Patchouli ketone acylhydrazone compound as well as preparation method and application thereof

Abstract

The invention discloses a pogostemon cablin ketone acylhydrazone compound, a preparation method and application, an acylhydrazone group is introduced into pogostemon cablin ketone, so that a compound with a novel structure is obtained, the structure of the compound is shown as a formula I: # imgabs0 #, and the preparation method of the compound is relatively simple in operation, easily available in raw materials and low in cost. The compound has broad-spectrum bactericidal activity, especially has a remarkable inhibition effect on valsa mali, sclerotinia sclerotiorum and botrytis cinerea, and can be used as a bactericide for preventing and treating plant fungal diseases.

Description

Technical Field

[0001] The invention belongs to the technical field of pathogen control, and particularly relates to a patchouli ketoacylhydrazone compound, a preparation method and an application thereof. Background Art

[0002] Plant diseases caused by plant pathogens pose a serious threat to global food production, reducing crop yields, degrading the quality of cash crops, and threatening the health of humans and animals, resulting in significant economic losses. Chemical control can significantly reduce the harm caused by plant diseases, but in recent years, the unregulated use of chemical pesticides, such as excessive use, has led to increased resistance levels in plant pathogens and increased environmental residue levels. Therefore, the development of a low-toxic, highly effective, and environmentally friendly fungicide is an urgent need.

[0003] Patchouli ketone is a natural product extracted from the plant Patchouli. Patchouli ketone has a wide range of biological activities, such as bactericidal, anthelmintic, anti-tumor and anti-inflammatory. Our previous studies have shown that the natural product Patchouli ketone exhibits good agricultural antibacterial activity against the E. coli Sclerotinia sclerotiorum. 50 It is 3.02μg / mL.

[0004] To discover new agricultural fungicides, the inventors introduced different acylhydrazone compounds into patchouli ketone, resulting in a class of structurally novel compounds that were found to be effective in controlling plant pathogens. Currently, there are no reports of the patchouli ketone acylhydrazone compounds described in the present invention. Therefore, the present invention discloses a class of structurally novel patchouli ketone acylhydrazone compounds for use as agricultural fungicides. Summary of the Invention

[0005] The present invention aims to provide a patchouli ketoacylhydrazone compound, a preparation method and application thereof as an agricultural fungicide.

[0006] The technical solution adopted by the present invention is:

[0007] A patchouli ketoacylhydrazone compound, represented by formula I:

[0008]

[0009] Wherein: R is selected from one of hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkyl, halogenated C1-C4 alkoxy, cyano and nitro; or a salt of the compound represented by formula I.

[0010] A patchouli ketoacylhydrazone compound, represented by formula I:

[0011]

[0012] The specific substituents in Formula I are shown in the following table:

[0013]

[0014]

[0015] A method for preparing a patchouli ketoacylhydrazone compound, wherein the patchouli ketoacylhydrazone compound is the patchouli ketoacylhydrazone compound described in the present invention;

[0016] The preparation method comprises the following steps: reacting a compound represented by formula II with a compound represented by formula III in an organic solvent to obtain a compound represented by formula I;

[0017]

[0018] Optionally, an additive is mixed into the organic solvent, the additive being selected from one of 4-dimethylaminopyridine, dicyclohexylcarbodiimide and cerium chloride heptahydrate; and the organic solvent is selected from one of dichloromethane, toluene, anhydrous ethanol and ethyl acetate.

[0019] Optionally, the reaction temperature is -25 to 80° C., and the reaction time is 5 min to 24 h.

[0020] Optionally, the molar ratio of the compound represented by formula II to the compound represented by formula III is 1:(1-1.2).

[0021] Use of any patchouli ketoacylhydrazone compound of the present invention in preparing plant fungicides.

[0022] Optionally, the plant fungicide is used to prevent and control rice sheath blight, tomato gray mold, apple rot, rapeseed sclerotinia, wheat take-all disease and / or corn curvature spore disease.

[0023] The patchouli ketone acylhydrazone compounds prepared by any of the preparation methods of the present invention are used in preparing plant fungicides.

[0024] A botanical fungicide, comprising any of the patchouli ketoacylhydrazone compounds of the present invention as an active ingredient;

[0025] The weight percentage of the active component in the composition is 0.1% to 99%.

[0026] The beneficial effects of the present invention are:

[0027] The invention introduces different acylhydrazone compounds into the natural product patchouli ketone. The obtained compound has a novel structure and good fungicidal activity, especially having obvious inhibitory effect on apple rot bacteria, rapeseed sclerotinia bacteria or tomato gray mold bacteria. DETAILED DESCRIPTION

[0028] The present invention is further described below with reference to specific examples, but the present invention is not limited to these examples. The methods described are conventional methods unless otherwise specified. The materials described are commercially available unless otherwise specified.

[0029] The patchouli ketoacylhydrazone compound of the present invention refers to a compound having a structure as shown in Formula I:

[0030]

[0031] Wherein: R is selected from hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkyl, halogenated C1-C4 alkoxy, cyano, nitro; or a salt of the compound represented by formula I.

[0032] For more details, see the data listed in Table 1:

[0033] Table 1

[0034]

[0035]

[0036]

[0037] A method for preparing a patchouli ketoacylhydrazone compound, wherein the patchouli ketoacylhydrazone compound is the patchouli ketoacylhydrazone compound of the present invention;

[0038] The method comprises the following steps: reacting a compound represented by formula II with a compound represented by formula III in an organic solvent to obtain a compound represented by formula I;

[0039]

[0040] An additive is mixed into an organic solvent, wherein the additive is selected from one of 4-dimethylaminopyridine, dicyclohexylcarbodiimide and cerium chloride heptahydrate; and the organic solvent is selected from one of dichloromethane, toluene, anhydrous ethanol and ethyl acetate.

[0041] The reaction temperature is -25 to 80°C, and the reaction time is 5 minutes to 24 hours;

[0042] The molar ratio of the compound represented by formula II to the compound represented by formula III is 1:(1-1.2).

[0043] The patchouli ketoacylhydrazone compounds of the present invention are used for preparing plant fungicides.

[0044] Plant fungicides are used to control rice sheath blight, tomato gray mold, apple rot, rapeseed sclerotinia, wheat take-all disease and / or corn curvature spore disease.

[0045] The patchouli ketone acylhydrazone compounds prepared by the preparation method of the present invention are used in preparing plant fungicides.

[0046] Example 1: Preparation of (E)-3-chloro-N'-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-4-methylpentylidene)benzohydrazide (I-05)

[0047]

[0048] Patchouli ketone 1.12 g (5 mmol), 3-chlorobenzohydrazide 0.85 g (5 mmol), and cerium chloride heptahydrate 0.185 g (0.5 mmol) were added to a 25 ml single-necked flask in sequence. Anhydrous ethanol was used as the solvent and the mixture was reacted at 60°C for 8 hours. The mixture was purified by column chromatography (petroleum ether:ethyl acetate = 1:1). After drying, a white solid was obtained with a yield of 67.2%. mp 157.5-159.2°C. 1 H NMR (500MHz, DMSO-d6) δ11.61(s,1H),7.92(s,1H),7.86(d,J=7.3Hz,1H),7.72(d,J=7.7Hz,1H),7.61(t,J=7.8Hz,1H), 5.86(s,1H),3.15-3.12(m,2H),2.14(s,3H),1.65-1.61(m,1H),1.42(dd,J=10.5,5.7Hz,2H),0.88(d,J=6.5Hz,6H).13C NMR (126MHz, DMSO-d6) δ183.53,177.85,164.61,163.70,162.25,134.13,133.88,132 .70,131.18,127.99,126.94,106.75,94.79,35.47,28.46,26.98,22.43,19.71.HRMS Calcd.for C 19 H 21 Calcd. for ClN2O4+[M+H]+: 377.1262, found: 377.1263.

[0049] Example 2: Preparation of (E)-4-chloro-N'-(1-(4-hydroxy-6-methyl-2-oxo-2-hydrogen-pyran-3-yl)-4-methylpentylidene)benzohydrazide (I-06)

[0050]

[0051] To a 25ml single-necked flask, add 1.12g (5mmol) of patchouli ketone, 0.85g (5mmol) of 3-chlorobenzohydrazide, and 0.185g (0.5mmol) of cerium chloride heptahydrate in sequence. Use anhydrous ethanol as the solvent and react at 60°C for 8 hours. Purify by column chromatography (petroleum ether:ethyl acetate = 1:1). After drying, a white solid was obtained with a yield of 76.4%. mp 184.2-186.5°C. 1 H NMR (500MHz, DMSO-d6) δ11.57(s,1H),7.92(dd,J=8.6,1.9Hz,2H),7.65(dd,J=8.6,1.9Hz,2H),5.85(s,1H ),3.15-3.11(m,2H),2.13(s,3H),1.65-1.59(m,1H),1.42(dd,J=10.6,5.8Hz,2H),0.87(d,J=6.3Hz,6H). 13 C NMR(126M HRMS Calcd.for C 19 H 21 Calcd. for ClN2O4+[M+H]+: 377.1262, found: 377.1262.

[0052] Example 3: Preparation of (E)-N'-(1-(4-hydroxy-6-methyl-2-oxo-2-hydro-pyran-3-yl)-4-methylpentylidene)-3-nitrobenzoylhydrazide (I-011)

[0053]

[0054] Patchouli ketone 1.12 g (5 mmol), 3-nitrobenzoyl hydrazide 0.905 g (5 mmol), and cerium chloride heptahydrate 0.185 g (0.5 mmol) were added to a 25 ml single-necked flask in sequence. Anhydrous ethanol was used as the solvent and the reaction was carried out at 60°C for 8 hours. Purification was performed by column chromatography (petroleum ether:ethyl acetate = 1:1). After drying, a yellow solid was obtained with a yield of 80.5%. mp 173.6.0-175.8°C 1HNMR(500MHz,DMSO-d6)δ11.85(s,1H),8.71(s,1H),8.49(d,J=8.2Hz,1H),8.33(d,J=7.8Hz,1H),7.88(d,J=8.0Hz,1 H),5.88(s,1H),3.15(t,J=8.1Hz,2H),2.15(s,3H),1.66-1.62(m,1H),1.44(d,J=8.1Hz,2H),0.89(d,J=6.6Hz,6H). 13 C NMR(126MHz,DMSO-d6)δ183.48,177.87,164.04,163.79,162.26,148.24,134.58,133 .67,131.02,127.36,122.98,106.70,94.85,35.51,28.47,27.02,22.44,19.72.HRMS Calcd.for C 19 H 21 Calculated for N₃O₆+[M+H]+: 388.1503, found: 388.1501.

[0055] Example 4: Preparation of (E)-N'-(1-(4-hydroxy-6-methyl-2-oxo-2-hydrogen-pyran-3-yl)-4-methylpentylidene)-4-trifluoromethylbenzohydrazide (I-015)

[0056]

[0057] Patchouli ketone 1.12 g (5 mmol), 4-trifluoromethylbenzohydrazide 1.02 g (5 mmol), and cerium chloride heptahydrate 0.185 g (0.5 mmol) were added to a 25 ml single-necked flask in sequence. Anhydrous ethanol was used as the solvent and the reaction was carried out at 60°C for 8 hours. Purification was performed by column chromatography (petroleum ether:ethyl acetate = 1:1). After drying, a white solid was obtained with a yield of 68.5%. mp 174.3-176.2°C 1 H NMR (400MHz, DMSO-d6) δ11.76(s,1H),8.10(d,J=8.0Hz,2H),7.97(d,J=8.0Hz,2H),5.88(s,1H ),3.17-3.12(m,2H),2.14(s,3H),1.65-1.60(m,1H),1.46-1.41(m,2H),0.88(d,J=6.5Hz,6H). 13C NMR(101MHz,DMSO-d6)δ183.51,177.71,164.83,163.69,162.26,136.00,132.56(q,J=31.9Hz),129.1 3,126.11(d,J=3.9Hz),124.22(d,J=272.6Hz),106.72,94.76,35.48,28.47,27.03,22.41,19.67.HRMS Calcd.for C 20 H 21 Calcd for F3N2O4+[M+H]+: 411.1526, found: 411.1524.

[0058] Other compounds of the present invention can be prepared by referring to the above examples.

[0059] The appearance, melting point and structure identification data of some compounds are shown below:

[0060] Compound I-01: white solid, mp 171.4-172.9°C. 1 H NMR (500MHz, DMSO-d6) δ11.56(s,1H),7.76(t,J=7.0Hz,1H),7.66(d,J=6.6Hz,1H),7.40(d,J=10.0Hz,2H),5 .89(s,1H),3.15-3.11(m,2H),2.15(s,3H),1.69-1.64(m,1H),1.45-1.41(m,2H),0.91(d,J=6.5Hz,6H).13C NMR (126MHz, DMSO-d6) δ183.09,176.39,163.84,162.75,162.21,159.89(d,J=250.9Hz),134.24(d,J=8.3Hz),130.91,1 25.29(d,J=3.1Hz),121.54(d,J=14.2Hz),116.88(d,J=21.7Hz),106.44,94.71,35.35,28.62,27.13,22.44,19.73.HRMS Calcd.forC 19 H 21 Calculated for FN2O4+[M+H]+: 361.1558, found: 361.1556.

[0061] Compound I-02: white solid, mp 162.8-163.5°C. 1H NMR (500MHz, DMSO-d6) δ11.59(s,1H),7.76(d,J=7.5Hz,1H),7.69(d,J=9.6Hz,1H),7.64(d,J=7.1Hz,1H),7.51(t,J=8.6Hz, 1H),5.86(s,1H),3.16-3.11(m,2H),2.14(s,3H),1.65-1.60(m,1H),1.42(dd,J=10.6,5.8Hz,2H),0.88(d,J=6.7Hz,6H).13C NMR (126MHz, DMSO-d6) δ183.56,177.94,164.69,163.70,162.38(d,J=245.2Hz),162.29,134.37(d,J=6.8Hz),131.43(d,J=7.9 Hz),124.38(d,J=2.6Hz),119.84(d,J=21.0Hz),115.03(d,J=23.1Hz),106.76,94.78,35.48,28.46,26.98,22.42,19.70.HRMS Calcd.for C 19 H 21 Calculated for FN2O4+[M+H]+: 361.1558, found: 361.1556.

[0062] Compound I-03: white solid, mp 183.5-184.4°C. 1 H NMR (500MHz, DMSO-d6) δ11.52(s,1H),7.98(dd,J=8.6,5.5Hz,2H),7.40(d,J=8.7Hz,2H),5.85(s, 1H),3.15-3.12(m,2H),2.13(s,3H),1.65-1.60(m,1H),1.45-1.41(m,2H),0.87(d,J=6.7Hz,6H). 13 C NMR (126MHz, DMSO-d6) δ183.61, 178.01, 165.04 (d, J = 250.4Hz), 164.96, 163.66, 162.27, 130.99 (d, J = 9. 3Hz),128.50(d,J=3.0Hz),116.23(d,J=22.0Hz),106.79,94.73,35.47,28.47,26.97,22.43,19.68.HRMS Calcd.for C 19 H 21Calculated for FN2O4+[M+H]+: 361.1558, found: 361.1556.

[0063] Compound I-04: white solid, mp 154.0-155.2°C. 1 H NMR (500MHz, DMSO-d6) δ11.72(s,1H),7.68(dd,J=7.7,1.5Hz,1H),7.62-7.56(m,2H),7.51(t,J=7.4Hz,1H),5.90(s,1H ),3.16-3.10(m,2H),2.15(s,3H),1.66(dt,J=13.2,6.6Hz,1H),1.43(dt,J=11.8,6.8Hz,2H),0.92(d,J=6.6Hz,6H).13C NMR(126MHz,DMSO-d6)δ182.98,176.20,164.69,163.87,162.05,134.00,132.51,130 .94,130.36,130.15,127.84,106.36,94.67,35.54,28.73,27.21,22.53,19.73.HRMS Calcd.for C 19 H 21 Calcd. for ClN2O4+[M+H]+: 377.1262, found: 377.1261.

[0064] Compound I-07: white solid, mp 161.2-162.6°C. 1 H NMR (500MHz, DMSO-d6) δ11.72(s,1H),7.76(d,J=7.9Hz,1H),7.65(dd,J=7.6,1.8Hz,1H),7.55(t,J=7.5Hz,1H),7.48(td,J=7 .7,1.8Hz,1H),5.90(s,1H),3.16-3.11(m,2H),2.15(s,3H),1.70-1.63(m,1H),1.43(q,J=7.0Hz,2H),0.92(d,J=6.7Hz,6H). 13 C NMR (126MHz, DMSO-d6) δ182.90,175.83,165.49,163.82,162.18,136.23,133.47,132 .55,130.12,128.26,119.88,106.36,94.63,35.59,28.73,27.19,22.57,19.74.HRMS Calcd.for C 19 H21 Calcd. for BrN2O4+[M+H]+: 421.0757, found: 421.0757.

[0065] Compound I-08: white solid, mp 225.2-225.8°C. 1 H NMR (500MHz, DMSO-d6) δ11.59(s,1H),8.06(s,1H),7.90(d,J=7.2Hz,1H),7.84(d,J=7.6Hz,1H),7.54(t,J=7.7H z,1H),5.86(s,1H),3.16-3.12(m,2H),2.14(s,3H),1.66-1.61(m,1H),1.45-1.41(m,2H),0.88(d,J=6.5Hz,6H). 13 C NMR(126MHz,DMSO-d6)δ183.47,177.36,164.54,163.61,162.33,135.49,134.56,131 .40,130.84,127.30,122.24,106.80,94.73,35.46,28.47,26.97,22.46,19.71.HRMS Calcd.for C 19 H 21 Calcd. for BrN2O4+[M+H]+: 421.0757, found: 421.0755.

[0066] Compound I-09: white solid, mp 188.5-189.9°C. 1 H NMR(500MHz,DMSO-d6)δ11.57(s,1H),7.86-7.83(m,2H),7.80-7.78(m,2H),5.85(s,1H),3.14-3.1 0(m,2H),2.13(s,3H),1.64-1.59(m,1H),1.41(dd,J=10.6,5.8Hz,2H),0.87(dd,J=6.6,1.6Hz,6H). 13 C NMR(126MHz,DMSO-d6)δ183.59,178.01,165.11,163.70,162.26,132.24,131 .14,130.23,126.82,106.78,94.77,35.49,28.46,26.98,22.45,19.71.HRMS Calcd.for C 19 H 21Calcd. for BrN2O4+[M+H]+: 421.0757, found: 421.0757.

[0067] Compound I-10: yellow solid, mp 189.0-190.2℃ 1 H NMR (400MHz, DMSO-d6) δ11.85(s,1H),8.20(dd,J=8.1,1.2Hz,1H),7.93(td,J=7.5,1.2Hz,1H),7.86-7.80(m,2H),5.91( s,1H),3.14-3.08(m,2H),2.15(s,3H),1.66(dt,J=13.1,6.6Hz,1H),1.40(dt,J=11.9,6.8Hz,2H),0.91(d,J=6.6Hz,6H). 13 C NMR(101MHz,DMSO-d6)δ182.72,175.69,164.13,163.94,162.11,147.24,134.70,132 .32,130.28,129.97,125.00,106.20,94.66,35.51,28.64,27.10,22.49,19.73.HRMS Calcd.for C 19 H 21 Calculated for N₃O₆+[M+H]+: 388.1503, found: 388.1502.

[0068] Compound I-12: yellow solid, mp 215.9-216.4℃ 1 H NMR(500MHz,DMSO-d6)δ11.83(s,1H),8.41(dd,J=8.9,2.0Hz,2H),8.15-8.12(m,2H),5.88(s,1H),3.16 -3.11(m,2H),2.14(s,3H),1.66-1.61(m,1H),1.43(dt,J=11.3,6.6Hz,2H),0.88(dd,J=6.8,1.9Hz,6H). 13 CNMR(126MHz,DMSO-d6)δ183.45,177.78,164.36,163.80,162.24,150.13,13 7.78,129.76,124.27,106.67,94.83,35.53,28.47,27.05,22.46,19.71.HRMS Calcd.for C 19 H 21Calculated for N₃O₆+[M+H]+: 388.1503, found: 388.1501.

[0069] Compound I-13: white solid, mp 158.3-160.5℃ 1 H NMR (400MHz, DMSO-d6) δ15.74(s,1H),7.79(d,J=7.7Hz,1H),7.73(d,J=4.3Hz,2H),7.65(d,J=3.7Hz,1H),5 .78(s,1H),3.19-3.12(m,2H),2.10(s,3H),1.62-1.57(m,1H),1.39(d,J=8.4Hz,2H),0.88(d,J=6.6Hz,6H). 13 C NMR(101MHz,DMSO-d6)δ182.85,175.78,165.33,163.89,162.10,133.15,131.49,129.85,128.10,127.05(q,J =4.8Hz),126.96(q,J=31.6Hz),124.01(q,J=273.8Hz),106.27,94.59,35.47,28.67,27.07,22.42,19.70.HRMS Calcd.for C 20 H 21 Calcd for F3N2O4+[M+H]+: 411.1526, found: 411.1525.

[0070] Compound I-14: yellow solid, mp 146.6-148.1℃ 1 H NMR (400MHz, DMSO-d6) δ15.59(s,1H),8.36(d,J=2.1Hz,1H),8.26(d,J=7.7Hz,1H),7.69(d,J=7.7Hz,1H),7.58(t,J=7.7Hz, 1H),5.64(d,J=1.1Hz,1H),3.39(s,2H),2.06(s,3H),1.71-1.64(m,1H),1.51(dd,J=9.3,6.4Hz,2H),0.98(d,J=6.6Hz,6H). 13C NMR (101MHz, DMSO-d6) δ181.58,164.21,163.62,161.73,160.28,140.14,131.48,129.07,128.75(d,J=31.2Hz ),125.68,124.94(d,J=271.9Hz),124.28(d,J=4.0Hz),107.99,93.22,35.23,28.66,27.03,22.75,19.54.HRMS Calcd.for C 20 H 21 Calcd for F3N2O4+[M+H]+: 411.1526, found: 411.1524.

[0071] Compound I-16: white solid, mp 137.5-138.2℃ 1 H NMR (500MHz, DMSO-d6) δ11.60-11.37(m,1H),7.54(d,J=6.7Hz,1H),7.46(s,1H),7.35(d,J=7.2Hz,2H),5.88(s,1 H),3.16-3.12(m,2H),2.43(s,3H),2.14(s,3H),1.70-1.65(m,1H),1.43(d,J=8.0Hz,2H),0.92(d,J=6.4Hz,6H). 13 C NMR (126MHz, DMSO-d6) δ183.25,176.27,167.46,163.65,162.24,136.82,133.63,131.35 ,131.17,128.37,126.25,106.63,94.55,35.53,28.71,27.17,22.52,19.90,19.71.HRMS Calcd.for C 20 H 24 Calculated for N2O4+[M+H]+: 357.1808, found: 357.1807.

[0072] Compound I-17: white solid, mp 153.5-153.9 ° C 1H NMR (500 MHz, DMSO-d6) δ 11.63-11.38 (m, 1H), 7.71 (d, J = 9.7 Hz, 2H), 7.46 (s, 2H), 5.86 (s, 1H), 3.16-3.12 (m, 2H), 2.40 (s, 3H), 2.14 (s, 3H), 1.66-1.61 (m, 1H), 1.43 (d, J = 8.1 Hz, 2H), 0.88 (d, J = 6.3 Hz ,6H).13CNMR(126MHz,DMSO-d6)δ183.67,178.01,166.03,163.63,162.27,138.54,133.57,131.97 ,129.06,128.70,125.30,106.82,94.71,35.45,28.48,26.95,22.44,21.37,19.70.HRMSCalcd.for C 20 H 24 Calculated for N2O4+[M+H]+: 357.1808, found: 357.1808.

[0073] Compound I-18: white solid, mp 162.2-163.9℃ 1 H NMR(500MHz,DMSO-d6)δ11.43(s,1H),7.82-7.80(m,2H),7.38(d,J=7.9Hz,2H),5.85(s,1H),3.15- 3.12(m,2H),2.40(s,3H),2.13(s,3H),1.64-1.60(m,1H),1.45-1.41(m,2H),0.87(d,J=6.6Hz,6H). 13 C NMR(126MHz,DMSO-d6)δ183.72,178.15,165.84,163.62,162.31,143.23,129.69 ,129.10,128.19,106.87,94.70,35.45,28.47,26.94,22.44,21.53,19.69.HRMS Calcd.forC 20 H 24 Calculated for N2O4+[M+H]+: 357.1808, found: 357.1805.

[0074] Compound I-19: yellow solid, mp 167.8-168.3℃ 1H NMR (500MHz, DMSO-d6) δ11.52(s,1H),7.91(d,J=6.4Hz,2H),7.66(s,1H),7.58(d,J=6.8Hz,2H),5.86(s,1 H),3.15(dd,J=10.9,5.5Hz,2H),2.14(s,3H),1.65-1.61(m,1H),1.46-1.42(m,2H),0.88(d,J=6.3Hz,6H). 13 C NMR(126MHz,DMSO-d6)δ183.68,178.08,165.98,163.68,162.29,133.01,131 .98,129.18,128.19,106.83,94.72,35.47,28.49,26.97,22.46,19.72.HRMS Calcd.forC 19 H 22 Calculated for N2O4+[M+H]+: 343.1652, found: 343.1652.

[0075] Compound I-20: white solid, mp 183.9-184.3℃ 1 H NMR (500MHz, DMSO-d6) δ11.43(s,1H),7.85(d,J=8.3Hz,2H),7.58(d,J=8.2Hz,2H),5.85(s,1H),3.17 -3.13(m,2H),2.13(s,3H),1.66-1.61(m,1H),1.46-1.42(m,2H),1.32(s,9H),0.89(d,J=6.6Hz,6H). 13 C NMR(126MHz,DMSO-d6)δ183.62,177.77,165.85,163.60,162.29,156.00,129.22,12 8.09,125.96,106.82,94.67,35.47,35.24,31.31,28.51,26.98,22.48,19.69.HRMS Calcd.forC 23 H 30 Calculated for N2O4+[M+H]+: 399.2278, found: 399.2274.

[0076] Compound I-21: white solid, mp 183.9-184.3℃ 1H NMR (400MHz, DMSO-d6) δ11.58(s,1H),8.00(d,J=8.4Hz,2H),7.89(d,J=8.4Hz,2H),7.79-7.76(m,2H),7.52(d,J=1.7Hz,2H), 7.46-7.43(m,1H),5.87(s,1H),3.19-3.14(m,2H),2.14(s,3H),1.67-1.61(m,1H),1.47-1.42(m,2H),0.89(d,J=6.6Hz,6H). 13 C NMR(101MHz,DMSO-d6)δ183.52,177.91,165.65,163.71,162.57,144.47,139.31,130.69,129 .57,128.90,128.82,127.44,127.36,106.84,94.68,35.47,28.50,27.00,22.50,19.72.HRMS Calcd.for C 25 H 26 N2O4+[M+H]+calculated value: 419.1965, measured value: 419.1962

[0077] Compound I-22: white solid, mp 167.5-168.2℃ 1 H NMR (400MHz, DMSO-d6) δ11.13(s,1H),7.76(dd,J=7.8,1.8Hz,1H),7.60-7.55(m,1H),7.22(d,J=8.4Hz,1H),7.13-7.09(m,1H),5.9 0-5.89(m,1H),3.92(s,3H),3.14-3.09(m,2H),2.14(s,3H),1.68-1.61(m,1H),1.43(dd,J=10.8,5.7Hz,2H),0.90(d,J=6.6Hz,6H). 13 C NMR(101MHz,DMSO-d6)δ182.82,175.25,163.97,163.79,162.21,157.64,133.89,130.91 ,121.19,121.02,112.64,106.31,94.54,56.51,35.17,28.62,27.16,22.46,19.72.HRMS Calcd.for C 20 H 24 N2O5+[M+H]+calculated value: 373.1758, measured value: 373.1754

[0078] Compound I-23: white solid, mp 142.6-143.4℃ 1 H NMR (400MHz, DMSO-d6) δ11.51(s,1H),7.48(d,J=7.0Hz,2H),7.43-7.41(m,1H),7.22(dt,J=7.1,2.5Hz,1H),5.86(d,J=1.0H z,1H),3.83(s,3H),3.16-3.11(m,2H),2.13(s,3H),1.66-1.59(m,1H),1.43(dt,J=11.7,6.5Hz,2H),0.88(d,J=6.6Hz,6H). 13 C NMR(101MHz,DMSO-d6)δ183.70,178.09,165.73,163.71,161.71,159.71,133.32,130.42 ,120.34,118.74,113.33,106.83,94.71,55.81,35.44,28.48,26.94,22.45,19.70.HRMS Calcd.for C 20 H 24 N2O5+[M+H]+calculated value: 373.1758, measured value: 373.1755

[0079] Compound I-24: white solid, mp 189.7-191.5℃ 1 H NMR(500MHz,DMSO-d6)δ11.34(s,1H),7.91-7.88(m,2H),7.10(d,J=9.0Hz,2H),5.84(s,1H),3.85(s,3H) ,3.16-3.12(m,2H),2.13(s,3H),1.65-1.59(m,1H),1.44(dd,J=10.8,5.7Hz,2H),0.87(d,J=6.8Hz,6H). 13 C NMR(126MHz,DMSO-d6)δ183.71,178.01,165.46,163.57,163.11,162.33,130.18 ,123.92,114.46,106.89,94.65,55.96,35.44,28.47,26.93,22.44,19.68.HRMS Calcd.forC 20 H 24 N2O5+[M+H]+calculated value: 373.1758, measured value: 373.1755

[0080] Compound I-25: white solid, mp 224.2-225.4℃ 1 H NMR(400MHz,DMSO-d6)δ11.45(s,1H),9.90(s,1H),7.38-7.27(m,3H),7.05-7.01(m,1H),5.85(s,1H),3.16- 3.09(m,2H),2.13(s,3H),1.62(dt,J=13.2,6.6Hz,1H),1.42(dt,J=11.8,6.7Hz,2H),0.88(d,J=6.6Hz,6H). 13 C NMR(101MHz,DMSO-d6)δ183.72,177.94,166.02,163.66,162.22,157.99,133.28,130 .28,119.96,118.67,114.94,106.84,94.63,35.43,28.50,26.97,22.48,19.70.HRMS Calcd.for C 19 H 22 N2O5+[M+H]+ Calculated value: 359.1601, Measured value: 359.1597

[0081] Compound I-26: white solid, mp 224.9-226.3℃ 1 H NMR(500MHz,DMSO-d6)δ11.23(s,1H),10.28(s,1H),7.80-7.77(m,2H),6.92-6.89(m,2H),5.83(s,1H), 3.16-3.11(m,2H),2.12(s,3H),1.65-1.59(m,1H),1.43(dd,J=10.4,5.8Hz,2H),0.87(d,J=6.6Hz,6H). 13 CNMR(126MHz,DMSO-d6)δ183.71,177.84,165.66,163.51,162.34,161.90,13 0.33,122.30,115.77,106.91,94.59,35.42,28.47,26.92,22.45,19.68.HRMS Calcd.for C 19 H 22 N2O5+[M+H]+ Calculated value: 359.1601, Measured value: 359.1597

[0082] Compound I-27: yellow solid, mp182.7-184.2℃1 H NMR (400MHz, DMSO-d6) δ10.99(s,1H),7.61(d,J=8.7Hz,2H),6.61(d,J=8.7Hz,2H),5.95(s,2H),5.82(d,J=1.1Hz,1H), 3.15-3.08(m,2H),2.13-2.10(m,3H),1.62(dt,J=13.1,6.6Hz,1H),1.41(dt,J=11.8,6.7Hz,2H),0.87(d,J=6.6Hz,6H). 13 C NMR(101MHz,DMSO-d6)δ183.75,177.48,165.87,163.40,162.39,153.56,130 .02,117.62,113.16,106.98,94.44,35.36,28.46,26.88,22.47,19.68.HRMS Calcd.for C 19 H 23 N3O4+[M+H]+calcd: 358.1761, found: 358.1758

[0083] Compound I-28: yellow solid mp 154.6-155.2°C 1 H NMR(500MHz,DMSO-d6)δ11.05(s,1H),5.83(s,1H),3.04-3.01(m,2H),2.12(s, 3H), 2.02 (s, 3H), 1.67-1.62 (m, 1H), 1.37-1.33 (m, 2H), 0.91 (d, J = 6.6Hz, 6H). 13 C NMR (126MHz, DMSO-d6) δ182.90,174.61,168.05,163.49,162.25,106.44,94.25,35.35,28.45,26.80,22.47,20.94,19.67.HRMS Calcd.forC 14 H 20 N2O4+[M+H]+ Calculated: 281.1495, Measured: 281.1494

[0084] Compound I-29: white solid, mp 140.8-141.2℃ 1H NMR (400MHz, DMSO-d6) δ11.02(s,1H),5.83(s,1H),3.02(t,J=3.3Hz,2H),2.26( s,2H),2.11(s,3H),1.63-1.58(m,3H),1.35-1.32(m,2H),0.90(d,J=6.9Hz,9H). 13 C NMR (101MHz, DMSO-d6) δ183.16,175.46,171.00,163.55,162.27,106.56,94.27,35.46,35.36,28.52,26.84,22.47,19.67,18.73,13.98.HRMS Calcd.for C 16 H 24 N2O4+[M+H]+calculated value: 309.1808, measured value: 309.1805

[0085] Compound I-30: white solid, mp 172.1-173.5℃ 1 H NMR (400MHz, DMSO-d6) δ11.48(s,1H),8.01(d,J=1.7Hz,1H),7.34(d,J=3.4Hz,1H),6.74(dd,J=3.5,1.7Hz,1H),5. 86(s,1H),3.12-3.06(m,2H),2.14(s,3H),1.63-1.55(m,1H),1.39(dt,J=11.6,6.7Hz,2H),0.85(d,J=6.6Hz,6H). 13 C NMR(101MHz,DMSO-d6)δ183.65,178.78,163.80,162.21,156.97,147.11,145.63, 116.60,112.73,106.72,94.84,35.41,28.39,26.90,22.37,19.70.HRMSCalcd.for C 17 H 20 N2O5+[M+H]+calculated value: 333.1445, measured value: 333.1441

[0086] Compound I-31: white solid, mp 166.5-168.1℃ 1H NMR (400MHz, DMSO-d6) δ11.51(s,1H),7.95(dd,J=4.9,1.2Hz,1H),7.88(dd,J=3.8,1.2Hz,1H),7.26(dd,J=5.0,3.8Hz,1H) ,5.87-5.85(m,1H),3.14-3.09(m,2H),2.13(d,J=0.9Hz,3H),1.64-1.58(m,1H),1.44-1.39(m,2H),0.86(d,J=6.6Hz,6H). 13 C NMR(101MHz,DMSO-d6)δ183.64,178.41,163.73,162.22,160.68,135.98,133 .21,130.73,128.79,106.79,94.81,35.46,28.42,26.93,22.43,19.71.HRMS Calcd.for C 17 H 20 N2O4S+[M+H]+calcd: 349.1216, found: 349.1213

[0087] Example 5: In vitro antibacterial activity of the compound of formula I against six plant pathogens

[0088] The fungicidal activity of the compound of formula I was determined using the mycelial growth rate method. The test strains were rice sheath blight, tomato gray mold, apple rot, rapeseed sclerotinia, wheat take-all, and corn Curvularia spp.

[0089] Weigh each compound of Formula I and prepare a 10,000 mg / L stock solution using dimethyl sulfoxide. Use a pipette to pipette each of the 10,000 mg / L stock solutions and add them to sterilized, cooled potato dextrose agar (PDA) medium. Mix thoroughly to prepare a 50 mg / L drug-coated culture medium. Pour 15 mL into 9 cm diameter Petri dishes, repeating three times for each agent. After the drug-coated culture medium in the dish condenses, prepare drug-coated PDA plates. Use dimethyl sulfoxide as a solvent blank control. Use a microporator to punch a 0.5 cm diameter cake along the edge of the colony on the cultured pathogen plate. Inoculate each of the drug-coated and blank control PDA plates and incubate in the dark at 25°C. After the colonies on the blank control PDA plate have fully grown, measure the colony diameters of each treatment using the cross-hatch method and take the average value.

[0090] The mycelial growth inhibition rate was calculated using the following formula:

[0091]

[0092] Table 2 In vitro bactericidal activity results of the compound of formula I (inhibition rate %)

[0093]

[0094]

[0095] As can be seen from Table 1, the compound of formula I provided by the present invention has certain inhibitory activity against the six plant pathogens tested. Among them, compounds I-02, I-03, I-06, I-09, I-11, I-14, I-17, I-18, I-19, I-28, I-29, etc. have an inhibition rate of more than 95% against tomato gray mold; compounds I-01, I-02, I-04, I-05, I-07, I-08, I-11, I-13, I-17, I-19, I-29, etc. have an inhibition rate of 100% against apple rot pathogen; compounds I-10, I-15, I-23, I-29, I-30, I-31 have an inhibition rate of more than 95% against rapeseed sclerotinia; in addition, compounds I-01 to I-31 have certain antibacterial activity against rice sheath blight, wheat take-all pathogen and corn curvature spore pathogen.

[0096] Example 6: In vivo bactericidal activity of some compounds of formula I

[0097] Determination of efficacy against apple rot. The scald inoculation method was used to determine the control effect of the compound on apple branches. One-year-old branches were selected, cut into segments, and then disinfected with 75% alcohol. The branches were then removed and dried, and both ends of the branches were sealed with paraffin to prevent water loss and infection by bacteria. (1) Protective effect: Use a 10mm diameter puncher to punch holes in the apple branch skin, spray the wound site with the required concentration of the drug solution, and inoculate the pathogen 24 hours after spraying; (2) Curative effect: Use a 10mm diameter puncher to punch holes in the apple branch skin and inoculate the pathogen. Spray the required concentration of the drug solution again 24 hours after inoculation. Clear water was used as a blank control. The control effect was investigated after 7 days of moisturizing culture.

[0098] Table 3 Protective and therapeutic effects of some compounds at 200 mg / L on apple rot

[0099]

[0100]

[0101] As shown in Table 3, the above compounds exhibited both good protective and therapeutic effects against apple rot. Compounds I-08 and I-29, at a dose of 200 mg / L, exhibited protective and therapeutic activity exceeding 80% against apple rot, comparable to the control agent, thiophanate-methyl.

[0102] Determination of efficacy against Sclerotinia sclerotiorum of rapeseed. Determine the control effect of the compound on rapeseed leaves. Select fresh, healthy, and uniform rapeseed leaves, disinfect them with 75% alcohol, remove the branches, dry them, and wrap the petioles with wet absorbent cotton. (1) Protective effect: Use a sterilized inoculation needle to puncture the leaf surface, spray the wound with the desired concentration of the drug solution, and inoculate the pathogen 24 hours after spraying; (2) Curative effect: Use a sterilized inoculation needle to puncture the leaf surface and inoculate the pathogen. Spray the desired concentration of the drug solution again 24 hours after inoculation. Use clean water as a blank control. Investigate the control effect after 7 days of moisturizing and incubation.

[0103] Table 4 Protective and therapeutic effects of some compounds at 200 mg / L on rapeseed sclerotinia

[0104]

[0105] As shown in Table 4, the above compounds have both good protective and therapeutic effects against Sclerotinia sclerotiorum. Compounds I-23 and I-29, at a dose of 200 mg / L, showed protective and therapeutic activity against Sclerotinia sclerotiorum of rapeseed of over 85%, significantly outperforming the control agent, carbendazim.

[0106] Efficacy against tomato gray mold: The control effect of compound I-06 on tomato fruit was determined using the needle puncture method. Fresh, healthy, and uniformly sized tomato fruits were selected, disinfected with 75% alcohol, and allowed to dry.

[0107] (1) Protective effect: Use a sterile inoculation needle to puncture the surface of the tomato fruit, spray the wound with the desired concentration of the solution, and inoculate the pathogen 24 hours after spraying. (2) Curative effect: Use a sterile inoculation needle to puncture the surface of the tomato fruit and inoculate the pathogen. 24 hours after inoculation, spray the solution with the desired concentration again. Use clean water as a blank control. After 7 days of moisturizing and incubation, evaluate the control effect.

[0108] Table 5 Protective and therapeutic effects of some compounds at 200 mg / L on tomato gray mold

[0109]

[0110] As shown in Table 5, the above compounds exhibited both good protective and therapeutic effects against tomato gray mold. Compounds I-11, I-19, and I-29 exhibited protective and therapeutic activity exceeding 80% at a dose of 200 mg / L, demonstrating comparable or even slightly superior efficacy to the control agent, iprodione.

[0111] The results of biological activity assays show that the compound of formula I has a good inhibitory effect on rapeseed sclerotinia, tomato gray mold and apple rot pathogens, and can be used as an agricultural fungicide for the prevention and treatment of plant diseases caused by the above pathogens.

[0112] The preferred embodiments of the present disclosure are described in detail above. However, the present disclosure is not limited to the specific details of the above embodiments. Within the technical concept of the present disclosure, various simple modifications can be made to the technical solutions of the present disclosure, and these simple modifications all fall within the scope of protection of the present disclosure.

[0113] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any appropriate manner without contradiction. In order to avoid unnecessary repetition, the present disclosure will not further describe various possible combinations.

[0114] In addition, the various embodiments of the present disclosure may be arbitrarily combined, and as long as they do not violate the concept of the present disclosure, they should also be regarded as the contents disclosed by the present disclosure.

Claims

1. A patchouli ketoacylhydrazone compound, characterized in that: The compound represented by formula I: Wherein: R is selected from one of hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkyl, halogenated C1-C4 alkoxy, cyano and nitro; or a salt of the compound represented by formula I.

2. A patchouli ketoacylhydrazone compound, characterized in that: The compound represented by formula I: The specific substituents in Formula I are shown in the following table:

3. A method for preparing patchouli ketoacylhydrazone compounds, characterized in that: The patchouli ketone acylhydrazone compound is the patchouli ketone acylhydrazone compound according to claim 1 or 2; The preparation method comprises the following steps: reacting a compound represented by formula II with a compound represented by formula III in an organic solvent to obtain a compound represented by formula I; 4. The method for preparing patchouli ketone compounds according to claim 3, wherein An additive is also mixed into the organic solvent, the additive being selected from one of 4-dimethylaminopyridine, dicyclohexylcarbodiimide and cerium chloride heptahydrate; and the organic solvent is selected from one of dichloromethane, toluene, anhydrous ethanol and ethyl acetate.

5. The method for preparing patchouli ketoacylhydrazone compounds according to claim 3 or 4, characterized in that: The reaction temperature of the reaction is -25 to 80° C., and the reaction time is 5 minutes to 24 hours.

6. The method for preparing patchouli ketoacylhydrazone compounds according to claim 3 or 4, characterized in that: The molar ratio of the compound represented by formula II to the compound represented by formula III is 1:(1-1.2).

7. Use of the patchouli ketoacylhydrazone compound according to any one of claims 1 to 2 for preparing a botanical fungicide.

8. The use according to claim 7, characterized in that The plant fungicide is used for preventing and controlling rice sheath blight, tomato gray mold, apple rot, rapeseed sclerotinia, wheat take-all disease and / or corn curvature spore disease.

9. Use of the patchouli ketoacylhydrazone compounds prepared by the preparation method according to any one of claims 3 to 6 in preparing botanical fungicides.

10. A botanical fungicide, characterized in that: The plant fungicide comprises the patchouli ketone acylhydrazone compound according to any one of claims 1-2 as an active ingredient; The weight percentage of the active component in the composition is 0.1% to 99%.

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