MICROBIOCIDAL OXADIAZOLE DERIVATIVES

Abstract

Compounds of the formula (I), wherein the substituents are as defined as claim 1, useful as a pesticides, especially as fungicides.

##STR00001##

Claims

1. A compound of Formula (I): ##STR00043## wherein A.sup.1 represents CR.sup.1, wherein R.sup.1 is hydrogen, halogen, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, or difluoromethoxy; A.sup.2 represents CR.sup.2, wherein R.sup.2 is hydrogen, halogen, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, or difluoromethoxy; A.sup.3 represents CR.sup.3, wherein R.sup.3 is hydrogen or halogen; A.sup.4 represents CR.sup.4, wherein R.sup.4 is hydrogen or halogen; wherein at least one of A.sup.1, A.sup.2, A.sup.3, or A.sup.4 is not CH; R.sup.5 represents hydrogen, C.sub.1-4alkyl, C.sub.3-6alkenyl, C.sub.3-6alkynyl, C.sub.1-4haloalkyl, C.sub.1-4alkoxy, C.sub.1-2alkoxyC.sub.1-4alkyl; R.sup.6 represents C.sub.1-6alkyl, C .sub.3-6 alkenyl, C.sub.3-6alkynyl, C.sub.1-4haloalkyl, C.sub.3-6haloalkenyl, C.sub.1-4alkoxy, C.sub.1-4alkoxyC.sub.1-4alkyl, hydroxyC.sub.1-4alkyl, hydroxyC.sub.1-4haloalkyl, cyanoC.sub.1-4alkyl, C.sub.1-4alkoxyamino, NC.sub.1-4alkoxyaminoC.sub.1-4alkyl, NC.sub.1-4alkoxy-NC.sub.1-4alkylamino, NC.sub.1-4alkoxy-NC.sub.1-4alkylaminoC.sub.1-4alkyl, C.sub.1-4alkylamino, N,N-di-C.sub.1-4alkylamino, N,N-di-C.sub.1-4alkylaminoC.sub.1-4alkyl, C.sub.3-6alkenoxyamino, C.sub.3-6alkenoxyaminoC.sub.1-4alkyl, NC.sub.3-6alkenoxy-NC.sub.1-4alkylamino; or a salt or an N-oxide thereof.

2. A compound according to claim 1, wherein A.sup.1 is CR.sup.1, wherein R.sup.1 is chloro, fluoro or methyl, and A.sup.2 to A.sup.4 are CH.

3. A compound according to claim 1, wherein R.sup.5 is hydrogen.

4. A compound according to claim 1, wherein R.sup.6 is C.sub.1-4alkyl, C.sub.3-4alkenyl, C.sub.3-4alkynyl, C.sub.1-4haloalkyl, C.sub.3-4haloalkenyl, C.sub.1-4alkoxy, C.sub.1-2alkoxyC.sub.1-4alkyl, hydroxyC.sub.1-2alkyl, hydroxyC.sub.1-4haloalkyl, cyanoC.sub.1-4alkyl, C.sub.1-2alkoxyamino, NC.sub.1-2alkoxyaminoC.sub.1-4alkyl, NC.sub.1-2alkoxy-NC.sub.1-4alkylamino, NC.sub.1-2alkoxy-NC.sub.1-2alkylaminoC.sub.1-2alkyl, C.sub.1-2alkylamino, N,N-di-C.sub.1-2alkylamino, N,N-di-C.sub.1-2alkylaminoC.sub.1-2alkyl, C.sub.3-6alkenoxyamino, C.sub.3-4alkenyloxyaminoC.sub.1-2alkyl, NC.sub.3-6alkenoxy-NC.sub.1-4alkylamino.

5. A compound according to claim 1, wherein R.sup.6 is C.sub.1-4alkyl, C.sub.1-4haloalkyl, C.sub.1-4alkoxy, C.sub.1-2alkoxyC.sub.1-4alkyl, hydroxyC.sub.1-4haloalkyl, cyanoC.sub.1-4 alkyl, NC.sub.1-2alkoxy-NC.sub.1-4alkylamino, C .sub.3-6 alkenoxyamino, NC.sub.3-6alkenoxy-NC.sub.1-4alkylamino.

6. A compound according to claim 1, wherein R.sup.6 is C.sub.1-4alkyl, C.sub.1-2haloalkyl, C.sub.1-4alkoxy, C.sub.1-2alkoxyC.sub.1-4alkyl, hydroxyC.sub.1-4haloalkyl, cyanoC.sub.1-2 alkyl, NC.sub.1-2alkoxy-NC.sub.1-2alkylamino, C .sub.3-4 alkenoxyamino, NC.sub.3-4alkenoxy-NC.sub.1-2alkylamino.

7. A compound according to claim 1, wherein R.sup.6 is methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, methoxy, ethoxy, n-propoxy, iso-propoxy, trifluoromethyl, 2,2,2-trifluoroethyl, methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, (1-methoxymethyl)propyl, (1-methyl)methoxymethyl, 1-chloro-2-hydroxymethyl-prop-2-yl, cyanomethyl, N-methoxy-N-methylamino, allyloxyamino, (2-methyl)allyloxyamino, N-allyloxy-N-methylamino.

8. A compound according to claim 1, wherein R.sup.6 is methyl, ethyl, iso-propyl, sec-butyl, ethoxy, 2,2,2-trifluoroethyl, methoxyethyl, methoxypropyl, (1-methoxymethyl)propyl, (1-methyl)methoxymethyl, (1-chloro-2-hydroxymethyl)prop-2-yl, cyanomethyl, N-methoxy-N-methylamino, allyloxyamino, (2-methyl)allyloxyamino, N-allyloxy-N-methylamino.

9. An agrochemical composition comprising a fungicidally effective amount of a compound of formula (I) according to claim 1.

10. The composition according to claim 9, further comprising at least one additional active ingredient and/or an agrochemically-acceptable diluent or carrier.

11. A method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound of formula (I) according to claim 1, or a composition comprising this compound as active ingredient, is applied to the plants, to parts thereof or the locus thereof.

12. Use of a compound of formula (I) according to claim 1 as a fungicide.

Description

EXAMPLES

[0205] The Examples which follow serve to illustrate the invention.

[0206] The compounds of the invention can be distinguished from known compounds by virtue of greater efficacy at low application rates, which can be verified by the person skilled in the art using the experimental procedures outlined in the Examples, using lower application rates if necessary, for example 50 ppm, 12.5 ppm, 6 ppm, 3 ppm, 1.5 ppm, 0.8 ppm or 0.2 ppm.

[0207] Compounds of Formula (I) may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against diseases that are caused by fungi or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (including improved crop tolerance), improved physico-chemical properties, or increased biodegradability).

[0208] Throughout this description, temperatures are given in degrees Celsius ( C.) and m.p. means melting point. LC/MS means Liquid Chromatography Mass Spectrometry and the description of the apparatus and the methods used for LC/MS analysis are given below.

The Description of the Apparatus and the Method A is:

[0209] SQ Detector 2 from Waters [0210] Ionisation method: Electrospray [0211] Polarity: positive and negative ions [0212] Capillary (kV) 3.0, Cone (V) 30.00, Extractor (V) 2.00, Source Temperature ( C.) 150, Desolvation Temperature ( C.) 350, Cone Gas Flow (L/Hr) 0, Desolvation Gas Flow (L/Hr) 650 [0213] Mass range: 100 to 900 Da [0214] DAD Wavelength range (nm): 210 to 500 [0215] Method Waters ACQUITY UPLC with the following HPLC gradient conditions [0216] (Solvent A: Water/Methanol 20:1+0.05% formic acid and Solvent B: Acetonitrile+0.05% formic acid)

TABLE-US-00002 Time (minutes) A (%) B (%) Flow rate (ml/min) 0 100 0 0.85 1.2 0 100 0.85 1.5 0 100 0.85
Type of column: Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60 C.

The Description of the Apparatus and the Method B is:

[0217] SQ Detector 2 from Waters [0218] Ionisation method: Electrospray [0219] Polarity: positive ions [0220] Capillary (kV) 3.5, Cone (V) 30.00, Extractor (V) 3.00, Source Temperature ( C.) 150, Desolvation Temperature ( C.) 400, Cone Gas Flow (L/Hr) 60, Desolvation Gas Flow (L/Hr) 700 [0221] Mass range: 140 to 800 Da [0222] DAD Wavelength range (nm): 210 to 400 [0223] Method Waters ACQUITY UPLC with the following HPLC gradient conditions [0224] (Solvent A: Water/Methanol 9:1+0.1% formic acid and Solvent B: Acetonitrile+0.1% formic acid)

TABLE-US-00003 Time (minutes) A (%) B (%) Flow rate (ml/min) 0 100 0 0.75 2.5 0 100 0.75 2.8 0 100 0.75 3.0 100 0 0.75
Type of column: Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60 C.

[0225] Where necessary, enantiomerically pure final compounds may be obtained from racemic materials as appropriate via standard physical separation techniques, such as reverse phase chiral chromatography, or through stereoselective synthetic techniques, eg, by using chiral starting materials.

FORMULATION EXAMPLES

[0226]

TABLE-US-00004 Wettable powders a) b) c) active ingredient [compound of formula (I)] 25% 50% 75% sodium lignosulfonate 5% 5% sodium lauryl sulfate 3% 5% sodium diisobutylnaphthalenesulfonate 6% 10% phenol polyethylene glycol ether 2% (7-8 mol of ethylene oxide) highly dispersed silicic acid 5% 10% 10% Kaolin 62% 27%

[0227] The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.

TABLE-US-00005 Powders for dry seed treatment a) b) c) active ingredient [compound of formula (I)] 25% 50% 75% light mineral oil 5% 5% 5% highly dispersed silicic acid 5% 5% Kaolin 65% 40% Talcum 20%

[0228] The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.

TABLE-US-00006 Emulsifiable concentrate active ingredient [compound of formula (I)] 10% octylphenol polyethylene glycol ether 3% (4-5 mol of ethylene oxide) calcium dodecylbenzenesulfonate 3% castor oil polyglycol ether (35 mol of ethylene oxide) 4% Cyclohexanone 30% xylene mixture 50%

[0229] Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.

TABLE-US-00007 Dusts a) b) c) Active ingredient [compound of 5% 6% 4% formula (I)] Talcum 95% Kaolin 94% mineral filler 96%

[0230] Ready-for-use dusts are obtained by mixing the active ingredient with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed.

TABLE-US-00008 Extruder granules Active ingredient [compound of formula (I)] 15% sodium lignosulfonate 2% Carboxymethylcellulose 1% Kaolin 82%

[0231] The active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.

TABLE-US-00009 Coated granules Active ingredient [compound of formula (I)] 8% polyethylene glycol (mol. wt. 200) 3% Kaolin 89%

[0232] The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.

TABLE-US-00010 Suspension concentrate active ingredient [compound of formula (I)] 40% propylene glycol 10% nonylphenol polyethylene glycol ether (15 mol of 6% ethylene oxide) Sodium lignosulfonate 10% Carboxymethylcellulose 1% silicone oil (in the form of a 75% emulsion in water) 1% Water 32%

[0233] The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.

TABLE-US-00011 Flowable concentrate for seed treatment active ingredient [compound of formula (I)] 40% propylene glycol 5% copolymer butanol PO/EO 2% tristyrenephenole with 10-20 moles EO 2% 1,2-benzisothiazolin-3-one (in the form of a 20% 0.5% solution in water) monoazo-pigment calcium salt 5% Silicone oil (in the form of a 75% emulsion in water) 0.2% Water 45.3%

[0234] The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.

Slow-Release Capsule Suspension

[0235] 28 parts of a combination of the compound of formula I are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51.6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed.

[0236] The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns.

[0237] The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.

List of Abbreviations:

[0238] DIEA=N-ethyl-N-isopropyl-propan-2-amine [0239] DIPEA=N,N-diisopropylethylamine [0240] DMA=dimethylacetamide [0241] DMF=dimethylformamide [0242] EtOAc=ethyl acetate [0243] EtOH=ethyl alcohol [0244] HCl=hydrochloric acid [0245] mp=melting point [0246] MeOH=methyl alcohol [0247] NaOH=sodium hydroxide [0248] TFAA=trifluoroacetic acid anhydride [0249] THF=tetrahydrofuran

PREPARATION EXAMPLES

Example 1

[0250] This example illustrates the preparation N-[2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]propanamide (Compound 1.6 of Table T1).

##STR00011##

Step 1: Preparation of 4-amino-3-fluoro-N-hydroxy-benzamidine

[0251] ##STR00012##

[0252] To a solution of 4-amino-3-fluoro-benzonitrile (5.0 g, 36.7 mmol) in ethanol (61 mL) was added 5 a hydroxylamine hydrochloride solution (5.16 g, 73.5 mmol) in 50 mL of water followed by potassium carbonate (8.12 g, 58.8 mmol) in 75 mL of water. To the cloudy solution was then introduced quinolin-8-ol (0.07 g, 0.48 mmol). The reaction mixture was stirred for 5 hours at 100 C. The reaction mixture was then cooled to 25 C., the ethanol was removed under reduced pressure, and the resulting mixture was then extracted with ethyl acetate. The total combined organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to give 5.83 g of 4-amino-3-fluoro-N-hydroxy-benzamidine as a yellow solid. The crude residue was used in the following step without further purification. LC/MS (Method A) retention time=0.20 min; 166 [M+H.sup.+].

[0253] .sup.1H NMR (400 MHz, CDCl.sub.3) ppm: 9.30 (s, 1H), 7.25 (m, 2H), 6.70 (t, 1H), 5.60 (brs, 2H), 5.30 (brs, 2H).

Step 2: Preparation of 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]aniline

[0254] ##STR00013##

[0255] To a solution of 4-amino-3-fluoro-N-hydroxy-benzamidine (6.99 g, 41.3 mmol) in 2-methyltetrahydrofuran (124 mL) was introduced TFAA (8.2 mL, 57.9 mmol) by dropwise addition. The reaction mixture was stirred for 2 hours at 25 C. and then slowly quenched with water and ethyl acetate. The aqueous phase was extracted with ethyl acetate and the total combined organic layer was washed with brine, dried over sodium sulfate, filtered, concentrated under reduced pressure and then subjected to flash chromatography over silica gel (cyclohexane:EtOAc eluent gradient 99:1 to 80:20) to afford a trifluoromethylated intermediate (7.02 g, 20.5 mmol) that was dissolved in methanol (82 mL), treated with 35% aqueous hydrochloric acid (3.01 mL, 30.7 mmol) and heated at 50 C. for 24 hours. The mixture was cooled to 25 C. and azoetroped with toluene under reduced pressure to afford 5.83 g of 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]aniline.

Step 3: Preparation of N-[2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]propanamide

[0256] To a solution of 2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]aniline (0.10 g, 0.35 mmol) in dichloromethane (6 mL) was introduced triethylamine (0.15 mL, 1.07 mmol) and propionyl chloride (0.038 mL, 0.42 mmol), The reaction mixture was stirred at 25 C. for 2 hours and then water and dichloromethane were added. The aqueous layer was extracted with dichloromethane and the total combined organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resultant crude residue was purified by flash chromatography over silica gel (heptane:EtOAc eluent gradient 99:1 to 80:20) to give 0.08 g of N-[2-fluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]propanamide as a white solid. mp: 123-128 C. LC/MS (Method A) retention time=1.09 minutes, 316 (M+H).

[0257] .sup.1H NMR (400 MHz, CDCl.sub.3) ppm: 8.50 (t, 1H), 7.85 (d, 1H), 7.80 (d, 1H), 7.65 (brs, 1H), 1.55 (m, 1H), 1.09 (m, 2H), 0.85 (m, 2H).

[0258] The following general procedure was used in a combinatorial fashion using appropriate building blocks (compounds (II) and (III)) to provide the compounds of Formula (I). The compounds prepared via the following combinatorial protocol were analyzed using LC/MS Method B.

##STR00014##

[0259] By way of exemplification, acid derivatives of formula (III) (0.0375 mmol in 375 L DMA) were transferred to a 96 slot deep well plate (DWP96) containing the [4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]aryl]methanamine derivative of formula (II) (0.03 mmol) and DIPEA (0.09 mmol) in 250 L DMA, followed by the addition of BOP-CI (0.06 mmol) dissolved in DMA (250 L). The DWP96 was sealed and stirred at 50 C. for 18 hours. The solvent was removed under a stream of nitrogen. The resultant crude residues were solubilized in a mixture of MeOH (250 L) and DMA (500 L) and directly submitted for preparative LC/MS purification which provided the compounds of formula (I) in 10-85% yields.

[0260] Where necessary, enantiomerically pure final compounds may be obtained from racemic materials as appropriate via standard physical separation techniques, such as reverse phase chiral chromatography, or through stereoselective synthetic techniques, (eg, by using chiral starting materials).

TABLE-US-00012 TABLE T1 Melting point (mp) data and/or retention times (RT) for compounds according to Formula (I): RT [M + H] mp Entry Compound name Structure (mins) (measured) Method ( C.) 1.1 N-[2-chloro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]acetamide [00015] 155-170 1.2 N-[2-chloro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]-2- methoxy-acetamide [00016] 77-84 1.3 N-[2-methyl-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]acetamide [00017] 153-179 1.4 N-[2-methyl-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]propanamide [00018] 178-185 1.5 2-methoxy-N-[2-methyl-4- [5-(trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]acetamide [00019] 73-80 1.6 N-[2-fluoro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]propanamide [00020] 123-128 1.7 N-[2-fluoro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]acetamide [00021] 120-126 1.8 N-[2-fluoro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]-2- methoxy-acetamide [00022] 42-46 1.9 ethyl N-[2-fluoro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]carbamate [00023] 86-91 1.10 1-methoxy-1-methyl-3-[2- methyl-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]urea [00024] 73-76 1.11 1-allyloxy-1-methyl-3-[2- methyl-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]urea [00025] 62-66 1.12 1-(2-methylallyloxy)-3-[2- methyl-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]urea [00026] 114-117 1.13 1-allyloxy-3-[2-methyl-4- [5-(trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]urea [00027] 101-104 1.14 N-[2-fluoro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]-2- methyl-propanamide [00028] 1.68 318.1 B 1.15 N-[2-fluoro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]-3- methoxy-propanamide [00029] 1.53 334.1 B 1.16 N-[2-fluoro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]-2- methyl-butanamide [00030] 1.78 332.1 B 1.17 2-(chloromethyl)-N-[2- fluoro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]-3- hydroxy-2-methyl- propanamide [00031] 1.67 346.4 B 1.18 N-[2-fluoro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]-2- (methoxymethyl) butanamide [00032] 1.77 362.1 B 1.19 N-[2-fluoro-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]-4- methoxy-butanamide [00033] 1.57 348.1 B 1.20 2-methyl-N-[2-methyl-4- [5-(trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]propanamide [00034] 1.62 314.2 B 1.21 3-methoxy-N-[2-methyl-4- [5-(trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]propanamide [00035] 1.50 330.1 B 1.22 2-methyl-N-[2-methyl-4- [5-(trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]butanamide [00036] 1.72 328.2 B 1.23 2-(chloromethyl)-3- hydroxy-2-methyl-N-[2- methyl-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]propanamide [00037] 1.64 378.1 B 1.24 2-(methoxymethyl)-N-[2- methyl-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]butanamide [00038] 1.73 358.2 B 1.25 4-methoxy-N-[2-methyl-4- [5-(trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]butanamide [00039] 1.52 344.2 B 1.26 2-cyano-N-[2-methyl-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]acetamide [00040] 1.39 311.1 B 1.27 2-methoxy-N-[2-methyl-4- [5-(trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]propanamide [00041] 1.64 330.1 B 1.28 3,3,3-trifluoro-N-[2- methyl-4-[5- (trifluoromethyl)-1,2,4- oxadiazol-3- yl]phenyl]propanamide [00042] 1.62 354.1 B

BIOLOGICAL EXAMPLES

[0261] General Examples of Leaf Disk Tests in Well Plates:

[0262] Leaf disks or leaf segments of various plant species are cut from plants grown in a greenhouse. The cut leaf disks or segments are placed in multiwell plates (24-well format) onto water agar. The leaf disks are sprayed with a test solution before (preventative) or after (curative) inoculation. Compounds to be tested are prepared as DMSO solutions (max. 10 mg/ml) which are diluted to the appropriate concentration with 0.025% Tween20 just before spraying. The inoculated leaf disks or segments are incubated under defined conditions (temperature, relative humidity, light, etc.) according to the respective test system. A single evaluation of disease level is carried out 3 to 14 days after inoculation, depending on the pathosystem. Percent disease control relative to the untreated check leaf disks or segments is then calculated.

[0263] General Examples of Liquid Culture Tests in Well Plates:

[0264] Mycelia fragments or conidia suspensions of a fungus prepared either freshly from liquid cultures of the fungus or from cryogenic storage, are directly mixed into nutrient broth. DMSO solutions of the test compound (max. 10 mg/ml) are diluted with 0.025% Tween20 by a factor of 50 and 10 l of this solution is pipetted into a microtiter plate (96-well format). The nutrient broth containing the fungal spores/mycelia fragments is then added to give an end concentration of the tested compound. The test plates are incubated in the dark at 24 C. and 96% relative humidity. The inhibition of fungal growth is determined photometrically after 2 to 7 days, depending on the pathosystem, and percent antifungal activity relative to the untreated check is calculated.

Example 1

Fungicidal Activity Against Puccinia Recondita f. sp. Tritici/Wheat/Leaf Disc Preventative (Brown Rust)

[0265] Wheat leaf segments cv. Kanzler were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf segments were incubated at 19 C. and 75% relative humidity (rh) under a light regime of 12 hours light/12 hours darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (7 to 9 days after application).

[0266] The following compounds at 200 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0267] Compounds (from Table T1): 1.3, 1.5, 1.7, 1.8, 1.9, 1.10, 1.12, 1.13, 1.17, 1.18, 1.19, 1.26, and 1.28.

Example 2

Fungicidal Activity Against Puccinia Recondita f. sp. Tritici/Wheat/Leaf Disc Curative (Brown Rust)

[0268] Wheat leaf segments cv. Kanzler are placed on agar in multiwell plates (24-well format). The leaf segments are then inoculated with a spore suspension of the fungus. Plates were stored in darkness at 19 C. and 75% relative humidity. The formulated test compound diluted in water was applied 1 day after inoculation. The leaf segments were incubated at 19 C. and 75% relative humidity under a light regime of 12 hours light/12 hours darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (6 to 8 days after application).

[0269] The following compounds at 200 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0270] Compounds (from Table T1): 1.3, 1.6, 1.7, 1.9, 1.10, 1.15, 1.18, and 1.27.

Example 3

Fungicidal Activity Against Phakopsora Pachyrhizi/Soybean/Leaf Disc Preventative (Asian Soybean Rust)

[0271] Soybean leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. One day after application leaf discs are inoculated by spraying a spore suspension on the lower leaf surface. After an incubation period in a climate cabinet of 24-36 hours in darkness at 20 C. and 75% rh leaf disc are kept at 20 C. with 12 h light/day and 75% rh. The activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (12 to 14 days after application).

[0272] The following compounds at 200 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0273] Compounds (from Table T1): 1.4, and 1.6.

Example 4

Fungicidal Activity Against Glomerella Lagenarium (Colletotrichum Lagenarium) Liquid Culture/Cucumber/Preventative (Anthracnose)

[0274] Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDBpotato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24 C. and the inhibition of growth is measured photometrically 3 to 4 days after application.

[0275] The following compounds at 20 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control under the same conditions, which show extensive disease development.

[0276] Compounds (from Table T1): 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.10, 1.11, 1.12, 1.13, 1.14, 1.15, 1.16, 1.17, 1.18, 1.19, 1.21, 1.23, 1.24, 1.25, 1.26, and 1.27.

Example 5

Fungicidal Activity Against Uromyces Viciae-Fabae/Field Bean/Leaf Disc Preventative (Faba-Bean Rust)

[0277] Field bean leaf discs are placed on water agar in multiwell plates (96-well format) and 10 l of the formulated test compound diluted in acetone and a spreader pipetted onto the leaf disc. Two hours after application leaf discs are inoculated by spraying a spore suspension on the lower leaf surface. The leaf discs are incubated in a climate cabinet at 22 C. with 18 hour day and 70% relative humidity. The activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (12 days after application).

[0278] The following compounds at 100 ppm in the applied formulation give at least 80% disease control in this test when compared to untreated control leaf discs under the same conditions, which show extensive disease development.

[0279] Compounds (from Table T1):