Avermectin B 2a Carbamate derivatives, process for their preparation and use thereof

Abstract

The present application relates to the field of agricultural organic chemistry, and provides an abamectin B 2a Carbamate derivatives, preparation method and application thereof, by introducing nitrogen-containing lipophilic functional groups at C4" position of abamectin B 2a Carbamate derivatives, by modifying and modifying the structure of abamectin B 2a Carbamate derivatives, by modifying and modifying the structure of abamectin B 2a Carbamate derivatives, by modifying and modifying the structure of abamectin B 2a Carbamate derivatives, by modifying and modifying the structure of abamectin B 2a Carbamate derivatives can be used for preventing and treating harmful organisms that harm ornamental plants and crops, especially organisms that harm fruits, flowers, leaves, stems, tubers or roots of plants, and also can be used for protecting growing plants from the invasion of harmful organisms.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of agricultural organic chemistry, and particularly relates to an avermectin B 2a carbamate derivative, a preparation method and application thereof. BACKGROUND

[0002] Avermectin is a kind of green pesticide with insecticidal, miticidal and nematicidal activity, which has made great contribution in the prevention and treatment of agricultural diseases. However, 20%-30% of waste residues are produced in the industrial production process of avermectin, which is usually dissolved in toluene or xylene to obtain avermectin ointment, and used for producing emulsion formulation. However, the avermectin ointment contains a large amount of harmful substances in addition to avermectin B 2a . The structural difference between avermectin B 2a and avermectin B 1a results in that the lipophilicity of avermectin B 2a is weaker than that of avermectin B 1a , which reduces the ability of passive diffusion of the compound to penetrate the biological membrane, and finally leads to that the activity of avermectin B 2a to most agricultural pests is worse than that of avermectin B 1a , so that the application of avermectin B 2a is limited, resulting in great waste of resources and environmental pollution. SUMMARY

[0003] The present application aims at at least one of the problems existing in the prior art. To this end, the present application provides an avermectin B 2a carbamate derivative, a preparation method and application thereof.

[0004]

[0005] wherein R l is one of hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, C-7cycloalkenyl, C6-14aryl, 5-6 membered heterocyclyl, 5-14 membered heteroaryl, halogen, cyano, nitro or amino;

[0006] R 2 is one of hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, C-7cycloalkenyl, C6-14aryl, 5-6 membered heterocyclyl, 5-14 membered heteroaryl, halogen, cyano, nitro or amino.

[0007] The present application also provides a preparation method of the avermectin B 2a carbamate derivative as described above, comprising the following steps:

[0008] S1: dissolving avermectin B2a The first compound is placed in an organic solvent and stirred to obtain a first mixed solution, a basic medium is added to the first mixed solution at -15°C to obtain a second mixed solution, chloroformic acid allyl ester is added dropwise to the second mixed solution, stirring is performed at -30-30°C for 1-2h, and then a quenching reaction is performed, and after concentration under reduced pressure, a first compound is obtained;

[0009] S2: The first compound is placed in an aprotic solvent and stirred to obtain a third mixed solution, a first catalyst and isocyanate are added to the third mixed solution, stirring is performed for 7-8h, and then a quenching reaction is performed, and after concentration under reduced pressure, a second compound is obtained;

[0010] S3: The second compound is placed in an organic solvent and stirred to obtain a fourth mixed solution, tetrakis(triphenylphosphine)palladium is added to the fourth mixed solution, stirring is performed to obtain a fifth mixed solution, sodium borohydride is added to the fifth mixed solution, stirring is performed for 20-30min, and then a quenching reaction is performed, and after concentration under reduced pressure, abamectin B 2a The carbamate derivative.

[0011] According to the present application, abamectin B 2a The preparation method of the carbamate derivative further comprises the following steps:

[0012] S4: The first compound, p-nitrophenyl chloroformate, and an acid binding agent are placed in an aprotic solvent and stirred for 8-9h to obtain a sixth mixed solution, the sixth mixed solution is subjected to a quenching reaction, and after concentration under reduced pressure, a fourth compound is obtained;

[0013] S5: The fourth compound, an organic amine compound, and a second catalyst are placed in an organic solvent and stirred to obtain a seventh mixed solution, the seventh mixed solution is subjected to a quenching reaction, and after concentration under reduced pressure, a fifth compound is obtained;

[0014] S6: The fifth compound is placed in an organic solvent and stirred to obtain an eighth mixed solution, tetrakis(triphenylphosphine)palladium is added to the eighth mixed solution, stirring is performed to obtain a ninth mixed solution, sodium borohydride is added to the ninth mixed solution, stirring is performed for 20-30min, and then a quenching reaction is performed, and after concentration under reduced pressure, abamectin B 2a The carbamate derivative.

[0015] According to the present application, abamectin B 2a The preparation method of the carbamate derivative, wherein the organic solvent comprises one of dichloromethane, n-hexane, benzene, toluene, chloroform, tetrachloromethane, chlorobenzene, dioxane, methanol, petroleum ether, tetrahydrofuran, 1,2-dichloroethane, isopropyl acetate, and dioxane.

[0016] Avermectin B provided according to the present invention 2a A method for preparing carbamate derivatives, wherein the alkaline medium includes at least one of pyridine, triethylamine, tetramethylethylenediamine, triethylenediamine, N-methylmorpholine, 4-dimethylaminopyridine, and 1,8-diazabicyclo[5.4.0]undec-7-ene.

[0017] Avermectin B provided according to the present invention 2a A method for preparing carbamate derivatives, wherein the aprotic solvent includes at least one selected from dichloromethane, trichloromethane, tetrachloromethane, benzene, toluene, chlorobenzene, dioxane, methanol, and tetrahydrofuran.

[0018] Avermectin B provided according to the present invention 2a A method for preparing carbamate derivatives, wherein the first catalyst is one of 1,8-diazabicycloundec-7-ene or 4-dimethylaminopyridine; and the second catalyst is one of 1,8-diazabicycloundec-7-ene, 4-dimethylaminopyridine, tetramethylethylenediamine or triethylamine.

[0019] Avermectin B provided according to the present invention 2a A method for preparing carbamate derivatives, wherein the acid-binding agent is selected from at least one of triethylamine, tetramethylethylenediamine, pyridine, 1,8-diazabicycloundec-7-ene, or 4-dimethylaminopyridine.

[0020] The present invention also provides an agent for controlling harmful biological organisms, comprising avermectin B as described above. 2a The formulation also includes carbamate derivatives, and further includes avermectin B. 2a Carbamate derivatives are pesticide-acceptable salts.

[0021] According to the pest control agent provided by the present invention, the organism is an insect pest, which includes at least one of the following genera: Lepidoptera, Coleoptera, Orthoptera, Isoptera, Pseudoratoides, Psyllids, Trichophala, Thysanoptera, Hemiptera, Hymenoptera, Diptera, Silicaria, Thysanura, Acari, Tetranychus, Gall mites, Flounder mites, Runner mites, Pedicular mites, Dwarf Pedicular mites, Leaf claw mites, Pedicular mites, Root mites, Beetle mites, Phytosei, Long-haired mites, Mussei, Giant crab mites, Half scabies mites, Giant scabbard mites, Entomopathogenic mites, Fleshy mites, Vellus mites, Large red mites, Cyst nematodes, Heterodermella, Root-knot nematodes, Perforating nematodes, Short-bodied nematodes, Small pad nematodes, Long needle nematodes, Hairy nematodes, Fasciola, Stem nematodes, Slippery nematodes, and Eel nematodes.

[0022] The above-described one or more technical solutions in the embodiments of the present invention have at least one of the following technical effects:

[0023] 1. The present application provides an avermectin B 2a carbamate derivatives, their preparation and use, by introducing a nitrogen-containing lipophilic functional group at the C4" position of avermectin B 2a carbamate derivatives, their preparation and use, by introducing a nitrogen-containing lipophilic functional group at the C4" position of avermectin B 2a carbamate derivatives, their preparation and use, by introducing a nitrogen-containing lipophilic functional group at the C4" position of avermectin B 2a carbamate derivatives, their preparation and use, by introducing a nitrogen-containing lipophilic functional group at the C4" position of avermectin B 2a carbamate derivatives, their preparation and use, by introducing a nitrogen-containing lipophilic functional group at the C4" position of avermectin B

[0024] 2. The present application provides an avermectin B 2a carbamate derivatives, their preparation and use, by introducing a nitrogen-containing lipophilic functional group at the C4" position of avermectin B

[0025] Additional aspects and advantages of the application will be set forth in part in the description which follows, and in part will become apparent to those having ordinary skill in the art upon examination of the following or can be learned from practice of the application. BRIEF DESCRIPTION OF DRAWINGS

[0026] In order to more clearly illustrate the technical solutions of the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or the prior art description. Obviously, the drawings in the following description are some embodiments of the present application, and other drawings can be obtained by those skilled in the art without any creative effort on the basis of these drawings.

[0027] Figure 1 The present application provides an avermectin B 2a Reaction flow chart of carbamate derivative Ia.

[0028] Figure 2 The present application provides an avermectin B 2a Reaction flow chart of carbamate derivative Iv. DETAILED DESCRIPTION

[0029] In order to make the objects, technical solutions and advantages of the present application clearer, the following will combine the drawings in the present application to clearly and completely describe the technical solutions in the present application. Obviously, the described embodiments are some embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without any creative effort belong to the protection scope of the present application. The following embodiments are used to illustrate the present application, but cannot be used to limit the scope of the present application.

[0030] In addition, the terms "first", "second", "third" are only for descriptive purpose, and cannot be understood as indicating or implying relative importance.

[0031] In the description of the present specification, the description referring to the terms "one embodiment", "some embodiments", "an example", "a specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the present specification, the illustrative description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any appropriate manner in any one or more embodiments or examples. In addition, the person skilled in the art can combine and combine the different embodiments or examples described in the present specification and the features of the different embodiments or examples without contradiction.

[0032] The application will be described below in conjunction with Figures 1 to 2 The application provides an avermectin B 2a The application provides an avermectin B

[0033] The application provides an avermectin B 2a The application provides an avermectin B

[0034]

[0035] Wherein, R l is one of hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, C-7cycloalkenyl, C6-14aryl, 5-6 membered heterocyclyl, 5-14 membered heteroaryl, halogen, cyano, nitro or amino;

[0036] R 2 is one of hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, C-7cycloalkenyl, C6-14aryl, 5-6 membered heterocyclyl, 5-14 membered heteroaryl, halogen, cyano, nitro or amino.

[0037] Due to the reaction activity of the C4" hydroxyl group of avermectin B 2a is slightly higher than that of the C23 hydroxyl group, between the C23 and C5 hydroxyl groups, the selective modification is difficult, so the modification and modification of avermectin B 2a focus on C23 and C5, and the research on C4" position is less. However, referring to the research experience of avermectin B 1a , it can be seen that the introduction of nitrogen-containing functional groups at C4" position can obviously improve the activity of the compound. In order to save resources and protect the environment, the avermectin B 2aTo develop greener and more efficient new pesticides, the screening of reagents and conditions has enabled the development of control over abamectin B. 2a Selective modification of the C4" structure in avermectin B 2a A carbamate functional group was introduced at the C4" position, improving the lipophilicity of the compound. A series of derivatives were designed and synthesized, and their bioactivity was tested. The results showed that the modified avermectin B... 2a The derivative's activity was significantly higher than that of avermectin B. 2a Some derivatives even have higher activity than avermectin B. 1a .

[0038] The present invention also provides an avermectin B as described above. 2a The preparation method of carbamate derivatives includes the following steps:

[0039] S1: Add ivermectin B 2a The mixture is placed in an organic solvent and stirred to obtain a first mixed solution. An alkaline medium is added to the first mixed solution at -15°C to obtain a second mixed solution. Allyl chloroformate is added dropwise to the second mixed solution, and the mixture is stirred at -30°C to 30°C for 1 to 2 hours. Then, a quenching reaction is carried out, and the mixture is concentrated under reduced pressure to obtain the first compound.

[0040] according to Figure 1 and Figure 2 As shown, the first compound is Figure 1 and Figure 2 Compound 2 in the compound.

[0041] S2: The first compound is placed in an aprotic solvent and stirred to obtain a third mixed solution. The first catalyst and isocyanate are added to the third mixed solution and stirred for 7-8 hours. Then, a quenching reaction is carried out and the solution is concentrated under reduced pressure to obtain the second compound.

[0042] according to Figure 1 As shown, the second compound is Figure 1 Compound 3 in the compound.

[0043] S3: The second compound is placed in an organic solvent and stirred to obtain a fourth mixed solution. Tetra(triphenylphosphine)palladium is added to the fourth mixed solution and stirred to obtain a fifth mixed solution. Sodium borohydride is added to the fifth mixed solution and stirred for 20-30 minutes. Then, a quenching reaction is performed, and the solution is concentrated under reduced pressure to obtain avermectin B. 2a Carbamate derivatives.

[0044] Among them, avermectin B with codes Ia to Iu... 2a All carbamate derivatives were prepared using steps S1 to S3.

[0045] The application also provides an avermectin B 2a The preparation method of the carbamate derivative further comprises the following steps:

[0046] S4: the first compound, p-nitrophenyl chloromethyl carbonate, and an acid binding agent are placed in an aprotic solvent, and stirred for 8-9 hours to obtain a sixth mixed solution; the sixth mixed solution is quenched, and the fourth compound is obtained after being concentrated under reduced pressure;

[0047] According to Figure 2 the fourth compound is compound 4 in Figure 2 .

[0048] S5: the fourth compound, an organic amine compound, and a second catalyst are placed in an organic solvent, and stirred to obtain a seventh mixed solution; the seventh mixed solution is quenched, and the fifth compound is obtained after being concentrated under reduced pressure;

[0049] According to Figure 2 the fourth compound is compound 5 in Figure 2 .

[0050] S6: the fifth compound is placed in an organic solvent, and stirred to obtain an eighth mixed solution; tetrakis(triphenylphosphine)palladium is added to the eighth mixed solution, and stirred to obtain a ninth mixed solution; sodium borohydride is added to the ninth mixed solution, and stirred for 20-30 minutes, then quenched, and avermectin B 2a carbamate derivative is obtained after being concentrated under reduced pressure.

[0051] The avermectin B 2a carbamate derivative is prepared by steps S4-S6.

[0052] According to the application, the preparation method of the avermectin B 2a carbamate derivative, the organic solvent comprises one of dichloromethane, n-hexane, benzene, toluene, chloroform, tetrachloromethane, chlorobenzene, dioxane, methanol, petroleum ether, tetrahydrofuran, 1,2-dichloroethane, isopropyl acetate, and dioxane.

[0053] According to the application, the preparation method of the avermectin B 2a carbamate derivative, the basic medium comprises at least one of pyridine, triethylamine, tetramethyl ethylenediamine, triethylenediamine, N-methyl morpholine, 4-dimethylamino pyridine, and 1,8-diazabicyclo[5.4.0]undec-7-ene.

[0054] According to the application, the preparation method of the avermectin B 2aThe preparation method of the carbamate derivative, the aprotic solvent includes at least one of dichloromethane, trichloromethane, tetrachloromethane, benzene, toluene, chlorobenzene, dioxane, methanol and tetrahydrofuran.

[0055] The avermectin B provided by the application 2a The preparation method of the carbamate derivative, the first catalyst is one of 1,8-diazabicycloundec-7-ene or 4-dimethylaminopyridine; the second catalyst is one of 1,8-diazabicycloundec-7-ene, 4-dimethylaminopyridine, tetramethylethylenediamine or triethylamine.

[0056] The avermectin B provided by the application 2a The preparation method of the carbamate derivative, the acid-binding agent is at least one of triethylamine, tetramethylethylenediamine, pyridine, 1,8-diazabicycloundec-7-ene or 4-dimethylaminopyridine.

[0057] Example 1: Preparation of compound 2.

[0058] The avermectin B provided by the application 2a (50.00 g, 56.11 mmol) was placed in a 1 L single-mouth flask with dry dichloromethane (300 mL), and cooled to -15 °C. Tetramethylethylenediamine (13.04 g, 112.22 mmol) was added, and DMAP (0.69 g, 5.61 mmol) was added and stirred for 5 min. The temperature was controlled at -15 °C, and allyl chloroformate (10.14 g, 84.17 mmol) was slowly added dropwise, and reacted at -15 °C for 1 h. The reaction was monitored by TLC until there was no starting material spot. Saturated sodium bicarbonate solution (50 mL) was added for quenching. Extraction was performed with 3 x 100 mL of dichloromethane, and the organic phase was combined, dried over anhydrous magnesium sulfate, filtered to remove the drying agent, and finally concentrated under reduced pressure to remove the solvent to obtain 57.23 g of a crude product. Column chromatography separation (petroleum ether: ethyl acetate = 1:1) was performed, and finally compound 2 shown in Figure 1 and Figure 2 The compound 2 shown in

[0059] Example 2: Preparation of compound 3.

[0060] Compound 2 (1.00 g, 1.03 mmol) was added to a 100 mL flask, tetrahydrofuran (10 mL) was added, DMAP (0.25 g, 2.06 mmol) was added, stirred to dissolve, p-chlorophenyl isocyanate (0.32 g, 2.06 mmol) was added, and the reaction was allowed to proceed at room temperature for 8 h. The reaction was monitored by TLC. After the reaction was stopped, saturated aqueous sodium bicarbonate solution (5 mL) was added to quench the reaction, and then 3 x 10 mL of dichloromethane was used to extract, the organic phase was combined, dried over anhydrous magnesium sulfate, filtered to remove the drying agent, and finally concentrated under reduced pressure to remove the solvent to obtain 1.13 g of crude product. Compound 3 as shown in Figure 1 and Figure 2 Compound 3 was used directly in the next step without purification.

[0061] Example 3: Preparation of Compound Ia.

[0062] Compound 3 (1.33 mmol, 1.50 g) was dissolved in a mixture of 30 mL of isopropyl acetate and ethanol (v / v = 7:3), and then tetrakis(triphenylphosphine)palladium (0.07 g, 0.07 mmol) was added at room temperature and stirred to dissolve. NaBH4(0.10 g, 2.66 mmol) was slowly added, and the reaction was allowed to proceed for 20 min. The reaction was monitored by TLC until there was no starting material spot. Water (10 mL) was added to quench the reaction, and then 30 mL of dichloromethane was used to extract, the organic phase was washed with water, and the organic phase was dried over anhydrous magnesium sulfate, filtered to remove the drying agent, and finally concentrated under reduced pressure to remove the solvent to obtain 1.38 g of crude product. Column chromatography separation (petroleum ether: ethyl acetate = 2:1) was performed, and finally avermectin B 2a The carbamate derivative Ia was 1.12 g of white solid with a yield of 81%. The melting point was 152-154 °C.

[0063] Example 4: Preparation of Compound 4.

[0064] Compound 2 (25.00 g, 25.64 mmol) was added to a 1 L flask, dichloromethane (250 mL) was added, and then tetramethylethylenediamine (5.96 g, 51.27 mmol) and DMAP (0.31 g, 2.56 mmol) were added after stirring to dissolve. At 0 °C, p-nitrophenyl chloroformate (10.33 g, 51.27 mmol) was slowly added, and then the temperature was increased to room temperature, and the reaction was allowed to proceed for 2 h. The reaction was monitored by TLC until there was no starting material spot. Saturated sodium bicarbonate solution (50 mL) was added to quench the reaction. 3 x 100 mL of dichloromethane was used to extract, the organic phase was combined, dried over anhydrous magnesium sulfate, filtered to remove the drying agent, and finally concentrated under reduced pressure to remove the solvent to obtain 30.47 g of crude product. Column chromatography separation (petroleum ether: ethyl acetate = 3:1) was performed, and finally compound 4 was obtained. Figure 2Compound 4 as shown in the above scheme was obtained as 24.16 g of yellow solid with a yield of 83% and a melting point of 158-160 °C.

[0065] Example 5: Preparation of compound 5.

[0066] Compound 4 was added to a 40 wt.% aqueous methylamine solution (0.14 g, 1.76 mmol) at room temperature and reacted for 1 h at room temperature. The reaction was monitored by TLC until no starting material was detected. The reaction was quenched by adding saturated sodium bicarbonate solution (10 mL). Extraction was performed with 3 x 10 mL dichloromethane, the organic phases were combined, dried over anhydrous magnesium sulfate, filtered to remove the drying agent and finally the solvent was removed by concentration under reduced pressure to obtain 0.97 g of crude product. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 2: 1) to obtain compound 5 as shown in the above scheme. Figure 2 Compound 5 as shown in the above scheme was used directly in the next reaction without purification.

[0067] Example 6: Preparation of compound Iv.

[0068] Compound 5 was dissolved in a mixture of 10 mL of isopropyl acetate and ethanol (v / v = 7:3), and tetrakis(triphenylphosphine)palladium (0.05 g, 0.04 mmol) was added at room temperature and stirred to dissolve. NaBH4(0.07 g, 1.76 mmol) was slowly added and reacted for 30 min. The reaction was monitored by TLC until no starting material was detected. The reaction was quenched by adding saturated aqueous sodium bicarbonate solution (5 mL), and extraction was performed with 3 x 10 mL dichloromethane, the organic phases were combined, dried over anhydrous magnesium sulfate, filtered to remove the drying agent and finally the solvent was removed by concentration under reduced pressure to obtain 0.92 g of crude product. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 2: 1) to obtain Iv as shown in the above scheme. Figure 2 Iv as shown in the above scheme was obtained as 0.57 g of white solid with a yield of 65% and a melting point of 159-161 °C.

[0069] According to Examples 1-6, the avermectin B1a derivative provided by the present application 2a The carbamate derivatives and the intermediate products generated in the preparation process thereof are summarized in Table 1:

[0070] Table 1 Avermectin B1a derivatives and the intermediate products generated in the preparation process thereof 2a The carbamate derivatives and the intermediate products generated in the preparation process thereof are summarized in Table 1:

[0071]

[0072]

[0073]

[0074]

[0075]

[0076]

[0077]

[0078]

[0079]

[0080]

[0081]

[0082]

[0083]

[0084]

[0085]

[0086]

[0087]

[0088]

[0089]

[0090] The present application also provides a preparation for controlling pests, comprising the avermectin B 2a carbamate derivative, the preparation further comprising an avermectin B 2a an agriculturally acceptable salt of the carbamate derivative.

[0091] The present application provides a preparation for controlling pests, the pests including at least one of Lepidoptera, Coleoptera, Orthoptera, Isoptera, Psocoptera, Anoplura, Trichodectidae, Thysanoptera, Heteroptera, Hemiptera, Diptera, Siphonaptera, Euliposcelis, Acarina, Tetranychidae, Eotetranychus, Carpoglyphus, Aleuroglyphus, Olalae, Dendrolimus, Phyllocoptruta, Rhizoglyphus, Oligonychus, Phytoseiulus, Tyrophagus, Carpoglyphus, Carpoglyphus, Carpoglyphus, Carpoglyphus, Carpoglyphus, Carpoglyphus, Globodera, Globodera, Meloidogyne, Pratylenchus, Rhabditis, Heterorhabditis, Longidorus, Aphelenchoides, Bursaphelenchus, and Ditylenchus.

[0092] The present application provides an avermectin B 2aThe application of the urethane derivatives is described.

[0093] Example 7: Test of the insecticidal activity of the target compounds against P. xylostella by leaf dipping method.

[0094] This example tests the insecticidal activity of the target compounds against P. xylostella by leaf dipping method, and the specific operation is as follows:

[0095] Corn leaves are cut into 5 cm leaf segments, dipped in the drug solution for 10 s, naturally dried, and then placed in a glass culture dish (75 mm in diameter). The development of the pests is selected and introduced into the treated leaves, and the acetone solvent is used as a control. The survival state of the pests is checked 72 h after treatment. The larvae are determined to be dead by gently touching the body surface with a brush, the number of dead and surviving pests is recorded, and the mortality and corrected mortality are calculated, as shown in Tables 2 and 3:

[0096] Table 2 Test of the insecticidal activity of Ia-Iu against P. xylostella

[0097]

[0098]

[0099] As can be seen from Table 2, at the application concentration of 25 mg / L, the activity of all target compounds Ia-Iu against P. xylostella is higher than that of abamectin B 2a (60%), and the activity of 18 compounds among them is 100%. When the application concentration is reduced to 2.5 mg / L, compounds Ia (100%), Ie (100%), II (43.3%), Ip (57%), and Iq (23%) still have certain activity against P. xylostella. The most notable is compound Ie, when the application concentration is reduced to 1 mg / L, the activity of compound Ie (43%) against P. xylostella is higher than that of abamectin B 1a (20%).

[0100] Table 3 Test of the insecticidal activity of Iv-Iak against P. xylostella

[0101]

[0102]

[0103] As can be seen from Table 3, the C4" alkyl urethane derivatives of abamectin B 2a show good activity against P. xylostella. When the application concentration is 10 mg / L, the test results of the insecticidal activity of the remaining compounds against P. xylostella are better than those of abamectin B 2aWhen the concentration of the administered drug is reduced to 1 mg / L, the insecticidal activity of compounds Iv, Iw, Ix, Iz, Iad and Iaj against P. xylostella is higher than that of abamectin B 1a . Among them, compounds Iv and Ix still have certain insecticidal activity even when the concentration of the administered drug is 0.25 mg / L.

[0104] Example 8: Test the insecticidal activity of the target compounds against Spodoptera exigua by the leaf dipping method.

[0105] The test method of this example is the same as that of Example 7, and the insecticidal activity of Ia-Iak against Spodoptera exigua is shown in Tables 4 and 5:

[0106] Table 4 Insecticidal activity test of Ia-Iu against Spodoptera exigua

[0107]

[0108]

[0109] As can be seen from Table 4, the introduction of a carbamate group at the C4" position of abamectin B 2a improves the activity of the parent compound against Spodoptera exigua. When the concentration of the administered drug is 50 mg / L, the activity of most of the compounds against Spodoptera exigua is higher than that of abamectin B 2a (40%). When the concentration of the administered drug is reduced to 5 mg / L, the activity of compounds Ia (100%) and Ie (100%) against Spodoptera exigua is higher than that of abamectin B 1a (60%), and the activity of compound Il (63.3%) is similar to that of abamectin B 1a . Moreover, when the concentration of the administered drug is reduced to 2.5 mg / L, compounds Ia (37%) and Ie (63%) still have certain activity against Spodoptera exigua.

[0110] Table 5 Insecticidal activity test of Iv-Iak against Spodoptera exigua

[0111]

[0112]

[0113] As can be seen from Table 5, the carbamate derivatives of abamectin B 2a at the C4" position also exhibit good insecticidal activity against Spodoptera exigua. When the concentration of the administered drug is 50 mg / L, the insecticidal activity of the remaining compounds against Spodoptera exigua is better than that of abamectin B 2a . Among them, the insecticidal activity of compound Iac is the best, and when the concentration of the administered drug is 2.5 mg / L, the mortality rate of Spodoptera exigua is still 40%.

[0114] In summary, by introducing a nitrogen-containing lipophilic functional group at the C4" position of abamectin B 2a The lipophilicity of the carbamate derivatives is improved, and the ability of the compounds to passively diffuse through the biological membrane is further improved, and the activity of abamectin B 2a The structure of the carbamate derivatives is modified and improved, and the activity of abamectin B 2a The lipophilicity of the carbamate derivatives is improved, and the ability of the compounds to passively diffuse through the biological membrane is further improved, and the activity of abamectin B 2a The activity of the carbamate derivatives is improved, and the activity of abamectin B 2a The carbamate derivatives can be used for preventing and treating harmful organisms that harm ornamental plants and crops, and have good killing effect on organisms that harm the fruits, flowers, leaves, stems, tubers or roots of plants, and can also be used for protecting growing plants from the attack of harmful organisms.

[0115] Finally, it should be noted that: the above examples are only used to illustrate the technical solutions of the present application, and not to limit them; although the present application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that: it can still modify the technical solutions recorded in the foregoing examples, or make equivalent replacement for part of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. An avermectin B2a carbamate derivative, characterized in that, Selected from avermectin B2a carbamate derivatives numbered Ia~Iu or Iv~Iak; Avermectin B, numbered Ia~Iu 2a The structural formulas of carbamate derivatives are shown below: The product code is Iv~Iak avermectin B. 2a The structural formulas of carbamate derivatives are shown below:

2. An avermectin B according to claim 1 2a A method for preparing carbamate derivatives, characterized in that, Avermectin B, numbered Ia~Iu 2a The preparation of carbamate derivatives includes the following steps: S1: Add ivermectin B 2a The mixture is placed in an organic solvent and stirred to obtain a first mixed solution. An alkaline medium is added to the first mixed solution at -15°C to obtain a second mixed solution. Allyl chloroformate is added dropwise to the second mixed solution, and the mixture is stirred at -30°C to 30°C for 1 to 2 hours. Then, a quenching reaction is carried out, and the mixture is concentrated under reduced pressure to obtain the first compound. S2: The first compound is placed in an aprotic solvent and stirred to obtain a third mixed solution. The first catalyst and isocyanate are added to the third mixed solution and stirred for 7-8 hours. Then, a quenching reaction is carried out and the solution is concentrated under reduced pressure to obtain the second compound. The first catalyst is 1,8-diazabicycloundec-7-ene or 4-dimethylaminopyridine; S3: The second compound is placed in an organic solvent and stirred to obtain a fourth mixed solution. Tetra(triphenylphosphine)palladium is added to the fourth mixed solution and stirred to obtain a fifth mixed solution. Sodium borohydride is added to the fifth mixed solution and stirred for 20-30 minutes. Then, a quenching reaction is performed, and the solution is concentrated under reduced pressure to obtain avermectin B. 2a Carbamate derivatives.

3. The avermectin B according to claim 1 2a A method for preparing carbamate derivatives, characterized in that, The product code is Iv~Iak avermectin B. 2a The preparation of carbamate derivatives includes the following steps: S1: Add ivermectin B 2a The mixture is placed in an organic solvent and stirred to obtain a first mixed solution. An alkaline medium is added to the first mixed solution at -15°C to obtain a second mixed solution. Allyl chloroformate is added dropwise to the second mixed solution, and the mixture is stirred at -30°C to 30°C for 1 to 2 hours. Then, a quenching reaction is carried out, and the mixture is concentrated under reduced pressure to obtain the first compound. S2: The first compound, p-nitrophenyl chloromethyl ester, and acid-binding agent are placed in an aprotic solvent and stirred for 8-9 hours to obtain a sixth mixed solution. The sixth mixed solution is subjected to a quenching reaction and concentrated under reduced pressure to obtain the fourth compound. S3: The fourth compound, organic amine compound, and second catalyst are placed in an organic solvent and stirred to obtain a seventh mixed solution. The seventh mixed solution is subjected to a quenching reaction and concentrated under reduced pressure to obtain the fifth compound. The second catalyst is one of 1,8-diazabicycloundec-7-ene, 4-dimethylaminopyridine, tetramethylethylenediamine, or triethylamine; S4: The fifth compound is placed in an organic solvent and stirred to obtain an eighth mixed solution. Tetra(triphenylphosphine)palladium is added to the eighth mixed solution and stirred to obtain a ninth mixed solution. Sodium borohydride is added to the ninth mixed solution and stirred for 20-30 minutes. Then, a quenching reaction is performed, and the solution is concentrated under reduced pressure to obtain avermectin B. 2a Carbamate derivatives.

4. The avermectin B according to claim 2 or 3 2a A method for preparing carbamate derivatives, characterized in that, The organic solvent is selected from one of dichloromethane, n-hexane, benzene, toluene, chloroform, tetrachloromethane, chlorobenzene, dioxane, methanol, ethanol, petroleum ether, tetrahydrofuran, 1,2-dichloroethane, isopropyl acetate, and dioxane.

5. The avermectin B according to claim 2 or 3 2a A method for preparing carbamate derivatives, characterized in that, The alkaline medium is selected from at least one of pyridine, triethylamine, tetramethylethylenediamine, triethylenediamine, N-methylmorpholine, 4-dimethylaminopyridine, and 1,8-diazabicyclo[5.4.0]undec-7-ene.

6. The avermectin B according to claim 2 or 3 2a A method for preparing carbamate derivatives, characterized in that, The aprotic solvent is selected from at least one of dichloromethane, trichloromethane, tetrachloromethane, benzene, toluene, chlorobenzene, dioxane, methanol, and tetrahydrofuran.

7. The avermectin B according to claim 3 2a A method for preparing carbamate derivatives, characterized in that, The acid-binding agent is selected from at least one of triethylamine, tetramethylethylenediamine, pyridine, 1,8-diazabicycloundec-7-ene, or 4-dimethylaminopyridine.

8. An agent for controlling harmful organisms, comprising avermectin B as described in claim 1. 2a Carbamate derivatives, characterized in that, The formulation also includes avermectin B. 2a Carbamate derivatives are pesticide-acceptable salts.

9. The application of the agent for controlling harmful biological organisms according to claim 8, characterized in that, For biological control, the organism is a pest, and the pest is selected from at least one of the following orders: Lepidoptera, Coleoptera, Orthoptera, Isoptera, Pseudoratoides, Psyllids, Trichophala, Thysanoptera, Hemiptera, Hymenoptera, Diptera, Siphonaptera, Thysanura, Acari, Tetranychus, Gall mites, Flounder mites, Runner mites, Pedicular mites, Dwarf Pedicular mites, Leaf claw mites, Pedicular mites, Root mites, Beetle mites, Phytosei, Long-haired mites, Mussei, Giant crab mites, Half scabies mites, Giant bearded mites, Entomopathogenic mites, Carnivorous mites, Velociraptor, Large red mite, Cyst nematodes, Heterodermella, Root-knot nematodes, Perforating nematodes, Short-bodied nematodes, Small pad nematodes, Long needle nematodes, Hairy nematodes, Fasciola, Stem nematodes, Slippery blade nematodes, and Eel nematodes.

10. The avermectin B as described in claim 1 2a The application of carbamate derivatives is characterized by, Used for the control of Eastern armyworm and / or fall armyworm.

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