influence the formation of supramolecular networks, which in turn directly influence the crystal formation. Within the eutectic system, the interactions between different molecules are mainly hydrogen bonding, pi-pi stacking, van der waals forces and halogen bases. The physical and chemical properties of the eutectic can be changed without changing the covalent structure of the drug, and compared with a single crystal form, the eutectic can greatly change the properties of the compound due to the introduced different components, so that the properties of the compound can be adjusted in different properties.
Acetamiprid is a neonicotinoid compound successfully researched and developed by Nippon Caoda corporation, in particular to a nicotinamide acetylcholine receptor stimulant, is a systemic pesticide, has interlayer conductivity activity and contact killing and stomach toxicity, is used for preventing and treating hemiptera (particularly aphids), thysanoptera and lepidoptera pests, is suitable for wide range of crops, and is particularly suitable for vegetables, fruit trees and tea trees. However, acetamiprid has a melting point of 98.9 ℃, and is slowly decomposed at pH9 and 45 ℃, and is easily mixed with impurities due to melting or degraded during hot melting in the process of preparing certain specific preparations (such as granules). In addition, the acetamiprid has poor water solubility which is only 4250mg/L (25 ℃), and the phenomenon of austenite ripening is easy to occur in the storage process (especially above 35 ℃) of the acetamiprid preparation, especially the aqueous suspension agent, and the sedimentation phenomenon of effective components can occur with the lapse of time, even the final service performance can be influenced. Therefore, the disadvantages of low water solubility and low melting point are always troubling the application of the compound in agriculture. The existing common method for changing the property of the product generally needs to change the structure, add an auxiliary agent and other modes, so that the cost is high, and the performance of the actual application of the product is influenced due to the change of the structure of part of the modes.
Basf european corporation disclosed crystalline complexes of 4-hydroxybenzoic acid and a selected pesticide in patent application No. CN201080050233.2 and specifically disclosed crystalline complexes of 4-hydroxybenzoic acid and acetamiprid (i.e., acetamiprid), it is known from the disclosure of this patent application that the crystalline complex of 4-hydroxybenzoic acid and acetamiprid has a melting point of about 126.1 ℃, a water solubility value of 1890mg/L at room temperature and that seeds treated with the acetamiprid-co-crystal show an increase in germination rate of 8%. The patent application with the application number of CN200810116936.5 of Jiangsuchun group Limited discloses an organic salt obtained by combining salicylic acid with pymetrozine or acetamiprid, but only discloses the safety and the efficacy of pymetrozine salicylate, and does not examine the organic salt obtained by combining acetamiprid and salicylic acid.
The applicant unexpectedly finds that by utilizing the eutectic mode, on the premise of not changing the covalent structure of the acetamiprid, the acetamiprid is combined with carboxylic acid such as oxalic acid and malonic acid to prepare the acetamiprid eutectic, so that the physicochemical properties of the acetamiprid can be effectively improved, the water solubility and the melting point of the acetamiprid can be improved, the stability and the processability of the acetamiprid can be enhanced, and a foundation is laid for further development and application of the acetamiprid.
Disclosure of Invention
The invention aims to overcome the inconvenience caused by the low water solubility and melting point of acetamiprid in the prior art in the preparation and storage processes of pesticide preparations. The method for changing the property of the acetamiprid has the advantages of high melting point, high water solubility value and high water solubility rate, and is suitable for being applied to the production process of pesticide preparations.
In order to achieve the technical purpose, the invention provides the following technical scheme: an acetamiprid cocrystal, comprising: acetamiprid (acetamiprid) and organic acids; wherein the molar ratio of the acetamiprid (acetamiprid) to the organic acid is 10;
further, the organic acid is a carboxylic acid; preferably any one of acetic acid, oxalic acid or malonic acid; oxalic acid is preferred;
further, the molar ratio of the acetamiprid to the organic acid is 5; the preferred molar ratio is 3; the more preferable molar ratio is 2;
further, the pesticide comprises acetamiprid (acetamiprid) and oxalic acid, wherein the molar ratio of the acetamiprid (acetamiprid) to the oxalic acid is 1-1; the preferred molar ratio is 1;
further, the acetamiprid (acetamiprid) comprises acetamiprid technical product, single crystal form of acetamiprid, mixture of different crystal forms of acetamiprid, amorphous acetamiprid, acetamiprid solvate or mixture of amorphous acetamiprid and crystal form;
further, at least 4 of the following diffraction peaks given as 2 θ values are shown in the spectrum: 7.591 degrees +/-0.2, 11.386 degrees +/-0.2, 12.834 degrees +/-0.2, 13.202 degrees +/-0.2, 15.120 degrees +/-0.2, 18.180 degrees +/-0.2, 19.181 degrees +/-0.2, 19.998 degrees +/-0.2, 20.955 degrees +/-0.2, 21.915 degrees +/-0.2, 22.670 degrees +/-0.2, 23.752 degrees +/-0.2, 24.731 degrees +/-0.2, 26.284 degrees +/-0.2, 27.404 degrees +/-0.2, 27.729 degrees +/-0.2 and 30.444 degrees +/-0.2;
still further, at least 5, usually at least 6, in particular all of the above diffraction peaks given as 2 θ values are shown in the spectrum;
still further, at least 4, in particular at least 5, usually at least 6, in particular all of the following diffraction peaks given as 2 θ values are shown in the spectrum: 7.591 degrees +/-0.1, 11.386 degrees +/-0.1, 12.834 degrees +/-0.1, 13.202 degrees +/-0.1, 15.120 degrees +/-0.1, 18.180 degrees +/-0.1, 19.181 degrees +/-0.1, 19.998 degrees +/-0.1, 20.955 degrees +/-0.1, 21.915 degrees +/-0.1, 22.670 degrees +/-0.1, 23.752 degrees +/-0.1, 24.731 degrees +/-0.1, 26.284 +/-0.1, 27.404 degrees +/-0.1, 27.729 degrees +/-0.1 and 30.444 degrees +/-0.1;
still further, at least 4, in particular at least 5, usually at least 6, in particular all of the following diffraction peaks given as 2 θ values are shown in the spectrum: 7.591 degrees, 11.386 degrees, 12.834 degrees, 13.202 degrees, 15.120 degrees, 18.180 degrees, 19.181 degrees, 19.998 degrees, 20.955 degrees, 21.915 degrees, 22.670 degrees, 23.752 degrees, 24.731 degrees, 26.284 degrees, 27.404 degrees, 27.729 degrees and 30.444 degrees.
The invention also provides a preparation method of the cocrystal, which comprises the steps of mixing acetamiprid and organic acid, adding an alcohol solvent, stirring under heating or non-heating conditions, filtering, standing the filtrate, and collecting a solid as the cocrystal;
further, the organic acid is a carboxylic acid; still further, any one of acetic acid, oxalic acid or malonic acid; still further, oxalic acid or malonic acid; still further, oxalic acid;
the heating condition is heating at 30-50 ℃;
the alcohol solvent is any one or a mixture of methanol, ethanol, propanol or butanol; preferably methanol or ethanol;
further, adding an alcohol solvent, stirring for 2-4h under a heating condition, and filtering;
further, standing the filtrate for 3-5 days;
further, the solid-to-liquid ratio of the mixture of the acetamiprid and the organic acid to the alcohol solvent is (0.3-0.4) g, (3-4) mL;
still further, the solid-to-liquid ratio of the mixture of the acetamiprid and the organic acid to the alcohol solvent is (0.311-0.313) g, (3-4) mL;
further, the preparation method of the eutectic specifically comprises the following steps: mixing acetamiprid and oxalic acid, adding methanol, heating in a water bath at 50 ℃, stirring for 2-4h, filtering, standing and volatilizing the filtrate for 3-5 days, and collecting the solid as the cocrystal;
or mixing acetamiprid and oxalic acid, adding ethanol, heating in water bath at 50 deg.C, stirring for 2-4 hr, filtering, standing the filtrate for volatilizing for 3-5 days, and collecting solid as the co-crystal;
still further, the filtration is hot filtration.
The invention also provides an agricultural preparation, which comprises an effective amount of the acetamiprid cocrystal; preferably, the composition also comprises an agriculturally acceptable preparation carrier or a preparation auxiliary agent.
The present invention also provides a method for controlling pests, which comprises applying a pesticidally effective amount of the acetamiprid cocrystal as described above or the agricultural formulation as described above to the pests and/or their habitat.
The invention also provides the use of an acetamiprid cocrystal as described above or an agricultural formulation as described above for controlling pests.
Due to the adoption of the technology, compared with the prior art, the invention has the remarkable advantages that:
1) According to the technical scheme, carboxylic acids such as acetic acid, oxalic acid and malonic acid are used as eutectic formers and form eutectic with acetamiprid, so that the acetamiprid eutectic crystal has the advantages of high melting point, high water solubility and high water solubility rate, particularly the melting point is increased to 142.5 ℃, the water solubility is increased to 7.4g/L, the water solubility rate is greatly increased, the acetamiprid eutectic crystal is suitable for being applied to the production process of pesticide preparations, and the inconvenience caused by the low water solubility and the low melting point of the acetamiprid in the prior art in the preparation and storage processes of the pesticide preparations is solved;
2) According to the preparation method of the acetamiprid-oxalic acid eutectic, the solvent volatilization method and the cooling method are adopted to prepare the high-purity eutectic, and PXRD, melting point measurement and other related characteristics and dissolution rate tests are performed on the eutectic, so that the prepared acetamiprid-oxalic acid eutectic has high purity and crystallinity, can be kept stable for a long time without deterioration, is simple in preparation process and low in cost, and is suitable for large-scale production.
Drawings
FIG. 1 is a PXRD spectrum of acetamiprid-oxalic acid eutectic prepared in example 1 of the present invention;
FIG. 2 is a comparison graph of PXRD spectra of acetamiprid-oxalic acid eutectic, acetamiprid and oxalic acid;
FIG. 3 is a comparison graph of dissolution rates of acetamiprid-oxalic acid eutectic crystal and excessive powder of acetamiprid in physiological saline.
Detailed Description
In order to make the technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments.
Example 1
The preparation method of the acetamiprid-oxalic acid eutectic crystal is implemented according to the following steps:
placing mixed powder of 2.226g of acetamiprid bulk drug and 0.900g of oxalic acid into a round-bottom flask according to the mol ratio of 1. The test is carried out by using a D8 type X-ray diffractometer of BRUKER company in Germany, the test conditions are that the Cu-Kalpha target tube voltage is 40kV, the tube current is 10mA, the scanning speed is 2 DEG/min, and the PXRD diffraction pattern of the product is shown in figure 1.
The PXRD characteristic diffraction peaks of the acetamiprid-oxalic acid eutectic of the embodiment appear at 7.591 degrees, 11.386 degrees, 12.834 degrees, 13.202 degrees, 15.120 degrees, 18.180 degrees, 19.181 degrees, 19.998 degrees, 20.955 degrees, 21.915 degrees, 22.670 degrees, 23.752 degrees, 24.731 degrees, 26.284 degrees, 27.404 degrees, 27.729 degrees and 30.444 degrees. As shown in fig. 2, compared with PXRD of acetamiprid bulk drug and oxalic acid bulk drug, the obtained acetamiprid-oxalic acid cocrystal has significant changes in characteristic diffraction peak position and diffraction intensity, indicating that a new phase is generated.
Example 2
The preparation method of the acetamiprid-oxalic acid eutectic crystal is implemented according to the following steps:
putting mixed powder of 0.222g of acetamiprid bulk drug and 0.090g of oxalic acid into a round-bottom flask according to the mol ratio of 1. The test was carried out using an X-ray diffractometer model D8 from BRUKER, germany under the conditions of a Cu-K.alpha.target tube voltage of 40kV, a tube current of 10mA and a scanning speed of 2 DEG/min, and the PXRD diffraction pattern of the product was the same as that of example 1.
Example 3
The preparation method of the acetamiprid-oxalic acid eutectic crystal is implemented according to the following steps:
putting mixed powder of 0.222g of acetamiprid bulk drug and 0.090g of oxalic acid into a round-bottom flask according to the mol ratio of 1. The test was carried out using an X-ray diffractometer model D8 from BRUKER, germany, under the test conditions of Cu-Ka target tube voltage 40kV, tube current 10mA, scanning speed 2 °/min, and PXRD diffraction pattern of the product was the same as that of example 1.
Example 4
The preparation method of the acetamiprid-acetic acid eutectic crystal is implemented according to the following steps:
putting mixed powder of 0.222g of acetamiprid raw material medicine and 0.060g of acetic acid into a round-bottom flask according to the mol ratio of 1. The test is carried out by using a D8 type X-ray diffractometer of BRUKER company in Germany, the test conditions are that the voltage of a Cu-K alpha target tube is 40kV, the tube current is 10mA, and the scanning speed is 2 DEG/min, and the PXRD diffraction pattern of the product is different from that of acetamiprid bulk drug and acetic acid.
Example 5
And (3) determining the melting point of the acetamiprid-oxalic acid eutectic:
the melting point of the eutectic compound prepared in example 1 is 142.5 ℃ and the melting point of acetamiprid is 102 ℃ and the melting point of oxalic acid is 101 ℃ by using a Shanghai Jiahang WRS-1C type melting point tester, and compared with the simple substances of acetamiprid and oxalic acid, the melting points of the two substances in the eutectic are respectively increased by 40.5 ℃ and 41.5 ℃, so that the eutectic compound has a great promotion effect on the stability of the acetamiprid.
Example 6
Solubility test of acetamiprid-oxalic acid eutectic:
the dissolution rates of the acetamiprid-oxalic acid eutectic sample prepared in example 1 and the acetamiprid excess powder in a normal saline solution were respectively measured by the method of dissolution rate of excess powder. Respectively placing an excessive acetamiprid-oxalic acid eutectic sample and an excessive acetamiprid sample in equal weight into 2 eggplant-shaped flasks with the volume of 100mL, placing the eggplant-shaped flasks into a water bath kettle, simultaneously adding 20mL of physiological saline solution, and starting timing, wherein the water bath temperature is 25 +/-0.5 ℃. The test lasted 180 minutes, and 0.5mL was sampled at 1, 2, 3, 4, 5, 10, 15, 30, 60, 120, 180 minutes, with the results shown in FIG. 3.
As can be seen from the figure, the maximum solubility of the acetamiprid-oxalic acid eutectic in physiological saline is 7430mg/L higher than 4230mg/L of acetamiprid, which shows that the pharmaceutical cocrystal provided by the invention can improve the solubility of acetamiprid, and research results provide scientific basis for improving the bioavailability of acetamiprid and further exerting the insecticidal effect of acetamiprid.
Example 7
Seed treatment test of acetamiprid-oxalic acid eutectic:
1) The preparation of the acetamiprid-oxalic acid eutectic-containing suspension seed coating agent comprises the following steps:
100g of acetamiprid-oxalic acid eutectic, 60g of sodium salt of naphthalene sulfonic acid formaldehyde polymer, 70g of sodium lauryl sulfate, 10g of silicone oil, 10g of sodium acrylate, 70g of glycerol and 20g of gelatin are added into 500g of water, and the mixture is supplemented to 1000g of deionized water, stirred uniformly, sheared at high speed, sanded by a wet method, homogenized and filtered to obtain the suspended seed coating agent.
2) The preparation of the acetamiprid-and-oxalic acid-containing suspension seed coating agent comprises the following steps:
adding 71.2g of acetamiprid, 28.8g of oxalic acid, 60g of sodium salt of a naphthalene sulfonic acid formaldehyde polymer, 70g of sodium lauryl sulfate, 10g of silicone oil, 10g of sodium acrylate, 70g of glycerol and 20g of gelatin into 500g of water, supplementing 1000g of deionized water, uniformly stirring, performing high-speed shearing, performing wet sanding, and finally performing homogenization and filtration to obtain the suspension seed coating agent.
3) Preparing the acetamiprid-containing suspension seed coating agent:
adding 71.2g of acetamiprid, 60g of sodium salt of naphthalene sulfonic acid formaldehyde polymer, 70g of sodium lauryl sulfate, 10g of silicone oil, 10g of sodium acrylate, 70g of glycerol and 20g of gelatin into 500g of water, supplementing to 1000g of deionized water, uniformly stirring, then carrying out high-speed shearing, wet sanding, and finally carrying out homogeneous filtration to obtain the suspended seed coating agent.
4) Seed treatment test:
1kg of corn seeds (Zhengdan 958, commercially available from science and technology limited of the south Henan Qiu Happy variety) and 5g of the above suspension seed coating agent containing acetamiprid-oxalic acid eutectic are mixed uniformly, a control group 1 is provided in which 1kg of corn seeds and 5g of the above suspension seed coating agent containing acetamiprid and oxalic acid are mixed uniformly, a control group 2 is provided in which 1kg of corn seeds and 5g of suspension seed coating agent containing acetamiprid are mixed uniformly, a control group 3 is provided in which 1kg of corn seeds and 5g of clear water are mixed uniformly, and the treated seeds are all placed in a ventilation place to be dried. 100 treated seeds are respectively taken and sowed in a germination box, a germination test is carried out according to GB/T3543.5-1995, the germination rate is counted on the 3 rd day, and the test result is as follows: the germination rate of the acetamiprid-oxalic acid eutectic test group is 94%, the germination rate of the control 1 group is 81%, the germination rate of the control 2 group is 82%, and the germination rate of the control 3 group is 94%.
The above-mentioned embodiments are merely preferred embodiments of the present invention, and should not be construed as limiting the present invention, and the scope of the present invention should be defined by the claims, and equivalents including technical features of the claims, i.e., equivalent modifications within the scope of the present invention.
Claims (8)
1. An acetamiprid cocrystal, wherein the cocrystal consists of acetamiprid and oxalic acid, wherein the molar ratio of acetamiprid to oxalic acid is 1, and the following diffraction peaks, given as 2 θ values, are shown in the spectrum: 7.591 degrees +/-0.2, 11.386 degrees +/-0.2, 12.834 degrees +/-0.2, 13.202 degrees +/-0.2, 15.120 degrees +/-0.2, 18.180 degrees +/-0.2, 19.181 degrees +/-0.2, 19.998 degrees +/-0.2, 20.955 degrees +/-0.2, 21.915 degrees +/-0.2, 22.670 degrees +/-0.2, 23.752 degrees +/-0.2, 24.731 degrees +/-0.2, 26.284 degrees +/-0.2, 27.404 degrees +/-0.2, 27.729 degrees +/-0.2 and 30.444 degrees +/-0.2.
2. The method for preparing the co-crystal according to claim 1, wherein acetamiprid and oxalic acid are mixed, the molar ratio of the acetamiprid to the oxalic acid is 1.
3. The method according to claim 2, wherein the heating condition is heating at 30 to 50 ℃;
the solid-to-liquid ratio of the mixture of the acetamiprid and the oxalic acid to the methanol or the ethanol is (0.3-0.4) g, (3-4) mL.
4. The preparation method according to claim 3, wherein the solid-to-liquid ratio of the mixture of acetamiprid and oxalic acid to methanol or ethanol is (0.311 to 0.313) g (3 to 4) mL.
5. An agricultural formulation comprising an effective amount of the acetamiprid cocrystal of claim 1.
6. The agricultural formulation of claim 5, further comprising an agriculturally acceptable formulation carrier or formulation adjuvant.
7. A method for controlling pests, which comprises applying a pesticidally effective amount of the acetamiprid cocrystal of claim 1 or the agricultural formulation of any one of claims 5 to 6 to the pests and/or their habitat.
8. Use of an acetamiprid cocrystal according to claim 1 or an agricultural formulation according to any one of claims 5 to 6 for controlling pests.
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| CN113999181A (en) * | 2021-12-08 | 2022-02-01 | 海利尔药业集团股份有限公司 | Eutectic crystal of tebuconazole and organic acid and preparation method and application thereof |
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