STABILIZED THIOKETONE FORMULATIONS

Abstract

The invention relates to storage-stable prothioconazole-containing formulations with specific antioxidants and having a particularly low content of 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol, to a process for their preparation, to a method for controlling phytopathogenic fungi in crop protection and to their use as crop protection agents.

Claims

1. A formulation, comprising a) an active ingredient having a thione group and b) at least one antioxidant selected from the group comprising ascorbic acid, tocotrienol, tocopherols (e.g. (+)-delta-tocopherol, (+/−)-alpha-tocopherol), mixtures of tocopherols, thiolactic acid, BHT, eugenol, caffeic acid (3,4-dihydroxycinnamic acid), mercaptopropionic acid and D,L-thiothreitol.

2. The formulation according to claim 1, wherein the antioxidant is selected from the group comprising ascorbic acid, tocotrienol, tocopherols and mixtures thereof.

3. The formulation according to claim 1, wherein the formulation is an aqueous formulation with ascorbic acid as antioxidant.

4. The formulation according to claim 1, wherein the formulation is a formulation based on an organic solvent and the antioxidant is selected from the group comprising tocotrienols and tocopherols and mixtures thereof.

5. The formulation according to claim 1, wherein the active ingredient a) is selected from the group comprising prothioconazole and 4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-mercapto-1H-1,2,4-triazol-1-yl)propyl)pyridin-3-yl)oxy)benzonitrile.

6. The formulation according to claim 1, wherein the active ingredient a) is prothioconazole.

7. The formulation according to claim 1, wherein the proportion of component a) is 1% by weight to 50% by weight.

8. The formulation according to claim 1, wherein the proportion of component b) is 0.01% by weight to 15.00% by weight.

9. The formulation according to claim 1, comprising an aqueous SC formulation and the proportion of component b) is 0.01% by weight to 10.00% by weight.

10. The formulation according to claim 1, comprising a non-aqueous EC or OD formulation and the proportion of component b) in an EC formulation is optionally 0.05% by weight to 15.00% by weight and the proportion of component b) in an OD formulation is optionally 0.1% by weight to 5.00% by weight.

11. The formulation according to claim 1, wherein said formulation comprises at least one of the following components: c) c1: non-ionic dispersant/emulsifier,  c2: ionic dispersant/emulsifier d) one or more other active agrochemical ingredients different from a) e) one or more solvents including OD carriers f) one or more carriers (WGs, and Aerosils for SC/TC/WG) g) g1: one or more organic thickeners  g2: one or more inorganic thickeners h) one or more further additives and auxiliaries.

12. The formulation according to claim 11, comprising a nonionic (c1) and/or anionic (c2) emulsifier.

13. The formulation according to claim 11, wherein said one or more active agrochemical ingredients d) comprise one or more active insecticidal or fungicidal ingredients.

14. The formulation according to claim 11, wherein the further active agrochemical ingredient d) is bixafen.

15. The formulation according to claim 11, comprising not more than 5% by weight of water.

16. The process for preparing the formulation according to claim 1 comprising mixing components a) and b) and optionally one or more further additives.

17. A method for controlling one or more harmful organisms, comprising contacting of the harmful organisms, a habitat thereof, one or more hosts, optionally plants and seed, and/or soil, an area and/or an environment in which plants grow or could grow, and/or one or more materials, plants, seeds, soil, surfaces or spaces which are to be protected from attack or infestation by organisms that are harmful to plants, with an effective amount of a formulation according to claim 1.

18. A product comprising the formulation according to claim 1 for protection of one or more plants including seed, optionally useful plants, from infestation by one or more harmful organisms.

19. A product comprising the formulation according to claim 1 for control of one or more organisms that are harmful to plants, optionally one or more phytopathogenic harmful fungi, insects, arachnids, nematodes and harmful plants.

20. The product according to claim 19, wherein the harmful organisms are phytopathogenic harmful fungi.

21. An emulsion, obtainable by mixing water with one or more formulations according to claim 1, wherein a mixing ratio of water to emulsion concentrate is in a range from 1000:1 to 1:1.

Description

EXAMPLES

Feedstocks Used

[0176] The terms used in the examples below have the following meanings:

TABLE-US-00003 prothioconazole PTZ (Bayer AG) Atlox Metasperse 500 Croda, acrylate-based copolymer Citric acid Sigma-Aldrich Vitamin C Sigma-Aldrich, ascorbic acid Vitamin E Sigma-Aldrich, alpha-tocopherol Pluronic PE 10500 propylene oxide/ethylene oxide (PO-EO) block polymer (BASF) Rhodopol ® 23 xanthan derivative (Solvay) Silcolapse ® 426 silicone defoamer (Solvay) Glycerol antifreeze Proxel ® GXL preservative (biozide, Proxel) Lucramul ® CO30 non-ionic emulsifier, ethoxylated castor oil, Levaco Chemicals, DE SAG1572 aqueous emulsion of polydimethylsiloxane Momentive ® Genagen ® 4296 dimethyldecanamide (DAA), Clariant

General Preparation of an Aqueous Suspension Concentrate (SC)

[0177] First of all, water is initially charged at room temperature. The active ingredients and the other components are added (in no particular order) with stirring. The mixture is pre-comminuted in a colloid mill, followed by wet grinding using, for example, a bead mill. Finally, the organic thickener is added.

General Preparation of an Emulsion Concentrate (EC)

[0178] The organic solvent is initially charged. All other components are then added (in no particular order) with stirring. Stirring is continued until a clear solution is formed.

Determination of 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol (compound III) in Formulations

[0179] 2-(1-Chlorocyclopropyl)-1-(2-chlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol is separated from the formulation constituents on a reverse phase column using an isocratic eluent. After MS/MS detection, the quantitative evaluation is conducted by comparing the peak areas with those of the reference object, using an external standard.

[0180] High-pressure liquid chromatograph: HP 1090

[0181] Sample injection: HP 1090 Autoinjector

[0182] Mass spectrometer: Quattro I, Fisons

[0183] Integration and evaluation: MassLynx from Micromass

[0184] In each case, the samples are, unless indicated otherwise, exposed to light and stored for 4 weeks.

Example 1

Recipe of a Prothioconazole Emulsion Concentrate Formulation (Storage in the Dark)

[0185]

TABLE-US-00004 1a (comparison) 1b 1c 1d 1e 1f 1g % by % by % by % by % by % by % by Component weight weight weight weight weight weight weight Prothioconazole 25 25 25 25 25 12.76 12.76 Lucramul CO 30 20 20 20 20 20 7.5 7.5 SAG1572 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Genagen ® 4296 54.90 53.90 51.90 49.90 44.90 54.39 Hallcomid 1025 54.39 alpha-Tocopherol 0 1 3 5 10 5 5 (according to the invention) tebuconazole 0 0 0 0 0 12.76 12.76 Soprophor 796/P 0 0 0 0 0 7.5 7.5

Rapid Storage Results

[0186]

TABLE-US-00005 CIPAC 1a 1d 1e Emulsion stability 0 h/1 h/24 h MT 36.3 ok ok ok/trace of crystals/2 ml sediment Emulsion stability 0 h/1 h/24 h ok ok ok/trace of after 2 weeks of storage at 54° C. crystals/2 ml sediment pH, 1% in distilled water MT 75.3 5.56 5.32 5.36 pH, 1% in distilled water after 2 5.38 5.25 5.48 weeks of storage at 54° C. Appearance, viscosity, separation ok ok turbidity Appearance, viscosity, separation ok ok yellow after 2 weeks of storage at 54° C. turbidity Proportion of compound III after  40 40 40 40 0 h ppm ppm ppm ppm Proportion of compound III after 900 80 80 80 irradiation ppm ppm ppm ppm with 460 nm LED, 24 h and 10% air over the sample

[0187] As shown in Example 1e, at a concentration of 10% vitamin E unwanted effects (crystallisation, sedimentation) occur in the formulation, whereas a positive effect on the reduction of compound III can be measured even at a content of 1% vitamin E in the formulation.

[0188] Example 1f was stored for 4 weeks at room temperature in a vessel filled only up to about 10%, at a clear laboratory window. Even under these untypical conditions (exposure to air and light), the proportion of compound III remained at 21 ppm and thus considerably below the permitted EU threshold of 62.5 ppm.

Example 2

Recipe of a Prothioconazole Suspension Concentrate

[0189]

TABLE-US-00006 2a (comparison) 2b 2c 2d % by % by % by % by Component weight weight weight weight Prothioconazole 41 41 41 41 Pluronic PE 10500 3 3 3 3 Atlox Metasperse 1 1 1 1 500 glycerol 6 6 6 6 Silcolapse 426R 0.1 0.1 0.1 0.1 Proxel GXL 0.2 0.2 0.2 0.2 Rhodopol G 0.24 0.24 0.24 0.24 Water 48.46 49.36 48.16 45.46 ascorbic acid 0 0.1 0.3 3

Rapid Storage Results

[0190]

TABLE-US-00007 CIPAC 2a 2c 2d Suspendability MT 184 ok ok ok Suspendability after 2 weeks MT 184 ok ok ok of storage at 54° C. Wet screening 150 μm sieve MT 185 ok ok ok Wet screening 150 μm sieve MT 185 ok ok ok after 2 weeks of storage at 54° C. Particle size d90 in μm MT 187 3 3 3 Particle size d90 in μm after MT 187 4 4 4 2 weeks of storage at 54° C. Appearance, viscosity, ok ok ok separation Appearance, viscosity, ok ok ok separation after 2 weeks of storage at 54° C. Proportion of compound III  40 ppm 40 ppm 40 ppm 40 ppm after 0 h Proportion of compound III 245 ppm 45 ppm 45 ppm 45 ppm after irradiation with 460 nm LED, 24 h and 10% air over the sample

[0191] Up to a proportion of 3% vitamin C in the formulations, there was no detrimental change of the properties of the formulations. Even at a content of 0.1% vitamin C, it was possible to achieve a positive effect with respect to the reduction of compound III.

Example 3

Recipe of a Prothioconazole Oil Dispersion (with Vitamin E)

[0192]

TABLE-US-00008 3a (comparison) 3b 3c 3d 3e % by % by % by % by % by Component weight weight weight weight weight bixafen 6.13 6.13 6.13 6.13 6.13 Prothioconazole 12.25 12.25 12.25 12.25 12.25 Tanemul Hot 7.5 7.5 7.5 7.5 7.5 5902 Emulsogen EL 5 5 5 5 5 400 Triton GR 7 ME 5 5 5 5 5 Rhodacal 60 BE 5 5 5 5 5 Morwet D-425 2 2 2 2 2 Aerosil R 812 S 0.5 0.5 0.5 0.5 0.5 Aerosil 200 0.7 0.7 0.7 0.7 0.7 Silfoam SC 1132 0.05 0.05 0.05 0.05 0.05 Vitamin E 0 0.1 0.3 0.5 1 Rapeseed oil ad 100 ad 100 ad 100 ad 100 ad 100 methyl ester

Rapid Storage Results

[0193]

TABLE-US-00009 CIPAC 3a 3c 3d 3e Dispersibility MT 180 ok ok ok ok Dispersibility after 2 weeks of MT 180 ok ok ok ok storage at 54° C. Wet screening 150 μm sieve MT 185 ok ok ok ok Wet screening 150 μm sieve after MT 185 ok ok ok ok 2 weeks of storage at 54° C. Particle size d90 in μm MT 187 15 15 15 15 Particle size d90 in um after 2 MT 187 20 20 20 20 weeks of storage at 54° C. Appearance, viscosity, separation ok ok ok ok Appearance, viscosity, separation ok ok ok ok after 2 weeks of storage at 54° C. Proportion of compound III after 11 11 11 11 0 h ppm ppm ppm ppm Proportion of compound III after 540 240 89 71 15 2 weeks of storage under light ppm ppm ppm ppm ppm and 10% air over the sample

[0194] Even small amounts of vitamin E stabilise prothioconazole under light and reduce the formation of compound III in an OD formulation.

Example 4

[0195] Effects of UV Blockers

[0196] Table Entry 1:

[0197] 0.4 g of prothioconazole and 1.6 g of N,N-dimethyldecanamide were combined in a 20 ml vial.

[0198] Table Entry 2:

[0199] As Table entry 1, with 60 mg of octocrylene added.

[0200] Table Entry 3:

[0201] 0.4 g of prothioconazole, 1.6 g of acetonitrile and 0.78 g of acetone were combined in a 20 ml vial.

[0202] All reaction mixtures were irradiated in a photoreactor with stirring (magnetic stirrer) using LED lamps (wavelength 450 nm, 47 mW/cm.sup.2) for 24 hours. Samples were then taken and the respective content of compound III was determined by HPLC chromatography (column: Agilent Zorbax Eclipse Plus C18, 50×4.6 mm, 1.8 μm, mobile phase: acetonitrile/0.1% by weight of aqueous phosphoric acid, gradient at 2 ml/min, temperature: 45° C., external standard).

TABLE-US-00010 Proportion of Experiment dethio in ppm 1 prothioconazole in DAA (purity, 98%) 1892 2 prothioconazole in DAA (purity, 98%)  795 with octocrylene (3% by weight) 3 prothioconazole in high-purity 1088 acetonitrile/acetone mixture (2:1 g/g)

[0203] Even in pure DAA and in combination with a UV blocker, on irradiation a significant proportion of dethio is formed, as in pure solvents (acetonitrile/acetone).

Example 5

Effect of 5% by Weight Additives on Prothioconazole in N,N-dimethyldecanamide

[0204] 0.4 g of prothioconazole, 1.5 g of N,N-dimethyldecanamide and 0.1 g of the respective stabiliser were combined in a 20 ml vial. The reaction mixtures were irradiated in a photoreactor with stirring (magnetic stirrer) using LED lamps (wavelength 350 nm, 19 mW/cm.sup.2) for 24 hours. Samples were then taken and the respective content of compound III was determined by HPLC chromatography (column: Agilent Zorbax Eclipse Plus C18, 50×4.6 mm, 1.8 μm, mobile phase: acetonitrile/0.1% by weight of aqueous phosphoric acid, gradient at 2 ml/min, temperature: 45° C., external standard).

TABLE-US-00011 Compound Antioxidant III (ppm) Comparison 1539 (+)-delta-Tocopherol 81 (+/−)-alpha-Tocopherol 96 Thiolactic acid 357 Butylated hydroxytoluene (BHT) 576 Eugenol 580 Caffeic acid 616 Mercaptopropionic acid 630 DL-Dithiothreitol 749 Sunflower oil 994 N-(Mercaptopropionyl)glycine 1102 Octocrylene 1377 Rapeseed oil 1513 4-Methoxyphenol 1706 Ferulic acid 2059 PEG-substituted tocopherol 2454 4-Hydroxycinnamic acid 2754 Gallic acid 3700

[0205] As can be seen from the table above, not all antioxidants lead to a stabilisation of prothioconazole with respect to a reduction of dethio formation. Rather, some of them even appear to have a negative effect (increased dethio formation).

Example 6

20% Prothioconazole with DAA

[0206] A quantity of (+/−)-alpha-tocopherol (see table below) was added to clear 50 ml glass bottles and the content was then made up to a total weight of 5 g using a solution of 20% by weight of prothioconazole in N,N-dimethyldecanamide. The bottles were shaken and, in an outdoor trial, exposed to direct sunlight for 2 weeks. Samples were then taken and the respective content of compound III was determined by HPLC chromatography (column: Agilent Zorbax Eclipse Plus C18, 50×4.6 mm, 1.8 μm, mobile phase: acetonitrile/0.1% by weight of aqueous phosphoric acid, gradient at 2 ml/min, temperature: 45° C., external standard).

TABLE-US-00012 EC250 Formulation of prothioconazole: Amount of % by weight Compound tocopherol (mg) of tocopherol III (ppm) 270 5% 11 158 3% 18 62 1% 57 0 0% 552

[0207] A quantity of (+/−)-alpha-tocopherol (see table below) was added to clear 50 ml glass bottles and the content was then made up to a total weight of 5 g using an EC250 formulation of prothioconazole. The bottles were shaken and, in an outdoor trial, exposed to direct sunlight for 2 weeks. Samples were then taken and the respective content of compound III was determined by HPLC chromatography (column: Agilent Zorbax Eclipse Plus C18, 50×4.6 mm, 1.8 μm, mobile phase: acetonitrile/0.1% by weight of aqueous phosphoric acid, gradient at 2 ml/min, temperature: 45° C., external standard).

TABLE-US-00013 Amount of tocopherol % by weight Compound (mg) of tocopherol III (ppm) 267 5% 44 156 3% 60 52 1% 230 0 0% 1253

[0208] As shown by the experiments described above, even on addition of 1 per cent by weight of (+/−)-alpha-tocopherol, based on the total weight of the composition, both in an EC250 formulation and in a solution of 20% by weight of prothioconazole in DAA, the formation of compound III in an outdoor trial was significantly reduced, with the effect being even more pronounced when the concentration was increased to 3 per cent by weight of tocopherol.

Example 7

[0209] 2 g of an SC325 (Fox325) formulation and an SC450 formulation (XPRO SC 450) of prothioconazole were combined with the amount of vitamin C stated in the table below in a 20 ml vial. The reaction mixtures were irradiated in a photoreactor with stirring (magnetic stirrer) using LED lamps (wavelength 450 nm, 47 mW/cm.sup.2) for 24 hours. Samples were then taken and the respective content of compound III was determined by HPLC chromatography (column: Agilent Zorbax Eclipse Plus C18, 50×4.6 mm, 1.8 μm, mobile phase: acetonitrile/0.1% by weight of aqueous phosphoric acid, gradient at 2 ml/min, temperature: 45° C., external standard).

TABLE-US-00014 Amount of % by vitamin C weight of Compound (mg) vitamin C III (ppm) FOX SC325 0 0 353 (16% PTZ + 2 0.1 101 14% 6 0.3 85 trifloxystrobin 10 0.5 77 in water) 14 0.7 75 20 1 64 60 3 47 100 5 42 FoX XPRO 0 0 173 Sc 450 2 0.1 117 (14.8% PTZ + 6 0.3 53 12.7% 10 0.5 50 trifloxystrobin + 14 0.7 48 10.6 % 20 1 33 bixafen in 60 3 27 water) 100 5 36.5

[0210] As shown by the experiments above, vitamin C protects SC formulations of prothioconazole very efficiently even with only 0.1 per cent by weight added. Up to a content of 3% by weight of vitamin C, the effect increases with increasing vitamin C content.

Example 8

[0211] 2 g of the EC formulation stated in the table (dispersant: N,N-dimethyldecanamide) were combined with 1 or 3 per cent by weight of (+/−)α-tocopherol in a 20 ml vial. The reaction mixtures were irradiated in a photoreactor with stirring (magnetic stirrer) using LED lamps (wavelength 365 nm, 19 mW/cm.sup.2) for 24 hours. Samples were then taken and the respective content of compound III was determined by HPLC chromatography (column: Agilent Zorbax Eclipse Plus C18, 50×4.6 mm, 1.8 μm, mobile phase: acetonitrile/0.1% by weight of aqueous phosphoric acid, gradient at 2 ml/min, temperature: 45° C., external standard).

TABLE-US-00015 Composition % active by weight Compound ingredients of (+/−)α- III Formulation (% by weight) tocopherol (ppm) Ascra Xpro 12% PTZ, 0 2189 EC260 6% bixafen, 6% fluopyram Ascra Xpro 12% PTZ, 1 258 EC260 6% bixafen, 6% fluopyram Ascra Xpro 12% PTZ, 3 126 EC260 6% bixafen, 6% fluopyram Input Xpro 10% PTZ, 25% 0 205 EC400 spiroxamine, 5% bixafen Input Xpro 10% PTZ, 25% 1 140 EC400 spiroxamine, 5% bixafen Input Xpro 10% PTZ, 25% 3 150 EC400 spiroxamine, 5% bixafen Tilmor 8% PTZ, 16% 0 1190 EC240 tebuconazole Tilmor % PTZ, 16% 1 219 EC240 tebuconazole Tilmor % PTZ, 16% 3 115 EC240 tebuconazole

[0212] As shown by the experiments above, the formation of dethio can also be reduced significantly in commercial prothioconazole-containing formulations by addition of (+/−)α-tocopherol.