Thiophene carboxamide derivative and plant disease control agent comprising same

Abstract

The present invention provides a thiophene carboxamide compound of the following General Formula (I), which is a novel fluorine-substituted biphenyl carboxamide-based compound, and provides a useful compound, as an agricultural and horticultural plant disease control agent, exhibiting an excellent control effect at a low dose. ##STR00001## wherein, R, R1, R2, R3, Xm, and Y are each as defined in the specification.

Claims

1. A difluoro biphenyl thiophene carboxamide compound represented by the following General Formula (I): ##STR00007## in the above Formula, Y is a hydrogen atom or a (C1˜C4)alkyl; X is a halogen atom or a (C1˜C4)alkyl; m is an integer of 0˜2; R is a hydrogen atom, (C1˜C6)alkyl, (C2˜C6)alkenyl, (C2˜C6)alkynyl, (C1˜C6)alkyl which may be substituted by 1 to 5 halogen atoms, (C1˜C3)alkyl which may be substituted with (C3˜C6)cycloalkyl, (C1˜C3)alkyl which may be substituted with phenyl or pyridine, phenyl(C1˜C3)alkyl (which may be substituted with a halogen atom), phenyl(C1˜C3)alkyl which may be substituted with (C1˜C4)alkyl, or phenyl(C1˜C3)alkyl which may be substituted with (C1˜C4)alkoxy; R1 is a halogen, (C1˜C4)alkyl, or (C1˜C4)alkyl substituted by 1 to 3 halogen atoms, and R2 and R3 are each independently hydrogen, (C1˜C4)alkyl, or halogen.

2. The compound of claim 1, wherein Y is a hydrogen atom and m is 0.

3. The compound of claim 2, wherein Y is a hydrogen atom; m is 0; R is (C1˜C6)alkyl, (C2˜C6)alkenyl, (C2˜C6)alkynyl, (C1˜C6)alkyl which may be substituted by 1 to 5 halogen atoms, (C1˜C3)alkyl which may be substituted with (C3˜C6)cycloalkyl, (C1˜C3)alkyl which may be substituted with phenyl or pyridine, phenyl(C1˜C3)alkyl (which may be substituted with a halogen atom), phenyl(C1˜C3)alkyl which may be substituted with (C1˜C4)alkyl, or phenyl(C1˜C3)alkyl which may be substituted with (C1˜C4)alkoxy; R1 is (C1˜C4)alkyl or (C1˜C4)alkyl substituted with 1 to 3 halogen atoms; and R2 and R3 are a hydrogen atom.

4. The compound of claim 3, wherein Y is a hydrogen atom, m is 0, R is (C1˜C6)alkyl or (C1˜C4)alkyl which may be substituted by 1 to 3 halogen atoms; R1 is methyl, and R2 and R3 are a hydrogen atom.

5. A plant disease control agent for agricultural and horticultural use, comprising as an active ingredient the compound of the General Formula (I) according to claim 1 or a salt thereof.

6. A method for controlling a plant disease, comprising applying to a plant of interest or soil an effective amount of a compound of the General Formula (I) according to claim 1 or a salt thereof.

Description

MODE FOR INVENTION

(1) Next, the present invention is specifically described with reference to Examples and Experimental Examples, but the present invention is not limited thereto unless the gist of the invention is exceeded.

MANUFACTURING EXAMPLE

Example 1

Synthesis of N-(3′,5′-difluoro-4′-((methoxyimino)methyl)-[1,1′-biphenyl]-2-yl)-3-methylthiophene-2-carboxamide (Compound 1)

(2) To a solution of N-(3′,5′-difluoro-4′-formyl-[1,1′-biphenyl]-2-yl)-3-methylthiophene-2-carboxamide (2.30 g, 6.42 mmol) in 15 mL of ethanol was added sequentially methylhydroxamide hydrochloride (1.33 g, 2.5 eq) and sodium acetate trihydrate (2.21 g, 2.5 eq) at room temperature and stirred for 2 hours. After the completion of the reaction was confirmed by TLC, the organic layer was separated using ethyl acetate (100 mL) and 20 mL of water. The organic layer was dried over magnesium sulfate, and concentrated. The obtained white solid was recrystallized using ethyl ether to give the white solid 2.01 g (yield 81%).

(3) .sup.1H NMR (CDCl.sub.3) δ 2.42 (s, 3H), 4.05 (s, 3H), 6.86 (d, J=5.1 Hz, 1H), 7.05 (d, J=8.9 Hz, 2H), 7.25 (m, 3H). 7.36 (t, J=6.0 Hz, 1H), 7.45 (s, 1H), 8.28 (s, 1H), 8.35 (d, J=8.3 Hz, 1H)

Example 1-1

Synthesis of N-(3′,5′-difluoro-4′-formyl-[1,1′-biphenyl]-2-yl)-3-methylthiophene-2-carboxamide

(4) To a solution of N-(2-bromophenyl)-3-methylthiophene-2-carboxamide (10.2 g, 34.6 mmol) in 100 mL of dimethylformamide was added 25 mL of distilled water, followed by sequential addition of 3,5-difluoro-4-formyl phenylboronic acid (10.9 g, 1.7 eq), palladium(II) acetate (388 mg, 0.05 eq), and potassium phosphate tribasic-trihydrate (9.0 g, 1.1 eq). The reaction mixture was stirred at 85° C. for 2 hours under nitrogen conditions. After the completion of the reaction was confirmed by TLC, ethyl acetate (1000 mL) and saturated brine (100 mL) were added to the reaction mixture to separate the layers, followed by filtration through Celite. The filtrate was diluted with ethyl acetate (200 mL), and the organic layer was washed with saturated Na.sub.2CO.sub.3 aqueous solution (30 mL×2) and saturated brine (50 mL×2). The organic layer was dried over magnesium sulfate, and concentrated. The obtained concentrate was recrystallized using ethyl ether to give the above solid 10.9 g (88%)

(5) .sup.1H NMR (CDCl.sub.3) δ 2.45 (s, 3H), 6.89 (d, 1H), 7.07 (d, 2H), 7.25 (s, 3H). 7.47 (m, 2H), 8.23 (d, 1H), 10.37 (s, 1H)

Example 1-2

Synthesis of N-(2-bromophenyl)-3-methylthiophene-2-carboxamide

(6) To a solution of 2-bromoaniline (50.0 g, 311.3 mmol) and pyridine (25 mL, 1.0 eq) in tetrahydrofuran (300 mL) was added 3-methyl-2-thienyl chloride (50.0 g, 1.0 eq) slowly at 0° C. After 30 minutes, the mixture was stirred for an additional 3 hours at room temperature. Ethyl acetate (100 mL) and water (40 mL) were added to the reaction mixture to separate the organic layer, and the organic layer was washed sequentially with 1.0 M HCl aqueous solution (30 mL), saturated aqueous sodium hydrogen carbonate solution (30 mL), and saturated brine (50 mL). The organic layers were collected, dried over magnesium sulfate, and concentrated. The obtained concentrate was recrystallized using ethyl ether to give the above white solid 79.8 g (yield 86%).

(7) .sup.1H NMR (CDCl.sub.3) δ 2.65 (s, 3H), 7.0 (m, 2H), 7.36 (m, 2H). 7.56 (d, 1H), 8.17 (brs, 1H), 8.5 (d, 1H)

(8) ##STR00006##

(9) Table 1 shows NMR data of the compounds.

(10) TABLE-US-00001 TABLE 1 Compound R2, No. R1 R3 Y Xm R .sup.1H NMR (300 MHz, Solvent) 1 Me H H — Me (CDCl.sub.3) δ 2.42 (s, 3H), 4.05 (s, 3H), 6.86 (d, J = 5.1 Hz, 1H), 7.05 (d, J = 8.9 Hz, 2H), 7.25 (m, 3H). 7.36 (t, J = 6.0 Hz, 1H), 7.45 (s, 1H), 8.28 (s, 1H), 8.35 (d, J = 8.3 Hz, 1H) 2 Me H H — t-Bu (CDCl.sub.3) δ 1.38 (s, 9H), 2.41 (s, 3H), 6.88 (d, J = 5.0 Hz, 1H), 7.01 (d, J = 8.9 Hz, 2H), 7.25 (m, 3H). 7.43 (t, J = 6.0 Hz, 1H), 7.59 (s, 1H), 8.23 (s, 1H), 8.34 (d, J = 8.3 Hz, 1H) 3 Me H H — Et (CDCl.sub.3) δ 1.35 (t, J = 7.1 Hz, 3H), 2.42 (s, 3H), 4.31 (q, J = 7.1 Hz, 2H), 6.89 (d, J = 5.0 Hz, 1H), 7.04 (d, J = 8.8 Hz, 2H), 7.26 (m, 3H). 7.44 (t, J = 9.0, 1H), 7.55 (s, 1H), 8.29 (s, 1H), 8.35 (d, J = 8.2 Hz, 1H) 4 Me H H — i-Pr (CDCl.sub.3) δ 1.33 (d, J = 6.2 Hz, 6H), 2.42 (s, 3H), 4.54 (m, 1H), 6.89 (d, J = 5.0 Hz, 1H), 7.04 (d, J = 8.7 Hz, 2H), 7.26 (m, 3H). 7.44 (t, J = 6.0, 1H), 7.55 (s, 1H), 8.26 (s, 1H), 8.36 (d, J = 8.3 Hz, 1H) 5 Me H H — benzyl (CDCl.sub.3) δ 2.42 (s, 3H), 5.28 (s, 2H), 6.89 (d, J = 5.0 Hz, 1H), 7.04 (d, J = 8.7 Hz, 2H), 7.35 (m, 9H), 7.53 (br, 1H), 8.36 (m, 2H) 6 Me H H — 4-F-benzyl (CDCl.sub.3) δ 2.42 (s, 3H), 5.23 (s, 2H), 6.89 (d, J = 5.0 Hz, 1H), 7.06 (m, 5H), 7.26 (m, 3H), 7.44 (m, 3H), 7.52 (br, 1H), 8.34 (m, 2H) 7 Me H H — 4-Cl-benzyl (CDCl.sub.3) δ 2.42 (s, 3H), 5.23 (s, 2H), 6.89 (d, J = 5.0 Hz, 1H), 7.04 (d, J = 8.8 Hz, 2H), 7.26 (m, 3H), 7.35 (m, 4H), 7.44 (m, 1H), 7.52 (s, 1H), 8.33 (s, 1H), 8.35 (d, J = 8.3 Hz, 1H) 8 Me H H — 4-OCH.sub.3-benzyl (CDCl.sub.3) δ 2.42 (s, 3H), 3.81 (s, 3H), 5.20 (s, 2H), 6.90 (m, 3H), 7.03 (d, J = 8.8 Hz, 2H), 7.26 (m, 3H), 7.43 (m, 3H), 7.53 (br, 1H), 8.31 (s, 1H), 8.35 (d, J = 8.3 Hz, 1H) 9 Me H H — CH.sub.2CF.sub.3 (CDCl.sub.3) δ 2.43 (s, 3H), 4.60 (q, J = 8.5 Hz, 2H), 6.90 (d, J = 5.1 Hz, 1H), 7.07 (d, J = 9.0 Hz, 2H), 7.27 (m, 3H). 7.46 (m, 2H), 8.32 (d, J = 8.3 Hz, 1H), 8.40 (s, 1H) 10 Me H H — CH.sub.2CH.sub.2Cl (CDCl.sub.3) δ 2.43 (s, 3H), 3.82 (t, J = 5.9 Hz, 2H), 4.46 (t, J = 5.8 Hz, 2H), 6.90 (d, J = 5.1 Hz, 1H), 7.06 (d, J = 9.0 Hz, 2H), 7.27 (m, 3H). 7.46 (t, J = 6.0 Hz, 1H), 7.53 (s, 1H), 8.35 (d, J = 9.0 Hz, 1H), 8.60 (s, 1H) 11 Me H H — allyl (CDCl.sub.3) δ 2.43 (s, 3H), 4.74 (d, 2H), 5.3(m, 2H), 6.05 (m, 1H), 6.90 (d, J = 5.1 Hz, 1H), 7.06 (d, J = 9.0 Hz, 2H), 7.27 (m, 3H). 7.46 (t, J = 6.0 Hz, 1H), 7.53 (s, 1H), 8.35 (d, 2H) 12 Me H H 4-F Me (CDCl.sub.3) δ 2.43 (s, 3H), 4.06 (s, 3H), 6.90 (d, J = 5.0 Hz, 1H), 7.03 (m, 3H), 7.16 (m, 1H), 7.30 (d, J = 5.0 Hz, 1H), 7.41 (br, 1H), 8.25 (m, 2H) 13 Me H H 4-F t-Bu (CDCl.sub.3) δ 1.38 (s, 9H), 2.42 (s, 3H), 6.90 (d, J = 5.1 Hz, 1H), 7.00 (m, 3H), 7.15 (m, 1H), 7.30 (d, J = 5.1 Hz, 1H), 7.43 (br, 1H), 8.23 (s, 1H), 8.23 (m, 1H) 14 Me H H 4-F CH.sub.2CF.sub.3 (CDCl.sub.3) δ 2.43 (s, 3H), 4.59 (q, J = 8.5 Hz, 2H), 6.90 (d, J = 5.0 Hz, 1H), 7.00 (dd, J = 8.6, 3.0 Hz, 1H), 7.05 (d, J = 8.7 Hz, 2H). 7.16 (td, J = 6.0, 3.0 Hz, 1H), 7.30 (d, J = 5.0 Hz, 1H), 7.38 (s, 1H), 8.21 (dd, J = 9.1, 5.2 Hz, 1H), 8.38 (s, 1H) 15 Me H H 4-F CH.sub.2CH.sub.2Cl (CDCl.sub.3) δ 2.43 (s, 3H), 3.81 (t, J = 5.8 Hz, 2H), 4.46 (t, J = 5.8 Hz, 2H), 6.90 (d, J = 5.0 Hz, 1H), 7.03 (m, 3H), 7.16 (m, 1H), 7.30 (d, J = 5.0 Hz, 1H), 7.41 (br, 1H), 8.23 (m, 1H), 8.35 (s, 1H)

(11) Next, examples of the bioactivity assay are described.

Experimental Example 1

(12) Wheat Rust Control Effect Test

(13) A predetermined amount of the present compound corresponding to the test concentration was dissolved in 10% acetone and then was sprayed to foliage in a single leafy wheat (variety: Baegjoong) grown in a circular pot (6×7 cm, diameter×height). One day after application, the wheat plants were inoculated by spraying a spore suspension which was prepared with spores obtained from wheat leaves infected with wheat rust pathogen (Puccinia recondita). After an inoculation period of 1 day at 20° C. humid conditions, the plants were kept in a chamber for 14 days at a constant temperature and humidity under constant light conditions. After 15 days of the compound treatment, the disease incidence was assessed according to the following equation (1), and the control value was determined according to the following criteria.
Control value (%)=(1−X/Y)×100  (Equation 1)

(14) here, X: ratio of diseased leaf area of treated plants Y: ratio of diseased leaf area of non-treated plants

(15) Criteria 0: less than 9% control value 1: Control value 10-29% 2: Control value 30-49% 3: Control value 50-69% 4: Control value 70-89% 5: Control value 90-100%

(16) As a result of the above test, the compounds of the present invention exhibited excellent control effects with respect at the active ingredient concentration of 200 ppm and the amount of spraying dose of 30 mL, and in particular, Compound Nos. 1, 4, and 9 exhibited high activity of the criterion 5.

Experimental Example 2

(17) Rice Sheath Blight Control Effect Test

(18) A predetermined amount of the present compound corresponding to the test concentration was dissolved in 10% acetone and then was sprayed to foliage in the 5-leaf stage rice (variety: Chucheongbyeo) grown in a circular pot (6×7 cm, diameter×height). One day after application, the rice plants were inoculated by spraying a mycelial suspension of a culture of rice sheath blight pathogen (Rhizoctonia solani) obtained by culturing in a rice bran culture medium and incubated to induce disease development for 5 days under a humid condition at 30° C. After 5 days of the compound treatment, the disease incidence was assessed according to the equation (1) of Experimental Example 1, and the control value was determined according to the criteria of Experimental Example 1.

(19) As a result of the above test, the compound of the present invention exhibited an excellent control effect at the active ingredient concentration of 200 ppm and the amount of spraying dose of 30 mL, and in particular, Compound No. 1 exhibited a high activity of the criterion 5 in the above equation 1.

Experimental Example 3

(20) Cucumber Powdery Mildew Control Effect Test

(21) A predetermined amount of the present compound corresponding to the test concentration was dissolved in 10% acetone and then was sprayed to foliage in a single leafy cucumber (variety: Baekdadagi) grown in a circular pot (6×7 cm, diameter×height). One day after application, the Cucumber plants were inoculated by spraying a spore suspension prepared with spores obtained from cucumber leaves infected with cucumber powdery mildew pathogen (Sphaerotheca fusca). After an incubation period of 1 day at 20° C. humid conditions, the plants were kept in a chamber for 12 days at a constant temperature and humidity under constant light conditions. After 13 days of the compound treatment, the disease incidence was assessed according to equation (1) of Experimental Example 1, and the control value was determined according to the criteria of Experimental Example 1.

(22) As a result of the above test, the compound of the present invention exhibits excellent control effect at the active ingredient concentration of 200 ppm and the amount of spraying dose of 30 mL, and in particular, Compound Nos. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14 showed high activity of criterion 5 in the equation 1 above.

Experimental Example 4

(23) Cucumber Sclerotinia Disease Control Effect Test

(24) A predetermined amount of the present compound corresponding to the test concentration was dissolved in 10% acetone and then was sprayed to foliage in a single leafy cucumber (cultivar: Baekdadagi) grown in a circular pot (6×7 cm, diameter×height). One day after application, the Cucumber plants were inoculated by spraying a mycelial suspension of a liquid culture of cucumber sclerotinia pathogen (Sclerotinia sclerotiorum) and incubated for 4 days under constant light conditions and high humidity conditions at 25° C. to induce disease development. Four days after the compound treatment, the disease incidence was assessed according to equation (1) of Experimental Example 1, and the control value was determined according to the criteria of Experimental Example 1.

(25) As a result of the above test, the compound of the present invention exhibited an excellent control effect at the active ingredient concentration of 200 ppm and the amount of spraying dose of 30 mL, and in particular, Compound No. 1 exhibited a high activity of the criterion 5 in the above equation 1.

Experimental Example 5

(26) Compound No. 1 and the following four compounds as a comparative control compound were evaluated for controlling cucumber powdery mildew as described in Experimental Example 3.

(27) Comparative compound A: 3-(difluoromethyl)-N-(4′-((methoxyimino)methyl)-[1,1′-biphenyl]-2-yl)-1-methyl-1H-pyrazole-4-carboxamide (Compound I-11 of WO 2002/008197 A1)

(28) Comparative compound B: N-(4′-((methoxyimino)methyl)-[1,1′-biphenyl]-2-yl)-3-methylthiophene-2-carboxamide (Compound 1-47 of WO 2002/008197 A1)

(29) Comparative compound C: 3-(difluoromethyl)-N-(3′-fluoro-4′-((methoxyimino)methyl)-[1,1′-biphenyl]-2-yl)-1-methyl-1H-pyrazole-4-carboxamide (Compound I-114 of WO 2002/008197 A1)

(30) Comparative compound D: 5-chloro-N-(3′,5′-difluoro-4′-((methoxyimino)methyl)-[1,1′-biphenyl]-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (Compound 23 of WO 2013/167550 A1)

(31) TABLE-US-00002 TABLE 2 Treatment Activity of Activity of Comparative Compound Concentration Compound 1 A B C D 10 ppm 5 0 1 0 1

INDUSTRIAL APPLICABILITY

(32) The compound of the present invention is useful as a plant disease control agent for agricultural and horticultural use, which has a broad control spectrum with a low drug amount against agricultural and horticultural plant diseases, and exhibits an excellent control effect.