MICROBIOCIDAL QUINOLINE/QUINOXALINE BENZOTHIAZINE DERIVATIVES

Abstract

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

##STR00001##

Claims

1. A compound of formula (I): ##STR00039## wherein: R.sup.1 is fluoro, chloro, cyano or methyl; R.sup.2 is hydrogen or fluoro; R.sup.3 is hydrogen, difluoromethyl or methyl; R.sup.4 is C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkenyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkylC.sub.1-C.sub.2alkyl or heteroarylC.sub.1-C.sub.2alkyl; wherein the heteroaryl group is a 5- or 6-membered monocyclic aromatic ring comprising 1, 2, 3 or 4 heteroatoms individually selected from N, O and S and is optionally substituted by 1, 2 or 3 substituents individually selected from halogen, C.sub.1-C.sub.2alkyl, C.sub.1-C.sub.3alkoxy or cyano; and R.sup.5 is hydrogen or C.sub.1-C.sub.4alkyl; or R.sup.4 and R.sup.5 together with the connecting carbon atom form a cyclobutyl, cyclopentyl or cyclohexyl ring, wherein the ring structure is optionally substituted with 1, 2, 3 or 4 substituents independently selected from fluoro, cyano, methyl, methoxy; R.sup.6 is chloro, bromo, iodo, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4haloalkenyl, C.sub.2-C.sub.4alkynyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkylthio, C.sub.3-C.sub.5cycloalkoxy, C.sub.1-C.sub.4haloalkoxy, cyano, C.sub.3-C.sub.5cycloalkyl or CR.sup.10(?NOR.sup.8); and R.sup.7 is hydrogen, halogen, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl or cyano, or R.sup.6 is fluoro and R.sup.7 is halogen or C.sub.1-C.sub.4alkyl; R.sup.8 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.5alkenyl, C.sub.3-C.sub.5haloalkenyl or C.sub.3-C.sub.5alkynyl; A is N or CR.sup.9; R.sup.9 is hydrogen, difluoromethyl or methyl; and R.sup.10 is C.sub.1-C.sub.4alkyl; or an agronomically acceptable salt, an N-oxide and/or S-oxide or a stereoisomer thereof.

2. The compound according to claim 1, wherein R.sup.1 is fluoro.

3. The compound according to claim 1, wherein R.sup.3 is hydrogen or methyl.

4. The compound according to claim 1, wherein R.sup.4 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.6cycloalkyl or (6-chloro-pyridin-3-yl)methyl.

5. The compound according to claim 1, wherein R.sup.5 is hydrogen or methyl.

6. The compound according to claim 1, wherein R.sup.4 and R.sup.5 together with the connecting carbon atom form a cyclopentyl ring, wherein the ring structure is optionally substituted with 1 or 2 substituents independently selected from fluoro, cyano, methyl, methoxy.

7. The compound according to claim 1, wherein R.sup.6 is chloro, bromo, iodo, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkylthio, cyano, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkoxy or C.sub.3-C.sub.5cycloalkyl, and preferably R.sup.6 is chloro, methyl, cyano, methylsulfanyl.

8. The compound according to claim 1, wherein R.sup.6 is chloro, bromo, iodo, methyl, ethyl, methylsufanyl, cyano, difluoromethyl, trifluoromethyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, and R.sup.7 is hydrogen, chloro or methyl.

9. The compound according to claim 1, wherein R.sup.6 is fluoro and R.sup.7 is methyl.

10. The compound according to claim 1, wherein A is CR.sup.9, and wherein R.sup.9 is hydrogen.

11. An agrochemical composition comprising a fungicidally effective amount of a compound according to claim 1.

12. The composition according to claim 11, further comprising at least one additional active ingredient and/or an agrochemically-acceptable diluent or carrier.

13. A method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound 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.

14. The method according to claim 13, wherein the phytopathogenic microorganism is Mycosphaerella graminicola and the useful plant is cereals, in particular wheat.

15. Use of a compound according to claim 1 as a fungicide.

Description

EXAMPLES

[0199] The Examples which follow serve to illustrate the invention.

[0200] 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.

[0201] 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).

[0202] 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 described below.

Formulation Examples

[0203]

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%

[0204] 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

[0205] 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%

[0206] 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%

[0207] 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%

[0208] 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%

[0209] 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%

[0210] 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% 0.5%.sup. solution in water) monoazo-pigment calcium salt 5% Silicone oil (in the form of a 75% emulsion in water) 0.2%.sup. Water 45.3%

[0211] 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

[0212] 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.

[0213] 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.

LIST OF ABBREVIATIONS

[0214] Aq=aqueous [0215] Ar=argon [0216] br s=broad singlet [0217] CaSO.sub.4=calcium sulfate [0218] CataCXium A Pd G3=Mesylate[(di(1-adamantyl)-n-butylphosphine)-2-(2-amino-1,1-biphenyl)]palladium(II) [0219] CDCl.sub.3=chloroform-d [0220] ? C.=degrees Celsius [0221] DCM=dichloromethane [0222] dd=doublet of doublets [0223] DMF=dimethylformamide [0224] d=doublet [0225] EtOAc=ethyl acetate [0226] equiv.=equivalent [0227] h=hour(s) [0228] HCl=hydrochloric acid [0229] M=molar [0230] m=multiplet [0231] MgSO.sub.4=magnesium sulfate [0232] min=minutes [0233] MHZ=mega hertz [0234] mp=melting point [0235] NaHCO.sub.3=sodium bicarbonate [0236] NaOH=sodium hydroxide [0237] NH.sub.4Cl=ammonium chloride [0238] PdCl.sub.2(dtbpf)=[1,1-Bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) [0239] ppm=parts per million [0240] RT=room temperature [0241] Rt=retention time [0242] s=singlet [0243] t=triplet [0244] TBME=tert-butylmethylether [0245] THF=tetrahydrofuran [0246] LC/MS=Liquid Chromatography Mass Spectrometry (description of the apparatus and the methods used for LC/MS analysis are given above)

Preparation Examples

Example A1: 7,8-dichloro-4-(8-fluoro-3-quinolyl)-2,2-dimethyl-1,3-benzothiazine (compound E.05)

Step 1:

[0247] A solution of 2-trimethylsilylethanethiol (0.50 g, 3.72 mmol) in THF (35 mL) was treated with triethyl amine (0.38 g, 3.72 mmol) and p-toluene sulfonyl chloride (0.36 g, 1.86 mmol) at 0 to 5? C. The resulting mixture was stirred for 45 min at 0 to 5? C., diluted with DCM and washed with aq. HCl (1 M). The organic layer was washed with aq. NaHCO.sub.3 and brine, dried over MgSO.sub.4, filtrated and concentrated in vacuo. The residual oil was filtrated through a short plug of silica gel (eluent: cyclohexane) to afford trimethyl-[2-(2-trimethylsilylethyldisulfanyl)ethyl]silane as colorless liquid.

[0248] .sup.1H NMR (400 MHZ, CDCl3) ? ppm: 2.68-2.83 (m, 4 H) 0.86-1.07 (m, 4 H) 0.05 (s, 18 H).

Step 2:

[0249] To a solution of 3,4-dichlorobenzoic acid (0.14 g, 0.73 mmol) in tetrahydrofuran (4 mL) cooled at ?70? C. was added dropwise under argon n-butyllithium (2.5 mol/L in hexane, 0.88 mL, 2.20 mmol). The solution was stirred for 2 h at ?70? C. before trimethyl-[2-(2-trimethylsilylethyldisulfanyl)ethyl]silane (0.39 g, 1.47 mmol) in THF (5 mL) was added. The reaction mixture was gradually warmed to RT over 4 h, diluted with TBME and extracted with H.sub.2O. The aq. layer was acidified with HCl (2 M) to pH 1 and extracted with TBME. The organic layer was washed with water, dried over MgSO.sub.4, filtrated and concentrated under reduce pressure. The residual solid was suspended in DCM, the undissolved solids were removed by filtration and the filtrate was concentrated under reduce pressure to afford 3,4-dichloro-2-(2-trimethylsilylethylsulfanyl)benzoic acid as white solid.

[0250] LC-MS (Method G), Rt=1.18 min, (M?H)=321.

[0251] .sup.1H NMR (400 MHZ, CDCl.sub.3) ? ppm: 8.06 (d, 1H), 7.63 (br d, 1H), 3.00-3.08 (m, 2H), 0.85-0.94 (m, 2H), 0.03 (s, 9H).

Step 3:

[0252] To a solution of 3,4-dichloro-2-(2-trimethylsilylethylsulfanyl)benzoic acid (0.18 g, 0.56 mmol) in toluene (1 mL) was added a drop of DMF and thionyl chloride (0.09 mL, 1.22 mmol) at RT. The reaction mixture was warmed to 70? C. and aged at this temperature for 2 h. All volatiles were then removed under reduced pressure, the residue was taken up in dioxane (0.6 mL) and ammonia (25% in water) (0.52 mL, 7.23 mmol) was added slowly at RT. The reaction mixture was stirred at RT for 45 min, diluted with water and extracted with EtOAc. The organic phase was washed with brine, dried over MgSO.sub.4, filtered and concentrated. The residue was purified by flash chromatography (silica gel, cyclohexane:EtOAc) to give 3,4-dichloro-2-(2-trimethylsilylethylsulfanyl)benzamide as beige solid.

[0253] LC-MS (Method G), Rt=1.10 min.

[0254] .sup.1H NMR (400 MHZ, CDCl3)? ppm : 7.67 (d, 1H), 7.53 (d, 1H), 7.10 (br s, 1H), 5.89 (br s, 1H), 2.91-3.09 (m, 2H), 0.82-0.92 (m, 2H), 0.02 (s, 9H).

Step 4:

[0255] To a solution of 3,4-dichloro-2-(2-trimethylsilylethylsulfanyl)benzamide (0.08 g, 0.25 mmol) in THF (1 mL) was added tetrabutylammonium fluoride (1M in THF, 0.74 mL, 0.74 mmol) at RT. The solution was stirred at for 20min at RT and then diluted with aq. HCl (1M). The mixture was extracted with EtOAc, the organic phase was washed with brine, dried over MgSO.sub.4, filtered and concentrated. The residue was purified by flash chromatography (silica gel, cyclohexane:EtOAc) to give 3,4-dichloro-2-sulfanyl-benzamide as orange solid.

[0256] LC-MS (Method G), R.sub.t=0.82 min, (M+H)=222.

[0257] .sup.1H NMR (400 MHZ, CDCl.sub.3) ? ppm=7.41 (d, 1H), 7.31 (d, 1H), 6.22 (s, 1H), 5.72 (br s, 2H).

Step 5:

[0258] A suspension of 3,4-dichloro-2-sulfanyl-benzamide (0.03 g, 0.14 mmol), 2,2-dimethoxypropane (0.03 mL, 0.27 mmol), p-toluene sulfonic acid (1 small crystal) and 4 ? molecular sieves in toluene (0.5 mL) was stirred for 18 h at 80? C. The reaction mixture cooled to RT, diluted with EtOAc and the solids removed by filtration. The filtrated was washed with water and brine, dried over MgSO.sub.4, filtrated and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, cyclohexane:EtOAc) to give 7,8-dichloro-2,2-dimethyl-3H-1,3-benzothiazin-4-one as an orange gum.

[0259] LC-MS (Method G), R.sub.t=0.99 min, (M+H)=262.

[0260] .sup.1H NMR (400 MHZ, CDCl.sub.3) ? ppm=8.06 (d, 1H), 7.39 (d, 1H), 6.17 (br s, 1H), 1.77 (s, 6H).

Step 6:

[0261] A solution of DMF (0.02 mL, 0.23 mmol) in DCM (0.2 mL) at 0? C. was treated with oxalyl chloride (0.014 mL, 0.15 mmol) and the resulting white suspension was stirred at 0? C. for 1 h. A solution of 7,8-dichloro-2,2-dimethyl-3H-1,3-benzothiazin-4-one (0.02 g 0.076 mmol) in DCM (0.2 mL) was then added to the suspension and the reaction mixture was allowed to warm to RT. After 40 min, LC-MS indicated full conversion. The reaction mixture was diluted with DCM and poured on a mixture of ice and aq. NaHCO.sub.3. The mixture was extracted with DCM and the organic phase was dried over MgSO.sub.4, filtered and concentrated under reduced pressure to give 4,7,8-trichloro-2,2-dimethyl-1,3-benzothiazine (LC-MS (Method G), R.sub.t=1.25 min, (M+H)=282) which was used as such for the coupling reaction.

[0262] To a degased solution of 8-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (0.027 g, 0.09 mmol, 1.1 equiv.) and 4,7,8-trichloro-2,2-dimethyl-1,3-benzothiazine (0.02 g, 0.089 mmol) in DMF (0.4 mL) was added K.sub.3PO.sub.4 (0.06 g, 0.27 mmol) and CataCXiumA Pd G3 (0.007 g, 0.009 mmol). The resulting mixture was warmed to 60? C. and stirred for 20 min at this temperature. The reaction mixture was allowed to cool to RT, diluted with EtOAc and washed with aq. NH.sub.4Cl solution. The organic phase was washed with brine, dried over MgSO.sub.4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, cyclohexane:EtOAc) to give 7,8-dichloro-4-(8-fluoro-3-quinolyl)-2,2-dimethyl-1,3-benzothiazine as orange solid.

[0263] LC-MS (Method G), Rt=1.25 min, (M+H)=391.

[0264] .sup.1H NMR (400 MHZ, CDCl.sub.3)? ppm: .sup.1H NMR (.sub.1-CDCl.sub.3) ?: 9.07 (d, 1H), 8.33 (t, 1H), 7.69 (d, 1H), 7.40-7.61 (m, 2H), 7.27 (d, 1H), 7.16 (d, 1H), 1.75 (s, 6H).

[0265] .sup.19F NMR (.sub.1-CDCl.sub.3) ?: ?124.91 (s).

Example A2: 8-chloro-4-(8-fluoro-3-quinolyl)-2,2-dimethyl-1,3-benzothiazine (compound E.02)

Step 1:

[0266] To an ice cooled solution of 2,3-dichlorobenzonitrile (3.0 g, 17.44 mmol) in DMSO (15 mL) was added K.sub.2CO.sub.3 (0.49 g, 3.49 mmol) and H.sub.2O.sub.2 (30% in H.sub.2O, 2.7 mL, 26.16 mmol). The reaction mixture was gradually warmed to RT and stirred for 2 h at this temperature. Ice cold water was then added and the precipitate was collected by filtration. Drying under reduce pressure afforded 2,3-dichlorobenzamide.

[0267] LC-MS (Method G1), R.sub.t=0.84 min, (M+H)=190.

[0268] .sup.1H NMR (400 MHZ, DMSO) ? ppm=7.98 (br s, 1H), 7.70-7.76 (m, 1H), 7.61-7.69 (m, 1H), 7.36-7.43 (m, 2H).

Step 2:

[0269] A solution of sodium sulfide (2.49 g, 31.6 mmol) in 1-methyl-2-pyrrolidine (150 mL) was aged for 2 h at 190? C. under a gentle stream of nitrogen. The resulting solution was cooled to 130? C., 3-chloro-2-sulfanyl-benzamide (5.0 g, 26.3 mmol) was added, the mixture was warmed to 175? C. and aged for 4 h at this temperature. The mixture was then cooled to 70? C. and MgSO.sub.4 (3.23 g, 26.3 mmol), p-toluene sulfonic acid (5.50 g, 28.9 mmol) and 2,2-dimethoxypropane (17 mL, 131 mmol) was added. The resulting suspension was warmed to 100? C. and stirred for 16 h at this temperature. The reaction mixture was cooled to RT, water was added and mixture acidified with aq. HCl (2M). The resulting emulsion was extracted with EtOAc, the organic phase was washed with brine, dried over MgSO.sub.4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, cyclohexane:EtOAc) to give 8-chloro-2,2-dimethyl-3H-1,3-benzothiazin-4-one as yellow solid.

[0270] LC-MS (Method G1), R.sub.t=1.02 min, (M+H)=228.

[0271] .sup.1H NMR (400 MHZ, CDCl.sub.3) ? ppm: 8.1 (dd, 1H), 7.51 (dd, 1H), 7.22 (t, 1H), 6.91 (br s, 1H), 1.75 (s, 6H).

Step 3:

[0272] A solution of DMF (0.06 mL, 0.79 mmol) in DCM (1.5 mL) at 0? C. was was treated with oxalyl chloride (0.07 mL, 0.79 mmol). The resulting white suspension was stirred at 0? C. for 1 h. A solution of 8-chloro-2,2-dimethyl-3H-1,3-benzothiazin-4-one (0.100 g 0.44 mmol) in DCM (1 mL) was then added to the suspension at 0? C. and the mixture was gradually warmed to RT. After 2 h, LC-MS indicated full conversion. The reaction mixture was diluted with DCM and poured on a mixture of ice and aq. NaHCO.sub.3. The mixture was extracted with DCM and the organic phase was dried over MgSO.sub.4, filtered and concentrated under reduced pressure to give 4,8-dichloro-2,2-dimethyl-1,3-benzothiazine (LC-MS (Method G1), R.sub.t=1.26 min, (M+H)=246) which was used as such for the coupling reaction.

[0273] To a degassed solution of (8-fluoro-3-quinolyl)boronic acid (0.10 g, 0.53 mmol) and 4,8-dichloro-2,2-dimethyl-1,3-benzothiazine (0.118 g, 0.44 mmol) in DMF (2 mL) was added K.sub.3PO.sub.4 (0.31 g, 1.44 mmol) and PdCl.sub.2(dtbpf) (0.016 g, 0.024 mmol). The resulting mixture was warmed to 60? C. and stirred for 1 h at this temperature. The reaction mixture was allowed to cool to RT and partitioned between ice water and EtOAc. The organic phase was washed with brine, dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, cyclohexane:EtOAc) to give 8-chloro-4-(8-fluoro-3-quinolyl)-2,2-dimethyl-1,3-benzothiazine as beige solid.

[0274] LC-MS (Method), R.sub.t=1.27 min, (M+H)=357.

[0275] .sup.1H NMR (400 MHZ, CDCl.sub.3) ? ppm: 9.07 (d, 1 H), 8.35 (t, 1 H), 7.69 (d, 1 H), 7.48-7.60 (m, 3 H), 7.20 (dd, 1 H), 7.11 (t, 1 H), 1.75 (s, 6 H).

[0276] .sup.19F NMR (.sub.1-CDCl.sub.3) ?: ?125.08 (s).

Analytical Methods

Method G:

[0277] 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 ?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.

Method G1:

[0278] 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: 0.8 kV, Cone range: 25 V, Source Temperature: 120? C., Desolvation Temperature: 600? C., Cone Gas Flow: 50 l/h, Desolvation Gas Flow: 1000 l/h, Mass range: 110 to 850 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment , diode-array detector and ELSD detector. Column: Waters UPLC HSS T3 C18, 1.8 ?m, 30?2.1 mm, Temp: 40? C., DAD Wavelength range (nm): 230 to 400, Solvent Gradient: A=water+0.05% HCOOH, B=Acetonitrile+0.05% HCOOH, gradient: 10-100% B in 1.6 min; Flow (mL/min) 0.60.

Method H1:

[0279] Spectra were recorded on a SFC Waters Acquity UPC.sup.2/QDa with detection on a PDA Detector Waters Acquity UPC.sup.2. Column: Daicel SFC CHIRALPAK? IE, 3 mm, 0.3 cm?10 cm, 40? C., Mobile phase: A: CO.sub.2 B: 2-propanol, isocratic: 15% B in 4.8 min, ABPR: 1800 psi, Flow rate: 2.0 ml/min, Detection: 240 nm, Sample concentration: 1 mg/ml in methanol/2-propanol, Injection: 2 ?L.

TABLE-US-00010 TABLE E Melting point (mp) and/or LC/MS data (retention time (R.sub.t)) for compounds of Formula (I): RT [M + H] mp Entry IUPAC name STRUCTURE (min) (measured) Method (? C.) E.01 4-(7,8-difluoro-3-quinolyl)-2,2,8- trimethyl-1,3-benzothiazine [00010] 1.37 355 G1 137- 139 E.02 8-chloro-4-(7,8-difluoro-3- quinolyl)-2,2-dimethyl-1,3- benzothiazine [00011] 1.30 374 G1 134- 136 E.03 7,8-difluoro-4-(8-fluoro-3- quinolyl)-2,2-dimethyl-1,3- benzothiazine [00012] 1.15 359 G E.04 4-(8-fluoro-3-quinolyl)-2,2- dimethyl-8-methylsulfanyl-1,3- benzothiazine [00013] 1.16 369 G E.05 7,8-dichloro-4-(8-fluoro-3- quinolyl)-2,2-dimethyl-1,3- benzothiazine [00014] 1.25 391 G E.06 (2R)-2-(difluoromethyl)-4-(8- fluoro-3-quinolyl)-2,8-dimethyl- 1,3-benzothiazine [00015] 2.85 H1 E.07 (2R)-2-(difluoromethyl)-4-(8- fluoro-3-quinolyl)-2,8-dimethyl- 1,3-benzothiazine [00016] 3.52 H1 E.08 8-fluoro-4-(8-fluoro-3-quinolyl)- 2,2,7-trimethyl-1,3- benzothiazine [00017] 1.18 355 G 159- 161 E.09 8-chloro-2-(difluoromethyl)-4-(8- fluoro-3-quinolyl)-2-methyl-1,3- benzothiazine [00018] 1.17 393 G E.10 4-(8-fluoro-3-quinolyl)-2,2,7- trimethyl-1,3-benzothiazine-8- carbonitrile [00019] 1.09 362 G E.11 4-(8-fluoro-3-quinolyl)-2,2,7,8- tetramethyl-1,3-benzothiazine [00020] 1.21 351 G E.12 8-chloro-4-(8-fluoro-3-quinolyl)- 2,2-dimethyl-1,3-benzothiazine [00021] 1.19 357 G 158- 160 E.13 8-chloro-4-(8-fluoro-3-quinolyl)- 2,2,7-trimethyl-1,3- benzothiazine [00022] 1.23 371 G E.14 4-(8-fluoro-3-quinolyl)-2,2,8- trimethyl-1,3-benzothiazine [00023] 1.20 337 G E.15 2-(difluoromethyl)-4-(8-fluoro-3- quinolyl)-2,8-dimethyl-1,3- benzothiazine [00024] 1.17 373 G E.16 4-(7,8-difluoro-3-quinolyl)-8- fluoro-2,2,7-trimethyl-1,3- benzothiazine [00025] 1.23 373 G1 E.17 8-chloro-4-(5-fluoroquinoxalin-2- yl)-2,2-dimethyl-1,3- benzothiazine [00026] 1.22 358 G1 E.18 8-chloro-2-[(6-chloro-3- pyridyl)methyl]-4-(7,8-difluoro-3- quinolyl)-2-methyl-1,3- benzothiazine [00027] 1.55 486 G1 108- 107 E.19 8-chloro-2-[(6-chloro-3- pyridyl)methyl]-4-(8-fluoro-3- quinolyl)-2-methyl-1,3- benzothiazine [00028] 1.30 468 G1 E.20 8-chloro-4-(8-fluoro-2-methyl-3- quinolyl)-2,2-dimethyl-1,3- benzothiazine [00029] 1.33 371 G1 134- 136 E.21 7-chloro-4-(7,8-difluoro-3- quinolyl)-2,2,8-trimethyl-1,3- benzothiazine [00030] 1.69 389 G1 161- 163 E.22 4-(7,8-difluoro-3-quinolyl)-2,2,8- trimethyl-1,3-benzothiazine-7- carbonitrile [00031] 1.57 380 G1 216- 218 E.23 4-(8-fluoro-3-quinolyl)-2,2,8- trimethyl-1,3-benzothiazine-7- carbonitrile [00032] 1.51 362 G1 88-90 E.24 7-chloro-4-(8-fluoro-3-quinolyl)- 8-methoxy-2,2-dimethyl-1,3- benzothiazine [00033] 1.30 387 G1 E.25 7-chloro-4-(8-fluoro-3-quinolyl)- 2,2,8-trimethyl-1,3- benzothiazine [00034] 1.35 371 G1 68-70

Mycosphaerella Graminicola (Septoria Tritici) on Wheat/Preventative

[0280] 2-week old wheat plants cv. Riband are sprayed in a spray chamber with formulated test compound diluted in water. The test plants are inoculated by spraying a spore suspension on them one day after spray 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 to 19 days after application).

[0281] The following compounds listed in Table E (above) gave at least 80% control of Mycosphaerella graminicola at 60 ppm when compared to untreated control under the same conditions, which showed extensive disease development.

[0282] E.01, E.02, E.03, E.05, E.08, E.11, E.12, E.13, E.14, E.16, E.25.

Fusarium Culmorum/Liquid Culture (Head Blight)

[0283] 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 to 4 days after application.

[0284] The following compounds in Table E (above) 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:

[0285] E.03, E.04, E.05, E.06, E.07, E.08, E.09, E.10, E.11, E.12, E.13, E.14, E.15, E.16, E.17, E.19, E.21, E.23, E.24, E.25.

Fusarium Culmorum/Wheat/Spikelet Preventative (Head Blight)

[0286] 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).

[0287] The following compounds in Table E (above) 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:

[0288] E.05, E.06, E.08, E.14, E.15, E.19.

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

[0289] 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 to 5 days after application.

[0290] The following compounds in Table E (above) 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:

[0291] E.03, E.04, E.05, E.06, E.07, E.08, E.09, E.11, E.12, E.13, E.14, E.15, E.16, E.17, E.18, E.19, E.20, E.21, E.23, E.24.

Botryotinia Fuckeliana (Botrytis Cinerea)/Liquid Culture (Gray Mould)

[0292] 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.

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:

[0293] E.01, E.02, E.03, E.04, E.05, E.06, E.07, E.08, E.09, 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.

Glomerella Lagenarium (Colletotrichum Lagenarium)/Liquid Culture (Anthracnose)

[0294] 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. 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:

E.01, E.02, E.03, E.04, E.05, E.06, E.07, E.08, E.09, E.11, E.12, E.13, E.14, E.15, E.17, E.18, E.19, E.20, E.25.

Comparative Examples

Mycosphaerella Graminicola (Septoria Tritici) on Wheat/Preventative

[0295] 2-week old wheat plants cv. Riband are sprayed in a spray chamber with the test compound formulated as emulsifiable concentrate 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 compared to untreated controls (16 to 19 days after application).

TABLE-US-00011 Rate of application Efficacy Compound (ppm) (% control) Comparative compound A (compound 1b-69 according to WO 2009/119089) [00035] 60 11 Compound E.12 (according to the invention) 60 92 Compound E.13 (according to the invention) 60 96 Compound E.01 (according to the invention) 60 72 Compound E.02 (according to the invention) 60 99 Compound E.08 (according to the invention) 60 89 Compound E.14 (according to the invention) 60 83

Botrytis Cinerea/Tomato/Preventative (Botrytis on Tomato)

[0296] 4-week old tomato plants are treated sprayed in a spray chamber with the test compound formulated as emulsifible concentrate diluted in water. The test plants are inoculated by spraying them with a spore suspension two days after application. The inoculated test plants are incubated at 20? C. and 95% rh in a greenhouse and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (5-6 days after application).

TABLE-US-00012 Rate of application Efficacy Compound (ppm) (% control) Comparative compound A (compound 1b-69 according to WO 2009/119089) 200 95 [00036] Compound E.12 (according to the invention) 200 95 Compound E.01 (according to the invention) 200 97 Compound E.02 (according to the invention) 200 95 Compound E.08 (according to the invention) 200 97 Compound E.14 (according to the invention) 200 93

Venturia Inaequalis/Apple/Preventative (Scab on Apple)

[0297] 3-week old apple seedlings are sprayed in a spray chamber with the test compound formulated as emulsifible concentrate diluted in water. The test plants are inoculated by spraying them with a spore suspension 1 day after application. After an incubation period of 2 days at 20? C. and 95% rh, the inoculated test plants are placed at 20? C./19? C. (day/night) and 60% rh in a greenhouse. The percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (11-13 days after application).

TABLE-US-00013 Rate of application Efficacy Compound (ppm) (% control) Comparative compound A (compound 1b-69 according to WO 2009/119089) [00037] 200 100 Compound E.12 (according to the invention) 200 100 Compound E.01 (according to the invention) 200 97 Compound E.02 (according to the invention) 200 97 Compound E.08 (according to the invention) 200 80 Compound E.14 (according to the invention) 200 100

Colletotrichum Lagenarium/Cucumber/Preventative (Anthracnose)

[0298] 1-week old cucumber plants cv. Wisconsin are sprayed in a spray chamber with the test compound formulated as emulsifible concentrate diluted in water. The test plants are inoculated by spraying them with a spore suspension one day after application. After an incubation period of 30 h in darkness at 23? C. and 100% rh, the inoculated test plants are kept at 23? C./21? C. (day/night) and 70% rh in a greenhouse. The percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (6-8 days after application).

TABLE-US-00014 Rate of application Efficacy Compound (ppm) (% control) Comparative compound A (compound 1b-69 according to WO 2009/119089) [00038] 200 80 Compound E.12 (according to the invention) 200 100 Compound E.01 (according to the invention) 200 97 Compound E.02 (according to the invention) 200 97 Compound E.14 (according to the invention) 200 97

[0299] In the comparative experimental examples above, it is shown for selected compounds according to the invention that control on Mycosphaerella graminicola (Septoria tritici) is significantly superior to that for compounds of the prior art (WO 2009/119089).

[0300] Additionally, it is demonstrated in the comparative examples above that the compounds according to this invention display excellent control of Mycosphaerella graminicola (Septoria tritici) without compromising the spectrum of other diseases controlled by the compounds of the prior art.