Syringic ester compound capable of preventing and treating barn pests as well as preparation method and application of syringic ester compound

Abstract

The invention discloses a syringate compound capable of preventing and treating barn pests as well as a preparation method and application of the syringate compound. The syringate compound has the following molecular structure expression, and according to the design, the light stability is enhanced by utilizing a rigid cyclic structure of chrysanthemic acid, and the CarE activity can be inhibited through a propenyl side chain of eugenol, so that self metabolism inactivation of pyrethrin is blocked; .

Description

Technical Field

[0001] This invention belongs to the field of bio-agricultural technology, specifically relating to a eugenol compound that can control pests in grain storage, its preparation method, and its application. Background Technology

[0002] Plant-derived insecticides, as an alternative to chemically synthesized pesticides, have shown unique potential in the control of grain pests. Current research hotspots mainly include the following categories: 1) Terpenoids (such as azadirachtin and eucalyptol), which regulate growth by interfering with insect ecdysone signaling pathways (e.g., inhibiting 20-hydroxyecdysone synthesis), but have low killing efficiency against adult insects; 2) Alkaloids (such as nicotinic acid and matrine), which act on nicotinic acetylcholine receptors (nAChR) to induce nerve excitation, but pose a risk of mammalian toxicity; 3) Flavonoids (such as rotenone and rotenone), which block energy metabolism by inhibiting mitochondrial complex I, but easily induce oxidative stress leading to deterioration of grain composition.

[0003] Against this backdrop, research on pyrethroids and eugenol has attracted much attention due to their specific target effects. Pyrethroids (such as permethrin and deltamethrin) induce neurological hyperexcitability by targeting the voltage-gated sodium ion channel (Vssc1) in insects, exhibiting rapid knockdown properties. However, their ester bonds are easily hydrolyzed by insect carboxylesterase (CarE) to generate chrysanthemic acid, leading to a decline in efficacy. Furthermore, although the cyclopropanecarboxylic acid structure of chrysanthemic acid retains some sodium channel binding capacity, its insecticidal activity is reduced by more than 90%. In addition, the high water solubility of chrysanthemic acid limits its penetration efficiency on the insect epidermis.

[0004] Eugenol, a natural phenylpropanoid compound, interferes with insect energy homeostasis by activating octopus amine receptors, and has an oviposition inhibition rate of 70%-85% in adults. However, its propenylphenol structure is easily oxidized and metabolized by insect P450 enzymes, and its monohydroxyl property leads to excessively high molecular polarity, making it difficult to penetrate the chitinous layer of larvae.

[0005] Molecular hybridization design based on the basic structures of pyrethroids and eugenol is of great significance for developing novel pest control drugs to improve pest control efficacy. Summary of the Invention

[0006] To address the above technical problems, this invention proposes a eugenol compound that can control pests in grain storage, along with its preparation method and application.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows: Based on the first aspect of the present invention, a eugenol compound for controlling grain storage pests is provided, having the following molecular structural expression: .

[0008] Based on a second aspect of the present invention, a method for preparing eugenol compounds for controlling grain storage pests as described above is also provided, comprising the following preparation process: S1. Eugenol and hydrobromic acid are mixed and refluxed to demethylate eugenol, generating 4-allyl catechol. S2. After drying chrysanthemic acid, excess thionyl chloride is added, and the mixture is purified after reaction to obtain its acyl chloride intermediate. The intermediate is mixed and dissolved with 4-allylcatechol, and reacted under the condition of pyridine as a catalyst to obtain the eugenol ester compound.

[0009] In a preferred embodiment of the present invention, in step S1, the amount of hydrobromic acid used, in molar terms, is 1.5-2 times that of eugenol; Preferably, the mass concentration of the hydrobromic acid is 40-70%.

[0010] In a preferred embodiment of the present invention, the reflux reaction conditions in step S1 are: heating to 100-110°C and reacting for 2-4 hours.

[0011] The reaction solvent in step S1 is one or more of acetonitrile, 1,4-dioxane, and toluene.

[0012] In a preferred embodiment of the present invention, after the reaction in step S1 is completed, the mixture is cooled, neutralized with alkali to pH 8-9, extracted with an organic solvent, dried, and purified by distillation to obtain 4-allyl catechol.

[0013] In a preferred embodiment of the present invention, the molar ratio of chrysanthemic acid to thionyl chloride is 1:(2-5); Preferably, the reaction conditions for chrysanthemic acid and thionyl chloride are 75-80°C for 2-4 hours.

[0014] In a preferred embodiment of the present invention, in step S2, the molar amount of 4-allyl catechol is 1 / 3 to 1 / 2 of the molar amount of chrysanthemic acid.

[0015] In a preferred embodiment of the present invention, in step S2, the amount of pyridine added is 2.2-3 times the molar amount of 4-allylcatechol.

[0016] In a preferred embodiment of the present invention, in step S2, the reaction between the intermediate and 4-allylcatechol is carried out in an organic solvent; the organic solvent is selected from one or more of anhydrous dichloromethane, chloroform, toluene, tetrahydrofuran, and ethyl acetate; Preferably, in step S2, the reaction between the intermediate and 4-allylcatechol is carried out at 0-30°C.

[0017] The possible reaction process expressions for the above reaction are as follows: .

[0018] Based on a third aspect of the present invention, the application of eugenol compounds as described above or eugenol compounds prepared by the methods described above in grain storage pest control drugs or methods is also provided.

[0019] This invention first demethylates the methoxy group on the benzene ring of eugenol to convert it into a phenolic hydroxyl group, then chlorinates chrysanthemic acid to a highly active chrysanthioyl chloride, which is then linked to the two phenolic hydroxyl groups in the eugenol demethylation product, constructing a dual-effect molecule with both sodium channel targeting and octopamine receptor regulatory functions. This design not only utilizes the rigid cyclic structure of chrysanthemic acid to enhance photostability but also inhibits CarE activity through the propenyl side chain of eugenol, thereby blocking the self-metabolism and inactivation of pyrethroids. This design concept breaks through the bottleneck of the single mode of action of traditional plant-derived components, providing a new paradigm for the development of multi-target synergistic insecticides. Detailed Implementation

[0020] The present invention will be further illustrated below with specific embodiments. These embodiments are merely illustrative and do not limit the scope of the invention.

[0021] Unless otherwise specified, the raw materials and reagents used in the following embodiments of the present invention can be purchased commercially.

Example 1

[0022] A method for preparing eugenol compounds that can control pests in grain storage facilities includes the following preparation process: .

[0023] S1. Eugenol (30 mmol) and hydrobromic acid (45 mmol, 48%) were mixed in 150 ml of acetonitrile and refluxed at 110 °C for 2 h to demethylate eugenol. After the reaction was completed, the mixture was cooled and neutralized to pH 8-9 with 10% NaHCO3 aqueous solution. The organic phase was extracted with dichloromethane, dried, and purified by distillation to obtain 4-allyl catechol.

[0024] 1H NMR (500 MHz, Chloroform-d) δ 6.79 (dt, J = 2.0, 1.0 Hz, 1H), 6.78– 6.75 (m, 3H), 6.69 (d, J = 7.5 Hz, 2H), 6.60 (dt, J = 2.0, 1.0 Hz, 2H), 6.29 (s, 2H), 5.88 (s, 2H), 5.17 (d, J = 12.4 Hz, 2H), 4.92 (d, J = 12.4 Hz, 2H), 3.27 (t, J = 1.0 Hz, 4H). S2. After drying chrysanthemic acid (50 mmol), excess thionyl chloride (100 mmol) was added, and the mixture was reacted at 75 °C for 3 h. After the reaction, the mixture was purified by distillation to obtain its acyl chloride intermediate. The obtained intermediate and 4-allyl catechol (25 mmol) were mixed and dissolved in 50 mL of anhydrous dichloromethane, and pyridine (55 mmol) was added dropwise to catalyze the reaction. During the reaction, the system temperature was controlled below 25 °C. After the reaction was completed, saturated NaHCO3 solution (100 mL) was added, the organic phase was separated, and the mixture was concentrated and purified to obtain eugenol compound A.

[0025] ¹H NMR (500 MHz, Chloroform-d) δ 6.94 (d, J = 7.5 Hz, 1H), 6.88 (ddt,J = 7.5, 2.0, 0.9 Hz, 1H), 6.75 (dt, J = 2.0, 1.0 Hz, 1H), 5.88 (s, 1H), 5.24(s, 2H), 5.17 (d, J = 12.5 Hz, 1H), 4.92 (d, J = 12.5 Hz, 1H), 3.32 (t, J =1.0 Hz, 2H), 2.42 (hept, J = 1.0 Hz, 2H), 2.18 (s, 2H), 1.70 (d, J = 1.0 Hz, 6H), 1.65 (s, 3H), 1.10 (s, 5H), 1.05 (s, 5H).

Example 2

[0026] A method for preparing eugenol compounds that can control pests in grain storage facilities includes the following preparation process: S1. Eugenol (30 mmol) and hydrobromic acid (60 mmol, 48%) were mixed in 150 ml of 1,4-dioxane and refluxed at 100 °C for 4 h to demethylate eugenol. After the reaction was completed, the mixture was cooled and neutralized to pH 8-9 with 10% NaHCO3 aqueous solution. The organic phase was extracted with dichloromethane, dried, and purified by distillation to obtain 4-allyl catechol.

[0027] S2. After drying chrysanthemic acid (50 mmol), excess thionyl chloride (180 mmol) was added, and the mixture was reacted at 75 °C for 4 h. After the reaction, the mixture was purified by distillation to obtain its acyl chloride intermediate. The obtained intermediate was mixed and dissolved with 4-allyl catechol (17 mmol) in 50 mL of anhydrous chloroform, and pyridine (51 mmol) was added dropwise to catalyze the reaction. During the reaction, the system temperature was controlled below 25 °C. After the reaction was completed, saturated NaHCO3 solution (100 mL) was added, the organic phase was separated, and the mixture was concentrated and purified to obtain eugenol compound A.

Example 3

[0028] A method for preparing eugenol compounds that can control pests in grain storage facilities includes the following preparation process: S1. Eugenol (30 mmol) and hydrobromic acid (52 mmol, 48%) were mixed in 150 ml of toluene and refluxed at 105 °C for 3 h to demethylate eugenol. After the reaction was completed, the mixture was cooled and neutralized to pH 8-9 with 10% NaHCO3 aqueous solution. The organic phase was extracted with dichloromethane, dried, and purified by distillation to obtain 4-allyl catechol.

[0029] S2. After drying chrysanthemic acid (50 mmol), excess thionyl chloride (250 mmol) was added, and the mixture was reacted at 80 °C for 2 h. After the reaction, the mixture was purified by distillation to obtain its acyl chloride intermediate. The obtained intermediate and 4-allyl catechol (20 mmol) were mixed and dissolved in 50 mL of anhydrous dichloromethane, and pyridine (52 mmol) was added dropwise to catalyze the reaction. During the reaction, the system temperature was controlled below 25 °C. After the reaction was completed, saturated NaHCO3 solution (100 mL) was added, the organic phase was separated, and the mixture was concentrated and purified to obtain eugenol compound A. <Insecticidal effect test>

[0030] 1. Experimental conditions Test insect: Adult corn weevil (7 days after emergence, healthy and disease-free, with uniform weight). Environmental conditions: Artificial climate chamber (temperature 28±1℃, relative humidity 70%±5%, photoperiod 12L:12D); Preparation of the drug solutions: Eugenol compound A solution (mass concentration 0.001%-0.1%, solvent acetone), pyrethroid solution (mass concentration 0.001%-0.1%, solvent acetone), eugenol solution (mass concentration 0.5%, solvent acetone), and acetone control solution.

[0031] 2. Group Design Multiple maize weevils were cultured in an artificial climate chamber for 2 days and then randomly divided into groups of 20 each, with 3 replicates.

[0032] 3. Experimental Procedure Take a 9 cm diameter glass culture dish, line it with qualitative filter paper of the same size, add 1 mL of the drug solution to each dish and spread it evenly; after the acetone has completely evaporated (about 30 min), inoculate 20 test insects, cover and seal (leaving 3 1 mm diameter vent holes); continuously observe and record the knockdown time (KT). 50 The mortality rate was calculated after 24 hours (the time it takes for 50% of the test insects to be knocked down) (mortality rate = number of dead test insects / total number of test insects × 100%), and the statistics are shown in Table 1.

[0033]

[0034] *: Compared with the negative control group (acetone control solution), the difference was statistically significant according to independent samples t-test analysis (P<0.05). As shown in Table 1, the KT of eugenol compound A at a concentration of 0.01% is... 50 The time to 24-hour mortality (25.1±3.1 min) was significantly shorter than that of pyrethroids at the same concentration (45.2±5.1 min), and the mortality rate at 24 hours (89.4±2.9%) was significantly higher than that of pyrethroids at the same concentration (67.8±4.1%), indicating that compound A of the eugenol family has superior insecticidal activity. <Light stability test>

[0035] 1. Experimental Objective To verify the difference in photostability of eugenol compound A compared to pyrethroids and eugenol, the molecular residue rate under ultraviolet light was used as the evaluation index.

[0036] 2. Experimental conditions Light source: UV aging test chamber (wavelength 254 nm, irradiance 100 μW / cm², simulating UV light conditions in a storage environment). Test samples: eugenol compound A (mass concentration 0.01%), pyrethroid (mass concentration 0.01%), and eugenol (mass concentration 0.5%), all prepared in acetone as solvent; Detection method: High performance liquid chromatography (HPLC, column: C18 column, mobile phase: methanol-water = 80:20, flow rate 1.0 mL / min, detection wavelength 280 nm).

[0037] 3. Experimental Procedure Take 5 mL of each of the three solutions and spread them evenly on a quartz glass slide (1 cm × 3 cm). After the acetone evaporates (about 30 min), record the initial peak area (S0). The glass slide was placed in a UV aging test chamber, and samples were taken after irradiation for 2 h, 4 h, 6 h, and 8 h. The residual compounds on the slide were eluted with 5 mL of methanol, and the peak area (S) of the eluent was measured. t ); Calculate the residual rate (residual rate = S) t / S0×100%), and fitted the half-life (t1 / 2) using a first-order kinetic equation. The results are shown in Table 2.

[0038]

[0039] As shown in Table 2, the UV half-life t1 / 2 of eugenol compound A is 4 times that of pyrethroid and 5.8 times that of eugenol, demonstrating that its photostability is significantly enhanced and can reduce the degradation of efficacy caused by UV light in the storage environment. <Drug efficacy decline period test>

[0040] 1. Experimental Objective To verify the rate of efficacy decline of eugenol compound A compared to pyrethroids, KT was measured at different time points. 50 The 24-hour mortality rate was used as the evaluation indicator.

[0041] 2. Experimental conditions Test insect: Adult corn weevil (7 days after emergence, healthy and disease-free, with uniform weight). Environmental conditions: Artificial climate chamber (temperature 28±1℃, relative humidity 70%±5%, photoperiod 12L:12D); Test samples: eugenol compound A (mass concentration 0.01%) and pyrethroid (mass concentration 0.01%), both prepared with acetone as solvent; Efficacy observation time points: 1 day, 7 days, 14 days, 21 days, and 28 days after application (covering typical storage cycles).

[0042] 3. Experimental Procedure Take a 9 cm diameter glass petri dish, line it with qualitative filter paper of the same size, add 1 mL of the drug solution to each dish and spread it evenly; seal the petri dish and place it in an artificial climate chamber (avoiding external interference); at 1, 7, 14, 21, and 28 days after drug application, open the petri dish and inoculate 20 adult corn weevils, and measure the KT. 50 The 24-hour mortality rate was measured, and each group was repeated three times. The results are shown in Table 3.

[0043]

[0044] As shown in Table 3, 28 days after application, the KT of eugenol compound A was... 50 The duration was only extended to 36.2±3.8 min, and the 24-hour mortality rate remained at 78.3±2.9%. Meanwhile, the KT of pyrethroid insecticide at 28 days... 50 The efficacy of eugenol compound A was extended to 120.3±9.6 min, and the 24-hour mortality rate decreased to 15.2±2.8%, demonstrating that the efficacy decline rate of eugenol compound A was significantly slower than that of pyrethroids, achieving the technical effect of "extending the efficacy decline period" and allowing a single application to cover the entire storage cycle.

[0045] The above description is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make several improvements and additions without departing from the method of the present invention, and these improvements and additions should also be considered within the scope of protection of the present invention.

Claims

1. A eugenol compound for controlling pests in grain storage, characterized in that, It has the following molecular structural expression: .

2. A method for preparing a eugenol compound as described in claim 1 for controlling grain storage pests, characterized in that, The preparation process includes the following: S1. Eugenol and hydrobromic acid are mixed and refluxed to demethylate eugenol, generating 4-allyl catechol. S2. After drying chrysanthemic acid, excess thionyl chloride is added, and the mixture is purified after reaction to obtain its acyl chloride intermediate. The intermediate is mixed and dissolved with 4-allylcatechol, and reacted under the condition of pyridine as a catalyst to obtain the eugenol ester compound.

3. The method for preparing eugenol compounds for controlling grain storage pests according to claim 2, characterized in that, In step S1, the amount of hydrobromic acid used, in molar terms, is 1.5-2 times that of eugenol; Preferably, the mass concentration of the hydrobromic acid is 40-70%.

4. The method for preparing eugenol compounds for controlling grain storage pests according to claim 2 or 3, characterized in that, The reflux reaction conditions in step S1 are: heating to 100-110℃ and reacting for 2-4 hours.

5. The method for preparing eugenol compounds for controlling grain storage pests according to any one of claims 1-4, characterized in that, After the reaction in step S1 is completed, the mixture is cooled, neutralized with alkali to pH 8-9, extracted with an organic solvent, dried, and purified by distillation to obtain 4-allyl catechol.

6. The method for preparing eugenol compounds for controlling grain storage pests according to any one of claims 1-5, characterized in that, The molar ratio of chrysanthemic acid to thionyl chloride is 1:(2-5); Preferably, the reaction conditions for chrysanthemic acid and thionyl chloride are 75-80°C for 2-4 hours.

7. The method for preparing eugenol compounds for controlling grain storage pests according to any one of claims 1-6, characterized in that, In step S2, the molar amount of 4-allyl catechol is 1 / 3 to 1 / 2 of the molar amount of chrysanthemic acid.

8. The method for preparing eugenol compounds for controlling grain storage pests according to any one of claims 1-7, characterized in that, In step S2, the amount of pyridine added is 2.2-3 times the molar amount of 4-allylcatechol.

9. The method for preparing eugenol compounds for controlling grain storage pests according to any one of claims 1-8, characterized in that, In step S2, the reaction between the intermediate and 4-allylcatechol is carried out in an organic solvent; the organic solvent is selected from one or more of anhydrous dichloromethane, chloroform, toluene, tetrahydrofuran, and ethyl acetate. Preferably, in step S2, the reaction between the intermediate and 4-allylcatechol is carried out at 0-30°C.

10. The use of a eugenol compound as described in claim 1 or a eugenol compound prepared by the method described in any one of claims 2-9 in a pesticide or method for controlling pests in grain storage areas.

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