MICROBIOCIDAL PHENYLAMIDINE DERIVATIVES WITH IMPROVED PLANT SAFETY PROPERTIES

Abstract

A method of improving plant safety and/or reducing phytotoxicity and/or reducing plant necrosis whilst combating, preventing or controlling phytopathogenic diseases, which comprises applying to a phytopathogen, to the locus of a phytopathogen, or to a plant susceptible to attack by a phytopathogen, or to propagation material thereof, a fungicidally effective amount of a compound of formula (I) wherein R.sup.1, R.sub.2, R.sup.3, R.sup.4 and R.sup.5 are as defined in claim 1. Furthermore, the present invention relates to novel compounds of formula (I) and to agrochemical compositions which comprise them, to the preparation of these compounds and compositions, and to the use of the compounds or compositions in the aforementioned methods.

##STR00001##

Claims

1. A method of improving plant safety whilst combating, preventing or controlling phytopathogenic diseases, which comprises applying to a phytopathogen, to the locus of a phytopathogen, or to a plant susceptible to attack by a phytopathogen, or to propagation material thereof, a fungicidally effective amount of a compound of formula (I) ##STR00056## wherein, R.sup.1 and R.sup.2 are each independently selected from C.sub.1-C.sub.4alkyl and C.sub.3-C.sub.8cycloalkyl; or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached form a three to six-membered saturated cyclic group which may optionally contain one oxygen or one sulphur atom; R.sup.3 is C.sub.1-C.sub.4 alkyl or halogen; or R.sup.3 is halomethyl (preferably CF.sub.3 or CHF.sub.2); R.sup.4 is C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4haloalkyl; R.sup.5 is aryl (optionally substituted with one to three R.sup.6 groups) or heteroaryl (optionally substituted with one to three R.sup.6 groups); and each R.sup.6 is independently selected from halogen, cyano, hydroxyl, amino, nitro, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6halocycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.3-C.sub.6cycloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4haloalkylthio, C.sub.3-C.sub.6cycloalkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkyl sulfonyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4alkoxycarbonyl, C.sub.1-C.sub.4alkylcarbonyloxy, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkenyloxy, C.sub.2-C.sub.6haloalkenyloxy, C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkylC.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6alkynyloxy, aryl, aryl(C.sub.1-C.sub.4)alkyl, aryloxy, heteroaryl, heteroaryl(C.sub.1-C.sub.4)alkyl and heteroaryloxy; or a salt or an N-oxide thereof.

2. A method according to claim 1 wherein R.sup.1 and R.sup.2 are each independently C.sub.1-C4 alkyl; R.sup.3 is C.sub.1-C.sub.3 alkyl; and R.sup.4 is C.sub.1-C.sub.4alkyl.

3. A method according to claim 1 wherein R.sup.5 is phenyl (optionally substituted with one to three R.sup.6 groups), pyridyl (optionally substituted with one to three R.sup.6 groups) or thiazolyl (optionally substituted with one to three R.sup.6 groups), and wherein each R.sup.6 is independently selected from halogen, cyano, C.sub.1-C.sub.4alkyl, C.sub.1-C4haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.3-C.sub.6cycloalkoxy, C.sub.1-C4alkylthio, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylsulfonyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, phenyl, benzyl, phenoxy, pyridyl, pyridylmethyl and pyridyloxy.

4. A method according to claim 1 wherein R.sup.1 and R.sup.2 are each independently selected from methyl, ethyl and isopropyl; R.sup.3 is methyl, ethyl or isopropyl; and R.sup.4 is C.sub.1-C.sub.3alkyl.

5. A method according to claim 1 wherein R.sup.5 is phenyl (optionally substituted with one or two R.sup.6 groups) or thiazolyl (optionally substituted with one or two R.sup.6 groups), and wherein each R.sup.6 is independently selected from halogen, cyano, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.2-C.sub.6alkynyl, phenyl, phenoxy and pyridyl.

6. A method according to claim 1 wherein R.sup.1 and R.sup.2 are each independently selected from methyl and ethyl; R.sup.3 is methyl or ethyl; R.sup.4 is methyl or ethyl; R.sup.5 is phenyl (optionally substituted with one or two R.sup.6 groups); and each R.sup.6 is independently selected from halogen, cyano, C.sub.1-C.sub.4alkyl, C.sub.1-C4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.2-C.sub.6alkynyl and phenyl.

7. A compound of formula (IH) ##STR00057## wherein R.sup.1 and R.sup.2 are each independently selected from C.sub.1-C.sub.4alkyl and C.sub.3-C.sub.8cycloalkyl; R.sup.3 is C.sub.1-C.sub.4 alkyl; or R.sup.3 is fluoro, chloro, bromo, iodo or halomethyl (preferably chloro, bromo or CHF.sub.2); R.sup.4 is C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4haloalkyl; R.sup.5 is aryl (optionally substituted with one to three R.sup.6 groups) or heteroaryl (optionally substituted with one to three R.sup.6 groups); and each R.sup.6 is independently selected from halogen, cyano, hydroxyl, amino, nitro, C.sub.1-C4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6halocycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C4haloalkoxy, C.sub.3-C.sub.6cycloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4haloalkylthio, C.sub.3-C6cycloalkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylsulfonyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.1-C.sub.4alkoxycarbonyl, C.sub.1-C.sub.4alkylcarbonyloxy, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkenyloxy, C.sub.2-C.sub.6haloalkenyloxy, C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkylC.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6alkynyloxy, aryl, aryl(C.sub.1-C.sub.4)alkyl, aryloxy, heteroaryl, heteroaryl(C.sub.1-C.sub.4)alkyl and heteroaryloxy; or a salt or an N-oxide thereof, provided that when R.sup.1 is methyl and R.sup.2 is methyl or R.sup.1 is methyl and R.sup.2 is ethyl and R.sup.3 and R.sup.4 are both methyl then R.sup.5 is not 4-Chloro-3-(trifluoromethyl)phenyl, 5-Chloro-3-(trifluoromethyl)phenyl, 4-Chloro-3-(isopropyl)phenyl, 4-Chloro-3-(tert-butyl)phenyl, or 5-cyclopropyl-1,3,4-thiadiazol-2-yl.

8. A compound according to claim 7, or a salt or an N-oxide thereof, wherein R.sup.1 and R.sup.2 are each independently C.sub.1-C.sub.4 alkyl; R.sup.3 is C.sub.1-C.sub.3 alkyl; and R.sup.4 is C.sub.1-C.sub.4alkyl.

9. A compound according to claim 7 wherein R.sup.1 and R.sup.2 are each independently C.sub.1-C.sub.4 alkyl; R.sup.3 is C.sub.1-C.sub.3 alkyl; R.sup.4 is C.sub.1-C.sub.4alky; R.sup.5 is phenyl (optionally substituted with one to three R.sup.6 groups), pyridyl (optionally substituted with one to three R.sup.6 groups) or thiazolyl (optionally substituted with one to three R.sup.6 groups); and each R.sup.6 is independently selected from halogen, cyano, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C3-C6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.3-C.sub.6cycloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylsulfonyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, phenyl, benzyl, phenoxy, pyridyl, pyridylmethyl and pyridyloxy; or a salt or N-oxide thereof, provided that when R.sup.1 is methyl and R.sup.2 is methyl or R.sup.1 is methyl and R.sup.2 is ethyl and R.sup.3 and R.sup.4 are both methyl then R.sup.5 is not 4-Chloro-3-(trifluoromethyl)phenyl, 5-Chloro-3-(trifluoromethyl)phenyl, 4-Chloro-3-(isopropyl)phenyl, or 4-Chloro-3-(tert-butyl)phenyl.

10. A compound according to claim 7 wherein R.sup.1 and R.sup.2 are each independently selected from methyl, ethyl and isopropyl; R.sup.3 is methyl, ethyl or isopropyl; R.sup.4 is C.sub.1-C.sub.3alkyl; R.sup.5 is phenyl (optionally substituted with one or two R.sup.6 groups) or thiazolyl (optionally substituted with one or two R.sup.6 groups); and each R.sup.6 is independently selected from halogen, cyano, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4alkylcarbonyl, C.sub.2-C.sub.6alkynyl, phenyl, phenoxy and pyridyl; or a salt or N-oxide thereof, provided that when R.sup.1 is methyl and R.sup.2 is methyl or R.sup.1 is methyl and R.sup.2 is ethyl and R.sup.3 and R.sup.4 are both methyl then R.sup.5 is not 4-Chloro-3-(trifluoromethyl)phenyl, 5-Chloro-3-(trifluoromethyl)phenyl, 4-Chloro-3-(isopropyl)phenyl, or 4-Chloro-3-(tert-butyl)phenyl.

11. A compound according to claim 7 wherein R.sup.1 and R.sup.2 are each independently selected from methyl and ethyl; R.sup.3 is methyl or ethyl; R.sup.4 is methyl or ethyl; R.sup.5 is phenyl (optionally substituted with one or two R.sup.6 groups); and each R.sup.6 is independently selected from halogen, cyano, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.2-C.sub.6alkynyl and phenyl; or a salt or N-oxide thereof, provided that when R.sup.1 is methyl and R.sup.2 is methyl or R.sup.1 is methyl and R.sup.2 is ethyl and R.sup.3 and R.sup.4 are both methyl then R.sup.5 is not 4-Chloro-3-(trifluoromethyl)phenyl, 5-Chloro-3-(trifluoromethyl)phenyl, 4-Chloro-3-(isopropyl)phenyl, or 4-Chloro-3-(tert-butyl)phenyl.

12. A compound according to claim 7 wherein R.sup.1 is methyl and R.sup.2 is ethyl; R.sup.3 is methyl; R.sup.4 is methyl; and R.sup.5 is phenyl, which is optionally substituted by one or two sub stituents independently selected from trifluoromethyl and halogen (preferably fluoro or chloro); or a salt or N-oxide thereof, provided that when R.sup.1 is methyl and R.sup.2 is methyl or R.sup.1 is methyl and R.sup.2 is ethyl and R.sup.3 and R.sup.4 are both methyl then R.sup.5 is not 4-Chloro-3-(trifluoromethyl)phenyl, or 5 -Chloro-3-(trifluoromethyl)phenyl.

13. A compound according to claim 7 wherein the compound is: ##STR00058## ##STR00059## or a salt or an N-oxide thereof; or wherein the compound is: ##STR00060## ##STR00061## ##STR00062## or a salt or an N-oxide thereof.

14. A composition comprising a fungicidally effective amount of a compound of formula (I) as defined in claim 7, wherein the composition optionally comprises one or more additional active ingredients and/or a diluent.

15. A method of reducing phytotoxicity whilst combating, preventing or controlling phytopathogenic diseases, which comprises applying to a phytopathogen, to the locus of a phytopathogen, or to a plant susceptible to attack by a phytopathogen, or to propagation material thereof, a fungicidally effective amount of a compound of formula (I), or a salt or an N-oxide thereof, as defined in claim 1.

16. A method of reducing plant necrosis whilst combating, preventing or controlling phytopathogenic diseases, which comprises applying to a phytopathogen, to the locus of a phytopathogen, or to a plant susceptible to attack by a phytopathogen, or to propagation material thereof, a fungicidally effective amount of a compound of formula (I), or a salt or an N-oxide thereof, as defined in claim 1.

17. A method of reducing phytotoxicity whilst combating, preventing or controlling phytopathogenic diseases, which comprises applying to a phytopathogen, to the locus of a phytopathogen, or to a plant susceptible to attack by a phytopathogen, or to propagation material thereof, a fungicidally effective amount of a compound of formula (I), or a salt or an N-oxide thereof, as defined in claim 7.

18. A method of reducing phytotoxicity whilst combating, preventing or controlling phytopathogenic diseases, which comprises applying to a phytopathogen, to the locus of a phytopathogen, or to a plant susceptible to attack by a phytopathogen, or to propagation material thereof, a fungicidally effective amount of a compound of formula (I), or a salt or an N-oxide thereof, as defined in claim 14.

19. A method of reducing plant necrosis whilst combating, preventing or controlling phytopathogenic diseases, which comprises applying to a phytopathogen, to the locus of a phytopathogen, or to a plant susceptible to attack by a phytopathogen, or to propagation material thereof, a fungicidally effective amount of a compound of formula (I), or a salt or an N-oxide thereof, as defined in claim 7.

20. A method of reducing plant necrosis whilst combating, preventing or controlling phytopathogenic diseases, which comprises applying to a phytopathogen, to the locus of a phytopathogen, or to a plant susceptible to attack by a phytopathogen, or to propagation material thereof, a fungicidally effective amount of a compound of formula (I), or a salt or an N-oxide thereof, as defined in claim 14.

Description

EXAMPLES

[0217] The Examples which follow serve to illustrate the invention. Certain compounds of formula (I) 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.

[0218] 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:

Formulation Examples

[0219]

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%

[0220] 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%

[0221] 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%

[0222] 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%

[0223] 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%

[0224] 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%

[0225] 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%

[0226] 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 0.5% in water) monoazo-pigment calcium salt 5% Silicone oil (in the form of a 75% emulsion in water) 0.2% Water 45.3%

[0227] 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

[0228] 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.

[0229] 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.

[0230] The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.

Preparation Examples

[0231] Using techniques described above and below, and also in WO 2000/046184, WO07031513, WO 2008/110313 WO 2010/086118 and WO 2008/110278, together with further techniques generally known to the person skilled in the art, compounds of formula (I) may be prepared.

Example 1

Preparation of N-ethyl-N-(5-methoxy-2-methyl-4-phenoxy-phenyl)-N-methyl-formamidine

Step 1. Preparation of 1-methoxy-4-methyl-5-nitro-2-phenoxy-benzene

[0232] A suspension of 1-chloro-2-methoxy-5-methyl-4-nitrobenzene (1.0 g, 4.96 mmol), phenol (0.56 g, 5.95 mmol) and K.sub.2CO.sub.3 (0.90 g, 6.45 mmol) in dry dimethyl formamide (10 mL) was warmed to 120 C. and stirred for 22 h at this temperature. The reaction was cooled to room temperature, diluted with ethyl acetate and washed with water (2). The organic layer was washed with brine, dried over MgSO.sub.4, solids were removed by filtration and volatiles were removed in vacuo. The residue was purified by flash chromatography on silica gel to afford the title compound as light yellow oil.

[0233] .sup.1H NMR (400 MHz, CDCl.sub.3): 7.73 (s, 1H), 7.35-7.45 (m, 2H), 7.14-7.24 (m, 1H), 6.99-7.08 (m, 2H), 6.69 (s, 1H), 3.94 (s, 3H), 2.49 (s, 3H).

Step 2. Preparation of 5-methoxy-2-methyl-4-phenoxy-aniline

[0234] 1-methoxy-4-methyl-5-nitro-2-phenoxy-benzene (0.99 g, 3.8 mmol) was dissolved in acetic acid (8 mL), warmed to 80 C. and iron dust (0.85 g, 15.3 mmol) was added portion wise at this temperature. Upon completed addition, the reaction mixture was stirred for an additional 60 min at 80 C. The mixture was cooled to room temperature, diluted with dichloromethane and filtrated through a pad of Celite. The filtrate was concentrated in vacuo to dark oil which was dissolved in ethyl acetate and washed with aq. NaHCO3. The organic layer was washed with brine, dried over MgSO.sub.4, solids were removed by filtration and volatiles were removed in vacuo. The residue was purified by flash chromatography on silica gel to afford the title compound as light brown solid.

[0235] .sup.1H NMR (400 MHz, CDCl.sub.3): 7.18-7.30 (m, 2H), 6.97 (t, 1H), 6.82-6.92 (m, 2H), 6.75 (s, 1H), 6.37 (s, 1H), 3.74 (s, 3H), 2.08 (s, 3H).

Step 3. Preparation of N-ethyl-N-(5-methoxy-2-methyl-4-phenoxy-phenyl)-N-methyl-formamidine

[0236] A solution of 5-methoxy-2-methyl-4-phenoxy-aniline (0.55 g, 2.40 mmol) and N-(dimethoxymethyl)-N-methyl-ethanamine (0.64 g, 4.80 mmol) in toluene (5 mL) was treated with p-toluene sulfonic acid (1 small crystal) and warmed to 60 C. After stirring for 18 h at 60 C., the reaction was cooled to room termperature, diluted with ethyl acetate and washed with aq. NaHCO3. The organic layer was washed with brine, dried over MgSO.sub.4, solids were removed by filtration and volatiles were removed in vacuo. The residue was purified by flash chromatography on silica gel to afford the title compound as light yellow oil.

[0237] .sup.1H NMR (400 MHz, CDCl.sub.3): 7.45 (br s, 1H), 7.16-7.32 (m, 2H), 6.94-7.06 (m, 1H), 6.91-6.89 (m, 2H), 6.81 (s, 1H), 6.44 (s, 1H), 3.78 (s, 3H), 3.38 (br s, 2H), 3.01 (s, 3H), 2.16 (s, 3H), 1.22 (t, 3H).

Example 2

Preparation of N-[4-(4,5-dichlorothiazol-2-yl)oxy-5-methoxy-2-methyl-phenyl]-N-ethyl-N-methyl-formamidine

Step 1. Preparation of 2-methoxy-5-methyl-4-nitro-phenol

[0238] A solution of 1,2-dimethoxy-4-methyl-5-nitro-benzene (0.50 g, 2.54 mmol) and lithium chloride (0.32 g, 7.61 mmol) in dimethyl formamide (10 mL) was heated to 170 C. using a microwave reactor and kept at this temperature for 3 h. The resulting dark solution was cooled to room temperature and poured into aq. NH4Cl solution. The mixture was extracted with tertbutyl methyl ether and the organic layer was washed with water to remove dimethyl formamide. The organic layer was extracted with aq. NaOH solution (1 M) and water. This combined aqueous extractes were then acified with conc. HCl to pH 1 and extracted with CH2Cl2. The dichloromethane layer was dried over MgSO4, filtrated and concentrated in vacuo to afford the title compound as yellow solid.

[0239] .sup.1H NMR (400 MHz, CDCl.sub.3): 7.68 (s, 1H), 6.83 (s, 1H), 6.01 (s, 1H), 3.96 (s, 3H), 2.58 (s, 3H).

Step 2. Preparation of 4,5-dichloro-2-(2-methoxy-5-methyl-4-nitro-phenoxy)thiazole

[0240] Sodium hydride (60% in paraffin oil, 0.052 g, 1.4 mmol) was added to a solution of 2-methoxy-5-methyl-4-nitro-phenol (0.19 g, 1.0 mmol) in dry dimethyl formamide (1 mL) at room temperature. The resulting red solution was stirred for 45 min at room temperature before 2,4,5-trichlorothiazole (0.19 g, 1.0 mmol) was added. The resulting solution was warmed to 70 C. and stirred for 5 d at this temperature. The reaction was cooled to room temperature and diluted with ice water. The precipitated brown solid was collected on a glass filter, washed with cold water and dried in vacuo to afford the title compound.

[0241] .sup.1H NMR (400 MHz, CDCl.sub.3): 7.69 (s, 1H), 7.22 (s, 1H), 3.89 (s, 3H), 2.57 (s, 3H).

Step 3. Preparation of 4-(4,5-dichlorothiazol-2-yl)oxy-5-methoxy-2-methyl-aniline

[0242] A solution of 4,5-dichloro-2-(2-methoxy-5-methyl-4-nitro-phenoxy)thiazole (0.28 g, 0.82 mmol) in ethanol (6 mL) was treated with NH4Cl (0.09 g, 1.64 mmol), water (1.5 mL) and iron dust (0.18 g, 3.28 mmol) at room temperature. The resulting mixture was warmed to 85 C. and stirred for 1 h at this temperature. After cooling to room temperature, the reaction was diluted with aq. NaHCO3 and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, filtrated and concentrated in vacuo. The residue was purified by flash chromatography on silica gel to afford the title compound as light brown oil.

[0243] .sup.1H NMR (400 MHz, CDCl.sub.3): 6.88 (s, 1H), 6.32 (s, 1H), 3.76 (s, 3H), 3.69 (br s, 2H), 2.09 (s, 3H).

Step 4. Preparation of N[4-(4,5-dichlorothiazol-2-yl)oxy-5-methoxy-2-methyl-phenyl]-N-ethyl-N-methyl-formamidine

[0244] A solution of 4-(4,5-dichlorothiazol-2-yl)oxy-5-methoxy-2-methyl-aniline (0.32 g, 1.04 mmol) and N-(dimethoxymethyl)-N-methyl-ethanamine (0.42 g, 3.15 mmol) in toluene (3 mL) was treated with p-toluene sulfonic acid (1 small crystal) and warmed to 70 C. After stirring for 18 h at 70 C., the reaction was cooled to room termperature, diluted with ethyl acetate and washed with aq. NaHCO3. The organic layer was washed with brine, dried over MgSO.sub.4, solids were removed by filtration and volatiles were removed in vacuo. The residue was purified by flash chromatography on silica gel to afford the title compound as light brown oil.

[0245] .sup.1H NMR (400 MHz, CDCl.sub.3): 7.43 (br s, 1H), 6.96 (s, 1H), 6.41 (s, 1H), 3.79 (s, 3H), 3.22-3.56 (m, 2H), 3.01 (s, 3H), 2.18 (s, 3H), 1.23 (t, 3H).

[0246] Table E: Physical data of compounds of formula (I) from Tables 1-32

[0247] The compounds of formula (I) were prepared using techniques described above and/or common synthetic techniques generally known to the person skilled in the art, as well as those described in WO 2000/046184, WO07031513, WO 2008/110313 WO 2010/086118 and WO 2008/110278.

TABLE-US-00010 TABLE E Compound No. Melting point ( C.) LC/MS 1.009 59-60 24.009 Rt = 0.82 min; MS: m/z 374 [M + 1].sup.+ 25.009 Rt = 0.61 min; MS: m/z 401 [M + 1].sup.+ 2.009 Rt = 0.63 min; MS: m/z 317 [M + 1].sup.+ 3.009 Rt = 0.82 min; MS: m/z 333 [M + 1].sup.+ 14.009 Rt = 0.65 min; MS: m/z 379 [M + 1].sup.+ 19.009 Rt = 0.71 min; MS: m/z 313 [M + 1].sup.+

[0248] 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 method is as follows:

[0249] Spectra were recorded on a Mass Spectrometer from Waters 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, 302.1 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: gradient: 0 min 0% B, 100% A; 1.2-1.5 min 100% B; Flow (ml/min) 0.85

Biological Examples

Phakopsora pachyrhizi on Soybean, Preventive Treatment

[0250] The compound activity was tested under 1 day preventive conditions. Soybean plants with a fully enfolded first trifoliate leaf were sprayed with a track sprayer and 50 I/ha spray volume with the test compounds and rates as shown in the table below.

[0251] 1 day after application leaf discs were cut from the first trifoliate leaf and placed in multiwell plates on water-agar. 5 leaf discs per treatment where infested with spores of a triazole- and strobilurine-tolerant soybean rust strain. The multiwell plates where sealed and placed in an incubator 48 h in darkness and 12 h light/dark cycle afterwards. Rust infestation on leaf discs was evaluated visually 10 days after application and average activity calculated in relation to disease severity on untreated check leaf discs.

Phytotoxicity on Soybean, Preventive Treatment

[0252] Soybean plants with a fully enfolded first trifoliate leaf were sprayed with a track sprayer and 50 l/ha spray volume with the test compounds and rates as shown in the table below.

[0253] The plants were then transferred to a greenhouse at 22 C. and a 14 h day and 10 h night cycle. 5 plants per treatment were sprayed and evaluated. Phytotoxicity on plant leaves was evaluated visually 8 days after application and average phytotoxicity calculated.

##STR00050##

TABLE-US-00011 g % soybean % PHAKPA g % soybean % PHAKPA a.i./ha phytotoxicity activity a.i./ha phytotoxicity activity 32 5 n.t. 32 22 n.t. 16 3 n.t. 16 11 n.t. 8 5 100 8 9 100 4 n.t. 99 4 n.t. 97

##STR00051##

TABLE-US-00012 g % soybean % PHAKPA g % soybean % PHAKPA a.i./ha phytotoxicity activity a.i./ha phytotoxicity activity 32 3 n.t. 32 22 n.t. 16 4 n.t. 16 18 n.t. 8 2 99 8 17 97 4 n.t. 96 4 n.t. 87

##STR00052##

TABLE-US-00013 g % soybean % PHAKPA g % soybean % PHAKPA a.i./ha phytotoxicity activity a.i./ha phytotoxicity activity 32 8 n.t. 32 35 n.t. 16 5 n.t. 16 25 n.t. 8 4 96 8 18 95 4 n.t. 89 4 n.t. 93

##STR00053##

TABLE-US-00014 g % soybean % PHAKPA g % soybean % PHAKPA a.i./ha phytotoxicity activity a.i./ha phytotoxicity activity 32 n.t. n.t. 32 35 n.t. 16 5 n.t. 16 32 n.t. 8 3 96 8 7 98 4 n.t. 95 4 n.t. 98

##STR00054##

TABLE-US-00015 g % soybean % PHAKPA g % soybean % PHAKPA a.i./ha phytotoxicity activity a.i./ha phytotoxicity activity 32 5 n.t. 32 33 n.t. 16 4 n.t. 16 15 n.t. 8 2 93 8 7 96 4 n.t. 91 4 n.t. 97

##STR00055##

TABLE-US-00016 g % soybean % PHAKPA g % soybean % PHAKPA a.i./ha phytotoxicity activity a.i./ha phytotoxicity activity 32 11 n.t. 32 27 n.t. 16 5 n.t. 16 22 n.t. 8 5 98 8 10 95 4 n.t. 84 4 n.t. 97