An isoxazoline compound containing a dihydrobenzofuranyl group, and its preparation method and application

Abstract

The present invention discloses a dihydrobenzofuranyl-containing isoxazoline compound, a preparation method thereof, and an application thereof. The dihydrobenzofuranyl-containing isoxazoline compound is shown in formula (I). The compound or its pharmaceutically acceptable salt has a simple preparation method, high yield, and low cost. The obtained 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-arylisoxazoline compound or its pharmaceutically acceptable salt exhibits high activity against plant pathogens such as cucumber downy mildew, has good control effects, and can be used as an alternative drug for plant fungicides.

Description

Technical Field

[0001] The present invention relates to the technical field of compound pesticides, in particular to an isoxazoline compound containing a dihydrobenzofuranyl group, and a preparation method and application thereof. Background Art

[0002] Isoxazoline derivatives and their substituted compounds have agricultural bactericidal, insecticidal, antiviral and herbicidal activities, and are therefore widely used in green pesticides. For example, the 3,5-disubstituted isoxazoline derivative synthesized by Ning Guohui in 2014 is a highly effective and broad-spectrum agricultural fungicide (Ning Guohui et al., Organic Chemistry, 2014, 34(09):1800). The target compound has a good control effect on eight fungi, including cucumber gray mold, tomato early blight, peanut brown spot, rapeseed sclerotium, apple ring spot, wheat fusarium, pepper phytophthora, and rice sheath blight, showing broad-spectrum antibacterial activity. Several fungicides have been developed, such as the antibacterial drugs sulfamethoxazole and benzyl oxacillin. Due to the advantages of high efficiency, low toxicity and environmental friendliness of isoxazoline compounds, isoxazoline compounds remain a hot topic in the creation of green pesticides today. However, the existing isoxazoline compounds have complex preparation methods or their activity needs to be improved. Therefore, it is necessary to develop new isoxazoline compounds for controlling plant pathogens. Summary of the Invention

[0003] One of the objects of the present invention is to provide an isoxazoline compound containing a dihydrobenzofuranyl group or a pharmaceutically acceptable salt thereof.

[0004] A second object of the present invention is to provide a method for preparing isoxazoline compounds containing dihydrobenzofuranyl.

[0005] The third object of the present invention is to provide an isoxazoline compound containing a dihydrobenzofuranyl group or a pharmaceutically acceptable salt thereof for use as an agricultural fungicide.

[0006] A fourth object of the present invention is to provide a pesticide composition.

[0007] One of the purposes of the present invention is achieved in that:

[0008] An isoxazoline compound containing a dihydrobenzofuranyl group or a pharmaceutically acceptable salt thereof, whose chemical structure is shown in formula (I):

[0009]

[0010]

[0011] Wherein, R is selected from C1~C6 straight chain or branched alkyl, halogen-substituted C1~C6 straight chain or branched alkyl, C3~C6 cycloalkyl, C1~C6 straight chain or branched alkyl substituted C3~C6 cycloalkyl, halogen-substituted C3~C6 cycloalkyl, phenyl, C1~C6 straight chain or branched alkyl substituted phenyl, halogen-substituted C1~C6 straight chain or branched alkylphenyl, phenyl C1~C6 straight chain or branched alkyl.

[0012] Optionally, the R is a C1-C4 straight or branched alkyl group, or a monohalogen-monosubstituted C1-C4 straight or branched alkyl group; preferably, the R is a C1-C4 straight or branched alkyl group; more preferably, the R is a methyl group, an ethyl group, a propyl group or an isopropyl group; more preferably, the R is a propyl group.

[0013] Optionally, the R is a C3~C6 cycloalkyl group, a C3~C6 cycloalkyl group substituted by a C1~C4 straight chain or branched alkyl group, or a C3~C6 cycloalkyl group mono-substituted or di-substituted by a halogen; preferably, the R is a C3~C6 cycloalkyl group, a C3~C6 cycloalkyl group mono-substituted by a C1~C4 straight chain or branched alkyl group, or a C3~C6 cycloalkyl group mono-substituted by a halogen; preferably, the R is a cyclohexyl group, a cyclohexyl group substituted by a C1~C6 straight chain or branched alkyl group, or a cyclohexyl group mono-substituted or di-substituted by a halogen; preferably, the R is a cyclohexyl group, a cyclohexyl group mono-substituted by a C1~C4 straight chain or branched alkyl group, or a cyclohexyl group mono-substituted by a halogen; more preferably, the R is a cyclohexyl group.

[0014] Optionally, R is phenyl, phenyl substituted by C1~C4 straight chain or branched alkyl, or phenyl substituted by halogen; preferably, R is phenyl, phenyl monosubstituted by C1~C4 straight chain or branched alkyl, or phenyl monosubstituted by halogen; preferably, R is phenyl, phenyl monosubstituted by halogen; more preferably, R is phenyl, tolyl, or phenyl substituted by chlorine; more preferably, R is phenyl or 4-methylphenyl.

[0015] Optionally, the R is a halogen-substituted C1-C4 straight-chain or branched alkylphenyl group; preferably, the R is a halogen-substituted tolyl group or ethylphenyl group.

[0016] Optionally, the R is a phenyl C1-C4 straight-chain or branched alkyl group; preferably, the R is a phenylethyl group.

[0017] Preferably, the isoxazoline compound containing a dihydrobenzofuranyl group or a pharmaceutically acceptable salt thereof is selected from one of the following compounds:

[0018]

[0019]

[0020] The second object of the present invention is achieved in this way:

[0021] The preparation method of the above-mentioned dihydrobenzofuranyl-containing isoxazoline compound or its pharmaceutically acceptable salt comprises the following steps:

[0022] (a) reacting 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)ethane-1-one, i.e., compound B, with a substituted benzaldehyde to obtain 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-3-arylprop-2-en-1-one, i.e., compound C;

[0023] (b) reacting 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-3-arylprop-2-en-1-one, i.e., compound C, with hydroxylamine hydrochloride to obtain compound E, i.e., target compound (I).

[0024] The reaction equation is:

[0025]

[0026] The specific steps of the above reaction include:

[0027] (a) dissolving 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)ethane-1-one, substituted benzaldehyde, and NaOH in a mixed solvent of ethanol and water, and reacting at room temperature for 6-10 hours to obtain 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-3-arylprop-2-en-1-one; wherein the amount ratio of 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)ethane-1-one, substituted benzaldehyde, and NaOH is 1 mmol: 1.0-1.3 mmol: 0.3-0.5 g;

[0028] (b) 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-3-arylprop-2-en-1-one was dissolved in a mixed solvent of ethanol and water, hydroxylamine hydrochloride and NaOH were added with stirring, and the mixture was reacted at room temperature for 20-28 hours to obtain the target compound (I); wherein the molar ratio of 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-3-arylprop-2-en-1-one, hydroxylamine hydrochloride and NaOH was 1:1.0-1.3:2.5-3.5.

[0029] More specifically, Compound B (1 mmol), substituted benzaldehyde (1.2 mmol), and 0.4 g of NaOH were added to a spinner flask. Dissolved in 15 mL of ethanol and 5 mL of water, the mixture was allowed to react at room temperature for approximately 8 hours, resulting in a light yellow solution. After completion of the reaction, the ethanol was removed by spinnereting, and ice water was added to precipitate a yellow solid, which was purified to yield Compound C.

[0030] Specifically, purified compound C (1 mmol) was dissolved in 15 mL of ethanol and 5 mL of water. NaOH (3 mmol) and hydroxylamine hydrochloride (1.2 mmol) were added with stirring and the reaction was allowed to proceed at room temperature. TLC monitoring was performed for approximately 24 hours. After completion of the reaction, the ethanol was dried, ice water was added, and a yellow solid precipitated. The solid was filtered and air-dried. The resulting yellow solid was purified by column chromatography using a 10:1 ratio of petroleum ether to ethyl acetate to afford the final product, isoxazoline E, the target compound (I).

[0031] In the aforementioned steps, the amount of each reaction raw material can refer to the reaction amount known to those skilled in the art.

[0032] The third object of the present invention is achieved in this way:

[0033] The above-mentioned isoxazoline compounds containing dihydrobenzofuranyl or pharmaceutically acceptable salts thereof are used as agricultural fungicides. The fungicides are used to prevent and control plant diseases.

[0034] Preferably, the plant disease is cucumber downy mildew.

[0035] Alternatively, the 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-arylisoxazoline compound represented by formula (I) is used alone as a fungicide.

[0036] Alternatively, the 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-arylisoxazoline compound represented by formula (I) is used in combination with other compounds having fungicidal activity as a fungicide.

[0037] The fourth object of the present invention is achieved in this way:

[0038] A pesticide composition comprises an active ingredient and one or more agriculturally acceptable carriers, wherein the active ingredient comprises a 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-arylisoxazoline compound represented by formula (I) or a pharmaceutically acceptable salt thereof.

[0039] The preparation method of the 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-arylisoxazoline compound or the pharmaceutically acceptable salt thereof of the present invention is simple, has high yield and low cost. The obtained 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-arylisoxazoline compound or the pharmaceutically acceptable salt thereof exhibits high activity against cucumber downy mildew, has good prevention and control effect, can be used as an alternative drug for plant fungicides, and has broad application prospects. DETAILED DESCRIPTION

[0040] The present invention will be further described below with reference to the following examples. The following examples are only for illustration and are not intended to limit the scope of protection of the present invention in any way.

[0041] The processes and methods not described in detail in the following examples are conventional methods known in the art. The reagents used in the examples are all analytically pure or chemically pure and are commercially available or prepared by methods well known to those skilled in the art. The following examples all achieve the objectives of the present invention.

[0042] Example 1

[0043] Synthesis of 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-3-arylprop-2-en-1-one (C):

[0044]

[0045] Compound B (1 mmol), substituted benzaldehyde (1.2 mmol), and 0.4 g of NaOH were added to a spinner flask. 15 mL of ethanol and 5 mL of water were added to dissolve the mixture. The reaction mixture became a light yellow solution. After the reaction was complete, the ethanol was removed by spinning, and ice water was added. Purification revealed the precipitation of a yellow solid C.

[0046] Example 2

[0047] Synthesis of 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-(3-nitrophenyl)isoxazoline (E1):

[0048]

[0049] Purified compound C (1 mmol) was dissolved in 15 mL of ethanol and 5 mL of water. NaOH (3 mmol) and hydroxylamine hydrochloride (1.2 mmol) were added with stirring and allowed to react at room temperature. TLC monitoring was performed for approximately 24 hours. After completion of the reaction, the ethanol was dried and ice water was added to precipitate a yellow solid, which was filtered and air-dried. The resulting yellow solid was purified by column chromatography using petroleum ether:ethyl acetate (10:1) to yield compound E. The yield of the isoxazoline was 12.3%.

[0050] 1H NMR (600MHz, CDCl3) δ8.24(s,1H),8.16(dd,J=8.2,1.1Hz,1H),7.75(d,J=7.7Hz,1H),7.55(t,J=7.9Hz,1H),7.22(s,1H),6.99(s,1H),5.80(d d,J=10.9,7.4Hz,1H),3.90(s,3H),3.85(dd,J=16.5,11.0Hz,1H),3.31(dd,J=16.5,7.4Hz,1H),3.03(d,J=1.8Hz,2H),1.52(d,J=5.5Hz,6H). 13 C NMR (151MHz, CDCl3) δ171.02,163.11,149.50,144.96,130.05,129.56,128.97 (d, J=19 .9Hz),126.97,120.57,115.90,109.19,96.04,88.96,56.23,43.20,28.39.HR-MS-ESI m / z calcd for C 20 H 20 N2O5[M+H] + 369.1450,found369.1441.

[0051] Example 3

[0052] Synthesis of 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-(3-bromophenyl)isoxazoline (E2):

[0053]

[0054] The preparation method of compound E2 is similar to that of Example 2.

[0055] 1 H NMR (600MHz, CDCl3) δ7.54(s,1H),7.43(d,J=7.9Hz,1H),7.31(d,J=7.7Hz,1H),7.23(dd,J=9.3,6.3Hz,2H),6.98(s,1H),5.66(dd ,J=10.9,7.7Hz,1H),3.90(s,3H),3.75(dd,J=16.5,11.0Hz,1H),3.27(dd,J=16.5,7.6Hz,1H),3.03(s,2H),1.52(d,J=4.1Hz,6H). 13C NMR (151MHz, CDCl3) δ191.14,153.07,145.03,135.99,129.27,129.03,128.86,128 .23,125.93,119.69,111.53,90.09,61.06,59.27,56.20,42.76,28.35.HR-MS-ESI m / z calcd for C 20 H 20 BrNO3[M+H] + 402.0705,found 402.0694.

[0056] Example 4

[0057] Synthesis of 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-(3-fluorophenyl)isoxazoline (E3):

[0058]

[0059] The preparation method of compound E3 is similar to that of Example 2.

[0060] 1 H NMR (600MHz, CDCl3) δ7.32(td,J=7.9,5.9Hz,1H),7.23(s,1H),7.15(d,J=7.7Hz,1H),7.11(d,J=9.6Hz,1H),7.01–6.96(m,2H),5.68( dd,J=10.9,7.6Hz,1H),3.89(s,3H),3.76(dd,J=16.4,10.9Hz,1H),3.28(dd,J=16.4,7.6Hz,1H),3.03(s,2H),1.52(d,J=4.2Hz,6H). 13 C NMR (151MHz, CDCl3) δ171.31,162.11,149.57,144.95,136.07,129.31,128.92,128 .21,128.01,120.31,115.90,109.08,95.84,89.04,56.20,43.15,28.38.HR-MS-ESI m / z calcd for C 20 H 20 FNO3[M+H] + 342.1505, found 342.1497.

[0061] Example 5

[0062] Synthesis of 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-(4-methylphenyl)isoxazoline (E4):

[0063]

[0064] The preparation method of E4 is similar to that of Example 2.

[0065] 1 H NMR (600MHz, CDCl3) δ7.28(d,J=8.0Hz,2H),7.24(s,1H),7.17(d,J=7.9Hz,2H),6.99(s,1H),5.66(dd,J=10.7,8.3Hz,1H), 3.90(s,3H),3.71(dd,J=16.4,10.8Hz,1H),3.29(dd,J=16.4,8.2Hz,1H),3.04(s,2H),2.34(s,3H),1.52(d,J=3.3Hz,6H). 13 CNMR (151MHz, CDCl3) δ156.32,149.38,144.81,138.23,138.08,129.51,128.13,126.0 1,122.36,116.94,109.28,88.80,82.41,56.09,43.64,43.14,28.35,21.27.HR-MS-ESI m / zcalcd for C 21 H 23 NO3[M+H] + 338.1756, found 338.1744.

[0066] Example 6

[0067] Synthesis of 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-phenylisoxazoline (E5):

[0068]

[0069] The preparation method of compound E5 is similar to that of Example 2.

[0070] 1H NMR(600MHz, CDCl3) δ7.38(dt,J=15.1,7.4Hz,4H),7.32(d,J=7.0Hz,1H),7.24(s,1H),6.99(s,1H),5.70(dd,J=10.8,8 .1Hz,1H),3.90(s,3H),3.74(dd,J=16.4,10.9Hz,1H),3.31(dd,J=16.4,8.1Hz,1H),3.04(s,2H),1.52(d,J=3.8Hz,6H). 13 C NMR (151MHz, CDCl3) δ191.14,153.07,145.03,135.99,129.27,129.03,128.86,128 .23,125.93,119.69,111.53,90.09,61.06,59.27,56.20,42.76,28.35.HR-MS-ESI m / z calcdfor C 20 H 21 NO3[M+H] + 324.1600,found324.1591.

[0071] Example 7

[0072] Synthesis of 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-(4-fluorophenyl)isoxazoline (E6):

[0073]

[0074] The preparation method of compound E6 is similar to that of Example 2.

[0075] 1 H NMR (600MHz, CDCl3) δ7.36(dd,J=8.5,5.4Hz,2H),7.23(s,1H),7.05(t,J=8.6Hz,2H),6.98(s,1H),5.67(dd,J=10.6,8. 2Hz,1H),3.89(s,3H),3.73(dd,J=16.4,10.8Hz,1H),3.27(dd,J=16.5,8.0Hz,1H),3.03(s,2H),1.52(d,J=3.7Hz,6H). 13C NMR (151MHz, CDCl3) δ190.92,164.07,162.43,153.14,145.04,131.76,129.21,128.28,127 .65,119.66,115.97,115.83,111.62,90.09,60.99,58.62,56.19,42.74,28.32.HR-MS-ESI m / z calcd for C 20 H 20 FNO3[M+H] + 342.1505, found 342.1493.

[0076] Example 8

[0077] Synthesis of 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-(4-chlorophenyl)isoxazoline (E7):

[0078]

[0079] The preparation method of compound E7 is similar to that of Example 2.

[0080] 1 H NMR (600MHz, CDCl3) δ7.36–7.29(m,4H),7.23(s,1H),6.98(s,1H),5.67(dd,J=10.8,7.9Hz,1H),3.89( s,3H),3.74(dd,J=16.4,10.9Hz,1H),3.25(dd,J=16.4,7.8Hz,1H),3.03(s,2H),1.52(d,J=4.0Hz,6H). 13 C NMR (151MHz, CDCl3) δ156.21,149.62,144.89,139.90,134.09,129.04,128.26,127 .36,122.06,117.01,109.52,88.84,81.62,56.14,43.78,43.15,28.33.HR-MS-ESI m / z calcd for C 20 H 20 ClNO3[M+H] + 358.1210,found358.1208.

[0081] Example 9

[0082] Synthesis of 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-(3-methylphenyl)isoxazoline (E8):

[0083]

[0084] The preparation method of compound E8 is the same as that in Example 2.

[0085] 1 H NMR (600MHz, CDCl3) δ7.26(dd,J=7.6,3.8Hz,2H),7.22(s,1H),7.19(d,J=7.6Hz,1H),7.13(d,J=7.5Hz,1H),7.01(s,1H),5.68(dd,J=10. 8,8.2Hz,1H),3.91(s,3H),3.74(dd,J=16.4,10.9Hz,1H),3.32(dd,J=16.4,8.1Hz,1H),3.05(s,2H),2.37(s,3H),1.54(d,J=3.6Hz,6H). 13 C NMR (151MHz, CDCl3) δ156.26,149.37,144.79,141.22,138.60,129.00,128.73,128.12,126.59 ,123.05,122.29,116.95,109.26,88.80,82.43,56.07,43.71,43.12,28.33,21.54.HR-MS-ESI m / z calcd for C 21 H 23 NO3[M+H] + 338.1756, found 338.1746.

[0086] Example 10

[0087] Synthesis of 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-(2-bromophenyl)isoxazoline (E9):

[0088]

[0089] The preparation method of compound E9 is similar to that of Example 2.

[0090] 1H NMR (600MHz, CDCl3) δ7.56(d,J=7.9Hz,2H),7.32(t,J=7.6Hz,1H),7.22(s,1H),7.16(td,J=7.8,1.4Hz,1H),6.98(s,1H),5.95 (dd,J=11.0,6.6Hz,1H),3.95(s,1H),3.90(s,3H),3.16(dd,J=16.6,6.6Hz,1H),3.02(d,J=3.3Hz,2H),1.51(d,J=7.5Hz,6H). 13 C NMR (151MHz, CDCl3) δ156.17,149.52,144.81,140.97,132.83,129.42,128.16,127.95,127 .05,121.97,120.95,117.10,109.29,88.86,81.32,56.09,43.48,43.09,28.33.HR-MS-ESI m / z calcd for C 20 H 20 BrNO3[M+H] + 402.0705,found 402.0695.

[0091] Example 11

[0092] Synthesis of 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-(3-nitrophenyl)isoxazoline (E10):

[0093]

[0094] The preparation method of compound E10 is similar to that of Example 2.

[0095] 1 H NMR (600MHz, CDCl3) δ7.47(dd,J=10.8,4.2Hz,1H),7.26–7.23(m,1H),7.21(s,1H),7.12(t,J=7.5Hz,1H),7.06–7.00(m,1H),6.96(s,1H),5.91 (dd,J=10.9,7.4Hz,1H),3.87(s,3H),3.78(dd,J=16.5,11.0Hz,1H),3.25(dd,J=16.5,7.3Hz,1H),3.00(d,J=1.5Hz,2H),1.49(d,J=5.5Hz,6H). 13C NMR (151MHz, CDCl3) δ156.46, 149.49, 144.81, 129.66 (d, J = 8.1Hz), 128.16, 127.32, 124.5 2,122.03,117.03,115.58,115.44,109.29,88.84,76.58,56.07,43.10,28.33.HR-MS-ESI m / z calcd for C 20 H 20 FNO3[M+H] + 342.1505, found 342.1504.

[0096] Example 12

[0097] Synthesis of 3-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-5-(4-bromophenyl)isoxazoline (E11):

[0098]

[0099] The preparation method of compound E11 is similar to that of Example 2.

[0100] 1 H NMR (600MHz, CDCl3) δ7.49(d,J=8.3Hz,2H),7.27(d,J=6.7Hz,2H),7.23(s,1H),6.97(s,1H),5.66(dd,J=10.7,7.9H z,1H),3.90(s,3H),3.75(dd,J=16.4,10.9Hz,1H),3.25(dd,J=16.4,7.8Hz,1H),3.04(s,2H),1.52(d,J=3.9Hz,6H). 13 C NMR (151MHz, CDCl3) δ156.22,149.62,144.90,140.45,132.01,128.26,127.69,122 .20,122.03,117.03,109.46,88.88,81.65,56.15,43.78,43.16,28.35.HR-MS-ESI m / z calcd for C 20 H 20 BrNO3[M+H] + 402.0705,found402.0694.

[0101] Example 13

[0102] The bactericidal activity test method is as follows:

[0103] 1. Preparation of drug solution

[0104] The compound sample was dissolved in dimethyl sulfoxide according to the sample weight to prepare a stock solution for use. During the test, the compound sample and the control drug were prepared into a 100 mg / L solution in water containing 0.1% Tween 80.

[0105] 2. Host Plant Cultivation

[0106] Set aside when the first true leaf of the cucumber is fully expanded.

[0107] 3. Spray treatment

[0108] The sprayer type is a three-dimensional crop sprayer with a spray pressure of 1.5kg / cm 2 , the spray volume is about 1000L / hm 2 The treated test materials were naturally dried in the shade and inoculated with pathogens 24 hours later.

[0109] 4. Inoculation of pathogens

[0110] The cucumber downy mildew spore suspension (3-5×10 6 The host crops were sprayed with 100 μg / ml of the test material and then transferred to an artificial climate chamber for incubation (24±1°C, RH>90, no light). After 24 hours, the test materials were transferred to the greenhouse for normal management and the fungicidal activity of the test samples was evaluated after 5-7 days.

[0111] 5. Results Survey

[0112] The results were investigated with reference to the "A Manual of Assessment Keys for Plant Diseases" compiled by the American Society of Plant Pathology. The fungicidal activity of the test samples was investigated visually based on the severity of the disease in the control, expressed on a scale of 100-0, with "100" representing no disease and "0" representing the most severe disease severity.

[0113] Control effect of compounds on plant pathogens (%, 100 mg / L)

[0114]

[0115] In vivo experiments showed that compound E2 had a good control effect on cucumber downy mildew at a concentration of 100 mg / L and could be used as an alternative drug for plant fungicides.

Claims

1. An isoxazoline compound containing a dihydrobenzofuranyl group or a pharmaceutically acceptable salt thereof, characterized in that: One of the following compounds: 。 2. The method for preparing the dihydrobenzofuranyl-containing isoxazoline compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein: The steps include: (a) reacting 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)ethan-1-one with a substituted benzaldehyde in the presence of sodium hydroxide to obtain 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-3-arylprop-2-en-1-one; (b) reacting 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-3-arylprop-2-en-1-one with hydroxylamine hydrochloride in the presence of sodium hydroxide to obtain the target compound (I); The reaction formula of the above steps is: ； wherein R is 3-Br, 3-F, 4-CH3, H, 4-F, 4-Cl, 2-Br, 2-F or 4-Br.

3. The preparation method according to claim 2, characterized in that The steps include: (a) dissolving 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)ethane-1-one, substituted benzaldehyde, and NaOH in a mixed solvent of ethanol and water, and reacting at room temperature for 6-10 hours to obtain 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-3-arylprop-2-en-1-one; wherein the amount ratio of 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)ethane-1-one, substituted benzaldehyde, and NaOH is 1 mmol: 1.0-1.3 mmol: 0.3-0.5 g; (b) 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-3-arylprop-2-en-1-one was dissolved in a mixed solvent of ethanol and water, hydroxylamine hydrochloride and NaOH were added with stirring, and the mixture was reacted at room temperature for 20-28 hours to obtain the target compound (I); wherein the molar ratio of 1-(7-methoxy-2,3-dihydrobenzofuran-5-yl)-3-arylprop-2-en-1-one, hydroxylamine hydrochloride and NaOH was 1:1.0-1.3:2.5-3.

5.

4. Use of the dihydrobenzofuranyl-containing isoxazoline compound or its pharmaceutically acceptable salt as an agricultural fungicide according to claim 1, wherein: The fungicide is used for preventing and controlling cucumber downy mildew.

5. The use according to claim 4, characterized in that The compound of formula (I) or its pharmaceutically acceptable salt is used alone as a fungicide, or the compound of formula (I) or its pharmaceutically acceptable salt is used in combination with other compounds having fungicidal activity.

6. A pesticide composition comprising an active ingredient and one or more agriculturally acceptable carriers, characterized in that: The active component comprises the dihydrobenzofuranyl-containing isoxazoline compound according to claim 1 or a pharmaceutically acceptable salt thereof.

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