Biphenyl compounds and applications thereof

Abstract

The present disclosure relates to acaricide, specifically to a kind of biphenyl compounds and uses thereof. The general formula I is as follows: ##STR00001##
wherein: each substituent is defined as that in the description. The compounds of the general formula I show high acaricidal activities and can be used for controlling various harmful mites.

Claims

1. A biphenyl compound represented by formula I: ##STR00010## wherein: R.sub.1 and R.sub.2 are independently selected from H, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8haloalkyl, C.sub.2-C.sub.8alkenyl, C.sub.2-C.sub.8haloalkenyl, C.sub.2-C.sub.8alkynyl, C.sub.2-C.sub.8haloalkynyl, cyano C.sub.1-C.sub.8 alkyl, or cyano C.sub.1-C.sub.8haloalkyl; m and n are independently selected from 0, 1, or 2.

2. The compound according to the claim 1, wherein R.sub.1 and R.sub.2 are independently selected from C.sub.1-C.sub.8haloalkyl, C.sub.2-C.sub.8haloalkenyl, C.sub.2-C.sub.8haloalkynyl, or cyano C.sub.1-C.sub.8haloalkyl; m and n are independently selected from 0, 1, or 2.

3. The compound according to the claim 2, wherein R.sub.1 and R.sub.2 are independently selected from C.sub.1-C.sub.3haloalkyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6haloalkynyl, or cyano C.sub.1-C.sub.3haloalkyl; m and n are independently selected from 0 or 1.

4. The compound according to the claim 3, wherein R.sub.1 and R.sub.2 are independently selected from trifluoromethyl, CH.sub.2CF.sub.3, CH.sub.2CHF.sub.2, CH.sub.2CH.sub.2F, or CHCF.sub.2; m and n are independently selected from 0 or 1.

5. A method of controlling harmful mites in agriculture, forestry, or public health, which comprises applying the compound of claim 1 as an insecticide or an acaricide.

6. An acaricidal composition, comprising the compound according to claim 1 as an active ingredient and acceptable carrier in agriculture, wherein the weight percentage of the active ingredient(s) in the composition is 0.1-99%.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) The following examples are illustrative of the present invention, but without being restricted thereby. (All the starting materials are commercially available except special explanation.)

PREPARATION EXAMPLE

Example 1: The Preparation of Compound 1

(2) ##STR00008##
1.1 the Preparation of Intermediate IV-1

(3) To 10.00 g (41.80 mmol) of 2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl)thio)aniline (Intermediate III-1, can be prepared according to the procedures disclosed in the WO2010100189, US2012053052, JP2012519662, EP2403837 and CN102341376) in a 500 mL flask was added concentrated hydrochloric acid (60 ml). The mixture was cooled and stirred for 30 minutes at 0-5 C. To the mixture was added dropwise a 100 ml solution of sodium nitrite (3.46 g, 50.15 mmol) in water at 0-5 C. The reaction mixture was stirred for an hour. To the reaction mixture was added dropwise a 100 ml solution of potassium iodide (13.88 g, 83.61 mmol) in water at 0-5 C. The resulting mixture was stirred for 3 hours at room temperature. After the reaction was over by Thin-Layer Chromatography monitoring, to the resulting mixture was added ethyl acetate (300 ml). The organic layer was washed by water (200 ml) and saturated brine (200 ml) in turn, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluent: ethyl acetate/petroleum ether (boiling point range 60-90 C.)=1/30 (volume ratio)) to yield the title compound (8.79 g) as an oil.

(4) 1.2 the Preparation of Compound 1

(5) A mixture of (4-fluoro-5-iodo-2-methylphenyl)(2,2,2-trifluoroethyl)sulfane (intermediate IV-1, 5.00 g, 14.28 mmol), bis(pinacolato)diboron (5.44 g, 21.42 mmol), cesium carbonate (9.32 g, 28.60 mmol), [1,1-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.06 g), 1,1-Bis(diphenylphosphino)ferrocene (0.04 g), 1,4-dioxane (100 ml) and water (3 ml) was refluxed for 3 hours. After the reaction was over by Thin-Layer Chromatography monitoring, to the mixture was added ethyl acetate (200 ml). The organic layer was washed by water (100 ml) and saturated brine (100 ml) in turn, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluent: ethyl acetate/petroleum ether (boiling point range 60-90 C.)=1/30 (volume ratio)) to yield the title compound (4.79 g) as a white solid (melting point: 59-60 C.).

(6) .sup.1H NMR spectrum (300 MHz, internal standard: TMS, solvent: CDCl.sub.3) (ppm): 2.53 (s, 6H), 3.35 (q, 4H), 7.05-7.09 (m, 2H), 7.53-7.56 (m, 2H). LC-MS (m/z): 446.9 (m+1).

Example 2: The Preparation of Compound 2 and 3

(7) ##STR00009##

(8) To compound 1 (2.00 g, 4.48 mmol) in chloroform (20 ml) was added 3-chloroperbenzoic acid (MCPBA) (85%, 0.98 g, 4.68 mmol) in three batches at 0-5 C. The mixture was stirred at 0-5 C. for 2 hours. After the reaction was over by Thin-Layer Chromatography monitoring, the mixture was washed by sodium subsulfite aqueous solution and sodium bicarbonate aqueous solution in turn, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluent: ethyl acetate/petroleum ether (boiling point range 60-90 C.)=1/6-1/3 (volume ratio)) to yield the title compound 2 (1.21 g) as a white solid and the title compound 3 (0.70 g) as a white solid.

(9) Compound 2: .sup.1H NMR spectrum (300 MHz, internal standard: TMS, solvent: CDCl.sub.3) (ppm): 2.45 (s, 3H), 2.54 (s, 3H), 3.34 (q, 2H), 3.48 (q, 2H), 7.07-7.12 (m, 2H), 7.58 (d, 1H), 7.99 (d, 1H). LC-MS (m/z): 463.0 (m+1).

(10) Compound 3: .sup.1H NMR spectrum (300 MHz, internal standard: TMS, solvent: CDCl.sub.3) (ppm): 2.46 (s, 3H), 2.49 (s, 3H), 3.97-4.08 (m, 4H), 7.30-7.32 (m, 2H), 7.93-7.95 (m, 2H). LC-MS (m/z): 479.0 (m+1).

(11) Other compounds of general formula I (When R.sub.1=R.sub.2) in the present disclosure were prepared according to the above examples. More specifically, according to Method 1 mentioned above, the reagents were changed to obtain the targets. Other compounds of general formula I (When R.sub.1 is different from R.sub.2) in the present disclosure were prepared according to Method 2 mentioned above, by using the different halogenating agent.

(12) Biological Testing

Example 3: Determination of Acaricidal Activity in Greenhouse

(13) According to the solubility of test compounds, the compounds are dissolved in acetone or dimethyl sulfoxide, and then diluted with 0.1% aqueous solution of Tween 80 to form 50 ml test liquid, the content of acetone or dimethyl suloxide in the total solution is not more than 10%.

(14) 3.1 Test Against Adult Spider Mite (Tetranychuscinnabarinus)

(15) The adult spider mites (Tetranychuscinnabarinus) were put into two true leaves of bean plants. After the number of mites were investigated, the solution of certain concentrations of test compounds was sprayed by using a sprinkler. Three replicates were set for each treatment. Then the leaves were maintained in standard observation room. After 72 h the survival mites in each leaf were observed, and mortality of the mites was determined.

(16) According to above method, the representative compounds of this invention were tested against adult spider mites. Some test results were listed in Table 2.

(17) TABLE-US-00002 TABLE 2 Acaricidal activity data against adult spider mites (mortality, %) Mortality (%) Compound 100 mg/L 5 mg/L Compound 1 100 100 Compound 2 100 / Compound 3 100 / Compound 62 100 / Compound 63 100 / Note: / stands for no data.

(18) The above table showed the compounds of general formula I in the present disclosure were acaricidal. Compound 1 was taken as an example to be further tested as follows.

(19) 3.2 Test Against Deutonymph of Spider Mite (Tetranychuscinnabarinus)

(20) Ten healthy female adult spider mites (Tetranychuscinnabarinus) were put into two true leaves of bean plants. The adult spider mites were removed after 24 h and the eggs were to be continued incubating. After ten days, the number of deutonymph were investigated and recorded. The solution of certain concentrations of test compounds was sprayed by using a sprinkler. Three replicates were set for each treatment. Then the deutonymph of spider mites were maintained in standard observation room. After 72 h, the survival mites in each leaf were observed, and mortality of the mites was determined.

(21) According to above method, high acaricidal compound 1 in this invention and commercial product 95% pyridaben TC were parallel tested against deutonymph of spider mite. The test results were listed in Table 3.

(22) TABLE-US-00003 TABLE 3 Acaricidal activity data against deutonymph of spider mites (mortality, %) Mortality (%) Compound 1 mg/L 0.5 mg/L 0.25 mg/L Compound 1 100 97 64 pyridaben 84 60 25
3.3 Test Against Egg of Spider Mite (Tetranychuscinnabarinus)

(23) Two true leaves of bean plants were taken and one true leaf was removed. Then ten healthy female adult spider mites were put into the true leaf. The adult spider mites were removed after 24 h and the eggs were investigated. The solution of certain concentrations of test compounds was sprayed by using a sprinkler. Three replicates were set for each treatment. The untreated eggs were all incubated after 5 days. The unincubation of treated eggs in leaf was observed, and incubation inhibition rate of the eggs was determined.

(24) According to above method, high acaricidal compound 1 in this invention and commercial product 98% spirodiclofen TC were parallel tested against eggs of spider mites. The test results were listed in Table 4.

(25) TABLE-US-00004 TABLE 4 Acaricidal activity data against eggs of spider mites (incubation inhibition rate, %) Incubation inhibition rate (%) Compound 5 mg/L 1 mg/L 0.25 mg/L Compound 1 100 34 18 spirodiclofen 100 37 13
3.4 Test of Systemic Activity Against Spider Mite Through Root Absorption

(26) The high acaricidal compound 1 were dissolved in acetone, and then diluted with 0.1% aqueous solution of Tween 80 to form test solution in different concentration. Three replicates were set for each treatment. Water is blank control. The 10 ml compound 1 solution was added into the tube. Two true leaves bean plants were taken and the soil in the root was removed. The bean plant was dipped into the test solution in different concentration. After absorbing 24 h, 30 to 50 spider mites were put onto the true leaves. Then the bean plants were maintained in observation room at 251 C. After 72 h, the death and survival mites in each leaf was observed, the mortality of the mites and systemic activity was determined. The test results were listed in Table 5.

(27) TABLE-US-00005 TABLE 5 Systemic activity against spider mites of compound 1 through root absorption (mortality, %) Mortality (%) Compound 200 mg/L 50 mg/L Compound 1 88 80

Example 4: Field Trial

(28) Field Trial Against Citrus Red Mite (Panonychuscitri) (Jiangxi, China)

(29) The trial was carried out in a 2-year-old Shatang orange orchard in Ganzhou city Jiangxi province, trifoliate orange trees were selected as stocks, the intervals between two plants was 1.502.50 m, the average height was 1.45 m and the crown width was 1.30 m. Two trees were selected in each plot, with random arrangement and 4 replications. Compound 1 (10% SC) was set at three different doses (100 mg/L, 50 mg/L and 25 mg/L), spirodiclofen (29% SC) was set at one dose (50 mg/L), and pyridaben (20% EC) was set at one dose (100 mg/L). MatabiSupergreen 16 Knapsack Sprayer 16 Liter was used to spray evenly with 2 L of spraying volume for each plant. The plants were treated once in May at that time, adults, nymphs, eggs of citrus red mite all existed, with adults/eggs=1/1.2. During the day the plants were treated, and the weather was good with the average temperature at 24 C. The first three days after treatment were all clear days. The number of mites was investigated before treatment and on the 1st, 3rd, 7th, 14th, 22nd and 28th day after treatment respectively. Two trees of each plot were investigated according to the five directions of the tree crown (east, south, west, north and central), 5 leaves in each direction were investigated to calculate the number of living mites, with 50 leaves each plot. The decline rate of mite population and corrected efficacy were calculated according to formulas below:
The decline rate of mite population (%)=[(the average number of mite on each leaf before treatmentthe average number of mite on each leaf after treatment)/the average number of mite on each leaf before treatment]100.
Corrected efficacy (%)=[(the decline rate of mite population in treated areathe decline rate of mite population in untreated area)/(100the decline rate of mite population in untreated area)]100.

(30) The field trial results for compound 1 against citrus red mite (Ganzhou Jiangxi) were listed in Table 6.

(31) TABLE-US-00006 TABLE 6 Field trial results for compound 1 against citrusred mite in Jiangxi Corrected efficacy (%) The 1st The 3rd The 7th The 14th The 22nd The 28th Concentrations day after day after day after day after day after day after Compound (mg/L) treatment treatment treatment treatment treatment treatment Compound 1 25 9 53 74 77 75 73 50 18 87 92 91 92 92 100 25 89 97 99 99 98 spirodiclofen 50 20 48 63 80 71 70 pyridaben 100 0 65 90 93 92 95

(32) The other compounds of general formula I in the present disclosure, prepared by the methods mentioned above, showed corresponding bioefficacy.