Eugenol derivative as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of insecticides, and provides an eugenol derivative as well as a preparation method and application thereof. The method comprises the following steps: mixing a compound 1, a compound 2, a condensing agent and dichloromethane, and reacting to obtain the eugenol derivative, the condensing agent comprises 2-(7-azabenzotriazole)-N, N, N ', N'-tetramethylurea hexafluorophosphate (hereinafter referred to as HATU) and N, N-diisopropylethylamine (hereinafter referred to as DIPEA). The eugenol derivative is designed according to the prodrug principle, hydroxyl easy to oxidize in the eugenol structural formula is protected, the physicochemical property of eugenol is improved, and the solubility and stability of the compound are improved; the eugenol derivative is synthesized through a condensation reaction, the insecticidal activity of the eugenol derivative on tribolium cavaleriei is improved, an important theoretical basis is provided for development of eugenol pilot insecticides, and a reference is provided for prevention and treatment of tribolium cavaleriei pests.

Description

Technical Field

[0001] The present invention relates to the technical field of pesticides, and particularly relates to an eugenol derivative, a preparation method thereof and an application thereof. Background Art

[0002] Tribolium castaneum, belonging to the family Tenebrionidae of Coleoptera, is an important worldwide stored-grain pest. Tribolium castaneum not only harms flour, but can also bore into grains, oilseeds, Chinese medicinal materials, and insect specimens. It feeds in grains and produces debris, thus causing serious economic losses. The reproductive ability and environmental adaptability of this insect are very strong. It has 4 - 5 generations a year, lays 327 - 956 eggs at a time, has a lifespan of 547 days for males and 226 days for females. At a relative humidity of 70% and a temperature of 30°C, it takes about 35 days to reproduce one generation. The adults of Tribolium castaneum have a gland that can secrete stinky gas. This stinky liquid can cause the contaminated grains to mold or emit a stinky smell, and contains carcinogenic benzoquinone, which has a great impact on the quality and edible value of grains.

[0003] Currently, the main method for controlling Tribolium castaneum is chemical fumigation, using chemical pesticides such as phosphine for fumigation. Phosphine uses calcium phosphide and aluminum phosphide as the main raw materials. However, due to the incomplete volatilization of some fumigants, they will remain in foods and agricultural products, causing certain pollution to the products and resulting in damages in terms of economy, ecology, human health, etc. In order to protect the safety of stored grains, not only should stored-grain pests such as Tribolium castaneum be controlled to prevent pollution and losses caused by stored-grain pests, but also it should be considered that the protected objects are not polluted during the control process, and the quality and quality of grains can be guaranteed to the greatest extent. Therefore, new environmentally friendly pesticides should ensure no residue and pollution.

[0004] In recent years, more and more plant essential oils have been found to have insecticidal biological activities. Most natural plant-derived pesticides have low toxicity to mammals, are relatively safe for humans and livestock during use, and show special potential as pesticides in organic agriculture. New plant-derived pesticides such as Artemisia vulgaris essential oil also show strong insecticidal effects. Eugenol is the main active ingredient of many plant essential oils. Through research, it has been found that eugenol has high selectivity and toxicity to insect cells, has a significant repellent effect on the adults of Tribolium castaneum, and also has a certain fumigant effect on larvae and adults, but has no toxicity to human cells, and is a powerful green pesticide.

[0005] Eugenol derivatives, as potential acetylcholinesterase inhibitors, have good or even excellent insecticidal activity against Spodoptera frugiperda. Some eugenol derivatives are toxic to insect cells, which can cause chromatin condensation or fragmentation in treated insect cells, leading to programmed cell death. Their insecticidal effect is better than that of the organophosphorus pesticide chlorpyrifos, which acts by disrupting the nervous system of the target organism, especially by irreversibly inhibiting acetylcholinesterase, resulting in elevated acetylcholine levels and ultimately causing the death of the organism. Eugenol derivatives act on insect cells through a different mechanism and are safer for human cells.

[0006] Therefore, it is of great value to study and obtain an eugenol derivative with good solubility and high insecticidal rate against Tribolium castaneum. Summary of the Invention

[0007] The purpose of the present invention is to provide an eugenol derivative, its preparation method and application in order to overcome the deficiencies of the prior art.

[0008] In order to achieve the above-mentioned invention purpose, the present invention provides the following technical solutions:

[0009] The present invention provides a preparation method of an eugenol derivative, which comprises the following steps:

[0010] Mix compound 1, compound 2, a condensing agent and dichloromethane and react to obtain an eugenol derivative;

[0011] The structural formula of compound 1 is:

[0012]

[0013] The structural formula of compound 2 is

[0014] The condensing agent includes 2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate and N,N-diisopropylethylamine.

[0015] Preferably, the molar ratio of compound 1, compound 2 and the condensing agent is 2:2.2 - 2.6:5 - 7; the molar volume ratio of the condensing agent and dichloromethane is 5 - 7 mmol:18 - 22 mL.

[0016] Preferably, the molar ratio of 2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate and N,N-diisopropylethylamine is 0.9 - 1.1:0.9 - 1.1.

[0017] Preferably, the reaction is carried out at room temperature and monitored by TLC.

[0018] Preferably, after the reaction is completed, the product is successively subjected to reduced pressure and column chromatography to obtain the eugenol derivative.

[0019] The present invention also provides the eugenol derivative prepared by the preparation method described above.

[0020] Preferably, the structural formula of the eugenol derivative is:

[0021]

[0022] The present invention also provides the application of the eugenol derivative in controlling stored-grain pests.

[0023] Preferably, the stored-grain pest is Tribolium castaneum.

[0024] The beneficial effects of the present invention include the following points:

[0025] 1) The present invention designs the eugenol derivative according to the prodrug principle, protects the hydroxyl group (-OH) which is easy to oxidize in the eugenol structural formula. The main functional groups of the eugenol derivative are phenolic hydroxyl group and allyl group connected to the benzene nucleus, improving the physicochemical properties of eugenol, enhancing the solubility and stability of the compound; synthesizing the eugenol derivative by condensation reaction, analyzing the solubility of the eugenol derivative, and measuring the insecticidal activity of the eugenol derivative.

[0026] 2) The eugenol derivative prepared by the present invention has improved insecticidal activity against Tribolium castaneum, providing an important theoretical basis for the development of eugenol lead insecticides and a reference for the control of Tribolium castaneum pests. Description of the Drawings

[0027] Figure 1 shows the insecticidal activity of the water-soluble eugenol derivative against Tribolium castaneum;

[0028] Figure 2 shows the insecticidal activity of the eugenol derivative dissolved in acetone (concentration 100 mg / mL) against Tribolium castaneum;

[0029] Figure 3 shows the insecticidal activity of the eugenol derivative dissolved in acetone (concentration 25 mg / mL) against Tribolium castaneum;

[0030] Among them, different letters in the figure indicate that the insecticidal activities of different derivatives are different. Detailed Embodiments

[0031] The present invention provides a preparation method of an eugenol derivative, comprising the following steps:

[0032] Mix compound 1, compound 2, a condensing agent and dichloromethane and react to obtain the eugenol derivative;

[0033] The structural formula of Compound 1 is as follows:

[0034]

[0035] The structural formula of Compound 2 is

[0036] The condensing agent comprises 2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate and N,N-diisopropylethylamine.

[0037] In the present invention, the molar ratio of Compound 1, Compound 2 and the condensing agent is preferably 2: 2.2-2.6: 5-7, more preferably 2: 2.3-2.5: 5.5-6.5, and still more preferably 2: 2.4: 6; the molar volume ratio of the condensing agent and dichloromethane is preferably 5-7 mmol: 18-22 mL, more preferably 5.5-6.5 mmol: 19-21 mL, and still more preferably 6 mmol: 20 mL.

[0038] In the present invention, the molar ratio of 2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU) and N,N-diisopropylethylamine (DIPEA) is preferably 0.9-1.1: 0.9-1.1, more preferably 1: 1.

[0039] In the present invention, the reaction is preferably carried out at room temperature, and the reaction is monitored by TLC. The reaction time is preferably 2-24 h, more preferably 5-20 h, and still more preferably 10-15 h.

[0040] In the present invention, the product after the reaction is sequentially subjected to reduced pressure and column chromatography to obtain the eugenol derivative.

[0041] In the present invention, the purpose of reduced pressure is to remove the solvent dichloromethane.

[0042] In the present invention, the synthesis route of the eugenol derivative is as follows:

[0043]

[0044] The present invention also provides the eugenol derivative prepared by the preparation method described above.

[0045] In the present invention, the structural formula of the eugenol derivative is as follows:

[0046]

[0047] The present invention also provides the application of the eugenol derivative in controlling stored grain pests.

[0048] In the present invention, the stored - grain pests are preferably Tribolium castaneum.

[0049] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0050] In the embodiment, the structural formula of Compound 1 is

[0051] Example 1

[0052] 2.0 mmol of Compound 1, 20 mL of dichloromethane, 2.4 mmol of Compound 2, 3.0 mmol of HATU, and 3.0 mmol of DIPEA were successively added to a 100 - mL round - bottom flask and reacted at room temperature. The reaction was monitored by TLC. After 15 h of reaction, dichloromethane was removed by a rotary evaporator, and then column chromatography was carried out to obtain the eugenol derivative.

[0053] The structural formula of Compound 2 in this example is:

[0054]

[0055] The structural formula of the eugenol derivative in this example is:

[0056]

[0057] 1 H NMR(600MHz,DMSO - d 6 )δ8.11(d,J = 8.4Hz,2H),7.67(d,J = 8.4Hz,2H),7.15(d,J = 8.0Hz,1H),7.01(s,1H),6.82(d,J = 8.0Hz,1H),6.00(dq,J = 16.9,8.1,7.0Hz,1H),5.13(d,J = 17.1Hz,1H),5.08(d,J = 9.9Hz,1H),3.74(s,3H),3.40(d,J = 6.4Hz,2H).

[0058] Example 2

[0059] The structural formula of Compound 2 in this example is

[0060] The reaction time was 20 h, and other conditions were the same as those in Example 1.

[0061] The structural formula of the eugenol derivative in this example is:

[0062]

[0063] 11H NMR (600 MHz, DMSO-d 6 ) δ 7.67 (d, J = 7.7 Hz, 2H), 7.60 (t, J = 8.1 Hz, 1H), 7.15 (d, J = 7.9 Hz, 1H), 7.04 (s, 1H), 6.85 (d, J = 8.0 Hz, 1H), 6.00 (td, J = 16.4, 6.8 Hz, 1H), 5.14 (d, J = 17.1 Hz, 1H), 5.08 (d, J = 10.0 Hz, 1H), 3.80 (s, 3H), 3.41 (d, J = 6.5 Hz, 2H).

[0064] Example 3

[0065] The structural formula of Compound 2 in this example is

[0066] The reaction time was 10 h, and other conditions were the same as in Example 1.

[0067] The structural formula of the eugenol derivative in this example is:

[0068]

[0069] 1 1H NMR (600 MHz, DMSO-d 6 ) δ 8.11 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 7.01 (s, 1H), 6.82 (d, J = 8.0 Hz, 1H), 6.00 (dq, J = 16.9, 8.1, 7.0 Hz, 1H), 5.13 (d, J = 17.1 Hz, 1H), 5.08 (d, J = 9.9 Hz, 1H), 3.74 (s, 3H), 3.40 (d, J = 6.4 Hz, 2H), 2.93 (d, J = 79.3 Hz, 3H).

[0070] Example 4

[0071] The structural formula of Compound 2 in this example is

[0072] The reaction time was 5 h, and other conditions were the same as in Example 1.

[0073] The structural formula of the eugenol derivative in this example is:

[0074]

[0075] 1 1H NMR (600 MHz, DMSO-d 6)δ6.94(d,J=8.0Hz,1H),6.92(s,1H),6.73(d,J=8.0Hz,1H),5.96(dq,J=16.8,6.8Hz,1H),5.11(d,J=17.0Hz,

[0076] 1H),5.06(d,J=10.0Hz,1H),3.73(s,3H),3.35(d,J=6.8Hz,2H),1.52(s,1H),1.20(s,12H).

[0077] Example 5

[0078] The structural formula of Compound 2 in this example is

[0079] The reaction time was 8 h, and other conditions were the same as in Example 1.

[0080] The structural formula of the eugenol derivative in this example is:

[0081]

[0082] 1 H NMR(600MHz,DMSO-d 6 )δ6.96(d,J=8.0Hz,1H),6.90(s,1H),6.72(d,J=7.4Hz,1H),5.97(td,J=16.8,6.8Hz,1H),5.11(d,J=17.0Hz,1H),5.05(d,J=10.0Hz,1H),3.73(s,3H),3.39(d,J=6.9Hz,1H),3.35(d,J=6.7Hz,2H),3.30–3.23(m,1H),2.93(d,J=79.3Hz,3H),1.12(dt,J=59.3,7.1Hz,3H).

[0083] Example 6

[0084] The structural formula of Compound 2 in this example is:

[0085] The reaction time was 20 h, and other conditions were the same as in Example 1.

[0086] The structural formula of the eugenol derivative in this example is:

[0087]

[0088] 1 H NMR(600MHz,DMSO-d 6) δ 6.94 (d, J = 8.0 Hz, 1H), 6.92 (s, 1H), 6.73 (d, J = 8.0 Hz, 1H), 5.96 (dq, J = 16.8, 6.8 Hz, 1H), 5.11 (d, J = 17.0 Hz, 1H), 5.06 (d, J = 10.0 Hz, 1H), 3.73 (s, 6H), 3.35 (d, J = 6.8 Hz, 2H), 1.52 (s, 1H).

[0089] Comparative Example 1

[0090] The structural formula of Compound 2 in this comparative example is Other conditions are the same as those in Example 1.

[0091] The structural formula of the eugenol derivative in this comparative example is:

[0092]

[0093] 1 H NMR (600 MHz, DMSO-d 6 ) δ 6.96 (d, J = 8.0 Hz, 1H), 6.90 (s, 1H), 6.72 (d, J = 6.4 Hz, 1H), 6.02–5.92 (m, 1H), 5.11 (d, J = 17.3 Hz, 1H), 5.05 (d, J = 9.5 Hz, 1H), 3.73 (s, 3H), 3.36 (s, 2H), 3.02 (s, 3H), 2.87 (s, 3H).

[0094] Comparative Example 2

[0095] The structural formula of Compound 2 in this comparative example is Other conditions are the same as those in Example 1.

[0096] The structural formula of the eugenol derivative in this comparative example is:

[0097]

[0098] 1 H NMR (600 MHz, DMSO-d 6 ) δ 7.76 (h, J = 7.4, 6.9 Hz, 1H), 7.33 (t, J = 8.8 Hz, 2H), 7.14 (d, J = 8.1 Hz, 1H), 7.07–6.99 (m, 1H), 6.83 (d, J = 8.0 Hz, 1H), 6.00 (tq, J = 13.5, 6.7 Hz, 1H), 5.14 (d, J = 17.0 Hz, 1H), 5.09 (d, J = 10.0 Hz, 1H), 3.41 (d, J = 6.7 Hz, 2H).

[0099] Comparative Example 3

[0100] The structural formula of Compound 2 in this comparative example is Other conditions are the same as those in Example 1.

[0101] The structural formula of the eugenol derivative in this comparative example is:[[]]

[0102]

[0103] 1 H NMR(600MHz,DMSO-d 6 )δ7.19(d,J = 8.2Hz,1H),7.02(s,1H),6.80(d,J = 8.2Hz,1H),5.97(dq,J = 17.6,7.6Hz,1H),5.12(d,J = 17.0Hz,1H),5.07(d,J = 10.0Hz,1H),3.82(s,3H),3.44(q,J = 7.4Hz,2H),3.38(d,J = 6.9Hz,2H),1.37(t,J = 7.4Hz,3H).

[0104] Comparative Example 4

[0105] The structural formula of Compound 2 in this comparative example is Other conditions are the same as those in Example 1.

[0106] The structural formula of the eugenol derivative in this comparative example is:[[]]

[0107]

[0108] 1 H NMR(600MHz,DMSO-d 6 )δ8.05(d,J = 8.7Hz,2H),7.11(d,J = 6.4Hz,3H),6.99(s,1H),6.81(d,J = 7.8Hz,1H),6.00(dq,J = 16.5,8.2,6.9Hz,

[0109] 1H),5.14(d,J = 16.9Hz,1H),5.08(d,J = 9.7Hz,1H),3.73(s,3H),3.40(d,J = 6.8Hz,2H).

[0110] Comparative Example 5

[0111] The structural formula of Compound 2 in this comparative example is Other conditions are the same as those in Example 1.

[0112] The structural formula of the eugenol derivative in this comparative example is:[[]]

[0113]

[0114] 1 H NMR(600 MHz, DMSO-d 6 ) δ 8.02 (d, J = 8.1 Hz, 2H), 7.82 (d, J = 7.8 Hz, 2H), 7.15 (d, J = 7.9 Hz, 1H), 7.01 (s, 1H), 6.82 (d, J = 7.8 Hz, 1H), 6.00 (td, J = 16.5, 6.5 Hz, 1H), 5.14 (d, J = 16.9 Hz, 1H), 5.08 (d, J = 9.9 Hz, 1H), 3.74 (s, 3H), 3.40 (d, J = 5.9 Hz, 2H).

[0115] Comparative Example 6

[0116] The structural formula of Compound 2 in this comparative example is Other conditions are the same as those in Example 1.

[0117] The structural formula of the eugenol derivative in this comparative example is:[[]]

[0118]

[0119] 1 H NMR(600 MHz, DMSO-d 6 ) δ 7.69 (d, J = 7.9 Hz, 2H), 7.44 (d, J = 7.9 Hz, 2H), 6.97 (d, J = 8.2 Hz, 1H), 6.87 (s, 1H), 6.73 (d, J = 8.4 Hz, 1H), 5.93 (dq, J = 16.3, 7.2 Hz, 1H), 5.11–5.02 (m, 2H), 3.48 (s, 3H), 3.34 (d, J = 3.9 Hz, 2H), 2.42 (s, 3H).

[0120] Comparative Example 7

[0121] The structural formula of Compound 2 in this comparative example is Other conditions are the same as those in Example 1.

[0122] The structural formula of the eugenol derivative in this comparative example is:[[]]

[0123]

[0124] 1 H NMR(600 MHz, DMSO-d 6)δ8.69(s,1H),8.49(d,J=7.5Hz,1H),7.66(d,J=5.7Hz,1H),7.24–7.18(m,1H),7.03(s,1H),6.84(d,J=7.6Hz,

[0125] 1H),6.00(td,J=16.3,6.2Hz,1H),5.13(d,J=17.0Hz,1H),5.08(d,J=9.8Hz,1H),3.79(s,3H),3.40(d,J=5.5Hz,2H).

[0126] Comparative Example 8

[0127] The structural formula of Compound 2 in this comparative example is Other conditions are the same as those in Example 1.

[0128] The structural formula of the eugenol derivative in this comparative example is:[[]]

[0129]

[0130] 1 H NMR(600MHz,DMSO-d 6 )δ6.94(d,J=8.0Hz,1H),6.92(s,1H),6.73(d,J=8.0Hz,6H),5.96(dq,J=16.8,6.8Hz,1H),5.11(d,J=17.0Hz,1H),5.06(d,J=10.0Hz,1H),3.73(s,6H),3.35(d,J=6.8Hz,2H),1.52(s,2H).

[0131] Comparative Example 9

[0132] The structural formula of Compound 2 in this comparative example is Other conditions are the same as those in Example 1.

[0133] The structural formula of the eugenol derivative in this comparative example is:[[]]

[0134]

[0135] 1 H NMR(600MHz,DMSO-d 6)δ 6.94 (d, J = 8.0 Hz, 1H), 6.92 (s, 1H), 6.73 (d, J = 8.0 Hz, 1H), 5.96 (dq, J = 16.8, 6.8 Hz, 1H), 5.11 (d, J = 17.0 Hz, 1H), 5.06 (d, J = 10.0 Hz, 1H), 3.73 (s, 3H), 3.35 (d, J = 6.8 Hz, 2H), 1.52 (s, 3H)..

[0136] The water solubility and acetone solubility of the eugenol derivatives of Examples 1 - 6 and Comparative Examples 1 - 9 were tested, and the results are shown in Table 1.

[0137] A small amount of the eugenol derivative of Example 1 was taken out and added to two centrifuge tubes (Ep tubes) respectively. 50 μL of acetone and 50 μL of sterilized water were added to the two Ep tubes respectively with a pipette to dissolve the eugenol derivative under the naked eye condition, and then marks were made on the Ep tubes. The Zeiss stereomicroscope V16 was turned on, and the Ep tube containing the eugenol derivative was placed under the microscope to observe the image displayed on the computer. If there is an obvious layered phenomenon of circles in the eugenol derivative solution, then the eugenol derivative is insoluble in this solvent; if there is no layered phenomenon in the eugenol derivative solution displayed on the image and it is uniform and stable, then the eugenol derivative is soluble in this solvent. The eugenol derivative that can dissolve in water or acetone is a colorless transparent solution, while the eugenol derivative that can only dissolve in acetone has crystals precipitated or shows a layered phenomenon in water. The above repeated experiments were carried out on the eugenol derivatives of Examples 2 - 6 and Comparative Examples 1 - 9 by the above method. The eugenol derivative that will precipitate again after dissolution was prepared and used immediately.

[0138] Table 1 Solubility of Eugenol Derivatives

[0139]

[0140] As can be seen from Table 1, the eugenol derivatives of Example 5, Example 6, Comparative Example 3, Comparative Example 6, and Comparative Example 9 are soluble in water; the eugenol derivatives of Examples and Comparative Examples are all soluble in acetone.

[0141] The insecticidal activities of the eugenol derivatives of Examples and Comparative Examples and eugenol against Tribolium castaneum were tested. The test method is as follows:

[0142] (1) Four hundred Tribolium castaneum were reared in a glass bottle with a volume of 330 mL. A mixed feed (the mass ratio of wheat flour to yeast powder was 19:1) was added to the glass bottle at 2 / 3 of the bottle volume, and then placed in an incubator for cultivation. The rearing temperature was 29 °C and the relative humidity was 75%. The late-stage larvae of Tribolium castaneum that had hatched for 18 days and were 5 - 6 mm in size were used as test insects. Fifteen 18-day-old Tribolium castaneum larvae were selected and placed into centrifuge tubes (Ep tubes); the ultra-clean bench was turned on and blown for 20 min, and a filter paper with a diameter of 9 cm, a No. 5 bristle flat brush, a marker pen, a eugenol solution or a eugenol derivative solution (the solvent was sterilized water or acetone), a pipette gun with a 100 μL range, and the corresponding pipette tips were placed into the ultra-clean bench.

[0143] (2) 50 μL of eugenol solution or eugenol derivative solution (the solvent was sterilized water or acetone, and the concentration of the solution was 25 mg / mL or 100 mg / mL) was added to the Ep tubes containing Tribolium castaneum larvae as the experimental group, and at the same time, acetone or sterilized water was used as the control group. Each treatment group was replicated three times independently.

[0144] (3) The Ep tubes were inverted on the table and left stationary for 1 min so that the surfaces of the Tribolium castaneum larvae were all soaked with the medicine. Then, the larvae were poured onto the filter paper with a brush and evenly spread out, and blown on the ultra-clean bench for 4 - 5 min to allow the surface of each Tribolium castaneum larva to air-dry naturally.

[0145] (4) After the Tribolium castaneum larvae resumed crawling on the filter paper and the liquid medicine on their body surfaces had dried, they were placed into labeled petri dishes and a little double-screened flour was added. The death status was observed every 12 h for 72 h continuously, and the mortality rate of Tribolium castaneum was counted. Mortality rate = (number of dead insects / total number of test insects)

[0146] × 100%.

[0147] The insecticidal activities of 5 water-soluble eugenol derivatives with a concentration of 100 mg / mL in Table 1 (the water-soluble eugenol derivatives of Example 5, Example 6, Comparative Example 3, Comparative Example 6, and Comparative Example 9) against Tribolium castaneum were tested, and the results are as Figure 1 shown. Different letters in the figure indicate that the insecticidal activities of different eugenol derivatives are different, and the error bars represent the standard error. As Figure 1 can be seen, only the eugenol derivatives of Example 5 and Example 6 have obvious insecticidal activities, and the average lethal rate is about 10%. While the eugenol derivatives of Comparative Example 3, Comparative Example 6, and Comparative Example 9 are the same as the sterile water control group and have no insecticidal activity.

[0148] The insecticidal activity of the eugenol derivative dissolved in acetone was detected. The mortality rate of Tribolium castaneum under the acetone solution of the eugenol derivative with a concentration of 100 mg / mL is as Figure 2As shown in the figure, different letters in the figure indicate the differences in the insecticidal activities of different eugenol derivatives, and the error bars represent the standard errors. Among them, the lethality rates of Comparative Example 1, Comparative Example 2, Comparative Example 5, Example 2, and Comparative Example 8 are the same as that of eugenol, all close to 100%, indicating that these five eugenol derivatives dissolved in acetone have strong insecticidal activities against Tribolium castaneum under high-concentration conditions. However, the insecticidal activity of Comparative Example 4 is the worst, being 40%.

[0149] Considering the issue of obtaining the maximum insecticidal efficiency and cost, the differences in insecticidal efficiency among eugenol derivatives were further explored. A pharmacodynamic experiment was conducted on Tribolium castaneum larvae using an acetone solution of eugenol derivative with a concentration of 25 mg / mL. The results are as Figure 3 shown in the figure. Different letters in the figure indicate the differences in the insecticidal activities of different eugenol derivatives, and the error bars represent the standard errors. From Figure 3 this, it can be seen that the mortality rates of Comparative Example 1, Example 4, Example 3, and Example 2 are the same as that of eugenol (about 40%); while the mortality rates of Comparative Example 4 and Comparative Example 5 are significantly lower compared with the eugenol treatment group; the mortality rate of Example 1 is significantly higher than that of eugenol, and the lethality rate is close to 60%. This indicates that the eugenol derivative of Example 1 has better insecticidal activity than eugenol and a better contact-killing effect on Tribolium castaneum, and is expected to be developed into a eugenol lead insecticide with more stable physical and chemical properties and more excellent insecticidal activity, providing a theoretical basis for the research and development of new, highly efficient, and environmentally friendly insecticides.

[0150] For the 5 water-soluble eugenol derivatives, insecticidal activity detection was carried out. Only the eugenol derivatives of Example 5 and Example 6 had obvious insecticidal activities, and the average lethality rate was about 10%. A pharmacodynamic experiment was conducted using an acetone solution of eugenol derivative with a concentration of 25 mg / mL. The eugenol derivative of Example 1 caused a significantly higher mortality rate of Tribolium castaneum than eugenol, and the lethality rate was close to 60%. The eugenol derivative of Example 2 also had good insecticidal activity. The chemical groups introduced in Example 1 and Example 2 contain chlorine (Cl) elements, and the presence of the chlorine chemical group will significantly enhance the insecticidal activity of the eugenol derivative.

[0151] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A method for preparing a eugenol derivative, characterized in that: The following steps are included: Compound 1, compound 2, a condensing agent and dichloromethane are mixed and reacted to obtain a eugenol derivative; The structural formula of compound 1 is: The structural formula of compound 2 is The condensing agent comprises 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate and N,N-diisopropylethylamine.

2. The preparation method according to claim 1, characterized in that: The molar ratio of compound 1, compound 2 and the condensing agent is 2:2.2-2.6:5-7; the molar volume ratio of the condensing agent and dichloromethane is 5-7 mmol:18-22 mL.

3. The preparation method according to claim 1 or 2, characterized in that: The molar ratio of the 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate to N,N-diisopropylethylamine is 0.9-1.1:0.9-1.

1.

4. The preparation method according to claim 3, characterized in that: The reaction was carried out at room temperature and monitored by TLC.

5. The preparation method according to claim 3, characterized in that: The product after the reaction is completed is subjected to decompression and column chromatography in sequence to obtain a eugenol derivative.

6. The eugenol derivative prepared by the preparation method according to any one of claims 1 to 5.

7. The eugenol derivative according to claim 6, characterized in that The structural formula of eugenol derivatives is:

8. Use of the eugenol derivative according to claim 6 or 7 in controlling stored-grain pests.

9. The use according to claim 8, characterized in that: The stored grain pest is Red Castanea paniculate.

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