Anthranilamide compound, preparation method thereof and application of anthranilamide compound as insecticide

Abstract

The invention relates to an anthranilamide compound, a preparation method thereof and an application of the anthranilamide compound as an insecticide, the anthranilamide compound is synthesized from the simplest raw materials, a target product is obtained through seven steps of reaction, an oxazine intermediate can be prepared through the reaction of M-4 and M-5, pyridine is used as an acid-binding agent, and the yield is obviously improved compared with that of triethylamine as the acid-binding agent; in the preparation process of the intermediate M-4, oxalyl chloride is used as an acylating chlorination reagent, N, N-dimethyl formyl chloride is used as a catalyst, the preparation can be smoothly carried out at normal temperature, and meanwhile, pyrazole-4-H is prevented from being substituted by chlorine. According to the route, a plurality of intermediates are obtained at the same time, many other types of compounds can be further expanded and designed through the intermediates, and the method is a precious wealth for new drug development; in addition, the route has the advantages of easily available raw materials and mild reaction conditions, and is suitable for industrial development.

Description

Technical Field

[0001] The present invention relates to the field of pesticides, in particular to an o-aminobenzamide compound and a preparation method thereof and application thereof as a pesticide. Background Art

[0002] Ryanodine is a compound extracted from the South American shrub Ryaniaspeciosa. It is very effective in preventing and controlling lepidopteran pests. Since it is also highly toxic to humans and animals, structural modification of ryanodine to change its toxicity and activity, that is, to make it highly effective against insects and low or non-toxic to mammals, has become a research hotspot. DuPont has developed a broad-spectrum o-formylaminobenzamide insecticide, chlorantraniliprole, which not only has excellent activity against insects, but is also very safe for mammals. At the same time, due to its unique chemical structure and novel mode of action, it has outstanding control effects on other insecticide-resistant pest groups. Summary of the invention

[0003] The invention is based on the molecular structure of chlorantraniliprole and changes the position of the formyl group on the pyridylpyrazole ring to obtain a series of new pyrazolecarboxamide compounds containing active pyridylpyrazole-4-carboxamide.

[0004] To achieve the above object, the present invention provides the following technical solutions: A method for preparing an o-aminobenzamide compound, which is prepared by the following synthetic route: ; Among them, a: R1 = CH3; b: R1 = CH2CH3; c: R1 = i -Pr;d:R1= t -Bu.

[0005] An o-aminobenzamide compound prepared by the preparation method.

[0006] A use of the above-mentioned o-aminobenzamide compound as an insecticide.

[0007] The beneficial effects of the present invention are as follows: the present invention starts with the simplest raw material for synthesis, and obtains the target product through 7 steps of reaction. The oxazine intermediate can be obtained by the reaction of M-4 and M-5. The pyridine is used as the acid-binding agent, and the yield is significantly improved compared with the triethylamine as the acid-binding agent. In the preparation process of the intermediate M-4, oxalyl chloride is used as the chlorination reagent, and N,N-dimethylformyl chloride is used as the catalyst, which can be carried out smoothly at room temperature, and the pyrazole-4-H is also avoided to be replaced by chlorine. This route obtains multiple intermediates at the same time, and many other types of compounds can be further expanded and designed through these intermediates, which is a valuable asset for the development of new drugs. In addition, this route has the advantages of easy availability of raw materials and mild reaction conditions, and is suitable for industrial development. DETAILED DESCRIPTION

[0008] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0009] In addition, the technical features involved in the different embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0010] 1.1 Instruments and reagents X-4 digital melting point instrument, Bell Analytical Instruments (Dalian) Co., Ltd.; Bruker 400Mz nuclear magnetic resonance instrument, Bruker, Germany. The reagents used in the experiment were analytically pure or chemically pure.

[0011] 1.2 Compound synthesis methods 1.2.1: Synthesis of ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoate (M-1) 18.4 g (0.1 mol) ethyl trifluoroacetoacetate, 29.6 g (0.2 mol) CH(OEt)3 and 30.6 g (0.3 mol) Ac2O were reacted at 120°C for 2 hours, and then the temperature was raised to 140°C for further reaction for 5 hours. The reactants were distilled under reduced pressure, and the 115 °C / 0.2 mm fraction was cut to obtain a colorless liquid, which was the product M-1, 19.0 g, with a yield of 79%.

[0012] 1.2.2: 5-trifluoromethyl-1-(3-chloropyridin-2-yl)-1 H -Synthesis of ethyl pyrazole-4-carboxylate (M-2) Add 14.55 g (0.10 mol) of 2-hydrazino-3-chloropyridine and 24.02 g (0.10 mol) of ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoate to the ethanol solution. Stir the reaction at 80°C for 1 hour. Dilute the reaction solution with ethyl acetate and wash with saturated brine. Dry the organic layer with anhydrous magnesium sulfate, filter, and concentrate. Obtain an orange solid, which is the product M-2, 27.39 g, with a yield of 85.7%.

[0013] 1.2.3: 5-trifluoromethyl-1-(3-chloropyridin-2-yl)-1 H -Synthesis of pyrazole-4-carboxylic acid (M-3) 2.83 g (0.012 mol) of 5-trifluoromethyl-1-(3-chloropyridin-2-yl)-1 H -Ethyl pyrazole-4-carboxylate (M-2) was added to 30 ml of ethanol, and the temperature was raised to 50 ° C, and then 10% potassium hydroxide solution was added and the temperature was controlled at 50-55 ° C. TLC tracking was performed, and the reaction was continued at 50-55 ° C for 3 hours. After the reaction solution was desolvated, 30 ml of water was added, and it was extracted three times with 100 ml of dichloromethane, and the pH was adjusted to about 2 with 15% hydrochloric acid solution. After vacuum filtration, a yellowish brown solid was obtained, which was the product M-3, 2.36 g, with a yield of 67.4%.

[0014] 1.2.4: 5-trifluoromethyl-1-(3-chloropyridin-2-yl)-1 H -Synthesis of pyrazole-4-carbonyl chloride (M-4) Suspend 10.00 g (0.034 mol) of M-3 in 150 mL of dichloromethane, add 1 mL of DMF, and dropwise add 6.53 g (0.0514 mol) of oxalyl chloride to the suspension after about 0.4 h. Stir and react overnight to obtain a clear solution. Concentrate to dryness under reduced pressure to obtain a semisolid, which is sealed for later use. Use it directly in the next step.

[0015] 1.2.5: Synthesis of 6-chloro-8-methyl-1H-benzo[d][1,3]oxazine-2,4-dione (M-5) Add acid anhydride (0.25 mol) and 25 mL of pyridine into a three-necked flask, heat up and stir until completely dissolved, add chloroaminobenzoic acid (0.1 mol) all at once, reflux for 8 h, track by TLC, wait for the reaction of the raw materials to be complete, cool to room temperature, slowly pour the reaction solution into 200 mL of ice-saturated sodium bicarbonate solution, stir for 1 h, filter, wash twice with 50 mL of ice-saturated brine, and dry to obtain the product with a yield of 88.7%.

[0016] 1.2.6: 6-chloro-2-(1-(3-chloropyridin-2-yl)-5-trifluoromethyl-1 H-pyrazol-4-yl)-8-methyl-4H-benzo[ d Synthesis of ][1,3]oxazine-4-one (M-6) Add 400 mL of acetonitrile and 150 mL of pyridine to M-4 obtained in the previous step, stir until dissolved, heat to reflux, slowly add 5.23 g (0.025 mol) of M-5, continue reflux reaction for 3 h after addition, cool naturally, a large amount of solid precipitates in the solution, filter, wash with a small amount of acetonitrile, and dry to obtain a white solid, namely M-6, 9.83 g, with a yield of 89.2%.

[0017] 1.2.7: Synthesis of target product (M-7) 1.98 g (0.0045 mol) of M-6 was suspended in 10 mL of DMF. RNH2(ab) solution (0.0069 mol) was added dropwise to the suspension at room temperature for about 1 h. The solution gradually became clear. After the addition, the reaction was continued for 2 h. The reaction solution was added dropwise to 50 mL of water to obtain a large amount of white solid precipitation. The solid was filtered and dried to obtain a white solid, which was the target product M-7.

[0018] 1.3 Biological activity assay The test method adopted was the dipped leaf disc method.

[0019] Preparation: Weigh 10 mg of the original drug and dissolve it in acetone, and prepare a 100 ppm mother solution with Tween water. Dilute the mother solution with 0.05% Tween water to obtain the desired concentration of drug solution. Each treatment is repeated 3 times, and a blank control is set.

[0020] Dip the prepared fresh cabbage leaf discs in the solution for 10 seconds, take them out and air dry them. Put 2 leaf discs in each culture dish, and inoculate 7 third-instar larvae at the same time, and seal them. Check the number of dead and alive insects on the 1st and 3rd day of the survey, and make statistical analysis.

[0021] 2 Results and discussion 2.1 Physicochemical parameters and structural characterization of intermediates and target compounds Intermediate physical and chemical parameters and NMR data: M-1: ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoate. Colorless liquid, yield 79%. 1 HNMR (500MHz, CDCl3) d : 1.21 (3H, t, CH3), 1.29 (3H, t, CH3), 4.20 (2H, m, CH2), 4.49 (2H, m, CH2), 7.84 (H, s, CH).

[0022] M-2: 5-trifluoromethyl-1-(3-chloropyridin-2-yl)-1H -Ethyl pyrazole-4-carboxylate, orange solid, yield 85.7%. MP: 63-67 °C. 1 H NMR: (400Hz, CDCl3) d : 1.39 (3H, t, CH3, J = 7.2 Hz), 4.39(2H, q, CH2, J = 14.4 Hz), 7.51 (1H, q, Pyridine-H, J = 7.8 Hz), 7.97 (1H, dd,Pyridine-H, J 1 = 1.6 Hz, J 2= ​​8.4 Hz), 8.23 ​​(1H, s, Pyrazole-H), 8.53 (1H, dd,Pyridine-H, J 1 = 1.2 Hz, J 2 = 4.4 Hz).

[0023] M-3: 5-trifluoromethyl-1-(3-chloropyridin-2-yl)-1 H -pyrazole-4-carboxylic acid, khaki solid, yield 67.4%. MP: 146-149 °C. 1 H NMR: (400Hz, DMSO- d 6 ) d :7.80 (1H, q, Pyridine-H, J = 8.0Hz), 8.37 (1H, d, Pyridine-H, J = 1.2 Hz), 8.40 (1H, d, Pyrazole-H, J = 0.8 Hz),8.65 (1H, dd, Pyridine-H, J 1 = 1.2 Hz, J 2 = 4.4 Hz). M-6: 6-chloro-2-(1-(3-chloropyridin-2-yl)-5-trifluoromethyl-1 H -pyrazol-4-yl)-8-methyl-4H-benzo[ d ][1,3]oxazin-4-one, white solid, yield 89.2%. MP: 173-176 °C. 1 H NMR: (300Hz, CDCl3) d:2.58 (3H, s, CH3), 7.54 (1H, q, Pyridine-H, J = 8.2 Hz), 7.64 (1H, d, Ar-H, J =1.6 Hz), 8.00 (1H, dd, Pyridine-H, J 1 = 1.6 Hz, J 2= ​​8.0 Hz), 8.05 (1H, d,Pyrazole-H, J = 2.0 Hz), 8.46 (1H, s, Ar-H), 8.57 (1H, dd, Pyridine-H, J 1 = 1.6 Hz, J 2 = 4.8 Hz).

[0024] Physicochemical parameters and NMR data of target compounds.

[0025] M-7a: white solid, yield 72.5%, MP: 231-232 °C. 1 H NMR: (400 MHz, DMSO- d 6 ) d :2.27 (3H, s, CH3), 2.71 (3H, d, CH3, J = 4.8 Hz), 7.40 (1H, d, Pyrazole-H, J = 2.4Hz), 7.53 (1H, d, Pyridine-H, J = 2.0 Hz), 7.80 (1H, q, Pyridine-H, J = 8.2 Hz),8.35 (1H, d, -NH-, J = 4.8 Hz), 8.39 (1H, dd, Pyridine-H, J 1 = 1.6 Hz, J 2= ​​8.0 Hz),8.42 (1H, s, Ar-H), 8.66 (1H, dd, Pyridine-H, J 1 = 1.6 Hz, J 2= ​​4.8 Hz), 9.99 (1H,s, -NH-); 13 C NMR (400 MHz, DMSO- d 6 ) d18.89, 26.75, 119.65, 124.66, 126.62,129.16, 131.98, 132.23, 132.44, 132.78, 138.55, 139.57, 140.92, 147.10,148.34,159.48, 168.33. M-7b: white solid, yield 76.1%, MP: 210-212 °C; 1 H NMR: (400 MHz, CDCl3) d :1.18(3H, t, CH3, J = 7.2 Hz), 2.27 (3H, s, CH3), 3.40 (2H, m, CH2, J = 10 Hz), 6.41(1H, q, -NH-, J = 5.4 Hz), 7.24 (1H, d, Ar-H, J = 2.0 Hz), 7.29 (1H, d, Pyrazole-H, J = 8.2 Hz), 7.51 (1H, q, Pyridine-H, J = 8.2 Hz), 7.98 (1H, dd, Pyridine-H, J 1 = 1.6 Hz, J 2= ​​8.0 Hz), 8.34 (1H, s, Ar-H), 8.54 (1H, dd, Pyridine-H, J 1 = 1.6 Hz, J 2= ​​4.4 Hz), 9.86 (1H, s, -NH-); 13 CNMR (400 MHz, CDCl3) d 14.48, 18.87, 35.06,117.58, 119.69, 120.43, 124.48, 126.61, 129.19, 132.04, 132.13, 132.76,133.00, 138.79, 139.55, 140.86, 147.09,148.36, 159.37, 167.77. M-7c: white solid, yield 73.7%, MP: 179-182 ° C; 1 H NMR: (400 MHz, CDCl3) d :1.19(6H, d, CH3, J =6.4 Hz), 2.29 (3H, s, CH3), 4.18 (1H, m, CH, J = 13.7 Hz), 6.13(1H, d, -NH-, J = 7.6 Hz), 7.22 (1H, d, Ar-H, J = 2.4 Hz), 7.29 (1H, d, Pyrazole-H, J = 2.4 Hz), 7.98 (1H, q, Pyridine-H, J = 8.0 Hz), 7.98 (1H, dd, Pyridine-H, J 1 = 1.6 Hz, J 2 = 8.0 Hz), 8.36 (1H, s, Ar-H), 8.54 (1H, dd, Pyridine-H, J 1 = 1.6 Hz, J 2 = 4.8 Hz), 9.85 (1H, s, -NH-); 13 C NMR (400 MHz, CDCl3) d 18.86, 22.39, 42.31, 117.73, 119.66, 120.42, 123.12, 124.34, 126.62, 129.20, 132.04, 132.13, 132.72, 133.23, 138.93, 139.54, 140.84, 147.10, 148.40, 159.29, 167.11, 179.44. M-7d: White solid, yield 73.4%, MP: 117 - 119 °C; 1 H NMR: (400 MHz, CDCl3) d : 1.36(9H, s, CH3), 2.22 (3H, s, CH3), 6.23 (1H, s, -NH-), 7.14 (1H, d, Ar-H, J = 2.0Hz), 7.17 (1H, d, Pyrazole-H, J = 2.4 Hz), 7.51 (1H, q, Pyridine-H, J = 8.2 Hz), 7.97 (1H, dd, Pyridine-H, J 1 = 1.6 Hz, J2= ​​8.0 Hz), 8.55 (1H, dd, Pyridine-H, J 1=1.6 Hz, J 2= ​​4.4 Hz), 8.59 (1H, s, Ar-H), 10.02 (1H, s, -NH-); 13 C NMR (400 MHz,CDCl3) d 8.46, 28.45, 52.35, 119.38, 120.42, 124.27, 126.61, 129.27, 130.98,131.97,132.52, 133.21, 136.12, 139.30, 139.48, 140.86, 147.13, 148.54,159.92, 167.75. 2.2 Biological activity of target compounds The biological activity of compound M-7(ab) was tested with Plutella xylostella as the target, and the test results are shown in Table 1: It can be seen from Table 1 that the target molecule M-7(ab) has a certain insecticidal activity against Plutella xylostella, indicating that the target molecule retains two highly active groups, pyrazole and amide, so that the target molecule still retains insecticidal activity. At 100 ppm, the insecticidal activity was observed. On the third day, the biological activity from high to low was M-7d>M-7c>M-7b>M-7a.

[0026] When the R group is tert-butyl, it exhibits higher insecticidal activity. When the R group is methyl, compound M-7 a still has a certain insecticidal activity of 23.82% at 10ppm. When the R group is tert-butyl, compound M-7 b still has a certain insecticidal activity of 66.67% at 10ppm. The insecticidal activity of M-7a and M-7b is further compared, and the experimental results are shown in Table 2.

[0027] Table 1 Insecticidal activity of compound M-7(ab) against Plutella xylostella Table 2 Comparative test of insecticidal activity of compounds M-7a and M-7d against Plutella xylostella Based on the test results in Table 2, the toxicity regression equations of compounds M-7a and M-7d, as well as their LC 50 and LC 90 , the results are shown in Table 3: Table 3 Statistical comparison of toxicity Through the biological activity test on Plutella xylostella, it was found that it has certain biological activity, which has a certain guiding role in further research on this type of compound, including the selection and optimization of the synthesis route and the promotion and application of the agent.

[0028] Although the embodiments of the present invention have been disclosed as above, they are not limited to the applications listed in the specification and the implementation modes. They can be fully applied to various fields suitable for the present invention. For those familiar with the art, additional modifications can be easily implemented. Therefore, without departing from the general concept defined by the claims and the scope of equivalents, the present invention is not limited to specific details.

Claims

1. A method for preparing an o-aminobenzamide compound, characterized in that: Prepared by the following synthetic route: ； Among them, a: R1 = CH3; b: R1 = CH2CH3; c: R1 = i -Pr;d:R1= t -Bu.

2. An o-aminobenzamide compound prepared by the preparation method according to claim 1.

3. Use of the o-aminobenzamide compound as claimed in claim 2 as an insecticide.

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