Solid quinoline carboxamide compound

Abstract

The present invention relates to formula (I): [Formula 1] The crystalline polymorphs of compound JPEG2026519101000016.jpg49161 are 7.1±0.2°, 7.8±0.2°, 8.9±0.2°, 11.4±0.2°, 13.5±0.2°, 14.2±0.2°, 14.7±0.2°, 16.2±0.2°, 17.7±0.2°, 18.4±0.2°, 20.0±0.2°, 20.8±0.2°, 21.2±0.2°, and 21.5±0. This relates to a crystalline polymorph having a powder X-ray diffraction pattern that includes at least three 2θ angular values ​​selected from the group consisting of 2°, 22.3±0.2°, 22.9±0.2°, 23.6±0.2°, 24.0±0.2°, 24.3±0.2°, 25.0±0.2°, 26.2±0.2°, 27.3±0.2°, 27.710±0.2°, 28.6±0.2°, 29.6±0.2°, and 30.3±0.2°.

Description

[Technical Field]

[0001] The present invention relates to a solid quinoline carboxamide derivative, a method for preparing the solid, a composition containing the solid, and a method for using the solid as a fungicide. [Background technology]

[0002] International Publication No. 2017 / 153380 discloses that certain quinoline carboxamide derivatives possess antimicrobial activity, such as fungal activity. In particular, compound of formula I: N-(1-benzyl-1,3-dimethyl-butyl)-8-fluoroquinoline-3-carboxamide: [ka]

[0003] A mixture of this compound with other fungicides is disclosed in International Publication No. 2019 / 052930, and a process for preparing quinoline carboxamide derivatives is also disclosed.

[0004] Two enantiomers of the compound of formula I: compound IR and IS, shown below: [ka] There is. [Overview of the Initiative] [Means for solving the problem]

[0005] A new solid form and preparation thereof of this compound have now been discovered. Therefore, the present invention relates to a novel crystalline form of a quinoline carboxamide derivative, wherein the derivative is a crystalline polymorph of the compound of formula (IR). The novel crystalline form is designated Form A. Different enantiomers have the same physical properties and therefore have the same polymorph. Compound (IS) has the same solid Form A as compound (IR). [Modes for carrying out the invention]

[0006] When compounds (I-R) and (I-S) are present together, it has also been found that they combine to form a complex racemic solid, designated Form RAC. The crystalline Form RAC causes crystal growth in an aqueous suspension. When formulating a compound, such as compound (I-R), it is desirable to limit crystal growth.

[0007] The crystalline polymorph Form A according to the present invention presents optimized handling and processing, especially on a production scale. More specifically, the crystalline polymorph Form A can provide higher purity, easier washing of the solid, or can guarantee a significant improvement in shortening the filtration time.

[0008] More specifically, the crystalline Form A of the compound of formula (I-R) can be characterized by a powder X-ray diffraction pattern represented in terms of 2θ angle and / or d-spacing.

[0009] The crystalline Form A of the compound of formula (I-R) can have a powder X-ray diffraction pattern comprising at least 3 2θ angle values, preferably at least 6 2θ angle values, preferably at least 8 2θ angle values, more preferably at least 10 2θ angle values selected from the group consisting of 7.1±0.2, 7.8±0.2°, 8.9±0.2°, 11.4±0.2°, 13.5±0.2°, 14.2±0.2°, 14.7±0.2°, 16.2±0.2°, 17.7±0.2°, 18.4±0.2°, 20.0±0.2°, 20.8±0.2°, 21.2±0.2°, 21.5±0.2°, 22.3±0.2°, 22.9±0.2°, 23.6±0.2°, 24.0±0.2°, 24.3±0.2°, 25.0±0.2°, 26.2±0.2°, 27.3±0.2°, 27.7±0.2°, 28.6±0.2°, 29.6±0.2°, 30.3±0.2°.

[0010] In a preferred embodiment, the crystalline Form A of the compound of formula (I-R) can have a powder X-ray diffraction pattern comprising at least 3 2θ angle values selected from the group consisting of 7.1 ± 0.2, 7.8 ± 0.2°, 11.4 ± 0.2°, 13.5 ± 0.2°, 14.2 ± 0.2°, 14.7 ± 0.2°, 16.2 ± 0.2°, 17.7 ± 0.2°, 18.4 ± 0.2°, 25.0 ± 0.2°, 26.2 ± 0.2°, preferably at least 6 2θ angle values, preferably at least 8 2θ angle values, more preferably at least 10 2θ angle values.

[0011] More specifically, the crystalline Form A of the compound of formula (I-R) can have a powder X-ray diffraction pattern comprising at least the following 2θ angle values: 7.8 ± 0.2°, 11.4 ± 0.2°, 16.2 ± 0.2°, 17.7 ± 0.2°; preferably at least the following 2θ angle values: 7.1 ± 0.2, 7.8 ± 0.2°, 11.4 ± 0.2°, 13.5 ± 0.2°, 14.2 ± 0.2°, 14.7 ± 0.2°, 16.2 ± 0.2°, 17.7 ± 0.2°, 18.4 ± 0.2°, 25.0 ± 0.2°, 26.2 ± 0.2°; more preferably at least the following 2θ angle values: 7.1 ± 0.2, 7.8 ± 0.2°, 8.9 ± 0.2°, 11.4 ± 0.2°, 13.5 ± 0.2°, 14.2 ± 0.2°, 14.7 ± 0.2°, 16.2 ± 0.2°, 17.7 ± 0.2°, 18.4 ± 0.2°, 20.0 ± 0.2°, 20.8 ± 0.2°, 21.2 ± 0.2°, 21.5 ± 0.2°, 22.3 ± 0.2°, 22.9 ± 0.2°, 23.6 ± 0.2°, 24.0 ± 0.2°, 24.3 ± 0.2°, 25.0 ± 0.2°, 26.2 ± 0.2°, 27.3 ± 0.2°, 27.7 ± 0.2°, 28.6 ± 0.2°, 29.6 ± 0.2°, 30.3 ± 0.2°.

[0012] For example, the crystalline Form A of the compound of formula (IR) has the following crystalline values: 7.1±0.2°, 7.8±0.2°, 8.9±0.2°, 11.4±0.2°, 13.5±0.2°, 14.2±0.2°, 14.7±0.2°, 16.2±0.2°, 17.7±0.2°, 18.4±0.2°, 20.0±0.2°, 20.8±0.2°, 21.2±0.2°, 21.5±0.2°, and 22.3±0.2°. The powder X-ray diffraction pattern includes all 2θ angle values ​​selected from the group consisting of 22.9±0.2°, 23.6±0.2°, 24.0±0.2°, 24.3±0.2°, 25.0±0.2°, 26.2±0.2°, 27.3±0.2°, 27.7±0.2°, 28.6±0.2°, 29.6±0.2°, and 30.3±0.2°. These peak values, along with their corresponding d-interval values, are shown in Table 1 below.

[0013] [Table 1-1]

[0014] [Table 1-2]

[0015] These 2θ angle values ​​are derived from the powder X-ray diffraction patterns of the polymorphs specified in Equation I / Form A, obtained using the method of Example 1. These values ​​are generated using an average wavelength of 1.54056 Å with a 2θ step size of 0.02°.

[0016] The crystalline polymorph (Form A) of the present invention can be characterized by its single crystal unit cell parameters, as shown in Table 2. Polymorph Form A was obtained using the method described in Example 1.

[0017] [Table 2]

[0018] In Table 2, a, b, and c are the lengths of the edges of the unit cell; α, β, and γ are the angles of the unit cell; and Z is the number of molecules per lattice.

[0019] In certain embodiments of the present invention, the crystal polymorph may have the following lattice parameters: a = 12.9 ± 0.1 Å, b = 12.9 Å ± 0.1 Å, c = 21.0 Å ± 0.1 Å, α = 90°, β = 90°, γ = 120°, and volume = 3030 ± 20 Å 3 and can have.

[0020] In another embodiment, the crystal polymorph according to the present invention can have a melting point in the range of 143 to 148 °C (peak position), preferably in the range of 146 to 148 °C (peak position). This melting point is obtained using differential scanning calorimetry (DSC) at a heating rate of 10 °C / min. The variation in the melting point may depend on the enantiomeric purity.

[0021] The crystal polymorph designated as Form A can also be characterized by an IR spectrum represented in terms of IR shift (cm -1 ). Thus, in another embodiment of the present invention, the crystal polymorph has 3246 ± 2 cm -1 , 3077 ± 2 cm -1 , 3030 ± 2 cm -1 , 2983 ± 2 cm -1 , 2960 ± 2 cm -1 , 2946 ± 2 cm -1 , 2925 ± 2 cm -1 , 2866 ± 2 cm -1 , 1629 ± 2 cm -1 , 1608 ± 2 cm -1 , 1560 ± 2 cm -1 , 1495 ± 2 cm -1 , 1466 ± 2 cm -1 , 1451 ± 2 cm -1 , 1415 ± 2 cm -1 , 1374 ± 2 cm -1 , 1343 ± 2 cm -1 , 1318 ± 2 cm -1 , 1300 ± 2 cm -1 , 1280 ± 2 cm -1 , 1248 ± 2 cm -1, 1220±2cm -1 , 1199±2cm -1 , 1163±2cm -1 , 1142±2cm -1 , 1101±2cm -1 , 1076±2cm -1 , 1044±2cm -1 , 986±2cm -1 , 959±2cm -1 , 944±2cm -1 , 927±2cm -1 , 875±2cm -1 , 825±2cm -1 , 781±2cm -1 , 749±2cm -1 , 740±2cm -1 701±2, 648±2cm -1 , 633±2cm -1 , 623±2cm -1 , 606±2cm -1 , 581±2cm -1 , 564±2cm -1 and 543±2cm -1 It has an IR spectrum that includes at least 3, at least 6, at least 9, at least 12, at least 15, or all IR shift values ​​selected from the group consisting of the following.

[0022] Crystalline polymorph Form A of compound (IS) has the same physical properties as crystalline polymorph Form A of compound (IR), such as the same powder X-ray diffraction pattern, the same single crystal unit cell parameters, and the same melting point.

[0023] However, as shown in the examples, the solid FormRAC has a different melting point from that of Form A of compound (IR) and compound (IS).

[0024] In relation to the present invention, a polymorph is a specific crystalline form of a compound that can exist in two or more crystalline forms in the solid state. The crystalline form of a compound contains constituent molecules arranged in an ordered, repeating pattern extending across all three spatial dimensions (in contrast, amorphous solids do not have long-range order within the molecular positions). Different polymorphs of a compound have different arrangements of atoms and / or molecules in their crystalline structure. If the compound is a biologically active compound, such as a fungicide, differences in crystalline structure can result in different polymorphs having different chemical, physical, and biological properties. Properties that may be affected include crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspension properties, dissolution rate, and bioavailability. Therefore, a particular polymorph may possess properties that make it more advantageous in a particular use compared to another polymorph of the same compound: in particular, the physical, chemical, and biological properties listed above can significantly influence the development of manufacturing methods and formulations, especially on a production scale; the ease with which the compound can be combined with other active and formulation components in formulations; and / or the quality and efficacy of plant treatment agents, such as fungicides. It should be noted that it is not possible to predict whether a compound may exist in a solid state as two or more polymorphs, nor is it possible to predict the properties of any of these crystalline forms.

[0025] In particular, the use of specific polymorphs may enable the use of new formulations compared to existing polymorphic / amorphous forms of the compound. This can be advantageous for several reasons. For example, the absence of solvent in suspension concentrates may mean that SC formulations are likely to be less phytotoxic than equivalent EC formulations, so suspension concentrate (SC) formulations may be preferred over emulsion concentrates (EC). However, if the existing form of the compound is not stable in such SC formulations, polymorphic transformation may occur, leading to undesirable crystal growth. Such crystal growth is harmful, as it can lead to, for example, thickening of the formulation, and potentially even solidification of the formulation. The direct consequence may be clogging in sprayers, for example, in the spray nozzles of agricultural sprayers. The use of stable polymorphic forms would overcome these problems.

[0026] Solid-phase assays for the presence of crystals can be carried out by conventional methods known in the art. For example, powder X-ray diffraction is a convenient and routine technique. Other techniques that can be used include differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), infrared spectroscopy, near-infrared spectroscopy, mid-infrared spectroscopy, nuclear magnetic resonance (NMR), gas chromatography, or high-performance liquid chromatography (HPLC). Single-crystal X-ray diffraction is particularly useful for identifying crystal structures.

[0027] Another object of the present invention is a method for preparing a crystalline polymorph (Form A), comprising the following steps: (i) A step of mixing compound IR with an organic solvent such as ethyl acetate to obtain a solution of compound IR. (ii) A step of crystallizing the compound from the solution obtained in step (i) by either evaporating the organic solvent or cooling the solution to obtain a solid. Regarding methods including

[0028] In step (i), the solution may be saturated, meaning that it can no longer dissolve the solute (compound of formula I) in the solvent. Preferably, step (i) is carried out at a temperature below 30°C, more preferably below 25°C.

[0029] A filtration step may follow step (i). The filtration step can help remove all remaining solid particles, such as undissolved solids, crystals, and / or dust. This optional step can limit or prevent nucleation points throughout the preparation method.

[0030] Step (ii) can be advantageously carried out under constant stirring, more preferably under constant gentle stirring. Preferably, step (ii) is carried out by evaporation of the solvent.

[0031] Following step (ii), a suspension filtration step may be performed to isolate the crystals produced in step (ii) from their solvent and use them as solid seed crystals.

[0032] The polymorphs of the present invention can be applied in their original form, but more preferably they are incorporated into a pesticide composition by conventional means. Therefore, a further object of the present invention relates to a pesticide composition comprising a crystalline polymorph as defined in the present invention and at least one agriculturally acceptable carrier or diluent. A pesticide composition comprising the crystalline polymorph of the present invention can be used for the control of plant pathogenic fungi on a number of plant species.

[0033] Furthermore, the compositions of the present invention may contain two or more polymorphs of the present invention. In particular, the compounds of formula IR are more biologically active than the compounds of formula IS. Accordingly, the compositions of the present invention may contain mixtures of compounds IR and IS in the polymorphic forms disclosed herein or in any amount thereto, but they may also be enriched with the compounds of formula IR or polymorphs of the compounds of formula IR. In particular, they may be enriched with the polymorphs designated in Form A. "Enriched" means that the molar ratio of the compounds of formula IR or polymorphs to the total amount of the compounds of formula IR and IS is greater than 50%, for example, at least 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98 or at least 99%. Preferably, the molar ratio of the compounds of formula IR or polymorphs to the total amount of the compounds of formula IR and IS is greater than 90%, more preferably greater than 95%, for example greater than 98%.

[0034] If both compounds of formula (IR) and formula (IS) are present in a composition, they are expected to crystallize and form a complex racemic solid, Form RAC. The remainder of the most abundant enantiomer will either crystallize or remain as the pure enantiomer, Form A. As an example, if a composition contains compounds IR and IS in a ratio of 90:10 IR / IS, the composition will contain 80 mol% Form A and 20 mol% Form RAC after crystallization. Since compounds of formula (IS) and formula (IR) have the same molecular weight, the ratio IR / IS can be seen as both a molar ratio and a weight ratio. Other examples are shown in Table A below.

[0035] [Table 3]

[0036] Another object of the present invention relates to a method for preventing or controlling fungal infections on plants or plant propagation materials, comprising treating the plants or plant propagation materials with the pesticide composition, preferably in a fungicidal amount of the pesticide composition.

[0037] The term "plant" refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits.

[0038] The term “plant propagation material” is understood to mean all reproductive parts of a plant, such as seeds, that can be used for propagation, including asexual plant materials such as cuttings. Plant propagation material may refer to plant seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes, or parts thereof. Germinated plants and seedlings that will be transplanted after germination or emergence from the soil may also be referred to. These seedlings may be protected before transplanting by total or partial treatment by immersion. Plant propagation material may be treated with the composition of the present invention before the material is sown or planted. Alternatively, plant propagation material may be treated with the composition of the present invention during sowing or transplanting. Furthermore, the composition of the present invention may be applied to previously treated propagation material before or during transplanting. The composition of the present invention may be applied during seed sowing. The composition may also be used on plant propagation material derived from cultivated plants in a greenhouse and / or during transplanting.

[0039] More preferably, the plant propagation material is plant seeds. Seed treatment can be performed on seeds before sowing, and the term “seeds before sowing” means seeds at any time from harvesting to sowing in the soil for the purpose of germination and plant growth. Treatment of seeds before sowing does not mean the act of applying the composition to the soil, but would include any application act that targets seeds during the sowing / planting process. The treated plant propagation material of the present invention can be treated in the same way as conventional plant propagation materials. The treated propagation material can be stored, handled, sown and cultivated in the same way as any other pesticide-treated material.

[0040] The pesticide composition of the present invention can be used, for example, to control ascomycetes (e.g., genera Venturia, Podosphaera, Erysiphe, Monilinia, Mycosphaerella, Uncinula, Corynespora, Phyllachora); and imperfect fungi (also known as Deuteromycetes; e.g., genera Botrytis, Helminthosporium, Fusarium, Cercospora, Alternaria, and Pyricularia).

[0041] The pesticide compositions of the present invention are not limited to, but include the following target crops: cereals (wheat, barley, rye, oats, maize (including field corn, popcorn, and sweet corn), rice, sorghum, and related crops); legumes (beans, lentils, peas, soybeans); oil plants (rapeseed, mustard, sunflower); cucumber plants (mallow, cucumber, melon); fiber plants (cotton, flax, hemp, jute); vegetables (spinach, lettuce, asparagus, cabbage, eggplant, onion, pepper, tomato, potato); plantation crops (banana, fruit trees); ornamental plants (flowers, shrubs); as well as climbing plants, bush berries (e.g., blueberries), caneberries, cranberries, and cold-weather grasses (e.g., Kentucky bluegrass (Poa pratensis L.), annual bluegrass (Poa trivialis (Poa Bluegrasses such as trivialis (L.), Poa compressa (L.) and Poa annua (L.); creeping bentgrass (Agrostis palustris (Huds.), colonial bentgrass (Agrostis tenius (Sibth.), velvet bentgrass (Agrostis canina (L.) and Agrostis alba (L.)); and fetus arundinacea (Festuca Festuca arundinacea (Schreb.), broad-leaved fescue (Festuca elatior L.), and fine fescue, such as giant fescue (Festuca rubra L.), chewing fescue (Festuca rubra variety commutata Gaud.), and fescue (Festuca ovina L.).) and hard fescue (Festuca longifolia), etc., grasses of the Poaceae family ((Festuca) L.), as well as perennial ryegrass (Lolium perenne) L. and annual (Italian) ryegrass (Lolium multiflorum) Lam., etc., ryegrass (Lolium L.), and warm-season turfgrasses, such as hybrid and common Bermudagrass, etc., Bermudagrass (Cynodon LCRich); Zoysia grass (Zoysia Willd.), St. Augustine grass (Stenotaphrum secundatum (Walt.) Kuntze); and centipede grass (Eremochloa It is suitable for controlling such diseases in a large number of plants, including but not limited to turfgrass and other plants, including *Ophiuroides* (Munro.) Hack., and on their reproductive materials.

[0042] Furthermore, "crops" should be understood to include those crops that have been conferred resistance to herbicides such as bromoxynil or herbicides of the ALS-, EPSPS-, GS-, HPPD-, and PPO- inhibitor classes. An example of a crop conferred resistance to imidazolinone, such as imazamox, through conventional breeding methods is Clearfield® summer canola. Examples of crops conferred resistance to herbicides through genetic engineering include glyphosate- and glufosinate-resistant maize varieties, which are commercially available under trade names such as RoundupReady®, Herculex I®, and LibertyLink®.

[0043] Crops should also be understood as being either naturally occurring or conferred with resistance to harmful insects. This includes plants transformed using recombinant DNA technology so that one or more selectively acting toxins can be synthesized, for example, known toxins derived from toxin-producing bacteria. Examples of toxins that can be expressed include δ-endotoxin, vegetative insecticidal proteins (Vip), insecticidal proteins from nematode-symbiotic bacteria, and toxins produced by scorpions, arachnids, large wasps (wasp) and fungi.

[0044] An example of a crop modified to express Bacillus thuringiensis toxin is Bt maize KnockOut® (Syngenta Seeds). An example of a crop containing two or more genes encoding insecticide resistance and thus expressing two or more toxins is VipCot® (Syngenta Seeds). Crops or their seed materials can also be resistant to multiple types of pests (so-called superimposed transgenic events produced by genetic modification). For example, a plant may be herbicide resistant and simultaneously express insecticidal proteins, such as Herculex I® (Dow AgroSciences, Pioneer Hi-Bred International).

[0045] In particular, the compositions according to the present invention are especially effective against spotted species; early canker and fungi; Fusarium in cereals; Sclerotinia in vegetables and rapeseed; gray mold in climbing plants; Botrytis cinerea, Monilinia, and Venturia in fruits; and Phyllachora maydis in maize.

[0046] Therefore, the present invention also relates to the use of Form A of compound (IR), or compositions containing the same, for preventing or controlling fungal infections on plants, particularly for preventing or controlling fungal infections caused by Fusarium species in cereals such as wheat, barley, oats, or rye; for preventing or controlling fungal infections caused by Sclerotinia in vegetables or rapeseed; for preventing or controlling gray mold in climbing plants; for preventing or controlling fungal infections caused by Botrytis cinerea, Monilinia, or Venturia species in fruits; and for preventing or controlling fungal infections caused by Phyllachora maydis in maize.

[0047] The composition according to the present invention further includes Botrytis cinerea, species of the genus Cercospora, species of the genus Colletotrichum, Fusarium graminearum, Fusarium moniliforme, Fusarium oxysporum, Fusarium proliferatum, Fusarium solani, Fusarium subglutinans, and Pyricularia oryzae. It is particularly effective against seed-borne and soil-borne diseases such as oryzae and Sclerotinia species, as well as pathogens of cereals such as wheat, barley, rye, or oats; maize; rice; turf; and rapeseed.

[0048] The compositions according to the present invention are further effective against post-harvest diseases of Botrytis cinerea, Colletotrichum musae, Monilinia fructicola, Monilinia fructigena, and Monilinia laxa, and are particularly effective against pathogens of pear-like fruits, such as apples and pears, drupes, such as peaches and plums, and berries, such as strawberries.

[0049] The composition according to the present invention is effective against the following diseases on the following crops: Botrytis cinerea on grapes, strawberries, tomatoes, sunflowers, cereals, vegetables and Botrytis cinerea; Colletotrichum species on fruits and vegetables, such as Colletotrichum acutatum on strawberries; Fusarium species on cereals; Mycosphaerella fijiensis on bananas; Pyricularia oryzae on rice; Sclerotinia species on lawns, lettuce, vegetables and rapeseed, such as Sclerotinia sclerotiorum on rapeseed; Venturia inequaris on apples. It is particularly useful for controlling Venturia species on fruits, such as *Venturia inequalis*, and Monilinia species on fruits.

[0050] The application rate of the pesticide composition of the present invention will depend on the specific type of fungus to be controlled, the required degree of control, and the timing and method of application, and can be easily determined by those skilled in the art. Generally, the composition of the present invention can be applied at an application rate of 0.005 kilograms / hectare (kg / ha) to about 5.0 kg / ha, based on the total amount of active fungicide in the composition. An application rate of about 0.1 kg / ha to about 1.5 kg / ha is preferred, and an application rate of about 0.3 kg / ha to 0.8 kg / ha is particularly preferred.

[0051] In a preferred embodiment, the pesticide composition contains compound IR / compound in a molar ratio of at least 80:20, preferably at least 90:10. It may be applied at a ratio of approximately 100g to 200g of the active ingredient (i.e., compound I-R + compound IS) per hectare to target the pathogens listed in Table B below:

[0052] [Table 4-1]

[0053] [Table 4-2]

[0054] [Table 4-3]

[0055] In practice, the pesticide compositions containing the polymorphs of the present invention are applied as formulations containing various auxiliaries and carriers known or used in the art. Therefore, they can be formulated as granules, wettable powders, emulsifying concentrates, suspension concentrates (including oil dispersions) as powders or powders, flowables, liquids, suspensions or emulsions, suspend-emulsions, or controlled-release forms such as microcapsules. Preferably, the pesticide compositions of the present invention can be formulated as suspension concentrates, suspend-emulsions, emulsion concentrates, or wet granules. These formulations are described in more detail below and may contain as much as about 0.5% to about 95% or more of the active ingredient in polymorph form. The optimal amount will depend on the formulation, application device, and the nature of the plant pathogenic fungus to be controlled.

[0056] Wettable powders are in the form of finely ground particles that disperse easily in water or other liquid carriers. The particles contain the active ingredient held within a solid matrix. Typical solid matrices include Fuller's earth, kaolin clay, silica, and other easily humicable organic or inorganic solids. Wettable powders typically contain about 5% to 95% by weight of the active ingredient plus small amounts of wetting agents, dispersants, or emulsifiers.

[0057] Emulsifying concentrates are homogeneous liquid compositions that are dispersible in water or other liquids and may consist solely of the active compound and a liquid or solid emulsifier, or they may also contain liquid carriers such as xylene, heavy aromatic naphtha, isophorone, and other non-volatile organic solvents. When used, these concentrates are dispersed in water or other liquids and are typically applied as a spray to the area to be treated. The amount of active ingredient by weight may range from about 0.5% to about 95% of the concentrate.

[0058] A suspension concentrate is a formulation in which finely ground solid particles of an active compound are stably suspended therein. The solid particles may be suspended in an aqueous solution or in oil (as an oil dispersion). Such formulations may contain anti-settling agents and dispersants, as well as wetting agents to enhance activity, and may further contain antifoaming agents and crystal growth inhibitors. When used, these concentrates are diluted with water and usually applied as a spray to the area to be treated. The amount of active ingredient by weight may range from about 0.5% to about 95% of the concentrate.

[0059] Granular formulations include both extruded and relatively coarse particles and can be applied undiluted to areas where control of plant pathogenic fungi is required, for example, or dispersed in a spray tank before application. Typical carriers for granular formulations include sand, fuller's soil, attapulgite clay, bentonite clay, montmorillonite clay, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, gypsum, wood flour, crushed corn cobs, crushed peanut shells, sugar, sodium chloride, sodium sulfate, sodium silicate, sodium borate, magnesia, mica, iron oxide, zinc oxide, titanium oxide, antimony oxide, cryolite, gypsum, diatomaceous earth, calcium sulfate, and other organic or inorganic materials that can absorb or coat active compounds. Granular formulations intended for use without dilution typically contain about 5% to 25% by weight of the active ingredient, which may include heavy aromatic naphtha, kerosene and other petroleum fractions, or vegetable oils; and / or thickeners, such as surfactants like dextrin, glue, or synthetic resins. If the granules are to be dispersed in a spray tank before application, the active ingredient content by weight can be increased up to 80%.

[0060] The powder is a free-flowing mixture of the active ingredient and finely ground solids such as talc, clay, powder, and other organic and inorganic solids that act as dispersants and carriers.

[0061] Microcapsules are typically droplets or granules of an active ingredient encapsulated within an inert, porous shell that allows for the controlled release of the encapsulated material into the surroundings. Encapsulated droplets are typically about 1 to 50 microns in diameter. The encapsulated liquid typically constitutes about 50 to 95% of the capsule's weight and may include a solvent in addition to the active compound. Encapsulated granules are generally porous granules having a porous membrane that seals the openings of the granular pores, holding the active species in liquid form inside the granular pores. Granules are typically in the range of 1 millimeter to 1 centimeter (preferably 1 to 2 millimeters) in diameter. Granules are formed by extrusion, agglomeration, or prilling, or they exist naturally. Examples of such materials include vermiculite, sintered clay, kaolin, attapulgite clay, sawdust, and granular carbon. Examples of shell or membrane materials include natural and synthetic rubber, cellulose-based materials, styrene-butadiene copolymers, polyacrylonitrile, polyacrylates, polyesters, polyamides, polyureas, polyurethanes, and starch xanthetes.

[0062] Other useful formulations for agricultural applications include simple solutions of the active ingredient in solvents such as acetone, alkylated naphthalene, xylene, and other organic solvents, in which the active ingredient is completely dissolved at the desired concentration. Pressurized sprayers may also be used, in which the active ingredient is dispersed in a finely pulverized form as a result of evaporation of a low-boiling point dispersible solvent carrier.

[0063] Many of the above formulations contain wetting agents, dispersants, or emulsifiers. Examples include alkyl sulfonates and alkylaryl sulfonates and sulfates and their salts; polyhydric alcohols; polyethoxylated alcohols, esters, and fatty amines. When used, these reagents typically account for 0.1% to 40% by weight of the formulation.

[0064] Suitable agricultural additives and carriers useful for formulating the compositions of the present invention of the above-described formulation types are well known to those skilled in the art. Suitable examples of different classes can be found in the following non-limiting list.

[0065] The liquid carriers that can be used are water and any solvent in which the polymorph is insoluble or has limited solubility, such as toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetate, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol aviate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidinone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-Trichloroethane, 2-Heptanone, Alpha-Pinene, d-Limonene, Ethylene Glycol, Ethylene Glycol Butyl Ether, Ethylene Glycol Methyl Ether, Gamma-Butyrolactone, Glycerol, Glycerol Diacetate, Glycerol Monoacetate, Glycerol Triacetate, Hexadecane, Hexylene Glycol, Isoamyl Acetate, Isobornyl Acetate, Isooctane, Isophorone, Isopropylbenzene, Isopropyl Myristate, Lactic Acid, Laurylamine, Mesityl Oxide, Methoxypropanol, Methyl Isoamyl Ketone, Methyl Isobutyl Ketone, Methyl Laurate, Methyl Octanoate, Methyl Oleate, Methylene Chloride, m-Xylene, n-Hexane, n-Octyl Examples include amines, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol (PEG400), propionic acid, propylene glycol, propylene glycol monomethyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylene sulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, methanol, ethanol, isopropanol, and amyl alcohols, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerin, and other high molecular weight alcohols, as well as N-methyl-2-pyrrolidinone. Water is generally used as a carrier for diluting concentrates.

[0066] Suitable solid carriers include talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselgool, chalk, diatomaceous earth, lime, calcium carbonate, bentonite clay, fuller's earth, cottonseed husks, wheat flour, soybean flour, pumice, wood flour, walnut shell flour, and lignin.

[0067] A wide range of surfactants are advantageous for use in both the liquid and solid compositions, particularly those designed to be diluted with a carrier before application. Surfactants can be anionic, cationic, nonionic, or polymeric and can be used as emulsifiers, wetting agents, suspending agents, or for other purposes. Typical surfactants include alkyl sulfate salts such as diethanolammonium lauryl sulfate; alkylaryl sulfonate salts such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide addition products such as nonylphenol-C sub.18 ethoxylate; alcohol-alkylene oxide addition products such as tridecyl alcohol-C sub.16 ethoxylate; soaps such as sodium stearate; alkylnaphthalene sulfonate salts such as sodium dibutylnaphthalenesulfonate; dialkyl ester salts of sulfosuccinates 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 dialkyl phosphate esters.

[0068] Other additives commonly used in agricultural compositions include crystallization inhibitors, viscosity modifiers, suspending agents, spray droplet regulators, pigments, antioxidants, foaming agents, light-shielding agents, compatibilizers, defoaming agents, metal ion chelating agents, neutralizing and buffering agents, corrosion inhibitors, dyes, odorants, spreading agents, penetration aids, micronutrients, emollients, lubricants, and adhesives.

[0069] Each of the above formulations can be prepared as a package containing a fungicide together with other components of the formulation (diluents, emulsifiers, surfactants, etc.). The formulations can also be prepared by a tank mix method, in which the components are obtained separately and combined at the grower's site.

[0070] These formulations can be applied to areas where control is desired by conventional methods. For example, powders and liquid compositions can be applied using power sprayers, brooms, hand-cranked sprayers, and spray powderers. The formulations can also be applied from an airplane as powders or sprays, or by rope wick application. Both solid and liquid formulations can also be applied to the soil in the habitat of the plants to be treated, allowing the active ingredients to penetrate the plants through the roots. The formulations of the present invention can also be used for powder application on plant propagation materials, providing protection from fungal infections on the plant propagation materials and from plant pathogenic fungi that develop in the soil. Preferably, the active ingredients can be applied to plant propagation materials, in particular to plant propagation materials that should be protected by either impregnating the seeds with a liquid formulation of the fungicide or coating them with a solid formulation. In special cases, other types of application, such as specific treatment of plant cuttings or twigs that serve a propagation role, are also possible.

[0071] Preferably, the pesticide compositions and formulations of the present invention are applied before the onset of disease. The ratio and frequency of use of the formulations will be those conventionally used in the art and will depend on the risk of infestation by fungal pathogens.

[0072] The compositions and formulations of the present invention can also be used in combination with other active ingredients, such as other fungicides, and / or insecticides, and / or acaricides, and / or nematicides, and / or mollusk repellents, and / or biological formulations, and / or plant growth regulators. The use of such mixtures, as well as for controlling weed and / or undesirable plant growth, forms further embodiments of the present invention.

[0073] In preferred embodiments, the pesticide composition may further include at least one additional fungicide and optionally at least one insecticide and / or at least one nematicide.

[0074] When the crystalline polymorph of the present invention is combined with at least one additional fungicide, the following fungicidal mixing partners are available: - Strobilurin fungicides selected from the group consisting of azoxystrobin, dimoxystrobin, fluoxastrobin, kresoximmethyl, metminostrobin, orysastrobin, picoxystrobin, pyraclostrobin, and trifloxystrobin; - Azole fungicides selected from the group consisting of azaconazole, bromconazole, cyproconazole, difenoconazole, diniconazole, diniconazole-M, epoxyconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafole, hexaconazole, imazalil, imibenconazole, ipconazole, metconazole, mycrobutanil, oxoconazole, pefurazoate, penconazole, prochloraz, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triflumizole, triticonazole, diclobutrazol, etaconazole, fluconazole, fluconazole-cis, and quinconazole; - Morpholin fungicides selected from the group consisting of algimorph, dodemorph, fenpropimorph, toridemorph, fenpropidine, spiroxamine, and piperalin; - An anilino-pyrimidine fungicide selected from the group consisting of cyprodinil, mepanipyrim, and pyrimethanil; and / or - Benalaxyl, Benalaxyl-M, Benomyl, Vitertanol, Boscalid, Captan, Carboxyne, Carpropamide, Chlorothalonil, Copper, Cyazofamide, Cymoxanil, Dietofencarb, Dithianone, Famoxadone, Phenamidon, Fenhexamide, Phenoxycarb, Fenpiclonil, Fluazinam, Fludioxonil, Flutolanil, Forpet, Guazatin, Himexazole, Iprodione, Lufenuron, Mancozeb, Metalaxyl, Mefenoxam, Metraphenone A fungicide selected from the group consisting of nuarimol, paclobutrazol, pencyclon, petiopyrad, procymidone, proquinazide, pyroquilon, quinoxyfen, silthiofam, sulfur, thiabendazole, thyram, triazoxide, tricyclazole, isopyrazam, sedaxane, fluxapyroxad, benzovindiflupyr, and 3-(difluoromethyl)-N-methoxy-1-methyl-N-[1-methyl-2-(2,4,6-trichlorophenyl)ethyl]pyrazole-4-carboxamide. It is preferable.

[0075] Although compositions comprising polymorphs of the present invention and other fungicides are expressly disclosed above, those skilled in the art will fully understand that the present invention extends to ternary and further combinations, including the binary mixtures described above.

[0076] To avoid misunderstanding, even if not explicitly stated above, the mixing partner may be in any suitable agriculturally permissible ester or salt form, as described, for example, in The Pesticide Manual, Nineteenth Edition, British Crop Protection Council 2021.

[0077] The present invention is illustrated by the following non-limiting embodiments and figures. [Brief explanation of the drawing]

[0078] [Figure 1]This shows the powder X-ray diffraction pattern of the crystalline polymorph (Form A) according to the present invention. Legend: x axis: 2θ angle (°); y axis: count [Figure 2] The X-ray diffraction patterns of the crystalline polymorph (Form A) according to the present invention, calculated from the unit cell parameters shown in Table 2, are shown. Legend: x-axis: 2θ angle (°); y-axis: count. [Figure 3] The DSC trace of the crystalline polymorph (Form A) according to the present invention is shown. Legend: x axis: temperature (°C); y axis: normalized heat flow (W / g). [Figure 4] This shows the IR spectroscopic trace of the crystalline polymorph (Form A) according to the present invention. Legend: x axis: wavenumber (cm-1); y axis: transmittance (%). [Figure 5] DSC trace of a racemic mixture (Form RAC) is shown. Legend: x-axis: Temperature (°C); y-axis: Normalized heat flow (W / g). [Figure 6] The particle size distribution (logarithmic scale) of the suspension concentrate prepared as described in Example 3, before and after storage, is shown. [Examples]

[0079] Example 1 - Compound Form A of Formula IR 1. Preparation of polymorphs 0.08 g of the compound of formula (IR) was dissolved in ethyl acetate (1 mL) at room temperature (approximately 20°C). The solution was allowed to evaporate for at least 16 hours. Any crystals formed were harvested and analyzed by powder X-ray diffraction (pXRD), differential scanning calorimetry (DSC), and IR spectroscopy.

[0080] 2. Analysis of Polymorphs After preparation according to the methods detailed above, the samples were subjected to analysis by powder X-ray diffraction and / or single-crystal X-ray diffraction and / or differential scanning calorimetry and / or near-infrared spectroscopy and / or mid-infrared spectroscopy.

[0081] Powder X-ray diffraction analysis of solid materials was performed at room temperature (20°C) and relative humidity above approximately 40% using a Malvern Panalytical Empyrean powder diffractometer. The sample was placed in a standard PMMA sample holder and flattened. The sample holder was rotated, and X-rays were collected at 3.5–40°²θ with an incident X-ray of 0.02° step size and a wavelength of 1.5406 Å. Figure 1 shows the powder X-ray diffraction patterns of the crystalline polymorph (Form A) according to the present invention.

[0082] Single-crystal intensity data were collected using a Rigaku Supernova diffractometer with a graphite monochromator and CuKα radiation (α = 1.54056 Å). For data acquisition, the crystals were placed in NVH oil at -173°C. The data were solved using the CRYSTALS software package, and the results are compiled in Table 2 (unit cell parameters). The X-ray diffraction patterns calculated from the unit cell parameters of the crystal polymorph (Form A) are shown in Figure 2.

[0083] DSC was performed using a TA DSC2500, heating from 25 to 200°C at a rate of 1°C / min, using a standard 40 μL aluminum sample holder with a perforated lid (to allow escape of any gases formed during sample heating). The DSC trace of the crystalline polymorph (Form A) according to the present invention is shown in Figure 3. The peak temperature is approximately 146°C, starting at approximately 144°C.

[0084] Infrared (IR) analysis was performed using a Thermo Scientific® Nicolet iS5 FT-IR spectrometer with an iD7 ATR attachment. The analysis was performed over 16 repeated scans at a range of 500–4000 cm². -1 The scan was performed using the specified scan range. A background scan was measured in the absence of the sample before adding 1–10 mg of the sample to the cell. The IR spectroscopic trace of the crystalline polymorph (Form A) is shown in Figure 4.

[0085] Example 2 - Racemic Form RAC 1. Preparation of Form RAC Equal masses of compounds of formulas IR and IS were dissolved in ethyl acetate to prepare the RAC forms, and the solvent was then allowed to evaporate for at least 16 hours. The resulting solids were analyzed by DSC.

[0086] 2. Analysis of Form RAC DSC was performed using a TA DSC2500 heating at a rate of 10°C / min from 25 to 200°C, using a standard 40 μL aluminum sample holder with a perforated lid (to allow escape of any gases formed during sample heating). The DSC trace of the racemic mixture according to the present invention (Form RAC) is shown in Figure 5. The peak temperature is approximately 113°C, starting at approximately 111°C.

[0087] 3. Results of the analysis Crystalline polymorph Form RAC can have melting points in the range of 110–115°C (peak position), such as 111–113°C (peak position). This melting point is obtained using differential scanning calorimetry (DSC) at a heating rate of 1°C / min.

[0088] Example 3 - Formulation Stability Various suspension concentrate formulations (SCs) were prepared and stored under controlled conditions. The formulations contained 10 w / w% of the active ingredient at various enantiomer ratios, as shown in Table 3 below:

[0089] [Table 5]

[0090] Storage condition A: 4 weeks at 40°C Storage conditions B: 4 weeks of cycling at 10°C for 12 hours, followed by 40°C for 12 hours, then an additional 100 weeks at ambient conditions (approximately 20°C). Storage conditions C: 12 weeks of cycling at 10°C for 12 hours, followed by 12 weeks at 40°C, and then an additional 49 weeks at ambient conditions (approximately 20°C).

[0091] Typical suspension concentrate formulations are shown in Table 4 below:

[0092] [Table 6]

[0093] The particle size distribution was measured at the start of storage and after storage under storage conditions A, B, or C. Measurements were performed by static laser diffraction using a Malvern Mastersizer 3000 with a Hydro MV automated liquid sample dispersion unit. The SC sample was diluted in water in the dispersion unit until appropriate obscuration was achieved, and the median volume distribution (d(50)) for each sample was calculated at that point by MIE theoretical calculations. The d(50) results are shown in Table 5 below.

[0094] [Table 7]

[0095] Legend, size distribution, and logarithmic scale for Figure 6: Figure 6A: Initial state = solid line; after storage A = dotted line; after storage B = dashed line for SC1 Figures 6B, 6C, and 6D: Initial state = solid line; after storage C = dashed lines for SC2, SC3, and SC4, respectively.

[0096] This indicates that formulation SC1, which contains only Form RAC, undergoes crystal growth throughout the sample during storage, while SC2, SC3, and SC4, which contain a smaller proportion of Form RAC, show growth in only a smaller proportion of particles during storage.

Claims

1. Formula IR: 【Chemistry 1】 The crystalline polymorphs of the compound are 7.1±0.2°, 7.8±0.2°, 8.9±0.2°, 11.4±0.2°, 13.5±0.2°, 14.2±0.2°, 14.7±0.2°, 16.2±0.2°, 17.7±0.2°, 18.4±0.2°, 20.0±0.2°, 20.8±0.2°, 21.2±0.2°, 21.5±0.2°, and 22.3±0.2°. Crystalline polymorph having a powder X-ray diffraction pattern that includes at least three 2θ angular values ​​selected from the group consisting of °, 22.9±0.2°, 23.6±0.2°, 24.0±0.2°, 24.3±0.2°, 25.0±0.2°, 26.2±0.2°, 27.3±0.2°, 27.7±0.2°, 28.6±0.2°, 29.6±0.2°, and 30.3±0.2°.

2. The crystal polymorph according to claim 1, characterized in that the powder X-ray diffraction pattern includes at least six 2θ angle values ​​selected from the group consisting of 7.1±0.2°, 7.8±0.2°, 11.4±0.2°, 13.5±0.2°, 14.2±0.2°, 14.7±0.2°, 16.2±0.2°, 17.7±0.2°, 18.4±0.2°, 25.0±0.2°, and 26.2±0.2°.

3. The crystalline polymorph according to claim 1 or claim 2, characterized in that the powder X-ray diffraction pattern includes at least the following 2θ angle values: 7.8±0.2°, 11.4±0.2°, 16.2±0.2°, and 17.7±0.2°.

4. The crystalline polymorph according to any one of claims 1 to 3, characterized by having the following lattice parameters. Table 1

5. The crystalline polymorph according to any one of claims 1 to 4, characterized in having a melting point in the range of 143°C to 148°C (peak position), preferably in the range of 146°C to 148°C (peak position).

6. A pesticide composition comprising a crystalline polymorph as claimed in any one of claims 1 to 5 and at least one agriculturally acceptable carrier or diluent.

7. The composition according to claim 6, characterized by comprising at least one further fungicide.

8. The composition according to claim 6 or 7, characterized in that the further fungicide is strobilurin or azole.

9. The composition according to any one of claims 6 to 8, further comprising at least one insecticide and / or at least one nematicidal agent.

10. A method for preventing or controlling fungal infections on plants or plant propagation materials, comprising treating plants or plant propagation materials with a pesticide composition claimed in any one of claims 6 to 9.

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