Spiromesifen derivatives, processes for their preparation and use thereof

Abstract

The application discloses a spiromesifen derivative, belongs to the field of crop disease and pest control, and has the structure shown in the following formula 1001, a preparation method thereof is as follows: under the protection of inert gas, 3-(2, 4, 6-trimethylphenyl)-2-oxo-1-oxaspiro[4, 5]-non-3-ene-4-ol and dichloromethane are stirred and cooled to 0-5 DEG C, then triethylamine is added, fluorine ethyl chloroformate is added dropwise, after dropwise addition is completed, the reaction is continued after being raised to room temperature, and then purification is conducted, and the spiromesifen derivative is obtained; the spiromesifen derivative has higher safety for citrus, watermelon and Chinese rose and has better pest control activity than that of spiromesifen.

Description

Technical Field

[0001] This invention relates to the field of crop pest and disease control, and in particular to a spirodiclofen derivative, its preparation method and its application. Background Technology

[0002] Spirodiclofen, with the following structural formula:

[0003]

[0004] Spirodiclofen is the second ketene-enol insecticide / acaricide developed by Bayer, primarily used for controlling whiteflies and spider mites on cotton, vegetables, and ornamental plants. Its mechanism of action involves affecting the development of whiteflies and mites, interfering with their liposome biosynthesis, particularly showing good activity against larvae. It also induces ovariectomy, reducing the reproductive capacity of adult mites and whiteflies and significantly decreasing egg production. Spirodiclofen is effective against whiteflies resistant to pyriproxyfen, and when combined with methomyl, it effectively controls resistant whiteflies. However, it is necessary to develop derivatives with even better activity than spirodiclofen to meet specific control needs. Summary of the Invention

[0005] One of the objectives of this invention is to provide a spirodiclofen derivative to solve the above-mentioned problems.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: a spirodiclofen derivative having the structure shown in formula 1001:

[0007]

[0008] Through extensive experimentation, the applicant of this invention obtained the aforementioned derivative, which exhibits superior activity compared to spirodiclofen. Its activity is also significantly better than other similar compounds, such as:

[0009]

[0010] wait.

[0011] The second objective of this invention is to provide a method for preparing the above-mentioned spirodiclofen derivative. The technical solution includes the following steps: under inert gas protection, 3-(2,4,6-trimethylphenyl)-2-oxo-1-oxaspiro[4,5]-non-3-en-4-ol and 1,2-dichloroethane are stirred and cooled to 0-5°C. Then, N,N-diisopropylethylamine is added, followed by the dropwise addition of fluoroethyl chloroformate. After the addition is complete, the mixture is raised to room temperature and the reaction continues. The mixture is then purified to obtain the final product.

[0012] As a preferred technical solution, the inert gas is N2.

[0013] As a preferred technical solution, the purification method is as follows: water is added to separate the layers, then the aqueous layer is extracted with dichloromethane, the organic layers are combined, washed with saturated brine, then washed with water, concentrated, and the residue is recrystallized with petroleum ether.

[0014] The third objective of this invention is to provide the application of the above-mentioned spirodiclofen derivative, and the technical solution adopted is: for the control of crop mites.

[0015] As a preferred technical solution, the crop pest is the citrus red spider mite.

[0016] As a preferred technical solution, the crop pest is the watermelon two-spotted spider mite.

[0017] As a preferred technical solution, the crop pest is the two-spotted spider mite of the rose.

[0018] Compared with the prior art, the advantages of the present invention are: the spirodiclofen derivative of the present invention has higher safety for citrus, watermelon and rose, etc., and has better mite control activity than spirodiclofen. Attached Figure Description

[0019] Figure 1 The image shows the 1H NMR spectrum of the spirodiclofen derivative 1001 prepared in Example 1 of this invention. Detailed Implementation

[0020] The invention will now be further described with reference to the accompanying drawings.

[0021] Example 1:

[0022] A spirodiclofen derivative having the structure shown in Formula 1001:

[0023]

[0024] Its synthesis method includes the following steps:

[0025] Under N2 protection, 27.2 g (0.1 mol) of 3-(2,4,6-trimethylphenyl)-2-oxo-1-oxaspiro[4,5]-non-3-en-4-ol and 150 mL of dichloromethane were stirred and cooled to 5 °C. Then, 12.2 g (0.12 mol) of triethylamine was added, followed by dropwise addition of 12.64 g (0.1 mol) of fluoroethyl chloroformate. After the addition was complete, the mixture was brought to room temperature and the reaction was continued for 15 h before stopping. 200 mL of water was added to separate the layers. The aqueous layer was extracted with dichloromethane, the organic layers were combined, washed with saturated brine, then washed with water, concentrated, and the residue was recrystallized from petroleum ether to give 33.66 g (93% yield) of a white powdery solid, compound 1001. Its 1H NMR spectrum is shown below. Figure 1 As shown;

[0026] 1 HNMR(400MHz, CDCl3)δ6.88(s,2H),4.52–4.38(m,1H),4.38–4.29(m,1H),4.27–4.18(m,1H),4.2 0–4.11(m,1H),2.27(s,3H),2.22–2.08(m,8H),2.09–1.95(m,4H),1.90(dd,J=13.1,6.3Hz,2H).

[0027] Example 2:

[0028] Safety test and field efficacy test of spirodiclofen derivative 1001 against citrus in Example 1:

[0029] 1. Materials and Methods

[0030] 1.1 Test reagents

[0031] Using the spirodiclofen derivative 1001 obtained in Example 1, a microemulsion with a mass percentage of 20% was prepared using existing technology, namely "20% 1001 microemulsion"; and a commercially available spirodiclofen suspension with a mass percentage of 20% was prepared, namely "20% spirodiclofen suspension".

[0032] 1.2 Test Target

[0033] Citrus red spider mite;

[0034] 1.3 Test Methods

[0035] 1.3.1 Citrus Safety Test

[0036] Two mass concentrations of 20% 1001 microemulsion were set at 133 mg / L and 200 mg / L (i.e., 20% 1001 microemulsion diluted with water to the corresponding concentration; "133 mg / L" means 133 mg of "20% 1001 microemulsion" per L of water, and the rest have the same meaning), and a blank control was also set up. After preparing the solution, three varieties of citrus trees—Wogan, 091 seedless Wogan, and Satsuma mandarin orange—were selected for outdoor planting and sprayed using a backpack electric sprayer. The spray volume was 3 L per tree, and the experiment was repeated three times. The growth of citrus trees was observed daily after treatment. After 14 days, the color, morphology, and growth changes of flowers, leaves, and new shoots of the tested citrus trees were investigated and recorded to evaluate the crop safety; 1.3.2 Field trial for the control of citrus red spider mites (Nanning, Guangxi, April 2022)

[0037] The experiment was conducted in Tengxiang Village, Shuangqiao Town, Wuming District, Nanning City, Guangxi Province. The test crop was a 6-year-old Wogan mandarin orange, with an average tree height of 1.65m and a canopy width of 2.55m. Two concentrations of 20% 1001 microemulsion were set at 133mg / L and 200mg / L, and the control agent, 20% spirodiclofen suspension, was set at a concentration of 133mg / L. Water was also used as a blank control. Each treatment was replicated four times in a randomized block design.

[0038] Using a Huayou brand electric backpack sprayer, the pesticide solution was evenly sprayed onto both sides of the leaves of the Wogan mandarin orange trees. The initial insect population was assessed before application, and again at 1, 5, 10, 15, and 30 days after application. The number of active mites on the marked leaves was checked and recorded. The mite population reduction rate was calculated, and the control effect was determined.

[0039] Methods for calculating drug efficacy:

[0040]

[0041]

[0042] 1.3.3 Field trial for the control of citrus red spider mites (Guilin, Guangxi, September 2022)

[0043] The experiment was conducted in Nian Village, Xiuren Town, Lipu City, Guilin, Guangxi Province, using 7-year-old Satsuma mandarins as the test crop. Two concentrations of 20% 1001 microemulsion were set at 133 mg / L and 200 mg / L, while the control agent, 20% spirodiclofen suspension, was set at one concentration of 133 mg / L. A water control was also included. Each treatment was replicated four times in a randomized block design.

[0044] A Huayou brand electric backpack sprayer was used for conventional spraying. The initial insect population was assessed before application, and again at 1, 5, 10, 15, and 30 days after application. The number of active mites on marked leaves was checked and recorded. The mite population reduction rate was calculated, and the control effect was determined. The efficacy calculation method was the same as in 1.3.2.

[0045] 2 Results and Analysis

[0046] 2.1 The test results show that, at the tested mass concentration, 20% 1001 microemulsion is safe for Wogan, seedless Wogan, and Satsuma mandarin oranges at a mass concentration of 133–200 mg / L.

[0047] 2.2 Field trial for the control of citrus red spider mites (Nanning, Guangxi, April 2022)

[0048] At a water concentration of 133 mg / L, the 20% 1001 microemulsion showed control efficacy of 78.54% and 81.22% against citrus red spider mites 1 day after application, respectively, which was superior to the control agent spirodiclofen. From 10 to 20 days after application, both treatments with 1001 were superior to spirodiclofen. At 30 days after application, the efficacy of low-dose 1001 decreased, while high-dose treatments showed better efficacy. The experimental results are shown in Table 1.

[0049] Table 1. Results of the trial using 20% ​​1001 microemulsion to control citrus red spider mites.

[0050]

[0051] Note: The efficacy (%) in the table is the average of each replicate; the same applies to the following table.

[0052] 2.3 Field trial for the control of citrus red spider mites (Guilin, Guangxi, September 2022)

[0053] Five days after application, the 20% 1001 microemulsion achieved a control efficacy of over 89.07%, superior to spirodiclofen. Ten to fifteen days after application, all 1001 treatments showed significantly better control efficacy than spirodiclofen. Thirty days after application, the 20% 1001 microemulsion maintained a control efficacy of over 95.00% at all dosages, superior to spirodiclofen. The experimental results are shown in Table 2.

[0054] Table 2. Results of the trial on the control of citrus red spider mite with 20% 1001 microemulsion.

[0055]

[0056]

[0057] The results above indicate that the spirodiclofen derivative 1001 of the present invention is safe for citrus growth.

[0058] Spirodiclofen derivative 1001 exhibits superior rapid efficacy against citrus red spider mites compared to spirodiclofen, achieving over 89% control efficacy 5 days after application. Its duration of action is also longer than the control agent, reaching approximately 30 days. Therefore, spraying at concentrations of 133 mg / L and 200 mg / L can effectively control citrus red spider mites.

[0059] Example 3:

[0060] Safety tests and field efficacy tests of the prepared spirodiclofen derivative 1001 against watermelon and rose in Example 1:

[0061] 1. Materials and Methods

[0062] 1.3 Test reagents

[0063] Same as Example 2.

[0064] 1.4 Test Target

[0065] Watermelon two-spotted spider mite, rose two-spotted spider mite

[0066] 1.3 Test Methods

[0067] 1.3.1 Safety Test

[0068] The designed concentrations of the 20% 1001 microemulsion were 133 mg / L and 200 mg / L, with a blank control. After preparing the solution, two crops were selected: watermelon (variety 8424) grown outdoors and rose (variety Honey Peach Snow Mountain) grown in greenhouses. Spraying was performed using a backpack electric sprayer at a flow rate of 2 L / m², with three replicates. The growth of the watermelon and roses was observed daily after treatment. At 14 days, the color, morphology, and growth changes of the flowers, leaves, and new shoots of the tested watermelon and roses were recorded to evaluate crop safety.

[0069] 1.3.2 Field trial for the control of watermelon two-spotted spider mite (Duqiao, Linhai, Zhejiang, May 2022)

[0070] The experiment was conducted in Duqiao Town, Linhai City, Zhejiang Province, using watermelons transplanted 25 days prior. Two concentrations of 20% 1001 microemulsion were set: 133 mg / L and 200 mg / L. The control agent, 20% spirodiclofen suspension, was set at 133 mg / L. Water served as a blank control. Each treatment was replicated four times in a randomized block design.

[0071] Using a Huayou brand electric backpack sprayer, the pesticide solution was evenly sprayed onto both sides of the watermelon leaves. The initial insect population was assessed before application, and again at 1, 3, 10, 15, and 30 days after application. The number of active mites on the marked leaves was checked and recorded. The mite population reduction rate was calculated, and the control effect was determined.

[0072] Methods for calculating drug efficacy:

[0073]

[0074]

[0075] 1.3.3 Field trial for the control of two-spotted spider mite on rose (Nancun Village, Jinning District, Kunming City, Yunnan Province, August 2022)

[0076] The experiment was conducted in Nancun Village, Kunyang Street, Jinning District, Kunming City, Yunnan Province. The test crop was a four-year-old rose of the variety "Mitao Xueshan". Two concentrations of 20% 1001 microemulsion were set at 133 and 200 mg / L, while the control agent, 20% spirodiclofen suspension, was set at 133 mg / L. A water control was also included. Each treatment was replicated four times in a randomized block design.

[0077] A Huayou brand electric backpack sprayer was used for conventional spraying. The initial insect population was assessed before application, and again at 1, 3, 10, 15, and 30 days after application. The number of active mites on marked leaves was checked and recorded. The mite population reduction rate was calculated to determine the control effect. The efficacy calculation method was the same as in 1.3.2.

[0078] 2 Results and Analysis

[0079] 2.1 The test results show that, at the tested mass concentration, 20% 1001 microemulsion is safe for 8424 watermelon and rose at a mass concentration of 133-200 mg / L.

[0080] 2.2 Field trial for the control of watermelon two-spotted spider mite (Duqiao, Linhai, Zhejiang, July 2022)

[0081] At concentrations of 133 and 200 mg / L, the 20% 1001 microemulsion showed control efficacy of 78.54% and 81.22% against the watermelon two-spotted spider mite, respectively, one day after application, significantly better than the control agent spirodiclofen. From 10 to 15 days after application, the two 1001 treatments were superior to spirodiclofen. At 30 days after application, the control efficacy of low-dose 1001 decreased, while the high-dose treatment showed better results. The experimental results are shown in Table 3.

[0082] Table 3. Results of the trial on the control of watermelon two-spotted spider mite with 20% 1001 microemulsion.

[0083]

[0084] Note: The efficacy (%) in the table is the average of each replicate; the same applies to the following table.

[0085] 2.3 Field trial for the control of two-spotted spider mite on rose (Kunming, Yunnan, June 2022)

[0086] Three days after application, the 20% 1001 microemulsion achieved a control efficacy of over 85.33%, superior to spirodiclofen. Ten to five days after application, all 1001 treatments showed better control efficacy than spirodiclofen. Thirty days after application, the 20% 1001 microemulsion at all dosages maintained a control efficacy of over 93.00%, superior to spirodiclofen. The test results are shown in Table 4.

[0087] Table 4. Results of the trial on the control of two-spotted spider mite on rose using 20% ​​1001 microemulsion.

[0088]

[0089] Based on the above results, it can be concluded that the spirodiclofen derivative 1001 of the present invention is safe for the growth of watermelon and rose.

[0090] The spirodiclofen derivative 1001 of this invention exhibits superior rapid efficacy against the watermelon two-spotted spider mite compared to spirodiclofen, achieving over 88% control efficacy 3 days after application and maintaining a longer effective period of approximately 30 days compared to the control agent. Therefore, spraying at a concentration of 100–150 mg / L can effectively control the watermelon two-spotted spider mite. Similarly, 1001 demonstrates superior rapid efficacy against the rose two-spotted spider mite compared to spirodiclofen, achieving over 85% control efficacy 3 days after application and maintaining a longer effective period of approximately 30 days compared to the control agent. Therefore, spraying at a concentration of 133–200 mg / L can effectively control the rose two-spotted spider mite.

[0091] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A spiromesifen derivative, characterized by It has the structure shown in Equation 1001: 。 2. The process for the preparation of spiromesifen derivatives according to claim 1, characterized in that, The process includes the following steps: Under an inert gas atmosphere, 3-(2,4,6-trimethylphenyl)-2-oxo-1-oxaspiro[4,5]-non-3-en-4-ol and 1,2-dichloroethane are stirred and cooled to 0-5°C. Then, N,N-diisopropylethylamine is added, followed by the dropwise addition of fluoroethyl chloroformate. After the addition is complete, the mixture is brought to room temperature and the reaction continues. The mixture is then purified to obtain the final product.

3. The method of claim 2, wherein, The inert gas is N2.

4. The method of claim 2, wherein, The purification method is as follows: water is added to separate the layers, then the aqueous layer is extracted with dichloromethane, the organic layers are combined, washed with saturated brine, then washed with water, concentrated, and the residue is recrystallized with petroleum ether.

5. Use of a spiromesifen derivative according to claim 1, characterized in that Used for the control of crop mites.

6. Use according to claim 5, characterized in that, The crop pest is the citrus red spider mite.

7. Use according to claim 5, characterized in that, The crop pest is the watermelon two-spotted spider mite.

8. Use according to claim 5, characterized in that, The crop pest is the two-spotted spider mite of the rose.

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