WO2010038008A2

WO2010038008A2 - Co-crystals

Info

Publication number: WO2010038008A2
Application number: PCT/GB2009/002300
Authority: WO
Inventors: James Owen Forrest; Neil George; Rebecca Claire Burton; Manish Maheshbhai Parmar; Gordon Alastair Bell
Original assignee: Syngenta Ltd
Current assignee: Syngenta Ltd
Priority date: 2008-10-01
Filing date: 2009-09-29
Publication date: 2010-04-08
Anticipated expiration: 2011-04-01
Also published as: GB0817976D0; WO2010038008A3; AR073526A1

Abstract

The present invention relates to co-crystals of cyprodinil or pyrimethanil and a co-crystal forming compound which has at least one functional group selected from methyl, ether, hydroxyl (including alcohol and phenol), thiol, ketone, amide, primary amine, secondary amine, tertiary amine, sp2 amine, nitrile, pyrrole, pyridine, pyrimidine and thiazole.

Description

CO-CRYSTALS

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

Both cyprodinil and pyrimethanil are anilinopyrimidine fungicides and are thought to act by inhibiting the biosynthesis of methionine and the secretion of fungal hydrolytic enzymes. Cyprodinil is used as a foliar fungicide on cereals, grapes, pome fruit, stone fruit, strawberries, vegetables, field crops and ornamentals and as a seed dressing on barley to control a wide range of pathogens such as Tapesia yallundae and T. acuformis, Erysiphe spp., Pyrenophora teres, Rhynchosporium secalis, Botrγtis spp., Alternaria spp., Venturia spp. and Monilinia spp. Pyrimethanil is used to control grey mould {Botrγtis cinerea) on vines, fruit, vegetables and ornamentals and in the control of leaf scab {Venturia inaequalis or V. pinna) on pome fruit. Both are available commercially and are described in The Pesticide Manual" [The Pesticide Manual - A World Compendium; Thirteenth Edition; Editor: C. D. S. Tomlin; The British Crop Protection Council]. Two polymorphic forms of cyprodinil are known to exist, both of which exhibit characteristic, but different, melting ranges: form A exhibits between 70 and 72⁰C and form B between 74 and 76⁰C. The thermodynamic stability of polymorphic forms A and B is enantiotropically related and exhibits a phase transition temperature, which, although sensitive to other conditions, is typically at between 15 and 4O⁰C - certainly within the range of temperature fluctuations that may occur during the processing and storage of agrochemical formulations (typically -1O⁰C and +5O⁰C). Below the phase transition temperature form A is the thermodynamically stable form and above, form B is the thermodynamically stable form. Therefore, under storage conditions a solid state of cyprodinil may undergo transformation by recrystallisation between the two polymorphic forms leading to the generation of large and undesirable particles, which could, for example, block spray nozzles during application of the product. In addition, such recrystallisation events mean that it may be difficult to maintain the product as a homogeneous formulation and this may lead to issues during transfer to dilution tanks and in ensuring the correct concentration on dilution. Accordingly, this behaviour currently limits the formulation of cyprodinil to formats in which cyprodinil is solubilised e.g. emulsion concentrates. Similar issues exist with pyrimethanil, which may also crystallise under normal formulation and storage conditions. In addition, pyrimethanil is a rather volatile compound. These issues make formulation as, for example, a suspension concentrate difficult and restrict the use or pyrimethanil in certain situations. As such, therefore, these issues mean that problems similar to those seen with cyprodinil occur during formulation, storage and application of pyrimethanil. The formation of new solid states of cyprodinil and pyrimethanil which do not exhibit phase transformation within the storage temperature fluctuation window and/or which do not undergo crystallisation on formulation and storage and/or which are less volatile, would enable formulation as solid dispersions (i.e. suspension concentrates, suspo- emulsions and wet granulations) which may have desirable toxicology, controlled release or chemical stability properties.

Accordingly, the present invention provides novel co-crystalline forms of cyprodinil or pyrimethanil with improved properties as compared to the commercially available versions of this fungicide.

In particular, the invention provides a co-crystal of cyprodinil or pyrimethanil with a co-crystal forming compound which has at least one functional group selected from methyl, ether, hydroxyl (including alcohol and phenol), thiol, ketone, amide, primary amine, secondary amine, tertiary amine, sp2 amine, nitrile, pyrrole, pyridine, pyrimidine, thiazole.

Suitable co-crystal forming compounds containing at least one hydroxyl functional group include, but are not limited to, 1,8-octanediol, 2-hydroxybenzonitrile, ethyl maltol and N,N-dimethyllactamide.

Suitable co-crystal forming compounds containing at least one ketone group include, but are not limited to, 5-methylhydantoin, acethydrazide, ethyl maltol, nicotinic hydrazide, propionamide, succinamide and urea.

Suitable co-crystal forming compounds containing at least one amide functional group include, but are not limited to, nicotinic hydrazide, propionamide, urea and N,N- dimethyllactamide.

Suitable co-crystal forming compounds containing at least one amine functional group include, but are not limited to, l,5,7-triazabicyclo[4.4.0]dec-5-ene, 2- aminopyrimidine, 5-methylhydantoin, acethydrazide, nicotinic hydrazide, propionamide, succinamide and urea. Suitable co-crystal forming compounds containing at least one nitrile functional group include, but are not limited to, 2-hydroxybenzonitrile.

Suitable co -crystal forming compounds containing at least one pyrimidine functional group include, but are not limited to, l,5,7-triazabicyclo[4.4.0]dec-5-ene and 2- aminopyrimidine.

More suitably, the present invention provides a co-crystal of cyprodinil with a co- crystal forming compound as defined above.

In one embodiment, the co-crystal of cyprodinil is formed using a co-former selected from the group consisting of l,5,7-triazabicyclo[4.4.0]dec-5-ene, 1,-8-octanediol, 2- aminopyrimidine, 2-hydroxybenzonitrile, 5-methylhydantoin, acethydrazide, ethyl maltol, nicotinic hydrazide, propionamide, succinimide, urea and N,N-dimethyllactamide.

The co-crystalline form of cyprodinil or pyrimethanil and the crystal forming compound may be characterised by a crystal morphology (described in terms of the unit cell) 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 co-crystal form of cyprodinil and l,5,7-triazabicyclo[4.4.0]dec-5-ene. In a further embodiment, the co-crystal form of cyprodinil and l,5,7-triazabicyclo[4.4.0]dec-5-ene is characterised by a powder X-ray diffraction pattern expressed in terms of 20 angles, wherein the powder X-ray diffraction pattern comprises the 20 angle values listed in Table IA. Table IA shows the 20 values of selected peak positions of the powder X-ray diffraction pattern of a cyprodinil-1,5,7- triazabicyclo[4.4.0]dec-5-ene co-crystal obtained using the method of Example I a, as well as the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 1. TABLE IA

In a further embodiment, the co-crystal form of cyprodinil and 1,5,7- triazabicyclo[4.4.0]dec-5-ene is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises at least three 2Θ angle values selected from the group comprising 9.1 ± 0.2, 11.9 ± 0.2, 14.1 ± 0.2, 17.4 ± 0.2, 18.9 ± 0.2, 21.0 ± 0.2 and 25.8 ± 0.2. More preferably, the powder X-ray diffraction pattern comprises all of these 2Θ values. These 2Θ angle values are derived from those peaks of the powder X-ray diffraction pattern ascribable purely to the co-crystal; Table IB comprises these 2Θ values as well as values of further peaks which appear in the powder X-ray diffraction pattern of cyprodinil and/or l,5,7-triazabicyclo[4.4.0]dec-5-ene as well as the co-crystal. In one embodiment, the co-crystal form of cyprodinil and 1,5,7- triazabicyclo[4.4.0]dec-5-ene is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises all the 2Θ angle values listed in Table IB, that is, the powder X-ray diffraction pattern comprises the 20 angle values 6.1 ± 0.2, 9.1 ± 0.2, 9.5 ± 0.2, 11.9 ± 0.2, 14.1 ± 0.2, 17.4 ± 0.2, 18.1 ± 0.2, 18.9 ± 0.2, 19.3 ± 0.2, 21.0 ± 0.2, 21.8 ± 0.2, 22.5 ± 0.2, 23.6 ± 0.2, 24.3 ± 0.2, 24.8 ± 0.2, 25.8 ± 0.2 and 27.0 ± 0.2. All of the peaks are derived from the powder X-ray diffraction pattern of a cyprodinil-l,5,7-triazabicyclo[4.4.0]dec-5-ene co-crystal obtained using the method of Example Ib. Table IB also lists the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 2.

TABLE IB

In one embodiment of the invention, there is provided a co-crystal form of cyprodinil and 1,8-octanediol. In a further embodiment, the co-crystal form of cyprodinil and 1,8- octanediol is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises the 20 angle values (a) or (b) listed in Table 2 A. Table 2 A shows the 2Θ values of selected peak positions of the powder X-ray diffraction pattern of two cyprodinil- 1,8-octanediol co-crystals obtained using the methods of Example Ia and Ic, respectively, as well as the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffrac to grams from which these peak positions are derived are shown in Figures 3 and 4, respectively.

TABLE 2A

In a further embodiment, the co-crystal form of cyprodinil and 1,8-octanediol is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises at least three 2Θ angle values selected from the group comprising 20.1 ± 0.2, 20.5 ± 0.2, 22.7 ± 0.2, 23.6 ± 0.2, 25.6 ± 0.2 and 27.4 ± 0.2. More preferably, the powder X-ray diffraction pattern comprises all of these 2Θ values. These 2Θ angle values are derived from those peaks of the powder X-ray diffraction pattern ascribable purely to the co-crystal; Table 2B comprises these 2Θ values as well as values of further peaks which appear in the powder X-ray diffraction pattern of cyprodinil and/or 1 ,8- octanediol as well as the co-crystal. In one embodiment, the co-crystal form of cyprodinil and 1,8-octanediol is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises all the 2Θ angle values listed in Table 2B, that is, the powder X-ray diffraction pattern comprises the 20 angle values 6.9 ± 0.2, 11.4 ± 0.2, 13.7 ± 0.2, 15.6 ± 0.2, 18.6 ± 0.2, 20.1 ± 0.2, 20.5 ± 0.2, 22.7 ± 0.2, 23.1 ± 0.2, 23.6 ± 0.2, 25.2 ± 0.2, 25.6 ± 0.2, 26.7 ± 0.2, 27.4 ± 0.2, 31.2 ± 0.2 and 32.0 ± 0.2. All of the peaks are derived from the powder X-ray diffraction pattern of a cyprodinil- 1,8 -octanediol co-crystal obtained using the method of Example Ib. Table 2B also lists the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 5. TABLE 2B

In one embodiment of the invention, there is provided a co-crystal form of cyprodinil and 2-aminopyrimidine. In a further embodiment, the co-crystal form of cyprodinil and 2- aminopyrimidine is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises the 2Θ angle values listed in Table 3 A. Table 3 A shows the 2Θ values of selected peak positions of the powder X-ray diffraction pattern of a cyprodinil-2-aminopyrimidine co-crystal obtained using the method of Example Ia, as well as the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 6.

TABLE 3A

In a further embodiment, the co-crystal form of cyprodinil and 2-aminopyrimidine is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises at least three 2Θ angle values selected from the group comprising 4.2 ± 0.2, 12.0 ± 0.2, 12.5 ± 0.2, 13.8 ± 0.2, 17.3 ± 0.2, 20.6 ± 0.2, 22.1 ± 0.2, 24.6 ± 0.2, 25.9 ± 0.2 and 31.9 ± 0.2. More preferably, the powder X-ray diffraction pattern comprises all of these 2Θ values. These 2Θ angle values are derived from those peaks of the powder X-ray diffraction pattern ascribable purely to the co-crystal; Table 3B comprises these 2Θ values as well as values of further peaks which appear in the powder X- ray diffraction pattern of cyprodinil and/or 2-aminopyrirnidine as well as the co-crystal. In one embodiment, the co-crystal form of cyprodinil and 2-aminopyrimidine is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises all the 2Θ angle values listed in Table 3B, that is, the powder X-ray diffraction pattern comprises the 29 angle values 4.2 ± 0.2, 8.3 ± 0.2, 10.2 ± 0.2, 12.0 ± 0.2, 12.5 ± 0.2, 13.8 ± 0.2, 14.6 ± 0.2, 17.3 ± 0.2, 20.6 ± 0.2, 20.9 ± 0.2, 22.1 ± 0.2, 24.2 ± 0.2, 24.6 ± 0.2, 25.2 ± 0.2, 25.9 ± 0.2, 29.4 ± 0.2 and 31.9 ± 0.2. AU of the peaks are derived from the powder X-ray diffraction pattern of a cyprodinil-2-aminopyrimidine co- crystal obtained using the method of Example Ib. Table 3B also lists the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 7.

TABLE 3B

In one embodiment of the invention, there is provided a co-crystal form of cyprodinil and 2-hydroxybenzonitrile. In a further embodiment, the co-crystal form of cyprodinil and 2-hydroxybenzonitrile is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises the 2Θ angle values listed in Table 4A. Table 4A shows the 20 values of selected peak positions of the powder X-ray diffraction pattern of a cyprodinil-2-hydroxybenzonitrile co-crystal obtained using the method of Example Ia, as well as the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 8.

TABLE 4A

In a further embodiment, the co-crystal form of cyprodinil and 2-hydroxybenzonitrile is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises at least three 2Θ angle values selected from the group comprising 14.4 ± 0.2, 17.5 ± 0.2, 21.6 ± 0.2, 22.9 ± 0.2, 26.7 ± 0.2 and 30.8 ± 0.2. More preferably, the powder X-ray diffraction pattern comprises all of these 2Θ values. These 2θ angle values are derived from those peaks of the powder X-ray diffraction pattern ascribable purely to the co-crystal; Table 4B comprises these 2Θ values as well as values of further peaks which appear in the powder X-ray diffraction pattern of cyprodinil and/or 2-hydroxybenzonitrile as well as the co-crystal. In one embodiment, the co-crystal form of cyprodinil and 2-hydroxybenzonitrile is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises all the 20 angle values listed in Table 4B, that is, the powder X-ray diffraction pattern comprises the 20 angle values 6.8 ± 0.2, 11.3 ± 0.2, 13.4 ± 0.2, 14.4 ± 0.2, 15.1 ± 0.2, 15.5 ± 0.2, 16.8 ± 0.2, 17.5 ± 0.2, 18.6 ± 0.2, 19.5 ± 0.2, 20.3 ± 0.2, 21.6 ± 0.2, 22.6 ± 0.2, 22.9 ± 0.2, 25.2 ± 0.2, 26.7 ± 0.2, 30.8 ± 0.2 and 32.1 ± 0.2. All of the peaks are derived from the powder X-ray diffraction pattern of a cyprodinil-2-hydroxybenzonitrile co- crystal obtained using the method of Example Ie. Table 4B also lists the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 9.

TABLE 4B

In one embodiment of the invention, there is provided a co-crystal form of cyprodinil and 5-methylhydantoin. In a further embodiment, the co-crystal form of cyprodinil and 5- methylhydantoin is characterised by a powder X-ray diffraction pattern expressed in terms of 20 angles, wherein the powder X-ray diffraction pattern comprises the 20 angle values listed in Table 5 A. Table 5 A shows the 20 values of selected peak positions of the powder X-ray diffraction pattern of a cyprodinil-5-methylhydantoin co-crystal obtained using the method of Example Ia as well as the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 10. TABLE 5A

In a further embodiment, the co-crystal form of cyprodinil and 5-methylhydantoin is characterised by a powder X-ray diffraction pattern expressed in terms of 20 angles, wherein the powder X-ray diffraction pattern comprises at least three 20 angle values selected from the group comprising 4.5 ± 0.2, 8.9 ± 0.2, 9.9 ± 0.2, 10.7 ± 0.2, 11.7 ± 0.2, 17.8 ± 0.2, 22.1 ± 0.2 and 24.7 ± 0.2. More preferably, the powder X-ray diffraction pattern comprises all of these 20 values. These 2Θ angle values are derived from those peaks of the powder X-ray diffraction pattern ascribable purely to the co-crystal; Table 5B comprises these 2Θ values as well as values of further peaks which appear in the powder X-ray diffraction pattern of cyprodinil and/or 5-methylhydantoin as well as the co-crystal. In one embodiment, the co- crystal form of cyprodinil and 5-methylhydantoin is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises all the 2θ angle values listed in Table 5B, that is, the powder X-ray diffraction pattern comprises the 20 angle values 4.5 ± 0.2, 8.9 ± 0.2, 9.9 ± 0.2, 10.7 ± 0.2, 11.7 ± 0.2, 13.3 ± 0.2, 17.8 ± 0.2, 18.3 ± 0.2, 19.5 ± 0.2, 20.0 ± 0.2, 20.2 ± 0.2, 22.1 ± 0.2, 24.3 ± 0.2, 24.7 ± 0.2, 25.5 ± 0.2, 26.7 ± 0.2, 31.3 ± 0.2 and 32.9 ± 0.2. All of the peaks are derived from the powder X-ray diffraction pattern of a cyprodinil-5-methylhydantoin co- crystal obtained using the method of Example Ib. Table 5B also lists the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 11. TABLE 5B

In one embodiment of the invention, there is provided a co-crystal form of cyprodinil and acethydrazide. In a further embodiment, the co-crystal form of cyprodinil and acethydrazide is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises the 2Θ angle values listed in Table 6A. Table 6A shows the 2Θ values of selected peak positions of the powder X-ray diffraction pattern of a cyprodinil-acethydrazide co-crystal obtained using the method of Example Ia as well as the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 12.

TABLE 6A

In a further embodiment, the co-crystal form of cyprodinil and acethydrazide is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises at least three 2Θ angle values selected from the group comprising 7.2 ± 0.2, 14.2 ± 0.2, 25.6 ± 0.2, 26.6 ± 0.2 and 28.6 ± 0.2. More preferably, the powder X-ray diffraction pattern comprises all of these 2Θ values. These 20 angle values are derived from those peaks of the powder X-ray diffraction pattern ascribable purely to the co-crystal; Table 6B comprises these 2Θ values as well as values of further peaks which appear in the powder X-ray diffraction pattern of cyprodinil and/or acethydrazide as well as the co-crystal. In one embodiment, the co-crystal form of cyprodinil and acethydrazide is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises all the 2Θ angle values listed in Table 6B, that is, the powder X-ray diffraction pattern comprises the 20 angle values 7.2 ± 0.2, 14.2 ± 0.2, 15.6 ± 0.2, 24.3 ± 0.2, 25.6 ± 0.2, 26.6 ± 0.2, 28.6 ± 0.2, 29.1 ± 0.2 and 31.9 ± 0.2. All of the peaks are derived from the powder X-ray diffraction pattern of a cyprodinil-acethydrazide co-crystal obtained using the method of Example Ib. Table 6B also lists the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 13. TABLE 6B

In one embodiment of the invention, there is provided a co-crystal form of cyprodinil and ethyl maltol. In a further embodiment, the co-crystal form of cyprodinil and ethyl maltol is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises the 2Θ angle values listed in Table 7A. Table 7A shows the 2θ values of selected peak positions of the powder X-ray diffraction pattern of a cyprodinil-ethyl maltol co-crystal obtained using the method of Example Ia as well as the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 14.

TABLE 7A

In a further embodiment, the co-crystal form of cyprodinil and ethyl maltol is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises at least three 2Θ angle values selected from the group comprising 4.1 ± 0.2, 7.9 ± 0.2, 10.8 ± 0.2, 11.9 ± 0.2, 13.4 ± 0.2, 15.2 ± 0.2, 21.8 ± 0.2, 23.9 ± 0.2, 30.9 ± 0.2 and 31.8 ± 0.2. More preferably, the powder X-ray diffraction pattern comprises all of these 2Θ values. These 2Θ angle values are derived from those peaks of the powder X-ray diffraction pattern ascribable purely to the co-crystal; Table 7B comprises these 2Θ values as well as values of further peaks which appear in the powder X- ray diffraction pattern of cyprodinil and/or ethyl maltol as well as the co-crystal. In one embodiment, the co-crystal form of cyprodinil and ethyl maltol is characterised by a powder X-ray diffraction pattern expressed in terms of 2θ angles, wherein the powder X-ray diffraction pattern comprises all the 20 angle values listed in Table 7B, that is, the powder X- ray diffraction pattern comprises the 2Θ angle values 4.1 ± 0.2, 7.9 ± 0.2, 10.8 ± 0.2, 11.9 ± 0.2, 13.4 ± 0.2, 15.2 ± 0.2, 15.8 ± 0.2, 17.6 ± 0.2, 18.4 ± 0.2, 20.0 ± 0.2, 20.8 ± 0.2, 21.8 ± 0.2, 22.8 ± 0.2, 23.9 ± 0.2, 25.0 ± 0.2, 25.7 ± 0.2, 27.0 ± 0.2, 28.6 ± 0.2, 30.2 ± 0.2, 30.9 ± 0.2, 31.3 ± 0.2 and 31.8 ± 0.2. All of the peaks are derived from the powder X-ray diffraction pattern of a cyprodinil-ethyl maltol co-crystal obtained using the method of Example Ib. Table 7B also lists the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 15.

TABLE 7B

In one embodiment of the invention, there is provided a co-crystal form of cyprodinil and nicotinic hydrazide. In a further embodiment, the co-crystal form of cyprodinil and nicotinic hydrazide is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises the 2Θ angle values listed in Table 8 A. Table 8 A shows the 2θ values of selected peak positions of the powder X- ray diffraction pattern of a cyprodinil-nicotinic hydrazide co-crystal obtained using the method of Example Ic as well as the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 16.

TABLE 8A

In a further embodiment, the co-crystal form of cyprodinil and nicotinic hydrazide is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises at least three 2Θ angle values selected from the group comprising 5.1 ± 0.2, 9.9 ± 0.2, 17.0 ± 0.2, 18.9 ± 0.2, 19.9 ± 0.2, 25.1 ± 0.2 and 29.9 ± 0.2. More preferably, the powder X-ray diffraction pattern comprises all of these 2Θ values. These 2Θ angle values are derived from those peaks of the powder X-ray diffraction pattern ascribable purely to the co-crystal; Table 8B comprises these 2θ values as well as values of further peaks which appear in the powder X-ray diffraction pattern of cyprodinil and/or nicotinic hydrazide as well as the co-crystal. In one embodiment, the co-crystal form of cyprodinil and nicotinic hydrazide is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises all the 2Θ angle values listed in Table 8B, that is, the powder X-ray diffraction pattern comprises the 20 angle values 5.1 ± 0.2, 7.0 ± 0.2, 9.9 ± 0.2, 11.3 ± 0.2, 14.2 ± 0.2, 17.0 ± 0.2, 18.9 ± 0.2, 19.9 ± 0.2, 22.5 ± 0.2, 24.0 ± 0.2, 25.1 ± 0.2, 27.0 ± 0.2, 28.3 ± 0.2 and 29.9 ± 0.2. All of the peaks are derived from the powder X-ray diffraction pattern of a cyprodinil-nicotinic hydrazide co-crystal obtained using the method of Example Id. Table 8B also lists the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 17.

TABLE 8B

In one embodiment of the invention, there is provided a co-crystal form of cyprodinil and propionamide. In a further embodiment, the co-crystal form of cyprodinil and propionamide is characterised by a powder X-ray diffraction pattern expressed in terms of 20 angles, wherein the powder X-ray diffraction pattern comprises the 20 angle values listed in Table 9 A. Table 9 A shows the 20 values of selected peak positions of the powder X-ray diffraction pattern of a cyprodinil-propionamide co-crystal obtained using the method of Example Ia as well as the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 18. TABLE 9A

In a further embodiment, the co-crystal form of cyprodinil and propionamide is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises at least three 2Θ angle values selected from the group comprising 4.9 ± 0.2, 9.6 ± 0.2, 11.9 ± 0.2, 13.4 ± 0.2, 14.4 ± 0.2 and 21.2 ± 0.2. More preferably, the powder X-ray diffraction pattern comprises all of these 2Θ values. These 2Θ angle values are derived from those peaks of the powder X-ray diffraction pattern ascribable purely to the co-crystal; Table 9B comprises these 2Θ values as well as values of further peaks which appear in the powder X-ray diffraction pattern of cyprodinil and/or propionamide as well as the co-crystal. In one embodiment, the co-crystal form of cyprodinil and propionamide is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises all the 2Θ angle values listed in Table 9B, that is, the powder X-ray diffraction pattern comprises the 2Θ angle values 4.9 ± 0.2, 6.7 ± 0.2, 9.6 ± 0.2, 10.2 ± 0.2, 10.7 ± 0.2, 11.9 ± 0.2, 13.4 ± 0.2, 14.4 ± 0.2, 15.8 ± 0.2, 20.5 ± 0.2, 21.2 ± 0.2, 22.6 ± 0.2, 24.9 ± 0.2, 25.9 ± 0.2 and 26.5 ± 0.2. All of the peaks are derived from the powder X-ray diffraction pattern of a cyprodinil- propionamide co-crystal obtained using the method of Example Ib. Table 9B also lists the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 19.

TABLE 9B

In one embodiment of the invention, there is provided a co-crystal form of cyprodinil and succinamide. In a further embodiment, the co-crystal form of cyprodinil and succinamide is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises the 2Θ angle values listed in Table 1OA. Table 1OA shows the 2Θ values of selected peak positions of the powder X-ray diffraction pattern of a cyprodinil-succinamide co-crystal obtained using the method of Example Ia as well as the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 20.

TABLE 1OA

In a further embodiment, the co-crystal form of cyprodinil and succinamide is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises at least three 2Θ angle values selected from the group comprising 6.4 ± 0.2, 9.8 ± 0.2, 12.8 ± 0.2, 17.5 ± 0.2, 19.2 ± 0.2, 20.1 ± 0.2, 21.4 ± 0.2, 23.8 ± 0.2 and 28.6 ± 0.2. More preferably, the powder X-ray diffraction pattern comprises all of these 20 values. These 20 angle values are derived from those peaks of the powder X-ray diffraction pattern ascribable purely to the co-crystal; Table 1OB comprises these 20 values as well as values of further peaks which appear in the powder X-ray diffraction pattern of cyprodiiiil and/or succinamide as well as the co-crystal. In one embodiment, the co-crystal form of cyprodinil and succinamide is characterised by a powder X-ray diffraction pattern expressed in terms of 2θ angles, wherein the powder X-ray diffraction pattern comprises all the 2Θ angle values listed in Table 1OB, that is, the powder X-ray diffraction pattern comprises the 20 angle values 6.4 ± 0.2, 9.8 ± 0.2, 12.8 ± 0.2, 13.2 ± 0.2, 15.0 ± 0.2, 17.1 ± 0.2, 17.5 ± 0.2, 19.2 ± 0.2, 20.1 ± 0.2, 20.6 ± 0.2, 21.4 ± 0.2, 23.0 ± 0.2, 23.8 ± 0.2, 24.3 ± 0.2, 24.9 ± 0.2, 26.2 ± 0.2, 27.2 ± 0.2, 28.6 ± 0.2. All of the peaks are derived from the powder X-ray diffraction pattern of a cyprodinil-succinamide co-crystal obtained using the method of Example Ib. Table 1OB also lists the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 21.

TABLE 1OB

In one embodiment of the invention, there is provided a co-crystal form of cyprodinil and urea. In a further embodiment, the co-crystal form of cyprodinil and urea is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises the 2Θ angle values listed in Table 1 IA. Table 1 IA shows the 2Θ values of selected peak positions of the powder X-ray diffraction pattern of a cyprodinil-urea co-crystal obtained using the method of Example Ic as well as the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 22.

TABLE I lA

In a further embodiment, the co-crystal form of cyprodinil and urea is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises at least three 2Θ angle values selected from the group comprising 4.9 ± 0.2, 9.7 ± 0.2, 13.8 ± 0.2, 16.2 ± 0.2, 16.8 ± 0.2, 17.8 ± 0.2 and 21.3 ± 0.2. More preferably, the powder X-ray diffraction pattern comprises all of these 2Θ values. These 2Θ angle values are derived from those peaks of the powder X-ray diffraction pattern ascribable purely to the co-crystal; Table 1 IB comprises these 2Θ values as well as values of further peaks which appear in the powder X-ray diffraction pattern of cyprodinil and/or urea as well as the co-crystal. In one embodiment, the co-crystal form of cyprodinil and urea is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises all the 2Θ angle values listed in Table 1 IB, that is, the powder X-ray diffraction pattern comprises the 2Θ angle values 4.9 ± 0.2, 6.9 ± 0.2, 9.7 ± 0.2, 10.2 ± 0.2, 13.8 ± 0.2, 14.7 ± 0.2, 16.2 ± 0.2, 16.8 ± 0.2, 17.8 ± 0.2, 18.8 ± 0.2, 19.6 ± 0.2, 21.3 ± 0.2, 22.3 ± 0.2, 23.3 ± 0.2, 24.3 ± 0.2, 24.6 ± 0.2, 25.3 ± 0.2, 29.4 ± 0.2 and 31.7 ± 0.2. All of the peaks are derived from the powder X-ray diffraction pattern of a cyprodinil-urea co-crystal obtained using the method of Example Ib. Table 1 IB also lists the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 23.

TABLE I lB

In one embodiment of the invention, there is provided a co-crystal form of cyprodinil and N,N-dimethyllactamide. In a further embodiment, the co-crystal form of cyprodinil and N,N-dimethyllactamide is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises at least three 2Θ angle values selected from the group comprising 8.6 ± 0.2, 14.4 ± 0.2, 17.5 ± 0.2, 21.2 ± 0.2, 23.8 ± 0.2, 25.2 ± 0.2 and 31.9 ± 0.2. More preferably, the powder X-ray diffraction pattern comprises all of these 2Θ values. These 2Θ angle values are derived from those peaks of the powder X-ray diffraction pattern ascribable purely to the co-crystal; Table 12 comprises these 2Θ values as well as values of further peaks which appear in the powder X-ray diffraction pattern of cyprodinil and/or N,N-dimethyllactamide as well as the co-crystal. In one embodiment, the co-crystal form of cyprodinil and N,N-dimethyllactamide is characterised by a powder X-ray diffraction pattern expressed in terms of 2Θ angles, wherein the powder X-ray diffraction pattern comprises all the 2Θ angle values listed in Table 12, that is, the powder X-ray diffraction pattern comprises the 2Θ angle values 8.6 ± 0.2, 14.4 ± 0.2, 15.8 ± 0.2, 17.5 ± 0.2, 18.2 ± 0.2, 19.5 ± 0.2, 21.2 ± 0.2, 22.4 ± 0.2, 22.9 ± 0.2 and 23.8 ± 0.2. All of the peaks are derived from the powder X-ray diffraction pattern of a cyprodinil- N,N-dimethyllactamide co-crystal obtained using the method of Example 2. Table 12 also lists the intensity of these peaks (strong (S), medium (M) or weak (W)). The diffractogram from which these peak positions are derived is shown in Figure 24.

TABLE 12

As used herein 'co-crystal' means a crystalline material which comprises two or more unique components in a stoichiometric ratio each containing distinctive physical characteristics such as structure, melting point and heat of fusion. As used herein, a co- crystal is distinct from a crystalline salt as it consists of neutral components and not charged components as would be found in a salt. The co-crystal can be constructed through several modes of molecular recognition including hydrogen-bonding, II (pi)-stacking, guest-host complexation and Van-Der-Waals interactions. Of the interactions listed above, hydrogen- bonding is the dominant interaction in the formation of the co-crystal, whereby a non- covalent bond is formed between a hydrogen bond donor of one of the moieties and a hydrogen bond acceptor of the other. Preferred co-crystals of the present invention are those where hydrogen bonding occurs between the co-crystal forming compound and the cyprodinil or pyrimethanil. It is noted that, where a co-former has more than one functional group capable of forming, for example, hydrogen bonds, multi-point contacts may be formed in the crystal. For example, two molecules of cyprodinil may form contacts with different functional groups on the same co-former, or, indeed, there may be multi -point contacts between a single molecule of cyprodinil and a single co-former molecule.

It is noted that hydrogen bonding can result in several different intermolecular assemblies and, as such, the co-crystals of the present invention may exist in one or more polymorphic forms. A polymorphic co-crystal may contain any molar ratio of cyprodinil to co-former, but typically will be in the range of 5:1 to 1:5. In systems where the cyprodinil or the co-former exhibit isomerism, a polymorphic form may also contain a different isomeric ratio. Each polymorphic form can be defined by one or more solid state analytical techniques including single crystal X-ray diffraction, powder X-ray diffraction, DSC, Raman or Infra-red spectroscopy. In Table 2, above, multiple and differing diffraction traces and, consequently, 2Θ values, for co-crystals of cyprodinil and a specific co-former suggest that these co-crystals may exist in a number of polymorphic forms.

Suitably, the molar ratio of cyprodinil or pyrimethanil to co-crystal forming compound in the co-crystal is in the range of from 5:1 to 1:5. More suitably, the ratio of cyprodinil or pyrimethanil to co-crystal forming compound in the co-crystal is in the range of from 3:1 to 1 :3. Even more suitably, the ratio of cyprodinil or pyrimethanil to co-crystal forming compound is in the range of 2:1 to 1 :1.

The co-crystals of the present invention are formed by contacting the cyprodinil or pyrimethanil with the co-crystal forming compound. This may be done by (i) grinding two solids together, (ii) melting, or partially melting, one or both components and allowing them to recrystallise, (iii) solubilising, or partially solubilising, the cyprodinil or pyrimethanil and adding the co-crystal forming compound or (iv) solubilising, or partially solubilising, the co- crystal forming compound and adding the cyprodinil or pyrimethanil. It may also be possible to solubilise, or partially solubilise, the cyprodinil or pyrimethanil in the co-crystal forming compound and vice versa. Crystallisation is then allowed to occur under suitable conditions. For example, crystallisation may require alteration of a property of the solutions, such as pH or temperature and may require concentration of solute, usually by removal of the solvent and typically by drying the solution. Solvent removal results in the concentration of cyprodinil or pyrimethanil increasing over time so as to facilitate crystallisation. In some cases, microwave irradiation and/or sonication may be used to facilitate crystallisation. Once the solid phase comprising any crystals is formed, this may be tested as described herein. Accordingly, the present invention provides a process for the production of a co- crystal of the invention comprising

(a) grinding, heating or contacting in solution the cyprodinil or pyrimethanil with the co- crystal forming compound, under crystallisation conditions so as to form a solid phase; (b) isolating co-crystals comprising the cyprodinil or pyrimethanil and the co-crystal forming compound.

The co-crystal forming compound for use in the process of the invention is as defined above. In one embodiment of the process, the co-crystal forming compound is selected from the group consisting of l,5,7-triazabicyclo[4.4.0]dec-5-ene, 1,8-octanediol, 2- aminopyrimidine, 2-hydroxybenzonitrile, 5-methylhydantoin, acethydrazide, ethyl maltol, nicotinic hydrazide, propionamide, succinimide, urea and N,N-dimethyllactamide.

Assaying the solid phase for the presence of co-crystals of the cyprodinil or pyrimethanil and the co-crystal forming compound may be carried out by conventional methods known in the art. For example, it is convenient and routine to use powder X-ray diffraction techniques to assess the presence of the co-crystals. This may be effected by comparing the spectra of cyprodinil or pyrimethanil, the co-crystal forming compound and putative co-crystals in order to establish whether or not true co-crystals have been formed. Other techniques used in an analogous fashion, include differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Raman or Infra-red spectroscopy, NMR, gas chromatography or HPLC. Single crystal X-ray diffraction is especially useful in identifying co-crystal structures.

The co-crystals of the invention may be readily incorporated into fungicidal compositions (including agrochemical compositions) by conventional means. Accordingly, the invention also provides a fungicidal composition comprising a co-crystal of the invention as defined above. In one embodiment, the fungicidal composition is an agrochemical composition. The agrochemical compositions comprising the co-crystals of the present invention can be used for the control of plant pathogenic fungi on a number of plant species. Accordingly, the invention also provides a method of preventing/controlling fungal infection on plants or plant propagation material comprising treating the plant or plant propagation material with a fungicidally effective amount of an agricultural composition of the invention. By 'plant propagation material' is meant seeds of all kinds (fruit, tubers, bulbs, grains etc), cuttings, cut shoots and the like.

In particular, the agrochemical compositions of the invention can be used to control, for example, Cochliobolus sativus, Erysiphe spp. including E. graminis, Leptosphaeria nodorum, Puccinia spp., Pyrenophora teres, Pyrenophora tήtici-repentis, Rhynchosporium secalis, Septoria spp, Mycosphaerella musicola, Mycosphaerella fijiensis var. difformis, Sclerotinia homoeocarpa, Rhizoctonia solani, Helminthosporium spp. including Helminthosporium oryzae, dirty panicle complex, Hemileia vastatrix, Cercospora spp., Monilinia spp., Podosphaera spp., Sphaerotheca spp., Tranzschelia spp., Tapesia yallundae and T. acuformis, Botrytis spp., Alternaria spp. and Venturia spp.

The agrochemical compositions of the present invention are suitable for controlling such disease on a number of plants and their propagation material including, but not limited to the following target crops: cereals (wheat, barley, rye, oats, maize (including field corn, pop corn and sweet corn), rice, sorghum and related crops); beet (sugar beet and fodder beet); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, sunflowers); cucumber plants (marrows, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); vegetables (spinach, lettuce, asparagus, cabbages, carrots, eggplants, onions, pepper, tomatoes, potatoes, paprika, okra); plantation crops (bananas, fruit trees, rubber trees, tree nurseries), ornamentals (flowers, shrubs, broad-leaved trees and evergreens, such as conifers); as well as other plants such as vines, bushberries (such as blueberries), caneberries, cranberries, peppermint, rhubarb, spearmint, sugar cane and turf grasses including, but not limited to, cool-season turf grasses (for example, bluegrasses (Poa L), such as Kentucky bluegrass (Poa pratensis L.), rough bluegrass (Poa trivialis L.), Canada bluegrass (Poa compressa L.) and annual bluegrass (Poa annua L.); bentgrasses (Agrostis L.), such as creeping bentgrass (Agrostis palustris Huds.), colonial bentgrass (Agrostis tenius Sibth.), velvet bentgrass (Agrostis canina L.) and redtop (Agrostis alba L.); fescues (Festuca L.), such as tall fescue (Festuca arundinacea Schreb.), meadow fescue (Festuca elatior L.) and fine fescues such as creeping red fescue (Festuca rubra L.), chewings fescue (Festuca rubra var. commutata Gaud.), sheep fescue (Festuca ovina L.) and hard fescue {Festuca longifolia); and ryegrasses (Lolium L.), such as perennial ryegrass (Lolium perenne L.) and annual (Italian) ryegrass (Lolium multiflorum Lam.)) and warm-season turf grasses (for example, Bermudagrasses (Cynodon L. C. Rich), including hybrid and common

Bermudagrass; Zoysiagrasses (Zoysia Willd.), St. Augustinegrass (Stenotaphrum secundatum (Walt.) Kuntze); and centipedegrass (Eremochloa ophiuroides (Munro.) Hack.)).

In addition 'crops' are to be understood to include those crops that have been made tolerant to pests and pesticides, including herbicides or classes of herbicides, as a result of conventional methods of breeding or genetic engineering. Tolerance to e.g. herbicides means a reduced susceptibility to damage caused by a particular herbicide compared to conventional crop breeds. Crops can be modified or bred so as 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 upon the particular type of fungus to be controlled, the degree of control required and the timing and method of application and can be readily determined by the person skilled in the art. In general, the compositions of the invention can be applied at an application rate of between 0.005 kilograms/hectare (kg/ha) and about 5.0kg/ha, based on the total amount of active fungicide in the composition. An application rate of between about 0.1 kg/ha and about 1.5 kg/ha is preferred, with an application rate of between about 0.3 kg/ha and 0.8 kg/ha being especially preferred.

In practice, the agrochemical compositions comprising the co-crystals of the invention are applied as a formulation containing the various adjuvants and carriers known to or used in the industry. They may thus be formulated as granules, as wettable powders, as emulsifiable concentrates, as suspension concentrates (including oil dispersions), as powders or dusts, as flowables, as solutions, as suspensions or emulsions, 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 suspo-emulsion 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 optimum amount will depend on formulation, application equipment and nature of the plant pathogenic fungi to be controlled. Wettable powders are in the form of finely divided particles which disperse readily in water or other liquid carriers. The particles contain the active ingredient retained in a solid matrix. Typical solid matrices include fuller's earth, kaolin clays, silicas and other readily wet organic or inorganic solids. Wettable powders normally contain about 5% to about 95% of the active ingredient 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 naphthas, isophorone and other non-volatile organic solvents. In use, these concentrates are dispersed in water or other liquid and normally 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 formulations in which finely divided solid particles of the active compound are stably suspended. The solid particles may be suspended in an aqueous solution or in an oil (as an oil dispersion). Such formulations include anti-settling agents and dispersing agents and may further include a wetting agent to enhance activity as well an anti-foam and a crystal growth inhibitor. In use, these concentrates are diluted in water and normally 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 extrudates and relatively coarse particles and may be applied without dilution to the area in which control of plant pathogenic fungi is required or dispersed in a spray tank before application, for example. Typical carriers for granular formulations include sand, fuller's earth, attapulgite clay, bentonite clays, montmorillonite clay, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, plaster, wood flour, ground corn cobs, ground peanut hulls, sugars, sodium chloride, sodium sulphate, sodium silicate, sodium borate, magnesia, mica, iron oxide, zinc oxide, titanium oxide, antimony oxide, cryolite, gypsum, diatomaceous earth, calcium sulphate and other organic or inorganic materials which absorb or which can be coated with the active compound. Granular formulations for use without dilution normally contain about 5% to about 25% active ingredients which may include surface-active agents such as heavy aromatic naphthas, kerosene and other petroleum fractions, or vegetable oils; and/or stickers such as dextrins, glue or synthetic resins. When the granules are to be dispersed in a spray tank before application, the active ingredient content may be increased up to 80%.

Dusts are free-flowing admixtures of the active ingredient with finely divided solids such as talc, clays, flours and other organic and inorganic solids which act as dispersants and carriers.

Microcapsules are typically droplets or granules of the active ingredient enclosed in an inert porous shell which allows escape of the enclosed material to the surroundings at controlled rates. Encapsulated droplets are typically about 1 to 50 microns in diameter. The enclosed 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 inside the granule pores. Granules typically range from 1 millimetre to 1 centimetre and preferably 1 to 2 millimetres in diameter. Granules are formed by extrusion, agglomeration or prilling, 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 useful formulations for agrochemical applications include simple solutions of the active ingredient in a solvent in which it is completely soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene and other organic solvents. Pressurised sprayers, wherein the active ingredient is dispersed in finely-divided form as a result of vaporisation of a low boiling dispersant solvent carrier, may also be used.

Many of the formulations described above include wetting, dispersing or emulsifying agents. Examples are alkyl and alkylaryl sulphonates and sulphates and their salts, polyhydric alcohols; polyethoxylated alcohols, esters and fatty amines. These agents, when used, normally comprise from 0.1% to 40% by weight of the formulation.

Suitable agricultural adjuvants and carriers that are useful in formulating the compositions of the invention in the formulation types 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 can be employed include water and any solvents in which the co- crystal has no or limited solubility e.g. toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetates, diacetonalcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, di ethylene 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, diproxitol, 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, glycerol monoacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropyl benzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxy-propanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n- hexane, n-octylamine, octadecanoic acid, octyl amine acetate, oleic acid, oleylamine, o- xylene, phenol, polyethylene glycol (PEG400), propionic acid, propylene glycol, propylene glycol monomethyl ether, p-xylene, toluene, triethyl phosphate, Methylene glycol, xylene sulphonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, methanol, ethanol, isopropanol, and higher molecular weight alcohols such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, etc. ethylene glycol, propylene glycol, glycerine, N-methyl-2-pyrrolidinone, and the like. Water is generally the carrier of choice for the dilution of concentrates.

Suitable solid carriers include talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, chalk, diatomaxeous earth, lime, calcium carbonate, bentonite clay, fuller's earth, cotton seed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour, lignin and the like.

A broad range of surface-active agents are advantageously employed in both said liquid and solid compositions, especially those designed to be diluted with carrier before application. The surface-active agents can be anionic, cationic, non-ionic or polymeric in character and can be employed as emulsifying agents, wetting agents, suspending agents or for other purposes. Typical surface active agents include salts of alkyl sulphates, such as diethanolammonium lauryl sulphate; alkylarylsulphonate salts, such as calcium dodecylbenzenesulphonate; 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; alkylnaphthalenesulphonate salts, such as sodium dibutylnaphthalenesulphonate; dialkyl esters of sulphosuccinate salts, such as sodium di(2-ethylhexyl) sulphosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryl trimethylammonium 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 utilized in agricultural compositions include crystallisation inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, antioxidants, foaming agents, light-blocking agents, compatibilizing agents, antifoam agents, sequestering agents, neutralising agents and buffers, corrosion inhibitors, dyes, odorants, spreading agents, penetration aids, micronutrients, emollients, lubricants, sticking agents, and the like.

In addition, further, other biocidally 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. Each of the above formulations can be prepared as a package containing the fungicides together with other ingredients of the formulation (diluents, emulsifiers, surfactants, etc.). The formulations can also be prepared by a tank mix method, in which the ingredients are obtained separately and combined at the grower site.

These formulations can be applied to the areas where control is desired by conventional methods. Dust and liquid compositions, for example, can be applied by the use of power-dusters, broom and hand sprayers and spray dusters. The formulations can also be applied from airplanes as a dust or a spray or by rope wick applications. Both solid and liquid formulations may also be applied to the soil in the locus of the plant to be treated allowing the active ingredient to penetrate the plant through the roots. The formulations of the invention may also be used for dressing applications on plant propagation material to provide protection against fungus infections on the plant propagation material as well as against phytopathogenic fungi occurring in the soil. Suitably, the active ingredient may be applied to plant propagation material to be protected by impregnating the plant propagation material, in particular, seeds, either with a liquid formulation of the fungicide or coating it with a solid formulation. In special cases, other types of application are also possible, for example, the specific treatment of plant cuttings or twigs serving propagation. Suitably, the agrochemical compositions and formulations of the present invention are applied prior to disease development. Rates and frequency of use of the formulations are those conventionally used in the art and will depend on the risk of infestation by the fungal pathogen.

The present invention will now be described by way of the following non-limiting examples and figures, wherein:

FIG.l shows the powder X-Ray diffraction patterns of cyprodinil- 1,5,7- triazabicyclo[4.4.0]dec-5-ene co-crystal obtained using the technique described in Example Ia. FIG.2 shows the powder X-Ray diffraction patterns of (a) 1,5,7- triazabicyclo[4.4.0]dec-5-ene (b) cyprodinil-l,5,7-triazabicyclo[4.4.0]dec-5-ene co-crystal obtained using the technique described in Example Ib, (c) cyprodinil form A and (d) cyprodinil form B.

FIG.3 shows the powder X-Ray diffraction patterns of cyprodinil- 1 ,8-octanediol co- crystal obtained using the technique described in Example Ia.

FIG .4 shows the powder X-Ray diffraction patterns of cyprodinil- 1,8-octanediol co- crystal obtained using the technique described in Example Ic.

FIG.5 shows the powder X-Ray diffraction patterns of (a) 1,8-octanediol, (b) cyprodinil- 1,8-octanediol co-crystal obtained using the technique described in Example Ib, (c) cyprodinil form A and (d) cyprodinil form B.

FIG.6 shows the powder X-Ray diffraction patterns of cyprodinil-2-arninopyrimidine co-crystal obtained using the technique described in Example 1 a.

FIG.7 shows the powder X-Ray diffraction patterns of (a) 2-aminopyrimidine, (b) cyprodinil-2-aminopyrimidine co-crystal obtained using the technique described in Example Ib, (c) cyprodinil form A and (d) cyprodinil form B. FIG.8 shows the powder X-Ray diffraction patterns of cyprodinil-2- hydroxybenzonitrile co-crystal obtained using the technique described in Example Ia.

FIG.9 shows the powder X-Ray diffraction patterns of (a) 2-hydroxybenzonitrile, (b) cyprodinil-2-hydroxybenzonitrile co-crystal obtained using the technique described in Example Ie, (c) cyprodinil form A and (d) cyprodinil form B.

FIG.10 shows the powder X-Ray diffraction patterns of cyprodinil-5- methylhydantoin co-crystal obtained using the technique described in Example Ia.

FIG.l 1 shows the powder X-Ray diffraction patterns of (a) 5-methylhydantoin, (b) cyprodinil-5-methylhydantoin co-crystal obtained using the technique described in Example Ib, (c) cyprodinil form A and (d) cyprodinil form B.

FIG.12 shows the powder X-Ray diffraction patterns of cyprodinil-acethydrazide co- crystal obtained using the technique described in Example Ia.

FIG.13 shows the powder X-Ray diffraction patterns of (a) accethydrazide, (b) cyprodinil-acethydrazide co-crystal obtained using the technique described in Example Ib, (c) cyprodinil form A and (d) cyprodinil form B.

FIG.14 shows the powder X-Ray diffraction patterns of cyprodinil-ethyl maltol co- crystal obtained using the technique described in Example Ia.

FIG.15 shows the powder X-Ray diffraction patterns of (a) ethyl maltol, (b) cyprodinil-ethyl maltol co-crystal obtained using the technique described in Example Ib, (c) cyprodinil form A and (d) cyprodinil form B.

FIG.16 shows the powder X-Ray diffraction patterns of cyprodinil-nicotinic hydrazide co-crystal obtained using the technique described in Example Ic.

FIG.17 shows the powder X-Ray diffraction patterns of (a) nicotinic hydrazide, (b) cyprodinil-nicotinic hydrazide co-crystal obtained using the technique described in Example Id, (c) cyprodinil form A and (d) cyprodinil form B.

FIG.18 shows the powder X-Ray diffraction patterns of cyprodinil-propionamide co- crystal obtained using the technique described in Example Ia.

FIG.19 shows the powder X-Ray diffraction patterns of (a) propionamide, (b) cyprodinil-propionamide co-crystal obtained using the technique described in Example Ib, (c) cyprodinil form A and (d) cyprodinil form B. FIG.20 shows the powder X-Ray diffraction patterns of cyprodinil-succinamide co- crystal obtained using the technique described in Example Ia.

FIG.21 shows the powder X-Ray diffraction patterns of (a) succinamide, (b) cyprodinil-succinamide co-crystal obtained using the technique described in Example Ib, (c) cyprodinil form A and (d) cyprodinil form B.

FIG.22 shows the powder X-Ray diffraction patterns of cyprodinil-urea co-crystal obtained using the technique described in Example Ib.

FIG.23 shows the powder X-Ray diffraction patterns of (a) urea, (b) cyprodinil-urea co-crystal obtained using the technique described in Example Ib, (c) cyprodinil form A and (d) cyprodinil form B.

FIG.24 shows the powder X-Ray diffraction patterns of (a) cyprodinil form A, (b) cyprodinil form B and (c) cyprodinil-N,N-dimethyllactamide co-crystal obtained using the technique described in Example 2.

FIG. 25 shows the DSC trace of (a) 2-aminopyrimidine, (b) co-crystal product obtained using the technique described in Example Ib and (c) cyprodinil form B.

FIG. 26 shows the DSC trace of (a) 5-methylhydantoin, (b) co-crystal product obtained using the technique described in Example Ib and (c) cyprodinil form B.

FIG. 27 shows the DSC trace of (a) ethyl maltol, (b) co-crystal product obtained using the technique described in Example Ib and (c) cyprodinil form B. Figure 28 shows the DSC trace of (a) succinimide, (b) co-crystal product obtained using the technique described in Example Ib and (c) cyprodinil form B.

FIG. 29 shows a DSC trace of (a) cyprodinil form B and (b) cyprodinil-N,N- dimethyllactamide co-crystal obtained using the technique described in Example 2.

EXAMPLES

Ia. Preparation of cyprodinil co-crystals by cooling (method 1)

Cyprodinil was dissolved in acetone to make a solution of 0.85 M/l. 94 μ\ of this solution was charged to a reaction vial and evaporated to dryness under nitrogen. 308 μ\ of a 0.72 M/l solution of l ,5,7-triazabicyclo[4.4.0]dec-5-ene in methanol was added to the reaction vial and also evaporated to dryness under nitrogen. 500μl of methanol was then added and the reaction vial heated to 50°C for 2 hours with stirring to solubilise. The mixture was then cooled to 10°C over 5 hours and then held at 10°C for a further 5 hours. The supernatant liquid was removed from the solution by filtration, any residual solvent allowed to evaporate and the resultant crystals collected.

Further co-crystals were prepared using other co-formers. The concentrations and volumes of cyprodinil and co-former as well as the solvent used during the cooling stage are shown in Table 13 below:

TABLE 13

Ib. Preparation of cyprodinil co-crystals by cooling (method 2)

1.Og of cyprodinil and 1.24g of l,5,7-triazabicyclo[4.4.0]dec-5-ene were added to a reaction vial. 16ml of methanol was added and the vial heated to 50°C for two hours with stirring to solubilise. The mixture was cooled to 5°C over 5 hours and held at 5°C overnight, after which the crystallised product was isolated.

Further co-crystals were prepared using other co-formers. The concentrations and volumes of cyprodinil and co-former as well as the solvent used are shown in Table 14 below:

TABLE 14

Ic. Preparation of cyprodinil co-crystals by evaporation (method 1)

Cyprodinil was dissolved in acetone to make a solution of 1.2 M/l. 100 μl of this solution was charged to a reaction vial and evaporated to dryness under nitrogen. 64 μl of a 1.2 M/l solution of 1,8-octanediol 1 in methanol was added to the reaction vial and also evaporated to dryness under nitrogen. 500μl of acetonitrile was then added and the reaction vial heated to 50°C for 2 hours with stirring to solubilise. The mixture was then evaporated to dryness under nitrogen and the resultant crystals collected.

Further co-crystals were prepared using other co-formers. The concentrations and volumes of cyprodinil and co-former as well as the solvent used during the evaporation stage are shown in Table 15 below:

TABLE 15

Id. Preparation of cyprodinil co-crystals by evaporation (method 2) 2.0 g of cyprodinil and 0.6 Ig of nicotinic hydrazide were added to a reaction vial. 6ml of xylene was added and the vial stirred for two hours to solubilise the reactants. The mixture was evaporated to dryness and the resultant crystals collected.

Ie. Preparation of cyprodinil co-crystals by slurry maturation

1.5g of cyprodinil and 0.793 Ig of 2-hydroxybenzonitrile were added to a reaction vial. 7.5ml of isohexane was added and the vial was heated to 50°C, ensuring that the solids remain out of solution. The mixture was stirred at 50°C for 8 hours and then left at 4°C overnight. The cycle of heating, stirring and cooling was repeated for 7 days and the resultant crystals collected.

2. Preparation of cyprodinil-N,N-dimethyllactamide co-crystals

Ig cyprodinil and 5ml ethanol were charged to a 30ml vial with a magnetic stirrer and heated to 50⁰C. Once the cyprodinil was dissolved, 0.5g N,N-dimethyllactamide was added to the vial at 50⁰C with stirring. The reaction mixture was then cooled and allowed to stir for 48 hours at room temperature. The resultant crystals were isolated by Buchner filtration.

3. Analysis of co-crystals All samples of co-crystal were subject to analysis by powder X-ray diffraction.

Powder X-ray diffraction patterns for each of the resultant crystals are shown in Figures 1 to 24 as described above. These powder X-ray diffraction traces clearly show that the product co-crystals bear no resemblance to either of their constituent phases suggesting that a new solid state has been formed. The 2Θ values of selected peak positions of the powder X-ray diffraction patterns of these crystals are shown in Tables 1 to 12 above.

Where possible, those samples showing novel diffractograms were further analysed by DSC and ¹H NMR.

DSC traces are shown in Figures 25 to 29 as described above. Cyprodinil-2-aminopyrimidine crystals obtained from Example Ib were analysed by 1H NMR and displayed a 1 :1 stoichiometric ratio of cyprodinil and 2-aminopyrimidine.

Cyprodinil-ethyl maltol crystals obtained from Example Ib were analysed by NMR and displayed a 1 :1 stoichiometric ratio of cyprodinil and ethyl maltol. Cyprodinil-succinamide crystals obtained from Example Ib were analysed by NMR and displayed a 1 :1 stoichiometric ratio of cyprodinil and succinamide.

Although the invention has been described with reference to preferred embodiments and examples thereof, the scope of the present invention is not limited only to those described embodiments. As will be apparent to persons skilled in the art, modifications and adaptations to the above-described invention can 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 to the same extent as if each individual publication were specifically and individually indicated to be so incorporated by reference.

Claims

1. A co-crystal comprising an anilinopyrimidine fungicide selected from cyprodinil and pyrimethanil and a co-crystal forming compound which has at least one functional group selected from the group consisting of methyl, ether, hydroxyl (including alcohol and phenol), thiol, ketone, amide, primary amine, secondary amine, tertiary amine, sp2 amine, nitrile, pyrrole, pyridine, pyrimidine and thiazole.

2. The co-crystal according to claim 1, wherein the anilinopyrimidine fungicide is cyprodinil.

3. The co-crystal according to claim 2 wherein the co-crystal forming compound is selected from the group consisting of l,5,7-triazabicyclo[4.4.0]dec-5-ene, 1 ,8- octanediol, 2-aminopyrimidine, 2-hydroxybenzonitrile, 5-methylhydantoin, acethydrazide, ethyl maltol, nicotinic hydrazide, propionamide, succinimide, urea and

N,N-dimethyllactamide.

4. The co-crystal according to claim 3, wherein the co-crystal forming compound is 1 ,5,7 triazabicyclo[4.4.0]dec-5-ene.

5. The co-crystal according to claim 4, having a powder X-ray diffraction pattern expressed in of 2Θ angle values, said powder X-ray diffraction pattern comprising at least three 2Θ angle values selected from the group comprising 9.1 ± 0.2, 11.9 ± 0.2, 14.1 ± 0.2, 17.4 ± 0.2, 18.9 ± 0.2, 21.0 ± 0.2 and 25.8 ± 0.2.

6. The co-crystal according to claim 3, wherein the co-crystal forming compound is 1,8- octanediol.

7. The co-crystal according to claim 6, having a powder X-ray diffraction pattern expressed in of 2Θ angle values, said powder X-ray diffraction pattern comprising at least three 2Θ angle values selected from the group comprising 20.1 ± 0.2, 20.5 ± 0.2, 22.7 ± 0.2, 23.6 ± 0.2, 25.6 ± 0.2 and 27.4 ± 0.2.

8. The co-crystal according to claim 3, wherein the co-crystal forming compound is 2- aminopyrimidine.

9. The co-crystal according to claim 8, having a powder X-ray diffraction pattern expressed in of 2Θ angle values, said powder X-ray diffraction pattern comprising at least three 20 angle values selected from the group comprising 4.2 ± 0.2, 12.0 ± 0.2, 12.5 ± 0.2, 13.8 ± 0.2, 17.3 ± 0.2, 20.6 ± 0.2, 22.1 ± 0.2, 24.6 ± 0.2, 25.9 ± 0.2 and

31.9 ± 0.2.

10. The co-crystal according to claim 3, wherein the co-crystal forming compound is 2- hydroxybenzonitrile.

11. The co-crystal according to claim 10, having a powder X-ray diffraction pattern expressed in of 2Θ angle values, said powder X-ray diffraction pattern comprising at least three 2Θ angle values selected from the group comprising 14.4 ± 0.2, 17.5 ± 0.2, 21.6 ± 0.2, 22.9 ± 0.2, 26.7 ± 0.2 and 30.8 ± 0.2.

12. The co-crystal according to claim 3, wherein the co-crystal forming compound is 5- methylhydantoin.

13. The co-crystal according to claim 1 1, having a powder X-ray diffraction pattern expressed in of 2Θ angle values, said powder X-ray diffraction pattern comprising at least three 2Θ angle values selected from the group comprising 4.5 ± 0.2, 8.9 ± 0.2, 9.9 ± 0.2, 10.7 ± 0.2, 1 1.7 ± 0.2, 17.8 ± 0.2, 22.1 ± 0.2 and 24.7 ± 0.2.

14. The co-crystal according to claim 3, wherein the co-crystal forming compound is acethydrazide.

15. The co-crystal according to claim 14, having a powder X-ray diffraction pattern expressed in of 2θ angle values, said powder X-ray diffraction pattern comprising at least three 20 angle values selected from the group comprising 7.2 ± 0.2, 14.2 ± 0.2, 25.6 ± 0.2, 26.6 ± 0.2 and 28.6 ± 0.2.

16. The co-crystal according to claim 3, wherein the co-crystal forming compound is ethyl maltol.

17. The co-crystal according to claim 16, having a powder X-ray diffraction pattern expressed in of 20 angle values, said powder X-ray diffraction pattern comprising at least three 20 angle values selected from the group comprising 4.1 ± 0.2, 7.9 ± 0.2, 10.8 ± 0.2, 11.9 ± 0.2, 13.4 ± 0.2, 15.2 ± 0.2, 21.8 ± 0.2, 23.9 ± 0.2, 30.9 ± 0.2 and

31.8 ± 0.2.

18. The co-crystal according to claim 3, wherein the co-crystal forming compound is nicotinic hydrazide.

19. The co-crystal according to claim 18, having a powder X-ray diffraction pattern expressed in of 2Θ angle values, said powder X-ray diffraction pattern comprising at least three 20 angle values selected from the group comprising 5.1 ± 0.2, 9.9 ± 0.2, 17.0 ± 0.2, 18.9 ± 0.2, 19.9 ± 0.2, 25.1 ± 0.2 and 29.9 ± 0.2.

20. The co-crystal according to claim 3, wherein the co-crystal forming compound is propionamide.

21. The co-crystal according to claim 20, having a powder X-ray diffraction pattern expressed in of 20 angle values, said powder X-ray diffraction pattern comprising at least three 20 angle values selected from the group comprising 4.9 ± 0.2, 9.6 ± 0.2,

11.9 ± 0.2, 13.4 ± 0.2, 14.4 ± 0.2 and 21.2 ± 0.2.

22. The co-crystal according to claim 3, wherein the co-crystal forming compound is succinamide.

23. The co-crystal according to claim 22, having a powder X-ray diffraction pattern expressed in of 20 angle values, said powder X-ray diffraction pattern comprising at least three 2Θ angle values selected from the group comprising 6.4 ± 0.2, 9.8 ± 0.2, 12.8 ± 0.2, 17.5 ± 0.2, 19.2 ± 0.2, 20.1 ± 0.2, 21.4 ± 0.2, 23.8 ± 0.2 and 28.6 ± 0.2.

24. The co-crystal according to claim 3, wherein the co-crystal forming compound is urea.

25. The co-crystal according to claim 24, having a powder X-ray diffraction pattern expressed in of 2θ angle values, said powder X-ray diffraction pattern comprising at least three 2Θ angle values selected from the group comprising 4.9 ± 0.2, 9.7 ± 0.2, 13.8 ± 0.2, 16.2 ± 0.2, 16.8 ± 0.2, 17.8 ± 0.2 and 21.3 ± 0.2.

26. The co-crystal according to claim 3, wherein the co-crystal forming compound is N,N-dimethyllactamide.

27. The co-crystal according to claim 26, having a powder X-ray diffraction pattern expressed in of 2Θ angle values, said powder X-ray diffraction pattern comprising at least three 2Θ angle values selected from the group comprising 8.6 ± 0.2, 14.4 ± 0.2, 17.5 ± 0.2, 21.2 ± 0.2, 23.8 ± 0.2, 25.2 ± 0.2 and 31.9 ± 0.2.

28. A process of preparing a co-crystal of any one of claims 1 to 27 comprising a) grinding, heating or contacting in solution cyprodinil or pyrimethanil with the co-crystal forming compound, under crystallisation conditions so as to form a solid phase; b) isolating co-crystals comprising cyprodinil or pyrimethanil and the co-crystal forming compound.

29. A fungicidal composition comprising the co-crystal of any one of claims 1 to 27.

30. The composition of claim 29 which is an agrochemical composition.

31. A method of preventing/controlling fungal infection on plants comprising treating the plant with a fungicidally effective amount of an agricultural composition of claim 30.