CN110128409B - Preparation and application of difluoromethylpyrazole oxime derivative containing pyridine bipyrazole structure - Google Patents
Preparation and application of difluoromethylpyrazole oxime derivative containing pyridine bipyrazole structure Download PDFInfo
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- CN110128409B CN110128409B CN201910361413.5A CN201910361413A CN110128409B CN 110128409 B CN110128409 B CN 110128409B CN 201910361413 A CN201910361413 A CN 201910361413A CN 110128409 B CN110128409 B CN 110128409B
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- difluoromethylpyrazole
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
Abstract
The invention relates to a preparation method and application of difluoromethylpyrazole oxime derivative (I) containing a pyridine bipyrazole structure. Obtained by condensing pyridine dipyrazolyl formyl chloride (II) and difluoromethyl pyrazole oxime (III). The difluoromethylpyrazole oxime derivative containing the pyridine bipyrazole structure has an effective control effect on harmful insects, and can be used for preparing pesticides in the fields of agriculture, horticulture and the like.
Description
Technical Field
The invention relates to the field of chemical pesticides, and particularly relates to preparation and application of a difluoromethylpyrazole oxime derivative containing a pyridine bipyrazole structure.
Background
The prevention and control of pests are always the core field of pesticide science research, and the wide use of pesticides enables most pests to be effectively treated. However, with the continuous expansion of the application scale of the pesticide, the problem of drug resistance of the traditional pesticide varieties becomes more and more prominent, and the continuous research and development of new pesticides become necessary choices due to the continuous emergence of new plant diseases and insect pests.
Pyrazole oximes have wide application in the field of pesticides, wherein the representative compounds are fenpyroximate:
the pyrazole ring is a common active fragment in drug molecules and pesticide molecules, can effectively change the physicochemical properties of the compound, and the compound containing the pyrazole ring has stronger physiological activity in organisms.
Therefore, in order to further search compounds with excellent biological activity from pyrazole oxime derivatives, the invention discloses a difluoromethyl pyrazole oxime derivative containing a pyridine bipyrazole structure, which has agricultural insecticidal application value, by adopting an active group splicing method and reasonably connecting a pyrazole group and a pyrazole oxime skeleton together.
Disclosure of Invention
The invention aims to provide a difluoromethylpyrazole oxime derivative containing a pyridine bipyrazole structure, which has an excellent control effect on various pests, is efficient, safe and environment-friendly, and meets the requirement of crop protection on efficient pesticides.
It is a further object of the present invention to provide the use of the above compounds in the preparation of insecticides.
Another object of the present invention is to provide a process for the preparation of the above compounds.
In order to solve the technical problems, the invention provides a difluoromethylpyrazole oxime derivative containing a pyridine bipyrazole structure, which has a structure shown in a general formula I,
preferably, the difluoromethylpyrazole oxime derivative containing a pyridine bipyrazole structure has the following structure:
the second aspect of the present invention provides a preparation method of the difluoromethylpyrazole oxime derivative containing a pyridine bipyrazole structure, which comprises the following steps:
dissolving a compound III in an organic solvent, adding an acid-binding agent, adding a mixed solution of an intermediate II and a small amount of solvent, finally reacting for a period of time, concentrating the mother liquor under reduced pressure, separating and purifying the obtained residue to obtain a target compound,
preferably, the acid-binding agent is selected from triethylamine, pyridine, sodium acetate and sodium bicarbonate, the solvent is selected from N, N-Dimethylformamide (DMF), dichloromethane, trichloromethane, acetonitrile and Tetrahydrofuran (THF), the reaction temperature is 0-90 ℃, and the reaction time is 8-26 hours.
Preferably, the difluoromethylpyrazole oxime derivative containing the pyridine bipyrazole structure is prepared by the following method:
wherein, the synthesis of the intermediate pyridine dipyrazolyl formyl chloride refers to the conventional method reported in the literature (organic chemistry, 2011,31, 1943-; the synthesis of difluoromethylpyrazole oxime intermediates is referred to the conventional methods reported in the literature (J.Agric.food Chem.2008,56, 10805-10810).
The compound of the general formula I has excellent control activity on insects, so that the compound can be used for preparing pesticides to protect plants in agriculture, horticulture and the like. The insects comprise lepidoptera pests such as cotton bollworms, asparagus caterpillars, diamond back moths, cabbage caterpillars, rice leaf rollers, chilo suppressalis and the like; homoptera pests such as leafhopper, plant hopper, vermin, whitefly, coccid of psyllidae, etc.; dipteran pests such as houseflies, leaf miner, mosquitoes, etc.; locusts of the order orthoptera, pests of the order Coleoptera, longicorn beetles, scarab beetles, weevils, and the like; stinkbugs of the order hemiptera, and the like. Of course, the pests which the compounds of the invention can control are not limited to the above exemplified ranges.
When the compound of the invention represented by the general formula I is used as an insecticide in the fields of agriculture, horticulture and the like, the compound can be used alone or in the form of an insecticidal composition, for example, the compound is prepared into an aqueous emulsion, a suspending agent, a water dispersible granule, an emulsion and the like by taking the formula I as an active ingredient and adding pesticide auxiliaries commonly used in the field.
Commonly used pesticide adjuvants include liquid carriers such as water; organic solvents such as toluene, xylene, cyclohexanol, methanol, butanol, ethylene glycol, acetone, dimethylformamide, acetic acid, dimethyl sulfoxide, animal and vegetable oils and fatty acids; common surfactants such as emulsifiers and dispersants, including anionic surfactants, cationic surfactants, nonionic surfactants, and amphoteric surfactants; other adjuvants, such as wetting agents, thickeners, and the like.
When the compound of the present invention represented by the general formula I is used as an active ingredient in an insecticide, the content in the insecticide is selected in the range of 0.1% to 99.5%, and an appropriate content of the active ingredient may be determined according to the formulation form and the application method. In general, the aqueous emulsion contains 5% to 50% (by weight, the same applies hereinafter) of the active ingredient, preferably 10% to 40%; the suspension concentrate contains 5% to 50% of active ingredient, preferably 5% to 40%.
For the use of the insecticide of the present invention, a commonly used application method such as stem and leaf spraying, water surface application, soil treatment, seed treatment, and the like can be selected. For example, when spray application from stems and leaves is employed, the compounds represented by the general formula I as active ingredients can be used in the form of aqueous emulsions, suspensions, water-dispersible granules, emulsifiable concentrates in the concentration range of 1 to 1000. mu.g/mL, preferably in the concentration range of 1 to 500. mu.g/mL.
The difluoromethylpyrazole oxime derivative containing the pyridine bipyrazole structure disclosed by the invention has an excellent control effect on harmful insects, and therefore, can be used for preparing insecticides used in the fields of agriculture, horticulture and the like.
Detailed Description
The above-described scheme is further illustrated below with reference to specific examples. It should be understood that these examples are for illustrative purposes and are not intended to limit the scope of the present invention. The conditions used in the examples may be further adjusted according to the conditions of the particular manufacturer, and the conditions not specified are generally the conditions in routine experiments.
Example 1:
a50 mL round-bottom flask was charged with 4mmol of IIIa, 1mL of triethylamine and 20mL of N, N-Dimethylformamide (DMF), and a mixed solution of 6mmol of IIa and 2mL of DMF was slowly dropped thereinto with stirring in an ice bath. After dropping, the mixture was heated to 90 ℃ and reacted for 8 hours. Evaporating the solvent under reduced pressure, and separating and purifying the residue by column chromatography to obtain a target compound Ia;1H NMR(400MHz,CDCl3)δ:8.54(dd,J1＝4.8Hz,J2＝1.6Hz,1H,Py-H),8.26(s,1H,CH＝N),8.23(s,1H,Pyrazole-H),7.98(dd,J1＝8.4Hz,J2＝1.6Hz,1H,Py-H),7.50～7.53(m,1H,Py-H),7.33(d,J＝9.2Hz,2H,Ar-H),6.78～7.04(m,3H,Ar-H and CHF2),3.78(s,3H,CH3).
example 2:
in a 50mL round bottom flask, 3mmol IIIb, 2mL pyridine and 25mL dichloromethane were added. While stirring in an ice bath, a mixed solution of 4.5mmol of II a and 2mL of methylene chloride was slowly dropped thereinto. After dropping, stirring in ice bath was continued for 12 hours. Evaporating the solvent under reduced pressure, and subjecting the residue to column chromatographySeparating and purifying to obtain a target compound Ib;1H NMR(400MHz,CDCl3)δ:8.51(dd,J1＝4.8Hz,J2＝1.6Hz,1H,Py-H),8.10(s,1H,CH＝N),7.94(dd,J1＝8.0Hz,J2＝1.6Hz,1H,Py-H),7.46～7.49(m,1H,Py-H),7.28(s,1H,Pyrazole-H),7.25(d,J＝9.2Hz,1H,Ar-H),7.13～7.15(m,1H,Ar-H),6.70～6.96(m,3H,Ar-H and CHF2),3.75(s,3H,CH3).
example 3:
in a 100mL round bottom flask, 6mmol IIIc, 12mmol sodium acetate and 30mL chloroform were added. A mixed solution of 8mmol of IIa and 3mL of chloroform was slowly dropped thereinto with stirring at room temperature. After dropping, stirring was continued at room temperature for 26 hours. Evaporating the solvent under reduced pressure, and separating and purifying the residue by column chromatography to obtain a target compound IC;1H NMR(400MHz,CDCl3)δ:8.51(dd,J1＝4.8Hz,J2＝1.6Hz,1H,Py-H),8.02(s,1H,CH＝N),7.94(dd,J1＝8.0Hz,J2＝1.6Hz,1H,Py-H),7.47～7.50(m,1H,Py-H),7.26(s,1H,Pyrazole-H),7.04～7.20(m,3H,Ar-H),6.68～6.99(m,2H,Ar-H and CHF2),3.81(s,3H,CH3).
example 4:
a50 mL round-bottom flask was charged with 3mmol of IIId, 2mL of triethylamine and 20mL of Tetrahydrofuran (THF), and a mixed solution of 4.5mmol of II b and 2mL of THF was slowly dropped thereinto with stirring in an ice bath. After dropping, the ice-bath reaction was continued for 10 hours. Evaporating the solvent under reduced pressure, and separating and purifying the residue by column chromatography to obtain a target compound Id;1H NMR(400MHz,CDCl3)δ:8.51(dd,J1＝4.8Hz,J2＝1.6Hz,1H,Py-H),8.08(s,1H,CH＝N),7.93(dd,J1＝8.0Hz,J2＝1.2Hz,1H,Py-H),7.45～7.48(m,1H,Py-H),7.25(s,1H,Pyrazole-H),6.64～7.04(m,6H,Ar-H and CHF2),3.76(s,3H,CH3).
example 5:
a100 mL round bottom flask was charged with 8mmol IIIe, 16mmol sodium bicarbonate, and 40mL acetonitrile. While stirring in an ice bath, a mixture of 10mmol of II b and 4mL of acetonitrile was slowly dropped thereinto. After dropping, the reaction was heated under reflux for 20 hours. Evaporating the solvent under reduced pressure, and separating and purifying the residue by column chromatography to obtain a target compound ie;1H NMR(400MHz,CDCl3)δ:8.52(dd,J1＝4.8Hz,J2＝1.6Hz,1H,Py-H),8.10(s,1H,CH＝N),7.94(dd,J1＝8.4Hz,J2＝1.6Hz,1H,Py-H),7.62(d,J＝8.8Hz,2H,Ar-H),7.45～7.48(m,1H,Py-H),7.26(s,1H,Pyrazole-H),6.64～6.96(m,4H,Ar-H and CHF2),3.74(s,3H,CH3).
example 6:
insecticidal activity screening of samples against armyworm
The leaf soaking method proposed by the International Resistance Action Committee (IRAC) was adopted: the target for testing is armyworm, namely, a proper amount of corn leaves are fully soaked in prepared liquid medicine and then naturally dried in the shade, the corn leaves are placed into a culture dish filled with filter paper, 10 heads/dish of armyworm larvae in the 3-instar middle stage are connected, the corn leaves are placed into an observation room for culture at 24-27 ℃, and the result is investigated after 2 days. If the body of the insect is touched by a brush pen, no response is regarded as dead insect. The assay concentration was 500. mu.g/mL.
The insecticidal activity test result shows that all the compounds show better armyworm killing activity. At a test dose of 500. mu.g/mL (Table 1), the killing effects of the compounds Ia to ie on armyworm were 100%, 100%, 100%, 100% and 100%, respectively.
TABLE 1 insecticidal Activity data of Ia-Ie
The experimental data show that the pyridine bipyrazole structural unit and the pyrazole oxime active unit are reasonably combined together to obtain the novel compound which shows good biological activity, and the compound can be selected as a pesticidal lead to be used for further research on structural derivation and structure-activity relationship. The experimental data also provide important theoretical basis for continuing to carry out molecular design, synthesis and biological activity research of novel pyrazole oxime compounds in the future.
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited by the foregoing examples, which are provided to illustrate the principles of the invention, and that various changes and modifications may be made without departing from the spirit and scope of the invention, which is also intended to be covered by the appended claims. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (4)
1. A difluoromethylpyrazole oxime derivative (I) containing a pyridine bipyrazole structure is characterized by having a structure as follows:
2. a process for producing difluoromethylpyrazole oxime derivative (I) containing a pyridinebipyrazole structure according to claim 1, characterized by the following:
3. use of difluoromethylpyrazole oxime derivative (I) containing a pyridylpyrazole structure according to claim 1 for the preparation of a pesticidal agent, characterized in that: the compound is used alone; or an insecticidal composition comprising the compound (I) as claimed in claim 1 as an active ingredient, in addition to conventional agricultural adjuvants in the art, in the form of an aqueous emulsion, a suspension, a water-dispersible granule, or an emulsifiable concentrate.
4. Use of difluoromethylpyrazole oxime derivative (I) containing a pyridylpyrazole structure according to claim 3 for the preparation of a pesticidal agent, characterized in that: when the compound (I) according to claim 1 is used as an active ingredient of an anti-mythimnicidal agent, the content in the anti-mythimnicidal agent is selected in the range of 0.1% to 99.5%.
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| CN110305115A (en) * | 2019-08-19 | 2019-10-08 | 南通大学 | The preparation and application of pyrazoles 9 oxime derivate of the one kind containing 1- (6- chloropyrazine -2- base) -3- methoxyl group pyrazoles unit |
| CN110845478B (en) * | 2019-11-25 | 2022-07-08 | 南通大学 | Preparation and use of pyrazole formyloxime derivatives containing 1-substituted pyridyl-3-trifluoromethylpyrazole units |
| CN110804040B (en) * | 2019-11-25 | 2022-04-22 | 南通大学 | Preparation method and application of pyrazole oxime compound containing difluoromethyl pyrazole bipyridyl |
| CN110746356B (en) * | 2019-11-28 | 2021-06-29 | 南通大学 | Preparation method and application of difluoromethyl pyrazole oxime ester containing 3-trifluoromethyl-5-chloropyrazole structure |
| CN110845412B (en) * | 2019-11-28 | 2021-11-23 | 南通大学 | Preparation and application of pyrazole oxime compound containing 1-methyl-3-difluoromethyl-5-chloropyrazole unit |
| CN111518079B (en) * | 2020-06-04 | 2022-07-12 | 南通大学 | Preparation and application of pyrazole derivative containing N-pyridyl-3-pyrazolophenylmethoxypyrazole unit |
| CN111925359B (en) * | 2020-08-31 | 2022-07-12 | 南通大学 | Preparation method and application of pyrazole derivative containing 1, 3-disubstituted pyrazole group |
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