CN108822082B - Fluorine-containing pyridine piperazine amide compound and application thereof - Google Patents
Fluorine-containing pyridine piperazine amide compound and application thereof Download PDFInfo
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- CN108822082B CN108822082B CN201810587086.0A CN201810587086A CN108822082B CN 108822082 B CN108822082 B CN 108822082B CN 201810587086 A CN201810587086 A CN 201810587086A CN 108822082 B CN108822082 B CN 108822082B
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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
- C07D401/02—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 two hetero rings
- C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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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
- A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
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- 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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Abstract
The invention provides a fluorine-containing pyridine piperazine amide compound, which has a structure shown as a general formula I:
Description
Technical Field
The invention belongs to the field of acaricides in pesticides, and particularly relates to a fluorine-containing pyridine piperazine amide compound and application thereof.
Background
Mites destroy the normal physiological functions of plants, so that the yield of crops is reduced, the crops grow normally, and various acaricides for preventing mite damage are provided, such as fenisobromolate, abamectin, spirodiclofen, fenpyroximate and the like. The spirodiclofen has good killing effect on mites, but with the use of a large amount of pesticides, the drug resistance of the mites to the pesticides is enhanced. 2, 3-dichloro-5- (trifluoromethyl) pyridine is a fluorine-containing organic intermediate with high activity and low toxicity, and is also a key intermediate of a plurality of high-efficiency insecticides, acaricides and bactericides. Such as pyridalyl, fluazinam, and fluopyram, and the like. Piperazine has excellent bioactivity and is widely applied to pesticides. In the prior art, the compound shown in the general formula I and the application thereof as the acaricide for agriculture and forestry are not reported.
Disclosure of Invention
The invention aims to provide a fluorine-containing pyridine piperazine amide compound with a novel structure, which is used as an efficient and safe acaricide for preventing and treating agricultural and forestry acarids.
The technical scheme of the invention is as follows:
the invention provides a fluorine-containing pyridine piperazine compound, which is shown as a general formula I:
wherein R is: C1-C5 alkyl, C1-C4 alkoxy, substituted phenyl and heterocyclic aryl.
The compounds of formula I can be prepared by the following reaction:
wherein each group is as defined above.
And reacting the compound III and the compound II in ethyl acetate or dichloromethane by taking triethylamine as an acid-binding agent to obtain the compound shown in the formula I. Specific preparations of intermediate III and compounds of formula I are described in the examples of the invention.
Table 1 shows the structure and physical properties of some of the compounds of formula I.
Table 1 structural and physical properties of some of the compounds of formula I
The compound of the invention shows higher activity to mite eggs, so the invention also comprises the application of the compound of the formula I in preventing and controlling the mite damage in agriculture and forestry.
The invention has the advantages and positive effects that:
as the resistance of mites to traditional acaricides is continuously enhanced, the efficacy of the existing acaricides is less and less obvious, the invention takes piperazine as bridging and combines fluorine-containing pyridine and acyl chloride or carboxylic acid components into amide, thus designing a novel acaricide. The compound of the invention avoids the problem of high drug resistance of mites, has unexpected excellent acaricidal activity (see the biological activity determination example of the invention), and has the characteristics of low dosage, low toxicity and high drug effect. The compound of the invention has good biodegradability, safe use and little environmental pollution. In addition, the compound shown in the formula I has the advantages of simple synthesis process and low production cost, and has the industrialization prospect of being used as a new variety of creative acaricides.
When the compound is used for preventing and controlling mites, the compound can be used alone or combined with other active substances according to actual needs so as to provide comprehensive performance of products.
The invention also comprises a miticidal composition containing the compound shown in the formula I as an active ingredient, wherein the weight percentage of the active composition in the miticidal composition is 1-99%. The acaricidal composition also comprises a forestry and agricultural acceptable carrier.
The compositions of the invention may be used in the form of formulations: the compound of formula I as active component is dissolved or dispersed in carrier or solvent, and is added with proper amount of surfactant to prepare missible oil, suspending agent, microemulsion, etc.
It should be understood that various changes and modifications may be made within the scope of the present invention as defined by the claims.
Detailed Description
The following synthetic examples and results of the biological tests are provided to further illustrate the invention and are not meant to limit the invention.
Synthesis examples:
example 1 preparation of intermediate III
Adding 17.2g (0.2mol) of anhydrous piperazine and 60mL of methanol into a 250mL reaction bottle, stirring for dissolving, heating to 40 ℃, then diluting 21.6g (0.1mol) of 2, 3-dichloro-5- (trifluoromethyl) pyridine with 50mL of methanol, slowly dripping, reacting at constant temperature of 40 ℃ for 6h after dripping, tracking by TLC until the raw materials are completely reacted, cooling to room temperature, carrying out suction filtration, carrying out vacuum rotary evaporation on filtrate to remove methanol, separating out white solid, adding water, stirring and dissolving the residual anhydrous piperazine, carrying out suction filtration, washing a filter cake with water, obtaining 22.6g of white solid, wherein the melting point is 65.8-67.3 ℃, and the yield is 85%.
1H NMR(500MHz,DMSO-d6),(ppm)8.53(s,1H),8.15(s,1H),3.37–3.35(t,4H),2.82–2.80(t,4H).
Example 2 Compound I1Preparation of
Adding 5.3g (0.02mol) of the intermediate III into a 250mL reaction bottle, then adding 35mL of ethyl acetate, adding 2.22g of triethylamine, dropwise adding a mixed solution of 10mL of ethyl acetate and 3.45g (0.02mol) of 3-ethyl-1-methyl-1H-pyrazole-5-formyl chloride under stirring, reacting at room temperature for 30min after dropwise adding, tracking the completion of the reaction of the intermediate III by TLC, adding 100mL of water, stirring, separating, drying an organic phase by using anhydrous sodium sulfate, removing the ethyl acetate by rotary evaporation, and cooling to obtain 7.3g of a white solid, wherein the melting point is 103.0-105.1 ℃, and the yield is 91%.
1H NMR(500MHz,DMSO-d6)(ppm)8.56(s,1H),8.23(s,1H),6.38(s,1H),3.97(s,2H),3.82(s,3H),3.58–3.44(m,6H),2.57–2.51(m,2H),1.24–1.21(t,3H).
According to I in example 21Synthesis of other Compounds I2-I13Compounds, their hydrogen spectrum nuclear magnetic data are as follows:
I2a compound:1H NMR(500MHz,DMSO-d6)(ppm)8.56(s,1H),8.23(s,1H),3.79(s,2H),3.74(s,3H),3.56–3.46(m,6H),2.56–2.50(m,2H),1.17–1.14(t,3H).
I3a compound:1H NMR(500MHz,DMSO-d6)(ppm)8.59(s,1H),8.25(s,1H),6.26(s,1H),4.12–4.08(m,2H),3.78–3.66(d,4H),3.52–3.48(d,4H),2.18(d,3H),1.31–1.28(m,3H).
I4a compound:1H NMR(500MHz,DMSO-d6)(ppm)8.59(s,1H),8.26(s,1H),4.06(s,2H),3.85–3.79(d,2H),3.51–3.42(d,6H),2.16(s,3H),1.31–1.29(t,3H).
I5a compound:1H NMR(500MHz,DMSO-d6)(ppm)8.58(s,1H),8.23(s,1H),7.73–7.72(t,1H),7.54(d,2H),3.77(s,2H),3.60–3.42(m,6H).
I6a compound:1H NMR(500MHz,DMSO-d6)(ppm)8.57(s,1H),8.22(s,1H),7.47(d,Hz,2H),7.39(d,Hz,2H),3.76–3.60(m,8H),1.30(s,9H).
I7a compound:1H NMR(500MHz,DMSO-d6)(ppm)8.59(s,1H),8.25(s,1H),3.87–3.82(m,2H),3.56–3.52(m,4H),3.46–3.40(m,2H).
I8compound (I)：1H NMR(500MHz,DMSO-d6)(ppm)8.58(s,1H),8.24(s,1H),7.84–7.83(d,1H),7.79–7.76(t,1H),7.69–7.66(t,1H),7.56–7.55(d,1H),3.87–3.73(m,2H),3.63–3.39(m,4H),3.30–3.19(m,2H).
I9A compound:1H NMR(500MHz,DMSO-d6)(ppm)8.56(s,1H),8.21(s,1H),3.58–3.56(dd,4H),3.47–3.45(t,2H),3.40–3.38(t,2H),2.02(s,3H).
I10a compound:1H NMR(500MHz,DMSO-d6)(ppm)8.56(s,1H),8.21(s,1H),3.71–3.69(dd,3.4Hz,4H),3.45–3.43(dd,3.5Hz,4H),1.63–1.59(m,2H),1.17(s,6H),0.82–0.79(t,3H).
I11a compound:1H NMR(500MHz,DMSO-d6)(ppm)8.54(s,1H),8.20(s,1H),3.97–3.94(t,2H),3.52–3.50(dd,4H),3.42–3.40(dd,4H),1.61–1.57(m,2H),0.89–0.86(t,3H).
I12a compound:1H NMR(500MHz,DMSO-d6)(ppm)8.55(s,1H),8.20(s,1H),4.01(t,2H),3.51(t,4H),3.45–3.40(m,4H),1.59–1.50(m,2H),1.37–1.30(m,2H),0.88(t,3H).
I13a compound:1H NMR(500MHz,DMSO-d6)(ppm)8.56(s,1H),8.22(s,1H),7.81–7.70(m,1H),7.47–7.46(d,1H),7.14–7.12(dd,1H),3.81–3.79(t,4H),3.54–3.52(dd,4H).
biological activity assay
Example 3 acaricidal Activity assay
The acarid killing activity is measured by adopting an immersion method and a method for statistically correcting the mortality of pests. The specific process is as follows: the test reagents are respectively diluted to required concentration according to effective components, 50mL of liquid medicine is respectively absorbed under aseptic condition and injected into a culture dish, and then the test reagents are respectively immersed into the leaves of cinnabar mite eggs (a group in which the mite eggs are normally raised according to an indoor standardized method), and a flat plate added with 50mL of sterilized water is used as a blank control. The petri dish was placed in a 24 + -1 deg.C incubator. And after 48h, investigating and counting the mortality.
Table 1 acaricidal Activity test results for series of Compounds
According to the test results, the compound of the invention has excellent acaricidal activity, and the compound I of the invention has the same dosage1～I13The acaricidal activity in (A) is generally higher than that of spirodiclofen, especially I1、I2、I4、I6、I7、I12The killing rate of the acaricidal ova at 1ppm is more than 90 percent, which is obviously higher than that of the spirodiclofen serving as a contrast agent. Wherein the compound I12The activity of the acaricide is the highest, and the killing rate of the acarid egg still reaches 96% at 1 ppm.
It should be noted that, only a few embodiments are mentioned in the present invention, the present invention is not limited to the above embodiments, and other similar inventions are within the scope of protection of this patent.
Claims (3)
1. An agricultural acaricide fluorine-containing pyridine piperazine amide compound has a structure shown in a formula I:
2. the use of the fluorine-containing pyridine piperazine amide compound as claimed in claim 1, wherein the compound of formula I is used as acaricide for preventing and treating agricultural or forestry pest mites.
3. A miticidal composition comprising a compound of formula I according to claim 1 as active ingredient and an agriculturally acceptable carrier.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011072174A1 (en) * | 2009-12-09 | 2011-06-16 | Agios Pharmaceuticals, Inc. | Therapeutically active compounds for use in the treatment of cancer characterized as having an idh mutation |
| US20130072497A1 (en) * | 2005-06-30 | 2013-03-21 | Dow Agrosciences Llc | N- substituted piperazines |
| CN104418800A (en) * | 2013-09-06 | 2015-03-18 | 中国中化股份有限公司 | Aryl pyridine/pyrimidine compound and application thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130072497A1 (en) * | 2005-06-30 | 2013-03-21 | Dow Agrosciences Llc | N- substituted piperazines |
| WO2011072174A1 (en) * | 2009-12-09 | 2011-06-16 | Agios Pharmaceuticals, Inc. | Therapeutically active compounds for use in the treatment of cancer characterized as having an idh mutation |
| CN104418800A (en) * | 2013-09-06 | 2015-03-18 | 中国中化股份有限公司 | Aryl pyridine/pyrimidine compound and application thereof |
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