Fluorophenyl ether derivative containing trifluoromethyl as well as preparation method and application of fluorophenyl ether derivative

Abstract

The embodiment of the invention discloses a fluorophenyl ether derivative containing trifluoromethyl as well as a preparation method and application thereof, and belongs to the technical field of pesticides. The phenyl ether derivative containing trifluoromethyl has a structure as shown in a general formula (I), in the general formula (I), A is S or S = O, X is halogen, R is hydrogen, alkyl or halogen substituted thiazolyl, alkyl or aryl substituted acylamino, and n is 0, 1, 2 or 3. The phenyl ether derivative containing trifluoromethyl provided by the invention has better anti-mite activity. The synthesis method provided by the invention is simple, the raw materials are cheap and easy to obtain, and a novel anti-mite pesticide is expected to be developed. (I).

Description

Technical Field

[0001] The embodiments of this invention relate to the field of pesticide technology, specifically to fluorophenyl ether derivatives containing trifluoromethyl, their preparation methods, and applications. Background Technology

[0002] Mites are a group of small arthropods with diverse morphology, habits, and habitats, mainly divided into two categories: herbivorous and predatory. Among them, herbivorous mites are recognized as major global agricultural pests because they damage almost all crops worldwide. In addition, agricultural mites are also characterized by their small size, rapid growth and reproduction, short generation cycle, strong environmental adaptability, and susceptibility to resistance, making them one of the most difficult groups of pests to control in the world.

[0003] Therefore, the search for a new and highly effective acaricide is urgently needed. To date, there are no reports in the art regarding the application of the trifluoromethyl-containing fluorophenyl ether derivatives of this invention in mite pests. Summary of the Invention

[0004] Therefore, embodiments of the present invention provide fluorophenyl ether derivatives containing trifluoromethyl, their preparation methods, and applications.

[0005] To achieve the above objectives, the embodiments of the present invention provide the following technical solutions:

[0006] According to a first aspect of the present invention, the present invention provides a trifluoromethyl-containing fluorophenyl ether derivative having a structure as shown in general formula (I).

[0007] (I),

[0008] Where A is S or S=O, X is a halogen, R is a hydrogen, alkyl or halogen-substituted thiazolyl, alkyl or aryl-substituted amide, and n is 0, 1, 2 or 3.

[0009] Further, for compounds represented by formulas cs-001 to cs-015,

[0010] .

[0011] According to a second aspect of the present invention, the present invention provides a method for preparing a trifluoromethyl-containing fluorophenyl ether derivative as described above, the method comprising: a condensation reaction of a compound of general formula (II) and a compound of general formula (III) in the presence of an acid-binding agent and an organic solvent;

[0012] (II), (III),

[0013] The definitions of A, X, R, and n are the same as in claim 1.

[0014] Furthermore, the molar ratio of the compound represented by general formula (II) to the compound represented by general formula (III) is 1:1-1.05;

[0015] The molar ratio of the compound represented by general formula (II) to the acid-binding agent is 1:2.5-5.

[0016] Furthermore, the conditions for the condensation reaction are: room temperature to reflux temperature, 5-20 hours.

[0017] Furthermore, the acid-binding agent is cesium carbonate, potassium carbonate, or potassium tert-butoxide;

[0018] The organic solvent is tetrahydrofuran, acetonitrile, 1,4-dioxane, N,N-dimethylformamide, or dimethyl sulfoxide.

[0019] According to a third aspect of the present invention, the present invention provides a composition comprising, as described above, a trifluoromethyl-containing fluorophenyl ether derivative and a pharmaceutically acceptable pharmaceutical carrier and / or excipient.

[0020] According to a fourth aspect of the present invention, the present invention provides the use of the trifluoromethyl-containing fluorophenyl ether derivatives or the compositions described above in the preparation of anti-mite agents.

[0021] The pharmaceutical carrier or excipient is one or more solid, semi-solid, and liquid diluents, fillers, and pharmaceutical excipients. The compositions of this invention are used in doses per unit body weight. The compositions of this invention are prepared into various dosage forms, such as liquid formulations (solutions, suspensions) and solid formulations (tablets, powders), using methods recognized in the pesticide and pharmaceutical fields. The drugs of this invention can be administered via spraying, dusting, pouring, spreading, seed dressing, and other routes for the prevention and treatment of mite pests.

[0022] The embodiments of the present invention have the following advantages:

[0023] The trifluoromethyl-containing fluorophenyl ether derivatives provided by this invention have superior anti-mite activity (LC). 50 (0.1-4.6 μg / mL). Furthermore, the synthesis method of this compound is simple, and the raw materials are inexpensive and readily available, making it a promising candidate for development into a novel anti-mite pesticide. Detailed Implementation

[0024] The following specific embodiments illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] Example 1

[0026] This embodiment provides the preparation of compound cs-001:

[0027]

[0028] 4-Chloro-2-fluoro-5-((2,2,2-trifluoroethyl)sulfinyl)phenol (27.6 g, 100.0 mmol) was dissolved in DMF (70 mL). Potassium carbonate (300.0 mmol) and 2-chloro-5-(chloromethyl)thiazole (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 70°C and reacted for 8 h. HPLC analysis showed the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with water (50 mL) and dried to give a white solid compound CS-001 (37.5 g), with a yield of 92% and a purity of 98.9%.

[0029] NMR and MS of cs-001:

[0030] 1 H NMR (500 MHz, DMSO-d6) δ 9.17 (dd, J = 2.3, 1.6 Hz, 1H), 8.81 (s,1H), 8.73 (ddd, J = 4.5, 2.6, 1.6 Hz, 1H), 8.28 (dt, J = 7.9, 2.4 Hz, 1H), 7.50 (dd, J = 7.9, 4.8 Hz, 1H), 7.35 (t, J = 7.6 Hz, 2H), 7.10 (t, J = 7.4Hz, 1H), 7.00 (dd, J = 7.9, 1.3 Hz, 2H), 6.83 (s, 2H), 3.15 (qd, J = 6.9, 6.3Hz, 2H), 1.28 (d, J = 6.5 Hz, 11H).

[0031] 13C NMR (125 MHz, DMSO-d6) δ 155.9, 153.1, 148.7, 143.1, 138.1, 137.6,123.4, 119.9, 112.2, 110.5, 64.1, 62.9.

[0032] ESI-MS m / z: 409 [M+H] + .

[0033] Example 2

[0034] This embodiment provides the preparation of compound cs-002:

[0035]

[0036] 4-Bromo-2-fluoro-5-((2,2,2-trifluoroethyl)sulfinyl)phenol (32.1 g, 100.0 mmol) was dissolved in DMF (70 mL). Potassium carbonate (300.0 mmol) and 2-chloro-5-(chloromethyl)thiazole (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 70°C and reacted for 8 h. HPLC analysis showed the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with water (50 mL) and dried to give a white solid compound CS-002 (40.7 g), with a yield of 90% and a purity of 97.6%.

[0037] NMR and MS of cs-002:

[0038] 1 H NMR (500 MHz, DMSO-d6) δ 9.24 (d, J = 1.5 Hz, 1H), 8.91 – 8.65 (m,3H), 7.42 – 7.23 (m, 2H), 7.10 (tt, J = 7.3, 1.3 Hz, 1H), 7.05 – 6.94 (m,2H), 6.83 (s, 2H), 3.24 – 2.94 (m, 2H), 1.28 (d, J = 6.5 Hz, 12H).

[0039] 13 C NMR (125 MHz, DMSO-d6) δ 156.7, 153.1, 149.6, 146.0, 138.1, 137.6,122.8, 113.0, 112.0, 110.5, 63.9, 62.9.

[0040] ESI-MS m / z: 453 [M+H]+ .

[0041] Example 3

[0042] This embodiment provides the preparation of compound cs-003:

[0043]

[0044] 4-Chloro-2-fluoro-5-((2,2,2-trifluoroethyl)-thio)phenol (26.0 g, 100.0 mmol) was dissolved in DMF (70 mL). Potassium carbonate (300.0 mmol) and 2-chloro-N-(3-trifluoromethylphenyl)acetamide (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 65°C and reacted for 10 h. HPLC analysis showed the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with water (50 mL) and dried to give a white solid compound CS-003 (36.9 g), with a yield of 80% and a purity of 98.0%.

[0045] NMR and MS of cs-003:

[0046] 1 H NMR (500 MHz, DMSO-d6) δ 8.94 (s, 1H), 8.67 (dd, J = 4.2, 1.7 Hz, 1H), 8.21 (dd, J = 7.8, 1.5 Hz, 1H), 7.94 (td, J = 7.5, 1.7 Hz, 1H), 7.43(ddd, J = 7.3, 4.2, 1.5 Hz, 1H), 7.39 – 7.32 (m, 2H), 7.10 (tt, J = 7.3, 1.3Hz, 1H), 7.03 – 6.97 (m, 2H), 6.83 (s, 2H), 3.15 (qd, J = 6.9, 6.3 Hz, 2H),1.28 (d, J = 6.5 Hz, 12H).

[0047] 13 C NMR (125 MHz, DMSO-d6) δ 122.7, 132.6, 149.9, 147.8, 138.8, 131.2,119.0, 114.5, 124.9, 125.7, 120.7, 129.2, 44.9, 124.1, 114.9, 167.6, 66.6.

[0048] ESI-MS m / z: 462 [M+H]+ .

[0049] Example 4

[0050] This embodiment provides the preparation of compound cs-004:

[0051]

[0052] 4-Chloro-2-fluoro-5-((2,2,2-trifluoroethyl)sulfinyl)phenol (27.6 g, 100.0 mmol) was dissolved in DMF (70 mL). Potassium carbonate (300.0 mmol) and 2-chloro-N-(2,2,2-trifluoroethyl)acetamide (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 70°C and reacted for 12 h. HPLC analysis showed the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with water (50 mL) and dried to give a white solid compound CS-004 (35.3 g), with a yield of 85% and a purity of 99.6%.

[0053] NMR and MS of cs-004:

[0054] 1 H NMR (500 MHz, DMSO-d6) δ 8.23 ​​(s, 1H), 7.39 – 7.32 (m, 2H), 7.10 (tt, J = 7.3, 1.3 Hz, 1H), 7.03 – 6.97 (m, 2H), 6.78 (s, 2H), 3.14 – 3.02 (m,2H), 2.35 (t, J = 8.7 Hz, 2H), 1.65 (tt, J = 8.6, 6.6 Hz, 2H), 1.45 – 1.34(m, 2H), 1.28 (d, J = 6.6 Hz, 12H), 0.92 (t, J = 7.4 Hz, 3H).

[0055] 13 C NMR (125 MHz, DMSO-d6) δ 123.4, 143.1, 155.9, 148.7, 119.9, 112.2, 64.1, 110.5, 124.7, 168.6, 67.0, 39.4.

[0056] ESI-MS m / z: 416 [M+H] + .

[0057] Example 5

[0058] This embodiment provides the preparation of compound cs-005:

[0059]

[0060] 4-Chloro-2-fluoro-5-((2,2,2-trifluoroethyl)-thio)phenol (26.0 g, 100.0 mmol) was dissolved in DMF (70 mL). Potassium carbonate (300.0 mmol) and 2-chloro-N-ethylacetamide (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 70°C and reacted for 12 h. HPLC analysis showed the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with water (50 mL) and dried to give a white solid compound CS-005 (32.8 g), with a yield of 95% and a purity of 96.3%.

[0061] NMR and MS of cs-005:

[0062] 1 H NMR (500 MHz, DMSO-d6) δ 7.39 – 7.32 (m, 2H), 7.10 (tt, J = 7.3,1.3 Hz, 1H), 7.03 – 6.97 (m, 2H), 6.78 (s, 2H), 3.14 – 3.02 (m, 2H), 1.28 (d,J = 6.6 Hz, 12H).

[0063] 13 C NMR (125 MHz, DMSO-d6) δ 122.7, 132.6, 149.9, 147.8, 119.0, 114.5,44.9, 114.9, 168.6, 67.0, 34.1, 15.0.

[0064] ESI-MS m / z: 346 [M+H] + .

[0065] Example 6

[0066] This embodiment provides the preparation of compound cs-006:

[0067]

[0068] 4-Chloro-2-fluoro-5-((2,2,2-trifluoroethyl)-thio)phenol (26.0 g, 100.0 mmol) was dissolved in DMF (70 mL). Potassium carbonate (300.0 mmol) and 2-chloro-N-benzylacetamide (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 70°C and reacted for 14 h. HPLC analysis showed the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with water (50 mL) and dried to give a white solid compound CS-006 (30.5 g), with a yield of 75% and a purity of 98.1%.

[0069] NMR and MS of cs-006:

[0070] 1 H NMR (500 MHz, DMSO-d6) δ 8.02 (s, 1H), 7.39 – 7.32 (m, 2H), 7.10 (tt, J = 7.3, 1.3 Hz, 1H), 7.03 – 6.97 (m, 2H), 6.78 (s, 2H), 3.14 – 3.02 (m,2H), 2.37 (q, J = 7.1 Hz, 2H), 1.28 (d, J = 6.6 Hz, 12H), 1.18 (t, J = 7.1Hz, 3H).

[0071] 13 C NMR (125 MHz, DMSO-d6) δ 122.7, 132.6, 149.9, 147.8, 137.9, 119.0,114.5, 126.9, 128.5, 128.5, 126.7, 44.9, 114.9, 168.9, 67.0, 43.6.

[0072] ESI-MS m / z: 408 [M+H] + .

[0073] Example 7

[0074] This embodiment provides the preparation of compound cs-007:

[0075]

[0076] 4-Chloro-2-fluoro-5-((2,2,2-trifluoroethyl)-thio)phenol (26.0 g, 100.0 mmol) was dissolved in DMF (70 mL). Potassium carbonate (300.0 mmol) and 2-bromo-5-(chloromethyl)thiazole (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 70°C and reacted for 14 h. HPLC analysis showed the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with water (50 mL) and dried to give a white solid compound CS-007 (39.2 g), with a yield of 90% and a purity of 97.8%.

[0077] NMR and MS of cs-007:

[0078] 1 H NMR (500 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.39 – 7.32 (m, 2H), 7.10 (tt, J = 7.3, 1.3 Hz, 1H), 7.03 – 6.97 (m, 2H), 6.78 (s, 2H), 3.14 – 3.02 (m,2H), 2.29 (t, J = 6.2 Hz, 2H), 1.62 (dtd, J = 13.7, 7.5, 6.1 Hz, 2H), 1.28(d, J = 6.6 Hz, 12H), 0.98 (t, J = 7.6 Hz, 3H).

[0079] 13 C NMR (125 MHz, DMSO-d6) δ 136.7, 139.9, 140.7, 122.7, 132.6, 149.9,147.8, 119.0, 114.5, 44.9, 114.9, 62.7.

[0080] ESI-MS m / z: 437 [M+H] + .

[0081] Example 8

[0082] This embodiment provides the preparation of compound cs-008:

[0083]

[0084] 4-Chloro-2-fluoro-5-((2,2,2-trifluoroethyl)-thio)phenol (26.0 g, 100.0 mmol) was dissolved in DMF (70 mL). Potassium carbonate (300.0 mmol) and 5-chloromethyl-thiazole (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 70°C and reacted for 4 h. HPLC analysis showed the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with water (50 mL) and dried to give a white solid compound CS-008 (34.6 g), with a yield of 97% and a purity of 98.5%.

[0085] NMR and MS of cs-008:

[0086] 1 H NMR (500 MHz, DMSO-d6) δ 8.23 ​​(s, 1H), 7.39 – 7.32 (m, 2H), 7.10 (tt, J = 7.3, 1.3 Hz, 1H), 7.03 – 6.97 (m, 2H), 6.78 (s, 2H), 3.14 – 3.02 (m,2H), 2.32 (t, J = 8.0 Hz, 2H), 1.68 – 1.58 (m, 2H), 1.39 – 1.29 (m, 8H), 1.27(s, 8H), 0.92 – 0.86 (m, 3H).

[0087] 13 C NMR (125 MHz, DMSO-d6) δ 153.9, 133.3, 141.5, 122.7, 132.6, 149.9,147.8, 119.0, 114.5, 44.9, 114.9, 63.47.

[0088] ESI-MS m / z: 358 [M+H] + .

[0089] Example 9

[0090] This embodiment provides the preparation of compound cs-009:

[0091]

[0092] 4-Chloro-2-fluoro-5-((2,2,2-trifluoroethyl)-thio)phenol (26.0 g, 100.0 mmol) was dissolved in DMF (70 mL). Potassium carbonate (300.0 mmol) and 2-methyl-5-(chloromethyl)thiazole (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 70°C and reacted for 8 h. HPLC analysis showed the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with water (50 mL) and dried to give a white solid compound CS-009 (31.5 g), with a yield of 85% and a purity of 98.8%.

[0093] NMR and MS of cs-009:

[0094] 1 H NMR (500 MHz, DMSO-D6) δ 9.17 (dd, J = 2.3, 1.6 Hz, 1H), 8.81 (s,1H), 8.73 (ddd, J = 4.5, 2.6, 1.6 Hz, 1H), 8.32 (dd, J = 4.1, 1.7 Hz, 1H),8.28 (dt, J = 7.9, 2.4 Hz, 1H), 7.56 – 7.47 (m, 2H), 6.81 – 6.73 (m, 2H),3.14 (qd, J = 6.9, 6.3 Hz, 2H), 1.28 (d, J = 6.5 Hz, 12H).

[0095] 13 C NMR (125 MHz, DMSO-D6) δ 167.2, 133.4, 139.2, 122.7, 132.6, 149.9,147.8, 119.0, 114.5, 44.9, 114.9, 6.37, 19.3.

[0096] ESI-MS m / z: 372 [M+H] + .

[0097] Example 10

[0098] This embodiment provides the preparation of compound cs-0010:

[0099]

[0100] 4-Chloro-2-fluoro-5-((2,2,2-trifluoroethyl)-thio)phenol (26.0 g, 100.0 mmol) was dissolved in DMF (70 mL). Sodium carbonate (300.0 mmol) and N-(2,2,2-trifluoroethyl)acrylamide (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 50°C and reacted for 10 h. HPLC showed that the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with water (50 mL) and dried to give a white solid compound CS-0010 (31.1 g), with a yield of 74% and a purity of 96.8%.

[0101] NMR and MS of cs-010:

[0102] 1 H NMR (500 MHz, DMSO-D6) 6.78 (s, 2H),3.14 – 3.02 (m, 2H), 1.28 (d, J = 6.6 Hz, 12H).

[0103] 13 C NMR (125 MHz, DMSO-D6) δ 122.0, 132.2, 150.0, 144.6, 118.6, 114.6, 44.9, 114.9, 124.7, 173.3, 64.5, 39.4, 34.6.

[0104] ESI-MS m / z: 414 [M+H] + .

[0105] Example 11

[0106] This embodiment provides the preparation of compound cs-0011:

[0107]

[0108] 4-Chloro-2-fluoro-5-((2,2,2-trifluoroethyl)-thio)phenol (26.0 g, 100.0 mmol) was dissolved in DMF (70 mL). Potassium carbonate (300.0 mmol) and 4-chloro-N-(2,2,2-trifluoroethyl)butyramide (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 70°C and reacted for 15 h. HPLC analysis showed the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with water (50 mL) and dried to give a white solid compound CS-0011 (36.3 g), with a yield of 85% and a purity of 97.8%.

[0109] NMR and MS of cs-0011:

[0110] 1 H NMR (500 MHz, DMSO-D6) δ 7.94 (s, 1H), 7.38 (td, J = 7.7, 5.0 Hz, 1H), 6.92 (tdd, J = 7.9, 2.2, 1.2 Hz, 1H), 6.85 (ddd, J = 7.7, 2.2, 1.2 Hz,1H), 6.80 (s, 2H), 6.73 (dt, J = 8.0, 2.2 Hz, 1H), 3.14 – 3.02 (m, 2H), 1.28(d, J = 6.6 Hz, 12H).

[0111] 13 C NMR (125 MHz, DMSO-D6) δ 122.0, 132.2, 150.0, 144.6, 118.6, 114.6,44.9, 114.9, 124.7, 172.6, 67.7, 39.4, 32.8, 2.49.

[0112] ESI-MS m / z: 428 [M+H] + .

[0113] Example 12

[0114] This embodiment provides the preparation of compound cs-0012:

[0115]

[0116] 4-Chloro-2-fluoro-5-((2,2,2-trifluoroethyl)-thio)phenol (26.0 g, 100.0 mmol) was dissolved in DMF (70 mL). Potassium carbonate (300.0 mmol) and 2,2,2-trifluoroethylamine chloroformic acid (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 40°C and reacted for 3 h. HPLC analysis showed the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with water (50 mL) and dried to give a white solid compound CS-0012 (35.4 g), with a yield of 92% and a purity of 98.3%.

[0117] NMR and MS of cs-0012:

[0118] 1 H NMR (500 MHz, DMSO-D6) δ 7.94 (s, 1H), 7.36 (d, J = 7.9 Hz, 1H), 7.11 (ddd, J = 8.0, 2.2, 1.1 Hz, 1H), 7.01 (t, J = 2.2 Hz, 1H), 6.91 (ddd, J= 7.9, 2.2, 1.1 Hz, 1H), 6.78 (s, 2H), 3.14 – 3.02 (m, 2H), 1.28 (d, J = 6.6Hz, 12H).

[0119] 13 C NMR (125 MHz, DMSO-D6) δ 127.2, 132.0, 157.2, 135.9, 118.4, 121.8,44.9, 114.9, 124.6, 153.4, 40.9.

[0120] ESI-MS m / z: 386 [M+H] + .

[0121] Example 13

[0122] This embodiment provides the preparation of compound cs-0013:

[0123]

[0124] 26.0 g (100.0 mmol) of 4-chloro-2-fluoro-5-((2,2,2-trifluoroethyl)-thio)phenol was dissolved in 70 mL of DMF. Potassium carbonate (300.0 mmol) and 2-chloro-5-(chloromethyl)thiazole (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 70°C and reacted for 3 h. HPLC analysis showed the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with 50 mL of water and dried to give a white solid compound CS-0013 (40.5 g), with a yield of 93% and a purity of 98.5%.

[0125] NMR and MS of cs-0013:

[0126] 1 H NMR (500 MHz, DMSO-d6) δ 9.24 (d, J = 1.5 Hz, 1H), 8.91 – 8.65 (m,3H), 7.42 – 7.23 (m, 2H), 7.10 (tt, J = 7.3, 1.3 Hz, 1H), 7.05 – 6.94 (m,2H), 5.86 (s, 2H), 3.24 – 2.94 (m, 2H), 1.28 (d, J = 6.5 Hz, 12H).

[0127] 13 C NMR (125 MHz, DMSO-d6) δ 156.7, 153.1, 149.6, 146.0, 138.1, 137.6,131.3, 113.0, 112.0, 110.5, 63.9, 62.9.

[0128] ESI-MS m / z: 437 [M+H] + .

[0129] Example 14

[0130] This embodiment provides the preparation of compound cs-0014:

[0131]

[0132] 4-Chloro-2-fluoro-5-((2,2,2-trifluoroethyl)-thio)phenol (27.6 g, 100.0 mmol) was dissolved in DMF (70 mL). Potassium carbonate (300.0 mmol) and 2-chloro-N-(2,2,2-trifluoroethyl)acetamide (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 70°C and reacted for 15 h. HPLC analysis showed the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with water (50 mL) and dried to give a white solid compound CS-0014 (35.9 g), with a yield of 90% and a purity of 97.6%.

[0133] NMR and MS of cs-0014:

[0134] 1 H NMR (500 MHz, DMSO-d6) δ 8.23 ​​(s, 1H), 7.39 – 7.32 (m, 2H), 7.10 (tt, J = 7.3, 1.3 Hz, 1H), 7.03 – 6.97 (m, 2H), 6.78 (s, 2H), 3.14 – 3.02 (m,2H), 2.35 (t, J = 8.7 Hz, 2H), 1.65 (tt, J = 8.6, 6.6 Hz, 2H), 1.45 – 1.34(m, 2H), 1.28 (d, J = 6.6 Hz, 12H), 0.92 (t, J = 7.4 Hz, 3H).

[0135] 13 C NMR (125 MHz, DMSO-d6) δ 123.4, 143.1, 155.9, 148.7, 119.9, 112.2, 64.1, 110.5, 124.7, 168.6, 67.0, 39.4.

[0136] ESI-MS m / z: 400 [M+H] + .

[0137] Example 15

[0138] This embodiment provides the preparation of compound cs-0015:

[0139]

[0140] 4-Chloro-2-fluoro-5-((2,2,2-trifluoroethyl)-thio)phenol (27.6 g, 100.0 mmol) was dissolved in DMF (70 mL). Potassium carbonate (300.0 mmol) and 2-chloro-N-(2,2-difluoroethyl)acetamide (100.0 mmol) were added sequentially at room temperature. The mixture was heated to 70°C and reacted for 10 h. HPLC analysis showed the reaction was complete. 210 mL of water was added, and the mixture was filtered to obtain a white solid. The filter cake was washed with water (50 mL) and dried to give a white solid compound CS-0014 (31.2 g), with a yield of 90% and a purity of 98.6%.

[0141] NMR and MS of cs-0015:

[0142] 1 H NMR (500 MHz, DMSO-d6) δ 8.23 ​​(s, 1H), 7.39 – 7.32 (m, 2H), 7.10 (tt, J = 7.3, 1.3 Hz, 1H), 7.03 – 6.97 (m, 2H), 6.78 (s, 2H), 5.78 (m, 1H)3.14 – 3.02 (m, 2H), 2.35 (t, J = 8.7 Hz, 2H), 1.65 (tt, J = 8.6, 6.6 Hz,2H), 1.45 – 1.34 (m, 2H), 1.28 (d, J = 6.6 Hz, 12H), 0.92 (t, J = 7.4 Hz, 3H).

[0143] 13 C NMR (125 MHz, DMSO-d6) δ 123.4, 143.1, 155.9, 148.7, 119.9, 112.2, 64.1, 110.5, 124.7, 168.6, 67.0, 39.4.

[0144] ESI-MS m / z: 368 [M+H] + .

[0145] Test Example 1: Activity Test

[0146] Test insect: Adult female Tetranychus carmineus, derived from a sensitive strain continuously reared indoors. Rearing conditions: 16 hours of light, 8 hours of darkness, temperature 26℃, and air humidity 70%.

[0147] Host plant: Bean leaves (free of pesticide residues) are selected.

[0148] 1. Preparation of the medicinal solution

[0149] Concentration gradient settings: A total of 6 concentration gradients were set up, using water containing 0.2% acetone and 0.1% Tween-80 as solvents to prepare drug solutions of 0.1 μg / mL, 0.2 μg / mL, 0.5 μg / mL, 1 μg / mL, 2.5 μg / mL and 5 μg / mL.

[0150] Control group: Water containing 0.1% acetone and 0.1% Tween-80.

[0151] 2. Handling Method

[0152] (1) Take a clean glass slide, stick a 1cm wide double-sided tape on one end, peel off the protective layer of the tape, pick out the mites with a No. 0 brush, stick their backs on the tape (do not stick the mouthparts / legs), 30 mites per slide, examine under a microscope after 4 hours to remove dead / weak mites, and count the number of active mites.

[0153] (2) Chemical treatment

[0154] Immerse one end of the glass slide containing the mites into the medication solution for 5 seconds, then remove it and absorb any excess medication with absorbent paper. Repeat 3 times for each medication concentration.

[0155] 3. Observation and Recording

[0156] Observe the mortality symptoms at 24h, 48h, and 72h after treatment, and count the number of dead mites. Gently touch the adult mites with a size 0 paintbrush; those whose legs do not move are considered dead.

[0157] LC of compounds cs-001~cs-0015 50 The test results (μg / mL) are shown in Table 1 below.

[0158] Table 1

[0159]

[0160] The results showed that the compounds provided by the present invention all had good anti-mite activity, among which cs-001, cs-002, cs-003, cs-004, cs-007, cs-0012, cs-0013, and cs-0015 had better insect-resistant activity, while cs-003, cs-004, cs-007, and cs-0015 showed even better anti-mite activity.

[0161] Test Example 2: Field Control Efficacy Test

[0162] Overview of the test site

[0163] The experiment was conducted in a greenhouse at a vegetable base in Lanshan District, Linyi City, Shandong Province. The greenhouse area was 2000 m². 2 Cowpeas were planted. The experiment was conducted from October 15 to 22, 2025, when the plants were in the flowering stage.

[0164] Test reagent preparation method

[0165] The test reagents and dosages are shown in Table 2 below. Preparation method: Dissolve the technical grade (CS-001~CS-0015) in a mixed solvent of N,N-dimethylformamide / xylene (1:1, v / v) to obtain a candidate drug formulation with a mass fraction of 10%. Then dilute it with water 200 times and spray it on the crops using an electric sprayer (Guangnong brand 3WBD-16 model, working pressure 0.15~0.4MPa). The effective content is 12g / ha.

[0166] Before applying the pesticide, the population of mites (adults and nymphs) was investigated. The number of live mites in each plot was investigated 1 day and 3 days after application. The five-point sampling method was used, with two seedlings fixed at each point in each plot. One leaf from the top, middle and bottom of each seedling was taken and tagged. The number of live mites and the total number of mites were counted and recorded under a stereomicroscope. When counting, the mites were gently touched. Those that did not move at all were considered dead and were not included in the count of live mites.

[0167] The data was compiled using Excel software, and the formula for calculating the insect population decline rate is as follows:

[0168] Insect population reduction rate (%) = (Number of insects before application - Number of insects after application) / Number of insects before application × 100.

[0169] The results of the anti-mite activity tests of compounds cs-001~cs-0015 are shown in Table 2 below.

[0170] Table 2

[0171]

[0172] The results showed that the compounds provided by this invention all had a certain inhibitory effect on mites. At the same concentration of active ingredient, the tested compounds cs-001, cs-002, cs-003, cs-004, cs-007, cs-0012, cs-0013, and cs-0015 all showed significant control effects. Among them, compounds cs-004, cs-007, and cs-0015 were particularly outstanding, not only having high rapid-acting properties but also significantly longer-lasting effects than other compounds.

[0173] Although the present invention has been described in detail above with general descriptions and specific embodiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. A fluorophenyl ether derivative containing trifluoromethyl, characterized in that, It has a structure as shown in general formula (I), (I)， Where A is S or S=O, X is a halogen, R is a hydrogen, alkyl or halogen-substituted thiazolyl, alkyl or aryl-substituted amide, and n is 0, 1, 2 or 3.

2. The trifluoromethyl-containing fluorophenyl ether derivative according to claim 1, characterized in that, The compounds are represented by the formulas cs-001 to cs-0015. 。 3. The method for preparing the trifluoromethyl-containing fluorophenyl ether derivative according to claim 1, characterized in that, The method comprises: a condensation reaction of a compound of general formula (II) and a compound of general formula (III) in the presence of an acid-binding agent and an organic solvent; (II), (III), The definitions of A, X, R, and n are the same as in claim 1.

4. The method for preparing the trifluoromethyl-containing fluorophenyl ether derivative according to claim 3, characterized in that, The molar ratio of the compound represented by general formula (II) to the compound represented by general formula (III) is 1:1-1.05; The molar ratio of the compound represented by general formula (II) to the acid-binding agent is 1:2.5-5.

5. The method for preparing the trifluoromethyl-containing fluorophenyl ether derivative according to claim 3, characterized in that, The conditions for the condensation reaction are: room temperature to reflux temperature, 5-20 hours.

6. The method for preparing the trifluoromethyl-containing fluorophenyl ether derivative according to claim 3, characterized in that, The acid-binding agent is cesium carbonate, potassium carbonate, or potassium tert-butoxide; The organic solvent is tetrahydrofuran, acetonitrile, 1,4-dioxane, N,N-dimethylformamide, or dimethyl sulfoxide.

7. A composition, characterized in that, It contains a trifluoromethyl-containing phenyl ether derivative as described in claim 1 and a pharmaceutically acceptable pharmaceutical carrier and / or excipient.

8. The use of the trifluoromethyl-containing phenyl ether derivative of claim 1 or the composition of claim 7 in the preparation of an anti-mite agent.

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