WO2020074364A1 - Co-cristaux de difénoconazole - Google Patents

Co-cristaux de difénoconazole Download PDF

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Publication number
WO2020074364A1
WO2020074364A1 PCT/EP2019/076838 EP2019076838W WO2020074364A1 WO 2020074364 A1 WO2020074364 A1 WO 2020074364A1 EP 2019076838 W EP2019076838 W EP 2019076838W WO 2020074364 A1 WO2020074364 A1 WO 2020074364A1
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WIPO (PCT)
Prior art keywords
crystal
difenoconazole
fumaric acid
composition
fungicide
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PCT/EP2019/076838
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English (en)
Inventor
James Owen Forrest
Neil George
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Syngenta Crop Protection Ag
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Publication of WO2020074364A1 publication Critical patent/WO2020074364A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • 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
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/12—Powders or granules
    • 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
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles

Definitions

  • the present invention relates to novel co-crystals of difenoconzaole and their use in fungicidal compositions, in particular agrochemical compositions.
  • Difenconazole (l-[2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-l,3-dioxolan-2- yl-methyl]-lH-l, 2, 4-triazole) is a broad spectrum fungicide which acts by inhibition of demethylation during ergosterol biosynthesis. It is available commercially and is described in “The Pesticide Manual” [The Pesticide Manual, Seventeenth Edition; Editor J. Turner; The British Crop Protection Council]
  • difenoconazole is normally produced in a ratio of about 60:40 cisdrans, with a ratio of 1 : 1 between cis and trans racemates, i.e. 60:40 2S, 4R (la) and 2R, 4S (lb) : 2R, 4R (Ic) and 2S, 4S (Id) and 1 : 1 of 2S, 4R (la): 2R, 4S (lb) and 1 :1 2R, 4R (Ic): 2S, 4S (Id).
  • the resulting difenoconazole contains about 30% (la), about 30% (lb), about 20% (Ic) and about 20% (Id).
  • Difenoconazole has a melting point around 79°C, but the onset of melting may occur at temperatures closer to 70°C. The melting point may be further depressed in the presence of other organic compounds and this may lead to difficulties in formulating difenoconazole.
  • difenoconazole A number of technologies are used to formulate difenoconazole. For example, it may be co-milled with other active ingredients and their co-formulants - this ensures a homogenous distribution of all components in the mixture as well as reducing capital overhead costs and providing greater speed and efficiency. Alternatively, granulation may be used. In both of these methods, mixing the components will depress the melting point of the difenoconazole - this can result in partial melting of the solids and a failure of the milling and/or granulation process.
  • Spray granulation may also be used to formulate difenoconazole.
  • the active ingredient is mixed with other formulation components, wet milled to reduce the particle size and then spray-dried to create a porous‘raspberry- like’ structure.
  • Use of a material with a low melting point in spray granulation can lead to milling failures as detailed above and, in addition, the high temperatures that the granules experience during the spray drying process (70-90°C) can also lead to complete melting and clogging of the spray-drying equipment or partial melting leading to granules that do not redisperse on dilution in the spray tank.
  • the present invention provides a co-crystal of difenoconazole with fumaric acid which has a higher melting point that difenoconazole alone.
  • the co-crystalline form of difenoconazole and the crystal forming compound may be characterised by a crystal morphology or by selected peaks of the powder X-ray diffraction pattern expressed in terms of 2 theta angles.
  • the present invention provides a co-crystal of the cis racemate of difenoconazole (i.e. (Ia) and (lb)) with fumaric acid.
  • the co-crystal form of difenoconazole cis racemate and fumaric acid is characterised by the unit cell parameters of its single crystal as shown in Table 1.
  • the co-crystal was obtained using the method of Example la and crystallographic data was obtained at 100°K.
  • the co-crystal form of difenoconazole cis racemate and fumaric acid is characterised by a powder X-ray diffraction pattern expressed in terms of 20 angles or d spacings, wherein the powder X-ray diffraction pattern comprises at least three, at least 6, at least 9 or all 20 angle values selected from the group comprising 4.9 ⁇ 0.2, 9.8 ⁇ 0.2, 10.7 ⁇ 0.2, 11.2 ⁇ 0.2, 14.4 ⁇ 0.2, 18.6 ⁇ 0.2, 20.5 ⁇ 0.2, 20.9 ⁇ 0.2, 23.2 ⁇ 0.2, 23.9 ⁇ 0.2 and 24.9 ⁇ 0.2.
  • the co-crystal form of difenoconazole cis racemate and fumaric acid has a melting point of l34°C. This melting point is obtained using Differential Scanning Calorimetry (DSC), with a heating rate of l0°C/minute.
  • DSC Differential Scanning Calorimetry
  • the present invention provides a co-crystal of the trans racemate of difenoconazole (i.e. (Ic) and (Id)) with fumaric acid.
  • the co-crystal form of difenoconazole trans racemate and fumaric acid is characterised by the unit cell parameters of its single crystal as shown in Table 3.
  • the co-crystal was obtained using the method of Example lb and crystallographic data was obtained at 100°K.
  • the co-crystal form of difenoconazole trans racemate and fumaric acid is characterised by a powder X-ray diffraction pattern expressed in terms of 2Q angles or d spacings, wherein the powder X-ray diffraction pattern comprises at least three, at least 6, at least 9, at least 12 or all 2Q angle values selected from the group comprising 6.0 ⁇ 0.2, 10.0 ⁇ 0.2, 12.7 ⁇ 0.2, 16.7 ⁇ 0.2, 17.0 ⁇ 0.2, 17.4 ⁇ 0.2, 18.0 ⁇ 0.2, 18.9 ⁇ 0.2, 19.6 ⁇ 0.2, 20.0 ⁇ 0.2, 20.4 ⁇ 0.2, 21.0 ⁇ 0.2, 22.8 ⁇ 0.2, 23.0 ⁇ 0.2 and 24.0 ⁇ 0.2.
  • the co-crystal form of difenoconazole trans racemate and fumaric acid has a melting point of l23°C. This melting point is obtained using Differential Scanning Calorimetry (DSC), with a heating rate of l0°C/minute.
  • DSC Differential Scanning Calorimetry
  • the co-crystals of the present invention are formed by contacting the difenoconazole with the fumaric acid. This may be done by (i) grinding two solids together; (ii) melting one or both components and allowing them to recrystallise; and (iiia) solubilising, or partially solubilising, the difenoconazole and adding the co-crystal forming compound or (iiib) solubilising, or partially solubilising, the co-crystal forming compound and adding the difenoconazole. It may also be possible to solubilise, or partially solubilise, the
  • the co- crystals of the invention are formed by grinding two solids together.
  • the difenoconazole and the fumaric acid may be mixed in a high sheer mixer and then milled. Crystallisation is then allowed to occur under suitable conditions. For example,
  • crystallisation may require alteration of a property of the solutions, such as pH or temperature and may require concentration of solute, usually by removal of the solvent and typically by drying the solution. Solvent removal results in the concentration of difenoconazole increasing over time so as to facilitate crystallisation.
  • microwave irradiation or sonication (or both microwave irradiation and sonication) may be used to facilitate crystallisation.
  • the present invention provides a process for the production of a co- crystal of the invention comprising
  • co-crystal means a crystalline material which comprises two or more unique components in a stoichiometric ratio each containing distinctive physical
  • a co- crystal is distinct from a crystalline salt as it consists of neutral components and not charged components as would be found in a salt.
  • the co-crystal can be constructed through several modes of molecular recognition including hydrogen-bonding, P (pi)-stacking, guest-host complexation and Van-Der-Waals interactions. Of the interactions listed above, hydrogen bonding is the dominant interaction in the formation of the co-crystal, whereby a non- covalent bond is formed between a hydrogen bond donor of one of the moieties and a hydrogen bond acceptor of the other.
  • Preferred co-crystals of the present invention are those where hydrogen bonding occurs between the fumaric acid and the difenoconazole. It is noted that multi-point contacts may be formed in the crystal. For example, two molecules of difenoconazole may form contacts with different functional groups on the same fumaric acid molecule, or, indeed, there may be multi-point contacts between a single molecule of difenoconazole and a single fumaric acid molecule.
  • the co-crystals of the present invention may exist in one or more polymorphic forms fumaric acid, but typically will be in the range of from 5 : 1 to 1 :5Each polymorphic form may be defined by one or more solid state analytical techniques including single crystal X-ray diffraction, powder X-ray diffraction, DSC, Raman or infra-red spectroscopy.
  • the molar ratio of difenoconazole to co-crystal forming compound in the co crystal is in the range of from 5:1 to 1 :5. More suitably, the molar ratio of difenoconazole to co-crystal forming compound in the co-crystal is in the range of from 3:1 to 1 :3. Even more suitably, the molar ratio of difenoconazole to co-crystal forming compound is in the range of 2:1 to 1 :1 and, in particular, may be 2: 1.
  • Assaying the solid phase for the presence of co-crystals of the difenoconazole and fumaric acid may be carried out by conventional methods known in the art. For example, it is convenient and routine to use powder X-ray diffraction techniques to assess the presence of the co-crystals. This may be effected by comparing the spectra of difenoconazole, fumaric acid and putative co-crystals in order to establish whether or not true co-crystals have been formed. Other techniques used in an analogous fashion, include differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Raman or Infra-red spectroscopy, NMR, gas chromatography or HPLC. Single crystal X-ray diffraction is especially useful in identifying co-crystal structures.
  • DSC differential scanning calorimetry
  • TGA thermogravimetric analysis
  • Raman or Infra-red spectroscopy NMR, gas chromatography or HPLC.
  • the co-crystals of the invention may applied in unchanged form but are more preferably incorporated into fungicidal compositions (including agrochemical compositions) by conventional means. Accordingly, the invention also provides a fungicidal composition comprising a co-crystal of the invention as defined above and one or more carriers or diluents.
  • the present invention provides a composition comprising (i) the co crystal of difenoconazole cis racemate and fumaric acid or (ii) the co-crsytal of
  • the ratio of cis co-crystal to trans co-crystal in the composition is from 99: 1 to 1 :99, more preferably from 70:30 to 40:60 and, most preferably, from 60:40 to 50:50.
  • the fungicidal composition is an agrochemical composition.
  • the agrochemical compositions comprising the co-crystals of the present invention can be used for the control of plant pathogenic fungi on a number of plant species.
  • the invention also provides a method of preventing or controlling fungal infection on plants or plant propagation material comprising treating the plant or plant propagation material, or locus thereof, with a fungicidally effective amount of an agricultural composition of the invention.
  • fungicide as used herein means a compound that controls, modifies, or prevents the growth of fungi.
  • fungicidally effective amount means the quantity of such a compound or combination of such compounds that is capable of producing an effect on the growth of fungi. Controlling or modifying effects include all deviation from natural development, such as killing, retardation and the like, and prevention includes barrier or other defensive formation in or on a plant to prevent fungal infection.
  • locus means fields in or on which plants are growing, or where seeds of cultivated plants are sown, or where seed will be placed into the soil. It includes soil, seeds, and seedlings, as well as established vegetation.
  • plants refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits.
  • plant propagation material denotes all generative parts of a plant, for example seeds or vegetative parts of plants such as cuttings and tubers. It includes seeds in the strict sense, as well as roots, fruits, tubers, bulbs, rhizomes, and parts of plants.
  • Crops of useful plants in which the composition according to the invention can be used include perennial and annual crops, such as berry plants for example blackberries, blueberries, cranberries, raspberries and strawberries; cereals for example barley, maize (com), millet, oats, rice, rye, sorghum triticale and wheat; fibre plants for example cotton, flax, hemp, jute and sisal; field crops for example sugar and fodder beet, coffee, hops, mustard, oilseed rape (canola), poppy, sugar cane, sunflower, tea and tobacco; fruit trees for example apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear and plum; grasses for example Bermuda grass, bluegrass, bentgrass, centipede grass, fescue, ryegrass,
  • Crops are to be understood as being those which are naturally occurring, obtained by conventional methods of breeding, or obtained by genetic engineering. They include crops which contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).
  • output traits e.g. improved storage stability, higher nutritional value and improved flavour.
  • Crops are to be understood as also including those crops which have been rendered tolerant to herbicides like bromoxynil or classes of herbicides such as ALS-, EPSPS-, GS-, HPPD- and PPO-inhibitors.
  • herbicides like bromoxynil or classes of herbicides such as ALS-, EPSPS-, GS-, HPPD- and PPO-inhibitors.
  • An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield® summer canola.
  • crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady®, Herculex I® and
  • Crops are also to be understood as being those which naturally are or have been rendered resistant to harmful insects. This includes plants transformed by the use of recombinant DNA techniques, for example, to be capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria. Examples of toxins which can be expressed include d-endotoxins, vegetative insecticidal proteins (Vip), insecticidal proteins of bacteria colonising nematodes, and toxins produced by scorpions, arachnids, wasps and fungi.
  • Vip vegetative insecticidal proteins
  • insecticidal proteins of bacteria colonising nematodes and toxins produced by scorpions, arachnids, wasps and fungi.
  • An example of a crop that has been modified to express the Bacillus thuringiensis toxin is the Bt maize KnockOut® (Syngenta Seeds).
  • An example of a crop comprising more than one gene that codes for insecticidal resistance and thus expresses more than one toxin is VipCot® (Syngenta Seeds).
  • Crops or seed material thereof can also be resistant to multiple types of pests (so-called stacked transgenic events when created by genetic modification).
  • a plant can have the ability to express an insecticidal protein while at the same time being herbicide tolerant, for example Herculex I® (Dow AgroSciences, Pioneer Hi-Bred International).
  • compositions according to the invention are particularly effective against powdery mildews; rusts; leafspot species; early blights and molds; especially against Septoria, Puccinia, Erysiphe, Pyrenophora and Tapesia in cereals; Phakopsora in soybeans; Hemileia in coffee; Phragmidium in roses; Altemaria in potatoes, tomatoes and cucurbits; Sclerotinia in turf, vegetables, sunflower and oil seed rape; black rot, red fire, powdery mildew, grey mold and dead arm disease in vine; Botrytis cinerea in fruits; Monilinia spp. in fruits and Penicillium spp. in fruits.
  • compositions according to the invention are furthermore particularly effective against seedbome and soilbome diseases, such as Altemaria spp., Ascochyta spp., Botrytis cinerea, Cercospora spp., Claviceps purpurea, Cochliobolus sativus, Colletotrichum spp., Epicoccum spp., Fusarium graminearum, Fusarium moniliforme, Fusarium oxysporum, Fusarium proliferatum, Fusarium solani, Fusarium subglutinans, Gaumannomyces graminis , Helminthosporium spp., Microdochium nivale, Phoma spp., Pyrenophora graminea,
  • seedbome and soilbome diseases such as Altemaria spp., Ascochyta spp., Botrytis cinerea, Cercospora spp., Claviceps purpure
  • compositions according to the invention are furthermore particularly effective against post harvest diseasese such as Botrytis cinerea, Colletotrichum musae, Curvularia lunata, Fusarium semitecum, Geotrichum candidum, Monilinia fructicola, Monilinia fructigena, Monilinia laxa, Mucor piriformis, Penicilium italicum, Penicilium solitum, Penicillium digitatum or Penicillium expansum in particular against pathogens of fruits, such as pomefruits, for example apples and pears, stone fruits, for example peaches and plums, citrus, melons, papaya, kiwi, mango, berries, for example strawberries, avocados,
  • post harvest diseasese such as Botrytis cinerea, Colletotrichum musae, Curvularia lunata, Fusarium semitecum, Geotrichum candidum, Monilinia fructicola, Monilinia fructigena, Monilinia laxa, Mucor
  • compositions according to the invention are particularly useful for controlling the following diseases on the following crops:
  • Pseudocercosporella species in cereals such as Pseudocercosporella herpotrichoides in wheat; Phragmidium mucronatum in roses; Podosphaera species in fruits; Pyrenophora species in barley, such as Pyrenophora teres on barley; Pyricularia oryzae in rice; Ramularia collo-cygni in barley; Rhizoctonia species in cotton, soybean, cereals, maize, potatoes, rice and lawns, such as Rhizoctonia solani on potato, rice, turf and cotton; Rhynchosporium secalis on barley, Rhynchosporium secalis on rye; Sclerotinia species in lawns, lettuce, vegetables and oil seed rape, such as Sclerotinia sclerotiorum on oilseed rape and Sclerotinia homeocarpa on turf; Septoria species in cereals, soybean and vegetables, such as Septoria tritici on wheat,
  • the rate at which the agrochemical composition of the invention is applied will depend upon the particular type of fungus to be controlled, the degree of control required and the timing and method of application and can be readily determined by the person skilled in the art.
  • the compositions of the invention can be applied at an application rate of between 0.005 kilograms/hectare (kg/ha) and about 5.0kg/ha, based on the total amount of active fungicide in the composition.
  • An application rate of between about 0.1 kg/ha and about l.5kg/ha is preferred, with an application rate of between about 0.3kg/ha and 0.8kg/ha being especially preferred.
  • the co-crystals according to the invention can be used as pesticidal agents in unmodified form, but they are generally incorporated in compositions in various ways using formulation adjuvants, such as carriers, solvents and surface-active substances.
  • formulation adjuvants such as carriers, solvents and surface-active substances.
  • the formulations can be in various physical forms, e.g.
  • Such formulations can either be used directly or diluted prior to use.
  • the dilutions can be made, for example, with water, liquid fertilisers, micronutrients, biological organisms, oil or solvents.
  • the formulations can be prepared e.g. by mixing the co-crystals of the invention (‘active ingredients’) with the formulation adjuvants in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions.
  • active ingredients can also be formulated with other adjuvants, such as finely divided solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surface-active substances or combinations thereof.
  • the active ingredients can also be contained in very fine microcapsules.
  • Microcapsules contain the active ingredients in a porous carrier. This enables the active ingredients to be released into the environment in controlled amounts (e.g. slow-release). Microcapsules usually have a diameter of from 0.1 to 500 microns. They contain active ingredients in an amount of about from 25 to 95 % by weight of the capsule weight.
  • the active ingredients can be in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution.
  • the encapsulating membranes can comprise, for example, natural or synthetic rubbers, cellulose, styrene/butadiene copolymers, polyacrylonitrile, polyacrylate, polyesters, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other polymers that are known to the person skilled in the art.
  • very fine microcapsules can be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of base substance, but the microcapsules are not themselves encapsulated.
  • compositions according to the invention are known per se.
  • liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone,
  • cyclohexanone acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, l,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N, /V- dimethyl formamidc, dimethyl sulfoxide, l,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate
  • Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed husks, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances.
  • a large number of surface-active substances can advantageously be used in both solid and liquid formulations, especially in those formulations which can be diluted with a carrier prior to use.
  • Surface-active substances may be anionic, cationic, non-ionic or polymeric and they can be used as emulsifiers, wetting agents or suspending agents or for other purposes.
  • Typical surface-active substances include, for example, salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; salts of alkylarylsulfonates, such as calcium dodecyl- benzenesulfonate; alkylphenol/alkylene oxide addition products, such as nonylphenol ethoxylate; alcohol/alkylene oxide addition products, such as tridecylalcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium
  • dibutylnaphthalenesulfonate dialkyl esters of sulfosuccinate salts, such as sodium di(2- ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride, polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and di-alkylphosphate esters; and also further substances described e.g. in McCutcheon's Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood New Jersey (1981).
  • Further adjuvants that can be used in pesticidal formulations include crystallisation inhibitors, viscosity modifiers, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing auxiliaries, antifoams, complexing agents, neutralising or pH-modifying substances and buffers, corrosion inhibitors, fragrances, wetting agents, take-up enhancers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides, and liquid and solid fertilisers.
  • compositions according to the invention can include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters of such oils or mixtures of such oils and oil derivatives.
  • the amount of oil additive in the composition according to the invention is generally from 0.01 to 10 %, based on the mixture to be applied.
  • the oil additive can be added to a spray tank in the desired concentration after a spray mixture has been prepared.
  • Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow.
  • Preferred oil additives comprise alkyl esters of CVC22 fatty acids, especially the methyl derivatives of C12-C18 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate and methyl oleate, respectively).
  • methyl esters of lauric acid, palmitic acid and oleic acid methyl laurate, methyl palmitate and methyl oleate, respectively.
  • Many oil derivatives are known from the Compendium of Herbicide
  • compositions generally comprise from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, of compounds of the present invention and from 1 to 99.9 % by weight of a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance.
  • a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance.
  • commercial products may preferably be formulated as concentrates, the end user will normally employ dilute formulations.
  • the rates of application vary within wide limits and depend on the nature of the soil, the method of application, the crop plant, the pest to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop.
  • a general guideline compounds may be applied at a rate of from 1 to 2000 l/ha, especially from 10 to 1000 l/ha.
  • Preferred formulations can have the following compositions (weight %):
  • Emulsifiable concentrates active ingredient: 1 to 95 %, preferably 60 to 90 %
  • surface-active agent 1 to 30 %, preferably 5 to 20 %
  • liquid carrier 1 to 80 %, preferably 1 to 35 %
  • Dusts active ingredient: 0.1 to 10 %, preferably 0.1 to 5 %
  • solid carrier 99.9 to 90 %, preferably 99.9 to 99 %
  • Suspension concentrates active ingredient: 5 to 75 %, preferably 10 to 50 %
  • surface-active agent 1 to 40 %, preferably 2 to 30 %
  • Wettable powders active ingredient: 0.5 to 90 %, preferably 1 to 80 %
  • surface-active agent 0.5 to 20 %, preferably 1 to 15 %
  • solid carrier 5 to 95 %, preferably 15 to 90 %
  • Granules active ingredient: 0.1 to 30 %, preferably 0.1 to 15 % solid carrier: 99.5 to 70 %, preferably 97 to 85 %
  • the combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.
  • the combination is thoroughly mixed with the adjuvants and the mixture is thorough y ground in a suitable mill, affording powders that can be used directly for seed treatment.
  • Emulsions of any required dilution which can be used in plant protection, can be obtained from this concentrate by dilution with water.
  • Ready- for-use dusts are obtained by mixing the combination with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed.
  • the combination is mixed and ground with the adjuvants, and the mixture is moistened with water.
  • the mixture is extruded and then dried in a stream of air.
  • the finely ground combination is uniformly app red, in a mixer, to the kaolin moistened with polyethylene glycol.
  • Non-dusty coated granules are obtained in this manner.
  • the finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
  • the finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
  • 28 parts of the active ingredients are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1).
  • This mixture is emulsified in a mixture of 1.2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51.6 parts of water until the desired particle size is achieved.
  • a mixture of 2.8 parts 1, 6-diamino hexane in 5.3 parts of water is added.
  • the mixture is agitated until the polymerization reaction is completed.
  • the obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent.
  • the capsule suspension formulation contains 28% of the active ingredients.
  • the medium capsule diameter is 8-15 microns.
  • the resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.
  • Each of the above formulations can be prepared as a package containing the fungicides together with other ingredients of the formulation (diluents, emulsifiers, surfactants, etc.).
  • the formulations can also be prepared by a tank mix method, in which the ingredients are obtained separately and combined at the grower site.
  • Dust and liquid compositions for example, can be applied by the use of power-dusters, broom and hand sprayers and spray dusters.
  • the formulations can also be applied from airplanes as a dust or a spray or by rope wick applications.
  • Both solid and liquid formulations may also be applied to the soil in the locus of the plant to be treated allowing the active ingredient to penetrate the plant through the roots.
  • the formulations of the invention may also be used for dressing applications on plant propagation material to provide protection against fungus infections on the plant propagation material as well as against phytopathogenic fungi occurring in the soil.
  • the active ingredient may be applied to plant propagation material to be protected by impregnating the plant propagation material, in particular, seeds, either with a liquid formulation of the fungicide or coating it with a solid formulation.
  • plant propagation material in particular, seeds
  • other types of application are also possible, for example, the specific treatment of plant cuttings or twigs serving propagation.
  • the agrochemical compositions and formulations of the present invention are applied prior to disease development. Rates and frequency of use of the formulations are those conventionally used in the art and will depend on the risk of infestation by the fungal pathogen.
  • agronomic chemicals include pesticides, such as acaricides, bactericides, fungicides, herbicides, insecticides, nematicides, as well as plant nutrients and plant fertilizers.
  • pesticides such as acaricides, bactericides, fungicides, herbicides, insecticides, nematicides, as well as plant nutrients and plant fertilizers.
  • the composition of the present invention may be used in combination at lease one further fungicides.
  • the co-crystals of the invention may be mixed with one or more of compounds selected from those in the following chemical or functional classes:- l,2,4-thiadiazoles, 2,6- dinitroanilines, acylalanines, aliphatic nitrogenous compounds, amidines, aminopyrimidinols, anilides, anilino-pyrimidines, anthraquinones, antibiotics, aryl-phenylketones, benzamides, benzene-sulfonamides, benzimidazoles, benzothiazoles, benzothiodiazoles, benzothiophenes, benzoylpyridines, benzthiadiazoles, benzylcarbamates, butylamines, carbamates,
  • carboxamides carpropamids, chloronitriles, cinnamic acid amides, copper containing compounds, cyanoacetamideoximes, cyanoacrylates, cyanoimidazoles, cyanomethylene- thiazolidines, dicarbonitriles, dicarboxamides, dicarboximides, dimethylsulphamates, dinitrophenol carbonates, dinitrophenysl, dinitrophenyl crotonates, diphenyl phosphates, dithiino compounds, dithiocarbamates, dithioethers, dithiolanes, ethyl- amino -thiazole carboxamides, ethyl-phosphonates, furan carboxamides, glucopyranosyls, glucopyranoxyls, glutaronitriles, guanidines, herbicides/plant growth regulatosr, hexopyranosyl antibiotics, hydroxy(2-amino)pyrimidines, hydroxy
  • imidazolinones insecticides/plant growth regulators, isobenzofuranones, isoxazo lidinyl- pyridines, isoxazo lines, maleimides, mandelic acid amides, mectin derivatives, morpholines, norpho lines, n-phenyl carbamates, organotin compounds, oxathiin carboxamides, oxazoles, oxazolidine-diones, phenols, phenoxy quinolines, phenyl-acetamides, phenylamides, phenylbenzamides, phenyl-oxo-ethyl-thiophenes amides, phenylpyrroles, phenylureas, phosphorothiolates, phosphorus acids, phthalamic acids, phthalimides, picolinamides, piperazines, piperidines, plant extracts, polyoxins, propionamides, pthalimides, pyrazole
  • Particularly preferred fungicidal combinations include the following where“I” designates the co-crsytals of the invention: I + etridiazole, I + fluazinam, I + benalaxyl, I + benalaxyl-M (kiralaxyl), I + furalaxyl, I + metalaxyl, I + metalaxyl-M (mefenoxam), I + dodicin, I + N'-(2,5-Dimethyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine, I + N'-[4- (4,5-Dichloro-thiazol-2-yloxy)-2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine, I + N'- [4-[[3-[(4-chlorophenyl)methyl]-l,2,4-thiadiazol-5-yl]oxy]-2,5-dimethyl
  • I + benzovindiflupyr I + bixafen, I + fluxapyroxad, I + furametpyr, I + isopyrazam, I + penflufen, I + penthiopyrad, I + sedaxane, I + fenpyrazamine, I + diclomezine, I + pyrifenox, I + boscalid, I + fluopyram, I + diflumetorim, I + fenarimol, I + 5-fluoro-2-(p-tolylmethoxy)pyrimidin-4-amine I + ferimzone, I + dimetachlone
  • I + azoxystrobin I + coumoxystrobin, I + dimoxystrobin, I + enestroburin, enoxastrobin I + fenamistrobin, I + flufenoxystrobin, I + fluoxastrobin, I + kresoxim- methyl, I + mandestrobin, I + metaminostrobin, I + metominostrobin, I + orysastrobin, I + picoxystrobin, I + pyraclostrobin, I + pyrametostrobin, I + pyraoxystrobin, I +
  • I + trifloxystrobin I + amisulbrom, I + dichlofluanid, I + tolylfluanid, I + but-3 -ynyl N- [6- [ [(Z)- [( 1 -methyltetrazol-5 -yl)-phenyl-methylene]amino]oxymethyl] -2- pyridyl] carbamate
  • I + dazomet I + isotianil, I + tiadinil, I + thifluzamide, I + benthiazole (TCMTB), I + silthiofam, I + zoxamide, I + anilazine, I + tricyclazole, I + ( +-.)-cis-l-(4- chlorophenyl)-2-(lH-l,2,4-triazol-l-yl)-cycloheptanol (huanjunzuo), I + l-(5-bromo-2- pyr
  • a strobilurin fungicide selected from the group consisting of azoxystrobin, dimoxystrobin, fluoxastrobin, kresoxim-methyl, metominostrobin, orysastrobin,
  • an azole fungicide selected from the group consisting of azaconazole, bromuconazole, cyproconazole, difenoconazole, diniconazole, diniconazole-M, epoxiconazole,
  • fenbuconazole fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil,
  • imibenconazole imibenconazole, ipconazole, metconazole, myclobutanil, oxpoconazole, pefurazoate, penconazole, prochloraz, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triflumizole, triticonazole, diclobutrazol, etaconazole, furconazole, furconazole-cis and quinconazole.
  • SDHI succinate dehydrogenase inhibitor selected from the group consisting of flutolanil, mepronil, isofetamid, fluopyram, carboxin, oxycarboxin, thifluzamide,
  • compositions comprising the co-crystals of the invention and another fungicide are explicitly disclosed above, the skilled man will appreciate that the invention extends to three-way, and further multiple combinations comprising the above two-way mixtures.
  • the co-crystals of the invention may be combined with a strobilurin and an SDHI fungicide.
  • Pesticidal agents referred to herein using their common name are known, for example, from “The Pesticide Manual”, 15th Ed., British Crop Protection Council 2009.
  • the mixing partners of may also be in the form of any suitable agrochemically acceptable ester or salt, as mentioned e.g. in “The Pesticide Manual", 15th Ed., British Crop Protection Council 2009.
  • the invention provides a composition comprising:
  • the strobilurin fungicide is selected from the group consisting of azoxystrobin, dimoxystrobin, fluoxastrobin, kresoxim-methyl, metominostrobin,
  • the strobilurin is azoxystrobin.
  • the SDHI fungicide is selected from the group consisting of flutolanil, mepronil, isofetamid, fluopyram, carboxin, oxycarboxin, thifluzamide, benzovindiflupyr, bixafen, fluxapyroxad, furametpyr, isopyrazam, penflufen, penthiopyrad, pydiflumetofen, sedaxane, boscalid, isopyrazam, benodanil and fenfuram. More preferably, the SDHI fungicide is benzovindiflupyr, isopyrazam, sedaxane or pydiflumetofen. Most preferably the SDHI fungicide is benzovindiflupyr.
  • the formulation is a wettable granule.
  • FIG. 1 shows the measured powder X-ray diffraction pattern of the co-crystal of the cis (racemate) of difenoconazole and fumaric acid.
  • FIG. 2 shows the predicted powder X-ray diffraction pattern of the co-crystal of the cis (racemate) of difenoconazole and fumaric acid.
  • FIG. 3 shows the measured powder X-ray diffraction pattern of the co-crystal of the trans (racemate) of difenoconazole and fumaric acid.
  • FIG. 4 shows the predicted powder X-ray diffraction pattern of the co-crystal of the cis (racemate) of difenoconazole and fumaric acid.
  • FIG. 5 shows a DSC trace of the co-crystal of the cis (racemate) of difenoconazole and fumaric acid.
  • FIG. 6 shows a DSC trace of the co-crystal of the trans (racemate) of difenoconazole and fumaric acid.
  • Difenoconazole (cis-racemate) (0.l2g) was added to fumaric acid (0.02g) and 20 pL of ethanol or acetonitrile. The resulting mixture was milled using the Retsch MM200 at 500rpm for 1 hour. The resulting crystals were filtered and dried.
  • Difenoconazole (trans-racemate) (0.l4g) was added to fumaric acid (0.02g) and 20 pL of ethanol. The resulting mixture was milled using the Retsch MM200 at 500rpm for 1 hour. The resulting crystals were filtered and dried.
  • the samples were subject to analysis by powder X-ray diffraction and/or single crystal X-ray diffraction and/or differential scanning calorimetry (DSC).
  • Powder X-ray diffraction analysis of solid material was carried out using the Bruker D8 powder diffractometer at room temperature and at relative humidities above 40%. Samples were mounted in Perspex sample holders and the samples flattened. The sample holder was rotated and X-rays were collected from 4° to 34° 2-theta, with a scan time of 25 to 30 minutes depending on the pattern intensity. Measured powder X-ray diffraction patterns for the co crystals of the invention are shown in FIG. 1 (cis-racemate), and FIG. 3 (trans-racemate).
  • DSC was carried out using a Mettler Toledo DSC1. A sample loading of around 5mg was used and this was heated from from 25°C to 300°C at a rate of l0°C/minute. The lid of the DSC crucible was pierced to allow the escape of any gas formed during the heating of the sample.
  • the DSC analysis confirmed the presence of the co-crystals of the invention with a melting point of l34°C (cis-racemate) and l23°C (trans-racemate).
  • a DSC trace of the co crystals of the invention is shown in FIG. 5 (cis-racemate) and FIG. 6 (trans-racemate).

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Abstract

La présente invention concerne de nouveaux co-cristaux de difénoconzaole et d'acide fumarique et leur utilisation dans des compositions fongicides, en particulier des compositions agrochimiques.
PCT/EP2019/076838 2018-10-09 2019-10-03 Co-cristaux de difénoconazole WO2020074364A1 (fr)

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WO2021214463A1 (fr) * 2020-04-24 2021-10-28 UPL Corporation Limited Composition fongicide comprenant du prothioconazole et au moins un acide faible

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021214463A1 (fr) * 2020-04-24 2021-10-28 UPL Corporation Limited Composition fongicide comprenant du prothioconazole et au moins un acide faible
CN115697060A (zh) * 2020-04-24 2023-02-03 Upl有限责任公司 杀真菌组合物

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