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

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

Cyclohexadiene oxime ether compound and its synthesis method and application Technical field

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.

Background technique

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.

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.

Summary of the invention

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.

Specifically, the present invention provides a cyclohexadiene oxime ether compound, the structural formula of which is:

_{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;

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.

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.

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 ,

-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 .

Preferably, the group R _{2 is} selected from, for example, cis-trans -CH ₂ CH=CHCl, -CH ₂ CCl=CH ₂ ,

in

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.

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 ⁺ .

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,

Where Z is O, S or N.

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

Preferably, 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

Preferably, 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:

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.

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.

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

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.

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

The alkaline agent is sodium bicarbonate, sodium carbonate, potassium bicarbonate or potassium carbonate.

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.

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

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.

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

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.

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

The basic catalyst is sodium bicarbonate, sodium carbonate, potassium bicarbonate or potassium carbonate.

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.

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

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.

Taking compound II as an example, the synthetic route of cyclohexadiene oxime ether compound intermediate 7 is as follows:

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.

Preferably, the gramineous weeds are gramineous resistant weeds that grow in the fields of gramineous crops.

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.

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.

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.

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.

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.

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, α-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.

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.

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. .

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.

Detailed ways

The technical solutions of the present invention will be further described in detail below through specific implementations.

Example 1

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:

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.

The second step is to synthesize 2-(4-chloro-phenoxy)-propionic acid methyl ester:

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.

The third step is to synthesize 2-(4-chlorophenoxy)-propanol:

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.

The fourth step is to synthesize 2-(4-chloro-phenoxy)-propyl methanesulfonate:

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.

The fifth step is to synthesize 2-[2-(4-chloro-phenoxy)-propoxy]-isoindole-1,3-dione:

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.

The sixth step is to synthesize O-[2-(4-chloro-phenoxy)-propyl]-hydroxylamine:

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.

The seventh step is to synthesize compound 1

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%.

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).

Example 2

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%.

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).

Example 3

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℃ 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%.

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).

Example 4

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℃ 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%.

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).

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:

Example 5

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%.

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).

Example 6

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℃ 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%.

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).

Example 7

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%.

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).

Example 8

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℃ 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%.

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).

Example 9

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℃ 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%.

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).

Example 10

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%.

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).

Example 11

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℃ 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%.

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).

Example 12

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%.

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).

Example 13

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℃ 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%.

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).

Example 14

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

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.

The second step is to synthesize methyl 2-(4-chloro-phenoxy)-3-methylbutyrate

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.

The third step is to synthesize 2-(4-chloro-phenoxy)-3-methyl-butane-1-ol

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.

The fourth step is to synthesize 2-(4-chloro-phenoxy)-3-methyl-butyl methanesulfonate

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.

The fifth step is to synthesize 2-[2-(4-chloro-phenoxy)-3-methyl-butoxy]-isoindole-1,3-dione

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.

The sixth step is to synthesize O-[2-(4-chloro-phenoxy)-3-methyl-butyl]-hydroxylamine

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.

The seventh step is to synthesize compound 14

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%.

Example 15

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

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.

The second step is to synthesize 2-(3-chloro-allyloxy)-propionic acid methyl ester

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.

The third step is to synthesize 2-(3-chloro-allyloxy)-propyl-1-ol

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.

The fourth step is to synthesize 2-(3-chloro-allyloxy)-propyl methanesulfonate

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.

The fifth step is to synthesize 2-[2-(3-chloro-allyloxy)-propoxy]-isoindole-1,3-dione

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.

The sixth step is to synthesize O-[2-(3-chloropropenoxy)-propyl]-hydroxylamine

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 .

The seventh step is to synthesize compound 15

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%.

Example 16

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

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.

The second step is to synthesize 2-(4-nitro-phenoxy)-propionic acid methyl ester

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.

The third step is to synthesize 2-(4-nitrophenoxy)-propanol

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.

The fourth step is to synthesize 2-(4-nitro-phenoxy)-propyl methanesulfonate

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.

The fifth step is to synthesize 2-[2-(4-nitro-phenoxy)-propoxy]-isoindole-1,3-dione

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.

The sixth step is to synthesize O-[2-(4-nitro-phenoxy)-propyl]-hydroxylamine

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.

The seventh step is to synthesize compound 16

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%.

Example 17

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

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.

The second step is to synthesize 2-(3,5-difluoro-phenoxy)-propionic acid methyl ester

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.

The third step is to synthesize 2-(3,5-difluorophenoxy)-propanol

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.

The fourth step is to synthesize 2-(3,5-difluoro-phenoxy)-propyl methanesulfonate

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.

The fifth step is to synthesize 2-[2-(3,5-difluoro-phenoxy)-propoxy]-isoindole-1,3-dione

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.

The sixth step is to synthesize O-[2-(3,5-difluoro-phenoxy)-propyl]-hydroxylamine

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.

The seventh step is to synthesize compound 17

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%.

Application verification experiment

1. The control effect of gramineous weeds in soybean fields

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. 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.

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 = Damage to plant integrity;

4 = Great influence on growth;

3=Greater influence on growth;

2=Mild inhibition or chlorosis;

1=Slightly seen symptoms, local color changes;

0=No damage to plants.

Table 1 Test results of control effect of gramineous weeds in soybean fields (25% oil suspension)

Table 2 Test results of the control effect of gramineous weeds in soybean fields (25% EC)

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. The control effect of gramineous weeds in rice fields

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

Table 5 The results of the control effect test of gramineous resistant weeds in rice fields

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.

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.

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. A cyclohexadiene oxime ether compound, the structural formula is:

   

   _{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;

   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.
2. 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 ,

   

   -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. 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 ,

   

   in

   

   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. 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. 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,

   

   Where Z is O, S or N.
6. 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

   
7. The cyclohexadiene oxime ether compound according to claim 5 or 6, characterized in that it is one of the compounds having the following groups:

   
8. 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

   

   The structural formula of the intermediate 8 is

   
9. 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. 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

    
11. 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

    

    The alkaline agent is sodium bicarbonate, sodium carbonate, potassium bicarbonate or potassium carbonate.
12. 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

    
13. 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

    
14. 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

    

    The basic catalyst is sodium bicarbonate, sodium carbonate, potassium bicarbonate or potassium carbonate.
15. 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

    
16. 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. 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. The application of the cyclohexadiene oxime ether compound according to claim 17, wherein the gramineous crop is corn, rice or wheat.
19. 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.