A substituted organosilicon compound for nicotinamide, its preparation method and application

Abstract

This invention relates to a substituted nicotinamide organosilicon compound, its preparation method, and its application. A silicon-containing pharmacophore group is incorporated into the 4-(trifluoromethyl)nicotinamide molecule to prepare a substituted nicotinamide organosilicon compound that can be used as an active ingredient in insecticides. The substituted nicotinamide organosilicon compound exhibits excellent efficacy against piercing-sucking pests such as aphids and brown planthoppers. Even at low concentrations, it demonstrates superior aphid-killing effects, particularly against cotton aphids, where its efficacy is significantly better than flonicamid and other commercially available insecticides that inhibit nicotinamide enzymes (Naam) in insects.

Description

Technical Field

[0001] This invention belongs to the field of pesticides and insecticides, and in particular relates to a substituted nicotinamide organosilicon compound, its preparation method, and its application. Background Technology

[0002] Piercing-sucking pests are among the major pests affecting agricultural products such as grains, fruits, vegetables, and cotton. They are also vectors for viruses, impacting human food security and health. Unscientific and improper pesticide use has led to serious resistance problems in these pests, necessitating the development of pesticides with novel mechanisms of action to address this resistance issue.

[0003] Flupyradifurone is a patented compound (CN1044233C) filed in China by Ishihara Sangyo Co., Ltd. on July 23, 1993. The patent describes the preparation method of the compound and its salts, as well as the insecticidal effect of the pesticide composition. Specifically, in insecticidal and systemic tests against the peach aphid (Myzus persicae), a 100% mortality rate was achieved on the fifth day after application at a concentration of 800 ppm. Furthermore, in a systemic test against the brown thrips (Thrips palmi), a highly effective insecticidal activity was demonstrated on the eighth day after application at a concentration of 800 ppm. In addition, Japanese patent JPH11180957A reported a nicotinamide compound that, at a concentration of 500 ppm, resulted in a mortality rate of over 90% for aphids after 6 days of application (foliar spraying test). According to information released by the Institute for the Control of Agrochemicals of the Ministry of Agriculture of my country in July 2014, Ishihara Sangyo Co., Ltd. of Japan officially registered 96% flonicamid technical and 10% flonicamid WG in my country; Zhejiang Ishihara Jinniu Pesticide Co., Ltd. obtained the repackaging registration for 10% flonicamid WG. This formulation is registered for use on cucumbers, apples, and potatoes for spraying to control aphids, with an effective ingredient dosage of 45–75 g / hm². 2 20–40 g / kg and 52.5–75 g / hm 2 High pesticide concentrations can easily lead to pest resistance, and the effectiveness of pesticide application will be affected as the duration of application increases. Other insecticides currently on the market, such as imidacloprid, acetamiprid, and pymetrozine, are less effective against aphids, especially cotton aphids, and exhibit significant resistance. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention provides a substituted nicotinamide organosilicon compound, its preparation method, and its application.

[0005] The technical solution adopted in this invention is: a substituted nicotinamide organosilicon compound, characterized in that its structure is as shown in Formula 1.

[0006]

[0007] Among them, R1, R2, and R3 are each independently selected from C1 to C2. 10 Alkyl or C1-C 10 One or more of the following: haloalkyl, C3-C8 cycloalkyl or C3-C8 halocycloalkyl, aryl, heterocyclic, heterocyclic C1-C6 alkyl, wherein the halogen is F, Cl or Br;

[0008] R1, R2, and R3 can be the same group or different groups.

[0009] Preferably, R1, R2, and R3 are C1 to C2. 10 Alkyl, aryl, or heterocyclic;

[0010] Preferably, R1, R2 and R3 are methyl, ethyl, isopropyl, tert-butyl, phenyl or imidazole.

[0011] Preferably, the compound of Formula 1 is one of the following compounds;

[0012]

[0013] A method for preparing substituted nicotinamide organosilicon compounds, wherein compound 2 reacts with compound 3 under the action of an alkali to generate compound 1;

[0014]

[0015] Among them, R1, R2, and R3 are each independently selected from C1 to C2. 10 Alkyl or C1-C 10 One or more of the following: haloalkyl, C3-C8 cycloalkyl or C3-C8 halocycloalkyl, aryl, heterocyclic, heterocyclic C1-C6 alkyl, wherein the halogen is F, Cl or Br;

[0016] R1, R2, and R3 can be the same group or different groups.

[0017] Preferably, the reaction conditions are -10 to 150°C and the reaction time is 0.5 to 48 hours.

[0018] Preferably, the molar ratio of compound 2 to compound 3 is 1:1, and the molar ratio of compound 2 to base is 1:1.

[0019] Preferably, the solvent is dichloromethane, trichloromethane, toluene, xylene, N,N-dimethylformamide, methyl tert-butyl ether, or tetrahydrofuran;

[0020] The alkaline substance is one or more of the following: pyridine, dimethylaminopyridine, triethylamine, diisopropylethylamine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, sodium tert-butoxide, and potassium tert-butoxide.

[0021] The application of organosilicon compounds that replace nicotinamide in insecticides.

[0022] Preferably, one or more of the organosilicon compounds that replace nicotinamide are used as the active ingredient in the insecticide for killing piercing-sucking pests.

[0023] Preferably, the content of the active ingredient is 1-96 wt%, more preferably 5-60 wt%.

[0024] The advantages and positive effects of this invention are that the substituted nicotinamide organosilicon compounds prepared by the method of this invention can have excellent control effects when used as insecticides at low concentrations. Detailed Implementation

[0025] The embodiments of the present invention will be described below.

[0026] This invention relates to a substituted nicotinamide organosilicon compound, its preparation method, and its application. The structure of the substituted nicotinamide organosilicon compound is shown in Formula 1.

[0027]

[0028] Among them, R1, R2, and R3 are each independently selected from C1 to C2. 10 Alkyl or C1-C 10 Halogenated alkyl groups (halogens include F, Cl, Br), C3-C8 cycloalkyl groups or C3-C8 halocycloalkyl groups (halogens include F, Cl, Br), aryl groups, heterocyclic groups, heterocyclic C1-C6 alkyl groups, etc., where R1, R2 and R3 can be the same group or different groups.

[0029] In some embodiments of the present invention, R1, R2 and R3 are preferably C1 to C2. 10 Alkyl, aryl, or heterocyclic compounds, more preferably methyl, ethyl, isopropyl, tert-butyl, phenyl, or imidazole.

[0030] Compound of formula 1 can be prepared according to the following reaction formula;

[0031]

[0032] Compound 2 is mixed with compound 3 under the action of a base and reacted at -10 to 150°C for 0.5 to 48 h to produce compound 1. The molar ratio of compound 2 to compound 3 is 1:1, and the molar ratio of compound 2 to the base is 1:1. The solvent is selected from one or more combinations of dichloromethane, trichloromethane, toluene, xylene, N,N-dimethylformamide, methyl tert-butyl ether, and tetrahydrofuran. The base is selected from one or more combinations of pyridine, dimethylaminopyridine, triethylamine, diisopropylethylamine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, sodium tert-butoxide, and potassium tert-butoxide.

[0033] The substituted nicotinamide organosilicon compounds prepared by the above method can be used as insecticides, especially suitable for killing piercing-sucking pests such as aphids and brown planthoppers, and can be used in agriculture, forestry and horticulture.

[0034] Nicotinamide-substituted organosilicon compounds are formulated by adding a silicon-containing pharmacodynamic group to the 4-(trifluoromethyl)nicotinamide molecule, enhancing the compound's penetration into organisms. Once inside the organism, the compound is rapidly decomposed into 4-(trifluoromethyl)nicotinamide under the catalysis of organic acids, alkaloids, and various enzymes. This nicotinamide then acts on nicotinamide enzymes, causing poisoning and death, thus achieving a control effect. Even at low concentrations, nicotinamide-substituted organosilicon compounds exhibit excellent aphid-killing effects, especially against cotton aphids, showing significantly better efficacy than flonicamid and other commercially available insecticides that inhibit nicotinamide enzymes (Naam) in insects.

[0035] The present invention will now be described. Experimental methods that do not specify the operation steps are performed in accordance with the corresponding product manuals. Unless otherwise specified, the instruments, reagents and consumables used in the embodiments can be purchased from commercial companies.

[0036] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0037] In this invention, the terms used are uniformly interpreted as follows:

[0038] Alkyl refers to a straight-chain or branched alkyl group, excluding cycloalkyl groups, wherein the C1-C 10Alkyl refers to an alkyl group having 1 to 10 carbon atoms, such as including but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, etc.

[0039] In this invention, heteroatoms include, but are not limited to, O, S, and N atoms.

[0040] Other groups have similar definitions as described above, except that they have different substituents or different numbers of carbon atoms, and will not be described in detail here.

[0041] Other terms used in this invention may be interpreted in the manner commonly used in the art.

[0042] Example 1: Preparation of 4-(trifluoromethyl)-N-(trimethylsilyl)nicotinamide (Compound 1)

[0043] Under nitrogen protection, dichloromethane (200 mL), 4-(trifluoromethyl)nicotinamide (200.13 g, 1 mol), and triethylamine (103.26 g, 1 mol) were added sequentially to a 1000 mL round-bottom flask. The system was cooled to 0 °C, and trimethylchlorosilane (110.86 g, 1 mol) was slowly added dropwise while stirring. After the addition was complete, the system was brought back to room temperature and stirred for 10 hours. After the reaction was complete, the mixture was filtered under reduced pressure and washed to obtain a brown product with a purity of 99% and a yield of 97%.

[0044] Example 2: Preparation of 4-(trifluoromethyl)-N-(triethylsilyl)nicotinamide (Compound 2)

[0045] Under nitrogen protection, chloroform (200 mL), 4-(trifluoromethyl)nicotinamide (100.06 g, 0.5 mol), and triethylamine (51.63 g, 0.5 mol) were added sequentially to a 1000 mL round-bottom flask. The system was cooled to -5 °C, and triethylchlorosilane (76.90 g, 0.5 mol) was slowly added dropwise while stirring. After the addition was complete, the system was brought back to room temperature and stirred for 3 hours. After the reaction was complete, the mixture was filtered under reduced pressure and washed to obtain a brown product with a purity of 99% and a yield of 96%.

[0046] Example 3: Preparation of 4-(trifluoromethyl)-N-(dimethylisopropylsilyl)nicotinamide (Compound 3)

[0047] Under nitrogen protection, toluene (200 mL), 4-(trifluoromethyl)nicotinamide (100.06 g, 0.5 mol), and pyridine (40.36 g, 0.5 mol) were added sequentially to a 1000 mL round-bottom flask. The system was cooled to -5 °C, and dimethylisopropylchlorosilane (69.74 g, 0.5 mol) was slowly added dropwise while stirring. After the addition was complete, the system was brought back to room temperature and stirred for 20 hours. After the reaction was complete, the mixture was filtered under reduced pressure and washed to obtain a brown product with a purity of 99% and a yield of 95%.

[0048] Example 4: Preparation of 4-(trifluoromethyl)-N-(di-tert-butylmethylsilyl)nicotinamide (Compound 4)

[0049] Under nitrogen protection, toluene (250 mL), 4-(trifluoromethyl)nicotinamide (100.06 g, 0.5 mol), and triethylamine (51.63 g, 0.5 mol) were added sequentially to a 1000 mL round-bottom flask. The system was cooled to -5 °C, and di-tert-butylmethylchlorosilane (98.37 g, 0.5 mol) was slowly added dropwise while stirring. After the addition was complete, the system was heated to maintain a temperature of 60 °C and stirred for 30 hours. After the reaction was complete, the mixture was filtered under reduced pressure and washed to obtain a brown product with a purity of 99% and a yield of 96%.

[0050] Example 5: Preparation of 4-(trifluoromethyl)-N-(triisopropylsilyl)nicotinamide (Compound 5)

[0051] Under nitrogen protection, xylene (250 mL), 4-(trifluoromethyl)nicotinamide (100.06 g, 0.5 mol), and dimethylaminopyridine (62.33 g, 0.5 mol) were added sequentially to a 500 mL round-bottom flask. The system was cooled to -5 °C, and triisopropylchlorosilane (98.37 g, 0.5 mol) was slowly added dropwise while stirring. After the addition was complete, the system was heated to maintain a temperature of 120 °C and stirred for 35 hours. After the reaction was complete, the mixture was filtered under reduced pressure and washed to obtain a brown product with a purity of 99% and a yield of 95%.

[0052] The NMR characterization of compounds 1-5 prepared in Examples 1-5 is detailed in Table 1:

[0053] Table 1. NMR spectra of substituted nicotinamide organosilicon compounds 1-5 1 H NMR structural data

[0054]

[0055]

[0056] Example 6: Application of organosilicon compounds that replace nicotinamide in insecticides

[0057] Compounds 1-5 obtained in Examples 1-5 were prepared into emulsifiable concentrates. The preparation method for the 40% compound 1 emulsifiable concentrate was as follows: 40 parts of compound 1 were dissolved in 13 parts of methyl oleate, and 14 parts of calcium dodecylbenzenesulfonate and 7 parts of tristyrenephenol polyoxyethylene ether polyoxypropylene ether were added respectively. Then, methylnaphthalene was added to bring the total to 100 parts. The mixture was stirred until homogeneous to obtain the 40% compound 1 emulsifiable concentrate. Emulsifiable concentrates of compounds 2-5 were prepared using the same method for insecticidal tests.

[0058] Example 7: Cotton Aphis (Aphis gossypii Glover) Experiment

[0059] Compounds 1-5 were dissolved in acetone and diluted to the desired concentration with 0.1% Tween 80 solution, with the acetone content not exceeding 5%. One true leaf was removed from bean seedlings that had grown to two true leaves. The seedlings were inoculated with cotton aphids, and the initial population was assessed. The entire plant was sprayed with a handheld sprayer, with each treatment repeated three times. After treatment, the seedlings were observed in a constant-temperature observation room. The number of surviving aphids was assessed after 72 hours, and the mortality rate was calculated. The number of aphids inoculated each time was 100–200.

[0060] Mortality rate = (Number of inoculated worms - Number of surviving worms after treatment) ÷ Number of inoculated worms × 100%.

[0061] The following compounds showed a mortality rate of over 90% in aphids at 10 ppm (10 mg / L).

[0062] Table 2. Experimental data on cotton aphid (Aphis gossypii Glover)

[0063]

[0064]

[0065] The experimental results are shown in Table 2. Compounds 1-5 all achieved good aphid control effects, which were significantly higher than those of the comparative compound flonicamid.

[0066] Example 8: Brown planthopper (Nilaparvata lugens) test

[0067] Compounds 1-5 were dissolved in acetone and diluted to the desired concentration with 0.1% Tween 80 solution, with the acetone content not exceeding 5%. One true leaf was removed from bean seedlings that had grown to two true leaves. The seedlings were inoculated with cotton aphids, and the initial population was assessed. The entire plant was sprayed with a handheld sprayer, with each treatment repeated three times. After treatment, the seedlings were observed in a constant-temperature observation room. The number of surviving aphids was assessed after 72 hours, and the mortality rate was calculated. The number of aphids inoculated each time was 100–200.

[0068] Mortality rate = (Number of inoculated worms - Number of surviving worms after treatment) ÷ Number of inoculated worms × 100%.

[0069] The following compounds showed a mortality rate of over 90% in aphids at 10 ppm (10 mg / L).

[0070] Table 3. Experimental data of brown planthopper (Nilaparvata lugens)

[0071] Compound numbering Insect body concentration Effect 1 Brown planthopper 10ppm 91％ 2 Brown planthopper 10ppm 99％ 3 Brown planthopper 10ppm 95％ 4 Brown planthopper 10ppm 99％ 5 Brown planthopper 10ppm 95％ Flupyradifurone Brown planthopper 10ppm 40％

[0072] The experimental results are shown in Table 3. Compounds 1-5 all achieved good killing effects on brown planthoppers, which were significantly higher than those of the comparative compound flonicamid.

[0073] Example 9: Aerial spraying test of agricultural drone against Xinjiang resistant cotton aphid (Aphis gossypii Glover)

[0074] Taking Compound 1 as an example, a drone-based aerial spraying experiment was conducted in a portion of the cotton planting experimental area in Xinjiang. The dosage of Compound 1 was 10g (the active ingredient of Compound 1) / hm. 2 Within one day of spraying, the number of cotton aphids on the cotton plants decreased significantly, and the control effect reached over 90% after three days. When imidacloprid, acetamiprid, and flonicamid were used as control pesticides and sprayed at the same effective dosage, the control effects of imidacloprid, acetamiprid, and flonicamid were 20%, 30%, and 40%, respectively. It is evident that, under the same pesticide dosage, the substituted nicotinamide organosilicon compound prepared in this example, when used as an insecticide, has a significantly higher killing effect than imidacloprid, acetamiprid, and flonicamid, achieving high killing efficacy at low pesticide concentrations.

[0075] The embodiments of the present invention have been described in detail above, but the content described is only a preferred embodiment of the present invention and should not be considered as limiting the scope of the present invention. All equivalent changes and improvements made within the scope of the present invention should still fall within the patent coverage of the present invention.

Claims

1. A substituted nicotinamide organosilicon compound, characterized in that: The structure is shown in Equation 1. Formula 1; Among them, R1, R2, and R3 are each independently selected from C1 to C2. 10 Alkyl group; R1, R2 and R3 can be the same group or different groups.

2. The substituted nicotinamide organosilicon compound according to claim 1, characterized in that: R1, R2 and R3 are methyl, ethyl, isopropyl or tert-butyl.

3. The substituted nicotinamide organosilicon compound according to claim 1, characterized in that: The compound of Formula 1 is specifically one of the following compounds; a b c d e。 4. A method for preparing the substituted nicotinamide organosilicon compound according to any one of claims 1-3, characterized in that: Compound 2 reacts with compound 3 under the action of a base to produce compound 1; Formula 2; Formula 3; Among them, R1, R2, and R3 are each independently selected from C1 to C2. 10 Alkyl group; R1, R2 and R3 can be the same group or different groups.

5. The method for preparing the substituted nicotinamide organosilicon compound according to claim 4, characterized in that: The reaction conditions are -10 to 150℃, and the reaction time is 0.5 to 48 hours.

6. The method for preparing the substituted nicotinamide organosilicon compound according to claim 4, characterized in that: The molar ratio of compound 2 to compound 3 is 1:1, and the molar ratio of compound 2 to base is 1:

1.

7. The method for preparing the substituted nicotinamide organosilicon compound according to any one of claims 4-6, characterized in that: The solvent is dichloromethane, trichloromethane, toluene, xylene, N,N-dimethylformamide, methyl tert-butyl ether, or tetrahydrofuran; The alkaline substance is one or more of the following: pyridine, dimethylaminopyridine, triethylamine, diisopropylethylamine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methoxide, sodium ethoxide, sodium tert-butoxide, and potassium tert-butoxide.

8. The use of the substituted nicotinamide organosilicon compound according to any one of claims 1-3 in insecticides.

9. The application according to claim 8, characterized in that: One or more of the substituted nicotinamide organosilicon compounds described in any of claims 1-3 may be used as the active ingredient in an insecticide for killing piercing-sucking pests.

10. The application according to claim 9, characterized in that: The content of active ingredients is 1-96 wt%.

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