BRPI0808947A2 - CO-CRYSTAL, PROCESS TO PREPARE THE SAME, FUNGICIDE COMPOSITION, METHOD TO PREVENT / CONTROL FUNGAL INFECTION IN PLANTS, AGRICULTURAL FORMULATION, AND METHOD FOR PROTECTION OF INDUSTRIAL ATTACK - Google Patents

Description

“CO-CRYSTAL, PROCESS FOR PREPARING THE SAME, FUNGICIDE COMPOSITION, METHOD FOR PREVENTING / CONTROLING FUNGAL INFECTION IN PLANTS, AGRICULTURAL FORMULATION, AND METHOD FOR PROTECTION OF INDUSTRIAL MATERIAL”

The present invention relates to novel propiconazole co-crystals, and their use in fungicidal compositions, in particular in agrochemical compositions.

Propiconazole is a triazole group fungicide and is an inhibitor of steroid demethylation (ergosterol biosynthesis). It is a protective and curative systemic foliar fungicide, translocating acropetally into the xylem. In labeled application rates, propiconazole controls numerous diseases caused, for example, by Cochliobolus sativus, Erysiphe graminis, Leptosphaeria nodorum, Puccinia spp., Pyrenophora teres, Pyrenophora tritici-repentis, Rhynchosporium secalis and Septoria spp. in cereals; Mycosphaerella musicola and Mycosphaerella fijiensis var. difformis in bananas; Selerotinia homoeoearpa, Rhizoetonia solani, Pueeinia spp., Erysiphe graminis on the pitch; Rhizoetonia solani, Helminthosporium oryzae and the dirty panicle complex. in rice; Hematea vastatrix in coffee; Cercospora spp. in peanuts; Monilinia spp., Podosphaera spp., Sphaerotheea spp. and Tranzsehelia spp. to stone fruits; and Helminthosporium spp. in corn. Propiconazole is described in The Pestieide Manua The Pesticide Manual The World Compendium Thirteenth Edition; Publisher: C. D. S. Tomlin; The British Crop Protection Council] under the entry number (675).

Depending on the isomeric composition, propiconazole is typically a yellowish, odorless viscous liquid between -10 and 60 ° C. It is known to crystallize at room temperature over long periods of time. In addition, because of the substantial fluctuations in temperature that may occur during processing and storage of agrochemical formulations, propiconazole may follow through melting and recrystallization cycles, leading to generation of large and undesirable particles. Such particles may, for example, block the spray nozzles during application of the product. Furthermore, such melting and recrystallization events mean that it is difficult to maintain the product as a homogeneous formulation, and this can lead to problems during transfer to dilution tanks and ensuring the correct dilution concentration. There is thus a need for new forms of propiconazole which will overcome these 10 problems while still retaining their advantageous fungicidal properties.

Accordingly, the present invention provides novel co-crystalline forms of propiconazole with a higher boiling point than commercially available versions of propiconazole. Suitably, the melting point of the co-crystal, measured as a single differential scanning calorimetry (DSC) melting exotherm, is above 50 ° C and preferably between 80 and 140 ° C. More suitably, the melting point is between 100 and 130 ° C. Most suitably, the melting point is between 125 and 135 ° C.

In particular, the invention provides a co-crystal of

propiconazole with a co-crystal forming compound having at least one functional group selected from hydroxyl (including alcohol and phenol), ketone, carboxylic acid, amide, primary amine, secondary amine, tertiary amine, sp2 amine, diazo, N-heterocyclic ring pyrimidine or pyridine, or with a biphenyl derivative wherein at least one of the ortho, meta or para positions of one or both phenyl rings is independently substituted by a suitable hydrogen bonding functional group selected from -OH, -ROH, -C (O) H, -C (O) R 5, -COOH, -RCOOH, -NH 2, -RNH 2, -NHR ', RNHR', -NR52, -RNR52, -NHOR5, -RNHOR5 where R is an alkylene group or an acyl group [-C (O) R ”-], R 'is an alkyl group and R” is an alkylene group.

Suitable co-crystal forming compounds containing at least one hydroxyl functional group include, but are not limited to, 1-5 hydroxy-2-naphthoic acid, 7-oxo-DHEA, acetohydroxamic acid, allopurinaol, ascorbic acid, chrysin, acid citric acid, D-ribose, galactic acid, genistein, gentisic acid, N-methyl glucamine, glyconic acid, glycosamine, glycaronic acid, glycolic acid, hydroquinone, lactobionic acid, malic acid, mandelic acid, pamoic acid, pyridoxamine, pyridoxine, quercetin, resveratrol, 4-amino salicylic acid, salicylic acid, serine, threonine, TRIS, tyrosine, vitamin K5 and xylitol.

Preferred co-crystal forming compounds which have hydroxyl groups are C4.20 alkane diols such as 1,9-nonane diol and cyclic polyols such as 2,3,5,6-tetrahydrobenzoquinone.

Suitable co-crystal forming compounds containing

at least one carboxylic acid functional group includes, but is not limited to, 1-hydroxy-2-naphthoic acid, 4-aminobenzoic acid, acetic acid, adipic acid, alanine, arginine, ascorbic acid, asparagine, aspartic acid, benzenesulfonic acid, benzoic acid, 2-phenoxybenzoic acid, 2-20 acetoxybenzoic acid, camphoric acid, capric acid, cinnamic acid, citric acid, cysteine, dimethylglycine, formic acid, fumaric acid, galactaric acid, gentisic acid, glycolic acid, glutamic acid, glutamine, glutaric acid, glycine, glycolic acid, hypuric acid, histidine, isoleucine, lactic acid, lactobionic acid, lauric acid, leucine, lysine, 25 maleic acid, malic acid, malonic acid, mandelic acid, methionine, nicotinic acid , orotic acid, oxalic acid, palmitic acid, pamoic acid, phenylalanine, proline, propionic acid, pyroglutamic acid, pi acid carboxylic razin, 4-amino salicylic acid, salicylic acid, sebacic acid, serine, stearic acid, succinic acid, tartaric acid, thiocyanic acid, threonine, trichloroacetic acid, trifluoroacetic acid, tryptophan, tyrosine, valine. Preferred co-crystal forming compounds having carboxylic acid groups are C4-20 alkanoic acids optionally substituted by one to three hydroxyl or amine groups, such as 15-hydroxypentadecanoic acid.

Suitable co-crystal forming compounds containing

at least one amine functional group includes, but is not limited to, 4-aminobenzoic acid, 4-aminopyridine, 4-ethoxyphenyl urea, acetohydroxamic acid, adenine, alanine, allopurinaol, arginine, asparagine, aspartic acid, cyclamic acid, cysteine , dimethylglycine, N-methyl glucamine, 10 glutamic acid, glutamine, glycine, hyperuric acid, histidine, imidazole, isoleucine, leucine, lysine, methionine, phenylalanine, piperazine, procaline, pyridoxamine, saccharin, serine, threonine, TRIS, tryptophan , tyrosine, urea, valine and vitamin K5. Preferred co-crystal forming compounds having amino groups include methyl hydrazinecarboxylate.

Suitable co-crystal forming compounds containing

At least one pyridine group includes, but is not limited to, 4-aminopyridine, nicotinamide, nicotinic acid, pyridoxamine and pyridoxine. Preferred co-crystal forming compounds having pyridine groups are pyridines substituted by one or more alkyl groups, hydroxyl groups or amide groups such as 5-hydroxy-2-methyl pyridine, 2-hydroxy-6-methyl pyridine, nicotinamide and isonicotinamide.

Suitable co-crystal forming compounds containing at least one pyrimidine group include 4- (3H) -pyrimidinone.

Preferably, the hydrogen bonding functional group in the biphenyl derivative is selected from one or more of -OH, -ROH, COOH, -RCOOH, -NH2, -RNH2, -NHR 'and -RNHR'.

Examples of biphenyl derivatives are 4-aminobiphenyl, 2-aminobiphenyl, 4-phenylbenzylamine, 2-amino-4-phenylphenol, 5-phenyl-o-anisidine, 3,3'-diaminobenzidine, o-dianisidine, biphenyl-4-acid carboxylic acid, biphenyl-2-carboxylic acid, 4'-methyl-2-biphenylcarboxylic acid, 4-biphenylacetic acid, 4'-hydroxy-4-biphenylcarboxylic acid, fenbufene, 2-phenylphenol, 4-phenylphenol, 3-phenylphenol, 2- biphenylmethanol, biphenyl-4-methanol, 4,4'-dihydroxybiphenyl, 2,2'-biphenol, 2-phenylhydroquinone, 2-methyl-3-biphenylmethanol, 1-5 (4-biphenylyl) -1-ethanol and 2,2 ' -biphenyldimethanol, Ν, Ν, Ν ', Ν'-tetramethylbenzidine, 2-methyl-3-biphenylmethanol, 1- (4-biphenylyl) -1-ethanol, biphenyl-4-carboxaldehyde, 4-acetyl-biphenyl and 4,4 '-diacetylbiphenyl.

The most preferred biphenyl derivative is 4,4'-dihydroxybiphenyl or 4,4-dihydroxycycloexylidine bisphenol.

In the context of the present invention "alkyl" means a

linear saturated monovalent hydrocarbon radical of one to six carbon atoms, or branched saturated monovalent hydrocarbon radical of three to six carbon atoms, and "alkylene" means a linear saturated divalent hydrocarbon radical of one to six carbon atoms or one radical branched saturated divalent hydrocarbon of three to six carbon atoms. Suitable alkyl groups are, for example, methyl, ethyl, npropyl, z-propyl, β-butyl, sec-butyl, w-butyl, tert-butyl, w-pentyl, nhexyl and the like. Suitably alkylene groups are, for example, methylene, ethylene, propylene, 2-methylpropylene and the like.

A preferred group of co-crystal forming compounds

comprises 1,9-nonane diol, 2,3,5,6-tetrahydroxybenzoquinone, 15-hydroxypentadecanoic acid, 5-hydroxy-2-methylpyridine, 2-hydroxy-6-methylpyridine, nicotinamide, isonicotinamide, 4- (3H) -pyrimidinone methyl hydrazinecarboxylate, 4,4'-dihydroxybiphenyl. or 4,4-dihydroxycycloexylidine bisphenol, and particularly preferred are 2,3,5,6-tetrahydroxybenzoquinone, 5-hydroxy-2-methylpyridine, nicotinamide, isonicotinamide, 4,4'-dihydroxybiphenyl and 4,4-dihydroxycycloexylidine bisphenol

The co-crystalline form of propiconazole and the co-crystal formation compound may be characterized by crystal morphology or by selected peaks of the powder X-ray diffraction pattern expressed in terms of 2 theta angles.

In one embodiment of the invention there is provided a form of propiconazole and 4,4-dihydroxybiphenyl cocrystals, which is characterized by a powder X-ray diffraction pattern expressed in terms of 2 theta angles, in that the powder X-ray diffraction pattern comprises the values of the 2 theta angles listed in Table I. Table 1 shows the 2 theta values, the d spacings, and the relative intensity of the selected peak positions of the diffraction pattern. X-ray powder of 10 µm propiconazole-4,4'-dihydroxybiphenyl co-crystal.

TABLE 1

2Θ (°) Relative Intensity (Â) Spacing 7,689 11,488 100,0 11,513 7,680 85.8 16,964 5,222 60.5 18,618 4,762 66.9 19,178 4,624 62,3 21,008 4,225 60,5 21,357 4,157 60,9 21,923 4,051 83, 2 22,415 3,963 69.5 23,566 3,772 69.2 26,254 3,392 66,5 26,958 3,305 63.6 It has surprisingly been observed that when propiconazole and a co-crystal forming compound are allowed to form co-crystals, the resulting co-crystals give rise to improved properties of propiconazole compared to propiconazole in free form. In particular, co-crystals exhibit substantially higher melting points than propiconazole alone: for example, differential scanning calorimetry results for propiconazole and 4,4'-dihydroxybiphenyl co-crystals showed that co-crystals have a single fusion endotherm 20 at a temperature between 126 and 130 ° C, substantially higher than that observed for propiconazole alone. This increased melting point is important as it has benefits during manufacturing, formulation and storage. In particular, this new solid state of propiconazole, which has a melting point above the temperature range normally associated with processing and storage, will not undergo melting and recrystallization events during its formulation nor will it undergo recrystallization events during processing. storage of both the technical grade material and the formulated material - the technical material and the formulation will therefore retain their homogeneity. In addition, the higher melting point will enable new formulation solids such as suspension concentrates, suspo emulsions and wet granulations to be developed which will lead to potential purity benefits (because of the ability to isolate the solid state). rather than a liquid) as well as improved handling characteristics (eg reduced toxicity). Finally, blends of this new solid state of propiconazole with other active ingredients should exhibit improved stability as the potential melting point depression of the other active ingredients will not be as crucial.

As used herein, "co-crystal" means a crystalline material comprising two or more unique components in a stoichiometric relationship, each containing distinctive physical characteristics such as structure, melting point and melting heat. The co-crystal can be constructed through various molecular recognition modes, including hydrogen bonding, Stacking II (pi), host-host complexation, and Van-Der-Waals interactions. Of the interactions listed above, hydrogen bonding is the dominant interaction in co-crystal formation, whereby a non-covalent bond is formed between a hydrogen bond donor of one of the components and a hydrogen bond acceptor of the one. other. Preferred cocrystals of the present invention are those wherein hydrogen bonding occurs between the cocrystal forming compound and propiconazole.

It is noted that hydrogen bonding may result in several different intermolecular assemblies and, as such, the co-crystals of the present invention may exist in one or more polymeric forms. A polymorphic co5 crystal may contain any ratio of active ingredient to coform, but typically will be in the range of 3: 1 to 1: 3. Since propiconazole has isomerism, a polymorphic form may also contain a different isomeric relationship. This will also be the case when the co-crystal forming compound isomeric. Each polymorphic form 10 may be defined by one or more solid state analytical techniques, including single crystal X-ray diffraction, powder X-ray diffraction, DSC, Raman spectroscopy or Infrared.

As used herein, the term 'propiconazole' refers to (±) -1- [2- (2,4-dichlorophenyl) -4-propyl-1,3-dioxolan-2-ylmethyl] -1 / 7-1 2,4-triazole, its

four stereoisomers (2R, 4S; 2S, 4R; 2R, 4R; 2S, 4S), their diastereomeric pairs and mixtures of the diastereomeric pairs. In particular, "propiconazole" refers to commercially available propiconazole technical material.

Suitably, the ratio of propiconazole to co-crystal forming compounds in the co-crystal is in the range of 3: 1 to 1: 3. More suitably, the ratio of propiconazole to the cocrystal forming compounds in the co-crystal is in the range of 2: 1 to 1: 1. More suitably the ratio of propiconazole to the cocrystal-forming co-crystal compound is approximately 2: 1.

The co-crystals of the present invention are formed by contact

propiconazole with a compound forming the co-crystal. This can be done by (i) grinding two solids together, (ii) melting one or both components and allowing them to recrystallize, (iii) solubilizing propiconazole and adding the co-crystal forming compound, or (iv) solubilization of the co-crystal forming compound and addition of propiconazole. It may also be possible to solubilize propiconazole in the co-crystal forming compound and vice versa. Crystallization is then allowed to occur under suitable conditions. For example, crystallization may require alteration of a property of the solutions, such as pH or temperature, and may require concentration of the solute, usually by removal of the solvent and typically by drying of the solution. Removal of the solvent results in increased propiconazole concentration over time to facilitate crystallization. Once solid phase 10 comprising any crystals is formed, this can be tested as described in this report.

Accordingly, the present invention provides a process for the production of a propiconazole co-crystal and a co-crystal forming compound comprising (a) grinding, heating or contacting the propiconazole of the

solution with the co-crystal forming compound under crystallization conditions to form a solid phase;

(b) isolating the co-crystals comprising propiconazole and the co-crystal forming compound.

The co-crystal forming compound for use in the process of

invention is as defined above. In one embodiment of the process, the biphenyl derivative is 1,9-nonane diol, 2,3,5,6-tetrahydroxybenzoquinone, 15-hydroxypentadecanoic acid, 5-hydroxy-2-methyl pyridine, 2-hydroxy-2- methyl pyridine, nicotinamide, isonicotinamide, 4- (3H) -pyrimidinone, methyl hydrazinecarboxylate, 4,4'-dihydroxybiphenyl or 4,4-dihydroxycyclohexylidine bisphenol.

The solid phase assay for the presence of propiconazole co-crystals and the co-crystal forming compound can be performed 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 co-crystals. This can be done by comparing propiconazole spectra, co-crystal forming compound and putative co-crystals to establish whether or not true crystals have been formed. Other techniques used in an analogous form include differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Raman spectroscopy. Single crystal X-ray diffraction is especially useful in identifying co-crystal structures.

The co-crystals of the invention may be readily incorporated into fungicidal compositions (including agrochemical compositions and compositions for use in protecting industrial materials) by conventional means. Accordingly, the invention also provides a fungicidal composition comprising a propiconazole co-crystal and the co-crystal forming compound, wherein the co-crystal forming compound is as defined above. In another embodiment, the fungicidal composition is an agrochemical composition.

Agrochemical compositions comprising the co-crystals of the present invention may be used for the control of plant pathogenic fungi in various plant species. Accordingly, the invention also provides a method for preventing / controlling fungal infection in plants or plant propagating material comprising treating the plant or plant propagating material with a fungicidally effective amount of an agricultural composition of the invention. By "plant propagating material" is meant seeds of all species (fruits, tubers, 25 bulbs, grains, etc.), seedlings, sprouts and others.

In particular, the agrochemical compositions of the invention may be used to control, for example, Cochliobolus sativus, Erysiphe graminis, Leptosphaeria nodorum, Puecinia spp., Pyrenophora tritiei-repentis, Rhynchosporium seealis, Septoria spp. . difformis, Sclerotinia homoeoearpa, Rhizoctonia solani, Puecinia spp., Erysiphe gramini, Rhizoetonia solani, Helminthosporium oryzae, dirty panicle complex, Cereospora spp., Monilinia spp., Podosphaera spp. and Helminthosporium spp.

The agrochemical compositions of the present invention are suitable for controlling such diseases in various plants and their propagating material, including, but not limited to, the following target crops: cereals [wheat, barley, rye, oats, maize (including field maize, popcorn and sweet corn), rice, sorghum and related crops); sugar beet (sugar beet and fodder beet); legumes (beans, lentils, peas, soybeans); oily plants (rapeseed, mustard, sunflower); cucumbers (squash, cucumbers, melons); fibrous plants (cotton, flax, hemp, jute); vegetables (spinach, lettuce, asparagus, cabbages, 15 carrots, eggplants, onions, pepper, tomatoes, potatoes, sweet pepper, okra); cultivation crops (bananas, fruit trees, rubber trees, nurseries), ornamental (flowers, shrubs, broadleaf and evergreen trees such as conifers); as well as other plants such as vines, berries (such as vaccines), cane, cranberry, peppermint, rhubarb, mint, sugar cane and lawn grasses including, but not limited to, cold season grasses. (for example bluish stalk grasses (Poa L.), such as Kentucky bluish stalk grasses (Poa pratensis L.), crude bluish stalk grasses (Poa trivialis L.), bluish stalk grasses from Canada (Poa compressa L.) and 25 the annual bluish-stalk grasses (Poa annua L.); agrostides (Agrostis L.), such as creeping agrostides (Agrostis palustris Huds.), colonial agrostides {Agrostis tenius Sibth.), velvet agrostides {Agrostis canina L.) and panasco grass {Agrostis alba L.); festuca {Festuca L.), such as the high fescue {Festuca arundinacea Schreb.), the field fescue {Festuca elatior L.) and the thin fescue such as the red creeping fescue (Festuca rubra L.), the chewing feast (Festuca rubra var. commutata Gaud.), lamb fescue (Festuca ovina L.) and fescue dura (Festuca longifolia); and ryegrass (Lolium L.), such as perennial ryegrass (Lolium perenne L.) and annual (Italian) ryegrass 5 (Lolium multiflorum Lam.)] and grams of warm season turf (for example, grass (Cynodon LC Rich), including hybrid and common donkey grass, Zoysiagrasses (Zoysia Willd.), St. Augustine grass [Stenotaphrum secundatum (Walt.) Kuntze], and centipede grass [Eremochloa ophiuroides (Munro.) Hack .)].

In addition, 'crops' should be understood as

including those crops that have been taken pest and pesticide tolerant, including herbicides or herbicide classes, as a result of conventional breeding methods or genetic engineering. Tolerance, for example, to herbicides means reduced susceptibility to damage caused by a particular herbicide compared to conventional crop reproductions. Cultures may be modified or reproduced to be tolerant, for example, to HPPD inhibitors such as mesotrione or EPSPS inhibitors such as glyphosate.

The rate at which the agrochemical composition of the invention is

applied will depend on the particular type of fungus to be controlled, the degree of control required and the timing and method of application. In general, the compositions of the invention may be applied at an application rate of from 0.005 kilogram / hectare (kg / ha) to about 5.0 kg / ha based on the total amount of active propiconazole in the composition. An application rate between about 0.1 kg / ha and about 3.0 kg / ha is preferred, with an application rate between about 0.2 kg / ha and 1 kg / ha being especially preferred.

In practice, agrochemical compositions comprising the co-crystals of the invention are applied as a formulation containing various adjuvants and carriers known or used in the industry. They can thus be formulated as granules, as wettable powders, as emulsifiable concentrates, as suspension concentrates, as powders or powders, as circulable, as solutions, as suspensions or emulsions or suspo-emulsions, or as controlled release forms. , such as microcapsules. Suitably, the agrochemical composition of the invention may be formulated as a suspension concentrate, a suspoemulsion or a wet granulation. These formulations are described in more detail below, and may contain as little as about 0.5% to as much as about 95% or more by weight of the active ingredient in the form of the co-crystal. The optimal amount will depend on the formulation, application equipment and nature of the pathogenic fungi of the plants to be controlled.

Wetting powders are in the form of finely divided particles which readily disperse in water or other liquid carriers. The particles contain the active ingredient retained in a solid matrix. Typical solid matrices include fuller earth, kaolin clays, silicas and other easily moist organic or inorganic solids. Wetting powders usually contain from about 5% to about 95% of active ingredient 20 plus a small amount of wetting, dispersing or emulsifying agent.

Emulsifiable concentrates are homogeneous liquid compositions dispersible in water or other liquid, and may consist entirely of the active compound with a liquid or solid emulsifying agent, or may also contain a liquid carrier such as xylene, heavy aromatic naphtha, isophorone and other organic solvents. non volatile. In use, these concentrates are dispersed in water or other liquid and are usually applied as a spray to the area to be treated. The amount of active ingredient may range from about 0.5% to about 95% of the concentrate.

Suspension concentrates are aqueous formulations in which the finely divided solid particles of the active compound are stably suspended. Such formulations include anti-settling agents and dispersing agents, and may further include an activity enhancing wetting agent as well as an antifoam and a crystal growth inhibitor. In use, these concentrates are diluted with water and are usually applied as a spray to the area to be treated. The amount of active ingredient may range from about 0.5% to about 95% of the concentrate.

Granular formulations include both extruded and relatively coarse particles and are usually applied undiluted to the area where control of plant pathogenic fungi is required. Typical carriers for granular formulations include sand, 15 fuller earth, attapulgite clay, bentonite clays, montmorillonite clay, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, gypsum, sawdust, ground corncobs, ground peanut shells, sugars, sodium chloride, sodium sulfate, sodium silicate, sodium borate, magnesia, mica, iron oxide, 20 zinc oxide, titanium oxide, oxide antimony, cryolite, plaster, diatomaceous earth, calcium sulfate and other organic or inorganic materials which absorb or may be coated with the active compound. Granular formulations typically contain from about 5% to about 25% of active ingredients which may include surface active agents, such as heavy aromatic naphtha, kerosene and other petroleum fractions, or vegetable oils; and / or thickeners such as dextrins, glue or synthetic resins.

Sprinkles are free-circulating mixtures of the active ingredient with finely divided solids such as talc, clays, flour and other organic and inorganic solids that act as dispersants and carriers.

Microcapsules are typically droplets or granules of the active ingredient enclosed in an inert porous shell that allows the enclosed material to escape to the vicinity at controlled rates. The encapsulated droplets are typically about 1 to 50 microns in diameter. The included liquid typically constitutes about 50 to 95% of the weight of the capsule and may include solvent in addition to the active compound. Encapsulated granules are generally porous granules with porous membranes sealing the granule pore openings, retaining the active species in liquid form within the granule pores. The granules typically range from 1 millimeter to 1 centimeter and preferably from 1 to 2 millimeters in diameter. The granules are formed by extrusion, agglomeration or padding, or are naturally occurring. Examples of such materials are vermiculite, sintered clay, kaolin, attapulgite clay, sawdust and granular carbon. Shell or membrane materials include natural and synthetic rubbers, cellulosic materials, styrene-butadiene copolymers, polyacrylonitriles, polyacrylates, polyesters, polyamides, polyureas, polyurethanes and starch xanthates.

Other formulations useful for agrochemical applications include simple active ingredient solutions in a solvent in which it is completely soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene and other organic solvents. Pressurized sprayers, wherein the active ingredient is dispersed in finely divided form as a result of vaporization of a low boiling dispersing solvent carrier, may also be used.

Many of the formulations described above include wetting, dispersing or emulsifying agents. Examples are alkyl and alkylaryl sulfonates and sulfates and their salts, polyhydric alcohols, alcohols, esters and polyethoxylated fatty amines. These agents, when used, typically comprise from 0.1% to 15% by weight of the formulation.

Suitable agricultural adjuvants and carriers which are useful in formulating the compositions of the invention in the types of formulations described above are well known to those skilled in the art.

Suitable examples of the different classes are found in the non-limiting list below.

Liquid carriers that may be employed include water, toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate 10, 2-butanone, chlorobenzene cyclohexane, cyclohexanol , alkyl acetates, diacetonalcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N, N-dimethyl formamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxytol, alkyl pyrrolidinone, ethyl acetate, 2-ethyl hexanol, 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, glyce monoacetate rol, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobomyl acetate, isooctane, isophorone, isopropyl benzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isone methyl ketone, ketone isobutyl, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, amine octyl 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, trichlorethylene, perchlorethylene, ethyl acetate, amyl, butyl acetate, methanol, ethanol, isopropanol, and higher molecular weight alcohols such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol etc., ethylene glycol, propylene glycol, glycine N-methyl-2-pyrrolidinone, and others. Water is generally the carrier of choice for concentrating dilution.

Suitable solid carriers include talc, carbon dioxide and

titanium, pyrophyllite clay, silica, attapulgite clay, kieselguhr. chalk, diatomaceous earth, lime, calcium carbonate, bentonite clay, fuller earth, cottonseed hulls, wheat flour, soy flour, pumice, sawdust, nutshell flour, lignin and others.

A wide range of surface active agents is

It is advantageously employed in both liquid and solid compositions, especially those intended to be carrier diluted prior to application. Surface active agents may be anionic, cationic, nonionic or polymeric in character, and may be employed as emulsifying agents, wetting agents, suspending agents, or for other purposes. Typical surface active agents include alkyl sulfate salts, such as diethanolammonium lauryl sulfate; alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide addition products such as nonylphenol-C.sub 18 20 ethoxylate; alcohol-alkylene oxide addition products such as tridecyl alcohol-C.sub. Ethoxylate; soaps, such as sodium stearate; alkylnaphthalenesulfonate salts, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di (2-ethylexyl) sulfosuccinate; sorbitol esters such as sorbitol oleate; quaternary amines, such as trimethylammonium lauryl 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.

Other adjuvants commonly used in agricultural compositions include crystallization inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, antioxidants, foaming agents, light blocking agents, compatibilizing agents, antifoaming agents, sequestering agents. , neutralizing agents and buffers, corrosion inhibitors, dyes, odorants, spreading agents, penetration aids, micronutrients, emollients, lubricants, adhesives, and others.

In addition, further biocidal active ingredients or compositions may be combined with the agrochemical composition of this invention. For example, the compositions may contain other fungicides, herbicides, insecticides, bactericides, acaricides, nematicides and / or plant growth regulators in order to broaden the spectrum of activity or to reduce the risk of resistance development.

Each of the above formulations can be prepared as

a pack containing the fungicides together with other formulation ingredients (diluents, emulsifiers, surfactants etc.). The formulations may also be prepared by a tank mixing method, wherein the ingredients are obtained separately and combined at the culture site.

These formulations may be applied to areas where the

control is desired by conventional methods. Powder and liquid compositions, for example, may be applied by the use of motor-driven sprayer, broom and hand sprayers and spray atomizers. The formulations may also be applied from airplanes 25 as a powder or spray or by viscous wick applications. Both solid and liquid formulations can also be applied to the soil at the site of the plant to be treated, enabling the active ingredient to penetrate the plant through the roots. The formulations of the invention may also be used to prepare plant propagation material applications to provide protection against background infections in plant propagating material as well as against phytopathogenic fungi that occur in the soil. Suitably, the active ingredient may be applied to the plant propagation material to be protected by impregnating the plant propagation material, in particular seeds, or with a liquid formulation of the fungicide or by covering it with a solid formulation. In special cases, other types of application are also possible, for example the specific treatment of plant seedlings or propagating sprouts.

Suitably, the agrochemical compositions and formulations of the present invention are applied prior to disease development. The rates and frequency and use of the formulations are those conventionally used in the art and will depend on the risk of fungal pathogen infestation.

The compositions of the invention may also be used for the protection of industrial materials. In yet another aspect of the invention, there is thus provided a method for protecting the industrial material against fungal attack, comprising treating the industrial material with a composition containing the co-crystal of the invention. In another aspect, the present invention provides the use of a composition comprising the cocrystal of the invention for the protection of industrial materials. In a particular embodiment, said industrial material is selected from the group consisting of: wood, plastic, plastic-wood composite, paint, paper and wall covering boards.

“Industrial material” includes, but is not limited to, those materials used in construction etc. For example, the industrial material may be structural timber, doors, cupboard, storage units, rugs, particularly natural fiber rugs such as hemp or jute wool and burlap, plastics, wood (including worked wood) and plastic and wood composite.

In a particular embodiment, the industrial material is a coating. "Coating" includes, but is not limited to, compositions applied to a substrate, for example paints, dyes, varnishes, lacquers, base coatings, semi-gloss coatings, gloss coatings, flat coatings, coatings, stain-block coatings, 5 sealers. penetration for porous substrates, concrete and marble, elastomeric coatings, mastics, caulking and sealants, board and panel coatings, transport coatings, furniture and coil coatings, bridge and tank coatings and surface marking paints, coatings and leather treatments, floor protection coatings, paper coatings, personal care coatings such as hair, skin, nails, braided and unbraided fabric coatings and pigment printing pastes, and adhesive coatings such as such as pressure sensitive adhesives and lamination adhesives wet and dry, and plaster.

In the particular embodiment, coating means;

paint, varnish, coloring, lacquer or plaster. In another embodiment, said coating is a lacquer. In a specific embodiment, coating means painting. The paint may comprise, for example, a film former and a carrier (carrier which may be water and / or an organic solvent) and optionally a pigment.

In addition, industrial material includes adhesives, sealants, joint and joint materials, and insulation material. In a particular embodiment, "industrial material" means building timber. In another embodiment, "industrial material" means worked wood. In another embodiment, "industrial material" means plastic.

Plastics include plastic polymers and copolymers, including: acrylonitrile styrene butadiene, butyl rubber, epoxies, fluoropolymers, isoprene, nylon, polyethylene, polyurethane, polypropylene, polyvinyl chloride, polystyrene, polycarbonate, polyvinylidene fluoride, polyacrylate methacrylate, polyacrylate methacrylate , polyurethane, polybutylene, polybutylene terephthalate, polyether sulfone, polyphenylene oxide, polyphenylene ether, polyphenylene sulfide, polyphthalamide, polysulfene, polyester, silicon, styrene butadiene rubber, and polymer combinations. In another embodiment, "industrial material" means polyvinyl chloride (PVC). In another embodiment, "industrial material" means polyurethane (PU). In another embodiment, "industrial material" means plastic and wood composite (WPC). Plastic and wood composite is a material that is well known in the art. A review of the WPCs can be found in the following publication - Craig Clemons - Forrest Products Journal. June 2002 Volume 52. No. 6. pp 10-18.

“Wood” shall be understood to mean wood and wood products, for example derived timber products, cut wood, plywood, chipboard, flake panel, 15 laminated beams, oriented filament log, pressed fiberboard, and particle board, tropical wood, structural wood products, wood beams, railroad sleepers, bridge components, jetties, vehicles made of wood, boxes, vanes, containers, telegraph poles, wood fences, wood liners, windows and doors made of wood, plywood, trim panels, joinery, or wood products which are most commonly used to build houses or roofs, in building joinery or in wood products which are generally used in house building , including prepared wood, construction and carpentry.

“Industrial material” also includes cooling lubricants and heating and cooling systems, ventilation and air conditioning systems, and parts of production plants, for example cooling water circuits.

“Industrial material” also includes wall cladding boards such as plaster-based wall cladding. In yet another aspect of the invention there is provided an industrial material comprising a composition containing a cocrystal of the invention. In a particular embodiment, said industrial materials are selected from the group consisting of wood, plastic, wood and plastic composite, paint, paper and wall boards. In a particular embodiment, said industrial materials comprise wood.

The industrial material may be treated with a composition according to the invention in various ways, including, but not limited to, including the composition in the industrial material itself, absorbing, impregnating, treating (in closed pressure or vacuum systems) said material. with said composition by dipping or impregnating the building material, or applying the building material for example by applying curtain coating, roller, brushing, spraying, atomizing, dusting, dispersing or pouring. The composition of the invention may be formulated for use in treating industrial materials using techniques well known to the skilled person. Such formulations may use, for example, the formulation materials listed above in relation to agrochemical formulations.

The present invention will now be described by means of the following

non-limiting examples and figures.

EXAMPLES

1. Preparation of propiconazole / 4,4'-dihydroxybiphenyl co-crystals

A 2 liter round bottom flask was fitted with a suspended stirrer, thermometer, hopper and condenser. 405.5 g of propiconazole (technical grade) was charged with 400 ml of ethanol. The propiconazole solution was stirred for 30 minutes at 40 ° C until solubilized. 111.76 g of 4,4'-dihydroxybiphenyl were then added. The reaction mixture was heated to 40 ° C. After heating, 4,4'dihydroxybiphenyl dissolves to form a clear solution and crystallization results with the formation of a white precipitate. The reaction mixture was stirred for 1 hour at 40 ° C and was subsequently cooled to 5 ° C. The solids were isolated by filtration in the Buchner apparatus and allowed to air dry.

Figure 1 shows the powder X-ray diffraction patterns of the

(a) technical grading of propiconazole, (b) propiconazole-4,4'dihydroxybiphenyl co-crystal and (c) 4,4'-dihydroxybiphenyl.

Figure 2 shows the Differential Scanning Calorimetry traces of (a) propiconazole-4,4'-dihydroxybiphenyl and (b) 4,4'-dihydroxybiphenyl co-crystal.

Figure 3 shows the Raman spectra of (a) graduation

propiconazole technique, (b) propiconazole-4,4'-dihydroxybiphenyl co-crystal and

(c) 4,4'-dihydroxybiphenyl.

Powder X-ray diffraction analysis clearly shows that the product does not carry any similar to any of its constituent phases, suggesting that a new solid state has been formed.

A differential scanning calorimetry trace of the product has a single melting endotherm at 130 ° C. The constituent phases fuse at 61 ° C for the technical grading of propiconazole, and at 292 ° C for 4,4'-dihydroxybiphenyl.

Stability of propiconazole / 4,4'-dihydroxybiphenyl co-crystals

The following propiconazole / 4,4'-dihydroxybiphenyl co-crystal suspension concentrate was prepared:

TABLE 2

% w / v Co-crystal 38.6 Morwet D425 3.86 Atlox 4913 1.2 Kelzan ASX 0.3 Proxel GXL 0.2 Water remaining The formulation was evaluated after 2 weeks, 1 month and 3 months in various storage programs. accelerated. In all cases, minimal changes were observed in pH, viscosity, particle size and dispersion and suspension characteristics, suggesting that the formulations were physically stable.

Propiconazole / 4,4'-dihydroxybiphenyl co-crystals biological activity The activity of the above formulation was evaluated against

Leptosphaeria spp., Pueeinia spp., Rhynchosporium spp. and Septoria spp. under greenhouse and field conditions compared to commercially available propiconazole formulations. Co-crystal activity against all fungal species was very similar to commercially available forms of propiconazole.

2. Propiconazole-4,4-cyclohexylidene bisphenol co-crystal

Figure 4: Powder X-ray Diffraction Patterns of Propiconazole (a), Propiconazole Co-Crystal - 4,4-Cyclohexylidene Bisphenol (b) and 4,4-Cycloexylidene Bisphenol (c).

Figure 5: DSC traces of Propiconazole (a), Co-Crystal of

Propiconazole - 4,4-Cyclohexylidene Bisphenol (b) and 4,4-Cyclohexylidene Bisphenol (c).

Table 3: 2Θ Values of Selected Peak Positions

X-ray powder diffraction of propiconazole-4,4-cyclohexylidene bisphenol co-crystal.

TABLE 3

PPZ-4,4-CYCLOEXYLIDENE BISPHENOL CO-CRYSTAL

_20_

_6,968_

_13.833_

_15,073_

_15,656_

_17,437_

_18,357_

_21,120_

_21,857_

_22,686_

_24,159_

_25,541_

_26,001_

_27,045_

_27,536_

_28,426_

_29,347_

EXPERIMENTAL To a 1: 2 Co-Crest by evaporative crystallization 2 g of PPZ was added to a 40 ml vial of 5 ml

of Isoexane.

3.14 g of 4,4-Cyclohexylidene bisphenol in 5 ml Ethanol was added to this mixture.

The sample was kept at 50 ° C for 2 hours and then allowed to cool and evaporate before being filtered on a Buchner.

3 Propiconazole-isonicotinamide co-crystal

Figure 6: Powder X-ray Diffraction Patterns of Propiconazole (a), Propiconazole-Isonicotinamide Co-Crystal (b) and Isonicotinamide (c).

Figure 7: DSC traces of Propiconazole (a), Propiconazole - Isonicotinamide Co-Crystal (b) and Isonicotinamide (c).

Table 4: Values 20 of the selected peak positions of the powder X-ray diffraction patterns of propiconazole isonicotinamide co-crystal.

TABLE 4 PPZ-ISOCOTINAMIDE CO-CRYSTAL

_29_

_7,832_

_11.67_

_22,965_

_3,339_

_24,213_

_25,804_

____ 33.23_

EXPERIMENTAL

For a 2: 1 Co-Crystal by cooling crystallization

2 g of PPZ was added to a 40 ml vial of 5 ml

of Isoexane.

1.5 g Isonicotinamide in 5 ml Methanol was added to this mixture.

The sample was kept at 50 ° C for 2 hours, then kept at 40 ° C for one hour, then kept at 30 ° C for one hour, and then finally kept at 20 ° C for one hour before being left overnight in the refrigerator. The product was then isolated in a Buchner.

4 Propiconazole-2,3,5,6-tetrahydroxy-1,4-benzoquinone co-crystal

Figure 8: Powder X-ray Diffraction Patterns of Propiconazole (a), Propiconazole Co-Crystal - 2,3,5,6-Tetrahydroxy-1,4-benzoquinone (b) and 2,3,5 2,6-Tetrahydroxy-1,4-benzoquinone (c).

Figure 9: DSC traces of Propiconazole (a), Propiconazole Co-Crystal - 2,3,5,6-Tetrahydroxy-1,4-benzoquinone (b) and 2,3,5,6-Tetrahydroxy-1 4,4-benzoquinone (c).

Table 5: Values of 29 of the selected peak positions of the propiconazole-2,3,5,6-tetrahydroxy-1,4-benzoquinone co-crystal powder X-ray diffraction patterns.

TABLE 5

PPZ-2,3,5,6-TETRAHYDROXY-1,4-BENZOQUINONE CO-CRYSTAL

_20_

_6,131_

_11,946_

_15,835_

_21.23_

_23.577_

_24,908_

_26,625_

_29,462_

_33,141_

EXPERIMENTAL

For a 1: 2 Co-Crystal by evaporative crystallization

1.286 g of PPZ was added to a 40 ml vial of 5 ml

of acetone.

1.57 g of 2,3,5,6-Tetrahydroxy-1,4-benzoquinone in 5 ml of Methanol was added to this mixture.

The sample was kept at 50 ° C for 2 hours and then allowed to cool and evaporate before being filtered on a Buchner. 5 Propiconazole - 5-hydroxy-2-methylpyridine co-crystal Figure 10: X-ray powder diffraction patterns of Propiconazole (a), Propiconazole - 5-Hydroxy-2-methylpyridine Co-Crystal (b) and 5-Hydroxy-2-methylpyridine (c).

Figure 11: DSC traces of Propiconazole (a), Propiconazole-5-Hydroxy-2-Methylpyridine Co-Crystal (b) and 5-Hydroxy-2-methylpyridine (c).

Table 6: Values of 29 of the selected peak positions of propiconazole-5-hydroxy-2-methylpyridine co-crystal powder X-ray diffraction patterns.

TABLE 6

PPZ-5-HYDROXY-2-Methylpyridine CO-CRYSTAL

_20_

_6,119_

_11,777_

_12.023_

_12,238_

_17,526_

_23,492_

_23.799_

_24.23_

_24,445_

_26,659_

_26,966_

_27.55_

EXPERIMENTAL

For a 2: 1 Co-Crystal by cooling crystallization

2 g of PPZ was added to a 40 ml vial of 5 ml

of xylene.

1.3 g of 5-Hydroxy-2-methylpyridine in 5 ml of Methanol was added to this mixture.

The sample was kept at 50 ° C for 2 hours, then kept at 40 ° C for one hour, then kept at 30 ° C for one hour, and then finally kept at 20 ° C for one hour before being left overnight in the refrigerator. The product was then isolated in a Buchner. 6 Propiconazole - nicotinamide co-crystal

Figure 12: Powder X-ray Diffraction Patterns of Propiconazole (a), Propiconazole-Nicotinamide Co-Crystal (b) and Nicotinamide (c).

Figure 13: DSC traces of Propiconazole (a), Co-Crystal

Propiconazole - Nicotinamide (b) and Nicotinamide (c).

Table 7: Values of 20 of the selected peak positions of the propiconazole nicotinamide co-crystal powder X-ray diffraction patterns.

TABLE 7 PPZ-NICOTINAMIDE CO-CRYSTAL

_2Θ_

_14,875_

_15,499_

_22,608_

_23.024_

_23.509_

_24,029_

_25.52_

_26,179_

_27,843_

_33,495_

_34,605_

EXPERIMENTAL

For a 2: 1 Co-Crystal by cooling crystallization

2 g of PPZ was added to a 40 ml vial with 5 ml of

Acetone.

1.3 g Nicotinamide in 5 ml Ethyl Acetate was added to this mixture.

propiconazole - methyl hydrazine carboxylate

Figure 14: Powder X-ray Diffraction Patterns of Propiconazole (a), Hydrazine Methyl Carboxylate Co-Crystal (b) and Hydrazine Methyl Carboxylate (c).

Table 8: Values of 2Θ from the selected peak positions of the powdered X-ray diffraction patterns of methyl hydrazine propiconazole carboxylate co-crystal.

TABLE 8

HYDRAZINE PPZ-CARBOXYLATE CO-CRYSTAL

_20_

_17,447_

_20.5_

_21,922_

_24,662_

_25,807_

_26,396_

_28,547_

_31.53_

_32,987_

EXPERIMENTAL

For a 1: 2 Co-Crystal by cooling crystallization

0.5 g of PPZ was added to a 40 ml vial with 5 ml of

Acetone.

3.8 g of methyl hydrazino carboxylate in 5 ml of methanol was added to this mixture.

The sample was kept at 50 ° C for 2 hours, then kept at 40 ° C for one hour, then kept at 30 ° C for one hour, and then finally kept at 20 ° C for one hour before being left overnight in the refrigerator. The product was then isolated in a Buchner.

8 Propiconazole Co-Crystal - 4 (3h> pyrimidinone

Figure 15: Powder X-ray Diffraction Patterns of Propiconazole (a), Propiconazole Co-Crystal - 4 (3H) -Pyrimidinone (b) and 4 (3H) -Pyrimidinone (c).

Table 9: 2Θ values of selected peak positions of propiconazole-4 (3H) pyrimidinone co-crystal powder X-ray diffraction patterns. TABLE 9

PPZ-4 (3H) -PYRIMIDINONE CO-CRYSTAL

_29_

_11,922_

_15.85_

_16,997_

_17,761_

_27,632_

_32,325_

EXPERIMENTAL

For a 1: 1 Co-Crystal by evaporative crystallization

0.5 g of PPZ was added to a 40 ml vial with 5 ml of

Acetone.

1.8 g of 4 (3H) -pyrimidinone in 5 ml of Methanol was

added to this mixture.

The sample was kept at 50 ° C for 2 hours and then allowed to cool and evaporate before being filtered on a Buchner.

9 Propiconazole Co-Crystal - 15-Hydroxypenta-Decanoic Acid

Figure 16: Powder X-ray Diffraction Patterns of

Propiconazole (a), Propiconazole Co-Crystal - 15-Hydroxypentadecanoic Acid (b) and 15-Hydroxypentadecanoic Acid (c).

Table 10: 2Θ values of the selected peak positions of the powder X-ray diffraction patterns of propiconazole hydroxypentadecanoic acid co-crystal.

TABLE 10

PPZ-15-HYDROXYPECANIC ACID CO-CRYSTAL

__29_

_16,232_

_18,178_

_33,228_

EXPERIMENTAL

For a 2: 1 Co-Crystal by cooling crystallization

2 g of PPZ was added to a 40 ml vial of 5 ml

of acetone.

1.3 g of 15-hydroxypentadecanoic acid in 5 ml of ethyl acetate was added to this mixture.

The sample was kept at 50 ° C for 2 hours, then kept at 40 ° C for one hour, then kept at 30 ° C for one hour, and then finally kept at 20 ° C for one hour before being left overnight in the refrigerator. The product was then isolated in a Buchner.

10 Propiconazole Co-Crystal - Urea

Figure 17: Powder X-ray Diffraction Patterns of Propiconazole (a), Propiconazole Co-Crystal - Urea (b) and Urea (c).

Table 11: Values of 20 of the selected peak positions of the

powder X-ray diffraction patterns of propiconazole - urea co-crystal.

TABLE 11 PPZ CO-CRYSTAL - UREIA

_2Θ_

_20 / 7_

_2 ^ 6_

_24.0_

_27J_

EXPERIMENTAL

For a 1: 2 Co-Crystal by cooling crystallization

0.5 g PPZ was added to a 40 ml flask with 5 ml Acetone.

2.8 g Urea in 5 ml Isoexane was added to this mixture.

The sample was kept at 50 ° C for 2 hours, then kept

at 40 ° C for one hour, then kept at 30 ° C for one hour, and then finally kept at 20 ° C for one hour before being left overnight in the refrigerator. The product was then isolated in a Buchner.

11 Propiconazole Co-Crystal - 1,9-Nonanediol Acid

Figure 18: Powder X-ray Diffraction Patterns of

Propiconazole (a), Propiconazole - 1,9-Nonanediol Co-Crystal (b) and

1,9-Nonanediol (c).

Table 12: Values of 20 of Selected Peak Positions

of powder X-ray diffraction patterns of propiconazole co-crystal

1,9-nonanediol acid.

PPZ-1,9-NONANODIOL CO-CRYSTAL _10,406_

_10,461_

_13.833_

_15,533_

_17,068_

_20,659_

_24,404_

_27,229_

EXPERIMENTAL

For a 2: 1 Co-Crest by cooling crystallization

2 g of PPZ was added to a 40 ml vial of 5 ml

of Isoexane.

1.9 g 1.9-Nonanediol in 5 ml Ethanol was added to

this mixture.

The sample was kept at 50 ° C for 2 hours and then allowed to cool and evaporate before being filtered on a Buchner.

Propiconazole - 2-hydroxy-6-methyl-pyridine co-crystal Figure 19: Powder X-ray Diffraction Patterns of

Propiconazole (a) from Propiconazole - 2-Hydroxy-6-methylpyridine Co-Crystal

(b) and 2-Hydroxy-6-methylpyridine (c).

Table 13: 2Θ Values of Selected Peak Positions

of X-ray powder diffraction patterns of propiconazole co-crystal - 2-

hydroxy-6-methylpyridine.

~ PPZ-2-HYDROXY-6-Methylpyridine CO-CRYSTAL

_29_

_6,537_

_9,851_

_12,951_

_16,511_

_19,396_

_21,421_

_25,196_

_26,025_

_32,653_

EXPERIMENTAL

For a 1: 2 Co-Crystal by evaporative crystallization

2 g PPZ was added to a 40 ml vial with 5 ml Acetonitrile.

0.7 g of 2-Hydroxy-6-methylpyridine (5% in Ethanol) was added to this mixture.

The sample was kept at 50 ° C for 2 hours and then allowed to cool and evaporate before being filtered on a Buchner.

Although the invention has been described with reference to preferred embodiments and examples thereof, the scope of the present invention is not limited solely to those described embodiments. As will be apparent to those skilled in the art, modifications and adaptations of the invention described above may be made without departing from the spirit and scope of the invention, which is defined and circumscribed by the appended claims. All publications cited herein are hereby incorporated by reference in their entirety for all purposes as if each individual publication were specifically and individually indicated to be incorporated by reference.

Claims (16)

1. Co-crystal, characterized in that it is propiconazole with a co-crystal forming compound which has at least one functional group selected from hydroxyl (including alcohol and phenol), ketone, carboxylic acid, amide, primary amine, amine. secondary, tertiary amine, sp2 amine, diazo, N-heterocyclic ring, pyrimidine or pyridine, or a biphenyl derivative, wherein at least one of the ortho, meta or para positions of one or both phenyl rings is independently substituted by a suitable hydrogen bonding functional group selected from -OH, -ROH, -C (O) H5 -C (O) R ', -COOH, -RCOOH, -NH2, -RNH2, -NHR5, -RNHR', -NR'2, -RNR52, -NHOR ', -RNHOR' where R is an alkylene group or an acyl group [-C (O) R "-], R 'is an alkyl group and R" is an alkylene group . Co-crystal, characterized in that it comprises propiconazole and a phenyl derivative, wherein at least one of the ortho, meta or para positions of one or both of the phenyl rings is independently substituted by a functional bond group. suitable hydrogen selected from -OH, -ROH, -C (O) H, -C (O) R, -COOH, -RCOOH, -NH2, -RNH2, -NHR, -RNHR, -NR2, -RNR2, -NHOR Wherein R is an alkylene group or -C (O) R '-, R' is an alkyl group and R 'is an alkylene group. Co-crystal according to claim 2, characterized in that the hydrogen bonding functional group is selected from -OH, -ROH, -COOH, -RCOOH, -NH2, -RNH2, -NHR 'and - RNHR '. Co-crystal according to Claim 1, characterized in that the co-crystal forming compound is selected from the group comprising 1,9-nonanediol, 2,3,5,6-tetrahydroxybenzoquinone, 15-hydroxypentadecanoic acid , 5-hydroxy-3-methyl pyridine, 2-hydroxy-6-methyl-pyridine, nicotinamide, isonicotinamide, 4- (3H) -pyrimidinone, methyl hydrazinecarboxylate, 4,4'-dihydroxybiphenyl or 4,4-dihydroxy cyclohexylidine bisphenol . Co-crystal according to Claim 4, characterized in that the co-crystal forming compound is 2,3,5,6-tetrahydroxybenzoquinone. Co-crystal according to Claim 4, characterized in that the co-crystal forming compound is 5-hydroxy-2-methyl pyridine. Co-crystal according to Claim 4, characterized in that the co-crystal forming compound is nicotinamide. Co-crystal according to Claim 4, characterized in that the co-crystal forming compound is isonicotinamide. Co-crystal according to Claim 4, characterized in that the co-crystal forming compound is 4,4'-dihydroxybiphenyl. Co-crystal according to Claim 1, characterized in that the co-crystal forming compound is 4,4-dihydroxy cyclohexylidine bisphenol. Process for preparing a co-crystal as defined in any one of claims 1 to 10, characterized in that it comprises: a) grinding, heating or contacting the solution of propiconazole with the co-crystal forming compound under crystallization conditions to form a solid phase; b) isolating the co-crystals containing propiconazole and the co-crystal forming compound. Fungicidal composition, characterized in that it comprises the co-crystal as defined in any one of claims 1 to 10. Composition according to Claim 12, characterized in that it is an agrochemical composition. A method for preventing / controlling fungal infection in plants, comprising treating the plant with a fungicidally effective amount of an agricultural composition as defined in claim 13. Agrochemical formulation, characterized in that it comprises the composition as defined in claim 13, which is a suspension concentrate. Method for the protection of industrial material against fungal attack, characterized in that it comprises treating industrial material with a composition as defined in claim 12.