Crystal form of sulfoxaflor as well as preparation method and application thereof

Abstract

The invention discloses a sulfoxaflor crystal form as well as a preparation method and application thereof. According to the present invention, amorphous sulfoxaflor or amorphous sulfoxaflor is subjected to recrystallization to obtain the sulfoxaflor crystal form, and the sulfoxaflor crystal form is called the sulfoxaflor solid form I; the crystal is analyzed through various analysis methods, and the crystal form is used for preparing stable agricultural chemical preparations with good physical properties, including SC preparations and WG preparations. The preparation method of the sulfoxaflor solid form I, provided by the invention, is high in efficiency, short in process time, mild in condition, simple and convenient in process and relatively high in recovery rate. The ratio of the first diastereoisomer group A to the second diastereoisomer group B in the sulfoxaflor prepared by the method disclosed by the invention can be more than 99: 1. Meanwhile, the crystal form of the sulfoxaflor solid form I shows high stability and / or good physical properties during preparation of a preparation, and has a good application prospect.

Description

Technical Field

[0001] This invention relates to a crystal form of flonicamid, its preparation method and its uses, belonging to the field of agricultural insecticide technology. Background Technology

[0002] Sulfoxaflor (CAS Registry Number: 946578-00-3) is a sulfonamide insecticide with the chemical name {1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxo-λ. 4 -Thionylaminonitrile, molecular formula C 10 H 10 F3N3OS, melting point 112.9℃. Its structural formula is as follows: Formula A:

[0003]

[0004] Flupyradifurone acts on the insect's nervous system (a unique binding site within cholinergic receptors) and exhibits no cross-resistance with other chemical insecticides. It is characterized by high efficiency, broad spectrum, safety, rapid action, and long residual effect. It is used to control various piercing-sucking pests such as aphids, mirid bugs, stink bugs, whiteflies, scale insects, planthoppers, certain psyllids, and thrips on cotton, rapeseed, fruit trees, soybeans, fruits, small grains, vegetables, rice, lawns, and ornamental plants. It is effective against piercing-sucking pests resistant to neonicotinoids, pyrethroids, organophosphates, and carbamates, making it a preferred agent for integrated pest management.

[0005] Commercially available methods for manufacturing flonicamid products are known, typically by methods described in patents CN101384552A, CN102153506A, and CN102271516A. For example, Example II of patent CN101384552A discloses a method for preparing flonicamid products from sulfinylimide (1) according to the reaction scheme shown in route 1 below.

[0006]

[0007] Also known is flonicamid, which is typically a stereoisomer mixture, usually containing a first diastereomer group A and a second diastereomer group B. For example, Example II of patent CN101384552A discloses that flonicamid contains the first diastereomer group A and the second diastereomer group B in a ratio of about 1:2. In addition, patent CN102271516A also discloses, as a more specific example, that after the initial synthesis of flonicamid, the first diastereomer group A and the second diastereomer group B are present in a mixture of about 1:2. Furthermore, commercially available amorphous flonicamid typically contains the first diastereomer group A and the second diastereomer group B in a ratio of about 2:3.

[0008] Patent CN102271516A also discloses four stereoisomers of flonicamid. These four stereoisomers define two pairs of diastereomers, designated as diastereomer group A and diastereomer group B. Diastereomer group A consists of {(R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(R)-(methyl)oxo-λ 4 -Thionylaminonitrile (A) 1 ) and {(S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(S)-(methyl)oxo-λ 4 -Thionylaminonitrile (A) 2 )definition;

[0009] diastereomer group A

[0010]

[0011] {(R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(R)-(methyl)oxo-λ 4 -Thionylaminonitrile (A1)

[0012]

[0013] {(S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(S)-(methyl)oxo-λ 4 -Thionylaminonitrile (A2)

[0014] Diastereomer group B consists of {(R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(S)-(methyl)oxo-λ 4 -Thionylaminonitrile (B 1 ) and {(S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(R)-(methyl)oxo-λ 4 -Thionylaminonitrile (B 2 )definition.

[0015] diastereomer group B

[0016]

[0017] {(R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(S)-(methyl)oxo-λ 4 -Thionylaminonitrile (B1).

[0018]

[0019] {(S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(R)-(methyl)oxo-λ 4 -Thionylaminonitrile (B2).

[0020] Furthermore, patent CN102271516A also discloses that the conversion between diastereomeric group A and diastereomeric group B of flonicamid over time is possible. Diastereomeric group B has relatively poor stability and can be converted into diastereomeric group A under certain conditions. The patent embodiment discloses that heating the formulation composition of flonicamid and spinosad for a certain period of time promotes the conversion of diastereomeric group B of flonicamid in the formulation composition into diastereomeric group A. The method described in this patent has the problem of low conversion efficiency. For example, at 54°C, after 4 hours, diastereomeric group B is 37.37%, and after 8 hours, it is 25.98%. Even at 74°C, after 4 hours, diastereomeric group B is 5.02%, and after 8 hours, it is still 4.45%.

[0021] Based on currently available literature on flonicamid, no methods have been found to efficiently, mildly, and easily prepare diastereomer A of flonicamid technical. Furthermore, no literature reports the crystal structure or related data of flonicamid technical; the crystal form of diastereomer A of flonicamid technical has also been reported. It is well-known in the pesticide field that different isomers in pesticide technicals lead to different efficacy and effects, and different crystal forms of pesticide technicals also result in different efficacy and effects, potentially leading to different performance characteristics in economically important formulations. It was also discovered that flonicamid prepared by a known patented method (such as the method described in Example II of patent CN101384552A) existed in a ratio of approximately 1:2 for the first diastereomer group A and the second diastereomer group B. This patent document discloses that it exists as a colorless oily substance in an amorphous state. Similarly, flonicamid prepared by this known method is essentially as follows: Figure 1As shown, a resolvable X-ray powder diffraction pattern could not be obtained. It was also found that the commercially available amorphous flupyradifurone technical grade existed in a ratio of approximately 2:3 between the first diastereomer group A and the second diastereomer group B, essentially as shown... Figure 1 As shown, a resolvable X-ray powder diffraction pattern could not be obtained.

[0022] Furthermore, flonicamid containing a high proportion of the second diastereomer group B, or flonicamid in its amorphous state, is not entirely satisfactory as an insecticidal ingredient. For example, there is still room for improvement in its formulation stability, insecticidal activity, and physical properties. For instance, flonicamid prepared according to Example II of patent CN101384552A, containing the first diastereomer group A and the second diastereomer group B in a ratio of approximately 1:2, or commercially available amorphous flonicamid containing the first diastereomer group A and the second diastereomer group B in a ratio of approximately 2:3, exhibits relatively poor storage stability, particularly showing aggregation problems after prolonged storage. It has also been found that water-dispersible granules (WG formulation) prepared from these formulations have relatively poor physical properties, making them unsuitable for preparation into compositions or formulations. Formulations are economically relevant and should possess good storage stability and good physical properties. Therefore, there is a need to develop new solid forms of flonicamid that exhibit one or more improved properties, such as improved storage stability, improved physical properties, and improved diastereomeric group A and B ratios. Summary of the Invention

[0023] The purpose of this invention is to address the problems of unstable storage, aggregation after storage, and / or relatively poor physical properties of existing flonicamid, and / or a high proportion of diastereomer group B. This invention provides a flonicamid crystal form, its preparation method, and its uses.

[0024] To achieve the above objectives, the present invention adopts the following technical solution:

[0025] In a first aspect, the present invention provides a crystal form of flupyradifurone diastereomer group A, denoted as flupyradifurone solid form I, which exhibits, in any combination, the following reflectance as 2θ ± 0.200 degrees in an X-ray powder diffraction (X-RPD) pattern recorded using Cu-Ka radiation at 25°C:

[0026] 2θ = 12.359 ± 0.200 (1)

[0027] 2θ = 16.421 ± 0.200 (2)

[0028] 2θ = 18.381 ± 0.200 (3)

[0029] 2θ = 19.102 ± 0.200 (4)

[0030] 2θ = 21.300 ± 0.200 (5)

[0031] 2θ = 22.761 ± 0.200 (6)

[0032] 2θ = 24.801 ± 0.200 (7)

[0033] 2θ = 27.739 ± 0.200 (8)

[0034] 2θ = 28.761 ± 0.200 (9)

[0035] 2θ = 29.462 ± 0.200 (10)

[0036] 2θ = 29.819 ± 0.200 (11).

[0037] Preferably, the present invention provides a crystal form of flupyradifurone diastereomer group A, denoted as flupyradifurone solid form I, which exhibits, in any combination, the following reflectance as 2θ ± 0.200 degrees in an X-ray powder diffraction (X-RPD) pattern recorded using Cu-Ka radiation at 25°C:

[0038] 2θ = 9.198 ± 0.200 (1)

[0039] 2θ = 12.359 ± 0.200 (2)

[0040] 2θ = 16.421 ± 0.200 (3)

[0041] 2θ = 18.381 ± 0.200 (4)

[0042] 2θ = 19.102 ± 0.200 (5)

[0043] 2θ = 21.300 ± 0.200 (6)

[0044] 2θ = 22.761 ± 0.200 (7)

[0045] 2θ = 24.801 ± 0.200 (8)

[0046] 2θ = 25.540 ± 0.200 (9)

[0047] 2θ = 26.089 ± 0.200 (10)

[0048] 2θ = 26.556 ± 0.200 (11)

[0049] 2θ = 27.739 ± 0.200 (12)

[0050] 2θ = 28.761 ± 0.200 (13)

[0051] 2θ = 29.462 ± 0.200 (14)

[0052] 2θ = 29.819 ± 0.200 (15).

[0053] Preferably, in the solid form I of flonicamid nitrile, the ratio of the first diastereomer group A and the second diastereomer group B is ≥93:7, wherein the first diastereomer group A is composed of {(R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(R)-(methyl)oxo-λ4-thionylaminonitrile (A 1 ) and {(S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(S)-(methyl)oxo-λ4-thionylaminonitrile (A 2 The second diastereomeric group B is defined as {(R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(S)-(methyl)oxo-λ4-thionylaminonitrile (B 1 ) and {(S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(R)-(methyl)oxo-λ4-thionylaminonitrile (B 2 )definition.

[0054] More preferably, the ratio of the first diastereomer group A and the second diastereomer group B in the flupyradifurone solid form I is ≥96:4.

[0055] Preferably, it exhibits values ​​of 3055, 3029, 2936, 2189, 1413, 1387, 1343, 992, 985, 864, 1243, 823, 785, 772, 743, 623, 603, 589, 497, and 460cm. -1 One or more wavenumbers (cm) -1 Infrared (IR) spectra with characteristic functional group vibration peaks at (±0.2%).

[0056] And / or, it exhibits a differential scanning calorimetry (DSC) curve with an endothermic melting peak at 162.3 °C. Preferably, it has a melting enthalpy of 160.2 J / g.

[0057] And / or, it exhibits a differential scanning calorimetry (DSC) curve with an exothermic decomposition peak at 255.6 °C. Preferably, it has a decomposition enthalpy of 316.7 J / g.

[0058] Preferably, it is through substantially as Figure 2 or Figure 3 The X-ray powder diffraction pattern shown is used to characterize and / or by substantially as Figure 4 The IR spectra shown are used to characterize and / or by substantially as Figure 5 The DSC thermogram shown is used to characterize it.

[0059] This flonicamid solid form I exhibits significantly improved storage stability, substantially reducing the long-term storage stability issues encountered with currently commercially available flonicamid formulations, particularly the SC formulation. Furthermore, compared to the amorphous flonicamid prepared according to Example II of patent CN101384552A, this flonicamid solid form I demonstrates higher stability when formulated. Moreover, due to its excellent thermodynamic stability and physical properties, this flonicamid solid form I does not transform into other forms even during prolonged storage. Simultaneously, the physical properties of the water-dispersible granules (WG formulation) of this flonicamid solid form I are significantly superior to those of amorphous flonicamid water-dispersible granules or the amorphous flonicamid water-dispersible granules prepared according to Example II of CN101384552A, making it suitable for economically relevant applications, providing the desired long shelf life and excellent physical properties for formulations.

[0060] Methods for preparing amorphous or non-crystalline flonicamid are known in the art. A particularly suitable method for preparing amorphous flonicamid is described in patent CN101384552A. Furthermore, we have found that the amorphous flonicamid (colorless oil) prepared according to Example II of patent CN101384552A can be solidified by high vacuum and / or cryopreservation to obtain amorphous flonicamid. Fluonicamid is also commercially available.

[0061] The solid form I of flonicamid of the present invention can be prepared by crystallization from a solution of flonicamid. This solution can be prepared using any form of flonicamid, particularly amorphous or non-crystalline flonicamid.

[0062] A second aspect of the present invention provides a method for preparing the solid form I of flonicamid as described in the first aspect of the present invention, comprising the following steps:

[0063] Step 1: Provide a solution of flonicamid;

[0064] Step 2: Crystallize the dissolved flonicamid to flonicamid solid form I;

[0065] Step 3: Separate the crystallized flonicamid nitrile solid form I.

[0066] Preferably, the present invention provides a method for preparing the solid form I of flonicamid as described in the first aspect of the present invention, comprising the following steps:

[0067] Step 1: Dissolve the appropriate form of flonicamid in a solvent by heating for a certain time to obtain a flonicamid solution;

[0068] Step 2: Crystallize the dissolved flonicamid to flonicamid solid form I;

[0069] Step 3: Separate the crystallized flonicamid nitrile solid form I.

[0070] As described above, a flonicamid solution can be formed by dissolving a suitable form of flonicamid in a solvent system. Commercially available amorphous flonicamid (melting point measured by a melting point apparatus: 110-115°C, purity 98.0%) or amorphous flonicamid prepared according to the method described in patent CN101384552A (disclosed as a colorless oil in the patent) is a preferred starting material for forming this solution. Preferably, the ratio of the first diastereomeric group A to the second diastereomeric group B in the starting material flonicamid is <3:1; more preferably, the ratio of the first diastereomeric group A to the second diastereomeric group B in the starting material flonicamid is about 1:2 or about 2:3.

[0071] Preferably, the solvent in step 1 is selected from any one of the following solvents: methanol, ethanol, ethyl acetate, isopropyl acetate, methyl tert-butyl ether, acetone, butanone, pentanone, acetonitrile, dichloromethane, 1,2-dichloroethane, chloroform or any combination thereof, or toluene and n-hexane, toluene and cyclohexane, ethyl acetate and n-hexane, 1,2-dichloroethane and n-hexane, THF and water, DMF and water, and mixtures of methanol and water, and mixtures of ethanol and water.

[0072] More preferably, the solvent is selected from one or two of acetone, butanone, acetonitrile, dichloromethane, 1,2-dichloroethane, and chloroform.

[0073] More preferably, the solvent is selected from any one of the following: a mixed solvent of acetonitrile and 1,2-dichloroethane, a mixed solvent of acetonitrile and dichloromethane, a mixed solvent of acetone and 1,2-dichloroethane, and a mixed solvent of acetone and dichloromethane, wherein the weight content of the chloroalkane solvent (1,2-dichloroethane or dichloromethane) in the mixed solvent is less than 50%.

[0074] More preferably, the solvent is selected from any one of the following: a mixed solvent of acetonitrile:1,2-dichloroethane = 7:3, a mixed solvent of acetonitrile:dichloromethane = 7:3, a mixed solvent of acetone:1,2-dichloroethane = 8:2, and a mixed solvent of acetone:dichloromethane = 8:2; wherein the ratio of solvents is the mass ratio of solvents.

[0075] Preferably, in step 1, flonicamid is dissolved in a solvent by heating.

[0076] Preferably, flonicamid is dissolved in the solvent in step 1 by heating from room temperature to or below the reflux temperature of the solvent, and then heating is continued for a certain period of time after dissolution.

[0077] Preferably, the heating temperature is 30–80°C; more preferably, the heating temperature is 35–55°C.

[0078] Preferably, the heating time after dissolution is 0.5-8 hours; more preferably, the heating time after dissolution is 1-4 hours.

[0079] Preferably, the solution prepared in step 1 is then cooled to a temperature of approximately 5°C to 30°C to crystallize from the solvent to obtain the desired crystal form. Alternatively, by applying or not applying a vacuum and cooling to below the reflux temperature of the solvent or solvent mixture, the homogeneous solution can be concentrated by removing the solvent to a certain amount, thereby crystallizing flonicamid in solid form I.

[0080] Preferably, flupyradifurone solid form I can also be produced by adding seed crystals of the desired crystalline form (which can promote or accelerate crystallization) to the solution prepared in step 1 during crystallization. The amount of seed crystals added to the solution is typically 0.001% to 5% by weight, more preferably 0.005% to 1.0% by weight, based on the weight of the solution formed by dissolving flupyradifurone in the solvent in step 1. Optionally, the seed crystals are added to the concentrated solution at a temperature below the boiling point of the corresponding solvent or solvent mixture.

[0081] Preferably, the crystalline flonicamid solid form I obtained in step 2 is separated from the solution using common solid component separation techniques (e.g., filtration, centrifugation, or decantation). The separated solid is then washed once or multiple times with a solvent. Preferably, the solvent used in the washing stage can be the same as the solvent used for dissolution in step 1 as described above. Depending on the solubility of the crystals, washing is typically performed using the appropriate solvent between room temperature and 5°C to minimize the loss of crystalline material in the washing solvent.

[0082] Preferably, flonicamid nitrile solid form I is prepared by dissolution and recrystallization.

[0083] Preferably, step 2, which crystallizes the dissolved flonicamid into flonicamid solid form I, specifically includes: concentrating the solution and / or cooling and / or adding a solvent that reduces solubility and / or adding seed crystals of the flonicamid solid form I.

[0084] Preferably, in step 2, the dissolved flonicamid is crystallized into flonicamid solid form I by gradient cooling, and finally cooled to 5°C to 30°C to precipitate crystals. Preferably, the gradient cooling method is to slowly and uniformly decrease the temperature by about 10°C every 20 minutes. Then, after maintaining this temperature for 5 minutes, the temperature is further decreased, and the above slow and uniform cooling operation is repeated 2-4 times until the system temperature reaches 5°C to 30°C and crystals precipitate.

[0085] Surprisingly, the key condition affecting the conversion of diastereomeric group B to diastereomeric group A in flonicamid is not the heating temperature and heating time, but the solvent or solvent combination is more important. Using the solvent or solvent combination of the present invention, flonicamid with a ratio of first diastereomeric group A to second diastereomeric group B of ≥95:5 can be obtained at a lower heating temperature and a shorter heating time. In a more suitable embodiment of the present invention, the ratio of first diastereomeric group A to second diastereomeric group B in the obtained flonicamid is about >99:1. However, when the solvent system used is not suitable, even if the heating temperature is increased and the heating time is extended, flonicamid containing a high proportion of first diastereomeric group A cannot be obtained.

[0086] A third aspect of the invention provides a flonicamid solid form I, obtained by the method described in the second aspect of the invention, and having a content of at least 95% flonicamid solid form I by weight. Diastereomers typically require liquid chromatography or complex processes to obtain high proportions of pure products; simple, efficient, and industrially feasible methods are scarce. Surprisingly, the simple process described in the second aspect of the invention can efficiently obtain flonicamid containing essentially only the first diastereomer group A, and simultaneously obtain flonicamid solid form I containing essentially only the first diastereomer group A. The ratio of the first diastereomer group A to the second diastereomer group B in the solid form I of flonicamid obtained by the method of the second aspect of the present invention is ≥93:7; preferably, the ratio of the first diastereomer group A to the second diastereomer group B in the solid form I of flonicamid obtained by the method of the second aspect of the present invention is ≥95:5; more preferably, the ratio of the first diastereomer group A to the second diastereomer group B in the solid form I of flonicamid obtained by the method of the second aspect of the present invention is ≥96:4. In a preferred embodiment of the present invention, the ratio of the first diastereomer group A to the second diastereomer group B in the solid form I of flonicamid is about 97.4:2.6; in another preferred embodiment of the present invention, the ratio of the first diastereomer group A to the second diastereomer group B in the solid form I of flonicamid is about >99:1, and the second diastereomer group B is essentially undetectable by high-performance liquid chromatography (HPLC). The ratio of the first diastereomer group A and the second diastereomer group B described in this invention can preferably be detected by the area normalization method of high-performance liquid chromatography (HPLC). Furthermore, it is known that, under suitable high-performance liquid chromatography conditions, the first diastereomer group A and the second diastereomer group B can be separated into two groups of peaks in the HPLC chromatogram, preferably substantially as follows. Figure 8 As shown, the ratio of the peak area of ​​the first diastereomer group A (elution time 11.08 min) to the peak area of ​​the second diastereomer group B (elution time 11.23 min) in liquid chromatography (HPLC) is the ratio of the first diastereomer group A and the second diastereomer group B in flonicamid.

[0087] A fourth aspect of the present invention provides a composition comprising the flupyradifurone solid form I as described in the first or third aspect of the present invention and at least one adjuvant selected from one or more of the following: surfactants, diluents, dispersants, wetting agents, antioxidants, defoamers, antifreeze agents, thickeners, and pH adjusters.

[0088] Preferably, the composition is in the form of: suspending agent (SC), soluble agent (SL), dispersible liquid (DC), emulsifiable concentrate (EC), emulsion seed dressing agent, granules (GR), suspension emulsion (SE), oil-based suspension (OD), soluble granules (SG), microparticles (MG), wettable powder (WP), or water-dispersible granules (WG).

[0089] Preferably, the composition is in the form of a suspension concentrate (SC) or a water-dispersible granule (WG).

[0090] Preferably, the composition comprises less than 85% by weight of the flupyradifurone solid form I.

[0091] Preferably, the composition comprises 22% or 25% or 40% or 50% by weight of the flupyradifurone solid form I.

[0092] The use of flonicamid as an insecticide is well known in the art and is used on a commercial scale. This solid form of flonicamid I is also active in controlling agricultural pests. Therefore, techniques known in the art for the formulation and application of amorphous flonicamid (e.g., disclosed in the prior art literature described above) can be applied in a similar manner to the solid form of flonicamid I of this invention.

[0093] Therefore, the present invention provides an insecticide composition comprising flonicamid in solid form I as defined above.

[0094] In this invention, flonicamid solid form I is present at a concentration sufficient to achieve the desired dosage when applied to the plant or its location, preferably at a concentration of about 1% to about 80% by weight of the total mixture. For example, it can be prepared into a liquid formulation, such as a suspension (SC), by incorporating water, a solvent, and a carrier into flonicamid solid form I, and, if suitable, using emulsifiers and / or dispersants and / or other adjuvants; it can also be prepared into a solid formulation, such as a water-dispersible granule (WG), by incorporating a carrier and / or a solvent into flonicamid solid form I, and, if suitable, using emulsifiers and / or dispersants and / or other adjuvants.

[0095] These formulations are prepared by mixing flonicamid solid form I with at least one adjuvant (e.g., surfactant, diluent, wetting agent, dispersant, thickener, antifreeze, defoamer, antioxidant, and any necessary adjuvants and other formulation components).

[0096] Surfactants can be ionic or nonionic emulsifiers, dispersants, or wetting agents. Examples that can be used include, but are not limited to, salts of polyacrylic acid, lignin sulfonates, salts or naphthalene sulfonates of benzene sulfonic acid or naphthalene sulfonic acid, condensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines, substituted phenols (especially alkylphenols), sulfosuccinate salts, taurine derivatives (especially alkyl taurine), nonylphenol polyoxyethylene ethers, or phosphate esters of polyethoxylated phenols or alcohols, sodium docusate, and polycarboxylate complexes.

[0097] Diluents include, but are not limited to, water, N,N-dimethylamide, ethylene glycol, polypropylene glycol, propylene carbonate, diesters, paraffin wax, alkylbenzenes, alkylnaphthalenes, glycerin, olive oil, castor oil, linseed oil, sesame oil, corn oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil, and coconut oil, ketones (such as cyclohexanone, 2-heptanone, and 4-hydroxy-4-methyl-2-pentanone), acetates (such as hexyl acetate, heptyl acetate, and octyl acetate), water, and alcohols (such as methanol, cyclohexanol, decanol, benzyl alcohol, and tetrahydrofurfuryl alcohol), salts such as alkali metal phosphates (e.g., sodium dihydrogen phosphate), alkaline earth metal phosphates, sulfates of sodium, potassium, magnesium, and zinc, sodium chloride, potassium chloride, sodium acetate, sodium carbonate, and sugars and sugar derivatives such as sorbitol, lactose, sucrose, and mannitol, clay, synthetic silica and diatomaceous earth, calcium silicate, titanium dioxide, aluminum oxide, calcium oxide, and zinc oxide, and mixtures thereof.

[0098] Wetting agents include, but are not limited to: phosphate esters, acetylation glycol, ethoxylated silicone, sodium lauryl sulfate, chelating agents, soap powder, detergent LS (sodium p-methoxy fatty amide benzenesulfonate), alkyl-substituted naphthalene sulfonates, and polyalkylene glycol ethers. Preferred wetting agents are selected from polyalkylene glycol ethers, alkyl-substituted naphthalene sulfonates, sodium lauryl sulfate, and soap powder.

[0099] Dispersants include, but are not limited to: polycarboxylates or polycarboxylate complexes, alkylphenol polyoxyethylene ether formaldehyde condensate sulfates, sodium salts of naphthalene sulfonate formaldehyde condensate, naphthalene sulfonate condensates, calcium salts of alkylbenzene sulfonate, alkylphenol polyoxyethylene ethers, nonylphenol polyoxyethylene ethers, fatty amine polyoxyethylene ethers, fatty acid polyoxyethylene esters and glycerol fatty acid polyoxyethylene ethers, sodium, calcium and ammonium salts of lignin sulfonate, and naphthalene sulfonate formaldehyde condensates. Preferred dispersants are selected from naphthalene sulfonate condensates (such as sodium salts of naphthalene sulfonate formaldehyde condensate), lignin sulfonates (such as calcium lignin sulfonate), calcium salts of alkylbenzene sulfonate, nonylphenol polyoxyethylene ethers, polycarboxylates or polycarboxylate complexes (such as TERSPERSE 2700, Agrilan 700, SP-2836, GeroponT / 36).

[0100] Thickeners include, but are not limited to, guar gum, pectin, casein, carrageenan, xanthan gum, alginate, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and carboxymethylcellulose. Synthetic thickeners include derivatives of the aforementioned categories, as well as polyvinyl alcohol, polyacrylamide, polyvinylpyrrolidone, various polyethers, copolymers thereof, polyacrylic acid, and their salts. Preferred thickeners are xanthan gum and polyvinyl alcohol.

[0101] Suitable antifreeze agents are liquid polyols, such as ethylene glycol, propylene glycol, or glycerin. The amount of antifreeze is typically from about 1% to about 20% by weight, and particularly from about 5% to 10% by weight, based on the total weight of the composition.

[0102] Defoamers encompass all substances commonly used for this purpose in agricultural chemical compositions. Suitable defoamers are known in the art and are commercially available. Preferred defoamers are mixtures of polydimethylsiloxane, perfluoroalkylphosphonic acids, polyether-modified silicones, silicone compounds, and C8-C... 10 Fatty alcohols, etc.

[0103] Disintegrants include all substances that can typically be used for this purpose in agrochemical compositions. Suitable disintegrants are known in the art and are commercially available. Preferred disintegrants are bentonite, urea, ammonium sulfate, aluminum chloride, citric acid, succinic acid, and sodium bicarbonate.

[0104] Antioxidants include all substances known in the art that are commonly used for this purpose in agrochemical compositions. Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are preferred.

[0105] pH adjusters include all substances known in the art that are commonly used for this purpose in agricultural chemical compositions. Citric acid and tartaric acid are preferred.

[0106] Other formulation ingredients can also be used in this invention, such as preservatives and penetrants. Other insecticidal active ingredients can also be added to the composition containing flonicamid in solid form I according to this invention. Suitable insecticidal combinations, such as the addition of appropriate amounts of one or more insecticidal ingredients, may result in better combined herbicidal effects. These ingredients are known to those skilled in the art.

[0107] A fifth aspect of the invention provides the use of the flupyradifurone solid form I described in the first or third aspect of the invention, or the composition described in the fourth aspect of the invention, in the preparation of an insecticide.

[0108] The insecticides described in this invention can be used to control agricultural pests, and the flupyradifurone solid form I of this invention can be used to control invertebrates, including insects. Therefore, this invention also relates to a method of insect control, comprising applying an insect-inhibiting amount of flupyradifurone solid form I to the insect's location, the area under protection, or directly to the insect to be controlled. The flupyradifurone solid form I of this invention can also be used to control other invertebrate pests, such as termites and nematodes. As used herein, "location" of insects or other pests refers to the environment in which the insects or other pests live or where their eggs are present, including the air around them, the food they eat, or the objects they come into contact with. For example, by applying flupyradifurone solid form I to the seeds of a plant (before planting), to seedlings, or to planted cuttings, leaves, stems, fruits, grains, and / or roots, or to the soil or other growing medium (before or after crop planting), insects that consume, damage, or come into contact with edible agricultural products, ornamental plants, turf, or pasture plants can be controlled.

[0109] The term "insect suppression" refers to reducing the number of surviving insects or the number of viable insect eggs. Of course, the degree of reduction achieved by flupyradifurone solid form I depends on the application rate, the target insect species, etc. Generally, at least an inactivating dose should be used. The term "insect inactivating dose" describes the amount sufficient to cause a measurable reduction in the number of treated insects. Typically, 1 to 1000 ppm (by weight) of the active compound is used. For example, insects or other pests that can be suppressed include, but are not limited to: Lepidoptera, Coleoptera, Homoptera, Hemiptera, Thysanoptera, Isoptera, Diptera, Hymenoptera, Trichophyton, Pseudocoptera, Orthoptera, Parrotida, Mites, and Nematodes.

[0110] As used herein, the term “about” when used in conjunction with a numerical quantity or range means slightly greater than or slightly less than the numerical quantity or range, and deviating from the endpoints of the numerical quantity or range by ±10%.

[0111] Treatment of plants and plant parts with the insecticidal composition or formulation of the present invention is carried out directly or by conventional treatment methods that allow the composition or formulation to act on their surrounding environment, habitat, or storage space. Examples of such conventional treatment methods include impregnation, spraying, vaporization, atomization, broadcasting, brushing, mixing (such as soil treatment), etc.

[0112] The term "room temperature" as used in this article refers to a temperature range of approximately 20°C to 25°C.

[0113] Generally, crystalline materials can be identified, for example, by the presence of diffraction peaks upon exposure to X-rays and / or by the appearance of endothermic melting peaks or exothermic decomposition peaks with characteristic peaks under differential scanning calorimetry (DSC). Unless otherwise stated, all percentages in this invention are given in weight percent.

[0114] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0115] 1. This invention provides a novel crystal form of flonicamid for the first time, referred to as "solid form I", and provides X-ray powder diffraction pattern, IR infrared spectrum, differential scanning calorimetry (DSC) data, enthalpy of fusion, etc. of this flonicamid solid form I;

[0116] 2. This flonicamid solid form I can significantly reduce the long-term storage stability problems of current flonicamid formulations, especially flonicamid suspensions (SC formulations). This flonicamid solid form I exhibits high stability when formulated with SC formulations. At the same time, this flonicamid solid form I can improve the physical properties of amorphous flonicamid or amorphous flonicamid water-dispersible granules (WG formulations). Furthermore, due to its good thermodynamic stability and good physical properties, this flonicamid solid form I is sufficient for economically relevant applications, providing the desired long shelf life and good physical properties of the formulation.

[0117] 3. This invention provides a method for preparing flonicamid in solid form I, including a particularly suitable solvent combination. This method is highly efficient, has a short processing time, mild conditions, is simple, and has a high recovery rate. Simultaneously, this invention also provides a method for preparing the first diastereomeric group A of flonicamid, including a particularly suitable solvent combination. This method is highly efficient, has a short processing time, mild conditions, is simple, and has a high recovery rate. The ratio of the first diastereomeric group A to the second diastereomeric group B in the flonicamid of this invention can be as high as >99:1. Attached Figure Description

[0118] Figure 1 This is the X-ray powder diffraction pattern (X-RPD) of amorphous flonicamid.

[0119] Figure 2 X-ray powder diffraction (X-RPD) pattern of flupyradifurone solid form I (in which diastereomers A and B are present in a ratio of >99:1).

[0120] Figure 3 X-ray powder diffraction (X-RPD) pattern of flupyradifurone solid form I (in which diastereomer groups A and B are present in a ratio of approximately 97.4:2.6).

[0121] Figure 4 The infrared (IR) spectrum of flupyradifurone solid form I.

[0122] Figure 5 The image shows the differential scanning calorimetry (DSC) thermogram of flupyradifurone solid form I.

[0123] Figure 6 The liquid phase (HPLC) spectrum of flupyradifurone solid form I (in which diastereomer groups A and B are present in a ratio of >99:1).

[0124] Figure 7 The liquid phase (HPLC) spectrum of flonicamid in solid form I (in which diastereomer groups A and B are present in a ratio of approximately 97.4:2.6).

[0125] Figure 8 The image shows the liquid chromatography (HPLC) spectrum of commercially available amorphous flupyradifurone technical (in which diastereomers A and B are present in a ratio of approximately 2:3). Detailed Implementation

[0126] To make the present invention more apparent and understandable, preferred embodiments are described in detail below with reference to the accompanying drawings.

[0127] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available.

[0128] In the following embodiments of the present invention, all X-ray diffraction patterns were measured using a powder diffractometer at 25°C with the following acquisition parameters:

[0129] Ultima IV X-ray diffractometer θ-compensated slit and graphite monochromator Copper (Ka) radiation, 40kV, 40mA Step size: 0.02 degrees 2-θ Counting time: 1.0 second Maximum peak intensity: 9285 counts / second Scan range: 3-70 degrees 2-θ

[0130] Example 1: Preparation of amorphous flonicamid

[0131] Amorphous flonicamid is prepared according to the disclosure of patent CN101384552A. Several synthetic methods for preparing flonicamid exist in the prior art, and therefore it can be manufactured on a commercial scale using one of the reported methods or purchased in bulk by various manufacturing industries. Fluonicamid can be prepared using the starting material sulfinylimide (1) of formula (1) shown in route 1 below, according to the procedure reported in patent CN101384552A.

[0132]

[0133]

[0134] At -78°C, potassium hexamethyldisilazane (KHMDS, 0.5 M toluene solution, 420 mL, 210 mmol) was added dropwise to a solution of tetrahydrofuran (THF, 2000 mL) containing sulfinimide (1) (50 g, 190 mmol) and hexamethylphosphoramide (HMPA, 17 mL, 100 mmol). After the addition was complete, methyl iodide (13 mL, 210 mmol) was added, and the solution was stirred at -78°C for another 20 minutes. The reaction was brought to room temperature over 1 hour, quenched with a saturated aqueous ammonium chloride solution, and extracted with dichloromethane. The organic layer was dried with anhydrous sodium sulfate, concentrated, and the crude product was purified by chromatographic column (chromatotron, 70% acetone / dichloromethane). After solvent concentration, flonicamid (colorless oil, 31 g, 58%) was obtained. The product was found to contain diastereomer group A and diastereomer group B in a ratio of approximately 1:2.

[0135] like Figure 1 As shown, the X-ray powder diffraction pattern of the obtained amorphous flonicamid product showed no significant signal.

[0136] Example 2: Preparation of flupyradifurone solid form I

[0137] Eight grams of the amorphous flonicamid sample prepared in Example 1 (containing diastereomer group A and diastereomer group B in a ratio of approximately 1:2) were placed in a three-necked round-bottom flask along with 16 grams of a mixed solvent of acetonitrile:1,2-dichloroethane = 7:3 (mass ratio). The resulting slurry was heated to 50°C to obtain a homogeneous solution. The homogeneous solution was stirred at 50°C for 2 hours, and insoluble particles (if present) were filtered off. The resulting solution was slowly and uniformly cooled to 40±2°C over 20 minutes and held at that temperature for 5 minutes; then slowly and uniformly cooled to 30±2°C over 20 minutes and held at that temperature for 5 minutes; then slowly cooled to 20±2°C over 20 minutes to form fine crystals, and the resulting heterogeneous mixture was stirred at 20±2°C for 5 minutes. The slurry was then filtered and washed with 5 grams of cold acetonitrile:1,2-dichloroethane mixed solvent = 7:3 (mass ratio). The filtered crystals were dried at 50°C. The purity of the obtained crystalline product was >98%, the mass of the crystalline product was 6.8 g, and the yield of the crystalline product was 81%. HPLC analysis showed that the HPLC properties of the crystals were essentially as follows. Figure 6 As shown, diastereomers A and B exist in a ratio >99:1. The melting point, as determined by a melting point apparatus, is 160-164℃.

[0138] The crystals obtained by X-RPD, IR spectroscopy, and DSC analysis are fundamentally as follows: Figure 2 , Figure 4 and Figure 5 The solid form of flonicamid nitrile I is shown. The IR spectrum of this solid form of flonicamid nitrile I is... Figure 4 The IR spectra of flonicamid in solid form I are given in [reference]. These spectra are observed at 3055, 3029, 2936, 2189, 1413, 1387, 1343, 992, 985, 864, 1243, 823, 785, 772, 743, 623, 603, 589, 497, and 460 cm⁻¹. -1 One or more wavenumbers (cm) -1 The infrared (IR) spectrum of the flupyradifurone solid form I exhibits characteristic functional group vibration peaks at (±0.2%). The differential scanning calorimetry (DSC) thermogram of this flupyradifurone solid form I is shown in... Figure 5 The results show that it exhibits a differential scanning calorimetry (DSC) curve with an endothermic melting peak at 162.3℃ and a melting enthalpy of 160.2 J / g; and a differential scanning calorimetry (DSC) curve with an exothermic decomposition peak at 255.6℃ and a decomposition enthalpy of 316.7 J / g.

[0139] The X-ray powder diffraction pattern of the crystal shows the following Figure 2 The reflections are shown, and the values ​​are summarized in List 1 below:

[0140] Table 1. X-ray powder diffraction pattern of flupyradifurone solid form I.

[0141]

[0142] Example 3: Preparation of flupyradifurone solid form I

[0143] Take 8 grams of commercially available amorphous flupyradifurone technical sample (containing diastereomer group A and diastereomer group B in a ratio of approximately 2:3) and 16 grams of a mixed solvent of acetone:dichloromethane = 8:2 (mass ratio), and place them together in a three-necked round-bottom flask. Heat the resulting slurry to 45°C to obtain a homogeneous solution. Stir the homogeneous solution at 45°C for 3 hours, and filter out insoluble particles (if any). Slowly and uniformly cool the resulting solution to 35±2°C over 20 minutes, hold at that temperature for 5 minutes; then slowly and uniformly cool to 25±2°C over 20 minutes, hold at that temperature for 5 minutes; then slowly cool to 15±2°C over 20 minutes to form fine crystals, and stir the resulting heterogeneous mixture at 15±2°C for 5 minutes. Then filter the slurry and wash with 5 grams of cold acetone:dichloromethane mixed solvent = 8:2 (mass ratio). Dry the filtered crystals at 50°C. The purity of the obtained crystalline product was >98%, the mass of the crystalline product was 7.04 grams, and the yield of the crystalline product was 87%. HPLC analysis showed that the HPLC properties of the crystal were essentially as follows: Figure 7As shown, diastereomers A and B exist in a ratio of approximately 97.4:2.6. The melting point, as determined by a melting point apparatus, is 154-158℃.

[0144] The crystals obtained by X-RPD analysis are basically as follows: Figure 3 The solid form of flonicamid shown is I.

[0145] The X-ray powder diffraction pattern of the crystal shows the following Figure 3 The reflections are shown below, and the values ​​are summarized in Table 2:

[0146] Table 2. X-ray powder diffraction patterns of flupyradifurone solid form I.

[0147]

[0148] Examples 4-6

[0149] A method for preparing flonicamid in solid form I differs from that in Examples 2 or 3 in that the source of the flonicamid sample used is different, or the solvent system and / or solvent mass is different, or the heating temperature is different, or the heating time is different, while other conditions are the same, as shown in Table 3.

[0150] Table 3. Information on process parameters used in Examples 4-6, crystal purity, yield of crystal products, ratio of diastereomer groups A and B, and crystal melting point.

[0151]

[0152] X-RPD analysis of the crystals obtained in Examples 4-6 revealed that these crystals were basically as follows: Figure 3 The solid form of flonicamid shown is I.

[0153] Comparative Example 1

[0154] Eight grams of the flonicamid sample prepared in Example 1 and 16 grams of ethanol were placed together in a three-necked round-bottom flask, and the resulting slurry was heated to 50°C to obtain a homogeneous solution. The homogeneous solution was stirred at 50°C for 2 hours, and insoluble particles (if present) were filtered out. The resulting solution was slowly and uniformly cooled to 40±2°C over 20 minutes and held at that temperature for 5 minutes; then slowly and uniformly cooled to 30±2°C over 20 minutes and held at that temperature for 5 minutes; then slowly cooled to 20±2°C over 20 minutes to form fine crystals, and the resulting heterogeneous mixture was stirred at 20±2°C for 5 minutes. The slurry was then filtered and washed with 5 grams of cold ethanol. The filtered crystals were dried at 50°C. The purity of the obtained crystalline product was >98%, the mass of the crystalline product was 6.0 grams, and the yield of the crystalline product was 75%. HPLC analysis showed that diastereomers A and B were present in the crystals in a ratio of approximately 50.7:49.3. The melting point was determined by a melting point apparatus to be 114-118℃.

[0155] Comparative Examples 2-12

[0156] A method for preparing flonicamid in solid form I differs from Example 1 in that the source of the flonicamid sample used is different, or the solvent system and / or solvent mass is different, or the heating temperature is different, or the heating time is different, while other conditions are the same, as shown in Table 4.

[0157] Table 4. Information on process parameters used in Comparative Examples 1–12, yield of crystal products, ratio of diastereomer groups A and B, and crystal melting point.

[0158]

[0159]

[0160] Comparative data from Examples 1-6 and Comparative Examples 1-12 show that the key condition affecting the conversion of diastereomeric group B to diastereomeric group A in flonicamid is not the heating temperature and heating time, but the solvent or solvent combination is more important. Using the solvent or solvent combination of the present invention, flonicamid with a ratio of first diastereomeric group A to second diastereomeric group B of ≥95:5 can be obtained at a lower heating temperature and a shorter heating time. In a more suitable embodiment of the present invention, the ratio of first diastereomeric group A to second diastereomeric group B in the obtained flonicamid is about >99:1. However, when the solvent system or solvent combination system used is not suitable, even if the heating temperature is increased and the heating time is extended, flonicamid containing a high proportion of first diastereomeric group A cannot be obtained. This invention provides a particularly suitable method for preparing flonicamid in solid form I, including a particularly suitable solvent combination. This method is highly efficient, has a short processing time, mild conditions, is simple, and has a high recovery rate. Simultaneously, this invention also provides a method for preparing the first diastereomer group A of flonicamid, including a particularly suitable solvent combination. This method is highly efficient, has a short processing time, mild conditions, is simple, and has a high recovery rate. The ratio of the first diastereomer group A to the second diastereomer group B in the flonicamid of this invention can be as high as >99:1.

[0161] Formulation Example 1: Preparation of Flupyradifurone Suspension (SC)

[0162] Mix all the components listed in Table 5 evenly and grind the resulting mixture with a grinder to obtain a suspending agent.

[0163] Table 5. Components of Flupyradifurone Suspension (SC)

[0164]

[0165]

[0166] Formulation Example 2: Preparation of amorphous flonicamid nitrile suspension (SC)

[0167] The following components were uniformly mixed: 22.0 parts of amorphous flonicamid (98%, consistent with the source of the raw material sample in Example 3, obtained commercially), 5.0 parts of calcium lignosulfonate, 3.0 parts of sodium dodecyl sulfate, 0.2 parts of butylated hydroxyanisole (BHA), 0.5 parts of polydimethylsiloxane, 8.0 parts of glycerol, 0.3 parts of xanthan gum, 0.02 parts of citric acid, and water to a final volume of 100 parts. The mixture was then ground using a grinder to obtain a suspending agent.

[0168] Formulation Example 3: Preparation of Flupyradifurone Solid Form I Suspension (SC)

[0169] The following components were uniformly mixed: 22.0 parts of flonicamid solid form I (98%, prepared in Example 2), 5.0 parts of calcium lignosulfonate, 3.0 parts of sodium dodecyl sulfate, 0.2 parts of butylated hydroxyanisole (BHA), 0.5 parts of polydimethylsiloxane, 8.0 parts of glycerol, 0.3 parts of xanthan gum, 0.02 parts of citric acid, and water to a final volume of 100 parts. The mixture was then ground using a grinder to obtain a suspending agent.

[0170] Formulation Example 4: Preparation of Flupyradifurone Solid Form I Suspension (SC)

[0171] The following components were uniformly mixed: 22.0 parts of flupyradifurone solid form I (98%, prepared in Example 3), 5.0 parts of calcium lignosulfonate, 3.0 parts of sodium dodecyl sulfate, 0.2 parts of butylated hydroxyanisole (BHA), 0.5 parts of polydimethylsiloxane, 8.0 parts of glycerol, 0.3 parts of xanthan gum, 0.02 parts of citric acid, and water to a final volume of 100 parts. The mixture was then ground using a grinder to obtain a suspending agent.

[0172] Formulation Example 5: Preparation of Flupyradifurone Solid Form I Suspension (SC)

[0173] The following components were uniformly mixed: 22.0 parts of flupyradifurone solid form I (98%, prepared in Example 6), 5.0 parts of calcium lignosulfonate, 3.0 parts of sodium dodecyl sulfate, 0.2 parts of butylated hydroxyanisole (BHA), 0.5 parts of polydimethylsiloxane, 8.0 parts of glycerol, 0.3 parts of xanthan gum, 0.02 parts of citric acid, and water to a total of 100 parts. The mixture was then ground using a grinder to obtain a suspending agent.

[0174] Formulation Example 6: Preparation of Flupyradifurone Water Dispersible Granules (WG)

[0175] The following components were uniformly mixed: 50 parts of flonicamid sample (98%, consistent with the raw material sample in Example 2, prepared from Example 1), 5 parts of polycarboxylate (TERSPERSE 2700), 10 parts of sodium naphthalenesulfonic acid formaldehyde condensate, 5 parts of calcium lignin sulfonate, 5 parts of sodium dodecyl sulfate, and 25 parts of kaolin. The mixture was then pulverized using an ultra-micro airflow pulverizer, kneaded, and then added to a fluidized bed granulator for granulation, drying, and sieving. After sampling and analysis, flonicamid water-dispersible granules were obtained.

[0176] Formulation Example 7: Preparation of amorphous flonicamid water-dispersible granules (WG)

[0177] The following components were uniformly mixed: 50 parts of amorphous flonicamid (98%, consistent with the raw material sample in Example 3, obtained commercially), 5 parts of polycarboxylate (TERSPERSE 2700), 10 parts of sodium naphthalenesulfonic acid formaldehyde condensate, 5 parts of calcium lignin sulfonate, 5 parts of sodium dodecyl sulfate, and 25 parts of kaolin. The mixture was then pulverized using an ultra-micro airflow pulverizer, kneaded, and then added to a fluidized bed granulator for granulation, drying, and sieving. After sampling and analysis, amorphous flonicamid water-dispersible granules were obtained.

[0178] Formulation Example 8: Preparation of Flupyradifurone Solid Form I Water Dispersible Granules (WG)

[0179] The following components were uniformly mixed: 50 parts of flonicamid solid form I (98%, prepared in Example 2), 5 parts of polycarboxylate (TERSPERSE 2700), 10 parts of sodium naphthalenesulfonic acid formaldehyde condensate, 5 parts of calcium lignosulfonate, 5 parts of sodium dodecyl sulfate, and 25 parts of kaolin. The mixture was then pulverized using an ultra-micro airflow pulverizer, kneaded, and then added to a fluidized bed granulator for granulation, drying, and sieving. After sampling and analysis, water-dispersible granules of flonicamid solid form I were obtained.

[0180] Formulation Example 9: Preparation of Flupyradifurone Solid Form I Water Dispersible Granules (WG)

[0181] The following components were uniformly mixed: 50 parts of flonicamid solid form I (98%, prepared in Example 3), 5 parts of polycarboxylate (TERSPERSE 2700), 10 parts of sodium naphthalenesulfonic acid formaldehyde condensate, 5 parts of calcium lignosulfonate, 5 parts of sodium dodecyl sulfate, and 25 parts of kaolin. The mixture was then pulverized using an ultra-micro airflow pulverizer, kneaded, and then added to a fluidized bed granulator for granulation, drying, and sieving. After sampling and analysis, water-dispersible granules of flonicamid solid form I were obtained.

[0182] Formulation Comparative Example 1: Preparation of Flupyradifurone Suspension (SC)

[0183] The following components were uniformly mixed: 22.0 parts of flonicamid sample (98%, prepared in Comparative Example 1), 5.0 parts of calcium lignosulfonate, 3.0 parts of sodium dodecyl sulfate, 0.2 parts of butylated hydroxyanisole (BHA), 0.5 parts of polydimethylsiloxane, 8.0 parts of glycerol, 0.3 parts of xanthan gum, 0.02 parts of citric acid, and water to a final volume of 100 parts. The mixture was then ground using a grinder to obtain a suspending agent.

[0184] Formulation Comparative Example 2: Preparation of Flupyradifurone Suspension (SC)

[0185] The following components were uniformly mixed: 22.0 parts of flonicamid sample (98%, prepared in Comparative Example 5), 5.0 parts of calcium lignosulfonate, 3.0 parts of sodium dodecyl sulfate, 0.2 parts of butylated hydroxyanisole (BHA), 0.5 parts of polydimethylsiloxane, 8.0 parts of glycerol, 0.3 parts of xanthan gum, 0.02 parts of citric acid, and water to a final volume of 100 parts. The mixture was then ground using a grinder to obtain a suspending agent.

[0186] Formulation Comparative Example 3: Preparation of Flupyradifurone Suspension (SC)

[0187] The following components were uniformly mixed: 22.0 parts of flonicamid sample (98%, prepared in Comparative Example 9), 5.0 parts of calcium lignosulfonate, 3.0 parts of sodium dodecyl sulfate, 0.2 parts of butylated hydroxyanisole (BHA), 0.5 parts of polydimethylsiloxane, 8.0 parts of glycerol, 0.3 parts of xanthan gum, 0.02 parts of citric acid, and water to a final volume of 100 parts. The mixture was then ground using a grinder to obtain a suspending agent.

[0188] Formulation Comparative Example 4: Preparation of Flupyradifurone Suspension (SC)

[0189] The following components were uniformly mixed: 22.0 parts of flonicamid sample (98%, prepared in Comparative Example 12), 5.0 parts of calcium lignosulfonate, 3.0 parts of sodium dodecyl sulfate, 0.2 parts of butylated hydroxyanisole (BHA), 0.5 parts of polydimethylsiloxane, 8.0 parts of glycerol, 0.3 parts of xanthan gum, 0.02 parts of citric acid, and water to a final volume of 100 parts. The mixture was then ground using a grinder to obtain a suspending agent.

[0190] Formulation Comparison Example 5: Preparation of Flupyradifurone Water Dispersible Granules (WG)

[0191] The following components were uniformly mixed: 50 parts of flonicamid sample (98%, prepared in Comparative Example 1), 5 parts of polycarboxylate (TERSPERSE 2700), 10 parts of sodium naphthalenesulfonic acid formaldehyde condensate, 5 parts of calcium lignosulfonate, 5 parts of sodium dodecyl sulfate, and 25 parts of kaolin. The mixture was then pulverized using an ultra-micro airflow pulverizer, kneaded, and then added to a fluidized bed granulator for granulation, drying, and sieving. After sampling and analysis, flonicamid water-dispersible granules were obtained.

[0192] Formulation Comparative Example 6: Preparation of Flupyradifurone Water Dispersible Granules (WG)

[0193] The following components were uniformly mixed: 50 parts of flonicamid sample (98%, prepared in Comparative Example 5), 5 parts of polycarboxylate (TERSPERSE 2700), 10 parts of sodium naphthalenesulfonic acid formaldehyde condensate, 5 parts of calcium lignosulfonate, 5 parts of sodium dodecyl sulfate, and 25 parts of kaolin. The mixture was then pulverized using an ultra-micro airflow pulverizer, kneaded, and then added to a fluidized bed granulator for granulation, drying, and sieving. After sampling and analysis, flonicamid water-dispersible granules were obtained.

[0194] Formulation Comparison Example 7: Preparation of Flupyradifurone Water Dispersible Granules (WG)

[0195] The following components were uniformly mixed: 50 parts of flonicamid sample (98%, prepared in Comparative Example 9), 5 parts of polycarboxylate (TERSPERSE 2700), 10 parts of sodium naphthalenesulfonic acid formaldehyde condensate, 5 parts of calcium lignosulfonate, 5 parts of sodium dodecyl sulfate, and 25 parts of kaolin. The mixture was then pulverized using an ultra-micro airflow pulverizer, kneaded, and then added to a fluidized bed granulator for granulation, drying, and sieving. After sampling and analysis, flonicamid water-dispersible granules were obtained.

[0196] Example 7: Comparison of storage stability

[0197] Samples prepared in Formulation Examples 1–5 and Comparative Examples 1–4 were stored in a heated oven at 54°C under the same atmosphere for 1 month, 3 months, and 6 months, respectively. The procedure followed was in accordance with CIPAC MT46.3. At the end of each storage period, the concentration of flonicamid was measured by high-performance liquid chromatography (HPLC). By observing the aggregates, the original concentration of flonicamid in each formulation was 22%. The results are listed in Table 6.

[0198] Table 6 Comparison of storage stability data for flupyridine SC samples

[0199]

[0200] In Table 6 above, "+" indicates a small number of clusters; "+++" indicates a large number of clusters; and "-" indicates no clusters.

[0201] The comparison data on the storage stability of flonicamid SC samples in Table 6 above show that, compared with commercially available amorphous flonicamid or amorphous flonicamid samples prepared according to the method described in patent CN101384552A, the storage stability of flonicamid solid form I prepared by the method of this invention is significantly better. At the same time, different proportions of diastereomer groups A and B in flonicamid solid form I also have a certain impact on storage stability. Overall, the higher the proportion of diastereomer groups A and B in flonicamid solid form I, the better the storage stability.

[0202] Samples prepared in formulation examples 6-9 and formulation comparative examples 5-7 were selected and their physical properties were compared and tested. The test results are shown in Table 7 below:

[0203] Table 7. Physical property test results of formulation examples and comparative samples.

[0204] Formulation samples Particle strength of formulation particles Viscosity of formulation particles Granulation Suspension rate test Thermal storage decomposition rate (14 days) Formulation Example 6 Weak particle strength, substandard Sticky, not up to standard difficulty ≥90％ ＞5％ Formulation Example 7 Weak particle strength, substandard Sticky, not up to standard difficulty ≥90％ ＞5％ Formulation Example 8 High particle strength, qualified Low viscosity, acceptable easy ≥90％ ≤5％ Formulation Example 9 High particle strength, qualified Low viscosity, acceptable easy ≥90％ ≤5％ Formulation Comparison 5 Weak particle strength, substandard Sticky, not up to standard difficulty ≥90％ ≤5％ Formulation Comparison Example 6 High particle strength, qualified Sticky, not up to standard difficulty ≥90％ ≤5％ Formulation Comparison 7 Weak particle strength, substandard Sticky, not up to standard difficulty ≥90％ ≤5％

[0205] The physical property test results of the flonicamid WG samples in Table 7 above show that, under the same formulation and dosage form, the flonicamid solid form I prepared by the method of this invention exhibits better physical properties than commercially available amorphous flonicamid or flonicamid samples prepared according to the method described in patent CN101384552A. Furthermore, the ratio of diastereomer groups A and B in flonicamid solid form I also affects the physical properties of the formulation. Overall, a higher ratio of diastereomer groups A and B in flonicamid solid form I results in relatively better physical properties. The flonicamid solid form I prepared by the method of this invention is more easily processed into solid dosage forms such as water-dispersible granules (WG) for insecticides, and has better commercial prospects.

[0206] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any form or substance. It should be noted that those skilled in the art can make several improvements and additions without departing from the present invention, and these improvements and additions should also be considered within the scope of protection of the present invention.

Claims

1. A crystalline form of flonicamid, denoted as flonicamid solid form I, characterized in that, In X-ray powder diffraction patterns (X-RPD) recorded using Cu-Ka radiation at 25 °C, the following reflections, in any combination, are observed as 2θ ± 0.200 degrees: 2θ=12.359±0.200 (1) 2θ=16.421±0.200 (2) 2θ=18.381±0.200 (3) 2θ=19.102±0.200 (4) 2θ=21.300±0.200 (5) 2θ = 22.761 ± 0.200 (6) 2θ = 24.801 ± 0.200 (7) 2θ = 27.739 ± 0.200 (8) 2θ = 28.761 ± 0.200 (9) 2θ = 29.462 ± 0.200 (10) 2θ=29.819±0.200 (11).

2. The flupyradifurone solid form I as described in claim 1, characterized in that, In X-ray powder diffraction patterns (X-RPD) recorded using Cu-Ka radiation at 25 °C, the following reflections, in any combination, are observed as 2θ ± 0.200 degrees: 2θ=9.198±0.200 (1) 2θ=12.359±0.200 (2) 2θ=16.421±0.200 (3) 2θ=18.381±0.200 (4) 2θ = 19.102 ± 0.200 (5) 2θ=21.300±0.200 (6) 2θ = 22.761 ± 0.200 (7) 2θ=24.801±0.200 (8) 2θ=25.540±0.200 (9) 2θ = 26.089 ± 0.200 (10) 2θ=26.556±0.200 (11) 2θ = 27.739 ± 0.200 (12) 2θ = 28.761 ± 0.200 (13) 2θ = 29.462 ± 0.200 (14) 2θ=29.819±0.200 (15).

3. The flupyradifurone solid form I as described in claim 1 or 2, characterized in that, The ratio of the first diastereomer group A and the second diastereomer group B in the solid form I of flonicamid nitrile is ≥93:7, wherein the first diastereomer group A is composed of {(R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(R)-(methyl)oxo-λ4-thionylaminonitrile (A) 1 ) and {(S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(S)-(methyl)oxo-λ4-thionylaminonitrile (A 2 The second diastereomeric group B is defined as {(R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(S)-(methyl)oxo-λ4-thionylaminonitrile (B 1 ) and {(S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-(R)-(methyl)oxo-λ4-thionylaminonitrile (B 2 )definition.

4. The flupyradifurone solid form I as described in claim 1, 2, or 3, characterized in that, The ratio of the first diastereomer group A and the second diastereomer group B in the flupyradifurone solid form I is ≥96:

4.

5. The flupyradifurone solid form I as described in claim 1 or 2, characterized in that, It is presented at 3055, 3029, 2936, 2189, 1413, 1387, 1343, 992, 985, 864, 1243, 823, 785, 772, 743, 623, 603, 589, 497 and 460cm. -1 One or more wavenumbers (cm) -1 Infrared (IR) spectra with characteristic functional group vibration peaks at (±0.2%). And / or, it exhibits a differential scanning calorimetry (DSC) curve with an endothermic melting peak at 162.3 °C, preferably with a melting enthalpy of 160.2 J / g; And / or, it exhibits a differential scanning calorimetry (DSC) curve with an exothermic decomposition peak at 255.6 °C, preferably with a decomposition enthalpy of 316.7 J / g.

6. A method for preparing flonicamid in solid form I as described in claim 1, 2, 3, 4, or 5, characterized in that, Includes the following steps: Step 1: Dissolve the appropriate form of flonicamid in a solvent by heating for a certain time to obtain a flonicamid solution; Step 2: Crystallize the dissolved flonicamid to flonicamid solid form I; Step 3: Separate the crystallized flonicamid nitrile solid form I.

7. The method as described in claim 6, characterized in that, The solvent in step 1 is selected from any one of the following: a mixed solvent of acetonitrile and 1,2-dichloroethane, a mixed solvent of acetonitrile and dichloromethane, a mixed solvent of acetone and 1,2-dichloroethane, and a mixed solvent of acetone and dichloromethane, wherein the weight content of the chloroalkane solvent (1,2-dichloroethane or dichloromethane) in the mixed solvent is less than 50%.

8. The method as described in claim 7, characterized in that, The solvent in step 1 is selected from any one of the following: a mixed solvent of acetonitrile:1,2-dichloroethane = 7:3, a mixed solvent of acetonitrile:dichloromethane = 7:3, a mixed solvent of acetone:1,2-dichloroethane = 8:2, or a mixed solvent of acetone:dichloromethane = 8:2; wherein, the ratio of solvents is the mass ratio of solvents.

9. The method as described in claim 6, characterized in that, In step 1: the heating temperature is 35-55℃, and / or, after heating until dissolved, continue heating for 1-4 hours.

10. The method as described in claim 6, characterized in that, In step 2, the dissolved flonicamid is crystallized into flonicamid solid form I by gradient cooling, and finally needs to be cooled to 5°C to 30°C to precipitate crystals.

11. A solid form of flonicamid nitrile, characterized in that, It is obtained by the method of any one of claims 6, 7, 8, 9 and 10, and has a content of at least 95% by weight of the solid form I of flonicamid as described in any one of claims 1, 2, 3, 4 and 5.

12. A composition, characterized in that, It comprises flupyradifurone solid form I as described in any one of claims 1, 2, 3, 4 and 5 and at least one adjuvant selected from one or more of the following: surfactants, diluents, dispersants, wetting agents, antioxidants, defoamers, antifreeze agents, thickeners, and pH adjusters.

13. The composition according to claim 12, characterized in that, The composition comprises less than 80% by weight of the flupyradifurone solid form I.

14. The use of the flupyradifurone solid form I as described in any one of claims 1, 2, 3, 4 and 5, or the composition as described in claim 12 or 13, in the preparation of insecticides or the control of insects.

15. A method for controlling insects, characterized in that, This includes the application of an insect-inhibiting amount of flupyradifurone solid form I as described in any one of claims 1, 2, 3, 4, and 5 to the location of the insect, the area under protection, or directly to the insect to be controlled, or the composition as described in claim 12 or 13.

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