WO2021143617A1 - Cyclohexadiene oxime ether compound, synthesis method therefor and application thereof - Google Patents

Cyclohexadiene oxime ether compound, synthesis method therefor and application thereof Download PDF

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Publication number
WO2021143617A1
WO2021143617A1 PCT/CN2021/070793 CN2021070793W WO2021143617A1 WO 2021143617 A1 WO2021143617 A1 WO 2021143617A1 CN 2021070793 W CN2021070793 W CN 2021070793W WO 2021143617 A1 WO2021143617 A1 WO 2021143617A1
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Prior art keywords
group
cyclohexadiene
oxime ether
resistant
carbon atoms
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PCT/CN2021/070793
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French (fr)
Chinese (zh)
Inventor
邓照西
胡合伟
郭少雄
岑金
谭宾
杜兵兵
杨莉娜
李君沛
Original Assignee
郑州手性药物研究院有限公司
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Priority claimed from CN202010044702.5A external-priority patent/CN111205208B/en
Priority claimed from CN202010887632.XA external-priority patent/CN114105842A/en
Application filed by 郑州手性药物研究院有限公司 filed Critical 郑州手性药物研究院有限公司
Publication of WO2021143617A1 publication Critical patent/WO2021143617A1/en

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N35/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical
    • A01N35/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical at least one of the bonds to hetero atoms is to nitrogen
    • A01N35/10—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical at least one of the bonds to hetero atoms is to nitrogen containing a carbon-to-nitrogen double bond
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P13/00—Herbicides; Algicides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/46—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having at least one of the nitrogen atoms, not being part of nitro or nitroso groups, further bound to other hetero atoms
    • C07C323/47—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having at least one of the nitrogen atoms, not being part of nitro or nitroso groups, further bound to other hetero atoms to oxygen atoms

Definitions

  • the invention relates to the field of pesticides and herbicides, in particular to a cyclohexadiene oxime ether compound, and a synthesis method and application thereof.
  • the cyclohexenone herbicide developed in the 1960s is a very important class of herbicides. It inhibits the activity of acetyl-Coenzyme A carboxylase (ACCase) to destroy fatty acid biosynthesis, thereby eliminating Drop weeds.
  • ACCase acetyl-Coenzyme A carboxylase
  • This type of herbicide is a highly effective, safe, and highly selective ACCase inhibitor, which has specific effects on most annual and perennial grassy weeds. For this reason, many researchers have devoted themselves to the research and development of such herbicides in order to discover New and efficient herbicide varieties.
  • the present invention provides a cyclohexadiene oxime ether compound, the structural formula of which is:
  • the group R 1 and the group R 3 in the structural formula I, II or III are respectively selected from -H, aliphatic substituents containing 1 to 6 carbon atoms, and halogenated groups containing 1 to 6 carbon atoms.
  • the group R 2 is selected from -H, aliphatic substituents containing 1 to 6 carbon atoms, halogenated aliphatic substituents containing 1 to 6 carbon atoms, cyano substituted aliphatic substituents containing 1 to 6 carbon atoms Substituents, amine groups containing 1 to 6 carbon atoms, amides containing 1 to 6 carbon atoms, phenyl groups, halogenated aromatic substituents, cyano substituted aromatic substituents, nitro substituted aromatic substituents or Heterocyclic aromatic substituents; wherein the heterocyclic aromatic substituents are selected from And X is selected from -H, halogen, -CN, -NO 2 , -CF 3 , -C(CF 3 ) 3 , n is the number of substituents, taken from 1, 2, 3;
  • the group R 4 and the group R 5 are respectively selected from -H, a hydrocarbon group or carbonyl group containing 1 to 6 carbon atoms, and a metal ion;
  • the group R 6 is selected from -H, ether group, thioether group, alkyl group containing 1-10 carbon atoms, cycloalkyl group, alkenyl group, halo group, five-membered heterocyclic substituent, six-membered heterocyclic substituent base.
  • the aliphatic substituent containing 1 to 6 carbon atoms is selected from alkyl, cycloalkyl, alkenyl, or alkynyl, etc., and the total number of carbon atoms is 1 to 6;
  • the halogenated group contains 1 to 6
  • the aliphatic substituent with three carbon atoms is selected from haloalkyl, halocycloalkyl, haloalkenyl or haloalkynyl, etc., and the total number of carbon atoms in the alkyl, cycloalkyl, alkenyl or alkynyl group is 1 ⁇ 6;
  • the cyano substituted aliphatic substituent containing 1 to 6 carbon atoms is selected from the group consisting of cyano-substituted alkyl, cyano-substituted cycloalkyl, cyano-substituted alkenyl, cyano-substituted alkynyl, etc
  • the substituent Y is selected from -Cl, -F, -CN, -Br, -NO 2 or -CF 3 , and n is the number of substituent Y, which is 1, 2 or 3.
  • the group R 4 and the group R 5 are respectively selected from -H, -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 , -CH 2 CH 2 CH 2 CH 3 , -COCH 3 , -COCH 2 CH 3 , -COCH 2 CH 2 CH 3 , Na + , K + , NH 4 + or Li + .
  • the group R 6 is selected from -OCH 3 , -CH 2 OCH 3 , -CH 2 OCH 2 CH 3 , -CH 2 SCH 2 CH 3 , -CH 2 SCH(CH 3 )CH 2 CH 3 , -CH 2 CH(CH 3 )SCH 2 CH 3 , -CH 3 , -CH(CH 3 ) 2 , -CF 3 , -CH 2 CH 2 Cl, Where Z is O, S or N.
  • the cyclohexadiene oxime ether compound is one of the compounds having the following groups:
  • the present invention also provides a method for synthesizing the above cyclohexadiene oxime ether compound, which comprises: dissolving intermediate 7 and intermediate 8 in an organic solvent, and reacting to synthesize the cyclohexane-1 at 0-100°C. 3-diketone compounds; wherein the structural formula of the intermediate 7 is The structural formula of the intermediate 8 is
  • the organic solvent is one or a combination of dichloromethane, acetone, toluene, DMF, petroleum ether and methanol.
  • the synthesis mechanism of the above cyclohexadiene oxime ether compound is: in the organic solvent and at a temperature of 0-100°C, the amino group in the intermediate 7 and the carbonyl group in the intermediate 8 undergo an addition reaction to form unstable
  • the alcohol amine compound, the alcohol amine compound is dehydrated to generate Schiff base. Therefore, taking the compound II as an example, its synthetic route is as follows:
  • the intermediate 7 and the intermediate 8 are dissolved in the organic solvent, and reacted at 60-100°C for 1 to 48 hours under the catalysis of acetic acid. After the reaction, the organic solvent is removed, washed and dried. The pure product of the cyclohexane-1,3-dione compound is obtained.
  • the molar ratio of the intermediate 7 to the intermediate 8 is 0.8 to 1.2:1.
  • the synthesis temperature of the cyclohexadiene oxime ether compound is preferably 60°C, 70°C, 80°C, 90°C, 100°C, or the like.
  • the synthesis method of the intermediate 7 includes: dissolving the intermediate 6 and hydrazine hydrate in dichloromethane, and reacting at 10 to 80° C. to obtain the intermediate 7; wherein, the structural formula of the intermediate 6 for
  • the intermediate 6 is dissolved in dichloromethane, and then hydrazine hydrate is added dropwise.
  • the molar ratio of intermediate 6 to hydrazine hydrate is 1:1 ⁇ 3.
  • the reaction is carried out at 10 ⁇ 80°C for 1 ⁇ 3h, after the reaction is completed, water is added for extraction, and the organic layer is collected to remove the second solvent to obtain the pure intermediate 7 product.
  • the preparation method of the intermediate 6 includes: intermediate 5 and N-hydroxyphthalimide are reacted to synthesize the intermediate 6 under the action of a basic agent at 0-100°C; wherein, The structural formula of the intermediate 5 is The alkaline agent is sodium bicarbonate, sodium carbonate, potassium bicarbonate or potassium carbonate.
  • the intermediate 5, N-hydroxyphthalimide and the alkaline agent are mixed according to a molar ratio of 1:1 ⁇ 3:0.5 ⁇ 3, and dissolved in DMF at 0 ⁇ 100°C After reacting for 3-8 hours, after removing DMF, water and toluene are added, the organic layer is collected, and the solvent in the organic layer is removed to obtain the pure intermediate 6 product.
  • the preparation method of the intermediate 5 includes: intermediate 4 and methanesulfonyl chloride are dissolved in toluene at 0-20°C, and a synthesis reaction occurs under the action of triethylamine to prepare the intermediate 5 ;
  • the structural formula of the intermediate 4 is
  • Step 4 first dissolve Intermediate 4 in toluene, then add triethylamine dropwise, and then add methanesulfonyl chloride dropwise at 0-20°C, and keep it at 0-20°C for 1 to 3 hours after the addition is complete, and the reaction is complete Afterwards, the precipitate was removed by filtration, acidic water was added to the filtrate for extraction, the organic layer was taken and the solvent in the organic layer was removed to obtain the pure intermediate 5.
  • the molar ratio of the intermediate 4, methylsulfonyl chloride and triethylamine is 1:1 to 3:0.5 to 3
  • the acid water is an aqueous ammonium chloride solution, an aqueous hydrochloric acid solution or an aqueous sulfuric acid solution.
  • the preparation method of the intermediate 4 includes: the intermediate 3, calcium chloride and sodium borohydride are dissolved in ethanol, and the synthesis reaction occurs at 20-60°C to obtain the intermediate 3; wherein The structural formula of Intermediate 3 is
  • the intermediate 3, calcium chloride and sodium borohydride are dissolved in ethanol, and then the temperature is increased to 20-60° C. and the temperature is maintained for 3-8 hours.
  • the acid water is added to the reaction system to remove the solvent Afterwards, water and toluene are added, the organic layer is collected and the solvent is removed to obtain the intermediate 4, wherein the molar ratio of the intermediate 3 to sodium borohydride is 1:0.3-2.
  • the preparation method of the intermediate 3 includes: intermediate 2 and the hydroxyl compound R 2 OH are reacted under reduced pressure at 40-100° C. under the action of a basic catalyst to prepare the intermediate 3; wherein, The structural formula of the intermediate 2 is The basic catalyst is sodium bicarbonate, sodium carbonate, potassium bicarbonate or potassium carbonate.
  • the intermediate 2, the hydroxyl compound R 2 OH and the basic catalyst are dissolved in toluene, and then reacted under reduced pressure at 40 to 100° C. for 1 to 3 hours, wherein the intermediate 2, the hydroxyl compound R
  • the molar ratio of 2 OH to the basic catalyst is 1:1 ⁇ 2:0.5 ⁇ 3; after the reaction is completed, the precipitate is removed by filtration, and the acid water is added to the filtrate for extraction, and the organic layer is taken to remove the solvent.
  • the preparation method of the intermediate 2 includes: intermediate 1, 4-dimethylaminopyridine (DMAP) and p-toluenesulfonyl chloride are dissolved in toluene, and triethylamine is added dropwise at -20 ⁇ 10°C, and then The reaction is kept at 10 to 60°C to prepare the intermediate 2; wherein the structural formula of the intermediate 1 is
  • the intermediate 1, DMAP and p-toluenesulfonyl chloride are first dissolved in toluene, and then triethylamine is dropped at -20 ⁇ 10°C, and after the dropping, the temperature is raised to 10 ⁇ 60°C and the temperature is kept for 1 ⁇ 3h.
  • the molar ratio of the intermediate 1, DMAP and p-toluenesulfonyl chloride is 1:0.01 ⁇ 3:1 ⁇ 1.5; after the reaction, the precipitate is removed by filtration, and the acid water is added to the filtrate for extraction, and the organic layer is removed The solvent in it obtains the pure product of the intermediate 2.
  • the present invention also provides an application of the above cyclohexadiene oxime ether compound, wherein the cyclohexadiene oxime ether compound is used as an active ingredient in the preparation of a herbicide for controlling gramineous weeds.
  • the gramineous weeds are gramineous resistant weeds that grow in the fields of gramineous crops.
  • the gramineous crops are corn, rice or wheat, etc.
  • the gramineous resistant weeds are resistant barnyardgrass, resistant wild oats, resistant crabgrass, resistant yardgrass, resistant setaria, resistant sexual gooseweed, resistance see wheat nipples, resistant bluegrass, resistant stephanotis or resistant hard grass.
  • the cyclohexadiene oxime ether compound is used as an active ingredient to be compounded with other herbicides, specifically, it can be combined with oxfentrazone, bispyribac-methyl, cyhalofop-butyl chloride, and pyriflufenazone.
  • the cyclohexadiene oxime ether compound as the active ingredient of the herbicide, can also be compounded with safeners, such as dibenzoxazole acid, naphthalene dicarboxylic anhydride, dichloropropenylamine, chlorfenazone, chlorfenazone, Nitrofuran, pyrazolam, pyraclosporin or benzidine amide, etc.
  • safeners such as dibenzoxazole acid, naphthalene dicarboxylic anhydride, dichloropropenylamine, chlorfenazone, chlorfenazone, Nitrofuran, pyrazolam, pyraclosporin or benzidine amide, etc.
  • the above herbicide also includes auxiliary materials.
  • the auxiliary materials are one or more of emulsifiers, dispersants, wetting agents, fillers, solvents, co-solvents, thickeners, antifreeze agents, stabilizers, defoamers, and preservatives.
  • the emulsifier mainly includes octylphenol polyoxyethylene (polyoxypropylene) ether, nonylphenol polyoxyethylene ether, benzylphenol polyoxyethylene ether, styryl polyoxyethylene ether, fatty alcohol polyoxyethylene One or more of vinyl ether, fatty acid polyoxyethylene ester, fatty amine polyoxyethylene ether, alkylbenzene sulfonate, etc.
  • the dispersant mainly includes alkyl naphthalene sulfonate, naphthalene sulfonate formaldehyde condensate, aralkyl naphthalene sulfonate formaldehyde condensate, naphthol sulfonic acid formic acid condensate, alkyl benzene sulfonate, alkyl phosphate ester , Alkylphenol polyoxyethylene ether, lignin sulfonate, fatty acid polyoxyethylene ester, fatty amine polyoxyethylene ether, vegetable oil ethylene oxide adduct, ethylene oxide-propylene oxide block copolymer, One or more of ethylenediamine polyoxyethylene polyoxypropylene ether.
  • the wetting agent/penetrant mainly includes fatty alcohol sulfate, alkylbenzene sulfonate, ⁇ -olefin sulfonate, dialkyl succinate sulfonate, fatty amide sodium N-methyl taurate One or more of salt, sodium alkyl naphthalene sulfonate, etc.
  • the filler includes one or more of diatomite, attapulgite, bentonite, sepiolite, kaolin, clay, and white carbon black.
  • the solvent or co-solvent is a solvent commonly used in pesticides, mainly including benzene, toluene, naphthalene, white oil, heavy oil, paraffin liquid, methanol, ethanol, propionate alcohol, methyl acetate, cyclohexanone, acetone, vegetable oil, two One or more of methyl chloride, chloroform, acetonitrile, cresol, etc.
  • the thickening agent mainly includes one or more of starch, xanthan gum, agar, methyl cellulose, hydroxypropyl methyl cellulose, organic bentonite, diatomaceous earth, polyvinyl alcohol and the like.
  • the antifreeze agent mainly includes one or more of ethylene glycol, propylene glycol, glycerol, polyethylene glycol, and urea.
  • the stabilizer mainly includes one or more of phosphite, epichlorohydrin, epoxidized soybean oil, epoxidized linseed oil and the like.
  • the defoaming agent mainly includes one or more of propanol, butanol, tributyl phosphate, polyether surfactants, polyethylene glycol fatty acid ester, mineral oil, silicone oil and the like.
  • the preservatives mainly include one or more of benzoic acid, sorbic acid, p-hydroxybenzoic acid, hydroquinone and the like.
  • the above-mentioned cyclohexadiene oxime ether compound provided by the present invention has a structural unit of cyclohexenone or can have a structural unit of cyclohexenone after being applied to crops after being absorbed and transformed, and the cyclohexadiene has been verified by experiments
  • Oxime ether compounds can inhibit ACCase, can be used as ACCase inhibitors, have herbicidal activity, can be used as herbicides for controlling various grass weeds, and used to control grasses in broad-leaved crop fields such as soybean, cotton, peanut, and rape Weeds; at the same time, it was found through experimental research that the different R 1 and R 2 groups in the above cyclohexadiene oxime ether compounds make the compounds have higher selectivity to gramineous crops, thereby making the above cyclohexadiene oxime ethers Compounds broaden the application range of this type of herbicides, not only can be used
  • the method for synthesizing the above cyclohexadiene oxime ether compound provided by the present invention uses Intermediate 7 and Intermediate 8 as raw materials for one-step synthesis.
  • the synthesis method is simple, the reaction temperature is mild, the receipt rate is high, and the cost is low, and it can realize industrial production. .
  • the above synthetic route uses Intermediate 1 as the starting material, and sequentially synthesizes Intermediate 2, Intermediate 3, Intermediate 4, Intermediate 5, Intermediate 6, and Intermediate 7, and then uses Intermediate 7 and Intermediate 8 It is the reactant to synthesize the target compound. Therefore, the synthetic method of the cyclohexane-1,3-dione compound provided by the present invention has a short synthetic route, simple purification method, mild reaction temperature, high yield, low cost, and can be Realize industrialized production.
  • This embodiment provides a compound 1, and the structural formula of the compound 1 is as follows:
  • the synthetic method of the above compound 1 includes:
  • the first step is to synthesize 2-(toluene-4-sulfonic acid)-propionic acid methyl ester:
  • the second step is to synthesize 2-(4-chloro-phenoxy)-propionic acid methyl ester:
  • the third step is to synthesize 2-(4-chlorophenoxy)-propanol:
  • the fourth step is to synthesize 2-(4-chloro-phenoxy)-propyl methanesulfonate:
  • the fifth step is to synthesize 2-[2-(4-chloro-phenoxy)-propoxy]-isoindole-1,3-dione:
  • the sixth step is to synthesize O-[2-(4-chloro-phenoxy)-propyl]-hydroxylamine:
  • the seventh step is to synthesize compound 1
  • the hydrogen nuclear magnetic spectrum of the compound 1 1HNMR (400MHz CDCl3): ⁇ 7.2(2H,m), ⁇ 6.8(2H,m), ⁇ 4.6(1H,m), ⁇ 4.1(2H, m), ⁇ 2.8(2H,m), ⁇ 2.5(2H,m), ⁇ 2.2(2H,m), ⁇ 2.1(1H,m), ⁇ 1.5(2H,m), ⁇ 1. 2(11H,m), ⁇ 0.9 ⁇ 1.1(4H,m).
  • This embodiment provides a compound 2 whose structural formula is as follows:
  • the synthesis method of the above compound 2 includes: adding 15.3g 4-(1-aminooxymethyl-butyl-2-enoxy)-benzonitrile and 17.8g 5-ethoxymethyl-2 into the reactor -Ventylcyclohexane-1,3-dione, 150ml petroleum ether, 3ml acetic acid, react at 30°C for 12h, remove the solvent after the reaction, wash and concentrate to obtain 30g of red-brown viscous liquid, namely compound 2, and The yield was 94%.
  • the hydrogen nuclear magnetic spectrum of the compound 2 1HNMR (400MHz CDCl3): ⁇ 7.3(2H,d), ⁇ 6.9(2H,d), ⁇ 5.5(2H,m), ⁇ 4.1(1H, m), ⁇ 3.8(2H,d), ⁇ 3.3(5H,m), ⁇ 2.3(5H,m), ⁇ 1.8(3H,d), ⁇ 1 ⁇ 1.3(12H,m).
  • This embodiment provides a compound 3, and the structural formula of the compound 3 is as follows:
  • the synthesis method of the above compound 3 includes: adding 14g O-[2-(4-chloro-phenoxy)-propyl]-hydroxylamine and 20.9g 1-(4-ethylthiomethyl-2, 6-Dimethoxy-cyclohexyl-1,5-dienyl)-pentane-1-one, 120ml petroleum ether, 15ml acetic acid, reacted at 15°C for 28h, after the reaction, the solvent is removed, and it is obtained after washing and concentrating 31 g of red-brown viscous liquid, namely compound 3, and the yield was 92%.
  • This embodiment provides a compound 4, and the structural formula of the compound 4 is as follows:
  • the synthesis method of the above compound 4 includes: adding 18.9g O-[3-chloro-2-(3,5-dichloro-phenoxy)-propyl]-hydroxylamine and 21.3g 2-(3- Chloro-propionyl)-5-(2-ethylsulfanyl-propyl)-3-hydroxy-cyclohex-2-enone, 180ml petroleum ether, 8ml acetic acid, reacted at 60°C for 10h, and removed after the reaction The solvent was washed with water and concentrated to obtain 37.8 g of a red-brown viscous liquid, namely compound 4, and the yield was 97%.
  • the compound 4 provided in this embodiment can react with sodium hydroxide to form a corresponding sodium salt, and the structural formula of the sodium salt is:
  • This embodiment provides a compound 5, and the structural formula of the compound 5 is as follows:
  • the synthesis method of the above compound 5 includes: adding 14.8g O-[2-(4-chloro-phenoxy)-propyl]-hydroxylamine and 20g butyryl trione, 100ml petroleum ether, 5ml acetic acid into the reactor. The reaction was carried out at 25° C. for 24 hours. After the reaction, the solvent was removed. After washing and concentration, 31.5 g of a reddish brown viscous liquid, namely compound 5, was obtained, and the yield was 96%.
  • This embodiment provides a compound 6 whose structural formula is as follows:
  • the synthesis method of the above compound 6 includes: adding 12.8g O-[2-(pyridine-2-oxy)-butyl]-hydroxylamine and 16.5g 2-butyryl-5-cyclopropylmethyl- into the reactor. 3-Hydroxy-cyclohex-2-enone, 150ml petroleum ether, 5ml acetic acid, react at 20°C for 48h, remove the solvent after the reaction, wash and concentrate to obtain 25.2g red-brown viscous liquid, namely compound 6, and produce The rate is 90%.
  • the hydrogen nuclear magnetic spectrum of the compound 6 1HNMR (400MHz CDCl3): ⁇ 7.5(4H,m), ⁇ 3.8(3H,m), ⁇ 2.8(2H,d), ⁇ 1.8(2H, d), ⁇ 1.6(3H,m), ⁇ 1.1 ⁇ 1.4(6H,m), ⁇ 0.9(6H,t),0.7(5H,m).
  • This embodiment provides a compound 7 whose structural formula is as follows:
  • the synthesis method of the above compound 7 includes: adding 13.6g O-[2-(3-chloro-allyloxy)-3-methyl-butyl]-hydroxylamine and 19.6g 2-(3-ene into the reactor -1-pentanone)-3-hydroxy-5-cyclopropylthiomethyl-cyclohex-2-enone, 100ml petroleum ether, 5ml acetic acid, react at 28°C for 30h, remove the solvent after the reaction, After washing and concentrating with water, 30.3 g of red-brown viscous liquid, namely compound 7, was obtained, and the yield was 95%.
  • the hydrogen nuclear magnetic spectrum of the compound 7 1HNMR (400MHz CDCl3): ⁇ 6.3(2H,m), ⁇ 5.2(2H,m), ⁇ 4.1(2H,d), ⁇ 3.6(2H, d), ⁇ 2.8(3H,m), ⁇ 2.5(2H,d), ⁇ 2.1(6H,m), ⁇ 1.8(3H,d), ⁇ 1.3(1H,m), ⁇ 1. 0 (6H, d), ⁇ 0.8 (4H, m).
  • This embodiment provides a compound 8 whose structural formula is as follows:
  • the synthesis method of the above compound 8 includes: adding 14.4g O-[2-(3-chloro-allyloxy)-2-(2-methyl-cyclopropyl)-ethyl]-hydroxylamine and 19.8g 5-sec-butylthiomethyl-2-cyclopropanecarbonyl-cyclohexane-1,3-dione, 100ml petroleum ether, 4ml acetic acid, react at 80°C for 5h, after the reaction, remove the solvent, wash and concentrate Then, 29.3 g of a red-brown viscous liquid, compound 8, was obtained, and the yield was 89%.
  • the proton nuclear magnetic spectrum of the compound 8 1HNMR (400MHz CDCl3): ⁇ 6.2(2H,m), ⁇ 4.0(2H,d), ⁇ 3.6(2H,d), ⁇ 3.2(1H, s), ⁇ 2.9(1H,m), ⁇ 2.8(1H,m), ⁇ 2.5(4H,d), ⁇ 2.2(2H,d), ⁇ 2.1(1H,m), ⁇ 1 ⁇ 1.5(11H,m), ⁇ 0.5 ⁇ 0.8(9H,m).
  • This embodiment provides a compound 9 whose structural formula is as follows:
  • the synthesis method of the above compound 9 includes: adding 16.5g O-[2-(3-trifluoromethyl-phenoxy)-propyl]-hydroxylamine and 21.6g 1,5-diacetic acid-6- to the reactor. Butyryl-3-isopropyl-cyclohexyl-1,5-dienyl ester, 160ml petroleum ether, 5ml acetic acid, reacted at 50°C for 48h. After the reaction, the solvent was removed. After washing and concentrating, 31.3g of reddish brown sticky substance was obtained. Thick liquid, compound 9, and the yield was 85%.
  • This embodiment provides a compound 10, and the structural formula of the compound 10 is as follows:
  • the synthesis method of the above compound 10 includes: adding 24.9g O-[3-amino-2-(3,5-dibromo-phenoxy)-propyl]-hydroxylamine and 19.9g butyryl triketone into the reactor, 150ml petroleum ether and 5ml acetic acid were reacted at 25°C for 24h. After the reaction, the solvent was removed. After washing and concentration, 41.6g of red-brown viscous liquid was obtained, namely compound 10, and the yield was 98%.
  • the hydrogen nuclear magnetic spectrum of the compound 10 1HNMR (400MHz CDCl3): ⁇ 7.1 (1H, m), ⁇ 6.9 (2H, m), ⁇ 4.0 (3H, m), ⁇ 3.1 (2H, d), ⁇ 2.9(2H,d), ⁇ 2.7(1H,m), ⁇ 2.5(2H,q), ⁇ 1.9(2H,d), ⁇ 1.7(1H,m), ⁇ 1. 5(4H,m), ⁇ 1.3(8H,m), ⁇ 0.9(3H,m).
  • This embodiment provides a compound 11, and the structural formula of the compound 11 is as follows:
  • the synthesis method of the above compound 11 includes: adding 18.3g O-[2-(3-chloro-allyloxy)-2-(4-chloro-phenyl)-ethyl]-hydroxylamine and 19.9g into the reactor 2-Butyryl-5-(2-ethylsulfanyl-propyl)-3-hydroxy-cyclohex-2-enone, 150ml petroleum ether, 6ml acetic acid, react at 30°C for 30h, remove the solvent after the reaction After washing and concentrating, 34.8 g of red-brown viscous liquid, namely compound 11, was obtained, and the yield was 94%.
  • This embodiment provides a compound 12, and the structural formula of the compound 12 is as follows:
  • the synthesis method of the above compound 12 includes: adding 13.9g O-[2-(3H-pyrrole-3-oxy)-hexyl]-hydroxylamine and 17.1g 2-butyryl-5-(2-chloroethyl into the reactor Base)-3-hydroxy-cyclohex-2-enone, 120ml petroleum ether, 8ml acetic acid, react at 45°C for 18h, remove the solvent after the reaction, wash and concentrate to obtain 27.1g of red-brown viscous liquid, namely compound 12. , And the yield was 91%.
  • This embodiment provides a compound 13 whose structural formula is as follows:
  • the synthesis method of the above compound 13 includes: adding 16.5g O-[2-(3,5-dichloro-phenoxy)-propyl]-hydroxylamine and 23.7g 2-butyl-5-(2) to the reactor. -Cyclohexylsulfanyl-propyl)-3-hydroxy-cyclohex-2-enone, 150ml petroleum ether, 6ml acetic acid, reacted at 35°C for 16h, after the reaction, the solvent is removed, washed with water and concentrated to obtain 35.1g of reddish brown Viscous liquid, compound 13, and the yield was 90%.
  • This embodiment provides a compound 14 whose structural formula is as follows:
  • the synthetic method of compound 14 includes the following steps:
  • the first step is to synthesize 3-methyl-2-(toluene-4-sulfonyloxy)-butyric acid methyl ester
  • the second step is to synthesize methyl 2-(4-chloro-phenoxy)-3-methylbutyrate
  • the third step is to synthesize 2-(4-chloro-phenoxy)-3-methyl-butane-1-ol
  • the fourth step is to synthesize 2-(4-chloro-phenoxy)-3-methyl-butyl methanesulfonate
  • the fifth step is to synthesize 2-[2-(4-chloro-phenoxy)-3-methyl-butoxy]-isoindole-1,3-dione
  • the sixth step is to synthesize O-[2-(4-chloro-phenoxy)-3-methyl-butyl]-hydroxylamine
  • the seventh step is to synthesize compound 14
  • This embodiment provides a compound 15 whose structural formula is as follows:
  • the synthetic method of compound 15 includes the following steps:
  • the first step is to synthesize 2-(toluene-4-sulfonyloxy)-propionic acid methyl ester
  • the second step is to synthesize 2-(3-chloro-allyloxy)-propionic acid methyl ester
  • the third step is to synthesize 2-(3-chloro-allyloxy)-propyl-1-ol
  • the fourth step is to synthesize 2-(3-chloro-allyloxy)-propyl methanesulfonate
  • the fifth step is to synthesize 2-[2-(3-chloro-allyloxy)-propoxy]-isoindole-1,3-dione
  • the sixth step is to synthesize O-[2-(3-chloropropenoxy)-propyl]-hydroxylamine
  • the seventh step is to synthesize compound 15
  • This embodiment provides a compound 16 whose structural formula is as follows:
  • the synthetic method of compound 16 includes the following steps:
  • the first step is to synthesize 2-(toluene-4-sulfonic acid)-propionic acid methyl ester
  • the second step is to synthesize 2-(4-nitro-phenoxy)-propionic acid methyl ester
  • the third step is to synthesize 2-(4-nitrophenoxy)-propanol
  • the fourth step is to synthesize 2-(4-nitro-phenoxy)-propyl methanesulfonate
  • the fifth step is to synthesize 2-[2-(4-nitro-phenoxy)-propoxy]-isoindole-1,3-dione
  • the sixth step is to synthesize O-[2-(4-nitro-phenoxy)-propyl]-hydroxylamine
  • the seventh step is to synthesize compound 16
  • This embodiment provides a compound 17 whose structural formula is as follows:
  • the synthesis method of compound 17 includes the following steps:
  • the first step is to synthesize 2-(toluene-4-sulfonic acid)-propionic acid methyl ester
  • the second step is to synthesize 2-(3,5-difluoro-phenoxy)-propionic acid methyl ester
  • the third step is to synthesize 2-(3,5-difluorophenoxy)-propanol
  • the fourth step is to synthesize 2-(3,5-difluoro-phenoxy)-propyl methanesulfonate
  • the fifth step is to synthesize 2-[2-(3,5-difluoro-phenoxy)-propoxy]-isoindole-1,3-dione
  • the sixth step is to synthesize O-[2-(3,5-difluoro-phenoxy)-propyl]-hydroxylamine
  • the seventh step is to synthesize compound 17
  • Test sample (1) 10% oxfenacet EC; (2) 20% cyhalofop-butyl EC; (3) active ingredient 2% EC: active substance, 10% dodecyl sulfonic acid Sodium, 85% naphtha, wherein the active substance is compounds 1-17 provided in Examples 1-17.
  • Test conditions The pre-soaked seeds of rice, barnyardgrass, crabgrass, crabgrass, calamus, setaria, etc., as well as resistant barnyardgrass seeds, resistant crabgrass seeds, resistant stephengrass seeds, etc., were sown in standard soil in a plastic pot After the weeds are unearthed, spray the emulsifiable concentrates of the following experimental samples; evaluate the damage of the plants after 7-15 days. The evaluation results are shown in Table 3, Table 4 and Table 5. Among them, the evaluation criteria of plant damage can be found in the aforementioned "1. Experiments on the control of gramineous weeds in soybean fields".
  • Table 3 The control effect test results of common gramineous weeds in rice fields Table 1
  • Table 4 The control effect test results of common gramineous weeds in rice fields Table 2
  • the cyclohexadiene oxime ether compounds provided in the examples of the present invention have good properties for common gramineous weeds such as barnyardgrass, crabgrass, stephengrass, calamus, setaria, etc. It has a good control effect on some resistant gramineous weeds, such as resistant barnyardgrass, resistant crabgrass, resistant stephen, etc.
  • the cyclohexadiene oxime ether compound provided by the embodiments of the present invention not only has a control effect on grass weeds in soybean fields, but also has a good control effect on grass weeds in rice fields; in addition, the cyclohexanone
  • the diene oxime ether compounds not only have control effects on common grass weeds in rice fields, but also have significant control effects on some grass resistant weeds, and have industrial and commercial application prospects.

Abstract

The present invention provides a cyclohexadiene oxime ether compound having the following structural formula: (I) or (II) or (III); group R1 and group R3 are each selected from -H, an aliphatic substituent containing 1-6 carbon atoms, a halogenated aliphatic substituent, a cyano-substituted aliphatic substituent, amino or amide, phenyl, and a halogenated aromatic substituent or a cyano-substituted aromatic substituent; group R2 is selected from -H, an aliphatic substituent containing 1-6 carbon atoms, a halogenated aliphatic substituent, a cyano-substituted aliphatic substituent, amino or amide, phenyl, a halogenated aromatic substituent, and a cyano-substituted aromatic substituent, a nitro-substituted aromatic substituent or a heterocyclic aromatic substituent; and the heterocyclic aromatic substituent is selected from (iv), (v) or (vi), wherein X is selected from -H, halogen, -CN, -NO2, and -CF3, -C(CF3)3, and n is the number of substituents and is selected from 1, 2, and 3. The present invention also provides a preparation method for the above-mentioned cyclohexadiene oxime ether compound and an application thereof.

Description

环己二烯肟醚类化合物及其合成方法和应用Cyclohexadiene oxime ether compound and its synthesis method and application 技术领域Technical field
本发明涉及农药除草剂领域，尤其涉及一种环己二烯肟醚类化合物及其合成方法和应用。The invention relates to the field of pesticides and herbicides, in particular to a cyclohexadiene oxime ether compound, and a synthesis method and application thereof.
背景技术Background technique
除草剂在植物保护领域发挥着十分重要的作用，但其长期、大量使用，使得一些杂草对传统除草剂产生抗性，为此需要不断的开发新型高效的除草剂品种。Herbicides play a very important role in the field of plant protection, but their long-term and large-scale use has made some weeds resistant to traditional herbicides. For this reason, it is necessary to continuously develop new and efficient herbicide varieties.
在20世纪60年代开发出的环己烯酮类除草剂，是除草剂中非常重要的一类，其通过抑制乙酰辅酶A羧化酶(ACCase)的活性，来破坏脂肪酸的生物合成，进而除掉杂草。此类除草剂是一种高效安全、高选择性的ACCase抑制剂，对大多数一年生和多年生的禾本科杂草有特效，为此，不少研究者致力于此类除草剂的研发，以期发现新型高效的除草剂品种。The cyclohexenone herbicide developed in the 1960s is a very important class of herbicides. It inhibits the activity of acetyl-Coenzyme A carboxylase (ACCase) to destroy fatty acid biosynthesis, thereby eliminating Drop weeds. This type of herbicide is a highly effective, safe, and highly selective ACCase inhibitor, which has specific effects on most annual and perennial grassy weeds. For this reason, many researchers have devoted themselves to the research and development of such herbicides in order to discover New and efficient herbicide varieties.
发明内容Summary of the invention
有鉴于此，确有必要提供一种环己二烯肟醚类化合物及其合成方法和应用，以解决上述问题。In view of this, it is indeed necessary to provide a cyclohexadiene oxime ether compound and its synthesis method and application to solve the above problems.
具体地，本发明提供一种环己二烯肟醚类化合物，其结构式为：Specifically, the present invention provides a cyclohexadiene oxime ether compound, the structural formula of which is:
Figure PCTCN2021070793-appb-000001
Figure PCTCN2021070793-appb-000001
其中，所述结构式I、II或III中的基团R 1和基团R 3分别选自-H、含1～6个碳原子的脂肪族取代基、卤代含1～6个碳原子的脂肪族取代基、氰基取代含1～6个碳原子的脂肪族取代基、含1～6个碳原子的胺基、含1～6个碳原子的酰胺、苯基、卤代芳香族取代基或氰基取代芳香族取代基； Wherein, the group R 1 and the group R 3 in the structural formula I, II or III are respectively selected from -H, aliphatic substituents containing 1 to 6 carbon atoms, and halogenated groups containing 1 to 6 carbon atoms. Aliphatic substituents, cyano substituted aliphatic substituents containing 1 to 6 carbon atoms, amino groups containing 1 to 6 carbon atoms, amides containing 1 to 6 carbon atoms, phenyl, halogenated aromatic substituents Group or cyano substituted aromatic substituent;
基团R 2选自-H、含1～6个碳原子的脂肪族取代基、卤代含1～6个碳原子的脂肪族取代基、氰基取代含1～6个碳原子的脂肪族取代基、含1～6个碳原子的胺基、含1～6个碳原子的酰胺、苯基、卤代芳香族取代基、氰基取代芳香族取代基、硝基取代芳香族取代基或杂环芳香族取代基；其中，所述杂环芳香族取代基选自
Figure PCTCN2021070793-appb-000002
且X选自-H、卤素、-CN、-NO 2、-CF 3、-C(CF 3) 3，n为取代基的个数，取自1、2、3； The group R 2 is selected from -H, aliphatic substituents containing 1 to 6 carbon atoms, halogenated aliphatic substituents containing 1 to 6 carbon atoms, cyano substituted aliphatic substituents containing 1 to 6 carbon atoms Substituents, amine groups containing 1 to 6 carbon atoms, amides containing 1 to 6 carbon atoms, phenyl groups, halogenated aromatic substituents, cyano substituted aromatic substituents, nitro substituted aromatic substituents or Heterocyclic aromatic substituents; wherein the heterocyclic aromatic substituents are selected from
Figure PCTCN2021070793-appb-000002
And X is selected from -H, halogen, -CN, -NO 2 , -CF 3 , -C(CF 3 ) 3 , n is the number of substituents, taken from 1, 2, 3;
基团R 4和基团R 5分别选自-H、含1～6个碳原子的烃基或羰基、金属离子； The group R 4 and the group R 5 are respectively selected from -H, a hydrocarbon group or carbonyl group containing 1 to 6 carbon atoms, and a metal ion;
基团R 6选自-H、醚基、硫醚基、含1～10个碳原子的烷基、环烷基、烯基、卤代基、五元杂环取代基、六元杂环取代基。 The group R 6 is selected from -H, ether group, thioether group, alkyl group containing 1-10 carbon atoms, cycloalkyl group, alkenyl group, halo group, five-membered heterocyclic substituent, six-membered heterocyclic substituent base.
其中，所述含1～6个碳原子的脂肪族取代基选自烷基、环烷基、烯基或炔基等，且碳原子总数为1～6个；所述卤代含1～6个碳原子的脂肪族取代基选自卤代烷基、卤代环烷基、卤代烯基或卤代炔基等，且烷基、环烷基、烯基或炔基中的碳原子总数为1～6个；所述氰基取代含1～6个碳原子的脂肪族取代基选自氰基取代烷基、氰基取代环烷基、氰基取代烯基、氰基取代炔基等，且烷基、环烷基、烯基或炔基中的碳原子总数为1～6个；所述卤代芳香族取代基选自卤代苯基、二卤代苯基、多取代苯基等；所述氰基取代芳香族取代基选自氰基取代苯基、二氰基取代苯基、多氰基取代苯基等；所述硝基取代芳香族取代基基选自硝基取代苯基、二硝基取代苯基、多硝基取代苯基等。Wherein, the aliphatic substituent containing 1 to 6 carbon atoms is selected from alkyl, cycloalkyl, alkenyl, or alkynyl, etc., and the total number of carbon atoms is 1 to 6; the halogenated group contains 1 to 6 The aliphatic substituent with three carbon atoms is selected from haloalkyl, halocycloalkyl, haloalkenyl or haloalkynyl, etc., and the total number of carbon atoms in the alkyl, cycloalkyl, alkenyl or alkynyl group is 1 ~6; the cyano substituted aliphatic substituent containing 1 to 6 carbon atoms is selected from the group consisting of cyano-substituted alkyl, cyano-substituted cycloalkyl, cyano-substituted alkenyl, cyano-substituted alkynyl, etc., and The total number of carbon atoms in the alkyl group, cycloalkyl group, alkenyl group or alkynyl group is 1 to 6; the halogenated aromatic substituent is selected from halogenated phenyl, dihalogenated phenyl, polysubstituted phenyl, etc.; The cyano substituted aromatic substituent is selected from cyano substituted phenyl, dicyano substituted phenyl, polycyano substituted phenyl, etc.; the nitro substituted aromatic substituent is selected from nitro substituted phenyl, Dinitro substituted phenyl, polynitro substituted phenyl, etc.
优选地，基团R 1和基团R 3分别选自-CH 3、-CH 2Cl、-CH 2CH 2Cl、-CH 2CH 3、-(CH 2) 2CH 3、-CH(CH 3) 2、-(CH 2) 3CH 3、-CH(CH 3)C 2H 5、 -CH 2CH(CH 3) 2、-C(CH 3) 3、卤代苯基、-CH 2NH 2、-CH 2CH 2NH 2、-(CH 2) 2CH 2NH 2、-CH(CH 3)CH 2CH 2NH 2、
Figure PCTCN2021070793-appb-000003
-CH 2CH＝CH 2、-CH＝CHCH 3、-CH 2CH 2CH＝CH 2、-CH 2CH＝CHCH 3或-CH＝CHCH 2CH 3。 Preferably, the group R 1 and the group R 3 are respectively selected from -CH 3 , -CH 2 Cl, -CH 2 CH 2 Cl, -CH 2 CH 3 , -(CH 2 ) 2 CH 3 , -CH(CH 3 ) 2 , -(CH 2 ) 3 CH 3 , -CH(CH 3 )C 2 H 5 , -CH 2 CH(CH 3 ) 2 , -C(CH 3 ) 3 , halogenated phenyl, -CH 2 NH 2 , -CH 2 CH 2 NH 2 , -(CH 2 ) 2 CH 2 NH 2 , -CH(CH 3 )CH 2 CH 2 NH 2 ,
Figure PCTCN2021070793-appb-000003
-CH 2 CH=CH 2 , -CH=CHCH 3 , -CH 2 CH 2 CH=CH 2 , -CH 2 CH=CHCH 3 or -CH=CHCH 2 CH 3 .
优选地，基团R 2选自如顺反-CH 2CH＝CHCl、-CH 2CCl＝CH 2、
Figure PCTCN2021070793-appb-000004
Figure PCTCN2021070793-appb-000005
其中
Figure PCTCN2021070793-appb-000006
中的取代基Y选自-Cl、-F、-CN、-Br、-NO 2或-CF 3，n为取代基Y的个数，为1、2或3。 Preferably, the group R 2 is selected from, for example, cis-trans -CH 2 CH=CHCl, -CH 2 CCl=CH 2 ,
Figure PCTCN2021070793-appb-000004
Figure PCTCN2021070793-appb-000005
in
Figure PCTCN2021070793-appb-000006
The substituent Y is selected from -Cl, -F, -CN, -Br, -NO 2 or -CF 3 , and n is the number of substituent Y, which is 1, 2 or 3.
优选地，基团R 4和基团R 5分别选自-H、-CH 3、-CH 2CH 3、-CH 2CH 2CH 3、-CH 2CH 2CH 2CH 3、-COCH 3、-COCH 2CH 3、-COCH 2CH 2CH 3、Na +、K +、NH 4 +或Li +。 Preferably, the group R 4 and the group R 5 are respectively selected from -H, -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 , -CH 2 CH 2 CH 2 CH 3 , -COCH 3 , -COCH 2 CH 3 , -COCH 2 CH 2 CH 3 , Na + , K + , NH 4 + or Li + .
优选地，基团R 6选自-OCH 3、-CH 2OCH 3、-CH 2OCH 2CH 3、-CH 2SCH 2CH 3、-CH 2SCH(CH 3)CH 2CH 3、-CH 2CH(CH 3)SCH 2CH 3、-CH 3、-CH(CH 3) 2、-CF 3、-CH 2CH 2Cl、
Figure PCTCN2021070793-appb-000007
其中Z为O、S或N。 Preferably, the group R 6 is selected from -OCH 3 , -CH 2 OCH 3 , -CH 2 OCH 2 CH 3 , -CH 2 SCH 2 CH 3 , -CH 2 SCH(CH 3 )CH 2 CH 3 , -CH 2 CH(CH 3 )SCH 2 CH 3 , -CH 3 , -CH(CH 3 ) 2 , -CF 3 , -CH 2 CH 2 Cl,
Figure PCTCN2021070793-appb-000007
Where Z is O, S or N.
优选地，当所述基团R 3为-CH 2CH 3、所述基团R 4为-H、所述基团R 6为-CH 2CH(CH 3)SCH 2CH 3时，所述结构式II的变式为
Figure PCTCN2021070793-appb-000008
Preferably, when the group R 3 is -CH 2 CH 3 , the group R 4 is -H, and the group R 6 is -CH 2 CH(CH 3 )SCH 2 CH 3 , the The variant of structural formula II is
Figure PCTCN2021070793-appb-000008
优选地，所述环己二烯肟醚类化合物为具有以下基团的化合物之一：Preferably, the cyclohexadiene oxime ether compound is one of the compounds having the following groups:
Figure PCTCN2021070793-appb-000009
Figure PCTCN2021070793-appb-000009
Figure PCTCN2021070793-appb-000010
Figure PCTCN2021070793-appb-000010
本发明还提供一种上述环己二烯肟醚类化合物的合成方法，包括：中间体7和中间体8溶解在有机溶剂中，于0～100℃下反应合成所述环己烷-1,3-二酮类化合物；其中，所述中间体7的结构式为
Figure PCTCN2021070793-appb-000011
所述中间体8的结构式为
Figure PCTCN2021070793-appb-000012
The present invention also provides a method for synthesizing the above cyclohexadiene oxime ether compound, which comprises: dissolving intermediate 7 and intermediate 8 in an organic solvent, and reacting to synthesize the cyclohexane-1 at 0-100°C. 3-diketone compounds; wherein the structural formula of the intermediate 7 is
Figure PCTCN2021070793-appb-000011
The structural formula of the intermediate 8 is
Figure PCTCN2021070793-appb-000012
优选地，所述有机溶剂为二氯甲烷、丙酮、甲苯、DMF、石油醚和甲醇中的一种或几种的组合物。Preferably, the organic solvent is one or a combination of dichloromethane, acetone, toluene, DMF, petroleum ether and methanol.
上述环己二烯肟醚类化合物的合成机理为：在所述有机溶剂及0～100℃的温度下，所述中间体7中的氨基与中间体8中的羰基发生加成反应 生成不稳定的醇胺化合物，醇胺化合物脱水生成希夫碱。所以，以所述化合物II为例，其合成路线如下所示：The synthesis mechanism of the above cyclohexadiene oxime ether compound is: in the organic solvent and at a temperature of 0-100°C, the amino group in the intermediate 7 and the carbonyl group in the intermediate 8 undergo an addition reaction to form unstable The alcohol amine compound, the alcohol amine compound is dehydrated to generate Schiff base. Therefore, taking the compound II as an example, its synthetic route is as follows:
Figure PCTCN2021070793-appb-000013
Figure PCTCN2021070793-appb-000013
基于上述，所述中间体7和所述中间体8溶解于所述有机溶剂中，在乙酸的催化下，于60～100℃反应1～48h，反应结束后除去所述有机溶剂、清洗并干燥得到所述环己烷-1,3-二酮类化合物的纯品。Based on the above, the intermediate 7 and the intermediate 8 are dissolved in the organic solvent, and reacted at 60-100°C for 1 to 48 hours under the catalysis of acetic acid. After the reaction, the organic solvent is removed, washed and dried. The pure product of the cyclohexane-1,3-dione compound is obtained.
优选地，在合成环己二烯肟醚类化合物的过程中，所述中间体7和中间体8的摩尔比为0.8～1.2:1。该环己二烯肟醚类化合物的合成温度优选为60℃、70℃、80℃、90℃或100℃等。Preferably, in the process of synthesizing the cyclohexadiene oxime ether compound, the molar ratio of the intermediate 7 to the intermediate 8 is 0.8 to 1.2:1. The synthesis temperature of the cyclohexadiene oxime ether compound is preferably 60°C, 70°C, 80°C, 90°C, 100°C, or the like.
基于上述，所述中间体7的合成方法包括：将中间体6与水合肼溶于二氯甲烷中，在10～80℃反应，得到所述中间体7；其中，所述中间体6的结构式为
Figure PCTCN2021070793-appb-000014
Based on the above, the synthesis method of the intermediate 7 includes: dissolving the intermediate 6 and hydrazine hydrate in dichloromethane, and reacting at 10 to 80° C. to obtain the intermediate 7; wherein, the structural formula of the intermediate 6 for
Figure PCTCN2021070793-appb-000014
优选地，所述中间体6溶解于二氯甲烷中，然后滴加水合肼，中间体6与水合肼的摩尔比为1:1～3，滴加完毕后在10～80℃下反应1～3h，反应结束后加入水进行萃取，收集有机层除去所述第二溶剂得到所述中间体7的纯品。Preferably, the intermediate 6 is dissolved in dichloromethane, and then hydrazine hydrate is added dropwise. The molar ratio of intermediate 6 to hydrazine hydrate is 1:1~3. After the addition, the reaction is carried out at 10~80°C for 1~ 3h, after the reaction is completed, water is added for extraction, and the organic layer is collected to remove the second solvent to obtain the pure intermediate 7 product.
基于上述，所述中间体6的制备方法包括：中间体5和N-羟基邻苯二甲酰亚胺在碱性剂的作用下，在0～100℃反应合成所述中间体6；其中，所述中间体5的结构式为
Figure PCTCN2021070793-appb-000015
所述碱性剂为碳酸氢钠、碳酸钠、碳酸氢钾或碳酸钾。 Based on the above, the preparation method of the intermediate 6 includes: intermediate 5 and N-hydroxyphthalimide are reacted to synthesize the intermediate 6 under the action of a basic agent at 0-100°C; wherein, The structural formula of the intermediate 5 is
Figure PCTCN2021070793-appb-000015
The alkaline agent is sodium bicarbonate, sodium carbonate, potassium bicarbonate or potassium carbonate.
优选地，按照1：1～3：0.5～3的摩尔比混合所述中间体5、N-羟基邻苯二甲酰亚胺和所述碱性剂，并用DMF溶解，在0～100℃下反应3～8 h，除去DMF后，加入水和甲苯，收集有机层，并除去所述有机层中的溶剂得到所述中间体6的纯品。Preferably, the intermediate 5, N-hydroxyphthalimide and the alkaline agent are mixed according to a molar ratio of 1:1～3:0.5～3, and dissolved in DMF at 0～100℃ After reacting for 3-8 hours, after removing DMF, water and toluene are added, the organic layer is collected, and the solvent in the organic layer is removed to obtain the pure intermediate 6 product.
基于上述，所述中间体5的制备方法包括：中间体4和甲基磺酰氯在0～20℃溶于甲苯中，并在三乙胺的作用下发生合成反应，制得所述中间体5；其中所述中间体4的结构式为
Figure PCTCN2021070793-appb-000016
Based on the above, the preparation method of the intermediate 5 includes: intermediate 4 and methanesulfonyl chloride are dissolved in toluene at 0-20°C, and a synthesis reaction occurs under the action of triethylamine to prepare the intermediate 5 ; Wherein the structural formula of the intermediate 4 is
Figure PCTCN2021070793-appb-000016
优选地，先将中间体4溶解于甲苯中，再滴加三乙胺，然后在0～20℃下滴加甲基磺酰氯，滴加完毕后维持0～20℃保温1～3h，反应结束后过滤除去沉淀，并向滤液中加入酸水进行萃取，取有机层并除去该有机层中的溶剂得到所述中间体5的纯品。其中，所述中间体4、甲基磺酰氯和三乙胺的摩尔比为1：1～3：0.5～3，所述酸水为氯化铵水溶液、盐酸水溶液或硫酸水溶液。Preferably, first dissolve Intermediate 4 in toluene, then add triethylamine dropwise, and then add methanesulfonyl chloride dropwise at 0-20°C, and keep it at 0-20°C for 1 to 3 hours after the addition is complete, and the reaction is complete Afterwards, the precipitate was removed by filtration, acidic water was added to the filtrate for extraction, the organic layer was taken and the solvent in the organic layer was removed to obtain the pure intermediate 5. Wherein, the molar ratio of the intermediate 4, methylsulfonyl chloride and triethylamine is 1:1 to 3:0.5 to 3, and the acid water is an aqueous ammonium chloride solution, an aqueous hydrochloric acid solution or an aqueous sulfuric acid solution.
基于上述，所述中间体4的制备方法包括：中间体3、氯化钙和硼氢化钠溶于乙醇中，在20～60℃发生合成反应，制得所述中间体3；其中，所述中间体3的结构式为
Figure PCTCN2021070793-appb-000017
Based on the above, the preparation method of the intermediate 4 includes: the intermediate 3, calcium chloride and sodium borohydride are dissolved in ethanol, and the synthesis reaction occurs at 20-60°C to obtain the intermediate 3; wherein The structural formula of Intermediate 3 is
Figure PCTCN2021070793-appb-000017
优选地，将所述中间体3、氯化钙和硼氢化钠溶解于乙醇中，然后升温至20～60℃保温3～8h，反应结束后，向反应体系中加入所述酸水，除去溶剂后，加入水和甲苯，收集有机层除去溶剂得到所述中间体4，其中所述中间体3和硼氢化钠的摩尔比为1：0.3～2。Preferably, the intermediate 3, calcium chloride and sodium borohydride are dissolved in ethanol, and then the temperature is increased to 20-60° C. and the temperature is maintained for 3-8 hours. After the reaction is completed, the acid water is added to the reaction system to remove the solvent Afterwards, water and toluene are added, the organic layer is collected and the solvent is removed to obtain the intermediate 4, wherein the molar ratio of the intermediate 3 to sodium borohydride is 1:0.3-2.
基于上述，所述中间体3的制备方法包括：中间体2和羟基化合物R 2OH在碱性催化剂的作用下，在40～100℃下减压反应，制得所述中间体3；其中，所述中间体2的结构式为
Figure PCTCN2021070793-appb-000018
所述碱性催化剂为碳酸氢钠、碳酸钠、碳酸氢钾或碳酸钾。 Based on the above, the preparation method of the intermediate 3 includes: intermediate 2 and the hydroxyl compound R 2 OH are reacted under reduced pressure at 40-100° C. under the action of a basic catalyst to prepare the intermediate 3; wherein, The structural formula of the intermediate 2 is
Figure PCTCN2021070793-appb-000018
The basic catalyst is sodium bicarbonate, sodium carbonate, potassium bicarbonate or potassium carbonate.
优选地，将所述中间体2、羟基化合物R 2OH和所述碱性催化剂溶解于甲苯中，然后在40～100℃下减压反应1～3h，其中所述中间体2、羟基 化合物R 2OH和所述碱性催化剂的摩尔比为1：1～2：0.5～3；反应结束后过滤除去沉淀，并向滤液中加入所述酸水进行萃取，取有机层除去其中的溶剂得到所述中间体3的纯品。 Preferably, the intermediate 2, the hydroxyl compound R 2 OH and the basic catalyst are dissolved in toluene, and then reacted under reduced pressure at 40 to 100° C. for 1 to 3 hours, wherein the intermediate 2, the hydroxyl compound R The molar ratio of 2 OH to the basic catalyst is 1:1～2:0.5～3; after the reaction is completed, the precipitate is removed by filtration, and the acid water is added to the filtrate for extraction, and the organic layer is taken to remove the solvent. The pure product of intermediate 3.
基于上述，所述中间体2的制备方法包括：中间体1、4-二甲氨基吡啶(DMAP)和对甲苯磺酰氯溶于甲苯中，在-20～10℃下滴加三乙胺，然后10～60℃保温反应，制得所述中间体2；其中，所述中间体1的结构式为
Figure PCTCN2021070793-appb-000019
Based on the above, the preparation method of the intermediate 2 includes: intermediate 1, 4-dimethylaminopyridine (DMAP) and p-toluenesulfonyl chloride are dissolved in toluene, and triethylamine is added dropwise at -20～10°C, and then The reaction is kept at 10 to 60°C to prepare the intermediate 2; wherein the structural formula of the intermediate 1 is
Figure PCTCN2021070793-appb-000019
优选地，先将所述中间体1、DMAP和对甲苯磺酰氯溶于甲苯中，然后在-20～10℃滴入三乙胺，滴加完毕后升温至10～60℃保温1～3h，其中所述中间体1、DMAP和对甲苯磺酰氯的摩尔比为1：0.01～3：1～1.5；反应结束后过滤除去沉淀，并向滤液中加入所述酸水进行萃取，取有机层除去其中的溶剂得到所述中间体2的纯品。Preferably, the intermediate 1, DMAP and p-toluenesulfonyl chloride are first dissolved in toluene, and then triethylamine is dropped at -20～10°C, and after the dropping, the temperature is raised to 10～60°C and the temperature is kept for 1～3h. The molar ratio of the intermediate 1, DMAP and p-toluenesulfonyl chloride is 1:0.01～3:1～1.5; after the reaction, the precipitate is removed by filtration, and the acid water is added to the filtrate for extraction, and the organic layer is removed The solvent in it obtains the pure product of the intermediate 2.
以化合物Ⅱ为例，环己二烯肟醚类化合物中间体7的合成路线如下所示：Taking compound II as an example, the synthetic route of cyclohexadiene oxime ether compound intermediate 7 is as follows:
Figure PCTCN2021070793-appb-000020
Figure PCTCN2021070793-appb-000020
本发明还提供一种上述环己二烯肟醚类化合物的应用，其中，所述环己二烯肟醚类化合物作为活性成分在制备用于控制禾本科杂草的除草剂中的应用。The present invention also provides an application of the above cyclohexadiene oxime ether compound, wherein the cyclohexadiene oxime ether compound is used as an active ingredient in the preparation of a herbicide for controlling gramineous weeds.
优选地，所述禾本科杂草为生长于禾本科农作物田地中的禾本科抗性杂草。Preferably, the gramineous weeds are gramineous resistant weeds that grow in the fields of gramineous crops.
优选地，所述禾本科作物为玉米、水稻或小麦等，所述禾本科抗性杂 草为抗性稗草、抗性野燕麦、抗性马唐、抗性菵草、抗性狗尾草、抗性牛筋草、抗性看麦娘、抗性早熟禾、抗性千金子或抗性硬草。Preferably, the gramineous crops are corn, rice or wheat, etc., and the gramineous resistant weeds are resistant barnyardgrass, resistant wild oats, resistant crabgrass, resistant yardgrass, resistant setaria, resistant Sexual gooseweed, resistance see wheat nipples, resistant bluegrass, resistant stephanotis or resistant hard grass.
在上述除草剂中，所述环己二烯肟醚类化合物作为活性成分与其它除草剂进行复配，具体地可以与噁唑酰草胺、双草醚、氰氟草酯氯、吡嘧磺隆、噁嗪草酮、敌稗、嘧草醚、五氟磺草胺、嘧啶肟草醚、吡嘧磺隆、二氯喹啉酸、噁草酮、西草净、***磺草酮、丙炔噁草酮、乙氧氟草醚、二甲戊灵、环酯草醚、灭草松、丙草胺、苄嘧磺隆、双环磺草酮、精噁唑禾草灵、硝磺草酮、扑草净、唑草酮、莎稗磷、禾草丹及异噁草松中的一种或几种进行复配。Among the above-mentioned herbicides, the cyclohexadiene oxime ether compound is used as an active ingredient to be compounded with other herbicides, specifically, it can be combined with oxfentrazone, bispyribac-methyl, cyhalofop-butyl chloride, and pyriflufenazone. Propan, oxaflutole, propanil, safentrazone, penoxsulam, saflufenacil, pyrsulfuron-methyl, quinclorac, oxadiazone, siquan, trifentrazone, c Mesotrione, oxyfluorfen, pendimethalin, fenfentrazone, fentrazone, pretilachlor, bensulfuron-methyl, sulcotrione, fenoxaprop-p-ethyl, mesotrione , Promethazine, carfentrazone, sabaphos, grass pine and clomazone one or more of them for compounding.
所述环己二烯肟醚类化合物作为除草剂的活性成分，还可以与安全剂复配，如双苯噁唑酸、萘二甲酸酐、二氯丙烯胺、解草唑、解草酮、呋喃解草唑、吡唑解草酯、解草啶或苯叉酰胺等。The cyclohexadiene oxime ether compound, as the active ingredient of the herbicide, can also be compounded with safeners, such as dibenzoxazole acid, naphthalene dicarboxylic anhydride, dichloropropenylamine, chlorfenazone, chlorfenazone, Nitrofuran, pyrazolam, pyraclosporin or benzidine amide, etc.
上述除草剂中除了包括作为活性成分的所述环己二烯肟醚类化合物外，还包括辅料。其中，所述辅料为乳化剂、分散剂、润湿剂、填料、溶剂、助溶剂、增稠剂、防冻剂、稳定剂、消泡剂、防腐剂中的一种或几种。In addition to the cyclohexadiene oxime ether compound as the active ingredient, the above herbicide also includes auxiliary materials. Wherein, the auxiliary materials are one or more of emulsifiers, dispersants, wetting agents, fillers, solvents, co-solvents, thickeners, antifreeze agents, stabilizers, defoamers, and preservatives.
具体地，所述乳化剂主要包括辛基酚聚氧乙烯(聚氧丙烯)醚、壬基酚聚氧乙烯醚、苄基酚聚氧乙烯醚、苯乙烯基聚氧乙烯醚、脂肪醇聚氧乙烯醚、脂肪酸聚氧乙烯酯、脂肪胺聚氧乙烯醚、烷基苯磺酸盐等中的一种或几种。Specifically, the emulsifier mainly includes octylphenol polyoxyethylene (polyoxypropylene) ether, nonylphenol polyoxyethylene ether, benzylphenol polyoxyethylene ether, styryl polyoxyethylene ether, fatty alcohol polyoxyethylene One or more of vinyl ether, fatty acid polyoxyethylene ester, fatty amine polyoxyethylene ether, alkylbenzene sulfonate, etc.
所述分散剂主要包括烷基萘磺酸盐、萘磺酸盐甲醛缩合物、芳烷基萘磺酸甲醛缩合物、萘酚磺酸甲酸缩合物、烷基苯磺酸盐、烷基磷酸酯、烷基酚聚氧乙烯醚、木质素磺酸盐、脂肪酸聚氧乙烯酯、脂肪胺聚氧乙烯醚、植物油环氧乙烷加成物、环氧乙烷-环氧丙烷嵌段共聚物、乙二胺聚氧乙烯聚氧丙烯醚中的一种或几种。The dispersant mainly includes alkyl naphthalene sulfonate, naphthalene sulfonate formaldehyde condensate, aralkyl naphthalene sulfonate formaldehyde condensate, naphthol sulfonic acid formic acid condensate, alkyl benzene sulfonate, alkyl phosphate ester , Alkylphenol polyoxyethylene ether, lignin sulfonate, fatty acid polyoxyethylene ester, fatty amine polyoxyethylene ether, vegetable oil ethylene oxide adduct, ethylene oxide-propylene oxide block copolymer, One or more of ethylenediamine polyoxyethylene polyoxypropylene ether.
所述润湿剂/渗透剂主要包括脂肪醇硫酸盐、烷基苯磺酸盐、α-烯烃磺酸盐、二烷基丁二酸酯磺酸盐、脂肪酰胺N-甲基牛磺酸钠盐、烷基萘磺 酸钠等中的一种或几种。The wetting agent/penetrant mainly includes fatty alcohol sulfate, alkylbenzene sulfonate, α-olefin sulfonate, dialkyl succinate sulfonate, fatty amide sodium N-methyl taurate One or more of salt, sodium alkyl naphthalene sulfonate, etc.
所述填料包括硅藻土、凹凸棒土、膨润土、海泡石、高岭土、陶土、白炭黑中的一种或几种。The filler includes one or more of diatomite, attapulgite, bentonite, sepiolite, kaolin, clay, and white carbon black.
所述溶剂或助溶剂为农药中常用的溶剂，主要包括苯、甲苯、萘、白油、重油、石蜡液体、甲醇、乙醇、丙酸醇、醋酸甲酯、环己酮、丙酮、植物油、二氯甲烷、三氯甲烷、乙腈、甲酚等中的一种或几种。The solvent or co-solvent is a solvent commonly used in pesticides, mainly including benzene, toluene, naphthalene, white oil, heavy oil, paraffin liquid, methanol, ethanol, propionate alcohol, methyl acetate, cyclohexanone, acetone, vegetable oil, two One or more of methyl chloride, chloroform, acetonitrile, cresol, etc.
所述增稠剂主要包括淀粉、黄原胶、琼脂、甲基纤维素、羟丙基甲基纤维素、有机膨润土、硅藻土、聚乙烯醇等中的一种或几种。The thickening agent mainly includes one or more of starch, xanthan gum, agar, methyl cellulose, hydroxypropyl methyl cellulose, organic bentonite, diatomaceous earth, polyvinyl alcohol and the like.
所述防冻剂主要包括乙二醇，丙二醇，丙三醇，聚乙二醇、尿素等中的一种或几种。The antifreeze agent mainly includes one or more of ethylene glycol, propylene glycol, glycerol, polyethylene glycol, and urea.
所述稳定剂主要包括亚磷酸酯、环氧氯丙烷、环氧化大豆油、环氧化亚麻仁油等中的一种或几种。The stabilizer mainly includes one or more of phosphite, epichlorohydrin, epoxidized soybean oil, epoxidized linseed oil and the like.
所述消泡剂主要包括丙醇、丁醇、磷酸三丁酯、聚醚类表面活性剂，聚乙二醇脂肪酸酯、矿物油、硅氧烷油等中的一种或几种。The defoaming agent mainly includes one or more of propanol, butanol, tributyl phosphate, polyether surfactants, polyethylene glycol fatty acid ester, mineral oil, silicone oil and the like.
所述防腐剂主要包括苯甲酸、山梨酸、对羟苯甲酸、对苯二酚等中的一种或几种。The preservatives mainly include one or more of benzoic acid, sorbic acid, p-hydroxybenzoic acid, hydroquinone and the like.
因此，本发明提供的上述环己二烯肟醚类化合物具有环己烯酮的结构单元或施加于农作物后经过吸收转化能够具有环己烯酮的结构单元，经试验验证所述环己二烯肟醚类化合物能够抑制ACCase，可以作为ACCase抑制剂，具有除草活性，能够用作控制各种禾本科杂草的除草剂，用于防治大豆、棉花、花生和油菜等阔叶作物田中的禾本科杂草；同时通过实验研究发现，上述环己二烯肟醚类化合物中不同的R 1和R 2基团使化合物对禾本科作物具有较高的选择性，从而使得上述环己二烯肟醚类化合物拓宽了该类除草剂的应用范围，不仅可用于防除阔叶作物田中的禾本科杂草，还可用于防除水稻、小麦、玉米等禾本科作物田中的禾本科杂草；另外，上述环己二烯肟醚类化合物不但能够防除常见的稗草、野燕麦、马唐、菵 草、狗尾草、牛筋草、看麦娘、千金子、早熟禾、硬草等禾本科杂草，同时对一些抗性杂草具有良好的防治效果，比如禾本科农作物田中的抗性稗草、抗性野燕麦、抗性马唐、抗性菵草、抗性狗尾草、抗性牛筋草、抗性看麦娘、抗性千金子、抗性早熟禾、抗性硬草等。 Therefore, the above-mentioned cyclohexadiene oxime ether compound provided by the present invention has a structural unit of cyclohexenone or can have a structural unit of cyclohexenone after being applied to crops after being absorbed and transformed, and the cyclohexadiene has been verified by experiments Oxime ether compounds can inhibit ACCase, can be used as ACCase inhibitors, have herbicidal activity, can be used as herbicides for controlling various grass weeds, and used to control grasses in broad-leaved crop fields such as soybean, cotton, peanut, and rape Weeds; at the same time, it was found through experimental research that the different R 1 and R 2 groups in the above cyclohexadiene oxime ether compounds make the compounds have higher selectivity to gramineous crops, thereby making the above cyclohexadiene oxime ethers Compounds broaden the application range of this type of herbicides, not only can be used to control grass weeds in broad-leaved crop fields, but also can be used to control grass weeds in rice, wheat, corn and other grass crop fields; in addition, the above-mentioned ring Hexadiene oxime ether compounds can not only control common grass weeds such as barnyard grass, wild oats, crabgrass, calamus, setaria, goosegrass, gladiolus, stephanotis, bluegrass, hard grass and other gramineous weeds, but also Some resistant weeds have a good control effect, such as resistant barnyardgrass, resistant wild oats, resistant crabgrass, resistant calamus, resistant setaria, resistant goosegrass, resistant to Mai Niang, resistant Lyceum, resistant Poa, resistant hard grass, etc.
本发明提供的上述环己二烯肟醚类化合物的合成方法，以中间体7和中间体8为原料一步合成，合成方法简单，反应温度温和，收到率高，成本低，可实现工业化生产。The method for synthesizing the above cyclohexadiene oxime ether compound provided by the present invention uses Intermediate 7 and Intermediate 8 as raw materials for one-step synthesis. The synthesis method is simple, the reaction temperature is mild, the receipt rate is high, and the cost is low, and it can realize industrial production. .
进一步，上述合成路线以中间体1为起始原料，并依次合成中间体2、中间体3、中间体4、中间体5、中间体6和中间体7，然后以中间体7和中间体8为反应物合成目标化合物，因此，本发明提供的上述环己烷-1,3-二酮类化合物的合成方法合成路线短，纯化方法简单，反应温度温和，收到率高，成本低，可实现工业化生产。Further, the above synthetic route uses Intermediate 1 as the starting material, and sequentially synthesizes Intermediate 2, Intermediate 3, Intermediate 4, Intermediate 5, Intermediate 6, and Intermediate 7, and then uses Intermediate 7 and Intermediate 8 It is the reactant to synthesize the target compound. Therefore, the synthetic method of the cyclohexane-1,3-dione compound provided by the present invention has a short synthetic route, simple purification method, mild reaction temperature, high yield, low cost, and can be Realize industrialized production.
具体实施方式Detailed ways
下面通过具体实施方式，对本发明的技术方案做进一步的详细描述。The technical solutions of the present invention will be further described in detail below through specific implementations.
实施例1Example 1
本实施例提供一种化合物1，该化合物1的结构式如下：This embodiment provides a compound 1, and the structural formula of the compound 1 is as follows:
Figure PCTCN2021070793-appb-000021
Figure PCTCN2021070793-appb-000021
上述化合物1的合成方法包括：The synthetic method of the above compound 1 includes:
第一步，合成2-(甲苯-4-磺酸基)-丙酸甲酯：
Figure PCTCN2021070793-appb-000022
The first step is to synthesize 2-(toluene-4-sulfonic acid)-propionic acid methyl ester:
Figure PCTCN2021070793-appb-000022
向反应器中加入10.4g乳酸甲酯、0.36g DMAP和19g对甲苯磺酰氯，用甲苯溶解，维持温度0℃，然后向反应体系中滴入10.1g三乙胺，滴加完毕后升温至50℃保温1h；反应结束后过滤除去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到24.5g 2-(甲苯-4-磺酸基)-丙酸甲酯。Add 10.4g methyl lactate, 0.36g DMAP and 19g p-toluenesulfonyl chloride into the reactor, dissolve it with toluene, maintain the temperature at 0℃, then drop 10.1g triethylamine into the reaction system, and raise the temperature to 50 after the addition is complete. Incubate at °C for 1 hour; after the reaction is completed, the insoluble matter is removed by filtration, acid water is added to the filtrate for extraction, and the organic layer is taken to remove the solvent to obtain 24.5 g of 2-(toluene-4-sulfonic acid)-propionic acid methyl ester.
第二步，合成2-(4-氯-苯氧基)-丙酸甲酯：
Figure PCTCN2021070793-appb-000023
The second step is to synthesize 2-(4-chloro-phenoxy)-propionic acid methyl ester:
Figure PCTCN2021070793-appb-000023
向反应器中加入24.5g 2-(甲苯-4-磺酸基)-丙酸甲酯、14.7g对氯苯酚和8.5g碳酸氢钠，用甲苯溶解，在60℃下减压反应3h，反应结束后离心除去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到18.6g 2-(4-氯-苯氧基)-丙酸甲酯。Add 24.5g of 2-(toluene-4-sulfonyl)-propionic acid methyl ester, 14.7g of p-chlorophenol and 8.5g of sodium bicarbonate into the reactor, dissolve with toluene, and react under reduced pressure at 60°C for 3h. After the end, the insoluble matter was removed by centrifugation, acidic water was added to the filtrate for extraction, and the organic layer was taken to remove the solvent to obtain 18.6 g of 2-(4-chloro-phenoxy)-propionic acid methyl ester.
第三步，合成2-(4-氯苯氧基)-丙醇：
Figure PCTCN2021070793-appb-000024
The third step is to synthesize 2-(4-chlorophenoxy)-propanol:
Figure PCTCN2021070793-appb-000024
向反应器中加入18.6g 2-(4-氯-苯氧基)-丙酸甲酯、7.7g氯化钙和6.6g硼氢化钠，用乙醇溶解，然后升温至30℃保温5h，反应结束后，向反应体系中加入硫酸水溶液，除去溶剂后，加入水和甲苯，收集有机层除去溶剂得到15.8g 2-(4-氯苯氧基)-丙醇。Add 18.6g of 2-(4-chloro-phenoxy)-propionic acid methyl ester, 7.7g of calcium chloride and 6.6g of sodium borohydride to the reactor, dissolve with ethanol, and then heat to 30℃ for 5h, the reaction is over Afterwards, an aqueous sulfuric acid solution was added to the reaction system, after removing the solvent, water and toluene were added, and the organic layer was collected and the solvent was removed to obtain 15.8 g of 2-(4-chlorophenoxy)-propanol.
第四步，合成甲磺酸2-(4-氯-苯氧基)-丙酯：
Figure PCTCN2021070793-appb-000025
The fourth step is to synthesize 2-(4-chloro-phenoxy)-propyl methanesulfonate:
Figure PCTCN2021070793-appb-000025
向反应器中加入15.8g 2-(4-氯苯氧基)-丙醇，用甲苯溶解，向反应体系中滴加12.9g三乙胺，然后在10℃下滴加9.7g甲基磺酰氯，滴加完毕后维持10℃保温3h，反应结束后过滤或离心除去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到21.9g甲磺酸2-(4-氯-苯氧基)-丙酯。Add 15.8g 2-(4-chlorophenoxy)-propanol to the reactor, dissolve it with toluene, add 12.9g triethylamine dropwise to the reaction system, and then drop 9.7g methanesulfonyl chloride at 10°C After the dropwise addition is completed, maintain 10°C for 3 hours. After the reaction, filter or centrifuge to remove insoluble materials, add acidic water to the filtrate for extraction, and remove the solvent from the organic layer to obtain 21.9g of methanesulfonic acid 2-(4-chloro-benzene Oxy)-propyl ester.
第五步，合成2-[2-(4-氯-苯氧基)-丙氧基]-异吲哚-1,3-二酮：
Figure PCTCN2021070793-appb-000026
The fifth step is to synthesize 2-[2-(4-chloro-phenoxy)-propoxy]-isoindole-1,3-dione:
Figure PCTCN2021070793-appb-000026
向反应器中加入21.9g甲磺酸2-(4-氯-苯氧基)-丙酯、20.3g N-羟基邻苯二甲酰亚胺、3.8g碳酸氢钠，用DMF溶解，在90℃下反应4h，除去溶剂后，加入水和甲苯，收集有机层除去溶剂得到24.8g 2-[2-(4-氯-苯氧基)-丙氧基]-异吲哚-1,3-二酮。Add 21.9g of 2-(4-chloro-phenoxy)-propyl methanesulfonic acid, 20.3g of N-hydroxyphthalimide, and 3.8g of sodium bicarbonate into the reactor, dissolve it in DMF, React at ℃ for 4h, after removing the solvent, add water and toluene, collect the organic layer and remove the solvent to obtain 24.8g 2-[2-(4-chloro-phenoxy)-propoxy]-isoindole-1,3- Diketone.
第六步，合成O-[2-(4-氯-苯氧基)-丙基]-羟胺：
Figure PCTCN2021070793-appb-000027
The sixth step is to synthesize O-[2-(4-chloro-phenoxy)-propyl]-hydroxylamine:
Figure PCTCN2021070793-appb-000027
向反应器中加入24.8g 2-[2-(4-氯-苯氧基)-丙氧基]-异吲哚-1,3-二酮，用二 氯甲烷溶解，然后滴加8.4g水合肼，滴加完毕后在40℃下反应1h，反应结束后加入水进行萃取，收集有机层除去溶剂得到14.8g O-[2-(4-氯-苯氧基)-丙基]-羟胺。Add 24.8g 2-[2-(4-chloro-phenoxy)-propoxy]-isoindole-1,3-dione into the reactor, dissolve it with dichloromethane, and then add 8.4g dropwise to hydrate Hydrazine was added dropwise and reacted at 40°C for 1 hour. After the reaction was completed, water was added for extraction, and the organic layer was collected and the solvent was removed to obtain 14.8 g of O-[2-(4-chloro-phenoxy)-propyl]-hydroxylamine.
第七步，合成化合物1The seventh step is to synthesize compound 1
向反应器中加入14.8g O-[2-(4-氯-苯氧基)-丙基]-羟胺和19g丙酰三酮，100ml石油醚，5ml乙酸，在25℃下反应24h，反应结束后除去溶剂，水洗浓缩后得到31g红棕色粘稠液体，总产率71％。Add 14.8g O-[2-(4-chloro-phenoxy)-propyl]-hydroxylamine and 19g trione, 100ml petroleum ether, 5ml acetic acid to the reactor, and react at 25℃ for 24h, the reaction is complete After removing the solvent, after washing and concentrating with water, 31 g of a reddish brown viscous liquid was obtained, with a total yield of 71%.
其中，所述化合物1的核磁氢谱：1HNMR(400MHz CDCl3):δ7.2(2H,m),δ6.8(2H,m),δ4.6(1H,m),δ4.1(2H,m),δ2.8(2H,m),δ2.5(2H,m),δ2.2(2H,m),δ2.1(1H,m),δ1.5(2H,m),δ1.2(11H,m),δ0.9～1.1(4H,m)。Wherein, the hydrogen nuclear magnetic spectrum of the compound 1: 1HNMR (400MHz CDCl3): δ7.2(2H,m), δ6.8(2H,m), δ4.6(1H,m), δ4.1(2H, m),δ2.8(2H,m),δ2.5(2H,m),δ2.2(2H,m),δ2.1(1H,m),δ1.5(2H,m),δ1. 2(11H,m),δ0.9～1.1(4H,m).
实施例2Example 2
本实施例提供一种化合物2，该化合物2的结构式如下：This embodiment provides a compound 2 whose structural formula is as follows:
Figure PCTCN2021070793-appb-000028
Figure PCTCN2021070793-appb-000028
上述化合物2的合成方法包括：向反应器中加入15.3g 4-(1-氨基氧甲基-丁基-2-烯氧基)-苯甲腈和17.8g 5-乙氧基甲基-2-戊酰环己烷-1,3-二酮，150ml石油醚，3ml乙酸，在30℃下反应12h，反应结束后除去溶剂，水洗浓缩后得到30g红棕色粘稠液体，即化合物2，且产率为94％。The synthesis method of the above compound 2 includes: adding 15.3g 4-(1-aminooxymethyl-butyl-2-enoxy)-benzonitrile and 17.8g 5-ethoxymethyl-2 into the reactor -Ventylcyclohexane-1,3-dione, 150ml petroleum ether, 3ml acetic acid, react at 30°C for 12h, remove the solvent after the reaction, wash and concentrate to obtain 30g of red-brown viscous liquid, namely compound 2, and The yield was 94%.
其中，所述化合物2的核磁氢谱：1HNMR(400MHz CDCl3):δ7.3(2H,d),δ6.9(2H,d),δ5.5(2H,m),δ4.1(1H,m),δ3.8(2H,d),δ3.3(5H,m),δ2.3(5H,m),δ1.8(3H,d),δ1～1.3(12H,m)。Wherein, the hydrogen nuclear magnetic spectrum of the compound 2: 1HNMR (400MHz CDCl3): δ7.3(2H,d), δ6.9(2H,d), δ5.5(2H,m), δ4.1(1H, m),δ3.8(2H,d),δ3.3(5H,m),δ2.3(5H,m),δ1.8(3H,d),δ1～1.3(12H,m).
实施例3Example 3
本实施例提供一种化合物3，该化合物3的结构式如下：This embodiment provides a compound 3, and the structural formula of the compound 3 is as follows:
Figure PCTCN2021070793-appb-000029
Figure PCTCN2021070793-appb-000029
上述化合物3的合成方法包括：向反应器中加入14g O-[2-(4-氯-苯氧基)-丙基]-羟胺和20.9g 1-(4-乙基硫甲基-2,6-二甲氧基-环己基-1,5-二烯基)-戊烷-1-酮，120ml石油醚，15ml乙酸，在15℃下反应28h，反应结束后除去溶剂，水洗浓缩后得到31g红棕色粘稠液体，即化合物3，且产率为92％。The synthesis method of the above compound 3 includes: adding 14g O-[2-(4-chloro-phenoxy)-propyl]-hydroxylamine and 20.9g 1-(4-ethylthiomethyl-2, 6-Dimethoxy-cyclohexyl-1,5-dienyl)-pentane-1-one, 120ml petroleum ether, 15ml acetic acid, reacted at 15℃ for 28h, after the reaction, the solvent is removed, and it is obtained after washing and concentrating 31 g of red-brown viscous liquid, namely compound 3, and the yield was 92%.
其中，所述化合物3的核磁氢谱：1HNMR(400MHz CDCl3):δ7.2(2H,d),δ6.6(2H,d),δ4.6(1H,d),δ3.8(3H,m),δ3.4(6H,s),δ2.2(7H,m),δ1.5(3H,d),δ1.2～1.4(9H,m),δ0.9(3H,t)。Wherein, the hydrogen nuclear magnetic spectrum of the compound 3: 1HNMR (400MHz CDCl3): δ7.2(2H,d), δ6.6(2H,d), δ4.6(1H,d), δ3.8(3H, m),δ3.4(6H,s),δ2.2(7H,m),δ1.5(3H,d),δ1.2～1.4(9H,m),δ0.9(3H,t).
实施例4Example 4
本实施例提供一种化合物4，该化合物4的结构式如下：This embodiment provides a compound 4, and the structural formula of the compound 4 is as follows:
Figure PCTCN2021070793-appb-000030
Figure PCTCN2021070793-appb-000030
上述化合物4的合成方法包括：向反应器中加入18.9g O-[3-氯-2-(3,5-二氯-苯氧基)-丙基]-羟胺和21.3g 2-(3-氯-丙酰基)-5-(2-乙基硫基-丙基)-3-羟基-环己-2-烯酮，180ml石油醚，8ml乙酸，在60℃下反应10h，反应结束后除去溶剂，水洗浓缩后得到37.8g红棕色粘稠液体，即化合物4，且产率为97％。The synthesis method of the above compound 4 includes: adding 18.9g O-[3-chloro-2-(3,5-dichloro-phenoxy)-propyl]-hydroxylamine and 21.3g 2-(3- Chloro-propionyl)-5-(2-ethylsulfanyl-propyl)-3-hydroxy-cyclohex-2-enone, 180ml petroleum ether, 8ml acetic acid, reacted at 60℃ for 10h, and removed after the reaction The solvent was washed with water and concentrated to obtain 37.8 g of a red-brown viscous liquid, namely compound 4, and the yield was 97%.
其中，所述化合物4的核磁氢谱：1HNMR(400MHz CDCl3):δ6.9(1H,s),δ6.6(2H,s),δ3.8(3H,m),δ3.4(4H,m),δ2.8(2H,d),δ2.5(3H,m),δ1.9(2H,d),δ1.6(5H,m),δ1.2(6H,m)。Wherein, the proton nuclear magnetic spectrum of the compound 4: 1HNMR (400MHz CDCl3): δ6.9(1H,s), δ6.6(2H,s), δ3.8(3H,m), δ3.4(4H, m),δ2.8(2H,d),δ2.5(3H,m),δ1.9(2H,d),δ1.6(5H,m),δ1.2(6H,m).
另外，本实施例提供的化合物4可以与氢氧化钠反应形成对应的钠盐， 该钠盐的结构式为：
Figure PCTCN2021070793-appb-000031
In addition, the compound 4 provided in this embodiment can react with sodium hydroxide to form a corresponding sodium salt, and the structural formula of the sodium salt is:
Figure PCTCN2021070793-appb-000031
实施例5Example 5
本实施例提供一种化合物5，该化合物5的结构式如下：This embodiment provides a compound 5, and the structural formula of the compound 5 is as follows:
Figure PCTCN2021070793-appb-000032
Figure PCTCN2021070793-appb-000032
上述化合物5的合成方法包括：向反应器中加入14.8g O-[2-(4-氯-苯氧基)-丙基]-羟胺和20g丁酰三酮，100ml石油醚，5ml乙酸，在25℃下反应24h，反应结束后除去溶剂，水洗浓缩后得到31.5g红棕色粘稠液体，即化合物5，且产率为96％。The synthesis method of the above compound 5 includes: adding 14.8g O-[2-(4-chloro-phenoxy)-propyl]-hydroxylamine and 20g butyryl trione, 100ml petroleum ether, 5ml acetic acid into the reactor. The reaction was carried out at 25° C. for 24 hours. After the reaction, the solvent was removed. After washing and concentration, 31.5 g of a reddish brown viscous liquid, namely compound 5, was obtained, and the yield was 96%.
其中，所述化合物5的核磁氢谱：1HNMR(400MHz CDCl 3):δ7.23(2H,m),δ6.87(2H,d),δ4.6(1H,m),δ4.18(1H,m),δ2.83(3H,m),δ2.58(3H,m),δ2.2(2H,m),δ2.1(2H,m),δ1.61(3H,m),δ1.34(9H,m),δ0.9(5H,m)。 Wherein, the hydrogen nuclear magnetic spectrum of the compound 5: 1HNMR (400MHz CDCl 3 ): δ7.23 (2H, m), δ 6.87 (2H, d), δ4.6 (1H, m), δ4.18 (1H ,m),δ2.83(3H,m),δ2.58(3H,m),δ2.2(2H,m),δ2.1(2H,m),δ1.61(3H,m),δ1 .34(9H,m),δ0.9(5H,m).
实施例6Example 6
本实施例提供一种化合物6，该化合物6的结构式如下：This embodiment provides a compound 6 whose structural formula is as follows:
Figure PCTCN2021070793-appb-000033
Figure PCTCN2021070793-appb-000033
上述化合物6的合成方法包括：向反应器中加入12.8g O-[2-(吡啶-2-氧基)-丁基]-羟胺和16.5g 2-丁酰基-5-环丙基甲基-3-羟基-环己-2-烯酮，150ml石油醚，5ml乙酸，在20℃下反应48h，反应结束后除去溶剂，水洗浓缩后得到25.2g红棕色粘稠液体，即化合物6，且产率为90％。The synthesis method of the above compound 6 includes: adding 12.8g O-[2-(pyridine-2-oxy)-butyl]-hydroxylamine and 16.5g 2-butyryl-5-cyclopropylmethyl- into the reactor. 3-Hydroxy-cyclohex-2-enone, 150ml petroleum ether, 5ml acetic acid, react at 20℃ for 48h, remove the solvent after the reaction, wash and concentrate to obtain 25.2g red-brown viscous liquid, namely compound 6, and produce The rate is 90%.
其中，所述化合物6的核磁氢谱：1HNMR(400MHz CDCl3):δ7.5(4H,m), δ3.8(3H,m),δ2.8(2H,d),δ1.8(2H,d),δ1.6(3H,m),δ1.1～1.4(6H,m),δ0.9(6H,t),0.7(5H,m)。Wherein, the hydrogen nuclear magnetic spectrum of the compound 6: 1HNMR (400MHz CDCl3): δ7.5(4H,m), δ3.8(3H,m), δ2.8(2H,d), δ1.8(2H, d),δ1.6(3H,m),δ1.1～1.4(6H,m),δ0.9(6H,t),0.7(5H,m).
实施例7Example 7
本实施例提供一种化合物7，该化合物7的结构式如下：This embodiment provides a compound 7 whose structural formula is as follows:
Figure PCTCN2021070793-appb-000034
Figure PCTCN2021070793-appb-000034
上述化合物7的合成方法包括：向反应器中加入13.6g O-[2-(3-氯-烯丙氧基)-3-甲基-丁基]-羟胺和19.6g 2-(3-烯基-1-戊酮)-3-羟基-5-环丙基硫基甲基-环己-2-烯酮，100ml石油醚，5ml乙酸，在28℃下反应30h，反应结束后除去溶剂，水洗浓缩后得到30.3g红棕色粘稠液体，即化合物7，且产率为95％。The synthesis method of the above compound 7 includes: adding 13.6g O-[2-(3-chloro-allyloxy)-3-methyl-butyl]-hydroxylamine and 19.6g 2-(3-ene into the reactor -1-pentanone)-3-hydroxy-5-cyclopropylthiomethyl-cyclohex-2-enone, 100ml petroleum ether, 5ml acetic acid, react at 28°C for 30h, remove the solvent after the reaction, After washing and concentrating with water, 30.3 g of red-brown viscous liquid, namely compound 7, was obtained, and the yield was 95%.
其中，所述化合物7的核磁氢谱：1HNMR(400MHz CDCl3):δ6.3(2H,m),δ5.2(2H,m),δ4.1(2H,d),δ3.6(2H,d),δ2.8(3H,m),δ2.5(2H,d),δ2.1(6H,m),δ1.8(3H,d),δ1.3(1H,m),δ1.0(6H,d),δ0.8(4H,m)。Wherein, the hydrogen nuclear magnetic spectrum of the compound 7: 1HNMR (400MHz CDCl3): δ6.3(2H,m), δ5.2(2H,m), δ4.1(2H,d), δ3.6(2H, d),δ2.8(3H,m),δ2.5(2H,d),δ2.1(6H,m),δ1.8(3H,d),δ1.3(1H,m),δ1. 0 (6H, d), δ 0.8 (4H, m).
实施例8Example 8
本实施例提供一种化合物8，该化合物8的结构式如下：This embodiment provides a compound 8 whose structural formula is as follows:
Figure PCTCN2021070793-appb-000035
Figure PCTCN2021070793-appb-000035
上述化合物8的合成方法包括：向反应器中加入14.4g O-[2-(3-氯-烯丙氧基)-2-(2-甲基-环丙基)-乙基]-羟胺和19.8g 5-仲丁基硫甲基-2-环丙烷羰基-环己烷-1,3-二酮，100ml石油醚，4ml乙酸，在80℃下反应5h，反应结束后除去溶剂，水洗浓缩后得到29.3g红棕色粘稠液体，即化合物8， 且产率为89％。The synthesis method of the above compound 8 includes: adding 14.4g O-[2-(3-chloro-allyloxy)-2-(2-methyl-cyclopropyl)-ethyl]-hydroxylamine and 19.8g 5-sec-butylthiomethyl-2-cyclopropanecarbonyl-cyclohexane-1,3-dione, 100ml petroleum ether, 4ml acetic acid, react at 80℃ for 5h, after the reaction, remove the solvent, wash and concentrate Then, 29.3 g of a red-brown viscous liquid, compound 8, was obtained, and the yield was 89%.
其中，所述化合物8的核磁氢谱：1HNMR(400MHz CDCl3):δ6.2(2H,m),δ4.0(2H,d),δ3.6(2H,d),δ3.2(1H,s),δ2.9(1H,m),δ2.8(1H,m),δ2.5(4H,d),δ2.2(2H,d),δ2.1(1H,m),δ1～1.5(11H,m),δ0.5～0.8(9H,m)。Wherein, the proton nuclear magnetic spectrum of the compound 8: 1HNMR (400MHz CDCl3): δ6.2(2H,m), δ4.0(2H,d), δ3.6(2H,d), δ3.2(1H, s),δ2.9(1H,m),δ2.8(1H,m),δ2.5(4H,d),δ2.2(2H,d),δ2.1(1H,m),δ1～ 1.5(11H,m),δ0.5～0.8(9H,m).
实施例9Example 9
本实施例提供一种化合物9，该化合物9的结构式如下：This embodiment provides a compound 9 whose structural formula is as follows:
Figure PCTCN2021070793-appb-000036
Figure PCTCN2021070793-appb-000036
上述化合物9的合成方法包括：向反应器中加入16.5g O-[2-(3-三氟甲基-苯氧基)-丙基]-羟胺和21.6g 1,5-二乙酸-6-丁酰基-3-异丙基-环己-1,5-二烯基酯，160ml石油醚，5ml乙酸，在50℃下反应48h，反应结束后除去溶剂，水洗浓缩后得到31.3g红棕色粘稠液体，即化合物9，且产率为85％。The synthesis method of the above compound 9 includes: adding 16.5g O-[2-(3-trifluoromethyl-phenoxy)-propyl]-hydroxylamine and 21.6g 1,5-diacetic acid-6- to the reactor. Butyryl-3-isopropyl-cyclohexyl-1,5-dienyl ester, 160ml petroleum ether, 5ml acetic acid, reacted at 50℃ for 48h. After the reaction, the solvent was removed. After washing and concentrating, 31.3g of reddish brown sticky substance was obtained. Thick liquid, compound 9, and the yield was 85%.
其中，所述化合物9的核磁氢谱：1HNMR(400MHz CDCl3):δ7.0(2H,m),δ6.8(2H,m),δ5.2(1H,d),δ3.9(3H,m),δ2.1(4H,m),δ1.9(6H,s),δ1.6(2H,m),δ1.3(3H,d),δ1.1(2H,t),δ0.9～1(9H,m)。Wherein, the proton nuclear magnetic spectrum of the compound 9: 1HNMR (400MHz CDCl3): δ7.0 (2H, m), δ6.8 (2H, m), δ5.2 (1H, d), δ3.9 (3H, m),δ2.1(4H,m),δ1.9(6H,s),δ1.6(2H,m),δ1.3(3H,d),δ1.1(2H,t),δ0. 9～1(9H,m).
实施例10Example 10
本实施例提供一种化合物10，该化合物10的结构式如下：This embodiment provides a compound 10, and the structural formula of the compound 10 is as follows:
Figure PCTCN2021070793-appb-000037
Figure PCTCN2021070793-appb-000037
上述化合物10的合成方法包括：向反应器中加入24.9g O-[3-氨基-2-(3,5-二溴-苯氧基)-丙基]-羟胺和19.9g丁酰三酮，150ml石油醚，5ml乙酸，在25℃下反应24h，反应结束后除去溶剂，水洗浓缩后得到41.6g 红棕色粘稠液体，即化合物10，且产率为98％。The synthesis method of the above compound 10 includes: adding 24.9g O-[3-amino-2-(3,5-dibromo-phenoxy)-propyl]-hydroxylamine and 19.9g butyryl triketone into the reactor, 150ml petroleum ether and 5ml acetic acid were reacted at 25°C for 24h. After the reaction, the solvent was removed. After washing and concentration, 41.6g of red-brown viscous liquid was obtained, namely compound 10, and the yield was 98%.
其中，所述化合物10的核磁氢谱：1HNMR(400MHz CDCl3):δ7.1(1H,m),δ6.9(2H,m),δ4.0(3H,m),δ3.1(2H,d),δ2.9(2H,d),δ2.7(1H,m),δ2.5(2H,q),δ1.9(2H,d),δ1.7(1H,m),δ1.5(4H,m),δ1.3(8H,m),δ0.9(3H,m)。Wherein, the hydrogen nuclear magnetic spectrum of the compound 10: 1HNMR (400MHz CDCl3): δ7.1 (1H, m), δ6.9 (2H, m), δ4.0 (3H, m), δ3.1 (2H, d),δ2.9(2H,d),δ2.7(1H,m),δ2.5(2H,q),δ1.9(2H,d),δ1.7(1H,m),δ1. 5(4H,m),δ1.3(8H,m),δ0.9(3H,m).
实施例11Example 11
本实施例提供一种化合物11，该化合物11的结构式如下：This embodiment provides a compound 11, and the structural formula of the compound 11 is as follows:
Figure PCTCN2021070793-appb-000038
Figure PCTCN2021070793-appb-000038
上述化合物11的合成方法包括：向反应器中加入18.3g O-[2-(3-氯-烯丙氧基)-2-(4-氯-苯基)-乙基]-羟胺和19.9g 2-丁酰基-5-(2-乙基硫基-丙基)-3-羟基-环己-2-烯酮，150ml石油醚，6ml乙酸，在30℃下反应30h，反应结束后除去溶剂，水洗浓缩后得到34.8g红棕色粘稠液体，即化合物11，且产率为94％。The synthesis method of the above compound 11 includes: adding 18.3g O-[2-(3-chloro-allyloxy)-2-(4-chloro-phenyl)-ethyl]-hydroxylamine and 19.9g into the reactor 2-Butyryl-5-(2-ethylsulfanyl-propyl)-3-hydroxy-cyclohex-2-enone, 150ml petroleum ether, 6ml acetic acid, react at 30℃ for 30h, remove the solvent after the reaction After washing and concentrating, 34.8 g of red-brown viscous liquid, namely compound 11, was obtained, and the yield was 94%.
其中，所述化合物11的核磁氢谱：1HNMR(400MHz CDCl3):δ7.3(2H,m),δ7.1(2H,m),δ6.3(1H,d),δ6.1(1H,d),δ4.1(1H,t),δ3.9(4H,m),δ3.0(2H,d),δ2.8(1H,m),δ2.4(2H,q),δ1.9(2H,d),δ1.7(1H,m),δ1.6(4H,m),δ1.3(8H,m),δ0.9(3H,m)。Wherein, the hydrogen nuclear magnetic spectrum of the compound 11: 1HNMR (400MHz CDCl3): δ7.3(2H,m), δ7.1(2H,m), δ6.3(1H,d), δ6.1(1H, d), δ4.1 (1H, t), δ3.9 (4H, m), δ3.0 (2H, d), δ2.8 (1H, m), δ2.4 (2H, q), δ1. 9(2H,d),δ1.7(1H,m),δ1.6(4H,m),δ1.3(8H,m),δ0.9(3H,m).
实施例12Example 12
本实施例提供一种化合物12，该化合物12的结构式如下：This embodiment provides a compound 12, and the structural formula of the compound 12 is as follows:
Figure PCTCN2021070793-appb-000039
Figure PCTCN2021070793-appb-000039
上述化合物12的合成方法包括：向反应器中加入13.9g O-[2-(3H-吡 咯-3-氧基)-己基]-羟胺和17.1g 2-丁酰基-5-(2-氯乙基)-3-羟基-环己-2-烯酮，120ml石油醚，8ml乙酸，在45℃下反应18h，反应结束后除去溶剂，水洗浓缩后得到27.1g红棕色粘稠液体，即化合物12，且产率为91％。The synthesis method of the above compound 12 includes: adding 13.9g O-[2-(3H-pyrrole-3-oxy)-hexyl]-hydroxylamine and 17.1g 2-butyryl-5-(2-chloroethyl into the reactor Base)-3-hydroxy-cyclohex-2-enone, 120ml petroleum ether, 8ml acetic acid, react at 45°C for 18h, remove the solvent after the reaction, wash and concentrate to obtain 27.1g of red-brown viscous liquid, namely compound 12. , And the yield was 91%.
所述化合物12的核磁氢谱：1HNMR(400MHz CDCl3):δ7.4(1H,s),δ5.6(2H,m),δ3.6(3H,m),δ3.4(2H,t),δ3.0(3H,m),δ1.9(2H,m),δ1.7(1H,m),δ1.6(4H,m),δ1.3～1.4(8H,m),δ0.9(6H,t)。The hydrogen nuclear magnetic spectrum of the compound 12: 1HNMR (400MHz CDCl3): δ7.4(1H,s), δ5.6(2H,m), δ3.6(3H,m), δ3.4(2H,t) ,δ3.0(3H,m),δ1.9(2H,m),δ1.7(1H,m),δ1.6(4H,m),δ1.3～1.4(8H,m),δ0. 9(6H,t).
实施例13Example 13
本实施例提供一种化合物13，该化合物13的结构式如下：This embodiment provides a compound 13 whose structural formula is as follows:
Figure PCTCN2021070793-appb-000040
Figure PCTCN2021070793-appb-000040
上述化合物13的合成方法包括：向反应器中加入16.5g O-[2-(3,5-二氯-苯氧基)-丙基]-羟胺和23.7g 2-丁基-5-(2-环己基硫基-丙基)-3-羟基-环己-2-烯酮，150ml石油醚，6ml乙酸，在35℃下反应16h，反应结束后除去溶剂，水洗浓缩后得到35.1g红棕色粘稠液体，即化合物13，且产率为90％。The synthesis method of the above compound 13 includes: adding 16.5g O-[2-(3,5-dichloro-phenoxy)-propyl]-hydroxylamine and 23.7g 2-butyl-5-(2) to the reactor. -Cyclohexylsulfanyl-propyl)-3-hydroxy-cyclohex-2-enone, 150ml petroleum ether, 6ml acetic acid, reacted at 35℃ for 16h, after the reaction, the solvent is removed, washed with water and concentrated to obtain 35.1g of reddish brown Viscous liquid, compound 13, and the yield was 90%.
所述化合物13的核磁氢谱：1HNMR(400MHz CDCl3):δ6.8(1H,s),δ6.6(2H,s),δ3.9(3H,m),δ2.8(2H,d),δ2.6(1H,m),δ2.4(1H,m),δ2.0(2H,d),δ1.6(5H,m),δ1.5(4H,m),δ1.4(9H,m),δ1.3(5H,m),δ0.9(3H,t)。The hydrogen nuclear magnetic spectrum of the compound 13: 1HNMR (400MHz CDCl3): δ6.8(1H,s), δ6.6(2H,s), δ3.9(3H,m), δ2.8(2H,d) ,δ2.6(1H,m),δ2.4(1H,m),δ2.0(2H,d),δ1.6(5H,m),δ1.5(4H,m),δ1.4( 9H, m), δ1.3 (5H, m), δ0.9 (3H, t).
实施例14Example 14
本实施例提供一种化合物14，该化合物14的结构式如下：This embodiment provides a compound 14 whose structural formula is as follows:
Figure PCTCN2021070793-appb-000041
Figure PCTCN2021070793-appb-000041
该化合物14的合成方法包括以下步骤：The synthetic method of compound 14 includes the following steps:
第一步，合成3-甲基-2-(甲苯-4-磺酰氧基)-丁酸甲酯The first step is to synthesize 3-methyl-2-(toluene-4-sulfonyloxy)-butyric acid methyl ester
向反应器中加入13.2g 2-羟基-3-甲基丁酸甲酯、0.6g DMAP和19g对甲苯磺酰氯，用甲苯溶解，维持温度-10℃，然后向反应体系中滴入11.1g三乙胺，滴加完毕后升温至10℃保温1h；反应结束后过滤除去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到26.3g 3-甲基-2-(甲苯-4-磺酰氧基)-丁酸甲酯。Add 13.2g 2-hydroxy-3-methylbutyric acid methyl ester, 0.6g DMAP and 19g p-toluenesulfonyl chloride into the reactor, dissolve it with toluene, maintain the temperature at -10℃, and then drop 11.1g three into the reaction system. After the addition of ethylamine, the temperature was raised to 10°C and kept for 1h; after the reaction, the insoluble matter was removed by filtration, and acid water was added to the filtrate for extraction, and the organic layer was removed from the solvent to obtain 26.3g 3-methyl-2-(toluene- 4-sulfonyloxy)-butyric acid methyl ester.
第二步，合成2-(4-氯-苯氧基)-3-甲基丁酸甲酯The second step is to synthesize methyl 2-(4-chloro-phenoxy)-3-methylbutyrate
向反应器中加入26.3g 3-甲基-2-(甲苯-4-磺酰氧基)-丁酸甲酯、11.9g对氯苯酚和10.5g碳酸钠，用甲苯溶解，在40℃下减压反应1h，反应结束后离心除去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到21.4g2-(4-氯-苯氧基)-3-甲基丁酸甲酯。Add 26.3g of 3-methyl-2-(toluene-4-sulfonyloxy)-butyric acid methyl ester, 11.9g of p-chlorophenol and 10.5g of sodium carbonate to the reactor, dissolve it with toluene, and reduce the temperature at 40°C. The reaction was pressured for 1 h. After the reaction was completed, the insoluble matter was removed by centrifugation, acidic water was added to the filtrate for extraction, and the organic layer was taken to remove the solvent to obtain 21.4 g of methyl 2-(4-chloro-phenoxy)-3-methylbutyrate.
第三步，合成2-(4-氯-苯氧基)-3-甲基-丁烷-1-醇The third step is to synthesize 2-(4-chloro-phenoxy)-3-methyl-butane-1-ol
向反应器中加入21.4g 2-(4-氯-苯氧基)-3-甲基丁酸甲酯、7.9g氯化钙和6.4g硼氢化钠，用乙醇溶解，然后升温至20℃保温3h，反应结束后，向反应体系中加入硫酸水溶液，除去溶剂后，加入水和甲苯，收集有机层除去溶剂得到16.9g 2-(4-氯-苯氧基)-3-甲基-丁烷-1-醇。Add 21.4g 2-(4-chloro-phenoxy)-3-methylbutyric acid methyl ester, 7.9g calcium chloride and 6.4g sodium borohydride into the reactor, dissolve it with ethanol, and then heat to 20℃ to keep warm 3h, after the reaction is over, add aqueous sulfuric acid to the reaction system, after removing the solvent, add water and toluene, collect the organic layer and remove the solvent to obtain 16.9g 2-(4-chloro-phenoxy)-3-methyl-butane -1-alcohol.
第四步，合成甲基磺酸2-(4-氯-苯氧基)-3-甲基-丁基酯The fourth step is to synthesize 2-(4-chloro-phenoxy)-3-methyl-butyl methanesulfonate
向反应器中加入16.9g 2-(4-氯-苯氧基)-3-甲基-丁烷-1-醇，用甲苯溶解，向反应体系中滴加12.4g三乙胺，然后在5℃下滴加9.9g甲基磺酰氯，滴加完毕后维持5℃保温1h，反应结束后过滤或离心除去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到22.6g甲基磺酸2-(4-氯-苯氧基)-3-甲基-丁基酯。16.9g 2-(4-chloro-phenoxy)-3-methyl-butan-1-ol was added to the reactor, dissolved in toluene, 12.4g triethylamine was added dropwise to the reaction system, and then 5 Add 9.9g of methanesulfonyl chloride dropwise at ℃, keep it at 5℃ for 1h after the addition, filter or centrifuge to remove the insoluble matter after the reaction, and add acidic water to the filtrate for extraction, remove the solvent from the organic layer to obtain 22.6g of formazan Sulfonic acid 2-(4-chloro-phenoxy)-3-methyl-butyl ester.
第五步，合成2-[2-(4-氯-苯氧基)-3-甲基-丁氧基]-异吲哚-1,3-二酮The fifth step is to synthesize 2-[2-(4-chloro-phenoxy)-3-methyl-butoxy]-isoindole-1,3-dione
向反应器中加入22.6g甲基磺酸2-(4-氯-苯氧基)-3-甲基-丁基酯、21.3g N-羟基邻苯二甲酰亚胺、4.2g碳酸钠，用DMF溶解，在10℃下反应3h，除去溶剂后，加入水和甲苯，收集有机层除去溶剂得到23.6g 2-[2-(4-氯-苯氧基)-3-甲基-丁氧基]-异吲哚-1,3-二酮。Add 22.6g methanesulfonic acid 2-(4-chloro-phenoxy)-3-methyl-butyl ester, 21.3g N-hydroxyphthalimide, 4.2g sodium carbonate to the reactor, Dissolve in DMF, react at 10℃ for 3h, after removing the solvent, add water and toluene, collect the organic layer and remove the solvent to obtain 23.6g 2-[2-(4-chloro-phenoxy)-3-methyl-butoxy Base]-isoindole-1,3-dione.
第六步，合成O-[2-(4-氯-苯氧基)-3-甲基-丁基]-羟胺The sixth step is to synthesize O-[2-(4-chloro-phenoxy)-3-methyl-butyl]-hydroxylamine
向反应器中加入23.6g 2-[2-(4-氯-苯氧基)-3-甲基-丁氧基]-异吲哚-1,3-二酮，用二氯甲烷溶解，然后滴加4.2g水合肼，滴加完毕后在10℃下反应1h，反应结束后加入水进行萃取，收集有机层除去溶剂得到14.5g O-[2-(4-氯-苯氧基)-3-甲基-丁基]-羟胺。Add 23.6g of 2-[2-(4-chloro-phenoxy)-3-methyl-butoxy]-isoindole-1,3-dione into the reactor, dissolve it with dichloromethane, and then Add 4.2g of hydrazine hydrate dropwise, and react at 10°C for 1h after the addition is complete. After the reaction is complete, add water for extraction, collect the organic layer and remove the solvent to obtain 14.5g O-[2-(4-chloro-phenoxy)-3 -Methyl-butyl]-hydroxylamine.
第七步，合成化合物14The seventh step is to synthesize compound 14
向反应器中加入14.5g O-[2-(4-氯-苯氧基)-3-甲基-丁基]-羟胺和17g丙酰三酮，用二氯甲烷溶解，在10℃下反应1h，反应结束后除去溶剂，水洗干燥后得到28g化合物14纯品，总产率58％。Add 14.5g of O-[2-(4-chloro-phenoxy)-3-methyl-butyl]-hydroxylamine and 17g of triketone to the reactor, dissolve with dichloromethane, and react at 10°C After 1 h, the solvent was removed after the reaction, and 28 g of pure compound 14 was obtained after washing and drying, with a total yield of 58%.
实施例15Example 15
本实施例提供一种化合物15，该化合物15的结构式如下：This embodiment provides a compound 15 whose structural formula is as follows:
Figure PCTCN2021070793-appb-000042
Figure PCTCN2021070793-appb-000042
该化合物15的合成方法包括以下步骤：The synthetic method of compound 15 includes the following steps:
第一步，合成2-(甲苯-4-磺酰氧基)-丙酸甲酯The first step is to synthesize 2-(toluene-4-sulfonyloxy)-propionic acid methyl ester
向反应器中加入10.4g乳酸甲酯、0.4g DMAP和19.8g对甲苯磺酰氯，用甲苯溶解，维持温度5℃，然后向反应体系中滴入11.1g三乙胺，滴加完毕后升温至45℃保温1h；反应结束后过滤除去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到24.2g 2-(甲苯-4-磺酰氧基)-丙酸甲酯。Add 10.4g methyl lactate, 0.4g DMAP and 19.8g p-toluenesulfonyl chloride into the reactor, dissolve it with toluene, maintain the temperature at 5℃, then drop 11.1g triethylamine into the reaction system, and raise the temperature to Incubate at 45°C for 1 hour; after the reaction, filter to remove insoluble materials, add acidic water to the filtrate for extraction, and remove the solvent from the organic layer to obtain 24.2 g of 2-(toluene-4-sulfonyloxy)-propionic acid methyl ester.
第二步，合成2-(3-氯-烯丙基氧基)-丙酸甲酯The second step is to synthesize 2-(3-chloro-allyloxy)-propionic acid methyl ester
向反应器中加入24.2g 2-(甲苯-4-磺酰氧基)-丙酸甲酯、8.8g 3-氯-丙基-2-烯-1-醇和10g碳酸氢钠，用甲苯溶解，在50℃下减压反应3h，反应结束后离心除去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到15.6g 2-(3-氯-烯丙基氧基)-丙酸甲酯。Add 24.2g 2-(toluene-4-sulfonyloxy)-propionic acid methyl ester, 8.8g 3-chloro-propyl-2-en-1-ol and 10g sodium bicarbonate into the reactor, dissolve it with toluene, React under reduced pressure at 50°C for 3 hours. After the reaction is completed, the insoluble matter is removed by centrifugation, and acid water is added to the filtrate for extraction, and the organic layer is taken to remove the solvent to obtain 15.6 g of 2-(3-chloro-allyloxy)-propane Methyl acid.
第三步，合成2-(3-氯-烯丙基氧基)-丙基-1-醇The third step is to synthesize 2-(3-chloro-allyloxy)-propyl-1-ol
向反应器中加入15.6g 2-(3-氯-烯丙基氧基)-丙酸甲酯、8.7g氯化钙和7.2g硼氢化钠，用乙醇溶解，然后升温至35℃保温6h，反应结束后，向反应体系中加入硫酸水溶液，除去溶剂后，加入水和甲苯，收集有机层除去溶剂得到12.8g 2-(3-氯-烯丙基氧基)-丙基-1-醇。Add 15.6g of 2-(3-chloro-allyloxy)-propionic acid methyl ester, 8.7g of calcium chloride and 7.2g of sodium borohydride to the reactor, dissolve with ethanol, and then heat to 35°C for 6h, After the reaction, an aqueous sulfuric acid solution was added to the reaction system, after removing the solvent, water and toluene were added, and the organic layer was collected and the solvent was removed to obtain 12.8 g of 2-(3-chloro-allyloxy)-propyl-1-ol.
第四步，合成甲磺酸2-(3-氯-烯丙基氧基)-丙酯The fourth step is to synthesize 2-(3-chloro-allyloxy)-propyl methanesulfonate
向反应器中加入12.8g 2-(3-氯-烯丙基氧基)-丙基-1-醇，用甲苯溶解，向反应体系中滴加14.5g三乙胺，然后在10℃下滴加10.8g甲基磺酰氯，滴加完毕后维持15℃保温3h，反应结束后过滤或离心除去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到19g甲磺酸2-(3-氯-烯丙基氧基)-丙酯。Add 12.8g of 2-(3-chloro-allyloxy)-propyl-1-ol to the reactor, dissolve it with toluene, add 14.5g of triethylamine dropwise to the reaction system, and then drop it at 10°C. Add 10.8g of methanesulfonyl chloride and keep it at 15°C for 3h after the addition is complete. After the reaction, filter or centrifuge to remove insoluble materials, add acidic water to the filtrate for extraction, take the organic layer and remove the solvent to obtain 19g of methanesulfonic acid 2- (3-Chloro-allyloxy)-propyl ester.
第五步，合成2-[2-(3-氯-烯丙基氧基)-丙氧基]-异吲哚-1,3-二酮The fifth step is to synthesize 2-[2-(3-chloro-allyloxy)-propoxy]-isoindole-1,3-dione
向反应器中加入19g甲磺酸2-(3-氯-烯丙基氧基)-丙酯、22g N-羟基邻苯二甲酰亚胺、4.8g碳酸氢钠，用DMF溶解，在85℃下反应4h，除去溶剂后，加入水和甲苯，收集有机层除去溶剂得到22.5g 2-[2-(3-氯-烯丙基氧基)-丙氧基]-异吲哚-1,3-二酮。Add 19g methanesulfonic acid 2-(3-chloro-allyloxy)-propyl ester, 22g N-hydroxyphthalimide, 4.8g sodium bicarbonate into the reactor, dissolve it with DMF, React at ℃ for 4h, after removing the solvent, add water and toluene, collect the organic layer and remove the solvent to obtain 22.5g 2-[2-(3-chloro-allyloxy)-propoxy]-isoindole-1, 3-Diketone.
第六步，合成O-[2-(3-氯丙烯氧基)-丙基]-羟胺The sixth step is to synthesize O-[2-(3-chloropropenoxy)-propyl]-hydroxylamine
向反应器中加入22.5g 2-[2-(3-氯-烯丙基氧基)-丙氧基]-异吲哚-1,3-二酮，用二氯甲烷溶解，然后滴加9.4g水合肼，滴加完毕后在50℃下反应1h，反应结束后加入水进行萃取，收集有机层除去溶剂得到12.3g O-[2-(3-氯丙烯氧基)-丙基]-羟胺。Add 22.5g of 2-[2-(3-chloro-allyloxy)-propoxy]-isoindole-1,3-dione into the reactor, dissolve with dichloromethane, and then add 9.4 g hydrazine hydrate, react at 50°C for 1 hour after the dropwise addition is complete, add water for extraction after the completion of the reaction, collect the organic layer and remove the solvent to obtain 12.3g O-[2-(3-chloropropenoxy)-propyl]-hydroxylamine .
第七步，合成化合物15The seventh step is to synthesize compound 15
向反应器中加入12.3g O-[2-(3-氯丙烯氧基)-丙基]-羟胺和21g丙酰三酮，用甲苯溶解，然后加入0.6ml乙酸，在70℃下反应2h，反应结束后除去溶剂，水洗干燥后得到29.7g化合物15纯品，总产率71％。Add 12.3g of O-[2-(3-chloropropenoxy)-propyl]-hydroxylamine and 21g of propionyl triketone to the reactor, dissolve with toluene, then add 0.6ml of acetic acid, and react at 70°C for 2h, After the reaction, the solvent was removed, and 29.7 g of pure compound 15 was obtained after washing and drying, with a total yield of 71%.
实施例16Example 16
本实施例提供一种化合物16，该化合物16的结构式如下：This embodiment provides a compound 16 whose structural formula is as follows:
Figure PCTCN2021070793-appb-000043
Figure PCTCN2021070793-appb-000043
该化合物16的合成方法包括以下步骤：The synthetic method of compound 16 includes the following steps:
第一步，合成2-(甲苯-4-磺酸基)-丙酸甲酯The first step is to synthesize 2-(toluene-4-sulfonic acid)-propionic acid methyl ester
向反应器中加入10.4g乳酸甲酯、2.4g DMAP和19g对甲苯磺酰氯，用甲苯溶解，维持温度10℃，然后向反应体系中滴入20.1g三乙胺，滴加完毕后升温至60℃保温1h；反应结束后过滤除去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到24g 2-(甲苯-4-磺酸基)-丙酸甲酯。Add 10.4g methyl lactate, 2.4g DMAP and 19g p-toluenesulfonyl chloride into the reactor, dissolve it with toluene, maintain the temperature at 10℃, then drop 20.1g triethylamine into the reaction system, and raise the temperature to 60 after the addition is complete. Incubate at °C for 1 hour; after the reaction, filter to remove insoluble materials, add acidic water to the filtrate for extraction, and remove the solvent from the organic layer to obtain 24 g of 2-(toluene-4-sulfonic acid)-propionic acid methyl ester.
第二步，合成2-(4-硝基-苯氧基)-丙酸甲酯The second step is to synthesize 2-(4-nitro-phenoxy)-propionic acid methyl ester
向反应器中加入24g 2-(甲苯-4-磺酸基)-丙酸甲酯、11.8g对硝基苯酚和10.1g碳酸氢钾，用甲苯溶解，在90℃下减压反应3h，反应结束后离心除去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到17.6g 2-(4-硝基-苯氧基)-丙酸甲酯。Add 24g of 2-(toluene-4-sulfonic acid)-propionic acid methyl ester, 11.8g of p-nitrophenol and 10.1g of potassium bicarbonate into the reactor, dissolve with toluene, and react under reduced pressure at 90°C for 3h. After the end, the insoluble matter was removed by centrifugation, acidic water was added to the filtrate for extraction, and the organic layer was taken to remove the solvent to obtain 17.6 g of 2-(4-nitro-phenoxy)-propionic acid methyl ester.
第三步，合成2-(4-硝基苯氧基)-丙醇The third step is to synthesize 2-(4-nitrophenoxy)-propanol
向反应器中加入17.6g 2-(4-硝基-苯氧基)-丙酸甲酯、8.7g氯化钙和5.6g硼氢化钠，用乙醇溶解，然后升温至60℃保温6h，反应结束后，向反应体系中加入硫酸水溶液，除去溶剂后，加入水和甲苯，收集有机层除去溶剂得到15.4g 2-(4-硝基苯氧基)-丙醇。Add 17.6g of 2-(4-nitro-phenoxy)-propionic acid methyl ester, 8.7g of calcium chloride and 5.6g of sodium borohydride to the reactor, dissolve with ethanol, and then heat to 60℃ for 6h, and react After the completion, an aqueous sulfuric acid solution was added to the reaction system, after removing the solvent, water and toluene were added, and the organic layer was collected and the solvent was removed to obtain 15.4 g of 2-(4-nitrophenoxy)-propanol.
第四步，合成甲磺酸2-(4-硝基-苯氧基)-丙酯The fourth step is to synthesize 2-(4-nitro-phenoxy)-propyl methanesulfonate
向反应器中加入15.4g 2-(4-硝基苯氧基)-丙醇，用甲苯溶解，向反应体系中滴加18.9g三乙胺，然后在20℃下滴加9.8g甲基磺酰氯，滴加完毕后维持20℃保温3h，反应结束后过滤或离心除去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到20.9g甲磺酸2-(4-硝基-苯氧基)-丙酯。Add 15.4g of 2-(4-nitrophenoxy)-propanol to the reactor, dissolve it with toluene, add 18.9g of triethylamine dropwise to the reaction system, and then dropwise add 9.8g of methylsulfonate at 20°C After the addition of the acid chloride, keep it at 20°C for 3 hours. After the reaction, filter or centrifuge to remove insoluble materials. Add acidic water to the filtrate for extraction. Remove the solvent from the organic layer to obtain 20.9g of methanesulfonic acid 2-(4-nitro -Phenoxy)-propyl ester.
第五步，合成2-[2-(4-硝基-苯氧基)-丙氧基]-异吲哚-1,3-二酮The fifth step is to synthesize 2-[2-(4-nitro-phenoxy)-propoxy]-isoindole-1,3-dione
向反应器中加入20.9g甲磺酸2-(4-硝基-苯氧基)-丙酯、20.3g N-羟基邻 苯二甲酰亚胺、4.8g碳酸氢钾，用DMF溶解，在100℃下反应3h，除去溶剂后，加入水和甲苯，收集有机层除去溶剂得到23.9g 2-[2-(4-氯-苯氧基)-丙氧基]-异吲哚-1,3-二酮。Add 20.9g methanesulfonic acid 2-(4-nitro-phenoxy)-propyl ester, 20.3g N-hydroxyphthalimide, 4.8g potassium bicarbonate into the reactor, dissolve it with DMF, React at 100℃ for 3h, after removing the solvent, add water and toluene, collect the organic layer and remove the solvent to obtain 23.9g 2-[2-(4-chloro-phenoxy)-propoxy]-isoindole-1,3 -Diketone.
第六步，合成O-[2-(4-硝基-苯氧基)-丙基]-羟胺The sixth step is to synthesize O-[2-(4-nitro-phenoxy)-propyl]-hydroxylamine
向反应器中加入23.9g 2-[2-(4-硝基-苯氧基)-丙氧基]-异吲哚-1,3-二酮，用二氯甲烷溶解，然后滴加14.8g水合肼，滴加完毕后在80℃下反应2h，反应结束后加入水进行萃取，收集有机层除去溶剂得到14.2g O-[2-(4-硝基-苯氧基)-丙基]-羟胺。Add 23.9g 2-[2-(4-nitro-phenoxy)-propoxy]-isoindole-1,3-dione into the reactor, dissolve it with dichloromethane, and then add 14.8g dropwise Hydrazine hydrate, react at 80°C for 2 hours after the dropwise addition is complete, add water for extraction after the completion of the reaction, collect the organic layer and remove the solvent to obtain 14.2g O-[2-(4-nitro-phenoxy)-propyl]- Hydroxylamine.
第七步，合成化合物16The seventh step is to synthesize compound 16
向反应器中加入14.2g O-[2-(4-硝基-苯氧基)-丙基]-羟胺和18.2g丙酰三酮，用甲醇溶解，在90℃下反应2h，反应结束后除去溶剂，水洗干燥后得到28.3g化合物16纯品，总产率61％。Add 14.2g O-[2-(4-nitro-phenoxy)-propyl]-hydroxylamine and 18.2g trione into the reactor, dissolve it with methanol, and react at 90℃ for 2h. After the reaction is complete The solvent was removed, washed with water and dried to obtain 28.3 g of pure compound 16 with a total yield of 61%.
实施例17Example 17
本实施例提供一种化合物17，该化合物17的结构式如下：This embodiment provides a compound 17 whose structural formula is as follows:
Figure PCTCN2021070793-appb-000044
Figure PCTCN2021070793-appb-000044
该化合物17的合成方法包括以下步骤：The synthesis method of compound 17 includes the following steps:
第一步，合成2-(甲苯-4-磺酸基)-丙酸甲酯The first step is to synthesize 2-(toluene-4-sulfonic acid)-propionic acid methyl ester
向反应器中加入10.4g乳酸甲酯、0.36g DMAP和19g对甲苯磺酰氯，用甲苯溶解，维持温度0℃，然后向反应体系中滴入10.1g三乙胺，滴加完毕后升温至45℃保温1h；反应结束后过滤除去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到24.3g 2-(甲苯-4-磺酸基)-丙酸甲酯。Add 10.4g methyl lactate, 0.36g DMAP and 19g p-toluenesulfonyl chloride into the reactor, dissolve it with toluene, maintain the temperature at 0℃, then drop 10.1g triethylamine into the reaction system, and raise the temperature to 45 after the addition is complete Incubate at °C for 1 hour; after the reaction is completed, the insoluble matter is removed by filtration, acid water is added to the filtrate for extraction, and the organic layer is taken to remove the solvent to obtain 24.3 g of 2-(toluene-4-sulfonic acid)-propionic acid methyl ester.
第二步，合成2-(3,5-二氟-苯氧基)-丙酸甲酯The second step is to synthesize 2-(3,5-difluoro-phenoxy)-propionic acid methyl ester
向反应器中加入24.3g 2-(甲苯-4-磺酸基)-丙酸甲酯、12.2g 3,5-二氟苯酚和8.8g碳酸氢钠，用甲苯溶解，在60℃下减压反应3h，反应结束后离心除 去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到18.5g2-(3,5-二氟-苯氧基)-丙酸甲酯。Add 24.3g 2-(toluene-4-sulfonic)-propionic acid methyl ester, 12.2g 3,5-difluorophenol and 8.8g sodium bicarbonate into the reactor, dissolve with toluene, and reduce pressure at 60℃ After reacting for 3 hours, after the reaction, the insoluble matter was removed by centrifugation, acidic water was added to the filtrate for extraction, and the organic layer was taken to remove the solvent to obtain 18.5 g of 2-(3,5-difluoro-phenoxy)-propionic acid methyl ester.
第三步，合成2-(3,5-二氟苯氧基)-丙醇The third step is to synthesize 2-(3,5-difluorophenoxy)-propanol
向反应器中加入18.5g 2-(3,5-二氟-苯氧基)-丙酸甲酯、7.8g氯化钙和6.8g硼氢化钠，用乙醇溶解，然后升温至40℃保温5h，反应结束后，向反应体系中加入硫酸水溶液，除去溶剂后，加入水和甲苯，收集有机层除去溶剂得到15.4g 2-(3,5-二氟苯氧基)-丙醇。Add 18.5g of 2-(3,5-difluoro-phenoxy)-propionic acid methyl ester, 7.8g of calcium chloride and 6.8g of sodium borohydride into the reactor, dissolve it with ethanol, and then heat to 40℃ for 5h After the reaction is completed, an aqueous sulfuric acid solution is added to the reaction system, after removing the solvent, water and toluene are added, and the organic layer is collected and the solvent is removed to obtain 15.4 g of 2-(3,5-difluorophenoxy)-propanol.
第四步，合成甲磺酸2-(3,5-二氟-苯氧基)-丙酯The fourth step is to synthesize 2-(3,5-difluoro-phenoxy)-propyl methanesulfonate
向反应器中加入15.4g 2-(3,5-二氟-苯氧基)-丙醇，用甲苯溶解，向反应体系中滴加13.2g三乙胺，然后在10℃下滴加9.8g甲基磺酰氯，滴加完毕后维持10℃保温3h，反应结束后过滤或离心除去不溶物，并向滤液中加入酸水进行萃取，取有机层除去溶剂得到21g甲磺酸2-(3,5-二氟-苯氧基)-丙酯。Add 15.4g of 2-(3,5-difluoro-phenoxy)-propanol to the reactor, dissolve it with toluene, add 13.2g of triethylamine dropwise to the reaction system, and then drop 9.8g at 10°C After the addition of methanesulfonyl chloride, keep it at 10℃ for 3h. After the reaction, filter or centrifuge to remove insoluble materials, add acidic water to the filtrate for extraction, and remove the solvent from the organic layer to obtain 21g of methanesulfonic acid 2-(3, 5-Difluoro-phenoxy)-propyl ester.
第五步，合成2-[2-(3,5-二氟-苯氧基)-丙氧基]-异吲哚-1,3-二酮The fifth step is to synthesize 2-[2-(3,5-difluoro-phenoxy)-propoxy]-isoindole-1,3-dione
向反应器中加入21g甲磺酸2-(4-氯-苯氧基)-丙酯、20.3g N-羟基邻苯二甲酰亚胺、4.8g碳酸氢钠，用DMF溶解，在80℃下反应4h，除去溶剂后，加入水和甲苯，收集有机层除去溶剂得到23.7g 2-[2-(3,5-二氟-苯氧基)-丙氧基]-异吲哚-1,3-二酮。21g of 2-(4-chloro-phenoxy)-propyl methanesulfonic acid, 20.3g of N-hydroxyphthalimide, and 4.8g of sodium bicarbonate were added to the reactor, dissolved in DMF, and heated at 80°C. React for 4 hours, after removing the solvent, add water and toluene, collect the organic layer and remove the solvent to obtain 23.7g 2-[2-(3,5-difluoro-phenoxy)-propoxy]-isoindole-1, 3-Diketone.
第六步，合成O-[2-(3,5-二氟-苯氧基)-丙基]-羟胺The sixth step is to synthesize O-[2-(3,5-difluoro-phenoxy)-propyl]-hydroxylamine
向反应器中加入23.7g 2-[2-(3,5-二氟-苯氧基)-丙氧基]-异吲哚-1,3-二酮，用二氯甲烷溶解，然后滴加10.2g水合肼，滴加完毕后在50℃下反应1h，反应结束后加入水进行萃取，收集有机层除去溶剂得到13.7g O-[2-(3,5-二氟-苯氧基)-丙基]-羟胺。Add 23.7g of 2-[2-(3,5-difluoro-phenoxy)-propoxy]-isoindole-1,3-dione into the reactor, dissolve it with dichloromethane, and then add dropwise 10.2g of hydrazine hydrate, react at 50℃ for 1h after the dropwise addition is complete, add water for extraction after the completion of the reaction, collect the organic layer and remove the solvent to obtain 13.7g O-[2-(3,5-difluoro-phenoxy)- Propyl]-hydroxylamine.
第七步，合成化合物17The seventh step is to synthesize compound 17
向反应器中加入13.7g O-[2-(3,5-二氟-苯氧基)-丙基]-羟胺和18.1g丙酰三酮，用甲醇溶解，然后加入0.2ml乙酸，在80℃下反应2h，反应结束后除去溶剂，水洗干燥后得到29.2g化合物17纯品，总产率64％。Add 13.7g O-[2-(3,5-difluoro-phenoxy)-propyl]-hydroxylamine and 18.1g triketone to the reactor, dissolve it with methanol, and then add 0.2ml acetic acid. The reaction was carried out at °C for 2 hours, the solvent was removed after the reaction, and 29.2 g of pure compound 17 was obtained after washing and drying, with a total yield of 64%.
应用验证实验Application verification experiment
1、大豆田中禾本科杂草的防效试验1. The control effect of gramineous weeds in soybean fields
a.有效质量为25％的油悬剂：活性物质、10％十二烷基磺酸钠、65％矿物油，其中所述活性物质为实施例1和14～17提供的化合物1和14～17。a. An oil suspension with an effective mass of 25%: active substance, 10% sodium dodecyl sulfonate, 65% mineral oil, wherein the active substance is the compounds 1 and 14 provided in Examples 1 and 14-17 17.
b.有效质量为25％的乳油：活性物质、10％十二烷基苯磺酸钠、65％二甲苯，其中所述活性物质为本发明实施例1、5和14～17提供的化合物1、5和14～17。b. Emulsifiable concentrate with an effective mass of 25%: active substance, 10% sodium dodecylbenzene sulfonate, 65% xylene, wherein the active substance is compound 1 provided in Examples 1, 5 and 14-17 of the present invention , 5 and 14-17.
实验条件将大豆、稗草、野燕麦、马唐、狗尾草、早熟禾、看麦娘、硬草的种子播种于塑料盆中的标准土壤里，置于温室培养(温度：30℃，湿度：30％)，出苗后3～5叶期喷施上述药剂，7～15天后评价植物损害情况，评价结果如下表1和表2所示。其中，植物损害情况的评价标准如下：Experimental conditions: Soybean, barnyardgrass, wild oats, crabgrass, setaria, bluegrass, cornflower, hard grass seeds were sown in standard soil in plastic pots and cultivated in a greenhouse (temperature: 30°C, humidity: 30°C). %), spray the above medicament at the 3 to 5 leaf stage after emergence, and evaluate the damage of the plant 7 to 15 days later. The evaluation results are shown in Table 1 and Table 2 below. Among them, the evaluation criteria for plant damage are as follows:
5＝对植物完全性的损害；5 = Damage to plant integrity;
4＝对生长影响大；4 = Great influence on growth;
3＝对生长影响较大；3=Greater influence on growth;
2＝轻度抑制或失绿；2=Mild inhibition or chlorosis;
1＝微见症状，局部颜色变化；1=Slightly seen symptoms, local color changes;
0＝对植物没有损害。0=No damage to plants.
表1 大豆田中禾本科杂草的防效试验结果表(25％油悬剂)Table 1 Test results of control effect of gramineous weeds in soybean fields (25% oil suspension)
Figure PCTCN2021070793-appb-000045
Figure PCTCN2021070793-appb-000045
表2 大豆田中禾本科杂草的防效试验结果表(25％乳油)Table 2 Test results of the control effect of gramineous weeds in soybean fields (25% EC)
Figure PCTCN2021070793-appb-000046
Figure PCTCN2021070793-appb-000046
从表1和表2中可以看出：本发明实施例提供的环己二烯肟醚类化合物对于大豆田中广泛发生的稗草、野燕麦、马唐、狗尾草、早熟禾、看麦娘、硬草等杂草具有良好的防治效果，具备工商业化应用前景。It can be seen from Table 1 and Table 2 that the cyclohexadiene oxime ether compounds provided in the examples of the present invention are effective against barnyardgrass, wild oats, crabgrass, setaria, bluegrass, cornflower, hard Grass and other weeds have good control effects and have prospects for industrial and commercial applications.
2、水稻田中禾本科杂草的防效试验2. The control effect of gramineous weeds in rice fields
试验样品：(1)10％噁唑酰草胺乳油；(2)20％氰氟草酯乳油；(3)活性成分有效质量为2％的乳油：活性物质、10％十二烷基磺酸钠、85％石脑 油，其中所述活性物质为实施例1～17提供的化合物1～17。Test sample: (1) 10% oxfenacet EC; (2) 20% cyhalofop-butyl EC; (3) active ingredient 2% EC: active substance, 10% dodecyl sulfonic acid Sodium, 85% naphtha, wherein the active substance is compounds 1-17 provided in Examples 1-17.
试验条件将预先浸种的水稻、稗草、马唐、千金子、菵草、狗尾草等种子以及抗性稗草种子、抗性马唐种子、抗性千金子种子等播种于塑料盆中的标准土壤里，置于温室中培养(温度30℃，湿度30％)，待杂草出土后喷施下述实验样品的乳油；7～15天后评价植物损伤情况，评价结果见表3、表4和表5。其中，植物损害情况的评价标准参见前述“1、大豆田中禾本科杂草的防效实验”。Test conditions: The pre-soaked seeds of rice, barnyardgrass, crabgrass, crabgrass, calamus, setaria, etc., as well as resistant barnyardgrass seeds, resistant crabgrass seeds, resistant stephengrass seeds, etc., were sown in standard soil in a plastic pot After the weeds are unearthed, spray the emulsifiable concentrates of the following experimental samples; evaluate the damage of the plants after 7-15 days. The evaluation results are shown in Table 3, Table 4 and Table 5. Among them, the evaluation criteria of plant damage can be found in the aforementioned "1. Experiments on the control of gramineous weeds in soybean fields".
表3 水稻田中常见的禾本科杂草的防效试验结果表一Table 3 The control effect test results of common gramineous weeds in rice fields Table 1
Figure PCTCN2021070793-appb-000047
Figure PCTCN2021070793-appb-000047
表4 水稻田中常见的禾本科杂草的防效试验结果表二Table 4 The control effect test results of common gramineous weeds in rice fields Table 2
Figure PCTCN2021070793-appb-000048
Figure PCTCN2021070793-appb-000048
表5 水稻田中禾本科抗性杂草的防效试验结果表Table 5 The results of the control effect test of gramineous resistant weeds in rice fields
Figure PCTCN2021070793-appb-000049
Figure PCTCN2021070793-appb-000049
因此，从上述各表中可以看出：本发明实施例提供的环己二烯肟醚类化合物对于常见的禾本科杂草如稗草、马唐、千金子、菵草、狗尾草等具有良好的防效，同时对一些抗性禾本科杂草如抗性稗草、抗性马唐、抗性千金子等具有良好的防治效果。Therefore, it can be seen from the above tables that the cyclohexadiene oxime ether compounds provided in the examples of the present invention have good properties for common gramineous weeds such as barnyardgrass, crabgrass, stephengrass, calamus, setaria, etc. It has a good control effect on some resistant gramineous weeds, such as resistant barnyardgrass, resistant crabgrass, resistant stephen, etc.
所以，本发明实施例提供的环己二烯肟醚类化合物不仅对大豆田中的禾本科杂草有防治效果，还对水稻田中的禾本科杂草有良好的防治效果；另外，所述环己二烯肟醚类化合物不但对水稻田中常见的禾本科杂草有防效，还对一些禾本科抗性杂草有显著的防治效果，具备工商业化应用前景。Therefore, the cyclohexadiene oxime ether compound provided by the embodiments of the present invention not only has a control effect on grass weeds in soybean fields, but also has a good control effect on grass weeds in rice fields; in addition, the cyclohexanone The diene oxime ether compounds not only have control effects on common grass weeds in rice fields, but also have significant control effects on some grass resistant weeds, and have industrial and commercial application prospects.
最后应当说明的是：以上实施例仅用以说明本发明的技术方案而非对其限制；尽管参照较佳实施例对本发明进行了详细的说明，所属领域的普通技术人员应当理解：依然可以对本发明的具体实施方式进行修改或者对部分技术特征进行等同替换；而不脱离本发明技术方案的精神，其均应涵盖在本发明请求保护的技术方案范围当中。Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it; although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that: The specific implementation of the invention is modified or some technical features are equivalently replaced; without departing from the spirit of the technical solution of the present invention, all of them shall be covered by the scope of the technical solution claimed by the present invention.

Claims (19)

  1. 一种环己二烯肟醚类化合物，结构式为：A cyclohexadiene oxime ether compound, the structural formula is:
    Figure PCTCN2021070793-appb-100001
    Figure PCTCN2021070793-appb-100001
    其中，所述结构式I、II或III中的基团R 1和基团R 3分别选自-H、含1～6个碳原子的脂肪族取代基、卤代含1～6个碳原子的脂肪族取代基、氰基取代含1～6个碳原子的脂肪族取代基、含1～6个碳原子的胺基、含1～6个碳原子的酰胺、苯基、卤代芳香族取代基或氰基取代芳香族取代基； Wherein, the group R 1 and the group R 3 in the structural formula I, II or III are respectively selected from -H, aliphatic substituents containing 1 to 6 carbon atoms, and halogenated groups containing 1 to 6 carbon atoms. Aliphatic substituents, cyano substituted aliphatic substituents containing 1 to 6 carbon atoms, amino groups containing 1 to 6 carbon atoms, amides containing 1 to 6 carbon atoms, phenyl, halogenated aromatic substituents Group or cyano substituted aromatic substituent;
    基团R 2选自-H、含1～6个碳原子的脂肪族取代基、卤代含1～6个碳原子的脂肪族取代基、氰基取代含1～6个碳原子的脂肪族取代基、含1～6个碳原子的胺基、含1～6个碳原子的酰胺、苯基、卤代芳香族取代基、氰基取代芳香族取代基、硝基取代芳香族取代基或杂环芳香族取代基；其中，所述杂环芳香族取代基选自
    Figure PCTCN2021070793-appb-100002
    且X选自-H、卤素、-CN、-NO 2、-CF 3、-C(CF 3) 3，n为取代基的个数，取自1、2、3；     The group R 2 is selected from -H, aliphatic substituents containing 1 to 6 carbon atoms, halogenated aliphatic substituents containing 1 to 6 carbon atoms, cyano substituted aliphatic substituents containing 1 to 6 carbon atoms Substituents, amine groups containing 1 to 6 carbon atoms, amides containing 1 to 6 carbon atoms, phenyl groups, halogenated aromatic substituents, cyano substituted aromatic substituents, nitro substituted aromatic substituents or Heterocyclic aromatic substituents; wherein the heterocyclic aromatic substituents are selected from
    Figure PCTCN2021070793-appb-100002
    And X is selected from -H, halogen, -CN, -NO 2 , -CF 3 , -C(CF 3 ) 3 , n is the number of substituents, taken from 1, 2, 3;
    基团R 4和基团R 5分别选自-H、含1～6个碳原子的烃基或羰基、金属离子； The group R 4 and the group R 5 are respectively selected from -H, a hydrocarbon group or carbonyl group containing 1 to 6 carbon atoms, and a metal ion;
    基团R 6选自-H、醚基、硫醚基、含1～10个碳原子的烷基、环烷基、烯基、卤代基、五元杂环取代基、六元杂环取代基。 The group R 6 is selected from -H, ether group, thioether group, alkyl group containing 1-10 carbon atoms, cycloalkyl group, alkenyl group, halo group, five-membered heterocyclic substituent, six-membered heterocyclic substituent base.
  2. 根据权利要求1所述的环己二烯肟醚类化合物，其特征在于，所述 基团R 1和所述基团R 3分别选自：-CH 3、-CH 2Cl、-CH 2CH 2Cl、-CH 2CH 3、-(CH 2) 2CH 3、-CH(CH 3) 2、-(CH 2) 3CH 3、-CH(CH 3)C 2H 5、-CH 2CH(CH 3) 2、-C(CH 3) 3、卤代苯基、-CH 2NH 2、-CH 2CH 2NH 2、-(CH 2) 2CH 2NH 2、-CH(CH 3)CH 2CH 2NH 2、
    Figure PCTCN2021070793-appb-100003
    -CH 2CH＝CH 2、-CH＝CHCH 3、-CH 2CH 2CH＝CH 2、-CH 2CH＝CHCH 3或-CH＝CHCH 2CH 3。     The cyclohexadiene oxime ether compound according to claim 1, wherein the group R 1 and the group R 3 are respectively selected from: -CH 3 , -CH 2 Cl, -CH 2 CH 2 Cl, -CH 2 CH 3 , -(CH 2 ) 2 CH 3 , -CH(CH 3 ) 2 , -(CH 2 ) 3 CH 3 , -CH(CH 3 )C 2 H 5 , -CH 2 CH (CH 3 ) 2 , -C(CH 3 ) 3 , halophenyl, -CH 2 NH 2 , -CH 2 CH 2 NH 2 , -(CH 2 ) 2 CH 2 NH 2 , -CH(CH 3 ) CH 2 CH 2 NH 2 ,
    Figure PCTCN2021070793-appb-100003
    -CH 2 CH=CH 2 , -CH=CHCH 3 , -CH 2 CH 2 CH=CH 2 , -CH 2 CH=CHCH 3 or -CH=CHCH 2 CH 3 .
  3. 根据权利要求2所述的环己二烯肟醚类化合物，其特征在于，所述基团R 2选自：顺反-CH 2CH＝CHCl、-CH 2CCl＝CH 2、
    Figure PCTCN2021070793-appb-100004
    其中
    Figure PCTCN2021070793-appb-100005
    中的取代基Y选自-Cl、-F、-CN、-Br、-NO 2或-CF 3，n为取代基Y的个数，为1、2或3。     The cyclohexadiene oxime ether compound according to claim 2, wherein the group R 2 is selected from: cis-trans -CH 2 CH=CHCl, -CH 2 CCl=CH 2 ,
    Figure PCTCN2021070793-appb-100004
    in
    Figure PCTCN2021070793-appb-100005
    The substituent Y is selected from -Cl, -F, -CN, -Br, -NO 2 or -CF 3 , and n is the number of substituent Y, which is 1, 2 or 3.
  4. 根据权利要求3所述的环己二烯肟醚类化合物，其特征在于，所述基团R 4和所述基团R 5分别选自：-H、-CH 3、-CH 2CH 3、-CH 2CH 2CH 3、-CH 2CH 2CH 2CH 3、-COCH 3、-COCH 2CH 3、-COCH 2CH 2CH 3、Na +、K +、NH 4 +或Li +。 The cyclohexadiene oxime ether compound according to claim 3, wherein the group R 4 and the group R 5 are respectively selected from: -H, -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 , -CH 2 CH 2 CH 2 CH 3 , -COCH 3 , -COCH 2 CH 3 , -COCH 2 CH 2 CH 3 , Na + , K + , NH 4 + or Li + .
  5. 根据权利要求4所述的环己二烯肟醚类化合物，其特征在于，所述基团R 6选自：-OCH 3、-CH 2OCH 3、-CH 2OCH 2CH 3、-CH 2SCH 2CH 3、-CH 2SCH(CH 3)CH 2CH 3、-CH 2CH(CH 3)SCH 2CH 3、-CH 3、-CH(CH 3) 2、-CF 3、-CH 2CH 2Cl、
    Figure PCTCN2021070793-appb-100006
    其中Z为O、S或N。     The cyclohexadiene oxime ether compound according to claim 4, wherein the group R 6 is selected from: -OCH 3 , -CH 2 OCH 3 , -CH 2 OCH 2 CH 3 , -CH 2 SCH 2 CH 3 , -CH 2 SCH(CH 3 )CH 2 CH 3 , -CH 2 CH(CH 3 )SCH 2 CH 3 , -CH 3 , -CH(CH 3 ) 2 , -CF 3 , -CH 2 CH 2 Cl,
    Figure PCTCN2021070793-appb-100006
    Where Z is O, S or N.
  6. 根据权利要求5所述的环己二烯肟醚类化合物，其特征在于，当所述基团R 3为-CH 2CH 3、所述基团R 4为-H、所述基团R 6为-CH 2CH(CH 3)SCH 2CH 3时，所述结构式II的变式为
    Figure PCTCN2021070793-appb-100007
    The cyclohexadiene oxime ether compound according to claim 5, wherein when the group R 3 is -CH 2 CH 3 , the group R 4 is -H, and the group R 6 When it is -CH 2 CH(CH 3 )SCH 2 CH 3 , the variant of the structural formula II is
    Figure PCTCN2021070793-appb-100007
  7. 根据权利要求5或6所述的环己二烯肟醚类化合物，其特征在于，为具有以下基团的化合物之一：The cyclohexadiene oxime ether compound according to claim 5 or 6, characterized in that it is one of the compounds having the following groups:
    Figure PCTCN2021070793-appb-100008
    Figure PCTCN2021070793-appb-100008
  8. 一种权利要求1所述的环己二烯肟醚类化合物的合成方法，包括：中间体7和中间体8溶解在有机溶剂中，于0～100℃下反应合成所述环己烷-1,3-二酮类化合物；其中，所述中间体7的结构式为
    Figure PCTCN2021070793-appb-100009
    所述中 间体8的结构式为
    Figure PCTCN2021070793-appb-100010
    A method for synthesizing the cyclohexadiene oxime ether compound according to claim 1, comprising: dissolving intermediate 7 and intermediate 8 in an organic solvent, and reacting to synthesize the cyclohexane-1 at 0-100°C ,3-Diketone compounds; wherein the structural formula of the intermediate 7 is
    Figure PCTCN2021070793-appb-100009
    The structural formula of the intermediate 8 is
    Figure PCTCN2021070793-appb-100010
  9. 根据权利要求8所述的环己二烯肟醚类化合物的合成方法，其特征在于，所述中间体7和所述中间体8溶解于所述有机溶剂中，在乙酸的催化下，于60～100℃反应1～3h，反应结束后除去所述有机溶剂、清洗并干燥得到所述环己烷-1,3-二酮类化合物的纯品。The method for synthesizing cyclohexadiene oxime ether compounds according to claim 8, wherein the intermediate 7 and the intermediate 8 are dissolved in the organic solvent, under the catalysis of acetic acid, at 60 After the reaction is completed, the organic solvent is removed, washed and dried to obtain the pure product of the cyclohexane-1,3-dione compound.
  10. 根据权利要求9所述的环己二烯肟醚类化合物的合成方法，其特征在于，所述中间体7的合成方法包括：将中间体6与水合肼溶于二氯甲烷中，在10～80℃反应，得到所述中间体7；其中，所述中间体6的结构式为
    Figure PCTCN2021070793-appb-100011
    The method for synthesizing cyclohexadiene oxime ether compounds according to claim 9, wherein the method for synthesizing intermediate 7 comprises: dissolving intermediate 6 and hydrazine hydrate in dichloromethane at a temperature between 10 and Reaction at 80°C to obtain the intermediate 7; wherein the structural formula of the intermediate 6 is
    Figure PCTCN2021070793-appb-100011
  11. 根据权利要求10所述的环己二烯肟醚类化合物的合成方法，其特征在于，所述中间体6的制备方法包括：中间体5和N-羟基邻苯二甲酰亚胺在碱性剂的作用下，在0～100℃反应合成所述中间体6；其中，所述中间体5的结构式为
    Figure PCTCN2021070793-appb-100012
    所述碱性剂为碳酸氢钠、碳酸钠、碳酸氢钾或碳酸钾。     The method for synthesizing cyclohexadiene oxime ether compounds according to claim 10, characterized in that, the preparation method of intermediate 6 comprises: intermediate 5 and N-hydroxyphthalimide in alkaline Under the action of an agent, the intermediate 6 is synthesized by reaction at 0-100°C; wherein the structural formula of the intermediate 5 is
    Figure PCTCN2021070793-appb-100012
    The alkaline agent is sodium bicarbonate, sodium carbonate, potassium bicarbonate or potassium carbonate.
  12. 根据权利要求11所述的环己二烯肟醚类化合物的合成方法，其特征在于，所述中间体5的制备方法包括：中间体4和甲基磺酰氯在0～20℃溶于甲苯中，并在三乙胺的作用下发生合成反应，制得所述中间体5；其中所述中间体4的结构式为
    Figure PCTCN2021070793-appb-100013
    The method for synthesizing cyclohexadiene oxime ether compounds according to claim 11, wherein the preparation method of intermediate 5 comprises: intermediate 4 and methylsulfonyl chloride dissolved in toluene at 0-20°C , And a synthesis reaction occurs under the action of triethylamine to prepare the intermediate 5; wherein the structural formula of the intermediate 4 is
    Figure PCTCN2021070793-appb-100013
  13. 根据权利要求12所述的环己二烯肟醚类化合物的合成方法，其特征在于，所述中间体4的制备方法包括：中间体3、氯化钙和硼氢化钠溶于乙醇中，在20～60℃发生合成反应，制得所述中间体3；其中，所述中间体3的结构式为
    Figure PCTCN2021070793-appb-100014
    The method for synthesizing cyclohexadiene oxime ether compounds according to claim 12, wherein the preparation method of intermediate 4 comprises: intermediate 3, calcium chloride and sodium borohydride dissolved in ethanol, A synthesis reaction occurs at 20-60°C to prepare the intermediate 3; wherein the structural formula of the intermediate 3 is
    Figure PCTCN2021070793-appb-100014
  14. 根据权利要求13所述的环己二烯肟醚类化合物的合成方法，其特征在于，所述中间体3的制备方法包括：中间体2和羟基化合物R 2OH在碱性催化剂的作用下，在40～100℃下减压反应，制得所述中间体3；其中，所述中间体2的结构式为
    Figure PCTCN2021070793-appb-100015
    所述碱性催化剂为碳酸氢钠、碳酸钠、碳酸氢钾或碳酸钾。     The method for synthesizing cyclohexadiene oxime ether compounds according to claim 13, wherein the preparation method of the intermediate 3 comprises: intermediate 2 and the hydroxyl compound R 2 OH under the action of a basic catalyst, Reaction under reduced pressure at 40-100°C to prepare the intermediate 3; wherein the structural formula of the intermediate 2 is
    Figure PCTCN2021070793-appb-100015
    The basic catalyst is sodium bicarbonate, sodium carbonate, potassium bicarbonate or potassium carbonate.
  15. 根据权利要求14所述的环己二烯肟醚类化合物的合成方法，其特征在于，所述中间体2的制备方法包括：中间体1、4-二甲氨基吡啶和对甲苯磺酰氯溶于甲苯中，在-20～10℃下滴加三乙胺，然后10～60℃保温反应，制得所述中间体2；其中，所述中间体1的结构式为
    Figure PCTCN2021070793-appb-100016
    The method for synthesizing cyclohexadiene oxime ether compounds according to claim 14, wherein the preparation method of the intermediate 2 comprises: intermediate 1, 4-dimethylaminopyridine and p-toluenesulfonyl chloride dissolved in In toluene, triethylamine was added dropwise at -20～10℃, and the reaction was kept at 10～60℃ to prepare the intermediate 2; wherein the structural formula of the intermediate 1 is
    Figure PCTCN2021070793-appb-100016
  16. 一种权利要求1～7任一项所述的环己二烯肟醚类化合物的应用，其特征在于，所述环己二烯肟醚类化合物作为活性成分在制备用于控制禾本科杂草的除草剂中的应用。An application of the cyclohexadiene oxime ether compound according to any one of claims 1 to 7, wherein the cyclohexadiene oxime ether compound is used as an active ingredient in preparation for controlling gramineous weeds Application of herbicides.
  17. 根据权利要求16所述的环己二烯肟醚类化合物的应用，其特征在于，所述禾本科杂草为生长于禾本科农作物田地中的禾本科抗性杂草。The application of the cyclohexadiene oxime ether compound according to claim 16, characterized in that the grass weeds are grass resistant weeds that grow in gramineous crop fields.
  18. 根据权利要求17所述的环己二烯肟醚类化合物的应用，其特征在于，所述禾本科作物为玉米、水稻或小麦。The application of the cyclohexadiene oxime ether compound according to claim 17, wherein the gramineous crop is corn, rice or wheat.
  19. 根据权利要求18所述的环己二烯肟醚类化合物的应用，其特征在于，所述禾本科抗性杂草为抗性稗草、抗性野燕麦、抗性马唐、抗性菵草、抗性狗尾草、抗性牛筋草、抗性看麦娘、抗性早熟禾、抗性千金子或抗性硬草。The use of the cyclohexadiene oxime ether compound according to claim 18, wherein the gramineous resistant weeds are resistant barnyardgrass, resistant wild oats, resistant crabgrass, and resistant calamus , Resistant Setaria, Resistant Gooseweed, Resistant Seedlings, Resistant Poa, Resistant Stephanotis or Resistant Hardweed.
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