A type of 3,3-diaryl acrylate / amide compound containing triaryl phosphonium salt and its preparation method and application

Abstract

The present invention discloses a triarylphosphonium salt-based 3,3-diaryl acrylate / amide fungicidal compound of Formula I, its preparation method, and the use of a formulation prepared with the compound as an active ingredient in controlling various pathogens in crops, horticulture, and vegetables. The compound of Formula I, as an active ingredient, is highly active in controlling pathogens in crops, horticulture, and vegetables, exhibiting excellent control effects even at very low doses and exhibiting a broad control spectrum. #imgabs0#

Description

Technical Field

[0001] The present invention relates to a pesticide compound, in particular to a 3,3-diaryl acrylate / amide compound containing a triaryl phosphonium salt, and a preparation method and application thereof. Background Art

[0002] Mitochondria are an important organelle present in most eukaryotic cells and are closely involved in various physiological and biochemical processes of cells, such as cell differentiation, information transmission, apoptosis, cell energy supply, and regulation of cell growth and cycle. Therefore, the creation of new pesticides targeting mitochondria has been a research hotspot in recent years. Butyroxine is a dual-site fungicide independently developed in my country. It has a significant inhibitory effect on the cell wall of fungi and complex III on the mitochondrial respiratory chain. Studies have shown that the diaryl functional group of Butyroxine can hinder the entry of panthenol (QH2) into the Q of complex III. o sites, thereby disrupting electron transport.

[0003] The technical solution provided by the present invention combines a diaryl functional group module with a triaryl quaternary phosphonium salt with mitochondrial targeting function to synthesize a class of mitochondrial respiratory chain complex-targeted fungicidal compounds, which have extensive and excellent fungicidal activity against plant fungi. Summary of the Invention

[0004] The first object of the present invention is to provide a class of 3,3-diaryl acrylate / amide compounds containing triaryl phosphonium salts and a preparation method thereof.

[0005] The general structural formula of the 3,3-diaryl acrylate / amide compound containing triaryl phosphonium salt provided by the present invention is shown in Formula I:

[0006]

[0007] In Formula 1:

[0008] X is selected from O, NR1(R1=H, CH3 or CH(CH3)2;

[0009] Y is selected from Cl, Br, I, CH3SO3, CF3CO2, CH3CO2, CF3SO3 or PhCO2; n is an integer from 1 to 18; Ar1 is selected from the substituted phenyl group shown below:

[0010]

[0011] In the substituted phenyl group Ar1:

[0012] R2=H, C1-C5 linear or branched alkyl, C1-C5 linear or branched alkyloxy, F, Cl, Br, CF3, CF3O, CF2HCH2O or NO2;

[0013] m=0-5. When m>1, R2 are the same or different.

[0014] Ar2 is selected from substituted phenyl groups that are the same as or different from Ar1; in different cases, the substituents are defined the same as R2 or Q:

[0015] Ar2=Ar1 or Q

[0016] Q is selected from any one of the following aromatic heterocyclic groups Q1-Q4:

[0017]

[0018] In formula Q1:

[0019] R3=H, F, Cl, OCH3, CF3; N can be at the 2nd, 3rd or 4th position.

[0020] Ar3 is selected from monosubstituted phenyl groups:

[0021]

[0022] Wherein R4=H, CH3, CH3O or CF3.

[0023] In addition, in the compound of formula I described in the present invention, the carbon-carbon double bond is connected to different substituents to form different geometric isomers, including Z isomers, E isomers, or mixtures of these two isomers in any ratio.

[0024] The compound of formula I of the present invention is selected from I n a~I n Any numbered compound shown in d:

[0025]

[0026]

[0027]

[0028]

[0029]

[0030]

[0031]

[0032]

[0033]

[0034]

[0035]

[0036]

[0037]

[0038]

[0039]

[0040]

[0041]

[0042]

[0043]

[0044]

[0045]

[0046]

[0047]

[0048]

[0049]

[0050] The second object of the present invention is to provide a method for preparing the compound represented by formula I.

[0051] The method for preparing the compound of formula I provided by the present invention comprises the following steps: subjecting a compound of formula II and a compound of formula III to a nucleophilic reaction in an organic solvent to obtain the compound of formula I.

[0052]

[0053] In the formula II and formula III, the definitions of Ar1, Ar2, Ar3, X, Y and n are the same as those of the corresponding groups in the compound of formula I.

[0054] The molar ratio of the compounds of formula II and formula III is 1:1.5;

[0055] The temperature of the nucleophilic reaction is 30-200° C., and the reaction time is 3-36 hours. The organic solvent is selected from acetonitrile, benzene, toluene, xylene, ethylene glycol dimethyl ether or 1,2-dichloroethane or a mixed solvent thereof in any proportion.

[0056] The nucleophilic reaction step comprises: adding an organic solvent to a mixture of the compounds represented by formula II and formula III mixed in the stated proportion under nitrogen protection, stirring at room temperature for 5-10 minutes, and then reacting at 30-200° C. for 3-36 hours to obtain the compound represented by formula I.

[0057] The preparation method of the compound represented by formula II comprises: reacting the compound represented by formula IV, an acid-binding agent and the compound represented by formula V in an organic solvent to obtain the compound represented by formula II.

[0058]

[0059] In the formula V and formula IV:

[0060] The definitions of Ar1, Ar2, X, Y and n are the same as those of the corresponding groups in Formula I; the compounds of Formula V are all commercially available compounds.

[0061] The acid binding agent is selected from pyridine, triethylamine, ethylenediamine, potassium carbonate, cesium carbonate or NaH.

[0062] The molar ratio of the acid binding agent to the compound of formula IV is: (2-3): 1; wherein the molar ratio of the compound of formula IV to the compound of formula V is 1:1.05;

[0063] The reaction temperature of the reaction is -20 to 35° C., and the reaction time is 0.5 to 6 hours.

[0064] The organic solvent is selected from dichloromethane, tetrahydrofuran, acetonitrile, N,N-dimethylformamide (DMF), 1,4-dioxane or toluene.

[0065] The reaction comprises the following steps: adding an acid-binding agent, a compound represented by formula V, and a magnetron into a reaction flask, evacuating the flask, adding an organic solvent under nitrogen protection, lowering the temperature to -10°C using an ice-salt bath, stirring for 5-10 minutes, and then dripping the compound represented by formula IV into the reaction flask and reacting for 0.5-4 hours to obtain the compound represented by formula II.

[0066] In the above preparation method, the compound represented by formula IV is prepared as follows: the compound represented by formula VI and a chlorinating agent are reacted in the presence or absence of an organic solvent in the presence or absence of a catalyst to obtain the compound represented by formula IV.

[0067]

[0068] The definitions of Ar1 and Ar2 in Formula V and Formula IV are the same as those of Ar1 and Ar2 in Formula I;

[0069] In the above preparation method, the catalyst is any one of N'N-dimethylformamide (DMF), pyridine, 4-dimethylaminopyridine and triethylamine.

[0070] The chlorinating agent is any one of oxalyl chloride, thionyl chloride, phosphorus trichloride, triphosgene and phosphorus pentachloride.

[0071] The molar ratio of the catalyst to the compound represented by formula VI is (0.01-0.1):1.

[0072] The molar ratio of the chlorinating agent to the compound represented by formula VI is (1-3):1.

[0073] The reaction temperature of the reaction is -20 to 80° C., and the reaction time is 0.5 to 6 hours.

[0074] The organic solvent is dichloromethane, dichloroethane, toluene and benzene.

[0075] The reaction is preferably carried out according to the following steps: stirring the compound represented by formula VI and a chlorinating agent in an organic solvent at room temperature, adding a catalyst dropwise, and reacting for 0.5-4 hours to obtain a compound represented by formula IV.

[0076] In the above preparation method, the compound represented by formula VI is prepared as follows: under low temperature conditions of -20°C to 0°C, a base is added to an organic solvent containing the compound represented by formula VIII, and then the compound represented by formula VII is added to react to obtain the compound represented by formula VI.

[0077]

[0078] In the formula VII, the definitions of Ar1 and Ar2 are the same as those of Ar1 and Ar2 in formula I.

[0079] The base is any one of sodium hydride, sodium methoxide, sodium ethoxide, sodium tert-butoxide, n-butyl lithium and lithium diisopropylamide.

[0080] The molar ratio of the compound represented by formula VIII and the base is 1:(1-1.5), and the molar ratio of the compounds represented by formula VII and formula VIII is 1:(1-3).

[0081] The reaction temperature of the reaction is -20 to 60° C., and the reaction time is 2 to 15 hours.

[0082] The organic solvent is dichloromethane, dichloroethane, tetrahydrofuran, toluene and benzene.

[0083] The reaction is carried out according to the following steps: slowly adding a base to an organic solvent containing the compound represented by formula VIII under ice bath, stirring until hydrogen gas stops being released, then dropwise adding an organic solvent containing the compound represented by formula VII, and reacting for 5-15 hours to obtain a compound represented by formula VI.

[0084] In the above preparation method, the compound represented by formula VII is prepared as follows: in the presence of a Lewis acid, the compound represented by formula XI and the compound represented by formula VIIII are reacted in an organic solvent to obtain the compound represented by formula VII.

[0085]

[0086] In Formula VIIII and Formula XI, Ar2, R2 and m are defined the same as in Formula I.

[0087] In the above preparation method, the ratio of formula VIIII, formula XI and Lewis acid is (1-1.5):1:(1-3)

[0088] In the above preparation method, the catalyst is AlCl3, FeCl3, SnCl4, BF3, TiCl4, ZnCl2, HF, H2SO4 and H3PO4.

[0089] The reaction temperature of the reaction is -20 to 100° C., and the reaction time is 4 to 15 hours.

[0090] The organic solvent is dichloromethane, dichloroethane, 1,3-dichlorobenzene, nitrobenzene, ether, DMSO, DMF and tetrachloroethylene.

[0091] The reaction is carried out according to the following steps: dissolving compound XI in an organic solvent, stirring under ice bath, adding dropwise a solution of a compound represented by formula VIIII, continuing stirring for 10-15 minutes, then adding the Lewis acid to the reaction flask in 3-5 portions within 0.5-1 hour, and reacting for 4-15 hours to obtain a compound represented by formula VII.

[0092] The compounds of formula III, VIII and VIIII can all be purchased from commercial sources or obtained through a one-step reaction of raw materials.

[0093] Another object of the present invention is to provide a fungicide and a method for preparing the same. The composition comprises a phosphonium salt compound (a compound represented by Formula I) and an agriculturally acceptable carrier, wherein the weight percentage of the phosphonium salt compound (active ingredient) in the composition is 0.1 to 99%, specifically 30 to 60%.

[0094] The preparation method of the fungicide provided by the present invention comprises the following steps: mixing a phosphonium salt compound (compound represented by formula I) with an agriculturally acceptable carrier to prepare the fungicide.

[0095] The phosphonium salt compound can be a single compound of the present invention or a mixture of several compounds of the present invention.

[0096] Agriculturally acceptable carriers have the following characteristics: 1) they facilitate application to the site to be treated, such as plants, seeds, or soil, after formulation with the active ingredient; 2) they facilitate storage, transportation, or handling; and 3) they can be solid or liquid, including substances that are normally gases but have been compressed into liquids. In short, any carrier commonly used in formulating agricultural fungicide compositions can be used.

[0097] The agriculturally acceptable carrier may specifically be selected from solid carriers and / or liquid carriers.

[0098] The solid carrier is selected from at least one of natural or synthetic silicates, ammonium sulfate, calcium sulfate, aluminum silicate, natural or synthetic resins, polychlorinated phenols, starch, bentonite and wax, wherein the natural or synthetic silicate can be specifically selected from at least one of attapulgite, talc, aluminum silicate, diatomaceous earth, mica, montmorillonite and calcium silicate; the natural or synthetic resin can be specifically selected from at least one of coumarone resin, styrene polymer (molecular weight of 50,000-200,000) and styrene copolymer (such as styrene-butadiene copolymer); the wax can be specifically selected from beeswax and / or paraffin.

[0099] The liquid carrier is selected from water, C1-C4 alcohol, C3-C8 ketone, aromatic hydrocarbon, petroleum fraction and C6-C 12 At least one of the chlorinated hydrocarbons, wherein the alcohol may specifically be ethanol and / or ethylene glycol, the ketone may specifically be at least one of acetophenone, acetone, methyl ethyl ketone and cyclohexanone, the aromatic hydrocarbon may specifically be at least one of benzene, toluene and xylene, the petroleum fraction may specifically be kerosene and / or mineral oil, and the chlorinated hydrocarbon may specifically be at least one of carbon tetrachloride, dichloromethane and trichloroethane.

[0100] Generally, fungicides are processed and shipped in the form of concentrates, which are then diluted by the user before application.

[0101] To facilitate dilution, the fungicide composition provided by the present invention may further include a surfactant.

[0102] The added amount of the surfactant may be any amount acceptable for agricultural fungicides.

[0103] The surfactant is selected from at least one of an emulsifier, a dispersant, a wetting agent and a penetrant.

[0104] The emulsifier can be specifically selected from at least one of Nongru 500# (alkyl phenylsulfonate calcium), Nongru 600# phosphate (phenylphenol polyoxyethyl ether), Nongru 700# (alkylphenol formaldehyde resin polyoxyethyl ether), Nongru 1600# (phenylethylphenol polyoxyethyl polypropylene ether), polyoxyalkylene alkyl aryl ether and ethylene oxide-propylene oxide block copolymer.

[0105] The dispersant can be specifically selected from at least one of polycarboxylates, lignin sulfonates, alkylphenol polyoxyethylene formaldehyde condensate sulfates, alkylbenzenesulfonic acid calcium salts, benzenesulfonic acid formaldehyde condensate sodium salts, sodium laurate sulfate, sulfonated castor oil sodium salts, sodium alkyl aryl sulfonate, alkylphenol polyoxyethylene pyrimidines, fatty acid polyoxyethylene esters and ester polyoxyethylene pyrimidines.

[0106] The wetting agent can be specifically selected from at least one of sodium lauryl sulfate, sodium dodecylbenzene sulfonate, lakai powder BX, saponin powder, silkworm feces and soapberry powder.

[0107] The penetrant can be specifically selected from at least one of silicone polyoxyethylene ether, alkyl aryl sulfonate, alcohol ether succinate and phenol ether succinate.

[0108] Of course, other auxiliary agents may be appropriately added to the fungicide of the present invention.

[0109] The amount of the other adjuvants added is any amount acceptable for agricultural fungicides.

[0110] The other auxiliary agents may be selected from at least one of a disintegrant, a defoaming agent, an antifreeze agent and a thickener.

[0111] The disintegrant is selected from at least one of bentonite, urea, ammonium sulfate, aluminum chloride and glucose.

[0112] The defoaming agent is selected from at least one of silicone oil, silicone compounds, C10-C20 saturated fatty acid compounds, and C8-C10 fatty alcohol compounds.

[0113] The antifreeze agent is selected from at least one of ethylene glycol, propylene glycol, glycerol and polyethylene glycol.

[0114] The thickener is selected from at least one of xanthan gum, polyvinyl alcohol and polyethylene glycol.

[0115] The fungicide prepared by the present invention can be added with corresponding ingredients according to methods known to those skilled in the art to prepare various dosage forms such as wettable powders, dusts, granules, concentrated emulsions, emulsifiable concentrates, suspensions, aerosols or mists.

[0116] At the same time, an effective amount of the fungicide composition of the present invention can be applied according to different crops and diseases, and can be implemented by foliar spraying, seed treatment or soil treatment.

[0117] In certain aspects, one or more other fungicides may be added to the fungicide of the present invention to produce additional advantages and effects; the compound represented by Formula I may also be mixed with other fungicides.

[0118] In addition, the use of the compound represented by formula I and the composition thereof provided by the present invention in the preparation of fungicides also falls within the scope of protection of the present invention.

[0119] Compared with the closest existing technology, the technical solution provided by the present invention has the following excellent effects:

[0120] The triphenylphosphonium cation of the compound of Formula I provided by the present invention has a particularly prominent mitochondrial-targeting specificity due to its large ionic radius and delocalized charge, resulting in broad-spectrum and excellent fungicidal activity. The technical solution provided by the present invention can be used to control diseases of various crops caused by four major pathogenic fungi: Ascomycetes, Basidiomycetes, Deuteromycetes, and Oomycetes. Good control effects can be achieved even at very low doses. The diseases that can be prevented include: pepper blight, tomato early blight, tomato late blight, rice blast, wheat leaf spot, apple ring rot, rice sheath blight, rice blast, rice false smut, rice bakanae, wheat powdery mildew, rapeseed sclerotinia, cucumber downy mildew, cucumber wilt, cucumber gray mold, cucumber powdery mildew, or apple powdery mildew, cotton wilt, cotton verticillium wilt, and cotton damping-off. BRIEF DESCRIPTION OF THE DRAWINGS

[0121] Figure 1 The figure is a flow chart for the preparation of the compound represented by formula I. DETAILED DESCRIPTION

[0122] The present invention is described below by means of specific examples, but the present invention is not limited thereto.

[0123] Unless otherwise specified, the reagents and materials in the examples of the present invention are commercially available.

[0124] 1. Preparation of the compound of formula I, the corresponding flow chart is shown in Figure 1 :

[0125] Example 1. Preparation of compound I3a-60:

[0126] 1. Preparation of 2-chloroisonicotinoyl chloride

[0127] To a 250 mL single-necked flask, add 15.8 g (0.1 mol) of 2-chloroisonicotinic acid and 100 mL of dichloromethane. Stir at room temperature, then dropwise add 19 g of oxalyl chloride (1.5 eq) and one drop of DMF as a catalyst. Allow to react at room temperature for 2 h, monitored by TLC. Upon completion, concentrate and dry to yield 17.4 g of 2-chloroisonicotinyl chloride (98% yield).

[0128] 2. Preparation of (4-(tert-butyl)phenyl)(2-chloropyridin-4-yl)methanone

[0129] Take a 250mL three-necked flask and install a condenser and thermometer. Add 13.4g (0.1mol) of tert-butylbenzene and 100mL of dichloromethane. Stir in an ice bath for 15 minutes. Add dropwise a dichloromethane solution of 17.4g of the prepared 2-chloroisonicotinoyl chloride. Continue stirring in the ice bath for 10 minutes. Add 26.6g of AlCl3 in batches, maintaining the temperature at 5°C. After the addition is complete, continue the ice bath and react for 6 hours. TLC spot plate detection. After the reaction is complete, pour the reaction solution into ice water containing 5% anhydrous sodium sulfate, extract with ethyl acetate, combine the organic layers, and dry over anhydrous sodium sulfate. After concentration, recrystallize with petroleum ether and filter to obtain 20g of (4-(tert-butyl)phenyl)(2-chloropyridin-4-yl)methanone in a 74% yield. 1 H NMR (300MHz, CDCl3) δ8.46(d,J=4.8Hz,1H),7.69(d,J=8.2Hz,2H),7.56–7.36(m,4H),1.29(s,9H).

[0130] 3. Preparation of 3-(4-(tert-butyl)phenyl)-3-(2-chloropyridin-4-yl)acrylic acid

[0131] Under stirring, a mixture of 60% sodium hydride (15 mmol) and tetrahydrofuran (THF, 10 mL) was added dropwise to a THF solution containing triethyl phosphinoacetate (3 mL, 10 mmol) at 0°C. After hydrogen evolution ceased, a THF solution of the prepared (4-(tert-butyl)phenyl)(2-chloropyridin-4-yl)methanone (6 mL, 5 mmol) was added dropwise, and the mixture was stirred and reacted at room temperature for 10 hours. TLC monitoring was performed. After the reaction was complete, water (30 mL) was slowly added, and the mixture was extracted with ethyl acetate (10 mL x 4). The combined organic phases were washed with water, dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness in vacuo to yield ethyl 3-(4-(tert-butyl)phenyl)-3-(2-chloropyridin-4-yl)acrylate. The resulting oil was dissolved in methanol (30 mL) and a NaOH solution (7.5 mL, 2 mol / L) and stirred at room temperature for 10 hours. The reaction mixture was evaporated in vacuo to remove the solvent. The crude product was dissolved in water (40 mL) and extracted twice with diethyl ether (20 mL). The pH was then adjusted to 2-3 and extracted again with diethyl ether (20 mL x 3). The organic phases were combined, washed with water, and dried over anhydrous Na2SO4. The crude product was filtered and the filtrate evaporated to dryness. The crude product was recrystallized from ethanol to obtain 3-(4-(tert-butyl)phenyl)-3-(2-chloropyridin-4-yl)acrylic acid as a white powder in an 85% yield. 1 H NMR (300MHz, CDCl3) δ10.96 (s, 1H), 8.45 (d, J = 5.0Hz, 1H), 7.39 (d, J = 8.5Hz, 2 H),7.25–7.15(m,3H),7.12(dd,J=5.1,1.4Hz,1H),6.47(s,1H),1.33(s,9H).

[0132] 4. Preparation of 3-bromopropyl-3-(4-(tert-butyl)phenyl)-3-(2-chloropyridin-4-yl)acrylate

[0133] 3.16 g of 3-(4-(tert-butyl)phenyl)-3-(2-chloropyridin-4-yl)acrylic acid was dissolved in 50 mL of acetonitrile, and 2 g (1 eq) of 1,3-dibromopropane and 2.76 g of potassium carbonate (2 eq) were added. The mixture was heated under reflux for 3 h. TLC spot plate monitoring was performed. After the reaction was complete, the reaction solution was concentrated and separated by column chromatography to obtain 3.74 g of 3-bromopropyl-3-(4-(tert-butyl)phenyl)-3-(2-chloropyridin-4-yl)acrylate in a yield of 85.6%. 1H NMR (300MHz, CDCl3) δ8.45–8.29(m,1H),7.47–7.34(m,2H),7.24–7.07(m,4H),6.49–6. 37(m,1H),4.21–4.08(m,2H),3.38–3.04(m,2H),2.13–1.89(m,2H),1.41–1.28(m,9H).

[0134] 5. Preparation of I3a-60

[0135] 2.18 g of the obtained 3-bromopropyl-3-(4-(tert-butyl)phenyl)-3-(2-chloropyridin-4-yl)acrylate was dissolved in acetonitrile, and 1.5 eq of triphenylphosphine was added. The mixture was heated under reflux for 5 h. After the reaction was complete, the reaction solution was concentrated and separated by column chromatography to obtain compound I3a-60 as a viscous substance in a 64% yield.

[0136] I3a-60: 1 H NMR (300MHz, DMSO) δ8.30–8.23(m,1H),7.83–7.72(m,9H),7.69–7.61(m,6H),7.34–7.27(m,2H),7.20–7.11(m,2H), 7.07–6.96(m,2H),6.46–6.41(m,1H),4.29(q,J=6.3Hz,2H),3.90–3.75(m,2H),1.86(d,J=7.6Hz,2H),1.24(s,9H).

[0137] I6a-60: 1 H NMR (300MHz, DMSO) δ8.23–8.18(m,1H),7.77–7.66(m,9H),7.64–7.56(m,6H),7.27–7.22(m,2H),7.08–6.94(m,4H),6.32–6.24(m,1H) ,6.32–6.24(m,1H),3.87–3.78(m,2H),3.68–3.54(m,2H),1.58–1.46(m,4H),1.39–1.28(m,2H),1.22–1.17(m,9H),1.14–0.96(m,2H).

[0138] I9a-60: 1H NMR (300MHz, DMSO) δ8.21–8.10(m,1H),7.68–7.59(m,9H),7.57–7.50(m,6H),7.22–7.15(m,2H),7.02–6.87(m,4H),6. 27–6.16(m,1H),3.82–3.72(m,2H),3.47(s,2H),1.44(s,4H),1.31–1.19(m,2H),1.15–1.09(m,9H),1.07–0.94(m,8H).

[0139] I 11 a-60: 1 H NMR (300MHz, DMSO) δ8.41–8.27(m,1H),7.41–7.30(m,2H),7.21–7.04(m,4H),6.39(d,J=18.6Hz,1H),4.03–3. 94(m,2H),3.37(t,J=6.8Hz,2H),1.87–1.76(m,2H),1.50–1.37(m,4H),1.33–1.28(m,9H),1.27–1.17(m,12H).

[0140] Example 2, Preparation of Compound I6b-27:

[0141] 1. Preparation of Isonicotinoyl Chloride

[0142] To a 250 mL single-necked flask, add 12.3 g (0.1 mol) of isonicotinic acid and 100 mL of dichloromethane. Stir at room temperature, then dropwise add 19 g of oxalyl chloride (1.5 eq) and one drop of DMF as a catalyst. Allow to react at room temperature for 2 h. Monitor by TLC. Upon completion, concentrate and dry to yield 16.9 g of isonicotinic acid chloride (95% yield).

[0143] 2. Preparation of 4-(4-chlorobenzoyl)pyridine

[0144] Take a 250mL three-necked flask and install a condenser and a thermometer. Add 11.2g (0.1mol) of chlorobenzene and 100mL of dichloromethane. Stir under ice bath for 15min, add dropwise a dichloromethane solution containing 17.8g of 2-chloroisonicotinoyl chloride, and continue stirring in ice bath for 10min. Add 26.6g of AlCl3 in batches, keeping the temperature at 5°C. After the feeding is completed, continue the ice bath and react for 6h. TLC spot plate detection, after the reaction is complete, pour the reaction solution into ice water containing 5% anhydrous sodium sulfate, extract with ethyl acetate, combine the organic layers, and dry over anhydrous sodium sulfate. After concentration, recrystallize with petroleum ether and filter to obtain 15.6g of 4-(4-chlorobenzoyl)pyridine with a yield of 71.7%, white crystals, 1H NMR (300MHz, CDCl3) δ8.91-8.75(m,2H),7.86-7.67(m,2H),7.63–7.53(m,2H),7.53-7.45(m,2H).

[0145] 3. Preparation of 3-(4-chlorophenyl)-3-(pyridin-4-yl)acrylic acid

[0146] Under stirring, a mixture of 60% sodium hydride (15 mmol) and tetrahydrofuran (THF, 10 mL) was added dropwise to a THF solution containing triethyl phosphinoacetate (3 mL, 10 mmol) at 0°C. After hydrogen evolution ceased, a THF solution of 4-(4-chlorobenzoyl)pyridine (6 mL, 5 mmol) was added dropwise, and the mixture was stirred at room temperature for 10 hours. TLC monitoring was performed. After the reaction was complete, water (30 mL) was slowly added, and the mixture was extracted with ethyl acetate (10 mL x 4). The combined organic phases were washed with water, dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness in vacuo to yield ethyl 3-(4-chlorophenyl)-3-(pyridin-4-yl)acrylate. The oil was dissolved in methanol (30 mL) and NaOH solution (7.5 mL, 2 mol / L) and stirred at room temperature for 10 hours. The reaction mixture was evaporated in vacuo to remove the solvent, and the crude product was dissolved in water (40 mL) and extracted twice with diethyl ether (20 mL). The pH was then adjusted to 2-3 and extracted again with diethyl ether (20 mL x 3). The combined organic phases were washed with water and dried over anhydrous Na2SO4. The filtrate was filtered and evaporated to dryness. The crude product was recrystallized from ethanol to obtain 3-(4-chlorophenyl)-3-(pyridin-4-yl)acrylic acid as a light yellow powder in an 87% yield. 1 H NMR (300MHz, CDCl3) δ10.87(s,1H),8.85-8.69(m,2H),7.74-7.61(m,2H),7.50–7.43(m,2H),7.36-7.25(m,2H),6.35(s,1H).

[0147] 4. Preparation of N-6-bromohexyl 3-(4-chlorophenyl)-3-(pyridin-4-yl)acrylamide

[0148] 2.59 g of 3-(4-chlorophenyl)-3-(pyridin-4-yl)acrylic acid was dissolved in 50 mL of acetonitrile, and 2 g (1 eq) of 6-bromohexylamine and 2.76 g of potassium carbonate (2 eq) were added. The mixture was heated under reflux for 3 h. TLC spot plate monitoring was performed. After the reaction was complete, the reaction solution was concentrated and separated by column chromatography to obtain 3.04 g of N-6-bromohexyl 3-(4-chlorophenyl)-3-(pyridin-4-yl)acrylamide in a yield of 69.2%. 1H NMR(300MHz, CDCl3)8.95-8.79(m,2H),7.84-7.53(m,4H),7.47-7.36(m,2 H),6.56(s,1H),4.02–3.88(m,2H),3.48–3.04(m,4H),2.23–1.78(m,4H).

[0149] 5. Preparation of I6b-27

[0150] 4.20 g of N-6-bromohexyl 3-(4-chlorophenyl)-3-(pyridin-4-yl)acrylamide was dissolved in acetonitrile, and 1.5 eq of triphenylphosphine was added. The mixture was heated under reflux for 5 h. After completion of the reaction, the reaction solution was concentrated and separated by column chromatography to obtain compound I6b-27 as a viscous substance in a 54% yield.

[0151] I6b-27: 1 H NMR (300MHz, DMSO) δ8.23–8.18(m,1H),7.77–7.66(m,9H),7.60–7.56(m,6H),7.27–7.22(m,2H),7.08–6.94(m,4H) ,6.32–6.24(m,1H),3.87–3.78(m,2H),3.68–3.54(m,2H),1.58–1.46(m,4H),1.39–1.28(m,2H),1.14–0.96(m,2H).

[0152] Example 3, Preparation of Compound I6c-27:

[0153] 1. Preparation of N-(6-bromohexyl)-3-(4-chlorophenyl)-N-methyl-3-(pyridin-4-yl)acrylamide

[0154] 4.20 g of N-6-bromohexyl 3-(4-chlorophenyl)-3-(pyridin-4-yl)acrylamide was dissolved in dichloromethane, 1 eq of iodomethane and 2 eq of K2CO3 were added, and the mixture was allowed to react at room temperature for 3 h. TLC was performed. After the reaction was complete, the reaction solution was filtered and concentrated, and then purified by column chromatography to obtain N-(6-bromohexyl)-3-(4-chlorophenyl)-N-methyl-3-(pyridin-4-yl)acrylamide as a light yellow solid. 1 HNMR(300MHz, CDCl3)8.93-8.75(m,2H),7.80-7.39(m,4H),7.30-7.25(m,2H),6. 46(s,1H),4.12–3.90(m,2H),3.75(s,3H),3.58–3.14(m,4H),2.17–1.69(m,4H).

[0155] 2. Preparation of I6c-27

[0156] 4.34 g of N-(6-bromohexyl)-3-(4-chlorophenyl)-N-methyl-3-(pyridin-4-yl)acrylamide was dissolved in acetonitrile, and 1.5 eq of triphenylphosphine was added. The mixture was heated under reflux for 5 h. After completion of the reaction, the reaction solution was concentrated and separated by column chromatography to obtain compound I6c-27 as a viscous substance in a 57% yield.

[0157] I9c-27: 1 H NMR (300MHz, DMSO)8.80-8.61(m,2H),7.81-7.73(m,2H),7.68–7.59(m,9H),7.57–7.43(m,8H),7.33-7 .21(m,2H),6.22(s,1H),3.82–3.72(m,2H),3.68(s,3H),3.47(s,2H),1.44(s,4H),1.31–1.19(m,2H).

[0158] Example 4, Preparation of Compound I6d-27:

[0159] 1. Preparation of N-(6-bromohexyl)-3-(4-chlorophenyl)-N-isopropyl-3-(pyridin-4-yl)acrylamide

[0160] 4.20 g of N-6-bromohexyl-3-(4-chlorophenyl)-3-(pyridin-4-yl)acrylamide was dissolved in dichloromethane, 1 eq of 2-iodopropane and 2 eq of K2CO3 were added, and the mixture was allowed to react at room temperature for 3 h. TLC was performed. After the reaction was complete, the reaction solution was filtered and concentrated, and then purified by column chromatography to obtain N-(6-bromohexyl)-3-(4-chlorophenyl)-N-isopropyl-3-(pyridin-4-yl)acrylamide as a light yellow solid. 1 H NMR(300MHz, CDCl3)8.63-8.52(m,2H),7.53-7.39(m,4H),7.33-7.28(m,2H),6.72(s,1H) ,3.80-3.52(m,3H),3.04–2.89(m,2H),2.35–2.26(m,2H),2.17–1.69(m,4H),1.26(s,6H).

[0161] 2. Preparation of I6d-27

[0162] 4.62 g of N-(6-bromohexyl)-3-(4-chlorophenyl)-N-isomethyl-3-(pyridin-4-yl)acrylamide was dissolved in acetonitrile, and 1.5 eq of triphenylphosphine was added. The mixture was heated under reflux for 5 h. After completion of the reaction, the reaction solution was concentrated and separated by column chromatography to obtain compound I6d-27 as a viscous substance in a 43% yield.

[0163] 1 H NMR(300MHz, CDCl3)8.76-8.63(m,2H),7.64–7.59(m,9H),7.57-7.39(m,10H),7.32-7.24(m,2H),6. 65(s,1H),3.76-3.48(m,3H),3.00–2.85(m,2H),2.31–2.20(m,2H),2.11–1.67(m,4H),1.28(s,6H).

[0164] Unless otherwise stated, in the following embodiments of the present invention, the amount of each component is calculated as a percentage by weight, and the active component is added after being 100% reduced.

[0165] Example 5: Preparation of a wettable powder containing 50% of the compound of formula I:

[0166] The wettable powder comprises: 50% of the compound of formula I, 5% of a dispersant polycarboxylate, 3% of a wetting agent sodium lauryl sulfate, and 42% of a solid carrier or disintegrant bentonite. The components are mixed in the proportions and then air flow-pulverized to obtain a wettable powder containing 50% of the compound of formula I.

[0167] Example 6: Preparation of an emulsifiable concentrate containing 30% of the compound of formula I:

[0168] The emulsifiable concentrate comprises: 30% of the compound of formula I, 12% of an emulsifier, polyoxyalkylene alkyl aryl ether, 10% of a penetrant, and 48% of a liquid carrier, cyclohexanone. The components are mixed in the proportions to obtain a transparent emulsifiable concentrate containing 30% of the compound of formula I.

[0169] Example 7: Preparation of water-dispersible granules containing 60% of the compound of formula I:

[0170] The water-dispersible granules comprise: 70% of the compound of formula I, 3% of alkylbenzene sulfonic acid calcium salt as a dispersant, 3% of lignin sulfonate as a dispersant, 4% of sodium lauryl sulfate as a wetting agent, and 20% of solid carrier or filler starch. The components are mixed in the proportions to obtain water-dispersible granules containing 60% of the compound of formula I.

[0171] Example 8, determination of bactericidal activity:

[0172] The method for detecting the fungicidal activity of the compound of formula I of the present invention against fungal diseases of plants is as follows:

[0173] Mycelial Growth Rate Assay: This test is conducted in accordance with the Agricultural Industry Standard of the People's Republic of China (NY / T1156.2-2006) using the mycelial growth rate method. Activated pathogens are aseptically punched with a 5mm diameter borer on a clean bench. A bacterial cake is cut and inoculated with a No. 11 scalpel onto the center of a cooled, medicated culture medium. The dish is covered and inverted in a 25°C incubator for incubation. Three replicates are prepared, and the average value is used for statistical analysis.

[0174] When the diameter of CK reaches 6-8 cm, the diameter of each treated colony is measured by the cross method, and the colony growth diameter is calculated according to the following formula (1), and the average value is taken.

[0175] Colony growth diameter = colony diameter - cake diameter (1)

[0176] The mycelial growth inhibition rate of the compound of formula I on pathogenic bacteria was calculated using the growth diameter of the blank control colony and the growth diameter of the colony treated with the agent according to the following formula (2):

[0177] Mycelial growth inhibition rate (%) = (control colony growth diameter - drug-treated colony growth diameter) /

[0178] Control colony growth diameter × 100 (2)

[0179] Select Ar1=[(R2) m =C(CH3)3], Ar2 = Q1 [N = 4, R3 = 3-Cl], Ar3 = [R4 = H], X is O, Y is Br, the length of the carbon chain n is different I3a-180, I6a-180, I9a-180 and I 11 The fungicidal activity of a-180 and the existing product pyrimorph were tested. The test results are listed in Table 1 below:

[0180] Table 1. Comparative test results of bactericidal activity characterized by inhibition rate (0.07 mM)

[0181] Cotton withering Pythium aphanidermatum Rapeseed sclerotia Tomato gray mold Phytophthora capsici Cotton wilt Wheat Gibberella Rice blast Grape anthrax Pyrimorph 77.46 13.80 31.15 23.63 97.29 30.23 33.09 23.82 24.22 <![CDATA[I3a-60]]> 92.71 100.00 96.28 82.70 83.26 85.78 38.69 74.04 80.67 <![CDATA[I6a-60]]> 94.31 100.00 96.01 51.05 83.75 82.89 29.93 67.49 70.44 <![CDATA[I9a-60]]> 82.47 99.54 81.39 46.84 72.67 79.99 17.52 57.06 67.11 <![CDATA[I 11 a-60]]> 75.64 90.60 59.33 37.34 34.76 75.51 26.03 51.97 34.00

[0182] Industrial Applications

[0183] The above test results demonstrate that the compounds of Formula I provided herein possess broad-spectrum and excellent fungicidal activity and can be used to control diseases of a variety of crops caused by four major pathogenic fungi: Ascomycetes, Basidiomycetes, Deuteromycetes, and Oomycetes. Even at low doses, these compounds exhibit excellent control effects against harmful fungi and are widely used as fungicides.

Claims

1. A compound represented by formula I, characterized in that: In Formula 1: X is selected from O; Y is selected from Cl, Br, and I; n is an integer from 1 to 18; Ar1 is selected from the group consisting of substituted phenyl groups represented by the following formula: In the substituted phenyl group Ar1: R2=C1-C5 straight chain alkyl or branched chain alkyl; m=0-5, when m>1, R2 are the same or different; Ar2 is the same as Q; Q is selected from any one of the following aromatic heterocyclic groups Q1 to Q4: Wherein formula Q1: R3=H, F, Cl, OCH3 or CF3; N is at the 2-, 3- or 4-position; Ar3 is selected from the monosubstituted phenyl group represented by the following formula: Wherein R4=H, CH3, CH3O or CF3.

2. The method for preparing the compound of formula I according to claim 1, characterized in that: The method comprises the following steps: in an organic solvent, subjecting the following compounds of formula II and formula III to a nucleophilic reaction to obtain a compound of formula I: In the formula II and formula III, the definitions of Ar1, Ar2, Ar3, X, Y and n are the same as those of the corresponding groups in the compound of formula I.

3. The method for preparing the compound of formula I according to claim 2, wherein: The molar ratio of the compounds of formula II and formula III is 1:1.5; The temperature of the nucleophilic reaction is 30-200°C, and the reaction time is 3-36h; The organic solvent is selected from acetonitrile, ethylene glycol dimethyl ether, benzene, toluene or 1,2-dichloroethane.

4. A composition, characterized in that Calculated by weight percentage, the composition comprises 0.1-99% of the compound of formula I according to claim 1 and an agriculturally acceptable carrier thereof.

5. The composition according to claim 4, characterized in that: The agriculturally acceptable carrier is selected from a solid carrier and / or a liquid carrier; The solid carrier is at least one compound selected from the group consisting of natural or synthetic silicates, ammonium sulfate, calcium sulfate, aluminum oxide silicate, natural or synthetic resins, starch, bentonite and wax; Wherein, the natural or synthetic silicate is at least one selected from the group consisting of attapulgite, talc, aluminum silicate, diatomaceous earth, mica, montmorillonite and calcium silicate; the natural or synthetic resin is selected from styrene polymers; and the wax is selected from beeswax and / or paraffin wax; The liquid carrier is selected from at least one of water, C1-C4 alcohol, C3-C8 ketone, and petroleum fractions, wherein the alcohol is ethanol and / or ethylene glycol; the ketone is at least one of acetophenone, acetone, methyl ethyl ketone, and cyclohexanone; and the petroleum fraction is kerosene and / or mineral oil.

6. The composition according to claim 4, characterized in that: The composition includes a surfactant; The surfactant is selected from at least one of an emulsifier, a dispersant, a wetting agent and a penetrant; The emulsifier is at least one selected from calcium alkylbenzene sulfonate, phenylphenol polyoxyethyl ether, alkylphenol formaldehyde resin polyoxyethyl ether, phenylethylphenol polyoxyethyl polypropylene ether, polyoxyalkylene alkyl aryl ether and ethylene oxide-propylene oxide block copolymer; The dispersant is at least one selected from polycarboxylates, lignin sulfonates, alkylphenol polyoxyethylene formaldehyde condensate sulfates, alkylbenzenesulfonic acid calcium salts, benzenesulfonic acid formaldehyde condensate sodium salts, sulfonated castor oil sodium salts, sodium alkyl aryl sulfonates, fatty acid polyoxyethylene esters and ester polyoxyethylene ethers; The wetting agent is at least one selected from sodium lauryl sulfate, sodium dodecylbenzene sulfonate, lakai powder BX, saponin powder, silkworm excrement and soapberry powder; The composition further includes other auxiliary agents; The other auxiliary agent is at least one selected from disintegrants, defoaming agents, antifreeze agents and thickeners; The disintegrant is at least one selected from bentonite, urea, ammonium sulfate, aluminum chloride and glucose; The defoaming agent is selected from silicone compounds, C 10 -C 20 Saturated fatty acid compounds and C8-C 10 At least one selected from fatty alcohol compounds; The antifreeze agent is at least one selected from ethylene glycol, propylene glycol, and glycerol; The thickener is at least one selected from xanthan gum, polyvinyl alcohol and polyethylene glycol.

7. Use of the compound of formula I according to claim 1 and / or the composition according to any one of claims 4 to 6 in the preparation of a botanical fungicide.

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