WO2018137387A1 - Crystalline form of indoxacarb, process for its preparation and use thereof - Google Patents

Crystalline form of indoxacarb, process for its preparation and use thereof Download PDF

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Publication number
WO2018137387A1
WO2018137387A1 PCT/CN2017/110978 CN2017110978W WO2018137387A1 WO 2018137387 A1 WO2018137387 A1 WO 2018137387A1 CN 2017110978 W CN2017110978 W CN 2017110978W WO 2018137387 A1 WO2018137387 A1 WO 2018137387A1
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Prior art keywords
indoxacarb
crystalline modification
solvent
crystalline
composition
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PCT/CN2017/110978
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French (fr)
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James Timothy Bristow
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Jiangsu Rotam Chemistry Co., Ltd
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Priority to CN201780058578.4A priority Critical patent/CN109843859B/en
Publication of WO2018137387A1 publication Critical patent/WO2018137387A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
    • C07D273/02—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00 having two nitrogen atoms and only one oxygen atom
    • C07D273/04—Six-membered 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/38—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the group >N—CO—N< where at least one nitrogen atom is part of a heterocyclic ring; Thio analogues thereof

Definitions

  • the present disclosure relates to a novel crystalline polymorph of methyl (4aS) -7-chloro-2, 5-dihydro-2- [ [ (methoxycarbonyl) [4- (trifluoromethoxy) phenyl] amino] carbonyl] indeno [1, 2-e] [1, 3, 4] oxadiazine-4a (3H) -carboxylate (indoxacarb) , to its preparation processes and to its use in agrochemical preparations.
  • Indoxacarb is a potent insecticide.
  • Indoxacarb has molecular formula of C22H17ClF3N3O7. Its chemical structure is:
  • Indoxacarb was first launched by DuPont in Spain in 1998 as Avaunt TM for use on cotton, and as Steward TM for use on vines, apples and pears. It has a novel mode of action, now known to be through blocking of sodium channels in the nerve cells, leading to paralysis and death of the target insect.
  • Indoxacarb is a semicarbazone compound developed for use against Lepidopteran species. It demonstrates effective control of lepidopteran insects including Cydia, Helicoverpa, Heliothis, Lobesia, Plutella and Spodoptera spp. Safety and environmental profiles lend the product to use in IPM programmes. In the United States, indoxacarb was approved as a reduced risk pesticide in 2000 as Steward TM for cotton and as Avaunt TM for fruit and vegetables.
  • indoxacarb which is usually manufactured by the process described in US PAT. NO. 5,869,657, is present in an amorphous state. It has been found that indoxacarb in an amorphous state is not suitable for being prepared as compositions or formulations due to its high tendency to aggregate, in particular after prolonged storage.
  • Chinese Pub. No. 103694193A disclosed a polymorphic form of indoxacarb, termed “crystalline form A” .
  • this polymorphic form is not suitable for being prepared as compositions or formulations as it also has high tendency to aggregate after prolonged storage.
  • the stability of indoxacarb is of great concern for the commercially available formulations. Therefore, there is a need to develop a new polymorphic form of indoxacarb, exhibiting improved properties, such as an improved stability in formulations or compositions.
  • the invention provides a novel crystalline polymorph of methyl (4aS) -7-chloro-2, 5-dihydro-2- [ [ (methoxycarbonyl) [4- (trifluoromethoxy) phenyl] amino] carbonyl] indeno [1, 2-e] [1, 3, 4] oxadiazine-4a (3H) -carboxylate (indoxacarb) termed “crystalline modification I” , exhibiting at least 3 of the following reflexes, in any combination, as 2 ⁇ 0.20 degree in an X-ray powder diffractogram (X-RPD) recorded using Cu-K ⁇ radiation at 25°C:
  • the crystalline modification I of indoxacarb according to the first aspect of the invention exhibits at least 3, 4, 5, 6, 7, 8 or all of the following reflexes, in any combination, as 2 ⁇ 0.20 degree in an X-ray powder diffractogram recorded using Cu-K ⁇ radiation at 25°C:
  • the present invention provides a crystalline modification I of indoxacarb, optionally according to the first aspect of the invention, exhibiting an infrared (IR) with characteristic functional group vibration peaks at wavenumbers (cm -1 , ⁇ 0.2%) of about 2160.9 and 1979.3cm -1 .
  • IR infrared
  • the present invention provides a crystalline modification I of indoxacarb according to the first or second aspect of the invention, 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.
  • the present invention provides a crystalline modification I of indoxacarb according to any one of the first to third aspects of the invention, obtainable by the process substantially as described in Example 2 or 3.
  • the present invention provides a crystalline modification I of indoxacarb according to any one of the first to third aspects of the invention, obtainable by the process of the sixth aspect of the invention.
  • the crystalline modification I shows improved storage stability, which may significantly reduce the aggregation problem encountered with current commercially available formulations.
  • the crystalline modification I of indoxacarb exhibits a high degree of stability when formulated compared to amorphous indoxacarb prepared in accordance with the disclosure of US PAT. NO. 5,869,657 and crystal A of indoxacarb prepared in accordance with the disclosure of CN103694193A.
  • the crystalline modification I of indoxacarb exhibits a very low tendency to aggregate when formulated. This may allow the preparation of commercial formulations such as suspension concentrates (SC) .
  • SC suspension concentrates
  • the present invention provides a process for preparing a crystalline modification I of indoxacarb, comprising the steps of:
  • the indoxacarb in step i) is amorphous indoxacarb.
  • Amorphous indoxacarb is manufactured and available on a commercial scale.
  • a particularly suitable method for preparing amorphous indoxacarb is described in US PAT. NO. 5,869,657.
  • the solvents is selected from the group consisting of halogenated hydrocarbons (for example, chlorobenzene, bromobenzene, dichlorobenzene, chlorotoluene and trichlorobenzene) , nitrated hydrocarbons (for example, nitromethane, nitroethane, nitropropane, nitrobenzene, chloronitrobenzene and o-nitrotoluene) , and aliphatic, cycloaliphatic or aromatic hydrocarbons (for example, pentane, n-hexane, n-heptane, n-octane, nonane, white spirits with components having boiling points in the range, for example, of from 40°C to 250°C, cymene, petroleum fractions having a boiling range of from 70°C to 190°C, cyclohexane, methylcyclohexane, ligroin, and
  • the solvent is selected from nitrobenzene, n-hexane, chlorobenzene or a mixture thereof. Solvent mixtures of more than 2 components are also possible. In this invention, n-hexane and nitrobenzene are highly preferred.
  • crystalline modification I of indoxacarb is prepared by dissolving amorphous indoxacarb in a solvent or a solvent mixture as a concentrated solution by heating from ambient temperature to a temperature at or below the reflux temperature of the solvent or the solvent mixture.
  • the concentrated solutions can be prepared at the reflux temperature of the solvent (s) .
  • the concentration of the solution depends on the solubility of indoxacarb in the corresponding solvent or solvent mixture.
  • the concentrated homogeneous solution thus prepared as in step (i) is then cooled to room temperature or to a temperature of about 0°C to 20°C to crystallize the desired crystalline form from the solvent.
  • the crystalline modification I of indoxacarb can also be crystallized out by concentrating the homogeneous solution by removing the solvent or solvent mixture to a certain volume with or without applying vacuum and cooling to below the reflux temperature of the solvent or the solvent mixture.
  • crystalline modification I of indoxacarb can also be effected by adding seed crystals of the desired crystalline form during crystallization into a solution prepared in step (i) , which can promote or accelerate the crystallization.
  • the seed crystal amount added to the concentrated solution is typically in the range of 0.001%to 10%by weight, optionally 0.001%to 2.5%by weight, further optionally 0.005 to 0.5%by weight based on the weight of indoxacarb used for the preparation of concentrated solution in step (i) .
  • the seed crystals are added to the concentrated solution at the temperature below the boiling point of the corresponding solvent or the solvent mixture.
  • the precipitated crystalline modification I of indoxacarb obtained from step (ii) is isolated by the usual solid component separation techniques from solutions, such as filtration, centrifugation or decantation. Then, the isolated solid is washed with solvent one or more times.
  • the solvent employed in the washing stage consists of one or more components of the solvent or solvent mixture employed for preparation of concentrated solution in step (i) , as described hereinbefore.
  • the washing is usually carried out using the corresponding solvent or solvent mixture between room temperature and 0°C, depending on the solubility of the crystal, in order to minimize or avoid the loss of crystalline material in the corresponding washing solvent as much as possible.
  • crystalline modification I of indoxacarb is dissolved and recrystallized.
  • the washings and/or the solvent of crystallization in any of the methods may be concentrated to obtain solid indoxacarb which may be recycled.
  • the present invention provides a crystalline modification I of indoxacarb obtained according to the process of the sixth aspect of the invention, having a crystalline modification I of indoxacarb content of at least 98%by weight.
  • the present invention provides a composition comprising the crystalline modification I of indoxacarb according to any one of the first to fifth and seventh aspects of the invention, and at least one auxiliary.
  • the present invention provides a use of the crystalline modification I of indoxacarb according to any one of the first to fifth and seventh aspects of the invention, or a composition according to the eighth aspect of the invention, for insect control.
  • the amount of the crystalline modification I of indoxacarb is less than 50%by weight of the composition, further optionally less than 30%by weight of the composition, still further optionally about 15%by weight of the composition.
  • indoxacarb as an insecticidal agent is known in the art and is used on a commercial scale. It has been found that the crystalline modification I of indoxacarb is also active in controlling pests and pest infestations. As a result, the techniques of formulating and applying indoxacarb that are known in the art with respect to amorphous indoxacarb, for example as disclosed in the prior art documents discussed hereinbefore, can also be applied in an analogous manner to indoxacarb in the crystalline modification I of the invention.
  • indoxacarb in the crystalline modification I of an embodiment of the present invention may be formulated and applied in an analogous manner.
  • the present invention provides an insecticidal composition comprising indoxacarb in the crystalline modification I as hereinbefore defined.
  • the invention furthermore provides processes for preparing compositions for controlling pests using the crystalline modification I of indoxacarb and compositions comprising the crystalline modification I of indoxacarb.
  • the composition is in the form of a suspension concentrate (SC) , oil-based suspension concentrate (OD) , water-soluble granule (SG) , dispersible concentrate (DC) , emulsifiable concentrate (EC) , emulsion seed dressing, suspension seed dressing, a granule (GR) , a microgranule (MG) , suspoemulsion (SE) or a water-dispersible granule (WG) .
  • Crystalline modification I of indoxacarb can be included into these customary formulations in a known manner using suitable auxiliaries, carriers and solvents and the like, in a manner analogous to that known for amorphous indoxacarb.
  • the composition is in the form of a suspension concentrate (SC) .
  • the crystalline modification I of indoxacarb is present in an amount sufficient to achieve the required dosage when applied to plants or the loci thereof, and is desirably provided in a concentration of about 0.1 to 50%by weight of the total mixture.
  • the formulations are prepared, for example, by extending the crystalline modification I of indoxacarb with water, solvents and/or carriers, using, if appropriate, emulsifiers and/or dispersants, and/or other auxiliaries.
  • formulations are prepared in a known manner by mixing the crystalline modification I of indoxacarb with at least one auxiliary, for example, liquid diluents, solid diluents, wetting agents, dispersants, thickener, antifreeze agents, biocide and any necessary adjuvants and other formulation ingredients.
  • auxiliary for example, liquid diluents, solid diluents, wetting agents, dispersants, thickener, antifreeze agents, biocide and any necessary adjuvants and other formulation ingredients.
  • Liquid diluents include, but are not limited to, water, N, N-dimethylmamide, dimethyl sulfoxide, 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, and alcohols such as, 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, ethoxyfluornated 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, 2-ethylhexanol propylene ethyleneglycol ether and alcohol ethoxylates and mixtures thereof.
  • 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; Ammonium salt of polyarylphenyl ether sulphate and naphthalene sulfonate-formaldehyde condensates. Of note are compositions comprising up to 10%by weight of dispersant. Ammonium salt of polyarylphenyl ether sulphate is particularly useful for the composition of the invention.
  • Thickeners 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 composition of the invention.
  • Suitable antifreeze agents are 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 composition according to the invention. Suitable Biocides are 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.
  • formulation ingredients can also be used in the present invention, such as dyes, antifoaming agents, drying agents, and the like. These ingredients are known to one skilled in the art.
  • the crystalline modification I of indoxacarb according to the invention can be present in its commercially available formulations and in its use forms, prepared from these formulations, and as a mixture with other active compounds (such as insecticides, attractants, sterilizing agents, bactericides, acaricides, nematicides, fungicides, growth-regulating substances, herbicides, safeners, fertilizers and semiochemicals) or with agents for improving plant properties.
  • active compounds such as insecticides, attractants, sterilizing agents, bactericides, acaricides, nematicides, fungicides, growth-regulating substances, herbicides, safeners, fertilizers and semiochemicals
  • the crystalline modification I of indoxacarb according to the invention when used as insecticide, can furthermore be present in formulations and its use forms, prepared from these formulations, and as a mixture with inhibitors which reduce degradation of the active compounds after their use in the environment of the plant, on the surface of plant parts or in plant tissues.
  • 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 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.
  • Treatment according to the invention of the plants and plant parts with the compositions or formulations of the inventions is carried out directly or by allowing the compositions or formulations to act on their surroundings, habitat or storage space by the customary treatment methods.
  • 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 benefits of the present invention are seen most when the insecticidal composition is applied to kill boll weevil, bollworm and other Lepidoptera in growing crops of useful plants: such as cotton and corn.
  • references to properties are –unless stated otherwise –to properties measured under ambient conditions, i.e. at atmospheric pressure and at a temperature of about 20°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.
  • Precipitation refers to the sedimentation of a solid material (aprecipitate) , 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.
  • Figure 1 is a an infrared (IR) spectrograph of crystalline modification I of indoxacarb;
  • Figure 2 is an X-ray powder diffractogram of crystalline modification I of indoxacarb.
  • Figure 3 is an X-ray powder diffractogram of amorphous indoxacarb.
  • 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 indoxacarb can be identified by its characteristic functional group vibration peaks at wavenumbers (cm -1 , ⁇ 0.2%) of one or more of about 2160.89 and 1979.31 cm -1 as shown in Figure 1.
  • Example 1 Preparation of amorphous indoxacarb in accordance with the disclosure of US PAT. NO. 5,869,657, Example 1, step d
  • the X-ray powder diffraction pattern of the resulting indoxacarb product has no significant signals, which indicates the indoxacarb product prepared in accordance with the disclosure of US PAT. NO. 5,869,657 is amorphous.
  • Example 2 Preparation of crystal A of indoxacarb in accordance with the disclosure of CN103694193, example 2.
  • Methyl (4aS) -7-chloro-2, 5-dihydro-2- [ [ (methoxycarbonyl) [4- (trifluoromethoxy) phenyl] amino] carbonyl] indeno [1, 2-e] [1, 3, 4] oxadiazine-4a (3H) -carboxylate (indoxacarb) was undergone crystallization from methanol. It was heated to reflux for 0.5-2 hour and the solution was then cooled down to -10°C –5°C quickly. The slurry was then filtered and dried in oven at 30°C for 24 hours. Crystal A was then obtained.
  • the IR spectrum of the crystalline modification I of indoxacarb exhibits the functional group characteristic vibrations peaks at wavenumbers of one or more of 2160.89 and 1979.31cm -1 as shown in Figure 1.
  • the crystals were characterized as being the crystalline modification I of indoxacarb using IR spectrometry and X-ray powder diffraction as described in Example 3.

Abstract

Provides a crystalline form of indoxacarb, the crystal preparation process, the analyses of the crystal through various analytical methods and using the crystal to prepare stable agrochemical formulation. Also provides the use of various solvents towards the crystalline form preparation conditions.

Description

[Title established by the ISA under Rule 37.2] CRYSTALLINE FORM OF INDOXACARB, PROCESS FOR ITS PREPARATION AND USE THEREOF
CROSS REFERENCE TO RELATED APPLICATIONS
This application claims priority to Australian Patent Application No. 2017200535, titled “A NOVEL CRYSTALLINE FORM OF INDOXACARB, A PROCESS FOR ITS PREPARATION AND USE OF THE SAME” , filed with IP Australia on January 27, 2017, the entire contents of which are incorporated herein by reference.
FIELD
The present disclosure relates to a novel crystalline polymorph of methyl (4aS) -7-chloro-2, 5-dihydro-2- [ [ (methoxycarbonyl) [4- (trifluoromethoxy) phenyl] amino] carbonyl] indeno [1, 2-e] [1, 3, 4] oxadiazine-4a (3H) -carboxylate (indoxacarb) , to its preparation processes and to its use in agrochemical preparations.
BACKGROUND
Methyl (4aS) -7-chloro-2, 5-dihydro-2- [ [ (methoxycarbonyl) [4- (trifluoromethoxy) phenyl] amino] carbonyl] indeno [1, 2-e] [1, 3, 4] oxadiazine-4a (3H) -carboxylate) (indoxacarb) is a potent insecticide. Indoxacarb has molecular formula of C22H17ClF3N3O7. Its chemical structure is:
Figure PCTCN2017110978-appb-000001
Indoxacarb was first launched by DuPont in Spain in 1998 as AvauntTM for use on  cotton, and as StewardTM for use on vines, apples and pears. It has a novel mode of action, now known to be through blocking of sodium channels in the nerve cells, leading to paralysis and death of the target insect.
Indoxacarb is a semicarbazone compound developed for use against Lepidopteran species. It demonstrates effective control of lepidopteran insects including Cydia, Helicoverpa, Heliothis, Lobesia, Plutella and Spodoptera spp. Safety and environmental profiles lend the product to use in IPM programmes. In the United States, indoxacarb was approved as a reduced risk pesticide in 2000 as StewardTM for cotton and as AvauntTM for fruit and vegetables.
The commercially available indoxacarb, which is usually manufactured by the process described in US PAT. NO. 5,869,657, is present in an amorphous state. It has been found that indoxacarb in an amorphous state is not suitable for being prepared as compositions or formulations due to its high tendency to aggregate, in particular after prolonged storage. Chinese Pub. No. 103694193A disclosed a polymorphic form of indoxacarb, termed “crystalline form A” . However, this polymorphic form is not suitable for being prepared as compositions or formulations as it also has high tendency to aggregate after prolonged storage. As a result, the stability of indoxacarb is of great concern for the commercially available formulations. Therefore, there is a need to develop a new polymorphic form of indoxacarb, exhibiting improved properties, such as an improved stability in formulations or compositions.
SUMMARY
In an attempt to resolve some or all of the problems with existing amorphous forms and ‘crystalline form A’ of indoxacarb, a new crystalline polymorphic form of indoxacarb has been prepared.
In a first aspect, the invention provides a novel crystalline polymorph of methyl (4aS) -7-chloro-2, 5-dihydro-2- [ [ (methoxycarbonyl) [4- (trifluoromethoxy) phenyl] amino] carbonyl] indeno [1, 2-e] [1, 3, 4] oxadiazine-4a (3H) -carboxylate (indoxacarb) termed “crystalline modification I” , exhibiting at least 3 of the following reflexes, in any combination, as 2θ±0.20 degree in an X-ray powder diffractogram (X-RPD) recorded using Cu-Kα radiation at 25℃:
2θ = 9.17 ± 0.20     (1)
2θ = 9.48 ± 0.20     (2)
2θ = 10.08 ± 0.20    (3)
2θ = 12.86 ± 0.20    (4)
2θ = 14.26 ± 0.20    (5)
2θ = 15.05 ± 0.20    (6)
2θ = 17.53 ± 0.20    (7)
2θ = 18.09 ± 0.20    (8)
2θ = 18.42 ± 0.20    (9)
2θ = 19.01 ± 0.20    (10)
2θ = 19.50 ± 0.20    (11)
2θ = 20.35 ± 0.20    (12)
2θ = 20.56 ± 0.20    (13)
2θ = 20.81 ± 0.20    (14)
2θ = 21.99 ± 0.20    (15)
2θ = 23.15 ± 0.20    (16)
2θ = 23.37 ± 0.20    (17)
2θ = 23.73 ± 0.20    (18)
2θ = 23.90 ± 0.20    (19)
2θ = 24.75 ± 0.20    (20)
2θ = 25.08 ± 0.20    (21)
2θ = 25.38 ± 0.20    (22)
2θ = 29.40 ± 0.20    (23)
2θ = 31.58 ± 0.20    (24)
In an embodiment, the crystalline modification I of indoxacarb according to the first aspect of the invention, exhibits at least 3, 4, 5, 6, 7, 8 or all of the following reflexes, in any combination, as 2θ±0.20 degree in an X-ray powder diffractogram recorded using Cu-Kαradiation at 25℃:
2θ = 9.17 ± 0.20     (1)
2θ = 10.08 ± 0.20    (3)
2θ = 12.86 ± 0.20    (4)
2θ = 15.05 ± 0.20    (6)
2θ = 17.53 ± 0.20    (7)
2θ = 19.01 ± 0.20    (10)
2θ = 19.50 ± 0.20    (11)
2θ = 20.35 ± 0.20    (12)
2θ = 20.56 ± 0.20    (13)
2θ = 20.81 ± 0.20    (14)
2θ = 23.15 ± 0.20    (16)
2θ = 24.75 ± 0.20    (20)
In a second aspect, the present invention provides a crystalline modification I of indoxacarb, optionally according to the first aspect of the invention, exhibiting an infrared (IR) with characteristic functional group vibration peaks at wavenumbers (cm-1, ±0.2%) of about 2160.9 and 1979.3cm-1.
In a third aspect, the present invention provides a crystalline modification I of indoxacarb according to the first or second aspect of the invention, 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.
In a fourth aspect, the present invention provides a crystalline modification I of indoxacarb according to any one of the first to third aspects of the invention, obtainable by the  process substantially as described in Example 2 or 3.
In a fifth aspect, the present invention provides a crystalline modification I of indoxacarb according to any one of the first to third aspects of the invention, obtainable by the process of the sixth aspect of the invention.
It has been found that the crystalline modification I shows improved storage stability, which may significantly reduce the aggregation problem encountered with current commercially available formulations. In addition, it has been found that the crystalline modification I of indoxacarb exhibits a high degree of stability when formulated compared to amorphous indoxacarb prepared in accordance with the disclosure of US PAT. NO. 5,869,657 and crystal A of indoxacarb prepared in accordance with the disclosure of CN103694193A. In particular, the crystalline modification I of indoxacarb exhibits a very low tendency to aggregate when formulated. This may allow the preparation of commercial formulations such as suspension concentrates (SC) .
In a sixth aspect, the present invention provides a process for preparing a crystalline modification I of indoxacarb, comprising the steps of:
i) dissolving indoxacarb in a solvent or mixture of solvents;
ii) precipitating the dissolved indoxacarb into crystalline modification I of indoxacarb; and
iii) isolating the precipitated crystalline modification I.
In an embodiment of the sixth aspect of the invention, the indoxacarb in step i) is amorphous indoxacarb.
Methods for preparing amorphous indoxacarb are well known in the art. Amorphous indoxacarb is manufactured and available on a commercial scale. A particularly suitable method for preparing amorphous indoxacarb is described in US PAT. NO. 5,869,657.
In an embodiment of the sixth aspect of the invention, the solvents is selected from the group consisting of halogenated hydrocarbons (for example, chlorobenzene, bromobenzene, dichlorobenzene, chlorotoluene and trichlorobenzene) , nitrated hydrocarbons (for example, nitromethane, nitroethane, nitropropane, nitrobenzene, chloronitrobenzene and o-nitrotoluene) ,  and aliphatic, cycloaliphatic or aromatic hydrocarbons (for example, pentane, n-hexane, n-heptane, n-octane, nonane, white spirits with components having boiling points in the range, for example, of from 40℃ to 250℃, cymene, petroleum fractions having a boiling range of from 70℃ to 190℃, cyclohexane, methylcyclohexane, ligroin, and octane) .
In an embodiment of the sixth aspect of the invention, the solvent is selected from nitrobenzene, n-hexane, chlorobenzene or a mixture thereof. Solvent mixtures of more than 2 components are also possible. In this invention, n-hexane and nitrobenzene are highly preferred.
According to an embodiment of the sixth aspect of the present invention, crystalline modification I of indoxacarb is prepared by dissolving amorphous indoxacarb in a solvent or a solvent mixture as a concentrated solution by heating from ambient temperature to a temperature at or below the reflux temperature of the solvent or the solvent mixture. Optionally, the concentrated solutions can be prepared at the reflux temperature of the solvent (s) . The concentration of the solution depends on the solubility of indoxacarb in the corresponding solvent or solvent mixture.
In an embodiment of the sixth aspect of the invention, the concentrated homogeneous solution thus prepared as in step (i) is then cooled to room temperature or to a temperature of about 0℃ to 20℃ to crystallize the desired crystalline form from the solvent. The crystalline modification I of indoxacarb can also be crystallized out by concentrating the homogeneous solution by removing the solvent or solvent mixture to a certain volume with or without applying vacuum and cooling to below the reflux temperature of the solvent or the solvent mixture.
In an embodiment of the sixth aspect of the invention, crystalline modification I of indoxacarb can also be effected by adding seed crystals of the desired crystalline form during crystallization into a solution prepared in step (i) , which can promote or accelerate the crystallization.
The seed crystal amount added to the concentrated solution is typically in the range of 0.001%to 10%by weight, optionally 0.001%to 2.5%by weight, further optionally 0.005 to 0.5%by weight based on the weight of indoxacarb used for the preparation of concentrated solution in step (i) . Optionally, the seed crystals are added to the concentrated solution at the temperature below the boiling point of the corresponding solvent or the solvent mixture.
In an embodiment of the sixth aspect of the invention, the precipitated crystalline modification I of indoxacarb obtained from step (ii) is isolated by the usual solid component separation techniques from solutions, such as filtration, centrifugation or decantation. Then, the isolated solid is washed with solvent one or more times. Optionally, the solvent employed in the washing stage consists of one or more components of the solvent or solvent mixture employed for preparation of concentrated solution in step (i) , as described hereinbefore. The washing is usually carried out using the corresponding solvent or solvent mixture between room temperature and 0℃, depending on the solubility of the crystal, in order to minimize or avoid the loss of crystalline material in the corresponding washing solvent as much as possible.
In an embodiment of the sixth aspect of the invention, crystalline modification I of indoxacarb is dissolved and recrystallized. The washings and/or the solvent of crystallization in any of the methods may be concentrated to obtain solid indoxacarb which may be recycled.
In a seventh aspect, the present invention provides a crystalline modification I of indoxacarb obtained according to the process of the sixth aspect of the invention, having a crystalline modification I of indoxacarb content of at least 98%by weight.
In an eighth aspect, the present invention provides a composition comprising the crystalline modification I of indoxacarb according to any one of the first to fifth and seventh aspects of the invention, and at least one auxiliary.
In a ninth aspect, the present invention provides a use of the crystalline modification I of indoxacarb according to any one of the first to fifth and seventh aspects of the invention, or a composition according to the eighth aspect of the invention, for insect control.
In an embodiment of the eighth aspect of the invention, the amount of the crystalline modification I of indoxacarb is less than 50%by weight of the composition, further optionally less than 30%by weight of the composition, still further optionally about 15%by weight of the composition.
The activity of indoxacarb as an insecticidal agent is known in the art and is used on a commercial scale. It has been found that the crystalline modification I of indoxacarb is also active in controlling pests and pest infestations. As a result, the techniques of formulating and applying indoxacarb that are known in the art with respect to amorphous indoxacarb, for example as  disclosed in the prior art documents discussed hereinbefore, can also be applied in an analogous manner to indoxacarb in the crystalline modification I of the invention.
Techniques of formulating and using indoxacarb are well known in the art, for example as disclosed in the documents discussed hereinbefore. Indoxacarb in the crystalline modification I of an embodiment of the present invention may be formulated and applied in an analogous manner.
Accordingly, in a further aspect, the present invention provides an insecticidal composition comprising indoxacarb in the crystalline modification I as hereinbefore defined.
Accordingly, the invention furthermore provides processes for preparing compositions for controlling pests using the crystalline modification I of indoxacarb and compositions comprising the crystalline modification I of indoxacarb.
In an embodiment of the eighth aspect of the invention, the composition is in the form of a suspension concentrate (SC) , oil-based suspension concentrate (OD) , water-soluble granule (SG) , dispersible concentrate (DC) , emulsifiable concentrate (EC) , emulsion seed dressing, suspension seed dressing, a granule (GR) , a microgranule (MG) , suspoemulsion (SE) or a water-dispersible granule (WG) . Crystalline modification I of indoxacarb can be included into these customary formulations in a known manner using suitable auxiliaries, carriers and solvents and the like, in a manner analogous to that known for amorphous indoxacarb.
In an embodiment of the eighth aspect of the invention, the composition is in the form of a suspension concentrate (SC) .
In an embodiment of the eighth aspect of the invention, the crystalline modification I of indoxacarb is present in an amount sufficient to achieve the required dosage when applied to plants or the loci thereof, and is desirably provided in a concentration of about 0.1 to 50%by weight of the total mixture. The formulations are prepared, for example, by extending the crystalline modification I of indoxacarb with water, solvents and/or carriers, using, if appropriate, emulsifiers and/or dispersants, and/or other auxiliaries.
These formulations are prepared in a known manner by mixing the crystalline modification I of indoxacarb with at least one auxiliary, for example, liquid diluents, solid diluents, wetting agents, dispersants, thickener, antifreeze agents, biocide and any necessary  adjuvants and other formulation ingredients.
Liquid diluents include, but are not limited to, water, N, N-dimethylmamide, dimethyl sulfoxide, 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, and alcohols such as, 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, ethoxyfluornated 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, 2-ethylhexanol propylene ethyleneglycol ether and alcohol ethoxylates and mixtures thereof. 2-ethylhexanol propylene ethyleneglycol ether is particularly useful for the composition 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; Ammonium salt of polyarylphenyl ether sulphate and naphthalene sulfonate-formaldehyde condensates. Of note are compositions comprising up to 10%by weight of dispersant. Ammonium salt of polyarylphenyl ether sulphate  is particularly useful for the composition of the invention.
Thickeners 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 composition of the invention.
Suitable antifreeze agents are 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 composition according to the invention. Suitable Biocides are those based on isothiazolones, for example
Figure PCTCN2017110978-appb-000002
from ICI or
Figure PCTCN2017110978-appb-000003
RS from Thor Chemie or
Figure PCTCN2017110978-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.
Other formulation ingredients can also be used in the present invention, such as dyes, antifoaming agents, drying agents, and the like. These ingredients are known to one skilled in the art.
In an embodiment of the eighth aspect of the invention, the crystalline modification I of indoxacarb according to the invention can be present in its commercially available formulations and in its use forms, prepared from these formulations, and as a mixture with other active compounds (such as insecticides, attractants, sterilizing agents, bactericides, acaricides, nematicides, fungicides, growth-regulating substances, herbicides, safeners, fertilizers and semiochemicals) or with agents for improving plant properties.
In an embodiment of the eighth aspect of the invention, when used as insecticide, the crystalline modification I of indoxacarb according to the invention can furthermore be present in formulations and its use forms, prepared from these formulations, and as a mixture with inhibitors which reduce degradation of the active compounds after their use in the environment of the plant, on the surface of plant parts or in plant tissues.
All plants and plant parts can be treated in accordance with the 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.
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.
Treatment according to the invention of the plants and plant parts with the compositions or formulations of the inventions is carried out directly or by allowing the compositions or formulations to act on their surroundings, habitat or storage space by the customary treatment methods. 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 benefits of the present invention are seen most when the insecticidal composition is applied to kill boll weevil, bollworm and other Lepidoptera in growing crops of useful plants: such as cotton and corn.
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 about 20℃.
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.
"Precipitation" as used herein, refers to the sedimentation of a solid material (aprecipitate) , 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.
All percentages are given 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.
Embodiments of the present invention will now be described by way of the following examples which are provided for illustrative purposes only, and not intended to limit the scope of the disclosure.
BRIEF DESCRIPTION OF DRAWINGS
The invention can be more clearly understood by reference to the drawings, which are described below, and are intended to exemplify and illustrate embodiments of the invention, but not to limit, the scope of the invention, wherein:
Figure 1 is a an infrared (IR) spectrograph of crystalline modification I of indoxacarb;
Figure 2 is an X-ray powder diffractogram of crystalline modification I of indoxacarb; and
Figure 3 is an X-ray powder diffractogram of amorphous indoxacarb.
DETAILED DESCRIPTION
The present invention will now be described by the following examples, and in which the following measurement techniques have been employed, and which the examples are provided for illustrative purposes only, and not intended to limit the scope of the disclosure.
All X-ray diffractograms were determined using powder diffractometer in reflection geometry at 25℃, using the following acquisition parameters:
X’Pert Pro MPD from PANalytical B.V.
Theta compensating slit and graphite monochromator
Copper (K-alpha) radiation, 40 kV, 40 mA
Step size: 0.03 degree 2-theta
Count time: 1.0 second
Maximum peak intensity: 1705 counts per second
Scan range: 3-60 degrees 2-theta
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 indoxacarb can be  identified by its characteristic functional group vibration peaks at wavenumbers (cm-1, ± 0.2%) of one or more of about 2160.89 and 1979.31 cm-1 as shown in Figure 1.
All IR spectra were obtained using the following acquisition parameters:
FT-IR spectrometer NicoletTM iS 5
Diamond ATR unit Thermo ScientificTM iD5 ATR
Wavelength range 550-4000 cm-1
Resolution 4 cm-1
Number of scans 16
Examples
Example 1: Preparation of amorphous indoxacarb in accordance with the disclosure of US PAT. NO. 5,869,657, Example 1, step d
To the organic phase containing methyl 7-chloro-2, 5-dihydroindeno [1, 2-e] [1, 3, 4] oxadiazine-4a (3H) -carboxylate was added aqueous saturated NaHCO3 (140g, about 0.15mol) , followed by 41g (0.14mol) of methyl (chlorocarbonyl) 4- (trifluoromethoxy) phenyl carbamate and the mixture was stirred for about 1 h at 10℃-15℃. The organic phase was separated, dried (MgSO4) , concentrated under vacuum to remove about 400 ml of methyl acetate, and the residual solvent was exchanged by distillation with 300 mL of methanol until the head temperature reached 64℃. The mixture was cooled to 5℃ and the product was filtered, washed with 70 mL of cold methanol and suction-dried to yield 58g of indoxacarb, with a melting point of 139℃-141℃.
Figure PCTCN2017110978-appb-000005
Scheme 1. Synthesis of Indoxacarb
As shown in Figure 3, the X-ray powder diffraction pattern of the resulting indoxacarb product has no significant signals, which indicates the indoxacarb product prepared in accordance with the disclosure of US PAT. NO. 5,869,657 is amorphous.
Example 2: Preparation of crystal A of indoxacarb in accordance with the disclosure of CN103694193, example 2.
Methyl (4aS) -7-chloro-2, 5-dihydro-2- [ [ (methoxycarbonyl) [4- (trifluoromethoxy) phenyl] amino] carbonyl] indeno [1, 2-e] [1, 3, 4] oxadiazine-4a (3H) -carboxylate (indoxacarb) was undergone crystallization from methanol. It was heated to reflux for 0.5-2 hour and the solution was then cooled down to -10℃ –5℃ quickly. The slurry was then filtered and dried in oven at 30℃ for 24 hours. Crystal A was then obtained.
Example 3: Preparation of the crystalline modification I of indoxacarb
Crystallization from n-hexane
10 g of indoxacarb sample prepared in Example 1 was taken in a 3 neck round bottom flask along with 50 mL of n-hexane and the resulting slurry was heated to 65℃ to get a homogeneous solution. The insoluble particles, if any, were filtered and the solution was slowly cooled to 20-25℃. Upon cooling, fine crystals were formed and the resulting heterogeneous mixture was stirred at 20℃ for 2h. Then, the slurry was filtered and washed with 3 mL of n-hexane at 20℃. The filtered crystals were dried under vacuum at 40℃. The crystal product thus obtained had a purity of >98%and the recovered product as crystal was found to be not less than 90%yield.
The obtained crystals were analyzed by IR spectrometry and X-ray powder diffraction and found to crystalline modification I of indoxacarb as shown in Figure 1and Figure 2 respectively.
The IR spectrum of the crystalline modification I of indoxacarb exhibits the functional group characteristic vibrations peaks at wavenumbers of one or more of 2160.89 and 1979.31cm-1  as shown in Figure 1.
The X-ray powder diffractogram of the crystalline modification I of indoxacab exhibited the reflexes in Figure 2 and the values are summarized in Table 1.
Table 1
Figure PCTCN2017110978-appb-000006
Figure PCTCN2017110978-appb-000007
Example 4: Preparation of the crystalline modification I of indoxacarb
Crystallization from nitrobenzene
5 g of amorphous indoxacarb sample prepared in Example 1 was taken in a 3 neck round bottom flask along with 30 mL of nitrobenzene and the resulting slurry was heated to 83℃ to get a homogeneous solution. The insoluble particles, if any, were filtered and the solution was slowly cooled to 20-25℃. Upon cooling, fine crystals were formed and the resulting heterogeneous mixture was stirred at 20℃ for 2h. Then, the slurry was filtered, washed with 3 mL of nitrobenzene at 20℃. The filtered crystals were dried under vacuum at 45℃. The crystal product thus obtained had a purity of >98%and the recovered product as crystal was found to be not less than 90%yield.
The crystals were characterized as being the crystalline modification I of indoxacarb using IR spectrometry and X-ray powder diffraction as described in Example 3.
Formulation examples
Example 5: Preparation of suspension concentrate (SC) of amorphous indoxacarb
All 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 PCTCN2017110978-appb-000008
Example 6: Preparation of Suspension Concentrate (SC) of indoxacarb crystal A
All 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 PCTCN2017110978-appb-000009
Figure PCTCN2017110978-appb-000010
Example 7: Preparation of Suspension Concentrate (SC) of indoxacarb crystalline modification I
All the components listed in Table 4 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 4
Figure PCTCN2017110978-appb-000011
Figure PCTCN2017110978-appb-000012
Example 8: Comparison of the storage stability
Samples prepared in Examples 5, 6 and 7 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 indoxacarb was tested at the end of each storage time by high pressure liquid chromatography (HPLC) . The aggregation was measured by observation. The original concentration of indoxacarb in each formulation was 15 %. The results are listed in Table 5.
Table 5
Figure PCTCN2017110978-appb-000013
Remark: “+” means small amount of aggregation. “+++++” means a lot of aggregation. “-” means no aggregation.

Claims (18)

  1. A crystalline modification I of methyl (4aS) -7-chloro-2, 5-dihydro-2-[ [ (methoxycarbonyl) [4- (trifluoromethoxy) phenyl] amino] carbonyl] indeno [1, 2-e] [1, 3, 4] oxadiazine-4a (3H) -carboxylate (indoxacarb) , exhibiting at least 3 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 ＝ 9.17 ± 0.20                (1)
    2θ ＝ 9.48 ± 0.20                (2)
    2θ ＝ 10.08 ± 0.20               (3)
    2θ ＝ 12.86 ± 0.20               (4)
    2θ ＝ 14.26 ± 0.20               (5)
    2θ ＝ 15.05 ± 0.20               (6)
    2θ ＝ 17.53 ± 0.20               (7)
    2θ ＝ 18.09 ± 0.20               (8)
    2θ ＝ 18.42 ± 0.20               (9)
    2θ ＝ 19.01 ± 0.20               (10)
    2θ ＝ 19.50 ± 0.20               (11)
    2θ ＝ 20.35 ± 0.20               (12)
    2θ ＝ 20.56 ± 0.20               (13)
    2θ ＝ 20.81 ± 0.20               (14)
    2θ ＝ 21.99 ± 0.20               (15)
    2θ ＝ 23.15 ± 0.20               (16)
    2θ ＝ 23.37 ± 0.20               (17)
    2θ ＝ 23.73 ± 0.20               (18)
    2θ ＝ 23.90 ± 0.20               (19)
    2θ ＝ 24.75 ± 0.20               (20)
    2θ ＝ 25.08 ± 0.20               (21)
    2θ ＝ 25.38 ± 0.20               (22)
    2θ ＝ 29.40 ± 0.20               (23)
    2θ ＝ 31.58 ± 0.20               (24) .
  2. The crystalline modification I of indoxacarb according to claim 1, exhibiting at least 3 of the following reflexes, in any combination, in an X-ray powder diffractogram recorded using Cu—Kα radiation at 25 ℃:
    2θ ＝ 9.17 ± 0.20                (1)
    2θ ＝ 10.08 ± 0.20               (3)
    2θ ＝ 12.86 ± 0.20               (4)
    2θ ＝ 15.05 ± 0.20               (6)
    2θ ＝ 17.53 ± 0.20               (7)
    2θ ＝ 19.01 ± 0.20               (10)
    2θ ＝ 19.50 ± 0.20               (11)
    2θ ＝ 20.35 ± 0.20               (12)
    2θ ＝ 20.56 ± 0.20               (13)
    2θ ＝ 20.81 ± 0.20               (14)
    2θ ＝ 23.15 ± 0.20               (16)
    2θ ＝ 24.75 ± 0.20               (20) .
  3. The crystalline modification I of indoxacarb according to claim 1 or claim 2, exhibiting an  IR spectrum with characteristic functional group vibration peaks at wavenumbers (cm-1, ± 0.2％) of one or more of about 2160.89 and 1979.31cm-1.
  4. A crystalline modification I of indoxacarb according to any one of claims 1 to 3, 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.
  5. A process for the preparation of the crystalline modification I of indoxacarb crystal according to any one of the preceding claims, comprising the steps of:
    i) dissolving indoxacarb in a solvent or mixture of solvents；
    ii) precipitating the dissolved indoxacarb into crystalline modification I of indoxacarb； and
    iii) isolating the precipitated crystalline modification I.
  6. The process according to claim 5, where the indoxacarb in step i) is amorphous indoxacarb.
  7. The process according to either of claims 5 or 6, wherein the solvent is selected from the group consisting of nitrobenzene, n-hexane or a mixture thereof.
  8. The process according to any one of claims 5 to 7, wherein step ii) comprises concentrating the solution and/or by cooling and/or by the addition of a solubility reducing solvent and/or by adding a seed crystal of the crystalline modification I of indoxacarb.
  9. The process according to claim 8, wherein step ii) is effected by cooling to about 0 to 20℃.
  10. A crystalline modification I of indoxacarb obtained according to any one of claims 5 to 9, having a crystalline modification I of indoxacarb content of at least 98％by weight.
  11. A composition comprising the crystalline modification I of indoxacarb according to any one of claims 1 to 4 and claim 10 and at least one auxiliary.
  12. The composition of claim 11, which is in form of a suspension concentrate (SC) , an oil-based suspension concentrate (OD) , a water-soluble granule (SG) , a dispersible concentrate (DC) , an emulsifiable concentrate (EC) , an emulsion seed dressing, a suspension seed dressing, a granule (GR) , a microgranule (MG) , a suspoemulsion (SE) or a water-dispersible granule (WG) .
  13. The composition according to claim 11, which is in form of a suspension concentrate (SC) .
  14. The composition according to any one of claims 11 to 13, wherein the auxiliary is selected from one or more of a solvent, a diluent, a wetting agent, a dispersants, a thickener, an antifreeze agent and a biocide.
  15. The composition according to any one of claims 11 to 14, which comprises crystalline modification I of indoxacarb in an amount of less than 50 ％by weight.
  16. The composition according to any one of claims 11 to 15, which comprises crystalline modification I of indoxacarb in an amount of 15 ％by weight.
  17. A use of the crystalline modification I of indoxacarb according to any one of claims 1 to 4 or the composition according to any one of claims 11 to 16 for the control of lepidopteran insects.
  18. A use of the crystalline modification I of indoxacarb according to any one of claims 1 to 4 or the composition according to any one of claims 11 to 16 for the control of boll weevil, bollworm and other Lepidoptera on cotton and corn.
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WO2023148735A1 (en) * 2022-02-02 2023-08-10 Adama Makhteshim Ltd. Novel solid state forms of indoxacarb
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CN104311502A (en) * 2014-09-15 2015-01-28 南通施壮化工有限公司 Method for separation purification of indoxacarb S-isomer from indoxacarb mixture

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CN113607836A (en) * 2021-07-23 2021-11-05 京博农化科技有限公司 Method for analyzing content of indoxacarb key intermediate
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WO2023183353A3 (en) * 2022-03-22 2023-11-02 Fmc Corporation Processes for crystallization of amorphous pesticides and formulations thereof

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