BIPHENYL COMPOUNDS CONTAINING SUBSTITUTED SULFIDE (SULFOXIDE) GROUPS AND USES THEREOF

Abstract

The present invention belongs to the field of agricultural insecticides and acaricides. In particular, the present invention relates to a biphenyl compound containing substituted sulfide (sulfoxide) groups and a use thereof. The structure is shown in Formula I. The definitions of each substituent in the formula are described in the description. The compound of Formula I has excellent insecticidal and acaricidal activities, and can be used for preventing and treating various pests and pest mites.

##STR00001##

Claims

1-10. (canceled)

11. A biphenyl compound containing substituted sulfide (sulfoxide) groups, shown in Formula I: ##STR00019## wherein: R.sub.1 is selected from hydrogen or a halogen; R.sub.2 and R.sub.3 are each independently selected from hydrogen, cyano, cyclopropyl, C.sub.1-C.sub.3 alkyl, or C.sub.1-C.sub.3 haloalkyl; m and n are each independently selected from 0 or 1.

12. The compound according to claim 11, wherein in Formula I, R.sub.1 is selected from hydrogen, fluorine, chlorine, or bromine; R.sub.2 and R.sub.3 are each independently selected from hydrogen, cyano, cyclopropyl, methyl, ethyl, n-propyl, isopropyl, CF.sub.3, CHF.sub.2, CH.sub.2F, CH.sub.2CF.sub.3, CH.sub.2CHF.sub.2, or CH.sub.2CH.sub.2F; m and n are each independently selected from 0 or 1.

13. The compound according to claim 12, wherein in Formula I, R.sub.1 is selected from fluorine; R.sub.2 and R.sub.3 are each independently selected from hydrogen, cyano, cyclopropyl, methyl, ethyl, n-propyl, isopropyl, CF.sub.3, CHF.sub.2, CH.sub.2F, CH.sub.2CF.sub.3, CH.sub.2CHF.sub.2, or CH.sub.2CH.sub.2F; m and n are each independently selected from 0 or 1.

14. The compound according to claim 13, wherein in Formula I, R.sub.1 is selected from fluorine; R.sub.2 and R.sub.3 are selected from CF.sub.3; m and n are each independently selected from 0 or 1.

15. A compound, being an intermediate for preparing the biphenyl compound containing substituted sulfide (sulfoxide) groups according to claim 11, wherein the compound has a structure shown in Formula II: ##STR00020## wherein: R.sub.1 is selected from hydrogen or a halogen.

16. A compound, being an intermediate for preparing the biphenyl compound containing substituted sulfide (sulfoxide) groups according to claim 11, wherein the compound has a structure shown in Formula III: ##STR00021## wherein: R.sub.1 is selected from hydrogen or a halogen.

17. A compound, being an intermediate for preparing the compound according to claim 15, wherein the compound has a structure shown in Formula IV: ##STR00022## wherein: R.sub.1 is selected from hydrogen or a halogen.

18. A compound, being an intermediate for preparing the compound according to claim 16, wherein the compound has a structure shown in Formula IV: ##STR00023## wherein: R.sub.1 is selected from hydrogen or a halogen.

19. An insecticide in the fields of agriculture, forestry, and health, which is the compound of Formula I according to claim 11.

20. An acaricide in the fields of agriculture, forestry, and health, which is the compound of Formula I according to claim 11.

21. An insecticidal and acaricidal composition, comprising the compound of Formula I according to claim 11 and an agriculturally acceptable carrier, wherein the active component in the composition accounts for 0.1-99% by weight.

22. A method for controlling agricultural or forestry pests and pest mites, comprising applying an effective amount of the composition according to claim 21 to pests and pest mites in need of control or a growth medium thereof.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0093] The following specific examples are provided to further describe the present invention, but the present invention is by no means limited to such examples. (Unless otherwise indicated, all raw materials used are commercially available.) Synthesis Examples According to the synthesis schemes described above, the compounds of Formula I, Formula II, Formula III, and Formula IV of the present invention may be prepared by using different raw material compounds, respectively, which will be further described specifically below.

Example 1: the Preparation of Compound 1.22

(1) Preparation of Intermediate 4-chloro-2-fluoro-1-iodobenzene (VI-1)

[0094] ##STR00013##

[0095] 5.00 g (34.35 mmol) of 4-chloro-2-fluoroaniline (VII-1) was weighted and added into 200 mL of water and 35 mL of concentrated hydrochloric acid, cooled to a range of 0 C. to 5 C., and stirred for 30 min. 100 mL of an aqueous solution of 2.40 g (34.79 mmol) of sodium nitrite was added dropwise thereto, during which the reaction temperature was maintained not to exceed a range of 0 C. to 5 C. After the completion of dropwise addition, stirring was continued for reaction for 1 h.

[0096] 100 mL of an aqueous solution of 5.70 g (34.34 mmol) of potassium iodide was added dropwise into the diazonium salt solution, during which the reaction temperature was maintained not to exceed a range of 0 C. to 5 C. After the completion of dropwise addition, an ice bath was removed and stirring was continued at room temperature for reaction for 3 h. After the reaction was finished under TLC monitoring, 300 mL of ethyl acetate was added thereto for dilution. The organic layer was washed with 200 mL of water and 200 mL of saturated salt solution in sequence, dried with anhydrous magnesium sulfate, filtered, and desolventized under reduced pressure, and the residue was purified by column chromatography to obtain 5.70 g of a rufous liquid, i.e., the intermediate VI-1.

(2) Preparation of Intermediate 4,4-dichloro-2,2-difluoro-1,1-biphenyl (V-1)

[0097] ##STR00014##

[0098] 5.00 g (19.54 mmol) of the intermediate 4-chloro-2-fluoro-1-iodobenzene (VI-1), 7.44 g (29.31 mmol) of bis(pinacolato)diboron, 12.74 g (39.08 mmol) of cesium carbonate, 0.09 g (0.12 mmol) of [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II), and 0.06 g (0.10 mmol) of 1,1-bis(diphenylphosphino)ferrocene were added into 100 mL of 1,4-dioxane and 3 mL of water, and subjected to heating reflux for reaction for 3 h. After the reaction was finished under TLC monitoring, 200 mL of ethyl acetate was added thereto for dilution. The organic layer was washed with 200 mL of water and 200 mL of saturated salt solution in sequence, dried with anhydrous magnesium sulfate, filtered, and desolventized under reduced pressure. The residue was purified by column chromatography to obtain 2.00 g of a white solid, i.e., the intermediate V-1.

(3) Preparation of Intermediate 4,4-dichloro-6,6-difluoro-[1,1-biphenyl]-3,3-disulfonyl dichloride (IV-1)

[0099] ##STR00015##

[0100] 481.6 g (4.14 mol) of chlorosulfonic acid was added to a reaction flask, cooled using ice water to a range of 0 C. to 5 C., and 50 g (0.19 mol) of the intermediate 4,4-dichloro-2,2-difluoro-1,1-biphenyl (V-1) was added thereto, during which the temperature of the reaction mixture did not exceed 10 C. The temperature was increased to a range of 25 C. to 30 C. and maintained for reaction for 3 h. After the reaction was finished under TLC monitoring, the reaction mixture was slowly poured into crushed ice, and a solid was precipitated, which was filtered, and the filtrate was extracted with ethyl acetate and water. The organic layer was washed with saturated salt solution, dried with anhydrous magnesium sulfate, filtered, and desolventized under reduced pressure to obtain a yellowy solid. The yellowy solid was combined with the filter cake, and dried to obtain 56.0 g of another yellowy solid, i.e., the intermediate IV-1. Nuclear magnetic resonance (NMR) data of the intermediate III-1 were shown below:

[0101] .sup.1H NMR (600 MHz, DMSO-d.sub.6) 7.92-7.86 (m, 2H), 7.55-7.50 (m, 2H).

(4) Preparation of Intermediate 4,4-dichloro-6,6-difluoro-[1,1-biphenyl]-3,3-dithiol (II-1)

[0102] ##STR00016##

[0103] 0.70 g (11.69 mmol) of acetic acid, 0.39 g (0.86 mmol) of the intermediate 4,4-dichloro-6,6-difluoro-[1,1-biphenyl]-3,3-disulfonyl dichloride (IV-1), 0.16 g (5.16 mmol) of red phosphorus, 0.02 g (0.09 mmol) of iodine, and 0.35 g (3.44 mmol) of acetic anhydride were added into a reaction flask in sequence, and warmed for reflux reaction for 1 h. After the reaction was finished under TLC monitoring, the reaction mixture was hot filtered, and the mother solution was concentrated, and extracted with 100 mL of ethyl acetate and 100 mL of water such that the mother solution was layered. The organic layer was added with sodium bicarbonate to adjust the pH to a range of 6 to 7. The organic layer was then concentrated under reduced pressure to obtain 0.28 g of a yellow solid, i.e., the intermediate III-1.

[0104] 0.28 g of the yellow solid (III-1), 10 mL of tetrahydrofuran, and 0.12 g (12.86 mmol) of sodium formaldehyde sulfoxylate were added to a reaction flask, and cooled using an ice-water bath to a range of 0 C. to 5 C. An aqueous solution of sodium hydroxide (0.17 g dissolved in 10 mL of water) was added dropwise thereto, during which the temperature was controlled to a range of 0 C. to 5 C. After the completion of dropwise addition, stirring was continued for reaction for 30 min. After the reaction was finished under TLC monitoring, 20 mL of water and 20 mL of ethyl acetate were added into the reaction mixture for extraction and layering, and the organic phase was removed. Concentrated hydrochloric acid (0.44 g, 4.30 mmoL) was added dropwise into the water phase. After the completion of dropwise addition, stirring was continued for 30 min, during which a solid was precipitated continuously. 20 mL of ethyl acetate was added thereto for extraction, and the organic phase was dried with anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 0.17 g of a white solid, i.e., the intermediate II-1.

(5) Preparation of Compound 1.22

[0105] ##STR00017##

[0106] 8.00 g (24.85 mmol) of the intermediate 4,4-dichloro-6,6-difluoro-[1,1-biphenyl]-3,3-dithiol (II-1), 80 mL of acetone, 11.48 g (54.67 mmol) of potassium carbonate, 3.23 g (27.34 mmol) of sodium formaldehyde hydrosulfite, and 11.48 g (54.67 mmol) of trifluoroiodoethane were added into a reaction flask in sequence, and the reaction mixture was warmed to 50 C. for reaction for 5 h. After the reaction was finished under TLC monitoring, the reaction mixture was concentrated, and the residue was purified by column chromatography to obtain 8.45 g of a white solid, i.e., the target compound 1.22. The NMR data of the compound 1.22 were shown below: .sup.1H NMR (400 MHz, Chloroform-d) 7.65-7.61 (m, 2H), 7.36-7.32 (m, 2H), 3.45 (q, 4H).

Example 2: Preparation of Compounds 1.23 and 1.24

[0107] ##STR00018##

[0108] 0.30 g (0.62 mmol) of the compound 1.22 was dissolved in 10 mL of chloroform, cooled to a range of 0 C. to 5 C., then 0.12 g (0.70 mmol, with a purity of 85%) of metachloroperbenzoic acid was added thereto, and stirred for reaction for 1 h. After the reaction was finished under TLC monitoring, the reaction mixture was washed with an aqueous solution of sodium thiosulfate and an aqueous solution of sodium bicarbonate in sequence, dried with anhydrous magnesium sulfate, filtered, and desolventized under reduced pressure. The residue was purified by column chromatography to obtain 0.16 g of the compound 1.23 (a white solid) and 0.12 g of the compound 1.24 (a white solid). The NMR data were shown below:

[0109] Compound 1.23: .sup.1H NMR (600 MHz, Chloroform-d) 7.98 (d, 1H), 7.68 (d, 1H), 7.40-7.34 (m, 2H), 3.84-3.74 (m, 1H), 3.51-3.40 (m, 3H).

[0110] Compound 1.24: .sup.1H NMR (600 MHz, Chloroform-d) 8.05-8.00 (m, 2H), 7.41-7.36 (m, 2H), 3.84-3.73 (m, 2H), 3.53-3.41 (m, 2H).

[0111] Other compounds of Formula I of the present invention may be prepared with reference to the above examples.

Bioactivity Determination

Example 3: Bioactivity Determination on Mythimna separata and Plutella xylostella

[0112] Insecticidal activity determination experiments were conducted on several insects using the compound of the present invention and control compounds KC1, KC2, and KC3. Determination methods were described below.

[0113] The compounds to be determined were each dissolved in a mixed solvent of acetone/methanol (1:1), and diluted using water containing 0.1% (wt) tween-80 to desired concentrations.

[0114] With Mythimna separata and Plutella xylostella as targets, Airbrush spray method was adopted for activity determination.

(1) Determination of Activity Against Mythimna separata Determination Method: maize leaves were cut into 2 cm leaf pieces, and the front and back of each leaf piece were sprayed under an Airbrush spray treatment pressure of 10 psi (approximate to 0.7 kg/cm.sup.2) and with a spray volume of 0.5 mL. After drying in the shade, 10 3rd-instar larvae were inoculated for each treatment, and each treatment was repeated for 3 times. After the treatment, the leaf pieces were put into an observation chamber at 25 C. and with a relative humidity of 60% to 70%, and the number of living larvae was investigated 3 days after the administration of the compounds, and the death rates were calculated.

[0115] Partial test results for Mythimna separata were as follows:

[0116] At a dosage of 500 mg/L, 3 days after the administration of the compounds, the death rates of the compounds 1.22, 1.23, and 1.24 for Mythimna separata were above 90%, and the death rates of the control compounds KC1, KC2, and KC3 for Mythimna separata were 0.

(2) Determination of Activity Against Plutella xylostella

[0117] Determination Method: cabbage leaves were formed into leaf discs having a diameter of 2 cm using a puncher, and the front and back of each leaf disc were sprayed under an Airbrush spray treatment pressure of 10 psi (approximate to 0.7 kg/cm.sup.2) and with a spray volume of 0.5 mL. After drying in the shade, 10 3rd-instar larvae were inoculated for each treatment, and each treatment was repeated for 3 times. After the treatment, the leaf discs were placed into an observation chamber at 25 C. and with a relative humidity of 60% to 70%, and the number of living larvae was investigated 3 days after the administration of the compounds, and the death rates were calculated.

Partial Test Results for Plutella xylostella were as Follows:

[0118] At a dosage of 500 mg/L, 3 days after the administration of the compounds, the death rates of the compounds 1.22, 1.23, and 1.24 for Plutella xylostella were above 90%, and the death rates of the control compounds KC1, KC2, and KC3 for Plutella xylostella were 0.

Example 4: Acaricidal Activity Determination

[0119] Greenhouse acaricidal activity determination was carried out on the compounds of the present invention. A determination method was described below.

[0120] Each compound to be determined was dissolved in acetone or dimethyl sulfoxide according to the solubility thereof, and prepared into 50 mL of a solution to be determined at a desired concentration with a tween-80 solution of 0.1%, where a content of the acetone or dimethyl sulfoxide in the solution did not exceed 10%.

[0121] Two true leaves of Phaseolus vulgaris seedlings were inoculated with adult Tetranychus cinnabarinus and a basic number was investigated. An entire seedling was then sprayed using a hand-held sprayer. Each treatment was repeated for 3 times. After the treatment, the seedlings were placed into a standard observation chamber, and the number of living mites was investigated 72 hours later, and the death rates were calculated.

Test Results were as Follows:

[0122] When the concentration of the solution was 5 mg/L, the death rates of the compounds 1.22, 1.23, and 1.24 for Tetranychus cinnabarinus were above 90%.

[0123] Parallel comparison experiments on acaricidal activity were conducted for Tetranychus cinnabarinus using the compounds 1.22, 1.23, and 1.24 and control compounds (3 days after the administration of the compounds), and the determination method was as described above; and the results were shown in Table 14:

TABLE-US-00006 TABLE 14 Parallel comparison experiments on acaricidal activity for Tetranychus cinnabarinus using the compounds 1.22, 1.23, and 1.24 and control compounds Death Rate (%, 3 days after the Compound administration of the compounds) No. 2.5 mg/L 1.25 mg/L 1.22 92.4 87.7 KC1 52.0 22.9 1.23 93.8 43.9 KC2 50.0 0 1.24 80.0 20.2 KC3 0 0

[0124] By a comparison between the compound 1.22 of the present invention and the control compound KC1, a comparison between the compound 1.23 of the present invention and the control compound KC2, and a comparison between the compound 1.24 of the present invention and the control compound KC3, it could be seen that the compounds of the present invention have higher acaricidal activity than those in the prior art.

[0125] The inventors of the present invention conducted a lot of experiments, and replaced the methyl on the biphenyl structure in the prior art with the chlorine atom on the basis of the molecular skeletons of existing compounds, thus obtaining the compound of Formula I of the present invention. As can be seen from the activity comparison experiments of Example 3 and Example 4, compared with the prior art, the compound of the present invention have unexpected better insecticidal and acaricidal activities.

[0126] In an organic molecule, due to different electronegativeties, volumes, or spatial configurations of substituents, the entire molecule may differ greatly in conduction performance or receptor-binding in organisms such as insects, mites, and plants, and may also exhibit a great bioactivity difference, and the conduction performance and the receptor-binding suitability of the molecule are unpredictable and can be known with a lot of creative efforts. Therefore, the present invention possesses prominent substantive features and represents a notable progress.