A benzoxazine-tioxazafen derivative and its preparation method and application

Abstract

The present invention provides a benzoxazine-tioxazafen derivative and its preparation method and application, belonging to the technical field of pesticide compound preparation. The benzoxazine-tioxazafen derivative described in the present invention is a derivative of 3-(5-(thiophene-2-yl)-1,2,4-oxadiazole-3-yl)-2H-benzo[b][1,4]oxazine. The present invention uses tioxazafen as the parent structure and splices active substructures with differently substituted benzoxazine derivatives to synthesize a series of new compounds with novel chemical structures. The compounds can be used to control plant parasitic nematodes such as root-knot nematodes and pine wood nematodes. Bioassay results show that the activity of the benzoxazine-tioxazafen derivative against pine wood nematodes is significantly better than that of the commercial agent tioxazafen and is comparable to that of thiazophos, indicating high commercialization prospects.

Description

Technical Field

[0001] The present invention relates to the technical field of pesticide compound preparation, and in particular to a benzoxazine-tioxazafen derivative and a preparation method and application thereof. Background Art

[0002] Plant parasitic nematodes have become a significant class of plant pathogens. According to conservative estimates by the Food and Agriculture Organization (FAO), annual global losses due to nematodes are approximately 12% for food and fiber crops, and exceed 20% or even 50% for vegetables, peanuts, tobacco, and some fruit trees. Pine wood nematodes, root-knot nematodes, and sweet potato stem nematodes are three important plant parasitic nematodes. Currently, chemical pesticides remain a key measure for nematode control. Nematode control has long been a challenge in agricultural production. However, with increasing awareness of environmental protection, highly toxic nematicides are no longer suitable for the demands of modern agricultural development. Long-term and repeated use of traditional nematicides has led to the development of nematode resistance, resulting in ineffective control. New nematicides are urgently needed. Therefore, the search for new nematicides with high efficacy, broad spectrum, novel mechanisms of action, and safety against non-target organisms is a pressing issue in plant protection.

[0003] Heterocyclic compounds have always played a crucial role in the development and research of pesticides and are widely used in the research and development of new pesticides. Tioxazafen is a novel, broad-spectrum, systemic seed treatment nematicide developed by Monsanto, primarily for soybeans, corn, and cotton. With its novel mechanism of action and long-lasting effect, it is a promising 1,2,4-oxadiazole nematicide. Currently, relatively little research has been conducted on the nematicidal properties of 1,2,4-oxadiazole compounds. Their structures are highly similar to tioxazafen, resulting in a relatively simple molecular structure and a lack of necessary flexibility. Furthermore, only monocyclic oxadiazole compounds have been reported for agricultural use, and no compounds with high activity have been found. Summary of the Invention

[0004] The present invention aims to provide a benzoxazine-tioxazafen derivative and its preparation method and application, so as to solve the technical problems that existing nematicides are highly toxic and new nematicides have a single structure and lack the necessary flexibility.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The present invention provides a benzoxazine-tioxazafen derivative having the following structural formula:

[0007]

[0008] Wherein, R1 is H, F, Cl, Br, CH3 or C4H9; R2 is H or Cl.

[0009] Furthermore, the benzoxazine-tioxazafen derivative is selected from one of the following structural formulas:

[0010]

[0011] The present invention also provides a method for preparing a benzoxazine-tioxazafen derivative, comprising the following steps:

[0012] 1) mixing p-cyanoacetophenone, N-bromosuccinimide and p-toluenesulfonic acid hydrate in a solvent to carry out a substitution reaction to obtain 2-bromo-4'-cyanoacetophenone;

[0013] 2) mixing 2-bromo-4'-cyanoacetophenone and an o-aminophenol substituted compound in a solvent for reaction to obtain a benzonitrile-4-(2H-1,4-benzoxazin-3-yl) substituted compound;

[0014] 3) dissolving the benzonitrile-4-(2H-1,4-benzoxazin-3-yl) substituted compound in a solvent, and then adding hydroxylamine hydrochloride to react to obtain a 4-(2H-benzo[b][1,4]oxazin-3-yl)-N-hydroxybenzimidamide substituted compound;

[0015] 4) dissolving the 4-(2H-benzo[b][1,4]oxazin-3-yl)-N-hydroxybenzimidamide substituted compound in a solvent, and then adding 2-thiophenecarbonyl chloride to react to obtain a benzoxazine-tioxazafen derivative;

[0016] The structural formula of the o-aminophenol substituted compound is:

[0017] Wherein R is H, F, Cl, Br, CH3 or C4H9.

[0018] Furthermore, in the step 1), the molar ratio of p-cyanoacetophenone, N-bromosuccinimide and p-toluenesulfonic acid hydrate is 1:1-3:1-3, and the amount ratio of p-cyanoacetophenone to solvent is 20-40 mmol:400 mL.

[0019] Furthermore, in the step 1), the temperature of the substitution reaction is 60 to 90° C., and the time of the substitution reaction is 4 to 12 hours.

[0020] Furthermore, in the step 2), the ratio of 2-bromo-4'-cyanoacetophenone, o-aminophenol substituted compound and solvent is 20-40 mmol: 20-40 mmol: 100-150 mL;

[0021] The reaction temperature is 20-40° C., and the reaction time is 6-12 hours.

[0022] Furthermore, in the step 3), the ratio of the benzonitrile-4-(2H-1,4-benzoxazin-3-yl) substituted compound, hydroxylamine hydrochloride and solvent is 10-40 mmol: 30-50 mmol: 80-120 mL;

[0023] The reaction temperature is 15-20° C., and the reaction time is 4-10 hours.

[0024] Furthermore, in the step 4), the ratio of the amount of the 4-(2H-benzo[b][1,4]oxazin-3-yl)-N-hydroxybenzimidamide substituted compound, 2-thiophenecarbonyl chloride and solvent is 10-30 mmol: 10-30 mmol: 80-120 mL;

[0025] The temperature for adding the 4-(2H-benzo[b][1,4]oxazin-3-yl)-N-hydroxybenzimidamide substituted compound is 15 to 20°C;

[0026] The reaction temperature is 15-70° C., and the reaction time is 2-6 hours.

[0027] Furthermore, the solvents used in step 1), step 2), step 3) and step 4) independently comprise one or more of acetonitrile, dichloromethane, anhydrous ethanol and 2-methyltetrahydrofuran.

[0028] The present invention also provides a use of a benzoxazine-tioxazafen derivative in the preparation of a drug for preventing and treating nematode diseases or plant diseases. The nematode diseases include root knot nematode disease and pine wood nematode disease; the plant diseases include rice sheath blight, wheat take-all disease, wheat head blight, and rice blast.

[0029] Beneficial effects of the present invention:

[0030] The series of compounds synthesized by the present invention use Tioxazafen as the parent structure and have novel compound structures. Bioassay results show that most of the compounds have excellent fungicidal activity against certain pathogenic fungi and nematodes, and have high commercialization prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 is the hydrogen spectrum of intermediate A16 in Example 1 of the present invention;

[0032] Figure 2 This is a high-resolution mass spectrum of intermediate A16 in Example 1 of the present invention;

[0033] Figure 3 This is the hydrogen spectrum of compound A6 prepared in Example 1 of the present invention;

[0034] Figure 4 This is a high-resolution mass spectrum of compound A6 prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0035] The present invention provides a benzoxazine-tioxazafen derivative having the following structural formula:

[0036]

[0037] Wherein, R1 is H, F, Cl, Br, CH3 or C4H9; R2 is H or Cl.

[0038] In the present invention, the benzoxazine-tioxazafen derivative is preferably selected from one of the following structural formulas:

[0039]

[0040] The present invention also provides a method for preparing a benzoxazine-tioxazafen derivative, comprising the following steps:

[0041] 1) mixing p-cyanoacetophenone, N-bromosuccinimide and p-toluenesulfonic acid hydrate in a solvent to carry out a substitution reaction to obtain 2-bromo-4'-cyanoacetophenone;

[0042] 2) mixing 2-bromo-4'-cyanoacetophenone and an o-aminophenol substituted compound in a solvent for reaction to obtain a benzonitrile-4-(2H-1,4-benzoxazin-3-yl) substituted compound;

[0043] 3) dissolving the benzonitrile-4-(2H-1,4-benzoxazin-3-yl) substituted compound in a solvent, and then adding hydroxylamine hydrochloride to react to obtain a 4-(2H-benzo[b][1,4]oxazin-3-yl)-N-hydroxybenzimidamide substituted compound;

[0044] 4) dissolving the 4-(2H-benzo[b][1,4]oxazin-3-yl)-N-hydroxybenzimidamide substituted compound in a solvent, and then adding 2-thiophenecarbonyl chloride to react to obtain a benzoxazine-tioxazafen derivative;

[0045] The structural formula of the o-aminophenol substituted compound is:

[0046] Wherein R is H, F, Cl, Br, CH3 or C4H9.

[0047] In the present invention, the synthesis route of the benzoxazine-tioxazafen derivative is as follows:

[0048]

[0049] In the present invention, the molecular structures and physicochemical properties of the benzoxazine-tioxazafen derivatives and intermediate A16 are shown in Table 1 below.

[0050] Table 1 Molecular structures and physicochemical properties of benzoxazine-tioxazafen derivatives and intermediate A16

[0051]

[0052]

[0053] Table 2 1H NMR and high resolution mass spectrometry (HRMS) data of benzoxazine-tioxazafen derivatives and intermediate A16

[0054]

[0055]

[0056]

[0057] In the present invention, in step 1), the molar ratio of p-cyanoacetophenone, N-bromosuccinimide and p-toluenesulfonic acid hydrate is 1:1-3:1-3, preferably 1:1.5:1.5; the amount ratio of p-cyanoacetophenone and solvent is 20-40 mmol:400 mL, preferably 30 mmol:400 mL.

[0058] In the present invention, in step 1), the temperature of the substitution reaction is 60-90° C., preferably 65-85° C., more preferably 70-80° C.; the time of the substitution reaction is 4-12 h, preferably 6-10 h, more preferably 8 h.

[0059] In the present invention, in the step 2), the ratio of 2-bromo-4'-cyanoacetophenone, o-aminophenol substituted compound and solvent is 20-40 mmol: 20-40 mmol: 100-150 mL, preferably 20 mmol: 30 mmol: 120 mL;

[0060] The reaction temperature is 20-40° C., preferably 25-35° C., more preferably 30° C.; the reaction time is 6-12 h, preferably 8-10 h.

[0061] In the present invention, in step 3), the ratio of the benzonitrile-4-(2H-1,4-benzoxazin-3-yl) substituted compound, hydroxylamine hydrochloride and solvent is 10-40 mmol: 30-50 mmol: 80-120 mL, preferably 20-30 mmol: 35-45 mmol: 90-110 mL, and more preferably 30 mmol: 40 mmol: 100 mL;

[0062] The reaction temperature is 15-20° C., preferably 18° C.; the reaction time is 4-10 h, preferably 6 h.

[0063] In the present invention, in step 4), the ratio of the 4-(2H-benzo[b][1,4]oxazin-3-yl)-N-hydroxybenzimidamide substituted compound, 2-thiophenecarbonyl chloride and solvent is 10-30 mmol:10-30 mmol:80-120 mL, preferably 20 mmol:20 mmol:90-100 mL.

[0064] In the present invention, the temperature for adding the 4-(2H-benzo[b][1,4]oxazin-3-yl)-N-hydroxybenzimidamide substituted compound is 15-20°C, preferably 18°C.

[0065] In the present invention, in step 4), the reaction temperature is 15-70° C., preferably 20-60° C., more preferably 30-50° C.; the reaction time is 2-6 h, preferably 4 h.

[0066] Furthermore, the solvents used in step 1), step 2), step 3) and step 4) independently comprise one or more of acetonitrile, dichloromethane, anhydrous ethanol and 2-methyltetrahydrofuran, preferably one or more of acetonitrile, dichloromethane and anhydrous ethanol.

[0067] The present invention also provides a use of a benzoxazine-tioxazafen derivative in the preparation of a drug for preventing and treating nematode diseases or plant diseases. The nematode diseases include root knot nematode disease and pine wood nematode disease; and the plant diseases include rice sheath blight, wheat scab, rice blast, and wheat take-all disease.

[0068] The technical solutions provided by the present invention are 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.

[0069] Example 1

[0070] Synthesis of compound A6

[0071] (1) Synthesis of 2-bromo-4'-cyanoacetophenone

[0072] Reaction type: electrophilic substitution

[0073] 4-Cyanoacetophenone (20 mmol) and 4-toluenesulfonic acid hydrate (30 mmol) were dissolved in 400 mL of acetonitrile and stirred evenly. Then, N-bromosuccinimide (20 mmol) was slowly added dropwise and refluxed at 80° C. for 2 h. After the reaction was completed, the reaction solution was extracted to remove excess 4-toluenesulfonic acid hydrate, and the solvent was concentrated under reduced pressure to obtain 2-bromo-4'-cyanoacetophenone as a white solid with a yield of 95%.

[0074]

[0075] (2) Synthesis of benzonitrile, 4-(2H-1,4-benzoxazin-3-yl)

[0076] Reaction type: nucleophilic substitution-cyclocondensation reaction

[0077] o-Aminophenol (30 mmol), TBASH (tetrabutylammonium hydrogen sulfate) (10 mmol), and 20% K2CO3 (22 mmol) were dissolved in 100 mL of DCM (dichloromethane) and stirred at 25°C for 2 h. 2-Bromo-4'-cyanoacetophenone (20 mmol) was then added dropwise. The mixture was allowed to react at 25°C for 6 h. Upon completion, the reaction solution was extracted, concentrated under reduced pressure to remove the solvent, and monitored by TLC until completion. Completion of the reaction was monitored by thin-layer chromatography (TLC, V (petroleum ether):V (ethyl acetate) = 15:1). The mixture was concentrated under reduced pressure to dryness, and 80 mL of water was added. The mixture was extracted three times with dichloromethane (30 mL). The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was concentrated under reduced pressure and separated by silica gel column chromatography (V (petroleum ether):V (ethyl acetate) = 60:1) to obtain a yellow needle-shaped solid in a 95% yield.

[0078]

[0079] (3) Synthesis of the intermediate 4-(2H-benzo[b][1,4]oxazin-3-yl)-N-hydroxybenzimidamide (A16)

[0080] Reaction type: nucleophilic addition reaction

[0081] Hydroxylamine hydrochloride (40 mmol) was dissolved in 100 mL of anhydrous ethanol. Na₂CO₃ (22 mmol) was added at 18°C, followed by 110 mL of benzonitrile and 20 mmol of 4-(2H-1,4-benzoxazin-3-yl). The reaction was allowed to proceed at 25°C for 2 h, then the temperature was raised to 80°C and refluxed for 4 h. The reaction was monitored by TLC until completion. Completion was monitored by thin-layer chromatography (TLC, V (petroleum ether):V (ethyl acetate) = 2:1). The solution was concentrated under reduced pressure to dryness to obtain a white solid in an 85% yield.

[0082]

[0083] (4) Synthesis of 3-(4-(5-(thiophen-2-yl)-1,2,4-oxadiazol-3-yl)phenyl)-2H-benzo[b][1,4]oxazine (A6)

[0084] Reaction type: intramolecular dehydration cyclization reaction

[0085] 4-(2H-Benzo[b][1,4]oxazin-3-yl)-N-hydroxybenzimidamide (20 mmol) was weighed and dissolved in 100 mL of 2-methyltetrahydrofuran at 20°C. 40% NaOH (40 mmol) and tetrabutylammonium hydroxide (40 mmol) were added, followed by 2-thiophenecarbonyl chloride (20 mmol). The mixture was reacted at 25°C for 30 minutes, then heated to 70°C and refluxed for 2 hours. TLC monitoring was performed until the reaction was complete. Completion of the reaction was monitored by thin-layer chromatography (TLC, V (petroleum ether):V (ethyl acetate) = 15:1). The mixture was concentrated to dryness under reduced pressure and separated by silica gel column chromatography (V (petroleum ether):V (ethyl acetate) = 30:1) to obtain a pale yellow solid in an 80% yield.

[0086]

[0087] This route was used to synthesize the series of benzoxazine-tioxazafen derivatives A1-A7 of the present invention. Compounds A8-A15, in step (4), employ 5-chloro-2-thiophenecarbonyl chloride as the reactant, with all other conditions remaining unchanged. The only difference is the structure of the o-aminophenol-substituted compound employed. See Table 3 below for specific starting materials.

[0088] Table 3 Raw materials

[0089]

[0090]

[0091]

[0092] Experimental example

[0093] We conducted nematicidal activity tests on the compounds of this invention. The nematicidal activity of the target compounds was determined using a direct contact method. Pine wood nematodes and Caenorhabditis elegans were selected as test nematodes. The initial screening concentration of the agent was set at 100 mg / L. The test compound was dissolved in 1 mL of DMF and then diluted to 20 mL with a 0.1% Tween 80 aqueous solution. The cultured nematodes were eluted with sterile water, and the eluate was centrifuged and concentrated to prepare a nematode suspension at a specific ratio (80-120 per 100 μL). Using a pipette, 100 μL of the nematode suspension was transferred to a 96-well biochemical culture plate, followed by the addition of 80 μL of sterile water and 20 μL of the test solution. After the addition was complete, the biochemical culture plate was placed in a 20°C constant temperature incubator. After 48 hours of treatment, the total number of nematodes in each treatment and the number of dead nematodes were observed under a stereomicroscope. Each treatment was repeated in triplicate. The criterion for nematode death is that the nematode body becomes rigid and does not move when stimulated with a fine needle. The nematode is considered dead. The nematocidal activity of the test compound against nematodes is calculated. Based on the preliminary screening results, compounds with nematocidal activity greater than 80% are selected for further determination of their LC 50 The LC values ​​were calculated using the data processing software DPS18.10. 50 The values ​​and 95% confidence intervals are shown in Tables 4 and 5 below.

[0094] Table 4 Toxicity of target compounds to Caenorhabditis elegans (100 mg / L)

[0095] Compound Corrected mortality % Compound Corrected mortality % A1 6.13 A10 71.24 A2 12.14 A11 4.07 A3 13.42 A12 57.16 A4 73.28 A13 41.17 A5 2.42 A14 27.75 A6 6.13 A15 26.45 A7 9.76 Tioxazafen 70.42 A8 72.65 thiazolyl 56.11 A9 55.07

[0096] Table 5 Toxicity of target compounds to pine wood nematodes (100 mg / L)

[0097] Compound Corrected mortality % Compound Corrected mortality % A1 0 A10 2.48 A2 39.39 A11 1.91 A3 5.66 A12 27.56 A4 44.02 A13 55.99 A5 0 A14 0 A6 0 A15 10.31 A7 0 Tioxazafen 24.69 A8 70.31 thiazolyl 29.92 A9 14.42

[0098] Note: Each treatment was repeated 3 times. T: Tioxazafen S: Thiazophos

[0099] The results in Tables 4 and 5 show that at a concentration of 100 mg / L, the newly synthesized compounds A4, A8, and A10 exhibited high bioactivity against C. elegans, outperforming the control agents thiazophos and tioxazafen. At a concentration of 100 mg / L, the lethality of compounds A2, A4, A8, and A13 against pine wood nematodes was also higher than that of the control agents thiazophos and tioxazafen.

[0100] We conducted a bactericidal activity test on the compounds of the present invention. The mycelium growth rate method was used to determine the bactericidal activity of the compounds against various fungi in culture dishes. The cultured pathogens were cut from the edge of the colony using a 7mm diameter puncher under sterile operating conditions. The cakes were inoculated with an inoculation needle in the center of the drug-containing culture medium dish with the mycelium facing down. The dish was covered with a lid, inverted, and placed in a 25°C incubator for culture. When the colonies in the blank control grew to about two-thirds of the plate area, the colony diameters of each treatment were measured using the cross-cross method. Each sample was repeated 3 times and the average value was taken. The mycelium growth inhibition rate of each drug treatment on the pathogen was calculated by the ratio of the difference between the blank control colony diameter and the drug-treated colony diameter to the blank control colony diameter. The preliminary screening test results of the compounds of the present invention on rice sheath blight, wheat fusarium, rice blast, and wheat take-all pathogen are shown in Table 6, as well as the EC values ​​of some of the pre-screened high-activity compounds on wheat take-all pathogen. 50 Values ​​are shown in Table 7.

[0101] The results in Table 6 indicate that the newly synthesized compounds exhibited high bioactivity against agricultural pathogens such as A4. At a concentration of 50 mg / L, compounds A4, A9, and A14 were more potent against Rhizoctonia solani than the control agent, fluopyram. Compound A4 was more potent against Pseudomonas aeruginosa than fluopyram and tioxazafen.

[0102] Table 6 Toxicity of target compounds to four pathogenic fungi (50 mg / L)

[0103]

[0104] As shown in Table 7, the EC value of compound A4 against wheat take-all pathogen 50 The value was significantly better than that of silthiopyrad.

[0105] Table 7 EC of compound A4 against Rhizoctonia solani 50

[0106]

[0107] As can be seen from the above examples, the present invention provides benzoxazine-tioxazafen derivatives, their preparation methods, and applications. The experimental results above demonstrate that the series of compounds synthesized by the present invention are based on tioxazafen as the parent structure and possess novel compound structures. Bioassay results indicate that most of the compounds exhibit excellent fungicidal activity against certain pathogenic fungi and nematodes, suggesting promising commercialization prospects.

[0108] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A benzoxazine-tioxazafen derivative, characterized in that: The benzoxazine-Tioxazafen derivative is selected from one of the following structural formulas:

2. The method for preparing the benzoxazine-tioxazafen derivative according to claim 1, characterized in that: The following steps are involved: 1) mixing p-cyanoacetophenone, N-bromosuccinimide and p-toluenesulfonic acid hydrate in a solvent to carry out a substitution reaction to obtain 2-bromo-4'-cyanoacetophenone; 2) mixing 2-bromo-4'-cyanoacetophenone and an o-aminophenol substituted compound in a solvent for reaction to obtain a benzonitrile-4-(2H-1,4-benzoxazin-3-yl) substituted compound; 3) dissolving the benzonitrile-4-(2H-1,4-benzoxazin-3-yl) substituted compound in a solvent, and then adding hydroxylamine hydrochloride to react to obtain a 4-(2H-benzo[b][1,4]oxazin-3-yl)-N-hydroxybenzimidamide substituted compound; 4) dissolving the 4-(2H-benzo[b][1,4]oxazin-3-yl)-N-hydroxybenzimidamide substituted compound in a solvent, and then adding 2-thiophenecarbonyl chloride to react to obtain a benzoxazine-tioxazafen derivative; The structural formula of the o-aminophenol substituted compound is: Wherein R is H, F, Cl, Br, CH3 or C4H9.

3. The method for preparing the benzoxazine-tioxazafen derivative according to claim 2, characterized in that: In the step 1), the molar ratio of p-cyanoacetophenone, N-bromosuccinimide and p-toluenesulfonic acid hydrate is 1:1-3:1-3, and the amount ratio of p-cyanoacetophenone to solvent is 20-40 mmol:400 mL.

4. The method for preparing a benzoxazine-tioxazafen derivative according to claim 2 or 3, characterized in that: In the step 1), the temperature of the substitution reaction is 60 to 90° C., and the time of the substitution reaction is 4 to 12 hours.

5. The method for preparing the benzoxazine-tioxazafen derivative according to claim 4, characterized in that: In the step 2), the ratio of 2-bromo-4'-cyanoacetophenone, o-aminophenol substituted compound and solvent is 20-40 mmol: 20-40 mmol: 100-150 mL; The reaction temperature is 20-40° C., and the reaction time is 6-12 hours.

6. The method for preparing the benzoxazine-tioxazafen derivative according to claim 2, 3 or 5, characterized in that: In the step 3), the ratio of the benzonitrile-4-(2H-1,4-benzoxazin-3-yl) substituted compound, hydroxylamine hydrochloride and solvent is 10-40 mmol: 30-50 mmol: 80-120 mL; The reaction temperature is 15-20° C., and the reaction time is 4-10 hours.

7. The method for preparing the benzoxazine-tioxazafen derivative according to claim 6, characterized in that: In the step 4), the ratio of the 4-(2H-benzo[b][1,4]oxazin-3-yl)-N-hydroxybenzimidamide substituted compound, 2-thiophenecarbonyl chloride and solvent is 10-30 mmol: 10-30 mmol: 80-120 mL; The temperature for adding the 4-(2H-benzo[b][1,4]oxazin-3-yl)-N-hydroxybenzimidamide substituted compound is 15 to 20°C; The reaction temperature is 15-70° C., and the reaction time is 2-6 hours.

8. The method for preparing a benzoxazine-tioxazafen derivative according to claim 2, wherein: The solvents used in step 1), step 2), step 3) and step 4) independently comprise one or more of acetonitrile, dichloromethane, anhydrous ethanol and 2-methyltetrahydrofuran.

9. Use of the benzoxazine-tioxazafen derivative according to claim 1 in the preparation of a drug for preventing and treating nematodes or plant diseases, characterized in that: The nematode diseases include Caenorhabditis elegans and pine wood nematode disease; the plant diseases include rice sheath blight and wheat take-all disease; In claim 1, the use of compounds A4, A8, and A10 in the preparation of drugs for preventing and treating Caenorhabditis elegans; In claim 1, the use of compounds A2, A4, A8, and A13 in the preparation of drugs for preventing and treating pine wood nematode disease; In claim 1, the use of compounds A4, A9, and A14 in the preparation of a drug for preventing and treating rice sheath blight; In claim 1, the use of compound A4 in the preparation of a medicament for preventing and treating wheat take-all disease.

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