NOVEL TRIAZOLE DERIVATIVES

Abstract

The present invention relates to novel triazole derivatives of formula

##STR00001##

to processes for preparing these compounds, to certain intermediates, to compositions comprising these compounds, and to the use thereof as biologically active compounds, especially for control of harmful microorganisms in crop protection and in the protection of materials and as plant growth regulators.

Claims

1. A triazole derivative of formula (I) ##STR00068## wherein R.sup.1 represents 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.8-cycloalkyl, C.sub.3-C.sub.8-cycloalkyl-C.sub.1-C.sub.4-alkyl, phenyl, phenyl-C.sub.1-C.sub.4-alkyl, phenyl-C.sub.2-C.sub.4-alkenyl or phenyl-C.sub.2-C.sub.4-alkynyl, R.sup.2 represents 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.8-cycloalkyl, C.sub.3-C.sub.8-cycloalkyl-C.sub.1-C.sub.4-alkyl, phenyl, phenyl-C.sub.1-C.sub.4-alkyl, phenyl-C.sub.2-C.sub.4-alkenyl or phenyl-C.sub.2-C.sub.4-alkynyl, wherein the aliphatic moieties, excluding cycloalkyl moieties, of R.sup.1 and/or R.sup.2 may carry 1, 2, 3 or up to the maximum possible number of identical or different groups R.sup.a which independently of one another are selected from halogen, CN, nitro, phenyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-halogenalkoxy, wherein the phenyl may be substituted by 1, 2, 3, 4 or 5 substituents selected independently from each other from halogen, CN, nitro, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-halogenalkyl, C.sub.1-C.sub.4-halogenalkoxy, and wherein the cycloalkyl and/or phenyl moieties of R.sup.1 and/or R.sup.2 may carry 1, 2, 3, 4, 5 or up to the maximum number of identical or different groups R.sup.b which independently of one another are selected from halogen, CN, nitro, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-halogenalkyl and C.sub.1-C.sub.4-halogenalkoxy; each R.sup.4 represents independently of one another C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halogencycloalkyl, C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.6-cycloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-halogenalkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.2-C.sub.6-halogenalkynyl, C.sub.1-C.sub.4-alkylsulfanyl, C.sub.1-C.sub.4-halogenalkylsulfanyl, C.sub.1-C.sub.6-alkylsulfonyl, C.sub.6-C.sub.10-arylsulfonyl, C.sub.1-C.sub.6-alkyl-SO.sub.2NH, C.sub.6-C.sub.10-aryl-SO.sub.2NH, formyl, 5-, 6- or 7-membered saturated heterocycloalkyl containing up to 4 heteroatoms selected from N, O and S, or C(R.sup.4a)NOR.sup.4b, wherein R.sup.4a and R.sup.4b represent independently from each other hydrogen, C.sub.1-C.sub.6-alkyl or phenyl; m is an integer and is 1, 2, 3, 4 or 5; Y represents a 6-membered aromatic heterocycle containing 1 or 2 nitrogen atom(s) as heteroatom(s) selected from ##STR00069## wherein Y is connected to the O of formula (I) via the bonds identified with U and Y is connected to the CR.sup.1(OR.sup.2) moiety of formula (I) via the bonds identified with V and wherein R represents hydrogen, C.sub.1-C.sub.2-halogenalkyl, C.sub.1-C.sub.2-halogenalkoxy, C.sub.1-C.sub.2-alkylcarbonyl or halogen; each R.sup.3 represents independently from each other halogen, CN, nitro, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-halogenalkyl, C.sub.1-C.sub.4-alkoxy or C.sub.1-C.sub.4-halogenalkoxy; n is an integer and is 0 or 1; and/or a salt or N-oxide thereof.

2. The triazole derivative of formula (I) according to claim 1, wherein R.sup.1 represents hydrogen, methyl, ethyl, propyl, isopropyl, butyl, cyclopropyl, CF.sub.3, benzyl, allyl, CH.sub.2CCCH.sub.3 or CH.sub.2CCH, and/or R.sup.2 represents hydrogen and/or a salt or N-oxide thereof.

3. The triazole derivative of formula (I) according to claim 1, wherein each R.sup.4 represents independently from each other cyclopropyl, 1-fluorocyclopropyl, 1-chlorocyclopropyl, 1-methylcyclopropyl, vinyl, allyl, ethynyl, prop-2-ynyl, SCH.sub.3, SCH.sub.2CH.sub.3, SCH.sub.2F, SCHF.sub.2, SCF.sub.3, methylsulfonyl, phenylsulfonyl, methyl-SO.sub.2NH, phenyl-SO.sub.2NH, formyl, dioxolanyl, dioxanyl, or C(R.sup.4a)NOR.sup.4b, wherein R.sup.4a and R.sup.4b represent independently from each other hydrogen or C.sub.1-C.sub.4-alkyl, optionally hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert.-butyl, optionally hydrogen or methyl, and/or m is 1 and/or a salt or N-oxide thereof.

4. The triazole derivative of formula (I) according to claim 1, wherein Y represents a 6-membered aromatic heterocycle containing 1 or 2 nitrogen atom(s) as heteroatom(s) selected from ##STR00070## wherein Y is connected to the O of formula (I) via the bonds identified with U and Y is connected to the CR.sup.1(OR.sup.2) moiety of formula (I) via the bonds identified with V and/or a salt or N-oxide thereof.

5. The triazole derivative of formula (I) according to claim 1, wherein R represents CF.sub.3 or Cl, and/or n is 0 and/or a salt or N-oxide thereof.

6. The triazole derivative of formula (I) according to claim 1, wherein R.sup.1 represents hydrogen or C.sub.1-C.sub.4-alkyl; R.sup.2 represents hydrogen; R.sup.4 represents cyclopropyl, ethynyl, SCH.sub.3, SCF.sub.3, formyl, 1,3-dioxolan-2-yl, or C(R.sup.4a)NOR.sup.4b, wherein R.sup.4a represents hydrogen, and R.sup.4b represents hydrogen; m is 1; Y represents ##STR00071## wherein Y is connected to the O of formula (I) via the bonds identified with U and Y is connected to the CR.sup.1(OR.sup.2) moiety of formula (I) via the bonds identified with V and R represents C.sub.1-halogenalkyl, F or Cl; n is 0; and/or a salt or N-oxide thereof.

7. The triazole derivative of formula (I) according to claim 1, wherein R.sup.4 is located in the 4-position of the phenyl moiety of formula (I), and/or a salt or N-oxide thereof.

8. The triazole derivative of formula (I) according to claim 1, wherein Y represents ##STR00072## wherein Y is connected to the O of formula (I) via the bonds identified with U and Y is connected to the CR.sup.1(OR.sup.2) moiety of formula (I) via the bonds identified with V, and/or a salt or N-oxide thereof.

9. A compound of formula (VII) ##STR00073## wherein each R.sup.4 represents independently of one another C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halogencycloalkyl, C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.6-cycloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-halogenalkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.2-C.sub.6-halogenalkynyl, C.sub.1-C.sub.4-alkylsulfanyl, C.sub.1-C.sub.4-halogenalkylsulfanyl, C.sub.1-C.sub.6-alkylsulfonyl, C.sub.6-C.sub.10-arylsulfonyl, C.sub.1-C.sub.6-alkyl-SO.sub.2NH, C.sub.6-C.sub.10-aryl-SO.sub.2NH, formyl, 5-, 6- or 7-membered saturated heterocycloalkyl containing up to 4 heteroatoms selected from N, O and S, or C(R.sup.4a)NOR.sup.4b, wherein R.sup.4a and R.sup.4b represent independently from each other hydrogen, C.sub.1-C.sub.6-alkyl or phenyl; m is an integer and is 1, 2, 3, 4 or 5; Y represents a 6-membered aromatic heterocycle containing 1 or 2 nitrogen atom(s) as heteroatom(s) selected from ##STR00074## wherein Y is connected to the O of formula (VII) via the bonds identified with U and Y is connected to the C(O)CH.sub.2 moiety of formula (VII) via the bonds identified with V and wherein R represents hydrogen, C.sub.1-C.sub.2-halogenalkyl, C.sub.1-C.sub.2-halogenalkoxy, C.sub.1-C.sub.2-alkylcarbonyl or halogen; each R.sup.3 represents independently from each other halogen, CN, nitro, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-halogenalkyl, C.sub.1-C.sub.4-alkoxy or C.sub.1-C.sub.4-halogenalkoxy; n is an integer and is 0 or 1; and/or a salt or N-oxide thereof.

10. A composition for controlling one or more harmful microorganisms, optionally for controlling phytopathogenic harmful fungi, comprising at least one compound according to claim 1 and/or at least one compound of formula (VII) (VII). ##STR00075## wherein each R.sup.4 represents independently of one another C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halogencycloalkyl, C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.6-cycloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-halogenalkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.2-C.sub.6-halogenalkynyl, C.sub.1-C.sub.4-alkylsulfanyl, C.sub.1-C.sub.4-halogenalkylsulfanyl, C.sub.1-C.sub.6-alkylsulfonyl, C.sub.6-C.sub.10-arylsulfonyl, C.sub.1-C.sub.6-alkyl-SO.sub.2NH, C.sub.6-C.sub.10-aryl-SO.sub.2NH, formyl, 5-, 6- or 7-membered saturated heterocycloalkyl containing up to 4 heteroatoms selected from N, O and S, or C(R.sup.4a)NOR.sup.4b, wherein R.sup.4a and R.sup.4b represent independently from each other hydrogen, C.sub.1-C.sub.6-alkyl or phenyl; m is an integer and is 1, 2, 3, 4 or 5; Y represents a 6-membered aromatic heterocycle containing 1 or 2 nitrogen atom(s) as heteroatom(s) selected from ##STR00076## wherein Y is connected to the O of formula (VII) via the bonds identified with U and Y is connected to the C(O)CH.sub.2 moiety of formula (VII) via the bonds identified with V and wherein R represents hydrogen, C.sub.1-C.sub.2-halogenalkyl, C.sub.1-C.sub.2-halogenalkoxy, C.sub.1-C.sub.2-alkylcarbonyl or halogen; each R.sup.3 represents independently from each other halogen, CN, nitro, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-halogenalkyl, C.sub.1-C.sub.4-alkoxy or C.sub.1-C.sub.4-halogenalkoxy; n is an integer and is 0 or 1; and/or a salt or N-oxide thereof and at least one extender and/or surfactant.

11. A method for controlling one or more harmful microorganisms in crop protection and/or in protection of one or more materials, comprising applying at least one compound according to claim 1 and/or at least one compound of formula (VII) ##STR00077## wherein each R.sup.4 represents independently of one another C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halogencycloalkyl, C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.6-cycloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-halogenalkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.2-C.sub.6-halogenalkynyl, C.sub.1-C.sub.4-alkylsulfanyl, C.sub.1-C.sub.4-halogenalkylsulfanyl, C.sub.1-C.sub.6-alkylsulfonyl, C.sub.6-C.sub.10-arylsulfonyl, C.sub.1-C.sub.6-alkyl-SO.sub.2NH, C.sub.6-C.sub.10-aryl-SO.sub.2NH, formyl, 5-, 6- or 7-membered saturated heterocycloalkyl containing up to 4 heteroatoms selected from N, O and S, or C(R.sup.4a)NOR.sup.4b, wherein R.sup.4a and R.sup.4b represent independently from each other hydrogen, C.sub.1-C.sub.6-alkyl or phenyl; m is an integer and is 1, 2, 3, 4 or 5; Y represents a 6-membered aromatic heterocycle containing 1 or 2 nitrogen atom(s) as heteroatom(s) selected from ##STR00078## wherein Y is connected to the O of formula (VII) via the bonds identified with U and Y is connected to the C(O)CH.sub.2 moiety of formula (VII) via the bonds identified with V and wherein R represents hydrogen, C.sub.1-C.sub.2-halogenalkyl, C.sub.1-C.sub.2-halogenalkoxy, C.sub.1-C.sub.2-alkylcarbonyl or halogen; each R.sup.3 represents independently from each other halogen, CN, nitro, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-halogenalkyl, C.sub.1-C.sub.4-alkoxy or C.sub.1-C.sub.4-halogenalkoxy; n is an integer and is 0 or 1; and/or a salt or N-oxide thereof and/or a composition thereof to the harmful microorganisms and/or a habitat thereof.

12. A product comprising at least one compound according to claim 1 and/or a composition thereof for control of one or more harmful microorganisms, optionally phytopathogenic harmful fungi, in crop protection and/or in protection of one or more materials.

13. (canceled)

14. (canceled)

15. (canceled)

16. (canceled)

17. (canceled)

18. (canceled)

19. (canceled)

20. (canceled)

Description

PREPARATION EXAMPLES

[0503] Preparation of Compounds of Formula (I) According to Process A:

Preparation of 2-[6-(4-methylsulfanylphenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol (I-03)

[0504] ##STR00036##

[0505] To a solution of 1-[6-(4-methylsulfanylphenoxy)-2-(trifluoromethyl)-3-pyridyl]-2-(1,2,4-triazol-1-yl)ethanone (1.60 g, 4.06 mmol) in dry THF (15 mL) was added methylmagnesium bromide (2.7 mL, 8.11 mmol, 3M solution in ethyl ether) drop wise at 0 C., then warmed to 21 C. (room temperature, rt), and stirred for 1 hour (h) at rt, before the mixture was quenched with water, NH.sub.4Cl (saturated aqueous solution), extracted with dichloromethane, dried (over MgSO.sub.4), and concentrated. To improve the yield, the crude material was taken up in dry THF (15 mL), magnesium bromide diethyl etherate (2.1 g, 8.11 mmol) added and cooled to 0 C., before methylmagnesium bromide (2.7 mL, 8.11 mmol, 3M solution in ethyl ether) was added, the mixture warmed to rt, and stirred for 1 h at rt, before the mixture was quenched with water, NH.sub.4Cl (saturated aqueous solution), extracted with dichloromethane, dried (over MgSO.sub.4), and concentrated. In order to further improve the yield, the crude material was taken up in dry THF (15 mL), magnesium bromide diethyl etherate (2.1 g, 8.11 mmol) added and cooled to 0 C., before methylmagnesium bromide (2.7 mL, 8.11 mmol, 3M solution in ethyl ether) was added, the mixture warmed to rt, and stirred for 1 h at rt, before the mixture was quenched with water, NH.sub.4Cl (saturated aqueous solution), extracted with dichloromethane, dried (over MgSO.sub.4), and concentrated. Preparative HPLC gave 356.1 mg (21% yield, 99% pure) of the target compound as colorless glass.

[0506] MS (ESI): 411.10 ([M+H].sup.+)

Preparation of 1-[6-(4-methylsulfanylphenoxy)-2-(trifluoromethyl)-3-pyridyl]-2-(1,2,4-triazol-1-yl)ethanol (I-02)

[0507] ##STR00037##

[0508] To a solution of 1-[6-(4-methylsulfanylphenoxy)-2-(trifluoromethyl)-3-pyridyl]-2-(1,2,4-triazol-1-yl)ethanone (600 mg, 1.52 mmol) in dry methanol (5.0 mL) at 5 C. was added sodium borohydride (115 mg, 3.04 mmol), the cooling bath was removed, the mixture warmed to rt and stirred for 1 h. The mixture was then quenched with water, diluted with dichloromethane, filtered over ChemElut, filtered over a small plug of silica, and concentrated to give 605 mg (98% yield, 98% pure) of the target compound as a colorless oil.

[0509] MS (ESI): 397.09 ([M+H].sup.+)

Preparation of 1-[6-[4-(hydroxymethyl)phenoxy]-2-(trifluoromethyl)-3-pyridyl]-2-(1,2,4-triazol-1-yl)ethanol and 1-[6-[4-(1,3-dioxolan-2-yl)phenoxy]-2-(trifluoromethyl)-3-pyridyl]-2-(1,24-triazol-1-yl)ethanol

[0510] ##STR00038##

[0511] To a solution of a mixture of 4-[[5-[2-(1,2,4-triazol-1-yl)acetyl]-6-(trifluoromethyl)-2-pyridyl]oxy]benzaldehyde and 1-[6-[4-(1,3-dioxolan-2-yl)phenoxy]-2-(trifluoromethyl)-3-pyridyl]-2-(1,2,4-triazol-1-yl)ethanone (1.5 g) in dry methanol (10.0 mL) at 5 C. was added sodium borohydride (300 mg, 7.97 mmol), the cooling bath was removed, the mixture warmed to rt and stirred for 1 h. The mixture was then quenched with water, diluted with dichloromethane, filtered over ChemElut, and concentrated. Flash column chromatography (gradient, up to DCM/10% MeOH in DCM=70/30, 254 nm) yielded 550 mg of the target compound 1-[6-[4-(1,3-dioxolan-2-yl)phenoxy]-2-(trifluoromethyl)-3-pyridyl]-2-(1,2,4-triazol-1-yl)ethanol (29% yield, 90% pure) as a colorless oil.

[0512] MS (ESI): 423.12 ([M+H].sup.+)

[0513] Preparation of Compounds of Formula (I) Via Derivatization:

Preparation of 4-[[5-[1-hydroxy-2-(1,2,4-triazol-1-yl)ethyl]-6-(trifluoromethyl)-2-pyridyl]oxy]benzaldehyde (I-01)

[0514] ##STR00039##

[0515] To a solution of 1-[6-[4-(1,3-dioxolan-2-yl)phenoxy]-2-(trifluoromethyl)-3-pyridyl]-2-(1,2,4-triazol-1-yl)ethanol (550 mg, 3.98 mmol) in THF (5.0 mL) was added a solution of HCl (0.1 mL of a 0.1 M solution of HCl in water), the resulting mixture stirred at 40 C. for 3 h, quenched with water, diluted with dichloromethane (DCM), filtered over ChemElut, and concentrated. Preparative HPLC yielded 264 mg (53% yield, 98% pure) of the target compound as a colorless oil.

Preparation of 4-[[5-[1-hydroxy-2-(1,2,4-triazol-1-yl)ethyl]-6-(trifluoromethyl)-2-pyridyl]oxy]benzaldehyde Oxime (I-04)

[0516] ##STR00040##

[0517] To a solution of 4-[[5-[1-hydroxy-2-(1,2,4-triazol-1-yl)ethyl]-6-(trifluoromethyl)-2-pyridyl]oxy]benzaldehyde (128 mg, 0.338 mmol) in ethanol (3.0 mL) was added at room temperature hydroxylamine (1.7 mL of a 50% solution in H.sub.2O), stirred for 1 h at rt, quenched with NH.sub.4Cl (saturated aqueous solution), diluted with water, extracted with CH.sub.2Cl.sub.2, filtered over phase separation filter, and concentrated. Preparative HPLC gave 100.3 mg (74% yield, 98% pure) of the target compound as a colorless solid.

[0518] MS (ESI): 393.10 ([M].sup.+)

[0519] Preparation of Compounds of the Formula (VII) According to Process A:

Preparation of 1-[6-(4-methylsulfanylphenoxy)-2-(trifluoromethyl)-3-pyridyl]-2-(1,2,4-triazol-1-yl)ethanone (VII-02)

[0520] ##STR00041##

[0521] A mixture of 2-bromo-1-[6-(4-methylsulfanylphenoxy)-2-(trifluoromethyl)-3-pyridyl]ethanone (22.8 g, 28.6 mmol) and 1H-1,2,4-triazole (2.37 g, 34.3 mmol) in acetonitrile (100 mL) was heated to 50 C., before potassium carbonate (5.14 g, 37.2 mmol) was added. The heating was continued for 2 h, before water was added, the mixture extracted with dichloromethane, dried (over Na.sub.2SO.sub.4), and concentrated. Flash column chromatography (gradient, up to DCM/10% MeOH in DCM=80/20, 254 nm) gave 7.7 g (67% yield, 99% pure) of the target compound as a colorless solid.

[0522] MS (ESI): 395.07 ([M+H].sup.+)

Preparation of 4-[[5-[2-(1,2,4-triazol-1-yl)acetyl]-6-(trifluoromethyl)-2-pyridyl]oxy]benzaldehyde (VII-01) and 1-[6-[4-(1,3-dioxolan-2-yl)phenoxy]-2-(trifluoromethyl)-3-pyridyl]-2-(1,2,4-triazol-1-yl)ethanone

[0523] ##STR00042##

[0524] A 50/50 mixture of 4-[[5-(2-bromoacetyl)-6-(trifluoromethyl)-2-pyridyl]oxy]benzaldehyde and 2-bromo-1-[6-[4-(1,3-dioxolan-2-yl)phenoxy]-2-(trifluoromethyl)-3-pyridyl]ethanone (4.00 g) and 1H-1,2,4-triazole (0.68 g, 8.24 mmol) in acetonitrile (30 mL) was heated to 70 C., before potassium carbonate (1.48 g, 10.7 mmol) was added. The heating was continued for 30 min, before water was added, the mixture extracted with dichloromethane, dried (over Na.sub.2SO.sub.4), and concentrated. Flash column chromatography (gradient, up to DCM/10% MeOH in DCM=80/20, 254 nm) gave 1.8 g (34% yield, 59% pure) of the target compound (VII-01) as a colorless oil. The impurity was the corresponding dioxolane-protected analog. A small portion was further purified by HPLC for analysis.

[0525] MS (ESI)[VII-01]: 377.08 ([M+H].sup.+)

[0526] Preparation of Compounds of the Formula (VII) in Analogy to Process F:

Preparation of 1-[6-(4-ethynylphenoxy)-2-(trifluoromethyl)-3-pyridyl]-2-(1,2,4-triazol-1-yl)ethanone (VII-04)

[0527] ##STR00043##

[0528] In a sealed tube under argon, 1-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-2-(1,2,4-triazol-1-yl)ethanone (250 mg, 0.585 mmol), trimethylsilylacetylene (63.2 mg, 0.644 mmol), dichlorobis(triphenylphosphine)palladium(II) (22.6 mg, 0.032 mmol), copper(I) iodide (6.13 mg, 0.032 mmol), triphenylphosphine (30.7 mg, 0.11 mmol), diethylamine (0.91 mL, 8.8 mmol) and 5 mL of dry degassed DMF were heated for 2 h at 90 C. The mixture was then quenched with water and filtered over ChemElut, filter column washed with dichloromethane, and concentrated. The crude mixture was then taken up in THF (5.0 mL), treated with tetra-n-butylammonium fluoride (153 mg, 0.585 mmol), stirred for 1 h at rt, then concentrated. Preparative HPLC gave 21 mg (9% yield, 96% purity) of the target compound as a colorless solid.

[0529] MS (ESI): 373.08 ([M+H].sup.+)

[0530] Preparation of Compounds of the Formula (VI) According to Process A:

Preparation of 2-bromo-1-[6-(4-methylsulfanylphenoxy)-2-(trifluoromethyl)-3-pyridyl]ethanone

[0531] ##STR00044##

[0532] A mixture of 1-[6-(4-methylsulfanylphenoxy)-2-(trifluoromethyl)-3-pyridyl]ethanone (15.0 g, 36.7 mmol) and phenyltrimethylammonium tribromide (14.5 g, 38.5 mmol) in THF (150 mL) was stirred at rt for 2 h, before the mixture was concentrated, dried (over Na.sub.2SO.sub.4), and concentrated, to give 22.8 g (78% yield, 51% pure) of the target compound as a pale yellow oil, which was used in the next step without further purification.

[0533] MS (ESI): 404.96 ([M].sup.+)

Preparation of 2-bromo-1-[6-[4-(1,3-dioxolan-2-yl)phenoxy]-2-(trifluoromethyl)-3-pyridyl]ethanone and 4-[[5-(2-bromoacetyl)-6-(trifluoromethyl)-2-pyridyl]oxy]benzaldehyde

[0534] ##STR00045##

[0535] A mixture of 1-[6-[4-(1,3-dioxolan-2-yl)phenoxy]-2-(trifluoromethyl)-3-pyridyl]ethanone (7.00 g, 19.8 mmol) and tetrabutylammonium tribromide (10.0 g, 20.8 mmol) in acetonitrile (100 mL) was stirred at rt for 16 h, before the mixture was concentrated, dried (over Na.sub.2SO.sub.4), and concentrated. Flash column chromatography (gradient, heptane/ethyl acetate=80/20, 254 nm) gave 4.0 g of a mixture that contained roughly 50/50 of the target compound 2-bromo-1-[6-[4-(1,3-dioxolan-2-yl)phenoxy]-2-(trifluoromethyl)-3-pyridyl]ethanone and its de-protected analogue 4-[[5-(2-bromoacetyl)-6-(trifluoromethyl)-2-pyridyl]oxy]benzaldehyde as a colorless oil, which was used in the next step without further purification.

[0536] MS (ESI) [2-bromo-1-[6-[4-(1,3-dioxolan-2-yl)phenoxy]-2-(trifluoromethyl)-3-pyridyl]ethanone]: 432.00 ([M].sup.+)

[0537] MS (ESI) [4-[[5-(2-bromoacetyl)-6-(trifluoromethyl)-2-pyridyl]oxy]benzaldehyde]: 388.01 ([M].sup.+)

[0538] Preparation of Compounds of the Formula (V) According to Process B:

Preparation of 1-[6-(4-methylsulfanylphenoxy)-2-(trifluoromethyl)-3-pyridyl]ethanone (V-02)

[0539] ##STR00046##

[0540] A mixture of 1-[6-chloro-2-(trifluoromethyl)-3-pyridyl]ethanone (11.0 g, 49.2 mmol), 4-methylsulfanylphenol (7.24 g, 51.6 mmol), and potassium carbonate (10.2 g, 73.8 mmol) in acetonitrile (100 mL) was heated for 16 h at 80 C. The reaction mixture was then cooled to rt, water added, extracted with dichloromethane, dried (over Na.sub.2SO.sub.4), and concentrated. Flash column chromatography (gradient, up to heptane/ethyl acetate=90/10, 254 nm) gave 15.0 g (76% yield, 82% pure) of the target compound as a colorless oil.

[0541] MS (ESI): 328.05 ([M+H].sup.+)

[0542] Preparation of Compounds of the Formula (V) According to Process D:

Preparation of 1-[6-[4-(1,3-dioxolan-2-yl)phenoxy]-2-(trifluoromethyl)-3-pyridyl]ethanone (V-01)

[0543] ##STR00047##

[0544] To a solution of 6-[4-(1,3-dioxolan-2-yl)phenoxy]-N-methoxy-N-methyl-2-(trifluoromethyl)pyridine-3-carboxamide (11.9 g, 29.9 mmol) in THF (100 mL) at rt was added methyl magnesium bromide (19.9 mL, 59.7 mmol, 3M solution in ethyl ether). The mixture was stirred for 1 h at rt, before the mixture was quenched with water, NH.sub.4Cl (saturated aqueous solution), extracted with dichloromethane, dried (over Na.sub.2SO.sub.4), and concentrated. Purification via flash column chromatography (gradient, up to heptane/ethyl acetate=70/30, 254 nm) gave 7.50 g (68% yield, 96% pure) of the target compound as a colorless oil.

[0545] MS (ESI): 354.09 ([M+H].sup.+)

[0546] Preparation of Compounds of the Formula (XVI) According to Process D:

Preparation of 6-(4-formylphenoxy)-N-methoxy-N-methyl-2-(trifluoromethyl)pyridine-3-carboxamide

[0547] ##STR00048##

[0548] A mixture of 6-chloro-N-methoxy-N-methyl-2-(trifluoromethyl)pyridine-3-carboxamide (18.0 g, 67.0 mmol), 4-hydroxybenzaldehyde (8.18 g, 67.0 mmol), potassium carbonate (23.1 g, 167 mmol), copper(I) iodide (638 mg, 3.35 mmol), and tetramethylethylenediamine (TMEDA) (1.0 mL, 6.70 mmol) in DMSO (80 mL) was heated for 2.5 h at 100 C. The reaction mixture was then cooled to rt, water added, extracted with ethyl acetate, dried (over Na.sub.2SO.sub.4), concentrated and purified via flash column chromatography (gradient, up to heptane/ethyl acetate=70/30, 254 nm) to give 19.0 g (84% yield, 92% pure) of the target compound as a pale green oil.

[0549] MS (ESI): 354.08 ([M].sup.+)

[0550] Preparation of Compounds of the Formula (XVI) Via Derivatization:

Preparation of 6-[4-(1,3-dioxolan-2-yl)phenoxy]-N-methoxy-N-methyl-2-(trifluoromethyl)pyridine-3-carboxamide

[0551] ##STR00049##

[0552] Using a Dean-Stark apparatus, 6-(4-formylphenoxy)-N-methoxy-N-methyl-2-(trifluoromethyl)pyridine-3-carboxamide (19.0 g, 53.6 mmol), 1,2-ethanediol (15.0 mL, 268 mmol) and 4-toluenesulfonic acid (923 mg, 5.63 mmol) in toluene (300 mL) were heated at 130 C. for 16 h. The solution was then concentrated, taken up in water and DCM, phases separated, washed with brine, concentrated and purified via flash column chromatography (gradient, up to heptane/ethyl acetate=60/40, 254 nm) to give 12.3 g (43% yield, 75% pure) of the target compound. A small portion was purified further via flash column chromatography (gradient, DCM 10% MeOH in DCM=90/10, 254 nm) for analysis.

[0553] MS (ESI): 399.11 ([M+1].sup.+)

[0554] The following tables illustrate in a non-limiting manner examples of compounds according to the invention.

TABLE-US-00001 TABLE 1 Compounds according to formula (I) (I) [00050] Ex No Y n R.sup.3 R R.sup.1 R.sup.2 m R.sup.4 LogP I-01 [00051] 0 CF.sub.3 H H 1 4-CHO 1.91.sup.[a] I-02 [00052] 0 CF.sub.3 H H 1 4-S(CH.sub.3) 2.59.sup.[a] I-03 [00053] 0 CF.sub.3 CH.sub.3 H 1 4-S(CH.sub.3) 2.74.sup.[a] I-04 [00054] 0 CF.sub.3 H H 1 4-hydroxyiminomethyl 2.26.sup.[a] I-05 [00055] 0 CF.sub.3 CH.sub.3 H 1 4-cyclopropyl 3.04.sup.[a] I-06 [00056] 0 CF.sub.3 H H 1 4-cyclopropyl 2.86.sup.[a]

TABLE-US-00002 TABLE 2 Compounds according to formula (VII) (VII) [00057] Ex No Y n R.sup.3 R m R.sup.4 LogP VII-01 [00058] 0 CF.sub.3 1 4-CHO 2.12.sup.[a] VII-02 [00059] 0 CF.sub.3 1 4- S(CH.sub.3) 2.92.sup.[a] VII-03 [00060] 0 CF.sub.3 1 4-cyclo- propyl 3.11.sup.[a] VII-04 [00061] 0 CF.sub.3 1 4- ethynyl 2.63.sup.[a]

TABLE-US-00003 TABLE 3 Compounds according to formula (V) (V) [00062] Ex No Y n R.sup.3 R m R.sup.4 LogP V-01 [00063] 0 CF.sub.3 1 4-(1,3- dioxolan- 2-yl) 2.98.sup.[a] V-02 [00064] 0 CF.sub.3 1 4-S(CH.sub.3) 3.70.sup.[a] V-03 [00065] 0 CF.sub.3 1 4-cyclo- propyl 4.03.sup.[a]

[0555] Log P Values:

[0556] Measurement of Log P values was performed according to EEC directive 79/831 Annex V.A8 by HPLC (High Performance Liquid Chromatography) on reversed phase columns with the following methods: [0557] .sup.[a] Log P value is determined by measurement of LC-UV, in an acidic range, with 0.1% formic acid in water and acetonitrile as eluent (linear gradient from 10% acetonitrile to 95% acetonitrile). [0558] .sup.[b] Log P value is determined by measurement of LC-UV, in a neutral range, with 0.001 molar ammonium acetate solution in water and acetonitrile as eluent (linear gradient from 10% acetonitrile to 95% acetonitrile). [0559] .sup.[c] Log P value is determined by measurement of LC-UV, in an acidic range, with 0.1% phosphoric acid and acetonitrile as eluent (linear gradient from 10% acetonitrile to 95% acetonitrile).

[0560] If more than one Log P value is available within the same method, all the values are given and separated by +.

[0561] Calibration was done with straight-chain alkan2-ones (with 3 to 16 carbon atoms) with known Log P values (measurement of Log P values using retention times with linear interpolation between successive alkanones). Lambda-max-values were determined using UV-spectra from 200 nm to 400 nm and the peak values of the chromatographic signals.

[0562] NMR-Peak lists

[0563] 1H-NMR data of selected examples are written below in form of 1H-NMR-peak lists. To each signal peak are listed the -value in ppm and the signal intensity in round brackets. Between the -valuesignal intensity pairs are semicolons as delimiters.

[0564] The peak list of an example has therefore the form:

[0565] .sub.1 (intensity.sub.1); .sub.2 (intensity.sub.2); . . . ; .sub.i (intensity.sub.i); . . . .sub.n (intensity.sub.n)

[0566] Intensity of sharp signals correlates with the height of the signals in a printed example of a NMR spectrum in cm and shows the real relations of signal intensities. From broad signals several peaks or the middle of the signal and their relative intensity in comparison to the most intensive signal in the spectrum can be shown.

[0567] For calibrating chemical shift for 1H spectra, we use tetramethylsilane and/or the chemical shift of the solvent used, especially in the case of spectra measured in DMSO. Therefore in NMR peak lists, tetramethylsilane peak can occur but not necessarily.

[0568] The 1H-NMR peak lists are similar to classical 1H-NMR prints and contains therefore usually all peaks, which are listed at classical NMR-interpretation.

[0569] Additionally they can show like classical 1H-NMR prints signals of solvents, stereoisomers of the target compounds, which are also object of the invention, and/or peaks of impurities.

[0570] To show compound signals in the delta-range of solvents and/or water the usual peaks of solvents, for example peaks of DMSO in DMSO-D.sub.6 and the peak of water are shown in our 1H-NMR peak lists and have usually on average a high intensity.

[0571] The peaks of stereoisomers of the target compounds and/or peaks of impurities have usually on average a lower intensity than the peaks of target compounds (for example with a purity >90%).

[0572] Such stereoisomers and/or impurities can be typical for the specific preparation process. Therefore their peaks can help to recognize the reproduction of our preparation process via side-products-fingerprints.

[0573] An expert, who calculates the peaks of the target compounds with known methods (MestreC, ACD-simulation, but also with empirically evaluated expectation values) can isolate the peaks of the target compounds as needed optionally using additional intensity filters. This isolation would be similar to relevant peak picking at classical 1H-NMR interpretation.

[0574] Further details of NMR-data description with peak lists you find in the publication Citation of NMR Peaklist Data within Patent Applications of the Research Disclosure Database Number 564025.

TABLE-US-00004 I-01: .sup.1H-NMR(300.2 MHz, d.sub.6-DMSO): = 10.0243 (9.4); 8.4861 (8.8); 8.3238 (3.0); 8.2950 (3.2); 8.0531 (1.0); 8.0448 (7.4); 8.0382 (2.5); 8.0224 (2.5); 8.0157 (8.1); 8.0074 (1.2); 7.9885 (8.8); 7.5578 (3.4); 7.5290 (3.2); 7.4629 (1.0); 7.4547 (7.2); 7.4488 (2.4); 7.4321 (2.2); 7.4262 (6.6); 7.4182 (0.9); 6.2270 (3.4); 6.2112 (3.5); 5.7780 (16.0); 5.2931 (1.0); 5.2790 (1.1); 4.4704 (1.0); 4.4431 (0.9); 4.4239 (2.0); 4.3966 (1.9); 4.3501 (1.8); 4.3379 (1.9); 4.3037 (0.9); 4.2912 (0.8); 3.3505 (6.8); 2.5339 (1.6); 2.5280 (3.4); 2.5219 (4.7); 2.5158 (3.4); 2.5099 (1.6); 1.0750 (0.4); 0.0182 (5.8) I-02: .sup.1H-NMR(300.2 MHz, CDCl.sub.3): = 8.1279 (3.5); 8.0933 (1.3); 8.0644 (1.4); 8.0137 (3.7); 7.3612 (2.8); 7.3542 (1.0); 7.3390 (1.1); 7.3318 (3.8); 7.3223 (0.5); 7.2987 (7.0); 7.1837 (0.5); 7.1741 (3.9); 7.1669 (1.1); 7.1518 (1.0); 7.1448 (2.8); 7.1041 (1.5); 7.0752 (1.4); 5.5434 (0.5); 5.5174 (0.5); 5.3365 (4.6); 4.5183 (0.6); 4.5107 (0.7); 4.4714 (1.0); 4.4639 (1.0); 4.2971 (1.0); 4.2700 (0.9); 4.2503 (0.7); 4.2233 (1.7); 4.2116 (1.1); 2.5481 (16.0); 1.6349 (6.2); 0.1059 (2.4); 0.0359 (6.2) I-03: .sup.1H-NMR(300.2 MHz, d.sub.6-DMSO): = 8.3597 (5.1); 8.0890 (1.6); 8.0596 (1.8); 7.8735 (5.1); 7.3760 (0.4); 7.3660 (3.5); 7.3591 (1.2); 7.3438 (1.4); 7.3367 (4.8); 7.3270 (0.6); 7.1967 (2.8); 7.1879 (5.1); 7.1809 (1.6); 7.1665 (3.1); 7.1588 (3.6); 5.8745 (4.6); 5.7794 (6.2); 4.5676 (0.4); 4.5198 (2.9); 4.5102 (2.9); 4.4631 (0.4); 3.3455 (16.0); 2.5339 (5.7); 2.5280 (11.6); 2.5219 (16.5); 2.5157 (29.7); 1.5613 (8.1); 1.2553 (0.4); 0.0311 (0.6); 0.0203 (13.7); 0.0093 (0.6) I-04: .sup.1H-NMR(300.2 MHz, d.sub.6-DMSO): = 12.0696 (3.5); 8.3343 (6.4); 8.2993 (2.0); 8.0160 (5.7); 7.5112 (1.6); 7.5044 (0.7); 7.4863 (3.2); 7.4647 (1.0); 7.4586 (2.8); 7.3914 (2.1); 7.3626 (2.0); 7.3136 (1.3); 7.3100 (0.8); 7.2890 (2.0); 7.2642 (0.8); 7.2607 (0.5); 7.2371 (2.9); 7.2332 (3.7); 7.2263 (0.9); 7.2116 (1.7); 7.2082 (2.9); 7.2051 (2.3); 6.1427 (2.3); 6.1277 (2.4); 5.2942 (0.6); 4.8294 (0.8); 4.8018 (0.7); 4.7830 (0.9); 4.7556 (0.8); 4.4038 (0.8); 4.3894 (0.9); 4.3575 (0.7); 4.3426 (0.7); 3.3433 (16.0); 2.5345 (5.6); 2.5285 (12.2); 2.5224 (16.9); 2.5163 (12.1); 2.5103 (5.6); 0.0317 (0.7); 0.0209 (19.4); 0.0099 (0.6) I-05: .sup.1H-NMR(300.2 MHz, d.sub.6-DMSO): = 8.3589 (5.4); 8.0715 (1.8); 8.0422 (1.9); 7.8727 (5.3); 7.1754 (2.7); 7.1688 (1.2); 7.1535 (1.6); 7.1465 (5.4); 7.1336 (2.6); 7.1040 (2.5); 7.0905 (5.6); 7.0834 (1.6); 7.0683 (1.1); 7.0616 (2.8); 5.8627 (5.2); 4.5644 (0.3); 4.5171 (3.4); 4.5092 (3.4); 4.4617 (0.3); 3.3453 (16.0); 2.5361 (1.4); 2.5302 (2.8); 2.5242 (3.8); 2.5182 (2.8); 2.5124 (1.3); 1.9971 (0.6); 1.9860 (0.6); 1.9692 (1.2); 1.9523 (0.7); 1.9413 (0.6); 1.5598 (8.9); 1.0076 (0.8); 0.9931 (2.1); 0.9859 (2.3); 0.9799 (1.2); 0.9723 (1.2); 0.9650 (2.2); 0.9578 (2.1); 0.9445 (0.9); 0.7201 (1.0); 0.7063 (2.4); 0.7030 (2.1); 0.6996 (2.5); 0.6897 (2.3); 0.6830 (2.5); 0.6679 (0.7); 0.0223 (2.7) I-06: .sup.1H-NMR(300.2 MHz, d.sub.6-DMSO): = 8.4680 (4.7); 8.2316 (1.6); 8.2027 (1.6); 7.9780 (4.5); 7.3272 (1.7); 7.2983 (1.7); 7.1878 (2.2); 7.1810 (0.9); 7.1660 (1.2); 7.1589 (4.7); 7.1512 (0.9); 7.1183 (0.8); 7.1105 (4.9); 7.1033 (1.3); 7.0885 (0.9); 7.0815 (2.2); 6.1519 (1.8); 6.1365 (1.9); 5.2560 (0.6); 5.2514 (0.6); 5.2422 (0.5); 4.4365 (0.5); 4.4090 (0.4); 4.3899 (1.0); 4.3626 (1.0); 4.3207 (1.0); 4.3084 (1.0); 4.2743 (0.4); 4.2618 (0.4); 3.3426 (16.0); 2.5342 (1.4); 2.5282 (2.8); 2.5222 (3.9); 2.5161 (2.9); 2.5102 (1.4); 2.0023 (0.5); 1.9912 (0.5); 1.9860 (0.4); 1.9745 (1.0); 1.9577 (0.6); 1.9466 (0.6); 1.0118 (0.6); 0.9973 (1.8); 0.9900 (2.0); 0.9841 (1.0); 0.9764 (1.0); 0.9692 (1.9); 0.9619 (1.8); 0.9487 (0.8); 0.7252 (0.8); 0.7114 (2.0); 0.7080 (1.7); 0.7046 (2.1); 0.6947 (1.9); 0.6879 (2.1); 0.6729 (0.6); 0.0206 (3.0) VII-01: .sup.1H-NMR(300.2 MHz, d.sub.6-DMSO): = 10.0400 (10.2); 8.6139 (3.6); 8.5852 (3.8); 8.5577 (9.9); 8.5439 (0.4); 8.0762 (1.4); 8.0661 (14.0); 8.0456 (2.8); 8.0393 (8.6); 8.0310 (1.1); 7.6757 (4.1); 7.6472 (3.9); 7.5234 (1.1); 7.5156 (7.9); 7.5096 (2.5); 7.4928 (2.4); 7.4869 (7.1); 7.4789 (0.9); 5.8940 (16.0); 5.7789 (8.3); 3.3560 (15.2); 2.5338 (3.5); 2.5280 (7.4); 2.5220 (10.1); 2.5160 (7.4); 2.5102 (3.6); 0.0185 (8.1); 0.0089 (0.4) VII-02: .sup.1H-NMR(300.2 MHz, CDCl.sub.3): = 8.2138 (4.1); 8.0012 (4.0); 7.9026 (1.8); 7.8741 (2.0); 7.3627 (0.4); 7.3530 (3.2); 7.3462 (1.1); 7.3307 (1.3); 7.3237 (4.2); 7.3141 (0.5); 7.2984 (1.2); 7.1639 (0.6); 7.1545 (4.5); 7.1465 (3.1); 7.1320 (1.2); 7.1251 (3.3); 7.1172 (2.2); 5.4217 (7.8); 5.3232 (1.2); 2.5384 (16.0); 0.1012 (0.6); 0.0254 (0.9) VII-03: .sup.1H-NMR(300.2 MHz, d.sub.6-DMSO): = 8.5442 (4.1); 8.5164 (1.4); 8.4876 (1.5); 8.0544 (3.9); 7.4424 (1.6); 7.4137 (1.6); 7.2121 (1.5); 7.2047 (0.7); 7.1906 (1.0); 7.1828 (4.6); 7.1759 (1.0); 7.1595 (0.9); 7.1526 (4.7); 7.1448 (1.1); 7.1308 (0.7); 7.1232 (1.6); 5.8644 (6.5); 3.3404 (16.0); 2.5343 (1.3); 2.5283 (2.8); 2.5222 (3.8); 2.5161 (2.8); 2.5102 (1.3); 2.0141 (0.4); 2.0032 (0.5); 1.9978 (0.3); 1.9863 (0.9); 1.9752 (0.3); 1.9695 (0.5); 1.9585 (0.5); 1.0209 (0.6); 1.0064 (1.5); 0.9991 (1.7); 0.9931 (0.8); 0.9854 (0.9); 0.9782 (1.7); 0.9709 (1.6); 0.9576 (0.7); 0.7389 (0.7); 0.7251 (1.8); 0.7217 (1.5); 0.7183 (1.8); 0.7084 (1.7); 0.7016 (1.8); 0.6866 (0.6); 0.0205 (3.5) VII-04: .sup.1H-NMR(300.2 MHz, CDCl.sub.3): = 8.2231 (8.3); 8.0196 (8.7); 7.9314 (4.0); 7.9029 (4.3); 7.6197 (1.0); 7.6112 (7.8); 7.6045 (2.5); 7.5888 (2.8); 7.5821 (8.6); 7.5737 (1.1); 7.2983 (17.2); 7.2083 (5.5); 7.2016 (10.0); 7.1946 (3.0); 7.1794 (6.8); 7.1723 (7.9); 7.1638 (1.0); 5.4265 (16.0); 3.1376 (11.1); 1.6290 (11.2); 0.1056 (0.7); 0.0462 (0.4); 0.0354 (10.5); 0.0245 (0.3) V-01: .sup.1H-NMR(300.2 MHz, CDCl.sub.3): = 7.8552 (2.9); 7.8269 (3.1); 7.6095 (0.8); 7.6011 (5.6); 7.5949 (2.0); 7.5789 (2.2); 7.5726 (6.6); 7.5642 (0.9); 7.2986 (6.5); 7.2630 (1.1); 7.2545 (7.2); 7.2478 (2.3); 7.2322 (2.1); 7.2257 (6.0); 7.2170 (0.8); 7.1083 (3.4); 7.0800 (3.1); 5.8715 (6.9); 4.2275 (1.4); 4.2062 (4.8); 4.2021 (3.2); 4.1965 (3.1); 4.1900 (2.9); 4.1812 (3.4); 4.1514 (2.1); 4.1491 (2.0); 4.1192 (3.5); 4.1104 (3.0); 4.1039 (3.2); 4.0983 (3.4); 4.0943 (4.9); 4.0730 (1.4); 2.6104 (16.0); 2.6082 (15.8); 1.6027 (3.8); 1.3031 (0.7); 0.9179 (0.7); 0.1069 (1.3); 0.0360 (6.2) V-02: .sup.1H-NMR(300.2 MHz, CDCl.sub.3): = 7.8581 (1.4); 7.8298 (1.5); 7.3642 (2.8); 7.3572 (1.0); 7.3421 (1.0); 7.3349 (3.9); 7.3253 (0.5); 7.2985 (4.9); 7.2759 (1.0); 7.2688 (0.3); 7.2541 (0.3); 7.2468 (1.1); 7.1836 (0.4); 7.1740 (3.9); 7.1668 (1.1); 7.1516 (0.9); 7.1446 (2.8); 7.1127 (1.6); 7.0845 (1.5); 6.8348 (1.2); 6.8275 (0.4); 6.8128 (0.3); 6.8056 (1.0); 4.8640 (1.3); 2.6312 (0.9); 2.6292 (0.9); 2.6123 (7.7); 2.6101 (7.8); 2.5508 (16.0); 2.4760 (5.4); 1.6144 (8.1); 0.1067 (1.8); 0.0361 (4.0) V-03: .sup.1H-NMR(300.2 MHz, d.sub.6-DMSO): = 9.0943 (0.6); 8.3551 (3.6); 8.3537 (3.6); 8.3265 (3.8); 8.3251 (3.8); 7.3571 (4.1); 7.3285 (3.9); 7.1977 (3.9); 7.1902 (1.7); 7.1763 (2.6); 7.1684 (11.7); 7.1614 (2.3); 7.1448 (2.3); 7.1377 (12.2); 7.1298 (2.6); 7.1160 (1.7); 7.1083 (4.0); 6.9009 (0.4); 6.8726 (0.5); 6.6653 (0.5); 6.6368 (0.4); 3.3431 (16.0); 2.6425 (1.5); 2.6033 (32.9); 2.5344 (1.2); 2.5284 (2.4); 2.5223 (3.3); 2.5163 (2.4); 2.5103 (1.1); 2.0225 (0.5); 2.0055 (1.1); 1.9944 (1.2); 1.9888 (0.8); 1.9776 (2.3); 1.9663 (0.8); 1.9607 (1.3); 1.9497 (1.2); 1.9327 (0.6); 1.0133 (1.5); 0.9989 (4.0); 0.9915 (4.4); 0.9855 (2.0); 0.9779 (2.3); 0.9707 (4.3); 0.9634 (3.9); 0.9500 (1.8); 0.7311 (1.9); 0.7173 (4.4); 0.7140 (3.6); 0.7104 (4.6); 0.7006 (4.2); 0.6936 (4.6); 0.6787 (1.5); 0.0183 (4.1)

USE EXAMPLES

Example A: In Vivo Preventive Test on Alternaria brassicae (Leaf Spot on Radish or Cabbage)

[0575] Solvent: 5% by volume of dimethyl sulfoxide [0576] 10% by volume of acetone

[0577] Emulsifier: 1 l of Tween 80 per mg of active ingredient

[0578] The active ingredients were made soluble and homogenized in a mixture of dimethyl sulfoxide/acetone//Tween 80 and then diluted in water to the desired concentration.

[0579] The young plants of radish or cabbage were treated by spraying the active ingredient prepared as described above. Control plants were treated only with an aqueous solution of acetone/dimethyl sulfoxide/Tween 80.

[0580] After 24 hours, the plants were contaminated by spraying the leaves with an aqueous suspension of Alternaria brassicae spores. The contaminated radish or cabbage plants were incubated for 6 days at 20 C. and at 100% relative humidity.

[0581] The test was evaluated 6 days after the inoculation. 0% means an efficacy which corresponds to that of the control plants while an efficacy of 100% means that no disease was observed.

[0582] In this test the following compounds according to the invention showed efficacy between 80% and 89% at a concentration of 500 ppm of active ingredient: I-05.

[0583] In this test the following compounds according to the invention showed efficacy between 90% and 100% at a concentration of 500 ppm of active ingredient: I-03; I-06; VII-03; VII-04.

Example B: In Vivo Preventive Test on Botrytis cinerea (Grey Mould)

[0584] Solvent: 5% by volume of dimethyl sulfoxide [0585] 10% by volume of acetone

[0586] Emulsifier: 1 l of Tween 80 per mg of active ingredient

[0587] The active ingredients were made soluble and homogenized in a mixture of dimethyl sulfoxide/acetone//Tween 80 and then diluted in water to the desired concentration.

[0588] The young plants of gherkin were treated by spraying the active ingredient prepared as described above. Control plants were treated only with an aqueous solution of acetone/dimethyl sulfoxide/Tween 80.

[0589] After 24 hours, the plants were contaminated by spraying the leaves with an aqueous suspension of Botrytis cinerea spores. The contaminated gherkin plants were incubated for 4 to 5 days at 17 C. and at 90% relative humidity.

[0590] The test was evaluated 4 to 5 days after the inoculation. 0% means an efficacy which corresponds to that of the control plants while an efficacy of 100% means that no disease was observed.

[0591] In this test the following compounds according to the invention showed efficacy between 70% and 79% at a concentration of 500 ppm of active ingredient: VII-03.

[0592] In this test the following compounds according to the invention showed efficacy between 90% and 100% at a concentration of 500 ppm of active ingredient: I-02; I-03; I-05; I-06; VII-04.

Example C: In Vivo Preventive Test on Puccinia recondita (Brown Rust on Wheat)

[0593] Solvent: 5% by volume of dimethyl sulfoxide [0594] 10% by volume of acetone

[0595] Emulsifier: 1 l of Tween 80 per mg of active ingredient

[0596] The active ingredients were made soluble and homogenized in a mixture of dimethyl sulfoxide/acetone//Tween 80 and then diluted in water to the desired concentration.

[0597] The young plants of wheat were treated by spraying the active ingredient prepared as described above. Control plants were treated only with an aqueous solution of acetone/dimethyl sulfoxide/Tween 80.

[0598] After 24 hours, the plants were contaminated by spraying the leaves with an aqueous suspension of Puccinia recondita spores. The contaminated wheat plants were incubated for 24 hours at 20 C. and at 100% relative humidity and then for 10 days at 20 C. and at 70-80% relative humidity.

[0599] The test was evaluated 11 days after the inoculation. 0% means an efficacy which corresponds to that of the control plants while an efficacy of 100% means that no disease was observed.

[0600] In this test the following compounds according to the invention showed efficacy between 80% and 89% at a concentration of 500 ppm of active ingredient: I-02; I-03; VII-02; VII-04.

[0601] In this test the following compounds according to the invention showed efficacy between 90% and 100% at a concentration of 500 ppm of active ingredient: I-05; I-06; VII-03.

Example D: In Vivo Preventive Test on Septoria tritici (Leaf Spot on Wheat)

[0602] Solvent: 5% by volume of dimethyl sulfoxide [0603] 10% by volume of acetone

[0604] Emulsifier: 1 l of Tween 80 per mg of active ingredient

[0605] The active ingredients were made soluble and homogenized in a mixture of dimethyl sulfoxide/acetone//Tween 80 and then diluted in water to the desired concentration.

[0606] The young plants of wheat were treated by spraying the active ingredient prepared as described above. Control plants were treated only with an aqueous solution of acetone/dimethyl sulfoxide/Tween 80.

[0607] After 24 hours, the plants were contaminated by spraying the leaves with an aqueous suspension of Septoria tritici spores. The contaminated wheat plants were incubated for 72 hours at 18 C. and at 100% relative humidity and then for 21 days at 20 C. and at 90% relative humidity.

[0608] The test was evaluated 24 days after the inoculation. 0% means an efficacy which corresponds to that of the control plants while an efficacy of 100% means that no disease was observed.

[0609] In this test the following compounds according to the invention showed efficacy between 70% and 79% at a concentration of 500 ppm of active ingredient: VII-01.

[0610] In this test the following compounds according to the invention showed efficacy between 80% and 89% at a concentration of 500 ppm of active ingredient: VII-03.

[0611] In this test the following compounds according to the invention showed efficacy between 90% and 100% at a concentration of 500 ppm of active ingredient: I-02; I-03; I-05; I-06; VII-02; VII-04.

Example E: In Vivo Preventive Test on Sphaerotheca fuliginea (Powdery Mildew on Cucurbits)

[0612] Solvent: 5% by volume of dimethyl sulfoxide [0613] 10% by volume of acetone

[0614] Emulsifier: 1 l of Tween 80 per mg of active ingredient

[0615] The active ingredients were made soluble and homogenized in a mixture of dimethyl sulfoxide/acetone//Tween 80 and then diluted in water to the desired concentration.

[0616] The young plants of gherkin were treated by spraying the active ingredient prepared as described above. Control plants were treated only with an aqueous solution of acetone/dimethyl sulfoxide/Tween 80.

[0617] After 24 hours, the plants were contaminated by spraying the leaves with an aqueous suspension of Sphaerotheca fuliginea spores. The contaminated gherkin plants were incubated for 72 hours at 18 C. and at 100% relative humidity and then for 12 days at 20 C. and at 70-80% relative humidity.

[0618] The test was evaluated 15 days after the inoculation. 0% means an efficacy which corresponds to that of the control plants while an efficacy of 100% means that no disease was observed.

[0619] In this test the following compounds according to the invention showed efficacy between 90% and 100% at a concentration of 500 ppm of active ingredient: I-01; I-03; I-04; I-05; I-06; VII-01; VII-03; VII-04.

Example F: In Vivo Preventive Test on Uromyces appendiculatus (Bean Rust)

[0620] Solvent: 5% by volume of dimethyl sulfoxide [0621] 10% by volume of acetone

[0622] Emulsifier: 1 l of Tween 80 per mg of active ingredient

[0623] The active ingredients were made soluble and homogenized in a mixture of dimethyl sulfoxide/acetone//Tween 80 and then diluted in water to the desired concentration.

[0624] The young plants of bean were treated by spraying the active ingredient prepared as described above. Control plants were treated only with an aqueous solution of acetone/dimethyl sulfoxide/Tween 80.

[0625] After 24 hours, the plants were contaminated by spraying the leaves with an aqueous suspension of Uromyces appendiculatus spores. The contaminated bean plants were incubated for 24 hours at 20 C. and at 100% relative humidity and then for 10 days at 20 C. and at 70-80% relative humidity.

[0626] The test was evaluated 11 days after the inoculation. 0% means an efficacy which corresponds to that of the control plants while an efficacy of 100% means that no disease was observed.

[0627] In this test the following compounds according to the invention showed efficacy between 80% and 89% at a concentration of 500 ppm of active ingredient: I-02.

[0628] In this test the following compounds according to the invention showed efficacy between 90% and 100% at a concentration of 500 ppm of active ingredient: I-05; I-06; VII-04.

Example G: Comparison of the Phenyloxy-Pyridyl Compound I-03 According to the Invention Vs. the Corresponding Phenyloxy-Phenyl Compound

[0629] Compound I-03:

##STR00066##

[0630] Comparative Compound:

##STR00067##

Example G1: In Vivo Preventive Test on Botrytis cinerea (Grey Mould)

[0631] The tested active ingredients were prepared by homogenization in a mixture of acetone/dimethyl sulfoxide/Tween, and then diluted with water to obtain the desired active material concentration.

[0632] Young plants of gherkin were treated by spraying the active ingredient prepared as described above. Control plants were treated only with an aqueous solution of acetone/dimethyl sulfoxide/Tween.

[0633] After 24 hours, the plants were contaminated by spraying the leaves with an aqueous suspension of Botrytis cinerea spores. The contaminated gherkin plants were incubated for 4 to 5 days at 17 C. and at 90% relative humidity.

[0634] The test was evaluated 4 to 5 days after the inoculation. 0% means an efficacy which corresponds to that of the control plants while an efficacy of 100% means that no disease was observed.

TABLE-US-00005 Rate of application of active Efficacy Active compound compound in ppm in % Comparative 500 69 compound I-03 500 90

Example G2: In Vivo Preventive Test on Puccinia recondita (Brown Rust on Wheat)

[0635] The tested active ingredients were prepared by homogenization in a mixture of acetone/dimethyl sulfoxide/Tween, and then diluted with water to obtain the desired active material concentration.

[0636] Young plants of wheat were treated by spraying the active ingredient prepared as described above. Control plants were treated only with an aqueous solution of acetone/dimethyl sulfoxide/Tween.

[0637] After 24 hours, the plants were contaminated by spraying the leaves with an aqueous suspension of Puccinia recondita spores. The contaminated wheat plants were incubated for 24 hours at 20 C. and at 100% relative humidity and then for 10 days at 20 C. and at 70-80% relative humidity.

[0638] The test was evaluated 11 days after the inoculation. 0% means an efficacy which corresponds to that of the control plants while an efficacy of 100% means that no disease was observed.

TABLE-US-00006 Rate of application of active Efficacy Active compound compound in ppm in % Comparative 500 88 compound 100 25 I-03 500 88 100 65

Example G3: In Vitro Test for the Calculation of the ED50-Value with Microorganisms

[0639] Solvent: DMSO [0640] Culture medium: 14.6 g anhydrous D-glucose (VWR), 7.1 g mycological peptone (Oxoid), 1.4 g granulated yeast extract (Merck), supplemented with water to a total volume of 1 liter [0641] Inoculum: spore suspension

[0642] Fungicides were solubilized in DMSO and the solution used to prepare the required range of concentrations. The final concentration of DMSO used in the assay was <1% by weight.

[0643] A spore suspension was prepared and diluted to the desired spore density.

[0644] Fungicides were evaluated for their ability to inhibit spore germination and mycelium growth in liquid culture assay. The compounds were added in the desired concentration to the culture medium with spores. After 4 to 7 days incubation, fungi-toxicity of compounds was determined by spectrometric measurement of mycelium growth. Inhibition of fungal growth was determined by comparing the absorbance values in wells containing the fungicides with the absorbance in control wells without fungicides.

TABLE-US-00007 Pyricularia Colletotrichum Active Fusarium culmorum oryzae ED50 lindemuthianum compound ED50 value in ppm value in ppm ED50 value in ppm Comparative 2.6 5.6 0.83 compound I-03 0.83 1.7 0.38

Example G4: In Vivo Preventive Test on Sphaerotheca Test (Cucumbers)

[0645] Solvent: 24.5 parts by weight of acetone [0646] 24.5 parts by weight of dimethylacetamide

[0647] Emulsifier: 1 part by weight of alkylaryl polyglycol ether

[0648] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.

[0649] To test for preventive activity, young plants are sprayed with the preparation of active compound at the stated rate of application. After the spray coating has dried on, the plants are inoculated with an aqueous spore suspension of Sphaerotheca fuliginea. The plants are then placed in a greenhouse at approximately 23 C. and a relative atmospheric humidity of approximately 70%.

[0650] The test is evaluated 7 days after the inoculation. 0% means an efficacy which corresponds to that of the untreated control, while an efficacy of 100% means that no disease is observed.

TABLE-US-00008 TABLE in vivo preventive test on Sphaerotheca test (cucumbers) Rate of application of active Efficacy Active compound compound in ppm in % Comparative 100 100 compound 10 28 I-03 100 100 10 78

Example G5: In Vivo Preventive Septoria tritici Test (Wheat)

[0651] Solvent: 49 parts by weight of N,N-dimethylacetamide

[0652] Emulsifier: 1 part by weight of alkylaryl polyglycol ether

[0653] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.

[0654] To test for preventive activity, young plants are sprayed with the preparation of active compound or active compound combination at the stated rate of application. After the spray coating has been dried, the plants are sprayed with a spore suspension of Septoria tritici. The plants remain for 48 hours in an incubation cabinet at approximately 20 C. and a relative atmospheric humidity of approximately 100% and afterwards for 60 hours at approximately 15 C. in a translucent incubation cabinet at a relative atmospheric humidity of approximately 100%. The plants are placed in the greenhouse at a temperature of approximately 15 C. and a relative atmospheric humidity of approximately 80%.

[0655] The test is evaluated 21 days after the inoculation. 0% means an efficacy which corresponds to that of the untreated control, while an efficacy of 100% means that no disease is observed.

TABLE-US-00009 TABLE in vivo preventive Septoria tritici test (wheat) Rate of application of active Efficacy Active compound compound in ppm in % Comparative 500 22 compound I-03 500 78

Example G6: In Vivo Curative Septoria tritici Test (Wheat)

[0656] Solvent: 49 parts by weight of N,N-dimethylacetamide

[0657] Emulsifier: 1 part by weight of alkylaryl polyglycol ether

[0658] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.

[0659] To test for curative activity, young plants are inoculated with a spore suspension of Septoria tritici and remain for 48 hours in an incubation cabinet at a temperature of approximately 20 C. and a relative atmospheric humidity of approximately 100%. 48 hours after the incubation, the plants are sprayed with the preparation of active compound at the stated rate of application. After application the plants remain for 60 hours at a temperature of approximately 15 C. in a translucent incubation cabinet at a relative atmospheric humidity of approximately 100%. Afterwards, the plants are placed in the greenhouse at a temperature of approximately 15 C. and a relative atmospheric humidity of approximately 80%.

[0660] The test is evaluated 21 days after the inoculation. 0% means an efficacy which corresponds to that of the untreated control, while an efficacy of 100% means that no disease is observed.

TABLE-US-00010 TABLE in vivo curative Septoria tritici test (wheat) Rate of application of active Efficacy Active compound compound in ppm in % Comparative 500 57 compound I-03 500 93

Example G7: In Vivo 5 Days Preventive Septoria tritici Test (Wheat)

[0661] Solvent: 49 parts by weight of N,N-dimethylacetamide

[0662] Emulsifier: 1 part by weight of alkylaryl polyglycol ether

[0663] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.

[0664] To test for preventive and long-lasting activity, young plants are sprayed with a preparation of active compound or active compound combination at the stated rate of application. After the spray coating has been dried, the plants are placed in the greenhouse at a temperature of approximately 15 C. and a relative atmospheric humidity of approximately 80%. 5 days later the plants are sprayed with a spore suspension of Septoria tritici. The plants remain for 48 hours in an incubation cabinet at approximately 20 C. and a relative atmospheric humidity of approximately 100% and afterwards for 60 hours at approximately 15 C. in a translucent incubation cabinet at a relative atmospheric humidity of approximately 100%. Then the plants are placed in the greenhouse at a temperature of approximately 15 C. and a relative atmospheric humidity of approximately 80%.

[0665] The test is evaluated 21 days after the inoculation. 0% means an efficacy which corresponds to that of the untreated control, while an efficacy of 100% means that no disease is observed.

TABLE-US-00011 TABLE in vivo 5 days preventive Septoria tritici test (wheat) Rate of application of active Efficacy Active compound compound in ppm in % Comparative 500 29 compound I-03 500 71