Microbiocidal quinoline (thio)carboxamide derivatives

Abstract

Compounds of the formula (I) wherein the substituents are as defined in claim 1. Furthermore, the present invention relates to agrochemical compositions which comprise compounds of formula (I), to preparation of these compositions, and to the use of the compounds or compositions in agriculture or horticulture for combating, preventing or controlling infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, in particular fungi. ##STR00001##

Claims

1. A compound of formula (I) ##STR00063## wherein X is O or S; R.sub.1 is hydrogen, halogen, methyl or cyano; R.sub.2 is hydrogen, methyl or halogen; R.sub.3 and R.sub.4 are each independently selected from hydrogen, halogen and methyl; R.sub.5 is C.sub.1-C.sub.4 alkyl, C.sub.2-C.sub.4 alkenyl or C.sub.3-C.sub.6 cycloalkyl, wherein the alkyl, alkenyl and cycloalkyl may be optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.3 alkoxy and C.sub.1-C.sub.3 alkylthio; R.sub.6 is hydrogen, cyano or C.sub.1-C.sub.4 alkyl; R.sub.7 is C.sub.4-C.sub.10 saturated or partially unsaturated heterocycle or heteroaryl, wherein the heterocycle or heteroaryl contains one, two or three heteroatoms selected from N, O and S, and is connected via a carbon or a nitrogen atom, and may be optionally substituted with one or more substituents independently selected from halogen, cyano, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3 alkylthio; C.sub.1-C.sub.3 haloalkyl, C.sub.1-C3 haloalkoxy, C.sub.1-C.sub.3 haloalkylthio and C.sub.3-C.sub.5 cycloalkyl; or a salt, enantiomer or N-oxide thereof.

2. The compound, or a salt, enantiomer or N-oxide thereof, according to claim 1 wherein R.sub.1 is hydrogen, fluoro, chloro, methyl or cyano.

3. The compound, or a salt, enantiomer or N-oxide thereof, according to claim 1 wherein R.sub.2 is hydrogen, methyl, chloro or fluoro.

4. The compound, or a salt, enantiomer or N-oxide thereof, according to claim 1 wherein R.sub.3 and R.sub.4 are each independently selected from hydrogen and methyl.

5. The compound, or a salt, enantiomer or N-oxide thereof, according to claim 1 wherein R.sub.5 is C.sub.1-C.sub.4 alkyl, C.sub.2-C.sub.4 alkenyl or C.sub.3-C.sub.6 cycloalkyl, wherein the alkyl, alkenyl and cycloalkyl may be optionally substituted with 1 to 3 substituents independently selected from fluoro, chloro and C.sub.1-C.sub.3 alkyl.

6. The compound, or a salt, enantiomer or N-oxide thereof, according to claim 1 wherein R.sub.6 is hydrogen or C.sub.1-C.sub.3 alkyl.

7. The compound, or a salt, enantiomer or N-oxide thereof, according to claim 1 wherein R.sub.7 is thienyl, azetidinyl, pyrazolyl, oxazolyl, 1,2,4-oxadiazolyl, thiazolyl, pyrrolidinyl, piperidyl pyridazinyl, oxazinanyl, thiomorpholinyl, morpholinyl, indazolyl, 4,5-dihydro-3H-pyridazinyl or pyridinyl, wherein the thienyl, azetidinyl, pyrazolyl, oxazolyl, 1,2,4-oxadiazolyl, thiazolyl, pyrrolidinyl, piperidyl, pyridazinyl, oxazinanyl, thiomorpholinyl, morpholinyl, indazolyl, 4,5-dihydro-3H-pyridazinyl and pyridinyl may be optionally substituted with one or more substituents independently selected from fluoro, chloro, cyano, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 haloalkyl and C.sub.3-C.sub.4 cycloalkyl.

8. The compound, or a salt, enantiomer or N-oxide thereof, according to claim 1 wherein R.sub.1 is hydrogen, fluoro, chloro or methyl; R.sub.2 is hydrogen, chloro or fluoro; R.sub.3 is methyl and R.sub.4 is hydrogen; or R.sub.3 is hydrogen and R.sub.4 is methyl; or R.sub.3 is hydrogen and R.sub.4 is hydrogen; R.sub.5is C.sub.1-C.sub.4 alkyl, C.sub.2-C.sub.3 alkenyl, cyclopropyl or cyclobutyl, wherein the alkyl, alkenyl, cyclopropyl and cyclobutyl may be optionally substituted with 1 to 3 substituents independently selected from fluoro and chloro or one methyl group; and R.sub.6 is hydrogen, methyl or ethyl.

9. The compound, or a salt, enantiomer or N-oxide thereof, according to claim 1 wherein R.sub.7 is thienyl, azetidinyl, pyrazolyl, oxazolyl, 1,2,4-oxadiazolyl, thiazolyl, pyrrolidinyl, piperidyl oxazinanyl, thiomorpholinyl, morpholinyl, indazolyl, 4,5-dihydro-3H-pyridazinyl or pyridinyl, wherein the thienyl, azetidinyl, pyrazolyl, oxazolyl, 1,2,4-oxadiazolyl, thiazolyl, pyrrolidinyl, piperidyl, oxazinanyl, thiomorpholinyl, morpholinyl, indazolyl, 4,5-dihydro-3H-pyridazinyl and pyridinyl may be optionally substituted with one or two substituents independently selected from fluoro, chloro, methyl, trifluoromethyl and cyclopropyl.

10. The compound according to claim 1 wherein X is O or S; R.sub.1 is hydrogen, fluoro, chloro or methyl; R.sub.2 is hydrogen, chloro or fluoro; R.sub.3 is methyl and R.sub.4 is hydrogen; or R.sub.3 is hydrogen and R.sub.4 is methyl; or R.sub.3 is hydrogen and R.sub.4 is hydrogen; R.sub.5 is C.sub.1-C.sub.4 alkyl, C.sub.2-C.sub.3 alkenyl, cyclopropyl or cyclobutyl, wherein the alkyl, alkenyl, cyclopropyl and cyclobutyl may be optionally substituted with 1 to 3 substituents independently selected from fluoro and chloro or one methyl group; R.sub.6 is hydrogen, methyl or ethyl; R.sub.7 is thienyl, azetidinyl, pyrazolyl, oxazolyl, 1,2,4-oxadiazolyl, thiazolyl, pyrrolidinyl, piperidyl oxazinanyl, thiomorpholinyl, morpholinyl, indazolyl, 4,5-dihydro-3H-pyridazinyl or pyridinyl, wherein the thienyl, azetidinyl, pyrazolyl, oxazolyl, 1,2,4-oxadiazolyl, thiazolyl, pyrrolidinyl, piperidyl, oxazinanyl, thiomorpholinyl, morpholinyl, indazolyl, 4,5-dihydro-3H-pyridazinyl and pyridinyl may be optionally substituted with one or two sub stituents independently selected from fluoro, chloro, methyl, trifluoromethyl and cyclopropyl; or a salt, enantiomer or N-oxide thereof.

11. The compound according to claim 1 wherein X is O or S; R.sub.1 is fluoro, chloro or methyl; R.sub.2 is hydrogen or fluoro; R.sub.3 and R.sub.4 are both hydrogen; R.sub.5 is trifluoromethyl, ethyl, isopropyl, tert-butyl, C.sub.2-alkenyl or cyclopropyl, wherein the ethyl, isopropyl, alkenyl and cyclopropyl may be optionally substituted with 1 to 3 substituents independently selected from fluoro and chloro or one methyl group; R.sub.6 is methyl; R.sub.7 is thienyl, azetidinyl, thiazolyl, pyrrolidinyl, piperidyl or pyridinyl, wherein the thienyl, azetidinyl, thiazolyl, pyrrolidinyl, piperidyl, and pyridinyl may be optionally substituted with one or two substituents independently selected from fluoro, chloro, methyl or trifluoromethyl; or a salt, enantiomer or N-oxide thereof.

12. The compound, or a salt, enantiomer or N-oxide thereof, according to claim 1 wherein X is O.

13. A composition comprising a fungicidally effective amount of a compound of formula (I) as defined in claim 1.

14. A composition according to claim 13, wherein the composition further comprises at least one additional active ingredient and/or a diluent.

15. A method of combating, preventing or controlling phytopathogenic fungi which comprises applying to phytopathogenic fungi, to the locus of phytopathogenic fungi, or to a plant susceptible to attack by phytopathogenic fungi, or to propagation material thereof, a fungicidally effective amount of a compound of formula (I) as defined in claim 1.

16. A compound of formula (I) ##STR00064## wherein X is O or S; R.sub.1 is hydrogen, halogen, methyl or cyano; R.sub.2 is hydrogen, methyl or halogen; R.sub.3 and R.sub.4 are each independently selected from hydrogen, halogen and methyl; R.sub.5 is C.sub.1-C.sub.4 alkyl, C.sub.2-C.sub.4 alkenyl or C.sub.3-C.sub.6 cycloalkyl, wherein the alkyl, alkenyl and cycloalkyl may be optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.3 alkoxy and C.sub.1-C.sub.3 alkylthio; R.sub.6 is hydrogen, cyano or C.sub.1-C.sub.4 alkyl; R.sub.7 is C.sub.4-C.sub.10 saturated or partially unsaturated heterocycle or heteroaryl, wherein the heterocycle or heteroaryl contains one, two or three heteroatoms selected from N, O and S, and is connected via a carbon or a nitrogen atom, and may be optionally substituted with one or more substituents independently selected from halogen, cyano, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3 alkylthio; C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 haloalkylthio and C.sub.3-C.sub.5 cycloalkyl, or wherein one of the ring-member methylene groups may optionally represent C═O, C═CH.sub.2 or C═CF.sub.2; or a salt, enantiomer or N-oxide thereof.

17. The compound according to claim 16 wherein X is O or S; R.sub.1 is fluoro, chloro or methyl; R.sub.2 is hydrogen or fluoro; R.sub.3 and R.sub.4 are both hydrogen; R.sub.5 is trifluoromethyl, ethyl, isopropyl, tert-butyl, C.sub.2-alkenyl or cyclopropyl, wherein the ethyl, isopropyl, alkenyl and cyclopropyl may be optionally substituted with 1 to 3 substituents independently selected from fluoro and chloro or one methyl group; R.sub.6 is methyl; R.sub.7 is piperidyl wherein one of the ring-member methylene groups may optionally represent C═CF.sub.2 wherein the piperidyl may be optionally substituted with one or two substituents independently selected from fluoro, chloro, methyl or trifluoromethyl; or a salt, enantiomer or N-oxide thereof.

18. The compound according to claim 16 wherein R.sub.7 is piperidyl wherein one of the ring-member methylene groups may optionally represent C═O, C═CH.sub.2 or C═CF.sub.2, and may be optionally substituted with one or more substituents independently selected from halogen, cyano, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3 alkylthio; C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 haloalkylthio and C.sub.3-C.sub.5 cycloalkyl.

19. A compound selected from ##STR00065## ##STR00066## ##STR00067## ##STR00068## ##STR00069## ##STR00070## ##STR00071##

Description

EXAMPLES

(1) The Examples which follow serve to illustrate the invention. Certain 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.

(2) Throughout this description, temperatures are given in degrees Celsius and “m.p.” means melting point. LC/MS means Liquid Chromatography Mass Spectroscopy and the description of the apparatus and the methods are:

(3) Method G:

(4) Spectra were recorded on a Mass Spectrometer (ACQUITY UPLC) from Waters (SQD, SQDII or ZQ Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.00 kV, Cone range: 30-60 V, Extractor: 2.00 V, Source Temperature: 150° C., Desolvation Temperature: 350° C., Cone Gas Flow: 0 L/Hr, Desolvation Gas Flow: 650 L/Hr, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment and diode-array detector. Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3, 1.8 m, 30×2.1 mm, Temp: 60° C., DAD Wavelength range (nm): 210 to 500, Solvent Gradient: A=water+5% MeOH+0.05% HCOOH, B=Acetonitrile+0.05% HCOOH, gradient: 10-100% B in 1.2 min; Flow (ml/min) 0.85

(5) Method H:

(6) Spectra were recorded on a Mass Spectrometer (ACQUITY UPLC) from Waters (SQD, SQDII or ZQ Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.00 kV, Cone range: 30-60 V, Extractor: 2.00 V, Source Temperature: 150° C., Desolvation Temperature: 350° C., Cone Gas Flow: 0 L/Hr, Desolvation Gas Flow: 650 L/Hr, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment and diode-array detector. Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3, 1.8 μm, 30×2.1 mm, Temp: 60° C., DAD Wavelength range (nm): 210 to 500, Solvent Gradient: A=water+5% MeOH+0.05% HCOOH, B=Acetonitrile+0.05% HCOOH, gradient: 10-100% B in 2.7 min; Flow (ml/min) 0.85

(7) Method I:

(8) Spectra were recorded on a Mass Spectrometer (ACQUITY UPLC) from Waters (SQD, SQDII or ZQ Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, 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, Mass range: 140 to 800 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment and diode-array detector. Solvent degasser, binary pump, heated column compartment and diode-array detector. Solvent degasser, binary pump, heated column compartment and diode-array detector. 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., DAD Wavelength range (nm): 210 to 400. Solvent Gradient A: Water/Methanol 9:1,0.1% formic acid and Solvent B: Acetonitrile, 0.1% formic acid

(9) TABLE-US-00002 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

FORMULATION EXAMPLES

(10) Wettable Powders a) b) c)

(11) TABLE-US-00003 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% —
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.

(12) Powders for Dry Seed Treatment a) b) c)

(13) TABLE-US-00004 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
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.

(14) Emulsifiable Concentrate

(15) TABLE-US-00005 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%
Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.

(16) Dusts a) b) c)

(17) TABLE-US-00006 a) b) c) Active ingredient [compound of formula (I)]  5%  6%  4% talcum 95% — — Kaolin — 94% — mineral filler — — 96%
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.

(18) Extruder Granules

(19) TABLE-US-00007 Active ingredient [compound of formula (I)] 15% sodium lignosulfonate  2% carboxymethylcellulose  1% Kaolin 82%
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.

(20) Coated Granules

(21) TABLE-US-00008 Active ingredient [compound of formula (I)] 8% polyethylene glycol (mol. wt. 200) 3% Kaolin 89% 
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.
Suspension Concentrate

(22) TABLE-US-00009 active ingredient [compound of formula (I)] 40% propylene glycol 10% nonylphenol polyethylene glycol ether (15  6% mol of ethylene oxide) Sodium lignosulfonate 10% carboxymethylcellulose  1% silicone oil (in the form of a 75% emulsion in  1% water) Water 32%
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.
Flowable Concentrate for Seed Treatment

(23) TABLE-US-00010 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%.sup.  solution in water) monoazo-pigment calcium salt 5% Silicone oil (in the form of a 75% emulsion in 0.2%.sup.  water) Water 45.3%  
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
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.
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.
The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.

PREPARATION EXAMPLES

Example 1: N-[1-[(5-chloro-2-thienyl)methyl]-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide

Step 1: Preparation of ethyl 2-[(5-chloro-2-thienyl)methyl]-2,4-dimethyl-pentanoate

(24) To a solution of ethyl 2,4-dimethylpentanoate (0.36 g, 2.28 mmol) in tetrahydrofuran (0.25 M, 9.1 mL) at −70° C. was added a solution of lithium diisopropylamide (2 M in THF, 1.3 equiv., 1.5 mL, 2.96 mmol). The solution was stirred at −70° C. for 1 h. 2-chloro-5-(chloromethyl)thiophene (1.3 equiv., 0.37 mL, 2.96 mmol) was then added and the orange solution was allowed to warmup to rt and stirred at this temperature for 16 h. The reaction mixture was quenched with saturated aqueous NH.sub.4Cl solution. The two phases were separated and the aqueous phase was extracted twice with ethyl acetate. The combined organic phase was washed with brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and concentrated. Purification of the residue by flash chromatography gave ethyl 2-[(5-chloro-2-thienyl)methyl]-2,4-dimethyl-pentanoate (0.25 g, 38% yield) as a yellow liquid: LC-MS (Method G), Rt=1.35 min;

(25) .sup.1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.91 (d, 6H) 1.15 (s, 3H) 1.28 (t, 3H) 1.45 (m, 1H) 1.68-1.75 (m, 2H) 2.71 (d, 1H) 3.19 (d, 1H) 4.14 (q, 2H) 6.52 (d, 1H) 6.70 (d, 1H).

Step 2: Preparation of 2-[(5-chloro-2-thienyl)methyl]-2,4-dimethyl-pentanoic acid

(26) To a solution of ethyl 2-[(5-chloro-2-thienyl)methyl]-2,4-dimethyl-pentanoate (0.17 g, 0.58 mmol) in dioxane (0.2 M, 2.9 mL) and water (0.5 M, 1.2 mL) was added an aqueous solution of sodium hydroxide (2 M) (5 equiv., 1.45 mL, 2.9 mmol) followed by an aqueous solution of tetrabutylammonium hydroxide (40% w/w) (2 equiv., 0.75 g, 1.16 mmol) dropwise. The brown solution was stirred at 110° C. for 26 h. The reaction mixture was then diluted with dichloromethane and the two phases were separated. The aqueous phase was then acidified with an aqueous solution of hydrochloric acid (2 M) and extracted twice with dichloromethane. This organic phase was washed with brine, dried over Na.sub.2SO.sub.4, filtered and concentrated to give 2-[(5-chloro-2-thienyl)methyl]-2,4-dimethyl-pentanoic acid (0.115 g, 75% yield) as a yellow gum: LC-MS (Method G), Rt=1.12 min; MS: (M+1)=259-261;

(27) .sup.1H NMR (400 MHz, MeOD-d) δ ppm 0.95 (dd, 6H) 1.15 (s, 3H) 1.45 (m, 1H) 1.70 (m, 1H) 1.80 (m, 1H) 2.80 (d, 1H) 3.20 (d, 1H) 6.68 (d, 1H) 6.80 (d, 1H).

Step 3: Preparation of 2-[(5-chloro-2-thienyl)methyl]-2,4-dimethyl-pentanamide

(28) To a solution of 2-[(5-chloro-2-thienyl)methyl]-2,4-dimethyl-pentanoic acid (0.11 g, 0.42 mmol) in dichloromethane (0.1 M, 4.2 mL) and 3 drops of dimethylformamide was added oxalyl chloride (0.048 mL, 1.3 equiv., 0.55 mmol). The solution was stirred at rt for 1 h, then concentrated under vacuum. The residue was dissolved in dichloromethane (0.1 M, 4.2 mL) and triethylamine (0.176 mL, 3 equiv., 1.27 mmol) was added followed by ammonium chloride (0.045 g, 2 equiv., 0.84 mmol). The reaction mixture was stirred at rt for 1 h, then diluted with dichloromethane and washed with water and with brine, dried over Na.sub.2SO.sub.4, filtered and concentrated. Purification by flash chromatography gave 2-[(5-chloro-2-thienyl)methyl]-2,4-dimethyl-pentanamide (0.055 g, 50% yield) as a yellow gum: LC-MS (Method G), Rt=1.01 min; MS: (M+1)=260-262;

(29) .sup.1H NMR (400 MHz, CDCl3-d) δ ppm 0.92 (t, 6H) 1.18 (s, 3H) 1.34 (m, 1H) 1.73 (m, 2H) 2.63 (d, 1H) 3.21 (d, 1H) 5.61 (b, 1H) 5.91 (b, 1H) 6.56 (d, 1H) 6.70 (d, 1H).

Step 4: Preparation of 1-(5-chloro-2-thienyl)-2,4-dimethyl-pentan-2-amine

(30) To a solution of 2-[(5-chloro-2-thienyl)methyl]-2,4-dimethyl-pentanamide (0.055 g, 0.21 mmol) in acetonitrile (0.33 M, 0.65 mL) and water (0.33 M, 0.65 mL) was added (Bis(trifluoroacetoxy)iodo)benzene (0.100 g, 1.1 equiv., 0.23 mmol) and the solution was stirred at 60° C. for 4 h. The reaction mixture was diluted with dichloromethane and water, acidified with an aqueous solution of hydrochloric acid (1 M) and washed with dichloromethane. The aqueous phase was then basified with an aqueous solution of NaOH (4 M) and extracted twice with dichloromethane. The organic phase was washed with brine, dried over Na.sub.2SO.sub.4, filtered and concentrated to give 1-(5-chloro-2-thienyl)-2,4-dimethyl-pentan-2-amine (0.040 g, 82% yield) as a colourless gum: LC-MS (Method G), Rt=0.70 min; MS: (M+1)=232-234;

(31) .sup.1H NMR (400 MHz, CDCl3-d) δ ppm 0.94 (dd, 6H) 1.08 (s, 3H) 1.30 (m, 2H) 1.77 (m, 1H) 2.73 (s, 2H) 6.53 (d, 1H) 6.73 (d, 1H).

Step 5: Preparation of N-[1-[(5-chloro-2-thienyl)methyl]-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide

(32) To a solution of 1-(5-chloro-2-thienyl)-2,4-dimethyl-pentan-2-amine (0.040 g, 0.17 mmol) in dichloromethane (1.7 mL, 0.1 M) and triethylamine (0.07 mL, 3 equiv., 0.52 mmol) was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.037 g, 1.1 equiv., 0.19 mmol) followed by O-(7-azabenzotriazole-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.074 g, 1.1 equiv., 0.19 mmol) and 8-fluoroquinoline-3-carboxylic acid (0.036 g, 1.1 equiv., 0.19 mmol). The solution was stirred at rt for 16 h. The reaction mixture was quenched with saturated aqueous NaHCO.sub.3. The two phases were separated and aqueous phase was extracted twice with dichloromethane. The combined organic phase was washed with brine, dried over Na.sub.2SO.sub.4 anhydrous, filtered and concentrated. Purification by flash chromatography gave N-[1-[(5-chloro-2-thienyl)methyl]-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide (0.054 g, 77% yield) as a white solid, mp=126-128° C., LC-MS (Method G), Rt=1.21 min; MS: (M+1)=405-407;

(33) .sup.1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.02 (d, 6H) 1.46 (s, 3H) 1.59 (dd, 1H) 1.88 (m, 1H) 2.11 (dd, 1H) 3.18 (d, 1H) 3.60 (d, 1H) 5.89 (b, 1H, NH) 6.59 (d, 1H) 6.71 (d, 1H) 7.49 (m, 1H) 7.58 (m, 1H) 7.70 (d, 1H) 8.49 (s, 1H) 9.19 (s, 1H).

Example 2: N-[1-[(3,3-difluoro-1-piperidyl)methyl]-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide

Step 1: Preparation of N-(1,3-dimethylbutylidene)-2-methyl-propane-2-sulfinamide

(34) To a solution of Isobutylmethylketone (13.7 mL, 108.73 mmol) in tetrahydrofuran (218 mL), was added (±) t-butylsulfinamide (13.585 g, 1 equiv., 108.73 mmol) was added followed by titanium (IV) ethoxide (34.19 mL, 1.50 equiv., 163.09 mmol) and the solution was stirred at 60° C. overnight. The reaction mixture was then cooled down to room temperature, and was slowly poured onto a mixture of 200 mL ethyl acetate and 200 mL saturated aqueous sodium bicarbonate solution. The mixture was stirred at room temperature for 30 min and filtered over a pad of celite. The filtrate was concentrated under reduce pressure and the residue was then filtered over a pad of silica gel and the silica pad was washed with cyclohexane/ethyl acetate (70:30).

(35) The filtrate was concentrated under reduce pressure to afford N-(1,3-dimethylbutylidene)-2-methyl-propane-2-sulfinamide (15.4 g, 70%) as a yellow liquid. LC-MS (Method G) UV Detection: 220 nm, Rt=0.94 min;

(36) .sup.1H NMR (CHLOROFORM-d) δ: 2.31-2.35 (s, 3H), 2.25-2.30 (m, 1H), 2.07-2.19 (m, 1H), 1.40-1.47 (m, 1H), 1.19-1.32 (s, 9H), 0.92-1.00 (dd, 6H).

Step 2: Preparation of 1-tert-butylsulfinyl-2-isobutyl-2-methyl-aziridine

(37) To a suspension of trimethylsulfoxonium iodide (8.93 g, 39.3 mmol) in dimethylsulfoxide (59.0 mL, 0.67 M) was added a solution of potassium t-butoxide (1 M in THF, 39.3 mL, 1 equiv., 39.3 mmol), and the reaction mixture was stirred at room temperature for 45 min. N-(1,3-dimethylbutylidene)-2-methyl-propane-2-sulfinamide (4.00 g, 19.7 mmol) was then added, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with water and extracted with ethyl acetate twice. The combined organic phase was washed with brine twice, dried over anhydrous magnesium sulfate, filtered and concentrated under reduce pressure to afford 1-tert-butylsulfinyl-2-isobutyl-2-methyl-aziridine (3.99 g, 93%) as an inseparable mixture of isomers (1:3) as a yellow liquid. The product was pure enough and used in the following step without further purification.

(38) Isomer 1: LC-MS (Method G)

(39) UV Detection: 220 nm, Rt=1.09 min; MS: (M+1)=218

(40) .sup.1H NMR (CHLOROFORM-d) δ: 2.61-2.65 (s, 1H), 2.44-2.47 (s, 1H), 1.82-1.90 (m, 1H), 1.41-1.48 (m, 1H), 1.29-1.35 (m, 1H), 1.26-1.28 (s, 3H), 1.19-1.25 (m, 9H), 0.88-0.97 (t, 6H);

(41) Isomer 2: LC-MS (Method G)

(42) UV Detection: 220 nm, Rt=1.11 min; MS: (M+1)=218;

(43) .sup.1H NMR (CHLOROFORM-d): 2.41-2.43 (s, 1H), 1.82-1.90 (m, 1H), 1.69-1.72 (s, 1H), 1.41-1.48 (m, 1H), 1.39-1.41 (s, 3H), 1.29-1.35 (m, 1H), 1.19-1.25 (s, 9H), 0.88-0.97 (t, 6H).

Step 3: Preparation of N-[1-[(3,3-difluoro-1-piperidyl)methyl]-1,3-dimethyl-butyl]-2-methyl-propane-2-sulfinamide

(44) To a solution of 3,3-difluoropiperidine hydrochloride (0.3624 g, 2.0 equiv., 2.300 mmol) in dry tetrahydrofuran (1.150 mL, 1 M) at room temperature under argon, was added dropwise a solution of isopropylmagnesium chloride-lithium chloride complex (1.3 M in THF, 1.8 mL, 2.0 equiv., 2.300 mmol). The solution was stirred at room temperature for 2 h before 1-tert-butylsulfinyl-2-isobutyl-2-methyl-aziridine (0.25 g, 1.150 mmol) was added. The reaction mixture was stirred at room temperature for 45 min and then at 90° C. for 2 days. The reaction mixture was then cooled down to room temperature and slowly quenched with water. The reaction mixture was then extracted with ethyl acetate twice. The combined organic phase was washed with water, saturated ammonium chloride solution, then dried over magnesium sulfate, filtered and concentrated under reduce pressure to afford N-[1-[(3,3-difluoro-1-piperidyl)methyl]-1,3-dimethyl-butyl]-2-methyl-propane-2-sulfinamide (282 mg, 72%) as a brown liquid as a mixture of isomers. The isomer mixture was used in the following step without further purification. Isomer 1: LC-MS (Method G) UV Detection: 220 nm, Rt=1.10 min; MS: (M+1)=338; .sup.1H NMR (CHLOROFORM-d) δ: 4.22-4.27 (s, 1H), 2.91-3.03 (m, 1H), 2.70-2.83 (m, 2H), 2.48-2.59 (m, 1H), 2.29-2.46 (m, 1H), 1.54-1.90 (m, 7H), 1.45-1.54 (m, 1H), 1.35-1.39 (s, 3H), 1.18-1.24 (s, 9H), 0.88-0.96 (m, 6H); Isomer 2: LC-MS (Method G) UV Detection: 220 nm, Rt=1.12 min; MS: (M+1)=338

(45) .sup.1H NMR (CHLOROFORM-d) δ: 4.22-4.27 (s, 1H), 2.91-3.03 (m, 1H), 2.70-2.83 (m, 2H), 2.48-2.59 (m, 1H), 2.29-2.46 (m, 1H), 1.54-1.90 (m, 7H), 1.45-1.54 (m, 1H), 1.28-1.33 (s, 3H), 1.18-1.24 (s, 9H), 0.88-0.96 (dd, 6H).

Step 4: Preparation of 1-(3,3-difluoro-1-piperidyl)-2,4-dimethyl-pentan-2-amine

(46) To a solution of N-[1-[(3,3-difluoro-1-piperidyl)methyl]-1,3-dimethyl-butyl]-2-methyl-propane-2-sulfinamide (0.28 g, 0.83 mmol) in methanol (2.585 mL, 0.4 M) was added dropwise a solution of hydrogen chloride (4 M in dioxane) (0.312 mL, 1.5 equiv., 1.24 mmol). The solution was stirred at room temperature for 2 h 30 min and then the volatiles were removed under reduce pressure. The residue was partitioned between diethyl ether and water. The two phases were separated and the aqueous phase was washed with diethyl ether. The aqueous phase was basified with an aqueous sodium hydroxide solution (8 N) and then extracted with ethyl acetate twice. The combined organic phase was dried over magnesium sulfate, filtered and concentrated under reduce pressure to afford 1-(3,3-difluoro-1-piperidyl)-2,4-dimethyl-pentan-2-amine (99 mg, 51%) as a brown liquid;

(47) .sup.1H NMR (CHLOROFORM-d) δ: 2.72-2.87 (t, 2H), 2.52-2.64 (broad s, 2H), 2.25-2.33 (s, 2H), 1.91-2.12 (m, 2H), 1.78-1.90 (m, 2H), 1.66-1.78 (m, 3H), 1.25-1.34 (dd, 2H), 1.03-1.12 (s, 3H), 0.86-1.00 (m, 6H)

Step 5: Preparation of N-[1-[(3,3-difluoro-1-piperidyl)methyl]-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide

(48) To a suspension of 8-fluoroquinoline-3-carboxylic acid (0.080 g, 0.42 mmol) in acetonitrile (2.1 mL, 0.2 M) was added triethylamine (0.178 mL, 3.0 equiv., 1.27 mmol), N,N-dimethylaminopyridine (2 mg), and then a solution of propylphosphonic anhydride (T3P®, 50% w/w in ethyl acetate, 0.503 mL, 2.0 equiv., 0.845 mmol). The solution was stirred at room temperature then 1-(3,3-difluoro-1-piperidyl)-2,4-dimethyl-pentan-2-amine (0.099 g, 1.0 equiv., 0.42 mmol) was added, and the solution was stirred at room temperature overnight. The reaction mixture was then diluted with ethylacetate and washed with water three times, dried over magnesium sulfate, filtered and concentrated under reduce pressure. The residue was purified by flash chromatography (cyclohexane/ethyl acetate=9:1 to 3:2) to give N-[1-[(3,3-difluoro-1-piperidyl)methyl]-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide (53 mg, 31%) as a yellow oil. LC-MS (Method G) UV Detection: 220 nm, Rt=1.00 min; MS: (M+1)=408;

(49) .sup.1H NMR (CHLOROFORM-d) δ: 9.26-9.36 (m, 1H), 8.53-8.60 (s, 1H), 7.67-7.75 (dd, 1H), 7.52-7.59 (m, 1H), 7.44-7.52 (q, 1H), 6.96-7.09 (broad s, 1H), 2.77-2.96 (m, 3H), 2.61-2.72 (m, 2H), 2.50-2.60 (dd, 1H), 1.84-1.99 (m, 3H), 1.69-1.83 (m, 4H), 1.37-1.47 (s, 3H), 0.90-1.05 (t, 6H).

Example 3: Preparation of the single isomers of N-[1-[(3,3-difluoro-1-piperidyl)methyl]-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide

N-[(1R)-[(3,3-difluoro-1-piperidyl)methyl]-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide

and

N-[(1 S)-[(3,3-difluoro-1-piperidyl)methyl]-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide

(50) The racemic N-[1-[(3,3-difluoro-1-piperidyl)methyl]-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide mixture was submitted to chiral resolution by preparative HPLC chromatography using the conditions outlined hereafter.

(51) Analytical HPLC Method:

(52) SFC:Waters Acquity UPC.sup.2/QDa

(53) PDA Detector Waters Acquity UPC.sup.2

(54) Column: Daicel SFC CHIRALPAK® IA, 3 μm, 0.3 cm×10 cm, 40° C.

(55) Mobile phase: A: CO.sub.2 B: EtOH gradient: 30% B in 1.8 min

(56) ABPR: 1800 psi

(57) Flow rate: 2.0 ml/min

(58) Detection: 235 nm

(59) Sample concentration: 1 mg/mL in ACN/iPr 50/50

(60) Injection: 1 μL

(61) Preparative HPLC Method:

(62) Autopurification System from Waters: 2767 sample Manager, 2489 UV/Visible Detector,

(63) 2545 Quaternary Gradient Module.

(64) Column: Daicel CHIRALPAK® IA, 5 μm, 1.0 cm×25 cm

(65) Mobile phase: Hept/EtOH 90/10

(66) Flow rate: 10 ml/min

(67) Detection: UV 265 nm

(68) Sample concentration: 37 mg/mL in EE

(69) Injection: 130 μl-260 μl,

(70) Results:

(71) TABLE-US-00011 First eluting enantiomer Second eluting enantiomer Retention time (min)~0.54 Retention time (min)~1.60 Chemical purity (area % at Chemical purity (area % at 235 nm) 99 235 nm) 99 Enantiomeric excess (%) >99 Enantiomeric excess (%) >99

(72) TABLE-US-00012 TABLE E Physical data of compounds of formula (I) RT [M + H] MP Entry STRUCTURE (min) (measured) Method ° C. E1 1.02 385 G E2 1.01 386 G E3 1.02 409 G E4 0.76 420 G E5 0.79 408 G E6 1.14 374 G E7 0.74 390 G E8 0 0.99 386 G 146-150 E9 1.10 406-408 G 171-173 E10 0.66 374 G E11 0.99 370 G E12 1.14 371 G E13 1.19 385 G E14 1.21 405-407 G 126-128 E15 1.20 437 G E16 1.14 437 G 140-144 E17 1.14 420 G E18 0 1.16 419 G E19 1.18 417 G 134-138 E20 1.15 397 G 140-144 E21 1.13 384 G E22 1.07 200 G E23 1.20 386 G E24 1.12 371 G E25 0.95 399 G 150-151 E26 0.90 410 G E27 1.01 424 G E28 0 0.92 428 G  76-86 E29 0.97 410 G  70-74 E30 0.97 410 G 136-142 E31 0.93 382 G E32 1.02 395 G E33 1.11 406 G E34 1.03 410 G E35 1.01 392 G 109-111 E36 0.95-0.97 (2 isomers) 381 G  81-84 E37 1.05 395 G E38 0 0.97-0.99 (2 isomers) 399 G  85-88

(73) TABLE-US-00013 TABLE F Physical data of compounds of formula (I) as individual enantiomers RT [M + H] No IUPAC name STRUCTURE (min) measured [α].sub.D.sup.20 method F-1 N-[(1R)-[(3,3- difluoro-1- piperidyl) methyl]-1,3- dimethyl- butyl]-8-fluoro- quinoline-3- carboxamide 1.60 408 −8.7° SFC: Waters Acquity UPC.sup.2/QDa PDA Detector Waters Acquity UPC.sup.2 Column: Daicel SFC CHIRALPAK ® IA, 3μm, 0.3 cm × 10 cm, 40° C. Mobile phase: A: CO.sub.2 B: EtOH gradient: 30% B in 1.8 min ABPR: 1800 psi Flow rate: 2.0 ml/min Detection: 235 nm Sample concentration: 1 mg/mL in ACN/iPr 50/50 Injection: 1 μL F-2 N-[(1S)-[(3,3- difluoro-1- piperidyl)methyl]- 1,3-dimethyl- butyl]-8-fluoro- quinoline-3- carboxamide 0.54 408 +6.1°

BIOLOGICAL EXAMPLES

(74) Botryotinia Fuckeliana (Botrytis cinerea)/Liquid Culture (Gray Mould)

(75) Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (Vogels 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 determined photometrically 3-4 days after application.

(76) The following compounds gave at least 80% control of Botryotinia fuckeliana at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

(77) E1, E2, E3, E4, E5, E6, E7, E8, E9, E11, E12, E13, E14, E17, E18, E19, E20, E21, E22, E23, E24, E25, E26, E27, E28, E29, E30, E31, E32, E33, E34, E35, E36, E37, E38, F1, F2

(78) Glomerella lagenarium (Colletotrichum lagenarium)/liquid culture (Anthracnose)

(79) Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato 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 3-4 days after application.

(80) The following compounds gave at least 80% control of Glomerella lagenarium at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

(81) E1, E2, E3, E4, E5, E6, E8, E11, E12, E13, E14, E15, E18, E19, E20, E21, E22, E23, E24, E25, E26, E27, E28, E29, E32, E33, E34, E35, E36, E37, E38, F1, F2

(82) Fusarium culmorum/Liquid Culture (Head Blight)

(83) Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato 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 determined photometrically 3-4 days after application.

(84) The following compounds gave at least 80% control of Fusarium culmorum at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

(85) E1, E2, E3, E4, E5, E6, E7, E8, E9, E11, E12, E13, E14, E15, E17, E18, E19, E20, E21, E22, E23, E25, E26, E27, E28, E29, E30, E32, E33, E34, E35, E36, E37, E38, F1, F2

(86) Fusarium culmorum/Wheat/Spikelet Preventative (Head Blight)

(87) Wheat spikelets cv. Monsun are placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The spikelets are inoculated with a spore suspension of the fungus 1 day after application. The inoculated spikelets are incubated at 20° C. and 60% rh under a light regime of 72 h semi darkness followed by 12 h light/12 h darkness in a climate chamber and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check spikelets (6-8 days after application).

(88) The following compounds gave at least 80% control of Fusarium culmorum at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

(89) E3, E6, E9, E12, E14, E15, E24, E26, E30, E33, E34, E35, F2

(90) Gaeumannomyces graminis/Liquid Culture (Take-all of Cereals)

(91) Mycelial fragments of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores iss added. The test plates are incubated at 24° C. and the inhibition of growth is determined photometrically 4-5 days after application.

(92) The following compounds gave at least 80% control of Gaeumannomyces graminis at ppm when compared to untreated control under the same conditions, which showed extensive disease development:

(93) E2, E5, E9, E12, E13, E14, E15, E18, E19, E30, E33, E34, E35

(94) Gibberella zeae (Fusarium graminearum)/Wheat/Spikelet Preventative (Head Blight)

(95) Wheat spikelets cv. Monsun are placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. One day after application, the spikelets are inoculated with a spore suspension of the fungus. The inoculated test leaf disks are incubated at 20° C. and 60% rh under a light regime of 72 h semi darkness followed by 12 h light/12 h darkness in a climate chamber, the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check spikelets (6-8 days after application).

(96) The following compounds gave at least 80% control of Gibberella zeae at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

(97) E3, E5, E30, E33, E34, E35

(98) Monographella Nivalis (Microdochium Nivale)/Liquid Culture (Foot Rot Cereals)

(99) Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato 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 determined photometrically 4-5 days after application.

(100) The following compounds gave at least 80% control of Monographella nivalis at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

(101) E1, E6, E14, E17, E19, E20, E21, E23, E24, E33, E37, E38, F2

(102) Magnaporthe grisea (Pyricularia oryzae)/Liquid Culture (Rice Blast)

(103) Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato 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 determined photometrically 3-4 days after application.

(104) The following compounds gave at least 80% control of Magnaporthe grisea at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

(105) E2, E3, E4, E5, E6, E7, E8, E9, E12, E13, E14, E15, E16, E21, E26, E27, E30, E32, E33, E34, E37, E38, F1, F2

(106) Magnaporthe grisea (Pyricularia oryzae)/Rice/Leaf Disc Preventative (Rice Blast)

(107) Rice leaf segments cv. Ballila are placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf segments are inoculated with a spore suspension of the fungus 2 days after application. The inoculated leaf segments are incubated at 22° C. and 80% rh under a light regime of 24 h darkness followed by 12 h light/12 h darkness in a climate cabinet and 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 segments (5-7 days after application).

(108) The following compounds gave at least 80% control of Magnaporthe grisea at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

(109) E27, E30, E37, E38

(110) Sclerotinia sclerotiorum/Liquid Culture (Cottony Rot)

(111) Mycelia fragments of a newly grown liquid culture of the fungus are directly mixed into nutrient broth (Vogels broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format) the nutrient broth containing the fungal material is added. The test plates are incubated at 24° C. and the inhibition of growth is determined photometrically 3-4 days after application.

(112) The following compounds gave at least 80% control of Sclerotinia sclerotiorum at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development:

(113) F1

(114) Mycosphaerella graminicola (Septoria tritici)/Liquid Culture (Septoria Blotch)

(115) Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato 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 determined photometrically 4-5 days after application.

(116) The following compounds gave at least 80% control of Mycosphaerella graminicola at ppm when compared to untreated control under the same conditions, which showed extensive disease development:

(117) E1, E21