Perilla acid formyl hydrazine compound as well as preparation method and application thereof

Abstract

The invention discloses a perillaldehyde formylhydrazine compound and a preparation method and application thereof.The preparation method comprises the steps that perillaldehyde is subjected to an oxidation reaction to synthesize perillaldehyde, the perillaldehyde reacts with phenylhydrazine hydrochloride with different substituent groups to synthesize the perillaldehyde formylhydrazine compound, the compound has a general formula I, and R is H, 4-F, 3-F, 2-F, 4-Cl, 3-Cl, 2-Cl, 4-Br, 3-Br, 2-Br, 4-I, 4-CH3, 4-OCH3 and 2-Cl-4-F; the compound has a good prevention effect on pythium aphanidermatum and botrytis cinerea under an in-vitro condition, and can be used for preventing and treating fungal diseases of agricultural or forestry plants. The preparation method of the compound is simple and convenient, the yield is high, and the product property is stable.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticide synthesis, and particularly relates to a perilla acid hydrazide compound, a preparation method and an application thereof. Background Art

[0002] Crop diseases and insect pests are a major constraint on the sustainable and healthy development of agricultural products and forest resources. Pesticides, as specialized commodities for controlling biological hazards such as crop diseases and insect pests, play a crucial role in protecting the normal growth of crops, improving agricultural production, and promoting food security. However, the long-term use of a single pesticide can lead to the development of resistance in plant pathogens, pests, and weeds. Therefore, the development of new, targeted pesticides is crucial for the effective control of plant diseases.

[0003] Hydrazide groups have broad applications and promising prospects in the pharmaceutical and pesticide fields. In the pesticide field, hydrazide groups are one of the key structural units of many pesticides. Due to their high biological activity and selectivity for target pests, hydrazide groups can be used to develop effective insecticides, herbicides, and fungicides. For example, hydrazide insecticides can achieve their insecticidal effects by inhibiting insect enzyme activity or disrupting their nervous system. Furthermore, hydrazide groups can be used as auxiliary ingredients in pesticides to improve their stability and delivery. Perillaldehyde, a major component of the volatile oil of the medicinal and edible plant Perilla frutescens, possesses safe and effective antibacterial activity. Furthermore, it also plays a role in antioxidant and anti-tumor properties, making it of great significance for drug development. With the increasing demand for environmentally friendly pesticides and highly effective drugs, the application prospects of hydrazide groups in the pharmaceutical and pesticide fields are very broad. Therefore, when designing compounds, the structure of perillaldehyde was modified by activating functional groups and introducing active groups, and a series of perillic acid hydrazide derivatives were designed and synthesized, and the antibacterial activity was improved. This has great theoretical and practical significance for finding drug lead compounds with excellent antifungal activity, developing new antifungal pesticides, and preventing and controlling agricultural and forestry crop diseases.

[0004] So far, there has been no report on the use of perilla acid hydrazide compounds as agricultural fungicides. Summary of the Invention

[0005] The purpose of this section is to summarize some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the abstract and title of this application to avoid obscuring the purpose of this section, the abstract and the title of the invention, and such simplifications or omissions should not be used to limit the scope of the present invention.

[0006] In view of the above problems and / or the problems existing in the prior art, the present invention is proposed.

[0007] Therefore, the purpose of the present invention is to overcome the deficiencies in the prior art and provide a perillic acid hydrazide compound having anti-plant pathogenic fungi activity.

[0008] In order to solve the above technical problems, the present invention provides the following technical solution: a perilla acid hydrazide compound, the structural formula of the perilla acid hydrazide compound is shown in the following formula I:

[0009]

[0010] Among them, R is one of 4-H, 4-F, 4-Cl, 4-Br, 4-I, 4-CH3, 4-OCH3, 2-F, 2-Cl, 2-Br, 3-F, 3-Cl, 3-Br, and 2-Cl-4-F.

[0011] Another object of the present invention is to overcome the deficiencies in the prior art and provide a method for preparing perilla acid hydrazide compounds, comprising:

[0012] The perillic acid is synthesized by oxidation reaction of perillic aldehyde;

[0013] Perillic acid was reacted with phenylhydrazine hydrochloride with different substituents to synthesize perillic acid hydrazide compounds.

[0014] As a preferred embodiment of the method for preparing the perillic acid hydrazide compound of the present invention, wherein: the perillic acid is synthesized by oxidation reaction of perillaldehyde, comprising:

[0015] Perillaldehyde was placed in a single-necked round-bottom flask and dimethyl sulfoxide was added as the reaction solvent;

[0016] Add potassium dihydrogen phosphate aqueous solution into the single-necked flask under stirring at room temperature and stir for 10 minutes to fully mix the system;

[0017] Then, a sodium chlorite aqueous solution was slowly added dropwise using a constant pressure dropping funnel, and the reaction was allowed to react for 15 h. The reaction progress was monitored by TLC. After the reaction was complete, the reaction was quenched with a 10% sodium hydroxide aqueous solution;

[0018] Next, the reaction solution was adjusted to pH 2-3 with 10% dilute hydrochloric acid, and white solid precipitation was observed. The white solid was collected by filtration under reduced pressure to obtain perillic acid.

[0019] As a preferred embodiment of the method for preparing the perillic acid hydrazide compounds of the present invention, the molar ratio of perillaldehyde, potassium dihydrogen phosphate and sodium chlorite is 1:0.3:2.2.

[0020] As a preferred embodiment of the method for preparing the perilla acid hydrazide compound of the present invention, the synthesis of the perilla acid hydrazide compound comprises:

[0021] Perillic acid was placed in a single-necked round-bottom flask, and dichloromethane was added as the reaction solvent. 4-Dimethylaminopyridine and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added under stirring at room temperature, and triethylamine solution was slowly added dropwise. After sufficient stirring and activation for 15 minutes, phenylhydrazine hydrochloride with different substituents was added and the reaction was carried out for 12 hours. TLC was used to detect the complete reaction of the raw materials.

[0022] After the reaction, the mixture was extracted with water and ethyl acetate and washed with saturated sodium chloride. The organic phase was concentrated by rotary evaporation to remove most of the ethyl acetate. Finally, the crude product was separated and purified by 200-300 mesh silica gel column chromatography to obtain the target compound, perillic acid hydrazide compound.

[0023] The eluent in the silica gel column chromatography separation is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 12:1 to 6:1.

[0024] As a preferred embodiment of the method for preparing the perillic acid hydrazide compounds of the present invention, the molar ratio of perillic acid, 4-dimethylaminopyridine, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, triethylamine and phenylhydrazine hydrochloride with different substituents is 1:0.1:1.2:1.

[0025] As a preferred embodiment of the preparation method of the perillic acid hydrazide compounds of the present invention, the phenylhydrazine hydrochloride with different substituents is phenylhydrazine hydrochloride, 4-fluorophenylhydrazine hydrochloride, 4-chlorophenylhydrazine hydrochloride, 4-bromophenylhydrazine hydrochloride, 4-iodophenylhydrazine hydrochloride, 4-methylphenylhydrazine hydrochloride, 4-methoxyphenylhydrazine hydrochloride, 2-fluorophenylhydrazine hydrochloride, 2-chlorophenylhydrazine hydrochloride, 2-bromophenylhydrazine hydrochloride, 3-fluorophenylhydrazine hydrochloride, 3-chlorophenylhydrazine hydrochloride, 3-bromophenylhydrazine hydrochloride, and 2-chloro-4-fluorophenylhydrazine hydrochloride.

[0026] Another object of the present invention is to overcome the deficiencies in the prior art and provide a perillic acid hydrazide compound for use in preventing and controlling plant fungi in agriculture or forestry.

[0027] As a preferred embodiment of the application of the present invention, the plant fungi are Sclerotinia sclerotiorum, stone fruit brown rot, tomato gray mold, apple rot, pepper phytophthora, potato late blight and wheat fusarium.

[0028] Beneficial effects of the present invention:

[0029] (1) The compound described in the present invention is a perillic acid hydrazide derivative with a novel molecular structure. All of them are new compounds with distinct chemical structure characteristics. The structural formula contains perillic acid and phenylhydrazine hydrochloride groups, wherein phenylhydrazine hydrochloride and perillic acid are connected by a hydrazide bond. The preparation method of the compound described in the present invention is simple, the raw materials are easily available, and the reaction conditions are mild and easy to control.

[0030] (2) The compound of the present invention is an agent for controlling plant fungi in the fields of agriculture or forestry, and exhibits good effects in controlling rapeseed sclerotinia sclerotiorum, stone fruit brown rot fungi and tomato gray mold fungi. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. Those skilled in the art can also derive other drawings based on these drawings without inventive effort. Among them:

[0032] Figure 1 Schematic diagram of the preparation method of perilla acid hydrazide compounds in the present invention.

[0033] Figure 2 Schematic diagram of the in vitro experiment (plate) of compound 1-2 in the examples of the present invention against stone fruit brown rot mold and tomato gray mold (concentrations from left to right are 0 mg / L, 6.25 mg / L, 3.13 mg / L, 1.56 mg / L, 0.78 mg / L, 0.39 mg / L and 0.18 mg / L).

[0034] Figure 3 Schematic diagram of the protective and therapeutic activity experiments of compound 1-2 against pears infected by stone fruit brown rot fungus. DETAILED DESCRIPTION

[0035] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0036] The schematic diagram of the preparation method of the perilla acid hydrazide compound of the present invention is shown in Figure 1 , including the following steps:

[0037] (1) Perillaldehyde (CAS: 18031-40-8, purchased from Shanghai Bid Pharmaceutical Co., Ltd.) was oxidized to synthesize perillic acid;

[0038] (2) Perillic acid reacts with phenylhydrazine hydrochloride with different substituents to synthesize perillic acid hydrazide compounds;

[0039] The specific steps are:

[0040] (1) Preparation of perilla acid

[0041] Take perillaldehyde (500 mg, 3.3 mol) into a 150 mL single-mouth round-bottom flask, and add dimethyl sulfoxide (3.5 mL) as a reaction solvent;

[0042] Dissolve potassium dihydrogen phosphate (136 mg, 1.0 mol) in 1.5 mL of water, and add into the single-mouth flask under stirring at room temperature. Stir for 10 min to allow the system to mix thoroughly;

[0043] Then slowly drop 5 mL of an aqueous sodium chlorite solution (660 mg, 7.3 mol) into the flask using a constant-pressure dropping funnel. React for 15 h, and detect the reaction progress by TLC. After the reaction is completed, quench the reaction using 15 mL of a 10% aqueous sodium hydroxide solution;

[0044] Next, adjust the reaction solution to pH 2-3 using 10% dilute hydrochloric acid. Observe the precipitation of white solids. Collect the white solids by filtration under reduced pressure to obtain white solid perilla acid.

[0045] (2) Preparation of perilla acid carbohydrazide compounds

[0046] Take perilla acid (1.0 mmol) into a 50 mL single-mouth round-bottom flask, and add 20 mL of dichloromethane as a reaction solvent;

[0047] Under stirring at room temperature, add 4-dimethylaminopyridine (0.1 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 mmol), and slowly drop in a triethylamine solution (2.0 mmol). After stirring for 15 min to activate, add phenylhydrazine hydrochloride, 4-fluorophenylhydrazine hydrochloride, 4-chlorophenylhydrazine hydrochloride, 4-bromophenylhydrazine hydrochloride, 4-iodophenylhydrazine hydrochloride, 4-methylphenylhydrazine hydrochloride, 4-methoxyphenylhydrazine hydrochloride, 2-fluorophenylhydrazine hydrochloride, 2-chlorophenylhydrazine hydrochloride, 2-bromophenylhydrazine hydrochloride, 3-fluorophenylhydrazine hydrochloride, 3-chlorophenylhydrazine hydrochloride, 3-bromophenylhydrazine hydrochloride, 2-chloro-4-fluorophenylhydrazine hydrochloride (1.0 mmol). React for 12 h, and detect the complete reaction of the raw material by TLC;

[0048] After the reaction is completed, extract the reaction solution using water and ethyl acetate, wash with saturated sodium chloride, and concentrate the organic phase to remove most of the ethyl acetate. Finally, purify the crude product by column chromatography using silica gel with a mesh size of 200-300, and elute with petroleum ether / ethyl acetate in a volume ratio of 12:1-6:1 to obtain the target perilla acid carbohydrazide compound.

[0049] Example 1

[0050] Under certain conditions, the effect of the ratio of perilla acid and phenylhydrazine hydrochloride on the yield of the product was investigated. The conditions and results are shown in Table 1.

[0051] Table 1

[0052]

[0053] It can be seen that the preferred range of the feed ratio of perillic acid (mmol) to phenylhydrazine hydrochloride (mmol) is 1:0.9-1:1. Beyond this range, the yield of the obtained product decreases.

[0054] Example 2

[0055] Prepared perillaldehyde formyl hydrazide derivatives (I-1):

[0056]

[0057] Perillic acid (1.0 mmol) was placed in a 50 mL single-necked round-bottom flask, and 20 mL of dichloromethane was added as the reaction solvent. 4-Dimethylaminopyridine (0.1 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 mmol) were added with stirring at room temperature, and triethylamine solution (2.0 mmol) was slowly added dropwise. After stirring for 15 minutes, phenylhydrazine hydrochloride (1.0 mmol) was added and the reaction was complete for 12 hours. TLC confirmed the reaction was complete. After completion of the reaction, the mixture was extracted with water and ethyl acetate, washed with saturated sodium chloride, and the organic phase was concentrated to remove most of the ethyl acetate. The crude product was purified by 200-300 mesh silica gel column chromatography using a petroleum ether / ethyl acetate ratio of 12:1 to 6:1 to obtain the target compound, perillic acid hydrazide derivative (I-1), as a white solid in a yield of 71.3%. The mp was 158.8-160.6°C. 1 H NMR (600MHz, CDCl3) δ7.71 (s, 1H), 7.23–7.20 (m, 2H), 6.90 (t, J = 7.4Hz, 1H), 6.87–6.83 ( m,2H),6.74(dd,J=5.5,2.7Hz,1H),5.87(s,1H),4.81–4.71(m,2H),2.47–2.41(m,1H),2 .34–2.23(m,2H),2.17(tt,J=11.3,3.4Hz,1H),2.08(dddd,J=17.4,10.6,4.2,2.3Hz,1H ),1.91(ddq,J=12.8,4.9,2.5Hz,1H),1.76(s,3H),1.49(dtd,J=12.9,11.2,5.3Hz,1H). 13C NMR (151MHz, CDCl3) δ168.50,148.74,148.27,134.85,129.26,121.45,121.42 ,113.91,109.47,40.18,30.90,27.02,24.59,20.84.HRMS(ESI)m / z:calcd.for C 16 H 21 N2O[M+H] + :257.1576; found 257.1660.

[0058] Example 3

[0059] Prepared perillaldehyde formyl hydrazide derivatives (I-2):

[0060]

[0061] Perillic acid (1.0 mmol) was placed in a 50 mL single-necked round-bottom flask, and 20 mL of dichloromethane was added as the reaction solvent. 4-Dimethylaminopyridine (0.1 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 mmol) were added with stirring at room temperature, and triethylamine solution (2.0 mmol) was slowly added dropwise. After stirring for 15 minutes, 4-fluorophenylhydrazine hydrochloride (1.0 mmol) was added and the reaction was complete for 12 hours. TLC confirmed the reaction was complete. After the reaction, the mixture was extracted with water and ethyl acetate, washed with saturated sodium chloride, and the organic phase was concentrated to remove most of the ethyl acetate. The crude product was purified by 200-300 mesh silica gel column chromatography using a petroleum ether / ethyl acetate ratio of 12:1 to 6:1. The target compound, perillic acid hydrazide derivative (I-2), was obtained as a white solid in a yield of 69.7%. The mp was 163.2-165.3°C. 1 H NMR (600MHz, CDCl3) δ7.62 (s, 1H), 6.93 (t, J = 8.7Hz, 2H), 6.85 (dt, J = 8.8, 4.4H z,2H),6.80–6.73(m,1H),5.36(s,1H),4.81–4.71(m,2H),2.45(dd,J=16.7,5.8 Hz,1H),2.38–2.25(m,2H),2.23–2.16(m,1H),2.11(ddt,J=16.4,6.2,2.9Hz,1H ),1.93(ddt,J=13.1,5.3,2.6Hz,1H),1.76(d,J=7.9Hz,3H),1.57–1.48(m,1H). 13CNMR (151 MHz, CDC13) δ 168.57, 159.00, 157.42, 148.64, 144.29, 144.28, 135.18, 131.21, 115.89, 115.74, 115.51, 115.46, 109.55, 40.16, 30.93, 27.00, 24.57, 20.84. HRMS (ESI) m / z: calcd. for C 16 H 20 FN2O[M+H] + : 275.1481; found 275.1563.

[0062] Example 4

[0063] The perillyl aldehyde carbohydrazide derivative (I-3) was prepared:

[0064]

[0065] The perillyl aldehyde carbohydrazide derivative (I-3) was prepared: 1 H NMR (600 MHz, CDC13) δ 7.61 (s, 1H), 7.20 - 7.10 (m, 2H), 6.84 - 6.71 (m, 3H), 4.80 - 4.69 (m, 2H), 2.47 - 2.41 (m, 1H), 2.36 - 2.24 (m, 2H), 2.18 (tt, J = 11.1, 3.2 Hz, 1H), 2.10 (dddd, J = 18.4, 10.4, 4.3, 2.3 Hz, 1H), 1.93 (ddt, J = 12.9, 5.0, 2.5 Hz, 1H), 1.76 (t, J = 1.0 Hz, 3H), 1.51 (dtd, J = 12.9, 11.1, 5.3 Hz, 1H). 13C NMR (151 MHz, CDC13) δ 167.57, 148.63, 146.95, 135.31, 131.17, 129.19, 126.20, 115.17, 109.57, 40.15, 30.94, 26.99, 24.58, 20.85. HRMS (ESI) m / z: calcd for C 16 H 20 ClN2O[M+H] + :291.1186; found 291.1267.

[0066] Example 5

[0067] The perillyl aldehyde carbohydrazide derivative (I-4) was prepared:

[0068]

[0069] The perillyl aldehyde carbohydrazide derivative (I-4) was prepared: 1 H NMR (600 MHz, CDC13) δ 7.66 (s, 1H), 7.33 - 7.27 (m, 2H), 6.78 - 6.74 (m, 1H), 6.73 - 6.68 (m, 2H), 4.81 - 4.68 (m, 2H), 2.46 - 2.39 (m, 1H), 2.36 - 2.23 (m, 2H), 2.17 (tt, J = 11.3, 3.1 Hz, 1H), 2.13 - 2.04 (m, 1H), 1.91 (ddt, J = 13.0, 4.7, 2.6 Hz, 1H), 1.75 (s, 3H), 1.50 (dtd, J = 12.9, 11.1, 5.3 Hz, 1H). 13C NMR (151MHz, CDCl3) δ168.54,148.62,147.38,135.40,132.08,131.11,115.60 ,113.48,109.57,40.14,30.94,26.98,24.57,20.85.HRMS(ESI)m / z:calcd.for C 16 H 20 BrN2O[M+H] + :335.0681; found335.0755.

[0070] Example 6

[0071] Prepare perillaldehyde formyl hydrazide derivatives (I-5):

[0072]

[0073] Perillic acid (1.0 mmol) was placed in a 50 mL single-necked round-bottom flask, and 20 mL of dichloromethane was added as the reaction solvent. 4-Dimethylaminopyridine (0.1 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 mmol) were added with stirring at room temperature, and triethylamine solution (2.0 mmol) was slowly added dropwise. After stirring for 15 minutes, 4-iodophenylhydrazine hydrochloride (1.0 mmol) was added and the reaction was complete for 12 hours. TLC confirmed the reaction was complete. After the reaction, the mixture was extracted with water and ethyl acetate, washed with saturated sodium chloride, and the organic phase was concentrated to remove most of the ethyl acetate. The crude product was purified by 200-300 mesh silica gel column chromatography using a petroleum ether / ethyl acetate ratio of 12:1 to 6:1. The target compound, perillic acid hydrazide derivative (I-5), was obtained as a white solid in a yield of 67.9%. The mp was 169.4-172.5°C. 1 H NMR (600MHz, CDCl3) δ7.66 (s, 1H), 7.52–7.41 (m, 2H), 6.74 (dt, J = 5.5, 2.5Hz, 1H),6.67–6.57(m,2H),4.81–4.69(m,2H),2.42(ddt,J=17.3,5.5,2.7Hz,1H) ,2.36–2.23(m,2H),2.17(tt,J=11.2,3.3Hz,1H),2.13–2.04(m,1H),1.92(dd q,J=13.0,4.6,2.4Hz,1H),1.76(s,3H),1.50(dtd,J=12.9,11.1,5.3Hz,1H). 13CNMR(151MHz,CDCl3)δ168.52,148.62,148.08,137.97,135.43,131.09,116.0 6,109.58,83.29,40.14,30.95,26.99,24.56,20.87.HRMS(ESI)m / z:calcd.for C 16 H 20 IN2O[M+H] + :383.0542; found 383.0619.

[0074] Example 7

[0075] Prepare perillaldehyde formyl hydrazide derivatives (I-6):

[0076]

[0077] Perillic acid (1.0 mmol) was placed in a 50 mL single-necked round-bottom flask, and 20 mL of dichloromethane was added as the reaction solvent. 4-Dimethylaminopyridine (0.1 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 mmol) were added with stirring at room temperature, and triethylamine solution (2.0 mmol) was slowly added dropwise. After stirring for 15 minutes, 4-methylphenylhydrazine hydrochloride (1.0 mmol) was added and the reaction was complete for 12 hours. TLC confirmed the reaction was complete. After completion of the reaction, the mixture was extracted with water and ethyl acetate, washed with saturated sodium chloride, and the organic phase was concentrated to remove most of the ethyl acetate. The crude product was purified by 200-300 mesh silica gel column chromatography using a petroleum ether / ethyl acetate ratio of 12:1 to 6:1 to obtain the target compound, perillic acid hydrazide derivative (I-6), as a white solid in a yield of 69.2%. The mp was 165.7-168.8°C. 1 H NMR (600MHz, CDCl3) δ7.68 (s, 1H), 7.02 (d, J = 8.0Hz, 2H), 6.77 (d, J = 8.0Hz, 2H),6.74–6.69(m,1H),4.79–4.71(m,2H),2.47–2.41(m,1H),2.34–2.26(m ,2H),2.26(s,3H),2.16(dq,J=11.4,5.6,3.3Hz,1H),2.12–2.04(m,1H),1. 91(ddd,J=13.0,5.5,2.6Hz,1H),1.75(s,3H),1.49(qd,J=11.6,5.3Hz,1H). 13C NMR (151MHz, CDCl3) δ168.42,148.78,145.85,134.70,131.38,130.88,129.78,11 4.25,109.46,40.21,30.91,27.04,24.59,20.85,20.70.HRMS(ESI)m / z:calcd.for C 17 H 23 N2O[M+H] + :271.1732; found 271.1814.

[0078] Example 8

[0079] Prepare perillaldehyde formyl hydrazide derivatives (I-7):

[0080]

[0081] Perillic acid (1.0 mmol) was placed in a 50 mL single-necked round-bottom flask, and 20 mL of dichloromethane was added as the reaction solvent. 4-Dimethylaminopyridine (0.1 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 mmol) were added with stirring at room temperature, and triethylamine solution (2.0 mmol) was slowly added dropwise. After stirring for 15 minutes, 4-methoxyphenylhydrazine hydrochloride (1.0 mmol) was added and the reaction was complete for 12 hours. TLC confirmed the reaction was complete. After the reaction, the mixture was extracted with water and ethyl acetate, washed with saturated sodium chloride, and the organic phase was concentrated to remove most of the ethyl acetate. The crude product was purified by 200-300 mesh silica gel column chromatography using a petroleum ether / ethyl acetate ratio of 12:1 to 6:1. The target compound, perillic acid hydrazide derivative (I-7), was obtained as a white solid in a yield of 70.3%. The mp was 118.5-120.6°C. 1 H NMR(600MHz, CDCl3)δ7.75(s,1H),6.87–6.80(m,2H),6.80–6.76(m,2H),6.72(dd, J=4.1,2.1Hz,1H),4.80–4.69(m,2H),3.74(s,3H),2.43(ddtd,J=17.2,5.8,2.9,1 .6Hz,1H),2.34–2.22(m,2H),2.16(ddd,J=14.7,11.2,3.3Hz,1H),2.12–2.04(m,1 H),1.94–1.87(m,1H),1.75(t,J=1.0Hz,3H),1.49(dtd,J=13.0,11.2,5.4Hz,1H). 13C NMR (151MHz, CDCl3) δ168.48,154.97,148.75,141.75,134.77,131.32,115.99,11 4.69,109.46,55.75,40.19,30.91,27.03,24.57,20.84.HRMS(ESI)m / z:calcd.for C 17 H 23 N2O2[M+H] + :287.1681; found 287.1764.

[0082] Example 9

[0083] Prepared perillaldehyde formyl hydrazide derivatives (I-8):

[0084]

[0085] Perillic acid (1.0 mmol) was placed in a 50 mL single-necked round-bottom flask, and 20 mL of dichloromethane was added as the reaction solvent. 4-Dimethylaminopyridine (0.1 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 mmol) were added with stirring at room temperature, and triethylamine solution (2.0 mmol) was slowly added dropwise. After stirring for 15 minutes, 2-fluorophenylhydrazine hydrochloride (1.0 mmol) was added and the reaction was complete for 12 hours. TLC confirmed the reaction was complete. After the reaction, the mixture was extracted with water and ethyl acetate, washed with saturated sodium chloride, and the organic phase was concentrated to remove most of the ethyl acetate. The crude product was purified by 200-300 mesh silica gel column chromatography using a petroleum ether / ethyl acetate ratio of 12:1 to 6:1 to obtain the target compound, perillic acid hydrazide derivative (I-8), as a white solid in a yield of 65.4%. The mp was 154.7-157.6°C. 1 H NMR(600MHz, CDCl3)δ7.58(s,1H),7.03–6.97(m,2H),6.91(td,J=8.4,1.7Hz ,1H),6.86–6.80(m,1H),6.75(dd,J=5.5,2.7Hz,1H),4.82–4.69(m,2H),2.45 (ddd,J=17.4,5.5,2.9Hz,1H),2.36–2.25(m,2H),2.20–2.06(m,2H),1.92(dd t,J=13.0,5.0,2.5Hz,1H),1.75(s,3H),1.50(dtd,J=12.9,11.1,5.3Hz,1H). 13C NMR (151MHz, CDCl3) δ168.41,152.70,151.10,148.69,136.39,136.32,135.08,131.28,124.53,124.50,121.45 ,121.41,115.45,115.33,115.00,114.98,109.52,40.17,30.91,27.00,24.60,20.85.HRMS(ESI)m / z:calcd.for C 16 H 20 FN2O[M+H] + :275.1481; found275.1564.

[0086] Example 10

[0087] Prepare perillaldehyde formyl hydrazide derivatives (I-9):

[0088]

[0089] Perillic acid (1.0 mmol) was placed in a 50 mL single-necked round-bottom flask, and 20 mL of dichloromethane was added as the reaction solvent. 4-Dimethylaminopyridine (0.1 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 mmol) were added with stirring at room temperature, and triethylamine solution (2.0 mmol) was slowly added dropwise. After stirring for 15 minutes, 2-chlorophenylhydrazine hydrochloride (1.0 mmol) was added and the reaction was complete for 12 hours. TLC confirmed the reaction was complete. After completion of the reaction, the mixture was extracted with water and ethyl acetate, washed with saturated sodium chloride, and the organic phase was concentrated to remove most of the ethyl acetate. The crude product was purified by 200-300 mesh silica gel column chromatography using a petroleum ether / ethyl acetate ratio of 12:1 to 6:1. The target compound, perillic acid hydrazide derivative (I-9), was obtained as a white solid in a yield of 62.7%. The mp was 137.3-140.2°C. 1H NMR(600MHz, CDCl3)δ7.62(s,1H),7.27(dd,J=8.0,1.4Hz,1H),7.16–7.11(m,1H),6.88(dd,J=8.1 ,1.5Hz,1H),6.82(td,J=7.6,1.5Hz,1H),6.75(dd,J=5.6,2.8Hz,1H),4.80–4.70(m,2H),2.48–2.4 1(m,1H),2.35–2.24(m,2H),2.17(tt,J=11.2,3.3Hz,1H),2.08(dddd,J=18.5,10.4,4.2,2.4Hz,1 H),1.91(ddq,J=12.9,5.0,2.4Hz,1H),1.75(d,J=1.4Hz,3H),1.49(dtd,J=12.9,11.1,5.3Hz,1H). 13 C NMR (151MHz, CDCl3) δ168.34,148.70,144.21,135.18,131.22,129.61,127.71,121.55 ,119.94,113.84,109.51,40.15,30.92,26.99,24.60,20.84.HRMS(ESI)m / z:calcd.for C 16 H 20 ClN2O[M+H] + :291.1186; found 291.1266.

[0090] Example 11

[0091] Prepared perillaldehyde formyl hydrazide derivatives (I-10):

[0092]

[0093] Perillic acid (1.0 mmol) was placed in a 50 mL single-necked round-bottom flask, and 20 mL of dichloromethane was added as the reaction solvent. 4-Dimethylaminopyridine (0.1 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 mmol) were added with stirring at room temperature, and triethylamine solution (2.0 mmol) was slowly added dropwise. After stirring for 15 minutes, 2-bromophenylhydrazine hydrochloride (1.0 mmol) was added and the reaction was complete for 12 hours. TLC confirmed the reaction was complete. After completion of the reaction, the mixture was extracted with water and ethyl acetate, washed with saturated sodium chloride, and the organic phase was concentrated to remove most of the ethyl acetate. The crude product was purified by 200-300 mesh silica gel column chromatography using a petroleum ether / ethyl acetate ratio of 12:1 to 6:1. The target compound, perillic acid hydrazide derivative (I-10), was obtained as a white solid in a yield of 65.5%. The mp was 152.6-154.8°C. 1 H NMR(600MHz, CDCl3)δ7.61(s,1H),7.44(dd,J=7.9,1.4Hz,1H),7.21–7.15(m,1H) ,6.87(dd,J=8.1,1.5Hz,1H),6.80–6.72(m,2H),4.79–4.71(m,2H),2.48–2.42(m, 1H),2.35–2.25(m,2H),2.17(ddt,J=11.3,7.4,3.4Hz,1H),2.13–2.05(m,1H),1.9 2(ddq,J=12.8,5.0,2.4Hz,1H),1.75(s,3H),1.49(dtd,J=12.9,11.1,5.3Hz,1H). 13 C NMR (151MHz, CDCl3) δ168.32,148.70,145.17,135.20,132.77,131.19,128.37,122.06 ,113.99,109.50,109.50,40.14,30.92,26.99,24.60,20.85.HRMS(ESI)m / z:calcd.for C 16 H 20 BrN2O[M+H] + :335.0681; found 335.0761.

[0094] Example 12

[0095] Prepared perillaldehyde formyl hydrazide derivatives (I-11):

[0096]

[0097] Perillic acid (1.0 mmol) was placed in a 50 mL single-necked round-bottom flask, and 20 mL of dichloromethane was added as the reaction solvent. 4-Dimethylaminopyridine (0.1 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 mmol) were added with stirring at room temperature, and triethylamine solution (2.0 mmol) was slowly added dropwise. After stirring for 15 minutes, 3-fluorophenylhydrazine hydrochloride (1.0 mmol) was added and the reaction was complete for 12 hours. TLC confirmed the reaction was complete. After the reaction, the mixture was extracted with water and ethyl acetate, washed with saturated sodium chloride, and the organic phase was concentrated to remove most of the ethyl acetate. The crude product was purified by 200-300 mesh silica gel column chromatography using a petroleum ether / ethyl acetate ratio of 12:1 to 6:1 to obtain the target compound, perillic acid hydrazide derivative (I-11), as a white solid in a yield of 67.4%. The mp was 154.7-156.3°C. 1 H NMR (600MHz, CDCl3) δ7.67(s,1H),7.14(td,J=8.1,6.3Hz,1H),6.76(dt,J=5.4,2.3Hz,1H ),6.61(dd,J=8.2,2.1Hz,1H),6.59–6.51(m,2H),4.80–4.71(m,2H),2.48–2.41(m,1H),2. 36–2.25(m,2H),2.18(tt,J=11.1,3.4Hz,1H),2.10(dddd,J=18.2,10.2,4.2,2.3Hz,1H),1 .92(ddt,J=12.9,4.9,2.3Hz,1H),1.79–1.70(m,3H),1.50(dtd,J=12.9,11.2,5.4Hz,1H). 13 C NMR (151MHz, CDCl3) δ168.60,164.71,163.09,150.30,150.24,148.65,135.45,131.11,130.55,130.49,109.55 ,109.51,109.50,107.98,107.84,101.12,100.95,40.14,30.94,26.98,24.58,20.84.HRMS(ESI)m / z:calcd.for C 16 H 20 FN2O[M+H] + :275.1481; found 275.1567.

[0098] Example 13

[0099] Prepared perillaldehyde formyl hydrazide derivatives (I-12):

[0100]

[0101] Perillic acid (1.0 mmol) was placed in a 50 mL single-necked round-bottom flask, and 20 mL of dichloromethane was added as the reaction solvent. 4-Dimethylaminopyridine (0.1 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 mmol) were added with stirring at room temperature, and triethylamine solution (2.0 mmol) was slowly added dropwise. After stirring for 15 minutes, 3-chlorophenylhydrazine hydrochloride (1.0 mmol) was added and the reaction was complete for 12 hours. TLC confirmed the reaction was complete. After completion of the reaction, the mixture was extracted with water and ethyl acetate, washed with saturated sodium chloride, and the organic phase was concentrated to remove most of the ethyl acetate. The crude product was purified by 200-300 mesh silica gel column chromatography using a petroleum ether / ethyl acetate ratio of 12:1 to 6:1. The target compound, perillic acid hydrazide derivative (I-12), was obtained as a white solid in a yield of 63.1%. The mp was 153.7-155.9°C. 1 H NMR (600MHz, CDCl3) δ7.73 (s, 1H), 7.10 (t, J = 8.0Hz, 1H), 6.84 (ddd, J = 7.9, 2.1, 0.9Hz, 1H), 6.81 (t,J=2.1Hz,1H),6.78–6.73(m,1H),6.70(ddd,J=8.2,2.2,0.9Hz,1H),4.75(dt,J=29.2,1.3Hz,2 H),2.46–2.39(m,1H),2.30(dddd,J=21.8,15.3,4.6,2.4Hz,2H),2.17(dddd,J=14.5,9.0,3.3Hz, 1H),2.12–2.05(m,1H),1.91(ddt,J=13.0,5.8,2.3Hz,1H),1.80–1.71(m,3H),1.53–1.45(m,1H). 13 C NMR (151MHz, CDCl3) δ168.62,149.60,148.66,135.57,135.09,131.01,130.31,121.28, 113.76,112.11,109.54,40.13,30.95,26.97,24.56,20.84.HRMS(ESI)m / z:calcd.forC 16 H 20 ClN2O[M+H] + :291.1186; found 291.1266.

[0102] Example 14

[0103] Preparation of perillyl aldehyde formylhydrazine derivative (I-13):

[0104]

[0105] Perillyl alcohol (1.0 mmol) was placed in a 50 mL single-necked round-bottom flask, and 20 mL of dichloromethane was added as a reaction solvent. 4-Dimethylaminopyridine (0.1 mmol) and l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 mmol) were added with stirring at room temperature, and a solution of triethylamine (2.0 mmol) was slowly added dropwise. After stirring for 15 min to activate, 3-bromophenylhydrazine hydrochloride (1.0 mmol) was added, and the reaction was allowed to proceed for 12 h, after which TLC detection showed that the starting material had completely reacted. After the reaction was completed, the mixture was extracted with water and ethyl acetate, and washed with saturated sodium chloride. The organic phase was concentrated to remove most of the ethyl acetate, and the crude product was finally purified by column chromatography on 200-300 mesh silica gel, using petroleum ether / ethyl acetate in a volume ratio of 12:1 to 6:1. The target compound, perillyl aldehyde formylhydrazine derivative (I-13), was obtained as a white solid in a yield of 64.6% and had a melting point of 154.7-157.5°C. 1 H NMR (600 MHz, CDC13) δ 7.70 (s, 1H), 7.04 (d, J = 8.0 Hz, 1H), 7.01-6.95 (m, 2H), 6.79-6.71 (m, 2H), 4.75 (d, J = 29.1 Hz, 2H), 2.47-2.40 (m, 1H), 2.36-2.24 (m, 2H), 2.17 (dq, J = 11.3, 5.6, 3.4 Hz, 1H), 2.09 (ddt, J = 17.8, 10.5, 3.1 Hz, 1H), 1.91 (ddt, J = 13.0, 5.1, 2.6 Hz, 1H), 1.75 (s, 3H), 1.49 (qd, J = 11.6, 5.3 Hz, 1H). 13 C NMR (151 MHz, CDC13) δ 168.59, 149.70, 148.66, 135.59, 131.03, 130.61, 124.28, 123.24, 116.69, 112.62, 109.56, 40.14, 30.97, 26.99, 24.59, 20.86. HRMS (ESI) m / z: calcd. for C 16 H 20 BrN2O [M+H] + : 335.0681; found 335.0756.

[0106] Example 15

[0107] Preparation of perillyl aldehyde formylhydrazine derivative (I-14):

[0108]

[0109] Perillic acid (1.0 mmol) was placed in a 50 mL single-necked round-bottom flask, and 20 mL of dichloromethane was added as the reaction solvent. 4-Dimethylaminopyridine (0.1 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 mmol) were added with stirring at room temperature, and triethylamine solution (2.0 mmol) was slowly added dropwise. After stirring for 15 minutes, 2-chloro-4-fluorophenylhydrazine hydrochloride (1.0 mmol) was added and allowed to react for 12 hours. TLC confirmed the complete reaction. After completion of the reaction, the mixture was extracted with water and ethyl acetate, washed with saturated sodium chloride, and the organic phase was concentrated to remove most of the ethyl acetate. The crude product was purified by 200-300 mesh silica gel column chromatography using a petroleum ether / ethyl acetate ratio of 12:1 to 6:1 to obtain the target compound, perillic acid hydrazide derivative (I-14), as a yellow solid in a yield of 58.7%. The mp was 134.2-136.0°C. 1 H NMR (600MHz, CDCl3) δ7.52 (s, 1H), 7.06 (dd, J = 8.1, 2.5Hz, 1H), 6.91–6.85 (m, 2H), 6 .77(dt,J=5.2,2.2Hz,1H),4.80–4.72(m,2H),2.49–2.43(m,1H),2.37–2.27(m,2H), 2.19(tt,J=11.1,3.4Hz,1H),2.11(dddd,J=18.4,10.5,4.2,2.3Hz,1H),1.93(ddq, J=12.8,4.7,2.5Hz,1H),1.76(d,J=1.3Hz,3H),1.51(dtd,J=13.0,11.2,5.4Hz,1H). 13 C NMR (151MHz, CDCl3) δ168.44,157.85,156.24,148.59,140.82,140.80,135.39,131.14,120.37,120.30,116.92, 116.74,114.81,114.75,114.58,114.43,109.57,40.13,30.93,26.96,24.57,20.83.HRMS(ESI)m / z:calcd.forC 16 H 19 ClFN2O[M+H] + :309.1092; found 309.1168.

[0110] Example 16

[0111] Bactericidal activity (in vitro) experiment

[0112] All the test strains in this experiment were purchased from the official website of China Agricultural Culture Collection Center (ACCC) and Beijing Beinachuanglian Biotechnology Research Institute (BNCC), including Sclerotinia sclerotiorum of rape (ACCC 30096), Brown rot of stone fruit (BNCC113562), Botrytis cinerea of ​​tomato (BNCC 123731), Apple rot (BNCC 116391), Phytophthora capsici (ACCC36279), Phytophthora infestans of potato ( MYA-1113 TM ) and wheat fusarium head blight (ACCC 31060). The culture medium used is potato agar-dextrose medium (PDA). PDA medium formula: 200g potatoes (peeled), 20g glucose, 15g agar, 1000mL distilled water. Preparation method: Wash and peel the potatoes, weigh 200g, cut into small pieces, add water and cook until soft (boil for 20-30 minutes, until it can be pierced by a glass rod), filter through eight layers of gauze into a beaker, add 15-20g agar and 20g glucose as needed, stir evenly, dissolve thoroughly, cool slightly, add water to 1000mL, sterilize at 121℃ for 15 minutes after packaging, and cool for later use.

[0113] Experimental method: Growth rate method was used.

[0114] (1) First, culture the seven plant fungi on a PDA plate at 25°C for about 3-6 days before use;

[0115] (2) Heat and melt the PDA culture medium, cool it to 45-50°C, add 25 mg / L of the test compound to prepare a culture medium containing 25 mg / L of the drug solution, and pour it into culture dishes to cool. Bixafen and carbendazim serve as positive controls.

[0116] (3) Using aseptic operation procedures, use a punch to punch a circular bacterial cake (0.50 cm in diameter) at the edge of the hyphae of each strain after 6 days of culture (growth conditions should be as consistent as possible), then use an inoculation needle to pick it to the center of the drug-containing plate, and then place the culture plate upside down in an incubator (28°C) for culture;

[0117] (4) Observe and measure the growth of mycelium at different times after treatment, measure the diameter using the cross-cross method, process the data, and calculate the inhibition rate;

[0118] (5) Inhibition rate (%) = (control mycelium diameter - treated mycelium diameter) / (control mycelium diameter - 0.5) × 100; (6) Each treatment was repeated 3 times.

[0119] Table 2 Test results of the inhibitory activity of perilla acid hydrazide compounds against seven agricultural pathogenic fungi

[0120]

[0121] Note: Each treatment was repeated three times in the experiment, and the data in the table are the average values ​​of the three repetitions.

[0122] Table 3 EC of some compounds 50 Value (mg / L)

[0123]

[0124]

[0125] The fungicidal activity results of experimental groups I-1 to I-14 and the control agents bixafen and carbendazim are shown in Tables 2 and 3. As shown in Tables 2 and 3, at a concentration of 25 mg / L, compounds I-1 to I-14 exhibited varying degrees of antifungal activity against seven plant fungi. Some compounds showed relatively good antifungal activity against Sclerotinia sclerotiorum, brown rot mold of stone fruit, and gray mold of tomato, and moderate to good inhibitory activity against rot fungus of apples and Phytophthora capsici. The inhibition rates of some compounds against Sclerotinia sclerotiorum, brown rot mold of stone fruit, and gray mold of tomato were higher than or equal to those of the control agents bixafen and carbendazim. Among them, compounds I-1, I-2, I-3, I-8, I-9, I-11 and I-12 had an inhibition rate of more than 95% against Sclerotinia sclerotiorum of rapeseed at a concentration of 25 mg / L, which was better than or equivalent to bixafen (100%) and carbendazim (95.4%); compounds I-1, I-2, I-3, I-4, I-8, I-9 and I-11 had an inhibition rate of more than 97% against brown rot mold of stone fruit at a concentration of 25 mg / L, which was better than or equivalent to bixafen (98.7%) and carbendazim (97.3%); compounds I-1, I-2, I-6, I-8 and I-11 had an inhibition rate of more than 96% against gray mold of tomato at a concentration of 25 mg / L, which was better than or equivalent to bixafen (96.6%) and carbendazim (98.9%). In addition, the inhibition rates of I-1 and I-2 against apple rot pathogens reached 100%, which was better than that of pyraclostrobin (99.3%) and carbendazim (96.8%); the inhibition rates of I-1 and I-2 against pepper phytophthora were 95.2% and 100%, respectively, which were equivalent to that of pyraclostrobin (100%) and carbendazim (67.3%).

[0126] Given that some target compounds have good inhibitory activity against Sclerotinia sclerotiorum, Brown Rot of Stone Fruit, Botrytis cinerea, Apple Rot and Phytophthora capsici, the EC values ​​of some compounds with higher inhibition rates were tested. 50 As can be seen from Table 3, the EC values ​​of the target compounds against Sclerotinia sclerotiorum are 50 The activity of compound I-2 against Sclerotinia sclerotiorum EC was between 1-6 mg / L. 50The value reached 1.659 mg / L, but was weaker than the positive control drugs of bixafen 0.132 mg / L and carbendazim 0.220 mg / L; the EC values ​​of some compounds against tomato gray mold 50 The EC values ​​of compounds I-1, I-2, I-3, I-4, I-8 and I-11 against Botrytis cinerea were between 0.5-4.5 mg / L. 50 The values ​​were 0.925, 0.530, 0.560, 0.712, 0.657 and 0.668 mg / L, which were better than the positive control drug bixafen 1.211 mg / L, but weaker than the positive control drug carbendazim 0.376 mg / L; the EC value of the target compound against stone fruit brown rot mold was 0. 50 The EC values ​​of compounds I-2, I-3, I-4, I-9, I-11 and I-14 against drupe brown rot fungus ranged from 0.1 to 2.5 mg / L. 50 The values ​​were 0.142, 0.621, 0.882, 0.537, 0.487 and 0.689 mg / L, respectively. Among them, the EC value of compound I-2 against stone fruit brown rot mold was 50 The EC50 values ​​of compounds I-1 and I-2 against Phytophthora capsici (Phthophthora capsici) reached 0.142 mg / L, surpassing the positive control drugs of 0.165 mg / L bixafen and 0.199 mg / L carbendazim. Furthermore, the EC50 values ​​of compounds I-1 and I-2 against P. malariae (Phytophthora capsici) were 10.555 mg / L and 5.625 mg / L, respectively, surpassing the positive control drugs of 0.732 mg / L bixafen and 1.693 mg / L carbendazim. The EC50 values ​​of compounds I-1 and I-2 against Phytophthora capsici (Phytophthora capsici) were 14.947 mg / L and 3.546 mg / L, respectively, surpassing the positive control drugs of 0.126 mg / L bixafen and 3.196 mg / L carbendazim. This series of compounds exhibited strong inhibitory activity against several fungi and has the potential to be developed as antifungal agents.

[0127] Example 19

[0128] Bactericidal in vivo experiment

[0129] Purchase pears of uniform texture and size from the market, wash their surfaces with sterile water, then with 75% ethanol, and dry them in the shade at room temperature.

[0130] Compound I-2 and bixafen were weighed and dissolved in a 0.2% Tween-80 aqueous solution at three concentrations: 200 mg / L and 100 mg / L. The pears were then sprayed evenly (3 mL for each concentration) and allowed to air dry. After the pears were free of liquid, the skin was scratched with a razor blade, with an area of ​​3 mm. Three cakes of brown rot fungus (0.5 mm diameter) were inoculated onto three pears for each concentration. Bixafen was used as a positive control, and DMSO was used as a blank control. After incubation at 25±2°C and 95% relative humidity for 6 days, the diameter of the lesions was measured, and the inhibition rate (%) was calculated. The inhibition rate (%) was calculated as follows: (blank control lesion diameter - test compound lesion diameter) / (blank control lesion diameter - 0.5) × 100.

[0131] Table 4 Biological activity of compound I-2 and bixafen against living bodies of drupe brown rot mold

[0132]

[0133] As shown in Table 4 and Figure 3 As shown, the colony diameters of I-2 and bixafen at different concentrations on day 6 were significantly smaller than those of the blank control. Regarding protective activity, I-2 exhibited inhibition rates of 54.23% and 74.03% at 100 mg / L and 200 mg / L, respectively, surpassing bixafen (68.72% and 51.99%). Regarding therapeutic activity, I-2 exhibited inhibition rates of 53.39% and 69.92% at 100 mg / L and 200 mg / L, respectively, both superior to bixafen (44.15% and 63.98%), particularly at the low-dose group. These results demonstrate that compound I-2 is an excellent antimicrobial agent with potential for controlling postharvest rot in pears.

[0134] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. A perillic acid hydrazide compound, characterized in that: The structural formula of the perillic acid hydrazide compound is shown in Formula I below: Among them, R is one of 4-H, 4-F, 4-Cl, 4-Br, 4-I, 4-CH3, 4-OCH3, 2-F, 2-Cl, 2-Br, 3-F, 3-Cl, 3-Br, and 2-Cl-4-F.

2. The method for preparing the perillic acid hydrazide compound according to claim 1, wherein: include, The perillic acid is synthesized by oxidation reaction of perillic aldehyde; Perillic acid was reacted with phenylhydrazine hydrochloride with different substituents to synthesize perillic acid hydrazide compounds.

3. The preparation method according to claim 2, wherein: The method of synthesizing perillic acid by oxidation of perillaldehyde comprises: Perillaldehyde was placed in a single-necked round-bottom flask and dimethyl sulfoxide was added as the reaction solvent; Add potassium dihydrogen phosphate aqueous solution into the single-necked flask under stirring at room temperature and stir for 10 minutes to fully mix the system; Then, a sodium chlorite aqueous solution was slowly added dropwise using a constant pressure dropping funnel, and the reaction was allowed to react for 15 h. The reaction progress was monitored by TLC. After the reaction was complete, the reaction was quenched with a 10% sodium hydroxide aqueous solution; Next, the reaction solution was adjusted to pH 2-3 with 10% dilute hydrochloric acid, and white solid precipitation was observed. The white solid was collected by filtration under reduced pressure to obtain perillic acid.

4. The preparation method according to claim 3, wherein: The molar ratio of perillaldehyde, potassium dihydrogen phosphate and sodium chlorite is 1:0.3:2.

2.

5. The preparation method according to any one of claims 2 to 4, characterized in that: The synthetic perillic acid hydrazide compound comprises: Perillic acid was placed in a single-necked round-bottom flask, and dichloromethane was added as the reaction solvent. 4-Dimethylaminopyridine and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added under stirring at room temperature, and triethylamine solution was slowly added dropwise. After sufficient stirring and activation for 15 minutes, phenylhydrazine hydrochloride with different substituents was added and the reaction was carried out for 12 hours. TLC was used to detect the complete reaction of the raw materials. After the reaction, the mixture was extracted with water and ethyl acetate and washed with saturated sodium chloride. The organic phase was concentrated by rotary evaporation to remove most of the ethyl acetate. Finally, the crude product was separated and purified by 200-300 mesh silica gel column chromatography to obtain the target compound, perillic acid hydrazide compound. The eluent in the silica gel column chromatography separation is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 12:1 to 6:

1.

6. The preparation method according to claim 5, wherein: The molar ratio of the perillic acid, 4-dimethylaminopyridine, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, triethylamine and phenylhydrazine hydrochloride with different substituents is 1:0.1:1.2:

1.

7. The preparation method according to claim 6, wherein: The phenylhydrazine hydrochloride with different substituents is phenylhydrazine hydrochloride, 4-fluorophenylhydrazine hydrochloride, 4-chlorophenylhydrazine hydrochloride, 4-bromophenylhydrazine hydrochloride, 4-iodophenylhydrazine hydrochloride, 4-methylphenylhydrazine hydrochloride, 4-methoxyphenylhydrazine hydrochloride, 2-fluorophenylhydrazine hydrochloride, 2-chlorophenylhydrazine hydrochloride, 2-bromophenylhydrazine hydrochloride, 3-fluorophenylhydrazine hydrochloride, 3-chlorophenylhydrazine hydrochloride, 3-bromophenylhydrazine hydrochloride, and 2-chloro-4-fluorophenylhydrazine hydrochloride.

8. Use of the perillic acid hydrazide compound according to claim 1 in preventing and controlling plant fungi in agriculture or forestry.

9. The use according to claim 8, characterized in that: The plant fungi are rapeseed sclerotinia disease, stone fruit brown rot fungi, tomato gray mold fungi, apple rot fungi, pepper phytophthora, potato late blight fungi and wheat fusarium.

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