Preparation method and application of a methoxyfenoxam II crystal sample

Abstract

The present invention provides a preparation method and application of a benzathine chlorpyrifos II crystal form sample, the preparation method comprising the following steps: (1) dissolving benzathine chlorpyrifos in a C1-C4 alcohol and toluene mixed solution, then adding acid to obtain a solid precipitate; (2) dissolving the solid precipitate obtained in step (1) with a methanol solution, then mixing with a sodium hydroxide solution, adjusting the pH value, and obtaining a pure benzathine chlorpyrifos; (3) dissolving the pure benzathine chlorpyrifos obtained in step (2) in a mixed solution of toluene and an organic solvent, heating, then cooling, and adding triethylamine to obtain the benzathine chlorpyrifos II crystal form sample. The preparation method of the benzathine chlorpyrifos II crystal form sample provided by the present invention is simple to operate, has a small solvent demand, and has a high product purity.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to a preparation method and application of a fenpyroxene II crystal sample, and in particular to a preparation method and application of a fenpyroxene II crystal sample with high purity. Background Art

[0002] Benpyrazone is a new type of pyrazolone post-emergence stem and leaf treatment systemic herbicide. It is an HPPD inhibitor with systemic conduction and can be absorbed by the leaves, roots and stems of plants. It has the advantages of a wide spectrum of weed control, high activity, strong miscibility, and safety for corn and subsequent crops. It is a cornfield herbicide with the highest safety. Among them, the conventional preparation method of benpyrazone crystal form II is to prepare it in toluene, and the solubility is extremely low. For example, 1g of benpyrazone requires 60g of toluene to dissolve. The crystallization process is natural volatilization, and the solvent demand is very large. If it is produced industrially, it will lead to extremely low equipment utilization, high solvent demand, and high energy consumption.

[0003] CN101687862B reports a method for preparing multiple crystal forms such as crystal forms I, II, and III using 96% raw material fenpyroxene, and provides characterization data for each crystal form. After the crystal form transformation, the melting range is only 1°C, showing the characteristics of high purity.

[0004] The existing preparation methods of benzathine chlorpyrifos crystal form II have the problems of extremely low equipment utilization, high solvent demand and high energy consumption. Therefore, how to provide a preparation method of benzathine chlorpyrifos crystal form II sample with high purity and low solvent demand has become an urgent problem to be solved. Summary of the invention

[0005] In view of the deficiencies in the prior art, the object of the present invention is to provide a preparation method and application of a methoxyfenoxam II crystal sample, and in particular to provide a preparation method and application of a methoxyfenoxam II crystal sample with high purity. The preparation method of the methoxyfenoxam II crystal sample provided by the present invention is simple to operate, requires less solvent, and has high product purity.

[0006] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0007] In one aspect, the present invention provides a method for preparing a crystalline sample of fenpyroxetine II, the preparation method comprising the following steps:

[0008] (1) dissolving fenpyroxetine in a mixed solution of a C1-C4 alcohol and toluene, and then adding an acid to obtain a solid precipitate;

[0009] (2) dissolving the solid precipitate obtained in step (1) with a methanol solution, then mixing with a sodium hydroxide solution, and adjusting the pH value to obtain a pure product of fenthion;

[0010] (3) dissolving the pure product of fenpyroxetine obtained in step (2) in a mixed solution of toluene and an organic solvent, heating, then cooling, and adding triethylamine to obtain the fenpyroxetine II crystal sample.

[0011] The preparation method selects a specific solution and conditions to treat fenpyroxil, and the purity of the obtained fenpyroxil II crystal form is as high as more than 99%. At the same time, the preparation process requires less solvent.

[0012] Preferably, the purity of the fenpyrotonic acid in step (1) is not less than 90%.

[0013] Preferably, the volume fraction of the C1-C4 alcohol in the mixed solution of the C1-C4 alcohol and toluene in step (1) is not higher than 50%.

[0014] Wherein, C1-C4 refers to a composition containing one carbon atom, two carbon atoms, three carbon atoms or four carbon atoms, respectively. The C1-C4 alcohol can be, for example, any one of methanol, ethanol, n-propanol or isopropanol.

[0015] The purity of fenpyrazone can be 90%, 91%, 92%, 93%, 94%, 95% or 96%, etc., and the volume fraction of C1-C4 alcohol can be 50%, 45%, 40%, 35%, 30% or 25%, etc., but are not limited to the values ​​listed above, and other values ​​not listed within the above numerical range are also applicable.

[0016] Preferably, the acid in step (1) is a C1-C5 hydroxyl-containing organic acid, and the C1-C5 hydroxyl-containing organic acid includes any one of L-malic acid, D-malic acid, L-tartaric acid, D-tartaric acid or D-lactic acid.

[0017] Preferably, the molar ratio of fenpyroxetine to acid in step (1) is 1:1-1:1.2.

[0018] Preferably, the pH value in step (2) is 6.8-8.

[0019] The molar ratio of fenpyroxil to acid may be 1:1, 1:1.05, 1:1.1, 1:1.15 or 1:1.2, and the pH value may be 6.8, 6.9, 7, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9 or 8, but is not limited to the values ​​listed above, and other values ​​not listed within the above numerical range are also applicable.

[0020] Preferably, the organic solvent in step (3) comprises any one of C1-C5 alcohol, acetonitrile, acetone, tetrahydrofuran or methyl tert-butyl ether, or a combination of at least two thereof, such as a combination of acetonitrile and acetone, a combination of C1-C5 alcohol and acetonitrile, or a combination of tetrahydrofuran and acetone, but is not limited to the combinations listed above. Other combinations not listed within the above combination range are also applicable.

[0021] The C1-C5 alcohol may be any one of methanol, ethanol, n-propanol or isopropanol.

[0022] Preferably, the volume fraction of the organic solvent in the mixed solution of toluene and organic solvent in step (3) is not greater than 30%.

[0023] Preferably, the molar amount of triethylamine in step (3) is 1-3% of the molar amount of fenpyroxetine in step (1).

[0024] Preferably, when triethylamine is added in step (3), the temperature of the mixed solution of toluene and organic solvent is 40-50°C.

[0025] Wherein, the volume fraction of the organic solvent can be 30%, 25%, 20%, 15% or 10%, etc., the molar amount of triethylamine can be 1%, 1.2%, 1.4%, 1.6%, 1.8%, 2%, 2.2%, 2.4%, 2.6%, 2.8% or 3% of the molar amount of the benzathine in step (1), etc., and the temperature can be 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C or 50°C, etc., but are not limited to the values ​​listed above, and other values ​​not listed within the above numerical range are equally applicable.

[0026] On the other hand, the present invention also provides the use of the preparation method of the methoxyfenoxam II crystal sample as described above in the preparation of herbicides.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] The invention provides a method for preparing a fenpyroxene II crystal sample. By selecting a specific solution and conditions to process fenpyroxene, the purity of the obtained fenpyroxene II crystal is as high as more than 99%. At the same time, the preparation process is simple to operate and requires a small amount of solvent. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The irregular flaky polarized light microscopic morphology of the methamidoprop-II crystal sample provided in Example 1;

[0030] Figure 2 The regular flaky polarized light microscopic morphology of the methamidoprop-II crystal sample provided in Example 1;

[0031] Figure 3 This is the regular granular polarized light microscopic morphology of the methamidoprop-II crystal sample provided in Example 1. DETAILED DESCRIPTION

[0032] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0033] Example 1

[0034] This embodiment provides a method for preparing a crystalline sample of fenpyroxetine II, and the operating steps are as follows:

[0035] The 95% pure benzathine (50g, 0.137mol) was dissolved in a mixed solvent (550mL) of methanol (50%) and toluene (50%), stirred, and then 18g (0.137mol) of L-malic acid was slowly added to form a solid precipitate. After all the addition was completed, the mixture was stirred for 2 hours, and the solid precipitate was fully precipitated. After vacuum filtration and drying, the solid precipitate was added to a mixed solvent (600mL) of methanol and water, and then the pH value was adjusted to 6.8 with a 0.1mol / L NaOH aqueous solution to obtain a pure product of benzathine with a purity of 98.8% and a yield of 87%.

[0036] 30g of the above-mentioned pure product of benzathiapiprolin was added to a mixed solution (250mL) of toluene (70%) and ethanol (30%), heated under reflux until it was just dissolved, and slowly cooled. When the temperature was 40°C, 0.17g of triethylamine was added dropwise, and a sample of benzathiapiprolin crystal form II was precipitated. After suction filtration and drying, 27.3g of a sample of benzathiapiprolin crystal form II was obtained, with a yield of 91% and a purity of 99.3%. The sample has irregular flaky polarized microscopic morphology, regular flaky polarized microscopic morphology, and regular granular polarized microscopic morphology, respectively. Figure 1-3 .

[0037] Example 2

[0038] This embodiment provides a method for preparing a crystalline sample of fenpyroxetine II, and the operating steps are as follows:

[0039] The 90% pure benzathine (50 g, 0.137 mol) was dissolved in a mixed solvent (550 mL) of isopropanol (40%) and toluene (60%), stirred, and then 21.6 g (0.164 mol) of D-malic acid was slowly added to precipitate a solid. After all the addition was completed, the mixture was stirred for 2 hours, and the solid precipitate was fully precipitated. After vacuum filtration and drying, the solid precipitate was added to a mixed solvent (600 mL) of methanol and water, and then adjusted to pH 8 with a 0.1 mol / L NaOH aqueous solution to obtain a pure benzathine with a purity of 98.6% and a yield of 84%.

[0040] 30 g of the above-mentioned pure product of benzathine was added to a mixed solution (250 mL) of toluene (80%) and methanol (20%), heated under reflux until it was just dissolved, and slowly cooled. When the temperature was 50°C, 0.1 g of triethylamine was added dropwise, and a benzathine crystal II sample was precipitated. After filtration and drying, 27.1 g of benzathine crystal II sample was obtained, with a yield of 90% and a purity of 99.4%.

[0041] Example 3

[0042] This embodiment provides a method for preparing a crystalline sample of fenpyroxetine II, and the operating steps are as follows:

[0043] The 90% pure benzathine (50 g, 0.137 mol) was dissolved in a mixed solvent (550 mL) of ethanol (30%) and toluene (70%), stirred, and then 19.8 g (0.151 mol) of L-malic acid was slowly added to form a solid precipitate. After all the addition was completed, the mixture was stirred for 2 hours, and the solid precipitate was fully precipitated. After vacuum filtration and drying, the solid precipitate was added to a mixed solvent (600 mL) of methanol and water, and then the pH value was adjusted to 7.5 with a 0.1 mol / L NaOH aqueous solution to obtain a pure product of benzathine with a purity of 98.9% and a yield of 87%.

[0044] 30 g of the above-mentioned pure product of benomyl was added to a mixed solution (250 mL) of toluene (85%) and isopropanol (15%), heated under reflux until it was just dissolved, and slowly cooled. When the temperature was 45°C, 0.25 g of triethylamine was added dropwise, and a benomyl crystalline II sample was precipitated. After filtration and drying, 27.9 g of a benomyl crystalline II sample was obtained, with a yield of 93% and a purity of 99.6%.

[0045] Example 4

[0046] This embodiment provides a method for preparing a crystalline sample of fenpyroxetine II, and the operating steps are as follows:

[0047] The 95% pure benzathine (50g, 0.137mol) was dissolved in a mixed solvent (550mL) of methanol (50%) and toluene (50%), stirred, and then 18g (0.137mol) of L-malic acid was slowly added to form a solid precipitate. After all the addition was completed, the mixture was stirred for 2 hours, and the solid precipitate was fully precipitated. After vacuum filtration and drying, the solid precipitate was added to a mixed solvent (600mL) of methanol and water, and then the pH value was adjusted to 6.8 with a 0.1mol / L NaOH aqueous solution to obtain a pure product of benzathine with a purity of 98.8% and a yield of 87%.

[0048] 30 g of the above-mentioned pure product of benzathine was added to a mixed solution (250 mL) of toluene (60%) and ethanol (40%), heated under reflux until it was just dissolved, and slowly cooled. When the temperature was 40°C, 0.17 g of triethylamine was added dropwise, and a benzathine crystal II sample was precipitated. After filtration and drying, 25 g of the benzathine crystal II sample was obtained, with a yield of 83% and a purity of 99.1%.

[0049] Example 5

[0050] This embodiment provides a method for preparing a crystalline sample of fenpyroxetine II, and the operating steps are as follows:

[0051] The 95% pure benzathine (50g, 0.137mol) was dissolved in a mixed solvent (550mL) of methanol (50%) and toluene (50%), stirred, and then 18g (0.137mol) of L-malic acid was slowly added to form a solid precipitate. After all the addition was completed, the mixture was stirred for 2 hours, and the solid precipitate was fully precipitated. After vacuum filtration and drying, the solid precipitate was added to a mixed solvent (600mL) of methanol and water, and then the pH value was adjusted to 6.8 with a 0.1mol / L NaOH aqueous solution to obtain a pure product of benzathine with a purity of 98.8% and a yield of 87%.

[0052] 30 g of the above-mentioned pure product of benzathine was added to a mixed solution (250 mL) of toluene (70%) and ethanol (30%), heated under reflux until it was just dissolved, and slowly cooled. When the temperature was 40°C, 0.04 g of triethylamine was added dropwise, and a benzathine crystal II sample was precipitated. After filtration and drying, 24.1 g of the benzathine crystal II sample was obtained, with a yield of 80% and a purity of 99.0%.

[0053] Example 6

[0054] This embodiment provides a method for preparing a crystalline sample of fenpyroxetine II, and the operating steps are as follows:

[0055] The 95% pure benzathine (50g, 0.137mol) was dissolved in a mixed solvent (550mL) of methanol (50%) and toluene (50%), stirred, and then 18g (0.137mol) of L-malic acid was slowly added to form a solid precipitate. After all the addition was completed, the mixture was stirred for 2 hours, and the solid precipitate was fully precipitated. After vacuum filtration and drying, the solid precipitate was added to a mixed solvent (600mL) of methanol and water, and then the pH value was adjusted to 6.8 with a 0.1mol / L NaOH aqueous solution to obtain a pure product of benzathine with a purity of 98.8% and a yield of 87%.

[0056] 30 g of the above-mentioned pure product of benzathine was added to a mixed solution (250 mL) of toluene (70%) and ethanol (30%), heated under reflux until it was just dissolved, and slowly cooled. When the temperature was 40°C, 0.35 g of triethylamine was added dropwise, and a benzathine crystal II sample was precipitated. After filtration and drying, 24.6 g of the benzathine crystal II sample was obtained, with a yield of 82% and a purity of 99.0%.

[0057] The above data show that the methoxyfenoxam II crystal sample prepared by the preparation method provided by the present invention has high purity and low solvent consumption.

[0058] The applicant declares that the present invention illustrates the preparation method of the methoxyfenoxam II crystal sample of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned embodiments, that is, it does not mean that the present invention must rely on the above-mentioned embodiments to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

[0059] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0060] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

Claims

1. A method for preparing fenpyrazone, characterized in that: The preparation method comprises the following steps: (1) dissolving fenpyroxetine in a mixed solution of C1-C4 alcohol and toluene, and then adding an acid to obtain a solid precipitate; (2) dissolving the solid precipitate obtained in step (1) with a methanol solution, then mixing with a sodium hydroxide solution, and adjusting the pH value to obtain a pure product of fenthion; (3) dissolving the pure product of fenpyrazone obtained in step (2) in a mixed solution of toluene and an organic solvent, heating, then cooling, and adding triethylamine to obtain the fenpyrazone; The acid in step (1) is a C1-C5 hydroxyl-containing organic acid.

2. The method for preparing fenpyrazone according to claim 1, characterized in that: The purity of the fenpyrotone in step (1) is not less than 90%.

3. The method for preparing fenpyrazone according to claim 1, characterized in that: The volume fraction of C1-C4 alcohol in the mixed solution of C1-C4 alcohol and toluene in step (1) is not higher than 50%.

4. The method for preparing fenpyrazone according to claim 1, characterized in that: The C1-C5 hydroxyl-containing organic acid is selected from any one of L-malic acid, D-malic acid, L-tartaric acid, D-tartaric acid or D-lactic acid.

5. The method for preparing fenpyrazone according to claim 1, characterized in that: In step (1), the molar ratio of fenpyrotone to acid is 1:1-1:1.

2.

6. The method for preparing fenpyrazone according to claim 1, characterized in that: The pH value of step (2) is 6.8-8.

7. The method for preparing fenpyrazone according to claim 1, characterized in that: The organic solvent in step (3) is selected from any one of C1-C5 alcohol, acetonitrile, acetone, tetrahydrofuran or methyl tert-butyl ether, or a combination of at least two thereof.

8. The method for preparing fenpyrazone according to claim 1, characterized in that: The volume fraction of the organic solvent in the mixed solution of toluene and organic solvent in step (3) is not more than 30%.

9. The method for preparing fenpyrazone according to claim 1, characterized in that: The molar amount of triethylamine in step (3) is 1-3% of the molar amount of fenthion in step (1).

10. The method for preparing fenpyrazone according to claim 1, characterized in that: When adding triethylamine in step (3), the temperature of the mixed solution of toluene and organic solvent is 40-50°C.

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