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WO2019128976A1 - Pyridine sulfone, dérivés de celle-ci, procédé de préparation associé, et application correspondante - Google Patents

Pyridine sulfone, dérivés de celle-ci, procédé de préparation associé, et application correspondante Download PDF

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Publication number
WO2019128976A1
WO2019128976A1 PCT/CN2018/123428 CN2018123428W WO2019128976A1 WO 2019128976 A1 WO2019128976 A1 WO 2019128976A1 CN 2018123428 W CN2018123428 W CN 2018123428W WO 2019128976 A1 WO2019128976 A1 WO 2019128976A1
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Prior art keywords
nitropyridin
amine
compound
formula
alkyl
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PCT/CN2018/123428
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English (en)
Chinese (zh)
Inventor
刘卫东
柳爱平
刘兴平
李建明
刘民华
何莲
任叶果
项军
马保德
闫忠忠
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Hunan Research Institute of Chemical Industry
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Hunan Research Institute of Chemical Industry
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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
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/61—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/70—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/73—Unsubstituted amino or imino radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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

Definitions

  • the present invention relates to pyridone and its derivatives having bactericidal, insecticidal/industrial activity, and a process for the preparation thereof, a bactericidal, insecticidal/sputum composition containing the same, and the use of these compounds for controlling harmful bacteria, pests/cockroaches Use and method.
  • Sulfone and its derivatives are important compounds in medicinal chemistry. They have a broad spectrum of biological activities. There are many reports on biologically active sulfones and their derivatives, but reports of pyridine sulfone and its derivatives are rare. Even the occasional reports of pyridine sulfone and its derivatives are mostly related to its medicinal activity. Reports of pyridylsulfone and its derivatives active against harmful bacteria and/or pests/caries are not easily found.
  • the sulfone compound represented by the formula (A) as reported in the literature belongs to the field of medicine.
  • Sulfone compounds especially pyridine sulfone and its derivatives, have been one of our research directions in order to obtain novel structural compounds active against harmful bacteria and/or pests/sputums.
  • Applicants have discovered a novel class of pyridylsulfone and its derivatives with broad-spectrum biological activity.
  • the applicant specifically synthesizes the phenyl sulfone represented by the formula (B), the formula (C) and the formula (D) and derivatives thereof and tests the organism thereof. active.
  • the compounds of the present invention not only have significantly different structural characteristics, but also these structural differences allow the compounds of the present invention to have a broader spectrum and superior biological activity, and some compounds such as 29, 244, etc. exhibit a formula (B), (C) and phenyl sulfone and its derivatives represented by formula (D) are more broad-spectrum and more efficient biological activities.
  • the present invention provides a pyridyl sulfone having a biological activity such as a pathogen, a pest, or a cockroach, and a derivative thereof, represented by the formula (I):
  • I.R represents a nitro group
  • R 1 represents hydrogen, C 1 -C 12 alkyl or C 3 -C 6 cycloalkyl
  • R 2 represents hydrogen, halogen, C 1 -C 12 alkyl or C 3 -C 6 cycloalkyl
  • R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
  • VR 4 represents hydrogen, C 1 -C 12 alkyl or C 3 -C 6 cycloalkyl
  • R 5 represents hydrogen, C 1 -C 12 alkyl, C 3 -C 8 cycloalkyl, phenyl, phenylmethyl, phenylethyl, thiazolyl, thiazolylmethyl, thiazolylethyl, Furanyl, furylmethyl, furylethyl, thiophenol, thiophenoxymethyl, thiophenethyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, pyridyl, halopyridyl, Pyridylmethyl, halopyridylmethyl, pyridylethyl, halopyridylethyl;
  • n does not represent 0;
  • the compound of the formula (I) does not represent N-ethyl-N-((2-chlorothiazol-5-yl)methyl)-6-methylthio-3-nitropyridin-2-amine and N- Cyclobutyl-6-methylthio-3-nitropyridin-2-amine;
  • Halogen means fluorine, chlorine, bromine, iodine
  • Alkyl means a straight or branched alkyl group
  • Cycloalkyl means a saturated or unsaturated cycloalkyl group
  • Heterocycloalkyl a saturated or unsaturated heterocycloalkyl group having at least one N, O and/or S;
  • Alkenyl means straight or branched and may have a double bond at any position
  • Alkynyl means straight or branched and may have a triple bond at any position.
  • Preferred compounds of the invention are: in formula (I):
  • R 1 represents hydrogen or C 1 -C 12 alkyl
  • R 2 represents hydrogen, halogen or C 1 -C 12 alkyl
  • R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
  • VR 4 represents hydrogen or C 1 -C 12 alkyl
  • R 5 represents hydrogen, C 1 -C 12 alkyl, C 3 -C 8 cycloalkyl, phenyl, phenylmethyl, phenylethyl, thiazolyl, thiazolylmethyl, thiazolylethyl, Furanyl, furylmethyl, furylethyl, thiophenol, thiophenoxymethyl, thiophenethyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, pyridyl, halopyridyl, Pyridylmethyl, halopyridylmethyl, pyridylethyl, halopyridylethyl;
  • n does not represent 0;
  • the compound of the formula (I) does not represent N-ethyl-N-((2-chlorothiazol-5-yl)methyl)-6-methylthio-3-nitropyridin-2-amine and N- Cyclobutyl-6-methylthio-3-nitropyridin-2-amine.
  • R 1 represents hydrogen or C 1 -C 12 alkyl
  • R 2 represents hydrogen, halogen or C 1 -C 12 alkyl
  • R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
  • VR 4 represents hydrogen or C 1 -C 12 alkyl
  • R 5 represents hydrogen, C 1 -C 12 alkyl, C 3 -C 8 cycloalkyl, phenyl, phenylmethyl, phenylethyl, thiazolyl, thiazolylmethyl, thiazolylethyl, Furanyl, furylmethyl, furylethyl, thiophenol, thiophenoxymethyl, thiophenethyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, pyridyl, halopyridyl, Pyridylmethyl, halopyridylmethyl, pyridylethyl, halopyridylethyl;
  • a still further preferred compound of the invention is: in formula (I):
  • R 1 represents hydrogen or C 1 -C 12 alkyl
  • R 2 represents hydrogen, halogen or C 1 -C 12 alkyl
  • R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
  • VR 4 represents hydrogen or C 1 -C 12 alkyl
  • R 5 represents hydrogen, C 1 -C 12 alkyl, cyclopropyl, phenyl, phenylmethyl, thiazolyl, thiazolylmethyl, furyl, furylmethyl, thiophenol, thiophenol Methyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, pyridyl, halopyridyl, pyridylmethyl, halopyridylmethyl;
  • Preferred compounds of formula (I) according to the invention are:
  • the compounds of the invention may exist in the form of one or more isomers.
  • Isomers include enantiomers, diastereomers, geometric isomers.
  • a compound represented by the formula (I) of the present invention may form a geometric isomer (a different configuration is represented by Z and E, respectively) because a carbon-carbon double bond is bonded to a different substituent, and the present invention includes Z-isomers and E-isomers and mixtures thereof in any ratio.
  • the compound of the formula (I) of the present invention since one of the carbon atoms is bonded to four different substituents to form a stereoisomer (representing different configurations by R and S, respectively), the present invention includes the R form. Isomers and S isomers and mixtures thereof in any ratio.
  • the compounds of the general formula (I) of the present invention and certain compounds disclosed in the prior art belong to pyridyl sulfone and its derivatives, they have significantly different structural features and synthetic methods compared to the prior art. And the difference in these structural features allows the compounds of the present invention to have a broader spectrum and superior biological activity.
  • the compound of the formula (I) exhibits excellent activity against various pathogens in agriculture or other fields, and some compounds also exhibit good activity against weeds or pests/cockroaches. Accordingly, the technical solution of the present invention also includes the use of the compound of the general formula (I) as a bactericide, insecticide/caries agent in agriculture or other fields.
  • the invention further relates to a biologically effective amount of a compound of formula (I) and at least one additional composition selected from the group consisting of surfactants, solid diluents and liquid diluents for controlling harmful bacteria, pests/caries.
  • the invention further relates to a composition
  • a composition comprising a biologically effective amount of a compound of formula (I) and an effective amount of at least one additional biologically active compound or formulation for controlling harmful bacteria, pests/caries.
  • the invention also relates to a method of controlling harmful germs, pests, pests, comprising contacting a biologically effective amount of a compound of formula (I) with a harmful pathogen, pest/sputum or its environment. Also relates to such a harmful pathogen, pest/clam control method, harmful bacteria, pests/sputum or its environmentally effective amount of a compound of formula (I) or a compound containing formula (I) and a biologically effective amount of at least one additional The compound or mixture of preparations is contacted to control harmful bacteria, pests/caries.
  • the compound of the formula (I) of the present invention has a broad spectrum activity at an amount of from 15 to 5000 g of active ingredient per hectare: some compounds can be used for controlling harmful bacteria, and can also be used for controlling pests/cockroaches; and some compounds for certain targets It has a high biological activity, so that good results can be obtained at very low doses.
  • compositions of the invention are compositions containing the preferred compounds described above.
  • a preferred method is the method using the above preferred compounds.
  • the compound of the formula (I) provided by the present invention has biological activity and some compounds have good biological activity, and particularly exhibits activity in the control of agricultural, horticultural, flower and hygienic harmful bacteria and pests/cockroaches.
  • the pests described herein include, but are not limited to, the invention.
  • Oomycetes diseases such as downy mildew, white rust, squatting, cotton rot, blight, late blight, etc.;
  • Semi-bacterial diseases such as blight, root rot, blight, anthracnose, verticillium, scab, gray mold, brown spot, black spot, spot blight, early blight, round disease , leaf blight, stem-based rot, etc.;
  • Basidiomycosis diseases such as rust and smut
  • Ascomycetes such as powdery mildew, sclerotinia sclerotiorum (flax sclerotium, rapeseed sclerotium, soybean sclerotium, peanut sclerotium, tobacco sclerotium, capsicum sclerotium, eggplant sclerotium, bean sclerotium Disease, pea sclerotium disease, cucumber sclerotium disease, bitter gourd sclerotium disease, melon sclerotium disease, watermelon sclerotium disease, celery sclerotium disease, and scab.
  • Orthoptera is like a scorpion, such as cotton scorpion horse, rice scorpion horse, melon scorpion horse, Homoptera such as spider mites, locusts, locusts, lepidoptera such as oriental armyworm, Spodoptera litura, Plutella xylostella, Beet armyworm, Spodoptera litura, Pieris rapae, Hymenoptera such as leaf bee larvae, Diptera such as Aedes aegypti, Culex pipiens, flies; ⁇ such as orange full claw ⁇ , cotton leaf ⁇ , two-leaf ⁇ ;
  • Monocotyledonous weeds such as crabgrass, valerian, foxtail, hard grass, valerian, bromegrass, maiden, wheat, alkali, star grass, wild oats, ryegrass, bentgrass, bluegrass ;
  • Dicotyledonous weeds such as castor, sorghum, longan, scorpion, scorpion, scorpion, chamomile, etc.
  • the compound of the formula (I) of the present invention has excellent activity against rice sheath blight, corn rust, cucumber gray mold, and the like, and has a good control effect at a lower dose.
  • the above compounds can be advantageously used to protect crops, livestock and stocks that are important in agriculture and horticulture, as well as the environment in which humans often go, from the damage of germs, pests and mites.
  • the amount of the compound varies depending on various factors such as the compound used, the preprotectant, the type of the pest, the degree of infection, the climatic conditions, the method of administration, and the dosage form employed.
  • the present invention also encompasses a bactericidal, insecticidal/sputum composition having a compound of the formula (I) as an active ingredient.
  • the active ingredient in the bactericidal, insecticidal/tantalum composition is present in an amount between 0.5 and 99% by weight.
  • the bactericidal, insecticidal/sputum composition also includes agricultural, forestry, and hygienic acceptable carriers.
  • the compound of the formula (I) of the present invention When used alone, it is effective for controlling diseases, weeds, pests/cockroaches, and they can also be used together with other biochemical substances including other fungicides, insecticides/cockroaches. Agents, herbicides, plant growth regulators or fertilizers, etc., and thereby produce additional advantages and effects.
  • the preparation of the compound of the formula (I) provided by the present invention as an active ingredient can be prepared into any desired dosage form such as dry compressed granules, a flowable mixture, granules, wettable powders, water-dispersible granules, Emulsifying concentrates, powders, powder concentrates, microemulsions, suspending agents, emulsifiable concentrates, aqueous emulsions, soluble liquids, aqueous agents, dispersible liquids, suitable adjuvants including carriers (diluents) and other adjuvants Such as spreading agents, emulsifiers, wetting agents, dispersants, adhesives and decomposers.
  • These formulations contain the compound of the present invention in admixture with an inert, pharmacologically acceptable solid or liquid diluent.
  • compositions of the present invention may also be formulated into any desired dosage form such as dry compressed granules, flowable mixtures, granules, wettable powders, water-dispersible granules, emulsifiable concentrates, powders, powders.
  • Concentrates, microemulsions, suspensions, emulsifiable concentrates, aqueous emulsions, soluble liquids, aqueous agents, dispersible liquids, suitable adjuvants include carriers (diluents) and other adjuvants such as spreading agents, emulsifiers, wetting agents , dispersants, adhesives and decomposers.
  • These formulations contain the compound of the present invention in admixture with an inert, pharmacologically acceptable solid or liquid diluent.
  • the invention will be further illustrated by the use of some of the compounds listed in Tables 1 to 2 below, but is not intended to limit the invention.
  • the melting point given in the present invention is not corrected.
  • the compound of the formula (I) synthesized by the present invention is a viscous solid, some of the viscous solid refrigerators are solidified into a non-tacky solid after being placed; the compound of the formula (I) synthesized by the present invention is In the case of viscous liquids, some viscous liquids will solidify when placed in the refrigerator. All of the compounds in Table 1 were observed to have molecular ion peaks in LC-Mass (Agilent 1260/6120) and/or GC-mass (7890-5975C).
  • the compound of the formula (I) of the present invention can be obtained by the following reaction formula.
  • (III), (IV) and (V) in the reaction formula can be prepared by purchasing or according to the relevant reference methods;
  • L in the reaction formula is a leaving group such as chlorine, bromine, etc.
  • M is hydrogen, sodium or Potassium and the like, other substituents are as defined above unless otherwise specified.
  • the compound of formula (I) can be prepared by using a suitable solvent such as tetrahydrofuran, dioxane, water, ethanol, methanol, acetonitrile, dichloromethane, dichloroethane or N,N-dimethylformamide.
  • a suitable solvent such as tetrahydrofuran, dioxane, water, ethanol, methanol, acetonitrile, dichloromethane, dichloroethane or N,N-dimethylformamide.
  • the compound can be prepared by oxidation with a conventional oxidizing agent such as hydrogen peroxide, m-chloroperoxybenzoic acid, peracetic acid, hypochlorite, oxalic acid, t-butanol, potassium persulfate or sodium perborate.
  • a conventional oxidizing agent such as hydrogen peroxide, m-chloroperoxybenzoic acid, peracetic acid, hypochlorite,
  • the compound of the formula (II) can be produced by using a suitable solvent such as ethanol, methanol, tetrahydrofuran, dioxane, acetonitrile, dichloromethane, dichloroethane or N,N-dimethylformamide. Reacting with a compound of formula (IV) and a compound of formula (V) in the absence of a base or a suitable base such as potassium carbonate, sodium carbonate, triethylamine, pyridine, sodium hydride, sodium hydroxide or potassium hydroxide A compound represented by the formula (II).
  • a suitable solvent such as ethanol, methanol, tetrahydrofuran, dioxane, acetonitrile, dichloromethane, dichloroethane or N,N-dimethylformamide. Reacting with a compound of formula (IV) and a compound of formula (V) in the absence of a base or a suitable base such as potassium carbonate, sodium carbonate, tri
  • EXAMPLE 1 This example illustrates the preparation of compound 28 in Table 1.
  • N-ethyl-6-methylthio-3-nitropyridin-2-amine (Compound 28 in Table 1) N-ethyl-6-chloro-3-nitropyridin-2-amine (9 mmol), 25
  • the sodium methylthiolate solution (5 mL) and tetrahydrofuran (20 mL) were reacted to completion at 0 ° C to 50 ° C, poured into ice water, extracted with ethyl acetate, and the organic phase was washed with water, dried over anhydrous sodium sulfate and evaporated.
  • the crude product was purified by column chromatography (EtOAcEtOAcEtOAcEtOAcEtOAcEtOAcEtOAc
  • EXAMPLE 2 This example illustrates the preparation of compound 29 in Table 1.
  • N-ethyl-6-methylsulfonyl-3-nitropyridin-2-amine (Compound 29 in Table 1) N-ethyl-6-methylthio-3-nitropyridin-2-amine (4 mmol , m-chloroperoxybenzoic acid (4mmol) and dichloromethane (10mL), after reacting to complete at 0 ° C to 35 ° C, adding ice brine, liquid separation, the aqueous layer is extracted with dichloromethane, the organic phase is combined and After washing with water and dried over anhydrous sodium sulfate, the solvent was evaporated.
  • EXAMPLE 3 This example illustrates the preparation of compound 30 in Table 1.
  • N-ethyl-6-methylsulfonyl-3-nitropyridin-2-amine (Compound 30 in Table 1) N-ethyl-6-methylthio-3-nitropyridin-2-amine (4 mmol) , m-chloroperoxybenzoic acid (10 mmol) and dichloromethane (10 mL) were reacted to completion at 25 ° C to reflux temperature, iced brine was added, the organic phase was separated, and the aqueous phase was extracted with dichloromethane. After washing with water and dried over anhydrous sodium sulfate, the solvent was evaporated.
  • N-(1-phenylethyl)-6-methylthio-3-nitropyridin-2-amine (Compound 98 in Table 1) N-(1-phenylethyl)-6-chloro-3- Nitropyridin-2-amine (8mmol), 25% sodium thiomethoxide solution (5mL) and tetrahydrofuran (10mL), after reacting at 0 ° C to 50 ° C to complete, add ice brine, ethyl acetate extraction, combined organic phase The mixture was washed with water and dried over anhydrous sodium sulfate and evaporated.
  • EXAMPLE 5 This example illustrates the preparation of compound 100 in Table 1.
  • N-(1-phenylethyl)-6-methylsulfonyl-3-nitropyridin-2-amine (Compound 100 in Table 1) N-(1-phenylethyl)-6-methylthio- 3-nitropyridin-2-amine (4mmol), m-chloroperoxybenzoic acid (10mmol) and dichloromethane (10mL), reacted at 25 ° C to the reflux temperature of the system to complete, add ice brine, liquid separation, two The aqueous layer was extracted with chloromethane. EtOAc was evaporated.
  • EXAMPLE 6 This example illustrates the preparation of compound 101 in Table 1.
  • EXAMPLE 8 This example illustrates the preparation of compound 242 in Table 1.
  • N-phenylethyl-6-chloro-3-nitropyridin-2-amine 2,6-dichloro-3-nitropyridine (10 mmol)
  • potassium carbonate (10 mmol)
  • ethanol (20 mL)
  • phenethylamine The (10 mmol) ethanol solution was reacted to completion at 0 °C to 50 °C.
  • the reaction mixture was poured into EtOAc EtOAc.
  • N-phenylethyl-6-methylthio-3-nitropyridin-2-amine (Compound 242 in Table 1) N-phenylethyl-6-chloro-3-nitropyridin-2-amine ( 8mmol), 25% sodium thiomethoxide solution (5mL) and tetrahydrofuran (20mL) were reacted to complete at 0 ° C to 50 ° C, poured into ice water, extracted with ethyl acetate, and the organic phase was washed with water and anhydrous sodium sulfate After drying, the solvent was evaporated. EtOAc m.
  • N-phenylethyl-6-methylsulfoxide-3-nitropyridin-2-amine (Compound 243 in Table 1) N-phenylethyl-6-methylthio-3-nitropyridine-2 -amine (4 mmol), m-chloroperoxybenzoic acid (4 mmol) and dichloromethane (10 mL), EtOAc EtOAc (EtOAc) The combined organic phases were dried with EtOAc EtOAc m.
  • EXAMPLE 10 This example illustrates the preparation of compound 244 in Table 1.
  • N-phenylethyl-6-methylsulfonyl-3-nitropyridin-2-amine (Compound 244 in Table 1) N-phenylethyl-6-methylthio-3-nitropyridine-2- Amine (4mmol), m-chloroperoxybenzoic acid (10mmol) and dichloromethane (10mL), after reaction at 25 ° C to the reflux temperature of the system to complete, add ice brine, separate the liquid, extract the aqueous layer with dichloromethane, and combine organic The mixture was washed with water and dried over anhydrous sodium sulfate.
  • the synthesized compounds were sterilized and tested for insecticidal/sputum.
  • the results of some experiments are as follows.
  • test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted to the desired concentration with sterile water containing 0.2% Tween80 emulsifier, and a blank containing no test compound is provided.
  • a suitable solvent such as N,N-dimethylformamide (DMF)
  • sterile water containing 0.2% Tween80 emulsifier 0.2% Tween80 emulsifier
  • the culture dish is placed in a constant temperature biochemical incubator at 28 °C, and the mycelial growth diameter is measured after 4 days.
  • the EXCEL statistical software was used for analysis and the mycelial growth inhibition rate (%) was calculated.
  • the activity is divided into four grades A, B, C, and D with respect to the blank control, 100 ⁇ inhibition rate (%) ⁇ 90 is A grade, 90 > inhibition rate (%) ⁇ 70 is B grade, 70 > inhibition Rate (%) ⁇ 50 is C level, 50> inhibition rate (%) ⁇ 0 is D level.
  • the synthesized compounds were determined for phytophythora capsici, Botrytis cinerea, and Sclerotonia sclerotiorum. Bactericidal activity.
  • compounds 03, 29, 45, 54, 96, 97, 243, 246, 339, 340, 343, 1096 have Class A activity against Fusarium graminearum, compounds 30, 32, 38, 39 , 91, 333, etc.
  • compounds 03, 29, 30, 54, 171, 172, 243 have Class A activity against Phytophthora capsici, compounds 30, 32, 33, 35, 36, 38, 39, 48, 96 , 97, 100, 333, 334, 340, etc. have class B activity against Phytophthora capsici, compounds 45, 85, 89, 103, 165, 166, 244, 246, 252, 270, 279, 328, 336, 337, 339, 343, 342, 345, 1094, etc.
  • compounds 29, 30, 36, 246, 342, 345 have Class A activity against Botrytis cinerea
  • compounds 01, 28, 29, 32, 35, 38, 45, 48, 54, 89 , 96, 100, 171, 243, 252, 270, 279, 328, 343, etc. have class B activity against Botrytis cinerea
  • compounds 03, 04, 33, 39, 43, 97, 103, 280, 333, 334, 335, 337, 339, 340, 341, 495, 496, 510, 1096 have C-level activity against Botrytis cinerea; at the test concentration of 10 mg/L, compounds 01, 28, 29, 30, 35, 36, 89, etc.
  • Grade B activity against Botrytis cinerea Compounds 32, 38, 45, 96, 243, 246 have Class C activity against Botrytis cinerea; Compounds 01, 28, 29, 32, 35 at 5 mg/L test concentration , 36, 38, etc. have C-class activity against Botrytis cinerea.
  • the pathogen has class A activity, and compounds 29, 35, 39, 48, 89, 100, 103, 243, 270, 333, 342 have class B activity against Sclerotinia sclerotiorum, compounds 01, 04, 101, 166, 171, 242, 244, 252, 271, 279, 280, 334, 337, 339, 340, 344, 496 have C-class activity against Sclerotinia sclerotiorum; at 10 mg/L test concentration, compounds 30, 33, 328, etc.
  • Sclerotinia sclerotiorum has class A activity
  • compounds 29, 30, 36, 45, 333 have class B activity against Sclerotinia sclerotiorum
  • compounds 35, 38, 39, 54, 89, 100 have C grade for Sclerotinia sclerotiorum Activity
  • compounds 29, 30, 33, 328 have B-level activity against Sclerotinia sclerotiorum
  • compounds 30, 36, 38, 39, 45, 89, 333 have C against Sclerotinia sclerotiorum Grade activity
  • Compounds 29, 30, 33, etc. have class C activity against Sclerotinia sclerotiorum at a concentration of 2.5 mg/L.
  • test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted to the desired concentration with sterile water containing 0.2% Tween80 emulsifier, and a blank containing no test compound is provided.
  • a suitable solvent such as N,N-dimethylformamide (DMF)
  • sterile water containing 0.2% Tween80 emulsifier 0.2% Tween80 emulsifier
  • a blank containing no test compound is provided for the control.
  • the treatment was repeated 4 times; the Cucumber ash pathogen was transferred to the PDA plate and cultured, transferred to the PD medium, and cultured in a constant temperature water bath for 4 days; the cultured hyphae ball was pulverized with a homogenizer and formulated with water.
  • test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted to the desired concentration with sterile water containing 0.2% Tween80 emulsifier, and a blank containing no test compound is provided.
  • a suitable solvent such as N,N-dimethylformamide (DMF)
  • compounds 29, 48, 100, 243, 244, 336, 337, 339, 340, etc. have more than 90% control activity against corn rust; compounds 30, 46, 98, 253, 280, 334, 346 It has more than 80% control activity against corn rust; compounds 274, 510 have more than 70% control activity against corn rust.
  • the compounds 243, 244 and the like have more than 80% control activity against corn rust.
  • the compounds 243, 244 and the like have a control activity against corn rust of 70% or more.
  • the phenyl sulfone or its derivative represented by the formula (B), the formula (C) and the formula (D) does not have a control effect on corn rust at a dose of 100 mg/L of not more than 50%.
  • compounds 29, 30, 85, 97, 100, 244, 252, 337 and the like have more than 90% control activity against rice sheath blight; compounds 83, 97, 171, 243, 246, 270, 328 339, 343, 344, etc. have more than 80% control activity against rice sheath blight; compounds 247, 333, 334, 340, 342 have more than 70% control activity against rice sheath blight.
  • compounds 97, 252, and 244 have more than 90% control activity against rice sheath blight; 83, 85, and 243 have more than 70% control activity against rice sheath blight.
  • compound 244 has more than 90% control activity against rice sheath blight; compound 97 has more than 80% control activity against rice sheath blight; compound 83, 85, 243, 252, etc. Blight has more than 70% control activity.
  • the phenyl sulfone or its derivative represented by formula (B), formula (C) and formula (D) has a control effect against rice sheath blight at a dose of 100 mg/L of not more than 50%; formula (B), formula The phenyl sulfone or its derivative represented by (C) and formula (D) does not have a control effect against rice sheath blight at a dose of 50 mg/L of not more than 30%.
  • Example 15 Bactericidal activity against wheat white powder pathogen (Erisiphe griminis) (pot method)
  • test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted to the desired concentration with sterile water containing 0.2% Tween80 emulsifier, and a blank containing no test compound is provided.
  • a suitable solvent such as N,N-dimethylformamide (DMF)
  • For the control take the pots with a stem of about 15cm, and soak the seeds of 20 full and healthy seeds of wheat, and use them for the test after growing the leaves; take the prepared wheat seedlings with a certain concentration of spray treatment, one Inoculation of the bacteria after the day. Each treatment was repeated 3 times, and a blank containing no test compound was set as a control. After moisturizing and warming culture until the onset of the blank control, the area of the lesion was examined and the drug control effect was calculated. Activity is relative to the blank control as a percentage.
  • compounds 341 and 343 have more than 90% control effect on wheat powdery mildew; compounds 168, 246, 344, 510 have more than 80% control effect on wheat powdery mildew; compounds 247, 252, etc. Wheat powdery mildew has more than 70% control effect.
  • the phenyl sulfone or the derivative thereof represented by the formula (B), the formula (C) and the formula (D) has a control effect against wheat powdery mildew of 0% at a concentration of 500 mg/L.
  • the aphid was selected as a subject, and the activity of the compound of the present invention against aphids was measured by a dipping method.
  • Impregnation method The test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and diluted with water containing 0.2% Tween80 emulsifier to the desired concentration, and the blank containing no test compound is Control, repeated 3 times per treatment.
  • a suitable solvent such as N,N-dimethylformamide (DMF)
  • Tween80 emulsifier to the desired concentration
  • the blank containing no test compound is Control, repeated 3 times per treatment.
  • the Aphis fabae is attached to the newly-extracted bean seedlings, and each plant is connected to more than 20 heads.
  • the bean seedlings are immersed together with the test insects in the liquid of the formula (I) provided by the present invention, and taken out after 5 seconds.
  • the excess liquid was aspirated, inserted into the absorbent sponge, covered with a glass tube, and the number of surviving and dead insects was checked after 24 hours, and the results were averaged.
  • the activity was divided into four levels A, B, C, and D, and 100% ⁇ mortality (%) ⁇ 90 for grade A, 90 > mortality (%) ⁇ 70 for grade B, relative to the blank control. 70> Mortality (%) ⁇ 50 is C grade, 50 > mortality (%) ⁇ 0 is D grade.
  • the results indicate that the compounds of the present invention are active against broad bean meal, and some of the results are listed below:
  • compounds 165 and 172 have Class A activity against aphids; Compounds 46, 247, 279, 326, 341, 343, 495 have Class B activity against aphids; Compounds 52, 54, 166, 246, 332 344, 345, 494, 524, etc. have class C activity on aphids.
  • compound 172 or the like has a class B activity against aphids
  • compound 165 or the like has a class C activity on aphids.
  • the phenyl sulfone or the derivative thereof represented by the formula (B), the formula (C) and the formula (D) has a mortality rate against aphids of less than 50% at a concentration of 500 mg/L.
  • test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted with the water containing 0.2% Tween80 emulsifier to the desired concentration, and the blank containing no test compound is used as a control. , repeated 3 times for each treatment.
  • a suitable solvent such as N,N-dimethylformamide (DMF)
  • Tween80 emulsifier to the desired concentration
  • the blank containing no test compound is used as a control. , repeated 3 times for each treatment.
  • compounds 36, 39 have A-grade activity against cotton red spider; compounds 33, 345, 495, 1114 have B-grade activity against cotton red spider; compounds 168, 1096 and other cotton-red spiders have grade C active.
  • compound 345 and the like had a class C activity against cotton red spider.
  • the phenyl sulfone or the derivative thereof represented by the formula (B), the formula (C) and the formula (D) has a mortality rate of less than 15% at a concentration of 500 mg/L.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
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  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

L'invention concerne une pyridine sulfone telle que représentée par la formule (I) et des dérivés de celle-ci, ainsi qu'un procédé de préparation et une application de la pyridine sulfone. Dans la formule (I), n, m, R, R1, R2, R3, R4 et R5 ont les définitions données dans la description. Le composé de formule (I) selon la présente invention a des activités biologiques à large spectre telles que des activités bactéricides et/ou insecticides/acariens, en particulier, des activités contre des maladies telles que le flétrissement de la gaine du riz et la rouille du maïs.
PCT/CN2018/123428 2017-12-27 2018-12-25 Pyridine sulfone, dérivés de celle-ci, procédé de préparation associé, et application correspondante Ceased WO2019128976A1 (fr)

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CN116082324A (zh) * 2022-12-13 2023-05-09 浙江工业大学 含杂环的1,2,4-噁二唑化合物及其制备方法和应用

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CN103242225A (zh) * 2012-02-13 2013-08-14 湖南化工研究院 吡啶甲胺基吡啶类化合物及其制备方法
CN105753779A (zh) * 2014-12-18 2016-07-13 湖南化工研究院有限公司 2-吡啶胺类化合物及其制备方法与应用
CN105777741A (zh) * 2014-12-18 2016-07-20 湖南化工研究院有限公司 噻唑烷基吡啶胺类化合物及其制备方法与应用

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JP3023794B2 (ja) * 1989-05-17 2000-03-21 日本バイエルアグロケム株式会社 殺虫性ニトロ置換ヘテロ環式化合物

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CN103242225A (zh) * 2012-02-13 2013-08-14 湖南化工研究院 吡啶甲胺基吡啶类化合物及其制备方法
CN105753779A (zh) * 2014-12-18 2016-07-13 湖南化工研究院有限公司 2-吡啶胺类化合物及其制备方法与应用
CN105777741A (zh) * 2014-12-18 2016-07-20 湖南化工研究院有限公司 噻唑烷基吡啶胺类化合物及其制备方法与应用

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116082324A (zh) * 2022-12-13 2023-05-09 浙江工业大学 含杂环的1,2,4-噁二唑化合物及其制备方法和应用

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