CN109879866A - A kind of preparation and application of the pyrazoles oxime derivatives of the sulfenyl of biphenyl containing oxazole structure - Google Patents
A kind of preparation and application of the pyrazoles oxime derivatives of the sulfenyl of biphenyl containing oxazole structure Download PDFInfo
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- CN109879866A CN109879866A CN201910107981.2A CN201910107981A CN109879866A CN 109879866 A CN109879866 A CN 109879866A CN 201910107981 A CN201910107981 A CN 201910107981A CN 109879866 A CN109879866 A CN 109879866A
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- sulfenyl
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Abstract
The present invention relates to the preparations and application of a kind of pyrazoles oxime derivatives (I) of the sulfenyl of biphenyl containing oxazole structure.It is condensed to yield with 2- substituted-phenyl -4- [(phenylsulfartyl) methyl] oxazoline compound (II) with pyrazoles oxime (III).The pyrazoles oxime derivatives of the sulfenyl of biphenyl containing the oxazole structure have effective control efficiency to harmful insect, which is used to prepare the insecticide in the fields such as agricultural, gardening.
Description
Technical field
The present invention relates to chemical pesticide fields, and in particular to a kind of pyrazoles oxime derivatives of the sulfenyl of biphenyl containing oxazole structure
Preparation and application.
Background technique
Prevention and treatment and inhibition insect pest are the core contents of pesticide science research field.Various types of insecticides are widely used
Insect pest is set to be constantly in controllable state.But the scale used with insecticide constantly expands and uses the gradually increasing of time
Long, pest starts to develop drug resistance to traditional pesticide gradually or even cross-resistance.In addition as new insect pest constantly goes out
It is existing, so that the research and development that continues of novel pesticide becomes inevitable choice.
Nitrogen-containing heterocycle compound is widely used in terms of agricultural production, and pyrazoles oxime compound is as a kind of important nitrogenous
Heterocyclic compound has excellent desinsection, mite killing isoreactivity, and wherein typicalness compound has fenpyroximate, in killing for pesticide field
It plays an important role in terms of worm.
In recent years, there are some researchs to report pyrazoles oxime derivatives and show good insecticidal action.Such as Dai synthesis
The pyrazoles oxime compound A and B containing 1,3,4- thiadiazoles heterocycle structures to show excellent desinsection to aphid, diamondback moth etc. living
Property, when proof load is 100 μ g/mL, compound A and B is 100% to the killing activity of aphid；Compound A and B are to small
The killing rate of diamond-back moth are respectively 60% and 100% (Bioorg.Med.Chem.Lett.2016,26,3818-3821).
Disliking azole compounds is also a kind of important nitrogen-containing heterocycle compound, has excellent bioactivity, in pesticide side
Face has a wide range of applications.
Therefore, in order to further find the compound with excellent bioactivity from pyrazoles oxime derivatives, using work
Property group joining method, reasonably substituted oxazoline group is engaged togather with pyrazoles oxime skeleton, the invention discloses one kind have
There are the pyrazoles oxime derivatives of the sulfenyl structure of biphenyl containing oxazole of agricultural insecticidal application value.
Summary of the invention
It is and efficient, safe, environmental-friendly the object of the present invention is to provide there is excellent control efficiency for various pests
The pyrazoles oxime derivatives of one kind sulfenyl structure of biphenyl containing oxazole, to meet crop protection to efficient pesticides demand.
It is a further object of the present invention to provide the preparation methods of above compound.
A further object of the present invention is to provide purposes of the above compound in terms of preparing insecticide.
In order to solve the above technical problems, the first aspect of the present invention provides a kind of pyrazoles oxime of the sulfenyl of biphenyl containing oxazole structure
Analog derivative, with general formula I,
Preferably, the pyrazoles oxime derivatives of the sulfenyl of biphenyl containing oxazole structure have the following structure:
The present invention provides the preparation method of the pyrazoles oxime derivatives of the above-mentioned sulfenyl of biphenyl containing oxazole structure, it is characterised in that
Include the following steps:
Compound III is dissolved in organic solvent, acid binding agent is added, then intermediate II, finally heated one section of reaction is being added
Time filters after being cooled to room temperature reaction solution, and mother liquor is concentrated under reduced pressure, and gained residue obtains target through column chromatographic isolation and purification
Compound,
Wherein, R1:CF3；F；Cl；CH3；R2:Cl；OCH3；Br；F；H.
Preferably, the acid binding agent is selected from potassium carbonate, 4-dimethylaminopyridine (DMAP), sodium carbonate, sodium bicarbonate, carbonic acid
Caesium；The organic solvent is selected from n,N-Dimethylformamide (DMF), acetone, acetonitrile, dimethyl sulfoxide (DMSO), N, N- diformazan
Yl acetamide (DMA).Heating reaction temperature is 35 DEG C~120 DEG C, and the reaction time is 12 hours~28 hours.
Preferably, the preparation method of the pyrazoles oxime derivatives of the sulfenyl of biphenyl containing oxazole structure, includes the following steps:
Wherein, intermediate 2- substituted-phenyl -4- [(phenylsulfartyl) methyl] oxazoline compound can refer to document
(Chin.Chem.Lett.2014,25,1014-1016) method synthesizes to obtain；The synthesis reference literature report of intermediate pyrazole oxime
The conventional method (Bioorg.Med.Chem.Lett.2016,26,4504-4507) in road.
Compound of Formula I has excellent prevention and treatment activity to insect, thus the compound of the present invention can be used as preparing desinsection
Agent, and then protect the plants such as agricultural, gardening.The insect include lepidoptera pest for example bollworm, beet armyworm, diamondback moth,
Cabbage caterpillar, rice leaf roller and striped rice borer etc.；Homoptera pest such as leafhopper, plant hopper, earthworm worm, aleyrodid, the scale insect of Psyllidae etc.；
Diptera pest such as housefly, Liriomyza, mosquito class etc.；The locust etc. of Orthoptera, longicorn, chafer, weevil, bean weevil of coleoptera etc.
Pest etc.；The stinkbug etc. of Semiptera.Certainly, the harmful organism that the compound of the present invention can prevent and treat is not limited to the range of the example above.
When the compound of the present invention indicated by general formula I is used as the insecticide in the fields such as agricultural, gardening, can individually make
With, or used in a manner of Pesticidal combination, such as using Formulas I as active constituent, in addition insecticides adjuvant commonly used in the art is processed into
Aqueous emulsion, suspending agent, water dispersion granule, missible oil etc..
Common insecticides adjuvant includes: liquid-carrier, such as water；Organic solvent such as toluene, dimethylbenzene, cyclohexanol, methanol, fourth
Alcohol, ethylene glycol, acetone, dimethylformamide, acetic acid, dimethyl sulfoxide, animal and plant oil and fatty acid；Common surface agent is such as
Emulsifier and dispersing agent, including anionic surfactant, cationic surfactant, nonionic surfactant and both sexes table
Face activating agent；Other auxiliary agents, such as wetting agent, thickener.
When being used as the active constituent in insecticide by the compound of the present invention that general formula I is indicated, in the insecticide
Content is selected in the range of 0.1% to 99.5%, and can determine activity appropriate according to dosage form and method of administration
Component content.In general, preferably it contains containing active constituent described in 5% to 50% (weight percent, similarly hereinafter) in aqueous emulsion
Amount is 10% to 40%；In suspending agent containing 5% to 50% active constituent, preferably its content be 5% to 40%.
Common application method may be selected in use for insecticide of the invention, as cauline leaf is spraying, used for ponds, native
Earth processing and seed treatment etc..For example, when spraying using cauline leaf, the compound indicated by general formula I as active constituent
Can be used concentration range be 1 to 1000 μ g/mL aqueous emulsion, suspending agent, water dispersion granule, missible oil, preferably its concentration be 1 to
500μg/mL。
The pyrazoles oxime derivatives of the sulfenyl of biphenyl containing oxazole structure disclosed by the invention prevent harmful insect with excellent
Effect is controlled, therefore can be used to prepare the insecticide for fields such as agricultural, gardening.
Specific embodiment
Above scheme is described further below in conjunction with specific embodiment.It should be understood that these embodiments are for illustrating
The present invention and be not limited to limit the scope of the invention.Implementation condition used in the examples can be done according to the condition of specific producer
Further adjustment, the implementation condition being not specified is usually the condition in routine experiment.
Embodiment 1:
5mmol compound III a is dissolved in 30mL DMF, 6mmol potassium carbonate is then added, is added thereto under room temperature
Intermediate II a 5mmol, finishes, and is heated to 120 DEG C, reacts 20 hours.Reaction solution is cooled to room temperature, is filtered, mother liquor decompression
Concentration, gained residue obtain target compound Ia through column chromatographic isolation and purification；1H NMR(400MHz,CDCl3): δ 8.13 (d, J=
8.4Hz, 2H, Ar-H), 7.78 (s, 1H, CH=N), 7.70 (d, J=8.4Hz, 2H, Ar-H), 7.50 (s, 1H, Oxazole-
), H 7.32 (d, J=8.4Hz, 2H, Ar-H), 7.25 (d, J=7.6Hz, 2H, Ar-H), 7.18 (d, J=8.0Hz, 2H, Ar-
), H 6.81 (d, J=9.2Hz, 2H, Ar-H), 4.93 (s, 2H, CH2),4.09(s,2H,CH2),3.60(s,3H,CH3),2.34
(s,3H,CH3).
Embodiment 2:
6mmol compound III b is dissolved in 25mL acetone, 12mmol 4-dimethylaminopyridine (DMAP) then is added, room temperature
Under the conditions of intermediate II b 5mmol is added thereto, finish, be warming up to 35 DEG C, react 16 hours.Reaction solution is cooled to room
Temperature filters, and mother liquor is concentrated under reduced pressure, and gained residue obtains target compound Ib through column chromatographic isolation and purification；1H NMR(400MHz,
CDCl3): δ 7.98~8.02 (m, 2H, Ar-H), 7.77 (s, 1H, CH=N), 7.43 (s, 1H, Oxazole-H), 7.31 (d, J
=8.0Hz, 2H, Ar-H), 7.21 (d, J=8.0Hz, 2H, Ar-H), 7.11 (d, J=8.8Hz, 2H, Ar-H), 6.81 (s, 4H,
Ar-H),4.96(s,2H,CH2),4.06(s,2H,CH2),3.77(s,3H,OCH3),3.60(s,3H,CH3),2.34(s,3H,
CH3).
Embodiment 3:
4mmol compound III c is dissolved in 30mL acetonitrile, 10mmol sodium carbonate is then added, is added thereto under room temperature
Enter intermediate II b 6mmol, finish, temperature rising reflux, reacts 18 hours.Reaction solution is cooled to room temperature, is filtered, mother liquor decompression is dense
Contracting, gained residue obtain target compound Ic through column chromatographic isolation and purification；1H NMR(400MHz,CDCl3): δ 7.99~8.03
(m, 2H, Ar-H), 7.79 (s, 1H, CH=N), 7.44 (s, 1H, Oxazole-H), 7.31 (d, J=8.4Hz, 2H, Ar-H),
6.78~7.24 (m, 8H, Ar-H), 4.93 (s, 2H, CH2),4.07(s,2H,CH2),3.60(s,3H,CH3),2.35(s,3H,
CH3).
Embodiment 4:
5mmol compound III d is dissolved in 30mL DMSO, under room temperature thereto be added 13mmol intermediate II c and
20mmol sodium bicarbonate, finishes, and is warming up to 100 DEG C, reacts 15 hours.Stop reaction, by reaction solution vacuum rotary steam to dry, gained
Residue obtains target compound Id through column chromatographic isolation and purification；1H NMR(400MHz,CDCl3): δ 7.94 (d, J=8.4Hz, 2H,
), Ar-H 7.78 (s, 1H, CH=N), 7.45 (s, 1H, Oxazole-H), 7.41 (d, J=8.8Hz, 2H, Ar-H), 7.31 (d, J
=8.4Hz, 2H, Ar-H), 7.19 (d, J=8.4Hz, 2H, Ar-H), 6.81~7.00 (m, 4H, Ar-H), 4.93 (s, 2H,
CH2),4.06(s,2H,CH2),3.60(s,3H,CH3),2.34(s,3H,CH3).
Embodiment 5:
5mmol compound III e is dissolved in 30mL acetonitrile, under room temperature thereto be added 6mmol intermediate II c and
12mmol potassium carbonate, finishes, temperature rising reflux, reacts 12 hours.Stop reaction, by reaction solution vacuum rotary steam to dry, gained remnants
Object obtains target compound Ie through column chromatographic isolation and purification；1H NMR(400MHz,CDCl3): δ 7.94 (d, J=8.4Hz, 2H, Ar-
), H 7.79 (s, 1H, CH=N), 7.44 (s, 1H, Oxazole-H), 7.42 (d, J=8.8Hz, 2H, Ar-H), 7.28~7.32
(m, 4H, Ar-H), 7.20 (d, J=8.4Hz, 2H, Ar-H), 7.07~7.11 (m, 1H, Ar-H), 6.87 (d, J=8.8Hz,
2H,Ar-H),4.94(s,2H,CH2),4.06(s,2H,CH2),3.59(s,3H,CH3),2.36(s,3H,CH3).
Embodiment 6:
4mmol compound III d is dissolved in 30mL DMA, under room temperature thereto be added 5mmol intermediate II d and
8mmol cesium carbonate, finishes, and is stirred at room temperature, and reacts 28 hours.Stop reaction, by reaction solution vacuum rotary steam to dry, gained residue
Target compound If is obtained through column chromatographic isolation and purification；δ 7.90 (d, J=8.0Hz, 2H, Ar-H), 7.78 (s, 1H, CH=N),
7.43 (s, 1H, Oxazole-H), 7.31 (d, J=8.8Hz, 2H, Ar-H), 7.18~7.26 (m, 4H, Ar-H), 6.81~
7.00(m,4H,Ar-H),4.93(s,2H,CH2),4.07(s,2H,CH2),3.60(s,3H,CH3),2.39(s,3H,CH3),
2.34(s,3H,CH3).
Embodiment 7:
Sample screens the insecticidal activity of mythimna separata
The leaf dipping method for using international resistance Action Committee (IRAC) to propose: for examination target for mythimna separata, i.e., by appropriate corn
Leaf dries in the shade naturally after sufficiently infiltrating in the medical fluid prepared, is put into the culture dish for being lined with filter paper, connects mythimna separata 3 age mid-term larva 10
Head/ware is placed in 24-27 DEG C of observation ward and cultivates, investigation result after 3d.Polypide is touched with writing brush, it is reactionless to be considered as dead worm.Test
500 μ g/mL of concentration.
Embodiment 8:
Sample screens the insecticidal activity of aphid
The spray-on process for using international resistance Action Committee (IRAC) to propose: for examination target for aphid, i.e., aphid will be connected to
Broad Bean Leaves under Potter spray tower spraying treatment, aphid is placed in 20-22 DEG C of observation ward and cultivates after processing, adjusts after 48h
Come to an end fruit.Polypide is touched with writing brush, it is reactionless to be considered as dead worm.500 μ g/mL of experimental concentration.
Insecticidal activity test result shows that all compounds all show preferable insecticidal activity.It is 500 in test concentrations
When μ g/mL (table 1), the f of chemical compounds I a~I is 100% to the killing effect of mythimna separata；The f of chemical compounds I a~I is living to the desinsection of aphid
Property is up to 100%.
The preliminary insecticidal activity data of table 1.Ia-If
The above experimental data shows reasonably to splice oxazole heterocycle structure and pyrazoles oxime skeleton, and what is obtained is novel
Compound shows that good biological activity, these experimental datas are also to continue to be engaged in novel pyrazole oxime derivatives from now on simultaneously
Molecule synthesis and bioactivity research provide important structure choice mode and theoretical foundation.
The basic principles, main features and advantages of the present invention have been shown and described above.The technology of the industry
Personnel only illustrate the present invention it should be appreciated that the present invention is not limited by examples detailed above described in examples detailed above and specification
Principle, various changes and improvements may be made to the invention without departing from the spirit and scope of the present invention, these variation and
Improvement all fall within the protetion scope of the claimed invention.The claimed scope of the invention is by appended claims and its is equal
Object defines.
Claims (4)
1. a kind of pyrazoles oxime derivatives (I) of the sulfenyl of biphenyl containing oxazole structure, it is characterised in that structure are as follows:
2. a kind of preparation method of the pyrazoles oxime derivatives of the sulfenyl of biphenyl containing oxazole structure as described in claim 1, feature
It is that method is as follows:
3. the pyrazoles oxime derivatives I of the sulfenyl of biphenyl containing oxazole structure is in terms of preparing insecticide as described in claim 1
Purposes, it is characterised in that: the compound is used alone；Or using compound I in claim 1 as active constituent, in addition this field
Common insecticides adjuvant be processed into aqueous emulsion, suspending agent, water dispersion granule, missible oil the mode of Pesticidal combination use.
4. the pyrazoles oxime derivatives I of the sulfenyl of biphenyl containing oxazole structure is in terms of preparing insecticide as claimed in claim 3
Purposes, it is characterised in that: when compound I is used as the active constituent of insecticide, content in the insecticide can 0.1% to
It is selected in the range of 99.5%.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01197471A (en) * | 1988-02-02 | 1989-08-09 | Nissan Chem Ind Ltd | Pyrazole oxime derivative and insecticide, acaricide and germicide |
| CN104892591A (en) * | 2015-04-09 | 2015-09-09 | 南通大学 | Preparation method of pyrazole oxime compound containing 3-aryl-1,2,4-oxdiazole heterocycle structure and application thereof |
| CN105693710A (en) * | 2016-03-07 | 2016-06-22 | 南通大学 | Preparation and application of pyrazole oxime ether compound with 5-(4-fluorophenyl) isoxazole structure |
-
2019
- 2019-02-02 CN CN201910107981.2A patent/CN109879866B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01197471A (en) * | 1988-02-02 | 1989-08-09 | Nissan Chem Ind Ltd | Pyrazole oxime derivative and insecticide, acaricide and germicide |
| CN104892591A (en) * | 2015-04-09 | 2015-09-09 | 南通大学 | Preparation method of pyrazole oxime compound containing 3-aryl-1,2,4-oxdiazole heterocycle structure and application thereof |
| CN105693710A (en) * | 2016-03-07 | 2016-06-22 | 南通大学 | Preparation and application of pyrazole oxime ether compound with 5-(4-fluorophenyl) isoxazole structure |
Non-Patent Citations (3)
| Title |
|---|
| CUILI CHEN ET AL.: ""Design, Synthesis, and Biological Activities of Novel Pyrazole Oxime Compounds Containing a Substituted Pyridyl Moiety"", 《MOLECULES》 * |
| 周家华等: ""新型含噁唑环结构的氰基丙烯酸酯类衍生物的合成及其生物活性研究"", 《CHIN.J.ORG.CHEM.》 * |
| 戴红等: ""新型含取代噁二唑结构的吡唑肟类化合物的合成与生物活性研究"", 《CHIN.J.ORG.CHEM》 * |
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