Substituted [1,2,4]triazole and imidazole compounds as fungicides

Abstract

The present invention relates to compounds of the formula I

##STR00001##

wherein the variables are defined in the claims and the specification, to their preparation and their use as fungicides.

Claims

1-14. (canceled)

15. A compound of the formula I ##STR00026## wherein A is CH or N; R.sup.1 is C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl or C.sub.3-C.sub.6-cycloalkyl; wherein the aliphatic moieties of R.sup.1 are not further substituted or carry one, two, three or up to the maximum possible number of identical or different groups R.sup.1a which independently of one another are selected from: R.sup.1a halogen, OH, CN, C.sub.1-C.sub.4-alkoxy, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halogencycloalkyl and C.sub.1-C.sub.4-halogenalkoxy; wherein the cycloalkyl moieties of R.sup.1 are not further substituted or carry one, two, three, four, five or up to the maximum number of identical or different groups R.sup.1b which independently of one another are selected from: R.sup.1b halogen, OH, CN, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-halogenalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halogencycloalkyl and C.sub.1-C.sub.4-halogenalkoxy; R.sup.2 is hydrogen, C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.4-alkenyl or C.sub.2-C.sub.4-alkynyl; wherein the aliphatic moieties of R.sup.2 are not further substituted or carry one, two, three or up to the maximum possible number of identical or different groups R.sup.2a which independently of one another are selected from: R.sup.2a halogen, OH, CN, C.sub.1-C.sub.4-alkoxy, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halogencycloalkyl and C.sub.1-C.sub.4-halogenalkoxy; R.sup.3 is selected from halogen, CN, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkoxy, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.3-C.sub.6-cycloalkyl and S(O).sub.p(C.sub.1-C.sub.4-alkyl), wherein each of R.sup.3 is unsubstituted or further substituted by one, two, three or four R.sup.1a; wherein R.sup.3a is independently selected from halogen, CN, OH, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-halogenalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halogencycloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-halogenalkoxy; p is 0, 1 or 2; Z is halogen, CN, C.sub.1-C.sub.6-alkyl, Si(C.sub.1-C.sub.4-alkyl).sub.3, C.sub.1-C.sub.6-alkoxy or C(O)O(C.sub.1-C.sub.6-alkyl); wherein the aliphatic moieties of Z are not further substituted or carry one, two, three or four identical or different groups R.sup.Z, which independently of one another are selected from R.sup.Z halogen, CN, OH, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-halogenalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halogencycloalkyl, OC.sub.6H.sub.5, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-halogenalkoxy; and the N-oxides and the agriculturally acceptable salts thereof.

16. The compound of claim 15, wherein A is N.

17. The compound of claim 15, wherein A is CH.

18. The compound of claim 15, wherein Z is halogen.

19. The compound of claim 15, wherein Z is C.sub.1-C.sub.6-alkyl that is unsubstituted or substituted as defined in claim 15.

20. The compound of claim 15, wherein Z is C.sub.1-C.sub.6-alkoxy that is unsubstituted or substituted as defined in claim 15.

21. The compound of claim 15, wherein Z is Si(C.sub.1-C.sub.4-alkyl).sub.3.

22. The compound of claim 15, wherein R.sup.2 is hydrogen.

23. The compound of claim 15, wherein R.sup.3 is F, Cl, Br, CN, C.sub.1-C.sub.4-halogenalkyl, C.sub.1-C.sub.4-alkoxy or S(C.sub.1-C.sub.4-alkyl).

24. A composition, comprising a compound of claim 15, an N-oxide or an agriculturally acceptable salt thereof.

25. The composition according to claim 24, comprising additionally a further active substance.

26. A method for combating phytopathogenic fungi, comprising treating the fungi or the materials, plants, the soil or seeds to be protected against fungal attack with an effective amount of a composition comprising the compound of claim 15.

27. Seed, coated with a composition comprising the compound of claim 15, and/or an agriculturally acceptable salt thereof in an amount of from 0.1 to 10 kg per 100 kg of seed.

28. A method for combating phytopathogenic fungi, comprising treating the fungi or the materials, plants, the soil or seeds to be protected against fungal attack with an effective amount of a composition comprising the compound of claim 16.

29. A method for combating phytopathogenic fungi, comprising treating the fungi or the materials, plants, the soil or seeds to be protected against fungal attack with an effective amount of a composition comprising the compound of claim 17.

30. A method for combating phytopathogenic fungi, comprising treating the fungi or the materials, plants, the soil or seeds to be protected against fungal attack with an effective amount of a composition comprising the compound of claim 18.

31. A method for combating phytopathogenic fungi, comprising treating the fungi or the materials, plants, the soil or seeds to be protected against fungal attack with an effective amount of a composition comprising the compound of claim 19.

32. A method for combating phytopathogenic fungi, comprising treating the fungi or the materials, plants, the soil or seeds to be protected against fungal attack with an effective amount of a composition comprising the compound of claim 20.

33. A method for combating phytopathogenic fungi, comprising treating the fungi or the materials, plants, the soil or seeds to be protected against fungal attack with an effective amount of a composition comprising the compound of claim 21.

34. A method for combating phytopathogenic fungi, comprising treating the fungi or the materials, plants, the soil or seeds to be protected against fungal attack with an effective amount of a composition comprising the compound of claim 22.

Description

I. SYNTHESIS EXAMPLES

Example 1

Step 1.1:

[0591] ##STR00020##

[0592] To a solution of the bromide (20.0 g, 1.0 eq) in 1,4-dioxane (200 mL) were added copper(I) iodide (410 mg, 0.05 eq), sodium iodide (12.8 g, 2.0 eq), and N,N-1,2-cyclohexanediamine (608 mg, 0.1 eq) and the mixture was warmed to reflux for 16 h. After cooling to room temperature, a saturated solution of NH.sub.4Cl was added and the product was extracted into EtOAc. The combined organic extracts were dried over MgSO.sub.4 and concentrated. Purification of the residual crude product over a short plug of silica gel yielded the title compound (13.0 g, 76%) as oil. HPLC: t.sub.R=1.011 min; .sup.1H NMR (298 K, CDCl.sub.3): [ppm]=1.60 (3H), 4.30 (1H), 4.50 (1H), 4.65 (1H), 7.36 (2H), 7.80 (2H), 8.05 (1H).

Step 1.2: Synthesis of Compound I-1

[0593] ##STR00021##

[0594] To a solution of the iodide (200 mg, 1.0 eq) in piperidine (2 mL) and pyridine (2 mL) was added Pd(PPh.sub.3).sub.2Cl.sub.2 (17.7 mg, 0.05 eq), CuI (4.8 mg, 0.05 eq), and propargylic alcohol (70.6 mg, 2.5 eq) successively. The reaction mixture was stirred at room temperature until HPLC indicated complete conversion before it was concentrated under reduced pressure. The residue was dissolved in MTBE and filtered over silica gel. After removal of the solvent, the crude product was purified by preparative HPLC to afford the title compound (73.0 mg, 45%) as oil. HPLC: t.sub.R=0.798 min.

Example 2

Step 2.1:

[0595] Corresponding to step 1.1, the following compound was prepared with a yield of 70% (HPLC: t.sub.R=1.149 min):

##STR00022##

Example 3: Compound I-22

[0596] ##STR00023##

[0597] To a cold (78 C.) solution of di-iso-propylamine (1.68 g, 3.3 eq) in THF (50 mL) was added/7-BuLi (8.31 mL, 2.0 M in hexanes, 3.3 eq) and the mixture was stirred at this temperature. After 30 minutes, 2-bromo-1,1,1-trifluoroprop-2-ene (1.32 g, 1.5 eq) and ZnCl.sub.2.TMEDA (2.1 g, 1.65 eq) were added successively. The reaction vessel was warmed to ambient temperature over 1 h before a solution of the aryl iodide (2.00 g, 1.0 eq) in THF (10 mL) and Pd(PPh.sub.3).sub.4 (0.29 g, 0.05 eq) were added. The mixture was stirred at rt for 6 h, before the reaction was quenched by the addition of a saturated aqueous solution of NH.sub.4Cl. The aqueous layer was separated and extracted with EtOAc. The combined organic extracts were dried over Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford a crude product which was further purified by column chromatography. The title compound was isolated as colorless oil (0.79 g, 43%). HPLC: t.sub.R=1.128 min; .sup.1H NMR (500 MHz, 298 K, CDCl.sub.3): [ppm]=1.65 (3H), 4.40-4.50 (2H), 4.70 (1H), 7.66 (1H), 7.75 (1H), 7.80 (1H), 7.90 (1H), 8.05 (1H).

[0598] The following target compounds I.A were prepared in analogy to the steps above:

TABLE-US-00008 I.A [00024] Example No. R.sup.1 R.sup.2 R.sup.3 Z HPLC** t.sub.R/min I-1 CH.sub.3 H CF.sub.3 CH.sub.2OH 0.798 I-2 CH.sub.3 H CF.sub.3 (CH.sub.2).sub.2CH.sub.2Cl 1.125 I-3 CH.sub.3 H CF.sub.3 CHCH.sub.3OH 0.852 I-4 CH.sub.3 H CF.sub.3 CH.sub.2OCH.sub.3 0.958 I-5 CH.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH.sub.3 1.153 I-6 CH.sub.3 H CF.sub.3 C(CH.sub.3).sub.3 1.207 I-7 CH.sub.3 H CF.sub.3 CH.sub.2CH(CH.sub.3).sub.2 1.234 I-8 CH.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH.sub.2CH.sub.3 1.222 I-9 CH.sub.3 H CF.sub.3 CH.sub.2(CH.sub.2).sub.3CH.sub.3 1.288 I-10 CH.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CN 0.916 I-11 CH.sub.3 H CF.sub.3 CH.sub.2OCH(CH.sub.3).sub.2 1.076 I-12 CH.sub.3 H CF.sub.3 C(CH.sub.3).sub.2OCH.sub.3 1.068 I-13 C.sub.3H.sub.5 H Cl CH.sub.2CH.sub.2CH.sub.2Cl 1.208 I-14 C.sub.3H.sub.5 H Cl CH.sub.2OH 0.875 I-15 C.sub.3H.sub.5 H Cl CH(CH.sub.3)OH 0.928 I-16 C.sub.3H.sub.5 H Cl CH.sub.2OCH.sub.3 1.039 I-17 C.sub.3H.sub.5 H Cl CH.sub.2CH.sub.2CH.sub.3 1.241 I-18 C.sub.3H.sub.5 H Cl C(CH.sub.3).sub.3 1.3 I-19 C.sub.3H.sub.5 H Cl CH.sub.2CH(CH.sub.3).sub.2 1.304 I-20 CH.sub.3 H CF.sub.3 CH.sub.2Ophenyl 1.149 I-21 C.sub.3H.sub.5 H Cl CH.sub.2Ophenyl 1.227 I-22 CH.sub.3 H CF.sub.3 CF.sub.3 1.128 I-23 C.sub.3H.sub.5 H Cl Br 1.125 I-24 C.sub.3H.sub.5 H Cl CH.sub.2CH.sub.2CH.sub.2OH 0.937 I-25 C.sub.3H.sub.5 H Cl C(C.sub.2H.sub.5).sub.2OH 1.087 I-26 CH.sub.3 H CF.sub.3 CH(CH.sub.3)OH 0.835 I-27 C.sub.2H.sub.5 H Cl CH.sub.2CH.sub.2CH.sub.2OH 0.889 I-28 C.sub.2H.sub.5 H Cl CH.sub.2Ophenyl 1.168 I-29 C.sub.2H.sub.5 H Cl CH.sub.2CH.sub.2CH.sub.2Cl 1.149 I-30 C.sub.2H.sub.5 H Cl CH.sub.2OH 0.811 I-31 C.sub.2H.sub.5 H Cl CH(CH.sub.3)OH 0.867 I-32 C.sub.2H.sub.5 H Cl CH.sub.2CH.sub.2CH.sub.3 1.181 I-33 C.sub.2H.sub.5 H Cl C(CH.sub.3).sub.3 1.242 I-34 C.sub.2H.sub.5 H Cl CH.sub.2CH.sub.2CH.sub.2CH.sub.3 1.254 I-35 C.sub.3H.sub.5 H Cl Cl 1.145 I-36 C.sub.3H.sub.5 H Cl CF.sub.3 1.186 I-37 CH.sub.3 H CF.sub.3 CH(CH.sub.3).sub.2 1.106 I-38 C.sub.2H.sub.5 H Cl CH(CH.sub.3).sub.2 1.155 I-39 C.sub.2H.sub.5 H Cl CF.sub.3 1.174 C.sub.3H.sub.5 = cyclopropyl **HPLC method Data: Mobile Phase: A: Wasser + 0.1% T FA; B: acetonitrile; Gradient: 5% B to 100% B in 1.5 min; Temperature: 60 C.; MS-Method: ESI positive; mass area (m/z): 100-700; Flow: 0.8 ml/min to 1.0 ml/min in 1.5 min; Column: Kinetex XB C18 1.7 50 2.1 mm; Aparatus: Shimadzu Nexera LC-30 LCMS-2020.

[0599] The following target compounds I.C were prepared in analogy to the steps above:

TABLE-US-00009 I.C [00025] Example No. R.sup.1 R.sup.2 Z HPLC** t.sub.R/min I.C-1 C(CH.sub.3).sub.3 H CH.sub.2CH.sub.2CH.sub.2OH 0.975 I.C-2 C(CH.sub.3).sub.3 H CH.sub.2CH(CH.sub.3).sub.2 1.312 I.C-3 C(CH.sub.3).sub.3 H C(C.sub.2H.sub.3).sub.2OH 1.137 I.C-4 C(CH.sub.3).sub.3 H CH.sub.2OH 0.903 I.C-5 C(CH.sub.3).sub.3 H CH(CH.sub.3)OH 0.952 I.C-6 C(CH.sub.3).sub.3 H CH.sub.2OCH.sub.3 1.062 I.C-7 C(CH.sub.3).sub.3 H CH.sub.2CH.sub.2CH.sub.3 1.252 I.C-8 C(CH.sub.3).sub.3 H C(CH.sub.3).sub.3 1.306 I.C-9 C(CH.sub.3).sub.3 H CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.3 1.381 I.C-10 C(CH.sub.3).sub.3 H CH.sub.2CH.sub.2CH.sub.2CH.sub.3 1.346 I.C-11 C(CH.sub.3).sub.3 H CH(CH.sub.3).sub.2 1.215 I.C-12 C(CH.sub.3).sub.3 H CF.sub.3 1.228 **HPLC method Data: Mobile Phase: A: Wasser + 0.1% T FA; B: acetonitrile; Gradient: 5% B to 100% B in 1.5 min; Temperature: 60 C.; MS-Method: ESI positive; mass area (m/z): 100-700; Flow: 0.8 ml/min to 1.0 ml/min in 1.5 min; Column: Kinetex XB C18 1.7 50 2.1 mm; Aparatus: Shimadzu Nexera LC-30 LCMS-2020.

II. Examples of the Action Against Harmful Fungi

[0600] The fungicidal action of the compounds of the formula I was demonstrated by the following experiments:

Microtest

[0601] The active compounds were formulated separately as a stock solution having a concentration of 10000 ppm in dimethyl sulfoxide.

M1. Activity Against the Grey Mold Botrytis cinerea in the Microtiterplate Test (Botrci)

[0602] The stock solutions were mixed according to the ratio, pipetted onto a micro titer plate (MTP) and diluted with water to the stated concentrations. A spore suspension of Botrci cinerea in an aqueous biomalt or yeast-bactopeptone-sodiumacetate solution was then added. The plates were placed in a water vapor-saturated chamber at a temperature of 18 C. Using an absorption photometer, the MTPs were measured at 405 nm 7 days after the inoculation. Compounds I-19, I-25, I-16, I-17, I-18, I-7, I-8, I-20, I-2, I-11, I-26, I-4, I-5, I-23, I-27, I-28, I-29, I-31, I-32, I-33, I-12, I-34, I-35, I-36, I-39 and I-22, respectively, showed a growth of 18% or less at 31 ppm.

[0603] Compounds C.I-1, C.I-2, C.I-3, C.I-6, C.I-7 and C.I-12, respectively, showed a growth of 13% or less at 31 ppm.

M2. Activity Against Net Blotch Pyrenophora teres on Barley in the Microtiter Test (Pyrnte)

[0604] The stock solutions were mixed according to the ratio, pipetted onto a micro titer plate (MTP) and diluted with water to the stated concentrations. A spore suspension of Pyrenophora teres in an aqueous biomalt or yeast-bactopeptone-glycerine solution was then added. The plates were placed in a water vapor-saturated chamber at a temperature of 18 C. Using an absorption photometer, the MTPs were measured at 405 nm 7 days after the inoculation. Compounds I-19, I-25, I-16, I-17, I-18, I-7, I-20, I-27, I-28, I-29, I-32, I-33, I-34 and I-35, respectively, showed a growth of 15% or less at 31 ppm.

[0605] Compounds C.1-2, C.1-3 and C.1-8, respectively, showed a growth of 12% or less at 31 ppm.

M3. Activity Against Leaf Blotch on Wheat Caused by Septoria tritici (Septtr)

[0606] The stock solutions were mixed according to the ratio, pipetted onto a micro titer plate (MTP) and diluted with water to the stated concentrations. A spore suspension of Septoria tritici in an aqueous biomalt or yeast-bactopeptone-glycerine solution was then added. The plates were placed in a water vapor-saturated chamber at a temperature of 18 C. Using an absorption photometer, the MTPs were measured at 405 nm 7 days after the inoculation. Compounds I-19, I-25, I-14, I-16, I-17, I-7, I-8, I-20, I-2, I-11, I-26, I-4, I-5, I-23, I-27, I-29, I-31, I-32, I-12, I-34, I-35, I-36, I-39 and I-22, respectively, showed a growth of 20% or less at 31 ppm.

[0607] Compounds C.I-1, C.I-3, I.C-5, C.I-6, C.I-7 and C.I-12, respectively, showed a growth of 15% or less at 31 ppm.

M4. Activity Against Early Blight Caused by Alternaria solani (Alteso)

[0608] The stock solutions were mixed according to the ratio, pipetted onto a micro titer plate (MTP) and diluted with water to the stated concentrations. A spore suspension of Alternaria solani in an aqueous biomalt or yeast-bactopeptone-glycerine solution was then added. The plates were placed in a water vapor-saturated chamber at a temperature of 18 C. Using an absorption photometer, the MTPs were measured at 405 nm 7 days after the inoculation. Compounds I-19, I-25, I-14, I-16, I-17, I-18, I-7, I-8, I-20, I-2, I-11, I-4, I-5, I-23, I-27, I-28, I-29, I-30, I-31, I-32, I-33, I-12, I-34 and I-35, respectively, showed a growth of 7% or less at 31 ppm.

[0609] Compounds C.I-1, C.I-2, C.I-5, C.I-6 and C.I-7, respectively, showed a growth of 13% or less at 31 ppm.

M5. Activity Against Root Rot Caused by Fusarium culmotum (Fusacu)

[0610] The stock solutions were mixed according to the ratio, pipetted onto a micro titer plate (MTP) and diluted with water to the stated concentrations. A spore suspension of Fusarium culmorum in an aqueous biomalt or yeast-bactopeptone-glycerine solution was then added. The plates were placed in a water vapor-saturated chamber at a temperature of 18 C. Using an absorption photometer, the MTPs were measured at 405 nm 7 days after the inoculation. Compounds I-19, I-25, I-16, I-17, I-18, I-7, I-8, I-5, I-23, I-28, I-29, I-32, I-33, I-34 and I-35, respectively, showed a growth of 17% or less at 31 ppm.

[0611] Compound C.I-2 showed a growth of 0% at 31 ppm.

[0612] M6. Activity Against Rice Blast Pyricularia Oryzae in the Microtiterplate Test (Pyrior)

[0613] The stock solutions were mixed according to the ratio, pipetted onto a micro titer plate (MTP) and diluted with water to the stated concentrations. A spore suspension of Pyricularia oryzae in an aqueous biomalt or yeast-bactopeptone-glycerine solution was then added. The plates were placed in a water vapor-saturated chamber at a temperature of 18 C. Using an absorption photometer, the MTPs were measured at 405 nm 7 days after the inoculation. Compounds I-19, I-25, I-16, I-17, I-18, I-7, I-8, I-20, I-2, I-11, I-5, I-23, I-27, I-28, I-29, I-31, I-32, I-33, I-12, I-34, I-35, I-36, I-39 and I-22, respectively, showed a growth of 9% or less at 31 ppm.

[0614] Compounds C.I-2, C.I-3, I.C-6, C.I-7, I.C-8 and C.I-12, respectively, showed a growth of 20% or less at 31 ppm.

[0615] The measured parameters were compared to the growth of the active compound-free control variant (100%) and the fungus-free and active compound-free blank value to determine the relative growth in % of the pathogens in the respective active compounds.