USE OF STROBILURIN TYPE COMPOUNDS FOR COMBATING PHYTOPATHOGENIC FUNGI CONTAINING AN AMINO ACID SUBSTITUTION F129L IN THE MITOCHONDRIAL CYTOCHROME B PROTEIN CONFERRING RESISTANCE TO QO INHIBITORS VI

Abstract

The present invention relates to the use of strobilurin type compounds of formula (I) and the N-oxides and the salts thereof for combating phytopathogenic fungi containing an amino acid substitution F129L in the mitochondrial cytochrome b protein (also referred to as F129L mutation in the mitochondrial cytochrome b gene) conferring resistance to Qo inhibitors, and to methods for combating such fungi. The invention also relates to novel compounds, processes for preparing these compounds, to compositions comprising at least one such compound, and to seeds coated with at least one such compound.

Claims

1. A compound of formula I ##STR00157## wherein R.sup.1 is selected from 0 and NH; R.sup.2 is selected from CH and N; R.sup.3 is selected from halogen, CN, C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.1-C.sub.4-haloalkyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.2-C.sub.4-haloalkynyl, C.sub.3-C.sub.6-cycloalkyl, —O—C.sub.1-C.sub.4-alkyl, —O—C.sub.1-C.sub.4-haloalkyl, —O—C.sub.3-C.sub.6-cycloalkyl, —C.sub.1-C.sub.2-alkyl-C.sub.3-C.sub.6-cycloalkyl, phenyl, 3- to 6-membered heterocycloalkyl and 5- or 6-membered heteroaryl, wherein said heterocycloalkyl and heteroaryl besides carbon atoms contain 1, 2 or 3 heteroatoms selected from N, O and S provided that such heterocycloalkyl and heteroaryl cannot contain 2 contiguous atoms selected from O and S, wherein said phenyl, heterocycloalkyl and heteroaryl are bound directly or via an oxygen atom or via a C.sub.1-C.sub.2-alkylene linker, and wherein said phenyl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 identical or different substituents selected from halogen, CN, NH.sub.2, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, —O—C.sub.1-C.sub.4-alkyl and —O—C.sub.1-C.sub.4-haloalkyl; R.sup.4 and R.sup.5, together with the three interjacent carbon atoms, form a partially unsaturated 5- to 6-membered carbo- or heterocycle, wherein the heterocycle includes beside carbon atoms 1, 2 or 3 heteroatoms independently selected from N, O and S as ring member atoms provided that such heterocycle cannot contain 2 contiguous atoms selected from O and S; and wherein the carbo- or heterocycle is unsubstituted or carries 1, 2 or up to the maximum possible number of identical or different groups R.sup.45; wherein R.sup.45 is selected from halogen, CN, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, phenyl, C.sub.3-C.sub.6-cycloalkyl and —C.sub.1-C.sub.2-alkyl-C.sub.3-C.sub.6-cycloalkyl; wherein it is possible that two R.sup.45 substituents which are bound to the same carbon atom or to two adjacent carbon atoms form a saturated 3- to 5-membered carbocycle; and wherein the cyclic moieties of R.sup.45 are unsubstituted or carry 1, 2 or 3 identical or different groups R.sup.45b: R.sup.45b is selected from halogen, CN, NH.sub.2, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, —O—C.sub.1-C.sub.4-alkyl and —O—C.sub.1-C.sub.4-haloalkyl; R.sup.a is selected from halogen, CN, —NR.sup.5R.sup.6, C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, —O—C.sub.1-C.sub.4-alkyl, —C(═N—O—C.sub.1-C.sub.4-alkyl)-C.sub.1-C.sub.4-alkyl, —C(═O)—C.sub.1-C.sub.4-alkyl, —O—CH.sub.2—C(═N—O—C.sub.1-C.sub.4-alkyl)-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkenyl, —C.sub.1-C.sub.2-alkyl-C.sub.3-C.sub.6-cycloalkyl, —O—C.sub.3-C.sub.6-cycloalkyl, phenyl, 3- to 6-membered heterocycloalkyl, 3- to 6-membered heterocycloalkenyl and 5- or 6-membered heteroaryl, wherein said heterocycloalkyl, heterocycloalkenyl and heteroaryl besides carbon atoms contain 1, 2 or 3 heteroatoms selected from N, O and S provided that such heterocycloalkyl, heterocycloalkenyl and heteroaryl cannot contain 2 contiguous atoms selected from O and S, wherein said phenyl, heterocycloalkyl, heterocycloalkenyl and heteroaryl are bound directly or via an oxygen atom or via a C.sub.1-C.sub.2-alkylene linker, and wherein the aliphatic and cyclic moieties of R.sup.a are unsubstituted or carry 1, 2, 3, 4 or up to the maximum number of identical or different groups R.sup.b: R.sup.b is selected from halogen, CN, NH.sub.2, NO.sub.2, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, —O—C.sub.1-C.sub.4-alkyl and —O—C.sub.1-C.sub.4-haloalkyl; R.sup.5, R.sup.6 are independently of each other selected from the group consisting of H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl and C.sub.2-C.sub.4-alkynyl; n is an integer selected from 0, 1, 2, 3 and 4; and in form of stereoisomers and tautomers thereof, and the N-oxides and the agriculturally acceptable salts thereof.

2. The compound according to claim 1, wherein R.sup.1 is selected from 0 and NH; and R.sup.2 is selected from CH and N, provided that R.sup.2 is N in case R.sup.1 is NH.

3. The compound according to claim 1, wherein R.sup.3 is selected from halogen, C.sub.1-C.sub.2-alkyl, C.sub.1-C.sub.2-haloalkyl, C.sub.3-C.sub.4-cycloalkyl, —O—C.sub.1-C.sub.2-alkyl and —O—C.sub.1-C.sub.2-haloalkyl.

4. The compound according to claim 3, wherein R.sup.3 is selected from halogen, C.sub.1-C.sub.2-alkyl and C.sub.1-C.sub.2-haloalkyl.

5. The compound according to claim 1, wherein R.sup.a is selected from halogen, C.sub.1-C.sub.3-alkyl, C.sub.2-C.sub.3-alkenyl, C.sub.2-C.sub.3-alkynyl, —O—C.sub.1-C.sub.3-alkyl, —C(═N—O—C.sub.1-C.sub.2-alkyl)-C.sub.1-C.sub.2-alkyl, —O—CH.sub.2—C(═N—O—C.sub.1-C.sub.2-alkyl)-C.sub.1-C.sub.2-alkyl, C.sub.3-C.sub.4-cycloalkyl, —C.sub.1-C.sub.2-alkyl-C.sub.3-C.sub.4-cycloalkyl, —O—C.sub.3-C.sub.4-cycloalkyl, phenyl, 3- to 5-membered heterocycloalkyl and 5- or 6-membered heteroaryl, wherein said heterocycloalkyl and heteroaryl besides carbon atoms contain 1 or 2 heteroatoms selected from N, O and S provided that such heterocycloalkyl and heteroaryl cannot contain 2 contiguous atoms selected from O and S, wherein said phenyl, heterocycloalkyl and heteroaryl are bound directly or via an oxygen atom or via a methylene linker, and wherein the aliphatic and cyclic moieties of R.sup.a are unsubstituted or carry 1, 2 or 3 of identical or different groups R.sup.b which independently of one another are selected from halogen, CN, methyl and C.sub.1-haloalkyl.

6. The compound according to claim 5, wherein R.sup.a is selected from halogen, C.sub.1-C.sub.3-alkyl, —O—C.sub.1-C.sub.3-alkyl, C.sub.3-C.sub.4-cycloalkyl and phenyl, and wherein the aliphatic and cyclic moieties of R.sup.a are unsubstituted or carry 1, 2 or 3 of identical or different groups R.sup.b which independently of one another are selected from halogen, methyl and C.sub.1-haloalkyl.

7. The compound according to claim 1, wherein n is 0, 1 or 2.

8. The compound according to claim 1, wherein R.sup.4 and R.sup.5, together with the three interjacent carbon atoms, form a partially unsaturated 5- to 6-membered carbocycle, wherein said carbocycle is unsubstituted or carries 1 or 2 identical or different groups R.sup.45, wherein R.sup.45 is selected from halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, phenyl and C.sub.3-C.sub.6-cycloalkyl, wherein it is possible that two R.sup.45 substituents which are bound to the same carbon atom form a cyclopropyl ring.

9. The compound according to claim 8, wherein R.sup.4 and R.sup.5, together with the three interjacent carbon atoms, form a cyclopentene ring, wherein said cyclopentene ring is unsubstituted or carries 1 or 2 identical or different groups R.sup.45, wherein R.sup.45 is selected from halogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, phenyl and C.sub.3-C.sub.6-cycloalkyl, wherein it is possible that two R.sup.45 substituents which are bound to the same carbon atom form a cyclopropyl ring.

10. An agrochemical composition comprising an auxiliary and at least one compound of formula I, as defined in claim 1 or in the form of a stereoisomer or an agriculturally acceptable salt or a tautomer or N-oxide thereof.

11. (canceled)

12. (canceled)

13. A method for combating phytopathogenic fungi comprising: treating curatively and/or preventively a plant or plant propagation material of said plant that is at risk of being diseased from the said phytopathogenic fungi, and/or applying to the said phytopathogenic fungi, at least one compound of formula I as defined in claim 1.

14. The method for combating phytopathogenic fungi according to claim 13 wherein said phytopathogenic fungi contain an amino acid substitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors.

15. The method according to claim 13, wherein the phytopathogenic fungi are soybean rust (Phakopsora pachyrhizi and/or P. meibomiae).

Description

EXAMPLES

Synthetic Process

Example 1: Methyl (2E)-2-[2-[[(E)-indan-1-ylideneamino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-acetate

[0195] ##STR00021##

[0196] Step 1: To a solution of indan-1-one (7 g, 1 eq.) in 70 mL methanol under nitrogen at about 25° C., pyridine (8.37 g, 2 eq.) and hydroxylamine hydrochloride (7.30 g, 2 eq.) were added and the reaction mixture was heated at 65° C. for 2 h. After TLC indicated completion of the reaction, the reaction mixture was cooled to about 25° C. and concentrated. To the residue 50 mL water was added and extracted with ethyl acetate (2×25 mL). The combined organic phase was dried with sodium sulfate and concentrated to obtain crude product which was purified by flash column chromatography using 10-15% ethyl acetate in heptane as eluent to afford the pure indan-1-one oxime (6 g, 77% yield) as white solid.

[0197] .sup.1H NMR (500 MHz, DMSO-d6) δ 10.84 (s, 1H), 7.56 (d, J=7.6 Hz, 1H), 7.39-7.30 (m, 2H), 7.29-7.22 (m, 1H), 3.02-2.96 (m, 2H), 2.82-2.75 (m, 2H).

[0198] Step 2: To a stirred solution of indan-1-one oxime (300 mg, 1 eq) in DMF (7 mL), cesium carbonate (1.32 g, 2 eq) and methyl (2E)-2-[2-(bromomethyl)-3-methyl-phenyl]-2-methoxyiminoacetate (670 mg, 1.1 eq) were added at 25° C. The reaction mixture was stirred for 3 h. After TLC showed completion of the reaction, the reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (2×15 mL). The combined organic phase was washed using brine and dried over sodium sulfate. The solvent was removed to obtain crude product, which was purified by flash column chromatography using 7-9% ethyl acetate in heptane as mobile phase to obtain the title compound (485 mg).

[0199] .sup.1H NMR (500 MHz, DMSO-d6) δ 7.49 (d, J=7.7 Hz, 1H), 7.40-7.33 (m, 2H), 7.28 (td, J=7.9, 7.2, 4.4 Hz, 3H), 7.02 (dd, J=6.6, 2.5 Hz, 1H), 4.97 (s, 2H), 3.91 (s, 3H), 3.72 (s, 3H), 3.01-2.95 (m, 2H), 2.74-2.68 (m, 2H), 2.44 (s, 3H).

Example 2: (2E)-2-[2-[[(E)-indan-1-ylideneamino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-N-methyl-acetamide

[0200] ##STR00022##

[0201] To a stirred solution of methyl (2E)-2-[2-[[(E)-indan-1-ylideneamino]oxymethyl]-3-methylphenyl]-2-methoxyimino-acetate (350 mg, 1 eq) in THF (5 mL), methyl amine (3 mL, 40% in MeOH) was added at 25° C. and the reaction mixture was stirred for 12 h. After TLC showed completion of the reaction, solvents were evaporated. The residue was triturated in n-pentane to provide the title compound as a white solid (290 mg, 83% yield).

[0202] .sup.1H NMR (500 MHz, DMSO-d6) δ 8.21 (q, J=4.6 Hz, 1H), 7.53 (d, J=7.7 Hz, 1H), 7.37 (d, J=4.2 Hz, 2H), 7.31-7.23 (m, 3H), 6.95 (dd, J=7.0, 2.1 Hz, 1H), 4.97 (s, 2H), 3.87 (s, 3H), 3.04-2.89 (m, 2H), 2.71 (dd, J=10.8, 5.6 Hz, 5H), 2.44 (s, 3H).

Example 3: Methyl (2E)-2-methoxyimino-2-[3-methyl-2-[[(E)-tetralin-1-ylideneamino]oxymethyl]-phenyl]acetate

[0203] ##STR00023##

[0204] To a stirred solution of tetralin-1-one oxime (350 mg, 1 eq) in DMF (7 mL), cesium carbonate (1.41 g, 2 eq) and methyl (2E)-2-[2-(bromomethyl)-3-methyl-phenyl]-2-methoxyimino-acetate (717 mg, 1.1 eq) were added at 25° C. The reaction mixture was stirred for 3 h. After TLC showed completion of the reaction, the reaction mixture was quenched with water (10 mL) and the resulting mixture extracted with ethyl acetate (2×15 mL). The combined organic phase was washed using brine and dried over sodium sulfate. The solvent was removed to obtain crude product, which was purified by combi flash column chromatography using 7-9% ethyl acetate in heptane as mobile phase to obtain the title compound (545 mg, 66% yield).

[0205] .sup.1H NMR (500 MHz, DMSO-d6) δ 7.50 (d, J=7.7 Hz, 1H), 7.37 (d, J=4.1 Hz, 2H), 7.28 (td, J=7.8, 7.3, 4.5 Hz, 3H), 7.02 (dd, J=6.4, 2.5 Hz, 1H), 4.98 (s, 2H), 3.91 (s, 3H), 3.72 (s, 3H), 3.33 (s, 2H), 3.01-2.95 (m, 2H), 2.74-2.68 (m, 2H), 2.44 (s, 3H).

Example 4: (2E)-2-methoxyimino-N-methyl-2-[3-methyl-2-[[(E)-tetralin-1-ylideneamino]oxymethyl]phenyl]acetamide

[0206] ##STR00024##

[0207] To a stirred solution of methyl (2E)-2-[2-[[(E)-indan-1-ylideneamino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-acetate (300 mg, 1 eq) in THF (5 mL), methyl amine (3 mL, 40% in MeOH) was added at 25° C. and the reaction mixture was stirred for 12 h. After TLC showed completion of the reaction, solvents were evaporated. The residue was triturated in n-pentane to provide the title compound as a white solid (240 mg, 80% yield).

[0208] .sup.1H NMR (500 MHz, DMSO-d6) δ 8.22 (q, J=4.7 Hz, 1H), 7.78 (d, J=7.8 Hz, 1H), 7.27 (d, J=7.7 Hz, 3H), 7.18 (t, J=7.1 Hz, 2H), 6.98-6.93 (m, 1H), 4.99 (s, 2H), 3.87 (s, 3H), 2.69 (dd, J=13.8, 5.5 Hz, 5H), 2.57 (t, J=6.6 Hz, 2H), 2.44 (s, 3H), 1.71 (p, J=6.2 Hz, 2H).

Example 15: Methyl (2E)-2-[2-[[(E)-(7-fluorochroman-4-ylidene)amino]oxymethyl]-3-methylphenyl]-2-methoxyimino-acetate

[0209] ##STR00025##

[0210] Step 1: To a solution of 7-fluorochroman-4-one (410 mg, 1 eq.) in 10 mL methanol under nitrogen, pyridine (0.39 mL, 2 eq.) and hydroxylamine hydrochloride (343 mg, 2 eq.) were added at about 25° C. and the reaction mixture was heated at 70° C. for 2 hours. After TLC indicated completion of the reaction, the reaction mixture was cooled to about 25° C. and concentrated. To the residue, 30 mL ethyl acetate was added. The organic phase was washed with water (3×20 mL) and with brine (1×20 mL) and then dried with sodium sulfate and concentrated to obtain crude 7-fluorochroman-4-one oxime (400 mg, 89.5% yield).

[0211] .sup.1H NMR (500 MHz, DMSO-d6) δ 11.24 (s, 1H), 7.81 (dd, J=8.8, 6.8 Hz, 1H), 6.85-6.75 (m, 2H), 4.22 (t, J=6.2 Hz, 2H), 2.83 (t, J=6.2 Hz, 2H).

[0212] Step 2: To a suspension of cesium carbonate (1.58 g, 2 eq) in DMF (15 mL), a solution of 7-fluorochroman-4-one oxime (440 mg, 1 eq) in DMF (5 mL) was added. To the resulting mixture, a solution of methyl (2E)-2-[2-(bromomethyl)-3-methyl-phenyl]-2-methoxyimino-acetate (765 mg, 1.05 eq) in DMF (5 mL) was added at about 25° C. and the reaction mixture was stirred for 6 h at about 25° C. After TLC showed completion of the reaction, the reaction mixture was diluted with ethyl acetate (50 mL) and washed with cold water (5×20 mL). The organic phase was dried over sodium sulfate. The solvent was removed to obtain crude product, which was purified by flash column chromatography using 0-30% ethyl acetate in heptane as mobile phase to obtain the title compound (350 mg, 35% yield).

[0213] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.81 (dd, J=8.8, 6.7 Hz, 1H), 7.34-7.27 (m, 2H), 7.01 (dd, J=7.3, 1.7 Hz, 1H), 6.64 (td, J=8.5, 2.6 Hz, 1H), 6.56 (dd, J=9.9, 2.6 Hz, 1H), 5.30 (s, OH), 5.09 (s, 2H), 4.17 (t, J=6.2 Hz, 2H), 4.01 (s, 3H), 3.81 (s, 3H), 2.82 (t, J=6.2 Hz, 2H), 2.47 (s, 3H).

Example 16: (2E)-2-[2-[[(E)-(7-fluorochroman-4-ylidene)amino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-N-methyl-acetamide

[0214] ##STR00026##

[0215] To a stirred solution of methyl (2E)-2-[2-[[(E)-(7-fluorochroman-4-ylidene)amino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-acetate (400 mg, 1 eq) in THF (10 mL), methyl amine (3 mL, 40% in H.sub.2O) was added at 25° C. and the reaction mixture was stirred for 1 h. After TLC showed completion of the reaction, solvents were evaporated, and the residue was diluted with ethyl acetate (25 mL) and washed with water (3×20 mL). The combined organic phase was washed with brine and dried over sodium sulfate. Solvent was removed and the residue was triturated in n-pentane to provide the title compound as a white solid (350 mg, 87% yield).

[0216] .sup.1H NMR (500 MHz, Chloroform-d) δ 7.81 (dd, J=8.9, 6.6 Hz, 1H), 7.33-7.22 (m, 3H), 7.01 (dd, J=7.5, 1.4 Hz, 1H), 6.74 (d, J=5.7 Hz, 1H), 6.63 (td, J=8.5, 2.6 Hz, 1H), 6.56 (dd, J=9.9, 2.6 Hz, 1H), 5.07 (d, J=51.3 Hz, 2H), 4.15 (t, J=6.2 Hz, 2H), 3.94 (s, 3H), 2.88 (d, J=5.0 Hz, 3H), 2.81 (t, J=6.2 Hz, 2H), 2.47 (s, 3H).

Example 25: Methyl (2E)-2-[2-[[(E)-(4-bromoindan-1-ylidene)amino]oxymethyl]-3-methylphenyl]-2-methoxyimino-acetate

[0217] ##STR00027##

[0218] Step 1: To a solution of 6-bromoindan-1-one (2.5 g, 1 eq.) in 25 mL methanol, under argon at about 25° C. pyridine (1.87 mL, 2 eq.) was added in one portion. Hydroxylamine hydrochloride (1.64 g, 2 eq.) was added and the reaction mixture was heated at 70° C. for 2 h. The reaction mixture was then cooled to about 25° C. and then concentrated by removing solvent. Then 100 mL ethyl acetate was added. The organic phase was washed with water (3×50 mL) and with brine (1×20 mL) and then dried with sodium sulfate and concentrated to obtain crude 4-bromoindan-1-one oxime as pale yellow solid (2.63 g, 98% yield).

[0219] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.07 (s, 1H), 7.56 (ddd, J=7.7, 4.2, 0.9 Hz, 2H), 7.23 (t, J=7.7 Hz, 1H), 3.03-2.87 (m, 2H), 2.87-2.73 (m, 2H).

[0220] Step 2: To a stirred solution of 4-bromoindan-1-one oxime (2.63 g, 1 eq) in acetonitrile (10 ml), cesium carbonate (7.58 g, 2 eq) was added followed by a solution of (2E)-2-[2-(bromomethyl)-3-methyl-phenyl]-2-methoxyimino-acetate (3.14 g, 0.9 eq) in acetonitrile (15 mL) at about 25° C. The reaction mixture was stirred for 12 h. The reaction mixture was filtered and the filtrate was evaporated. The resulting residue was purified by flash column chromatography to give the title compound (4.37 g, 93% yield).

[0221] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.60 (dd, J=7.8, 0.9 Hz, 1H), 7.49 (dd, J=7.7, 0.9 Hz, 1H), 7.34-7.18 (m, 3H), 7.07-6.96 (m, 1H), 4.96 (s, 2H), 3.91 (s, 3H), 3.72 (s, 3H), 2.97-2.84 (m, 2H), 2.84-2.68 (m, 2H), 2.43 (s, 3H).

Example 25: Methyl (2E)-2-[2-[[(E)-(5-bromoindan-1-ylidene)amino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-acetate

[0222] ##STR00028##

[0223] Step 1: To a solution of 5-bromoindan-1-one (2.5 g, 1 eq.) in 25 mL methanol, under argon at about 25° C. pyridine (1.90 mL, 2 eq.) was added in one portion. Hydroxylamine hydrochloride (1.64 g, 2 eq.) was added in two portions and heated the reaction mixture at 70° C. for 2 hours. A yellowish-brown reaction mixture was formed. The reaction mixture was then cooled to about 25° C. which resulted in precipitation of a pale yellow solid. The precipitate was filtered and washed with 20 mL pentane and the resulting reddish-brown solution was concentrated. After addition of 70 mL ethyl acetate the organic phase was washed with water (3×20 mL) and with brine (1×20 mL). Then it was dried with sodium sulfate and concentrated to obtain crude 5-bromoindan-1-one oxime (brown solid) as an isomeric mixture (2.58 g, 96% yield).

[0224] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.98 (s, 1H), 7.59 (d, J=1.8 Hz, 1H), 7.49-7.41 (m, 2H), 3.03-2.97 (m, 2H), 2.81-2.75 (m, 2H).

[0225] Step 2: To a stirred suspension of 5-bromoindan-1-one oxime (1.09 g, 1 eq) in acetonitrile (10 ml), cesium carbonate (3.16 g, 2 eq) was added. Then (2E)-2-[2-(bromomethyl)-3-methylphenyl]-2-methoxyimino-acetate (1.31 g, 0.9 eq) in acetonitrile (5 mL) was added dropwise at about 25° C. The reaction mixture was stirred for 12 h. Then, the reaction mixture was filtered and the filtrate was evaporated. The resulting residue was purified by flash column chromatography to give the title compound (1.29 g, 66% yield).

[0226] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.61-7.60 (m, 1H), 7.46 (dd, J=8.3, 1.8 Hz, 1H), 7.40 (d, J=8.3 Hz, 1H), 7.32-7.26 (m, 2H), 7.01 (dd, J=6.5, 2.5 Hz, 1H), 4.97 (s, 2H), 3.90 (s, 3H), 3.71 (s, 3H), 3.00-2.96 (m, 2H), 2.73-2.69 (m, 2H), 2.42 (s, 3H).

Example 11: Methyl (2E)-2-[2-[[(E)-(6-bromoindan-1-ylidene)amino]oxymethyl]-3-methylphenyl]-2-methoxyimino-acetate

[0227] ##STR00029##

[0228] Step 1: To a solution of 6-bromoindan-1-one (2.5 g, 1 eq.) in 25 mL methanol, under argon at at about 25° C. pyridine (1.87 mL, 2 eq.) was added in one portion. Hydroxylamine hydrochloride (1.64 g, 2 eq.) was and the reaction mixture was heated at 70° C. for 2 hours. After cooling to about 25° C., the reaction mixture was concentrated by removing solvent. Then 100 mL ethyl acetate was added. The organic phase was washed with water (3×50 mL) and with brine (1×20 mL), dried with sodium sulfate and concentrated to obtain crude 6-bromoindan-1-one oxime as white solid (2.47 g, 92% yield).

[0229] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.08 (s, 1H), 7.64 (d, J=1.9 Hz, 1H), 7.50 (dd, J=8.1, 2.0 Hz, 1H), 7.44-7.25 (m, 1H), 3.04-2.87 (m, 2H), 2.88-2.72 (m, 2H).

[0230] Step 2: To a stirred suspension of 6-bromoindan-1-one oxime (2.47 g, 1 eq) in acetonitrile (10 ml), cesium carbonate (7.12 g, 2 eq) was added. (2E)-2-[2-(bromomethyl)-3-methyl-phenyl]-2-methoxyimino-acetate (2.95 g, 0.9 eq) in acetonitrile (15 mL) was added dropwise at 25° C. The reaction mixture was stirred for 12 h. The reaction mixture was filtered and the filtrate was evaporated. The resulting residue was purified by flash column chromatography to give methyl the title compound (550 mg, 13% yield).

[0231] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.59-7.49 (m, 2H), 7.37-7.23 (m, 3H), 7.06-6.98 (m, 1H), 4.97 (s, 2H), 3.91 (s, 3H), 3.75 (s, 3H), 2.97-2.89 (m, 2H), 2.77-2.68 (m, 2H), 2.43 (s, 3H).

Example 22: (2E)-2-[2-[[(E)-(6-bromoindan-1-ylidene)amino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-N-methyl-acetamide

[0232] ##STR00030##

[0233] To a stirred solution of methyl (2E)-2-[2-[[(E)-(6-bromoindan-1-ylidene)amino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-acetate (300 mg, 1 eq) in THF (10 mL), methyl amine (0.6 mL, 40% solution in H.sub.2O, 10 eq) was added. Solvents were evaporated under reduced pressure and the residue purified by reverse phase chromatography using acetonitrile and water mixture as a mobile phase to give the title compound (297 mg, 99% yield).

[0234] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.21 (d, J=4.9 Hz, 1H), 7.61 (d, J=1.9 Hz, 1H), 7.51 (dd, J=8.1, 2.0 Hz, 1H), 7.35-7.20 (m, 3H), 6.99-6.91 (m, 1H), 4.96 (s, 2H), 3.87 (s, 3H), 2.95-2.87 (m, 2H), 2.73 (t, J=5.1 Hz, 4H), 2.42 (s, 3H).

Example 36: Methyl (2E)-2-[2-[[(E)-(7-bromoindan-1-ylidene)amino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-acetate

[0235] ##STR00031##

[0236] Step 1: To a solution of 7-bromoindan-1-one (3 g, 1 eq.) in 30 mL methanol, under argon at about 25° C. pyridine (2.29 mL, 2 eq.) was added in one portion. Hydroxylamine hydrochloride (1.98 g, 2 eq.) was added in two portions and the reaction mixture was heated at 70° C. for 3 h.

[0237] A yellowish suspension was formed. The reaction mixture was then cooled to about 25° C. and stirred for 48 h. Then, the reaction mixture was concentrated and 70 mL ethyl acetate was added. The organic phase was washed with water (3×20 mL) and with brine (1×20 mL), dried with sodium sulfate and concentrated to obtain crude 7-bromoindan-1-one oxime as pale yellow solid (3.6 g, 89.6% yield).

[0238] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.27 (s, 1H), 7.49 (dd, J=7.8, 1.0 Hz, 1H), 7.38 (dq, J=7.5, 1.1 Hz, 1H), 7.23 (t, J=7.7 Hz, 1H), 3.00 (dd, J=8.7, 5.0 Hz, 2H), 2.87-2.82 (m, 2H).

[0239] Step 2: To a stirred solution of 7-bromoindan-1-one oxime (1.39 g, 1 eq) in acetonitrile (10 ml), cesium carbonate (4.00 g, 2 eq) was added. (2E)-2-[2-(bromomethyl)-3-methyl-phenyl]-2-methoxyimino-acetate (1.66 g, 0.9 eq) in acetonitrile (10 mL) was added dropwise at 25° C. The reaction mixture was stirred for 12 h. The reaction mixture was filtered and the filtrate was evaporated. The resulting residue was purified by flash column chromatography to give the title compound (385 mg, 16% yield).

[0240] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.51-7.48 (m, 1H), 7.38 (d, J=7.6 Hz, 1H), 7.30-7.24 (m, 4H), 7.01 (dd, J=6.2, 2.8 Hz, 1H), 5.02 (s, 2H), 3.92 (s, 3H), 3.72 (s, 3H), 3.00-2.95 (m, 2H), 2.75-2.70 (m, 3H), 2.47 (s, 3H).

Example 14: Methyl (2E)-2-[2-[[(E)-(3,3-dimethylindan-1-ylidene)amino]oxymethyl]-3-methylphenyl]-2-methoxyimino-acetate

[0241] ##STR00032##

[0242] Step 1: To a solution of 3,3-dimethylindan-1-one (2.5 g, 1 eq.) in 30 mL methanol, under argon at about 25° C. pyridine (2.51 mL, 2 eq.) was added in one portion. Hydroxylamine hydrochloride (2.16 g, 2 eq.) was added and the reaction mixture was heated at 70° C. for 2 h. Then, the reaction mixture was cooled to about 25° C. and concentrated by removing solvent. After addition of 100 mL ethyl acetate, the organic phase was washed with water (3×50 mL) and 15 with brine (1×20 mL), dried with sodium sulfate and concentrated to obtain crude 3,3-dimethylindan-1-one oxime as a yellow oil (2.60 g, 95% yield).

[0243] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.87 (s, 1H), 7.51 (dt, J=7.6, 1.0 Hz, 1H), 7.43-7.32 (m, 2H), 7.30-7.20 (m, 1H), 2.66 (s, 2H), 1.28 (s, 6H).

[0244] Step 2: To a stirred solution of 3,3-dimethylindan-1-one oxime (2.60 g, 1 eq) in acetonitrile (10 ml), cesium carbonate (9.67 g, 2 eq) was added. (2E)-2-[2-(bromomethyl)-3-methyl-phenyl]-2-methoxyimino-acetate (4.00 g, 0.9 eq) in acetonitrile (15 mL) was added dropwise at 25° C. The reaction mixture was stirred for 12 h. The reaction mixture was filtered and the filtrate was evaporated. The resulting residue was purified by flash column chromatography to give the title compound (4.51 g, 85% yield).

Example 19: (2E)-2-[2-[[(E)-(3,3-dimethylindan-1-ylidene)amino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-N-methyl-acetamide

[0245] ##STR00033##

[0246] To a stirred solution of methyl 2E)-2-[2-[[(E)-(3,3-dimethylindan-1-ylidene)amino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-acetate (500 mg, 1 eq) in THF (10 mL), methyl amine (0.9 mL, 40% solution in H.sub.2O, 10 eq) was added and the reaction mixture was stirred for 3 h. Solvents were evaporated under reduced pressure and the residue purified by reverse phase chromatography using acetonitrile and water mixture as a mobile phase to give the title compound (372 mg, 75% yield).

[0247] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.19 (t, J=4.8 Hz, 1H), 7.47 (dt, J=7.6, 1.0 Hz, 1H), 7.41-7.36 (m, 2H), 7.30-7.21 (m, 3H), 6.94 (dd, J=6.8, 2.2 Hz, 1H), 4.96 (s, 2H), 3.87 (s, 3H), 2.70 (d, J=4.7 Hz, 3H), 2.58 (s, 2H), 2.43 (s, 3H), 1.24 (s, 6H).

Example 24: Methyl (2E)-2-[2-[[(E)-[6-fluoro-4-(trifluoromethyl)indan-1-ylidene]amino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-acetate

[0248] ##STR00034##

[0249] Step 1: To a solution of 6-fluoro-4-(trifluoromethyl)indan-1-one (2.5 g, 1 eq.) in 25 mL methanol, under argon pyridine (1.84 mL, 2 eq.) was added in one portion. Hydroxylamine hydrochloride (1.59 g, 2 eq.) was added in two portions and the reaction mixture was heated at 70° C. for 2 h.

[0250] A yellowish-brown reaction mixture was formed. Then, the reaction mixture was cooled to about 25° C. which resulted in the precipitation of a solid. The precipitate was filtered and the solid was washed with methanol in which it was fully soluble. The red-brown solution was evaporated, and 70 mL ethyl acetate was added to the resulting residue. The organic phase was washed with 15 water (3×20 mL) and with brine (1×20 mL), dried with sodium sulfate and concentrated to obtain crude 6-fluoro-4-(trifluoromethyl)indan-1-one oxime (brown solid) as an isomeric mixture (2.47 g, 92% yield).

[0251] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.35 (s, 1H), 7.60 (td, J=8.3, 2.5 Hz, 2H), 3.16-3.06 (m, 2H), 2.93-2.82 (m, 2H).

[0252] Step 2: To a stirred solution of 6-fluoro-4-(trifluoromethyl)indan-1-one oxime (2.47 g, 1 eq) in acetonitrile (10 ml), cesium carbonate (6.90 g, 2 eq) was added followed by a solution of (2E)-2-[2-(bromomethyl)-3-methyl-phenyl]-2-methoxyimino-acetate (2.86 g, 0.9 eq) in acetonitrile (15 mL) at about 25° C. The reaction mixture was stirred for 12 h. The reaction mixture was filtered and the filtrate was evaporated. The resulting residue was purified by flash column chromatography to give the title compound (3.81 g, 88% yield).

[0253] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.67 (dd, J=9.0, 2.4 Hz, 1H), 7.52-7.48 (m, 1H), 7.31-7.28 (m, 2H), 7.02 (dd, J=6.8, 2.4 Hz, 1H), 5.01 (s, 2H), 3.91 (s, 3H), 3.74 (s, 3H), 3.10 (s, 2H), 2.84-2.79 (m, 2H), 2.43 (s, 3H).

Example 28: (2E)-2-[2-[[(E)-[6-fluoro-4-(trifluoromethyl)indan-1-ylidene]amino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-N-methyl-acetamide

[0254] ##STR00035##

[0255] To a stirred solution of methyl methyl (2E)-2-[2-[[(E)-[6-fluoro-4-(trifluoromethyl)indan-1-ylidene]-amino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-acetate (800 mg, 1 eq) in THF (7 mL), methyl amine (1.5 mL, 40% solution in H.sub.2O, 10 eq) was added at about 25° C. and the reaction mixture was stirred for 3 h. Solvents were evaporated under reduced pressure and the residue purified by reverse phase chromatography using acetonitrile and water mixture as a mobile phase to give the title compound (513 mg, 64% yield).

[0256] 1H NMR (400 MHz, DMSO-d6) b 8.24 (d, J=4.8 Hz, 1H), 7.65 (dd, J=9.0, 2.4 Hz, 1H), 7.55 (d, J=8.0 Hz, 1H), 7.26 (d, J=2.1 Hz, 2H), 6.94 (dd, J=7.1, 2.0 Hz, 1H), 5.00 (s, 2H), 3.87 (s, 3H), 3.08 (d, J=7.0 Hz, 2H), 2.85-2.80 (m, 2H), 2.70 (d, J=4.7 Hz, 3H), 2.42 (s, 3H).

[0257] The following examples in Table S were synthesized as per general Schemes described above and characterized by LCMS as described in Table L.

TABLE-US-00004 TABLE L LCMS Methods Method details Device details LCMS Method A Column: Agilent Eclipse Plus C18 LCMS2020 (Shimadzu) (50 mm × 4.6 mm × 3 μm particles) Ionization source: ESI Mobile Phase: Mass range: 100-800 amu A: 10 mM Ammonium formate in water. Polarity: Dual (positive and B: 0.1% Formic acid in acetonitrile. negative simultaneous scan); Gradient: 10% B to 100% B in 1.5 min. Mode: Scan Hold 1 min 100% B. 1 min 10% B. LC System: Nexera High pressure Run time: 3.50 or 3.75 min. gradient system, Binary pump Flow: 1.2 ml/min; Detector: PDA Column oven: 30° C./40° C. Scanning wavelength: 220 nm/max plot LCMS Method B Column: Kinetex XB C18 LCMS2020 (Shimadzu) (50 mm × 2.1 mm × 1.7 μm particles) Ionization source: ESI Mobile Phase: Mass range: 100-800 amu A: Water + 0.1% TFA. Polarity: Dual (positive and B: Acetonitrile negative simultaneous scan); Gradient: 5% B to 100% B in 1.5 min. Mode: Scan Flow: 0.8 ml/min to 1.0 ml/min in 1.5 min; LC System: Nexera High pressure Column oven: 60° C. gradient system, Binary pump Detector: PDA Scanning wavelength: 220 nm/max plot LCMS Method C Column: Luna-C18 LCMS DELIVER-220 (Shimadzu) (30 mm × 2.0 mm × 3 μm particles) Ionization source: ESI Mobile Phase: Mass range: 100-1000 amu A: 0.037% Trifluoroacetic acid Polarity: Positive in water. Mode: Scan B: 0.018% Trifluoroacetic acid LC System: Nexera High pressure in HPLC grade acetonitrile. gradient system, Binary pump Gradient: 5-95% B in 3.00 min .5% B Detector: DAD in 0.01 min, 5-95% B (0.01-1.60 min), Scanning wavelength: 220 nm/max plot 95-100% B (1.60-2.50 min), 100-5% (2.50-2.52 min) with a hold at 5% B for 0.48 min. Flow: 0.8 mL/min; Column oven: 40° C.

TABLE-US-00005 TABLE S LCMS data Compound R.sub.t No. Structure [min] Mass Method  1 [00036] 2.1 367 A  2 [00037] 2.005 366 A  3 [00038] 2.176 381 A  4 [00039] 2.037 380 A  5 [00040] 2.176 385 A  6 [00041] 2.048 384 A  7 [00042] 2.176 435 A  8 [00043] 2.05 434 A  9 [00044] 2.112 385 A 10 [00045] 1.963 384 A 11 [00046] 1.371 447 B 12 [00047] 1.377 446.9 B 13 [00048] 1.328 403 B 14 [00049] 1.359 395 B 15 [00050] 2.187 401 B 16 [00051] 2.048 400 B 17 [00052] 1.26 402 B 18 [00053] 1.30 444 B 19 [00054] 2.05 380 A 20 [00055] 1.39 400.8 B 21 [00056] 1.31 396.9 B 22 [00057] 1.32 445.7 B 23 [00058] 1.33 384.4 B 24 [00059] 1.44 452.8 B 25 [00060] 1.40 446.6 B 26 [00061] 1.34 381.1 B 27 [00062] 1.20 384 B 28 [00063] 1.32 452 B 29 [00064] 1.28 444 B 30 [00065] 1.23 380 B 31 [00066] 1.21 396 B 32 [00067] 1.3 399.8 B 33 [00068] 1.35 380.9 B 34 [00069] 1.36 381 B 35 [00070] 1.42 443 B 36 [00071] 1.37 446.7 B 37 [00072] 1.40 434.8 B 38 [00073] 1.26 379.9 B 39 [00074] 1.34 442.1 B 40 [00075] 1.31 434.1 B 41 [00076] 1.26 379.9 B 42 [00077] 2.09 381 A 43 [00078] 1.3 365 B 44 [00079] 1.21 364 B 45 [00080] 1.82 410.2 C 46 [00081] 1.91 478.2 C 47 [00082] 1.72 412.2 C 48 [00083] 1.92 411.2 C 49 [00084] 1.99 479.2 C 50 [00085] 1.81 413.2 C 51 [00086] 1.77 382.1 C 52 [00087] 1.81 476.1 C 53 [00088] 1.86 383.1 C 54 [00089] 2.07 477.2 C 55 [00090] 1.90 451.1 C 56 [00091] 1.85 433.1 C 57 [00092] 1.75 432.2 C 58 [00093] 1.83 417.2 C 59 [00094] 1.74 416.2 C 60 [00095] 1.27 446 B 61 [00096] 62 [00097] 2.21 381 A 63 [00098] 1.39 395 B 64 [00099] 1.74 403.1 C 65 [00100] 1.64 402.1 C 66 [00101] 1.91 439.2 C 67 [00102] 1.82 438.2 C

Biological Studies

Green House

[0258] The compound was dissolved in a mixture of acetone and/or dimethylsulfoxide and the wetting agent/emulsifier Wettol, which is based on ethoxylated alkylphenoles, in a ratio (volume) solvent-emulsifier of 99 to 1 to give a total volume of 5 ml. Subsequently, water was added to total volume of 100 ml. This stock solution was then diluted with the described solvent-emulsifier-water mixture to the final concentration given in the table below.

Use Example 1. Protective Control of Soybean Rust on Soybeans Caused by Phakopsora pachyrhizi (PHAKPA P2)

[0259] Leaves of potted soybean seedlings were sprayed to run-off with the previously described spray solution, containing the concentration of active ingredient or their mixture as described below. The plants were allowed to air-dry. The trial plants were cultivated for 2 days in a greenhouse chamber at 23-27° C. and a relative humidity between 60 and 80%. Then the plants were inoculated with spores of Phakopsora pachyrhizi. The strain used contains the amino acid substitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors. To ensure the success the artificial inoculation, the plants were transferred to a humid chamber with a relative humidity of about 95% and 20 to 24° C. for 24 hr. The trial plants were cultivated for up to 14 days in a greenhouse chamber at 23 to 27° C. and a relative humidity between 60 and 80%. The extent of fungal attack on the leaves was visually assessed as % diseased leaf area, the disease level of untreated controls was usually higher than 85%.

Use Example 2. Protective Control of Soybean Rust on Soybeans Caused by Phakopsora pachyrhizi (PHAKPA P6)

[0260] Leaves of potted soybean seedlings were sprayed to run-off with the previously described spray solution, containing the concentration of active ingredient as described below. The plants were allowed to air-dry. The trial plants were cultivated for six days in a greenhouse chamber at 23-27° C. and a relative humidity between 60 and 80%. Then the plants were inoculated with spores of Phakopsora pachyrhizi. The strain used contains the amino acid substitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors. To ensure the success the artificial inoculation, the plants were transferred to a humid chamber with a relative humidity of about 95% and 23 to 27° C. for 24 hr. The trial plants were cultivated for up to 14 days in a greenhouse chamber at 23 to 27° C. and a relative humidity between 60 and 80%. The extent of fungal attack on the leaves was visually assessed as % diseased leaf area, the disease level of untreated controls was usually higher than 85%.

[0261] The results of the abovementioned use examples are given in the following Table 1. All test results in Table 1 are given for the control of phytopathogenic fungi containing the amino acid substitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors.

TABLE-US-00006 TABLE 1 PHAKPA (F129L) Disease level (%) Compound P2 at P6 at P2 at P6 at No. Structure 16 ppm 16 ppm 4 ppm 4 ppm  1 [00103] 8 1 28 25  2 [00104] 1 12 6 42  3 [00105] 100 90 100 100  4 [00106] 7 32 90 87  5 [00107] 3 1 30 40  6 [00108] 0 0 3 20  7 [00109] 10 5 25 30  8 [00110] 0 0 1 5  9 [00111] 7 20 40 90 10 [00112] 1 25 25 90 12 [00113] 97 100 100 100 13 [00114] 8 20 53 83 15 [00115] 25 25 80 90 16 [00116] 2 0 17 22 17 [00117] 8 4 26 25 18 [00118] 27 73 67 90 19 [00119] 90 100 100 100 20 [00120] 70 93 97 100 21 [00121] 4 11 31 36 22 [00122] 6 10 22 37 23 [00123] 18 32 53 70 25 [00124] 32 60 57 93 26 [00125] 57 83 80 90 27 [00126] 1 10 13 67 28 [00127] 100 100 70 100 29 [00128] 8 22 37 70 30 [00129] 3 32 47 93 31 [00130] 0 1 3 35 32 [00131] 3 4 23 53 33 [00132] 57 60 100 97 34 [00133] 93 97 100 100 38 [00134] 3 18 28 80 40 [00135] 83 93 100 100 43 [00136] 100 100 100 100 44 [00137] 100 100 100 100 45 [00138] 93 100 100 90 46 [00139] 100 93 100 97 47 [00140] 27 57 93 93 48 [00141] 100 100 100 100 49 [00142] 100 100 100 90 50 [00143] 87 73 100 93 51 [00144] 13 47 60 90 53 [00145] 57 53 97 80 54 [00146] 100 87 100 87 55 [00147] 100 93 100 87 56 [00148] 93 87 100 97 57 [00149] 22 33 70 77 58 [00150] 100 90 100 93 59 [00151] 97 67 100 87 60 [00152] 93 63 100 87 61 [00153] 87 80 100 90 63 [00154] 100 87 100 90

Comparative Trials

[0262]

TABLE-US-00007 TABLE C1 PHAKPA (F129L) Disease level (%) P2 at P2 at P6 at P6 at Compound Structure 4 ppm 16 ppm 4 ppm 16 ppm Trifloxystrobin as comparative example [00155] 83 24 100 67 Ex. 7 [00156] 27 9 25 4

[0263] The results in Table C1 show that the specific substituent at position R.sup.3 the improves the fungicidal activity against phytopathogenic fungi containing the amino acid substitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors compared to trifloxystrobin where the position R.sup.3 is unsubstituted.