Microbiocidal oxadiazole derivatives

Abstract

Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially as fungicides. ##STR00001##

Claims

1. A compound of formula (I): ##STR00061## wherein A.sup.1 represents N or CR.sup.1, wherein R.sup.1 is hydrogen, halogen, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, or difluoromethoxy; A.sup.2 represents N or CR.sup.2, wherein R.sup.2 is hydrogen, halogen, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, or difluoromethoxy; A.sup.3 represents N or CR.sup.3 wherein R.sup.3 is hydrogen or halogen; A.sup.4 represents CR.sup.4 wherein R.sup.4 is halogen; wherein no more than one of A.sup.1, A.sup.2, A.sup.3 are N; n is 0 or 1; R.sup.5 and R.sup.6 independently represent hydrogen or methyl; R.sup.7 is hydrogen, C.sub.1-4alkyl, C.sub.3-4alkenyl, C.sub.3-4alkynyl, C.sub.1-4haloalkyl, cyanoC.sub.1-4alkyl, hydroxyC.sub.1-4alkyl, C.sub.1-2alkoxyC.sub.1-4alkyl, heterocyclyl or heterocyclylC.sub.1-3alkyl, wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S; R.sup.8 is hydrogen, C.sub.1-8alkyl, C.sub.3-6alkenyl, C.sub.3-6alkynyl, C.sub.1-4haloalkyl, C.sub.3-6haloalkenyl, C.sub.1-4alkylsulfanylC.sub.1-4alkyl, C.sub.1-4alkylsulfonylC.sub.1-4alkyl, cyanoC.sub.1-6alkyl, hydroxyC.sub.1-6alkyl, C.sub.1-4alkoxyC.sub.1-6alkyl, di-(C.sub.1-4alkoxy)C.sub.1-4alkyl, C.sub.1-4haloalkoxyC.sub.1-6alkyl, C.sub.1-4alkylcarbonylC.sub.1-4alkyl, C.sub.1-4alkoxycarbonylC.sub.1-4alkyl, C.sub.1-2alkoxycarbonylC.sub.1-4fluoroalkyl, C.sub.1-4alkylaminocarbonylC.sub.1-4alkyl, di-C.sub.1-4alkylaminocarbonylC.sub.1-4alkyl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-3alkyl, phenyl, phenylC.sub.1-4alkyl, phenoxycyanoC.sub.1-4alkyl, carbobicyclyl, wherein the carbobicyclyl is a 9- or 10-membered saturated or partially unsaturated fused bicyclic ring system, heteroaryl, heteroarylC.sub.1-4alkyl, heteroarylC.sub.1-2alkylsulfanylC.sub.1-2alkyl, wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterodiaryl or heterodiarylC.sub.1-3alkyl, wherein the heterodiaryl moiety is a 9- or 10-membered aromatic fused bicyclic ring system which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclyl or heterocyclylC.sub.1-3alkyl, wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from O and S or a 6-membered non-aromatic ring which comprises 1, 2 or 3 nitrogen heteroatoms, heterobicyclyl or heterobicyclylC.sub.1-3alkyl, wherein the heterobicyclyl moiety is a 7- to 10-membered saturated, partially unsaturated or partially aromatic fused or spirocyclic bicyclic ring system which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, carbobicyclyl, heteroaryl, heterodiaryl, heterocyclyl or heterobicyclyl moieties of R.sup.8 are optionally substituted by 1, 2, 3, or 4 substituents, which may be the same or different, selected from R.sup.9, or any of said cycloalkyl, phenyl, carbobicyclyl, heteroaryl, heterodiaryl, heterocyclyl or heterobicyclyl moieties of R.sup.8 are optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R.sup.10, or any of said cycloalkyl, phenyl, carbobicyclyl, heteroaryl, heterodiaryl, heterocyclyl or heterobicyclyl moieties of R.sup.8 are substituted by 1 or 2 substituents, which may be the same or different, selected from R.sup.9, and are further substituted by 1 or 2 substituents, which may be the same or different, selected from R.sup.10; R.sup.9 is selected from cyano, amino, halogen, hydroxy, methyl, ethyl, propyl, isopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, C.sub.2-3alkynyl, C.sub.1-2alkoxyC.sub.1-2alkyl, C.sub.1-4alkoxycarbonyl, C.sub.1-4alkylaminocarbonyl, di-C.sub.1-4alkylaminocarbonyl or C.sub.1-4alkylsulfonyl; and R.sup.10 is C.sub.3-6cycloalkyl, benzyl or phenyl; or a salt or an N-oxide thereof.

2. The compound according to claim 1, wherein A.sup.1, A.sup.2, and A.sup.3 are CH.

3. The compound according to claim 1, wherein R.sup.4 is fluorine.

4. The compound according to claim 1, wherein n is 0.

5. The compound according to claim 1, wherein R.sup.7 is hydrogen, C.sub.1-4alkyl, cyanoC.sub.1-4alkyl, C.sub.1-2alkoxyC.sub.1-4alkyl or heterocyclylC.sub.1-2alkyl, wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1 or 2 oxygen atoms.

6. The compound according to claim 1, wherein R.sup.7 is hydrogen or C.sub.1-4alkyl.

7. The compound according to claim 1, wherein R.sup.8 is C.sub.1-8alkyl, C.sub.3-6alkenyl, C.sub.3-6alkynyl, C.sub.1-4alkylsulfanylC.sub.1-4alkyl, C.sub.1-4alkylsulfonylC.sub.1-4alkyl, cyanoC.sub.1-6alkyl, hydroxyC.sub.1-6alkyl, C.sub.1-4alkoxyC.sub.1-6alkyl, di-(C.sub.1-4alkoxy)C.sub.1-4alkyl, C.sub.1-4alkylcarbonylC.sub.1-4alkyl, C.sub.1-4alkoxycarbonylC.sub.1-4alkyl, C.sub.1-2alkoxycarbonylC.sub.1-4fluoroalkyl, C.sub.3-6cycloalkyl, C.sub.3-6cycloalkylC.sub.1-3alkyl, phenyl, phenylC.sub.1-4alkyl, phenoxycyanoC.sub.1-4alkyl, carbobicyclyl, wherein the carbobicyclyl is a 9- or 10-membered saturated or partially unsaturated fused bicyclic ring system, heteroaryl, heteroarylC.sub.1-4alkyl or heteroarylC.sub.1-2alkylsulfanylC.sub.1-2alkyl, wherein the heteroaryl moiety is a 5-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, or a 6-membered aromatic ring which comprises 1 or 2 nitrogen atoms, heterodiaryl, heterodiarylC.sub.1-3alkyl, wherein the heterodiaryl moiety is a 9-membered aromatic fused bicyclic ring system which comprises 1, 2, 3 or 4 nitrogen atoms, heterocyclyl or heterocyclylC.sub.1-3alkyl, wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from O and S or a 6-membered non-aromatic ring which comprises 1, 2 or 3 nitrogen heteroatoms, heterobicyclyl or heterobicyclylC.sub.1-3alkyl, wherein the heterobicyclyl moiety is a 7- to 10-membered saturated, partially unsaturated or partially aromatic fused ring system which comprises 1, 2 or 3 heteroatoms selected from N, O and S, and wherein any of said cycloalkyl, phenyl, carbobicyclyl, heteroaryl, heterodiaryl, heterocyclyl or heterobicyclyl moieties of R.sup.8 are optionally substituted by 1, 2, 3, or 4 substituents, which may be the same or different, selected from R.sup.9, or 1 or 2 substituents, which may be the same or different, selected from R.sup.10.

8. The compound according to claim 1, wherein R.sup.8 is C.sub.1-8alkyl, C.sub.1-4alkoxyC.sub.1-6alkyl, di-(C.sub.1-4alkoxy)C.sub.1-4alkyl, C.sub.3-6cycloalkyl, C.sub.3-6cycloalkylC.sub.1-3alkyl, phenyl, phenylC.sub.1-4alkyl, heteroaryl or heteroarylC.sub.1-4alkyl, wherein the heteroaryl moiety is a 5-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, or a 6-membered aromatic ring which comprises 1 or 2 nitrogen atoms, heterocyclyl or heterocyclylC.sub.1-3alkyl, wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from O and S or a 6-membered non-aromatic ring which comprises 1, 2 or 3 nitrogen heteroatoms, and wherein any of said cycloalkyl, phenyl, heteroaryl, or heterocyclyl moieties of R.sup.8 are optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R.sup.9.

9. The compound according to claim 1, wherein R.sup.8 is C.sub.1-8alkyl, C.sub.1-2alkoxyC.sub.1-3alkyl, di-(C.sub.1-4alkoxy)C.sub.1-4alkyl, C.sub.3-6cycloalkyl, C.sub.3-6cycloalkylC.sub.1-2alkyl, phenyl, phenylC.sub.1-4alkyl, heterocyclyl or heterocyclylC.sub.1-3alkyl, wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1 or 2 oxygen heteroatoms, and wherein any of said cycloalkyl, phenyl or heterocyclyl moieties of R.sup.8 are optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R.sup.9.

10. The compound according to claim 1, wherein R.sup.9 is independently selected from cyano, halogen, methyl, methoxy, ethoxy, C.sub.2-3alkynyl, C.sub.1-2alkoxyC.sub.1-2alkyl or C.sub.1-4alkoxycarbonyl.

11. The compound according to claim 1, wherein R.sup.9 is independently selected from cyano, fluoro, chloro, methyl, methoxy, ethoxy, ethynyl, methylcarboxylate, ethylcarboxylate, tert-butylcarboxylate, ethoxymethyl, and R.sup.10 is cyclopropyl.

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

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

14. A method comprising: applying a fungicidally effective amount of a compound of formula (I): ##STR00062## wherein A.sup.1 represents N or CR.sup.1, wherein R.sup.1 is hydrogen, halogen, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, or difluoromethoxy; A.sup.2 represents N or CR.sup.2, wherein R.sup.2 is hydrogen, halogen, methyl, ethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, or difluoromethoxy; A.sup.3 represents N or CR.sup.3 wherein R.sup.3 is hydrogen or halogen; A represents CR.sup.4 wherein R.sup.4 is halogen; wherein no more than one of A.sup.1, A.sup.2, A.sup.3 are N; n is 0 or 1; R.sup.5 and R.sup.6 independently represent hydrogen or methyl; R.sup.7 is hydrogen, C.sub.1-4alkyl, C.sub.3-4alkenyl, C.sub.3-4alkynyl, C.sub.1-4haloalkyl, cyanoC.sub.1-4alkyl, hydroxyC.sub.1-4alkyl, C.sub.1-2alkoxyC.sub.1-4alkyl, heterocyclyl or heterocyclylC.sub.1-3alkyl, wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S; R.sup.8 is hydrogen, C.sub.1-8alkyl, C.sub.3-6alkenyl, C.sub.3-6alkynyl, C.sub.1-4haloalkyl, C.sub.3-6haloalkenyl, C.sub.1-4alkoxy, C.sub.1-4alkylsulfanylC.sub.1-4alkyl, C.sub.1-4alkylsulfonylC.sub.1-4alkyl, cyanoC.sub.1-6alkyl, hydroxyC.sub.1-6alkyl, C.sub.1-4alkoxyC.sub.1-6alkyl, di-(C.sub.1-4alkoxy)C.sub.1-4alkyl, C.sub.1-4haloalkoxyC.sub.1-6alkyl, C.sub.1-4alkylcarbonylC.sub.1-4alkyl, C.sub.1-4alkoxycarbonylC.sub.1-4alkyl, C.sub.1-2alkoxycarbonylC.sub.1-4fluoroalkyl, C.sub.1-4alkylaminocarbonylC.sub.1-4alkyl, di-C.sub.1-4alkylaminocarbonylC.sub.1-4alkyl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-3alkyl, phenyl, phenylC.sub.1-4alkyl, phenoxycyanoC.sub.1-4alkyl, carbobicyclyl, wherein the carbobicyclyl is a 9- or 10-membered saturated or partially unsaturated fused bicyclic ring system, heteroaryl, heteroarylC.sub.1-4alkyl, heteroarylC.sub.1-2alkylsulfanylC.sub.1-2alkyl, wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterodiaryl or heterodiarylC.sub.1-3alkyl, wherein the heterodiaryl moiety is a 9- or 10-membered aromatic fused bicyclic ring system which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, heterocyclyl or heterocyclylC.sub.1-3alkyl, wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, heterobicyclyl or heterobicyclylC.sub.1-3alkyl, wherein the heterobicyclyl moiety is a 7- to 10-membered saturated, partially unsaturated or partially aromatic fused or spirocyclic bicyclic ring system which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein any of said cycloalkyl, phenyl, carbobicyclyl, heteroaryl, heterodiaryl, heterocyclyl or heterobicyclyl moieties of R.sup.8 are optionally substituted by 1, 2, 3, or 4 substituents, which may be the same or different, selected from R.sup.9, or any of said cycloalkyl, phenyl, carbobicyclyl, heteroaryl, heterodiaryl, heterocyclyl or heterobicyclyl moieties of R.sup.8 are optionally substituted by 1 or 2 substituents, which may be the same or different, selected from R.sup.10, or any of said cycloalkyl, phenyl, carbobicyclyl, heteroaryl, heterodiaryl, heterocyclyl or heterobicyclyl moieties of R.sup.8 are substituted by 1 or 2 substituents, which may be the same or different, selected from R.sup.9, and are further substituted by 1 or 2 substituents, which may be the same or different, selected from R.sup.10; R.sup.9 is selected from cyano, amino, halogen, hydroxy, methyl, ethyl, propyl, isopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, C.sub.2-3alkynyl, C.sub.1-2alkoxyC.sub.1-2alkyl, C.sub.1-4alkoxycarbonyl, C.sub.1-4alkylaminocarbonyl, di-C.sub.1-4alkylaminocarbonyl or C.sub.1-4alkylsulfonyl; and R.sup.10 is C.sub.3-6cycloalkyl, benzyl or phenyl; or a salt or an N-oxide thereof, or a composition comprising the compound of formula (I) as an active ingredient, to a plant, parts thereof, or the locus thereof.

15. The method of claim 14, wherein the fungicidally effective amount controls or prevents infestation of phytopathogenic microorganisms on the useful plants.

16. The compound according to claim 1, wherein any of said heterocyclyl or heterobicyclyl moieties of R.sup.8 are linked by a carbon atom.

17. The compound according to claim 1, wherein any of said heteroaryl, heterodiaryl, heterocyclyl or heterobicyclyl moieties of R.sup.8 are linked by a carbon atom.

18. The compound according to claim 17, wherein any of the heterocyclyl moieties of R.sup.7 are linked by a carbon atom.

19. The compound according to claim 1, wherein R.sup.7 is C.sub.1-4alkyl, C.sub.3-4alkenyl, C.sub.3-4alkynyl, C.sub.1-4haloalkyl, cyanoC.sub.1-4alkyl, hydroxyC.sub.1-4alkyl, C.sub.1-2alkoxyC.sub.1-4alkyl, heterocyclyl or heterocyclylC.sub.1-3alkyl, wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic ring which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S.

20. The compound according to claim 1, wherein A.sup.1, A.sup.2, and A.sup.3 are CH; A.sup.4 is CF; n is 0; R.sup.7 is hydrogen, C.sub.1-4alkyl, cyanoC.sub.1-4alkyl, or C.sub.1-2alkoxyC.sub.1-4alkyl; and wherein any of said cycloalkyl, phenyl, carbobicyclyl, heteroaryl, heterodiaryl, heterocyclyl or heterobicyclyl moieties of R.sup.8 are optionally substituted by 1 substituent selected from R.sup.9.

Description

EXAMPLES

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

(2) 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).

(3) Throughout this description, temperatures are given in degrees Celsius ( C.) and m.p. means melting point. LC/MS means Liquid Chromatography Mass Spectrometry and the description of the apparatus and the method (Method B) used for LC/MS analysis is as follows:

(4) The Description of the Apparatus and the Method B is:

(5) SQ Detector 2 from Waters

(6) Ionisation method: Electrospray

(7) Polarity: positive ions

(8) Capillary (kV) 3.5, Cone (V) 30.00, Extractor (V) 3.00, Source Temperature ( C.) 150, Desolvation

(9) Temperature ( C.) 400, Cone Gas Flow (L/Hr) 60, Desolvation Gas Flow (L/Hr) 700

(10) Mass range: 140 to 800 Da

(11) DAD Wavelength range (nm): 210 to 400

(12) Method Waters ACQUITY UPLC with the following HPLC gradient conditions

(13) (Solvent A: Water/Methanol 9:1+0.1% formic acid and Solvent B: Acetonitrile+0.1% formic acid)

(14) TABLE-US-00011 Time (minutes) A (%) B (%) Flow rate (ml/min) 0 100 0 0.75 2.5 0 100 0.75 2.8 0 100 0.75 3.0 100 0 0.75
Type of column: Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60 C.

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

FORMULATION EXAMPLES

(16) TABLE-US-00012 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%

(17) 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.

(18) TABLE-US-00013 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%

(19) 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.

(20) TABLE-US-00014 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%

(21) Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.

(22) TABLE-US-00015 Dusts a) b) c) Active ingredient [compound of Formula (I)] 5% 6% 4% Talcum 95% Kaolin 94% mineral filler 96%

(23) 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.

(24) TABLE-US-00016 Extruder granules Active ingredient [compound of Formula (I)] 15% sodium lignosulfonate 2% Carboxymethylcellulose 1% Kaolin 82%

(25) 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.

(26) TABLE-US-00017 Coated granules Active ingredient [compound of Formula (I)] 8% polyethylene glycol (mol. wt. 200) 3% Kaolin 89%

(27) 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.

(28) TABLE-US-00018 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%

(29) 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.

(30) TABLE-US-00019 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 water) 0.5% monoazo-pigment calcium salt 5% Silicone oil (in the form of a 75% emulsion in water) 0.2% Water 45.3%

(31) 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.

(32) Slow-Release Capsule Suspension

(33) 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.

(34) 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.

(35) The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.

List of Abbreviations

(36) C.=degrees Celsius Bop-Cl=bis(2-oxo-3-oxazolidinyl)phosphinic chloride CDCl.sub.3=chloroform-d DMSO=dimethyl sulfoxide d=doublet EtOAc=ethyl acetate EtOH=ethyl alcohol HCl=hydrochloric acid m=multiplet MHz=mega hertz mp=melting point NaOH=sodium hydroxide ppm=parts per million RT=room temperature s=singlet t=triplet TFAA=trifluoroacetic acid anhydride THF=tetrahydrofuran LC/MS=Liquid Chromatography Mass Spectrometry (description of the apparatus and the methods used for LC/MS analysis are given above)

PREPARATION EXAMPLES

Example 1: This example illustrates the preparation of 3-fluoro-N-(tetrahydrofuran-3-ylmethyl)-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide (Compound 1.14 of Table T1 below)

(37) ##STR00015##

Step 1: Preparation of 3-fluoro-4-(N-hydroxycarbamimidoyl)-benzoic acid

(38) ##STR00016##

(39) A solution of hydroxylamine hydrochloride (0.89 g) in water (8 mL) was added at room temperature to a stirred solution of 4-cyano-3-fluorobenzoic acid (1.0 g, 6.1 mmol) in ethanol (20 mL), followed by dropwise addition of potassium carbonate (1.3 g). Then 8-hydroxyquinoline (0.01 g, 0.08 mmol) was added and the resulting thick suspension was heated to 80 C. for 3 hours to obtain a yellow solution. After removal of ethanol under reduced pressure the residue was acidified with 2N HCl to pH 3. The white precipitate was filtered, washed with water, and dried under reduced pressure at 50 C. to yield 3-fluoro-4-(N-hydroxycarbamimidoyl)-benzoic acid as a light green solid that was used without further purification.

Step 2: Preparation of 3-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid

(40) ##STR00017##

(41) Trifluoroacetic anhydride (13.8 mL) was added dropwise at 10 C. to 15 C. to a stirred suspension of 3-fluoro-4-(N-hydroxycarbamimidoyl)-benzoic acid (13.1 g, 66.1 mmol) in THF (264 mL). The beige suspension was warmed to room temperature and stirred overnight. Additional trifluoroacetic anhydride (7 mL) was introduced and the reaction went to full conversion during additional 24 hours of stirring. A solid when then filtered off and volatiles were removed under reduced pressure, the crude product was stirred with heptane/ethyl acetate (95:5), filtered and dried under reduced pressure at 50 C. to yield 3-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid as a yellow solid.

(42) .sup.1H NMR (400 MHz, DMSO-d.sub.6) ppm: 8.24 (t, 1H), 8.03 (d, 1H), 7.94 (d, 1H).

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

(43) ##STR00018##

(44) A solution of tetrahydrofuran-3-ylmethyl amine (0.038 mmol) in dimethylacetamide (375 L) was transferred to a 96 slot deep well plate (DWP) containing the 3-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid (0.03 mmol) and DIPEA (0.09 mmol) in dimethylacetamide (250 L), followed by the addition of BOP-Cl (0.06 mmol) dissolved in dimethylacetamide (250 L). The DWP was sealed and stirred at 50 C. for 18 hours. The solvent was removed under a stream of nitrogen. The resultant crude residues were solubilized in a mixture of MeOH (250 l) and DMA (500 L) and directly submitted for preparative LC/MS purification which provided the 3 mg of 3-fluoro-N-(tetrahydrofuran-3-ylmethyl)-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide. LC/MS retention time=0.73 minutes, 360 (M+H).

(45) TABLE-US-00020 TABLE T1 Melting point (mp) data and/or retention times for the compounds of Formula (I): RT [M + H] MP Entry Compound name Structure (mins) (measured) Method ( C.) 1.1 3-fluoro-N-(4- phenylbutyl)-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 1.04 408.01 B 1.2 tert-butyl 3-[[3- fluoro-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzoyl]-methyl- amino]pyrrolidine- 1-carboxylate 0 0.95 458.98 B 1.3 N-[(2,5-dimethyl- phenyl)methyl]- 3-fluoro-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 1.01 393.99 B 1.4 3-fluoro-N-[2-(5- methoxy-1H-indol- 3-yl)ethyl]-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.88 448.94 B 1.5 3-fluoro-N-methyl- N-(2-pyridyl)-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.8 366.99 B 1.6 3-fluoro-N-(3- methylsulfanyl- propyl)-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.85 363.99 B 1.7 3-fluoro-N- tetrahydro- thiopyran-4- yl-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.87 376.01 B 1.8 N-(1- ethynylcyclohexyl)- 3-fluoro-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.99 382 B 1.9 3-fluoro-N- ([1,2,4]triazolo[1,5- a]pyrimidin-7-yl)-4- [5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.75 393.99 B 1.10 N-[2-[(6-chloro-3- pyridyl)methyl- sulfanyl]ethyl]- 3-fluoro-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.92 461.06 B 1.11 3-fluoro-N-(7- methyl-7- azaspiro[3.5]nonan- 2-yl)-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.44 413.4 B 1.12 N-(1,4-dioxan-2- ylmethyl)-3-fluoro- 4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0 0.7 376.06 B 1.13 methyl 4-[[3-fluoro- 4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzoyl]amino]- 1-methoxy- piperidine-4- carboxylate 0.81 447.24 B 1.14 3-fluoro-N- (tetrahydrofuran-3- ylmethyl)-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.73 360.04 B 1.15 3-fluoro-N-indan-1- yl-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.99 392 B 1.16 N-benzyl-3-fluoro- N-(2- methoxyethyl)-4- [5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.98 424 B 1.17 N-[(3,4- diethoxyphenyl) methyl]-3-fluoro- N-isopropyl-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 1.08 496.04 B 1.18 N-(1,3- benzodioxol-5- ylmethyl)-N-(1,3- dioxolan-2- ylmethyl)-3-fluoro- 4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.95 496.04 B 1.19 N-[(3,4- diethoxyphenyl) methyl]-N-(1,3- dioxolan-2- ylmethyl)-3-fluoro- 4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 1.02 540.06 B 1.20 N-(cyclo- propylmethyl)- 3-fluoro-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.85 329.91 B 1.21 N-[2-(2,6-dimethyl- 1-piperidyl)ethyl]- 3-fluoro-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.5 415.31 B 1.22 N-(1,1-dimethyl-2- methylsulfonyl- ethyl)-3-fluoro-4- [5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0 0.75 409.99 B 1.23 3-fluoro-N- [(2,2,3,3-tetrafluoro- cyclobutyl)methyl]- 4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.92 415.88 B 1.24 N-[1-cyano-1-[(4- cyanophenoxy) methyl]propyl]-3- fluoro-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.94 473.9 B 1.25 N-(1- cyclopropylethyl)- 3-fluoro-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.9 343.96 B 1.26 ethyl 4,4,4- trifluoro-2-[[3- fluoro-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzoyl]amino] butanoate 0.94 443.9 B 1.27 N-(1-cyclopropyl- cyclopropyl)- 3-fluoro-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.9 355.99 B 1.28 3-fluoro-N-[(5- methyl-2- furyl)methyl]-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.9 369.92 B 1.29 N,N-bis(2- cyanoethyl)-3- fluoro-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.7 381.95 B 1.30 N-(1-cyano-1,2- dimethyl-propyl)-3- fluoro-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.89 370.95 B 1.31 3-fluoro-N-(2- furylmethyl)-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.84 355.92 B 1.32 3-fluoro-N-(3- imidazol-1- ylpropyl)-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0 0.38 383.99 B 1.33 3-fluoro-N-phenyl- 4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.94 351.9 B 1.34 3-fluoro-N-(2- phenylcyclopropyl)- 4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.98 392.01 B 1.35 3-fluoro-N-[2-(2- thienyl)ethyl]-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0.92 385.99 B 1.36 N-(2,2- dimethoxyethyl)-3- fluoro-N-methyl-4- [5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 1.37 3-fluoro-N-(1,1,3,3- tetramethylbutyl)- 4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 1.38 N-(1,3- dimethylbutyl)-3- fluoro-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 1.39 N-cyclobutyl-3- fluoro-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 1.40 N-[1-(ethoxy- methyl)cyclopropyl]- 3-fluoro-4- [5-(trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 1.41 N-(cyclopropyl- methyl)-3- fluoro-N-propyl- 4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 1.42 3-fluoro-N-(1,2,4- triazin-3-yl)-4-[5- (trifluoromethyl)- 1,2,4-oxadiazol-3- yl]benzamide 0

BIOLOGICAL EXAMPLES

(46) General Examples of Leaf Disk Tests in Well Plates:

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

(48) General Examples of Liquid Culture Tests in Well Plates:

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

Example 1: Fungicidal Activity Against Puccinia recondita f. Sp. Tritici/Wheat/Leaf Disc Preventative (Brown Rust)

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

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

(52) Compounds (from Table T1) 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.8, 1.9, 1.10, 1.12, 1.13, 1.14, 1.15, 1.16, 1.17, 1.18, 1.20, 1.22, 1.23, 1.24, 1.25, 1.26, 1.27, 1.28, 1.30, 1.31, 1.35, 1.36, 1.38, 1.39, 1.40, and 1.42.

Example 2: Fungicidal Activity Against Puccinia recondita f. Sp. Tritici/Wheat/Leaf Disc Curative (Brown Rust)

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

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

(55) Compounds (from Table T1) 1.2, 1.5, 1.6, 1.12, 1.13, 1.14, 1.16, 1.20, 1.22, 1.25, 1.27, 1.28, 1.31, 1.35, 1.36, 1.39, 1.40, 1.41, and 1.42.

Example 3: Fungicidal Activity Against Phakopsora pachyrhizi/Soybean/Leaf Disc Preventative (Asian Soybean Rust)

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

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

(58) Compounds (from Table T1) 1.3, 1.4, 1.8, 1.10, 1.11, 1.12, 1.14, 1.15, 1.16, 1.20, 1.23, 1.25, 1.27, 1.28, 1.31, 1.35, 1.36, 1.38, 1.39, 1.40, and 1.41.

Example 4: Fungicidal Activity Against Glomerella lagenarium (Colletotrichum lagenarium) Liquid Culture/Cucumber/Preventative (Anthracnose)

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

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

(61) Compounds (from Table T1) 1.1, 1.2, 1.4, 1.5, 1.8, 1.9, 1.10, 1.12, 1.14, 1.16, 1.17, 1.18, 1.19, 1.20, 1.23, 1.25, 1.27, 1.28, 1.30, 1.31, 1.35, 1.36, 1.37, 1.38, 1.39, 1.40, 1.41, and 1.42.

Example 5: Fungicidal Activity Against Uromyces viciae-fabael Field Bean/Leaf Disc Preventative (Faba-Bean Rust)

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

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

(64) Compounds (from Table T1) 1.1, 1.2, 1.3, 1.4, 1.6, 1.7, 1.8, 1.9, 1.10, 1.11, 1.12, 1.13, 1.14, 1.15, 1.16, 1.17, 1.18, 1.19, 1.21, 1.22, 1.23, 1.25, 1.26, 1.27, 1.28, 1.29, 1.31, 1.32, 1.33, 1.34, 1.35, 1.36, 1.37, 1.38, 1.39, 1.40, and 1.41.