WO2023040759A1 - Crystalline form of methoxyfenozide, process for its preparation and use of the same - Google Patents

Crystalline form of methoxyfenozide, process for its preparation and use of the same Download PDF

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WO2023040759A1
WO2023040759A1 PCT/CN2022/118027 CN2022118027W WO2023040759A1 WO 2023040759 A1 WO2023040759 A1 WO 2023040759A1 CN 2022118027 W CN2022118027 W CN 2022118027W WO 2023040759 A1 WO2023040759 A1 WO 2023040759A1
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methoxyfenozide
crystalline modification
composition
crystalline
exhibiting
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PCT/CN2022/118027
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French (fr)
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James Timothy Bristow
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Rotam Agrochem International Company Limited
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
    • C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
    • C07C243/38—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to carbon atoms of six-membered aromatic rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/36—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids
    • A01N37/38—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids having at least one oxygen or sulfur atom attached to an aromatic ring system
    • A01N37/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids having at least one oxygen or sulfur atom attached to an aromatic ring system having at least one carboxylic group or a thio analogue, or a derivative thereof, and one oxygen or sulfur atom attached to the same aromatic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/04—Insecticides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C241/00—Preparation of compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
    • C07C241/04—Preparation of hydrazides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Definitions

  • the present invention relates to a crystalline form of N′-tert-butyl-N′- (3, 5-dimethylbenzoyl) -3-methoxy-2-methylbenzohydrazide (Methoxyfenozide) , a process for preparing this crystalline form and its use in agrochemical preparations.
  • Methoxyfenozide is a carbohydrazide exhibiting insecticidal activity. Methoxyfenozide acts as a molt accelerating compound (MAC) and is effective against a wide range of pests that belong to the species Lepidoptera. Upon intake of Methoxyfenozide, larval stage of the pests undergo incomplete and developmentally premature molts, which are ultimately lethal. Methoxyfenozide is employed in the protection of a wide range of crops including vegetables, cotton, fruit, maize and the like.
  • MAC molt accelerating compound
  • Methoxyfenozide has a molecular formula of C 22 H 28 N 2 O 3 . Its chemical structure may be represented by the following formula (I) :
  • Methoxyfenozide can be produced by a range of processes, such as the processes disclosed in US 5,530,028, CN 1435411A, CA 2103110C, CN 102040540A, CN 102584573A and CN 104803879A.
  • Methoxyfenozide in commercially available formulations containing formulated product is not satisfactory. Therefore, there is a need to improve the dispersibility of Methoxyfenozide. It would also be advantageous if the storage stability of Methoxyfenozide could also be improved.
  • Methoxyfenozide Surprisingly a novel crystalline modification of Methoxyfenozide has been found, which exhibits a much improved dispersibility and storage stability.
  • This novel crystalline modification of Methoxyfenozide may be prepared using a number of different solvents and/or solvent mixtures, in particular allowing this crystalline modification to be obtained in high yield.
  • the present invention provides a crystalline modification I of N′-tert-butyl-N′- (3, 5-dimethylbenzoyl) -3-methoxy-2-methylbenzohydrazide (Methoxyfenozide) exhibiting at least three of the following reflexes, in any combination, as 2 ⁇ ⁇ 0.20 degrees in an X-ray powder diffractogram (X-RPD) recorded using Cu-K ⁇ radiation at 25°C:
  • the crystalline modification I of Methoxyfenozide exhibits at least four of the aforementioned reflexes, more preferably at least five, still more preferably at least 6, more preferably still at least seven, especially at least eight, more especially at least nine, still more especially at least ten, in particular at least eleven, more particularly at least twelve of the aforementioned reflexes.
  • a preferred embodiment of the crystalline modification I of Methoxyfenozide exhibits two or more, more preferably three or more, still more preferably four or more, more preferably still at least five, especially at least six, more especially at least seven, still more especially at least eight, more especially still at least nine of the following reflexes:
  • a more preferred embodiment of the crystalline modification I of Methoxyfenozide exhibits two or more, more preferably three or more, still more preferably four or more, more preferably still at least five of the following reflexes:
  • Methoxyfenozide exhibits an X-ray powder diffractogram (X-RPD) recorded using Cu-K ⁇ radiation at 25°C substantially as shown in Figure 2.
  • the crystalline modification I of Methoxyfenozide may alternatively be characterized by its infrared (IR) spectrum. Accordingly, there is also provided a crystalline modification I of Methoxyfenozide exhibiting an infrared (IR) spectrum with characteristic functional group vibration peaks at wavenumbers (cm -1 , ⁇ 0.2%) of one or more of about 3305, 3006, 2966, 1683, 1639, 1587, 1494, 1274, 1244, 1027 and 861cm -1 , preferably the IR spectrum as shown in Figure 1.
  • the crystalline modification I of Methoxyfenozide may alternatively be characterized by its melting point. Accordingly, there is also provided a crystalline modification I of Methoxyfenozide exhibiting a differential scanning calorimetry (DSC) profile having an endothermic melting peak at 196.2°C, preferably with a melting enthalpy of 58.47 J/g.
  • DSC differential scanning calorimetry
  • the present invention provides a crystalline modification I of Methoxyfenozide characterized by X-ray powder diffraction (XRD) pattern as hereinbefore described, preferably substantially as shown in Figure 2, and/or characterized by an IR spectrum as hereinbefore described, preferably substantially as shown in Figure 1, and/or characterized by a melting point of 196.2°C.
  • XRD X-ray powder diffraction
  • the crystalline modification I of Methoxyfenozide of the present invention exhibits a high degree of stability when formulated, compared with known forms of Methoxyfenozide, such as prepared in accordance with the disclosure of CN104803879A. By virtue of its good stability properties, the crystalline modification I of Methoxyfenozide provides a desirable long storage period for formulations.
  • the present invention provides a process for preparing a crystalline modification I of Methoxyfenozide comprising the steps of:
  • step ii) precipitating the dissolved compound in step i) into the crystalline modification I of Methoxyfenozide
  • a solution is formed by dissolving Methoxyfenozide in a solvent system.
  • the Methoxyfenozide used to form in step i) is amorphous Methoxyfenozide or a crystalline form of Methoxyfenozide.
  • the Methoxyfenozide used to form the solution in step i) is amorphous, for example obtained commercially or prepared using a process of the prior art discussed hereinbefore.
  • the process to prepare the crystalline modification I of Methoxyfenozide employs a solvent system.
  • the solvent system comprises one or a mixture of two or more solvents. Any suitable solvent that dissolves Methoxyfenozide and yields the crystalline modification I may be used.
  • the solvent system comprises one or more solvents selected from ketones, for example alkanones and cycloalkanones; and sulfur-containing organic compounds, for example, sulfoxides.
  • Preferred alkanones are those having from 2 to 6 carbon atoms, more preferably from 2 to 4 carbon atoms.
  • Preferred cycloalkanones are those having from 3 to 8 carbon atoms, more preferably from 4 to 6 carbon atoms, with cyclohexanone being an especially preferred cycloalkanone.
  • Preferred sulfoxides are the dialkylsulfoxides having a general formula R-SO-R’, where R and R’ are each alkyl groups having from 1 to 6 carbon atoms, more preferably from 1 to 4 carbon atoms, still more preferably from 1 to 3 carbon atoms. Preferably R and R’ are the same.
  • a particularly preferred sulfoxide is dimethysulfoxide.
  • the solvent system consists of cyclohexanone, dimethysulfoxide or a mixture thereof.
  • the Methoxyfenozide may be dissolved in the solvent system in any suitable manner.
  • Methoxyfenozide is dissolved in the solvent system in step i) by heating the solvent system from ambient temperature to a temperature at or below the reflux temperature of the solvent system.
  • the solution of Methoxyfenozide is prepared by dissolving Methoxyfenozide at the reflux temperature of the solvent system.
  • concentration of the solution formed in step i) will depend upon the solubility of Methoxyfenozide in the solvent system.
  • the solution of Methoxyfenozide prepared in step i) is used in step ii) to form a precipitate of the crystalline modification I.
  • the precipitate of the crystalline modification I of Methoxyfenozide may be formed in any suitable manner.
  • the solution prepared in step i) may be cooled to cause Methoxyfenozide to precipitate from the solution.
  • the solution is cooled to a temperature of from about 0°C to 20°C to crystallize the desired crystalline form from the solvent.
  • the crystalline modification I of Methoxyfenozide may also be crystallized out of the solution by concentrating the solution by removing solvent, for example with or without applying vacuum and cooling to below the reflux temperature of the solvent system.
  • the crystalline modification I may be precipitated from the solution by the addition of a solvent or other component that reduces the solubility of Methoxyfenozide in the solvent system.
  • Formation of the crystalline modification I of Methoxyfenozide from the solution may also be effected or enhanced by adding seed crystals of Methoxyfenozide to the solution.
  • the seed crystals are crystals of the crystalline modification I of Methoxyfenozide.
  • the use seed crystals can promote or accelerate the crystallization.
  • Seed crystals may be employed in any suitable amount.
  • the seed crystal amount added to the solution is typically in the range of 0.001% to 10% by weight, preferably 0.005% to 0.5% by weight based on the weight of Methoxyfenozide used for the preparation of concentrated solution in step (i) .
  • the seed crystals are added to the solution at the temperature below the boiling point of the solvent system.
  • the precipitated crystalline modification I of Methoxyfenozide obtained from step ii) is isolated from the solvent system to yield the crystalline product.
  • Any suitable technique to separate the crystalline product from the solvent system may be used and suitable techniques are known in the art. Suitable techniques include filtration, centrifugation or decantation or a combination thereof.
  • the isolated crystalline solid is preferably washed with solvent one or more times.
  • the solvent employed in the washing stage consists of one or more components of the solvent system employed for preparation of the solution in step i) , as described hereinbefore.
  • the washing may be carried out using the solvent or solvent mixture at a temperature at or below ambient temperature, such as between room temperature and 0°C, depending on the solubility of the crystalline material in the solvent, in order to minimize the loss of crystalline material in the corresponding washing solvent.
  • the washings and/or the solvent of crystallization may be concentrated to obtain solid Methoxyfenozide which may be recycled.
  • the crystalline modification I of Methoxyfenozide of the present invention exhibits a significantly improved dispersibility and stability compared with known forms of Methoxyfenozide.
  • the crystalline modification I may be prepared by crystallization from solution in a suitable solvent system.
  • the present invention provides the use of a solvent system to increase the dispersibility and/or stability of Methoxyfenozide.
  • Suitable solvent systems are those comprising solvents that yield the crystalline modification I upon crystallization of Methoxyfenozide from solution in the solvent system and are as hereinbefore described.
  • the present invention further provides a crystalline material comprising the crystalline modification I of Methoxyfenozide obtainable by the process of the present invention, having a content of a crystalline modification I of Methoxyfenozide of at least 98% by weight.
  • Methoxyfenozide is known to be active as an insecticide and finds use in the prevention and control of insect infestations. It has been found that the crystalline modification I of Methoxyfenozide is also active in controlling insect pests. As a result, the techniques of formulating and applying Methoxyfenozide known in the art can also be applied in an analogous manner to Methoxyfenozide in the crystalline modification I of the invention.
  • the present invention provides an insecticide composition comprising crystalline modification I of Methoxyfenozide as defined hereinbefore.
  • the insecticidal composition comprising the crystalline modification I of Methoxyfenozide further comprises at least one auxiliary.
  • the present invention provides a use of the crystalline modification I of Methoxyfenozide or a composition as herein described for the control of insects.
  • the present invention provides an insecticidal composition
  • the crystalline modification I of Methoxyfenozide may be present in the composition in any suitable amount to provide the required insecticidal activity.
  • the amount of the crystalline modification I of Methoxyfenozide in the composition is less than 75% by weight of the composition, preferably less than 60% by weight of the composition.
  • the amount of the crystalline modification I of Methoxyfenozide is less than 50% by weight, more preferably less than 40%, still more preferably less than 30% by weight of the composition, for example about 24% by weight of the composition.
  • the insectidical composition may be provided in any suitable formulation.
  • Such formulation types are known in the art.
  • the composition is in the form of a suspension concentrate (SC) , soluble concentrate (SL) , oil-based suspension concentrate (OD) , water-soluble granules (SG) , dispersible concentrate (DC) , emulsifiable concentrate (EC) , emulsion seed dressing, suspension seed dressing, granules (GR) , microgranules (MG) , suspoemulsion (SE) or water-dispersible granules (WG) .
  • SC suspension concentrate
  • SL soluble concentrate
  • OD oil-based suspension concentrate
  • DC dispersible concentrate
  • EC emulsifiable concentrate
  • emulsion seed dressing emulsion seed dressing
  • suspension seed dressing granules
  • GR microgranules
  • SE suspoemulsion
  • WG water-dispersible granules
  • the composition is in the form of a suspension concentrate (SC) .
  • the crystalline modification I of Methoxyfenoxide is present in the formulations in a sufficient concentration to achieve the required dosage when applied to plants or the loci thereof, preferably in a concentration of about 1% to about 75% by weight of the total mixture.
  • the formulations are prepared, for example, by extending the crystalline modification I of Methoxyfenozide with water, solvents and carriers, using, where appropriate, emulsifiers and/or dispersants, and/or other auxiliaries.
  • the aforementioned formulations are prepared by mixing the crystalline modification I of Methoxyfenozide with at least one auxiliary as is known in the art, for example, surfactants, liquid diluents, solid diluents, wetting agents, dispersants, thickening agents, anti-freezing agents, biocides and any necessary adjuvants and other formulation ingredients.
  • auxiliary as is known in the art, for example, surfactants, liquid diluents, solid diluents, wetting agents, dispersants, thickening agents, anti-freezing agents, biocides and any necessary adjuvants and other formulation ingredients.
  • Surfactants can be an emulsifier, dispersant or wetting agent of ionic or nonionic type.
  • examples which may be used include, but are not limited to, salts of polyacrylic acids, salts of lignosulphonic acid, salts of phenylsulphonic or naphthalenesulphonic acids, polycondensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines, substituted phenols, especially alkylphenols, sulphosuccinic ester salts, taurine derivatives, especially alkyltaurates, or phosphoric esters of polyethoxylated phenols or alcohols.
  • Liquid diluents include, but are not limited to, water, N, N-dimethylamide, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, propylene carbonate, dibasic esters, paraffines, alkylbenzenes, alkyl naphthalenes, glycerine, triacetine, oils of olive, castor, linseed, sesame, corn, peanut, cotton-seed, soybean, rape-seed and coconut, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as hexyl acetate, heptyl acetate and octyl acetate, water and alcohols such methanol, cyclohexanol, decanol, benzyl and tetrahydrofurfuryl alcohol and mixtures thereof.
  • Solid diluents can be water-soluble or water-insoluble.
  • Water-soluble solid diluents include, but are not limited to, salts such as alkali metal phosphates (e.g., sodium dihydrogen phosphate) , alkaline earth phosphates, sulfates of sodium, potassium, magnesium and zinc, sodium and potassium chloride, sodium acetate, sodium carbonate and sodium benzoate, and sugars and sugar derivatives such as sorbitol, lactose, sucrose and mannitol.
  • alkali metal phosphates e.g., sodium dihydrogen phosphate
  • alkaline earth phosphates alkaline earth phosphates
  • sulfates of sodium, potassium, magnesium and zinc sodium and potassium chloride
  • sodium acetate sodium carbonate and sodium benzoate
  • sugars and sugar derivatives such as sorbitol, lactose, sucrose and mannitol.
  • Wetting agents include, but are not limited to, alkyl sulfosuccinates, laureates, alkyl sulfates, phosphate esters, acetylenic diols, ethoxyfluorinated alcohols, ethoxylated silicones, alkyl phenol ethyoxylates, benzene sulfonates, alkyl-substituted benzene sulfonates, alkyl a-olefin sulfonates, naphthalene sulfonates, alkyl-substituted napthalene sulfonates, condensates of naphthalene sulfonates and alkyl-substituted naphthalene sulfonates with formaldehyde, and alcohol ethoxylates.
  • Polyalkylene glycol ether is particularly useful for the compositions of the invention.
  • Dispersants include, but are not limited to, sodium, calcium and ammonium salts of ligninsulfonates (optionally polyethoxylated) ; sodium and ammonium salts of maleic anhydride copolymers; sodium salts of condensed phenolsulfonic acid; and naphthalene sulfonate-formaldehyde condensates.
  • compositions comprising up to 10% by weight of dispersant.
  • Ligninsulfonates such as sodium ligninsulfonates are particularly useful for the composition of the invention.
  • Sodium alkyl naphthalene sulfonate -formaldehyde condensate is particularly useful for the compositions of the invention.
  • Thickening agents include, but are not limited to, guar gum, pectin, casein, carrageenan, xanthan gum, alginates, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and carboxymethylcellulose.
  • Synthetic thickeners include derivatives of the former categories, and also polyvinyl alcohols, polyacrylamides, polyvinylpyrrolidones, various polyethers, their copolymers as well as polyacrylic acids and their salts.
  • Xanthan gum is particularly useful for the compositions of the invention.
  • Suitable anti-freezing agents include liquid polyols, for example ethylene glycol, propylene glycol or glycerol.
  • the amount of antifreeze agents is generally from about 1% to about 20% by weight, in particular from about 5% to about 10% by weight, based on the total weight of the composition.
  • Biocides may also be added to the compositions according to the invention. Suitable Biocides include those based on isothiazolones, for example from ICI or RS from Thor Chemie or MK from Rohm & Haas. The amount of biocides is typically from 0.05% to 0.5% by weight, based on the total weight of composition.
  • Antifoaming agents include all substances which can normally be used for this purpose in agrochemical compositions. Suitable anti-foam agents are known in the art and are available commercially. Particularly preferred antifoam agents are mixtures of polydimethylsiloxanes and perfluroalkylphosphonic acids, such as the silicone antifoaming agents available from GE or Compton.
  • Antioxidants include all substances which can normally be used for this purpose in agrochemical compositions, as is known in the art. Preference is given to butylated hydroxytoluene (BHT) .
  • BHT butylated hydroxytoluene
  • formulation ingredients can also be used in the present invention, such as dyes, drying agents, and the like. These ingredients are known to one skilled in the art.
  • the present invention furthermore provides processes for preparing compositions for controlling pests using the crystalline modification I of Methoxyfenozide.
  • the techniques for forming the compositions, such as aforementioned formulations, will be known to the person skilled in the art.
  • the present invention also provides a method for controlling or preventing insect infestations of plants, comprising applying to the plants, plant parts, or the surroundings of the plants, an insecticidally effective amount of the crystalline modification I of Methoxyfenozide as hereinbefore described, or a composition as hereinbefore described.
  • the method provides control of insects in the plants, plant parts, and/or their surroundings and comprises applying to the foliage or fruit of the plants, plant parts, or their surroundings, an effective amount of crystalline modification I of Methoxyfenozide.
  • plants are to be understood as meaning all plants and plant populations such as desired and undesired wild plants or crop plants (including naturally occurring crop plants) .
  • Crop plants can be plants which can be obtained by conventional breeding and optimization methods, by biotechnological and genetic engineering methods, or by combinations of these methods, including the transgenic plants and the plant cultivars which can or cannot be protected by plant breeders' rights.
  • Plant parts are to be understood as meaning all parts and organs of plants above and below the ground, such as shoot, leaves, needles, stalks, stems, flowers, fruit bodies, fruits, seeds, roots, tubers and rhizomes.
  • Harvested materials, and vegetative and generative propagation materials for example, cutting, tubers, meristem tissue, rhizomes, offsets, seeds, single and multiple plant cells and any other plant tissues, are also included.
  • the crystalline modification I of Methoxyfenozide according to the present invention may be used in combination with one or more other active compounds, such as insecticides, attractants, sterilizing agents, bactericides, acaricides, nematicides, fungicides, growth-regulating substances, herbicides, safeners and fertilizers.
  • active compounds such as insecticides, attractants, sterilizing agents, bactericides, acaricides, nematicides, fungicides, growth-regulating substances, herbicides, safeners and fertilizers.
  • compositions or formulations of the invention Treatment of the plants and plant parts with the compositions or formulations of the invention is carried out directly by application of the compositions or formulations to the plants or plant parts or by allowing the compositions or formulations to act on their surroundings, habitat or storage space.
  • Customary treatment methods are known in the art. Examples of these customary treatment methods include dipping, spraying, vaporizing, fogging, broadcasting, painting on in the case of propagation material, and applying one or more coats particularly in the case of seed.
  • the crystalline modification I of Methoxyfenozide may be used to control a wide range of insects and to protect a wide range of crop plants.
  • the benefits of the present invention are particularly marked when the crystalline modification I of Methoxyfenozide or its composition is applied to kill sucking pests, such as armyworm, borer, budworm, cabbageworm, caterpillar, corn borer, cutworm, earworm, fruitworm, hornworm, leafhopper, leafminer, leafroller, looper, melonworm, moth, pickleworm and webworm, in growing crops of useful plants: such as almond, apple, avocado, blueberry, citrus, coffee, custard apple, grapevines, kiwifruit, longan, lychee, macadamia, pear, pepper and tomato.
  • sucking pests such as armyworm, borer, budworm, cabbageworm, caterpillar, corn borer, cutworm, earworm, fruitworm, hornworm, leafhopper, leafminer, leafroller, looper,
  • the term “about, ” when used in connection with a numerical amount or range, means somewhat more or somewhat less than the stated numerical amount or range, to a deviation of ⁇ 10% of the stated numerical amount or endpoint of the range.
  • “Surrounding” as used herein, refers to the place on which the plants are growing, the place on which the plant propagation materials of the plants are sown or the place on which the plant propagation materials of the plants will be sown.
  • Precipitation refers to the sedimentation of a solid material (a precipitate) , including the sedimentation of a crystalline material, from a liquid solution in which the solid material is present in amounts greater than its solubility in the amount of liquid solution.
  • references to properties are, unless stated otherwise, to properties measured under ambient conditions, i.e. at atmospheric pressure and at a temperature of from about 20 °C – 26°C.
  • crystalline refers to a solid state form wherein molecules are arranged to form a crystal lattice comprising distinguishable unit cells.
  • crystalline material may, for example, be identified by yielding diffraction peaks when subjected to X-ray radiation and/or exhibiting an endothermic melting peak profile with a characteristic sharp peak under differential scanning calorimetry (DSC) .
  • DSC differential scanning calorimetry
  • Figure 1 is an Infrared (IR) spectrum of one embodiment of the crystalline modification I of Methoxyfenozide
  • Figure 2 is an X-ray diffraction (XRD) spectrum of one embodiment of the crystalline modification I of Methoxyfenozide;
  • Figure 3 is a differential scanning calorimetry (DSC) spectrum of one embodiment of the crystalline modification I of Methoxyfenozide.
  • Figure 4 is an X-ray diffraction (XRD) spectrum of amorphous Methoxyfenozide.
  • the IR spectrum was measured with the resolution of 4 cm -1 and with the number of scans of 16 for the crystallized samples.
  • the crystalline modification I of Methoxyfenozide can be identified by its characteristic functional group vibration peaks at wavenumbers (cm -1 , ⁇ 0.2%) of one or more of 3305, 3006, 2966, 1683, 1639, 1587, 1494, 1274, 1244, 1027 and 861 cm -1 as shown in Figure 1.
  • Example 1 Preparation of Amorphous Methoxyfenozide in accordance with the disclosure of CN104803879A
  • Tert-butyl hydrazine hydrochloride and dichloroethane were added to a reactor vessel at room temperature.
  • the reactor vessel was cooled with brine to about -5 to -6°C.
  • Liquid base was added into the reactor vessel.
  • the reactor vessel was then allowed to stand until layering of the contents occurred.
  • the aqueous layer was removed.
  • the organic layer was kept at -5 to -6°C.
  • 3-methoxy-2-methylbenzoyl chloride was added dropwise while keeping the temperature of the reactor no greater than 0°C. After 7 to 9 hours, a sample was isolated and analyzed. Water was added. The contents of the reactor vessel were stirred. The reactor vessel was then allowed to stand until layering of the contents again occurred.
  • the aqueous layer was removed.
  • the organic layer was heated to 75 to 85°C under atmospheric pressure to remove dichloroethane and then cooled to room temperature and finally dissolved in toluene.
  • the contents of the reactor vessel were kept at a temperature of less than 0°C while adding dropwise 3, 5-dimethylbenzoyl chloride and liquid base to adjust the pH to mildly acidic. After 7 to 9 hours, a sample was isolated and analyzed. The reactor vessel was then allowed to stand until layering of the contents occurred. The aqueous layer was removed. The organic layer was kept at a temperature of 100 to 120°C under atmospheric pressure to remove toluene. It was then cooled to room temperature and finally dissolved in toluene and water for re-crystallization. The product was dried at 60 to 70°C.
  • the product was subjected to analysis by X-ray diffraction.
  • the X-ray diffraction pattern obtained is shown in Figure 4.
  • Figure 4 the X-ray powder diffraction pattern of the resulting Methoxyfenozide product had no significant signals, which indicates the Methoxyfenozide product prepared in accordance with the disclosure of CN104803879A is amorphous.
  • Methoxyfenozide prepared in Example 1 (10 g) was placed in a 3 neck round bottom flask along with cyclohexanone (60 mL) and the resulting slurry was heated to 80°C to form a homogeneous solution. The homogeneous solution was stirred at 80°C for 2 hours and the insoluble particles, if any, were removed by filtration. Thereafter, the solution was slowly cooled to room temperature.
  • the product was characterized as crystalline modification I of Methoxyfenozide by IR spectrometry and XRD, exhibiting the spectra shown in Figures 1 and 2 respectively.
  • the IR spectrum of the Methoxyfenozide product shows characteristic vibrations of the functional group at 3305, 3006, 2966, 1683, 1639, 1587, 1494, 1274, 1244, 1027 and 861 cm -1 .
  • a DSC thermogram of the Methoxyfenozide product was obtained and exhibited an endothermic melting peak having an onset at 188.1°C and a peak at 196.2°C, and a melting enthalpy of 58.47 J/g.
  • the DSC thermogram is shown in Figure 3.
  • Methoxyfenozide prepared in Example 1 (5 g) sample was placed in a 3 neck round bottom flask along with dimethylsulfoxide (35 mL) and the resulting slurry was heated to 80°C to obtain a homogeneous solution. The resultant hot solution was stirred at 80°C for 2 hours and filtered to remove insoluble particles (if any) , and the solution was slowly cooled to ambient temperature. The desired crystalline product was precipitated out as fine crystals during cooling and the mixture was stirred at 20°C for 2 hours. The resulting slurry was then filtered, washed with cooled dimethylsulfoxide (6 mL) and dried under vacuum at 50°C, in order to remove the solvent traces from the crystals. The product obtained had a purity of 98% with a product yield of 85%.
  • the original concentration of Methoxyfenozide in each formulation was 20 %.
  • the concentration of the crystalline modification I of Methoxyfenozide in the suspension concentrate formulation remained constant at 20 %wt, indicating no degradation or loss of the component, in turn indicating that the crystalline modification I of Methoxyfenozide is stable.
  • the amorphous Methoxyfenozide exhibited a poor stability in the formulation, with a significant reduction in its concentration after 3 months and especially after 6 months.
  • the crystalline modification I of Methoxyfenozide remained well dispersed in the suspension concentrate formulation.
  • the amorphous Methoxyfenozide exhibited significant aggregation in the suspension concentrate over the test periods, especially after both 3 and 6 months.

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Abstract

A crystalline modification I of N'-tert-butyl-N'- (3, 5-dimethylbenzoyl) -3-methoxy-2-methylbenzohydrazide (Methoxyfenozide) is provided. There is also provided a process for preparing this crystalline form. The use of this novel crystalline form to combat insecticidal infestation in crops is also provided.

Description

CRYSTALLINE FORM OF METHOXYFENOZIDE, PROCESS FOR ITS PREPARATION AND USE OF THE SAME
The present invention relates to a crystalline form of N′-tert-butyl-N′- (3, 5-dimethylbenzoyl) -3-methoxy-2-methylbenzohydrazide (Methoxyfenozide) , a process for preparing this crystalline form and its use in agrochemical preparations.
N′-tert-butyl-N′- (3, 5-dimethylbenzoyl) -3-methoxy-2-methylbenzohydrazide (Methoxyfenozide) is a carbohydrazide exhibiting insecticidal activity. Methoxyfenozide acts as a molt accelerating compound (MAC) and is effective against a wide range of pests that belong to the species Lepidoptera. Upon intake of Methoxyfenozide, larval stage of the pests undergo incomplete and developmentally premature molts, which are ultimately lethal. Methoxyfenozide is employed in the protection of a wide range of crops including vegetables, cotton, fruit, maize and the like.
Methoxyfenozide has a molecular formula of C 22H 28N 2O 3. Its chemical structure may be represented by the following formula (I) :
Figure PCTCN2022118027-appb-000001
Commercially available Methoxyfenozide can be produced by a range of processes, such as the processes disclosed in US 5,530,028, CN 1435411A, CA 2103110C, CN 102040540A, CN 102584573A and CN 104803879A.
It is to be noted that the dispersibility of Methoxyfenozide in commercially available formulations containing formulated product is not satisfactory. Therefore, there is a need to improve the dispersibility of Methoxyfenozide. It would also be advantageous if the storage stability of Methoxyfenozide could also be improved.
Surprisingly a novel crystalline modification of Methoxyfenozide has been found, which exhibits a much improved dispersibility and storage stability. This novel crystalline modification of Methoxyfenozide may be prepared using a number of different solvents and/or solvent mixtures, in particular allowing this crystalline modification to be obtained in high yield.
In a first aspect, the present invention provides a crystalline modification I of N′-tert-butyl-N′- (3, 5-dimethylbenzoyl) -3-methoxy-2-methylbenzohydrazide (Methoxyfenozide) exhibiting at least three of the following reflexes, in any combination, as 2θ ± 0.20 degrees in an X-ray powder diffractogram (X-RPD) recorded using Cu-Kα radiation at 25℃:
2θ = 9.47 ± 0.20     (1)
2θ = 9.81 ± 0.20    (2)
2θ = 12.63 ± 0.20   (3)
2θ = 14.26 ± 0.20      (4)
2θ = 16.49 ± 0.20      (5)
2θ = 16.70 ± 0.20   (6)
2θ = 18.01 ± 0.20    (7)
2θ = 18.49 ± 0.20     (8)
2θ = 19.65 ± 0.20     (9)
2θ = 20.47 ± 0.20   (10)
2θ = 21.44 ± 0.20      (11)
2θ = 22.43 ± 0.20    (12)
2θ = 23.55 ± 0.20        (13)
2θ = 23.93 ± 0.20         (14)
2θ = 25.41 ± 0.20        (15)
2θ = 26.63 ± 0.20        (16) .
In a preferred embodiment, the crystalline modification I of Methoxyfenozide exhibits at least four of the aforementioned reflexes, more preferably at least five, still more preferably at least 6, more preferably still at least seven, especially at least eight, more especially at least nine, still more especially at least ten, in particular at least eleven, more particularly at least twelve of the aforementioned reflexes.
A preferred embodiment of the crystalline modification I of Methoxyfenozide exhibits two or more, more preferably three or more, still more preferably four or more, more preferably still at least five, especially at least six, more especially at least seven, still more especially at least eight, more especially still at least nine of the following reflexes:
2θ = 9.47 ± 0.20   (1)
2θ = 9.81 ± 0.20    (2)
2θ = 12.63 ± 0.20     (3)
2θ = 16.70 ± 0.20     (5)
2θ = 18.01 ± 0.20     (6)
2θ = 18.49 ± 0.20       (7)
2θ = 20.47 ± 0.20     (9)
2θ = 21.44 ± 0.20       (10)
2θ = 22.43 ± 0.20     (11)
2θ = 23.55 ± 0.20       (12) .
A more preferred embodiment of the crystalline modification I of Methoxyfenozide exhibits two or more, more preferably three or more, still more preferably four or more, more preferably still at least five of the following reflexes:
2θ = 9.47 ± 0.20     (1)
2θ = 9.81 ± 0.20      (2)
2θ = 12.63 ± 0.20    (3)
2θ = 16.70 ± 0.20       (5)
2θ = 18.01 ± 0.20       (6)
2θ = 18.49 ± 0.20     (7)
2θ = 23.55 ± 0.20      (12) .
One preferred crystalline modification I of Methoxyfenozide exhibits an X-ray powder diffractogram (X-RPD) recorded using Cu-Kα radiation at 25℃ substantially as shown in Figure 2.
The crystalline modification I of Methoxyfenozide may alternatively be characterized by its infrared (IR) spectrum. Accordingly, there is also provided a crystalline modification I of Methoxyfenozide exhibiting an infrared (IR) spectrum with characteristic functional group vibration peaks at wavenumbers (cm -1, ±0.2%) of one or more of about 3305, 3006, 2966, 1683, 1639, 1587, 1494, 1274, 1244, 1027 and 861cm -1, preferably the IR spectrum as shown in Figure 1.
The crystalline modification I of Methoxyfenozide may alternatively be characterized by its melting point. Accordingly, there is also provided a crystalline modification I of Methoxyfenozide exhibiting a differential scanning calorimetry (DSC) profile having an endothermic melting peak at 196.2℃, preferably with a melting enthalpy of 58.47 J/g.
In a preferred embodiment, the present invention provides a crystalline modification I of Methoxyfenozide characterized by X-ray powder diffraction (XRD) pattern as hereinbefore described, preferably substantially as shown in Figure 2, and/or characterized by an IR spectrum as hereinbefore described, preferably substantially as shown in Figure 1, and/or characterized by a melting point of 196.2℃.
It has been found that the crystalline modification I of Methoxyfenozide of the present invention exhibits a high degree of stability when formulated, compared with known forms of Methoxyfenozide, such as prepared in accordance with the disclosure of CN104803879A. By virtue of its good stability properties, the crystalline modification I of Methoxyfenozide provides a desirable long storage period for formulations.
In a further aspect, the present invention provides a process for preparing a crystalline modification I of Methoxyfenozide comprising the steps of:
i) dissolving Methoxyfenozide in a solvent system comprising one or more solvents;
ii) precipitating the dissolved compound in step i) into the crystalline modification I of Methoxyfenozide; and
iii) isolating the precipitated crystalline modification I.
In step i) of the process, a solution is formed by dissolving Methoxyfenozide in a solvent system. The Methoxyfenozide used to form in step i) is amorphous Methoxyfenozide or a crystalline form of Methoxyfenozide. In one preferred embodiment, the Methoxyfenozide used to form the solution in step i) is amorphous,  for example obtained commercially or prepared using a process of the prior art discussed hereinbefore.
The process to prepare the crystalline modification I of Methoxyfenozide employs a solvent system. The solvent system comprises one or a mixture of two or more solvents. Any suitable solvent that dissolves Methoxyfenozide and yields the crystalline modification I may be used. Preferably, the solvent system comprises one or more solvents selected from ketones, for example alkanones and cycloalkanones; and sulfur-containing organic compounds, for example, sulfoxides.
Preferred alkanones are those having from 2 to 6 carbon atoms, more preferably from 2 to 4 carbon atoms. Preferred cycloalkanones are those having from 3 to 8 carbon atoms, more preferably from 4 to 6 carbon atoms, with cyclohexanone being an especially preferred cycloalkanone.
Preferred sulfoxides are the dialkylsulfoxides having a general formula R-SO-R’, where R and R’ are each alkyl groups having from 1 to 6 carbon atoms, more preferably from 1 to 4 carbon atoms, still more preferably from 1 to 3 carbon atoms. Preferably R and R’ are the same. A particularly preferred sulfoxide is dimethysulfoxide.
In a preferred embodiment, the solvent system consists of cyclohexanone, dimethysulfoxide or a mixture thereof.
The Methoxyfenozide may be dissolved in the solvent system in any suitable manner. In one embodiment, Methoxyfenozide is dissolved in the solvent system in step i) by heating the solvent system from ambient temperature to a temperature at or below the reflux temperature of the solvent system. Preferably, the solution of Methoxyfenozide is prepared by dissolving Methoxyfenozide at the reflux temperature of the solvent system. The concentration of the solution formed in step i) will depend upon the solubility of Methoxyfenozide in the solvent system.
The solution of Methoxyfenozide prepared in step i) is used in step ii) to form a precipitate of the crystalline modification I. The precipitate of the crystalline modification I of Methoxyfenozide may be formed in any suitable manner. For example, the solution prepared in step i) may be cooled to cause Methoxyfenozide to precipitate from the solution. Preferably, the solution is cooled to a temperature of from about 0℃ to 20℃ to crystallize the desired crystalline form from the solvent. The crystalline modification I of Methoxyfenozide may also be crystallized out of the solution by concentrating the solution by removing solvent, for example with or without applying vacuum and cooling to below the reflux temperature of the solvent system. Alternatively, or in addition, the crystalline modification I may be precipitated from the solution by the addition of a solvent or other component that reduces the solubility of Methoxyfenozide in the solvent system.
Formation of the crystalline modification I of Methoxyfenozide from the solution may also be effected or enhanced by adding seed crystals of Methoxyfenozide to the solution. Preferably, the seed crystals are crystals of the crystalline modification I of Methoxyfenozide. The use seed crystals can promote or accelerate the crystallization.
Seed crystals, if used, may be employed in any suitable amount. The seed crystal amount added to the solution is typically in the range of 0.001% to 10% by weight, preferably 0.005% to 0.5% by weight based on the weight of Methoxyfenozide used for the preparation of concentrated solution in step (i) . Preferably, the seed crystals are added to the solution at the temperature below the boiling point of the solvent system.
The precipitated crystalline modification I of Methoxyfenozide obtained from step ii) is isolated from the solvent system to yield the crystalline product. Any suitable technique to separate the crystalline product from the solvent system may be used and suitable techniques are known in the art. Suitable techniques include filtration, centrifugation or decantation or a combination thereof.
Thereafter, the isolated crystalline solid is preferably washed with solvent one or more times. Preferably, the solvent employed in the washing stage consists of one or more components of the solvent system employed for preparation of the solution in step i) , as described hereinbefore. The washing may be carried out using the solvent or solvent mixture at a temperature at or below ambient temperature, such as between room temperature and 0℃, depending on the solubility of the crystalline material in the solvent, in order to minimize the loss of crystalline material in the corresponding washing solvent.
The washings and/or the solvent of crystallization may be concentrated to obtain solid Methoxyfenozide which may be recycled.
As noted above, the crystalline modification I of Methoxyfenozide of the present invention exhibits a significantly improved dispersibility and stability compared with known forms of Methoxyfenozide. As described above, the crystalline modification I may be prepared by crystallization from solution in a suitable solvent system.
Accordingly, in a further aspect, the present invention provides the use of a solvent system to increase the dispersibility and/or stability of Methoxyfenozide. Suitable solvent systems are those comprising solvents that yield the crystalline modification I upon crystallization of Methoxyfenozide from solution in the solvent system and are as hereinbefore described.
The present invention further provides a crystalline material comprising the crystalline modification I of Methoxyfenozide obtainable by the process of the present invention, having a content of a crystalline modification I of Methoxyfenozide of at least 98% by weight.
As described hereinbefore, Methoxyfenozide is known to be active as an insecticide and finds use in the prevention and control of insect infestations. It has been found that the crystalline modification I of Methoxyfenozide is also active in controlling insect pests. As a result, the techniques of formulating and applying  Methoxyfenozide known in the art can also be applied in an analogous manner to Methoxyfenozide in the crystalline modification I of the invention.
Accordingly, in a further aspect, the present invention provides an insecticide composition comprising crystalline modification I of Methoxyfenozide as defined hereinbefore. In many embodiments, the insecticidal composition comprising the crystalline modification I of Methoxyfenozide further comprises at least one auxiliary.
Still further, the present invention provides a use of the crystalline modification I of Methoxyfenozide or a composition as herein described for the control of insects.
As noted above, the present invention provides an insecticidal composition comprising the crystalline modification I of Methoxyfenozide and at least one auxiliary. Methoxyfenozide may be present in the composition in any suitable amount to provide the required insecticidal activity. In one embodiment, the amount of the crystalline modification I of Methoxyfenozide in the composition is less than 75% by weight of the composition, preferably less than 60% by weight of the composition. In one preferred embodiment, the amount of the crystalline modification I of Methoxyfenozide is less than 50% by weight, more preferably less than 40%, still more preferably less than 30% by weight of the composition, for example about 24% by weight of the composition.
The insectidical composition may be provided in any suitable formulation. Such formulation types are known in the art. In one embodiment, the composition is in the form of a suspension concentrate (SC) , soluble concentrate (SL) , oil-based suspension concentrate (OD) , water-soluble granules (SG) , dispersible concentrate (DC) , emulsifiable concentrate (EC) , emulsion seed dressing, suspension seed dressing, granules (GR) , microgranules (MG) , suspoemulsion (SE) or water-dispersible granules (WG) . These different formulations may be prepared using suitable auxiliaries, carriers and solvents, as is known in the art.
In one preferred embodiment, the composition is in the form of a suspension concentrate (SC) .
The crystalline modification I of Methoxyfenoxide is present in the formulations in a sufficient concentration to achieve the required dosage when applied to plants or the loci thereof, preferably in a concentration of about 1% to about 75% by weight of the total mixture. The formulations are prepared, for example, by extending the crystalline modification I of Methoxyfenozide with water, solvents and carriers, using, where appropriate, emulsifiers and/or dispersants, and/or other auxiliaries.
The aforementioned formulations are prepared by mixing the crystalline modification I of Methoxyfenozide with at least one auxiliary as is known in the art, for example, surfactants, liquid diluents, solid diluents, wetting agents, dispersants, thickening agents, anti-freezing agents, biocides and any necessary adjuvants and other formulation ingredients.
Surfactants can be an emulsifier, dispersant or wetting agent of ionic or nonionic type. Examples which may be used include, but are not limited to, salts of polyacrylic acids, salts of lignosulphonic acid, salts of phenylsulphonic or naphthalenesulphonic acids, polycondensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines, substituted phenols, especially alkylphenols, sulphosuccinic ester salts, taurine derivatives, especially alkyltaurates, or phosphoric esters of polyethoxylated phenols or alcohols.
Liquid diluents include, but are not limited to, water, N, N-dimethylamide, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, propylene carbonate, dibasic esters, paraffines, alkylbenzenes, alkyl naphthalenes, glycerine, triacetine, oils of olive, castor, linseed, sesame, corn, peanut, cotton-seed, soybean, rape-seed and coconut, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as hexyl acetate, heptyl acetate and octyl acetate, water and alcohols such methanol, cyclohexanol, decanol, benzyl and tetrahydrofurfuryl alcohol and mixtures thereof.
Solid diluents can be water-soluble or water-insoluble. Water-soluble solid diluents include, but are not limited to, salts such as alkali metal phosphates (e.g.,  sodium dihydrogen phosphate) , alkaline earth phosphates, sulfates of sodium, potassium, magnesium and zinc, sodium and potassium chloride, sodium acetate, sodium carbonate and sodium benzoate, and sugars and sugar derivatives such as sorbitol, lactose, sucrose and mannitol. Examples of water-insoluble solid diluents include, but are not limited to clays, synthetic and diatomaceous silicas, calcium and magnesium silicates, titanium dioxide, aluminum, calcium and zinc oxide and mixtures thereof.
Wetting agents include, but are not limited to, alkyl sulfosuccinates, laureates, alkyl sulfates, phosphate esters, acetylenic diols, ethoxyfluorinated alcohols, ethoxylated silicones, alkyl phenol ethyoxylates, benzene sulfonates, alkyl-substituted benzene sulfonates, alkyl a-olefin sulfonates, naphthalene sulfonates, alkyl-substituted napthalene sulfonates, condensates of naphthalene sulfonates and alkyl-substituted naphthalene sulfonates with formaldehyde, and alcohol ethoxylates. Polyalkylene glycol ether is particularly useful for the compositions of the invention.
Dispersants include, but are not limited to, sodium, calcium and ammonium salts of ligninsulfonates (optionally polyethoxylated) ; sodium and ammonium salts of maleic anhydride copolymers; sodium salts of condensed phenolsulfonic acid; and naphthalene sulfonate-formaldehyde condensates. Of note are compositions comprising up to 10% by weight of dispersant. Ligninsulfonates such as sodium ligninsulfonates are particularly useful for the composition of the invention. Sodium alkyl naphthalene sulfonate -formaldehyde condensate is particularly useful for the compositions of the invention.
Thickening agents include, but are not limited to, guar gum, pectin, casein, carrageenan, xanthan gum, alginates, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and carboxymethylcellulose. Synthetic thickeners include derivatives of the former categories, and also polyvinyl alcohols, polyacrylamides, polyvinylpyrrolidones, various polyethers, their copolymers as well as polyacrylic acids and their salts. Xanthan gum is particularly useful for the compositions of the invention.
Suitable anti-freezing agents include liquid polyols, for example ethylene glycol, propylene glycol or glycerol. The amount of antifreeze agents is generally from about 1% to about 20% by weight, in particular from about 5% to about 10% by weight, based on the total weight of the composition.
Biocides may also be added to the compositions according to the invention. Suitable Biocides include those based on isothiazolones, for example 
Figure PCTCN2022118027-appb-000002
from ICI or
Figure PCTCN2022118027-appb-000003
RS from Thor Chemie or
Figure PCTCN2022118027-appb-000004
MK from Rohm & Haas. The amount of biocides is typically from 0.05% to 0.5% by weight, based on the total weight of composition.
Antifoaming agents include all substances which can normally be used for this purpose in agrochemical compositions. Suitable anti-foam agents are known in the art and are available commercially. Particularly preferred antifoam agents are mixtures of polydimethylsiloxanes and perfluroalkylphosphonic acids, such as the silicone antifoaming agents available from GE or Compton.
Antioxidants include all substances which can normally be used for this purpose in agrochemical compositions, as is known in the art. Preference is given to butylated hydroxytoluene (BHT) .
Other formulation ingredients can also be used in the present invention, such as dyes, drying agents, and the like. These ingredients are known to one skilled in the art.
The present invention furthermore provides processes for preparing compositions for controlling pests using the crystalline modification I of Methoxyfenozide. The techniques for forming the compositions, such as aforementioned formulations, will be known to the person skilled in the art.
The present invention also provides a method for controlling or preventing insect infestations of plants, comprising applying to the plants, plant parts, or the surroundings of the plants, an insecticidally effective amount of the crystalline  modification I of Methoxyfenozide as hereinbefore described, or a composition as hereinbefore described.
The method provides control of insects in the plants, plant parts, and/or their surroundings and comprises applying to the foliage or fruit of the plants, plant parts, or their surroundings, an effective amount of crystalline modification I of Methoxyfenozide.
All plants and plant parts can be treated in accordance with the present invention. In the present context, plants are to be understood as meaning all plants and plant populations such as desired and undesired wild plants or crop plants (including naturally occurring crop plants) . Crop plants can be plants which can be obtained by conventional breeding and optimization methods, by biotechnological and genetic engineering methods, or by combinations of these methods, including the transgenic plants and the plant cultivars which can or cannot be protected by plant breeders' rights. Plant parts are to be understood as meaning all parts and organs of plants above and below the ground, such as shoot, leaves, needles, stalks, stems, flowers, fruit bodies, fruits, seeds, roots, tubers and rhizomes. Harvested materials, and vegetative and generative propagation materials, for example, cutting, tubers, meristem tissue, rhizomes, offsets, seeds, single and multiple plant cells and any other plant tissues, are also included.
The crystalline modification I of Methoxyfenozide according to the present invention may be used in combination with one or more other active compounds, such as insecticides, attractants, sterilizing agents, bactericides, acaricides, nematicides, fungicides, growth-regulating substances, herbicides, safeners and fertilizers.
Treatment of the plants and plant parts with the compositions or formulations of the invention is carried out directly by application of the compositions or formulations to the plants or plant parts or by allowing the compositions or formulations to act on their surroundings, habitat or storage space. Customary treatment methods are known in the art. Examples of these customary treatment methods include dipping, spraying,  vaporizing, fogging, broadcasting, painting on in the case of propagation material, and applying one or more coats particularly in the case of seed.
The crystalline modification I of Methoxyfenozide may be used to control a wide range of insects and to protect a wide range of crop plants. The benefits of the present invention are particularly marked when the crystalline modification I of Methoxyfenozide or its composition is applied to kill sucking pests, such as armyworm, borer, budworm, cabbageworm, caterpillar, corn borer, cutworm, earworm, fruitworm, hornworm, leafhopper, leafminer, leafroller, looper, melonworm, moth, pickleworm and webworm, in growing crops of useful plants: such as almond, apple, avocado, blueberry, citrus, coffee, custard apple, grapevines, kiwifruit, longan, lychee, macadamia, pear, pepper and tomato.
As used herein, the term “about, ” when used in connection with a numerical amount or range, means somewhat more or somewhat less than the stated numerical amount or range, to a deviation of ± 10% of the stated numerical amount or endpoint of the range.
“Surrounding” as used herein, refers to the place on which the plants are growing, the place on which the plant propagation materials of the plants are sown or the place on which the plant propagation materials of the plants will be sown.
"Precipitation" as used herein, refers to the sedimentation of a solid material (a precipitate) , including the sedimentation of a crystalline material, from a liquid solution in which the solid material is present in amounts greater than its solubility in the amount of liquid solution.
Throughout the description and claims of this specification, the words “comprise” and variations of the words, for example “comprising” and “comprises” , mean “including but not limited to” , and do not exclude other moieties, additives, components, integers or steps. Moreover the singular encompasses the plural unless the context otherwise requires: in particular, where the indefinite article is used, the specification is  to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.
Preferred features of each aspect of the invention may be as described in connection with any of the other aspects. Other features of the invention will become apparent from the following examples. Generally speaking, the invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims and drawings) . Thus features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. Moreover unless stated otherwise, any feature disclosed herein may be replaced by an alternative feature serving the same or a similar purpose.
Where upper and lower limits are quoted for a property then a range of values defined by a combination of any of the upper limits with any of the lower limits may also be implied.
In this specification, references to properties are, unless stated otherwise, to properties measured under ambient conditions, i.e. at atmospheric pressure and at a temperature of from about 20 ℃ – 26℃.
The term “crystalline” , as used herein, refers to a solid state form wherein molecules are arranged to form a crystal lattice comprising distinguishable unit cells. In general, crystalline material may, for example, be identified by yielding diffraction peaks when subjected to X-ray radiation and/or exhibiting an endothermic melting peak profile with a characteristic sharp peak under differential scanning calorimetry (DSC) .
All percentages are given herein in weight % unless otherwise indicated.
The reference to any prior art in this specification is not, and should not be taken as, an acknowledgement of any form of suggestion that such prior art forms part of the common general knowledge.
Reference is made herein to the accompanying figures, in which:
Figure 1 is an Infrared (IR) spectrum of one embodiment of the crystalline modification I of Methoxyfenozide;
Figure 2 is an X-ray diffraction (XRD) spectrum of one embodiment of the crystalline modification I of Methoxyfenozide;
Figure 3 is a differential scanning calorimetry (DSC) spectrum of one embodiment of the crystalline modification I of Methoxyfenozide; and
Figure 4 is an X-ray diffraction (XRD) spectrum of amorphous Methoxyfenozide.
The present invention will now be described by the following examples, which are provided for illustrative purposes only.
The following measurement techniques have been employed:
All X-ray diffractograms were determined using a powder diffractometer in reflection geometry at 25℃, using the following acquisition parameters:
Figure PCTCN2022118027-appb-000005
Figure PCTCN2022118027-appb-000006
The IR spectrum was measured with the resolution of 4 cm -1 and with the number of scans of 16 for the crystallized samples. The crystalline modification I of Methoxyfenozide can be identified by its characteristic functional group vibration peaks at wavenumbers (cm -1, ± 0.2%) of one or more of 3305, 3006, 2966, 1683, 1639, 1587, 1494, 1274, 1244, 1027 and 861 cm -1 as shown in Figure 1.
All IR spectra were obtained using the following acquisition parameters:
Figure PCTCN2022118027-appb-000007
EXAMPLES
Example 1: Preparation of Amorphous Methoxyfenozide in accordance with the disclosure of CN104803879A
Tert-butyl hydrazine hydrochloride and dichloroethane were added to a reactor vessel at room temperature. The reactor vessel was cooled with brine to about -5 to -6℃. Liquid base was added into the reactor vessel. The reactor vessel was then allowed to stand until layering of the contents occurred. The aqueous layer was removed. The organic layer was kept at -5 to -6℃. 3-methoxy-2-methylbenzoyl chloride was added dropwise while keeping the temperature of the reactor no greater than 0℃. After 7 to 9 hours, a sample was isolated and analyzed. Water was added. The contents of the reactor vessel were stirred. The reactor vessel was then allowed to stand until layering of the contents again occurred. The aqueous layer was removed. The organic layer was heated to 75 to 85℃ under atmospheric pressure to remove dichloroethane and then cooled to room temperature and finally dissolved in toluene.
The contents of the reactor vessel were kept at a temperature of less than 0℃ while adding dropwise 3, 5-dimethylbenzoyl chloride and liquid base to adjust the pH to mildly acidic. After 7 to 9 hours, a sample was isolated and analyzed. The reactor vessel was then allowed to stand until layering of the contents occurred. The aqueous layer was removed. The organic layer was kept at a temperature of 100 to 120℃ under atmospheric pressure to remove toluene. It was then cooled to room temperature and finally dissolved in toluene and water for re-crystallization. The product was dried at 60 to 70℃.
The reaction scheme for the preparation of Methoxyfenozide is as follows:
Figure PCTCN2022118027-appb-000008
The product was subjected to analysis by X-ray diffraction. The X-ray diffraction pattern obtained is shown in Figure 4. As can be seen in Figure 4, the X-ray powder diffraction pattern of the resulting Methoxyfenozide product had no significant signals, which indicates the Methoxyfenozide product prepared in accordance with the disclosure of CN104803879A is amorphous.
Example 2: Preparation of crystalline modification I of Methoxyfenozide with cyclohexanone
Methoxyfenozide prepared in Example 1 (10 g) was placed in a 3 neck round bottom flask along with cyclohexanone (60 mL) and the resulting slurry was heated to 80℃ to form a homogeneous solution. The homogeneous solution was stirred at 80℃ for 2 hours and the insoluble particles, if any, were removed by filtration. Thereafter, the solution was slowly cooled to room temperature.
Upon cooling, fine crystals were formed and the resulting heterogeneous mixture was stirred at 20℃ for 2 hours. The resulting slurry was then filtered and washed with cooled cyclohexanone (6 mL) . The filtered crystals were dried under vacuum at 50℃ in order to remove the traces of solvent from the crystalline product. The crystalline product obtained had a purity of 98% and a product yield of 85%.
The product was characterized as crystalline modification I of Methoxyfenozide by IR spectrometry and XRD, exhibiting the spectra shown in Figures 1 and 2 respectively.
The IR spectrum of the Methoxyfenozide product, as given in Figure 1, shows characteristic vibrations of the functional group at 3305, 3006, 2966, 1683, 1639, 1587, 1494, 1274, 1244, 1027 and 861 cm -1.
The X-ray powder diffractogram of the Methoxyfenozide product exhibited the reflexes shown in Figure 2 and the values are summarized in Table 1.
Table 1
Figure PCTCN2022118027-appb-000009
Figure PCTCN2022118027-appb-000010
A DSC thermogram of the Methoxyfenozide product was obtained and exhibited an endothermic melting peak having an onset at 188.1℃ and a peak at 196.2℃, and a melting enthalpy of 58.47 J/g. The DSC thermogram is shown in Figure 3.
Example 3: Preparation of crystalline modification I of Methoxyfenozide with dimethysulfoxide
Methoxyfenozide prepared in Example 1 (5 g) sample was placed in a 3 neck round bottom flask along with dimethylsulfoxide (35 mL) and the resulting slurry was heated to 80℃ to obtain a homogeneous solution. The resultant hot solution was stirred at 80℃ for 2 hours and filtered to remove insoluble particles (if any) , and the solution was slowly cooled to ambient temperature. The desired crystalline product was precipitated out as fine crystals during cooling and the mixture was stirred at 20℃ for 2 hours. The resulting slurry was then filtered, washed with cooled dimethylsulfoxide (6 mL) and dried under vacuum at 50℃, in order to remove the solvent traces from the crystals. The product obtained had a purity of 98% with a product yield of 85%.
The product was characterized by IR spectrometry, DSC and XRD, and the resulting spectra observed were substantially the same as those given in Figures 1, 2 and 3 respectively.
FORMULATION EXAMPLES
Example 4: Preparation of suspension concentrate (SC) of amorphous Methoxyfenozide
All of the components listed in Table 2 below were mixed uniformly and the resulting mixture was ground with a Dyno-Mill (manufactured by Willy A. Bachofen AG) to obtain a suspension concentrate.
Table 2
Figure PCTCN2022118027-appb-000011
Example 5: Preparation of Suspension Concentrate (SC) of crystalline modification I of Methoxyfenozide
All of the components listed in Table 3 below were mixed uniformly and the resulting mixture was ground with a Dyno-Mill (manufactured by Willy A. Bachofen AG) to obtain a suspension concentrate.
Table 3
Figure PCTCN2022118027-appb-000012
Example 6: Comparison of the storage stability
Samples of the formulations prepared in Examples 4 and 5 were stored at 54℃ in heated ovens having the same atmosphere for 1 month, 3 months and 6 months. The procedures followed were according to CIPAC MT 46.3. The concentration of Methoxyfenozide was measured at the end of each storage time by high pressure liquid chromatography (HPLC) . The aggregation of particles in the suspension was measured by observation.
The original concentration of Methoxyfenozide in each formulation was 20 %.
The results are listed in Table 4.
Table 4
Figure PCTCN2022118027-appb-000013
Remarks: “+” means small amount of aggregation;
“++++” means a lot of aggregation;
“-” means no aggregation observed.
As can be seen from the results set out in Table 4, the concentration of the crystalline modification I of Methoxyfenozide in the suspension concentrate formulation remained constant at 20 %wt, indicating no degradation or loss of the component, in turn indicating that the crystalline modification I of Methoxyfenozide is stable. In contrast, the amorphous Methoxyfenozide exhibited a poor stability in the formulation, with a significant reduction in its concentration after 3 months and especially after 6 months. It will also be noted that the crystalline modification I of Methoxyfenozide remained well dispersed in the suspension concentrate formulation. In contrast, the amorphous Methoxyfenozide exhibited significant aggregation in the suspension concentrate over the test periods, especially after both 3 and 6 months.

Claims (25)

  1. Crystalline modification I of N′-tert-butyl-N′- (3, 5-dimethylbenzoyl) -3-methoxy-2-methylbenzohydrazide (Methoxyfenozide) , exhibiting at least three of the following reflexes in any combination, as 2θ ± 0.20 degree in X-ray powder diffractogram (X-RPD) recorded using Cu-Kα radiation at 25℃:
    2θ = 9.47 ± 0.20        (1)
    2θ = 9.81 ± 0.20        (2)
    2θ = 12.63 ± 0.20       (3)
    2θ = 14.26 ± 0.20       (4)
    2θ = 16.49 ± 0.20       (5)
    2θ = 16.70 ± 0.20       (6)
    2θ = 18.01 ± 0.20       (7)
    2θ = 18.49 ± 0.20       (8)
    2θ = 19.65 ± 0.20       (9)
    2θ = 20.47 ± 0.20       (10)
    2θ = 21.44 ± 0.20       (11)
    2θ = 22.43 ± 0.20       (12)
    2θ = 23.55 ± 0.20       (13)
    2θ = 23.93 ± 0.20       (14)
    2θ = 25.41 ± 0.20       (15)
    2θ = 26.63 ± 0.20       (16) .
  2. The crystalline modification 1 of Methoxyfenozide according to claim 1, exhibiting at least two of the following reflexes in any combination:
    2θ = 9.47 ± 0.20        (1)
    2θ = 9.81 ± 0.20        (2)
    2θ = 12.63 ± 0.20       (3)
    2θ = 16.70 ± 0.20       (5)
    2θ = 18.01 ± 0.20       (6)
    2θ = 18.49 ± 0.20       (7)
    2θ = 20.47 ± 0.20       (9)
    2θ = 21.44 ± 0.20       (10)
    2θ = 22.43 ± 0.20       (11)
    2θ = 23.55 ± 0.20       (12) .
  3. The crystalline modification 1 of Methoxyfenozide according to claim 2, exhibiting at least two of the following reflexes in any combination:
    2θ = 9.47 ± 0.20        (1)
    2θ = 9.81 ± 0.20        (2)
    2θ = 12.63 ± 0.20       (3)
    2θ = 16.70 ± 0.20       (5)
    2θ = 18.01 ± 0.20       (6)
    2θ = 18.49 ± 0.20       (7)
    2θ = 23.55 ± 0.20       (12) .
  4. The crystalline modification I of Methoxyfenozide, according to any preceding claim, exhibiting an IR spectrum with characteristic functional group vibration peaks at  wavenumbers (cm -1, ± 0.2%) of one or more of about 3305, 3006, 2966, 1683, 1639, 1587, 1494, 1274, 1244, 1027 and 861 cm -1.
  5. The crystalline modification I of Methoxyfenozide according to any preceding claim, exhibiting a melting point of 196.2℃.
  6. The crystalline modification I of Methoxyfenozide according to any preceding claim, characterized by an X-ray powder diffraction pattern substantially as shown in Figure 2, and/or characterized by an IR spectrum substantially as shown in Figure 1, and/or exhibiting a melting point of 196.2℃.
  7. A process for the preparation of a crystalline modification I of Methoxyfenozide, according to any one of the preceding claims, comprising the steps of
    i) dissolving Methoxyfenozide in a solvent system comprising one or more solvents;
    ii) precipitating the dissolved compound into crystalline modification I of Methoxyfenozide; and
    iii) isolating the precipitated crystalline modification I.
  8. The process according to claim 7, wherein the Methoxyfenozide used in step i) is amorphous Methoxyfenozide or a crystalline form of Methoxyfenozide.
  9. The process according to either of claims 7 or 8, wherein the solvent system comprises a solvent selected from ketones and sulfur-containing organic compounds.
  10. The process according to claim 9, wherein the solvent system comprises a solvent selected from alkanones, cycloalkanones, or sulfoxides.
  11. The process according to claim 10, wherein the solvent system comprises cyclohexanone or dimethylsulfoxide or a mixture thereof.
  12. The process according to any of claims 7 to 11, wherein step ii) comprises concentrating the solution and/or cooling and/or the addition of a solubility reducing solvent and/or adding a seed crystal.
  13. The process according to claim 12, wherein step ii) comprises by cooling the solution to a temperature of from about 0 to 20℃.
  14. A crystalline modification I of Methoxyfenozide obtained by a process according to any one of claims 7 to 13 and having a content of crystalline modification I of Methoxyfenozide of at least 98% by weight.
  15. An insecticidal composition comprising the crystalline modification I of Methoxyfenozide according to any one of claims 1 to 6 and 14 and at least one auxiliary.
  16. The composition according to claim 15, wherein the composition is formulated as a suspension concentrate (SC) , an oil-based suspension concentrate (OD) , a soluble concentrate (SL) , water-soluble granules (SG) , a dispersible concentrate (DC) , an emulsifiable concentrate (EC) , an emulsion seed dressing, a suspension seed  dressing, granules (GR) , microgranules (MG) , a suspoemulsion (SE) or water-dispersible granules (WG) .
  17. The composition according to claim 16, wherein the composition is formulated as a suspension concentrate (SC) .
  18. The composition according to any one of claims 15 to 17, wherein the composition comprises crystalline modification I of Methoxyfenozide in an amount of less than 75 % by weight.
  19. The composition according to claim 18, wherein the composition comprises crystalline modification I of Methoxyfenozide in an amount of about 20 % by weight.
  20. Use of the crystalline modification I of Methoxyfenozide according to any one of claims 1 to 6 and 14, or a composition according to any one of claims 15 to 19, for the control of pests.
  21. The use of the crystalline modification I of Methoxyfenozide according to claim 20, wherein the pest is selected from armyworm, borer, budworm, cabbageworm, caterpillar, corn borer, cutworm, earworm, fruitworm, hornworm, leafhopper, leafminer, leafroller, looper, melonworm, moth, pickleworm and webworm.
  22. The use of the crystalline modification I of Methoxyfenozide according to either of claims 20 or 21, for the control of pests on almond, apple, avocado, blueberry, citrus, coffee, custard apple, grapevines, kiwifruit, longan, lychee, macadamia, pear, pepper and tomato.
  23. A method of controlling insects at a locus, the method comprising applying to the locus the crystalline modification I of Methoxyfenozide according to any one of claims 1 to 6 and 14, or a composition according to any one of claims 15 to 19.
  24. The method according to claim 23, wherein the insect is selected from armyworm, borer, budworm, cabbageworm, caterpillar, corn borer, cutworm, earworm, fruitworm, hornworm, leafhopper, leafminer, leafroller, looper, melonworm, moth, pickleworm and webworm.
  25. The method according to either of claims 23 or 24, wherein a crop selected from almond, apple, avocado, blueberry, citrus, coffee, custard apple, grapevines, kiwifruit, longan, lychee, macadamia, pear, pepper and tomato is being grown at the locus.
PCT/CN2022/118027 2021-09-16 2022-09-09 Crystalline form of methoxyfenozide, process for its preparation and use of the same WO2023040759A1 (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1088572A (en) * 1992-11-23 1994-06-29 罗姆和哈斯公司 Parasiticidal N '-replacement-N, N '-two hydrazides
CN1109049A (en) * 1993-08-19 1995-09-27 罗姆和哈斯公司 Preparation of 1,2-diacyl-2-(T-alkyl) hydrazines
CN103415211A (en) * 2011-03-09 2013-11-27 住友化学株式会社 Pest-control composition and pest-control method
CN104803879A (en) * 2015-03-27 2015-07-29 江苏长青农化南通有限公司 Preparation technology of methoxyfenozide
CN113248351A (en) * 2021-05-26 2021-08-13 绍兴上虞新银邦生化有限公司 Preparation method of 6-chloro-2-methoxytoluene and synthetic process of methoxyfenozide

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106699596A (en) * 2016-12-30 2017-05-24 江苏永安化工有限公司 Preparation process of methoxyfenozide

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1088572A (en) * 1992-11-23 1994-06-29 罗姆和哈斯公司 Parasiticidal N '-replacement-N, N '-two hydrazides
CN1109049A (en) * 1993-08-19 1995-09-27 罗姆和哈斯公司 Preparation of 1,2-diacyl-2-(T-alkyl) hydrazines
CN103415211A (en) * 2011-03-09 2013-11-27 住友化学株式会社 Pest-control composition and pest-control method
CN104803879A (en) * 2015-03-27 2015-07-29 江苏长青农化南通有限公司 Preparation technology of methoxyfenozide
CN113248351A (en) * 2021-05-26 2021-08-13 绍兴上虞新银邦生化有限公司 Preparation method of 6-chloro-2-methoxytoluene and synthetic process of methoxyfenozide

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"Handbook of Scientific Medication for Crops", 28 February 2018, CENTRAL PLAINS FARMERS PUBLISHING HOUSE, CN, ISBN: 978-7-5542-1618-7, article MAO DAN ET AL.: "methoxyfenozide", pages: 78 - 79, XP009544607 *
"Technical Manual for Pesticide Use", 31 January 2009, GOLDEN SHIELD PRESS, CN, ISBN: 978-7-5082-5125-7, article SHI CHUNXI ET AL.: "Specific Insect Growth Regulators", pages: 160 - 170, XP009544608 *

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