SUBSTITUTED PHENYL SULFIDE COMPOUND AND APPLICATION THEREOF

Abstract

The present invention belongs to the field of agricultural acaricides, and particularly relates to a substituted phenyl sulfide compound and an application thereof. The substituted phenyl sulfide compound is as represented in general formula I. Definitions of substituted groups in the formula are given in the description. The compound of the general formula I has excellent acaricidal activity and can be used for preventing and controlling various mites.

##STR00001##

Claims

1. A substituted phenyl sulfide compound represented by the general formula I: ##STR00009## wherein: R.sup.1 is selected from nitro, cyano, C.sub.1-C.sub.4 alkylthio, trifluoromethanesulfonyl or SCH.sub.2CF.sub.3; R.sup.2 is selected from halogen, cyano or C.sub.1-C.sub.4 alkyl; n is selected from 0, 1 or 2.

2. The compound according to claim 1, wherein: R.sup.1 is selected from nitro, cyano, C.sub.1-C.sub.4 alkylthio, trifluoromethanesulfonyl or SCH.sub.2CF.sub.3; R.sup.2 is selected from fluorine, chlorine or methyl; n is selected from 0 or 1.

3. The compound according to claim 2, wherein: R.sup.1 is selected from nitro, cyano, methylthio, ethylthio or SCH.sub.2CF.sub.3; R.sup.2 is selected from chlorine or methyl; n is selected from 0 or 1.

4. The compound according to claim 3, wherein: R.sup.1 is selected from nitro, cyano, methylthio, ethylthio or SCH.sub.2CF.sub.3; R.sup.2 is selected from methyl; n is selected from 0 or 1.

5. The compound according to claim 4, wherein: R.sup.1 is selected from nitro, methylthio or SCH.sub.2CF.sub.3; R.sup.2 is selected from methyl; n is selected from 0 or 1.

6. An application of the compound of the general formula I of claim 1 as an acaricide in the fields of agriculture, forestry or public health.

7. An acaricidal composition, comprising the compounds of the general formula I of claim 1 as an active ingredient and an acceptable carrier in agriculture, in which the weight percentage of the active ingredient(s) is 0.1-99%.

Description

DETAILED DESCRIPTION

[0055] The following specific embodiments are used to further illustrate the present invention, but the present invention is not limited to these examples.

Synthesis Embodiments

Embodiment 1: Preparation of Compound 1

[0056] 3-Cyanophenylboronic acid (1.47 g, 10.0 mmol), 2-fluoro-4-methyl-5-trifluoroethylthio bromobenzene (3.00 g, 10.0 mmol), 1,1′-bis (diphenylphosphino) ferrocene-palladium (II) dichloride dichloromethane complex (0.1 g) and potassium carbonate (2 g) were added to a 100 ml three-necked flask. Then a mixed solution of ethylene glycol dimethyl ether (20 ml) and water (10 ml) was added. The reaction mixture was heated at reflux for 4 hours under stirring, and the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature, and was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure; and the residue was purified by column chromatography to obtain white solid (2.60 g). .sup.1H NMR (600 MHz, CDCl.sub.3) δ (ppm): 7.80 (s, 1H), 7.74-7.72 (m, 1H), 7.66-7.65 (m, 1H), 7.60 (d, 1H), 7.55 (t, 1H), 7.10 (d, 1H), 3.35(q, 2H), 2.54 (s, 3H).

Embodiment 2: Preparation of Compound 5

[0057] 3-Nitrophenylboronic acid (1.67 g, 10.0 mmol), 2-fluoro-4-methyl-5-trifluoroethylthio bromobenzene (3.00 g, 10.0 mmol), 1,1′-bis (diphenylphosphino) ferrocene-palladium (II) dichloride dichloromethane complex (0.1 g) and potassium carbonate (2 g) were added to a 100 ml three-necked flask. Then a mixed solution of ethylene glycol dimethyl ether (20 ml) and water (10 ml) was added. The reaction mixture was heated at reflux for 4 hours under stirring, and the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature, and was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure; and the residue was purified by column chromatography to obtain pale yellow solid (2.80 g). .sup.1H NMR (600 MHz, CDCl.sub.3) δ (ppm): 8.39 (s, 1H), 8.25-8.23 (m, 1H), 7.86-7.84 (m, 1H), 7.66 (d, 1H), 7.63 (t, 1H), 7.12 (d, 1H), 3.36(q, 2H), 2.55 (s, 3H).

Embodiment 3: Preparation of Compound 6

[0058] Compound 5 (0.35 g, 1.0 mmol) was added to a flask with chloroform (10 ml), and then 3-chloroperoxybenzoic acid (0.25 g, 1.0 mmol, content of 70-75%) was added in an ice water bath. The reaction mixture was stirred for 2 hours, and diluted with chloroform, washed with aqueous sodium thiosulfate solution and aqueous sodium bicarbonate solution in sequence. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure; and the residue was purified by column chromatography to obtain white solid (0.31 g). .sup.1H NMR (600 MHz, CDCl.sub.3) δ (ppm): 8.46 (s, 1H), 8.29-8.27 (m, 1H), 8.10 (d, 1H), 7.92-7.90 (m, 1H), 7.66 (t, 1H), 7.16 (d, 1H), 3.54-3.45 (m, 2H), 2.37 (s, 3H).

Embodiment 4: Preparation of Compound 14

[0059] 3-(Methylthio)phenylboronic acid (1.68 g, 10.0 mmol), 2-fluoro-4-methyl-5-trifluoroethylthio bromobenzene (3.00 g, 10.0 mmol), 1,1′-bis (diphenylphosphino) ferrocene-palladium (II) dichloride dichloromethane complex (0.1 g) and potassium carbonate (2 g) were added to a 100 ml three-necked flask. Then a mixed solution of ethylene glycol dimethyl ether (20 ml) and water (10 ml) was added. The reaction mixture was heated at reflux for 4 hours under stirring, and the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature, and was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure; and the residue was purified by column chromatography to obtain an oil (2.75 g). .sup.1H NMR (600 MHz, CDCl.sub.3) δ (ppm): 7.61 (d, 1H), 7.39-7.34 (m, 2H), 7.28-7.26 (m, 2H), 7.05 (d, 1H), 3.34(q, 2H), 2.52-2.50 (m, 6H).

Embodiment 5: Preparation of Compound 17

[0060] 3-(Ethylthio)phenylboronic acid (1.82 g, 10.0 mmol), 2-fluoro-4-methyl-5-trifluoroethylthio bromobenzene (3.00 g, 10.0 mmol), 1,1′-bis (diphenylphosphino) ferrocene-palladium (II) dichloride dichloromethane complex (0.1 g) and potassium carbonate (2 g) were added to a 100 ml three-necked flask. Then a mixed solution of ethylene glycol dimethyl ether (20 ml) and water (10 ml) was added. The reaction mixture was heated at reflux for 4 hours under stirring, and the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature, and was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure; and the residue was purified by column chromatography to obtain an oil (2.80 g). .sup.1H NMR (600 MHz, CDCl.sub.3) δ (ppm): 7.61 (d, 1H), 7.45 (m, 1H), 7.37-7.30 (m, 3H), 7.05 (d, 1H), 3.34(q, 2H), 2.99(q, 2H), 2.52 (s, 3H), 1.35 (t, 3H).

Embodiment 6: Preparation of Compound 19

[0061] 3-(2,2,2-Trifluoroethylthio)phenylboronic acid (2.36 g, 10.0 mmol), 2-fluoro-4-methyl-5-trifluoroethylthio bromobenzene (3.00 g, 10.0 mmol), 1,1′-bis (diphenylphosphino) ferrocene-palladium (II) dichloride dichloromethane complex (0.1 g) and potassium carbonate (2 g) were added to a 100 ml three-necked flask. Then a mixed solution of ethylene glycol dimethyl ether (20 ml) and water (10 ml) was added. The reaction mixture was heated at reflux for 4 hours under stirring, and the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature, and was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure; and the residue was purified by column chromatography to obtain an oil (3.10 g). .sup.1H NMR (600 MHz, CDCl.sub.3) δ (ppm): 7.64-7.63 (m, 1H), 7.61 (d, 1H), 7.51-7.48 (m, 1H), 7.46-7.40 (m, 2H), 7.07 (d, 1H), 3.49(q, 2H), 3.34(q, 2H), 2.53 (s, 3H).

[0062] Determination of Biological Activity

Embodiment 7: Determination of Activity Against Adult Spider Mite(Tetranychus cinnabarinus)

[0063] According to the solubility of test compounds, the compounds were dissolved with acetone or dimethyl sulfoxide, and then diluted with 0.1% aqueous solution of Tween 80 to form 50 ml test liquid and the content of the acetone or the dimethyl sulfoxide in the total solution was not more than 10% for later use. The adult spider mites 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 handheld Airbrush. Three replicates were set for each treatment. Then the leaves were maintained in standard observation room. After 72 h, the number of surviving mites were observed, and the mortality rate was calculated.

[0064] Among some of the testing compounds, compounds 1, 2, 3, 5, 6, 8, 9, 11, 14, 17 and 19 showed better control effects against adult spider mites at a concentration of 10 mg/L, and the mortality was greater than 90%.

[0065] Among some of the testing compounds, compounds 1, 5, 6 and 14 showed better control effects against adult spider mites at a concentration of 5 mg/L, and the mortality was greater than 90%.

[0066] According to the above test method, compounds 5, 6 and 8 as well as compounds KC1, KC2, KC3, KC4, KC5 and KC6 were selected for parallel determination of activity against adult spider mites. See Table 2 for test results.

TABLE-US-00002 TABLE 2 Mortality (%) Compound 1.25 mg/L 0.625 mg/L 5 100 95.5 6 97.6 80.6 8 90.7 65.2 KC1 36.5 — KC2 56.6 — KC3 50.7 — KC4 16.4 — KC5 71.7 29.8 KC6 0 —

[0067] KC5 and KC6 are comparative compounds prepared by replacing 3-cyanophenylboronic acid with p-nitrophenylboronic acid and o-nitrophenylboronic acid respectively according to the method of synthesis embodiment 1. The physical property data of KC5: .sup.1H NMR (600 MHz, CDCl.sub.3) δ (ppm): 8.30 (d, 2H), 7.68 (d, 2H), 7.65 (d, 1H), 7.10 (d, 1H), 3.35(q, 2H), 2.54 (s, 3H); The physical property data of KC6: .sup.1H NMR (600 MHz, CDCl.sub.3) δ (ppm): 8.04 (d, 1H), 7.69-8.66 (m, 1H), 7.57-7.54 (m, 1H), 7.52 (d, 1H), 7.40 (d, 1H), 7.02 (d, 1H), 3.34(q, 2H), 2.53 (s, 3H). The specific structure is as follows.

##STR00008##

Embodiment 8: Determination of Activity Against Egg of Spider Mite (Tetranychus Cinnabarinus)

[0068] According to the solubility of test compounds, the compounds were dissolved with acetone or dimethyl sulfoxide, and then diluted with 0.1% aqueous solution of Tween 80 to form 50 ml test liquid and the content of the acetone or the dimethyl sulfoxide in the total solution was not more than 10% for later use. The leaves of bean were chopped into leaf discs and put into a petri dish. Female adult mites were inoculated. After laying eggs, the female adult mites were removed. After the number of eggs were investigated, the solution of certain concentrations of test compounds were sprayed with a POTTER spray tower, for 2 mL per treatment, and blank control was set. When all eggs in the blank control were incubated, the number of eggs which were incubated and unincubated was recorded, and incubation inhibition rate of the eggs was calculated.

[0069] Among some of the testing compounds, compounds 1, 5, 6, 11, 14, 17 and 19 showed better control effects against spider mite eggs at a concentration of 10 mg/L, and the mortality was greater than 90%.

[0070] Among some of the testing compounds, compounds 5, 6, 14 and 19 showed better control effects against spider mite eggs at a concentration of 5 mg/L, and the mortality was greater than 90%.

[0071] According to the above test method, compounds 5, 14 and 19 as well as known compounds KC1, KC2, KC3 and KC4 were selected for parallel determination of activity against spider mite eggs. See Table 3 for test results.

TABLE-US-00003 TABLE 3 Inhibition Rate (%) Compound 1.25 mg/L 0.625 mg/L 5 100 100 14 95.8 65.3 19 81.1 51.2 KC1 26.2 — KC2 36.7 — KC3 20.7 — KC4 40.8 —

Embodiment 9: Biological Activity for Controlling Panonychus ulmi (Field Trial)

[0072] The trial was carried out in the orchard of Research Institute of Pomology of Chinese Academy of Agricultural Sciences. The test sample was Starkrimson apple tree, whichwas 14 years old and the intervals between two plants was 2×4 m. The test compound 14 was set at two different doses of 50 mg/L and 100 mg/L, and Spirodiclofen suspension agent as the positive control was set at one dose of 50 mg/L. The test method was spraying by using the stretcher power sprayer, each treatment repeated three times. The number of initial mites was investigated before spraying, and the number of surviving mites was checked and recorded. The number of surviving mites was investigated on the 3 days, 7 days, 14 days and 21 days after spraying respectively. The decline rate of mite population was counted and the control efficiency was calculated.

[00001]$\mathrm{Control}\mathrm{efficiency}\left(\%\right)=\left(1-\frac{\mathrm{number}\mathrm{of}\mathrm{mites}\mathrm{before}\mathrm{CK}\mathrm{treatment}\times \mathrm{number}\mathrm{of}\mathrm{mites}\mathrm{after}\mathrm{pesticide}\mathrm{application}}{n\mathrm{umber}\mathrm{of}\mathrm{mites}\mathrm{after}\mathrm{CK}\mathrm{treatment}\times \mathrm{number}\mathrm{of}\mathrm{mites}\mathrm{before}\mathrm{pesticide}\mathrm{application}}\right)\times 100$

The field trial results for compound 14 against Panonychus ulmi (Xingcheng, Liaoning, May, 2018) were shown in Table 4.Table 4

TABLE-US-00004 TABLE 4 Control efficiency (%) 3 days after 7 days after 14 days after 21 days after Concentration pesticide pesticide pesticideg pesticide Compound (mg/L) application application application application 14 50 92.2 86.4 97.3 93.2 100 94.4 96.6 99.8 99.1 Spirodiclofen 50 49.6 45.8 90.3 94.9

Embodiment 10: Biological Activity Against Panonychus citri (Field Trial)

[0073] The trial was carried out in the citrus orchard in Yibin City, Sichuan Province. The test sample was “Dekopon”. The test citrus trees were 4 years old and the planting density was more than 70 plants/mu. The test compounds 6 and 14 were set at two different doses of 50 mg/L and 100 mg/L.

[0074] As the positive controls, Spirodiclofen suspension agent was set at one dose of 100 mg/L, and Pyridaben wettable powder was set at one dose of 100 mg/L. The test method was spraying by using Pentium 3WBD-20 sprayer, each treatment repeated three times. The number of initial mites was investigated before spraying, and the number of surviving mites was checked and recorded. The number of surviving mites was investigated on the 3 days, 7 days, 14 days, 21 days and 30 days after spraying respectively. The decline rate of mite populationg was counted and the control efficiency was calculated.

[00002]$\mathrm{Control}\mathrm{efficiency}\left(\%\right)=\left(1-\frac{\mathrm{number}\mathrm{of}\mathrm{mites}\mathrm{before}\mathrm{CK}\mathrm{treatment}\times \mathrm{number}\mathrm{of}\mathrm{mites}\mathrm{after}\mathrm{pesticide}\mathrm{application}}{n\mathrm{umber}\mathrm{of}\mathrm{mites}\mathrm{after}\mathrm{CK}\mathrm{treatment}\times \mathrm{number}\mathrm{of}\mathrm{mites}\mathrm{before}\mathrm{pesticide}\mathrm{application}}\right)\times 100$

[0075] The field trial results for compound 6 and 14 against Panonychus citri (Yibin, Sichuan, September, 2019) were shown in Table 5.

TABLE-US-00005 TABLE 5 Control efficiency (%) 21 days 3 days after 7 days after 14 days after after 30 days after Concentration pesticide pesticide pesticide pesticide pesticide Compound (mg/L) application application application application application 6 50 98.58 96.69 99.28 95.86 94.62 14 100 99.24 96.92 97.14 96.30 95.71 50 99.61 98.90 99.08 98.57 97.35 100 99.65 98.31 98.93 96.95 97.19 Spirodiclofen 100 91.09 80.88 80.88 72.63 73.60 Pyridaben 100 80.24 61.51 61.51 51.62 56.60

[0076] In order to discover new phenyl sulfide derivatives with higher acaricidal activity, it is not obvious to find that the acaricidal activity is greatly influenced by the position of substituent on the benzene ring, which is at the fifth position of the benzene in (4-fluoro-2-substituted phenyl)-2,2,2-trifluoroethyl sulfide (sulfoxide or sulphone) structure. Compounds with substituents at the intersite position have the best activity, and the substituents nitro, methylthio or SCH.sub.2CF.sub.3, at the intersite position are preferred. The new substituted phenyl sulfide compounds of the present invention show high acaricidal activity at 10 mg/L and exhibit excellent acaricidal activity at 1.25 mg/L as well, and are safe for crops.

[0077] Other compounds of general formula I in the present invention disclosure, prepared by the methods mentioned above, showed corresponding bioefficacy.