WO2019047978A1 - 含氟氯吡啶肟酯结构的化合物及其制备方法和应用及一种除草剂 - Google Patents

含氟氯吡啶肟酯结构的化合物及其制备方法和应用及一种除草剂 Download PDF

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WO2019047978A1
WO2019047978A1 PCT/CN2018/105074 CN2018105074W WO2019047978A1 WO 2019047978 A1 WO2019047978 A1 WO 2019047978A1 CN 2018105074 W CN2018105074 W CN 2018105074W WO 2019047978 A1 WO2019047978 A1 WO 2019047978A1
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compound
group
substituted
unsubstituted
phenyl
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French (fr)
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杨光富
李克建
王现全
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山东先达农化股份有限公司
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Priority to CN201880047028.7A priority Critical patent/CN111094245B/zh
Publication of WO2019047978A1 publication Critical patent/WO2019047978A1/zh

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    • 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • 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
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Definitions

  • the invention relates to the field of pesticide herbicides, in particular to a compound containing fluorine-containing chloropyridinium ester structure, a preparation method thereof, a compound of the fluorine-containing chloropyridinium ester structure in controlling weeds and a herbicide.
  • Phytohormone herbicides play an important role in the herbicide family, which can produce physiological responses similar to those of indole-3-acetic acid (IAA), which have a high intensity and duration in plants. Long and good stability advantages. At present, most of the varieties are represented by phenoxycarboxylic acid herbicides. They have been widely used for more than 60 years since the industrial production in the 1940s. The herbicide can selectively control wheat fields, corn fields and pastures. Dicotyledon weeds in grassland and turfgrass.
  • IAA indole-3-acetic acid
  • Phytohormone herbicides have become the most promising herbicides in recent years due to their high efficiency, broad-spectrum herbicidal activity and relatively low risk of resistance, and have attracted the attention of major pesticide companies around the world.
  • Dow AgroSciences developed in recent years chlorofluorocarbons pyridine herbicides of Arylex TM Active and Rinskor TM Active on the market and because of its wide spectrum herbicide and has good prospects for development.
  • the present invention designs and synthesizes a series of phytohormone herbicides containing chloropyridinium ester structure, and studies its herbicidal activity.
  • a first aspect of the present invention provides a compound having a fluorine-containing chloropyridinium ester structure or an agrochemically acceptable salt, hydrate, solvate thereof, or an isomer thereof, and a tautomer thereof. a derivative of the conformation, enantiomer, or optically active form, the compound having the structure represented by the formula (1),
  • R is a group represented by the formula (1-1),
  • R 1 and R 2 are each independently selected from H, cyano, halogen, substituted or unsubstituted C 1-30 alkyl, substituted or unsubstituted C 1-30 alkane.
  • the substituent is selected from the group consisting of halogen, C 1-12 alkyl, C 1-12 alkoxy, phenyl, C 1-12 alkyl-phenyl, phenyl substituted by 1-6 halogen, a phenoxy group substituted with 1 to 6 halogens, a thienyl group, a cyano group, a nitro group, a C 1-12 alkyl group substituted by 1 to 6 halogens, an amino group substituted by a C 1-12 alkyl group, C An ester group of 1 to 12 , or two of the substituents, together form a C 2-12 cycloalkyl group having no or at least one hetero atom selected from N, O and S, or a substituent Two of the rings are combined to form any one group selected from the group consisting of a phenyl group, a thienyl group, and a pyridyl group; or the carbon atoms in the above R 1 and R 2 together with the oxygen
  • the present invention provides a method for producing a compound of the fluorine-containing chloropyridinium ester structure represented by the formula (1) according to the first aspect, which comprises: formula (2) in the presence of a condensing agent The compound of the structure shown is subjected to a contact reaction with a compound of the structure represented by the formula (3),
  • the present invention provides the use of the compound of the fluorine-containing chloropyridinium ester structure according to the first aspect for controlling weeds.
  • the present invention provides a herbicide comprising an active ingredient and an auxiliary material, the active ingredient comprising the fluorine-containing chloropyridinium ester structure compound of the above first aspect or an agrochemically acceptable compound thereof At least one of a salt, a hydrate, a solvate, or a derivative thereof, a tautomer, an enantiomer, or an optically active form.
  • the novel compound provided by the present invention has good herbicidal activity against broad-leaved weeds, and in particular, the compound provided by the present invention is remarkably excellent in herbicidal activity against the calf. Further, the compound of the present invention has high herbicidal activity against grass weeds.
  • the compounds provided by the present invention have high safety to crops.
  • the first aspect of the present invention provides a compound having a fluorine-containing chloropyridinium ester structure or an agrochemically acceptable salt, hydrate, solvate thereof, or an isomer thereof, and an interconversion thereof.
  • Isomer, enantiomer, derivative of optically active form the compound having the structure represented by formula (1),
  • R is a group represented by the formula (1-1),
  • R 1 and R 2 are each independently selected from H, cyano, halogen, substituted or unsubstituted C 1-30 alkyl, substituted or unsubstituted C 1-30 alkane.
  • the substituent is selected from the group consisting of halogen, C 1-12 alkyl, C 1-12 alkoxy, phenyl, C 1-12 alkyl-phenyl, phenyl substituted by 1-6 halogen, a phenoxy group substituted with 1 to 6 halogens, a thienyl group, a cyano group, a nitro group, a C 1-12 alkyl group substituted by 1 to 6 halogens, an amino group substituted by a C 1-12 alkyl group, C An ester group of 1 to 12 , or two of the substituents, together form a C 2-12 cycloalkyl group having no or at least one hetero atom selected from N, O and S, or a substituent Two of the rings are combined to form any one group selected from the group consisting of a phenyl group, a thienyl group, and a pyridyl group; or the carbon atoms in the above R 1 and R 2 together with the oxygen
  • Halogen means fluorine, chlorine, bromine and iodine.
  • Substituted or unsubstituted C 1-30 alkyl means the total number of carbon atoms of R 1 and R 2 when R 1 and/or R 2 are "substituted or unsubstituted C 1-30 alkyl" All are 1-30, and may be a linear or branched alkyl group; if it is a "substituted C 1-30 alkyl group", the substituent on the alkyl group may be a substituent described in the present invention. Any one or two or more.
  • C 1-30 unsubstituted or unsubstituted alkoxy group means, when R 1 and / or R 2 is a "C 1-30 unsubstituted or unsubstituted alkoxy", R 1 and R 2 carbons
  • the total number of atoms is 1-30, and may be a linear or branched alkoxy group; if it is a "substituted C 1-30 alkoxy group", the substituent on the alkoxy group may be in the present invention Any one or two or more of the substituents described.
  • “Substituted or unsubstituted C 3-30 cycloalkyl” means a carbon of R 1 and R 2 when R 1 and/or R 2 is "substituted or unsubstituted C 3-30 cycloalkyl"
  • the total number of atoms is 3-30, and the members of the ring forming a cycloalkyl group are all carbon atoms; if it is a "substituted C 3-30 cycloalkyl group", the substituent on the cycloalkyl group can be described in the present invention. Any one or two or more of the substituents.
  • the cycloalkyl group in the "substituted or unsubstituted C 3-30 cycloalkyl group" of the present invention includes a monocyclic group and a bicyclo or higher cycloalkyl group.
  • Aryl means a group derived from a phenyl group which may be a phenyl group, a naphthyl group, or a group which may be obtained by substituting a carbon atom on a ring of a phenyl group or a naphthyl group, for example, N or the like.
  • Substituted or unsubstituted C 5-30 aryl group which does not contain or contains at least one hetero atom selected from N, O and S means that when R 1 and/or R 2 are "substituted or unsubstituted" In the case of a C 5-30 aryl group which does not contain or contain at least one hetero atom selected from N, O and S, the total number of carbon atoms of R 1 and R 2 is 5 to 30, and a ring forming an aryl group
  • the member may be a carbon atom, or may contain at least one hetero atom selected from N, O and S; if "the substitution does not contain or contains at least one hetero atom selected from N, O and S"
  • the aryl group of C 5-30 ", the substituent on the aryl group may be any one or two or more of the substituents described in the invention.
  • Substituted or unsubstituted C 4-30 cycloalkyl group containing at least one hetero atom selected from N, O and S means that when R 1 and/or R 2 are "substituted or unsubstituted” From the C 4-30 cycloalkyl group of at least one hetero atom of N, O and S, the total number of carbon atoms of R 1 and R 2 is 4 to 30, and the members of the ring forming the cycloalkyl group are excluded.
  • the carbon atom further contains at least one hetero atom selected from the group consisting of N, O and S; and the "substituted C 4-30 cycloalkyl group having at least one hetero atom selected from N, O and S"
  • the substituent on the cycloalkyl group may be any one or two or more of the substituents described in the invention.
  • the cycloalkyl group in the "substituted or unsubstituted C 4-30 cycloalkyl group having at least one hetero atom selected from N, O and S" of the present invention includes a monocyclic group and a bicyclo or higher cycloalkyl group. .
  • Substituted or unsubstituted carbonyl-phenyl means that when R 1 and/or R 2 is "substituted or unsubstituted carbonyl-phenyl", it is directly bonded to the carbon atom shown in formula (1-1).
  • the group is a carbonyl group, and the other side of the carbonyl group is bonded to a substituted or unsubstituted phenyl group; if it is a "substituted carbonyl-phenyl group", the substituent on the phenyl group may be any of the substituents described in the present invention. One or two or more.
  • Substituted or unsubstituted carbonyl-C 1-12 alkyl means that when R 1 and/or R 2 is "substituted or unsubstituted carbonyl-C 1-12 alkyl", and formula (1-1)
  • the group in which the carbon atom is directly bonded is a carbonyl group, and the other side of the carbonyl group is bonded to a substituted or unsubstituted linear or branched alkyl group having 1 to 12 carbon atoms; if it is a "substituted carbonyl group-C”
  • the substituent on the 1-12 alkyl group, the C 1-12 alkyl group may be any one or two or more of the substituents described in the invention; and, the "C 1-12 alkyl group” attached to the carbonyl group.
  • the total number of carbon atoms is from 1 to 12, even including the number of carbon atoms on the substituents that may be present.
  • R 1 and R 2 are cyclized together to form a substituted or unsubstituted monocyclic or bicyclic or higher 3-30 membered cycloalkyl group which does not contain or contain at least one hetero atom selected from N, O and S" It is shown that R 1 and R 2 , together with the carbon atom represented by the formula (1-1), form a monocyclic or bicyclo or higher cycloalkyl group, and the total number of atoms of each ring forming a cycloalkyl group is 3 to 30. .
  • R 1 and R 2 are each independently selected from H, cyano, halogen, substituted or unsubstituted C 1-20 alkyl, substituted or unsubstituted C 1-20 alkoxy, substituted or unsubstituted C 3-20 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted benzofuranyl, substituted or unsubstituted benzothienyl, substituted or unsubstituted quin a phenyl group, a substituted or unsubstituted fluorenyl group, a substituted or unsubstituted pyridyl group, a substituted or unsubstituted thienyl group, a substituted or unsubstituted C containing at least one hetero atom selected from N, O and S a 4-20 cycloalkyl group, a substituted or unsubstitute
  • the substituent is selected from the group consisting of fluorine, chlorine, bromine, C 1-6 alkyl, C 1-6 alkoxy, phenyl, C 1-6 alkyl-phenyl, selected from 1 to 4 a halogen-substituted phenyl group of fluorine, chlorine and bromine, a phenoxy group substituted with 1 to 4 halogens selected from fluorine, chlorine and bromine, a thienyl group, a cyano group, a nitro group, and 1 to 4 selected from fluorine.
  • a halogen-substituted C 1-6 alkyl group of chlorine and bromine, an amino group substituted by a C 1-6 alkyl group, an ester group of C 1-6 , or two of the substituents are combined to form a non-containing or a C 2-8 cycloalkyl group containing at least one hetero atom selected from N, O and S, or two cyclizations in the substituent to form any one selected from the group consisting of a phenyl group, a thienyl group and a pyridyl group A group, or a carbon atom in the above R 1 and R 2 together with an oxygen atom forms a carbon-oxygen double bond such that the R 1 and R 2 contain a carbonyl group.
  • R 1 and R 2 are each independently selected from H, cyano, fluoro, chloro, bromo, substituted or unsubstituted C 1-12 alkyl, substituted or unsubstituted C 1-12 alkoxy, substituted or Unsubstituted C 3-20 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted thienyl, substituted or unsubstituted containing selected from N, O and S At least one hetero atom of a C 4-20 cycloalkyl group, a substituted or unsubstituted carbonyl-phenyl group, a substituted or unsubstituted carbonyl-C 1-6 alkyl group, or a combination of R 1 and R 2 Forming a substituted or unsubstituted monocyclic or bicyclic or higher 3-20 membered cycloalkyl group containing no or at least
  • the substituent is selected from the group consisting of fluorine, chlorine, bromine, C 1-6 alkyl, C 1-6 alkoxy, phenyl, C 1-6 alkyl-phenyl, selected from 1 to 4 a halogen-substituted phenyl group of fluorine, chlorine and bromine, a phenoxy group substituted with 1 to 4 halogens selected from fluorine, chlorine and bromine, a thienyl group, a cyano group, a nitro group, and 1 to 4 selected from fluorine.
  • a halogen-substituted C 1-6 alkyl group of chlorine and bromine, an amino group substituted by a C 1-6 alkyl group, an ester group of C 1-6 , or two of the substituents are combined to form a non-containing or a C 2-8 cycloalkyl group containing at least one hetero atom selected from N, O and S, or two cyclizations in the substituent to form any one selected from the group consisting of a phenyl group, a thienyl group and a pyridyl group A group, or a carbon atom in the above R 1 and R 2 together with an oxygen atom forms a carbon-oxygen double bond such that the R 1 and R 2 contain a carbonyl group.
  • the compound of the structure represented by the formula (1) is selected from at least one of the compounds recited in claim 3.
  • the second aspect of the present invention provides a process for producing a compound of the fluorine-containing chloropyridinium ester structure represented by the formula (1) according to the first aspect, which comprises: in the presence of a condensing agent a compound having a structure represented by the formula (2) and a compound having a structure represented by the formula (3) are subjected to a contact reaction,
  • the conditions of the contact reaction include: a reaction temperature of 5 to 50 ° C, and a reaction time of 4 to 30 h.
  • the contacting reaction is carried out in the presence of a solvent; preferably, the solvent is selected from at least one of dichloromethane, methanol, ethanol, toluene, cyclohexane, DMF and DMSO.
  • a solvent is selected from at least one of dichloromethane, methanol, ethanol, toluene, cyclohexane, DMF and DMSO.
  • the condensing agent is a mixture of EDCI (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) and DMAP (4-dimethylaminopyridine).
  • the method of the present invention is not particularly limited to the source of the raw materials represented by the formula (2) and the formula (3), and can be obtained by a person skilled in the art by commercially available or by a synthetic method conventional in the art.
  • the present invention provides an exemplary synthesis method of the starting materials of the formula (2) and the formula (3), and the method for obtaining the raw materials of the present invention is not limited thereto, and those skilled in the art should not understand To limit the invention.
  • the post-treatment step of the present invention may also be subjected to a conventional post-treatment step.
  • the manner of the post-treatment step of the present invention is not particularly limited, and may be conventionally used in the art, for example, solvent removal, filtration treatment, drying treatment, recrystallization. Treatment, chromatography, and the like.
  • the third aspect of the present invention provides the use of the compound of the fluorine-containing chloropyridinium ester structure represented by the above formula (1) in the first aspect of the present invention for controlling weeds.
  • the weed is at least one of broadleaf weeds and grass weeds.
  • the weeds include ramie, amaranth, scorpion, valerian, crabgrass, foxtail, leeks, sage, cocklebur, sage, snail, lacquer, piglet, giant Amaranth, alfalfa, goosegrass, stalk grass, white stalk, sage, reed, thousand gold, double-spotted gar, sorrel, scented aconite, broken sedge, sedge, flatgrass, At least one of the cockroaches and the wild cockroaches.
  • the fourth aspect of the invention provides a herbicide comprising an active ingredient and an auxiliary material, the active ingredient comprising the fluorine-containing chlorine represented by the formula (1) according to the first aspect of the invention.
  • a compound of a pyridinium ester structure or an agrochemically acceptable salt, hydrate, solvate thereof, or a derivative thereof, a tautomer, an enantiomer or an optically active form thereof At least one.
  • the active ingredient is present in an amount of from 1 to 99.9% by weight.
  • the herbicide dosage form is selected from at least one of an emulsifiable concentrate, a suspending agent, a microemulsion, an aqueous emulsion, a capsule, a wettable powder, a powder, a granule, a liquid, a bait, a mother liquor, and a mother powder.
  • the substituted picolinic acid (4.83 mmol) was dissolved in 10 mL of methanol solution, and thionyl chloride (7.25 mmol) was added dropwise under ice bath. After the dropwise addition was completed, the reaction was further carried out at 65 ° C for 12 h, and the reaction was completed and added dropwise. Water, ethyl acetate extraction, drying, solvent removal of intermediate b.
  • the herbicidal activity (summer weed) of the target compound was determined by a pot experiment in a greenhouse, and fluorochloropyridyl ester (Arylex Active) was used as a control agent.
  • fluorochloropyridyl ester Arylex Active
  • the structural formula of fluorochloropyridinium is as follows:
  • the specific test method is: potted method (general sieve): the target is ramie, amaranth, sputum and valerian. Take the 7.5cm inner diameter flowerpot, install the composite soil (garden soil: seedling substrate, 1:2, v/v) to 3/4, directly sow the above weed target (bud rate ⁇ 85%), cover soil 0.2cm, wait Weeds grow to around 3 leaves for later use. Each compound was applied to an automatic spray tower (model: 3WPSH-700E) at a dose of 150g ai/ha. After the herb leaf foliar solution was dried, it was transferred to a greenhouse for cultivation. After 30 days, the fresh weight inhibition rate of weeds was investigated (%). After 30 days of test treatment, the target symptom and growth inhibition were visually observed, and the fresh weight of the aerial part was calculated, and the fresh weight inhibition rate (%) was calculated.
  • Fresh weight inhibition rate (%) (control fresh weight - treated fresh weight) / control fresh weight ⁇ 100%
  • Table 1 Results of the target compound on summer weed control activity (fresh weight inhibition rate /%) (30d after drug)
  • the compounds provided by the present invention have good herbicidal activity against broadleaf weeds and grass weeds at a concentration of 150 gai/ha, in particular, the compounds of the present invention are paralyzed.
  • the herbicidal activity of the intestine was significantly higher than that of the control agent.
  • Table 2 Screening test results of herbicidal activity after reduction of target compound (fresh weight inhibition rate /%)
  • the compounds provided by the present invention have high herbicidal activity against broadleaf weeds such as ramie, amaranth, and scorpion, and the herbicidal activity is generally compared with the control.
  • the effect of the medicine is equivalent.
  • the compounds provided by the present invention have higher herbicidal activity against gramineous weeds and foxtail grasses at lower concentrations than herbicide weeds of the control agents.
  • a part of the target compound synthesized was subjected to a living herbicidal activity (indoor to the intestine) by a greenhouse pot experiment, and fluorochloropyridyl ester (Arylex Active) was used as a control agent.
  • the specific test methods are: post-emergence stem and leaf spray, activity on weeds, take 7cm inner diameter paper cup, install composite soil (garden soil: seedling substrate, 1:2, v/v) to 3/4, direct sowing Grass, covering soil 0.2cm, to be used until 4-5 leaf period.
  • the new compound and the control drug chlorochloropyridinate were applied to the automatic spray tower at a dose of 3.75 gai/ha. After the crop foliar liquid was dried, it was transferred to a greenhouse culture (25 degrees-15 g.ai/ha 28 degrees, humidity 70%). ), the results of the survey after 25 days.
  • the compound provided by the present invention has high herbicidal activity against the calf.
  • the present invention provides a compound having a higher herbicidal activity against the calf than the control agent at a low concentration of 3.75 g a.i./ha.
  • the specific test method is: post-emergence stem and leaf spray: take 7cm inner diameter paper cup, install composite soil (garden soil: seedling substrate, 1:2, v/v) to 3/4, directly weed the weed, cover soil 0.2cm, Wait until the 4-5 leaf period is reserved.
  • the new compound and the control drug chlorochloropyridyl ester were applied to the greenhouse spray after being applied to the automatic spray tower at a dose of 37.5 gai/ha, 75 g.ai/ha, 150 g.ai/ha, and then transferred to the greenhouse for cultivation (25 degrees). -15g.ai/ha 28 degrees, humidity 70%), the results were investigated after 25 days.
  • test results are listed in Table 4.
  • safety (visual growth inhibition rate %) evaluation criteria are listed in Table 5.
  • the compounds provided by the present invention are highly safe for crops, and in particular, the compounds provided by the present invention are safer for wheat and indica than the control agents and even safer than the control agents.
  • the compound provided by the present invention has herbicidal activity comparable to that of the control agent for broad-leaved weeds.
  • the herbicidal activity of the compound provided by the present invention against the calf is significantly higher than that of the control agent. Be high.
  • the compound of the present invention has high herbicidal activity against grass weeds. Further, the compounds of the invention are safer for crops.
  • Potting method (screening of resistant weeds): The tested target was 2 populations of Valeriana, and the resistance status of weed population to ACCase herbicide is shown in Table 6. Take the 7.5cm inner diameter flowerpot, install composite soil (garden soil: seedling substrate, 1:2, v/v) to 3/4, directly sow the above 7 weed targets (bud rate ⁇ 85%), cover soil 0.2cm Wait until the weeds grow to around 3 weeks. Each compound was applied to an automatic spray tower (model: 3WP-2000, nozzle type TP605E) according to the dose of Table 7, and the weed leaf foliar solution was dried and transferred to a greenhouse culture, and the inhibitory activity against weeds was investigated 25 days later ( %).
  • the compound provided by the present invention exhibits a good inhibitory effect on valerian even at a low concentration, and the symptoms mainly manifest as that the base of the weed stem begins to expand at 10 days after the drug. Distortion, malformation, plant growth is inhibited; symptoms are aggravated 20 days after the drug, some weeds are twisted and undulated, leaves are yellowed and dead, and the whole plant is dead.
  • the compound of the present invention is on weeds. The inhibitory activity is higher than the control agent.

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Abstract

一种含氟氯吡啶肟酯结构的式(1)化合物及其制备方法和应用以及一种包含所述化合物的除草剂，该化合物具有优异的除草活性。

Description

含氟氯吡啶肟酯结构的化合物及其制备方法和应用及一种除草剂 技术领域
本发明涉及农药除草剂领域，具体涉及一种含氟氯吡啶肟酯结构的化合物及其制备方法、该含氟氯吡啶肟酯结构的化合物在防治杂草中的应用以及一种除草剂。
背景技术
植物激素类除草剂在除草剂家族中占有重要位置，它可对植物产生与吲哚乙酸(IAA，indole-3-acetic acid)相似的生理反应，在植物体内产生的作用具有强度高、持续时间长以及较好的稳定性的优点。目前用的较多的是以苯氧羧酸类除草剂为代表的品种，自20世纪40年代工业化生产以来已被广泛应用了60多年，该除草剂可选择性地防除麦田、玉米地、牧草草场、草坪草中的双子叶杂草。
植物激素类除草剂因其高效、广谱的除草活性和相对较低的抗性风险，近年来已经成为最有发展前景的一类除草剂，受到世界各大农药公司关注。例如陶氏益农公司近年开发的氟氯吡啶酯类除草剂Arylex TMActive和Rinskor TMActive已上市，因其具有较广的杀草谱而具有良好的发展前景。
为了开发更多的植物激素类除草剂，本发明设计合成了一系列含氟氯吡啶肟酯结构的植物激素类除草剂，并对其除草活性进行了研究。
发明内容
本发明的目的是提供一类新的植物激素类除草剂，以实现对阔叶杂草和禾本科杂草均具有良好的除草活性，且对作物的安全性高。
为了实现上述目的，本发明的第一方面提供一种含氟氯吡啶肟酯结构的化合物或其农业化学上可接受的盐、水合物、溶剂化物，或其同分异构体、互变异构体、对映异构体、光学活性形式的衍生物，该化合物具有式(1)所示的结构，
Figure PCTCN2018105074-appb-000001
其中，在式(1)中，R为式(1-1)所示的基团，
在式(1-1)中，R 1和R 2各自独立地选自H、氰基、卤素、取代或未取代的C 1-30的烷基、取代或未取代的C 1-30的烷氧基、取代或未取代的C 3-30的环烷基、取代或未取代的不含有或者含有选自N、O和S中的至少一种杂原子的C 5-30的芳基、取代或未取代的吡啶基、取代或未取代的噻吩基、取代或未取代的含有选自N、O和S中的至少一种杂原子的C 4-30的环烷基、取代或未取代的羰基-苯基、取代或未取代的羰基-C 1-12烷基，或者R 1和R 2环合而共同形成取代或未取代的不含有或者含 有选自N、O和S中的至少一种杂原子的单环或者二环以上的3-30元环烷基，且R 1和R 2不同时为H，
其中的取代基选自卤素、C 1-12的烷基、C 1-12的烷氧基、苯基、C 1-12的烷基-苯基、由1-6个卤素取代的苯基、由1-6个卤素取代的苯氧基、噻吩基、氰基、硝基、由1-6个卤素取代的C 1-12的烷基、由C 1-12的烷基取代的氨基、C 1-12的酯基，或者取代基中的两个环合而共同形成不含有或者含有选自N、O和S中的至少一种杂原子的C 2-12的环烷基，或者取代基中的两个环合而共同形成选自苯基、噻吩基和吡啶基中的任意一个基团；或者上述R 1和R 2中的碳原子与氧原子一起形成碳氧双键而使得所述R 1和R 2中含有羰基基团。
第二方面，本发明提供一种制备第一方面所述的式(1)所示的含氟氯吡啶肟酯结构的化合物的方法，该方法包括：在缩合剂存在下，将式(2)所示结构的化合物与式(3)所示结构的化合物进行接触反应，
Figure PCTCN2018105074-appb-000002
其中，式(3)中的R基团的定义与前述第一方面所述的定义相同。
第三方面，本发明提供第一方面所述的含氟氯吡啶肟酯结构的化合物在防治杂草中的应用。
第四方面，本发明提供一种除草剂，该除草剂由活性成分和辅料组成，所述活性成分包括前述第一方面所述的含氟氯吡啶肟酯结构的化合物或其农业化学上可接受的盐、水合物、溶剂化物，或其同分异构体、互变异构体、对映异构体、光学活性形式的衍生物中的至少一种。
本发明提供的新化合物对阔叶杂草具有良好的除草活性，特别地，本发明提供的化合物对鱧肠的除草活性显著优异。并且，本发明的化合物对禾本科杂草具有较高的除草活性。
另外，本发明提供的化合物对作物的安全性高。
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。
如前所述，本发明的第一方面提供了一种含氟氯吡啶肟酯结构的化合物或其农业化学上可接受的盐、水合物、溶剂化物，或其同分异构体、互变异构体、对映异构体、光学活性形式的衍生物，该化合物具有式(1)所示的结构，
Figure PCTCN2018105074-appb-000003
其中，在式(1)中，R为式(1-1)所示的基团，
在式(1-1)中，R 1和R 2各自独立地选自H、氰基、卤素、取代或未取代的C 1-30的烷基、取代或未取代的C 1-30的烷氧基、取代或未取代的C 3-30的环烷基、取代或未取代的不含有或者含有选自N、O和S中的至少一种杂原子的C 5-30的芳基、取代或未取代的吡啶基、取代或未取代的噻吩基、取代或未取代的含有选自N、O和S中的至少一种杂原子的C 4-30的环烷基、取代或未取代的羰基-苯基、取代或未取代的羰基-C 1-12烷基，或者R 1和R 2环合而共同形成取代或未取代的不含有或者含有选自N、O和S中的至少一种杂原子的单环或者二环以上的3-30元环烷基，且R 1和R 2不同时为H，
其中的取代基选自卤素、C 1-12的烷基、C 1-12的烷氧基、苯基、C 1-12的烷基-苯基、由1-6个卤素取代的苯基、由1-6个卤素取代的苯氧基、噻吩基、氰基、硝基、由1-6个卤素取代的C 1-12的烷基、由C 1-12的烷基取代的氨基、C 1-12的酯基，或者取代基中的两个环合而共同形成不含有或者含有选自N、O和S中的至少一种杂原子的C 2-12的环烷基，或者取代基中的两个环合而共同形成选自苯基、噻吩基和吡啶基中的任意一个基团；或者上述R 1和R 2中的碳原子与氧原子一起形成碳氧双键而使得所述R 1和R 2中含有羰基基团。
“卤素”表示氟元素、氯元素、溴元素和碘元素。
“取代或未取代的C 1-30的烷基”表示，当R 1和/或R 2为“取代或未取代的C 1-30的烷基”时，R 1和R 2的碳原子总数均为1-30，并且可以为直链或支链的烷基基团；若为“取代的C 1-30的烷基”，烷基上的取代基可以为本发明中描述的取代基中的任意一种或者两种以上。
“取代或未取代的C 1-30的烷氧基”表示，当R 1和/或R 2为“取代或未取代的C 1-30的烷氧基”时，R 1和R 2的碳原子总数均为1-30，并且可以为直链或支链的烷氧基基团；若为“取代的C 1-30的烷氧基”，烷氧基上的取代基可以为本发明中描述的取代基中的任意一种或者两种以上。
“取代或未取代的C 3-30的环烷基”表示，当R 1和/或R 2为“取代或未取代的C 3-30的环烷基”时，R 1和R 2的碳原子总数均为3-30，并且形成环烷基的环的成员均为碳原子；若为“取代的C 3-30的环烷基”，环烷基上的取代基可以为本发明中描述的取代基中的任意一种或者两种以上。本发明的“取代或未取代的C 3-30的环烷基”中的环烷基包括单环和二环以上的环烷基。
“芳基”表示，由苯基衍生的基团，可以为苯基、萘基，或者可以为苯基或者萘基的环上的碳原子被例如N等替换而获得的基团。
“取代或未取代的不含有或者含有选自N、O和S中的至少一种杂原子的C 5-30的芳基”表示，当R 1和/或R 2为“取代或未取代的不含有或者含有选自N、O和S中的至少一种杂原子的C 5-30的芳基”时，R 1和R 2的碳原子总数均为5-30，并且形成芳基的环的成员可以均为碳原子，也可以含有选 自N、O和S中的至少一种杂原子；若为“取代的不含有或者含有选自N、O和S中的至少一种杂原子的C 5-30的芳基”，芳基上的取代基可以为本发明中描述的取代基中的任意一种或者两种以上。
“取代或未取代的含有选自N、O和S中的至少一种杂原子的C 4-30的环烷基”表示，当R 1和/或R 2为“取代或未取代的含有选自N、O和S中的至少一种杂原子的C 4-30的环烷基”时，R 1和R 2的碳原子总数均为4-30，并且形成环烷基的环的成员除碳原子外还含有选自N、O和S中的至少一种杂原子；若为“取代的含有选自N、O和S中的至少一种杂原子的C 4-30的环烷基”，环烷基上的取代基可以为本发明中描述的取代基中的任意一种或者两种以上。本发明的“取代或未取代的含有选自N、O和S中的至少一种杂原子的C 4-30的环烷基”中的环烷基包括单环和二环以上的环烷基。
“取代或未取代的羰基-苯基”表示，当R 1和/或R 2为“取代或未取代的羰基-苯基”时，与式(1-1)中所示的碳原子直接相连的基团为羰基，且羰基的另一侧连接取代或者未取代的苯基；若为“取代的羰基-苯基”，苯基上的取代基可以为本发明中描述的取代基中的任意一种或者两种以上。
“取代或未取代的羰基-C 1-12烷基”表示，当R 1和/或R 2为“取代或未取代的羰基-C 1-12烷基”时，与式(1-1)中所示的碳原子直接相连的基团为羰基，且羰基的另一侧连接取代或者未取代的碳原子数为1-12的直链或者支链烷基；若为“取代的羰基-C 1-12烷基”，C 1-12烷基上的取代基可以为本发明中描述的取代基中的任意一种或者两种以上；并且，与羰基连接的“C 1-12烷基”的碳原子总数为1-12，甚至包括可能存在的取代基上的碳原子数。
“R 1和R 2环合而共同形成取代或未取代的不含有或者含有选自N、O和S中的至少一种杂原子的单环或者二环以上的3-30元环烷基”表示，R 1和R 2，以及式(1-1)中所示的碳原子一起形成单环或者二环以上的环烷基，并且，形成环烷基的各个环的原子总数为3-30。
根据第一种优选的具体实施方式，在式(1-1)中，
R 1和R 2各自独立地选自H、氰基、卤素、取代或未取代的C 1-20的烷基、取代或未取代的C 1-20的烷氧基、取代或未取代的C 3-20的环烷基、取代或未取代的苯基、取代或未取代的萘基、取代或未取代的苯并呋喃基、取代或未取代的苯并噻吩基、取代或未取代的喹啉基、取代或未取代的吲哚基、取代或未取代的吡啶基、取代或未取代的噻吩基、取代或未取代的含有选自N、O和S中的至少一种杂原子的C 4-20的环烷基、取代或未取代的羰基-苯基、取代或未取代的羰基-C 1-6烷基，或者R 1和R 2环合而共同形成取代或未取代的不含有或者含有选自N、O和S中的至少一种杂原子的单环或者二环以上的3-20元环烷基，且R 1和R 2不同时为H；
其中的取代基选自氟、氯、溴、C 1-6的烷基、C 1-6的烷氧基、苯基、C 1-6的烷基-苯基、由1-4个选自氟、氯和溴的卤素取代的苯基、由1-4个选自氟、氯和溴的卤素取代的苯氧基、噻吩基、氰基、硝基、由1-4个选自氟、氯和溴的卤素取代的C 1-6的烷基、由C 1-6的烷基取代的氨基、C 1-6的酯基，或者取代基中的两个环合而共同形成不含有或者含有选自N、O和S中的至少一种杂原子的C 2-8的环烷基，或者取代基中的两个环合而共同形成选自苯基、噻吩基和吡啶基中的任意一个基团，或者上述R 1和R 2中的碳原子与氧原子一起形成碳氧双键而使得所述R 1和R 2中含有羰基基团。
根据第二种优选的具体实施方式，在式(1-1)中，
R 1和R 2各自独立地选自H、氰基、氟、氯、溴、取代或未取代的C 1-12的烷基、取代或未取代的C 1-12的烷氧基、取代或未取代的C 3-20的环烷基、取代或未取代的苯基、取代或未取代的吡啶基、取代或未取代的噻吩基、取代或未取代的含有选自N、O和S中的至少一种杂原子的C 4-20的环烷基、取代或未取代的羰基-苯基、取代或未取代的羰基-C 1-6烷基，或者R 1和R 2环合而共同形成取代或未取代的不含有或者含有选自N、O和S中的至少一种杂原子的单环或者二环以上的3-20元环烷基，且R 1和R 2不同时为H；
其中的取代基选自氟、氯、溴、C 1-6的烷基、C 1-6的烷氧基、苯基、C 1-6的烷基-苯基、由1-4个选自氟、氯和溴的卤素取代的苯基、由1-4个选自氟、氯和溴的卤素取代的苯氧基、噻吩基、氰基、硝基、由1-4个选自氟、氯和溴的卤素取代的C 1-6的烷基、由C 1-6的烷基取代的氨基、C 1-6的酯基，或者取代基中的两个环合而共同形成不含有或者含有选自N、O和S中的至少一种杂原子的C 2-8的环烷基，或者取代基中的两个环合而共同形成选自苯基、噻吩基和吡啶基中的任意一个基团，或者上述R 1和R 2中的碳原子与氧原子一起形成碳氧双键而使得所述R 1和R 2中含有羰基基团。
根据第三种优选的具体实施方式，式(1)所示结构的化合物选自权利要求3中列举的化合物中的至少一种。
如前所述，本发明的第二方面提供了一种制备第一方面所述的式(1)所示的含氟氯吡啶肟酯结构的化合物的方法，该方法包括：在缩合剂存在下，将式(2)所示结构的化合物与式(3)所示结构的化合物进行接触反应，
Figure PCTCN2018105074-appb-000004
其中，式(3)中的R基团的定义与本发明第一方面所述的式(1)中的R基团的定义对应相同。
本发明第二方面涉及的化合物中的取代基均与本发明第一方面中涉及的化合物中的取代基的定义完全相同，本发明在此不再赘述，本领域技术人员不应理解为对本发明的限制。
优选情况下，所述接触反应的条件包括：反应温度为5～50℃，反应时间为4～30h。
优选地，所述接触反应在溶剂存在下进行；优选情况下，所述溶剂选自二氯甲烷、甲醇、乙醇、甲苯、环己烷、DMF和DMSO中的至少一种。
优选情况下，所述缩合剂为EDCI(1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐)和DMAP(4-二甲氨基吡啶)的混合物。
本发明的方法对式(2)和式(3)所示的原料的来源没有特别的限定，本领域技术人员可以通过商购或者采用本领域内常规的合成方法制备获得。本发明的后文通过列举部分实例提供了式(2) 和式(3)所示的原料的示例性合成方法，本发明的原料的获得方法并不局限与此，本领域技术人员不应理解为对本发明的限制。
本发明的所述接触反应后还可以进行常规的后处理步骤，本发明对后处理步骤的方式没有特别的限定，可以为本领域内常规的例如除溶剂处理、过滤处理、干燥处理、重结晶处理、层析处理等。
如前所述，本发明的第三方面提供前述第一方面所述式(1)所示的含氟氯吡啶肟酯结构的化合物在防治杂草中的应用。
优选情况下，所述杂草为阔叶杂草和禾本科杂草中的至少一种。
优选地，所述杂草包括苘麻、反枝苋、鱧肠、稗草、马唐、狗尾草、苋菜、播娘蒿、苍耳、婆婆纳、牛繁缕、泽漆、猪殃殃、巨荬菜、葎草、牛筋草、棒头草、白茅、节节草、芦苇、千金子、双穗雀稗、酸模叶蓼、香附子、碎米莎草、异型莎草、扁杆草、藜和野老鹳中的至少一种。
如前所述，本发明的第四方面提供一种除草剂，该除草剂由活性成分和辅料组成，所述活性成分包括本发明第一方面所述的式(1)所示的含氟氯吡啶肟酯结构的化合物或其农业化学上可接受的盐、水合物、溶剂化物，或其同分异构体、互变异构体、对映异构体、光学活性形式的衍生物中的至少一种。
优选情况下，在所述除草剂中，所述活性成分的含量为1-99.9重量％。
优选地，所述除草剂的剂型选自乳油、悬浮剂、微乳剂、水乳剂、胶囊剂、可湿性粉剂、粉剂、粒剂、水剂、毒饵、母液和母粉中的至少一种。
以下将通过实例对本发明进行详细描述。以下实例中，在没有特别说明的情况下，所述的原料均来自商购。
制备例1
Figure PCTCN2018105074-appb-000005
将吡啶甲酮(18.67mmol)、盐酸羟胺(37.34mmol)溶于乙醇/水(V/V＝2.5：1)溶液中，再逐滴加入20重量％氢氧化钠(41.1mmol)水溶液中，加热回流反应2h，反应液用乙酸乙酯萃取，无水硫酸钠干燥，除溶剂得中间体a。
制备例2
Figure PCTCN2018105074-appb-000006
将取代的吡啶甲酸(4.83mmol)溶于10mL甲醇溶液中，冰浴条件下逐滴加入氯化亚砜(7.25mmol)，滴加完毕，再移入65℃下反应12h，反应完毕后逐滴加入水，乙酸乙酯萃取，干燥，除溶剂得中间体b。
制备例3
Figure PCTCN2018105074-appb-000007
将中间体b(22.7mmol)，取代的硼酸(34.1mmol)，氟化钾(60mmol)，二氯二(三苯基膦)钯(2.27mmol)溶于乙腈/水40mL(V/V＝3:1)，加热至回流反应4h，反应完后，硅藻土抽滤，滤液用乙酸乙酯萃取，干燥，二氯甲烷/乙酸乙酯＝100:1(V/V)过硅胶柱得中间体c。
制备例4
Figure PCTCN2018105074-appb-000008
将中间体c(0.145mol)，氢氧化钠(0.291mol)，甲醇240mL，水40mL加入到圆底烧瓶中，反应8h，加入2mol/L的盐酸至pH试纸监测呈酸性后抽滤，得滤饼，干燥，得中间体d。
制备例5
Figure PCTCN2018105074-appb-000009
将中间体d(1.5eq)、中间体a(1eq)，EDCI(2.2eq)，DMAP(3eq)溶于50mL二氯甲烷中，反应完毕后用二氯甲烷萃取，收集有机相，用饱和碳酸氢钠溶液洗涤，收集有机相，无水硫酸钠干燥，石油醚/丙酮＝5:1(V/V)过硅胶柱得化合物1。
化合物1：收率84％.mp＝170.2-172.0. 1H NMR(400MHz,DMSO)δ8.69(s,2H),7.71(d,J＝1.6 Hz,2H),7.62(t,J＝8.0Hz,1H),7.42–7.33(m,1H),7.31(s,1H),7.02(s,2H),3.91(s,3H),2.46(s,3H).HRMS(ESI):计算值C 20H 15Cl 2FN 4O 3[M+H] +449.0578,实测值:449.0506.
采用与制备例1-5相似的方法制备以下化合物，仅是原料不同。
化合物2：收率82％.mp＝161.9-162.7. 1H NMR(600MHz,acetone)δ8.85(s,1H),7.97(dd,J＝6.0,2.4Hz,1H),7.76(t,J＝9.0Hz,1H),7.70–7.65(m,1H),7.47(d,J＝1.2Hz,1H),7.42–7.36(m,2H),6.47(s,2H),4.00(s,3H).HRMS(ESI):计算值C 20H 12Cl 3F 2N 3O 3[M+H] +485.99851,实测值:486.00192.
化合物3：收率85％.mp＝160.2-161.6. 1H NMR(600MHz,acetone)δ8.84(s,1H),8.01–7.92(m,1H),7.76(t,J＝9.0Hz,1H),7.45(s,1H),7.38(d,J＝9.0Hz,1H),7.01(d,J＝12.0Hz,1H),6.88(t,J＝9.0Hz,1H),6.43(s,2H),4.00(s,3H),3.98(s,3H).HRMS(ESI):计算值C 21H 15Cl 2F 2N 3O 4[M+H] +482.04804,实测值:482.04853.
化合物4：收率85％.mp＝157.2-159.7. 1H NMR(400MHz,DMSO)δ7.76(d,J＝7.2Hz,2H),7.63–7.56(m,1H),7.53–7.45(m,3H),7.40(d,J＝7.2Hz,1H),7.27(d,J＝2.0Hz,1H),6.93(s,2H),3.92(s,3H),2.43(s,3H).HRMS(ESI):计算值C 21H 16Cl 2FN 3O 3[M+H] +448.06255,实测值:448.05931.
化合物5：收率85％.mp＝191.8-193.6. 1H NMR(400MHz,DMSO)δ7.94(d,J＝8.0Hz,1H),7.60(t,J＝8.0Hz,1H),7.41(t,J＝8.0Hz,2H),7.31–7.24(m,3H),6.93(s,2H),3.93(s,3H),2.88(t,J＝6.0Hz,2H),2.78(s,2H),1.87–1.76(m,2H).
化合物6：收率82％.mp＝180.2-181.5. 1H NMR(400MHz,DMSO)δ7.67–7.21(m,12H),7.13(s,1H),6.78(s,2H),3.81(s,3H).HRMS(ESI):计算值C 26H 18Cl 2FN 3O 3[M+H] +510.07820,实测值:510.07832.
化合物7：收率87％.mp＝154.2-156.1. 1H NMR(400MHz,DMSO)δ7.65–7.49(m,1H),7.39(d,J＝8.4Hz,1H),7.24(d,J＝1.6Hz,1H),6.90(s,2H),4.14(q,J＝7.2Hz,2H),3.92(s,3H),2.06(s,3H),1.29(t,J＝7.2Hz,3H).HRMS(ESI):计算值C 17H 16Cl 2FN 3O 4[M+H] +416.05747,实测值:416.05811.
化合物8：收率81％.mp＝158.2-160.0. 1H NMR(400MHz,DMSO)δ7.56(d,J＝8.0Hz,1H),7.39(d,J＝8.4Hz,1H),7.24(s,1H),6.91(s,2H),3.92(s,3H),2.51(s,4H),1.75(s,4H).HRMS(ESI):计算值C 18H 16Cl 2FN 3O 3[M+H] +412.06255,实测值:412.06373.
化合物9：收率88％.mp＝160.4-162.2. 1H NMR(400MHz,DMSO)δ7.57(t,J＝8.4Hz,1H),7.40(d,J＝8.4Hz,1H),7.24(s,1H),6.91(s,2H),3.93(s,3H),2.53(d,J＝12.0Hz,2H),2.34(d,J＝6.0Hz,2H),1.70(s,2H),1.60(s,4H).HRMS(ESI):计算值C 19H 18Cl 2FN 3O 3[M+H] +426.0782,实测值:426.07879.
化合物10：收率85％.mp＝163.2-164.9. 1H NMR(400MHz,DMSO)δ7.57(t,J＝8.4Hz,1H),7.39(d,J＝8.8Hz,1H),7.23(s,1H),6.91(s,2H),3.90(d,J＝12.0Hz,3H),2.01(d,J＝10.0Hz,6H).HRMS(ESI):计算值C 16H 14Cl 2FN 3O 3[M+H] +386.0469,实测值:386.01770.
化合物11：收率83％.mp＝145.3-146.6. 1H NMR(400MHz,DMSO)δ7.57(t,J＝8.4Hz,1H),7.39(d,J＝8.8Hz,1H),7.23(s,1H),6.91(s,2H),3.92(s,3H),2.38(td,J＝12.0,8.0Hz,2H),2.12–1.93 (m,3H),1.20–0.99(m,3H).HRMS(ESI):计算值C 17H 16Cl 2FN 3O 3[M+H] +400.06255,实测值:400.05982.
化合物12：收率82％.mp＝146.2-148.1. 1H NMR(400MHz,DMSO)δ8.55(s,1H),7.59(t,J＝8.0Hz,1H),7.52(d,J＝8.8Hz,2H),7.40(d,J＝8.8Hz,1H),7.25(s,1H),6.93(s,2H),6.71(d,J＝8.8Hz,2H),3.92(s,3H),3.39(dt,J＝16.0,8.0Hz,4H),1.11(t,J＝6.0Hz,6H).HRMS(ESI):计算值C 24H 23Cl 2FN 4O 3[M+Na] +527.10235,实测值:527.10262.
化合物13：收率86％.mp＝163.2-163.9. 1H NMR(400MHz,DMSO)δ8.98(s,1H),7.91(d,J＝8.0Hz,1H),7.60(s,3H),7.48(s,1H),7.40(d,J＝8.8Hz,1H),7.26(s,1H),6.98(s,2H),3.92(s,3H).HRMS(ESI):计算值C 20H 13Cl 3FN 3O 3[M+Na] +489.98987,实测值:489.98955.
化合物14：收率85％.mp＝162.2-163.9. 1H NMR(400MHz,DMSO)δ8.86(s,1H),7.77(d,J＝8.0Hz,2H),7.64–7.46(m,4H),7.40(d,J＝8.4Hz,1H),7.27(s,1H),6.97(s,2H),3.93(s,3H).HRMS(ESI):计算值C 20H 14Cl 2FN 3O 3[M+Na] +456.02885,实测值:456.02898.
化合物15：收率88％.mp＝153.8-155.6. 1H NMR(400MHz,DMSO)δ8.92(s,1H),7.88(s,1H),7.77(s,1H),7.64–7.45(m,4H),7.27(s,1H),6.99(s,2H),3.93(s,3H).HRMS(ESI):计算值C 20H 13BrCl 2FN 3O 3[M+Na] +533.93936,实测值:533.93953.
化合物16：收率81％.mp＝151.2-153.7. 1H NMR(400MHz,DMSO)δ8.87(s,1H),7.84(s,2H),7.59(s,1H),7.36(dd,J＝12.0,6.0Hz,4H),6.98(s,2H),3.92(s,3H).HRMS(ESI):计算值C 20H 13Cl 2F 2N 3O 3[M+Na] +474.01942,实测值:474.01928.
化合物17：收率83％.mp＝151.5-152.6. 1H NMR(400MHz,DMSO)δ8.92(s,1H),7.85(d,J＝7.2Hz,1H),7.75–7.52(m,2H),7.46–7.19(m,4H),6.99(s,2H),3.92(s,3H).HRMS(ESI):计算值C 20H 13Cl 2F 2N 3O 3[M+Na] +474.01942,实测值:474.01984.
化合物18：收率82％.mp＝134.2-136.8. 1H NMR(400MHz,DMSO)δ8.88(s,1H),7.84(d,J＝7.2Hz,2H),7.64(s,1H),7.52–7.25(m,5H),7.17(d,J＝8.0Hz,3H),6.95(d,J＝8.4Hz,2H),3.96(s,3H).HRMS(ESI):计算值C 26H 17BrCl 2FN 3O 4[M+H] +603.98363,实测值:603.98403.
化合物19：收率84％.mp＝146.9-147.7. 1H NMR(600MHz,DMSO)δ8.91(s,1H),7.91–7.72(m,2H),7.62(m,3H),7.43(d,J＝9.0Hz,1H),7.30(s,1H),7.01(s,2H),3.94(s,3H).HRMS(ESI):计算值C 20H 13Cl 3FN 3O 3[M+H] +468.00793,实测值:468.00813.
化合物20：收率81％.mp＝161.2-162.6. 1H NMR(400MHz,DMSO)δ8.80(s,1H),7.66(d,J＝8.0Hz,2H),7.63–7.55(m,1H),7.40(d,J＝8.8Hz,1H),7.37–7.13(m,3H),6.96(s,2H),3.90(s,3H),2.37(s,3H).HRMS(ESI):计算值C 21H 16Cl 2FN 3O 3[M+H] +448.06255,实测值:448.06188.
化合物21：收率82％.mp＝160.4-161.8. 1H NMR(600MHz,DMSO)δ8.83(s,1H),7.66–7.57(m,3H),7.46–7.38(m,3H),7.30(s,1H),7.00(s,2H),3.91(s,3H),2.39(s,3H).HRMS(ESI):计算值C 21H 16Cl 2FN 3O 3[M+H] +448.06255,实测值:448.06191.
化合物22：收率85％.mp＝155.2-155.9. 1H NMR(400MHz,DMSO)δ8.71(s,1H),7.67(s,1H),7.59(t,J＝8.4Hz,1H),7.51(d,J＝8.4Hz,1H),7.40(d,J＝8.8Hz,1H),7.25(t,J＝8.0Hz,1H),6.92(d, J＝12.0Hz,2H),6.88(d,J＝8.0Hz,1H),4.61(t,J＝8.8Hz,2H),3.97–3.84(m,3H),3.23(t,J＝8.8Hz,2H).HRMS(ESI):计算值C 22H 16Cl 2FN 3O 4[M+H] +476.05747,实测值:476.05775.
化合物23：收率88％.mp＝154.6-155.1. 1H NMR(400MHz,CDCl 3)δ8.47(s,1H),7.65(dd,J＝16.0,8.4Hz,3H),7.60–7.47(m,3H),7.23(s,1H),4.98(s,2H),3.96(s,3H).HRMS(ESI):计算值C 20H 13BrCl 2FN 3O 3[M+H] +511.95741,实测值:511.95699.
化合物24：收率82％.mp＝152.1-154.3. 1H NMR(400MHz,DMSO)δ8.87(s,1H),7.98(d,J＝7.2Hz,1H),7.82(d,J＝6.0Hz,1H),7.59(dd,J＝16.0,8.0Hz,2H),7.40(d,J＝8.0Hz,1H),7.28(s,1H),6.99(s,2H),3.93(s,3H).HRMS(ESI):计算值C 20H 12Cl 3F 2N 3O 3[M+H] +485.99851,实测值:485.99788.
化合物25：收率85％.mp＝151.2-153.4. 1H NMR(400MHz,DMSO)δ8.83(s,1H),7.66–7.49(m,2H),7.47–7.30(m,3H),7.27(s,1H),6.98(s,2H),3.89(t,J＝12.0Hz,6H).HRMS(ESI):计算值C 21H 15Cl 2F 2N 3O 4[M+H] +482.04804,实测值:482.04787.
化合物26：收率83％.mp＝167.4-168.9. 1H NMR(400MHz,DMSO)δ8.73(s,1H),7.59(t,J＝8.1Hz,1H),7.40(d,J＝8.6Hz,1H),7.32(d,J＝8.6Hz,2H),7.26(s,1H),7.08(d,J＝8.0Hz,1H),6.96(s,2H),3.93(s,3H),3.82(d,J＝4.9Hz,6H).HRMS(ESI):计算值C 22H 18Cl 2FN 3O 5[M+H] +494.06803,实测值:494.06830.
化合物27：收率81％.mp＝178.4-180.1. 1H NMR(400MHz,DMSO)δ7.87(s,2H),7.62(d,J＝8.0Hz,4H),7.33(s,2H),7.03(s,2H),3.90(s,3H).HRMS(ESI):计算值C 21H 13Cl 2FN 4O 3[M+Na] +481.0241,实测值:481.02472.
化合物28：收率85％.mp＝112.3-114.6. 1H NMR(400MHz,DMSO)δ7.73(d,J＝8.8Hz,2H),7.60(t,J＝8.4Hz,1H),7.40(d,J＝8.8Hz,1H),7.26(d,J＝1.2Hz,1H),7.02(d,J＝8.8Hz,2H),6.93(s,2H),3.92(s,3H),3.85–3.75(m,3H),2.42–2.30(m,3H).HRMS(ESI):计算值C 22H 18Cl 2FN 3O 4[M+H] +478.07312,实测值:478.07217
化合物29：收率77％.mp＝172.5-174.3. 1H NMR(400MHz,CDCl 3)δ7.60(d,J＝8.0Hz,2H),7.40(d,J＝8.8Hz,1H),7.28(d,J＝8.8Hz,3H),6.97(s,2H),3.93(s,3H),2.38(s,3H).HRMS(ESI):计算值C 21H 14Cl 2F 3N 3O 3[M+H] +484.04371,实测值:484.04392.
化合物30：收率58％.mp＝159.2-161.1. 1H NMR(400MHz,DMSO)δ9.04(s,1H),8.34(d,J＝8.4Hz,2H),8.03(d,J＝8.8Hz,2H),7.59(s,1H),7.41(s,1H),7.28(s,1H),6.99(s,2H),3.92(s,3H).HRMS(ESI):计算值C 20H 13Cl 2FN 4O 5[M+H] +479.03198,实测值:479.03132.
化合物31：收率88％.mp＝175.3-176.6. 1H NMR(400MHz,DMSO)δ7.95(d,J＝8.4Hz,1H),7.71–7.53(m,3H),7.41(dd,J＝12.0,12.4Hz,2H),7.32(s,1H),7.04(s,2H),3.93(t,J＝8.0Hz,3H).HRMS(ESI):计算值C 20H 12Cl 4FN 3O 4[M+H] +501.96896,实测值:501.96844.
化合物32：收率65％.mp＝162.2-163.6. 1H NMR(600MHz,DMSO)δ8.79(s,1H),7.87(s,1H),7.79(d,J＝8.4Hz,1H),7.74(d,J＝8.4Hz,2H),7.43–7.35(m,1H),7.20(d,J＝8.4Hz,1H),7.08(s,1H),6.80(s,2H),3.75–3.64(m,3H).HRMS(ESI):计算值C 21H 13Cl 2FN 4O 3[M+H] +459.04215,实测 值:459.04414.
化合物33：收率85％.mp＝155.2-156.6. 1H NMR(600MHz,DMSO)δ8.94(s,1H),7.63(d,J＝8.4Hz,2H),7.47(dd,J＝12.0,6.0Hz,3H),7.30(s,1H),7.03(s,2H),4.05–3.86(m,3H).HRMS(ESI):计算值C 20H 12Cl 2F 3N 3O 3[M+Na] +492.0100,实测值:492.01255.
化合物34：收率81％.mp＝151.7-152.6. 1H NMR(400MHz,DMSO)δ8.87(s,1H),7.64(d,J＝8.0Hz,2H),7.58(d,J＝8.4Hz,2H),7.41(d,J＝8.8Hz,1H),7.26(d,J＝6.0Hz,1H),7.00(s,2H),3.92(s,3H).HRMS(ESI):计算值C 20H 12Cl 2F 3N 3O 3[M+Na] +492.0100,实测值:492.01277.
化合物35：收率75％.mp＝109.4-111.6. 1H NMR(400MHz,DMSO)δ8.97(s,1H),8.06(d,J＝7.2Hz,1H),7.90(d,J＝8.0Hz,1H),7.81(dt,J＝12.0,7.2Hz,2H),7.66–7.55(m,1H),7.45–7.36(m,1H),7.28(s,1H),7.01(s,2H),4.05–3.90(m,3H).HRMS(ESI):计算值C 21H 13Cl 2F 4N 3O 3[M+H] +502.03429,实测值:502.03423.
化合物36：收率88％.mp＝152.2-153.1. 1H NMR(400MHz,DMSO)δ8.97(s,1H),7.72(d,J＝7.2Hz,1H),7.59(t,J＝8.0Hz,1H),7.40(d,J＝8.4Hz,2H),7.34–7.16(m,3H),6.95(s,2H),3.92(s,3H),2.43(s,3H).HRMS(ESI):计算值C 21H 16Cl 2FN 3O 3[M+H] +448.06255,实测值:448.06258.
化合物37：收率81％.mp＝162.5-163.6. 1H NMR(400MHz,DMSO)δ8.88(s,1H),7.82–7.70(m,2H),7.62(t,J＝8.4Hz,1H),7.43(d,J＝8.8Hz,1H),7.31(s,1H),7.03(s,2H),3.94(s,3H).HRMS(ESI):计算值C 20H 11Cl 2F 4N 3O 3[M+H] +488.01864,实测值:488.01875.
化合物38：收率80％.mp＝198.2-199.6. 1H NMR(600MHz,DMSO)δ7.62(dd,J＝18.0,9.0Hz,4H),7.42(d,J＝9.0Hz,1H),7.28(s,1H),6.98(s,2H),3.95–3.91(m,3H),2.38(s,3H).HRMS(ESI):计算值C 21H 14Cl 4FN 3O 3[M+H] +515.98461,实测值:515.98415.
化合物39：收率85％.mp＝174.8-175.6. 1H NMR(600MHz,DMSO)δ7.60(s,2H),7.51(s,2H),7.44(d,J＝18.0Hz,2H),7.27(s,1H),6.97(s,2H),3.92(s,3H),2.37(s,3H).HRMS(ESI):计算值C 21H 15Cl 3FN 3O 3[M+H] +482.02358,实测值:482.02344.
化合物40：收率88％.mp＝146.7-148.6. 1H NMR(600MHz,DMSO)δ7.62(dd,J＝18.0,9.0Hz,5H),7.42(d,J＝9.0Hz,1H),7.28(s,1H),6.98(s,2H),3.95–3.90(m,3H),2.38(s,3H).HRMS(ESI):计算值C 21H 15Cl 3FN 3O 3[M+H] +482.02358,实测值:482.02338.
化合物41：收率82％.mp＝155.2-156.6. 1H NMR(600MHz,DMSO)δ8.74(s,1H),7.59(dd,J＝19.4,11.4Hz,1H),7.40(d,J＝9.0Hz,1H),7.29(d,J＝9.0Hz,3H),7.05(d,J＝7.8Hz,1H),6.89(s,2H),6.12(s,2H),3.93(d,J＝6.0Hz,3H).HRMS(ESI):计算值C 21H 14Cl 2FN 3O 5[M+H] +478.03673,实测值:478.03693.
化合物42：收率87％.mp＝136.2-137.6. 1H NMR(400MHz,DMSO)δ7.74(s,1H),7.65(t,J＝8.4Hz,1H),7.60(d,J＝8.8Hz,1H),7.46(d,J＝8.8Hz,1H),7.31(s,1H),7.01(s,2H),6.89(d,J＝8.4Hz,1H),4.64(t,J＝8.8Hz,2H),3.94(d,J＝16.0Hz,3H),3.26(t,J＝8.8Hz,2H),2.41(s,3H).HRMS(ESI):计算值C 23H 18Cl 2FN 3O 4[M+H] +490.07312,实测值:490.07214.
化合物43：收率81％.mp＝193.4-195.6. 1H NMR(400MHz,DMSO)δ7.65(t,J＝8.4Hz,1H), 7.55–7.42(m,4H),7.32(d,J＝8.0,1H),7.04(s,2H),3.96(s,3H),2.44(s,3H).HRMS(ESI):计算值C 21H 14Cl 2F 3N 3O 3[M+H] +484.04426,实测值:484.04431.
化合物44：收率82％.mp＝140.2-141.6. 1H NMR(600MHz,DMSO)δ8.90(s,1H),7.97(s,1H),7.81(dd,J＝12.0 7.9Hz,2H),7.62(t,J＝9.0Hz,1H),7.51(t,J＝9.0Hz,1H),7.43(d,J＝9.0Hz,1H),7.30(s,1H),7.02(s,2H),3.94(s,3H).HRMS(ESI):计算值C 20H 13BrCl 2FN 3O 3[M+H] +511.95741,实测值:511.95690.
化合物45：收率86％.mp＝137.4-139.1. 1H NMR(400MHz,DMSO)δ8.89(s,1H),7.69–7.56(m,2H),7.48–7.38(m,3H),7.33(s,1H),7.04(s,2H),3.97(s,3H),3.94(s,3H).HRMS(ESI):计算值C 21H 15Cl 2F 2N 3O 4[M+H] +482.04804,实测值:482.04753.
化合物46：收率85％.mp＝198.7-200.6. 1H NMR(400MHz,DMSO)δ7.79(d,J＝2.0Hz,1H),7.76(s,1H),7.74–7.70(m,1H),7.67(dd,J＝12.0,4.0Hz,1H),7.47(dd,J＝8.0,1.2Hz,1H),7.35(t,J＝2.8Hz,1H),7.08(dd,J＝20.0,12.8Hz,2H),3.96(s,3H).HRMS(ESI):计算值C 20H 11Cl 5FN 3O 3[M+H] +535.92998,实测值:535.92929.
化合物47：收率81％.mp＝126.2-128.1. 1H NMR(400MHz,DMSO)δ7.62(t,J＝8.4Hz,1H),7.45(d,J＝8.8Hz,1H),7.29(d,J＝6.0Hz,1H),6.97(s,2H),3.96(s,3H),2.23(d,J＝7.2Hz,2H),2.07–1.93(m,4H),0.92(t,J＝7.2Hz,6H).HRMS(ESI):计算值C 19H 20Cl 2FN 3O 3[M+H] +428.09385,实测值:428.09339.
化合物48：收率89％.mp＝114.8-115.6. 1H NMR(400MHz,DMSO)δ8.08(t,J＝6.0Hz,1H),7.62(t,J＝8.0Hz,1H),7.45(d,J＝8.8Hz,1H),7.28(s,1H),6.99(s,2H),3.96(s,3H),2.35(dd,J＝13.6,8.0Hz,2H),1.62–1.51(m,2H),0.96(t,J＝7.2Hz,3H).HRMS(ESI):计算值C 17H 16Cl 2FN 3O 3[M+H] +400.06255,实测值:400.06247.
化合物49：收率87％.mp＝149.2-151.1. 1H NMR(400MHz,DMSO)δ7.62(t,J＝8.4Hz,1H),7.45(d,J＝8.8Hz,1H),7.28(d,J＝1.2Hz,1H),6.96(s,2H),4.00–3.91(m,3H),2.41–2.31(m,2H),2.02(s,3H),1.56(td,J＝12.0,6.0Hz,1H),1.44(dd,J＝12.0,7.2Hz,2H),0.89(t,J＝12.0Hz,6H).HRMS(ESI):计算值C 20H 22Cl 2FN 3O 3[M+H] +442.1095,实测值:442.10949.
化合物50：收率84％.mp＝116.5-118.1. 1H NMR(400MHz,DMSO)δ7.60(t,J＝8.0Hz,1H),7.43(d,J＝8.8Hz,1H),7.26(s,1H),6.95(s,2H),3.93(s,3H),2.70–2.57(m,2H),2.51(s,2H),1.59(d,J＝12.0Hz,8H).HRMS(ESI):计算值C 20H 20Cl 2FN 3O 3[M+H] +440.09385,实测值:440.09360.
化合物51：收率85％.mp＝183.2-184.6. 1H NMR(400MHz,DMSO)δ7.63(t,J＝8.0Hz,1H),7.45(d,J＝8.8Hz,1H),7.29(s,1H),6.98(s,2H),3.96(s,3H),2.52–2.48(m,2H),2.48–2.37(m,2H),1.79(d,J＝12.0Hz,4H),1.48(dd,J＝16.0,8.0Hz,6H).HRMS(ESI):计算值C 21H 22Cl 2FN 3O 3[M+H] +454.1095,实测值:454.10968.
化合物52：收率88％.mp＝90.2-92.1. 1H NMR(400MHz,DMSO)δ8.04(d,J＝8.0Hz,2H),7.92(d,J＝8.4Hz,2H),7.66(t,J＝8.0Hz,1H),7.45(d,J＝8.8Hz,1H),7.34(s,1H),7.04(s,2H),3.96(s,3H),3.29–3.22(m,2H),3.11(s,3H),3.00(t,J＝7.2Hz,2H),1.55(dd,J＝8.0,4.0Hz,4H).HRMS(ESI):计算 值C 26H 23Cl 2F 4N 3O 4[M+H] +588.10745,实测值:588.10726.
化合物53：收率55％.mp＝162.9-164.6. 1H NMR(400MHz,DMSO)δ9.00(s,1H),7.64(t,J＝8.0Hz,1H),7.50(d,J＝3.6Hz,1H),7.45(d,J＝8.8Hz,1H),7.31(s,1H),6.98(d,J＝3.2Hz,3H),3.97(s,3H),2.55(s,3H).HRMS(ESI):计算值C 19H 14Cl 2FN 3O 3S[M+H] +454.01897,实测值:454.01885.
化合物54：收率74％.mp＝162.2-163.8. 1H NMR(600MHz,DMSO)δ8.99(s,1H),7.61(s,1H),7.49(s,1H),7.43(d,J＝7.2Hz,1H),7.28(s,1H),6.99(s,3H),3.93(s,3H),2.88(d,J＝6.6Hz,2H),1.27(s,3H).HRMS(ESI):计算值C 20H 16Cl 2FN 3O 3S[M+Na] +490.01657,实测值:490.01638.
化合物55：收率74％.mp＝151.2-152.0. 1H NMR(600MHz,DMSO)δ7.61(t,J＝7.2Hz,1H),7.43(d,J＝9.0Hz,1H),7.30(s,1H),7.03(s,2H),3.93(s,3H),2.41(s,3H),2.05(s,3H).HRMS(ESI):计算值C 17H 14Cl 2FN 3O 4[M+H] +414.04236,实测值:414.04242.
化合物56：收率82％.mp＝156.2-157.6. 1H NMR(600MHz,DMSO)δ7.59(s,1H),7.42(d,J＝8.3Hz,1H),7.25(s,1H),6.93(s,2H),3.93(s,3H),1.98(s,3H),1.15(s,9H).HRMS(ESI):计算值C 19H 20Cl 2FN 3O 3[M+Na] +450.0758,实测值:450.07508.
化合物57：收率85％.mp＝156.1-158.0. 1H NMR(600MHz,DMSO)δ7.58(t,J＝7.9Hz,1H),7.42(d,J＝8.5Hz,1H),7.25(s,1H),6.94(s,2H),3.93(s,3H),3.41(s,1H),2.70(s,1H),2.04(d,J＝12.0Hz,2H),1.95(d,J＝11.9Hz,4H),1.84(d,J＝15.0Hz,4H),1.77(d,J＝11.7Hz,2H).HRMS(ESI):计算值C 23H 22Cl 2FN 3O 3[M+Na] +500.09145,实测值:500.09152.
化合物58：收率72％.mp＝148.2-149.5. 1H NMR(600MHz,DMSO)δ8.09(s,1H),7.90(s,1H),7.76(s,1H),7.65(t,J＝7.8Hz,1H),7.54(s,1H),7.45(d,J＝8.4Hz,1H),7.33(s,1H),7.27(s,2H),7.02(s,2H),3.94(s,3H).HRMS(ESI):计算值C 22H 14Cl 2FN 3O 3S 2[M+Na] +543.97299,实测值:543.97122.
化合物59：收率81％.mp＝170.2-171.8. 1H NMR(600MHz,DMSO)δ7.62(t,J＝7.8Hz,1H),7.49–7.40(m,1H),7.32(s,1H),7.06(s,2H),3.94(s,3H),2.28(d,J＝15.6Hz,3H).HRMS(ESI):计算值C 16H 11Cl 2F 4N 3O 3[M+Na] +462.00113,实测值:462.00122.
化合物60：收率88％.mp＝143.2-145.0. 1H NMR(400MHz,DMSO)δ7.84(d,J＝7.2Hz,2H),7.61(t,J＝8.4Hz,1H),7.56–7.45(m,3H),7.41(d,J＝8.8Hz,1H),7.33(s,1H),7.27(d,J＝4.4Hz,4H),7.21(td,J＝8.8,4.2Hz,1H),7.08–6.95(m,2H),4.39(s,2H),3.94(s,3H).HRMS(ESI):计算值C 27H 20Cl 2FN 3O 3[M+Na] +546.0758,实测值:546.07531.
化合物61：收率80％.mp＝127.6-129.1. 1H NMR(600MHz,DMSO)δ7.59(t,J＝7.8Hz,1H),7.43(d,J＝8.4Hz,1H),7.26(s,1H),6.96(s,2H),3.93(s,3H),3.81(s,2H),3.70(s,2H),2.67(s,2H),2.49(s,2H).HRMS(ESI):计算值C 18H 16Cl 2FN 3O 4[M+Na] +450.03941,实测值:450.03955.
化合物62：收率84％.mp＝168.2-169.8. 1H NMR(600MHz,DMSO)δ8.03(d,J＝5.4Hz,1H),7.60(dd,J＝15.6,7.8Hz,1H),7.42(d,J＝8.4Hz,1H),7.26(s,1H),6.96(s,2H),3.94(s,3H),2.71–2.62(m,1H),1.12(d,J＝6.6Hz,6H).HRMS(ESI):计算值C 17H 16Cl 2FN 3O 3[M+Na] +422.0445,实测值:422.04480.
化合物63：收率86％.mp＝153.4-155.2 1H NMR(600MHz,DMSO)δ7.60(s,1H),7.43(d,J＝8.4 Hz,1H),7.26(s,1H),6.96(s,2H),3.92(d,J＝18.0Hz,3H),3.51(d,J＝9.0Hz,5H),2.65(s,2H),1.40(d,J＝18.6Hz,10H).HRMS(ESI):计算值C 23H 25Cl 2FN 4O 5[M+Na] +549.10782,实测值:549.10785.
化合物64：收率81％.mp＝143.2-145.0. 1H NMR(600MHz,DMSO)δ7.59(s,1H),7.40(d,J＝8.4Hz,1H),7.32(d,J＝6.6Hz,2H),7.27(d,J＝9.0Hz,6H),7.22(s,2H),7.12(s,1H),6.97(s,2H),3.92(s,3H),3.69(s,2H),3.64(s,2H).HRMS(ESI):计算值C 28H 22Cl 2FN 3O 3[M+Na] +560.09145,实测值:560.09125.
化合物65：收率89％.mp＝110.2-111.0. 1H NMR(600MHz,DMSO)δ7.58(s,1H),7.42(d,J＝8.5Hz,1H),7.33(s,4H),7.25(s,2H),6.95(s,2H),3.93(s,3H),3.55(s,2H),2.65(s,2H),2.60(s,2H),2.46(s,4H).HRMS(ESI):计算值C 25H 23Cl 2FN 4O 3[M+Na] +539.10235,实测值:539.10298.
化合物66：收率74％.mp＝151.2-152.6. 1H NMR(600MHz,DMSO)δ7.59(s,1H),7.43(d,J＝7.3Hz,1H),7.25(s,1H),6.93(s,2H),3.93(s,3H),2.61(d,J＝18.4Hz,1H),2.17(d,J＝17.9Hz,1H),1.94(s,1H),1.81(s,2H),1.44(s,1H),1.28(s,1H),1.03(s,3H),0.92(s,3H),0.79(s,3H).HRMS(ESI):计算值C 23H 24Cl 2FN 3O 3[M+H] +480.12515,实测值:480.12547.
化合物67：收率88％.mp＝136.4-138.2. 1H NMR(400MHz,DMSO)δ7.63(t,J＝8.0Hz,1H),7.44(d,J＝4.0Hz,1H),7.30(s,1H),6.97(s,2H),3.96(s,3H),2.36(t,J＝25.2Hz,4H),1.59(s,4H),1.31(s,20H).HRMS(ESI):计算值C 28H 36Cl 2FN 3O 3[M+Na] +574.201,实测值:574.20083.
化合物68：收率86％.mp＝122.8-124.2. 1H NMR(400MHz,DMSO)δ7.98(d,J＝7.2Hz,2H),7.70(d,J＝7.2Hz,1H),7.63(t,J＝8.0Hz,1H),7.52(t,J＝7.2Hz,2H),7.44(d,J＝8.4Hz,1H),7.30(s,1H),7.01(s,2H),3.94(s,3H),2.31(s,3H).HRMS(ESI):计算值C 22H 16Cl 2FN 3O 4[M+Na] +498.03996,实测值:498.04001.
化合物69：收率82％.mp＝143.2-145.0. 1H NMR(400MHz,DMSO)δ7.64(t,J＝8.4Hz,1H),7.44(d,J＝8.4Hz,1H),7.23(s,1H),6.85(s,2H),3.38(s,1H),3.29(t,J＝9.6Hz,1H),3.18(t,J＝9.6Hz,1H),2.13–2.07(m,1H),1.85(d,J＝13.2Hz,1H),1.63(t,J＝9.2Hz,1H),1.51–1.44(m,1H),1.25(s,2H),1.15(d,J＝6.4Hz,4H),1.07(s,2H),0.99(s,2H).HRMS(ESI):计算值C 23H 22Cl 2FN 3O 4[M+Na] +516.08636,实测值:516.08797.
化合物70：收率74％.mp＝177.4-179.2. 1H NMR(400MHz,DMSO)δ7.64(t,J＝8.2Hz,1H),7.47(dd,J＝12.8,7.0Hz,2H),7.35(d,J＝5.2Hz,1H),7.31(d,J＝1.2Hz,1H),7.02(d,J＝25.2Hz,2H),3.96(s,3H),2.93(t,J＝6.0Hz,2H),2.85(t,J＝6.4Hz,2H),2.01–1.92(m,2H).HRMS(ESI):计算值C 21H 16Cl 2FN 3O 3S[M+Na] +502.01657,实测值:502.01594.
化合物71：收率78％.mp＝183.8-185.4. 1H NMR(400MHz,DMSO)δ7.78(d,J＝7.6Hz,1H),7.65(t,J＝8.2Hz,1H),7.56(t,J＝7.3Hz,1H),7.50(d,J＝7.5Hz,1H),7.42(dd,J＝15.3,8.0Hz,2H),7.31(s,1H),6.99(s,2H),3.95(s,3H),3.08(s,4H).HRMS(ESI):计算值C 22H 16Cl 2FN 3O 3[M+Na] +482.0445,实测值:482.04493.
化合物72：收率78％.mp＝183.8-185.6. 1H NMR(400MHz,DMSO)δ8.93(d,J＝1.6Hz,1H),8.73–8.67(m,1H),8.16(dt,J＝8.0,1.8Hz,1H),7.61(t,J＝8.4Hz,1H),7.53(dd,J＝8.0,4.8Hz,1H),7.41(dd,J＝8.8,1.2Hz,1H),7.28(d,J＝1.2Hz,1H),6.99(s,2H),3.92(d,J＝6.8Hz,3H),2.46(s, 3H).HRMS(ESI):计算值C 20H 15Cl 2FN 4O 3[M+Na] +471.03975,实测值:4712.04104.
化合物73：收率85％.mp＝160.2-162.0. 1H NMR(400MHz,DMSO)δ7.61(t,J＝8.0Hz,1H),7.50–7.39(m,1H),7.28(s,1H),6.95(s,2H),3.97(d,J＝6.4Hz,3H),3.16(d,J＝13.2Hz,1H),2.31(td,J＝13.6,4.8Hz,1H),2.10–1.99(m,2H),1.95(d,J＝12.0Hz,1H),1.36(t,J＝11.6Hz,1H),1.25(dd,J＝12.4,8.8Hz,1H),1.15(dd,J＝24.0,11.6Hz,1H),0.88(s,10H).HRMS(ESI):计算值C 23H 26Cl 2FN 3O 3[M+Na] +504.12330,实测值:504.12337.
测试例1：除草活性测试
采用温室盆栽实验对所合成的部分目标化合物进行活体水平的除草活性(夏季杂草)的测定，以氟氯吡啶酯(Arylex Active)为对照药剂。氟氯吡啶酯的结构式如下所示：
Figure PCTCN2018105074-appb-000010
具体的测试方法为：盆栽法(普筛)：供试靶标为苘麻、反枝苋、鱧肠和稗草。取内径7.5cm花盆，装复合土(菜园土：育苗基质，1:2，v/v)至3/4处，直接播种上述杂草靶标(芽率≥85％)，覆土0.2cm，待杂草长至3叶期左右备用。各化合物按照150g a.i./ha剂量在自动喷雾塔(型号：3WPSH-700E)施药后，待杂草叶面药液晾干后移入温室培养，30天后调查对杂草的鲜重抑制率(％；试验处理30天后目测靶标受害症状及生长抑制情况，并称地上部分鲜重，计算鲜重抑制率(％)。
鲜重抑制率(％)＝(对照鲜重-处理鲜重)/对照鲜重×100％
实际结果的观察标准如下：
试验处理30天后目测施药杂草与未处理杂草相比，受害症状及生长抑制情况，按照0-100％的尺度目测防效，其中0相当于无生物活性，100％相当于完全杀死杂草。
测试结果列于表1中。
表1：目标化合物对夏季杂草除草活性普筛结果(鲜重抑制率/％)(药后30d)
化合物编号 剂量(gai/ha) 苘麻 反枝苋 鱧肠 稗草
1 150 100 100 100 100
3 150 100 100 100 100
5 150 100 100 100 100
7 150 100 100 100 100
9 150 100 100 100 100
11 150 100 100 100 100
12 150 100 100 100 100
13 150 100 100 100 100
15 150 100 100 100 100
16 150 100 100 100 100
氟氯吡啶酯 150 100 100 70 100
由表1的结果可以看出，本发明提供的化合物在浓度为150gai/ha的剂量条件下对阔叶杂草和禾本科杂草均具有良好的除草活性，特别地，本发明的化合物对鱧肠的除草活性明显比对照药剂对 鱧肠的除草活性要高。
测试例2
采用与测试例1相同的测试方法测试低浓度下的部分目标化合物的除草活性，浓度及结果列于表2中。
表2：目标化合物降低浓度后除草活性筛选试验结果(鲜重抑制率/％)
Figure PCTCN2018105074-appb-000011
Figure PCTCN2018105074-appb-000012
由表2的结果可以看出，即便是在低浓度下，本发明提供的化合物对苘麻、反枝苋、鳢肠等阔叶杂草均具有较高的除草活性，并且除草活性普遍与对照药剂的效果相当。特别地，本发明提供的化合物在低浓度下对禾本科杂草马唐和狗尾草的除草活性比对照药剂对禾本科杂草的除草活性更高。
测试例3：除草活性测试
采用温室盆栽实验对所合成的部分目标化合物进行活体水平的除草活性(室内对鳢肠)的测定，以氟氯吡啶酯(Arylex Active)为对照药剂。
具体的测试方法为：苗后茎叶喷雾，对杂草的活性，取内径7cm纸杯，装复合土(菜园土：育苗基质，1：2，v/v)至3/4处，直接播种杂草，覆土0.2cm，待长至4-5叶期备用。新化合物和对照药剂氟氯吡啶酯按照3.75g.a.i/ha剂量在自动喷雾塔施药后，待作物叶面药液晾干后移入温室培养(25度-15g.a.i/ha 28度，湿度70％)，25天后调查结果。
测试结果列于表3中(鲜重抑制率获得方法与测试例1中相同)。
表3：目标化合物对鳢肠室内除草活性(鲜重抑制率/％)(药后25d)
化合物编号 剂量g a.i./ha 鳢肠
56 3.75 100
62 3.75 100
65 3.75 100
68 3.75 100
氟氯吡啶酯 3.75 60
从上述表3的结果可以看出，即便是在低浓度下，本发明提供的化合物对鱧肠均具有较高的除草活性。具体地，本发明提供的化合物在剂量为3.75g a.i./ha的低浓度条件下，对鳢肠具有比对照药剂更高的除草活性。
测试例4：安全性测试
对所合成的部分目标化合物进行对作物的安全性测试，以氟氯吡啶酯(Arylex Active)为对照药剂。
具体的测试方法为：苗后茎叶喷雾：取内径7cm纸杯，装复合土(菜园土：育苗基质，1：2，v/v)至3/4处，直接播种杂草，覆土0.2cm，待长至4-5叶期备用。新化合物和对照药剂氟氯吡啶酯按照37.5g.a.i/ha、75g.a.i/ha、150g.a.i/ha剂量在自动喷雾塔施药后，待作物叶面药液晾干后移入温室培养(25度-15g.a.i/ha 28度，湿度70％)，25天后调查结果。
测试结果列于表4中。安全性(目测生长抑制率％)评价标准列于表5中。
表4：目标化合物对作物室内安全性实验(25d)
Figure PCTCN2018105074-appb-000013
Figure PCTCN2018105074-appb-000014
由表4中的结果可以看出，本发明提供的化合物对作物的安全性高，具体地，本发明提供的化合物对小麦和粳稻的安全性与对照药剂相当甚至比对照药剂安全性更高。
表5
目测生长抑制率(％) 评价(抑制、畸形、白化等)
0 对作物生长无影响，安全。
0-10 对作物生长稍有影响，无明显药害。
10-30 对作物生长有影响，轻微药害。
30-50 对作物生长影响较大，中度药害。
50-100 对作物生长影响极大，严重药害。
100 作物完全死亡。
由上述结果可以看出，本发明提供的化合物对阔叶杂草具有与对照药剂相当的除草活性，特别地，本发明提供的化合物对鱧肠的除草活性显著比对照药剂对鱧肠的除草活性要高。并且，本发明的化合物对禾本科杂草具有较高的除草活性。进一步地，本发明的化合物对作物的安全性较高。
测试例5：抗性杂草测试
盆栽法(抗性杂草筛选)：供试靶标为稗草2个种群，杂草种群对ACCase除草剂抗性状况见表6。取内径7.5cm花盆，装复合土(菜园土：育苗基质，1：2，v/v)至3/4处，直接播种上述7种杂草靶标(芽率≥85％)，覆土0.2cm，待杂草长至3叶期左右备用。各化合物按照表7的剂量在自动喷雾塔(型号：3WP-2000，喷头型号TP605E)施药后，待杂草叶面药液晾干后移入温室培养，25天后调查对杂草的抑制活性(％)。其中，对杂草的抑制活性调查方法按照十级目测法进行(0＝无明显反应，10＝植株完全死亡)，目测数据转换为处理杂草植株相对于空白对照的生物量抑制百分数(如1.5级＝15％)。结果(抑制率％)列于表7中。
表6供试杂草详情
种群编号 对ACCase除草剂抗性情况 ACCase氨基酸突变情况
稗草AR 抗恶唑酰草胺 未检测
稗草AS 敏感 无
表7
Figure PCTCN2018105074-appb-000015
由表7的结果可以看出，本发明提供的化合物即便是在低浓度下也对稗草均表现出良好的抑制作用，其症状主要表现为，药后10天开始出现杂草茎基部膨大、扭曲，畸形，植株生长受到抑制； 药后20天时症状加重，部分杂草扭曲倒伏，叶片黄化枯死，进而整株枯死，与对照药剂氟氯吡啶酯相比，本发明的化合物对杂草的抑制活性高于对照药剂。
以上详细描述了本发明的优选实施方式，但是，本发明并不限于此。在本发明的技术构思范围内，可以对本发明的技术方案进行多种简单变型，包括各个技术特征以任何其它的合适方式进行组合，这些简单变型和组合同样应当视为本发明所公开的内容，均属于本发明的保护范围。

Claims (10)

  1. 一种含氟氯吡啶肟酯结构的化合物或其农业化学上可接受的盐、水合物、溶剂化物，或其同分异构体、互变异构体、对映异构体、光学活性形式的衍生物，该化合物具有式(1)所示的结构，
    Figure PCTCN2018105074-appb-100001
    其中，在式(1)中，R为式(1-1)所示的基团，
    在式(1-1)中，R 1和R 2各自独立地选自H、氰基、卤素、取代或未取代的C 1-30的烷基、取代或未取代的C 1-30的烷氧基、取代或未取代的C 3-30的环烷基、取代或未取代的不含有或者含有选自N、O和S中的至少一种杂原子的C 5-30的芳基、取代或未取代的吡啶基、取代或未取代的噻吩基、取代或未取代的含有选自N、O和S中的至少一种杂原子的C 4-30的环烷基、取代或未取代的羰基-苯基、取代或未取代的羰基-C 1-12烷基，或者R 1和R 2环合而共同形成取代或未取代的不含有或者含有选自N、O和S中的至少一种杂原子的单环或者二环以上的3-30元环烷基，且R 1和R 2不同时为H，
    其中的取代基选自卤素、C 1-12的烷基、C 1-12的烷氧基、苯基、C 1-12的烷基-苯基、由1-6个卤素取代的苯基、由1-6个卤素取代的苯氧基、噻吩基、氰基、硝基、由1-6个卤素取代的C 1-12的烷基、由C 1-12的烷基取代的氨基、C 1-12的酯基，或者取代基中的两个环合而共同形成不含有或者含有选自N、O和S中的至少一种杂原子的C 2-12的环烷基，或者取代基中的两个环合而共同形成选自苯基、噻吩基和吡啶基中的任意一个基团；或者上述R 1和R 2中的碳原子与氧原子一起形成碳氧双键而使得所述R 1和R 2中含有羰基基团。
  2. 根据权利要求1所述的化合物，其中，在式(1-1)中，
    R 1和R 2各自独立地选自H、氰基、卤素、取代或未取代的C 1-20的烷基、取代或未取代的C 1-20的烷氧基、取代或未取代的C 3-20的环烷基、取代或未取代的苯基、取代或未取代的萘基、取代或未取代的苯并呋喃基、取代或未取代的苯并噻吩基、取代或未取代的喹啉基、取代或未取代的吲哚基、取代或未取代的吡啶基、取代或未取代的噻吩基、取代或未取代的含有选自N、O和S中的至少一种杂原子的C 4-20的环烷基、取代或未取代的羰基-苯基、取代或未取代的羰基-C 1-6烷基，或者R 1和R 2环合而共同形成取代或未取代的不含有或者含有选自N、O和S中的至少一种杂原子的单环或者二环以上的3-20元环烷基，且R 1和R 2不同时为H；
    其中的取代基选自氟、氯、溴、C 1-6的烷基、C 1-6的烷氧基、苯基、C 1-6的烷基-苯基、由1-4个选自氟、氯和溴的卤素取代的苯基、由1-4个选自氟、氯和溴的卤素取代的苯氧基、噻吩基、氰基、硝基、由1-4个选自氟、氯和溴的卤素取代的C 1-6的烷基、由C 1-6的烷基取代的氨基、C 1-6的酯基，或者取代基中的两个环合而共同形成不含有或者含有选自N、O和S中的至少一种杂原子的C 2-8 的环烷基，或者取代基中的两个环合而共同形成选自苯基、噻吩基和吡啶基中的任意一个基团，或者上述R 1和R 2中的碳原子与氧原子一起形成碳氧双键而使得所述R 1和R 2中含有羰基基团；
    优选地，
    在式(1-1)中，
    R 1和R 2各自独立地选自H、氰基、氟、氯、溴、取代或未取代的C 1-12的烷基、取代或未取代的C 1-12的烷氧基、取代或未取代的C 3-20的环烷基、取代或未取代的苯基、取代或未取代的吡啶基、取代或未取代的噻吩基、取代或未取代的含有选自N、O和S中的至少一种杂原子的C 4-20的环烷基、取代或未取代的羰基-苯基、取代或未取代的羰基-C 1-6烷基，或者R 1和R 2环合而共同形成取代或未取代的不含有或者含有选自N、O和S中的至少一种杂原子的单环或者二环以上的3-20元环烷基，且R 1和R 2不同时为H；
    其中的取代基选自氟、氯、溴、C 1-6的烷基、C 1-6的烷氧基、苯基、C 1-6的烷基-苯基、由1-4个选自氟、氯和溴的卤素取代的苯基、由1-4个选自氟、氯和溴的卤素取代的苯氧基、噻吩基、氰基、硝基、由1-4个选自氟、氯和溴的卤素取代的C 1-6的烷基、由C 1-6的烷基取代的氨基、C 1-6的酯基，或者取代基中的两个环合而共同形成不含有或者含有选自N、O和S中的至少一种杂原子的C 2-8的环烷基，或者取代基中的两个环合而共同形成选自苯基、噻吩基和吡啶基中的任意一个基团，或者上述R 1和R 2中的碳原子与氧原子一起形成碳氧双键而使得所述R 1和R 2中含有羰基基团。
  3. 根据权利2所述的化合物，其中，式(1)所示结构的化合物选自以下化合物中的至少一种：
    化合物1：R为
    Figure PCTCN2018105074-appb-100002
    化合物2：R为
    Figure PCTCN2018105074-appb-100003
    化合物3：R为
    Figure PCTCN2018105074-appb-100004
    化合物4：R为
    Figure PCTCN2018105074-appb-100005
    化合物5：R为
    Figure PCTCN2018105074-appb-100006
    化合物6：R为
    Figure PCTCN2018105074-appb-100007
    化合物7：R为
    Figure PCTCN2018105074-appb-100008
    化合物8：R为
    Figure PCTCN2018105074-appb-100009
    化合物9：R为
    Figure PCTCN2018105074-appb-100010
    化合物10：R为
    Figure PCTCN2018105074-appb-100011
    化合物11：R为
    Figure PCTCN2018105074-appb-100012
    化合物12：R为
    Figure PCTCN2018105074-appb-100013
    化合物13：R为
    Figure PCTCN2018105074-appb-100014
    化合物14：R为
    Figure PCTCN2018105074-appb-100015
    化合物15：R为
    Figure PCTCN2018105074-appb-100016
    化合物16：R为
    Figure PCTCN2018105074-appb-100017
    化合物17：R为
    Figure PCTCN2018105074-appb-100018
    化合物18：R为
    Figure PCTCN2018105074-appb-100019
    化合物19：R为
    Figure PCTCN2018105074-appb-100020
    化合物20：R为
    Figure PCTCN2018105074-appb-100021
    化合物21：R为
    Figure PCTCN2018105074-appb-100022
    化合物22：R为
    Figure PCTCN2018105074-appb-100023
    化合物23：R为
    Figure PCTCN2018105074-appb-100024
    化合物24：R为
    Figure PCTCN2018105074-appb-100025
    化合物25：R为
    Figure PCTCN2018105074-appb-100026
    化合物26：R为
    Figure PCTCN2018105074-appb-100027
    化合物27：R为
    Figure PCTCN2018105074-appb-100028
    化合物28：R为
    Figure PCTCN2018105074-appb-100029
    化合物29：R为
    Figure PCTCN2018105074-appb-100030
    化合物30：R为
    Figure PCTCN2018105074-appb-100031
    化合物31：R为
    Figure PCTCN2018105074-appb-100032
    化合物32：R为
    Figure PCTCN2018105074-appb-100033
    化合物33：R为
    Figure PCTCN2018105074-appb-100034
    化合物34：R为
    Figure PCTCN2018105074-appb-100035
    化合物35：R为
    Figure PCTCN2018105074-appb-100036
    化合物36：R为
    Figure PCTCN2018105074-appb-100037
    化合物37：R为
    Figure PCTCN2018105074-appb-100038
    化合物38：R为
    Figure PCTCN2018105074-appb-100039
    化合物39：R为
    Figure PCTCN2018105074-appb-100040
    化合物40：R为
    Figure PCTCN2018105074-appb-100041
    化合物41：R为
    Figure PCTCN2018105074-appb-100042
    化合物42：R为
    Figure PCTCN2018105074-appb-100043
    化合物43：R为
    Figure PCTCN2018105074-appb-100044
    化合物44：R为
    Figure PCTCN2018105074-appb-100045
    化合物45：R为
    Figure PCTCN2018105074-appb-100046
    化合物46：R为
    Figure PCTCN2018105074-appb-100047
    化合物47：R为
    Figure PCTCN2018105074-appb-100048
    化合物48：R为
    Figure PCTCN2018105074-appb-100049
    化合物49：R为
    Figure PCTCN2018105074-appb-100050
    化合物50：R为
    Figure PCTCN2018105074-appb-100051
    化合物51：R为
    Figure PCTCN2018105074-appb-100052
    化合物52：R为
    Figure PCTCN2018105074-appb-100053
    化合物53：R为
    Figure PCTCN2018105074-appb-100054
    化合物54：R为
    Figure PCTCN2018105074-appb-100055
    化合物55：R为
    Figure PCTCN2018105074-appb-100056
    化合物56：R为
    Figure PCTCN2018105074-appb-100057
    化合物57：R为
    Figure PCTCN2018105074-appb-100058
    化合物58：R为
    Figure PCTCN2018105074-appb-100059
    化合物59：R为
    Figure PCTCN2018105074-appb-100060
    化合物60：R为
    Figure PCTCN2018105074-appb-100061
    化合物61：R为
    Figure PCTCN2018105074-appb-100062
    化合物62：R为
    化合物63：R为
    Figure PCTCN2018105074-appb-100064
    化合物64：R为
    Figure PCTCN2018105074-appb-100065
    化合物65：R为
    Figure PCTCN2018105074-appb-100066
    化合物66：R为
    Figure PCTCN2018105074-appb-100067
    化合物67：R为
    Figure PCTCN2018105074-appb-100068
    化合物68：R为
    Figure PCTCN2018105074-appb-100069
    化合物69：R为
    Figure PCTCN2018105074-appb-100070
    化合物70：R为
    Figure PCTCN2018105074-appb-100071
    化合物71：R为
    Figure PCTCN2018105074-appb-100072
    化合物72：R为
    Figure PCTCN2018105074-appb-100073
    化合物73：R为
    Figure PCTCN2018105074-appb-100074
  4. 一种制备权利要求1-3中任意一项所述的式(1)所示的含氟氯吡啶肟酯结构的化合物的方法，该方法包括：在缩合剂存在下，将式(2)所示结构的化合物与式(3)所示结构的化合物进行接触反应，
    Figure PCTCN2018105074-appb-100075
    其中，式(3)中的R基团的定义与权利要求1-3中任意一项所述的定义相同。
  5. 根据权利要求4所述的方法，其中，所述接触反应的条件包括：反应温度为5～50℃，反应时间为4～30h；优选地，
    所述接触反应在溶剂存在下进行；优选地，
    所述溶剂选自二氯甲烷、甲醇、乙醇、甲苯、环己烷、DMF和DMSO中的至少一种。
  6. 根据权利要求4所述的方法，其中，所述缩合剂为EDCI和DMAP的混合物。
  7. 权利要求1-3中任意一项所述的式(1)所示的含氟氯吡啶肟酯结构的化合物在防治杂草中的应用。
  8. 根据权利要求7所述的应用，其中，所述杂草为阔叶杂草和禾本科杂草中的至少一种。
  9. 一种除草剂，该除草剂由活性成分和辅料组成，所述活性成分包括权利要求1-3所述的含氟氯吡啶肟酯结构的化合物或其农业化学上可接受的盐、水合物、溶剂化物，或其同分异构体、互变异构体、对映异构体、光学活性形式的衍生物中的至少一种。
  10. 根据权利要求9所述的除草剂，其中，在所述除草剂中，所述活性成分的含量为1-99.9 重量％；优选地，
    所述除草剂的剂型选自乳油、悬浮剂、微乳剂、水乳剂、胶囊剂、可湿性粉剂、粉剂、粒剂、水剂、毒饵、母液和母粉中的至少一种。
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