A benzotriazinone oxadiazole derivative, and a preparation method and application thereof
Patent Information
- Application Number
- CN202410140644.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-02-01
- Publication Date
- 2026-09-18
- Estimated Expiration
- 2044-02-01
AI Technical Summary
[0035] This invention uses benzotriazinone as the parent compound and splices it with 1,3,4-oxadiazole to synthesize a series of benzotriazinone oxadiazole derivatives. These benzotriazinone oxadiazole derivatives exhibit good killing effects against wheat scab, rice sheath blight, rice blast, Bletilla striata, tea anthracnose, rapeseed sclerotinia stem rot, as well as Echinochloa elegans and pine wilt nematodes, and have high commercial application prospects.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of organic compound preparation technology, and in particular to a benzotriazine oxadiazole derivative, its preparation method, and its application. Background Technology
[0002] Benzo[d][1,2,3]triazine-4(3H)ones are an important class of nitrogen-containing heterocyclic compounds widely used in pharmaceuticals and pesticides. 1,2,3-Benzotriazineones have been reported to possess a wide range of pharmacological activities, including insecticidal, sedative, anesthetic, and antitumor effects. They also exhibit numerous active sites and strong derivatization potential; for example, the insecticides phosmet and phosmet contain benzotriazineone structures. Metoxadiazone, oxadiazon, and oxadiargyl are three pesticides used to control agricultural pests and weeds. The oxadiazole ring is the active center of these pesticides.
[0003] Therefore, the discovery of a benzotriazine oxadiazole derivative with excellent control effects against pathogenic fungi based on benzotriazine oxadiazole is of great significance. Summary of the Invention
[0004] The purpose of this invention is to provide a benzotriazinone oxadiazole derivative, its preparation method, and its application, addressing the shortcomings of existing technologies.
[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution:
[0006] This invention provides a benzotriazinone oxadiazole derivative, the structural formula of which is:
[0007]
[0008] In Formulas 1 and 2, R1 and R2 are independently one or more of H, straight-chain or branched alkyl, halogen, nitro, methoxy, phenyl, thiazolyl, pyridyl, trifluoromethyl, trichloromethyl and cyano groups.
[0009] As a preferred embodiment, the structural formula of the benzotriazinone oxadiazole derivative is as follows:
[0010]
[0011]
[0012] This invention also provides a method for preparing the aforementioned benzotriazinone oxadiazole derivative, with the following structural formula:
[0013] The synthetic route for the benzotriazinone oxadiazole derivative of Formula 1 is as follows:
[0014]
[0015] The synthetic route for the benzotriazinone oxadiazole derivative with the structural formula of Formula 2 is as follows:
[0016]
[0017] The preparation method of benzotriazinone oxadiazole derivatives includes the following steps:
[0018] 1) The R1-substituted o-aminobenzamide was reacted with hydrochloric acid and sodium nitrite solution to obtain compound 1;
[0019] 2) Compound A, cesium carbonate, potassium iodide, acetonitrile, and ethyl bromoacetate were refluxed to give compound B;
[0020] 3) Compound B, methanol, and hydrazine hydrate solution were mixed and refluxed to obtain compound 3;
[0021] 4) Compound C, methanol and carbon disulfide are mixed and reacted. The reaction products, bromoethane, potassium carbonate and acetonitrile are refluxed to obtain Formula 1.
[0022] 5) React Equation 1, anhydrous ethanol, hydrogen peroxide solution and ammonium molybdate to obtain Equation 2;
[0023] R1 and R2 are independently one or more of the following: H, C1-C4 straight-chain or branched alkyl, halogen, nitro, methoxy, phenyl, thiazolyl, pyridyl, trifluoromethyl, trichloromethyl and cyano groups.
[0024] Preferably, in step 1), the molar ratio of o-aminobenzamide to sodium nitrite is 0.7–0.8:1.3–1.6; the molar volume ratio of sodium nitrite to hydrochloric acid is 1.3–1.6 mmol:1.8–2.2 mL; and the concentration of hydrochloric acid is 1.5–2.5 mol / L.
[0025] The reaction temperature is -2 to 2°C, and the reaction time is 0.5 to 1.5 h.
[0026] Preferably, in step 2), the molar ratio of compound A, cesium carbonate, potassium iodide and ethyl bromoacetate is 1–3:3–5:1:3–5; and the molar volume ratio of potassium iodide and acetonitrile is 1 mmol:25–35 mL.
[0027] The reflux reaction temperature is 80–88°C, and the reflux reaction time is 4–6 hours.
[0028] Preferably, in step 3), the molar ratio of compound B to hydrazine hydrate is 40–45:195–210; the molar volume ratio of compound B to methanol is 40–45 mmol:180–220 mL; and the mass concentration of the hydrazine hydrate solution is 77–83%.
[0029] The mixing time is 25–35 min, the reflux reaction temperature is 60–70 °C, and the reflux reaction time is 4–6 h.
[0030] Preferably, in step 4), the molar volume ratio of compound C, methanol, and carbon disulfide is 1 mmol: 50–55 mL: 4.5–5.5 mmol; the reaction temperature is 60–70 °C, and the reaction time is 5–7 h.
[0031] The molar ratio of the reaction product, bromoethane, and potassium carbonate is 1:1.2–1.8:1.5–2.5; the molar volume ratio of bromoethane and acetonitrile is 1.2–1.8 mmol:45–55 mL; the reflux reaction temperature is 80–90 °C, and the reflux reaction time is 7–9 h.
[0032] Preferably, in step 5), the molar ratio of Formula 1, hydrogen peroxide, and ammonium molybdate is 1:7-9:0.15-0.25; the mass concentration of the hydrogen peroxide solution is 25-35%; and the molar volume ratio of Formula 1 and anhydrous ethanol is 1 mmol:8-12 mL.
[0033] The present invention also provides the application of the benzotriazine oxadiazole derivative in fungicides and nematicides.
[0034] The beneficial effects of this invention are as follows:
[0035] This invention uses benzotriazinone as the parent compound and splices it with 1,3,4-oxadiazole to synthesize a series of benzotriazinone oxadiazole derivatives. These benzotriazinone oxadiazole derivatives exhibit good killing effects against wheat scab, rice sheath blight, rice blast, Bletilla striata, tea anthracnose, rapeseed sclerotinia stem rot, as well as Echinochloa elegans and pine wilt nematodes, and have high commercial application prospects. Detailed Implementation
[0036] This invention provides a benzotriazinone oxadiazole derivative, the structural formula of which is:
[0037]
[0038] In Formulas 1 and 2, R1 and R2 are independently one or more of H, straight-chain or branched alkyl, halogen, nitro, methoxy, phenyl, thiazolyl, pyridyl, trifluoromethyl, trichloromethyl and cyano groups.
[0039] In this invention, the preferred structural formulas of the benzotriazinone oxadiazole derivatives are compounds 1 to 21 shown in Table 1.
[0040] Table 1. Structural formulas, molecular formulas, and melting points of benzotriazinone oxadiazole derivatives
[0041]
[0042]
[0043]
[0044]
[0045] In Table 1, compounds 1 to 18 are specific compounds of Formula 1, and compounds 19 to 21 are specific compounds of Formula 2.
[0046] This invention also provides a method for preparing the aforementioned benzotriazinone oxadiazole derivative, wherein the synthetic route for the benzotriazinone oxadiazole derivative with structural formula 1 is as follows:
[0047]
[0048] The synthetic route for the benzotriazinone oxadiazole derivative with the structural formula of Formula 2 is as follows:
[0049]
[0050] The preparation method of benzotriazinone oxadiazole derivatives includes the following steps:
[0051] 1) The R1-substituted o-aminobenzamide was reacted with hydrochloric acid and sodium nitrite solution to obtain compound 1;
[0052] 2) Compound A, cesium carbonate, potassium iodide, acetonitrile, and ethyl bromoacetate were refluxed to give compound B;
[0053] 3) Compound B, methanol, and hydrazine hydrate solution were mixed and refluxed to obtain compound 3;
[0054] 4) Compound C, methanol and carbon disulfide are mixed and reacted. The reaction products, bromoethane, potassium carbonate and acetonitrile are refluxed to obtain Formula 1.
[0055] 5) React Equation 1, anhydrous ethanol, hydrogen peroxide solution and ammonium molybdate to obtain Equation 2;
[0056] R1 and R2 are independently one or more of the following: H, C1-C4 straight-chain or branched alkyl, halogen, nitro, methoxy, phenyl, thiazolyl, pyridyl, trifluoromethyl, trichloromethyl and cyano groups.
[0057] In step 1) of this invention, the molar ratio of o-aminobenzamide to sodium nitrite is preferably 0.7-0.8:1.3-1.6, more preferably 0.72-0.78:1.4-1.5, and even more preferably 0.75-0.753:1.45-1.471; the molar volume ratio of sodium nitrite to hydrochloric acid is preferably 1.3-1.6 mmol:1.8-2.2 mL, more preferably 1.4-1.5 mmol:1.9-2.1 mL, and even more preferably 1.45-1.471 mmol:2.0 mL; and the concentration of hydrochloric acid is preferably 1.5-2.5 mol / L, more preferably 1.8-2.2 mol / L, and even more preferably 1.9-2.0 mol / L.
[0058] The reaction temperature is preferably -2 to 2°C, more preferably -1 to 1°C, and even more preferably 0°C; the reaction time is preferably 0.5 to 1.5 h, and even more preferably 1 h.
[0059] In this invention, after the reaction described in step 1) is completed, preferably, the pH value of the reaction system is adjusted to 7-8 using sodium hydroxide solution after the temperature of the reaction system is raised to room temperature.
[0060] In this invention, the molar ratio of compound A, cesium carbonate, potassium iodide and ethyl bromoacetate in step 2) is preferably 1-3:3-5:1:3-5, more preferably 1.5-2.5:3.5-4.5:1:3.5-4.5, and even more preferably 2:4:1:4; the molar volume ratio of potassium iodide and acetonitrile is preferably 1 mmol:25-35 mL, more preferably 1 mmol:28-32 mL, and even more preferably 1 mmol:29-30 mL.
[0061] The reflux reaction temperature is preferably 80–88°C, more preferably 82–86°C, and even more preferably 83–85°C; the reflux reaction time is preferably 4–6 h, more preferably 4.5–5.5 h, and even more preferably 5 h.
[0062] In step 3) of this invention, the molar ratio of compound B to hydrazine hydrate is preferably 40-45:195-210, more preferably 42-43:198-205, and even more preferably 42.5-42.9:200-202.53; the molar volume ratio of compound B to methanol is preferably 40-45 mmol:180-220 mL, more preferably 42-43 mmol:190-210 mL, and even more preferably 42.5-42.9 mmol:200-205 mL; the mass concentration of the hydrazine hydrate solution is preferably 77-83%, more preferably 78-81%, and even more preferably 79-80%.
[0063] The mixing time is preferably 25-35 min, more preferably 27-32 min, and even more preferably 29-30 min; the mixing is carried out by stirring at room temperature; the reflux reaction temperature is preferably 60-70℃, more preferably 62-68℃, and even more preferably 64-65℃; the reflux reaction time is preferably 4-6 h, more preferably 4.5-5.5 h, and even more preferably 5 h.
[0064] In this invention, the preferred molar volume ratio of compound C, methanol, and carbon disulfide in step 4) is 1 mmol: 50-55 mL: 4.5-5.5 mmol, more preferably 1 mmol: 51-54 mL: 4.8-5.2 mmol, and even more preferably 1 mmol: 52-53 mL: 4.9-5.0 mmol; the preferred reaction temperature is 60-70°C, more preferably 62-68°C, and even more preferably 64-65°C; the preferred reaction time is 5-7 h, more preferably 5.5-6.5 h, and even more preferably 6 h.
[0065] The molar ratio of the reaction product, bromoethane, and potassium carbonate is preferably 1:1.2–1.8:1.5–2.5, more preferably 1:1.4–1.6:1.7–2.2, and even more preferably 1:1.5:1.9–2.0; the molar volume ratio of bromoethane and acetonitrile is preferably 1.2–1.8 mmol:45–55 mL, more preferably 1.4–1.6 mmol:47–52 mL, and even more preferably 1.5 mmol:49–50 mL; the reflux reaction temperature is preferably 80–90 °C, more preferably 82–88 °C, and even more preferably 84–85 °C; the reflux reaction time is preferably 7–9 h, more preferably 7.5–8.5 h, and even more preferably 8 h.
[0066] In step 5) of the present invention, the molar ratio of Formula 1, hydrogen peroxide and ammonium molybdate is preferably 1:7-9:0.15-0.25, more preferably 1:7.5-8.5:0.17-0.22, and even more preferably 1:8.0:0.19-0.20; the mass concentration of the hydrogen peroxide solution is preferably 25-35%, more preferably 27-32%, and even more preferably 29-30%; the molar volume ratio of Formula 1 and anhydrous ethanol is preferably 1 mmol:8-12 mL, more preferably 1 mmol:9-11 mL, and even more preferably 1 mmol:10 mL.
[0067] The present invention also provides the application of the benzotriazine oxadiazole derivative in fungicides and nematicides.
[0068] In this invention, the benzotriazine oxadiazole derivative is preferably used to control rice sheath blight, Bletilla striata var. chinensis, tea anthracnose, wheat scab, rice blast, rapeseed sclerotinia stem rot, pine wilt nematode, and Caenorhabditis elegans.
[0069] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.
[0070] Example 1
[0071] (1) Synthesis of benzotriazine
[0072]
[0073] 75.3 mmol of o-aminobenzamide was dissolved in 200 mL of 2 mol / L hydrochloric acid and stirred at 540 r / min until homogeneous. 80 mL of sodium nitrite solution (147.1 mmol of sodium nitrite) was added dropwise at a rate of 2 drops per second using a constant pressure titration funnel at 0 °C. The reaction was continued for 1 h under these conditions. After the reaction was completed, the temperature of the reaction system was raised to room temperature and then neutralized to pH 7 with 2 mol / L NaOH aqueous solution. The solution was filtered under vacuum at 0.09 MPa using a Niu SHZ-DIII circulating water vacuum pump. The filter cake was recrystallized from methanol to obtain a white solid, namely benzotriazinone, with a yield of 85%.
[0074] (2) Synthesis of ethyl 2-(4-oxobenzo[D][1,2,3]triazine-3(4H)-yl)
[0075]
[0076] 10 mmol of benzotriazine, 20 mmol of cesium carbonate, and 5 mmol of potassium iodide were placed in a 250 mL round-bottom flask, and 150 mL of acetonitrile was added. The mixture was stirred at 540 rpm at room temperature until the benzotriazine was completely dissolved. 20 mmol of ethyl bromoacetate was added dropwise at a rate of 1 drop per second using a constant-pressure titration funnel. After the addition was complete, the mixture was heated to 83 °C and refluxed for 5 h. The reaction was monitored for completion by thin-layer chromatography (TLC, petroleum ether to ethyl acetate volume ratio of 4:1). The solution was concentrated to dryness under reduced pressure at 0.09 MPa and 65 °C for 8 min using a Shanghai Yarong RE-5298 rotary evaporator and a Xiniu SHZ-DIII circulating water vacuum pump. The solution was added to 80 mL of water and extracted three times with dichloromethane (30 mL each time). The organic phases were combined and dried over anhydrous sodium sulfate. The solution was concentrated under reduced pressure and separated by silica gel column chromatography (petroleum ether to ethyl acetate volume ratio of 4:1) to give a white solid in 81% yield.
[0077] (3) Synthesis of 2-(4-oxobenzo[d][1,2,3]triazine-3(4H)-acetylhydrazine
[0078]
[0079] 42.90 mmol of ethyl 2-(4-oxobenzo[D][1,2,3]triazine-3(4H)-yl) was placed in a 500 mL round-bottom flask, and 200 mL of methanol was added. The mixture was stirred at 540 rpm at room temperature, and an 80% hydrazine hydrate solution (containing 202.53 mmol of hydrazine hydrate) was added dropwise at a rate of 1 drop per second. After the addition was complete, the mixture was stirred at 540 rpm at room temperature for 30 min, and then refluxed at 65 °C for 5 h. The reaction was monitored for completion by thin-layer chromatography (TLC, with a volume ratio of petroleum ether to ethyl acetate of 2:1). The solution was concentrated to dryness under reduced pressure at 0.09 MPa and 65 °C for 8 min. It was washed three times with water (100 mL each time). The solution was then filtered using a Niu SHZ-DIII circulating water vacuum pump (0.09 MPa), an 80 mm diameter Buchner funnel, a 250 mL suction filtration flask, and two layers of rapid qualitative filter paper. The solution was then dried in an oven at 55 °C to obtain a white solid.
[0080] (4) Synthesis of 3-((5-mercapto-1,3,4-oxadiazol-2-yl)methyl)benzo[d][1,2,3]triazine-4(3H)-one
[0081]
[0082] 4 mmol of 2-(4-oxobenzo[d][1,2,3]triazine-3(4H)-acetylhydrazine was added to a 500 mL round-bottom flask, followed by 200 mL of methanol. The mixture was stirred at 540 rpm at room temperature until completely dissolved. 20 mmol of carbon disulfide was added dropwise at a rate of 1 drop per second. After the addition was complete, the mixture was stirred at room temperature for 30 min, then refluxed at 65 °C for 6 h. The reaction was monitored for completion by thin-layer chromatography (TLC, with a petroleum ether to ethyl acetate volume ratio of 1:1). The reaction was carried out at 0.09 M... Concentrate to dryness under reduced pressure at 65℃ for 8 min. Pour the reaction system into water and adjust the pH to 4 by adding 2 mol of 5% hydrochloric acid at a rate of 1 drop per second under ice bath conditions. Use a Niu SHZ-DIII circulating water vacuum pump (0.09 MPa), an 80 mm diameter Buchner funnel, a 250 mL suction flask, and two layers of rapid qualitative filter paper for filtration. Separate and purify by column chromatography (volume ratio of petroleum ether to ethyl acetate of 5:1) to obtain a white solid with a yield of 78%.
[0083] (5) Synthesis of 3-(5-ethylthio)-1,3,4-oxadiazol-2-ylmethyl)benzo[d][1,2,3]triazine-4(3H)one (compound 3)
[0084]
[0085] 1 mmol of 3-((5-mercapto-1,3,4-oxadiazol-2-yl)methyl)benzo[d][1,2,3]triazine-4(3H)-one, 1.5 mmol of bromoethane, and 2 mmol of potassium carbonate were placed in a 150 mL round-bottom flask. 50 mL of acetonitrile was added, and the mixture was heated to 85 °C and refluxed for 8 h. The reaction was monitored by thin-layer chromatography (TLC, petroleum ether to ethyl acetate in a volume ratio of 1:1). The mixture was concentrated to dryness under reduced pressure at 0.09 MPa and 65 °C for 8 min. The solution was dissolved in 50 mL of dichloromethane and extracted three times with saturated sodium chloride solution. The organic phase was dried over anhydrous sodium sulfate, filtered under vacuum at 0.09 MPa to remove anhydrous sodium sulfate, concentrated to dryness under reduced pressure, and purified by column chromatography (petroleum ether to ethyl acetate in a volume ratio of 4:1). After drying at 55 °C, the target compound (compound 3) was obtained in 80% yield.
[0086] Example 2
[0087] Synthesis of 3-(5-ethylsulfonyl)-1,3,4-oxadiazol-2-methyl)benzo[d][1,2,3]triazine-4(3H)one (compound 20)
[0088]
[0089] 1.0 mmol of 3-(5-ethylthio)-1,3,4-oxadiazol-2-ylmethyl)benzo[d][1,2,3]triazine-4(3H)one and 10 mL of anhydrous ethanol from Example 1 were added separately to 100 mL three-necked flasks. After the solid dissolved, a solution of ammonium molybdate (0.2 mmol) dissolved in 30% hydrogen peroxide (8.0 mmol) was added dropwise. The mixture was stirred at 540 rpm at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction was stopped, the solvent was removed under reduced pressure at 0.09 MPa, ice water was added, the mixture was stirred and filtered, and then purified by column chromatography (petroleum ether and ethyl acetate in a volume ratio of 5:1). After drying at 55 °C, a white solid (compound 20) was obtained, with a yield of 67%.
[0090] Example 3
[0091] Compounds 1-2, 4-19, and 21 were prepared by replacing H with C1-C4 straight-chain or branched alkyl, halogen, nitro, methoxy, phenyl, thiazolyl, pyridyl, trifluoromethyl, trichloromethyl, and cyano groups, respectively, under the same conditions as in Example 1.
[0092] The bactericidal activity of compounds 1-21 prepared in the examples was tested. The mycelial growth rate method was used to determine the bactericidal activity of compounds 1-21 against various fungi in petri dishes. Under aseptic conditions, various pathogens were cultured, and mycelial cakes were cut from the edge of the colony using a 7 mm diameter punch. The mycelial cakes were inoculated into the center of a petri dish containing drug-containing medium using an inoculation needle (the drug concentration of each drug group was set at 50 mg / L. 25 mg of the test compound was dissolved in 250 μL of DMF, and then diluted to 50 mL with 0.1% Tween 80 aqueous solution. 20 mL of the drug solution was added to a pre-sterilized 180 mL / bottle of p-phenylenediamine (PDA) to prepare a 50 mg / L drug-containing medium). The mycelial side was facing down, the dish was covered, inverted, and incubated in a 25°C incubator. When the colonies in the blank control (containing only pathogens, without the drug) reached two-thirds of the plate area, the colony diameter of each treatment group was measured using the cross-sectional method. Each sample was repeated three times, and the average value was taken. The mycelial growth inhibition rate of each drug treatment against pathogens (rice sheath blight fungus, wheat scab fungus, tea anthracnose fungus, Bletilla striata fungus, rice blast fungus, and rapeseed sclerotinia stem rot fungus) was calculated by the ratio of the difference between the colony diameter of the blank control and the colony diameter of the drug-treated fungus to the colony diameter of the blank control. The results are shown in Table 2.
[0093] Table 2. Results of the bactericidal activity of different compounds against six pathogenic fungi in culture dishes.
[0094]
[0095] As shown in Table 2, the benzotriazine oxadiazole derivatives of this invention exhibit high bioactivity against six agricultural pathogenic fungi. At a concentration of 50 mg / L, compounds 3, 8, 11, 14, 19, and 21 showed higher toxicity against *Rhizoctonia solani* than oxadiazole; compounds 17 and 21 showed higher toxicity against *Fusarium graminearum* than oxadiazole; compounds 4 and 5 showed higher toxicity against *Bacillus oryzae* than oxadiazole; compound 20 showed higher toxicity against *Sclerotinia sclerotiorum* than oxadiazole; compound 19 showed higher toxicity against *Bacillus thuringiensis* than oxadiazole; and except for compounds 7, 10, 13, and 17, all other compounds showed higher toxicity against *Anthracnose* than oxadiazole.
[0096] A pot experiment was conducted on the control of rice sheath blight using the highly active compound 21, and the results are shown in Table 3. The results showed that compound 21 exhibited good control efficacy against rice sheath blight at concentrations of 100 mg / L and 200 mg / L. In the treatment experiment, the control efficacy of compound 21 at 100 mg / L was not significantly different from that of the control agent carbendazim at the same concentration.
[0097] Table 3 shows the control efficacy of compound 21 against rice sheath blight in potted plants.
[0098]
[0099] Nematicidal activity tests were conducted on compounds 1-21. The nematicidal activity of the compounds in this invention was determined using a direct contact method. Pine wood nematode and Caenorhabditis elegans were selected as test nematodes. The initial concentration of the agent was set at 100 mg / L. The test compounds were dissolved in 1 mL of DMF (DMF concentration was 4% of the initial solution), and then diluted to 20 mL with 0.1% Tween 80 aqueous solution. The cultured nematodes were eluted with sterile water, and the eluent was centrifuged and concentrated to prepare a nematode suspension (concentration of 100 nematodes / 100 μL). 100 μL of the nematode suspension was pipetted into a 96-well biochemical culture plate, and then 80 μL of sterile water and 20 μL of the test agent solution were added. After the addition was complete, the biochemical culture plate was placed in a 20°C incubator. After 48 hours, the total number of nematodes and the number of dead nematodes in each treatment group were observed under a stereomicroscope. Each treatment group was tested three times. The nematode mortality standard is defined as the nematode's body becoming rigid and not moving when stimulated with a fine needle; in this case, the nematode is considered dead. The nematode-killing activity of the compounds of this invention against nematodes was calculated, and the results are shown in Tables 4 and 5.
[0100] Table 4. Results of experiments on Caenorhabditis elegans with the compounds.
[0101]
[0102] Table 5 Results of tests on compounds against pine wood nematode.
[0103]
[0104]
[0105] The results in Tables 4 and 5 show that the benzotriazine oxadiazole derivatives of the present invention exhibit high biological activity against two types of nematodes. At a concentration of 100 mg / L, compounds 3, 5, 9, and 10 showed better lethality against *C. elegans* than thiazophos; compounds 3 and 11 also showed higher lethality against *Pinus fibrosum* than the control agent thiazophos, with compound 3 showing a lethality close to that of the control agent fluopyram.
[0106] This invention uses benzotriazinone as the parent compound and splices it with 1,3,4-oxadiazole to synthesize a series of benzotriazinone oxadiazole derivatives. These benzotriazinone oxadiazole derivatives exhibit good killing effects against wheat scab, rice sheath blight, rice blast, Bletilla striata, tea anthracnose, rapeseed sclerotinia stem rot, as well as Echinochloa elegans and pine wilt nematodes, and have high commercial application prospects.
[0107] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A benzotriazinone oxadiazole derivative, characterized in that, The structural formula of the benzotriazinone oxadiazole derivative is: or Formula 1 Formula 2 The structural formula of Equation 1 is as follows: 、 、 Compound 1 Compound 2 、 、 Compound 3 Compound 4 、 、 Compound 5 Compound 6 、 、 Compound 7 Compound 8 、 、 Compound 9 Compound 10 、 、 Compound 11 Compound 12 、 、 Compound 14 Compound 15 , or Compound 16 Compound 17 ； Compound 18 The structural formula of Equation 2 is as follows: , or Compound 19 Compound 20 Compound 21.
2. The method for preparing the benzotriazinone oxadiazole derivative according to claim 1, characterized in that, The preparation method of benzotriazinone oxadiazole derivatives includes the following steps: 1) The R1-substituted o-aminobenzamide was reacted with hydrochloric acid and sodium nitrite solution to obtain compound A; The structural formula of R1-substituted o-aminobenzamide is: ; The structural formula of compound A is: ; 2) Compound A, cesium carbonate, potassium iodide, acetonitrile, and ethyl bromoacetate were refluxed to give compound B; The structural formula of compound B is: ; 3) Compound B, methanol, and hydrazine hydrate solution were mixed and refluxed to obtain compound C; The structural formula of compound C is: ; 4) Compound C, methanol and carbon disulfide are mixed and reacted. The resulting reaction product, bromoethane, potassium carbonate and acetonitrile are refluxed to obtain Formula 1. 5) React Formula 1, anhydrous ethanol, hydrogen peroxide solution and ammonium molybdate to obtain Formula 2; The definitions of R1 and R2 are as described in claim 1.
3. The preparation method according to claim 2, characterized in that, In step 1), the molar ratio of R1-substituted o-aminobenzamide to sodium nitrite is 0.7~0.8:1.3~1.6; the molar volume ratio of sodium nitrite to hydrochloric acid is 1.3~1.6 mmol:1.8~2.2 mL; and the concentration of hydrochloric acid is 1.5~2.5 mol / L. The reaction temperature is -2~2℃, and the reaction time is 0.5~1.5h.
4. The preparation method according to claim 2 or 3, characterized in that, Step 2) The molar ratio of compound A, cesium carbonate, potassium iodide and ethyl bromoacetate is 1~3:3~5:1:3~5; the molar volume ratio of potassium iodide and acetonitrile is 1 mmol: 25~35 mL; The reflux reaction temperature is 80~88℃, and the reflux reaction time is 4~6h.
5. The preparation method according to claim 4, characterized in that, In step 3), the molar ratio of compound B to hydrazine hydrate is 40-45:195-210; the molar volume ratio of compound B to methanol is 40-45 mmol:180-220 mL; and the mass concentration of the hydrazine hydrate solution is 77-83%. The mixing time is 25-35 minutes, the reflux reaction temperature is 60-70°C, and the reflux reaction time is 4-6 hours.
6. The preparation method according to claim 5, characterized in that, Step 4) The molar volume ratio of compound C, methanol, and carbon disulfide is 1 mmol: 50~55 mL: 4.5~5.5 mmol; the reaction temperature is 60~70℃, and the reaction time is 5~7 h; The molar ratio of the reaction product, bromoethane, and potassium carbonate is 1:1.2~1.8:1.5~2.5; the molar volume ratio of bromoethane and acetonitrile is 1.2~1.8 mmol:45~55 mL; the reflux reaction temperature is 80~90℃, and the reflux reaction time is 7~9 h.
7. The preparation method according to claim 6, characterized in that, In step 5), the molar ratio of Formula 1, hydrogen peroxide and ammonium molybdate is 1:7~9:0.15~0.25; the mass concentration of hydrogen peroxide solution is 25~35%; and the molar volume ratio of Formula 1 and anhydrous ethanol is 1mmol:8~12mL.
8. The use of the benzotriazinone oxadiazole derivative according to claim 1 in fungicides and nematicides, characterized in that, The pathogenic fungi were selected from *Rhizoctonia solani*, *Fusarium graminearum*, *Bacillus thuringiensis*, *Pseudomonas aeruginosa*, *Sclerotinia sclerotiorum*, *Bletilla striata*, and *Anthracnose*; the nematodes were selected from *C. elegans* and *Pinus wiltii*. In claim 1, compounds 1, 3-5, 7-11, 14-15, and 17-21 are used to control rice sheath blight pathogens; In claim 1, compounds 17 and 19-21 are used to prevent and control wheat scab. In claim 1, compounds 4-5, 10, and 19 are used to control rice blast fungus. In claim 1, compounds 1, 3, 6-8, 14, and 19-21 are used to control Sclerotinia sclerotinia rot in rapeseed. In claim 1, compounds 1-2, 4-5, 7-12, 14-15, 18-19, and 21 are used to prevent and control the pathogen of Bletilla striata. In claim 1, compounds 2, 5-6, 8-9, 11-12, 15-16, and 20-21 are used to prevent and control anthracnose in tea leaves; In claim 1, compounds 1, 3, 5, 9-11, and 14 are used to control *C. elegans*. In claim 1, compounds 3 and 11 are used to control pine wilt disease.