WO2022068816A1 - 一种突烯酰胺类化合物、杀菌剂和应用 - Google Patents

一种突烯酰胺类化合物、杀菌剂和应用 Download PDF

Info

Publication number
WO2022068816A1
WO2022068816A1 PCT/CN2021/121315 CN2021121315W WO2022068816A1 WO 2022068816 A1 WO2022068816 A1 WO 2022068816A1 CN 2021121315 W CN2021121315 W CN 2021121315W WO 2022068816 A1 WO2022068816 A1 WO 2022068816A1
Authority
WO
WIPO (PCT)
Prior art keywords
substituted
alkyl
unsubstituted
independently selected
cyclopropyl
Prior art date
Application number
PCT/CN2021/121315
Other languages
English (en)
French (fr)
Inventor
杨光富
魏阁
朱晓磊
王文杰
张璞
吴耀军
姚凯诚
Original Assignee
江苏中旗科技股份有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 江苏中旗科技股份有限公司 filed Critical 江苏中旗科技股份有限公司
Priority to EP21874476.1A priority Critical patent/EP4223745A4/en
Priority to US18/247,393 priority patent/US20230391728A1/en
Publication of WO2022068816A1 publication Critical patent/WO2022068816A1/zh

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • 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
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C07D231/16—Halogen atoms or nitro radicals

Definitions

  • the invention relates to the field of new pesticide compounds, in particular to a denylamide compound and its application, a fungicide and its application.
  • Succinate dehydrogenase inhibitors (SDHIs, succinate dehydrogenase inhibitors) fungicides act on complex II (also known as succinate dehydrogenase or succinate ubiquinone reductase) on the respiratory electron transport chain of pathogenic bacteria, interfere with Succinate dehydrogenase on the respiratory electron transport chain can inhibit mitochondrial function, prevent it from producing energy, inhibit the growth of pathogenic bacteria, and eventually lead to its death, so as to achieve the purpose of disease prevention and control.
  • complex II also known as succinate dehydrogenase or succinate ubiquinone reductase
  • Succinate dehydrogenase inhibitor fungicides have become the most promising type of fungicides in recent years due to their high efficiency, broad-spectrum bactericidal activity and relatively low resistance risk, and have attracted the attention of major pesticide companies in the world.
  • the purpose of the present invention is to provide a new class of compounds with succinate dehydrogenase inhibitory effect in order to overcome the aforementioned defects in the prior art.
  • a first aspect of the present invention provides a pycnamide compound, the compound has the structure shown in formula (I),
  • X is selected from H, F, Cl;
  • R 1 and R 2 are each independently selected from H, halogen, C 1-6 alkyl; or R 1 and R 2 together with their common carbon atoms form cyclopropyl, cyclopentyl, or cyclohexyl;
  • R 31 , R 32 , R 33 , R 34 and R 35 are each independently selected from H, halogen, substituted or unsubstituted C 1-6 alkyl, C 1-6 alkoxy, cyano, C 1 -6 alkyl-sulfonyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenoxy, substituted or unsubstituted benzyloxy, substituted or unsubstituted C 2-4 alkynyl;
  • R 31 The optional substituents on , R 32 , R 33 , R 34 and R 35 are each independently selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkyl -sulfonyl, phenyl, phenoxy, benzyloxy, C 1-3 alkyl substituted with 1-3 halogens, phenyl substituted with 1-3 halogens, C 2- cyclopropyl substituted at least one of the al
  • R 4 is selected from C 1-4 alkyl, C 1-4 alkoxy, cyano, trifluoromethyl, propynyl;
  • R 51 is selected from C 1-3 alkyl substituted with 1-3 halogens; R 52 is selected from C 1-4 alkyl.
  • R 61 and R 62 are each independently selected from H, F, Cl, Br.
  • the second aspect of the present invention provides the use of the aforementioned compounds as succinate dehydrogenase inhibitors in pesticides.
  • a third aspect of the present invention provides the use of the aforementioned compounds for controlling fungal diseases of plants.
  • the fourth aspect of the present invention provides a bactericide, which contains an auxiliary material and a bactericidal effective amount of an active ingredient selected from at least one of the aforementioned compounds.
  • the fifth aspect of the present invention provides the use of the aforementioned fungicides in controlling fungal diseases of plants.
  • the pycnamide compounds provided by the invention have high inhibitory activity against succinate dehydrogenase, and also have high preventive effect on fungal diseases, especially against wheat powdery mildew, cucumber powdery mildew, wheat scab, rice scab It has excellent control effect against seedling disease, rape sclerotinia, corn small spot, wheat stripe rust, cucumber botrytis, etc.
  • Halogen includes fluorine, chlorine, bromine, and iodine.
  • C 1-6 alkyl group includes alkyl groups with a total number of carbon atoms of 1-6, including straight-chain alkyl groups, branched-chain alkyl groups and cycloalkyl groups, for example, can be 1, 2, 3, 4 in total carbon atoms , 5, 6 straight-chain alkyl, branched-chain alkyl or cycloalkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl cyclopropyl, isopentyl, n-hexyl, cyclopropyl, methylcyclopropyl, ethylcyclopropyl, cyclopentyl, methylcyclopentyl, cyclohexyl and the like.
  • C 1-6 alkoxy includes alkoxy with a total number of carbon atoms of 1-6, including straight-chain alkoxy, branched alkoxy and cycloalkoxy, for example, can be 1, 2, 3, 4, 5, 6 straight-chain alkoxy, branched-chain alkoxy or cycloalkoxy, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butyl Oxy, isobutoxy, tert-butoxy, n-pentyloxy, isopentyloxy, n-hexyloxy, cyclopropoxy, methylcyclopropoxy, ethylcyclopropoxy, cyclopentyloxy , methylcyclopentyloxy, cyclohexyloxy, etc.
  • C 1-6 alkyl-sulfonyl means a group represented by -SO 2 -R 1 , and wherein R 1 is a C 1-6 alkyl group.
  • R 1 is a C 1-6 alkyl group.
  • C 1-3 alkyl-sulfonyl and the like have similar interpretations.
  • Substituted or unsubstituted phenyl group means that there is no limit to the number of specific substituents on the phenyl group, and the phenyl group can be substituted at the position that can be substituted, and it can also be the case of no substituent group, that is, phenyl.
  • substituent group that is, phenyl.
  • C 1-3 alkyl substituted by 1-3 halogens includes alkyl groups with a total number of carbon atoms of 1-3, and 1-3 H atoms on the alkyl group are substituted by halogen, including straight-chain alkyl, Branched alkyl and cycloalkyl, for example, can be straight-chain, branched or cycloalkyl with a total number of carbon atoms of 1, 2, 3, such as methyl substituted with 1-3 halogens, Ethyl substituted with 1-3 halogens, n-propyl substituted with 1-3 halogens, isopropyl substituted with 1-3 halogens, cyclopropyl substituted with 1-3 halogens, and the like.
  • Phenyl substituted with 1-3 halogens includes groups in which 1-3 H atoms on the phenyl group are substituted with halogens.
  • the first aspect of the present invention provides a pycnamide compound, the compound has the structure shown in formula (I),
  • X is selected from H, F, Cl;
  • R 1 and R 2 are each independently selected from H, halogen, C 1-6 alkyl; or R 1 and R 2 together with their common carbon atoms form cyclopropyl, cyclopentyl, or cyclohexyl;
  • R 31 , R 32 , R 33 , R 34 and R 35 are each independently selected from H, halogen, substituted or unsubstituted C 1-6 alkyl, C 1-6 alkoxy, cyano, C 1 -6 alkyl-sulfonyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenoxy, substituted or unsubstituted benzyloxy, substituted or unsubstituted C 2-4 alkynyl;
  • R 31 The optional substituents on , R 32 , R 33 , R 34 and R 35 are each independently selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkyl -sulfonyl, phenyl, phenoxy, benzyloxy, C 1-3 alkyl substituted with 1-3 halogens, phenyl substituted with 1-3 halogens, C 2- cyclopropyl substituted at least one of the al
  • R 4 is selected from C 1-4 alkyl, C 1-4 alkoxy, cyano, trifluoromethyl, propynyl;
  • R 51 is selected from C 1-3 alkyl substituted with 1-3 halogens; R 52 is selected from C 1-4 alkyl.
  • R 61 and R 62 are each independently selected from H, F, Cl, Br.
  • X is selected from H, F.
  • R 1 and R 2 are each independently selected from H, F, Cl, Br, alkyl of C 1-3 ; more preferably, R 1 and R 2 are each independently selected from From H, F, Cl, Br, methyl, ethyl, n-propyl, isopropyl, cyclopropyl; further preferably, R 1 and R 2 are each independently selected from H, methyl, ethyl, n-propyl propyl.
  • R 31 , R 32 , R 33 , R 34 and R 35 are each independently selected from H, halogen, substituted or unsubstituted C 1-4 alkyl, C 1-4 alkoxy, cyano, C 1-3 alkyl-sulfonyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenoxy, substituted or unsubstituted benzyloxy, substituted or unsubstituted Ethynyl; the optional substituents on R 31 , R 32 , R 33 , R 34 and R 35 are each independently selected from halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1 -3 alkyl-sulfonyl, phenyl, phenoxy, benzyloxy, C 1-3 alkyl substituted with 1-3 halogens, phenyl substituted with 1-3 halogens, cyclopropyl at least one of substituted
  • R 4 is selected from C 1-3 alkyl, C 1-3 alkoxy; more preferably, R 4 is selected from methyl, ethyl, n-propyl, isopropyl propyl group, cyclopropyl group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group; further preferably, R 4 is selected from cyclopropyl group, methoxy group and ethoxy group.
  • R 51 is selected from difluoromethyl, trifluoromethyl
  • R 52 is selected from methyl, ethyl, n-propyl, isopropyl; more preferably, R 51 is selected from Difluoromethyl, trifluoromethyl
  • R 52 is selected from methyl, ethyl; particularly preferably, R 51 is difluoromethyl; R 52 is methyl.
  • R 61 and R 62 are each independently selected from H, F, Cl, Br.
  • X is selected from H, F, Cl;
  • R 1 and R 2 are each independently selected from H, F, Cl, Br, alkyl of C 1-3 ;
  • R 31 , R 32 , R 33 , R 34 and R 35 are each independently selected from H, halogen, substituted or unsubstituted C 1-4 alkyl, C 1-4 alkoxy, cyano, C 1 -3 alkyl-sulfonyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenoxy, substituted or unsubstituted benzyloxy, substituted or unsubstituted ethynyl;
  • the optional substituents on 33 , R 34 and R 35 are each independently selected from halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-3 alkyl-sulfonyl, benzene At least one of phenyl, phenoxy, benzyloxy, C 1-3 alkyl substituted by 1-3 halogens, phenyl substituted by 1-3 halogens, ethynyl substituted
  • R 4 is selected from C 1-3 alkyl, C 1-3 alkoxy, propynyl;
  • R 51 is selected from difluoromethyl, trifluoromethyl
  • R 52 is selected from methyl, ethyl, n-propyl, isopropyl;
  • R 61 and R 62 are each independently selected from H, F, Cl, Br.
  • X is selected from H, F, Cl;
  • R 1 and R 2 are each independently selected from H, F, Cl, Br, methyl, ethyl, n-propyl, isopropyl, cyclopropyl;
  • R 31 , R 32 , R 33 , R 34 and R 35 are each independently selected from H, F, Cl, Br, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, isopropyl Butyl, tert-butyl, methoxy, ethoxy, trifluoromethyl, n-propoxy, isopropoxy, cyclopropoxy, n-butoxy, isobutoxy, tert-butoxy, cyano, methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenoxy, substituted or Unsubstituted benzyloxy, substituted or unsubstituted ethynyl
  • R 4 is selected from methyl, ethyl, n-propyl, isopropyl, cyclopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, propynyl;
  • R 51 is selected from difluoromethyl, trifluoromethyl
  • R 52 is selected from methyl, ethyl
  • R 61 and R 62 are each independently selected from H, F, Cl, Br.
  • X is selected from H, F;
  • R 1 and R 2 are each independently selected from H, methyl, ethyl, n-propyl;
  • R 31 , R 32 , R 33 , R 34 and R 35 are each independently selected from H, F, Cl, Br, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, methyl Oxy, trifluoromethyl, C 1-3 alkyl-sulfonyl, ethoxy, substituted or unsubstituted phenyl, substituted or unsubstituted phenoxy, substituted or unsubstituted benzyloxy, substituted or unsubstituted ethynyl; the optional substituents on R 31 , R 32 , R 33 , R 34 and R 35 are selected from F, Cl, Br, methyl, ethyl, n-propyl, cyclopropyl, At least one of isopropyl, n-butyl, tert-butyl, cyclopropyl substituted ethynyl, C
  • R 4 is selected from cyclopropyl, methoxy, ethoxy, propynyl;
  • R 51 is difluoromethyl
  • R 52 is methyl
  • R 61 and R 62 are each independently selected from H, F, Cl, Br.
  • the compound represented by formula (I) is at least one selected from compound 1 to compound 219.
  • the aforementioned compounds provided by the present invention all have significantly higher inhibitory activity against succinate dehydrogenase. It is a good succinate dehydrogenase inhibitor.
  • the present invention has no special requirements on the specific preparation method of the aforementioned pycnamide compounds, and those skilled in the art can select a suitable synthetic route to prepare it according to the structural formula provided by the present invention in combination with the known synthetic methods in the field of organic chemistry.
  • Several specific synthesis methods are exemplarily provided in the following and in the examples of the present invention, which should not be construed as a limitation of the present invention by those skilled in the art.
  • the compound of the structure represented by the formula (I) of the present invention is prepared by the method comprising the following routes:
  • the aforementioned synthetic route provided by the present invention may include some post-processing means known in the art to improve the purity of the target product and the like.
  • the second aspect of the present invention provides the use of the aforementioned compounds as succinate dehydrogenase inhibitors in pesticides.
  • the third aspect of the present invention provides the use of the aforementioned compounds for controlling fungal diseases of plants.
  • the fourth aspect of the present invention provides a bactericide, the bactericide contains an auxiliary material and a bactericidal effective amount of an active ingredient selected from at least one of the aforementioned compounds.
  • the content of the active ingredient is 5-99.99% by weight.
  • the dosage form of the bactericide is selected from at least one of emulsifiable concentrate, suspending agent, wettable powder, powder, granule, water, poison bait, mother liquor and mother powder.
  • the present invention has no special requirements on the specific types of the auxiliary materials in the bactericide. Those skilled in the art can select the corresponding auxiliary materials known in the art according to the dosage form to prepare the bactericide of the present invention, and the present invention will not be described in detail here. , it should not be construed as a limitation of the present invention by those skilled in the art.
  • the fifth aspect of the present invention provides the use of the aforementioned fungicides in controlling fungal diseases of plants.
  • the plant fungal disease is selected from at least one of wheat powdery mildew, cucumber powdery mildew, wheat scab, rice bakanae, rape sclerotinia, corn small spot, wheat stripe rust and cucumber botrytis kind.
  • the room temperature in the following examples means 25 ⁇ 2°C.
  • the intermediate 2a (1eq.) was dissolved in chloroform, added NBS (2eq.), p-toluenesulfonic acid (0.5eq.), heated to reflux for about 2h, TLC monitored whether the reaction was completed, and stopped after the reaction was completed. After heating, cooling to room temperature, adding water, extracting with dichloromethane, washing 2-3 times with water and saturated brine respectively, drying, and desolventizing to obtain the brominated intermediate 3a without purification.
  • the enzyme used in this test example was succinate dehydrogenase, which was isolated from pig hearts.
  • the test method is: the total volume is 1.8ml, the system contains 100mM Na 2 HPO 4 -NaH 2 PO 4 buffer (pH is 7.4), 0.3mM EDTA, 20mM sodium succinate, 53 ⁇ M DCIP (2,6-di chloroindophenol sodium), 2nM of succinate dehydrogenase. 23°C constant temperature water bath and 600rpm magnetic stirring.
  • the decrease in the absorbance of the substrate DCIP was monitored at a wavelength of 600 nm, and experimental points within the linear range were collected, ie, the experimental points at which the substrate consumption was controlled to not exceed 5%.
  • the molar extinction coefficient of DCIP is 21 mM -1 cm -1 . Calculate the reduction yield of DCIP within the reaction time and fit the linear slope, and then deduct the slope of the baseline to obtain the initial velocity of the reaction.
  • the enzymatic activity test results show that the compounds provided by the present invention have excellent inhibitory activity on succinate dehydrogenase.
  • test and investigation methods refer to the SOP-SC-1116 wheat powdery mildew potted method in the Fungicide Volume of "Standard Practice for Pesticide Bioactivity Testing" compiled by Kang Zhuo and Gu Baogen.
  • test and investigation methods refer to SOP-SC-1101 Potted Cucumber Powdery Mildew Method in the Fungicide Volume of "Standard Practice for Pesticide Biological Activity Testing" compiled by Kang Zhuo and Gu Baogen.
  • a and B both represent the prevention level, and 80% ⁇ A ⁇ 100%; 70% ⁇ B ⁇ 80%; C ⁇ 70%.
  • a and B both represent the prevention level, and 80% ⁇ A ⁇ 100%; 70% ⁇ B ⁇ 80%; C ⁇ 70%.
  • Compound 1 was tested for in vitro mycelia.
  • the mycelial growth rate method was used to determine the inhibitory effect of the drug on the growth of several tested pathogens and mycelium.
  • a bacterial plate with a diameter of 5 mm was taken from the edge of the colony that was continuously transferred and cultured for 4 days, and the bacterial plate was inoculated on PDA plates containing 25 ⁇ g/mL, 6.25 ⁇ g/mL, and 1.5625 ⁇ g/mL. repetitions. All petri dishes were incubated in a sterile incubator at 25°C. When the blank control bacteria grew to 2/3 of the diameter of the petri dish, the colony diameters of the control and treated colonies were measured by the cross method and the inhibition rate of mycelial growth was calculated.
  • Inhibition rate (control colony diameter - treated colony diameter) / (control colony diameter - bacterial cake diameter) ⁇ 100%
  • the results of potted live bactericidal activity test and in vitro mycelium bactericidal activity show that the compounds provided by the present invention are effective against plant fungal diseases, such as wheat powdery mildew, cucumber powdery mildew, wheat scab, rice bakanae, rape sclerotinia, corn At least one of small spot, wheat stripe rust, and cucumber botrytis had excellent bactericidal activity, and most compounds outperformed the commercial controls Fluconazole, Triflufenacil, and Prothioconazole, and some The compounds are basically equivalent to the best commercial agents for powdery mildew at present.
  • the experiment was carried out in accordance with "Guidelines for Field Efficacy Test of Pesticide” GB/T 17980.30-2000.
  • the survey method was to randomly select four points in each plot, and survey all leaves of 2 plants at each point.
  • the incidence of powdery mildew was investigated before the first application, and the incidence of powdery mildew was investigated 7 and 14 days after the second application, and the disease index and control effect were calculated. The results are shown in Table 6.
  • test and investigation methods refer to the SOP-SC-1112 potted method for rice bakanae disease in the Fungicide Volume of the "Standard Practice for Pesticide Bioactivity Testing" compiled by Kang Zhuo and Gu Baogen.
  • Cyanostrobin is the current mainstream medicine for preventing and treating bakanae disease of rice. With the long-term use, there are more and more resistant strains.
  • the present invention selects two strains that show sensitivity to cyanobactin and one strain. The strains showing resistance to cyanobacterial were used as test strains.
  • the compound 1 of the present invention is superior to the current mainstream agent cyanobacteryl in both the therapeutic activity and the protective activity against rice bakanae disease, showing a huge development prospect.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Environmental Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Plant Pathology (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Pest Control & Pesticides (AREA)
  • General Health & Medical Sciences (AREA)
  • Dentistry (AREA)
  • Health & Medical Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

提供一种涉及农药领域的突烯酰胺类化合物、杀菌剂和应用，该化合物具有式(I)所示的结构。提供的突烯酰胺类化合物对于琥珀酸脱氢酶具有较高抑制活性，且对于真菌病害也有较高的防效。

Description

[根据细则37.2由ISA制定的发明名称]　一种突烯酰胺类化合物、杀菌剂和应用
相关申请的交叉引用
本申请要求2020年09月30日提交的中国专利申请202011064084.7的权益，该申请的内容通过引用被合并于本文。
技术领域
本发明涉及农药新化合物领域，具体涉及一种突烯酰胺类化合物及其应用、一种杀菌剂及其应用。
背景技术
琥珀酸脱氢酶抑制剂(SDHIs,succinate dehydrogenase inhibitors)类杀菌剂是通过作用于病原菌线粒体呼吸电子传递链上的复合体II(也称琥珀酸脱氢酶或琥珀酸泛醌还原酶)，干扰呼吸电子传递链上琥珀酸脱氢酶来抑制线粒体功能，阻止其产生能量，抑制病原菌生长，最终导致其死亡，以达到防治病害的目的。
琥珀酸脱氢酶抑制剂类杀菌剂因其高效、广谱的杀菌活性和相对较低的抗性风险，近年来已经成为最有发展前景的一类杀菌剂，受到世界各大农药公司关注。
发明内容
本发明的目的是为了克服现有技术存在的前述缺陷，提供一类新的具有琥珀酸脱氢酶抑制效果的化合物。
为了实现上述目的，本发明的第一方面提供一种突烯酰胺类化合物，该化合物具有式(I)所示的结构，
Figure PCTCN2021121315-appb-000001
其中，在式(I)中，
X选自H、F、Cl；
R 1和R 2各自独立地选自H、卤素、C 1-6的烷基；或者R 1和R 2与它们共有的碳原子一起形成环丙基、环戊基或环己基；
R 31、R 32、R 33、R 34和R 35各自独立地选自H、卤素、取代或未取代的C 1-6的烷基、C 1-6的烷氧基、氰基、C 1-6的烷基-磺酰基、取代或未取代的苯基、取代或未取代的苯氧基、取代或未取代的苄氧基、取代或未取代的C 2-4的炔基；R 31、R 32、R 33、R 34和R 35上任选存在的取代基各自独立地选自卤素、C 1-6的烷基、C 1-6的烷氧基、C 1-6的烷基-磺酰基、苯基、苯氧基、苄氧基、由1-3个卤素取代的C 1-3的烷基、由1-3个卤素取代的苯基、环丙基取代的C 2-4的炔基中的至少一种；
R 4选自C 1-4的烷基、C 1-4的烷氧基、氰基、三氟甲基、丙炔基；
R 51选自由1-3个卤素取代的C 1-3的烷基；R 52选自C 1-4的烷基。
R 61和R 62各自独立地选自H、F、Cl、Br。
本发明的第二方面提供前述化合物作为琥珀酸脱氢酶抑制剂在农药中的应用。
本发明的第三方面提供前述化合物在防治植物真菌病害中的应用。
本发明的第四方面提供一种杀菌剂，该杀菌剂中含有辅料和杀菌有效量的活性成分，所述活性成分选自前述化合物中的至少一种。
本发明的第五方面提供前述杀菌剂在防治植物真菌病害中的应用。
本发明提供的突烯酰胺类化合物对于琥珀酸脱氢酶具有较高抑制活性，且对于真菌病害也有较高的防效，特别是对小麦白粉病、黄瓜白粉病、小麦赤霉病、水稻恶苗病、油菜菌核病、玉米小斑病、小麦条锈病、黄瓜灰霉病等具有优异的防效。
具体实施方式
在本文中所披露的范围的端点和任何值都不限于该精确的范围或值，这些范围或值应当理解为包含接近这些范围或值的值。对于数值范围来说，各个范围的端点值之间、各个范围的端点值和单独的点值之间，以及单独的点值之间可以彼此组合而得到一个或多个新的数值范围，这些数值范围应被视为在本文中具体公开。
以下先对本发明中涉及的部分术语进行解释，在没有相反说明的情况下，以下解释对于本发明的全文相同术语均有效，并且，为了避免重复，本发明在后文中也不再对相同的术语进行重复的解释，本领域技术人员不应理解为对本发明的限制。
“卤素”包括氟、氯、溴、碘。
“C 1-6的烷基”包括碳原子总数为1-6的烷基，包括直链烷基、支链烷基和环烷基，例如可以为碳原子总数为1、2、3、4、5、6的直链烷基、支链烷基或者环烷基，例如可以为甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、正戊基、异戊基、正己基、环丙基、甲基环丙基、乙基环丙基、环戊基、甲基环戊基、环己基等。针对“C 1-4的烷基”、“C 1-3的烷基”具有与此相似的解释，所不同的是，碳原子总数不同而已。
“C 1-6的烷氧基”包括碳原子总数为1-6的烷氧基，包括直链烷氧基、支链烷氧基和环烷氧基，例如可以为碳原子总数为1、2、3、4、5、6的直链烷氧基、支链烷氧基或者环烷氧基，例如可以为甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、叔丁氧基、正戊氧基、异戊氧基、正己氧基、环丙氧基、甲基环丙氧基、乙基环丙氧基、环戊氧基、甲基环戊氧基、环己氧基等。针对“C 1-4的烷氧基”、“C 1-3的烷氧基”具有与此相似的解释，所不同的是，碳原子总数不同而已。
“C 1-6的烷基-磺酰基”表示-SO 2-R 1所示的基团，并且其中的R 1为C 1-6的烷基。“C 1-3的烷基-磺酰基”等具有与此相似的解释。
“取代或未取代的苯基”表示对苯基上的具体取代基的数目没有限制，可以在苯基上能够被取代的位置进行取代，并且，也可以为没有取代基的情况，也即为苯基。针对“取代或未取代的苯氧基”、“取代或未取代的苄氧基”、“取代或未取代的C 2-4的炔基”具有与此相似的解释。
“由1-3个卤素取代的C 1-3的烷基”包括碳原子总数为1-3的烷基，并且烷基上的1-3个H原子被卤素取代，包括直链烷基、支链烷基和环烷基，例如可以为碳原子总数为1、2、3的直链烷基、支链烷基或者环烷基，例如可以为由1-3个卤素取代的甲基、由1-3个卤素取代的乙基、由1-3个卤素取代的正丙基、由1-3个卤素取代的异丙基、由1-3个卤素取代的环丙基等。
“由1-3个卤素取代的苯基”包括苯基上的1-3个H原子被卤素取代的基团。
如前所述，本发明的第一方面提供了一种突烯酰胺类化合物，该化合物具有式(I)所示的结构，
其中，在式(I)中，
X选自H、F、Cl；
R 1和R 2各自独立地选自H、卤素、C 1-6的烷基；或者R 1和R 2与它们共有的碳原子一起形成环丙基、环戊基或环己基；
R 31、R 32、R 33、R 34和R 35各自独立地选自H、卤素、取代或未取代的C 1-6的烷基、C 1-6的烷氧基、氰基、C 1-6的烷基-磺酰基、取代或未取代的苯基、取代或未取代的苯氧基、取代或未取代的苄氧基、取代或未取代的C 2-4的炔基；R 31、R 32、R 33、R 34和R 35上任选存在的取代基各自独立地选自卤素、C 1-6的烷基、C 1-6的烷氧基、C 1-6的烷基-磺酰基、苯基、苯氧基、苄氧基、由1-3个卤素取代的C 1-3的烷基、由1-3个卤素取代的苯基、环丙基取代的C 2-4的炔基中的至少一种；
R 4选自C 1-4的烷基、C 1-4的烷氧基、氰基、三氟甲基、丙炔基；
R 51选自由1-3个卤素取代的C 1-3的烷基；R 52选自C 1-4的烷基。
R 61和R 62各自独立地选自H、F、Cl、Br。
优选情况下，在式(I)中，X选自H、F。
优选情况下，在式(I)中，R 1和R 2各自独立地选自H、F、Cl、Br、C 1-3的烷基；更优选地，R 1和R 2各自独立地选自H、F、Cl、Br、甲基、乙基、正丙基、异丙基、环丙基；进一步优选地，R 1和R 2各自独立地选自H、甲基、乙基、正丙基。
优选地，在式(I)中，R 31、R 32、R 33、R 34和R 35各自独立地选自H、卤素、取代或未取代的C 1-4的烷基、C 1-4的烷氧基、氰基、C 1-3的烷基-磺酰基、取代或未取代的苯基、取代或未取代的苯氧基、取代或未取代的苄氧基、取代或未取代的乙炔基；R 31、R 32、R 33、R 34和R 35上任选存在的取代基各自独立地选自卤素、C 1-4的烷基、C 1-4的烷氧基、C 1-3的烷基-磺酰基、苯基、苯氧基、苄氧基、由1-3个卤素取代的C 1-3的烷基、由1-3个卤素取代的苯基、环丙基取代的乙炔基中的至少一种；更优选地，R 31、R 32、R 33、R 34和R 35各自独立地选自H、F、Cl、Br、甲基、乙基、正丙基、异丙基、环丙基、正丁基、异丁基、叔丁基、甲氧基、乙氧基、三氟甲基、正丙氧基、异丙氧基、环丙氧基、正丁氧基、异丁氧基、叔丁氧基、氰基、甲基磺酰基、乙基磺酰基、正丙基磺酰基、异丙基磺酰基、环丙基磺酰基、取代或未取代的苯基、取代或未取代的苯氧基、取代或未取代的苄氧基、取代或未取代的乙炔基；R 31、R 32、R 33、R 34和R 35上任选存在的取代基各自独立地选自F、Cl、Br、甲基、乙基、正丙基、异丙基、环丙基、正丁基、叔丁基、甲氧基、乙氧基、正丙氧基、异丙氧基、环丙氧基、环丙基取代的乙炔基、甲基磺酰基、乙基磺酰基、正丙基磺酰基、异丙基磺酰基、环丙基磺酰基、苯基、苯氧基、苄氧基、由1-3个选自F和/或Cl的卤素取代的C 1-3的烷基、由1-3个选自F和/或Cl的卤素取代的苯基中的至少一种；进一步优选地，R 31、R 32、R 33、R 34和R 35各自独立地选自H、F、Cl、Br、甲基、乙基、正丙基、异丙基、正丁基、叔丁基、甲氧基、三氟甲基、C 1-3的烷基-磺酰基、乙氧基、取代或未取代的苯基、取代或未取代的苯氧基、取代或未取代的苄氧基、取代或未取代的乙炔基；R 31、R 32、R 33、R 34和R 35上任选存在的取代基选自F、Cl、Br、甲基、乙基、正丙基、环丙基、异丙基、正丁基、叔丁基、环丙基取代的乙炔基、C 1-3的烷基-磺酰基中的至少一种。
优选地，在式(I)中，R 4选自C 1-3的烷基、C 1-3的烷氧基；更优选地，R 4选自甲基、乙基、正丙基、异丙基、环丙基、甲氧基、乙氧基、正丙氧基、异丙氧基；进一步优选地，R 4选自环丙基、甲氧基、乙氧基。
优选地，在式(I)中，R 51选自二氟甲基、三氟甲基；R 52选自甲基、乙基、正丙基、异丙基；更优选地，R 51选自二氟甲基、三氟甲基；R 52选自甲基、乙基；特别优选地，R 51为二氟甲基；R 52为甲基。
优选地，在式(I)中，R 61和R 62各自独立地选自H、F、Cl、Br。
以下针对本发明所述的突烯酰胺类化合物提供几种特别优选的具体实施方式。
具体实施方式1：
在式(I)中，
X选自H、F、Cl；
R 1和R 2各自独立地选自H、F、Cl、Br、C 1-3的烷基；
R 31、R 32、R 33、R 34和R 35各自独立地选自H、卤素、取代或未取代的C 1-4的烷基、C 1-4的烷氧基、氰基、 C 1-3的烷基-磺酰基、取代或未取代的苯基、取代或未取代的苯氧基、取代或未取代的苄氧基、取代或未取代的乙炔基；R 31、R 32、R 33、R 34和R 35上任选存在的取代基各自独立地选自卤素、C 1-4的烷基、C 1-4的烷氧基、C 1-3的烷基-磺酰基、苯基、苯氧基、苄氧基、由1-3个卤素取代的C 1-3的烷基、由1-3个卤素取代的苯基、环丙基取代的乙炔基中的至少一种；
R 4选自C 1-3的烷基、C 1-3的烷氧基、丙炔基；
R 51选自二氟甲基、三氟甲基；R 52选自甲基、乙基、正丙基、异丙基；
R 61和R 62各自独立地选自H、F、Cl、Br。
具体实施方式2：
在式(I)中，
X选自H、F、Cl；
R 1和R 2各自独立地选自H、F、Cl、Br、甲基、乙基、正丙基、异丙基、环丙基；
R 31、R 32、R 33、R 34和R 35各自独立地选自H、F、Cl、Br、甲基、乙基、正丙基、异丙基、环丙基、正丁基、异丁基、叔丁基、甲氧基、乙氧基、三氟甲基、正丙氧基、异丙氧基、环丙氧基、正丁氧基、异丁氧基、叔丁氧基、氰基、甲基磺酰基、乙基磺酰基、正丙基磺酰基、异丙基磺酰基、环丙基磺酰基、取代或未取代的苯基、取代或未取代的苯氧基、取代或未取代的苄氧基、取代或未取代的乙炔基；R 31、R 32、R 33、R 34和R 35上任选存在的取代基各自独立地选自F、Cl、Br、甲基、乙基、正丙基、异丙基、环丙基、正丁基、叔丁基、甲氧基、乙氧基、正丙氧基、异丙氧基、环丙氧基、环丙基取代的乙炔基、甲基磺酰基、乙基磺酰基、正丙基磺酰基、异丙基磺酰基、环丙基磺酰基、苯基、苯氧基、苄氧基、由1-3个选自F和/或Cl的卤素取代的C 1-3的烷基、由1-3个选自F和/或Cl的卤素取代的苯基中的至少一种；
R 4选自甲基、乙基、正丙基、异丙基、环丙基、甲氧基、乙氧基、正丙氧基、异丙氧基、丙炔基；
R 51选自二氟甲基、三氟甲基；R 52选自甲基、乙基；
R 61和R 62各自独立地选自H、F、Cl、Br。
具体实施方式3：
在式(I)中，
X选自H、F；
R 1和R 2各自独立地选自H、甲基、乙基、正丙基；
R 31、R 32、R 33、R 34和R 35各自独立地选自H、F、Cl、Br、甲基、乙基、正丙基、异丙基、正丁基、叔丁基、甲氧基、三氟甲基、C 1-3的烷基-磺酰基、乙氧基、取代或未取代的苯基、取代或未取代的苯氧基、取代或未取代的苄氧基、取代或未取代的乙炔基；R 31、R 32、R 33、R 34和R 35上任选存在的取代基选自F、Cl、Br、甲基、乙基、正丙基、环丙基、异丙基、正丁基、叔丁基、环丙基取代的乙炔基、C 1-3的烷基-磺酰基中的至少一种；
R 4选自环丙基、甲氧基、乙氧基、丙炔基；
R 51为二氟甲基；R 52为甲基；
R 61和R 62各自独立地选自H、F、Cl、Br。
具体实施方式4：
式(I)所示的化合物选自化合物1至化合物219中的至少一种。
本发明提供的前述化合物对于琥珀酸脱氢酶均具有明显较高抑制活性。是良好的琥珀酸脱氢酶抑制剂。
本发明对前述突烯酰胺类化合物的具体制备方法没有特别的要求，本领域技术人员可以根据本发明提供的结构式结合有机化学领域的已知合成方法，选择合适的合成路线制备获得。本发明的下文和实例中示例性地提供了几种具体的合成方法，本领域技术人员不应理解为对本发明的限制。
示例性地，本发明所述式(I)所示结构的化合物采用包括如下路线的方法制备得到：
Figure PCTCN2021121315-appb-000002
本发明提供的前述合成路线中可以包括一些本领域公知的后处理手段，以提高目标产物的纯度等。
如前所述，本发明的第二方面提供了前述化合物作为琥珀酸脱氢酶抑制剂在农药中的应用。
如前所述，本发明的第三方面提供了前述化合物在防治植物真菌病害中的应用。
如前所述，本发明的第四方面提供了一种杀菌剂，该杀菌剂中含有辅料和杀菌有效量的活性成分，所述活性成分选自前述化合物中的至少一种。
优选情况下，在所述杀菌剂中，所述活性成分的含量为5-99.99重量％。
优选地，所述杀菌剂的剂型选自乳油、悬浮剂、可湿性粉剂、粉剂、粒剂、水剂、毒饵、母液和母粉中的至少一种。
本发明对所述杀菌剂中的辅料的具体种类没有特别的要求，本领域技术人员可以根据剂型选择本领域已知的相应辅料制备本发明的所述杀菌剂，本发明在此不再详述，本领域技术人员不应理解为对本发明的限制。
如前所述，本发明的第五方面提供了前述杀菌剂在防治植物真菌病害中的应用。
优选地，所述植物真菌病害选自小麦白粉病、黄瓜白粉病、小麦赤霉病、水稻恶苗病、油菜菌核病、玉米小斑病、小麦条锈病和黄瓜灰霉病中的至少一种。
以下将通过实例对本发明进行详细描述。以下实例中，在没有特别说明的情况下，使用的原料均为普通市售品。
在没有特别说明的情况下，以下实例中的室温表示25±2℃。
在没有特别说明的情况下，以下实例中的目标化合物采用如下的合成路线制备获得。具体地：
Figure PCTCN2021121315-appb-000003
R 61＝R 62＝H时，合成方法如下：
1、中间体2a的合成
取化合物1a(80mmol)于250ml烧杯中，加入120ml的THF，冰浴下缓慢加入叔丁醇钾(80mmol)，随后室温反应1h，在冰浴下缓慢加入各种取代的酮(40mmol)，待加完后，升温至室温，1h后TLC监测反应，待原料反应完成后，加水淬灭反应，并用乙酸乙酯进行萃取，再水洗3次，饱和食盐水洗3次，硅胶拌样，柱层析分离得油状化合物，即为中间体2a。
2、中间体3a的合成
将中间体2a(1eq.)溶于三氯甲烷中，加入NBS(2eq.)、对甲苯磺酸(0.5eq.)，加热至回流2h左右，TLC监测反应，待反应完成后，停止加热，冷却至室温后，加水，用二氯甲烷萃取，分别用水、饱和食盐水洗3次，干燥，脱溶剂，得溴化的中间体3a，无需纯化。
3、中间体4a的合成
取溴化的中间体3a(1eq.)于乙腈中，加入碳酸钾(3eq.)，然后冰浴下加入各种取代的胺(2.2eq.)，待加完后室温反应24h，TLC监测反应，待反应完成，则加水猝灭反应，乙酸乙酯萃取，再分别用水、饱和食盐 水洗3次，干燥脱溶得胺化的中间体4a，无需纯化。
4、目标产物的合成
取胺化的中间体4a(1eq.)于二氯甲烷中，加入三乙胺(2eq.)，最后缓慢加入吡唑酰氯(1.5eq.)，TLC监测反应，待反应完成，加水猝灭反应，二氯甲烷萃取，分别用水和饱和食盐水洗3次，硅胶拌样，柱层析分离，得到产物。
R 61＝R 62＝F、Cl、Br时，合成方法如下：
1、中间体2a的合成
取三苯基膦(4eq.)和取代的酮(1eq.)于合适大小的茄形瓶中，加入适量DCM，冰浴下缓慢滴加三氯溴甲烷(2eq.)，30min后监测反应是否完成，若反应完成，则加水猝灭反应，DCM萃取，再水洗2-3次，饱和食盐水洗2-3次，硅胶拌样，柱层析分离提纯，得油状化合物，即为中间体2a。
2、中间体3a的合成
将中间体2a(1eq.)溶于三氯甲烷中，加入NBS(2eq.)、对甲苯磺酸(0.5eq.)，加热至回流2h左右，TLC监测反应是否完成，待反应完成后，停止加热，冷却至室温后，加水，用二氯甲烷萃取，分别用水、饱和食盐水洗2-3次，干燥，脱溶得溴化中间体3a，无需纯化。
3、中间体4a的合成
取溴化中间体3a(1eq.)于适量乙腈中，加入碳酸钾(3eq.)，然后冰浴下加入各种取代的胺(2.2eq.)，待加完后室温反应24h，TLC监测反应是否完全，待反应完成，则加水猝灭反应，乙酸乙酯萃取，再分别用水、饱和食盐水洗2-3次，干燥脱溶得胺化中间体4a，无需纯化。
4、目标产物的合成
取胺化中间体4a(1eq.)于适量二氯甲烷中，加入三乙胺(2eq.)，最后缓慢加入吡唑酰氯(1.5eq.)，若大量反应则冰浴下缓慢加入，少量可以直接室温加入，TLC监测反应是否完成，待反应完成，加水猝灭反应，二氯甲烷萃取，分别用水和饱和食盐水洗2-3次，若少量则直接硅胶拌样，柱层析分离，若大量，可以用乙醇和乙酸乙酯进行重结晶，产物为白色固体。
以下示例性地提供化合物1的具体合成方法：
Figure PCTCN2021121315-appb-000004
取三苯基甲基溴化磷(80mmol,2eq.)于250ml茄型瓶中，加入120ml THF，冰浴下缓慢加入叔丁醇钾(80mmol,2eq.)，随后室温反应1h后，在冰浴下缓慢加入2,4-二氯苯乙酮(40mmol,1eq.)，待加完后，升温至室温，1h后TLC监测反应完成，待原料反应完成后，加水淬灭反应，并用乙酸乙酯进行萃取，再水洗3次，饱和食盐水洗3次，干燥脱溶得黄色油状化合物，此时包含产物和三苯基氧膦，分离，直接硅胶拌样，柱层析分离，洗脱剂为石油醚。
Figure PCTCN2021121315-appb-000005
将2,4-二氯苯乙烯(1eq.)溶于三氯甲烷中，加入NBS(1.05eq.)、对甲苯磺酸(0.3eq.)，70℃加热至回流2h，TLC监测反应完成，待反应完成后，停止加热，冷却至室温后，加水，用二氯甲烷萃取，分别用水、饱和食盐水洗2次，干燥，脱溶得溴化中间体，无需纯化。
Figure PCTCN2021121315-appb-000006
取溴化中间体(1eq.)于适量乙腈中，加入碳酸钾(3eq.),然后冰浴下加入环丙胺(2.2eq.)，待加完后室温反应24h，TLC监测反应完全，待反应完成，则加水猝灭反应，乙酸乙酯萃取，再分别用水、饱和食盐水洗3次，干燥脱溶得胺化产物，无需纯化。
Figure PCTCN2021121315-appb-000007
取胺化中间体(1eq.)于适量二氯甲烷中，加入三乙胺(2eq.)，最后缓慢加入含氟吡唑酰氯(1.5eq.)，TLC监测反应完成，待反应完成，加水猝灭反应，二氯甲烷萃取，分别用水和饱和食盐水洗3次，直接硅胶拌样，柱层析分离(洗脱剂用石油醚：乙酸乙酯＝8：1)，产物为白色固体。即为化合物1。
本发明的目标化合物的核磁数据列于表1中。
表1
Figure PCTCN2021121315-appb-000008
Figure PCTCN2021121315-appb-000009
Figure PCTCN2021121315-appb-000010
Figure PCTCN2021121315-appb-000011
Figure PCTCN2021121315-appb-000012
Figure PCTCN2021121315-appb-000013
Figure PCTCN2021121315-appb-000014
Figure PCTCN2021121315-appb-000015
Figure PCTCN2021121315-appb-000016
Figure PCTCN2021121315-appb-000017
Figure PCTCN2021121315-appb-000018
Figure PCTCN2021121315-appb-000019
测试例1
酶活性测试
用于测定对照药剂、目标化合物对琥珀酸脱氢酶的抑制活性。
本测试例中使用的酶为琥珀酸脱氢酶，从猪心中分离制得。
测试方法为：总体积1.8ml，体系中含100mM的Na 2HPO 4-NaH 2PO 4缓冲液(pH为7.4)、0.3mM的EDTA、20mM琥珀酸钠、53μM的DCIP(2,6-二氯靛酚钠)，2nM的琥珀酸脱氢酶。23℃恒温水浴及600rpm磁力搅拌。在波长为600nm处监测底物DCIP光吸收的降低，采集线性范围内的实验点，即控制底物消耗不超过5％的实验点。DCIP的摩尔消光系数为21mM -1cm -1。计算在反应时间内DCIP的还原产量并拟合线性斜率，再扣掉基线斜率即为反应的初速度。
测试结果见表2。
表2
Figure PCTCN2021121315-appb-000020
Figure PCTCN2021121315-appb-000021
酶活性测试结果显示，本发明提供的化合物对琥珀酸脱氢酶具有优异的抑制活性。
测试例2
杀菌活性测试
用于测定对照药剂、目标化合物的杀菌活性。
小麦白粉病(Erysiphe graminis)
测试和调查方法参照康卓、顾宝根编写的《农药生物活性测试标准操作规范》杀菌剂卷中的SOP-SC-1116小麦白粉病盆栽法。
黄瓜白粉病(Sphaerotheca fuliginea)
测试和调查方法参照康卓、顾宝根编写的《农药生物活性测试标准操作规范》杀菌剂卷中的SOP-SC-1101黄瓜白粉病盆栽法。
防效结果列于表3和表4中。
表3
Figure PCTCN2021121315-appb-000022
表3中，A和B均表示防效等级，且80％≦A≦100％；70％≦B<80％；C<70％。
表4
Figure PCTCN2021121315-appb-000023
Figure PCTCN2021121315-appb-000024
Figure PCTCN2021121315-appb-000025
表4中，A和B均表示防效等级，且80％≦A≦100％；70％≦B<80％；C<70％。
测试例3
化合物1进行离体菌丝试验。
首先对供试病原菌进行初步筛选。采用菌丝生长速率法测定药剂对几种供试病原菌、菌丝生长的抑制效果。在连续转接培养4d的菌落边缘打取直径为5mm的菌碟，分别将菌碟接种于含药剂浓度为25μg/mL，6.25μg/mL，1.5625μg/mL的PDA平板上，每个处理3个重复。将所有的培养皿置25℃的无菌培养箱进行培养。待空白对照菌长到培养皿直径的2/3时，采用十字交叉法测定对照及处理的菌落直径并计算菌丝生长抑制率。
抑制率＝(对照菌落直径-处理菌落直径)/(对照菌落直径-菌饼直径)×100％
结果如表5所示。
表5
Figure PCTCN2021121315-appb-000026
盆栽活体杀菌活性测试以及离体菌丝杀菌活性结果显示，本发明提供的化合物对植物真菌病害，例如小麦白粉病、黄瓜白粉病、小麦赤霉病、水稻恶苗病、油菜菌核病、玉米小斑病、小麦条锈病和黄瓜灰霉病中的至少一种均具有优异的杀菌活性，并且，大多数化合物优于商品化对照氟唑菌酰胺、烯肟菌胺和丙硫菌唑，部分化合物与目前白粉病最优的商品化药剂基本相当。
测试例4
化合物1进行黄瓜白粉病的田间试验
试验按照《农药田间药效试验准则》GB/T 17980.30—2000进行。调查方法为每个小区随机取四点，每点调查2株的全部叶片。第一次施药前调查白粉病发病情况，第二次施药后7、14天分别调查白粉病发病情况，计算病情指数和防治效果。结果如表6所示。
表6
处理 药剂 防效％
1 化合物1为50mg/L 82
2 化合物1为100mg/L 88
3 化合物1为200mg/L 92
4 氟唑菌酰羟胺100mg/L 92
5 29％吡萘嘧菌酯悬浮剂(绿妃)100mg/L 95
6 CK 72(病情指数)
从黄瓜白粉病的田间试验结果中可以看出，化合物1在50mg/L浓度下仍然能够维持80％以上的防治效果，在100mg/L浓度下与目前主流防治黄瓜白粉病的药剂的防效基本相当，具有极强的开发价值。
测试例5
化合物1进行水稻恶苗病的保护活性和治疗活性的试验
测试和调查方法参照康卓、顾宝根编写的《农药生物活性测试标准操作规范》杀菌剂卷中的SOP-SC-1112水稻恶苗病盆栽法。
氰烯菌酯是目前主流防治水稻恶苗病的药剂，随着长时间的使用，抗性菌株越来越多，本发明挑选了两种对氰烯菌酯表现出敏感性的菌株和一种对氰烯菌酯表现出抗性的菌株作为试验菌株。
选取四种藤仓镰刀菌菌株SX18-32、SX18-50、SX18-59以及SX18-63用于试验菌种，同时选取目前主流商品化杀菌剂氰烯菌酯作为阳性对照。其中SX18-32、SX18-50和SX18-59对氰烯菌酯表现出敏感，SX18-63对氰烯菌酯表现出抗性。其保护活性和治疗活性列于表7和表8。
表7：(治疗活性)测试浓度为5μg/mL(溶剂为DMSO)
Figure PCTCN2021121315-appb-000027
表8：(保护活性)测试浓度为5μg/mL(溶剂为DMSO)
Figure PCTCN2021121315-appb-000028
从治疗活性的测试中，可以明显看出本发明的化合物1特别对于抗性菌株SX18-63(R)的治疗效果远优于氰烯菌酯，氰烯菌酯对抗性菌株几乎无治疗活性，另外对于敏感性的菌株，氰烯菌酯最多也只有50％左右的治疗效 果，而本发明的化合物1对SX18-59(S)表现出96.8％的强治疗效果。
对于保护活性的测试中，本发明的化合物1对于三种菌株的保护活性均在90％以上，接近完全保护，同样远优于氰烯菌酯。
综合来看，本发明的化合物1对水稻恶苗病无论治疗活性还是保护活性均优于目前主流药剂氰烯菌酯，表现出巨大的开发前景。
以上详细描述了本发明的优选实施方式，但是，本发明并不限于此。在本发明的技术构思范围内，可以对本发明的技术方案进行多种简单变型，包括各个技术特征以任何其它的合适方式进行组合，这些简单变型和组合同样应当视为本发明所公开的内容，均属于本发明的保护范围。

Claims (10)

  1. 一种突烯酰胺类化合物，其特征在于，该化合物具有式(I)所示的结构，
    Figure PCTCN2021121315-appb-100001
    其中，在式(I)中，
    X选自H、F、Cl；
    R 1和R 2各自独立地选自H、卤素、C 1-6的烷基；或者R 1和R 2与它们共有的碳原子一起形成环丙基、环戊基或环己基；
    R 31、R 32、R 33、R 34和R 35各自独立地选自H、卤素、取代或未取代的C 1-6的烷基、C 1-6的烷氧基、氰基、C 1-6的烷基-磺酰基、取代或未取代的苯基、取代或未取代的苯氧基、取代或未取代的苄氧基、取代或未取代的C 2-4的炔基；R 31、R 32、R 33、R 34和R 35上任选存在的取代基各自独立地选自卤素、C 1-6的烷基、C 1-6的烷氧基、C 1-6的烷基-磺酰基、苯基、苯氧基、苄氧基、由1-3个卤素取代的C 1-3的烷基、由1-3个卤素取代的苯基、环丙基取代的C 2-4的炔基中的至少一种；
    R 4选自C 1-4的烷基、C 1-4的烷氧基、氰基、三氟甲基、丙炔基；
    R 51选自由1-3个卤素取代的C 1-3的烷基；R 52选自C 1-4的烷基。
    R 61和R 62各自独立地选自H、F、Cl、Br。
  2. 根据权利要求1所述的化合物，其中，在式(I)中，
    X选自H、F、Cl；
    R 1和R 2各自独立地选自H、F、Cl、Br、C 1-3的烷基；
    R 31、R 32、R 33、R 34和R 35各自独立地选自H、卤素、取代或未取代的C 1-4的烷基、C 1-4的烷氧基、氰基、C 1-3的烷基-磺酰基、取代或未取代的苯基、取代或未取代的苯氧基、取代或未取代的苄氧基、取代或未取代的乙炔基；R 31、R 32、R 33、R 34和R 35上任选存在的取代基各自独立地选自卤素、C 1-4的烷基、C 1-4的烷氧基、C 1-3的烷基-磺酰基、苯基、苯氧基、苄氧基、由1-3个卤素取代的C 1-3的烷基、由1-3个卤素取代的苯基、环丙基取代的乙炔基中的至少一种；
    R 4选自C 1-3的烷基、C 1-3的烷氧基、丙炔基；
    R 51选自二氟甲基、三氟甲基；R 52选自甲基、乙基、正丙基、异丙基；
    R 61和R 62各自独立地选自H、F、Cl、Br。
  3. 根据权利要求1所述的化合物，其中，在式(I)中，
    X选自H、F、Cl；
    R 1和R 2各自独立地选自H、F、Cl、Br、甲基、乙基、正丙基、异丙基、环丙基；
    R 31、R 32、R 33、R 34和R 35各自独立地选自H、F、Cl、Br、甲基、乙基、正丙基、异丙基、环丙基、正丁基、异丁基、叔丁基、甲氧基、乙氧基、三氟甲基、正丙氧基、异丙氧基、环丙氧基、正丁氧基、异丁氧基、叔丁氧基、氰基、甲基磺酰基、乙基磺酰基、正丙基磺酰基、异丙基磺酰基、环丙基磺酰基、取代或未取代的苯基、 取代或未取代的苯氧基、取代或未取代的苄氧基、取代或未取代的乙炔基；R 31、R 32、R 33、R 34和R 35上任选存在的取代基各自独立地选自F、Cl、Br、甲基、乙基、正丙基、异丙基、环丙基、正丁基、叔丁基、甲氧基、乙氧基、正丙氧基、异丙氧基、环丙氧基、环丙基取代的乙炔基、甲基磺酰基、乙基磺酰基、正丙基磺酰基、异丙基磺酰基、环丙基磺酰基、苯基、苯氧基、苄氧基、由1-3个选自F和/或Cl的卤素取代的C 1-3的烷基、由1-3个选自F和/或Cl的卤素取代的苯基中的至少一种；
    R 4选自甲基、乙基、正丙基、异丙基、环丙基、甲氧基、乙氧基、正丙氧基、异丙氧基、丙炔基；
    R 51选自二氟甲基、三氟甲基；R 52选自甲基、乙基；
    R 61和R 62各自独立地选自H、F、Cl、Br。
  4. 根据权利要求1所述的化合物，其中，在式(I)中，
    X选自H、F；
    R 1和R 2各自独立地选自H、甲基、乙基、正丙基；
    R 31、R 32、R 33、R 34和R 35各自独立地选自H、F、Cl、Br、甲基、乙基、正丙基、异丙基、正丁基、叔丁基、甲氧基、三氟甲基、C 1-3的烷基-磺酰基、乙氧基、取代或未取代的苯基、取代或未取代的苯氧基、取代或未取代的苄氧基、取代或未取代的乙炔基；R 31、R 32、R 33、R 34和R 35上任选存在的取代基选自F、Cl、Br、甲基、乙基、正丙基、环丙基、异丙基、正丁基、叔丁基、环丙基取代的乙炔基、C 1-3的烷基-磺酰基中的至少一种；
    R 4选自环丙基、甲氧基、乙氧基、丙炔基；
    R 51为二氟甲基；R 52为甲基；
    R 61和R 62各自独立地选自H、F、Cl、Br。
  5. 根据权利要求1-4中任意一项所述的化合物，其中，式(I)所示的化合物选自以下化合物中的至少一种：
    Figure PCTCN2021121315-appb-100002
    Figure PCTCN2021121315-appb-100003
    Figure PCTCN2021121315-appb-100004
    Figure PCTCN2021121315-appb-100005
    Figure PCTCN2021121315-appb-100006
    Figure PCTCN2021121315-appb-100007
    Figure PCTCN2021121315-appb-100008
    Figure PCTCN2021121315-appb-100009
    Figure PCTCN2021121315-appb-100010
    Figure PCTCN2021121315-appb-100011
    Figure PCTCN2021121315-appb-100012
    Figure PCTCN2021121315-appb-100013
    Figure PCTCN2021121315-appb-100014
    Figure PCTCN2021121315-appb-100015
    Figure PCTCN2021121315-appb-100016
  6. 权利要求1-5中任意一项所述的化合物作为琥珀酸脱氢酶抑制剂在农药中的应用。
  7. 权利要求1-5中任意一项所述的化合物在防治植物真菌病害中的应用。
  8. 一种杀菌剂，其特征在于，该杀菌剂中含有辅料和杀菌有效量的活性成分，所述活性成分选自权利要求1-5中任意一项所述的化合物中的至少一种。
  9. 根据权利要求8所述的杀菌剂，其中，所述杀菌剂的剂型选自乳油、悬浮剂、可湿性粉剂、粉剂、粒剂、水剂、毒饵、母液和母粉中的至少一种。
  10. 权利要求8或9所述的杀菌剂在防治植物真菌病害中的应用；
    优选地，所述植物真菌病害选自小麦白粉病、黄瓜白粉病、小麦赤霉病、水稻恶苗病、油菜菌核病、玉米小斑病、小麦条锈病和黄瓜灰霉病中的至少一种。
PCT/CN2021/121315 2020-09-30 2021-09-28 一种突烯酰胺类化合物、杀菌剂和应用 WO2022068816A1 (zh)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP21874476.1A EP4223745A4 (en) 2020-09-30 2021-09-28 DENDRENAMIDE COMPOUND, BACTERICIDE AND USE THEREOF
US18/247,393 US20230391728A1 (en) 2020-09-30 2021-09-28 Dendrene amide compound, bactericide and use thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202011064084 2020-09-30
CN202011064084.7 2020-09-30

Publications (1)

Publication Number Publication Date
WO2022068816A1 true WO2022068816A1 (zh) 2022-04-07

Family

ID=78980776

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2021/121315 WO2022068816A1 (zh) 2020-09-30 2021-09-28 一种突烯酰胺类化合物、杀菌剂和应用

Country Status (4)

Country Link
US (1) US20230391728A1 (zh)
EP (1) EP4223745A4 (zh)
CN (1) CN113845480B (zh)
WO (1) WO2022068816A1 (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117617257A (zh) * 2022-08-29 2024-03-01 江苏中旗科技股份有限公司 一种用于杀真菌的组合物及应用组合物的方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102918028A (zh) * 2010-06-03 2013-02-06 拜尔农科股份公司 N-[(杂)芳基烷基)]吡唑(硫代)羧酰胺及其杂取代的类似物
WO2014056956A1 (en) * 2012-10-11 2014-04-17 Bayer Cropscience Ag Use of n-phenylethylpyrazole carboxamide derivatives or salts thereof for resistance management of phytopathogenic fungi
CN104603128A (zh) * 2012-06-29 2015-05-06 杜邦公司 杀真菌杂环羰酰胺
CN109384722A (zh) * 2017-08-14 2019-02-26 华中师范大学 N-取代酰胺类化合物及其制备方法和应用和一种杀菌剂
CN109422691A (zh) * 2017-08-24 2019-03-05 华中师范大学 N-取代酰胺类化合物及其制备方法和应用及杀菌剂

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112012030580B1 (pt) * 2010-06-03 2018-06-05 Bayer Cropscience Ag Composto, composição fungicida e método para controlar fungos fitopatogênicos de culturas
UA114648C2 (uk) * 2012-10-19 2017-07-10 Байєр Кропсайнс Аг Спосіб обробки рослин проти грибів, стійких до фунгіцидів, із застосуванням карбоксамідних або тіокарбоксамідних похідних
EP3109234A4 (en) * 2014-02-18 2017-07-05 Nissan Chemical Industries, Ltd. Alkynylpyridine-substituted amide compound and noxious organism control agent
CN109068648B (zh) * 2016-04-27 2021-07-27 日产化学株式会社 杀菌或杀细菌组合物和病害的防除方法
CN111943975B (zh) * 2019-07-31 2023-04-07 华中师范大学 一种含硅原子吡唑酰胺类化合物及其制备方法和应用及一种杀菌剂
CN114560824B (zh) * 2021-02-10 2023-08-29 江苏中旗科技股份有限公司 三氟甲基噁二唑类化合物及其制备方法和应用、一种杀菌剂

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102918028A (zh) * 2010-06-03 2013-02-06 拜尔农科股份公司 N-[(杂)芳基烷基)]吡唑(硫代)羧酰胺及其杂取代的类似物
CN104603128A (zh) * 2012-06-29 2015-05-06 杜邦公司 杀真菌杂环羰酰胺
WO2014056956A1 (en) * 2012-10-11 2014-04-17 Bayer Cropscience Ag Use of n-phenylethylpyrazole carboxamide derivatives or salts thereof for resistance management of phytopathogenic fungi
CN109384722A (zh) * 2017-08-14 2019-02-26 华中师范大学 N-取代酰胺类化合物及其制备方法和应用和一种杀菌剂
CN109422691A (zh) * 2017-08-24 2019-03-05 华中师范大学 N-取代酰胺类化合物及其制备方法和应用及杀菌剂

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP4223745A4 *

Also Published As

Publication number Publication date
CN113845480B (zh) 2023-05-12
EP4223745A4 (en) 2024-04-03
EP4223745A1 (en) 2023-08-09
CN113845480A (zh) 2021-12-28
US20230391728A1 (en) 2023-12-07

Similar Documents

Publication Publication Date Title
US4643757A (en) Herbicidal 4-benzoyl-1-methyl-5-hydroxypyrazoles
US5958925A (en) Pyridazinones and their use as fungicides
WO2017107939A1 (zh) 一种丙二腈肟醚类化合物及其用途
CZ110696A3 (en) Dihydropyridazinones a pyridazinones, their use as fungicides and insecticides
JP2723554B2 (ja) 新規アシル化トリアゾール誘導体、その製造法及び該誘導体を活性成分としえ含有する農園芸用殺菌剤
US8865724B2 (en) Preparation of 2-methyl-4-amino-5(substituted-1H-1,2,3-triazolyl)methylpyrimidine derivatives and microbicidal activity thereof
WO2022068816A1 (zh) 一种突烯酰胺类化合物、杀菌剂和应用
Chang et al. The discovery of new scaffold of plant activators: from salicylic acid to benzotriazole
CN108069915B (zh) 一种吡嗪酰胺类化合物及其制备方法和应用以及一种杀菌剂
CN109956904B (zh) 吡唑酰胺类化合物及其应用和杀菌剂
WO2022171176A1 (zh) 三氟甲基噁二唑类化合物及其制备方法和应用、一种杀菌剂
TWI496540B (zh) 二硫雜己環并四（硫代）甲醯胺類
CN108570009B (zh) 3-卤素二芳胺基吡唑酰胺类化合物及其在农药中的应用
SE453829B (sv) Azolyl-penten-derivat, forfarande for framstellning derav samt biocida medel innehallande nemnda derivat med vexttillvextreglerande, fungicid, herbicid eller baktericid verkan
CN110294751B (zh) 具生物活性的咪唑[4,5-b]并吡啶类化合物及其制备方法和应用
CN115160303B (zh) 三氟甲基噁二唑类化合物及其制备方法和应用、一种杀菌剂
JPH0643423B2 (ja) 殺菌性３―イミノ―１，４―オキサチイン
CN105777640B (zh) 一种吡唑环己二醇醚类化合物及其应用
Majumder et al. Synthesis of Schiff bases of 4-amino-3-mercapto-5-pyridin-4yl-4H-1, 2, 4-triazole and their evaluation as SAR inducers
CN117567446B (zh) 一种含有杂环结构的***啉酮类化合物、制备方法及其应用
JPH0581599B2 (zh)
WO2017024971A1 (zh) 一种不饱和肟醚类化合物及其用途
WO2017008583A1 (zh) 一类含二苯醚结构的吡唑酰胺化合物、其制备方法及应用
JPH08193078A (ja) クロモン誘導体および農園芸用殺菌剤
JPH11292863A (ja) ２−置換−１，２，５−チアジアゾール−３−チオン誘導体および農園芸用殺菌剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21874476

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 18247393

Country of ref document: US

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2021874476

Country of ref document: EP

Effective date: 20230502