Crystallization purification method and application of benzoxazine compound

Abstract

The invention discloses a crystallization purification method of a benzoxazine compound and application of the benzoxazine compound, the crystallization purification method comprises the following steps: dissolving a compound I in a crystallization solvent, and then separating out crystals in a volatilization or cooling mode; wherein the compound I has the following chemical structure. The method disclosed by the invention is high in crystallization speed and high in crystallization efficiency, and overcomes the problems of easiness in caking, wall sticking and the like of raw material oily substances; the crystal obtained by the method is high in purity, low in impurity content and easy to obtain, and preparation processing and industrial production are facilitated; the crystal obtained by the method has a more excellent drug effect. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the agrochemical field, and particularly relates to an efficient crystallization purification method of a benzoxazine compound and its application. Background Art

[0002] The compound 3-(7-fluoro-3-oxo-4-(prop-2-yn-1-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)-1-methyl-6-(trifluoromethyl)pyrimidine-2,4(1H,3H)-dione (hereinafter referred to as "Compound I") and its preparation method and herbicidal activity have been reported in Patent US5084084A. This compound is similar in structure to the commercial herbicide flumioxazin and belongs to a protoporphyrinogen oxidase (PPO) inhibitor. By causing the accumulation of protoporphyrin, it enhances the lipid peroxidation of cell membranes, thereby inhibiting plant photosynthesis and causing the leaves to quickly wither and die. It has the characteristics of high efficiency, low toxicity, and broad spectrum. It has the following chemical structural formula:

[0003]

[0004] Patent US5084084A mentions that the synthesis of Compound I is purified by preparative thin-layer chromatography (PTLC), using hexane / ethyl acetate (3:1) as the developing agent, and finally obtaining a colorless viscous oil, which solidifies after standing. However, when synthesizing Compound I in the laboratory completely according to the method in the patent, it is found that this "solidification" process has the following defects:

[0005] 1. Non-crystalline property: Using preparative thin-layer chromatography (PTLC) with hexane / ethyl acetate (3:1) as the developing agent, a colorless viscous oil is finally obtained, which solidifies after standing. The XRD pattern shows no characteristic peaks, indicating that it is an amorphous solid and lacks a definite crystal structure.

[0006] 2. The content of impurities in the solidified product is relatively high (HPLC detection > 5%), and the solvent residue (GC detection > 3%). These impurities and solvent residues seriously affect the stability and efficacy of the formulation. Impurities may directly compete for the binding sites of the target enzyme, reducing the effective concentration of the drug; at the same time, solvent residues may cause metabolic interference or increased toxicity.

[0007] 3. During the industrial production process, the solidified product is prone to caking and sticking to the wall, resulting in difficult equipment cleaning and increasing production costs. In addition, the solidified product has poor fluidity (angle of repose > 45°) and is difficult to be made into a formulation by conventional processes, further limiting the feasibility of its large-scale production.

[0008] 4. The solidified product contains a relatively high content of impurities and solvent residues, resulting in its inhibitory activity against PPO enzyme being lower than that of the high-purity compound. The specific manifestations are as follows: Directly competing for the binding site of the target enzyme: Impurities compete with the target compound for the binding site, reducing the number of effective drug molecules. Changing the physicochemical properties of the drug: Impurities may affect the solubility, stability and other physicochemical properties of the drug, reducing its bioavailability. Off-target effects and toxicity: Impurities may inhibit other non-target enzymes or receptors, triggering unnecessary physiological reactions and increasing the risk of side effects. Direct toxicity or metabolic interference: Residual solvents may have direct toxicity to the target enzyme or cells, masking the true activity of the drug or causing off-target effects.

[0009] 5. Due to the presence of impurities, both the in vitro enzyme activity inhibition experiment and the herbicidal effect on living plants are significantly lower than the theoretical activity level of the compound. Summary of the Invention

[0010] The main object of the present invention is to solve the problems in the prior art that the crude oil-like herbicidal compound agglomerates after solidification, has low purity, is difficult for industrial production and formulation processing, and has poor drug efficacy, and to provide an efficient crystallization method to obtain high-purity and easy-to-process powdery crystals, and improve the enzyme activity and herbicidal activity.

[0011] The object of the present invention can be achieved by the following measures:

[0012] A method for crystallization purification of a benzoxazine compound, first dissolving Compound I in a crystallization solvent, and then precipitating crystals by volatilization or cooling; wherein Compound I has the following chemical structure:

[0013]

[0014] In a preferred embodiment, Compound I is dissolved in a crystallization solvent at room temperature; or Compound I is dissolved in a crystallization solvent by ultrasonic or heating means.

[0015] In a preferred embodiment, the heating temperature is 30 - 100 °C, preferably 30 - 80 °C.

[0016] In a preferred embodiment, when precipitating crystals by cooling, the temperature is cooled to less than 30 °C, preferably cooled to below room temperature, more preferably cooled to below 0 °C.

[0017] In a preferred embodiment, the crystallization solvent is selected from aromatic hydrocarbon solvents, halogenated hydrocarbon solvents, aliphatic hydrocarbon solvents, alcohol solvents, ether solvents, lipid solvents, ketone solvents or high-boiling solvents, or a mixed solvent of them, or a mixed solvent of them and water.

[0018] In a preferred embodiment, the crystallization purification method includes S1 or S2:

[0019] S1. Weigh compound I. Under ultrasonic or non-ultrasonic conditions, add a crystallization solvent until a clear solution is obtained. With or without filtration, place the solution in a stable environment for evaporation crystallization or cooling crystallization.

[0020] S2. Weigh compound I. Add a crystallization solvent that has been heated or heated to boiling until a clear solution is obtained. With or without filtration, slowly or rapidly cool the solution for crystallization.

[0021] In step S1, the preferred crystallization solvents are selected from one or more of the following solvents:

[0022] a1) Aromatic hydrocarbon solvents: toluene, o-xylene, m-xylene;

[0023] a2) Halogenated hydrocarbon solvents: 1,2-dichloroethane, chloroform, epichlorohydrin, propylene oxide, 1,6-dichlorohexane, 1-chlorobutane;

[0024] a3) Alcohol solvents: methanol;

[0025] a4) Ether solvents: 1,4-dioxane, diethoxymethane, methyl tert-butyl ether, tetrahydrofuran;

[0026] a5) Ester solvents: ethyl formate, butyl acetate, methyl acetate, ethyl acetate, isobutyl acetate, methyl propionate, ethyl propionate;

[0027] a6) Ketone solvents: 2-butanone, acetone, acetylacetone;

[0028] a7) High-boiling solvents: acetonitrile, dimethyl sulfoxide;

[0029] a8) Mixed solvents of the following solvents and water: propylene oxide, acetonitrile, methanol, 1,4-dioxane, methyl acetate, 2-butanone, acetone, N,N-dimethylformamide.

[0030] In a preferred embodiment, in step S2, slow cooling crystallization is to cool the solution to room temperature for crystallization; the rapid cooling crystallization is to cool the solution to below 0 °C for crystallization.

[0031] In a preferred embodiment, in the slow cooling crystallization of step S2, the crystallization solvent is selected from one or more of the following solvents:

[0032] b1) Aromatic hydrocarbon solvents: p-xylene;

[0033] b2) Halogenated hydrocarbon solvents: 1,2-dichloroethane, chloroform, 2,2-dimethoxypropane, 1,6-dichlorohexane;

[0034] b3) Summary of the results of recrystallization with alcohol solvents: methanol;

[0035] b4) Ether solvents: 1,4-dioxane, ethylene glycol diethyl ether;

[0036] b5) Ester solvents: butyl acetate, ethyl acetate, isopropyl acetate, n-propyl acetate, sec-butyl acetate, ethyl chloroacetate, ethyl propionate, diethyl malonate;

[0037] b6) Ketone solvents: 2-butanone;

[0038] b7) High-boiling solvents: acetonitrile, N,N-dimethylformamide, formamide.

[0039] In a preferred embodiment, in the rapid cooling crystallization of step S2, the crystallization solvent is selected from one or more of the following solvents:

[0040] c1) Aromatic hydrocarbons: ethylbenzene, m-xylene;

[0041] c2) Halogenated hydrocarbon solvents: epichlorohydrin, propylene oxide, 2,2-dimethoxypropane, 1,6-dichlorohexane;

[0042] c3) Alcohol solvents: methanol, isopropanol, isobutanol, isopentanol, n-propanol, n-butanol, n-pentanol, sec-butanol, 95% ethanol;

[0043] c4) Ether solvents: 1,4-dioxane;

[0044] c5) Ester solvents: butyl acetate, methyl acetate, n-propyl acetate, sec-butyl acetate, ethyl chloroacetate, butyl acrylate;

[0045] c6) Ketone solvents: 2-butanone, acetone, acetylacetone;

[0046] c7) High-boiling solvents: acetonitrile.

[0047] The high-boiling solvents referred to in the present invention refer to solvents with a boiling point above 81 °C under atmospheric pressure, and such solvents include, but are not limited to, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, formamide, etc.

[0048] The present invention also discloses another method for the crystallization and purification of a benzoxazine compound. After mixing and dissolving compound I with a good solvent, an antisolvent is slowly added to precipitate a solid, and the solid is collected and dried; compound I has the following chemical structure.

[0049] In one embodiment, the good solvent is selected from one or more of aromatic hydrocarbon solvents, halogenated hydrocarbon solvents, alcohol solvents, ketone solvents, ester solvents, and high-boiling solvents. Preferably, the good solvent is selected from 1,2-dichloroethane or toluene;

[0050] In one embodiment, the anti-solvent is selected from one or more of aliphatic hydrocarbon solvents and ether solvents; preferably, the anti-solvent is selected from petroleum ether, n-hexane, n-octane, n-pentane or n-heptane.

[0051] The method for crystallization purification of the benzoxazine compound of the present invention can be applied to the preparation of herbicidal compositions or herbicidal preparations.

[0052] Compared with the prior art, the method of the present invention has a fast crystallization rate and high crystallization efficiency, overcoming the problems of easy caking and wall sticking of the raw material oil; the crystals obtained by this method have high purity, low impurity content, are easy to obtain, facilitate formulation processing and industrial production; the crystals obtained by this method have more excellent drug efficacy and are more conducive to the application of Compound I. Detailed Embodiments

[0053] The present invention can be better understood according to the following examples. However, those skilled in the art can easily understand that the content described in the examples is only used to illustrate the present invention and should not and will not limit the present invention described in detail in the claims.

[0054] The compound shown in the formula I structure in the present invention can also be simply referred to as Compound I, Compound I or the compound of formula (I). The raw materials used in the examples are all the crude oil of Compound I prepared by the patent method of Patent US5084084A.

[0055] The information of the equipment and instruments used in each example is shown in Table 1.

[0056] Table 1. Information of Equipment and Instruments

[0057]

[0058] Example 1. Volatile Crystallization

[0059] Weigh about 30 mg of Compound I, and under ultrasonic conditions, add the solvent dropwise until it reaches a clear solution state; for slightly soluble cases, it can be added up to 10 ml, and in principle, it does not exceed 20 ml, and a filtration operation is required. The filtered solution is placed in a stable environment for volatile crystallization. After the solid precipitates, sampling, washing, and drying are carried out.

[0060] Crystallization treatments are carried out using different types of crystallization solvents respectively, and the results are shown in the following tables.

[0061] Table 2. Aromatic Hydrocarbon Single Solvents

[0062]

[0063] Note: "--" indicates that no sample / data was obtained (the same as the following tables)

[0064] Table 3. Summary of the results of volatile crystallization of halogenated hydrocarbon solvents

[0065]

[0066] Table 4. Summary of the results of crystallization by the method of volatile alcohol solvents

[0067]

[0068]

[0069] Table 5. Summary of the results of volatile crystallization of ether solvents

[0070]

[0071] Table 6. Summary of the results of volatile crystallization of ester solvents

[0072]

[0073] Table 7. Summary of the results of volatile crystallization of ketone solvents

[0074]

[0075]

[0076] Table 8. Summary of the results of volatile crystallization of other solvents

[0077]

[0078] Example 2. Crystallization by volatile mixed solvents

[0079] Prepare a mixed solvent by mixing solvents in a ratio of 1 ml of solvent to 1 drop of water.

[0080] Weigh about 30 mg of Compound I. Under ultrasonic conditions, add the solvent dropwise until the solution becomes clear; for slightly soluble cases, it can be added up to 10 ml, and in principle, it should not exceed 20 ml. Then, perform a filtration operation. Place the filtered solution in a stable environment for volatile crystallization. After the solid precipitates, take samples, wash, and drain.

[0081] Use different types of crystallization solvents for crystallization treatment respectively. The results are shown in the following tables.

[0082] Table 9. Summary of the results of volatile crystallization of mixed solvents

[0083]

[0084]

[0085] Example 3. Recrystallization - Slow cooling crystallization

[0086] Weigh approximately 200 mg of Compound I. Set the oil bath temperature according to the boiling point of the solvent. Add the solvent at the set temperature and continuously stir to promote dissolution. The amount of the solvent can be about 20% more than the original solution (the amount of solvent at the saturated state), and the total amount of the solvent should not exceed 15 ml at most. After the solution becomes clear, there is no need to filter it. Transfer it to a normal temperature environment for cooling and crystallization. If the solution is not clear, filter it while it is hot. After collecting the filtrate, transfer it to a normal temperature environment for cooling and crystallization.

[0087] Carry out crystallization treatment by respectively selecting different types of crystallization solvents. The results are shown in the following tables.

[0088] Table 10. Summary of recrystallization results of aromatic hydrocarbon solvents

[0089]

[0090] Table 11. Summary of recrystallization results of halogenated hydrocarbon solvents

[0091]

[0092] Table 12. Summary of recrystallization results of alcohol solvents

[0093]

[0094]

[0095] Table 13. Summary of recrystallization results of ether solvents

[0096]

[0097] Table 14. Summary of recrystallization results of ester solvents

[0098]

[0099] Table 15. Summary of recrystallization results of ketone solvents

[0100]

[0101] Table 16. Summary of recrystallization results of other solvents

[0102]

[0103]

[0104] Example 3. Recrystallization - Rapid cooling crystallization

[0105] Weigh about 200 mg of Compound I, set the oil bath temperature according to the boiling point of the solvent, add the solvent at the set temperature, and continuously stir to promote dissolution. The amount of the solvent can be about 20% more than the original solution (the amount of solvent at saturation), and the total amount of the solvent should not exceed 15 ml at most. After the solution becomes clear, there is no need to filter it, and transfer it to an ice-water bath for cooling and crystallization. If the solution is not clear, filter it while it is hot, collect the filtrate, and then transfer it to an ice-water bath for cooling and crystallization.

[0106] Carry out crystallization treatment by selecting different types of crystallization solvents respectively, and the results are shown in the following tables.

[0107] Table 17. Summary of recrystallization results of aromatic hydrocarbon solvents

[0108]

[0109] Table 18. Summary of recrystallization results of halogenated hydrocarbon solvents

[0110]

[0111] Table 19. Summary of recrystallization results of alcohol solvents

[0112]

[0113]

[0114] Table 20. Summary of recrystallization results of ether solvents

[0115]

[0116] Table 21. Summary of recrystallization results of ester solvents

[0117]

[0118] Table 22. Summary of recrystallization results of ketone solvents

[0119]

[0120] Table 23. Summary of recrystallization results of ketone solvents

[0121]

[0122]

[0123] The above 3 examples systematically verified the crystallization purification method of Compound I. Through the screening of different solvent systems and crystallization conditions, the preparation of crystals with high purity and regular crystal forms was successfully achieved, and their purity was all above 99% (detected by HPLC), which was much higher than 87% in the original patent.

[0124] In Example 1, through the evaporation crystallization method, solvents such as toluene, acetonitrile, and ethyl acetate were screened out, which could effectively precipitate solids and significantly reduce the impurity content; in Example 2, the mixed solvent system (such as acetonitrile - water, 1,4 - dioxane - water) was further optimized to improve the crystallization efficiency and product purity; in Example 3, by slow or rapid cooling crystallization, combined with halogenated hydrocarbons (such as 1,2 - dichloroethane), lipid solvents (such as butyl acetate), and alcohol solvents (such as methanol), the crystal form stability and yield were further optimized.

[0125] The final product obtained by the crystallization purification method of the present invention is a high - purity off - white powdery solid, which significantly improves the feasibility and efficiency of industrial production. Compared with the problems of wall sticking and caking of the amorphous technical drug in the prior art, the crystals obtained by the present invention have excellent physical properties: good fluidity (angle of repose < 30°), no adhesiveness, which can effectively avoid problems such as wall sticking of production equipment and material agglomeration, and greatly reduce the equipment cleaning difficulty and maintenance cost. In addition, the powdery solid is convenient for accurate weighing and packaging, providing a stable basic raw material for subsequent formulation processing (such as water - dispersible granules, suspension agents, etc.), and significantly simplifying the formulation design and production process.

[0126] Example 4: Enzyme activity experiment

[0127] Test enzyme: Plant protoporphyrinogen oxidase (PPO) enzyme - linked immunosorbent assay kit, Shanghai Tongwei Biotechnology Co., Ltd. (Shanghai, China).

[0128] Test agents: Select the oily technical drug and the technical drug crystallized according to the method of Example 1

[0129] Test method: First, the recombinant NtPPO protein (purity > 95%, concentration 10 μg / μL) was diluted to 20 μg / mL, and then mixed with protoporphyrin IX substrate (final concentration 2 μM) and other reaction components. The reaction system (200 μL) contains: 1 mM EDTA, 5 μM FAD, 100 mM PBS (pH 7.4), 0.03% Tween 80, 5 mM DTT, 200 mM imidazole, and the test agent (final concentration 1 μM). The change in fluorescence intensity within 30 minutes of the reaction was monitored by a fluorescence spectrophotometer (excitation wavelength 410 nm, emission wavelength 630 nm), and the inhibition rate was calculated (% Inhibition=(1 - ν / ν)×100). The data was fitted by Sigma Plot 10.0 software and then the corresponding IC 50 and K i were fitted according to the following two formulas. The IC 50 value was obtained according to the following formula:

[0130]

[0131] Inhibitor concentration in the x-system

[0132] y—Percentage of the residual activity of NtPPO enzyme under the action of the inhibitor at the corresponding concentration to the enzyme activity without the inhibitor, i.e., relative activity

[0133] max, min—Maximum and minimum values of the relative activity respectively

[0134] IC 50 —Inhibitor concentration corresponding to when the relative activity is half of the initial value

[0135] The IC 50 value obtained by fitting is used to calculate the K i value. K i is obtained by fitting with the following formula:

[0136]

[0137] K i —Inhibition constant of the inhibitor

[0138] [S]—Saturated substrate concentration

[0139] K m —Michaelis constant of the enzyme

[0140] Table 24. Summary of laboratory enzyme activity detection results

[0141] Sample Purity <![CDATA[K i (nM)]]> Oil-like technical material 87.2％ 26.9 Technical material sample 1 after crystallization 99.1％ 10.3 Technical material sample 2 after crystallization 99.5％ 12.4

[0142] K i The smaller the value, the stronger the inhibitory ability on the enzyme and the higher the activity of the compound. It can be seen from the table that the K i value of the sample after crystallization decreased by about 60% on average (from 26.9 nM to 11.35 nM), indicating that crystallization significantly enhanced the target inhibitory ability of the drug. The speculated reason: The amorphous structure may lead to disordered arrangement of drug molecules, insufficient exposure of active sites or interference from impurities and solvents; while after crystallization, due to the reduction of impurities, the molecular arrangement is orderly, and the active sites are more likely to bind to the target, and its activity is significantly improved. In practical applications, the crystallization process can improve the biological activity of drugs and provide a basis for selecting a preparation method of high-purity and high-activity drugs.

[0143] Example 5. Bioassay experiment

[0144] Test weeds: Echinochloa crusgalli, Setaria viridis, Digitaria sanguinalis.

[0145] Test agents: Select the oily crude drug and the crude drug crystallized according to the method of Example 1

[0146] Test method: After dissolving the original drug with acetone or DMF, prepare the test solution of the required concentration with 1‰ Tween 80 aqueous solution according to the test requirements. Use the stem and leaf spray method (NY / T 1155.4-2006): Fill a pot with a height of 11cm and a diameter of 9cm with a certain amount of soil to 3 / 4 of the pot, sow the test targets (barnyard grass, foxtail grass, and crabgrass) on the surface of the pot soil, cover with about 1cm of fine soil, and then culture in a greenhouse. When the weeds grow to 4-5 leaves, spray the stems and leaves. Set different dosage gradients of the drugs, and the application dosage: the three drugs are applied according to the effective ingredients of 30g.ai / ha, 15g.ai / ha, 7.5gai / ha, and 3.75gai / ha respectively. Each treatment is repeated 4 times, and the treatment without the drug is set as the control. After the treatment, the test materials are cultured in the greenhouse and the growth of the weeds is observed regularly.

[0147] Investigation method: Experimental treatment to visually observe the symptoms of target damage and growth inhibition

[0148] Table 25. Effect of post-emergence compounds on weed control in greenhouse

[0149]

[0150] As can be seen from the table, the table (Table 25) systematically shows the greenhouse post-emergence control effects of three samples (oil-based technical, crystallized technical sample 1 and crystallized technical sample 2) at different doses (3.75–30 g ai / ha) on barnyard grass, foxtail grass and crabgrass. The data show that the control effect significantly increases with the increase in dose, and the crystallized sample performs better at low doses: for example, the control rates of crystallized technical sample 1 on barnyard grass, foxtail grass and crabgrass at 15 g ai / ha are 90%, 95% and 85%, respectively, while the oil-based technical requires a dose of 30 g to achieve 100% control. The low-dose high efficiency of the crystallized sample (such as 60% control rate for barnyard grass at 3.75 g) is significantly better than that of the oil-based technical (only 50% at the same dose), and the dose sensitivity difference for difficult-to-control weeds such as crabgrass is particularly obvious, indicating that crystallization treatment improves the biological activity and cost-effectiveness of the compound by reducing impurities.

Claims

1. A method for the crystallization purification of a benzoxazine compound, characterized in that First, dissolve Compound I in a crystallization solvent, and then precipitate crystals by volatilization or cooling; Compound I has the following chemical structure:

2. The method according to claim 1, wherein Dissolve Compound I in a crystallization solvent at room temperature; or dissolve Compound I in a crystallization solvent by means of ultrasonic treatment or heating.

3. The method according to claim 2, wherein The temperature of the heating is 30 - 100 °C, preferably 30 - 80 °C; when precipitating crystals by cooling, cool to below 30 °C, preferably below room temperature, and more preferably below 0 °C.

4. The method according to claim 1, wherein The crystallization solvent is selected from aromatic hydrocarbon solvents, halogenated hydrocarbon solvents, aliphatic hydrocarbon solvents, alcohol solvents, ether solvents, ester solvents, ketone solvents or high-boiling solvents, or a mixed solvent of them, or a mixed solvent of them and water.

5. The method according to claim 4, wherein The crystallization purification method includes S1 or S2: S1. Weigh Compound I, and under ultrasonic or non-ultrasonic conditions, add a crystallization solvent until it reaches a clear solution state. With or without filtration, place the solution in a stable environment for volatile crystallization or cooling crystallization. S2. Weigh Compound I, add a crystallization solvent that has been heated or heated to a boiling state, reach a clear solution state, and with or without filtration, perform slow or rapid cooling crystallization on the solution.

6. The method according to claim 5, wherein In step S1, the crystallization solvent is selected from one or more of the following solvents: a1) Aromatic hydrocarbon solvents: toluene, o-xylene, m-xylene; a2) Halogenated hydrocarbon solvents: 1,2-dichloroethane, chloroform, epichlorohydrin, propylene oxide, 1,6-dichlorohexane, 1-chlorobutane; a3) Alcohol solvents: methanol; a4) Ether solvents: 1,4-dioxane, diethoxymethane, methyl tert-butyl ether, tetrahydrofuran; a5) Ester solvents: ethyl formate, butyl acetate, methyl acetate, ethyl acetate, isobutyl acetate, methyl propionate, ethyl propionate; a6) Ketone solvents: 2-butanone, acetone, acetylacetone; a7) High-boiling solvents: acetonitrile, dimethyl sulfoxide; a8) A mixed solvent of the following solvents and water: propylene oxide, acetonitrile, methanol, 1,4-dioxane, methyl acetate, 2-butanone, acetone, N,N-dimethylformamide.

7. The method according to claim 5, wherein In the slow cooling crystallization of step S2, the slow cooling crystallization is to cool the solution to room temperature for crystallization; the rapid cooling crystallization is to cool the solution to below 0 °C for crystallization.

8. The method according to claim 7, wherein In the slow cooling crystallization of step S2, the crystallization solvent is selected from one or more of the following solvents: b1) Aromatic hydrocarbon solvents: p-xylene; b2) Halogenated hydrocarbon solvents: 1,2-dichloroethane, chloroform, 2,2-dimethoxypropane, 1,6-dichlorohexane; b3) Alcohol solvents Recrystallization result summary: methanol; b4) Ether solvents: 1,4-dioxane, ethylene glycol diethyl ether; b5) Ester solvents: butyl acetate, ethyl acetate, isopropyl acetate, n-propyl acetate, sec-butyl acetate, ethyl chloroacetate, ethyl propionate, diethyl malonate; b6) Ketone solvents: 2-butanone; b7) High-boiling solvents: acetonitrile, N,N-dimethylformamide, formamide.

9. The method according to claim 7, wherein In the rapid cooling crystallization in step S2, the crystallization solvent is selected from one or more of the following solvents: c1) Aromatic hydrocarbons: ethylbenzene, m-xylene; c2) Halogenated hydrocarbon solvents: epichlorohydrin, propylene oxide, 2,2-dimethoxypropane, 1,6-dichlorohexane; c3) Alcohol solvents: methanol, isopropanol, isobutanol, isoamyl alcohol, n-propanol, n-butanol, n-pentanol, sec-butanol, 95% ethanol; c4) Ether solvents: 1,4-dioxane; c5) Ester solvents: butyl acetate, methyl acetate, n-propyl acetate, sec-butyl acetate, ethyl chloroacetate, butyl acrylate; c6) Ketone solvents: 2-butanone, acetone, acetylacetone; c7) High-boiling solvents: acetonitrile.

10. A method for the crystallization purification of a benzoxazine compound, characterized in that After dissolving compound I by mixing it with a good solvent, an anti-solvent is slowly added to precipitate a solid, and the solid is collected and dried; compound I has the following chemical structure:

11. The method according to claim 10, wherein The good solvent is selected from one or more of aromatic hydrocarbon solvents, halogenated hydrocarbon solvents, alcohol solvents, ketone solvents, ester solvents, and high-boiling solvents. Preferably, the good solvent is selected from 1,2-dichloroethane or toluene; The anti-solvent is selected from one or more of aliphatic hydrocarbon solvents and ether solvents; preferably, the anti-solvent is selected from petroleum ether, n-hexane, n-octane, n-pentane, or n-heptane.

12. Use of the crystallization purification method of the benzoxazine compound according to claim 1 or 10 in the preparation of a herbicidal composition or a herbicidal preparation.

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