Spirotetramat metastable crystal form II, preparation method and application thereof and insecticide

Abstract

The invention relates to the technical field of pesticide crystallization, in particular to a spirotetramat metastable crystal form II, a preparation method and application thereof and a pesticide. The preparation method of the spirotetramat metastable crystal form II comprises the following steps: 1) mixing a good solvent with a spirotetramat crystal form I to obtain a spirotetramat solution; and 2) adding an anti-solvent and a seed crystal of the spirotetramat metastable crystal form II into the spirotetramat solution obtained in the step 1), and carrying out solvent-out crystallization, crystal growing and solid-liquid separation to obtain the spirotetramat metastable crystal form II, the spirotetramat metastable crystal form II obtained by the preparation method provided by the invention is a spherical particle, the particle size is in a micron level and is uniformly distributed, and the particle size is uniform. A good solvent, an anti-solvent and a seed crystal suitable for the method are selected, so that the supersaturation degree of the system can be adjusted, and nucleation and growth of the crystal are facilitated.

Description

Technical Field

[0001] The invention relates to the technical field of pesticide crystallization, and in particular to a spirotetramat metastable crystal form II, a preparation method and application thereof, and an insecticide. Background Art

[0002] Spirotetramat is a modern tetronic acid derivative insecticide with a bidirectional systemic conduction type, which is mainly stomach poison and supplemented by contact poison. Its mechanism of action is to inhibit the activity of acetyl-CoA carboxylase (ACCase) in the process of fat synthesis in the pest body, inhibit fat synthesis, block the normal metabolic ability of the pest, and cause its death. Spirotetramat can be applied to most crops including but not limited to cotton, soybeans, tropical fruit trees, nuts, grapes, vegetables, etc. to effectively prevent and control various piercing-sucking mouthparts pests. It has the characteristics of thorough insecticide and has a good control effect on hidden pests and shelled pests. And it has the advantages of broad-spectrum insecticide and long-lasting effect. The chemical structure of spirotetramat is as follows:

[0003]

[0004] Spirotetramat is mainly reported in two solid forms: amorphous and crystal form I. This patent reports a new solution preparation method for metastable crystal form II. Crystal form II shows better stability than amorphous, and is stable in normal temperature and humidity stability and accelerated stability tests for up to three months. It can also be stable in water without crystal transformation, and can replace the current commercial crystal form I. Therefore, it is urgent to develop a stable preparation process for spirotetramat crystal form II, especially a solution crystallization preparation method. Spirotetramat crystal form II can be prepared by melt crystallization to create a very high supersaturation, but the melt crystallization preparation process has problems such as high temperature, severe product agglomeration, and difficult discharge, resulting in environmentally unfriendly problems such as long time consumption during the pre-treatment of formulation development, including but not limited to grinding, sieving and other operations, and severe flying powder. Therefore, it is necessary to further explore a crystallization method that can stably prepare spherical spirotetramat metastable crystal form II particles with uniform particle size. Summary of the invention

[0005] The purpose of the present invention is to overcome the problems of serious agglomeration of melt crystallization products and uneven particles in the preparation process of spirotetramat crystal form II, and provide a preparation method of spirotetramat metastable crystal form II. The spirotetramat metastable crystal form II obtained by the preparation method provided by the present invention is spherical particles with a particle size at the micron level and uniform distribution. In addition, the addition of a good solvent, an anti-solvent and a seed crystal suitable for the present invention can adjust the supersaturation of the system, which is conducive to the nucleation and growth of the crystal.

[0006] In order to achieve the above-mentioned object, the first aspect of the present invention provides a method for preparing the metastable crystal form II of spirotetramat, characterized in that the method comprises the following steps:

[0007] 1) mixing a good solvent with the spirotetramat crystal form I to obtain a spirotetramat solution;

[0008] 2) adding the spirotetramat solution obtained in step 1) to an anti-solvent, and then performing dissolution crystallization, crystal cultivation, and solid-liquid separation with spirotetramat metastable crystal form II seed crystals to obtain spirotetramat metastable crystal form II,

[0009] Wherein, the good solvent is one or more of alcohols with carbon atoms of 1-4, ketones with carbon atoms of 3-5, and benzene solvents with carbon atoms of 6-12;

[0010] The anti-solvent is water and / or n-hexane,

[0011] The volume ratio of the good solvent to the anti-solvent is 1:3-40, and the temperature of the anti-solvent is controlled at 0-10°C.

[0012] Preferably, the good solvent is one or more of methanol, ethanol, propanol, butanol, acetone, butanone, pentanone, toluene and xylene; more preferably, the good solvent is one or more of methanol, ethanol, acetone and toluene.

[0013] Preferably, the amount of the good solvent used is such that the spirotetramat crystalline form I solution is in a saturated state.

[0014] Preferably, the volume ratio of the good solvent to the anti-solvent is 1:5-20.

[0015] Preferably, the mixing conditions include: temperature of 25-60° C. and time of 0.3-24 h.

[0016] Preferably, before performing step 2), a step of controlling the temperature of the anti-solvent is also included.

[0017] Preferably, the temperature of the anti-solvent is controlled at 0-5°C.

[0018] Preferably, the amount of the metastable spirotetramat crystal form II seed added is 0.2-2 weight % of the amount of spirotetramat crystal form I added in step 1).

[0019] Preferably, the particle size of the metastable form II seed crystals of spirotetramat is 100-600 mesh; more preferably, the particle size of the metastable form II seed crystals of spirotetramat is 100-300 mesh.

[0020] Preferably, the dissolution crystallization comprises the steps of adding metastable crystal form II seed crystals of spirotetramat into an anti-solvent, and dripping the supernatant of the mixed spirotetramat solution into the anti-solvent for anti-dissolution.

[0021] Preferably, in step 2), the method further comprises a drying step after the solid-liquid separation.

[0022] Preferably, the drying conditions include: a drying temperature of 20-40° C. and a drying time of 8-60 min.

[0023] Preferably, the crystal growing conditions include: a crystal growing temperature of 1-10° C. and a crystal growing time of 2-300 min.

[0024] The second aspect of the present invention provides spirotetramat metastable crystal form II prepared by the preparation method of spirotetramat metastable crystal form II described in the first aspect of the present invention.

[0025] Preferably, the Dv(50) of the metastable crystal form II of spirotetramat is 60-150 μm; more preferably, the Dv(50) of the metastable crystal form II of spirotetramat is 90-120 μm.

[0026] The third aspect of the present invention provides the use of the spirotetramat metastable crystal form II described in the second aspect of the present invention in the preparation of insecticides.

[0027] The fourth aspect of the present invention provides an insecticide, wherein the insecticide contains the spirotetramat metastable crystal form II prepared by the preparation method of spirotetramat metastable crystal form II described in the first aspect of the present invention or the spirotetramat metastable crystal form II described in the second aspect of the present invention as an active ingredient.

[0028] The spirotetramat metastable crystal form II obtained by the above technical solution has the advantages of small particle size and uniform particle size distribution. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is the PXRD powder diffraction pattern of the metastable crystal form II of spirotetramat obtained in Example 1 of the present invention.

[0030] Figure 2 This is a desktop scanning electron microscope image of the metastable crystal form II of spirotetramat obtained in Example 1 of the present invention.

[0031] Figure 3 This is a particle size distribution diagram of the metastable crystal form II of spirotetramat obtained in Example 1 of the present invention.

[0032] Figure 4 This is the PXRD powder diffraction pattern of the mixed crystal product of spirotetramat crystal form I and crystal form II obtained in Comparative Example 1 of the present invention.

[0033] Figure 5 This is the PXRD powder diffraction pattern of the spirotetramat II mixed crystal product obtained in Comparative Example 2 of the present invention. DETAILED DESCRIPTION

[0034] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0035] According to a first aspect of the present invention, a method for preparing a metastable crystal form II of spirotetramat is provided, wherein the method comprises the following steps:

[0036] 1) mixing a good solvent with the spirotetramat crystal form I to obtain a spirotetramat solution;

[0037] 2) adding the spirotetramat solution obtained in step 1) to an anti-solvent, and then performing dissolution crystallization, crystal cultivation, and solid-liquid separation with spirotetramat metastable crystal form II seed crystals to obtain spirotetramat metastable crystal form II,

[0038] Wherein, the good solvent is one or more of alcohols with 1 to 4 carbon atoms, ketones with 3 to 5 carbon atoms, and benzenes with 6 to 12 carbon atoms;

[0039] The anti-solvent is water and / or n-hexane,

[0040] The volume ratio of the good solvent to the anti-solvent is 1:3-40, and the temperature of the anti-solvent is controlled at 0-10°C.

[0041] In the present invention, a specific good solvent is required to achieve the purpose of the present invention. In the present invention, a good solvent selected from alcohols with 1 to 4 carbon atoms, ketones with 3 to 5 carbon atoms, and benzene solvents with 6 to 12 carbon atoms is used in combination with the anti-solvent of the present invention to obtain a metastable crystal form and achieve the purpose of the present invention.

[0042] According to the present invention, preferably, the good solvent is one or more of methanol, ethanol, propanol, butanol, acetone, butanone, pentanone, toluene and xylene; more preferably, the good solvent is one or more of methanol, ethanol, acetone and toluene.

[0043] According to the present invention, preferably, the volume ratio of the good solvent to the anti-solvent is 1:5-20.

[0044] According to the present invention, preferably, the amount of the good solvent used is such that the spirotetramat crystalline form I solution is in a saturated state.

[0045] According to the present invention, in step 1), in order to avoid the occurrence of mixed crystals during reverse dissolution crystallization, the temperature and temperature uniformity of spirotetramat suspension in the good solvent are improved, and the mixing conditions include: temperature of 25-60° C. and time of 0.3-24 h; more preferably, the mixing conditions include: temperature of 40-60° C. and time of 1-5 h.

[0046] According to the present invention, after the mixing, a step of controlling the temperature of the anti-solvent is further included. Preferably, the temperature of the anti-solvent is controlled at 0-10°C; more preferably, the temperature of the anti-solvent is controlled at 0-5°C.

[0047] In a preferred embodiment of the present invention, the anti-solvent can be added to the crystallizer, and the temperature of the anti-solvent can be controlled by an ice machine, and then the temperature can be kept constant for 30-60 minutes at this temperature. For example, 40 mL of the anti-solvent is added to a 100 mL jacketed crystallizer, and the temperature is lowered to 2° C. by an ice machine and kept constant for 30 minutes.

[0048] According to the present invention, preferably, in step 2), the dissolution crystallization comprises: adding metastable crystal form II seed of spirotetramat to an anti-solvent, and dripping the supernatant of the mixed spirotetramat solution into the anti-solvent for anti-dissolution; more preferably, the dissolution crystallization comprises: adding metastable crystal form II seed of spirotetramat to an anti-solvent, and dripping the supernatant of the mixed spirotetramat solution into the anti-solvent for anti-dissolution.

[0049] The dripping speed may be, for example, 0.3-10 mL / s, preferably 0.3-5 mL / s, and more preferably 0.3-4 mL / s, relative to 40 mL of the anti-solvent.

[0050] In the present invention, "relative to 40 mL of anti-solvent" means that the dripping rate is relative to 40 mL of anti-solvent. Specifically, when the dripping rate of 40 mL of anti-solvent is 1 mL / s, the dripping rate when using 40 mL of anti-solvent should be 2 mL / s, and so on.

[0051] According to the present invention, in step 2), in order to obtain the metastable crystal form II of spirotetramat, it is necessary to add spirotetramat metastable crystal form II seed crystals. Preferably, the added amount of the spirotetramat metastable crystal form II seed crystals is 0.2-10 weight % of the amount of spirotetramat crystal form I added in step 1).

[0052] The metastable crystal form II of spirotetramat can reduce the supersaturation of the system, which is beneficial to the nucleation and growth of crystals. During the experiment, it was found that without adding the metastable crystal form II of spirotetramat, even if other process parameters were optimized, such as crystallization temperature and the dripping rate of spirotetramat solution, the crystals would still explode into nuclei in the crystallizer, agglomerate severely, and have uneven particle size distribution, showing stratification. This is because the metastable zone of spirotetramat is wide, which can accumulate a high supersaturation, and a large number of fine products are generated during the explosion of nucleation, making it difficult to post-process.

[0053] According to the present invention, in order to obtain spirotetramat metastable form II with small particle size and uniform particle size distribution, preferably, the particle size of the spirotetramat metastable form II seed crystals is 100-600 mesh; more preferably, the particle size of the spirotetramat metastable form II seed crystals is 100-300 mesh.

[0054] According to the present invention, the crystal growing refers to the process of continuously consuming the higher supersaturation in the system for a period of time. The generation of crystal nuclei and crystal growth require time, and too long a time will lead to the appearance of mixed crystals. Preferably, the crystal growing conditions include: a crystal growing temperature of 1-10°C and a crystal growing time of 2-300min; more preferably, the crystal growing conditions include: a crystal growing temperature of 2-5°C and a crystal growing time of 2-50min.

[0055] According to the present invention, the solid-liquid separation may be performed using methods commonly used in the art without particular limitation. For example, a filtration method may be used to obtain a solid.

[0056] According to the present invention, after the solid-liquid separation operation is performed, the step of drying the obtained solid is also included. Preferably, the drying conditions include: a drying temperature of 25-35°C and a drying time of 10-50min; more preferably, the drying conditions include: a drying temperature of 28-32°C and a drying time of 15-30min.

[0057] According to a second aspect of the present invention, there is provided a spirotetramat metastable crystal form II prepared by the method for spirotetramat metastable crystal form II described in the first aspect of the present invention.

[0058] According to the present invention, preferably, the Dv(50) of the spirotetramat metastable crystal form II is 60-150 μm; more preferably, the Dv(50) of the spirotetramat metastable crystal form II is 90-120 μm. At this time, the spirotetramat metastable crystal form II has a small particle size and a uniform particle size distribution, which can prevent agglomeration in the melt crystallization product and solve the problem of uneven particles.

[0059] According to the third aspect of the present invention, there is provided a use of the spirotetramat metastable crystal form II described in the second aspect of the present invention in the preparation of insecticides.

[0060] According to a fourth aspect of the present invention, there is provided an insecticide, which contains the spirotetramat metastable crystal form II prepared by the preparation method of spirotetramat metastable crystal form II described in the first aspect of the present invention or the spirotetramat metastable crystal form II described in the second aspect of the present invention as an active ingredient.

[0061] The present invention will be described in detail below by way of examples, but the present invention is not limited to the following examples.

[0062] 1) Crystal form testing instrument: powder diffractometer (PXRD)

[0063] Instrument model: MiniFlex600 from Rigaku, Japan

[0064] Test method: Tested at room temperature, Cu Kα radiation, 40kV, 15mA, scanning range 2-35°, scanning speed 8° / min

[0065] 2) Instrument for crystal morphology testing: desktop scanning electron microscope (SEM)

[0066] Instrument model: TM300 from Hitachi, Japan

[0067] 3) Instrument for testing product particle size distribution: Ultra-high-speed intelligent particle size analyzer

[0068] Instrument model: MASTER SIZER 3000, Malvern Instruments Ltd., UK

[0069] Test method: At room temperature, select the water phase test, use water as the dispersed phase, initialize the instrument, measure the background and add the product obtained in the embodiment until it meets the light shielding limit, start measuring and test 5 times, and take the average value, which is the particle size distribution of the product.

[0070] Purchased from Tianjin Xingke Instrument Co., Ltd., model XDH-C

[0071] Jacketed crystallizer: purchased from Tianjin Yipujia Technology Co., Ltd., specification: 100mL

[0072] Spirotetramat crystal form I: purchased from Jiangxi Huihe Chemical Co., Ltd., purity: 97%

[0073] Preparation method of spirotetramat crystal form II seed crystals: 500 mg of spirotetramat crystal form I is placed on a heating table and heated to 147°C until it is completely melted into a molten liquid, and the molten liquid is transferred to an ambient temperature of 85°C and maintained for 1 hour before crystallization to obtain spirotetramat crystal form II seed crystals, which are then ground and sieved to obtain spirotetramat crystal form II seed crystals with a particle size of 100-600 mesh.

[0074] Example 1

[0075] 1) Add 1.9 g of spirotetramat Form I into 10 mL of toluene, raise the temperature and maintain it at 50°C for 3.5 h;

[0076] 2) Add 40 mL of n-hexane to a 100 mL jacketed crystallizer and keep the temperature at 2°C for 30 min using an ice machine;

[0077] 3) After the constant temperature is completed, 20 mg of spirotetramat crystal form II seed (particle size of 100-300 mesh) is added to n-hexane, and 4 mL of the supernatant of 50°C spirotetramat toluene solution is quickly added dropwise to n-hexane for reverse dissolution-cooling coupled crystallization experiment (dropping time is 2 s). After crystal growth for 10 minutes, the product A of spirotetramat metastable crystal form II is obtained by rapid filtration and drying.

[0078] The crystal form, crystal morphology and crystal size distribution of the metastable crystal form II product A of spirotetramat were tested. The crystal form of the metastable crystal form II product A of spirotetramat obtained was pure metastable crystal form II, spherical, and Dv(50) was 90-120 μm, with uniform particle size distribution, such as Figure 3 shown.

[0079] The specific PXRD powder diffraction pattern of the metastable crystal form II of spirotetramat A is as follows Figure 1 As shown in the scanning electron microscope image Figure 2 The particle size distribution diagram is shown in Figure 3 As shown by Figure 1 It can be seen that the crystal form of spirotetramat metastable crystal form II product A is pure metastable crystal form II. Figure 2 It can be seen that the morphology of the metastable crystal form II of spirotetramat product A is spherical. Figure 3 It can be seen that the particle size distribution of spirotetramat metastable crystal form II product A is uniform.

[0080] Example 2

[0081] 1) Add 1.9 g of spirotetramat Form I into 10 mL of toluene, raise the temperature and maintain it at 50°C for 3.5 h;

[0082] 2) Add 40 mL of n-hexane to a 100 mL jacketed crystallizer and keep the temperature at 2°C for 30 min using an ice machine;

[0083] 3) After the constant temperature is completed, 10 mg of spirotetramat crystal form II seed (particle size of 100-300 mesh) is added to n-hexane, and 2 mL of the upper clear liquid of 50°C spirotetramat toluene solution is quickly dripped into n-hexane for reverse dissolution-cooling coupled crystallization experiment (dropping time is 1 s). After crystal growth for 10 minutes, the spirotetramat metastable crystal form II product B is quickly filtered and dried.

[0084] Through the PXRD powder diffraction pattern, scanning electron microscope image and particle size distribution diagram, it can be seen that the crystal form, crystal morphology and crystal particle size distribution of the tested spirotetramat metastable crystal form II product B are pure metastable crystal form II, spherical, with Dv(50) of 90-120μm and uniform particle size distribution.

[0085] Example 3

[0086] 1) Add 1.9 g of spirotetramat Form I into 10 mL of toluene, raise the temperature and maintain it at 50°C for 1.5 h;

[0087] 2) Add 40 mL of n-hexane to a 100 mL jacketed crystallizer and keep the temperature at 2°C for 30 min using an ice machine;

[0088] 3) After the constant temperature is completed, 30 mg of spirotetramat crystal form II seed (particle size of 100-300 mesh) is added to n-hexane, and 8 mL of the supernatant of 50°C spirotetramat toluene solution is quickly added dropwise to n-hexane for reverse dissolution-cooling coupled crystallization experiment (dropping time is 3 s). After crystal growth for 10 minutes, the product C of spirotetramat metastable crystal form II is obtained by rapid filtration and drying.

[0089] The PXRD powder diffraction pattern, scanning electron microscope image and particle size distribution diagram show that the crystal form, crystal morphology and crystal particle size distribution of spirotetramat metastable crystal form II product C are pure metastable crystal form II, spherical in shape, with a Dv(50) of 80-120 μm and uniform particle size distribution.

[0090] Example 4

[0091] 1) Add 3.2 g of spirotetramat Form I into 10 mL of acetone, raise the temperature and maintain it at 50°C for 1.5 h;

[0092] 2) Add 40 mL of deionized water to a 100 mL jacketed crystallizer and keep the temperature at 2°C for 30 min using an ice machine;

[0093] 3) After the constant temperature is completed, 10 mg of spirotetramat crystal form II seed (particle size of 100-300 mesh) is added to deionized water, and 8 mL of the supernatant of 50°C spirotetramat acetone solution is quickly added dropwise into deionized water for reverse dissolution-cooling coupled crystallization experiment (dropping time is 4 s). After crystal growth for 10 minutes, the product D of spirotetramat metastable crystal form II is obtained by rapid filtration and drying.

[0094] The PXRD powder diffraction pattern, scanning electron microscope image and particle size distribution diagram show that the crystal form, crystal morphology and crystal particle size distribution of spirotetramat metastable crystal form II product D are pure metastable crystal form II, spherical in shape, with a Dv(50) of 90-130 μm and a uniform particle size distribution.

[0095] Example 5

[0096] 1) Add 3.3 g of spirotetramat Form I into 10 mL of methanol, raise the temperature and maintain it at 50°C for 1.5 h;

[0097] 2) Add 40 mL of deionized water to a 100 mL jacketed crystallizer and keep the temperature at 2°C for 30 min using an ice machine;

[0098] 3) After the constant temperature is completed, 20 mg of spirotetramat crystal form II seed (particle size of 100-300 mesh) is added to deionized water, and 5 mL of the supernatant of spirotetramat methanol solution at 50°C is quickly dropped into deionized water for reverse dissolution-cooling coupled crystallization experiment (dropping time is 2 s). After crystal growth for 10 minutes, the product E of spirotetramat metastable crystal form II is obtained by rapid filtration and drying.

[0099] The PXRD powder diffraction pattern, scanning electron microscope image and particle size distribution diagram show that the crystal form, crystal morphology and crystal particle size distribution of spirotetramat metastable crystal form II product E are pure metastable crystal form II, spherical in shape, with a Dv(50) of 80-120 μm and uniform particle size distribution.

[0100] Example 6

[0101] The preparation was carried out according to Example 1, except that the crystal growing time in step 3) was 50 minutes, and the metastable crystal form II of spirotetramat product F was obtained.

[0102] The crystal form, crystal morphology and crystal particle size distribution of spirotetramat metastable crystal form II product F were tested. The crystal form of the obtained spirotetramat metastable crystal form II product F was pure metastable crystal form II, spherical, with a Dv(50) of 60-120 μm and a uniform particle size distribution.

[0103] Example 7

[0104] The preparation was carried out according to Example 1, except that the crystal growing time in step 3) was 5 hours, and the metastable crystal form II product G of spirotetramat was obtained.

[0105] The crystal form, crystal morphology and crystal particle size distribution of spirotetramat metastable crystal form II product G were tested. The crystal form of spirotetramat metastable crystal form II product G obtained was pure metastable crystal form II, spherical, with Dv(50) of 70-140μm and uniform particle size distribution.

[0106] Comparative Example 1

[0107] The method is the same as that in Example 5, except that the good solvent is acetonitrile, and spirotetramat product A is obtained.

[0108] The PXRD powder diffraction pattern of spirotetramat product A is as follows: Figure 4 As shown, the crystal form, crystal morphology and crystal particle size distribution of the spirotetramat product A crystals were tested. The obtained spirotetramat product A crystal form was a mixed crystal of crystal form I and crystal form II, which was agglomerated in blocks and strips. The particle size distribution was multimodal and wide.

[0109] Comparative Example 2

[0110] The method is the same as that in Example 5, except that the good solvent is propionitrile, and spirotetramat product B is obtained.

[0111] The crystal form, crystal morphology and crystal particle size distribution of spirotetramat product B crystals were tested, and the obtained spirotetramat product B crystals had a short rod-like shape and a wide particle size distribution.

[0112] The PXRD powder diffraction pattern of spirotetramat product B is as follows: Figure 5 As shown, the crystal form, crystal morphology and crystal particle size distribution of the spirotetramat product B crystals were tested, and the obtained spirotetramat product B crystals were form II mixed crystals, which were block-shaped and strip-shaped agglomerates, and the particle size distribution was multi-modal and wide.

[0113] Comparative Example 3

[0114] The method is the same as that in Example 5, except that the good solvent is N,N-dimethylformamide, and spirotetramat product C is obtained.

[0115] The crystal form, crystal morphology and crystal particle size distribution of spirotetramat product C crystals were tested, and the obtained crystal form of spirotetramat product C was crystal form I, which was short rod-shaped and had a multi-modal particle size distribution.

[0116] Comparative Example 4

[0117] The method is the same as that in Example 1, except that the good solvent is dimethyl sulfoxide, and spirotetramat product D is obtained.

[0118] The crystal form, crystal morphology and crystal particle size distribution of spirotetramat product D crystals were tested, and the obtained crystal form of spirotetramat product D was crystal form I, which was spherical and blocky, and the particle size distribution was multimodal.

[0119] Comparative Example 5

[0120] The method is the same as that in Example 5, except that the anti-solvent is n-heptane, and spirotetramat product E is obtained.

[0121] The crystal form, crystal morphology and crystal particle size distribution of the spirotetramat product E crystals were tested. The obtained crystal form of the spirotetramat product E was a mixed crystal of crystal form I and crystal form II, which was in the form of strip agglomeration and block. The particle size distribution was multi-modal and wide.

[0122] Comparative Example 6

[0123] 1) Add 3.3 g of spirotetramat Form I into 10 mL of methanol, raise the temperature and maintain it at 50°C for 1.5 h;

[0124] 2) After the constant temperature is completed, the supernatant of the 50°C spirotetramat methanol solution is quickly transferred to a constant temperature water bath at 2°C, and quenched and crystallized to obtain spirotetramat product F.

[0125] The PXRD powder diffraction pattern of spirotetramat product F is as follows: Figure 4 As shown, the crystal form, crystal morphology and crystal particle size distribution of spirotetramat product B were tested, and the obtained crystal form of spirotetramat product B was crystal form I, which was rod-shaped, and the particle size distribution was unimodal but wide.

[0126] Comparative Example 7

[0127] The method is the same as that in Example 5, except that the amount of deionized water used is 5 mL, and spirotetramat product G is obtained.

[0128] The crystal form, crystal morphology and crystal particle size distribution of spirotetramat product G were tested. The obtained crystal form of spirotetramat product G was a mixed crystal of crystal form I and crystal form II, which was in the form of strip agglomeration and block. The particle size distribution was multi-modal and wide.

[0129] Comparative Example 8

[0130] 1) Add 3.3 g of spirotetramat Form I into 10 mL of methanol and maintain at 25 °C for 1.5 h;

[0131] 2) 8 mL of the supernatant of the 25°C spirotetramat methanol solution was rapidly dissolved and crystallized with 8 mL of deionized water containing 20 mg of Form II seed crystals at 25°C, and the crystals were grown for 30 minutes to obtain spirotetramat product H.

[0132] The crystal form, crystal morphology and crystal size distribution of spirotetramat product H crystals were tested, and the obtained crystal form of spirotetramat product H crystals was crystal form I, which showed small particles and fine crystals with strip-like agglomeration and irregular morphology, and the particle size was obviously uneven.

[0133] By comparing Examples 1-7 and Comparative Examples 1-8, it can be seen that the product obtained by the present invention is a metastable crystal form II of spirotetramat, and the crystal form is a pure metastable crystal form II, which is spherical and micron-sized, and has a uniform particle size distribution. When a good solvent outside the scope of the present invention is used, the product crystal form is a mixed crystal, and the particle size distribution is also uneven. By Comparative Example 7, it can be seen that when the dosage ratio of a good solvent and an anti-solvent outside the scope of the present invention is used, the target product cannot be obtained. By Comparative Example 8, it can be seen that when the temperature of the added anti-solvent is not within the scope of the present invention, the target product cannot be obtained.

[0134] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A method for preparing a metastable crystal form II of spirotetramat, characterized in that: The method comprises the following steps: 1) mixing a good solvent with the spirotetramat crystal form I to obtain a spirotetramat solution; 2) adding the spirotetramat solution obtained in step 1) to an anti-solvent, and then performing dissolution crystallization, crystal cultivation, and solid-liquid separation with spirotetramat metastable crystal form II seed crystals to obtain spirotetramat metastable crystal form II, The good solvent is one or more of alcohols with 1 to 4 carbon atoms, ketones with 3 to 5 carbon atoms, and benzene solvents with 6 to 12 carbon atoms. The anti-solvent is water and / or n-hexane, The volume ratio of the good solvent to the anti-solvent is 1:3-40, and the temperature of the anti-solvent is controlled at 0-10°C.

2. The preparation method according to claim 1, wherein The good solvent is one or more of methanol, ethanol, propanol, butanol, acetone, butanone, pentanone, toluene and xylene; Preferably, the good solvent is one or more of methanol, ethanol, acetone and toluene; Preferably, the amount of the good solvent is such that the spirotetramat crystalline form I solution is saturated; Preferably, the volume ratio of the good solvent to the anti-solvent is 1:5-20.

3. The preparation method according to claim 1, wherein In step 1), the mixing conditions include: temperature of 25-60° C. and time of 0.3-24 h.

4. The preparation method according to claim 1, wherein Before performing step 2), the method further comprises the step of controlling the temperature of the anti-solvent; Preferably, the temperature of the anti-solvent is controlled at 0-5°C.

5. The preparation method according to claim 1, wherein The amount of the spirotetramat metastable crystal form II seed crystal added is 0.2-2% by weight of the amount of the spirotetramat crystal form I added in step 1); Preferably, the particle size of the spirotetramat metastable crystal form II seed is 100-600 mesh; Preferably, the particle size of the spirotetramat metastable form II seed crystals is 100-300 mesh.

6. The preparation method according to claim 5, wherein: The dissolution crystallization comprises the steps of adding a spirotetramat metastable crystal form II seed into an anti-solvent, and dripping the supernatant of the spirotetramat solution prepared in step 1) into the anti-solvent for anti-dissolution.

7. The preparation method according to claim 1, wherein In step 2), the method further comprises a step of drying after the solid-liquid separation; Preferably, the drying conditions include: drying temperature of 20-40°C, drying time of 8-60min; Preferably, the crystal growing conditions include: a crystal growing temperature of 1-10° C. and a crystal growing time of 2-300 min.

8. The spirotetramat metastable crystal form II prepared according to the method for preparing the spirotetramat metastable crystal form II according to any one of claims 1 to 7.

9. The spirotetramat metastable crystal form II according to claim 8, wherein The Dv(50) of the spirotetramat metastable crystal form II is 60-150 μm; Preferably, the Dv(50) of the metastable crystal form II of spirotetramat is 90-120 μm.

10. Use of the spirotetramat metastable crystal form II according to claim 8 in the preparation of insecticides.

11. An insecticide, characterized in that: The insecticide contains the spirotetramat metastable crystal form II prepared by the preparation method of spirotetramat metastable crystal form II described in any one of claims 1 to 7 or the spirotetramat metastable crystal form II described in claim 8 as an active ingredient.

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