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WO2019056246A1 - 含有磺酰基结构三嗪酮衍生物及其制备方法和在杀虫、杀菌方面的应用 - Google Patents

含有磺酰基结构三嗪酮衍生物及其制备方法和在杀虫、杀菌方面的应用 Download PDF

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Publication number
WO2019056246A1
WO2019056246A1 PCT/CN2017/102600 CN2017102600W WO2019056246A1 WO 2019056246 A1 WO2019056246 A1 WO 2019056246A1 CN 2017102600 W CN2017102600 W CN 2017102600W WO 2019056246 A1 WO2019056246 A1 WO 2019056246A1
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substituted
group
unsubstituted
formula
alkyl
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PCT/CN2017/102600
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English (en)
French (fr)
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汪清民
宋红健
杨岩
刘玉秀
王兹稳
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南开大学
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Priority to PCT/CN2017/102600 priority Critical patent/WO2019056246A1/zh
Priority to EP17892064.1A priority patent/EP3486237B1/en
Priority to US16/073,214 priority patent/US11203577B2/en
Publication of WO2019056246A1 publication Critical patent/WO2019056246A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
    • C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
    • C07D253/06—1,2,4-Triazines
    • 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
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/707—1,2,3- or 1,2,4-triazines; Hydrogenated 1,2,3- or 1,2,4-triazines
    • 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the invention belongs to the technical field of pesticides, and particularly relates to a sulfonyl-containing triazinone derivative, a preparation method thereof and application in insecticide and sterilization.
  • Pymetrozine is a new heterocyclic insecticide discovered by Ciba-Geigy in 1988. It has a unique mode of action, high selectivity, no cross-resistance with traditional insecticides, and environmental safety. It has a unique control effect on sucking mouthparts pests, especially aphids. Therefore, since the advent of pymetrozine, it has been widely used in farmland crops and ornamental plants to control the damage of aphids, whiteflies and black-tailed spider mites. However, due to the unique mode of action of pyridoxine, only three varieties of such insecticides have been commercialized so far, namely pyridone, R-768 and Pyrifluquinazon.
  • the sulfonyl-containing triazinone derivative of this patent exhibits excellent insecticidal activity and also has bactericidal activity.
  • a triazinone derivative containing a sulfonyl structure wherein the triazinone derivative is a compound represented by the formula (I a ):
  • R 1 is C1-C12 alkyl, C3-C6 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted benzyl, substituted or Unsubstituted phenethyl, substituted or unsubstituted phenylpropyl, substituted or unsubstituted phenylbutyl, nitrogen-containing heterocyclic ring containing 1 to 10 carbon atoms, oxygenated from 1 to 10 carbon atoms Heterocyclic ring, sulfur-containing heterocyclic ring having 1 to 10 carbon atoms; substituted phenyl group, substituted naphthyl group, substituted benzyl group, substituted phenethyl group, substituted phenylpropyl group and substituted phenylbutyl group
  • the substituents are each independently selected from the group consisting of hydroxyl, halogen, cyano,
  • the second aspect of the present invention provides a method for producing the above triazinone derivative, which comprises: formulating an aminotriazinone of the formula (II) with a formula (in the presence of an acid binding agent) in an organic solvent; The sulfonyl chloride compound shown in III) is subjected to a substitution reaction to obtain a compound represented by the formula (I a );
  • a triazinone derivative containing a sulfonyl structure wherein the triazinone derivative is a compound represented by the formula ( Ib ):
  • each R 1 is independently selected from a C1-C12 alkyl group, a C3-C6 cycloalkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a substituted or unsubstituted benzyl group.
  • the substituted phenylbutyl substituents are each independently selected from the group consisting of hydroxy, halo, cyano, nitro, ester, trifluoromethyl, trifluoromethoxy, amide, C1-C6 hydrocarbyl, C1-C6 One or more of an alkoxy
  • a process for the preparation of the above triazinone derivative which comprises: formulating an aminotriazinone of the formula (II) with a formula (in the presence of an acid-binding agent) in an organic solvent; The sulfonyl chloride compound shown in III) is subjected to a substitution reaction to obtain a compound represented by the formula ( Ib );
  • the fifth aspect of the present invention provides the use of the above triazinone derivative for insecticidal action.
  • the sixth aspect of the invention provides the use of the above triazinone derivative for sterilization.
  • the triazinone derivatives provided by the present invention exhibit very excellent insecticidal activity and bactericidal activity.
  • a triazinone derivative containing a sulfonyl structure wherein the triazinone derivative is a compound represented by the formula (I a ):
  • R 1 is C1-C12 alkyl, C3-C6 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted benzyl, substituted or Unsubstituted phenethyl, substituted or unsubstituted phenylpropyl, substituted or unsubstituted phenylbutyl, nitrogen-containing heterocyclic ring containing 1 to 10 carbon atoms, oxygenated from 1 to 10 carbon atoms Heterocyclic ring, sulfur-containing heterocyclic ring having 1 to 10 carbon atoms; substituted phenyl group, substituted naphthyl group, substituted benzyl group, substituted phenethyl group, substituted phenylpropyl group and substituted phenylbutyl group
  • the substituents are each independently selected from the group consisting of hydroxyl, halogen, cyano,
  • the sulfonyl-containing triazinone derivative provided by the first aspect and the third aspect of the present invention can be summarized by the following formula (I):
  • C1-C12 alkyl group may be, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentane Base, n-hexyl, n-heptyl, n-octyl, n-decyl, n-decyl, n-undecyl, n-dodecyl and the like.
  • the hydrocarbon group of C1-C6 and the alkyl group of C1-C4 may be selected from the specific examples of the above-mentioned alkyl group and may be appropriately defined.
  • the alkoxy group of C1-C6 may be an alkoxy group formed by the above specific examples satisfying the alkyl group defined by 1 to 6 carbon atoms.
  • cycloalkyl group of C3-C6 may be, for example: Wait.
  • the nitrogen-containing heterocyclic ring having 1 to 10 carbon atoms may be an unsaturated nitrogen heterocyclic ring or a saturated nitrogen heterocyclic ring as long as the ring structure of the heterocyclic ring has a nitrogen atom as a structural atom and the heterocyclic ring has a carbon atom Numbers from 1 to 10, such as unsubstituted or C1-C6 alkyl-substituted pyrrole, unsubstituted or C1-C6 alkyl-substituted hydropyrrole, unsubstituted or C1-C7 Alkyl substituted imidazole, unsubstituted or C1-C7 alkyl substituted hydrogenated imidazole, unsubstituted or C1-C5 alkyl substituted pyridine, unsubstituted or C1-C5 alkyl substituted hydrogenated pyridine , unsubstituted or C1-C7 alkyl-substituted pyrazole
  • the oxygen-containing heterocyclic ring having 1 to 10 carbon atoms may be an unsaturated oxygen heterocyclic ring or a saturated oxygen heterocyclic ring as long as the heterocyclic ring structure has oxygen as a structural atom and the heterocyclic ring has a carbon atom.
  • Numbers from 1 to 10 such as unsubstituted or C1-C6 alkyl-substituted furan, unsubstituted or C1-C6 alkyl-substituted hydrofuran, unsubstituted or C1-C7 alkyl substituted Oxazole, unsubstituted or C1-C7 alkyl-substituted hydrogenated oxazole, unsubstituted or C1-C3 alkyl-substituted 1,3-benzodioxan, unsubstituted or C1-C2 Alkyl-substituted 1,4-benzodioxins and the like.
  • the sulfur-containing heterocyclic ring having 1 to 10 carbon atoms may be an unsaturated sulfur heterocyclic ring or a saturated sulfur heterocyclic ring as long as the ring structure of the heterocyclic ring has sulfur as a structural atom and the heterocyclic ring has carbon atoms.
  • Numbers from 1 to 10 such as unsubstituted or C1-C6 alkyl-substituted thiophenes, unsubstituted or C1-C6 alkyl-substituted thiophenes, unsubstituted or C1-C7 alkyl substitutions Thiazole, unsubstituted or C1-C7 alkyl substituted thiazole or the like.
  • R 1 is C1-C8 alkyl, C3-C6 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted benzyl, substituted Or unsubstituted phenethyl, substituted or unsubstituted phenylpropyl, substituted or unsubstituted phenylbutyl, nitrogen-containing heterocyclic ring containing 2-8 carbon atoms, containing 2-8 carbon atoms Oxyheterocyclic ring, sulfur-containing heterocyclic ring having 2-8 carbon atoms; substituted phenyl group, substituted naphthyl group, substituted benzyl group, substituted phenethyl group, substituted phenylpropyl group and substituted phenyl group
  • the substituents of the group are each independently selected from the group consisting of hydroxyl, F, Cl, Br, I, hydroxy
  • the second aspect of the present invention provides a method for producing the above triazinone derivative, which comprises: formulating an aminotriazinone of the formula (II) with a formula (in the presence of an acid binding agent) in an organic solvent; The sulfonyl chloride compound shown in III) is subjected to a substitution reaction to obtain a compound represented by the formula (I a );
  • the preparation process can be represented by the following route 1:
  • the compound of the formula (III) can be specifically selected according to the desired formula (Ia), and R 1 is as described above, and the present invention will not be repeated herein.
  • the molar ratio of the aminotriazinone represented by the formula (II) to the sulfonyl chloride compound represented by the formula (III) is from 1:0.8 to 1.2, preferably from 1:1 to 1.1.
  • the acid binding agent is one or more of sodium carbonate, potassium carbonate, cesium carbonate, triethylamine and pyridine.
  • the amount of the acid binding agent can be varied within a wide range, for example, the molar ratio of the aminotriazinone and the acid binding agent represented by the formula (II) is 1:0.08-0.5, preferably 1:0.1. -0.3.
  • pyridine can also be used as a solvent for the above method, and when pyridine is used as a solvent, it is only necessary to satisfy the amount of the solvent, and it is not required to be limited by the amount.
  • the organic solvent is one or more of methanol, ethanol, pyridine, N,N-dimethylformamide, and dimethyl sulfoxide.
  • the organic solvent is used in an amount such that the concentration of the aminotriazinone represented by the formula (II) is from 0.05 to 0.5 mmol/mL.
  • the conditions of the substitution reaction include a temperature of 15 to 40 ° C (preferably 20 to 35 ° C) for 4 to 12 hours.
  • a triazinone derivative containing a sulfonyl structure wherein the triazinone derivative is a compound represented by the formula ( Ib ):
  • each R 1 is independently selected from a C1-C12 alkyl group, a C3-C6 cycloalkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a substituted or unsubstituted benzyl group.
  • the substituted phenylbutyl substituents are each independently selected from the group consisting of hydroxy, halo, cyano, nitro, ester, trifluoromethyl, trifluoromethoxy, amide, C1-C6 hydrocarbyl, C1-C6 One or more of an alkoxy
  • R 1 in the present invention may be selected from the group consisting of a 1-12 carbon alkyl group, a 3-6 carbon cycloalkyl group, a phenyl group, a benzyl group, a phenethyl group, a phenylpropyl group, and a phenyl group.
  • Base 1-10 carbon nitrogen-containing heterocycle, 1-10 carbon oxygen-containing heterocycle, 1-10 carbon sulfur-containing heterocycle, substituted phenyl (wherein the substituent may be hydrogen, hydroxyl, halogen atom, cyano group, nitrate Base, ester group, fluorine, trifluoromethyl, trifluoromethoxy, amide, 1-5 carbon, 1-6 alkoxy, 1-4 alkylcarbonyloxy, 1-4 carbona An oxycarbonyloxy group; and at the same time containing 2-3 of the above-mentioned substituents).
  • substituent may be hydrogen, hydroxyl, halogen atom, cyano group, nitrate Base, ester group, fluorine, trifluoromethyl, trifluoromethoxy, amide, 1-5 carbon, 1-6 alkoxy, 1-4 alkylcarbonyloxy, 1-4 carbona An oxycarbonyloxy group; and at the same time containing 2-3 of the above-mentioned substituents).
  • R 1 in the formula (I b ) may be the same or different, and each of them is independently selected, wherein R 1 in the formula (I b ) may be described by the above formula (I a ) The selection is made in the relevant group, and the invention is not limited herein.
  • each R 1 is independently selected from C1-C8 alkyl, C3-C6 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted Benzyl, substituted or unsubstituted phenethyl, substituted or unsubstituted phenylpropyl, substituted or unsubstituted phenylbutyl, nitrogen-containing heterocyclic ring containing 2-8 carbon atoms, containing 2-8 Oxygen-containing heterocyclic ring of one carbon atom, sulfur-containing hetero ring containing 2-8 carbon atoms; substituted phenyl group, substituted naphthyl group, substituted benzyl group, substituted phenethyl group, substituted phenylpropyl group
  • substituted phenylbutyl substituents are each independently selected from the group consisting of hydroxyl, F, Cl, Br
  • the compound of formula ( Ib ) is selected from one of the compounds shown in the formula:
  • a process for the preparation of the above triazinone derivative which comprises: formulating an aminotriazinone of the formula (II) with a formula (in the presence of an acid-binding agent) in an organic solvent; The sulfonyl chloride compound shown in III) is subjected to a substitution reaction to obtain a compound represented by the formula ( Ib );
  • the compound represented by the formula (III) can be specifically selected according to the desired formula (I b ), and R 1 is as described above, and the present invention will not be repeated herein.
  • the molar ratio of the aminotriazinone represented by the formula (II) to the sulfonyl chloride compound represented by the formula (III) is from 1:1.8 to 2.5, preferably from 1:2 to 2.4.
  • the acid binding agent is one or more of sodium carbonate, potassium carbonate, cesium carbonate, triethylamine and pyridine.
  • the amount of the acid binding agent can be varied within a wide range, for example, the molar ratio of the aminotriazinone and the acid binding agent represented by the formula (II) is 1:0.08-0.5, preferably 1:0.1. -0.3.
  • pyridine can also be used as a solvent for the above method, and when pyridine is used as a solvent, it is only necessary to satisfy the amount of the solvent, and it is not required to be limited by the amount.
  • the organic solvent is one or more of methanol, ethanol, pyridine, N,N-dimethylformamide, and dimethyl sulfoxide.
  • the organic solvent is used in an amount such that the concentration of the aminotriazinone represented by the formula (II) is from 0.05 to 0.5 mmol/mL.
  • the conditions of the substitution reaction include a temperature of 15 to 40 ° C (preferably 20 to 35 ° C) for 4 to 12 hours.
  • the fifth aspect of the present invention provides the use of the above triazinone derivative for insecticidal action.
  • the triazinone derivative provided by the invention has high insecticidal activity, and particularly has higher killing activity against one or more of aphids, mosquito larvae, cotton bollworm, corn borer and armyworm.
  • the sulfonyl-containing triazinone derivative of the present invention is preferably selected from one or more of the following compounds in view of obtaining higher insecticidal activity:
  • the sulfonyl-containing triazinone derivative of the present invention exhibits a good acaricidal activity, wherein the compound I a -10, I a -11, I a -12, I a -13, I a -14 I a -15 exhibited 25%, 15%, 30%, 10%, 35%, 10% insecticidal activity at a concentration of 2.5 mg/kg, while pymetrozine had no insecticidal activity at the same concentration.
  • some compounds showed good activity against mosquito larvae.
  • compounds I a -19, I a -23 and I a -26 showed 60%, 30% and 20% respectively for mosquito larvae.
  • the activity, especially the compound I a- 22, showed 40% insecticidal activity against mosquito larvae at a concentration of 0.5 mg/kg.
  • all compounds showed insecticidal activity against cotton bollworm, corn borer and armyworm.
  • the present invention also provides a method for insecticidal action using the above triazinone derivative as an insecticide.
  • the sixth aspect of the invention provides the use of the above triazinone derivative for sterilization.
  • the triazinone derivative provided by the invention has high insecticidal activity, especially for causing tomato early blight, wheat gibberella, potato late blight, Phytophthora capsici, rape sclerotia, cucumber gray mold, rice stalk, cucumber One or more of pathogens of withered, peanut brown spots, apple rings, wheat stalks, corn plaques, watermelon anthrax and rice seedlings.
  • the sulfonyl-containing triazinone derivative of the present invention is preferably selected from one or more of the following compounds in view of obtaining higher bactericidal activity:
  • the compounds I a -4, I a -12 and I b -5 showed good antibacterial activity against various pathogenic bacteria at a concentration of 50 mg/kg.
  • the present invention also provides a method of sterilizing using the above triazinone derivative as a bactericide.
  • aminotriazinone (0.26 g, 2 mmol, purchased from TCI (Shanghai) Chemical Industry Development Co., Ltd.
  • pyridine (20 mL) was stirred and dissolved, and methylsulfonyl chloride (0.24 g, 2.1 mmol) was added. It was purchased from Anheji Chemical Co., Ltd.) and stirred at room temperature overnight, and the reaction was completed by TLC.
  • Example 3 Determination of acaricidal, the measurement procedure is as follows:
  • the aphid activity was determined as follows: the test insect was Aphis laburni Kaltenbach, a normal population fed by laboratory broad bean leaves. Weigh the drug, add 1mL DMF to dissolve, add two drops of Tween-20 emulsifier, add a certain amount of distilled water, stir evenly, and prepare the liquid with the required concentration (the specific concentration is shown in the table). Immerse the leaves of the broad bean with aphids (about 60) into the medicine for 5 seconds, take them out and dry them, use the filter paper to blot the excess medicine, then insert the broad bean branches into the absorbent sponge, cover the branches with a glass cover, and seal with gauze. The results were checked 96 hours and each compound was repeated 3 times. The control only added emulsifier and solvent to the distilled water and stirred well.
  • the partial sulfonyl structural triazinone derivative exhibited a good 100% acaricidal activity at a concentration of 10 mg/kg.
  • I a -1, I a -9, I a -16, I a -17, I a -18, I a -19, I a -21, I a -22, I a - 23, I a -25, I a -26, I a -27, I b -1 exhibits activity comparable to that of pymetrozine.
  • the compounds I a -10, I a -11, I a -12, I a -13, I a -14, I a -15 still showed 25%, 15%, 30% at a concentration of 2.5 mg/kg. , 10%, 35%, 10% insecticidal activity, while pymetrozine has no insecticidal activity at the same concentration.
  • Example 4 Determination of the activity of mosquito larvae, the measurement procedure is as follows:
  • the experimental method of mosquito larvae the subspecies of Culex pipiens pallens, the normal population raised indoors. About 5 mg of the test compound was weighed into a penicillin vial, and 5 mL of acetone (or a suitable solvent) was added thereto, and dissolved by shaking to obtain a 1000 ppm mother liquor. Pipette 1 mL of mother liquor into a 100 mL beaker containing 89 mL of water, and select 10 4-year-old larvae of the first mosquito, and pour them into a beaker together with 10 mL of the stock solution. The concentration of the liquid solution is 10 ppm (the preparation of other chemical concentrations) Obtained by diluting the corresponding multiples). Place in a standard processing room and check the results 24h. An aqueous solution containing 0.5 mL of the test solvent was used as a blank control.
  • Example 5 Determination of the activity of cotton bollworm, corn borer, and armyworm, the measurement procedure is as follows:
  • the experimental method of cotton bollworm feed mixed method, 3mL was taken from the configured solution and added to about 27g of the newly configured feed, thereby obtaining the required concentration diluted ten times. After mixing the chemicals, evenly pour them into a clean 24-well plate. After cooling, connect to 24 third-instar cotton bollworms and observe the results after 3-4 days.
  • Test method for corn mash Dip leaf method, after the required concentration after the configuration, the leaves with a diameter of about 5-6 cm are immersed in the liquid for 5-6 seconds, taken out, placed on absorbent paper to dry, placed in the designated In the culture dish, 10 3rd instar larvae were inserted and the worms at 27 ⁇ 1°C were placed. The results were examined after 3-4 days of observation in the room.
  • Example 6 Determination of fungicidal activity, the measurement procedure is as follows:
  • In vitro test method The tomato Phytophthora infestans was cultured on PDA medium for 7 days, and inoculated with a 4 cm diameter dish at the edge of the colony to inoculate a PDA medium containing 50 mg/kg and no drug. The colony diameter was measured for 4 days, and the percentage inhibition of the drug was calculated in comparison with the control.

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Abstract

本发明属于农药技术领域，具体涉及含有磺酰基结构三嗪酮衍生物及其制备方法和在杀虫、杀菌方面的应用。所述含有磺酰基结构三嗪酮衍生物为式(Ia)或(Ib)所示的化合物。本发明提供的该含有磺酰基结构三嗪酮衍生物表现出很好的杀虫活性，同时还具有杀菌活性。

Description

含有磺酰基结构三嗪酮衍生物及其制备方法和在杀虫、杀菌方面的应用 技术领域
本发明属于农药技术领域，具体涉及含有磺酰基结构三嗪酮衍生物及其制备方法和在杀虫、杀菌方面的应用。
背景技术
吡蚜酮(Pymetrozine)是1988年由Ciba-Geigy公司发现的新型杂环杀虫剂，具有作用方式独特、高度的选择性、与传统杀虫剂无交互抗性、对环境安全等特点，它对刺吸式口器害虫特别是蚜虫具有独特的防治效果。因此，吡蚜酮问世以来，被广泛应用于农田作物和观赏植物防治蚜虫、粉虱和黑尾叶蝉的危害。但是由于吡蚜酮独特的作用方式，目前为止，此类杀虫剂商品化的品种仅有三种，分别是吡蚜酮、R-768和Pyrifluquinazon。通过总结文献，发现关于此类杀虫剂的研究主要集中在对三嗪酮环和吡啶环部分，而砜或亚砜作为医药和农药分子设计中常见的活性基团，文献中却没有报道。随着全世界对环境保护越来越重视，对于研发吡蚜酮类的高效、低毒、环境友好杀虫剂，已经是当前农业生产中的当务之急。
发明内容
本发明的目的是提供含有磺酰基结构三嗪酮衍生物及其制备方法和在杀虫、杀菌方面的应用。本专利的含有磺酰基结构三嗪酮衍生物表现出很好的杀虫活性，同时还具有杀菌活性。
本发明第一方面提供了一种含有磺酰基结构的三嗪酮衍生物，其中，该三嗪酮衍生物为式(Ia)所示的化合物：
Figure PCTCN2017102600-appb-000001
其中，R1为C1-C12的烷基、C3-C6的环烷基、取代的或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、取代的或未取代的苯乙基、取代的或未取代的苯丙基、取代的或未取代的苯丁基、含有1-10个碳原子的含氮杂环、含有1-10个碳原子的含氧杂环、含有1-10个碳原子的含硫杂环；所述取代的苯基、取代的萘基、取代的苄基、取代的苯乙基、取代的苯丙基和取代的苯丁基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、三氟甲基、三氟甲氧基、酰胺基、C1-C6的烃基、C1-C6的烷氧基、C1-C4的烷基取代的羰氧基和C1-C4的烷氧基取代的羰氧基中的一种或多种。
本发明第二方面提供了一种上述三嗪酮衍生物的制备方法，该方法包括：在缚酸剂存在下，在有机溶剂中，将式(II)所示的氨基三嗪酮与式(III)所示的磺酰氯类化合物进行取代反应，得到式(Ia)所示的化合物；
Figure PCTCN2017102600-appb-000002
本发明第三方面提供了一种含有磺酰基结构的三嗪酮衍生物，其中，该三嗪酮衍生物为式(Ib)所示的化合物：
Figure PCTCN2017102600-appb-000003
其中，各个R1各自独立地选自C1-C12的烷基、C3-C6的环烷基、取代的或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、取代的或未取代的苯乙基、取代的或未取代的苯丙基、取代的或未取代的苯丁基、含有1-10个碳原子的含氮杂环、含有1-10个碳原子的含氧杂环、含有1-10个碳原子的含硫杂环；所述取代的苯基、取代的萘基、取代的苄基、取代的苯乙基、取代的苯丙基和取代的苯丁基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、三氟甲基、三氟甲氧基、酰胺基、C1-C6的烃基、C1-C6的烷氧基、C1-C4的烷基取代的羰氧基和C1-C4的烷氧基取代的羰氧基中的一种或多种。
本发明第四方面提供了一种上述三嗪酮衍生物的制备方法，该方法包括：在缚酸剂存在下，在有机溶剂中，将式(II)所示的氨基三嗪酮与式(III)所示的磺酰氯类化合物进行取代反应，得到式(Ib)所示的化合物；
Figure PCTCN2017102600-appb-000004
本发明第五方面提供了上述三嗪酮衍生物在杀虫方面的应用。
本发明第六方面供了上述三嗪酮衍生物在杀菌方面的应用。
本发明提供的三嗪酮衍生物表现出非常优良的杀虫活性和杀菌活性。
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。
本发明第一方面提供了一种含有磺酰基结构的三嗪酮衍生物，其中，该三嗪酮衍生物为式(Ia)所示的化合物：
Figure PCTCN2017102600-appb-000005
其中，R1为C1-C12的烷基、C3-C6的环烷基、取代的或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、取代的或未取代的苯乙基、取代的或未取代的苯丙基、取代的或未取代的苯丁基、含有1-10个碳原子的含氮杂环、含有1-10个碳原子的含氧杂环、含有1-10个碳原子的含硫杂环；所述取代的苯基、取代的萘基、取代的苄基、取代的苯乙基、取代的苯丙基和取代的苯丁基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、三氟甲基、三氟甲氧基、酰胺基、C1-C6的烃基、C1-C6的烷氧基、C1-C4的烷基取代的羰氧基和C1-C4的烷氧基取代的羰氧基中的一种或多种。
根据本发明，本发明的第一方面和第三方面提供的含有磺酰基结构三嗪酮衍生物可以由以下式(I)所概括：
Figure PCTCN2017102600-appb-000006
在本发明中，C1-C12的烷基的具体实例例如可以为：甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、正己基、正庚基、正辛基、正壬基、正癸基、正十一烷基、正十二烷基等。
C1-C6的烃基、C1-C4的烷基可以从上述的烷基的具体实例进行选择并进行满足相应限定即可。
C1-C6的烷氧基可以是上述的满足1-6个碳原子限定的烷基的具体实例形成的烷氧基。
C3-C6的环烷基的具体实例例如可以为：
Figure PCTCN2017102600-appb-000007
等。
含有1-10个碳原子的含氮杂环可以是不饱和氮杂环，也可以是饱和氮杂环，只要其杂环的环结构中以氮为结构原子且该杂环具有的碳原子个数为1-10个，例如可以是未取代的或者C1-C6的烷基取代的吡咯、未取代的或者C1-C6的烷基取代的氢化吡咯、未取代的或者C1-C7 的烷基取代的咪唑、未取代的或者C1-C7的烷基取代的氢化咪唑、未取代的或者C1-C5的烷基取代的吡啶、未取代的或者C1-C5的烷基取代的氢化吡啶、未取代的或者C1-C7的烷基取代的吡唑、未取代的或者C1-C7的烷基取代的氢化吡唑、未取代的或者C1-C7的烷基取代的噻唑、未取代的或者C1-C7的烷基取代的氢化噻唑、未取代的或者C1-C7的烷基取代的噁唑、未取代的或者C1-C7的烷基取代的氢化噁唑等。其中，作为取代基的烷基可以从上文中所描述的烷基具体实例中进行相应的选择，这些烷基的取代可以是单点的，也可以是多点的取代，本发明对此并无特别的限定。
含有1-10个碳原子的含氧杂环可以是不饱和氧杂环，也可以是饱和氧杂环，只要其杂环的环结构中以氧为结构原子且该杂环具有的碳原子个数为1-10个，例如可以是未取代的或者C1-C6的烷基取代的呋喃、未取代的或者C1-C6的烷基取代的氢化呋喃、未取代的或者C1-C7的烷基取代的噁唑、未取代的或者C1-C7的烷基取代的氢化噁唑、未取代的或者C1-C3的烷基取代的1,3-苯并二噁茂、未取代的或者C1-C2的烷基取代的1,4-苯并二噁等。
含有1-10个碳原子的含硫杂环可以是不饱和硫杂环，也可以是饱和硫杂环，只要其杂环的环结构中以硫为结构原子且该杂环具有的碳原子个数为1-10个，例如可以是未取代的或者C1-C6的烷基取代的噻吩、未取代的或者C1-C6的烷基取代的氢化噻吩、未取代的或者C1-C7的烷基取代的噻唑、未取代的或者C1-C7的烷基取代的氢化噻唑等。
优选地，R1为C1-C8的烷基、C3-C6的环烷基、取代的或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、取代的或未取代的苯乙基、取代的或未取代的苯丙基、取代的或未取代的苯丁基、含有2-8个碳原子的含氮杂环、含有2-8个碳原子的含氧杂环、含有2-8个碳原子的含硫杂环；所述取代的苯基、取代的萘基、取代的苄基、取代的苯乙基、取代的苯丙基和取代的苯丁基的取代基各自独立地选自羟基、F、Cl、Br、I、氰基、硝基、-COOCH3、-COOCH2CH3、三氟甲基、三氟甲氧基、-NH-CO-CH3、-NH-CO-CH2CH3、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基、叔丁氧基、正戊氧基、C1-C5的烷基、C1-C5的烷氧基、-O-CO-CH3、-O-CO-CH2CH3、-O-CO-O-CH3和-O-CO-O-CH2CH3中的一种或多种。
在本发明的一种优选的实施方式中，式(Ia)所示的化合物选自下式中所示的化合物中的一种：
Figure PCTCN2017102600-appb-000008
Figure PCTCN2017102600-appb-000009
Figure PCTCN2017102600-appb-000010
Figure PCTCN2017102600-appb-000011
本发明第二方面提供了一种上述三嗪酮衍生物的制备方法，该方法包括：在缚酸剂存在下，在有机溶剂中，将式(II)所示的氨基三嗪酮与式(III)所示的磺酰氯类化合物进行取代反应，得到式(Ia)所示的化合物；
Figure PCTCN2017102600-appb-000012
该制备过程可以以下述路线一所表示：
路线一：
Figure PCTCN2017102600-appb-000013
根据本发明，式(III)所示的化合物可以根据所需的式(Ia)进行具体的选择，其R1如上文中所描述的，本发明在此不再赘述。
优选地，式(II)所示的氨基三嗪酮与式(III)所示的磺酰氯类化合物的用量的摩尔比为1：0.8-1.2，优选为1：1-1.1。
优选地，所述缚酸剂为碳酸钠、碳酸钾、碳酸铯、三乙胺和吡啶中的一种或多种。
其中，所述缚酸剂的用量可以在较宽范围内变动，例如式(II)所示的氨基三嗪酮和缚酸剂的用量的摩尔比为1：0.08-0.5，优选为1：0.1-0.3。其中，吡啶又可以作为上述方法的溶剂，为此在采用吡啶作为溶剂使用时，仅需满足溶剂的用量即可，无需受该用量限定。
优选地，所述有机溶剂为甲醇、乙醇、吡啶、N,N-二甲基甲酰胺和二甲基亚砜中的一种或多种。
优选地，所述有机溶剂的用量使得式(II)所示的氨基三嗪酮的浓度为0.05-0.5mmol/mL。
优选情况下，所述取代反应的条件包括：温度为15-40℃(优选为20-35℃)，时间为4-12h。
本发明第三方面提供了一种含有磺酰基结构的三嗪酮衍生物，其中，该三嗪酮衍生物为式(Ib)所示的化合物：
Figure PCTCN2017102600-appb-000014
其中，各个R1各自独立地选自C1-C12的烷基、C3-C6的环烷基、取代的或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、取代的或未取代的苯乙基、取代的或未取代的苯丙基、取代的或未取代的苯丁基、含有1-10个碳原子的含氮杂环、含有1-10个碳原子的含氧杂环、含有1-10个碳原子的含硫杂环；所述取代的苯基、取代的萘基、取代的苄基、取代的苯乙基、取代的苯丙基和取代的苯丁基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、三氟甲基、三氟甲氧基、酰胺基、C1-C6的烃基、C1-C6的烷氧基、C1-C4的烷基取代的羰氧基和C1-C4的烷氧基取代的羰氧基中的一种或多种。
在本发明的一种实施方式中，本发明中的R1可选自1－12碳烷基、3－6碳环烷基、苯基、苄基、苯乙基、苯丙基、苯丁基、1－10碳含氮杂环、1－10碳含氧杂环、1－10碳含硫杂环、取代的苯基(其中取代基可以是氢、羟基、卤素原子、氰基、硝基、酯基、氟、三氟甲基、三氟甲氧基、酰胺基、1－5碳烃基、1－6碳烷氧基、1－4碳烷基羰氧基、1－4碳烷氧基羰氧基；以及同时含有2－3个上述所述取代基)。
其中，该式(Ib)中的两个R1可以相同，也可以不同，各自独立地进行选择，其中，该式(Ib)中的R1可以从上文中式(Ia)描述的相关基团中进行选择，本发明在此不再限定。
优选地，各个R1各自独立地选自C1-C8的烷基、C3-C6的环烷基、取代的或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、取代的或未取代的苯乙基、取代的或未取代的苯丙基、取代的或未取代的苯丁基、含有2-8个碳原子的含氮杂环、含有2-8个碳原子的含氧杂环、含有2-8个碳原子的含硫杂环；所述取代的苯基、取代的萘基、取代的苄基、取代的苯乙基、取代的苯丙基和取代的苯丁基的取代基各自独立地选自羟基、F、Cl、Br、I、氰基、硝基、-COOCH3、-COOCH2CH3、三氟甲基、三氟甲氧基、-NH-CO-CH3、-NH-CO-CH2CH3、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基、叔丁氧基、正戊氧基、C1-C5的烷基、C1-C5的烷氧基、-O-CO-CH3、-O-CO-CH2CH3、-O-CO-O-CH3和-O-CO-O-CH2CH3中的一种或多种。
在本发明的一种优选的实施方式中，式(Ib)所示的化合物选自下式中所示的化合物中的一种：
Figure PCTCN2017102600-appb-000015
Figure PCTCN2017102600-appb-000016
本发明第四方面提供了一种上述三嗪酮衍生物的制备方法，该方法包括：在缚酸剂存在下，在有机溶剂中，将式(II)所示的氨基三嗪酮与式(III)所示的磺酰氯类化合物进行取代反应，得到式(Ib)所示的化合物；
Figure PCTCN2017102600-appb-000017
该方法可以大致概括为以下路线：三嗪酮(II)与不同的磺酰氯反应得到化合物Ib；
路线二：
Figure PCTCN2017102600-appb-000018
其中，该式(III)所示的化合物可以根据所需的式(Ib)进行具体的选择，其R1如上文中所描述的，本发明在此不再赘述。
优选地，式(II)所示的氨基三嗪酮与式(III)所示的磺酰氯类化合物的用量的摩尔比为1：1.8-2.5，优选为1：2-2.4。
优选地，所述缚酸剂为碳酸钠、碳酸钾、碳酸铯、三乙胺和吡啶中的一种或多种。
其中，所述缚酸剂的用量可以在较宽范围内变动，例如式(II)所示的氨基三嗪酮和缚酸剂的用量的摩尔比为1：0.08-0.5，优选为1：0.1-0.3。其中，吡啶又可以作为上述方法的溶剂，为此在采用吡啶作为溶剂使用时，仅需满足溶剂的用量即可，无需受该用量限定。
优选地，所述有机溶剂为甲醇、乙醇、吡啶、N,N-二甲基甲酰胺和二甲基亚砜中的一种或多种。
优选地，所述有机溶剂的用量使得式(II)所示的氨基三嗪酮的浓度为0.05-0.5mmol/mL。
优选情况下，所述取代反应的条件包括：温度为15-40℃(优选为20-35℃)，时间为4-12h。
本发明第五方面提供了上述三嗪酮衍生物在杀虫方面的应用。
本发明提供的三嗪酮衍生物具有较高的杀虫活性，特别是对蚜虫、蚊幼虫、棉铃虫、玉米螟和粘虫中的一种或多种具有更高的杀灭活性。
从获得较高的杀虫活性上考虑，本发明所述的含有磺酰基结构三嗪酮衍生物优选选自如下化合物中的一种或多种：
2-甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-10)；
3-甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-11)；
4-甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-12)；
2,4,6-三甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-13)；
4-甲氧基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-14)；
4-叔丁基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-15)；
4-溴-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-22)。
特别地，本发明含有磺酰基结构三嗪酮衍生物表现出很好的杀蚜虫活性，其中，化合物Ia-10，Ia-11，Ia-12，Ia-13，Ia-14，Ia-15在2.5mg/kg浓度下表现出25％，15％，30％，10％，35％，10％的杀虫活性，而吡蚜酮在相同浓度下没有杀虫活性。同时部分化合物对蚊幼虫表现出很好的活性，其中，在1mg/kg时，化合物Ia-19，Ia-23和Ia-26对蚊幼虫分别表现60％、30％、20％的活性，尤其是化合物Ia-22在0.5mg/kg浓度下对蚊幼虫表现出40％的杀虫活性。此外，所有化合物对棉铃虫、玉米螟及粘虫均表现出杀虫活性。
本发明还提供了一种采用上述三嗪酮衍生物作为杀虫剂进行杀虫的方法。
本发明第六方面供了上述三嗪酮衍生物在杀菌方面的应用。
本发明提供的三嗪酮衍生物具有较高的杀虫活性，特别是针对引起番茄早疫、小麦赤霉、马铃薯晚疫、辣椒疫霉、油菜菌核、黄瓜灰霉、水稻纹枯、黄瓜枯萎、花生褐斑、苹果轮纹、小麦纹枯、玉米小斑、西瓜炭疽和水稻恶苗的病原菌中的一种或多种。
从获得较高的杀菌活性上考虑，本发明所述的含有磺酰基结构三嗪酮衍生物优选选自如下化合物中的一种或多种：
2-甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-10)；
3-甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-11)；
4-甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-12)；
2,4,6-三甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-13)；
4-甲氧基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-14)；
4-叔丁基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-15)；
4-溴-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-22)。
其中，尤其是化合物Ia-4，Ia-12和Ib-5在50mg/kg浓度下对多种病原菌均表现出良好的抑菌活性。
本发明还提供了一种采用上述三嗪酮衍生物作为杀菌剂进行杀菌的方法。
下述的实施例和生测试验结果可用来进一步说明本发明，但不意味着限制本发明。
实施例1：
(1)N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)甲基磺酰胺(Ia-1)的合成
Figure PCTCN2017102600-appb-000019
在100mL单口瓶中，加入氨基三嗪酮(0.26g,2mmol，购自梯希爱(上海)化成工业发展有限公司)，吡啶(20mL)搅拌溶解，加入甲基磺酰氯(0.24g,2.1mmol，购自安耐吉化学公司)室温搅拌过夜，TLC监测反应完毕。将反应液减压脱溶后，加入水，用二氯甲烷萃取，用饱和氯化钠溶液洗两次，硫酸钠干燥，之后用二氯甲烷/甲醇(150:1—100:1)进行硅胶柱层析得到白色固体0.32g，产率78％，熔点191–192℃。1H NMR(300MHz,DMSO-d6)δ10.00(s,1H,NH),9.83(s,1H,NH),4.15(s,2H,CH2),3.01(s,3H,CH3),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ151.4,146.0,53.9,41.1,20.1.ESI-HRMS(m/z):Calcd.for C5H11N4O3S[M+H]+207.0546；found207.0548.
(2)化合物Ia-2至Ia-34通过重复Ia-1的步骤完成。
但是不同的是：
制备化合物Ia-2时，采用等摩尔量的乙基磺酰氯(购自安耐吉化学公司)代替甲基磺酰氯；
制备化合物Ia-3时，采用等摩尔量的正丙基磺酰氯(购自北京伊诺凯科技有限公司)代替甲基磺酰氯；
制备化合物Ia-4时，采用等摩尔量的正丁基磺酰氯(购自北京伊诺凯科技有限公司)代替甲基磺酰氯；
制备化合物Ia-5时，采用等摩尔量的
Figure PCTCN2017102600-appb-000020
(购自北京伊诺凯科技有限公司)代替甲基磺酰氯；
制备化合物Ia-6时，采用等摩尔量的
Figure PCTCN2017102600-appb-000021
(购自北京伊诺凯科技有限公司)代替甲基磺酰氯；
制备化合物Ia-7时，采用等摩尔量的
Figure PCTCN2017102600-appb-000022
(购自天津希恩思生化科技有限公司)代替甲基磺酰氯；
制备化合物Ia-8时，采用等摩尔量的
Figure PCTCN2017102600-appb-000023
(购自百灵威科技有限公司)代替甲基磺酰氯；
制备化合物Ia-9时，采用等摩尔量的
Figure PCTCN2017102600-appb-000024
(购自天津试剂公司)代替甲基磺酰氯；
制备化合物Ia-10时，采用等摩尔量的
Figure PCTCN2017102600-appb-000025
(购自安耐吉化学公司)代替甲基磺酰氯；
制备化合物Ia-11时，采用等摩尔量的
Figure PCTCN2017102600-appb-000026
(购自上海柏卡化学技术有限公司)代替甲基磺酰氯；
制备化合物Ia-12时，采用等摩尔量的
Figure PCTCN2017102600-appb-000027
(购自上海阿拉丁生化科技股份有限公司)代替甲基磺酰氯；
制备化合物Ia-13时，采用等摩尔量的
Figure PCTCN2017102600-appb-000028
(购自安耐吉化学公司)代替甲基磺酰氯；
制备化合物Ia-14时，采用等摩尔量的
Figure PCTCN2017102600-appb-000029
(购自上海阿拉丁生化科技股份有限公司)代替甲基磺酰氯；
制备化合物Ia-15时，采用等摩尔量的
Figure PCTCN2017102600-appb-000030
(购自安耐吉化学公司)代替甲基磺酰氯；
制备化合物Ia-16时，采用等摩尔量的
Figure PCTCN2017102600-appb-000031
(购自上海柏卡化学技术有限公司)代替甲基磺酰氯；
制备化合物Ia-17时，采用等摩尔量的
Figure PCTCN2017102600-appb-000032
(购自上海柏卡化学技术有限公司)代替甲基磺酰氯；
制备化合物Ia-18时，采用等摩尔量的
Figure PCTCN2017102600-appb-000033
(购自上海柏卡化学技术有限公司)代替甲基磺酰氯；
制备化合物Ia-19时，采用等摩尔量的
Figure PCTCN2017102600-appb-000034
(购自上海柏卡化学技术有限公司)代替甲基磺酰氯；
制备化合物Ia-20时，采用等摩尔量的
Figure PCTCN2017102600-appb-000035
(购自北京伊诺凯科技有限公司)代替甲基磺酰氯；
制备化合物Ia-21时，采用等摩尔量的
Figure PCTCN2017102600-appb-000036
(购自天津希恩思生化科技有限公司)代替甲基磺酰氯；
制备化合物Ia-22时，采用等摩尔量的
Figure PCTCN2017102600-appb-000037
(购自天津希恩思生化科技有限公司)代替甲基磺酰氯；
制备化合物Ia-23时，采用等摩尔量的
Figure PCTCN2017102600-appb-000038
(购自上海柏卡化学技术有限公司)代替甲基磺酰氯；
制备化合物Ia-24时，采用等摩尔量的
Figure PCTCN2017102600-appb-000039
(购自上海柏卡化学技术有限公司)代替甲基磺酰氯；
制备化合物Ia-25时，采用等摩尔量的
Figure PCTCN2017102600-appb-000040
(购自上海柏卡化学技术有限公司)代替甲基磺酰氯；
制备化合物Ia-26时，采用等摩尔量的
Figure PCTCN2017102600-appb-000041
(购自上海柏卡化学技术有限公司)代替甲基磺酰氯；
制备化合物Ia-27时，采用等摩尔量的
Figure PCTCN2017102600-appb-000042
(购自上海柏卡化学技术有限公司)代替甲基磺酰氯；
制备化合物Ia-28时，采用等摩尔量的
Figure PCTCN2017102600-appb-000043
(购自安耐吉化学公司)代替甲基磺酰氯；
制备化合物Ia-29时，采用等摩尔量的
Figure PCTCN2017102600-appb-000044
(购自安耐吉化学公司)代替甲基磺酰氯；
制备化合物Ia-30时，采用等摩尔量的
Figure PCTCN2017102600-appb-000045
(购自安耐吉化学公司)代替甲基磺酰氯；
制备化合物Ia-31时，采用等摩尔量的
Figure PCTCN2017102600-appb-000046
(购自安耐吉化学公司)代替甲基磺 酰氯；
制备化合物Ia-32时，采用等摩尔量的
Figure PCTCN2017102600-appb-000047
(购自安耐吉化学公司)代替甲基磺酰氯；
制备化合物Ia-33时，采用等摩尔量的
Figure PCTCN2017102600-appb-000048
(购自北京伊诺凯科技有限公司)代替甲基磺酰氯；
制备化合物Ia-34时，采用等摩尔量的
Figure PCTCN2017102600-appb-000049
(购自北京伊诺凯科技有限公司)代替甲基磺酰氯；
所得化合物的表征结果如下所示：
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)乙基磺酰胺(Ia-2)
白色固体，产率76％，熔点206–208℃。1H NMR(300MHz,DMSO-d6)δ9.98(s,1H,NH),9.79(s,1H,NH),4.15(s,2H,CH2),3.10(q,J＝7.2Hz,2H,CH2CH3),1.85(s,3H,CH3),1.27(t,J＝7.2Hz,3H,CH2CH3)；13C NMR(100MHz,DMSO-d6)δ151.2,145.7,53.8,46.7,19.8,7.9.ESI-HRMS(m/z):Calcd.for C6H13N4O3S[M+H]+221.0703；found 221.0701.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)正丙基磺酰胺(Ia-3)
白色固体，产率73％，熔点177–178℃。1H NMR(300MHz,DMSO-d6)δ9.98(s,1H,NH),9.81(s,1H,NH),4.15(s,2H,CH2),3.07(t,J＝7.5Hz,2H,CH2CH2CH3),1.85(s,3H,CH3),1.73–1.80(m,2H,CH2CH2CH3),0.95(t,J＝7.5Hz,3H,CH2CH2CH3)；13C NMR(100MHz,DMSO-d6)δ151.2,145.6,53.8,19.8,16.7,12.8.ESI-HRMS(m/z):Calcd.for C7H15N4O3S[M+H]+235.0859；found 235.0856.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)正丁基磺酰胺(Ia-4)
白色固体，产率71％，熔点167–169℃。1H NMR(300MHz,DMSO-d6)δ9.99(s,1H,NH),9.81(s,1H,NH),4.15(s,2H,CH2),3.10(t,J＝7.5Hz,2H,CH2CH2CH2CH3),1.85(s,3H,CH3),1.67–1.77(m,2H,CH2CH2CH2CH3),1.30–1.40(m,2H,CH2CH2CH2CH3),0.87(t,J＝7.2Hz,3H,CH2CH2CH2CH3)；13C NMR(100MHz,DMSO-d6)δ151.2,145.7,53.8,51.9,24.9,20.9,19.8,13.5.ESI-HRMS(m/z):Calcd.for C8H17N4O3S[M+H]+249.1016；found249.1018.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)环丙基磺酰胺(Ia-5)
白色固体，产率64％，熔点146–148℃。1H NMR(400MHz,DMSO-d6)δ9.96(s,1H,NH),9.79(s,1H,NH),4.13(s,2H,CH2),2.57-2.63(m,1H,CH(CH2)2),1.86(s,3H,CH3),0.93-0.98(m,4H,CH(CH2)2)；13C NMR(100MHz,DMSO-d6)δ151.3,145.6,53.3,29.9,19.8,5.4.ESI-HRMS(m/z):Calcd.for C7H13N4O3S[M+H]+233.0703；found 233.0703.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)环己基磺酰胺(Ia-6)
白色固体，产率43％，熔点166–168℃。1H NMR(400MHz,DMSO-d6)δ9.95(s,1H,NH),9.73(s,1H,NH),4.14(s,2H,CH2),2.99-3.06(m,1H),1.85(s,3H,CH3),1.76-1.79(m,2H),1.28-1.37(m,3H),1.07-1.25(m,5H)；13C NMR(100MHz,DMSO-d6)δ151.3,145.6,59.8,53.9,25.8,24.8,24.7,19.8.ESI-HRMS(m/z):Calcd.for C10H18N4O3S[M+H]+275.1172；found 275.1170.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯基甲基磺酰胺(Ia-7)
白色固体，产率78％，熔点189–190℃。1H NMR(300MHz,DMSO-d6)δ10.04(s,1H,NH),9.86(s,1H,NH), 7.46–7.50(m,2H,Ar–H),7.33–7.40(m,3H,Ar–H),4.46(s,2H,CH2),4.13(s,2H,CH2),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ151.3,145.6,131.2,129.4,128.4,128.2,58.7,53.8,19.8.ESI-HRMS(m/z):Calcd.for C11H15N4O3S[M+H]+283.0859；found 283.0860.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)萘-1-磺酰胺(Ia-8)
白色固体，产率72％，熔点174–175℃。1H NMR(400MHz,CDCl3)δ8.71(d,J＝8.4Hz,1H),8.27(d,J＝7.2Hz,1H),8.11(d,J＝8.4Hz,1H),7.93(d,J＝8.0Hz,1H),7.68(t,J＝7.2Hz,1H),7.60(t,J＝8.0Hz,1H),7.54(t,J＝7.6Hz,1H),4.24(s,2H,CH2),1.98(s,3H,CH3)；13C NMR(100MHz,CDCl3)δ150.9,146.7,135.7,134.1,132.1,131.4,129.4,129.1,128.6,127.0,124.3,124.1,52.5,20.5.ESI-HRMS(m/z):Calcd.for C14H14N4O3S[M+H]+319.0859；found 319.0860.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-9)
白色固体，产率77％，熔点206–208℃。1H NMR(400MHz,DMSO-d6)δ10.23(s,1H,NH),9.81(s,1H,NH),7.80–7.82(m,2H,Ar–H),7.64–7.67(m,1H,Ar–H),7.54–7.58(m,2H,Ar–H),4.05(s,2H,CH2),1.83(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ150.7,145.6,138.8,133.2,128.9,127.7,52.7,19.9.ESI-HRMS(m/z):Calcd.for C10H13N4O3S[M+H]+269.0703；found 269.0704.
2-甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-10)
白色固体，产率59％，熔点240–241℃。1H NMR(400MHz,DMSO-d6)δ10.15(s,1H,NH),9.76(s,1H,NH),7.84(d,J＝7.6Hz,1H,Ar–H),7.51(t,J＝6.8Hz,1H,Ar–H),7.31–7.37(m,2H,Ar–H),4.03(s,2H,CH2),2.65(s,3H,CH3),1.81(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ150.9,145.6,138.4,136.9,133.2,132.2,129.6,125.8,52.7,20.2,19.8.ESI-HRMS(m/z):Calcd.for C11H15N4O3S[M+H]+283.0859；found 283.0859.
3-甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-11)
白色固体，产率82％，熔点150–151℃。1H NMR(400MHz,DMSO-d6)δ10.16(s,1H,NH),9.79(s,1H,NH),7.60–7.63(m,2H,Ar–H),7.42–7.46(m,2H,Ar–H),4.03(s,2H,CH2),2.37(s,3H,CH3),1.82(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ150.7,145.6,138.8,138.5,133.8,128.7,127.8,124.9,52.7,20.8,19.8.ESI-HRMS(m/z):Calcd.for C11H15N4O3S[M+H]+283.0859；found 283.0858.
4-甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-12)
白色固体，产率68％，熔点199–200℃。1H NMR(300MHz,DMSO-d6)δ10.10(s,1H,NH),9.79(s,1H,NH),7.69(d,J＝8.4Hz,2H,Ar–H),7.36(d,J＝8.1Hz,2H,Ar–H),4.05(s,2H,CH2),2.38(s,3H,CH3),1.83(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ150.7,145.7,143.5,135.9,129.4,127.8,52.7,21.1,19.9.ESI-HRMS(m/z):Calcd.for C11H15N4O3S[M+H]+283.0859；found 283.0863.
2,4,6-三甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-13)
白色固体，产率67％，熔点224–226℃。1H NMR(400MHz,DMSO-d6)δ9.91(s,1H,NH),9.80(s,1H,NH),6.99(s,2H,Ar–H),4.01(s,2H,CH2),2.54(s,3H,CH3),2.24(s,3H,CH3),1.82(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ151.2,145.9,142.2,139.8,133.0,131.4,52.3,22.7,20.5,19.9.ESI-HRMS(m/z):Calcd.for C13H19N4O3S[M+H]+311.1172；found 311.1172.
4-甲氧基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-14)
白色固体，产率68％，熔点245–246℃。1H NMR(400MHz,DMSO-d6)δ9.99(s,1H,NH),9.78(s,1H,NH),7.73(d,J＝8.8Hz,2H,Ar–H),7.06(d,J＝8.8Hz,2H,Ar–H),4.04(s,2H,CH2),3.82(s,3H,OCH3),1.83(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ162.8,150.7,145.6,130.1,130.0,114.1,55.7,52.6,19.9.ESI-HRMS(m/z):Calcd.for C11H15N4O4S[M+H]+299.0809；found 299.0807.
4-叔丁基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-15)
白色固体，产率59％，熔点240–241℃。1H NMR(400MHz,DMSO-d6)δ10.08(s,1H,NH),9.85(s,1H,NH),7.74(d,J＝8.0Hz,2H,Ar–H),7.59(d,J＝8.0Hz,2H,Ar–H),3.98(s,2H,CH2),1.80(s,3H,CH3),1.29(s,9H,C(CH3)3)；13C NMR(100MHz,DMSO-d6)δ156.2,150.9,145.6,136.2,127.6,125.8,52.6,34.9,30.8,19.8.ESI-HRMS(m/z):Calcd.for C14H21N4O3S[M+H]+325.1329；found 325.1329.
2-氟-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-16)
白色固体，产率73％，熔点206–208℃。1H NMR(400MHz,DMSO-d6)δ10.49(s,1H,NH),9.80(s,1H,NH),7.79(t,J＝6.8Hz,1H,Ar–H),7.67-7.72(m,1H,Ar–H),7.39(t,J＝9.6Hz,1H,Ar–H),7.33(t,J＝7.6Hz,1H,Ar–H),4.13(s,2H,CH2),1.85(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ159.2(d,J＝254.0Hz),150.6,145.5,135.9(d,J＝8.7Hz),130.2,127.1(d,J＝14Hz),124.3(d,J＝3.2Hz),117.0(d,J＝20.9Hz),53.2,19.8.ESI-HRMS(m/z):Calcd.for C10H12FN4O3S[M+H]+287.0609；found 287.0609.
3-氟-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-17)
白色固体，产率81％，熔点180–181℃。1H NMR(400MHz,DMSO-d6)δ10.45(s,1H,NH),9.83(s,1H,NH),7.66(d,J＝8.0Hz,1H,Ar–H),7.59-7.63(m,2H,Ar–H),7.53(t,J＝8.4Hz,1H,Ar–H),4.11(s,2H,CH2),1.85(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ161.5(d,J＝246.1Hz),150.5,145.6,141.0(d,J＝7.0Hz),131.1(d,J＝7.7Hz),124.0(d,J＝2.7Hz),120.3(d,J＝20.9Hz),114.7(d,J＝24.3Hz),53.0,19.8.ESI-HRMS(m/z):Calcd.for C10H12FN4O3S[M+H]+287.0609；found 287.0605.
4-氟-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-18)
白色固体，产率65％，熔点216–217℃。1H NMR(400MHz,DMSO-d6)δ10.29(s,1H,NH),9.81(s,1H,NH),7.85-7.89(m,2H,Ar–H),7.40(t,J＝8.8Hz,2H,Ar–H),4.11(s,2H,CH2),1.85(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ164.7(d,J＝249.9Hz),150.6,145.7,135.1(d,J＝2.7Hz),130.9(d,J＝9.7Hz),116.0(d,J＝22.6Hz),52.9,19.9.ESI-HRMS(m/z):Calcd.for C10H12FN4O3S[M+H]+287.0609；found 287.0606.
2,4-二氟-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-19)
白色固体，产率77％，熔点211–213℃。1H NMR(400MHz,DMSO-d6)δ10.59(s,1H,NH),9.82(s,1H,NH),7.81-7.87(m,1H,Ar–H),7.50(t,J＝10.0Hz,1H,Ar–H),7.21(t,J＝8.4Hz,1H,Ar–H),4.14(s,2H,CH2),1.85(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ165.5(dd,J＝12.5,12.5Hz),160.2(dd,J＝14.1,14.2Hz),150.6,145.5,132.4(d,J＝10.8Hz),123.9(dd,J＝4.4,4.7Hz),111.7(dd,J＝4.1,3.6Hz),105.7(t,J＝25.7Hz),53.3,19.8.ESI-HRMS(m/z):Calcd.for C10H11F2N4O3S[M+H]+305.0514；found 305.0511.
2,3,4-三氟-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-20)
白色固体，产率71％，熔点214–216℃。1H NMR(400MHz,DMSO-d6)δ10.88(s,1H,NH),9.89(s,1H,NH),7.66-7.71(m,1H,Ar–H),7.45-7.51(m,1H,Ar–H),4.18(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ153.6(dd,J＝10.6,9.5Hz),150.7,148.9(dd,J＝8.5,8.1Hz),145.7,140.8(t,J＝15.6Hz),138.3(t,J＝15.3Hz),125.3(m),112.6(dd,J＝2.6,2.6Hz),53.4,19.8.ESI-HRMS(m/z):Calcd.for C10H10F3N4O3S[M+H]+323.0420；found 323.0414.
4-氯-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-21)
白色固体，产率74％，熔点214–215℃。1H NMR(400MHz,DMSO-d6)δ10.38(s,1H,NH),9.82(s,1H,NH),7.80(d,J＝8.4Hz,2H,Ar–H),7.63(d,J＝8.4Hz,2H,Ar–H),4.12(s,2H,CH2),1.85(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ150.5,145.6,138.1,137.7,129.7,129.0,53.0,19.9.ESI-HRMS(m/z):Calcd.for C10H12ClN4O3S[M+H]+303.0313；found 303.0316.
4-溴-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-22)
白色固体，产率75％，熔点230–232℃。1H NMR(400MHz,DMSO-d6)δ10.40(s,1H,NH),9.84(s,1H,NH),7.79(d,J＝8.4Hz,2H,Ar–H),7.73(d,J＝8.4Hz,2H,Ar–H),4.13(s,2H,CH2),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ150.6,145.7,138.1,132.0,129.8,127.2,53.0,19.9.ESI-HRMS(m/z):Calcd.for C10H12BrN4O3S[M+H]+346.9808；found 346.9804.
4-碘-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-23)
白色固体，产率81％，熔点241–243℃。1H NMR(400MHz,DMSO-d6)δ10.36(s,1H,NH),9.84(s,1H,NH),7.95(d,J＝8.4Hz,2H,Ar–H),7.56(d,J＝8.4Hz,2H,Ar–H),4.11(s,2H,CH2),1.85(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ150.5,145.6,138.5,137.7,129.4,101.5,52.9,19.8.ESI-HRMS(m/z):Calcd.for C10H12IN4O3S[M+H]+394.9669；found 394.9666.
N-(4-(N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨磺酰)苯基)乙酰胺(Ia-24)
白色固体，产率65％，熔点255–257℃。1H NMR(300MHz,DMSO-d6)δ10.32(s,1H,NH),10.02(s,1H,NH),9.77(s,1H,NH),7.72(brs,4H),4.05(s,2H,CH2),2.08(s,3H,CH3),1.83(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ169.1,150.7,145.6,143.5,132.0,129.0,118.2,52.6,24.2,19.9.ESI-HRMS(m/z):Calcd.for C12H16N5O4S[M+H]+326.0918；found 326.0921.
4-氰基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)苯磺酰胺(Ia-25)
白色固体，产率65％，熔点256–257℃。1H NMR(400MHz,DMSO-d6)δ10.66(s,1H,NH),9.85(s,1H,NH),8.06(d,J＝8.0Hz,2H,Ar–H),7.97(d,J＝8.0Hz,2H,Ar–H),4.15(s,2H,CH2),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ150.5,145.7,143.2,132.9,128.5,117.7,115.4,53.2,19.8.ESI-HRMS(m/z):Calcd.for C11H12IN5O3S[M+H]+294.0655；found 294.0659.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-4-(三氟甲基)-苯磺酰胺(Ia-26)
白色固体，产率74％，熔点243–244℃。1H NMR(400MHz,DMSO-d6)δ10.59(s,1H,NH),9.86(s,1H,NH),8.02(d,J＝8.4Hz,2H,Ar–H),7.95(d,J＝8.4Hz,2H,Ar–H),4.15(s,2H,CH2),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ150.6,145.7,143.0,132.7(q,J＝32Hz),128.8,126.0(q,J＝4.3Hz),123.6(q,J＝271.2Hz),53.2,19.9.ESI-HRMS(m/z):Calcd.for C11H12F3N4O3S[M+H]+337.0577；found 337.0577.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-4-(三氟甲氧基)-苯磺酰胺(Ia-27)
白色固体，产率70％，熔点215–216℃。1H NMR(400MHz,DMSO-d6)δ10.43(s,1H,NH),9.85(s,1H,NH),7.94(d,J＝8.4Hz,2H,Ar–H),7.55(d,J＝8.4Hz,2H,Ar–H),4.12(s,2H,CH2),1.85(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ151.4,150.6,145.7,137.9,130.5,120.9,119.9(q,J＝257.7Hz),53.1,19.8.ESI-HRMS(m/z):Calcd.for C11H12F3N4O4S[M+H]+353.0526；found 353.0525.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)噻吩-2-磺酰胺(Ia-28)
白色固体，产率69％，熔点191–193℃。1H NMR(400MHz,DMSO-d6)δ10.33(s,1H,NH),9.87(s,1H,NH),7.99(d,J＝5.2Hz,1H,Ar–H),7.63(d,J＝3.6Hz,1H,Ar–H),7.17(t,J＝4.0Hz,1H,Ar–H),4.04(s,2H,CH2),1.84(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ150.8,145.7,138.7,134.5,133.7,127.7,52.6,20.0.ESI-HRMS(m/z):Calcd.for C8H11N4O3S2[M+H]+275.0267；found 275.0262.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)噻吩-3-磺酰胺(Ia-29)
白色固体，产率42％，熔点214–215℃。1H NMR(400MHz,DMSO-d6)δ10.14(s,1H,NH),9.85(s,1H,NH),8.25(s,1H,Het-H),7.71(d,J＝2.4Hz,1H,Het-H),7.31(d,J＝4.8Hz,1H,Het-H),4.03(s,2H,CH2),1.83(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ150.8,145.6,141.0,138.4,132.7,128.5,126.1,52.6,19.9.ESI-HRMS(m/z):Calcd.for C8H10N4O3S2[M+H]+275.0267；found 275.0272.
3,5-二甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)异恶唑-4-磺酰胺(Ia-30)
无色油状液体，产率35％。1H NMR(400MHz,DMSO-d6)δ10.55(s,1H,NH),9.96(s,1H,NH),4.17(s,2H,CH2),2.53(s,3H,CH3),2.32(s,3H,CH3),1.88(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ173.8,157.9,150.7,146.1,114.7,52.9,19.9,12.2,10.5.ESI-HRMS(m/z):Calcd.for C9H13N5O4S[M+H]+288.0761；found 288.0759.
1-甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-1H-咪唑-4-磺酰胺(Ia-31)
黄色固体，产率43％，熔点188–190℃。1H NMR(400MHz,DMSO-d6)δ9.85(s,1H,NH),9.84(s,1H,NH),7.88(s,1H,Het-H),7.85(s,1H,Het-H),3.98(s,2H,CH2),3.75(s,3H,CH3),1.84(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ151.2,145.3,139.8,137.9,125.9,52.1,33.5,19.7.ESI-HRMS(m/z):Calcd.for C8H12N6O3S[M+H]+273.0764；found 273.0766.
1,2-二甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-1H-咪唑-4-磺酰胺(Ia-32)
黄色固体，产率47％，熔点180–182℃。1H NMR(400MHz,DMSO-d6)δ10.55(s,1H,NH),9.95(s,1H,NH),8.14(s,1H,Het-H),4.08(s,2H,CH2),3.71(s,3H,CH3),3.16(s,3H,CH3),1.84(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ151.1,147.7,145.7,127.0,120.4,52.9,34.0,19.9,11.4.ESI-HRMS(m/z):Calcd.for C9H14N6O3S [M+H]+287.0921；found 287.0927.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2,3-苯并二氢呋喃-5-磺酰胺(Ia-33)
白色固体，产率43％，熔点263–264℃。1H NMR(400MHz,DMSO-d6)δ9.95(s,1H,NH),9.80(s,1H,NH),7.65(s,1H,Ar-H),7.56(d,J＝8.4Hz,1H,Ar-H),6.88(d,J＝8.4Hz,1H,Ar-H),4.64(t,J＝8.4Hz,2H),4.04(s,2H,CH2),3.22(t,J＝8.8Hz,2H),1.83(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ163.6,150.8,145.6,130.0,129.4,128.3,125.2,108.8,72.2,52.6,28.4,19.9.ESI-HRMS(m/z):Calcd.for C12H14N4O4S[M+H]+311.0809；found 331.0812.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2,3-二氢苯并[b][1,4]二恶英-6-磺酰胺(Ia-34)
白色固体，产率36％，熔点213–214℃。1H NMR(400MHz,DMSO-d6)δ10.06(s,1H,NH),9.83(s,1H,NH),7.27(q,J＝2.0Hz,1H,Ar-H),7.25(d,J＝2.0Hz,1H,Ar-H),7.00(d,J＝8.4Hz,1H,Ar-H),4.32(d,J＝5.2Hz,2H,OCH2),4.29(d,J＝5.2Hz,2H,OCH2),4.03(s,2H,CH2),1.83(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ150.7,147.5,145.6,143.0,131.0,121.5,117.3,116.9,64.5,64.0,52.6,19.9.ESI-HRMS(m/z):Calcd.for C12H14N4O5S[M+H]+327.0758；found 327.0760.
实施例2：
(1)化合物Ib-1的合成
Figure PCTCN2017102600-appb-000050
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N-(甲磺酰)甲基磺酰胺(Ib-1)的合成
在100mL单口瓶中，加入氨基三嗪酮(0.26g,2mmol)，吡啶(30mL)搅拌溶解，加入甲基磺酰氯(0.55g,4.8mmol)室温搅拌过夜，TLC监测反应完毕。将反应液减压脱溶后，加入水，用二氯甲烷萃取，用饱和氯化钠溶液洗两次，硫酸钠干燥，之后用二氯甲烷/甲醇(150:1—130:1)进行硅胶柱层析得到白色固体0.48g，产率85％，熔点220–222℃。1H NMR(400MHz,DMSO-d6)δ10.34(s,1H,NH),4.39(s,2H,CH2),3.56(s,6H,CH3),1.89(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ149.9,146.0,54.3,44.8,19.7.ESI-HRMS(m/z):Calcd.for C6H13N4O5S2[M+H]+285.0322；found 285.0323.
(2)化合物Ib-2至Ib-9通过重复Ib-1的步骤完成。
但不同的是：
制备化合物Ib-2时，采用等摩尔量的乙基磺酰氯(购自安耐吉化学公司)代替甲基磺酰氯；
制备化合物Ib-3时，采用等摩尔量的正丙基磺酰氯(购自北京伊诺凯科技有限公司)代替甲基磺酰氯；
制备化合物Ib-4时，采用等摩尔量的正丁基磺酰氯(购自北京伊诺凯科技有限公司)代替甲基磺酰氯；
制备化合物Ib-5时，采用等摩尔量的
Figure PCTCN2017102600-appb-000051
(购自天津试剂公司)代替甲基磺酰氯；
制备化合物Ib-6时，采用等摩尔量的
Figure PCTCN2017102600-appb-000052
(购自上海阿拉丁生化科技股份有限公司)代替甲基磺酰氯；
制备化合物Ib-7时，采用等摩尔量的
Figure PCTCN2017102600-appb-000053
(购自上海阿拉丁生化科技股份有限公司)代替甲基磺酰氯；
制备化合物Ib-8时，采用等摩尔量的
Figure PCTCN2017102600-appb-000054
(购自上海柏卡化学技术有限公司)代替甲基磺酰氯；
制备化合物Ib-9时，采用等摩尔量的
Figure PCTCN2017102600-appb-000055
(购自北京伊诺凯科技有限公司)代替甲基磺酰氯；
所得化合物的表征结果如下所示：
N-(乙基磺酰)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-乙基磺酰胺(Ib-2)
白色固体，产率74％，熔点183–184℃。1H NMR(300MHz,DMSO-d6)δ10.33(s,1H,NH),4.31(s,2H,CH2),3.64(q,J＝7.5Hz,4H,CH2CH3),1.89(s,3H,CH3),1.33(t,J＝9.6Hz,6H,CH2CH3)；13C NMR(100MHz,DMSO-d6)δ150.1,146.1,54.0,51.3,19.8,7.6.ESI-HRMS(m/z):Calcd.for C8H17N4O5S2[M+H]+313.0635；found 313.0633.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N-(正丙基磺酰)丙烷-1-磺酰胺(Ib-3)
白色固体，产率84％，熔点177–178℃。1H NMR(300MHz,DMSO-d6)δ10.32(s,1H,NH),4.33(s,2H,CH2),3.54–3.69(m 4H,CH2CH2CH3),1.89(s,3H,CH3),1.77–1.86(m,4H,CH2CH2CH3),1.00(t,J＝7.5Hz,6H,CH2CH2CH3)；13C NMR(100MHz,DMSO-d6)δ150.1,146.0,58.2,54.1,19.8,16.5,12.5.ESI-HRMS(m/z):Calcd.for C10H21N4O5S2[M+H]+341.0948；found 341.0946.
N-(正丁基磺酰)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)丁烷-1-磺酰胺(Ib-4)
白色固体，产率85％，熔点157–158℃。1H NMR(300MHz,DMSO-d6)δ10.33(s,1H,NH),4.33(s,2H,CH2),3.56–3.72(m,4H,CH2CH2CH2H3),1.90(s,3H,CH3),1.71–1.83(m,4H,CH2CH2CH2H3),1.38–1.46(m,4H,CH2CH2CH2H3),0.9(t,J＝7.2Hz,6H,CH2CH2CH2CH3)；13C NMR(100MHz,DMSO-d6)δ150.1,146.0,56.4,54.1,24.5,20.7,19.8,13.3.ESI-HRMS(m/z):Calcd.for C12H25N4O5S2[M+H]+369.1261；found 369.1263.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N-(苯磺酰)苯磺酰胺(Ib-5)
白色固体，产率83％，熔点227–228℃。1H NMR(400MHz,DMSO-d6)δ10.25(s,1H,NH),7.90(d,J＝7.5Hz,4H,Ar–H),7.83(t,J＝7.5Hz,2H,Ar–H),7.68(t,J＝7.8Hz,4H,Ar–H),4.22(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ149.5,146.3,137.6,135.1,129.5,128.6,53.1,19.9.ESI-HRMS(m/z):Calcd.for C16H17N4O5S2[M+H]+409.0635；found 409.0639.
4-甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N-对甲基苯磺酰胺(Ib-6)
淡黄色固体，产率81％，熔点219–220℃。1H NMR(300MHz,DMSO-d6)δ10.22(s,1H,NH),7.77(d,J＝8.1Hz,4H,Ar–H),7.47(d,J＝8.1Hz,4H,Ar–H),4.20(s,2H,CH2),2.44(s,6H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ149.5,146.3,145.9,134.8,129.8,128.7,53.0,21.2,19.9.ESI-HRMS(m/z):Calcd.for C18H21N4O5S2[M+H]+437.0948；found 437.0947.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-4-硝基-N-(4-硝基苯磺酰)苯磺酰胺(Ib-7)
淡黄色固体，产率79％，熔点239–240℃。1H NMR(300MHz,DMSO-d6)δ10.37(s,1H,NH),8.49(d,J＝9.0Hz,4H,Ar–H),8.20(d,J＝9.0Hz,4H,Ar–H),4.41(s,2H,CH2),1.93(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ151.1,149.1,146.4,142.3,130.6,124.8,53.6,19.9.ESI-HRMS(m/z):Calcd.for C16H15N6O9S2[M+H]+499.0336；found 499.0329.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-4-乙酰氨基-N-(4-乙酰氨基苯磺酰)苯磺酰胺(Ib-8)
淡黄色固体，产率78％，熔点188–190℃。1H NMR(300MHz,DMSO-d6)δ10.51(s,2H,NH),10.18(s,1H,NH),7.80(s,8H,Ar–H),4.20(s,2H,CH2),2.12(s,6H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ169.4,149.5,146.2,144.9,130.6,130.1,118.3,53.1,24.3,19.9.ESI-HRMS(m/z):Calcd.for C20H23N6O7S2[M+H]+540.1330；found 540.1332.
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-N-(吡啶-3-磺酰基)吡啶-3-磺酰胺(Ib-9)
白色固体，产率42％，熔点213–214℃。1H NMR(400MHz,CDCl3)δ9.05(s,2H,Py-H),8.90(d,J＝4Hz,2H,Py-H),8.18-8.21(m,2H,Py–H),7.51(s,1H,NH),7.49(d,J＝3Hz,2H,Py-H),4.47(s,2H,CH23),2.03(s,3H,CH3)；13C NMR(100MHz,CDCl3)δ155.2,149.9,149.4,146.5,137.1,134.5,123.8,54.8,20.4.ESI-HRMS(m/z):Calcd.for C14H14N6O5S2[M+H]+411.0540；found 411.0534.
实施例3：杀蚜虫的测定，测定程序如下：
蚜虫的活性测试
杀蚜虫活性测定步骤如下：试虫为豆蚜(Aphis laburni Kaltenbach)，实验室蚕豆叶饲养的正常群体。称取药品，加1mL DMF溶解，加两滴吐温－20乳化剂，加入一定量的蒸馏水，搅拌均匀，配成所需浓度的药液(具体浓度见表所示)。将带蚜虫(约60只)蚕豆叶片浸入药剂中5秒钟，拿出轻轻甩干，用滤纸吸干多余药剂，然后将蚕豆枝插入吸水海绵中，并用玻璃罩罩住枝条，用纱布封口，96小时检查结果，每个化合物重复3次。对照只向蒸馏水中加入乳化剂和溶剂，搅拌均匀。
表1 吡蚜酮及磺酰基结构三嗪酮衍生物的杀蚜虫活性测试结果：
Figure PCTCN2017102600-appb-000056
Figure PCTCN2017102600-appb-000057
a–未测.
从表1中可见，在10mg/kg浓度时，部分磺酰基结构三嗪酮衍生物表现出很好的100％杀蚜虫活性。在5mg/kg浓度时，Ia-1，Ia-9，Ia-16，Ia-17，Ia-18，Ia-19，Ia-21，Ia-22，Ia-23，Ia-25，Ia-26，Ia-27，Ib-1表现出和吡蚜酮相当的活性。尤其是化合物Ia-10，Ia-11，Ia-12，Ia-13，Ia-14，Ia-15在2.5mg/kg浓度时仍表现出25％，15％，30％，10％，35％，10％的杀虫活性，而吡蚜酮在相同浓度下没有杀虫活性。
实施例4：杀蚊幼虫活性的测定，测定程序如下：
蚊幼虫的活性测试
蚊幼虫的实验方法：尖音库蚊淡色亚种，室内饲养的正常群体。称取供试化合物约5mg于盘尼西林药瓶中，加5mL丙酮(或适宜溶剂)，振荡溶解，即为1000ppm母液。移取1mL母液，加入盛有89mL水的100mL烧杯中，选取10头4龄初蚊子幼虫，连同10mL饲养液一并倒入烧杯中，其药液的浓度即为10ppm(其它药液浓度的配制通过稀释相应倍数得到)。放入标准处理室内，24h检查结果。以含有0.5mL试验溶剂的水溶液为空白对照。
表2 吡蚜酮及磺酰基结构三嗪酮衍生物的杀蚊幼虫活性测试结果：
Figure PCTCN2017102600-appb-000058
Figure PCTCN2017102600-appb-000059
a-未测
从表2中可见，大多数磺酰基结构三嗪酮衍生物对蚊幼虫均表现出杀虫活性。尤其是化合物Ia-19，Ia-22，Ia-23和Ia-26对蚊幼虫表现出较高的活性。在1mg/kg浓度下，化合物Ia-19，Ia-23和Ia-26对蚊幼虫分别表现出60％、30％、20％的杀虫活性。尤其是化合物Ia-22在0.5mg/kg浓度下对蚊幼虫表现出40％的杀虫活性。
实施例5：杀棉铃虫、玉米螟、粘虫活性的测定，测定程序如下：
棉铃虫的活性测试
棉铃虫的实验方法：饲料混药法，从配置好的溶液中移取3mL加入约27g的刚配置好的饲料中，从而得到稀释十倍的所需浓度。药剂混匀后均匀地倒入干净的24孔板中，晾凉后接入24头三龄棉铃虫，观察3-4天后检查结果。
玉米螟的活性测试
玉米螟的试验方法：浸叶法，配置后所需浓度后，把直径约为5-6㎝的叶片浸入药液中5-6秒，取出，放在吸水纸上晾干，放在指定的培养皿中，接入10头3龄幼虫，放入27±1℃的养虫 室中观察3-4天后检查结果。
粘虫的活性测试
粘虫的实验方法：浸叶法，配置后所需浓度后，把直径约为5-6cm的叶片浸入药液中5-6秒，取出，放在吸水纸上晾干，放在指定的培养皿中，接入10头3龄幼虫，放入27±1℃的养虫室中观察3-4天后检查结果。
表3 吡蚜酮及磺酰基结构三嗪酮结构衍生物(I)的杀棉铃虫、玉米螟、粘虫活性测试结果
Figure PCTCN2017102600-appb-000060
a200mg/kg浓度下死亡率。
从表3中可见，大多数磺酰基结构三嗪酮衍生物对棉铃虫、玉米螟和粘虫均表现出杀虫活性。尤其是化合物Ia-22，在200mg/kg时，对棉铃虫、玉米螟和粘虫分别表现出80％、65％和70％的杀虫活性。
实施例6：杀真菌活性的测定，测定程序如下：
以番茄早疫病菌为例，可以换成其他菌
离体测试方法：将番茄早疫病菌接到PDA培养基上培养7天，用打孔器在菌落边缘制取直径4cm的菌碟接种到含有50mg/kg和不含药剂的PDA培养基上培养4天，量取菌落直径，与对照比较计算出药剂的抑制百分率。
表4 含有磺酰基结构三嗪酮衍衍生物(I)的杀菌活性测试结果：
Figure PCTCN2017102600-appb-000061
从表4中可见，大多数含有磺酰基结构三嗪酮衍生物对13种病原菌表现出较好的杀菌活性，尤其是化合物Ia-4，Ia-12和Ib-5在50mg/kg浓度下对多种病原菌均表现出良好的抑菌活性。

Claims (16)

  1. 一种含有磺酰基结构的三嗪酮衍生物，其中，该三嗪酮衍生物为式(Ia)所示的化合物：
    Figure PCTCN2017102600-appb-100001
    其中，R1为C1-C12的烷基、C3-C6的环烷基、取代的或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、取代的或未取代的苯乙基、取代的或未取代的苯丙基、取代的或未取代的苯丁基、含有1-10个碳原子的含氮杂环、含有1-10个碳原子的含氧杂环、含有1-10个碳原子的含硫杂环；所述取代的苯基、取代的萘基、取代的苄基、取代的苯乙基、取代的苯丙基和取代的苯丁基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、三氟甲基、三氟甲氧基、酰胺基、C1-C6的烃基、C1-C6的烷氧基、C1-C4的烷基取代的羰氧基和C1-C4的烷氧基取代的羰氧基中的一种或多种。
  2. 根据权利要求1所述的三嗪酮衍生物，其中，R1为C1-C8的烷基、C3-C6的环烷基、取代的或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、取代的或未取代的苯乙基、取代的或未取代的苯丙基、取代的或未取代的苯丁基、含有2-8个碳原子的含氮杂环、含有2-8个碳原子的含氧杂环、含有2-8个碳原子的含硫杂环；所述取代的苯基、取代的萘基、取代的苄基、取代的苯乙基、取代的苯丙基和取代的苯丁基的取代基各自独立地选自羟基、F、Cl、Br、I、氰基、硝基、-COOCH3、-COOCH2CH3、三氟甲基、三氟甲氧基、-NH-CO-CH3、-NH-CO-CH2CH3、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基、叔丁氧基、正戊氧基、C1-C5的烷基、C1-C5的烷氧基、-O-CO-CH3、-O-CO-CH2CH3、-O-CO-O-CH3和-O-CO-O-CH2CH3中的一种或多种。
  3. 根据权利要求1或2所述的三嗪酮衍生物，其中，式(Ia)所示的化合物选自下式中所示的化合物中的一种：
    Figure PCTCN2017102600-appb-100002
    Figure PCTCN2017102600-appb-100003
    Figure PCTCN2017102600-appb-100004
    Figure PCTCN2017102600-appb-100005
  4. 一种权利要求1-3中任意一项所述的三嗪酮衍生物的制备方法，该方法包括：在缚酸剂存在下，在有机溶剂中，将式(II)所示的氨基三嗪酮与式(III)所示的磺酰氯类化合物进行取代反应，得到式(Ia)所示的化合物；
    Figure PCTCN2017102600-appb-100006
    Figure PCTCN2017102600-appb-100007
  5. 根据权利要求4所述的方法，其中，式(II)所示的氨基三嗪酮与式(III)所示的磺酰氯类化合物的用量的摩尔比为1：0.8-1.2，优选为1：1-1.1；
    优选地，所述缚酸剂为碳酸钠、碳酸钾、碳酸铯、三乙胺和吡啶中的一种或多种；
    优选地，所述有机溶剂为甲醇、乙醇、吡啶、N,N-二甲基甲酰胺和二甲基亚砜中的一种或多种；
    优选地，所述有机溶剂的用量使得式(II)所示的氨基三嗪酮的浓度为0.05-0.5mmol/mL。
  6. 根据权利要求4或5所述的方法，其中，所述取代反应的条件包括：温度为15-40℃，时间为4-12h。
  7. 一种含有磺酰基结构的三嗪酮衍生物，其中，该三嗪酮衍生物为式(Ib)所示的化合物：
    Figure PCTCN2017102600-appb-100008
    其中，各个R1各自独立地选自C1-C12的烷基、C3-C6的环烷基、取代的或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、取代的或未取代的苯乙基、取代的或未取代的苯丙基、取代的或未取代的苯丁基、含有1-10个碳原子的含氮杂环、含有1-10个碳原子的含氧杂环、含有1-10个碳原子的含硫杂环；所述取代的苯基、取代的萘基、取代的苄基、取代的苯乙基、取代的苯丙基和取代的苯丁基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、三氟甲基、三氟甲氧基、酰胺基、C1-C6的烃基、C1-C6的烷氧基、C1-C4的烷基取代的羰氧基和C1-C4的烷氧基取代的羰氧基中的一种或多种。
  8. 根据权利要求7所述的三嗪酮衍生物，其中，各个R1各自独立地选自C1-C8的烷基、C3-C6的环烷基、取代的或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、取代的或未取代的苯乙基、取代的或未取代的苯丙基、取代的或未取代的苯丁基、含有2-8个碳原子的含氮杂环、含有2-8个碳原子的含氧杂环、含有2-8个碳原子的含硫杂环；所述取代的苯基、取代的萘基、取代的苄基、取代的苯乙基、取代的苯丙基和取代的苯丁基的取代基各自独立地选自羟基、F、Cl、Br、I、氰基、硝基、-COOCH3、-COOCH2CH3、三氟甲基、三氟甲氧基、-NH-CO-CH3、-NH-CO-CH2CH3、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基、叔丁氧基、正戊氧基、C1-C5的烷基、C1-C5的烷氧基、-O-CO-CH3、-O-CO-CH2CH3、-O-CO-O-CH3和-O-CO-O-CH2CH3中的一种或多种。
  9. 根据权利要求7或8所述的三嗪酮衍生物，其中，式(Ib)所示的化合物选自下式中所示的化合物中的一种：
    Figure PCTCN2017102600-appb-100009
    Figure PCTCN2017102600-appb-100010
  10. 一种权利要求7-9中任意一项所述的三嗪酮衍生物的制备方法，该方法包括：在缚酸剂存在下，在有机溶剂中，将式(II)所示的氨基三嗪酮与式(III)所示的磺酰氯类化合物进行取代反应，得到式(Ib)所示的化合物；
    Figure PCTCN2017102600-appb-100011
    Figure PCTCN2017102600-appb-100012
  11. 根据权利要求10所述的方法，其中，式(II)所示的氨基三嗪酮与式(III)所示的磺酰氯类化合物的用量的摩尔比为1：1.8-2.5，优选为1：2-2.4；
    优选地，所述缚酸剂为碳酸钠、碳酸钾、碳酸铯、三乙胺和吡啶中的一种或多种；
    优选地，所述有机溶剂为甲醇、乙醇、吡啶、N,N-二甲基甲酰胺和二甲基亚砜中的一种或多种；
    优选地，所述有机溶剂的用量使得式(II)所示的氨基三嗪酮的浓度为0.05-0.5mmol/mL。
  12. 根据权利要求10或11所述的方法，其中，所述取代反应的条件包括：温度为15-40℃，时间为4-12h。
  13. 权利要求1-3和7-9中任意一项所述的三嗪酮衍生物在杀虫方面的应用。
  14. 根据权利要求13所述的应用，其中，该应用针对的害虫是蚜虫、蚊幼虫、棉铃虫、玉米螟和粘虫中的一种或多种。
  15. 权利要求1-3和7-9中任意一项所述的三嗪酮衍生物在杀菌方面的应用。
  16. 根据权利要求15所述的应用，其中，该应用针对的是引起番茄早疫、小麦赤霉、马铃薯晚疫、辣椒疫霉、油菜菌核、黄瓜灰霉、水稻纹枯、黄瓜枯萎、花生褐斑、苹果轮纹、小麦纹枯、玉米小斑、西瓜炭疽和水稻恶苗的病原菌中的一种或多种。
PCT/CN2017/102600 2017-09-21 2017-09-21 含有磺酰基结构三嗪酮衍生物及其制备方法和在杀虫、杀菌方面的应用 WO2019056246A1 (zh)

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EP17892064.1A EP3486237B1 (en) 2017-09-21 2017-09-21 Triazinone derivative containing sulfonyl structure and preparation method therefor, and insecticidal and bactericidal uses thereof
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CN111892549B (zh) * 2019-05-06 2023-10-27 南开大学 一种催化条件下制备单磺酰基取代三嗪酮化合物的方法

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