Substituted benzoxazinone-isoxazoline compound as well as preparation method and application thereof

Abstract

The invention discloses a substituted benzoxazinone-isoxazoline compound as well as a preparation method and application of the substituted benzoxazinone-isoxazoline compound. The preparation method comprises the following steps: by taking DMF (Dimethyl Formamide) as a solvent, reacting ethyl bromoacetate with a compound (II) to generate a compound (III), performing cyclization in the presence of acetic acid and reduced iron powder to obtain a compound (IV), reacting the compound (IV) with hydroxylamine hydrochloride to generate a compound (V), reacting the compound (V) with NCS and MMA (Methyl Methacrylate) in the presence of TEA (Tetraethyl Ammonium) to generate a compound (VI), and reacting the compound (VI) with NCS and MMA to generate a compound (V). Reacting the compound (VI) with propargyl bromide to obtain a substituted benzoxazinone-isoxazoline compound, performing alkaline hydrolysis on the substituted benzoxazinone-isoxazoline compound, and performing condensation reaction on the substituted benzoxazinone-isoxazoline compound and alcohol or amine to obtain a target product. According to the present invention, the weeding activity test results of the obtained product show that the inhibition effects of the compounds I1, I2, I4, I15 and I16 on the rape are good under the concentration of 100 ppm, the excellent weeding activity is provided, and the good prevention and control effect on the invasive organism zinnia elegans is provided.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical synthesis technology, specifically relating to substituted benzoxazinone-isoxazolinone compounds, their preparation methods, and applications. Background Technology

[0002] Heterocyclic compounds are widely distributed in nature and constitute the largest class of organic compounds. The most common heteroatoms in heterocyclic structures are nitrogen, sulfur, and oxygen atoms. Due to their broad biological activity and ease of structural modification, they often endow molecules with new biological functions. In particular, novel nitrogen- and oxygen-containing heterocyclic compounds (such as benzoxazinone and isoxazoline) have become a hot topic in the development of new pesticides. Developing novel heterocyclic compounds based on active natural products or known active skeletons to achieve highly efficient and broad-spectrum biological activity has become one of the most active directions in the field of pesticide chemistry in recent years.

[0003] Benzooxazinones, as an important class of nitrogen-oxygen-containing bicyclic heterocyclic skeletons, are the core structural unit of many protoporphyrinogen oxidase (PPO) inhibitor herbicides, exhibiting excellent herbicidal activity. Isoxazolines, as another five-membered heterocycle containing N and O atoms, possess unique electronic properties and broad biological activity, exhibit low toxicity to humans, and are easily modified in structure, often being introduced as pharmacophores into drug molecules. Given the multiple advantages of PPO inhibitors compared to other types of herbicides, including good selectivity, low dosage, environmental friendliness, broad herbicidal spectrum, and low likelihood of weed resistance, the development of novel PPO inhibitors is of great significance. Existing research indicates that introducing highly bioactive isoxazoline fragments into the benzooxazinone skeleton through molecular hybridization strategies holds promise for producing synergistic effects and addressing the resistance problem faced by existing herbicides. This invention is based on this design concept, using the classic benzoxazinone structure as the lead skeleton. Utilizing the principle of isosterism and substructure splicing methods, while retaining key active sites such as the N-substituted propargyl side chain, it innovatively introduces an isoxazoline active fragment, designing and synthesizing a series of novel isoxazoline-containing benzoxazinone compounds. This invention aims to obtain novel herbicides with higher herbicidal activity and greater crop safety through this structural optimization. Summary of the Invention

[0004] In view of the problems existing in the prior art, the purpose of this invention is to provide substituted benzoxazinone-isoxazoline compounds, their preparation methods, and applications.

[0005] To achieve the above objectives, the technical solution of the present invention is as follows: The present invention defines substituted benzoxazinone-isoxazolinone compounds, the structural formula of which is shown in formula (I):

[0006]

[0007] In formula (I), substituent R1 is hydrogen or chlorine; substituent R2 is alkyl or cycloalkyl; and substituent R3 is alkyl or alkoxy.

[0008] Furthermore, the present invention specifies that substituent R2 is methyl, ethyl, isopropyl, n-butyl, cyclopentyl, or cyclohexyl; and substituent R3 is methoxy, ethoxy, cyclopropyl, or isopropyl.

[0009] Furthermore, the present invention specifies a method for preparing the substituted benzoxazinone-isoxazolinone compound, which specifically includes the following steps:

[0010] 1) Using DMF as a solvent, ethyl bromoacetate was heated to react with the compound shown in formula (II) to produce the compound shown in formula (III);

[0011] 2) Using acetic acid as a solvent, the compound obtained in step 1) as shown in formula (Ⅲ) is heated and reacted with reduced iron powder. First, the nitro group is reduced to amino group, and then intramolecular cyclization occurs under the catalysis of acetic acid to generate the compound shown in formula (Ⅳ).

[0012] 3) Using anhydrous ethanol as solvent and TEA as acid-binding agent, the compound obtained in step 2) as shown in formula (Ⅳ) was heated to reflux to generate the compound shown in formula (Ⅴ).

[0013] 4) Using DMF as solvent and TEA as acid-binding agent, the compound obtained in step 3) as shown in formula (V) is reacted with NCS and MMA to generate the compound shown in formula (VI). In this step, the H on the benzene ring is not replaced by R1, and the product obtained is the main product. The H on the benzene ring is replaced by R1, that is, the chlorinated product is the by-product. The by-product is partially electrophilic aromatic chlorinated by the chlorinating agent NCS on the highly reactive electron-rich benzene ring.

[0014] 5) Using DMF as solvent and K2CO3 as acid-binding agent, the compound obtained in step 4) as shown in formula (VI) is reacted with bromopropyne to obtain the substituted benzoxazinone-isoxazolinone compound as shown in formula (VII).

[0015] 6) Using anhydrous solvent, react the compound of formula (VII) obtained in step 5) with sodium hydroxide to obtain the alkaline hydrolysis product of the substituted benzoxazinone-isoxazolinone compound of formula (VII);

[0016] 7) Using DCM as solvent and EDCl and DMAP as condensing agents, the alkaline hydrolysis product of the substituted benzoxazinone-isoxazoline compound obtained in step 6) as shown in formula (Ⅶ) is condensed with R2OH or R3NH2 to obtain the substituted benzoxazinone-isoxazoline compound as shown in (I).

[0017] The reaction process is as follows:

[0018]

[0019] Where R1 is hydrogen or chlorine; R2 is alkyl or cycloalkyl; and R3 is alkyl or alkoxy.

[0020] Furthermore, the present invention also specifies that the molar ratio of the compound represented by formula (II) in step 1) to ethyl bromoacetate is 1:1.5-2.

[0021] Furthermore, the present invention also specifies that the molar ratio of the compound shown in formula (Ⅲ) in step 2) to the reduced iron powder is 1:4-6.

[0022] Furthermore, the present invention also specifies that the molar ratio of the compound shown in formula (Ⅳ) in step 3) to hydroxylamine hydrochloride is 1:1.5-3.

[0023] Furthermore, the present invention also specifies that the molar ratio of the compound represented by formula (V) in step 4) to NCS, TEA and MMA is 1:1.2-2.5:1.2-2.5:1.2-2.5.

[0024] Furthermore, the present invention also specifies that the molar ratio of the compound represented by formula (VI) in step 5) to bromopropyne is 1:1.2-3.

[0025] Furthermore, the present invention also specifies that the molar ratio of the compound represented by formula (Ⅶ) in step 7), EDCl, DMAP and R2OH or R3NH2 is 1:1.2-2.5:0.1-0.2:2-2.5.

[0026] Furthermore, the present invention also defines the use of the substituted benzoxazinone-isoxazolinone compounds as herbicides.

[0027] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0028] 1) This invention first uses ethyl bromoacetate to react with a specific intermediate using DMF solvent. During the reaction, reducing iron powder, hydroxylamine hydrochloride, bromopropyne, NCS and MMA are used sequentially to synthesize a series of substituted benzoxazinone-isoxazoline compounds. The resulting compounds were tested for herbicidal activity, and the results showed that at a concentration of 100 ppm, they had a significant inhibitory effect on monocotyledonous wheat and dicotyledonous rapeseed.

[0029] 2) The preparation method of this invention is simple and convenient to operate. The structure of the obtained product was confirmed by NMR, and the herbicidal activity of the 16 target products was tested. Among the target compounds VII of series I, compounds I1, I2, I15, and I16 showed good inhibitory effects on rapeseed. Compound I4 showed a 100% inhibition rate against rapeseed stems and radicles at a concentration of 100 ppm. Compound I15 showed inhibition rates of 92.3% and 94.3% against rapeseed stems and radicles at 100 ppm, respectively. Compounds I1 and I6 showed inhibition rates of over 70% against rapeseed stems and roots at 100 ppm. Compound I2 showed good inhibitory activity against rapeseed seeds at both concentrations. In addition, at a concentration of 10 ppm, compound I2 showed an inhibition rate of 90% against wheat plant height and wheat roots, and compound VII16 showed an inhibition rate of 90% against wheat roots at a concentration of 100 ppm, while also showing good control effects against the invasive species zinnia. Detailed Implementation

[0030] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0031] Example 1: Preparation of the compound as shown in formula (III)

[0032] In a 250 mL round-bottom flask, the compound shown in formula (II) (10.00 g, 59.84 mmol) and anhydrous potassium carbonate (16.54 g, 119.67 mmol) were dissolved in 100 mL of DMF and stirred at room temperature for 15 min. Then, ethyl bromoacetate (15.0 g, 89.76 mmol) was slowly added dropwise at room temperature. The mixture was heated to 80 °C and stirred. The reaction was monitored by TLC (VL). EA :V PE =1:3) Monitor the reaction progress, stop the reaction after 6 hours, wait for the reaction to cool to room temperature, pour the reaction solution into 1000 mL of ice water to precipitate a white solid, filter, wash with water, and dry to obtain the compound shown in formula (III). Yield 91.6%. No purification is required, keep for later use. 1 H NMR(400Hz,DMSO-d6)δ9.71(s,1H,CHO),8.20(s,1H,Ph),7.92(d,J=6.7Hz,1H,Ph),7.26(d ,J=8.8Hz,1H,Ph),4.92(s,2H,CH2),3.94(q,J=7.1Hz,2H,CH2),0.97(t,J=7.1Hz,3H,CH3).

[0033] Example 1-1 Preparation of the compound as shown in formula (III)

[0034] In a 250 mL round-bottom flask, the compound shown in formula (II) (10.00 g, 59.84 mmol) and anhydrous potassium carbonate (16.54 g, 119.67 mmol) were dissolved in 100 mL of DMF and stirred at room temperature for 15 min. Then, ethyl bromoacetate (20.0 g, 119.68 mmol) was slowly added dropwise at room temperature. The mixture was heated to 85 °C and stirred. The reaction was monitored by TLC (VL). EA :V PE =1:3) Monitor the reaction progress, stop the reaction after 5.5 h, wait for the reaction to cool to room temperature, pour the reaction solution into 1000 mL of ice water to precipitate a white solid, filter, wash with water, and dry to obtain the compound shown in formula (Ⅲ), with a yield of 88.2%.

[0035] Example 2: Preparation of the compound as shown in formula (Ⅳ)

[0036] The compound (8.87 g, 39.91 mmol) of formula (III) prepared in Example 1 was added to a 250 mL round-bottom flask. The raw material was dissolved in acetic acid (90 mL) as a solvent. The temperature was raised to 80 °C and stirring was started. During stirring, iron powder (8.94 g, 159.65 mmol) was added in three batches. TLC (V EA :V PE =1:1) Monitor the reaction progress. After 3 hours, the reaction ends. Wait for the reaction to cool to room temperature. After multiple filtrations to remove iron powder, take the filtrate, add ice water to precipitate a yellow solid, filter, wash with water, and dry to obtain the crude product as shown in formula (Ⅳ), with a yield of 62.7%. No purification is required, and it can be used for later use. 1 H NMR (400MHz, DMSO-d6) δ10.99(s,1H,NH),9.84(s,1H,CHO),7.52(s,1H,Ph),7.44–7.34(m,1H,Ph),7.15(s,1H,Ph),4.71(s,2H,CH2).

[0037] Example 2-1 Preparation of the compound as shown in formula (Ⅳ)

[0038] The compound (8.87 g, 39.91 mmol) of formula (III) prepared in Example 1 was added to a 250 mL round-bottom flask. The raw material was dissolved in acetic acid (90 mL) as a solvent. The temperature was raised to 85 °C and stirring was started. During stirring, iron powder (13.41 g, 239.48 mmol) was added in three batches. TLC (V EA :V PE =1:1) Monitor the reaction progress. After 2.5 hours, the reaction ends. Wait for the reaction to cool to room temperature. After multiple filtrations to remove iron powder, take the filtrate and add ice water to precipitate a yellow solid. Filter, wash with water, and dry to obtain the crude product as shown in formula (Ⅳ), with a yield of 56.4%.

[0039] Example 3: Preparation of the compound as shown in formula (V)

[0040] In a 250 mL round-bottom flask, add the compound (3.00 g, 16.93 mmol) of formula (IV) prepared in Example 2, hydroxylamine hydrochloride (1.77 g, 25.40 mmol), and TEA (2.57 g, 25.40 mmol), dissolve in anhydrous ethanol (30 mL), and heat to reflux. TLC (VL) was then performed. MeOH :V DCM =1:30) Monitor the reaction progress. After 2 hours, the reaction ends. Wait for the reaction to cool to room temperature, pour the reaction solution into 600 mL of ice water to precipitate the solid, filter, wash with water, and dry to obtain the compound shown in formula (V), a white solid with a yield of 88.4%. No purification is required; keep it for later use. 1 H NMR(400MHz,DMSO-d6)δ10.88(s,1H,NH),10.53(s,1H,CHO),7.74(s,1H,OH),6.91 (s,1H,Ph),6.81(d,J=8.3Hz,1H,Ph),6.67(d,J=8.2Hz,1H,Ph),4.30(s,2H,CH2).

[0041] Example 3-1 Preparation of the compound as shown in formula (V)

[0042] In a 250 mL round-bottom flask, add the compound (3.00 g, 16.93 mmol) of formula (IV) prepared in Example 2, hydroxylamine hydrochloride (3.54 g, 50.80 mmol), and TEA (2.57 g, 25.40 mmol), dissolve in anhydrous ethanol (30 mL), and heat to reflux. TLC (VL) was then performed. MeOH :V DCM =1:30) Monitor the reaction progress. After 1.5 hours, the reaction ends. Wait for the reaction to cool to room temperature, pour the reaction solution into 600 mL of ice water to precipitate the solid, filter, wash with water, and dry to obtain the compound shown in formula (V), a white solid with a yield of 84.2%.

[0043] Example 4: Preparation of the compound as shown in formula (VI)

[0044] In a 250 mL round-bottom flask, add the compound (8.89 g, 25.64 mmol) prepared in Example 3 as shown in formula (V), NCS (4.11 g, 30.78 mmol), and DMF (100 mL). Stir the reaction mixture at room temperature and monitor the reaction by TLC (VL). EA :V PE=1:5) Monitor the reaction progress. After 1 hour of reaction, dissolve MMA (3.08 g, 30.77 mmol) and TEA (3.08 g, 30.77 mmol) in DMF (60 mL) and slowly add it dropwise to the reaction solution using a dropping funnel. Continue stirring the reaction at room temperature. TLC (V EA :V PE =1:3) Monitor the reaction progress. After 3 hours, the reaction is complete. Pour the reaction solution into 1600 mL of water, extract with EA, wash with saturated NaCl solution, dry with anhydrous Na2SO4, remove EA by rotary evaporation, and then perform column chromatography (V EA :V PE The mixture was purified at a ratio of 1:4 to give a white solid as shown in formula (VI), with a yield of 52.4%. No further purification is required; it can be kept for later use.

[0045] Example 4-1 Preparation of compounds as shown in formula (VI)

[0046] In a 250 mL round-bottom flask, add the compound (8.89 g, 25.64 mmol) prepared in Example 3 as shown in formula (V), NCS (8.56 g, 64.10 mmol), and DMF (100 mL). Stir the reaction mixture at room temperature and monitor the reaction by TLC (VL). EA :V PE =1:5) Monitor the reaction progress. After 1 hour of reaction, dissolve MMA (6.42 g, 64.10 mmol) and TEA (6.42 g, 64.10 mmol) in DMF (60 mL) and slowly add it dropwise to the reaction solution using a dropping funnel. Continue stirring the reaction at room temperature. TLC (V EA :V PE =1:3) Monitor the reaction progress. After 3 hours, the reaction is complete. Pour the reaction solution into 1600 mL of water, extract with EA, wash with saturated NaCl solution, dry with anhydrous Na2SO4, remove EA by rotary evaporation, and then perform column chromatography (V EA :V PE The mixture was purified at a ratio of 1:4 to give the compound shown in formula (VI), a white solid, in 49.2% yield.

[0047] Example 5: Preparation of the compound as shown in formula (VII)

[0048] In a 100 mL round-bottom flask, the compound prepared according to formula (VI) of Example 4 (2.00 g, 6.89 mmol), anhydrous potassium carbonate (1.90 g, 13.78 mmol), and DMF (20 mL) were added as solvent. After stirring at room temperature for 15 min, bromopropyne (0.98 g, 8.27 mmol) was added dropwise. The reaction was stirred at room temperature, and TLC (V1) was performed. EA :V PE=1:3) Monitor the reaction progress. After 6 hours, the reaction ends. Pour the reaction solution into ice water to precipitate a white solid. Filter, wash with water, and dry to obtain the compound shown in formula (VII), a gray solid, with a yield of 42.8%. No purification is required; keep for later use. 1 H NMR (400MHz, CDCl3) δ7.57(d,J=1.9Hz,1H,Ph),7.18(dd,J=8.3,1.9Hz,1H,Ph),6.98(d,J=8.3Hz,1H,Ph),4.67(d,J=2.5Hz,2H,CH2),4. 63(s,2H,CH2),3.84(d,J=16.9Hz,1H,CH2),3.77(s,3H,OCH3),3.19(d,J=16.9Hz,1H,CH2),2.27(t,J=2.5Hz,1H,CH),1.69(s,3H,CH3).

[0049] Example 5-1 Preparation of compounds as shown in formula (VII)

[0050] In a 100 mL round-bottom flask, the compound prepared according to formula (VI) of Example 4 (2.00 g, 6.89 mmol), anhydrous potassium carbonate (1.90 g, 13.78 mmol), and DMF (20 mL) were added as solvent. After stirring at room temperature for 15 min, bromopropyne (2.45 g, 20.67 mmol) was added dropwise. The reaction was stirred at room temperature, and the volume was measured by TLC (V1). EA :V PE =1:3) Monitor the reaction progress. After 6 hours, the reaction ends. Pour the reaction solution into ice water to precipitate a white solid. Filter, wash with water, and dry to obtain the compound shown in formula (VII), a gray solid, with a yield of 40.5%.

[0051] Example 6 Preparation of the compound as shown in formula (I)

[0052] Taking the synthesis of target product I2 as an example, the compound (1.00 g, 3.05 mmol) prepared in Example 5 as shown in formula (VII), anhydrous ethanol (4 mL), and prepared sodium hydroxide solution (2 M) were added sequentially to a 100 mL round-bottom flask. 10 mL of water was added, and the reaction was stirred at room temperature. TLC (V EA :V PE=1:2) Monitor the reaction progress. After the reaction is complete, adjust the pH to 1-2 with prepared dilute hydrochloric acid (1M), precipitate the solid, filter, wash with water, and dry to obtain the hydrolysis product, a gray solid. Weigh the gray solid (0.20 g, 0.64 mmol) into a 50 mL round-bottom flask, add EDCI (0.15 g, 0.76 mmol), DMAP (0.008 g, 0.06 mmol), and anhydrous ethanol (0.06 g, 1.59 mmol) in sequence, and dissolve the raw material with DCM (4 mL) as solvent. Stir overnight at room temperature. After the reaction is complete, remove DCM and excess anhydrous ethanol by rotary evaporation, extract with EA with water, wash with saturated NaCl solution, dry with anhydrous Na2SO4, remove EA by rotary evaporation, and perform column chromatography (V EA :V PE The target compound I2 was isolated by a ratio of 1:3, with a yield of 84.3%. The remaining target compounds I1 and I3 to I16 were synthesized by the same method. The physicochemical data of the obtained compounds I1 to I16 are shown in Table 1, and the proton NMR data are shown in Table 2.

[0053] Example 6-1 Preparation of compounds as shown in formula (I)

[0054] Taking the synthesis of target product I2 as an example, the compound (1.00 g, 3.05 mmol) prepared in Example 5 as shown in formula (VII), anhydrous ethanol (4 mL), and prepared sodium hydroxide solution (2 M) were added sequentially to a 100 mL round-bottom flask. 10 mL of water was added, and the reaction was stirred at room temperature. TLC (V EA :V PE =1:2) Monitor the reaction progress. After the reaction is complete, adjust the pH to 1-2 with prepared dilute hydrochloric acid (1M), precipitate the solid, filter, wash with water, and dry to obtain the hydrolysis product, a gray solid. Weigh the gray solid (0.20 g, 0.64 mmol) into a 50 mL round-bottom flask, add EDCI (0.31 g, 7.63 mmol), DMAP (0.016 g, 0.12 mmol), and anhydrous ethanol (0.075 g, 1.99 mmol) in sequence, and dissolve the raw material with DCM (4 mL) as solvent. Stir overnight at room temperature. After the reaction is complete, remove DCM and excess anhydrous ethanol by rotary evaporation, extract with EA with water, wash with saturated NaCl solution, dry with anhydrous Na2SO4, remove EA by rotary evaporation, and perform column chromatography (V EA :V PE The target compound I2 was isolated by a ratio of 1:3, with a yield of 79.4%.

[0055] Table 1 shows the physicochemical data of the compounds represented by formula (I).

[0056] target compound <![CDATA[R1 group]]> <![CDATA[Group R2]]> R3 group Appearance Melting point / °C Yield % I1 hydrogen methyl \ White solid 117-119 42.8 I2 hydrogen Ethyl \ White solid 118-120 84.3 I3 hydrogen n-Butyl \ Yellow liquid \ 87.1 I4 hydrogen Isopropyl \ Yellow solid 105-107 86.3 I5 hydrogen \ Cyclopropyl White solid 175-177 78.2 I6 hydrogen \ Isopropyl White solid \ 80.5 I7 chlorine methyl \ White solid 143-145 87.2 I8 chlorine Ethyl \ White solid 102-104 93.4 I9 chlorine Isopropyl \ White solid 101-103 89.3 I10 chlorine n-Butyl \ Yellow solid 83-85 92.5 I11 chlorine Cyclopentyl \ White solid 123-125 71.8 I12 chlorine Cyclohexyl \ White solid 113-115 80.2 I13 chlorine \ Cyclopropyl White solid 157-159 93.7 I14 chlorine \ Isopropyl White solid 169-171 91.4 I15 chlorine \ methoxy White solid 160-162 62.1 I16 chlorine \ ethoxy Yellow solid 122-124 62.7

[0057] Table 2(I) shows the proton NMR data of the compounds.

[0058]

[0059]

[0060]

[0061]

[0062] Example 7: Test Method for Herbicidal Activity

[0063] (1) Experimental subjects: seeds of dicotyledonous plant rapeseed (Brassica napus) and monocotyledonous plant wheat (Triticumaestivum).

[0064] (2) Experimental treatment: Seed pretreatment should be completed before conducting the herbicidal activity test to improve the seed germination rate and thus ensure the accuracy of the test. First, the seeds to be tested were disinfected by soaking them in a sodium hypochlorite solution of about 3% for 10 minutes. Then, they were rinsed repeatedly with deionized water from the Millipore ultrapure water system to remove the residual sodium hypochlorite solution. The seeds were then soaked in deionized water for 6 hours to allow them to absorb water and swell. After that, the seeds were removed and dried, and then placed in a constant temperature incubator at 25°C to germinate. The seeds were removed when they were just beginning to sprout.

[0065] (3) Solution preparation: Weigh 3 mg of the compound sample into a 5 mL EP tube, add 3 mL of acetone to the tube using a pipette, and shake well to completely dissolve the compound, preparing a 1 mg / L stock solution for later use. Take 1 mL of the stock solution into a 10 mL EP tube and dilute with 9 mL of deionized water to obtain a 100 ppm test solution. Take 0.1 mL of the stock solution into a 10 mL EP tube and dilute with 9.9 mL of deionized water to obtain a 10 ppm test solution.

[0066] (4) Test methods:

[0067] Wheat herbicidal activity test: Acetone was used as the solvent in the experiment. All biological tests were performed in duplicate in petri dishes. Contamination from the external environment should be avoided during the experiment. Filter paper with a diameter of 7.5 cm was laid flat in the petri dish, and 10 mL of a specific concentration of the compound sample solution was added. Ten or more wheat seeds were selected and cultured in a natural environment. After one week, the height of the wheat seedlings was measured and the growth of the wheat roots was visually observed. The herbicidal activity of the target compound was detected by inhibiting the growth of wheat plant height and seedling roots. The activity indicators were: stem growth inhibition rate (%) and radicle growth inhibition rate (%).

[0068] Rapeseed herbicidal activity test: Acetone was used as the solvent in the experiment. All biological tests were performed in duplicate in petri dishes. Contamination from the external environment should be avoided during the experiment. Filter paper with a diameter of 7.5 cm was laid flat in the petri dish, and 10 mL of a specific concentration of compound sample solution was added. Ten or more rapeseed seeds were selected and cultured in a natural environment. After one week, the length of rapeseed stems and radicles was measured. The herbicidal activity of the target compound was detected by inhibiting the growth of wheat seedling stems and roots. The activity indicators were: stem growth inhibition rate (%) and radicle growth inhibition rate (%).

[0069] Inhibition rate calculation:

[0070]

[0071] The herbicidal activity (inhibition rate %) of target compound I at 100 ppm and 10 ppm is shown in Table 3:

[0072] Table 3. Herbicidal activity of target compounds I1-I16 at 100 ppm and 10 ppm.

[0073]

[0074] The herbicidal activity results of the 16 substituted benzoxazinone-isoxazoline compounds in Table 3 show that compound I4 exhibited 100% inhibition rates against the stems and roots of rapeseed and wheat at a concentration of 100 ppm. Compound I15 showed inhibition rates of 92.3% and 94.3% against rapeseed stems and roots, respectively, at 100 ppm. Compounds I1 and I16 both showed inhibition rates exceeding 70% against rapeseed stems and roots at 100 ppm. Compound I2 demonstrated good inhibitory activity against rapeseed seeds at both concentrations; compound I16 showed a 90% inhibition rate against wheat roots at 100 ppm. Furthermore, at a concentration of 10 ppm, compound I2 showed inhibition rates of 94.2% and 80% against wheat stems and roots, respectively, but its inhibitory effect at 100 ppm was less pronounced than at lower concentrations, requiring further experimental replication for verification. At a concentration of 100 ppm, compound I1 showed inhibition rates of 62.3% and 70% on wheat stems and roots, respectively. These results indicate that the compound of the present invention has different herbicidal effects on both dicotyledonous and monocotyledonous plants.

[0075] Example 8: Test Method for Invasive Species Zinnia

[0076] Preparation of test herbicide solution: Accurately weigh 1 mg of the test compound I1, I2, and I3 powder into 5 mL EP tubes, add 1 mL of DMSO, shake thoroughly to dissolve, and prepare a 1 mg / mL stock solution for later use. Dilute the stock solution to obtain a 20 ppm working solution, which is used as the test compound solution.

[0077] Seed pretreatment: Select seeds that are uniform in size, free from disease and pests, and plump. Before conducting the activity test, soak the seeds in a 5% sodium hypochlorite solution for 10 minutes, then rinse them repeatedly with sterile deionized water 3-5 times to thoroughly remove any residual disinfectant. Finally, place the seeds in a clean bench to air dry for later use.

[0078] Application of reagents: The experiment used a three-layer filter paper method: the bottom layer was a filter paper disc sterilized at 121℃ for 15 minutes, on which 40 sterilized seeds were evenly placed. 5 mL of 20 ppm solution of test compounds I1, I2, and I3 was added, and then the top layer of filter paper was placed on top. Two treatment groups were set up (blank control: distilled water; experimental group: test compound solution). Each group was repeated three times and incubated in a 25℃ constant temperature incubator. On the third day, the filter paper was replaced, and 2 mL of distilled water was added to maintain humidity.

[0079] Data measurement: Germination rate was measured 3 days and 6 days after sowing and the average value was taken. The results are shown in Table 4.

[0080] Table 4. Germination rate of zinnia seeds at 20 ppm for target compounds I1-I3.

[0081]

[0082] As can be seen from Table 4, compounds I1, I2, and I3 of the present invention have a significant inhibitory effect on the invasive species Zinnia elegans.

Claims

1. A substituted benzoxazinone-isoxazolinone compound, characterized in that... Its structural formula is shown in equation (I): In formula (I), substituent R1 is hydrogen or chlorine; substituent R2 is alkyl or cycloalkyl; and substituent R3 is alkyl or alkoxy.

2. The substituted benzoxazinone-isoxazolinone compound according to claim 1, characterized in that... Substituent R2 is methyl, ethyl, isopropyl, n-butyl, cyclopentyl, or cyclohexyl; substituent R3 is methoxy, ethoxy, cyclopropyl, or isopropyl.

3. A method for preparing the substituted benzoxazinone-isoxazolinone compound as described in claim 1, characterized in that... Includes the following steps: 1) Using DMF as a solvent, ethyl bromoacetate was heated to react with the compound shown in formula (II) to produce the compound shown in formula (III); 2) Using acetic acid as a solvent, the compound obtained in step 1) as shown in formula (Ⅲ) is heated and reacted with reduced iron powder. First, the nitro group is reduced to amino group, and then intramolecular cyclization occurs under the catalysis of acetic acid to generate the compound shown in formula (Ⅳ). 3) Using anhydrous ethanol as solvent and TEA as acid-binding agent, the compound obtained in step 2) as shown in formula (Ⅳ) was reacted with hydroxylamine hydrochloride under reflux to generate the compound shown in formula (Ⅴ). 4) Using DMF as solvent and TEA as acid-binding agent, the compound obtained in step 3) as shown in formula (V) was reacted with NCS and MMA at room temperature to generate the compound shown in formula (VI); 5) Using DMF as solvent and K2CO3 as acid-binding agent, the compound obtained in step 4) as shown in formula (VI) was reacted with bromopropyne at room temperature to obtain the substituted benzoxazinone-isoxazolinone compound as shown in formula (VII); 6) Using anhydrous solvent, react the compound of formula (VII) obtained in step 5) with sodium hydroxide to obtain the alkaline hydrolysis product of the substituted benzoxazinone-isoxazolinone compound of formula (VII); 7) Using DCM as solvent and EDCl and DMAP as condensing agents, the alkaline hydrolysis product of the substituted benzoxazinone-isoxazoline compound obtained in step 6) as shown in formula (Ⅶ) is condensed with R2OH or R3NH2 to obtain the substituted benzoxazinone-isoxazoline compound as shown in (I). The reaction process is as follows: Where R1 is hydrogen or chlorine; R2 is alkyl or cycloalkyl; and R3 is alkyl or alkoxy.

4. The method for preparing substituted benzoxazinone-isoxazolinone compounds according to claim 3, characterized in that... In step 1), the molar ratio of the compound shown in formula (II) to ethyl bromoacetate is 1:1.5-2, the reaction temperature is 80℃-85℃, and the reaction time is 5.5-6.5h, preferably 6h.

5. The method for preparing substituted benzoxazinone-isoxazolinone compounds according to claim 3, characterized in that... In step 2), the molar ratio of the compound shown in formula (Ⅲ) to the reduced iron powder is 1:4-6, the reaction temperature is 80℃-85℃, and the reaction time is 2.5-3.5h, preferably 3h.

6. The method for preparing substituted benzoxazinone-isoxazolinone compounds according to claim 3, characterized in that... In step 3), the molar ratio of the compound shown in formula (Ⅳ) to hydroxylamine hydrochloride is 1:1.5-3.

7. The method for preparing substituted benzoxazinone-isoxazolinone compounds according to claim 3, characterized in that... The molar ratio of the compound shown in formula (V) in step 4) to NCS, TEA and MMA is 1:1.2-2.5:1.2-2.5:1.2-2.

5.

8. The method for preparing substituted benzoxazinone-isoxazolinone compounds according to claim 3, characterized in that... The molar ratio of the compound shown in formula (VI) in step 5) to bromopropyne is 1:1.2-3.

9. The method for preparing substituted benzoxazinone-isoxazolinone compounds according to claim 3, characterized in that... In step 7), the molar ratio of the compound shown in formula (Ⅶ), EDCl, DMAP and R2OH or R3NH2 is 1:1.2-2.5:0.1-0.2:2-2.

5.

10. The use of a substituted benzoxazinone-isoxazolinone compound according to claim 1 or 2 as a herbicide.

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