Patent Application
20080085924
0.300 g (1.126 mmol) of 1-(2′-aminobiphenyl-4-yl)ethanone O-allyl oxime and 0.114 g (1.126 mmol) of triethylamine are initially charged in 20 ml of toluene. At room temperature, 0.199 g (1.126 mmol) of 5-fluoro-1,3-dimethyl-1H-pyrazole-4-carbonyl chloride is added to the reaction mixture, and the mixture is stirred at 50° C. for 2 h. For work-up, the reaction mixture is cooled to room temperature, washed twice with in each case 100 ml of water, dried over sodium sulfate and concentrated under reduced pressure. The residue is recrystallized from n-hexane.
This gives 0.44 g (94.4% of theory) of N-(4′-{1-(allyloxyimino)-ethyl}-biphenyl-2-yl)-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide (compound 17, Table 1) of melting point 118° C.
0.300 g (1.000 mmol) of 2′-aminobiphenyl-4-carbaldehyde O-allyl oxime (III-1) and 0.120 g (1.000 mmol) of triethylamine are initially charged in 15 ml of toluene. At room temperature, 0.251 g (1.000 mmol) of 4-difluoromethyl-2-methylthiazole-5-carbonyl chloride, dissolved in 5 ml of toluene, is added to the reaction mixture, and the mixture is heated at 50° C. and stirred for 3 h. For work-up, the reaction mixture is cooled to room temperature and washed twice with in each case 80 ml of water, and the organic phase is dried over magnesium sulfate and then concentrated under reduced pressure. The residue is purified by silica gel column chromatography (hexane/methyl tert-butyl ether 3:1).
This gives 0.30 g (49.6% of theory) of N-[4′-(allyloxyimino-methyl)-biphenyl-2-yl]-4-difluoromethyl-2-methylthiazole-5-carboxamide (compound 9, Table 1).
1H-NMR (DMSO-D6): δ=2.71 ppm (s, 3H)
At room temperature, 1.00 g (2.75 mmol) of N-(2-iodophenyl)-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide, 0.61 g (2.78 mmol) of 4-[1-(allyloxyimino)ethyl]phenylboronic acid and 0.20 g of tetrakis(triphenylphosphine)palladium(0) are initially charged in 15 ml of dimethoxyethane. At room temperature, a solution of 1.18 g (11.14 mmol) of sodium carbonate in 15 ml of water is added with stirring. The mixture is heated at reflux temperature and stirred for 15 h. For work-up, the mixture is cooled to room temperature and extracted twice with in each case 50 ml of diethyl ether. The organic phases are washed with water, dried over sodium sulfate and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (hexane/methyl tert-butyl ether 3:1).
This gives 0.13 g (10.5% of theory) of N-(4′-{1-(allyloxyimino)ethyl}biphenyl-2-yl)-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide (compound 17, Table 1) of logP (pH 2.3)=3.80.
0.79 g (2.24 mmol) of N-(4′-acetylbiphenyl-2-yl)-2-chloronicotinamide (VIII-1), 0.40 g (2.24 mmol) of O-(3,3-dichloroallyl)hydroxylamine hydrochloride and 0.22 g of sodium acetate are initially charged in a mixture of 5 ml of methanol and 2 ml of water and stirred at room temperature for 15 h. For work-up, the mixture is stirred into 30 ml of water and then extracted with 30 ml of dichloromethane. The organic phase is washed with 15 ml of water, and the phases are separated. The organic phase is dried over sodium sulfate and then concentrated under reduced pressure. The residue is triturated in a little hot hexane and cooled, and the residue is filtered off with suction.
This gives 0.68 g (63.9% of theory) of 2-chloro-N-{4′-[1-(3,3-dichloroallyloxyimino)ethyl]-biphenyl-2-yl}nicotinamide (compound 63, Table 1) of logP (pH 2.3)=4.43.
At room temperature, 1.00 g (2.87 mmol) of N-{4′-[1-(hydroxyimino)ethyl]biphenyl-2-yl}-1,3-dimethyl-1H-pyrazole-4-carboxamide and 0.60 g of potassium carbonate (4.31 mmol) are initially charged in 50 ml of acetonitrile, and 0.417 g of 1,1,3-trichloropropene (2.870 mmol), dissolved in 5 ml of acetonitrile, are then added. The mixture is heated at reflux temperature and stirred for 15 h. For work-up, the mixture is cooled and filtered off with suction through a Nutsche filter, and the mother liquor is concentrated under reduced pressure. The residue is chromatographed on silica gel (hexane/acetone 9:1).
This gives 0.66 g (47.1% of theory) of N-(4′-{1-[3,3-dichloroallyloxyimino]ethyl}biphenyl-2-yl)-1,3-dimethyl-1H-pyrazole-4-carboxamide (compound 54, Table 1) as a solid of logP (pH 2.3)=3.97.
The biphenylcarboxamides of the formula (I-1) listed in the table below are likewise prepared according to Examples 1 to 5 and according to the general process descriptions and methods.
16.50 g (80.48 mmol) of 4-allyloxyiminomethylphenylboronic acid (V-1) and 13.84 g (80.48 mmol) of 2-bromoaniline together with 0.50 g (0.43 mmol) of tetrakis(triphenylphosphine)palladium are initially charged in a mixture of 100 ml of 1,2-dimethoxyethane and 100 ml of water. After addition of 34.12 g (321.92 mmol) of sodium carbonate, the mixture is heated at reflux for 12 h. For work-up, the reaction mixture is cooled to room temperature and extracted twice with in each case 200 ml of diethyl ether. The combined ether phases are washed with 400 ml of water and then dried over magnesium sulfate and concentrated under reduced pressure. The residue is chromatographed on silica gel (hexane/methyl tert-butyl ether 3:1).
This gives 4.3 g (15% of theory) of 2′-aminobiphenyl-4-carbaldehyde O-allyl oxime.
1H-NMR (DMSO-D6): δ=8.33 ppm (s, 1H)
In a mixture of 100 ml of methanol and 40 ml of water, 13.69 g (91.28 mmol) of formylphenylboronic acid, 10.0 g of O-allylhydroxylamine hydrochloride (91.28 mmol) and 9.36 g (114.10 mmol) of sodium acetate are stirred at room temperature for 12 h. For work-up, the mixture is concentrated under reduced pressure and the residue is triturated with 150 ml of water, filtered off with suction through a glass frit, washed with a little water and dried on a clay disk.
This gives 16.5 g (84.6% of theory) of 4-allyloxyiminomethylphenylboronic acid.
1H-NMR (DMSO-d6): δ=8.27 ppm (s, 1H)
At room temperature, 8.33 g (47.33 mmol) of 2-chloronicotinoyl chloride, dissolved in 20 ml of toluene, are added over a period of 5 minutes to 10.00 g (47.33 mmol) of 1-(2′-aminobiphenyl-4-yl)ethanone (XIV-1) and 4.79 g (47.33 mmol) of triethylamine, dissolved in 150 ml of toluene. The mixture is heated at 50° C. and allowed to react for 10 h. For work-up, the mixture is cooled, 100 ml of water are added and the phases are separated. The organic phase is dried over sodium sulfate and concentrated under reduced pressure. The residue is recrystallized from n-hexane.
This gives 13.7 g (82.3% of theory) of N-(4′-acetyl-biphenyl-2-yl)-2-chloronicotinamide of logP (pH 2.3)=2.12.
15.74 g (91.48 mmol) of 2-bromoaniline, 15.00 g of 4-acetylphenylboronic acid (91.48 mmol) and 0.529 g of tetrakis(triphenylphosphine)palladium(0) (0.457 mmol) are initially charged in 150 ml of dimethoxyethane. 38.78 g (365.93 mmol) of sodium carbonate, dissolved in 150 ml of water, are added over a period of 5 minutes. The mixture is heated at reflux temperature and stirred for 15 h. For work-up, the mixture is cooled and extracted twice with in each case 150 ml of ether. The combined organic phases are washed with water, dried over sodium sulfate and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (cyclohexane/ethyl acetate 3:1).
This gives 15.0 g (72.6% of theory) of 1-(2′-aminobiphenyl-4-yl)ethanone of logP (pH 2.3)=1.80.
The logP values given in Table 1 were determined with EEC Directive 79/831 Annex V.A8 by HPLC (High Performance Liquid Chromatography) on a reverse-phase column (C 18). Temperature: 43° C.
Mobile phases for the determination in the acidic range (pH 2.3): 0.1% aqueous phosphoric acid, acetonitrile; linear gradient from 10% acetonitrile to 90% acetonitrile. Calibration was carried out using unbranched alkan-2-ones (having 3 to 16 carbon atoms) with known logP values (determination of the logP values by the retention times using linear interpolation between two successive alkanones).
The lambda-max values were determined in the maxima of the chromatographic signals using the UV spectra from 200 nm to 400 nm.
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvents and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for protective activity, young plants are sprayed with the preparation of active compound at the stated application rate. After the spray coating has dried on, the plants are inoculated with an aqueous conidia suspension of the apple scab pathogen Venturia inaequalis and then remain in an incubation cabin at about 20° C. and 100% relative atmospheric humidity for 1 day.
The plants are then placed in a greenhouse at about 21° C. and a relative atmospheric humidity of about 90%.
Evaluation is carried out 10 days after the inoculation. 0% means an efficacy which corresponds to that of the control, whereas an efficacy of 100% means that no infection is observed.
In this test, for example, the following compounds according to the invention of the Preparation Examples show good activity:
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvents and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for protective activity, young plants are sprayed with the preparation of active compound at the stated application rate. After the spray coating has dried on, 2 small pieces of agar colonized by Botrytis cinerea are placed onto each leaf. The inoculated plants are placed in a dark chamber at about 20° C. and 100% relative atmospheric humidity.
2 days after the inoculation, the size of the infected areas on the leaves is evaluated. 0% means an efficacy which corresponds to that of the control, whereas an efficacy of 100% means that no infection is observed.
In this test, for example, the following compounds according to the invention of the Preparation Examples show good activity:
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for protective activity, young tomato plants are sprayed with the preparation of active compound at the stated application rate. 1 day after the treatment, the plants are inoculated with a spore suspension of Alternaria solani and then remain at 100% relative atmospheric humidity and 20° C. for 24 hours. The plants then remain at 96% relative atmospheric humidity and a temperature of 20° C.
Evaluation is carried out 7 days after the inoculation. 0% means an efficacy which corresponds to that of the control, whereas an efficacy of 100% means that no infection is observed.
In this test, for example, the following compounds according to the invention of the Preparation Examples show good activity:
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for protective activity, young plants are inoculated with a spore suspension of Puccinia recondita in a 0.1% strength aqueous agar solution. After the spray coating has dried on, the plants are sprayed with the preparation of active compound at the stated application rate. The plants remain in an incubation cabin at 20° C. and 100% relative atmospheric humidity for 24 hours.
The plants are then placed in a greenhouse at a temperature of about 20° C. and a relative atmospheric humidity of 80% to promote the development of rust pustules.
Evaluation is carried out 10 days after the inoculation. 0% means an efficacy which corresponds to that of the control, whereas an efficacy of 100% means that no infection is observed.
In this test, for example, the following compounds according to the invention of the Preparation Examples show good activity:
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with methanol to the desired concentrations.
A stated amount of the preparation of active compound of the desired concentration is pipetted onto a standardized amount of synthetic feed. After the methanol has evaporated, about 200-300 eggs of the diamond back moth (Plutella xylostella) are placed onto the feed.
After the desired period of time, the kill of the eggs in % is determined. 100% means that all animals have been killed; 0% means that none of the animals have been killed.
In this test, for example, the following compounds of the Preparation Examples show good activity:
| Number | Date | Country | Kind |
|---|---|---|---|
| 10102-58-314.5 | Dec 2002 | DE | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP03/13498 | 12/1/2003 | WO | 00 | 3/23/2007 |
