SUBSTITUTED OXADIAZOLES FOR COMBATING PHYTOPATHOGENIC FUNGI

Abstract

The present invention relates to novel trifluoromethyl oxadiazoles of the formula I, or an N-oxide, and/or their agriculturally useful salts; to their use for controlling phytopathogenic fungi; to a method for combating phytopathogenic harmful fungi, which process comprises treating the fungi or the plants, the soil or seeds to be protected against fungal attack, with an effective amount of at least one compound of the formula I, or an N-oxide, or an agriculturally acceptable salt thereof; to agrochemical compositions comprising at least one such compound; and to agrochemical compositions further comprising seeds.

##STR00001##

Claims

1-12. (canceled)

13. A compound of formula I, or an N-oxide or an agriculturally acceptable salt thereof, ##STR00011## wherein: A is phenyl or thiophenyl; and wherein the cyclic groups A are unsubstituted or substituted with 1, 2, 3 or 4 identical or different groups R.sup.A; wherein R.sup.A is OH, cyclopropyl, halogen, cyano, diC.sub.1-C.sub.6-alkylamino, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.3-C.sub.8-cycloalkyl or C.sub.3-C.sub.8-cycloalkoxy; and wherein any of the aliphatic or cyclic moieties are unsubstituted or substituted with 1, 2, 3 or 4 identical or different groups R.sup.a; wherein R.sup.a is halogen, cyano, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy or C.sub.1-C.sub.6-haloalkoxy; R.sup.1, R.sup.2 independently of each other are hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkenyl, C.sub.1-C.sub.4-alkoxy, C(O)(C.sub.1-C.sub.6-alkyl), C(O)(C.sub.1-C.sub.6-alkoxy), phenyl-C.sub.1-C.sub.4-alkyl, heteroaryl-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, phenyl, naphthyl or a 3- to 10-membered saturated, partially unsaturated or aromatic mono- or bicyclic heterocycle, wherein the ring member atoms of said mono- or bicyclic heterocycle include besides carbon atoms further 1, 2, 3 or 4 heteroatoms selected from N, O and S as ring member atoms and wherein 1 or 2 carbon ring member atoms of the heterocycle may be replaced by 1 or 2 groups independently selected from C(O) and C(S); and wherein the heteroaryl group in heteroaryl-C.sub.1-C.sub.4-alkyl is a 5- or 6-membered aromatic heterocycle, wherein the ring member atoms of the heterocyclic ring include besides carbon atoms 1, 2, 3 or 4 heteroatoms selected from N, O and S as ring member atoms; and wherein any of the above-mentioned aliphatic or cyclic groups are unsubstituted or substituted with 1, 2, 3 or up to the maximum possible number of identical or different groups R.sup.1a; or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are bound form a saturated or partially unsaturated mono- or bicyclic 3- to 10-membered heterocycle, wherein the heterocycle includes beside one nitrogen atom and one or more carbon atoms 1, 2 or 3 heteroatoms independently selected from N, O and S as ring member atoms; and wherein one or two CH.sub.2 groups of the heterocycle may be replaced by one or two groups independently selected from the group of C(O) and C(S); and wherein the heterocycle is unsubstituted or substituted with 1, 2, 3, 4 or up to the maximum possible number of identical or different groups R.sup.1a; wherein R.sup.1a is halogen, cyano, NO.sub.2, OH, SH, NH.sub.2, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, C.sub.3-C.sub.8-cycloalkyl, NHSO.sub.2C.sub.1-C.sub.4-alkyl, (CO)C.sub.1-C.sub.4-alkyl, C(O)C.sub.1-C.sub.4-alkoxy or C.sub.1-C.sub.6-alkylsulfonyl, hydroxyC.sub.1-C.sub.4-alkyl, C(O)NH.sub.2, C(O)NH(C.sub.1-C.sub.4-alkyl), C.sub.1-C.sub.4-alkylthio-C.sub.1-C.sub.4-alkyl, aminoC.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkylamino-C.sub.1-C.sub.4-alkyl, diC.sub.1-C.sub.4-alkylamino-C.sub.1-C.sub.4-alkyl, aminocarbonyl-C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl.

14. The compound of claim 13, wherein A is phenyl.

15. The compound of claim 14, wherein the trifluoromethyloxadiazole group and the C(S)NR.sup.2-R.sup.1 group are situated on the phenyl ring to which they are attached in a para-relationship.

16. The compound of claim 13, wherein R.sup.1 is hydrogen or methyl and R.sup.2 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or cyclopropyl; and wherein any of the aliphatic or cyclic groups are unsubstituted or substituted with 1, 2, 3, 4 or 5 or up to the maximum possible number of identical or different groups R.sup.1a as defined in claim 13.

17. The compound of claim 13, wherein R.sup.1 is hydrogen or methyl and R.sup.2 is phenyl-C.sub.1-C.sub.4-alkyl, heteroaryl-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl; and wherein any of the aliphatic or cyclic groups are unsubstituted or substituted with 1, 2, 3, 4 or 5 up to the maximum possible number of identical or different groups R.sup.1a.

18. The compound of claim 13, wherein R.sup.1 is hydrogen or methyl and R.sup.2 is phenyl; and wherein any of the aliphatic or cyclic groups are unsubstituted or substituted with 1, 2, 3, 4 or 5 up to the maximum possible number of identical or different groups R.sup.1a.

19. An agrochemical composition, which comprises an auxiliary and at least one compound of claim 13.

20. An agrochemical composition of claim 19, wherein the auxiliary is selected from the group of ionic or non-ionic surfactants.

21. An agrochemical composition of claim 19 comprising at least one further pesticidally active substance selected from the group consisting of herbicides, safeners, fungicides, insecticides, and plant growth regulators.

22. An agrochemical composition of claim 19 further comprising seed, wherein the amount of the compound of formula I, or an N-oxide, or an agriculturally acceptable salt thereof, is from 0.1 g to 10 kg per 100 kg of seed.

23. A method for combating phytopathogenic harmful fungi, which process comprises treating the fungi or the plants, the soil or seeds to be protected against fungal attack, with an effective amount of at least one compound of formula I or an N-oxide or an agriculturally acceptable salt thereof as defined in claim 13.

24. The method of claim 23, wherein A is phenyl.

25. The method of claim 24, wherein the trifluoromethyloxadiazole group and the C(S)NR.sup.2-R.sup.1 group are situated on the phenyl ring to which they are attached in a para-relationship.

26. The method of claim 23, wherein R.sup.1 is hydrogen or methyl and R.sup.2 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or cyclopropyl; and wherein any of the aliphatic or cyclic groups are unsubstituted or substituted with 1, 2, 3, 4 or 5 or up to the maximum possible number of identical or different groups R.sup.1a as defined in claim 13.

27. The method of claim 23, wherein R.sup.1 is hydrogen or methyl and R.sup.2 is phenyl-C.sub.1-C.sub.4-alkyl, heteroaryl-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl; and wherein any of the aliphatic or cyclic groups are unsubstituted or substituted with 1, 2, 3, 4 or 5 up to the maximum possible number of identical or different groups R.sup.1a.

28. The method of claim 23, wherein R.sup.1 is hydrogen or methyl and R.sup.2 is phenyl; and wherein any of the aliphatic or cyclic groups are unsubstituted or substituted with 1, 2, 3, 4 or 5 up to the maximum possible number of identical or different groups R.sup.1a.

29. A method for combating phytopathogenic harmful fungi, which process comprises treating the fungi or the plants, the soil or seeds to be protected against fungal attack, with an effective amount of the composition of claim 19.

30. A method for combating phytopathogenic harmful fungi, which process comprises treating the fungi or the plants, the soil or seeds to be protected against fungal attack, with an effective amount of the composition of claim 20.

31. A method for combating phytopathogenic harmful fungi, which process comprises treating the fungi or the plants, the soil or seeds to be protected against fungal attack, with an effective amount of the composition of claim 21.

32. A method for combating phytopathogenic harmful fungi, which process comprises treating the fungi or the plants, the soil or seeds to be protected against fungal attack, with an effective amount of the composition of claim 22.

Description

I. SYNTHESIS

I.1) Preparation of 4-[(Z)N-hydroxycarbamimidoyl]benzoic acid

[0192] To a solution of the 4-cyano benzoic acid (500 g, 1.0 eq.) in a mixture of ethanol and water (5 liter/2 liter) was added hydroxylamine hydrochloride (495 g, 2.0 eq.) and potassium carbonate (751 g, 1.5 eq.). To the resulting mixture, 8-hydroxyquinoline (6.5 g, 0.1 eq.) was added and it was heated under reflux until HPLC indicated complete conversion of the starting material. After cooling to ambient temperature, water was added and the resulting precipitate was collected and dried to afford the title compound sufficiently pure to be used directly without further purification.

I.2) Preparation of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid

[0193] A solution of 4-[(Z)N-hydroxycarbamimidoyl]benzoic acid (200 g, 1.0 eq.) in tetrahydrofurane (2.5 liter) was treated with trifluoroacetic anhydride (350 g, 1.5 eq.). The resulting mixture was stirred overnight at ambient temperature, before it was diluted with methyl tert-butyl ether and washed with a saturated aqueous solution of sodium bicarbonate. The organic layer was freed from solvent under reduced pressure to afford a crude product that was recrystallized from di-iso-propyl ether to furnish the title compound as light brown solid (220 g, 76%). 1H NMR (400 MHz, DMSO-d.sub.6, 298 K): [ppm]=13.40 (br. s, 1H), 8.22-8.10 (m, 4H).

I.3) Preparation of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride

[0194] A 250 mL round-bottom flask was charged with 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid (20 g, 1.0 eq.) and thionyl chloride was added dropwise (50 mL, 5 eq.). To the suspension were added 2 drops of N,N-dimethylformamide and the mixture was warmed to gentle reflux for 2 h. When HPLC indicated complete conversion of the starting material, the mixture was cooled to room temperature and all volatiles were removed under reduced pressure. The residue was taken up in toluene and coevaporated to remove residual thionyl chloride. The title compound was isolated as light brown solid (20.7 g, 97%). .sup.1H NMR (400 MHz, CDCl.sub.3, 298 K): [ppm]=8.35-8.25 (m, 4H).

I.4) Preparation of N,N-dimethyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide

[0195] A solution of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride (1.5 g, 1.0 eq.) and dimethylamine (10.8 mL, 2M in THF, 4 eq.) in tetrahydrofuran (120 ml) was stirred over night, before it was quenched by the addition of water and the product was extracted into methylen chloride. The combined organic layers were successively washed with diluted aqueous solutions of hydrochloric acid and sodium bicarbonate, successively, dried over sodium sulfate and freed from solvent under reduced pressure to afford the title compound (1.46 g) that was used directly without further purification.

I.5) Preparation of N,N-dimethyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzenecarbothioamide (compound Ex-7)

[0196] To a solution of N,N-dimethyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide (200 mg, 1.0 eq.) in toluene (2.5 mL) was added 2,4-Bis(4-methoxyphenyl)-2,4-dithioxo-1,3,2,4-dithiadiphosphetane (170 mg, 0.6 eq.). The resulting mixture was heated under reflux until HPLC indicated complete conversion of the starting material. After cooling to ambient temperature, the mixture was concentrated under reduced pressure. The residue was purified by flash chromatography to afford the title compound (0.10 g, 79%).

[0197] .sup.1H NMR (400 MHz, CDCl.sub.3, 298 K): 6 [ppm]=8.16 (d, 2H), 7.48 (d, 2H), 3.61 (s, 3H), 3.20 (s, 3H).

[0198] The compounds listed in Table I were prepared in an analogous manner.

TABLE-US-00002 TABLE I Compounds Ex-1 to Ex-29 of formula I, wherein A corresponds to subformula (A.2), wherein the group (A.2) is unsubstituted, and wherein the meaning of R.sup.1 and R.sup.2 are as defined in each line. HPLC R.sub.t Melting point Ex. no R.sup.1 R.sup.2 (min)* (C. ) Ex-1 CH.sub.3 benzyl 1.387 63 Ex-2 CH.sub.3 cyclopropyl 1.286 113 Ex-3 H cyclopropyl 1.170 135 Ex-4 H CH.sub.3 1.163 154 Ex-5 H benzyl 1.342 125 Ex-6 CH.sub.3 phenyl 1.295 114 Ex-7 CH.sub.3 CH.sub.3 1.129 82 Ex-8 H 2-chloro-4-fluorophenyl 1.279 142 Ex-9 CH.sub.3 2-fluorobenzyl 1.301 Ex-10 H 4-fluorobenzyl 1.273 133 Ex-11 H 2-fluorophenyl 1.250 123 Ex-12 H 4-fluorophenyl 1.266 186 Ex-13 H 2-methylphenyl 1.234 109 Ex-14 H 4-methylphenyl 1.263 186 Ex-15 H 2,4-difluorophenyl 1.239 164 Ex-16 H phenyl 1.335 165 Ex-17 H ethyl 1.246 134 Ex-18 H CH.sub.2cyclopropyl 1.318 136 Ex-19 H isopropyl 1.288 90 Ex-20 CH.sub.3 isopropyl 1.305 70 Ex-21 CH.sub.3 ethyl 1.255 65 Ex-22 CH.sub.3 2-fluorphenyl 1.373 Ex-23 CH.sub.3 4-fluorphenyl 1.356 107 Ex-24 CH.sub.3 2-methylphenyl 1.389 Ex-25 CH.sub.3 4-methylphenyl 1.267 Ex-26 CH.sub.3 2,4-difluorphenyl 1.379 88 Ex-27 CH.sub.3 4-fluorbenzyl 1.377 106 Ex-28 CH.sub.3 CH.sub.2CN 1.197 Ex-29 CH.sub.3 CH.sub.2-cyclopropyl 1.392 69 Ex-30 H 4-fluoro-2-methylphenyl 1.465 144 Ex-31 CH.sub.3 4-fluoro-2-methylphenyl 1.403 Ex-32 H 2-chlorophenyl 1.347 104 Ex-33 CH.sub.3 2-chlorophenyl 1.393 Ex-34 H 2-fluoro-4-methylphenyl 1.343 Ex-35 CH.sub.3 2-fluoro-4-methylphenyl 1.422 Ex-36 H 4-chlorophenyl 1.363 188 Ex-37 CH.sub.3 2-chloro-4-fluorophenyl 1.421 118 Ex-38 CH.sub.3 4-chlorophenyl 1.412 139 Ex-39 H tert-butyl 1.346 97 Ex-40 H 4-chloro-2-fluorophenyl 1.416 143 Ex-41 CH.sub.3 4-chloro-2-fluorophenyl 1.461 Ex-42 H 2,2-difluorocyclopropyl 1.244 95 Ex-43 H 2-ethylcyclopropyl 1.378 94 Ex-44 H 2-methylcyclopropyl 1.317 132 Ex-45 H 1-methylcyclopropyl 1.304 111 Ex-46 H 2-fluorobenzyl 1.331 139 *HPLC: High Performance Liquid Chromatography; HPLC-column Kinetex XB C18 1.7 (50 2.1 mm); eluent: acetonitrile/water + 0.1% trifluoroacetic acid (gradient from 5:95 to 100:0 in 1.5 min at 60 C., flow gradient from 0.8 to 1.0 ml/min in 1.5 min). MS: Quadrupol Electrospray Ionisation, 80 V (positive mode). R.sub.t: retention time in minutes.

II. BIOLOGICAL EXAMPLES FOR FUNGICIDAL ACTIVITY

[0199] A. Glass House Trials

[0200] The fungicidal action of the compounds of formula I was demonstrated by the following experiments. Spray solutions were prepared in several steps. A mixture was prepared of acetone and/or dimethylsulfoxide and the wetting agent/emulsifier Wettol, which is based on ethoxylated alkylphenoles, in a relation (volume) solvent-emulsifier of 99 to 1 was added to 25 mg of the compound to give a total of 5 ml. Water was then added to a total volume of 100 ml. This stock solution was diluted with the described solvent-emulsifier-water mixture to the given concentration.

[0201] 1. Curative Control of Soy Bean Rust on Soy Beans Caused by Phakopsora pachyrhizi

[0202] Leaves of pot-grown soy bean seedlings were inoculated with spores of Phakopsora pachyrhizi. To ensure the success of the artificial inoculation, the plants were transferred to a humid chamber with a relative humidity of about 95% and 20 to 24 C. for 24 h. The next day the plants were cultivated for 3 days in a greenhouse chamber at 23-27 C. and a relative humidity between 60 and 80%. Then the plants were sprayed to run-off with an aqueous suspension, containing the concentration of active ingredient or their mixture as described below. The plants were allowed to air-dry. Then the trial plants were cultivated for 14 days in a greenhouse chamber at 23-27 C. and a relative humidity between 60 and 80%. The extent of fungal attack on the leaves was visually assessed as % diseased leaf area.

[0203] In this test, the plants which had been treated with 32 ppm of the active compound Ex-1, Ex-2, Ex-3, Ex-4, Ex-5, Ex-7, Ex-8, Ex-9, Ex-11, Ex-12, Ex-13, Ex-15, Ex-16, Ex-17, Ex-18, Ex-19, Ex-20, Ex-21, Ex-28, Ex-32, Ex-39, Ex-43, Ex-44 and Ex-45 showed a diseased leaf area of at most 15%, whereas the untreated plants showed 90% diseased leaf area.

[0204] 2. Protective Control of Soy Bean Rust on Soy Beans Caused by Phakopsora pachyrhizi

[0205] Leaves of pot-grown soy bean seedlings were sprayed to run-off with an aqueous suspension, containing the concentration of active ingredient or their mixture as described below. The plants were allowed to air-dry. The trial plants were cultivated for 2 days in a greenhouse chamber at 23-27 C. and a relative humidity between 60 and 80%. Then the plants were inoculated with spores of Phakopsora pachyrhizi. To ensure the success the artificial inoculation, the plants were transferred to a humid chamber with a relative humidity of about 95% and 20 to 24 C. for 24 h. The trial plants were cultivated for fourteen days in a greenhouse chamber at 23-27 C. and a relative humidity between 60 and 80%. The extent of fungal attack on the leaves was visually assessed as % diseased leaf area.

[0206] In this test, the plants which had been treated with 32 ppm of the active compound Ex-1, Ex-2, Ex-3, Ex-4, Ex-5, Ex-6, Ex-7, Ex-8, Ex-9, Ex-10, Ex-11, Ex-12, Ex-13, Ex-14, Ex-15, Ex-16, Ex-17, Ex-18, Ex-19, Ex-20, Ex-21, Ex-23, Ex-25, Ex-27, Ex-28, Ex-30, Ex-32, Ex-34, Ex-35, Ex-36, Ex-39, Ex-40, Ex-42, Ex-43, Ex-44 and Ex-45 showed a diseased leaf area of at most 15%, whereas the untreated plants showed 90% diseased leaf area.

[0207] 3. Curative Control of Brown Rust on Wheat Caused by Puccinia recondita

[0208] The first two developed leaves of pot-grown wheat seedling were dusted with spores of Puccinia recondita. To ensure the success the artificial inoculation, the plants were transferred to a humid chamber without light and a relative humidity of 95 to 99% and 20 to 24 C. for 24 hours. The next day the plants were cultivated for 3 days in a greenhouse chamber at 20 to 24 C. and a relative humidity between 65 and 70%. Then the plants were sprayed to run-off with an aqueous suspension, containing the concentration of active ingredient or their mixture as described below. The plants were allowed to air-dry. Then the trial plants were cultivated for 8 days in a greenhouse chamber at 20 to 24 C. and a relative humidity between 65 and 70%. The extent of fungal attack on the leaves was visually assessed as % diseased leaf area.

[0209] In this test, the plants which had been treated with 63 ppm of the active compound Ex-1, Ex-2, Ex-3, Ex-4, Ex-9, Ex-10, Ex-17, Ex-18, Ex-19, Ex-21, Ex-28, Ex-29, Ex-43, Ex-44 and Ex-45 showed a diseased leaf area of at most 15%, whereas the untreated plants showed 90% diseased leaf area.

[0210] 4. Preventative Control of Brown Rust on Wheat Caused by Puccinia recondita

[0211] The first two developed leaves of pot-grown wheat seedling were sprayed to run-off with an aqueous suspension, containing the concentration of active ingredient or their mixture as described below. Seven days later the plants were inoculated with spores of Puccinia recondite. To ensure the success the artificial inoculation, the plants were transferred to a humid chamber without light and a relative humidity of 95 to 99% and 20 to 24 C. for 24 hours. Then the trial plants were cultivated for 6 days in a greenhouse chamber at 20 to 24 C. and a relative humidity between 65 and 70%. The extent of fungal attack on the leaves was visually assessed as % diseased leaf area.

[0212] In this test, the plants which had been treated with 63 ppm of the active compound Ex-1, Ex-3, Ex-4, Ex-8, Ex-9, Ex-10, Ex-12, Ex-13, Ex-16, Ex-17, Ex-18, Ex-19, Ex-28, Ex-43, Ex-44 and Ex-45 showed a diseased leaf area of at most 15%, whereas the untreated plants showed 80% diseased leaf area.