MICROBIOCIDAL QUINOLINE DIHYDRO-(THIAZINE)OXAZINE DERIVATIVES

Abstract

Compounds of formula (I), wherein the substituents are as defined in claim 1. Futhermore, the present invention relates to agrochemical compositions which comprise 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) ##STR00070## wherein X is O or S; R.sub.1 is hydrogen, halogen, methyl or cyano; R.sub.2 is hydrogen, halogen, methyl or cyano; R.sub.3 and R.sub.4 are each independently hydrogen, halogen or methyl; R.sub.5 and R.sub.6 are each independently selected from hydrogen, halogen, C.sub.1-C.sub.5 alkoxy, C.sub.1-C.sub.5 alkyl, C.sub.3-C.sub.5 cycloalkyl, C.sub.2-C.sub.5 alkenyl or C.sub.2-C.sub.5 alkynyl, wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups 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 alkoxy and C.sub.1-C.sub.3 alkylthio; or R.sub.5 and R.sub.6 together with the carbon atom to which they are attached represent C.sub.3-C.sub.6 cycloalkyl or C.sub.4-C.sub.6 cycloalkenyl, wherein the cycloalkyl and cycloalkenyl groups 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 alkoxy and C.sub.1-C.sub.3 alkylthio; R.sub.7 is hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl or C.sub.3-C.sub.4 cycloalkyl, wherein the alkyl 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 alkoxy and C.sub.1-C.sub.3 alkylthio; R.sub.8 and R.sub.9 are each independently selected from hydrogen, halogen, C.sub.1-C.sub.4 alkyl and C.sub.1-C.sub.4 alkoxy; or R.sub.8 and R.sub.9 together with the carbon atom to which they are attached represent ═O, ═NOR.sub.a, C.sub.3-C.sub.5 cycloalkyl, wherein the 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 alkoxy and C.sub.1-C.sub.3 alkylthio; each R.sub.10 independently represents halogen, nitro, cyano, formyl, C.sub.1-C.sub.5 alkyl, C.sub.2-C.sub.5 alkenyl, C.sub.2-C.sub.5 alkynyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.5 alkoxy, C.sub.3-C.sub.5 alkenyloxy, C.sub.3-C.sub.5 alkynyloxy, C.sub.1-C.sub.5 alkylthio, —C(═NOR.sub.b)C.sub.1-C.sub.5 alkyl, or C.sub.1-C.sub.5 alkylcarbonyl, wherein the alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy and alkylthio may be optionally substituted with 1 to 5 substituents independently selected from halogen, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 alkoxy, cyano and C.sub.1-C.sub.3 alkylthio; n is 0, 1, 2 or 3; R.sub.a is independently selected from hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.2-C.sub.4 alkenyl, C.sub.3-C.sub.4 alkynyl, C.sub.3-C.sub.4 cycloalkyl(C.sub.1-C.sub.2)alkyl and C.sub.3-C.sub.4 cycloalkyl, wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups may be optionally substituted with 1 to 3 substituents independently selected from halogen and cyano; and R.sub.b is independently selected from hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.2-C.sub.4 alkenyl, C.sub.3-C.sub.4 alkynyl, C.sub.3-C.sub.4 cycloalkyl(C.sub.1-C.sub.2)alkyl and C.sub.3-C.sub.4 cycloalkyl, wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups may be optionally substituted with 1 to 3 substituents independently selected from halogen and cyano; 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 or methyl.

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

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, chloro and methyl.

5. The compound, or a salt, enantiomer or N-oxide thereof, according to claim 1, wherein R.sub.5 and R.sub.6 are each independently selected from hydrogen, C.sub.1-C.sub.5 alkyl, C.sub.3-C.sub.5 cycloalkyl, wherein the alkyl and cycloalkyl groups may be optionally substituted with 1 to 3 substituents independently selected from fluoro, chloro, C.sub.1-C.sub.3 alkyl and C.sub.1-C.sub.3 alkoxy; or R.sub.5 and R.sub.6 together with the carbon atom to which they are attached represent C.sub.3-C.sub.6 cycloalkyl, wherein the cycloalkyl group may be optionally substituted with 1 to 3 substituents independently selected from fluoro, chloro, C.sub.1-C.sub.3 alkyl and C.sub.1-C.sub.3 alkoxy.

6. The compound, or a salt, enantiomer or N-oxide thereof, according to claim 1, wherein R.sub.7 is hydrogen, methyl, ethyl or cyclopropyl, wherein the methyl, ethyl and cyclopropyl may be optionally substituted with 1 to 3 substituents independently selected from fluoro, chloro, C.sub.1-C.sub.3 alkyl and C.sub.1-C.sub.3 alkoxy.

7. The compound, or a salt, enantiomer or N-oxide thereof, according to claim 1, wherein R.sub.8 and R.sub.9 are each independently selected from hydrogen, fluoro, methyl or ethyl.

8. The compound, or a salt, enantiomer or N-oxide thereof, according to claim 1, wherein each R.sub.10 independently represents halogen, cyano, C.sub.1-C.sub.3 alkyl, C.sub.2-C.sub.3 alkenyl, C.sub.2-C.sub.3 alkynyl, cyclopropyl, C.sub.1-C.sub.3 alkoxy, allyloxy, propargyloxy, C.sub.1-C.sub.3 alkylthio, wherein the alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, allyloxy, propargyloxy and alkylthio may be optionally substituted with 1 to 3 substituents independently selected from fluoro, methyl, methoxy, cyano and methylthio; n is 0, 1 or 2.

9. The compound, or a salt, enantiomer or N-oxide thereof, according to claim 1, wherein R.sub.1 is hydrogen or fluoro; R.sub.2 is hydrogen or fluoro; R.sub.3 and R.sub.4 are each independently selected from hydrogen and methyl; R.sub.7 is hydrogen or methyl, wherein the methyl may be optionally substituted with 1 to 3 fluoro substituents or one methyl, chloro or methoxy; R.sub.8 and R.sub.9 are both hydrogen; and each R.sub.10 independently represents fluoro, chloro, cyano, methyl or methoxy; n is 0 or 1.

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, fluoro, chloro or methyl; R.sub.3 and R.sub.4 are each independently hydrogen, chloro or methyl; R.sub.5 and R.sub.6 are each independently selected from hydrogen, C.sub.1-C.sub.5 alkyl, C.sub.3-C.sub.5 cycloalkyl, wherein the alkyl and cycloalkyl groups may be optionally substituted with 1 to 3 substituents independently selected from fluoro, chloro, C.sub.1-C.sub.3 alkyl and C.sub.1-C.sub.3 alkoxy; or R.sub.5 and R.sub.6 together with the carbon atom to which they are attached represent C.sub.3-C.sub.6 cycloalkyl, wherein the cycloalkyl group may be optionally substituted with 1 to 3 substituents independently selected from fluoro, chloro, C.sub.1-C.sub.3 alkyl and C.sub.1-C.sub.3 alkoxy; R.sub.7 is hydrogen, methyl, ethyl or cyclopropyl, wherein the methyl, ethyl and cyclopropyl may be optionally substituted with 1 to 3 substituents independently selected from fluoro, chloro, C.sub.1-C.sub.3 alkyl and C.sub.1-C.sub.3 alkoxy; R.sub.5 and R.sub.9 are each independently selected from hydrogen, fluoro, methyl or ethyl; each R.sub.10 independently represents halogen, cyano, C.sub.1-C.sub.3 alkyl, C.sub.2-C.sub.3 alkenyl, C.sub.2-C.sub.3 alkynyl, cyclopropyl, C.sub.1-C.sub.3 alkoxy, allyloxy, propargyloxy, C.sub.1-C.sub.3 alkylthio, wherein the alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, allyloxy, propargyloxy and alkylthio may be optionally substituted with 1 to 3 substituents independently selected from fluoro, methyl, methoxy, cyano and methylthio; n is 0, 1 or 2; 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 hydrogen or fluoro; R.sub.2 is hydrogen or fluoro; R.sub.3 and R.sub.4 are each independently hydrogen or methyl; R.sub.5 and R.sub.6 are each independently selected from methyl, ethyl, propyl, isopropyl, cyclopropyl, wherein the methyl, ethyl, propyl, isopropyl and cyclopropyl groups may be optionally substituted with 1 to 3 fluoro substituents or one methyl, chloro or methoxy; or R.sub.5 and R.sub.6 together with the carbon atom to which they are attached represent cyclobutyl or cyclopentyl; R.sub.7 is hydrogen or methyl, wherein the methyl may be optionally substituted with 1 to 3 fluoro substituents or one methyl, chloro or methoxy; R.sub.5 and R.sub.9 are both hydrogen; each R.sub.10 independently represents fluoro, chloro, cyano, methyl or methoxy; n is 0 or 1; or a salt, enantiomer or N-oxide thereof.

12. The compound 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. The 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.

Description

EXAMPLES

[0276] 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.

[0277] 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:

[0278] Method G:

[0279] Spectra were recorded on a Mass Spectrometer from Waters (SQD, SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions), Capillary: 3.00 kV, Cone range: 30 V, Extractor: 2.00 V, Source Temperature: 150° C., Desolvation Temperature: 350° C., Cone Gas Flow: 50 l/h, Desolvation Gas Flow: 650 l/h, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment , diode-array detector and ELSD 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 1.2 min; Flow (ml/min) 0.85

[0280] Method H:

[0281] Spectra were recorded on a Mass Spectrometer from Waters (SQD, SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions), Capillary: 3.00 kV, Cone range: 30V, Extractor: 2.00 V, Source Temperature: 150° C., Desolvation Temperature: 350° C., Cone Gas Flow: 50 l/h, Desolvation Gas Flow: 650 l/h, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment , diode-array detector and ELSD 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

[0282] Method W:

[0283] Spectra were recorded on a Mass Spectrometer (ACQUITY UPLC) from Waters (SQD, SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.0 kV, Cone: 30V, Extractor: 3.00 V, Source Temperature: 150° C., Desolvation Temperature: 400° C., Cone Gas Flow: 60 L/Hr, Desolvation Gas Flow: 700 L/Hr, Mass range: 140 to 800 Da), DAD Wavelength range (nm): 210 to 400, and an Acquity UPLC from Waters: 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/Methanol 9:1, 0.1% formic acid, B=Acetonitrile+0.1% formic acid, gradient: 0-100% B in 2.5 min; Flow (ml/min) 0.75

Formulation Examples

[0284]

TABLE-US-00002 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%  —

[0285] 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-00003 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
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-00004 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% 
Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.

TABLE-US-00005 Dusts 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.

TABLE-US-00006 Extruder granules 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.

TABLE-US-00007 Coated granules 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.

TABLE-US-00008 Suspension concentrate active ingredient [compound of formula (I)] 40% propylene glycol 10% nonylphenol polyethylene glycol ether (15 mol of ethylene oxide)  6% Sodium lignosulfonate 10% carboxymethylcellulose  1% silicone oil (in the form of a 75% emulsion in water)  1% 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.

TABLE-US-00009 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% solution in 0.5%   water) monoazo-pigment calcium salt 5% Silicone oil (in the form of a 75% emulsion in water) 0.2%   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

[0286] 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. [0287] 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. [0288] The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.

PREPARATION EXAMPLES

Example 1

Preparation of 4-benzyl-2-(8-fluoro-3-quinolyl)-4,6,6-trimethyl-5H-1,3-oxazine

Step 1: Preparation of 2-methyl-N-(1-methyl-2-phenyl-ethylidene)propane-2-sulfinamide

[0289] ##STR00020##

[0290] 1-Phenylpropan-2-one (8.30 g, 61.9 mmol) was dissolved in tetrahydrofuran (75 mL), titanium(IV)ethoxide (32.6 g, 92.8 mmol) and 2-methylpropane-2-sulfinamide (7.50 g, 61.9 mmol) were added sequentially at room temperature and the resulting mixture was warmed 30 to 60° C. After stirring for 2 h at 60° C., the reaction was cooled to room temperature and quenched with aqueous NaHCO.sub.3. The resulting mixture was filtrated and the filter cake was washed with ethyl acetate. The combined filtrates were extracted with ethyl acetate, the organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford the title compound as a light yellow oil (purity >80%, ca. 4:1 ratio of cis-trans isomers) which was used as such for the next step.

[0291] .sup.1H NMR (400 MHz, CDCl.sub.3, major isomer) δ 7.17-7.43 (m, 5H), 3.72 (d, 1H), 3.70 (d, 1H), 2.32 (s, 3H), 1.23 (s, 9H)

Step 2: Preparation of N-(1-benzyl-1,3-dimethyl-but-3-enyI)-2-methyl-propane-2-sulfinamide

[0292] ##STR00021##

[0293] A solution of crude 2-methyl-N-(1-methyl-2-phenyl-ethylidene)propane-2-sulfinamide (80% purity, 7.4 g, 24.9 mmol) in dichloromethane (100 mL) was added slowly to a commercially available solution of 2-methylallylmagnesium chloride in THF (0.5 M, 75 mL, 37.4 mmol) maintained at −50° C. The reaction mixture was gradually warmed to 20° C. over 4 h and stirred overnight at 20° C. Saturated NH.sub.4Cl solution was then added, the mixture was extracted with ethyl acetate and the organic layer was washed with brine, dried over sodium sulfate, filtrated and concentrated in vacuo. The residue was purified by flash chromatography on silica gel to afford the title compound as mixture diastereoisomers.

[0294] .sup.1H NMR (400 MHz, CDCl.sub.3, major isomer) δ 6.94-7.18 (m, 5H), 4.82 (s, 1H), 4.71 (s, 1H), 3.39 (s, 1H), 2.76 (d, 1H), 2.55 (d, 1H), 2.21 (d, 2H), 1.63 (s, 3H), 1.06 (s, 3H), 0.94 (s, 9H).

Step 3: Preparation of N-(1-benzyl-1,3-dimethyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide

[0295] ##STR00022##

[0296] To an ice cold solution of N-(1-benzyl-1,3-dimethyl-but-3-enyl)-2-methyl-propane-2-sulfinamide (5.2 g, 15.9 mmol) in methanol (16 mL) was added HCl in 1,4-dioxane (4 M, 6 mL, 24 mmol) and the resulting solution was stirred for 2 h at 0-5° C. All volatiles were then removed in vacuo to afford a brown, gummy residue which was triturated with a mixture of diethyl ether/heptane. The resulting light brown solid was dried in vacuo and used as such for the next step. A part of the solid hydrochloride salt obtained above (2 g, 8.0 mmol) was suspended in dichloromethane (40 mL) and 8-fluoroquinoline-3-carboxylic acid (1.68 g, 8.8 mmol), triethylamine (2.8 mL, 19.9 mmol), 1-hydroxy-7-azabenzotriazol (1.2 g, 8.8 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide-HCl (1.72 g, 8.8 mmol) was added sequentially at ambient temperature. The resulting mixture was aged for 2 h at 20° C. Water was then added and the mixture was extracted with dichloromethane. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel to afford the title compound as white solid, 10 m.p. 115-117° C.

[0297] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 9.11-9.26 (m, 1H), 8.50 (s, 1H), 7.72 (d, 1H), 7.45-7.64 (m, 2H), 7.19-7.37 (m, 5H), 5.96 (s, 1H), 5.01 (s, 1H), 4.84 (s, 1H), 3.57 (d, 1H), 3.08 (dd, 2H), 2.46 (d, 1H), 1.89 (s, 3H), 1.47 (s, 3H).

[0298] .sup.19F NMR (377 MHz, CDCl.sub.3) δ −124.64 (s).

Step 4: Preparation of 4-benzyl-2-(8-fluoro-3-quinolyl)-4,6,6-trimethyl-5H-1,3-oxazine

[0299] ##STR00023##

[0300] To a solution of N-(1-benzyl-1,3-dimethyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide (1.0 g, 2.8 mmol) in acetonitrile (8.3 mL) was added trifluoroacetic acid (2.8 mL, 36.6 mmol) and the resulting solution was stirred overnight at 80° C. After cooling to RT, the reaction mixture was poured onto a saturated Na2CO3 solution, extracted with ethyl acetate twice. The combined organic phases were washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel to afford the title compound as yellow oil (0.89 g, 2.5 mmol).

[0301] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 9.57-9.67 (1H, d), 8.64-8.71 (1H, t), 7.66-7.76 (1H, d), 7.49-7.56 (1H, m), 7.41-7.48 (1H, m), 7.29-7.34 (3H, m), 7.19-7.27 (2H, m), 2.87-2.95 (2H, s), 1.91-2.01 (1H, d), 1.76-1.86 (1H, d), 1.44-1.54 (6H, d), 1.40-1.43 (3H, s)

[0302] .sup.19F NMR (377 MHz, CDCl.sub.3) δ −125.38 (s)

Example 2

Preparation of (4R,6S)-4-benzyl-6-(chloromethyl)-2-(8-fluoro-3-quinolyl)-4,6-dimethyl-5H-1,3-oxazine and (4R,6R)-4-benzyl-6-(chloromethyl)-2-(8-fluoro-3-quinolyl)-4,6-dimethyl-5H-1,3-oxazine

[0303] To a solution of N-(1-benzyl-1,3-dimethyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide (0.25 g, 0.69 mmol) in acetonitrile (2.1 mL) was added trifluoroacetic acid (0.21 mL, 2.74 mmol) then N-Chlorosuccinimide (0.1 g, 0.76 mmol) and the resulting solution was stirred overnight at 80° C. After cooling to RT, the reaction mixture was poured onto a saturated Na2CO3 solution, extracted with ethyl acetate twice. The combined organic phases were washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel to afford the title compounds (4R,6S)-4-benzyl-6-(chloromethyl)-2-(8-fluoro-3-quinolyl)-4,6-dimethyl-5H-1,3-oxazine as an or ange oil (0.049 g, 0.12 mmol):

[0304] .sup.1H NMR (600 MHz, CDCl.sub.3) δ 9.59 (1H, d), 8.66 (1H, br d), 7.69 (1H, br d), 7.47-7.54 (1H, m), 7.40-7.46 (1H, m), 7.29-7.34 (3H, m), 7.23-7.29 (4H, m), 7.18-7.23 (1H, m), 3.57-3.68 (2H, m), 2.79-2.96 (2H, m), 2.14 (1H, d), 1.90 (1H, br d), 1.52 (3H, s), 1.40 (3H, s)

[0305] .sup.19F NMR (377 MHz, CDCl.sub.3) δ −125.16 (s) and (4R,6R)-4-benzyl-6-(chloromethyl)-2-(8-fluoro-3-quinolyl)-4,6-dimethyl-5H-1,3-oxazine as a yellow oil (0.037 g, 0.093 mmol):

[0306] .sup.1H NMR (600 MHz, CDCl.sub.3) δ 9.53-9.67 (1H, m), 8.68 (1H, br s), 7.70 (1H, d), 7.48-7.54 (1H, m), 7.45 (1H, ddd), 7.29-7.35 (2H, m), 7.25-7.29 (2H, m), 7.18-7.25 (1H, m), 3.56 (1H, d), 2.80-2.99 (2H, m), 2.09 (1H, br d), 1.86 (1H, d), 1.59 (3H, s), 1.44 (3H, s)

[0307] .sup.19F NMR (377 MHz, CDCl.sub.3) δ −124.78 (s)

Example 3

Preparation of 4-benzyl-2-(7,8-difluoro-3-quinolyI)-6,6-dimethyl-4,5-dihydro-1,3-oxazine

Step 1: Preparation of N-(1-benzyl-3-methyl-but-3-enyl)-7,8-difluoro-quinoline-3-carboxamide

[0308] To a suspension of 7,8-difluoroquinoline-3-carboxylic acid (0.12 g, 0.57 mmol) in dichloromethane (2.9 mL) was added trimethylamine (0.24 mL, 1.7 mmol) then 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide HCl (0.17 g, 0.86 mmol), 1-Hydroxy-7-azabenzotriazole (0.12g, 0.86mmol) and 4-dimethylaminopyridine (0.007 g, 0.057 mmol) and finally a solution of 4-methyl-1-phenyl-pent-4-en-2-amine (0.1 g, 0.57 mmol) in dichloromethane (1 mL) . The solution was stirred for 2 h 30 at RT. The reaction mixture was diluted with ethyl acetate and washed with citric acid 1M, a saturated NaHCO.sub.3 solution and brine. The organic phase was dried over MgSO.sub.4, filtered and concentrated under vacuo. The residue was purified by flash chromatography on silica gel to afford the title compound as a pale yellow solid (0.11 g, 0.30 mmol).

[0309] .sup.1H NMR (400 MHz, CDCl.sub.3) 9.18 (1H, d, J=2.2 Hz), 8.53 (1H, t, J=2.0 Hz), 7.70 (1H, ddd, J=9.4, 5.1, 2.2 Hz), 7.52 (1H, td, J=9.4, 6.8 Hz), 7.30-7.38 (3H, m), 7.24-7.29 (2H, m) 6.00 (1H, d, J=8.1 Hz), 4.89 (1H, s), 4.83 (1H, s), 4.63 (1H, m), 3.04 (2H, m), 2.40 (1H, d, J=5.5 Hz), 2.33 (1H, d, J=9.2 Hz), 1.81 (3H, s).

[0310] .sup.19F NMR (377 MHz, CDCl.sub.3) δ −150.2 (s), −153.9 (s)

Step 2: Preparation of 4-benzyl-2-(7,8-difluoro-3-quinolyl)-6,6-dimethyl-4,5-dihydro-1,3-oxazine

[0311] To a solution of N-(1-benzyl-3-methyl-but-3-enyl)-7,8-difluoro-quinoline-3-carboxamide (0.20 g, 0.55 mmol) in acetonitrile (1.6 mL) was added trifluoroacetic acid (0.55 mL, 7.2 mmol) and the resulting solution was stirred overnight at 80° C. After cooling to RT, the reaction mixture was poured onto a saturated Na2CO3 solution, extracted with ethyl acetate twice. The combined organic phases were washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel to afford the title compound as a beige oil that crystallized on standing (0.16 g, 0.44 mmol), m.p. 121-124° C.

[0312] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 9.60 (1H, d), 8.65 (1H, t), 7.68 (1H, ddd), 7.46 (1H, td), 7.36 (5H, m), 3.84 (1H, td), 3.18 (1H, dd), 2.81 (1H, dd), 1.85 (1H, dd), 1.48 (4H, br s), 1.36 (3H, s).

[0313] .sup.19F NMR (377 MHz, CDCl.sub.3) δ −151.04 (m), −157.80 (m)

Example 4

Preparation of 4-benzyl-2-(7,8-difluoro-3-quinolyI)-6,6-dimethyl-4,5-dihydro-1,3-thiazine

[0314] To a suspension of N-(1-benzyl-3-methyl-but-3-enyl)-7,8-difluoro-quinoline-3-carboxamide (0.20 g, 0.55 mmol) in toluene (4.4 mL) was added Lawesson reagent (0.14 g, 0.33 mmol) and the reaction mixture was stirred overnight at 110° C.

[0315] The solution was allowed to come back at RT before trifluoroacetic acid (1.1 mL, 14.4 mmol) was added and the solution was stirred overnight at 80° C.

[0316] After cooling to RT, the reaction mixture was poured onto a saturated Na2CO3 solution, extracted with ethyl acetate twice. The combined organic phases were washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo.

[0317] The residue was purified by flash chromatography on silica gel to afford the title compound as a yellow oil that crystallized (0.12 g, 0.31 mmol), m.p. 153-155° C.

[0318] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 9.49 (1H, d), 8.52 (1H, s), 7.67 (1H, ddd), 7.48 (1H, td), 7.38 (5H, m), 4.03 (1H, qd), 3.31 (1H, dd), 3.03 (1H, dd), 1.84 (1H, dd), 1.46 (6H, d), 1.42 (1H, m).

[0319] .sup.19F NMR (377 MHz, CDCl3): δ −133.99 (m), −150.88 (m).

Example 5

Preparation of the Single Isomers

[0320] (4S)-4-benzyl-2-(8-fluoro-3-quinolyI)-4,6,6-trimethyl-5H-1,3-oxazine and (4R)-4-benzyl-2-(8-fluoro-3-quinolyl)-4,6,6-trimethyl-5H-1,3-oxazine

[0321] The racemic 4-benzyl-2-(8-fluoro-3-quinolyI)-4,6,6-trimethyl-5H-1,3-oxazine mixture was submitted to chiral resolution by preparative HPLC chromathography using the conditions outlined hereafter.

Analytical HPLC Method:

[0322] SFC:Waters Acquity UPC.sup.2/QDa [0323] PDA Detector Waters Acquity UPC.sup.2 [0324] Column: Daicel SFC CHIRALPAK® IA, 3 μm, 0.3 cm×10 cm, 40° C. [0325] Mobile phase: A: CO2 B: iPr gradient: 7% B in 4.8 min [0326] ABPR: 1800 psi [0327] Flow rate: 2.0 ml/min [0328] Detection: 235 nm [0329] Sample concentration: 1 mg/mL in ACN/iPr 50/50 [0330] Injection: 1 μL

Preparative HPLC Method:

[0331] Autopurification System from Waters: 2767 sample Manager, 2489 UVNisible Detector, 2545 Quaternary Gradient Module. [0332] Column: Daicel CHIRALPAK® IE, 5 μm, 1.0 cm×25 cm [0333] Mobile phase: TBME/EtOH 100/00 [0334] Flow rate: 10 ml/min [0335] Detection: UV 265 nm [0336] Sample concentration: 50 mg/mL in ACN/EE, filtered [0337] Injection: 50-70 μl

TABLE-US-00010 First eluting enantiomer Second eluting enantiomer Retention time (min) ~3.59 Retention time (min) ~4.64 Chemical purity (area % at Chemical purity (area % at 240 nm) 99 240 nm) 99 Enantiomeric excess (%) >99 Enantiomeric excess (%) >89

TABLE-US-00011 TABLE E Physical data of compounds of formula (I) [M + H] RT measu- MP No. IUPAC name STRUCTURE (min) red Method ° C. E-1  4-benzyl-6- (chloromethyl)-2-(7,8- difluoro-3-quinolyl)-6- methyl-4,5-dihydro-1,3- oxazine [00024] 1.21 402 G E-2  3-(4-benzyl-6,6- dimethyl-4,5-dihydro- 1,3-oxazin-2- yl)quinoline-8- carbonitrile [00025] 1.11 356 G E-3  4-benzyl-2-(8-chloro-3- quinolyl)-6,6-dimethyl- 4,5-dihydro-1,3-oxazine [00026] 1.15 365 G 150- 152 E-4 4-benzyl-6,6-dimethyl-2- (8-methyl-3-quinolyl)- 4,5-dihydro-1,3-oxazine [00027] 1.08 345 G 120- 122 E-5  4-benzyl-6,6-dimethyl-2- (3-quinolyl)-4,5-dihydro- 1,3-oxazine [00028] 0.97 331 G E-6  4-benzyl-2-(7,8-difluoro- 3-quinolyl)-6,6-dimethyl- 4,5-dihydro-1,3-thiazine [00029] 1.30 383 G 153- 155 E-7  4-benzyl-2-(8-fluoro-3- quinolyl)-4,6,6-trimethyl- 5H-1,3-thiazine [00030] 1.30 379 G E-8  4-benzyl-2-(7,8-difluoro- 3-quinolyl)-6,6-dimethyl- 4,5-dihydro-1,3-oxazine [00031] 1.14 368 G 93- 96 E-9  4-benzyl-6-ethyl-2-(8- fluoro-3-quinolyl)-4,6- dimethyl-5H-1,3-oxazine [00032] 1.14 377 G E-10 (4R,6S)-4-benzyl-6- (chloromethyl)-2-(8- fluoro-3-quinolyl)-4,6- dimethyl-5H-1,3-oxazine [00033] 1.23 397 G 125- 130 E-11 (4R,6R)-4-benzyl-6- (chloromethyl)-2-(8- fluoro-3-quinolyl)-4,6- dimethyl-5H-1,3-oxazine [00034] 1.21 397 G E-12 4-benzyl-2-(8-fluoro-3- quinolyl)-6,6-dimethyl-4- (trifluoromethyl)-5H-1,3- oxazine [00035] 1.25 417 G E-13 4-benzyl-2-(8-fluoro-3- quinolyl)-6,6-dimethyl- 4,5-dihydro-1,3-oxazine [00036] 1.06 349 G 90- 92 E-14 4- [difluoro(phenyl)methyl]- 2-(8-fluoro-3-quinolyl)- 4,6,6-trimethyl-5H-1,3- oxazine [00037] 1.25 399 G 101- 105 E-15 4-benzyl-2-(8-fluoro-4- methyl-3-quinolyl)-4,6,6- trimethyl-5H-1,3-oxazine [00038] 0.99 378 G E-16 4-benzyl-2-(8-fluoro-2- methyl-3-quinolyl)-4,6,6- trimethyl-5H-1,3-oxazine [00039] 0.99 378 G E-17 4-benzyl-2-(8-fluoro-3- quinolyl)-4,6,6-trimethyl- 5H-1,3-oxazine [00040] 1.08 364 G 115- 116 E-18 2-(7,8-difluoro-3- quinolyl)-4-[(4- fluorophenyl)methyl]- 6,6-dimethyl-4,5- dihydro-1,3-oxazine [00041] 1.17 385 G 118- 121 E-19 2-(7,8-difluoro-3- quinolyl)-4-[(3- fluorophenyl)methyl]- 6,6-dimethyl-4,5- dihydro-1,3-oxazine [00042] 1.17 385 G 95- 98 E-20 2-(7,8-difluoro-3- quinolyl)-4-[(2- fluorophenyl)methyl]- 6,6-dimethyl-4,5- dihydro-1,3-oxazine [00043] 1.18 385 G E-21 9-benzyl-7-(7,8-difluoro- 3-quinolyl)-6-oxa-8- azaspiro[4.5]dec-7-ene [00044] 1.23 393 G E-22 4-benzyl-2-(7,8-difluoro- 2-methyl-3-quinolyl)-6,6- dimethyl-4,5-dihydro- 1,3-oxazine [00045] 1.08 381 100- 103 E-23 8-benzyl-6-(7,8-difluoro- 3-quinolyl)-5-oxa-7- azaspiro[3.5]non-6-ene [00046] 1.22 379 G 159- 162 E-24 2-(7,8-difluoro-2-methyl- 3-quinolyl)-4-[(4- fluorophenyl)methyl]- 6,6-dimethyl-4,5- dihydro-1,3-oxazine [00047] 1.12 399 G 128- 132 E-25 4-benzyl-2-(7,8-difluoro- 3-quinolyl)-6-methyl-5,6- dihydro-4H-1,3-oxazine [00048] 1.02 (isomer1) 1.11 (isomer 2) 353 G E-26 4-benzyl-2-(7,8-difluoro- 3-quinolyl)-6- (iodomethyl)-5,6- dihydro-4H-1,3-oxazine [00049] 1.23 479 G 137- 139 E-27 3-(9-benzyl-6-oxa-8- azaspiro[4.5]dec-7-en-7- yl)-7-fluoro-quinoline-8- carbonitrile [00050] 1.23 400 G E-28 3-(4-benzyl-6,6- dimethyl-4,5-dihydro- 1,3-oxazin-2-yl)-7-fluoro- quinoline-8-carbonitrile [00051] 1.15 374 G 126- 133 E-29 4-benzyl-2-(7-chloro-8- fluoro-3-quinolyl)-6,6- dimethyl-4,5-dihydro- 1,3-oxazine [00052] 1.24 383 G 135- 137 E-30 4-benzyl-2-(2,8-difluoro- 3-quinolyl)-6,6-dimethyl- 4,5-dihydro-1,3-oxazine [00053] 1.12 367 G 105- 107 E-31 2-(7,8-difluoro-3- quinolyl)-4-[(4- fluorophenyl)methyl]- 6,6-dimethyl-4,5- dihydro-1,3-thiazine [00054] 1.31 401 G E-32 4-benzyl-2-(7-fluoro-3- quinolyl)-6,6-dimethyl- 4,5-dihydro-1,3-oxazine [00055] 1.07 349 G E-33 4-benzyl-2-(7-chloro-3- quinolyl)-6,6-dimethyl- 4,5-dihydro-1,3-oxazine [00056] 1.18 365 G E-34 3-(4-benzyl-6,6- dimethyl-4,5-dihydro- 1,3-oxazin-2-yl)-8-fluoro- quinoline-7-carbonitrile [00057] 1.19 374 G E-35 9-benzyl-7-(8-chloro-7- fluoro-3-quinolyl)-6-oxa- 8-azaspiro[4.5]dec-7-ene [00058] 1.27 409 G 150- 151 E-36 4-benzyl-2-(2-chloro-8- fluoro-3-quinolyl)-6,6- dimethyl-4,5-dihydro- 1,3-oxazine [00059] 1.14 383 G E-37 4-[(4- chlorophenyl)methyl]-2- (7,8-difluoro-3-quinolyl)- 6,6-dimethyl-4,5- dihydro-1,3-oxazine [00060] 1.23 401 G E-38 2-(7,8-difluoro-3- quinolyl)-6,6-dimethyl-4- (p-tolylmethyl)-4,5- dihydro-1,3-oxazine [00061] 1.14 381 G

TABLE-US-00012 TABLE F Physical data of enantiomerically-pure compounds of formula (I) [M + H] RT meas- MP No IUPAC name STRUCTURE (min) ured Method ° C. F-1 (ent-1)-4- benzyl-2-(8- fluoro-3- quinolyl)- 4,6,6- trimethyl-5H- 1,3-oxazine [00062] 3.59 364 SFC: Waters Acquity UPC.sup.2/QDa PDA Detector Waters Acquity UPC.sup.2 Column: Daicel SFC CHIRALPAK .sup.® OZ, 3 μm, 0.3 cm × 10 cm, 40° C. 109- 111 F-2 (ent-2)-4- benzyl-2-(8- fluoro-3- quinolyl)- 4,6,6- trimethyl-5H- 1,3-oxazine [00063] 4.64 364 Mobile phase: A: CO.sub.2 B: iPr gradient 7% B in 4.8 min ABPR: 1800 psi Flow rate: 2.0 ml/min Detection: 235 nm Sample concentration: 1 111- 112 mg/mL in ACN/iPr 50/50 Injection: 1 μL F-3 (ent-1)-4- benzyl-2-(8- fluoro-3- quinolyl)-6,6- dimethyl-4,5- dihydro-1,3- oxazine [00064] 1.73 349 SFC: Waters Acquity UPC.sup.2/QDa PDA Detector Waters Acquity UPC.sup.2 Column: Daicel SFC CHIRALPAK .sup.® IC, 3 μm, 0.3 cm × 10 cm, 40° C. Mobile phase: A: CO.sub.2 B: iPr gradient: 30- 50% B in 1.8 min 109- 111 F-4 (ent-2)-4- benzyl-2-(8- fluoro-3- quinolyl)-6,6- dimethyl-4,5- dihydro-1,3- oxazine [00065] 1.24 349 ABPR: 1800 psi Flow rate: 2.0 ml/min Detection: 220 nm Sample concentration: 1 mg/mL in ACN/iPr 50/50 Injection: 1 μL F-5 (ent-1)-4- benzyl-2-(7,8- difluoro-3- quinolyl)-6,6- dimethyl-4,5- dihydro-1,3- oxazine [00066] 1.81 367 SFC: Waters Acquity UPC.sup.2/QDa PDA Detector Waters Acquity UPC.sup.2 Column: Daicel SFC CHIRALPAK .sup.® IC, 3 μm, 0.3 cm × 10 cm, 40° C. Mobile phase: A: CO.sub.2 B: iPrOH isocratic: 20% B in 4.8 min ABPR: 1800 psi F-6 (ent-2)-4- benzyl-2-(7,8- difluoro-3- quinolyl)-6,6- dimethyl-4,5- dihydro-1,3- oxazine [00067] 3.28 367 Flow rate: 2.0 ml/min Detection: 220 nm Sample concentration: 1 mg/mL in ACN/iPr 50/50 Injection: 1 μL 102- 105 F-7 (ent-1)-2- (7,8-difluoro- 3-quinolyl)-4- [(4- fluorophenyl) methyl]-6,6- dimethyl-4,5- dihydro-1,3- oxazine [00068] 1.47 385 SFC: Waters Acquity UPC.sup.2/QDa PDA Detector Waters Acquity UPC.sup.2 Column: Daicel SFC CHIRALPAK .sup.® IC, 3 μm, 0.3 cm × 10 cm, 40° C. Mobile phase: A: CO.sub.2 B: iPrOH isocratic: 20% B in 4.8 min ABPR: 1800 psi 117- 119 F-8 (ent-2)-2- (7,8-difluoro- 3-quinolyl)-4- [(4- fluorophenyl) methyl]-6,6- dimethyl-4,5- dihydro-1,3- oxazine [00069] 2.62 385 Flow rate: 2.0 ml/min Detection: 220 nm Sample concentration: 1 mg/mL in ACN/iPr 50/50 Injection: 1 μL 117- 119

BIOLOGICAL EXAMPLES

[0338] Botryotinia fuckeliana (Botrytis cinerea)/Liquid Culture (Gray Mould)

[0339] Conidia of the fungus from cryogenic stor age 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.

[0340] 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: [0341] E-1, E-3, E-4, E-5, E-6, E-7, E-8, E-9, E-10, E-11, E-12, E-13, E-14, E-15, E-16, E-17, E-18, E-19, E-20, E-21, E-22, E-23, E-24, E-25, E-26, E-27, E-28, E-30, E-32, E-35, F-1, F-2, F-3, F-4, F-5, F-6, F-7, F-8
Glomerella lagenarium (Colletotrichum lagenarium)/Liquid Culture (Anthracnose)

[0342] Conidia of the fungus from cryogenic stor age 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.

[0343] 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: [0344] E-5, E-6, E-7, E-8, E-9, E-10, E-11, E-12, E-13, E-14, E-15, E-16, E-17, E-25, E-29, E-34, F-2, F-4, F5
Fusarium culmorum/Liquid Culture (Head Blight)

[0345] Conidia of the fungus from cryogenic stor age 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.

[0346] 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: [0347] E-1, E-2, E-5, E-6, E-7, E-8, E-9, E-10, E-11, E-13, E-16, E-17, E-19, E-20, E-22, E-25, E-26, E-30, E-32, F-2, F-3, F-4, F-5, F-6, F-7, F-8
Monographella nivalis (Microdochium nivale)/Liquid Culture (Foot Rot Cereals)

[0348] Conidia of the fungus from cryogenic stor age 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.

[0349] 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: [0350] E-1, E-2, E-3, E-4, E-5, E-6, E-7, E-8, E-9, E-10, E-11, E-12, E-13, E-14, E-15, E-16, E-17, E-18, E-19, E-20, E-21, E-22, E-23, E-24, E-25, E-28, E-29, E-30, E-32, E-33, E-34, E-35, F-1, F-2, F-3, F-4, F-5, F-6, F-7, F-8
Magnaporthe grisea (Pyricularia oryzae)/Liquid Culture (Rice Blast)

[0351] Conidia of the fungus from cryogenic stor age 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.

[0352] 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: [0353] E-7, E-8, E-9, E-10, E-11, E-12, E-13, E-14, E-15, E-16, E-17, E-18, E-19, E-20, E-21, E-28, E-30, F-2, F-3, F-4, F-5, F-6
Sclerotinia sclerotiorum/Liquid Culture (Cottony Rot)

[0354] 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.

[0355] 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: [0356] E-7, E-8, E-9, E-10, E-13, E-16, E-18, E-19, E-22, F-2, F-3, F-4, F-5, F-6
Mycosphaerella graminicola (Septoria tritici) on Wheat/Preventative

[0357] 2-week old wheat plants cv. Riband are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants are inoculated by spraying a spore suspension on them one day after application and then kept at 22° C./21° C. (day/night) in a greenhouse. Disease damage is assessed directly when an appropriate level of disease appears on untreated check plants and efficacy was calculated compare to untreated controls (16-19 days after application).

[0358] The following compounds gave at least 80% control of Septoria tritici at 60 ppm when compared to untreated control under the same conditions, which showed extensive disease development. [0359] E-18, E-19, E-20, E-21, E-22, E-23, E-24, F-5, F-6, F-7, F-8
Mycosphaerella graminicola (Septoria tritici)/Liquid Culture (Septoria Blotch)

[0360] Conidia of the fungus from cryogenic stor age 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.

[0361] The following compounds gave at least 70% control of Mycosphaerella graminicola at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development: [0362] E-1, E-2, E-3, E-4, E-5, E-7, E-8, E-9, E-10, E-11, E-13, E-14, E-15, E-16, E-17, E-18, E-19, E-21, E-22, E-24, E-25, E-29, E-30, E-32, E-33, E-35, E-36, F-2, F-3, F-4, F-5, F-6