CN100430373C - Biologically active bistrifluoromethylphenyl-containing methoxyacrylate compound and preparation method thereof - Google Patents

Abstract

The present invention discloses a methoxyacrylate compound and a preparation method thereof. The methoxyacrylate compound is represented by general formulas I, II and III, has fungicidal, acaricidal and pesticidal biological activity and contains double trifluoromethylphenyl. The present invention also discloses a fungicidal, acaricidal and pesticidal composition containing the compound and a method for controlling fungi, acarids and pests by the compounds, wherein A, B, W, n, Y and K are defined in the specification.

Description

Biologically active bistrifluoromethylphenyl-containing methoxyacrylate compound and preparation method thereof

technical field

The present invention relates to bistrifluoromethylphenyl-containing methoxyacrylic acid ester compounds with fungicidal, acaricidal and insecticidal biological activities, a preparation method thereof, and a fungicidal, acaricidal and insecticide combination containing the compound substances, and uses and methods of using these compounds to control fungi, mites, and insects.

Background technique

In the world patent WO 96 16047, the first and only commercialized methoxyacrylate acaricide (test code: NA83, common name: fluacrypyrim, trade name: Titanon), its structural formula is as follows. Fluacrypyrim has a high acaricidal activity, but it needs a relatively high dose of 250mg/L to have bactericidal activity against some diseases. It can be seen that its bactericidal effect is not excellent enough, and its insecticidal effect is not very significant. Equally, in EP 472300, disclose a commercialized methoxyacrylate fungicide (test code: CGA 279202, common name: trifloxystrobin, trade name: Flint), its structural formula is as follows. EP 472300 describes that CGA 279202 is useful as a fungicide, but this compound has no acaricidal activity. In addition, most of the methoxyacrylate compounds reported in patents only have fungicidal activity, and there are few reports on methoxyacrylate compounds with acaricidal activity and/or insecticidal activity.

In order to obtain methoxyacrylate compounds with higher acaricidal activity and/or insecticidal activity; in order to obtain methoxyacrylate compounds that can control various fungal diseases in smaller doses; in order to obtain methoxyacrylate compounds in smaller doses It can control various fungal diseases, and also has a compound with higher acaricidal and/or insecticidal activity; study in depth.

Contents of the invention

The present invention provides bistrifluoromethylphenyl-containing methoxyacrylate compounds represented by general formulas (I), (II) and (III) and all geometric isomers and stereoisomers thereof:

in:

I.A is selected from the following groups:

U is CH or N;

g is 0 or 1;

V is O, S or NR ^S R ^V (when g=1), wherein R ^S and R ^V are the same or different, and represent H or an alkyl group;

R' is C ₁ ~ C ₆ alkyl or H;

II.B is selected from the following groups:

XR R ¹ CHXR R ²

B-1 B-2 B-3

X is O, S, SO, SO ₂ or NR ^S R ^V (RS ^and R ^V are the same or different and represent H or alkyl);

R is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl;

^R is hydrogen, alkyl, haloalkyl;

^R is hydrogen, haloalkyl, cyano;

III. W is hydrogen, cyano, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy or phenyl;

IV.n is 0 or an integer from 1 to 2, when n>1, W can be the same or different;

V.Y is selected from the following groups:

R³Z    Z

R ³ Z Z

Y-1 Y-2 Y-3 Y-4

B is as defined in B in II;

Z is O, S, SO, SO ₂ , NR ^S R ^V (RS ^and R ^V are the same or different, and represent H or alkyl);

^R is alkylene, haloalkylene, cyanoalkylene, alkylthioalkylene, sulfonylalkylene, sulfinylalkylene, alkoxyalkylene;

VI.K is selected from the following groups:

R³ON＝CH  R³Z    Z    N＝NOCH₂

R ³ ON = CH R ³ Z Z N = NOCH ₂

K-1 K-2 K-3 K-4 K-5

B is as defined in B in II;

Z is as defined in Z in V;

R ³ is as defined for R ³ in V;

In the definitions of compounds (I), (II) and (III) given above, the terms used, whether used alone or in compound words, generally represent the following substituents:

Halogen: refers to fluorine, chlorine, bromine and iodine;

Alkyl group: refers to a straight chain or branched chain alkyl group with 1-6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl or different butyl, pentyl, hexyl isomers;

Haloalkyl: refers to a straight chain or branched alkyl group with 1-6 carbon atoms, and the hydrogen atoms on these alkyl groups can be partially or completely replaced by halogen atoms, for example, C ₁ haloalkyl groups such as chloromethyl, bromomethyl fluoromethyl, dichloromethyl, dibromomethyl, difluoromethyl, trichloromethyl, tribromomethyl, trifluoromethyl, chlorofluoromethyl;

Alkoxy: refers to a straight-chain or branched alkoxy group with 1-6 carbon atoms, which is bonded to the structure through an oxygen atom, such as methoxy, ethoxy, n-propoxy, isopropoxy and different butoxy or pentoxy isomers;

Haloalkoxy: refers to a straight chain or branched alkoxy group with 1-6 carbon atoms, and the hydrogen atoms on these alkoxy groups can be partially or completely replaced by halogen atoms, for example, C ₁ haloalkoxy group such as chlorine Methoxy, bromomethoxy, fluoromethoxy, dichloromethoxy, dibromomethoxy, difluoromethoxy, trichloromethoxy, tribromomethoxy, trifluoromethoxy, Chlorofluoromethoxy;

Aryl: refers to phenyl having 6 carbon atoms and naphthyl having 12 carbon atoms.

The compounds shown in (I), (II) and (III) of the present invention can form geometric isomers (respectively represented by Z and E) due to the different substituents connected by the carbon-carbon double bond and the carbon-nitrogen double bond represent different configurations), the present invention includes Z-type isomers and E-type isomers and their mixtures in any ratio.

The compounds of the present invention can form stereoisomers (representing different configurations with R and S respectively) due to different substituents connected to carbon or nitrogen atoms. The present invention includes R-type isomers and S-type isomers bodies and their mixtures in any proportion.

The compounds of the present invention not only relate to geometric isomers (Z/E formula) and stereoisomers (R/S formula), but also to mixtures of geometric isomers and stereoisomers in any ratio.

The inventors of the present invention have synthesized the bis-trifluoromethylphenyl-containing methoxyacrylate compounds with general formulas (I), (II) and (III) and have broad-spectrum activity: some compounds can be used for Control various mites such as cotton spider mites, panonychia citrus and/or various harmful insects such as leafhoppers and aphids on various crops; Diseases caused by various fungi such as Phycomycetes, Oomycetes, Ascomycetes and Deuteromycetes; Mites and various harmful insects such as leafhoppers and aphids can also be used to control various crops caused by Hyphomycetes, Phycomycetes, Oomycetes, Ascomycetes and Deuteromycetes. Diseases caused by fungi. Moreover, because these compounds have high biological activity, they can achieve good effects at very low doses. In addition to showing good activity against powdery mildew, downy mildew and rice blast, some compounds also have good activity against gray mold, scab, sclerotinia and phytophthora. In particular, some compounds of the present invention not only have excellent activity against pathogenic bacteria such as powdery mildew and rice blast, but also have excellent activity against mites such as spider mites and harmful insects such as aphids.

The invention can be illustrated by the compounds listed in Table 1 below. However, it does not limit the present invention. Melting points given in this invention are uncorrected. The -CO ₂ CH ₃ and -OCH ₃ groups in the acrylate group in Table 1 are isomers located on both sides of the double bond (ie (E)-isomer configuration).

Table 1

Continued Table 1

Continued Table 1

Continued Table 1

Continued Table 1

Continued Table 1

Continued Table 1

Continued Table 1

Compounds represented by formulas (I), (II) and (III) of the present invention can be prepared by Reaction Formula 1, Reaction Formula 2 and Reaction Formula 3 shown below. The substituents are as defined above unless otherwise specified, and L is a leaving group such as halogen (chlorine, bromine).

Reaction 1:

Reaction 2:

Reaction 3:

The compound of general formula (I) and formula (II) that V≠NH can be prepared like this: in solvent N, N-dimethylformamide, treat general formula (V with alkali sodium hydride, potassium hydroxide or potassium carbonate ) or the compound of (VI), then add the compound of formula (IV).

The preparation method of formula (III) compound: in solvent N, N-dimethylformamide, process the compound of formula (VII) with alkali sodium hydride, potassium hydroxide or potassium carbonate, then add the compound of formula (VIII) namely Can.

Preferred solvents are N,N-dimethylformamide or tetrahydrofuran.

Preferred bases are potassium hydroxide, potassium carbonate, sodium hydroxide, sodium hydride or sodium methoxide.

The compound of formula (IV) can be prepared with reference to the following relevant documents:

European patents EP203606 and EP254426 respectively describe the preparation method of the compound of general formula (IV) when A is A-1, wherein U=CH, L is bromine and A is A-1, wherein U=N, L is bromine.

US Patent No. 5,869,517 describes the preparation method of the compound of general formula (IV) when A is A-2, wherein U=N.

US Pat. No. 6,103,717 describes the preparation method of the compound of general formula (IV) when A is A-3, wherein U=N.

When A is A-5, the preparation method of the compound of general formula (IV) is described in the world patent WO99/11129.

When A is A-4, the synthesis of the compound of general formula (IV) can refer to the preparation method of the compound of general formula (IV) when A is A-5.

European patents EP0382375 and EP0415569 describe the preparation of compounds of general formula (VII).

The oxime shown in general formula (V), when B is B-1, can react with chlorine or tert-butyl hypochlorite by corresponding aldoxime in suitable solvent (such as methanol, chloroform, methane or ethanol) Generate α-chloroaldoxime, then in a suitable solvent (such as methanol, ethanol or water), if necessary, add a suitable base (such as sodium alkoxide, triethylamine or sodium hydroxide), with the corresponding alcohol, mercaptan or Amine reaction obtained.

The oxime shown in general formula (V), when B is B-2, can be by corresponding ketone and hydroxylamine hydrochloride in suitable solvent (such as methyl alcohol or ethanol), if necessary, add suitable base (such as sodium hydroxide or carbonic acid Potassium) reaction obtained.

The oxime represented by general formula (V), when B is B-3, can be obtained by reacting corresponding raw materials such as benzyl cyanide and isoamyl nitrite or corresponding raw materials aldehyde, ketone and hydroxylamine hydrochloride in a suitable solvent.

The compound represented by the general formula (VI), when Y is Y-1, can be obtained by reacting the corresponding amine with the corresponding acid chloride to form an amide, and then reacting with phosphorus pentasulfide or phosphorus pentachloride.

The compound shown in general formula (VI), when Y is Y-2, can generate α, β-unsaturated aldehyde or α, β by corresponding bistrifluoromethyl benzaldehyde and corresponding aldehyde or ketone aldol condensation -unsaturated ketone, then synthesize with reference to the synthetic method of general formula (V).

The compound shown in general formula (VI), when Y is Y-3, can react with a suitable reducing agent (such as sodium borohydride) by corresponding ketone or ketone in suitable solvent (such as water and/or ethanol) get.

When A is A-1 and V=NH, the compounds of general formula (I), (II) and (III) can be obtained by corresponding A being A-1 and V=O of general formula (I), (II) and The compound of (III) is obtained by reacting a methanol solution of methylamine.

When Z=SO or _SO2 , the compound of general formula I), (II) and (III) can be by Z=S, the compound of corresponding general formula I), (II) and (III) and oxidizing agent such as It can be obtained by reacting sodium borate or hydrogen peroxide in a suitable solvent.

The bis-trifluoromethylphenyl-containing methoxyacrylate compounds provided by the present invention have biological activity and some compounds have excellent biological activity. Especially in the prevention and control of agriculture, gardening, flowers and sanitary pests. High activity. Pests described here include, but are not limited to:

Harmful insects: Orthoptera such as cockroaches, Thysanoptera such as cotton thrips, rice thrips, melon thrips, Homoptera such as leafhoppers, planthoppers, aphids, Lepidoptera such as Oriental Armyworm, Spodoptera litura, Plutella xylostella, Pieris rapae, Hymenoptera such as sawfly larvae, Diptera such as Aedes, Culex, and fly, Acarina such as Panonychus citrus and Tetranychus cotton;

Harmful pathogens: Phytophthora species, Phytophthora species, Phytophthora species, Gibberella species, Scrubella species, Sclerotinia species, Rhizoctonia species, Botrytis species, Pyrospora species, Fusarium species, Such as rice blast (Pyriculariaoryzae); wheat stripe rust (Puccinia striiformis), leaf rust (Puccinia recondita) and other rusts; barley stripe rust (Puccinia striiformis), leaf rust (Puccinia recondita) and other rusts; barley and wheat powdery mildew ( Erysiphe graminis), cucumber powdery mildew (Sphaerotheca fuligenea), apple powdery mildew (Podosphaera leucotricar) and grape powdery mildew (Podosphaera leucotricar); wheat sheath blight and leaf blight (Septoria nodorum). Helminthosporium, Cephalosporium, Septoria, Sclerotinia, Pseudocercosporella herpotrichoides and Gaeumannomycesgraminis on cereals. Peanut brown spot (Cercospora arachidicola) and peanut black spot (Cercosporidium personata); their Cercospora spp. on beets, soybeans, and rice. Tomato, Cucumber, Botrytis cinerea. Artichokes on vegetables such as cucumbers. Anthracnose on cucumbers, apple scab, downy mildew on cucumbers, downy mildew on grapes, blight on potatoes and tomatoes, Thanatephorus cucumeris on rice and other Rhizoctonia on other hosts such as wheat and barley, vegetables Sclerotonia sclerotiorum; Gibberella zeae; Phytophythora capsici.

With the bis-trifluoromethylphenyl-containing methoxyacrylate compound provided by the present invention, as the agricultural preparation of active ingredient, any desired dosage form can be made such as emulsifiable concentrate, wettable powder, suspension concentrate, granule , suitable adjuvants include carriers (diluents) and other adjuvants such as spreading agents, emulsifiers, wetting agents, dispersants, adhesives and disintegrating agents.

The present invention also provides a process for the preparation of a composition as defined above by mixing a compound of general formula (I), (II) and (III) and at least one carrier. Such compositions may contain a single compound of the invention or a mixture of several compounds.

The compositions according to the invention preferably contain from 1 to 99% by weight of active ingredient. The carrier system of the present invention is a substance that satisfies the following conditions: it is convenient to apply to the site to be treated, such as a plant, seed or soil after being formulated with an active ingredient; or it is convenient to store, transport or handle. The carrier may be a solid or a liquid, including a material which is normally gaseous but which has been compressed into liquid beads, and any carrier commonly used in formulating insecticidal, acaricidal and fungicidal compositions may be used.

Suitable solid carriers include natural and synthetic clays and silicates such as diatomaceous earth, talc, attapulgite, aluminum silicate (kaolin), montmorillonite and mica; calcium carbonate; calcium sulfate; ammonium sulfate; synthetic silica and synthetic calcium or aluminum silicates; elements such as carbon and sulfur; natural and synthetic resins such as benzofuran resins, polyvinyl chloride and styrene polymers and copolymers; solid polychlorinated phenols; bitumen; waxes such as beeswax ,paraffin.

Suitable liquid carriers include water; alcohols such as isopropanol, ethanol; ketones such as acetone, methyl ethyl ketone, cyclohexyl ketone; ethers; aromatic hydrocarbons such as benzene, toluene and xylene; Hydrocarbons such as carbon tetrachloride, perchlorethylene, and mixtures of these liquids.

Insecticidal, acaricidal, and fungicidal compositions are usually processed and transported in the form of concentrates, which are diluted by users before application. The presence of a small amount of surfactant carrier aids in the dilution process. Thus, in compositions according to the invention, at least one carrier is preferably a surfactant. For example, the composition contains at least two carriers, at least one of which is a surfactant.

A surfactant can be an emulsifying agent, a dispersing agent or a wetting agent; it can be a nonionic or an ionic surfactant. Sodium or calcium salts of polyacrylic acid and lignosulfonic acid; condensates of fatty acids or fatty amines or amides with at least 12 carbon atoms in the molecule with ethylene oxide and/or propylene oxide; glycols, sorbitol , sucrose or pentaerythritol fatty acid esters and condensates of these esters with ethylene oxide and/or propylene oxide; sulfate or sulfonate salts of these condensates; sulfuric acid or sulfonic acid containing at least 10 carbon atoms in the molecule Alkali metal or alkaline earth metal salts of esters.

Examples of compositions according to the invention are wettable powders, powders, granules and solutions, emulsifiable concentrates, emulsions, suspension concentrates, aerosols and aerosols. Wettable powders usually contain 15, 25, 50% by weight of active ingredients, and usually in addition to solid inert carriers, also contain 3-10% by weight of dispersants, and if necessary, 0-10% by weight of stabilizers and/or other additives such as Penetrants and adhesives. Powders are generally formable as powder concentrates having a composition similar to wettable powders but without a dispersing agent. Granules are usually prepared to have a size of 10-100 mesh (1.676-0.152 mm), and may be prepared by agglomeration or injection techniques. Usually, granules contain 0.5-50% by weight of active ingredient and 0-10% by weight of additives such as stabilizers, surfactants, sustained-release modifiers. Emulsifiable concentrates may contain, in addition to solvents, co-solvents if necessary, 1-50% W/V active ingredients, 2-20% W/V emulsifiers and 0-20% W/V other additives such as stabilizers, penetrants and corrosion inhibitors, suspension concentrates usually contain 10-75% by weight of active ingredients, 0.5-15% by weight of dispersants, 0.1-10% by weight of other additives such as defoamers, corrosion inhibitors, stabilizers, penetrants and adhesives.

Aqueous dispersions and emulsions, such as compositions obtained by diluting the wettable powders or concentrates according to the invention with water, are also within the scope of the invention. The emulsion referred to includes both water-in-oil and oil-in-water.

By adding one or more other acaricides to the composition, it can have a wider spectrum of activity than the compound of general formula (I), (II) and/or (III) alone. Furthermore, other acaricides may have a synergistic effect on the acaricidal activity of the compounds of the general formulas (I), (II) and/or (III). Examples of acaricidal compounds that may be included in the compositions of the present invention are: acetap, clofenac, fensulfuron, fenpyrid, hexythiazox, and pyridaben, among others.

By adding one or more other fungicides to the composition, it can have a wider spectrum of activity than the compound of general formula (I), (II) and/or (III) alone. Furthermore, other fungicides may have a synergistic effect on the fungicidal activity of the compounds of the general formulas (I), (II) and/or (III). Examples of acaricidal compounds that may be included in the compositions of the present invention are: benomyl, carbendazim, chlorothalonil, dimethomorph, trimethalin, cyconazole, mancozeb, and the like.

By adding one or more other insecticides in the composition, it can have a wider spectrum of activity than the compound of general formula (I), (II) and/or (III) alone. Furthermore, other insecticides may have a synergistic effect on the insecticidal activity of the compounds of the general formulas (I), (II) and/or (III). Suitable insecticides which may be mixed with the compounds of the present invention to form compositions include organophosphorus insecticides such as methamidophos, phoxim, monocrotophos, imidacloprid, imidacloprid, indoxacarb and pyrethroids. Insecticides such as fenvalerate, cyfluthrin, bifenthrin, etc.

The present invention will be further described below in conjunction with the examples, and the yields in the examples are not optimized.

Example 1

This example illustrates the preparation of compound 01 in Table 1.

3, the synthesis of 5-bis-trifluoromethylbenzaldehyde oxime: 3, 5-bistrifluoromethylbenzaldehyde (24.2g=0.10mol) and hydroxylamine hydrochloride (7.30g=0.105mol) in methanol (100ml) Reflux for 4-5hr, after cooling, pour into crushed ice (250g) under stirring, and filter to obtain 23.4g of 3,5-bistrifluoromethylbenzaldoxime white solid, yield 91.0%, melting point: 91.2-91.3°C .

GC-MS (M ⁺ ) (EI, 70eV, m/z) (relative intensity%) calc: 257; found: 257 (100), 238 (45), 214 (42), 213 (40), 182 (40 ), 163(35), 144(15).

¹ H NMR (CDCl ₃ /TMS, 300 MHz) δ (ppm): 7.885 (s, 1H), 8.032 (s, 2H), 8.221 (s, 1H).

Synthesis of α-chloro-3,5-bistrifluoromethylbenzaldehyde oxime: 3,5-bistrifluoromethylbenzaldehyde oxime (12.85g=0.05mol) was dissolved in methanol (200ml), and -5- At 0°C, tert-butyl hypochlorite (5.5g=0.05mol) was slowly added dropwise. After about 0.5-1.0hr, the solvent was removed under reduced pressure to obtain 13.08g of a viscous liquid with a content of 90.0% (GC-MS). The rate is 80.7%.

GC-MS (M ⁺ ) (EI, 70eV, m/z) (relative intensity%) calc: 291; found: 291 (15), 256 (20), 255 (100), 236 (30), 213 (25 ).

Synthesis of α-methylthio-3,5-bistrifluoromethylbenzaldehyde oxime: Dissolve α-chloro-3,5-bistrifluoromethylbenzaldehyde oxime (90%, 9.72g=0.03mol) in In absolute ethanol (80ml), under stirring at room temperature, add dropwise to an aqueous solution of sodium methyl mercaptide (20%, 14.7g=0.042mol), react at 30-40°C for 2-3hr, cool, and extract with ethyl acetate , washed with ice and brine until neutral, dried over anhydrous sodium sulfate, and removed the solvent under reduced pressure to obtain 8.1 g of α-methylthio-3,5-bistrifluoromethylbenzaldehyde oxime, content 90.0% (GC-MS) , as a yellow viscous solid with a yield of 80.2%.

GC-MS (M ⁺ ) (EI, 70eV, m/z) (relative intensity%) calc: 303; found: 303 (70), 286 (25), 256 (75), 240 (40), 213 (100 ), 170(25).

2-[2-[α-methylthio-(3,5-bistrifluoromethylbenzylidene)amineoxymethyl]phenyl]-3-methoxymethyl acrylate (compound 01): the Potassium carbonate (2.40g=17.4mmol) and N,N-dimethylformamide (15ml) were added to a dry three-necked flask, and after stirring for 5-10min, the above-mentioned oxime (90.0% , 2.36g=7.0mmol) in N,N-dimethylformamide solution (5ml). After stirring and reacting for 0.5 hr, (E)-2-[2-(bromomethyl)phenyl]-3-methoxymethyl acrylate (2.58g=9.0mmol) in N,N-dimethylformamide The solution (10ml) was added dropwise to the above reaction mixture, and the reaction was incubated at 40-50°C for 10-12hr. The mixture was poured into crushed ice, extracted twice with ethyl acetate, the combined extracts were washed with water 2-3 times, dried over anhydrous Na ₂ SO ₄ , concentrated to give a crude product. Column chromatography using a mixture of ethyl acetate and petroleum ether (1:15) as the eluent gave 1.08 g of the title compound as a white solid with a content of 95.0%, a yield of 28.9%, and a melting point of 79.6-80.1°C.

GC-MS (M ⁺ ) (EI, 70eV, m/z) (relative intensity%) calc: 507; found: 507 (1), 286 (8), 257 (12), 205 (12), 189 (30 ), 145(100).

¹ H NMR (CDCl ₃ /TMS, 300MHz) δ (ppm): 2.170 (s, 3H, SCH ₃ ), 3.680 (s, 3H, OCH ₃ ), 3.815 (s, 3H, OCH ₃ ), 5.210 (s, 2H, CH ₂ O), 7.155～7.591 (m, 5H, ph H+C=CH), 7.901 (s, 1H, ph H), 7.976 (s, 2H, ph H).

Example 2

This example illustrates the preparation of compound 02 in Table 1.

Synthesis of α-methoxy-3,5-bistrifluoromethylbenzaldehyde oxime: at 10-25°C, the α-chloro-3,5-bistrifluoromethylbenzaldehyde oxime prepared according to Example 1 (90.0%, 4.70g=14.5mmol) was slowly added dropwise into methanol solution of sodium methoxide (8%, 30.5g=45.0mmol), and the reaction was kept for 0.5-1.0hr. The mixture was poured into a large amount of ice water, extracted twice with ethyl acetate, the combined extracts were washed 2-3 times with ice brine, dried over anhydrous Na ₂ SO ₄ , and concentrated to obtain 4.08 g of white sticky solid with a content of 70.5% ( GC), yield 69.1%.

GC-MS (M ⁺ ) (EI, 70eV, m/z) (relative intensity%) calc: 287; found: 287 (20), 286 (40), 268 (18), 255 (15), 240 (100 ), 213(40).

Methyl 2-[2-[α-methoxy-(3,5-bistrifluoromethylbenzylidene)amineoxymethyl]phenyl]-3-methoxyacrylate (compound 02):

Add potassium hydroxide (0.56g=10mmol) and N,N-dimethylformamide (15ml) into a dry three-necked flask, stir for 5-10min, then add the above oxime (70.5ml) dropwise at -5-0°C %, 2.85g=7.0mmol) in N,N-dimethylformamide solution (3ml). After stirring for 0.5 hr, N, N-dimethylformamide ( 10ml) solution was added dropwise to the above reaction mixture, and the reaction was incubated at 15-25°C for 10-12hr. The mixture was poured into ice water, extracted twice with ethyl acetate, the combined extracts were washed with water 2-3 times, dried over anhydrous Na ₂ SO ₄ , concentrated to give a crude product. Column chromatography using a mixture of ethyl acetate and petroleum ether (1:10) as the eluent gave the title compound 1.01 g, 95.0% (GC-MS), as a white solid, yield 27.9%, melting point: 86.3- 86.6°C.

GC-MS (M ⁺ ) (EI, 70eV, m/z) (relative intensity%) calc: 491; found: 491 (0.5), 460 (1), 241 (10), 205 (12), 189 (40 ), 145(100).

¹ H NMR (CDCl ₃ /TMS, 300MHz) δ (ppm): 3.693 (s, 3H, OCH ₃ ), 3.832 (s, 3H, OCH ₃ ), 4.148 (s, 3H, OCH ₃ ), 5.064 (s, 2H, OCH ₂ ), 7.172-8.181 (m, 8H, PhH+CH=).

Example 3

This example illustrates the preparation of compound 03 in Table 1.

2-Bromo-3', the synthesis of 5'-bistrifluoromethylacetophenone: in the 250ml there-necked flask equipped with magnetic stirrer, condenser, thermometer, constant pressure funnel and drying tube, tail gas absorption device, add 3,5-bistrifluoromethylacetophenone (25.6g=0.1mol), anhydrous ether (100ml) and anhydrous aluminum trichloride (1g), after stirring evenly, cool to 5-10°C in an ice-water bath, Add liquid bromine (17.6g=0.11mol) dropwise from the dropping funnel, first drop 1-2 drops, after the color disappears, add dropwise at a controlled rate, after dropping, keep warm for 2-3 hours, and then react at room temperature Add ice water (200g) for 1-2hr, extract with ether, separate the organic layer, wash with saturated brine, dry over anhydrous sodium sulfate, and precipitate to obtain 26.6g of crude product with a yield of 79.4%.

GC-MS (M ⁺ ) (EI, 70eV, m/z) (relative intensity%) calc: 334; found: 334.

Synthesis of 2-methylthio-3', 5'-bistrifluoromethylacetophenone: 2-bromo-3', 5'-bistrifluoromethylacetophenone (8.38g=0.025mol), Sodium methyl mercaptide (20%, 11.0g=0.03mol) and water (10g) were stirred and reacted at 50-60°C for 2-3hrs, extracted with ethyl acetate, washed with water until neutral, dried over anhydrous sodium sulfate, and precipitated to obtain Crude product 6.2g, content 92.0% (GC-MS), yield 75.6%.

LC-MS (APCI, Neg) (M ⁺ -1): calc: 301 found: 301.

Synthesis of 2-methylthio-3',5'-bistrifluoromethylacetophenone oxime: at 20-25°C, to 2-methylthio-3',5'-bistrifluoromethylphenone Ketone (92.0%, 5.9g=18mmol), hydroxylamine hydrochloride (1.72g=24.7mmol) and ethanol (15ml) were added dropwise (30%, 4.8g=36mmol) sodium hydroxide aqueous solution in the mixture, after dropping, at 75 React at -80°C for 4-5 hours, cool, adjust to neutral with 10% hydrochloric acid, extract with ethyl acetate, wash with water until neutral, dry over anhydrous sodium sulfate, and remove the solvent under reduced pressure to obtain 2-methylthio-3', 4.1 g of 5'-bistrifluoromethylacetophenone oxime white solid, total content 92.1% (GC), yield 65.9%, melting point: 109.2-110.1°C.

GC-MS (M ⁺ ) (EI, 70eV, m/z) (relative intensity%) calc: 317; found: 317 (20), 298 (15), 271 (100), 270 (30), 255 (15 ), 240(30), 239(85), 219(25).

2-[2-[1-(3,5-bistrifluoromethylphenyl)-2-methylthio-ethyleneamineoxymethyl]-phenyl]-3-methoxymethyl acrylate ( 03 compound): Add sodium hydride (60%, 1.0g=25mmol and N,N-dimethylformamide (15ml) into a dry three-necked flask, stir for 5-10min, and drop Add the above-mentioned oxime (92.1%, 4.1g=11.9mmol) in N,N-dimethylformamide (10ml) solution. After stirring for 0.5hr, (E)-2-[2-(bromomethyl)benzene Base]-3-methoxymethyl acrylate (3.6g=12.6mmol of N,N-dimethylformamide (10ml) solution was added dropwise to the above reaction mixture, and kept for 0.5-1.0hr. Pour the mixture into In ice water, extracted twice with ethyl acetate, the combined extracts were washed 2-3 times with ice brine, dried over anhydrous Na ₂ SO ₄ , and concentrated to obtain a crude product. The mixed solution of ethyl acetate and petroleum ether (1 :20) was used as the eluent to perform column chromatography to obtain 1.52 g of the title compound, with a content of 90.2% (GC), as a viscous liquid, with a yield of 22.1%.

LC-MS (APCI, Pos) (M ⁺ +1) (relative intensity%): calc: 522, found: 522.2.

¹ H NMR (CDCl ₃ /TMS, 300MHz) δ (ppm): 2.037 (s, 3H, SCH ₃ ), 3.829 (s, 2H, CH ₂ ), 3.698 (s, 3H, OCH ₃ ), 3.830 (s, 3H, OCH ₃ ), 5.196(s, 2H, CH ₂ ), 7.180～7.608(m, 5H, Ph H), 7.859(s, 1H, Ph H), 8.174(s, 2H, Ph H).

Example 4

This example illustrates the preparation of compound 05 in Table 1.

Methyl 2-methoxyimino-2-[2-[α-methoxy-(3,5-bistrifluoromethylbenzylidene)aminooxymethyl]phenyl]acetate (Compound 05) : Potassium hydroxide (0.56g=10mmol) and N,N-dimethylformamide (15ml) were added in a dry there-necked flask, after stirring for 5-10min, at -5-0°C, dropwise α-methoxy-3,5-bistrifluoromethylbenzaldoxime (70.5%, 2.85g=7.0mmol) prepared by method 2 in N,N-dimethylformamide solution (3ml). After stirring for 0.5 hr, (E)-2-[2-(bromomethyl)phenyl]-2-methoxyiminoacetic acid methyl ester (2.58g=9.0mmol) in N,N-dimethylform Amide (10ml) solution was added dropwise to the above reaction mixture, and the reaction was incubated for 0.5-1.0hr. The mixture was poured into ice water, extracted twice with ethyl acetate, the combined extracts were washed with water 2-3 times, dried over anhydrous Na ₂ SO ₄ , concentrated to give a crude product. Column chromatography using a mixture of ethyl acetate and petroleum ether (1:15) as the eluent gave 1.12 g of the title compound, with a content of 91.0% (GC), as a white solid, with a yield of 29.6%, and a melting point of 71.6-73.7°C .

GC-MS (M ⁺ ) (EI, 70eV, m/z) (relative intensity%) calc: 492; found: 492 (0), 461 (8), 241 (35), 222 (40), 205 (15 ), 190(30). 146(25), 131(70), 116(100), 59(30).

¹ H NMR (CDCl ₃ /TMS, 300MHz) δ (ppm) _3.836 (s, 3H, OCH ₃ ), 4.042 (s, 3H, OCH 3 ), 4.114 (s, 3H, OCH ₃ ), 5.020 (s, 2H , CH ₂ ), 7.187～7.533 (m, 4H, ph H), 7.854 (s, 1H, ph H), 8.145 (s, 2H, ph H).

Example 5

This example illustrates the preparation of compound 06 in Table 1.

Methyl 2-methoxyimino-2-[2-[α-methylthio-(3,5-bistrifluoromethylbenzylidene)aminooxymethyl]phenyl]acetate (compound 06) : Add sodium hydride (60%, 0.36g=9.0mmol) and N,N-dimethylformamide (15ml) into a dry three-necked flask, stir for 5-10min, then add dropwise at -5-0°C A solution of α-methylthio-3,5-bistrifluoromethylbenzaldoxime (82%, 2.59g=7.0mmol) in N,N-dimethylformamide (5ml). After stirring the reaction for 0.5 hr, N, N-dimethyl The formamide (10ml) solution was added dropwise to the above reaction mixture, and the reaction was incubated for 0.5-1.0hr. The mixture was poured into ice water, extracted twice with ethyl acetate, the combined extracts were washed with water 2-3 times, dried over anhydrous Na ₂ SO ₄ , concentrated to give a crude product. Column chromatography was performed using a mixture of ethyl acetate and petroleum ether (1:10) as the eluent to obtain 1.06 g of the title compound as an oil, with a content of 92.0% (GC), and a yield of 27.4%.

LC-MS (APCI, Pos) (M ⁺ +1) (relative intensity%): calc: 509, found: 509.2.

¹ H NMR (CDCl ₃ /TMS, 300MHz) δ (ppm): 2.146 (s, 3H, SCH ₃ ), 3.821 (s, 3H, OCH ₃ ), 4.043 (s, 3H, OCH ₃ ), 5.167 (s, 2H, CH ₂ O), 7.184～7.493 (m, 4H, ph H), 7.901 (s, 1H, ph H), 7.949 (s, 2H, ph H).

Example 6

This example illustrates the preparation of compound 10 in Table 1.

2-Methoxyimino-N-methyl-2-[2-[α-methylthio-(3,5-bistrifluoromethylbenzylidene)aminooxymethyl]phenyl]acetamide (10 compounds): 2-methoxyimino-2-[2-[α-methylthio-(3,5-bistrifluoromethylbenzylidene)aminooxymethyl]phenyl]acetic acid Methyl ester (92%, 0.61g=1.1mmol) and methanol solution of 3-5 times molar ratio of methylamine, stirred at room temperature for 15-20hr, poured the mixture into ice water, extracted twice with ethyl acetate, The combined extracts were washed 2-3 times with water, dried over anhydrous Na ₂ SO ₄ , and concentrated to obtain a crude product. Column chromatography using a mixture of ethyl acetate and petroleum ether (1:10) as the eluent gave 0.38 g of the title compound as a white solid, content 93.4%, yield 63.3%, melting point: 132.1-133.9°C.

LC-MS (APCI, Pos) (M ⁺ +1) (relative intensity%): calc: 508, found: 508.2.

¹ H NMR (CDCl ₃ /TMS, 300MHz) δ (ppm): 2.150 (s, 3H, SCH ₃ ), 2.870 (d, 3H, NCH ₃ ), 3.945 (s, 3H, OCH ₃ ), 5.178 (s, 2H, CH ₂ ), 6.798(s, 1H, NH), 7.194～7.517(m, 4H, ph H), 7.900(s, 1H, ph H), 7.953(s, 2H, ph H).

Example 7

This example illustrates the preparation of compound 11 in Table 1.

2-Methoxyimino-N-methyl-2-[2-[α-methoxy-(3,5-bistrifluoromethylbenzylidene)aminooxymethyl]phenyl]acetamide (11 compounds): 2-methoxyimino-2-[2-[α-methoxy-(3,5-bistrifluoromethylbenzylidene)aminooxymethyl]phenyl]acetic acid Methyl ester (91.0%, 0.61g=1.1mmol) and 3-5 times the molar ratio of methylamine in methanol, stirred at room temperature for 15-20hr, poured the mixture into ice water, extracted twice with ethyl acetate, The combined extracts were washed 2-3 times with water, dried over anhydrous Na ₂ SO ₄ , and concentrated to give a crude product. Column chromatography using a mixture of ethyl acetate and petroleum ether (1:10) as the eluent gave 0.32 g of the title compound as a white solid, content 95.4%, yield 55.1%, melting point: 156.5-157.4°C.

LC-MS (APCI, Pos) (M ⁺ +1) (relative intensity%): calc: 491, found: 491.2.

¹ H NMR (CDCl ₃ /TMS, 300MHz) δ (ppm): 2.865 (d, 3H, NCH ₃ ), 3.950 (s, 3H, OCH ₃ ), 4.118 (s, 3H, OCH ₃ ), 5.169 (s, 2H, CH ₂ ), 6.808(s, 1H, NH), 7.214～7.521(m, 4H, ph H), 7.900(s, 1H, ph H), 7.948(s, 2H, ph H).

Example 8

This example illustrates the preparation of compound 16 in Table 1.

Synthesis of α-ethylthio-3,5-bistrifluoromethylbenzaldehyde oxime: 3,5-bistrifluoromethylbenzaldehyde oxime (12.85g=0.05mol) was dissolved in methanol (200ml),- At 5-0°C, slowly add tert-butyl hypochlorite (5.5g=0.05mol) dropwise, and after about 0.5-1.0hr, add equimolar triethylamine and ethanethiol successively, and continue the reaction after dropping 1-2hr, the reaction mixture was poured into water, extracted with ethyl acetate, washed with ice brine until neutral, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain α-methylthio-3,5-bistrifluoromethane 12.57 g of phenylbenzaldoxime, content 95.2% (GC-MS), is yellow viscous liquid, yield 75.5%.

GC-MS (M ⁺ ) (EI, 70eV, m/z) (relative intensity%) calc: 317; found: 317 (30), 289 (25), 257 (100), 240 (80), 239 (85 ), 220(70), 213(62), 189(15), 170(60), 61(70).

2-[2-[α-ethylthio-(3,5-bistrifluoromethylbenzylidene)aminooxymethyl]phenyl]-3-methoxymethyl acrylate (16 compounds): the Add potassium hydroxide (0.56g=10mmol) and N,N-dimethylformamide (15ml) into a dry three-necked flask, stir for 5-10min, then add the above oxime (95.2% , 2.33g=7.0mmol) in N,N-dimethylformamide solution (5ml). After stirring and reacting for 0.5 hr, (E)-2-[2-(bromomethyl)phenyl]-3-methoxymethyl acrylate (2.58g=9.0mmol) in N,N-dimethylformamide The solution (10ml) was added dropwise to the above reaction mixture, and the reaction was incubated at 15-25°C for 10-12hr. The mixture was poured into crushed ice, extracted twice with ethyl acetate, the combined extracts were washed with water 2-3 times, dried over anhydrous Na ₂ SO ₄ , concentrated to give a crude product. Column chromatography using a mixture of ethyl acetate and petroleum ether (1:15) as the eluent gave 1.08 g of the title compound as a white solid with a content of 95.0%, a yield of 28.9%, and a melting point of 79.6-80.1°C.

LC-MS (APCI, Pos) (M ⁺ +1) (relative intensity%): calc: 522, found: 522.2.

¹ H NMR (CDCl ₃ /TMS, 300MHz) δ (ppm): 1.138-1.187 (t, 3H, CH ₃ ), 2.684-2.757 (q, 2H, SCH ₂ ), .700 (s, 3H, OCH ₃ ) , 3.819 (s, 3H, OCH ₃ ), 5.222 (s, 2H, OCH ₂ ), 7.161-7.169 (d, 1H, CH), 7.327-7.600 (m, 4H, oximePhH), 7.896-8.043 (2s.2H , PhH).

Example 9

This example illustrates the preparation of compound 20 in Table 1.

Synthesis of α-ethoxy-3,5-bistrifluoromethylbenzaldehyde oxime: Synthesize with reference to the method for synthesizing α-methoxy-3,5-bistrifluoromethylbenzaldehyde oxime in Example 2.

GC-MS (M ⁺ ) (EI, 70eV, m/z) (relative intensity%) calc: 301: found: 301 (5), 282 (10), 241 (100), 213 (25), 170 (10 ).

2-[2-[α-ethoxy-(3,5-bistrifluoromethylbenzylidene)amineoxymethyl]phenyl]-3-methoxymethyl acrylate (20 compounds): the Potassium hydroxide (0.56g=10mmol) and N,N-dimethylformamide (15ml) were added to a dry three-necked flask, and after stirring for 5-10min, the above-mentioned oxime (85.5% , 2.47g=7.0mmol) in N,N-dimethylformamide solution (3ml). After stirring for 0.5 hr, N, N-dimethylformamide ( 10ml) solution was added dropwise to the above reaction mixture, and the reaction was incubated at 15-25°C for 10-12hr. The mixture was poured into ice water, extracted twice with ethyl acetate, the combined extracts were washed with water 2-3 times, dried over anhydrous Na ₂ SO ₄ , concentrated to give a crude product. Column chromatography was performed using a mixture of ethyl acetate and petroleum ether (1:10) as the eluent to obtain 1.17 g of the title compound in thick form, 95.4% (GC-MS), yield 31.58%.

LC-MS (APCI, Pos) (M ⁺ +1) (relative intensity%): calc: 505, found: 505.2.

¹ H NMR (CDCl ₃ /TMS, 300MHz) δ (ppm): 1.239-1.278 (t, 3H, CH ₃ ), 3.693 (s, 3H, OCH ₃ ), 3.832 (s, 3H, OCH ₃ ), 4.584- 4.667 (q, 2H, OCH ₂ ), 5.064 (s, 2H, OCH ₂ ), 7.172-8.181 (m, 8H, PhH+CH=).

Example 10

This example illustrates the preparation of compound 63 in Table 1.

Methyl N-methoxy-N-[2-[α-methylthio-(3,5-bistrifluoromethylbenzylidene)aminooxymethyl]phenyl]carbamate (Compound 63): Add sodium hydride (60%, 0.36g=9.0mmol) and N,N-dimethylformamide (15ml) into a dry three-necked flask, stir for 5-10min, then add α -Methylthio-3,5-bistrifluoromethylbenzaldoxime (82%, 2.59g=7.0mmol) in N,N-dimethylformamide (5ml). After stirring and reacting for 0.5 hr, N, N-dimethylformamide solution (10 ml) of methyl N-methoxy-N-(2-bromomethylphenyl) carbamate (2.47 g = 9.0 mmol) was added dropwise Add it to the above reaction mixture and keep it warm for 0.5-1.0hr. The mixture was poured into crushed ice, extracted twice with ethyl acetate, the combined extracts were washed with water 2-3 times, dried over anhydrous Na ₂ SO ₄ , concentrated to give a crude product. Column chromatography was performed using a mixture of ethyl acetate and petroleum ether (1:10) as the eluent to obtain 1.01 g of the title compound as a viscous liquid with a content of 90.0% and a yield of 26.2%.

LC-MS (APCI, Pos) (M ⁺ +1) (relative intensity%): calc: 537, found: 537.2.

¹ H NMR (CDCl ₃ /TMS, 300MHz) δ (ppm): 2.190 (s, 3H, SCH ₃ ), 3.745 (s, 3H, OCH ₃ ), 3.784 (s, 3H, OCH ₃ ), 5.344 (s, 2H, CH ₂ ), 7.261～7.573 (m, 4H, ph H), 7.910 (s, 1H, ph H), 7.959 (s, 2H, ph H).

Example 11

This example illustrates the preparation of compound 73 in Table 1.

[2-[α-Methylthio-(3,5-bistrifluoromethylbenzylidene)aminooxymethyl]phenyl](5,6-dihydro-1,4,2-dioxazine -3-yl)methanone O-methyloxime (compound 73): Add sodium hydride (60%, 0.36g=9.0mmol) and N,N-dimethylformamide (15ml) into a dry three-necked flask, After stirring for 5-10min, at -5-0°C, add α-methylthio-3,5-bistrifluoromethylbenzaldehyde oxime (82%, 2.59g=7.0mmol) dropwise in N,N-di Methylformamide (5ml) solution. After stirring for 0.5 hr, [2-(bromomethyl)phenyl](5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyloxime (2.58g =9.0mmol) of N,N-dimethylformamide (10ml) solution was added dropwise to the above reaction mixture, and the reaction was incubated for 0.5-1.0hr. The reactant was poured into crushed ice, extracted twice with ethyl acetate, and the combined extracts were washed with water 2-3 times, dried over anhydrous Na ₂ SO ₄ , and concentrated to obtain a crude product. Column chromatography was performed using a mixture of ethyl acetate and petroleum ether (1:10) as the eluent to obtain 1.11 g of the title compound as a viscous liquid with a content of 90% and a yield of 26.6%.

LC-MS (APCI, Pos) (M ⁺ +1) (relative intensity%): calc: 536, found: 536.2.

¹ H NMR (CDCl ₃ /TMS, 300MHz) δ (ppm): _2.174 (s, 3H, SCH ₃ ), 3.977 (s, 3H, OCH 3 ), 4.146-4.147 (t, 2H, CH ₂ ), 4.463- 4.490(t, 2H, CH ₂ ), 5.222(s, 2H, CH ₂ ), 7.178～7.488(m, 4H, ph H), 7.901(s, 1H, ph H), 7.981(s, 2H, ph H ).

Example 12

This example illustrates the preparation of compound 117 in Table 1.

4-[2-[α-Methylthio-(3,5-bistrifluoromethylbenzylidene)aminooxymethyl]phenyl]-2,4-dihydro-5-methoxy-2 -Methyl-3H-1,2,4-triazol-3-one (compound 117): Add aqueous sodium hydroxide solution (20%, 1.8g=9.0mmol) and toluene (10ml) into a three-necked flask, stir for 5 After -10 min, a toluene (5 ml) solution of α-methylthio-3,5-bistrifluoromethylbenzaldoxime (82%, 2.59 g = 7.0 mmol) was added dropwise at room temperature. After stirring for 0.5 hr, 4-(2-bromomethylphenyl)-2,4-dihydro-5-methoxy-2-methyl-3H-1,2,4-triazole-3- A solution of ketone (2.68g=9.0mmol) in toluene (5ml) and tetrabutylammonium bromide (0.8g) were added dropwise to the above reaction mixture. In ice, it was extracted twice with ethyl acetate, and the combined extracts were washed with water 2-3 times, dried over anhydrous Na ₂ SO ₄ , and concentrated to obtain a crude product. Column chromatography was performed using a mixture of ethyl acetate and petroleum ether (1:10) as the eluent to obtain 1.03 g of the title compound with a content of 90.0% and a yield of 25.5%.

LC-MS (APCI, Pos) (M ⁺ +1) (relative intensity%): calc: 521, found: 521.0.

Example 13

This example illustrates the preparation of compound 120 in Table 1.

Methyl 2-[2-(3,5-bistrifluoromethylphenoxymethyl)-phenyl]-3-methoxyacrylate (compound 51): Sodium hydride (60%, 0.92g=23mmol ) and N,N-dimethylformamide (8mL) were added into a dry three-necked flask, and after stirring for 5-10min, at 15-20°C, 3,5-bistrifluoromethylphenol (3.0g= 13mmol) in N,N-dimethylformamide (8mL). After stirring for 0.5 hr, N, N-dimethylformamide (8 ml ) solution was added dropwise to the above reaction mixture, and the reaction was incubated for 2-3hr. The mixture was poured into ice water, extracted twice with ethyl acetate, the combined extracts were washed with water 2-3 times, dried over anhydrous Na ₂ SO ₄ , concentrated to give a crude product. Column chromatography was performed using a mixture of ethyl acetate and petroleum ether (1:10) as the eluent to obtain 3.22 g of the viscous title compound, with a content of 95.0% (GC), and a yield of 54.2%.

LC-MS (APCI, Pos) (M ⁺ +1) (relative intensity%): calc: 435, found: 435.2.

¹ H NMR (CDCl ₃ /TMS, 300MHz) δ (ppm): 3.723 (s, 3H, OCH ₃ ), 3.836 (s, 3H, OCH ₃ ), 5.050 (s, 2H, CH ₂ O), 7.182～7.617 (m, 8H, ph H+=CH).

Example 14

This example illustrates the preparation of compound 124 in Table 1.

Synthesis of 1-(3,5-bistrifluoromethylphenyl)-2-methylthioethanol: at 10-20°C, to 2-methylthio-3',5'-bistrifluoromethylbenzene In the mixture of acetone (88%, 4.5g=13mmol) and ethanol (5ml), add dropwise After dropping the mixture, continue to insulate and react until there is no raw material. Extracted with ethyl acetate, washed with water until neutral, dried over anhydrous sodium sulfate, and precipitated to obtain 3.2 g of a crude product with a content of 92% (GC) and a yield of 73.8%.

Methyl 2-[[2-[1-(3,5-bistrifluoromethylphenyl)-2-methylthio]ethoxymethyl]phenyl]-3-methoxyacrylate (124 compounds) : Add sodium hydride (60%, 0.36g=9.0mmol) and tetrahydrofuran (15ml) into a dry there-necked flask, at room temperature, add dropwise methylhydrofuran (3ml) of the above alcohol (92%, 2.32g=7.0mmol) solution. After 0.5 hr, a solution of (E)-2-[2-(bromomethyl)phenyl]-3-methoxymethyl acrylate (2.58g=9.0mmol) in tetrahydrofuran (10ml) was added dropwise to the above reaction mixture In the heat preservation reaction 2-3hr. The mixture was poured into ice water, extracted twice with ethyl acetate, the combined extracts were washed with water 2-3 times, dried over anhydrous Na ₂ SO ₄ , concentrated to give a crude product. Column chromatography using a mixture of ethyl acetate and petroleum ether (1:10) as the eluent gave the title compound 0.80 g, 90.0% (GC), as a viscous liquid, yield 20.2%.

LC-MS (APCI, Pos) (M ⁺ +1) (relative intensity%): calc: 509, found: 509.2.

¹ H NMR (CDCl ₃ /TMS, 300MHz) δ (ppm): 2.036 (s, 3H, SCH ₃ ), 2.660～2.939 (m, 2H, CH ₂ ), 3.628 (s, 3H, OCH ₃ ), 3.737 ( s, 3H, OCH ₃ ), 4.218-4.426 (q, 2H, CH ₂ ), 4.537 (t, 1H, CH), 7.104-7.563 (m, 5H, Ph H+C=CH), 7.819 (s, 1H , ph H), 7.842 (s, 2H, ph H)

Example 15

This example illustrates the preparation of compound 139 in Table 1.

Synthesis of N-chloroacetyl-3,5-bistrifluoromethylaniline: to a dry there-necked flask equipped with a magnetic stirrer, a condenser tube, a thermometer, a constant pressure funnel, a drying tube, and a tail gas absorption device, add 3, 5-bistrifluoromethylaniline (22.9g=0.10mol), triethylamine (11.6g=0.115mol) and toluene (60ml), after stirring evenly, cool in an ice-water bath to 10-15°C, and remove from the dropping funnel Chloroacetyl chloride (12.5g = 0.11mol) was added dropwise. After the drop, react at room temperature for 2-3hrs, add ice water (200g), extract with ethyl acetate, separate the organic layer, wash with saturated brine, anhydrous sodium sulfate After drying and precipitation, 24.2 g of a white solid crude product was obtained, with a yield of 79.3%.

Synthesis of N-methylthioacetyl-3,5-bistrifluoromethylaniline: N-chloroacetyl-3,5-bistrifluoromethylaniline (15.28g=0.05mol), sodium methylthiolate Aqueous solution (20%, 24.5g=0.07mol) and ethanol (50ml), at 50-60°C, stirred for 2-3hr, added ice water (200g), extracted twice with ethyl acetate, separated the organic layer, saturated Washed with salt water, dried over anhydrous sodium sulfate, and precipitated to obtain 11.2 g of an oily crude product with a content of 92% and a yield of 65.0%.

Synthesis of N-methylthioacetyl-3,5-bistrifluoromethylaniline: N-methylthioacetyl-3,5-bistrifluoromethylaniline (92%, 11.2g=32.5mmol) , phosphorus pentasulfide (7.22g=32.5mmol) and toluene (40ml), at 80-90°C, stirred and reacted for 3-4hr, added ice water (200g), extracted twice with ethyl acetate, separated the organic layer, and saturated saline After washing, drying with anhydrous sodium sulfate, and precipitation, 6.5 g of oily crude product was obtained, with a content of 90% and a yield of 54.0%.

2-[2-[[1-(3,5-bistrifluoromethylphenylimino)-2-methylthio]ethyl]thiomethyl]phenyl]-3-methoxypropenomethacrylic acid Ester (compound 139): Add potassium carbonate (2.76g=0.02mol) and N,N-dimethylformamide (25ml) into a dry three-necked flask, stir for 5-10min, then add N-formazol dropwise at room temperature Thiothioacetyl-3,5-bistrifluoromethylaniline (90%, 3.7g=0.01mol) in N,N-dimethylformamide (8ml) solution. After stirring and reacting for 15 minutes, (E)-2-[2-(bromomethyl)phenyl]-3-methoxymethyl acrylate (2.85g=0.01mol) in N,N-dimethylformamide was added dropwise (10ml) solution, after dripping, continue to react for 3-4hr. The mixture was poured into ice water, extracted twice with ethyl acetate, the combined extracts were washed with water 2-3 times, dried over anhydrous Na ₂ SO ₄ , concentrated to give a crude product. Column chromatography was performed using a mixture of ethyl acetate and petroleum ether (1:10) as the eluent to obtain 1.48 g of the title compound with a content of 93% and a yield of 25.6%.

LC-MS (APCI, Pos) (M ⁺ +1) (relative intensity%): calc: 537, found: 537.2.

¹ H NMR (CDCl ₃ /TMS, 300MHz) δ (ppm): 2.164 (s, 3H, SCH ₃ ), 3.348 (s, 2H, SCH ₂ ), 3.678 (s, 3H, OCH ₃ ), 3.846 (s, 3H, OCH ₃ ), 4.185 (s, 2H, CH ₂ S), 7.017～7.746 (m, 8H, ph H+C=CH)

Example 16

Preparation of emulsifiable concentrate: 20 parts (by weight) of methoxyacrylate compounds containing bis-trifluoromethylphenyl provided by the invention, 73 parts of diluents such as xylene and 7 parts of suitable auxiliary agents are evenly mixed to prepare emulsifiable concentrates. It is applied by diluting with water (20% active compound content).

Example 17

(01) Compound 2-[2-[α-methylthio-(3,5-bistrifluoromethylbenzylidene)amineoxymethyl]phenyl]-3-methoxymethyl acrylate 20% Preparation of emulsifiable concentrate: 20 parts of compound 01 (by weight), 73 parts of diluent such as xylene and 7 parts of suitable adjuvants are evenly mixed to prepare emulsifiable concentrate, which can be applied by diluting with water (active compound content is 20%).

Example 18

Preparation of wettable powder: 20 parts (by weight) of two trifluoromethylphenyl methoxyacrylate compounds provided by the invention, 53 parts of clay, 20 parts of white carbon black, 5 parts of lignosilicate and Wettable powder (active compound content: 20%) can be obtained by mixing 2 parts of polyoxyethyl alkyl ether and grinding it into fine powder.

Bioassay example

The bactericidal, acaricidal and insecticidal activity tests of the synthesized compounds are carried out, and the experimental results of some compounds are listed here.

The bactericidal activity of embodiment 19 to wheat powdery mildew (Erysiphe graminis)

The method is as follows: the compound to be tested is dissolved in a suitable solvent such as acetone, and then diluted with water to the desired concentration. This solution was sprayed on the plants to be tested and allowed to dry for 2 hours, and the pathogen inoculation was carried out one day later. Relative to the blank control, the activity is calculated as a percentage and divided into four grades: A, B, C, and D. The control effect of 100%-90% is grade A, the control effect of 90%-70% is grade B, and the control effect of 70%-50% It is grade C, and the control effect of 0%-50% is grade D.

Inoculate one day after application. After inoculation, place it in the artificial climate greenhouse for 10-15 days and then investigate the results. Some test results are shown in Table 2 and Table 3.

The bactericidal activity of table 2 part compound and trifloxystrobin to wheat powdery mildew (Erysiphegraminis) when test concentration is 500mg/l

compound activity level compound activity level compound activity level compound activity level 01 A 12 A 28 A 94 A 02 A 13 B 63 A 124 D 03 D 14 B 64 A 135 A 04 A 16 A 65 A 136 A 05 A 17 A 70 A 139 A 06 A 18 A 73 A 140 A 08 A 19 A 74 A 149 A 09 A 20 A 75 A 151 A 10 A twenty one A 79 A 224 A 11 A 27 A 82 A Trifloxystrobin A

The bactericidal activity of table 3 part compound and trifloxystrobin to wheat powdery mildew (Erysiphegraminis) when test concentration is 25mg/l

compound activity level compound activity level compound activity level compound activity level 01 A 06 A 12 A 73 A 02 A 09 A 16 A 75 A 04 B 10 A 63 A 224 B 05 A 11 A 65 A Trifloxystrobin A

Example 20 Bactericidal activity to rice blast fungus (Pyricularia oryzae)

The method is as follows: the test compound is made into a mother solution of predetermined concentration with a suitable diluent (such as acetone), and 1 milliliter of the drug solution is taken with a pipette in 50 milliliters of dissolved PDA medium. In a petri dish as 3 repetitions, after cooling, pick a bacterium cake with a diameter of 5 mm and place it in the center of the petri dish with an inoculation needle, and set the diluent as a control simultaneously. The activity is calculated as a percentage relative to the blank control, and is divided into four grades: A, B, C, and D. The control rate of 100%-90% is grade A, the control rate of 90%-70% is grade B, and the control rate of 70%-50% It is grade C, and the control rate is 0%-50% is grade D.

After inoculation, put them into an incubator at a suitable temperature, measure the growth diameter of mycelia after 3 days, and calculate the inhibition rate of mycelium growth. Some test results are shown in Table 4.

The bactericidal activity of table 4 part compound and trifloxystrobin to rice blast fungus (Pyriculariaoryzae) when test concentration is 25mg/l

compound activity level compound activity level compound activity level compound activity level 01 A 10 A 19 A 75 A 02 A 11 A 20 A 119 A 03 D 12 A twenty one A 120 A 04 A 13 B 27 A 139 A 05 A 14 A 63 A 140 A 06 A 16 A 64 B 157 A

07 A 17 A 65 A Trifloxystrobin A 09 A 18 A 73 A

Example 21 Acaricidal activity against cotton red spider (Tetranychus urticae)

The method is as follows: Select good-growing bean sprouts to inoculate red spider mite. After the red spider colonizes, cut off the mite-bearing bean sprouts and soak them in the prepared medicinal solution for 10 seconds. In a beaker filled with water, cultivate in the observation room, check the number of surviving and dead mites after 24 hours, and there are 100-200 mites on each bean sprout. The experiment was repeated three times. The results are averaged. The activity is calculated as a percentage relative to the blank control, and is divided into four grades: A, B, C, and D. A mortality rate of 100%-90% is grade A, a mortality rate of 90%-70% is grade B, and a mortality rate of 70%-50% It is grade C, and the mortality rate is 0%-50% is grade D. Some test results are shown in Table 5.

The acaricidal activity of table 5 part compound and trifloxystrobin to cotton red spider (Tetranychus urticae)

compound Activity (500mg/L) Activity (100mg/L) compound Activity (500mg/L) Activity (100mg/L) 01 A A 17 A A 02 A A 18 A A 03 A B 19 A C 08 B D 63 A -* 09 A A 65 A - 10 A A 120 A A 11 A A Trifloxystrobin D D 16 A A

*No test

Embodiment 22 is to the insecticidal experiment of black-tailed leafhopper (Nephotettix cincticeps)

Dilute the emulsifiable concentrate or wettable powder of the bistrifluoromethylphenyl-containing methoxyacrylate compound prepared by the method of the above-mentioned agricultural preparation embodiment to prepare a pesticide solution with a predetermined concentration, and select two-core rice Immerse the seedlings in the liquid medicine, take them out after 5 seconds to dry, put them in a large test tube, 20 plants per tube, and then introduce 20 or more 5th instar nymphs of the black-tailed leafhopper, wrap the mouth of the tube with white gauze and place it in the greenhouse conditions, check the number of live and dead insects after 24 hours. The experiment was repeated three times. The results are averaged. The activity is calculated as a percentage relative to the blank control, and is divided into four grades: A, B, C, and D. A mortality rate of 100%-90% is grade A, a mortality rate of 90%-70% is grade B, and a mortality rate of 70%-50% It is grade C, and the mortality rate is 0%-50% is grade D. Some results are shown in Table 6.

The insecticidal activity of table 6 part compounds and trifloxystrobin to black-tailed leafhopper (Nephotettix cincticeps)

compound Mortality (500mg/L) Active level (500mg/L) 01 20 D 02 100 A 03 25 D 09 60 C Trifloxystrobin 90 A

Embodiment 23 is to the active experiment of bean aphid (Aphis fabae)

Dilute the emulsifiable concentrate or wettable powder of the bistrifluoromethylphenyl-containing methoxyacrylate compound prepared by the method of the above-mentioned agricultural preparation embodiment with water to prepare a predetermined concentration of pesticide solution, and inoculate the bean aphid On the freshly unearthed bean sprouts, connect more than 20 heads per plant, then soak the bean sprouts together with the test insects in the liquid medicine, take them out after 5 seconds, absorb the excess liquid medicine, insert them into a water-absorbing sponge, and wipe them with glass. Tubes were capped and checked for live and dead insect counts after 24 hours. Repeat 3 times, and the results are averaged. The activity is calculated as a percentage relative to the blank control, and is divided into four grades: A, B, C, and D. A mortality rate of 100%-90% is grade A, a mortality rate of 90%-70% is grade B, and a mortality rate of 70%-50% It is grade C, and the mortality rate is 0%-50% is grade D. Some test results are shown in Table 7.

The insecticidal activity of table 7 part compound and trifloxystrobin to bean aphid (Aphis fabae)

compound Active level (500mg/L) Active level (100mg/L) compound Active level (500mg/L) Active level (100mg/L) 01 B D 05 A C 02 A A Trifloxystrobin A - 03 A C

*No test

Claims (4)

1. have fungicidal, kill mite, the bioactive methoxy acrylate compound that contains bis trifluoromethyl phenyl of desinsection, it is characterized in that representing with general formula (I), (II) with (III):

Wherein:

I.A is selected from following group:

U is CH or N;

V is O, S or NH;

R ' is C ₁～C ₆Alkyl or H;

II.B is selected from following group:

XR R ¹CHXR

B-1 B-2

X is O, S, SO, SO ₂Or NH;

R is an alkyl;

R ¹It is hydrogen or alkyl;

V.Y is selected from following group:

R ³Z Z

Y-1 Y-2 Y-3 Y-4

B defines among B such as the II;

Z is O, S, SO, SO ₂Or NH;

R ³It is alkylidene group;

VI.K is selected from following group:

R ³Z Z

K-1 K-2 K-3 K-4

B defines among B such as the II;

Z defines among Z such as the V;

R ³As R among the V ³Define;

In the compound that provides above (I), (II) and the definition (III), no matter the separately use or be used in the compound word of used term, alkyl is meant the straight or branched alkyl with 1-6 carbon atom.

2. the methoxy acrylate compound that contains bis trifluoromethyl phenyl according to claim 1, it is characterized in that general formula (I), (II) and (III) shown in compound be:

2-[2-[α-methoxyl group-(3,5-bis trifluoromethyl Ben Yajiaji) amine oxygen methyl] phenyl]-the 3-methoxy-methyl acrylate;

2-methoxy imino-2-[2-[α-methoxyl group-(3,5-bis trifluoromethyl Ben Yajiaji) amine oxygen methyl] phenyl] methyl acetate;

2-[2-[alpha-methylmercapto-(3,5-bis trifluoromethyl Ben Yajiaji) amine oxygen methyl] phenyl]-the 3-methoxy-methyl acrylate;

2-[2-[α-ethylmercapto group-(3,5-bis trifluoromethyl Ben Yajiaji) amine oxygen methyl] phenyl]-the 3-methoxy-methyl acrylate;

2-[2-[α-oxyethyl group-(3,5-bis trifluoromethyl Ben Yajiaji) amine oxygen methyl] phenyl]-the 3-methoxy-methyl acrylate;

2-[2-[1-(3, the 5-bis trifluoromethyl phenyl)-2-methylthio group-ethyleneamines oxygen methyl]-phenyl]-the 3-methoxy-methyl acrylate;

2-methoxy imino-2-[2-[alpha-methylmercapto-(3,5-bis trifluoromethyl Ben Yajiaji) amine oxygen methyl] phenyl] methyl acetate;

2-methoxy imino-N-methyl-2-[2-[alpha-methylmercapto-(3,5-bis trifluoromethyl Ben Yajiaji) amine oxygen methyl] phenyl] ethanamide;

2-methoxy imino-N-methyl-2-[2-[α-methoxyl group-(3,5-bis trifluoromethyl Ben Yajiaji) amine oxygen methyl] phenyl] ethanamide;

[2-[alpha-methylmercapto-(3,5-bis trifluoromethyl Ben Yajiaji) amine oxygen methyl] phenyl] (5,6-dihydro-1,4,2-dioxazine-3-yl) ketone O-methyloxime;

[2-[α-methoxyl group-(3,5-bis trifluoromethyl Ben Yajiaji) amine oxygen methyl] phenyl] (5,6-dihydro-1,4,2-dioxazine-3-yl) ketone O-methyloxime;

2-[2-(3,5-dual-trifluoromethyl benzene oxygen ylmethyl)-phenyl]-the 3-methoxy-methyl acrylate;

2-[2-[α-(N-methylamino)-(3,5-bis trifluoromethyl Ben Yajiaji) amine oxygen methyl] phenyl]-the 3-methoxy-methyl acrylate.

3. the preparation method who contains the methoxy acrylate compound of bis trifluoromethyl phenyl according to claim 1 and 2, it is characterized in that at alkali potassium hydroxide, sodium hydride or salt of wormwood exist down, react general formula (I) or the compound (II) that promptly gets V ≠ NH with the compound of formula (IV) and the compound of formula V or formula (VI)

Y＝O，S

A, B, Y have the above-mentioned definition of giving in the formula, and L is leavings group Br.

4. the purposes that contains the methoxy acrylate compound of bis trifluoromethyl phenyl according to claim 1 and 2 is characterized in that having fungicidal under 18.75～375 gram effective constituent/hectare consumptions, killing mite, desinsection biological activity.