4-(aryl / alkoxy)-2,6-dialkylaniline derivatives, methods for preparing the same and use thereof in combating whiteflies

Abstract

This invention discloses a 4-(aryl / alkoxy)-2,6-dialkylaniline derivative and its preparation method, as well as its application in controlling whiteflies, belonging to the field of pesticide technology. The 4-(aryl / alkoxy)-2,6-dialkylaniline derivative has the structure shown in general formula (I), wherein R1 and R2 are isopropyl, cyclopropyl, or n-propyl; R3 is pyridyl, pyrazinyl, phenyl, halogenated or trifluoromethyl-substituted phenyl, or C3-C5 alkyl; and R4 is pyridyl, pyrazinyl, phenyl, or C1-C5 alkyl. The 4-(aryl / alkoxy)-2,6-dialkylaniline derivative provided by this invention exhibits superior activity against whiteflies. The synthesis method provided by this invention is simple, and the raw materials are inexpensive and readily available, making it a promising candidate for development into a novel whitefly-resistant pesticide. (I)

Description

Technical Field

[0001] The embodiments of this invention relate to the field of pesticide technology, specifically to 4-(aromatic / alkoxy)-2,6-dialkylaniline derivatives, their preparation methods, and their application in controlling whiteflies. Background Technology

[0002] The greenhouse whitefly (Trialeuro des vaporariorum Westwood) is a pest belonging to the family Amycidae in the order Hemiptera. Due to its small size and white wings, it is also known as the "little white moth." This insect has a wide host range, affecting more than 200 different crops. It is a significant pest of cucurbits, solanaceous crops, legumes, and other similar crops. It has a high reproductive rate, often with overlapping generations, and spreads rapidly. By sucking plant sap, it causes leaves to turn pale green, yellow, wilt, and dry out. It is also an important vector for viral diseases, and its honeydew secretions can easily induce sooty mold and other diseases, often causing serious losses to agricultural production.

[0003] Therefore, the development of superior anti-whitefly drugs has become an urgent task. To date, there are no reports in the art regarding the application of the 4-(aryl / alkoxy)-2,6-dialkylaniline derivative (I) of this invention in whiteflies. Summary of the Invention

[0004] Therefore, embodiments of the present invention provide a 4-(aromatic / alkoxy)-2,6-dialkylaniline derivative, its preparation method, and its application in combating whiteflies.

[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 4-(aryl / alkoxy)-2,6-dialkylaniline derivative, which is a compound as shown in general formula (I).

[0007] (I)

[0008] Wherein, R1 and R2 are isopropyl, cyclopropyl or n-propyl, R3 is pyridyl, pyrazinyl, phenyl, halogen or trifluoromethyl substituted phenyl, C3-C5 alkyl, and R4 is pyridyl, pyrazinyl, phenyl, C1-C5 alkyl.

[0009] Further, for compounds represented by formulas CS001 to CS020,

[0010] .

[0011] According to a second aspect of the present invention, the present invention provides a method for preparing the 4-(aryl / alkoxy)-2,6-dialkylaniline derivative as described above, the method comprising: condensing 4-(aryl / alkoxy)-2,6-dialkylaniline and carboxylic acid in the presence of EDCI and HOBt;

[0012] 4-(aryl / alkoxy)-2,6-dialkylaniline is a compound represented by general formula (II).

[0013] (II)

[0014] The general chemical formula of aryl carboxylic acids is R4COOH, where R1, R2, R3, and R4 are defined as above.

[0015] Furthermore, the molar ratio of 4-(aryl / alkoxy)-2,6-dialkylaniline to carboxylic acid is 1:1-2;

[0016] The molar ratio of 4-(aryl / alkoxy)-2,6-dialkylaniline to EDCI is 1:1-3;

[0017] The molar ratio of 4-(aryl / alkoxy)-2,6-dialkylaniline to HOBt is 1:1-3.

[0018] Furthermore, the conditions for the condensation reaction are: 20~25 ℃, 5-20 hours.

[0019] Furthermore, the condensation reaction is carried out in the presence of an organic solvent, which is dichloromethane, tetrahydrofuran, ethyl acetate, tert-butanol, 1,4-dioxane, N,N-dimethylformamide, or dimethyl sulfoxide.

[0020] Furthermore, the method further includes: cooling the product after reaction to 10-15°C, filtering, washing, and drying to obtain the 4-(aryl / alkoxy)-2,6-dialkylaniline derivative.

[0021] According to a third aspect of the present invention, the present invention provides the use of the 4-(aryl / alkoxy)-2,6-dialkylaniline derivatives or compositions thereof as described above in the preparation of an anti-whitefly drug.

[0022] According to a fourth aspect of the present invention, the present invention provides an anti-whitefly pharmaceutical composition comprising, as described above, a 4-phenoxy-2,6-diisopropylaniline derivative and a pharmaceutically acceptable pharmaceutical carrier and / or excipient.

[0023] The 4-(aryl / alkoxy)-2,6-dialkylaniline derivative provided by this invention can be used directly or in the form of a pharmaceutical composition when used as a drug for whiteflies. The pharmaceutical composition contains 0.1-99.5%, preferably 0.5-90%, of the 4-(aryl / alkoxy)-2,6-dialkylaniline derivative of this invention, with the remainder being pharmaceutically acceptable, non-toxic, and inert pharmaceutically acceptable carriers and / or excipients for humans and animals.

[0024] The pharmaceutical carrier or excipient is one or more solid, semi-solid, and liquid diluents, fillers, and pharmaceutical excipients. The whitefly drug composition of the present invention is used in the form of a dose per unit body weight. The whitefly drug composition of the present invention is prepared into various dosage forms, such as liquid preparations (solutions, suspensions) and solid preparations (tablets, powders), using methods recognized in the pesticide and pharmaceutical fields. The drug of the present invention can be administered via spraying, dusting, pouring, spreading, seed dressing, and other routes for the prevention and treatment of whiteflies.

[0025] The embodiments of the present invention have the following advantages:

[0026] The 4-(aryl / alkoxy)-2,6-dialkylaniline derivative provided by this invention exhibits superior anti-whitefly activity (EC). 50 (2.2-24.5 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 pesticide against whiteflies. Detailed Implementation

[0027] 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.

[0028] Example 1

[0029] This embodiment provides the preparation of compound CS001:

[0030]

[0031] 4-Phenoxy-2,6-diisopropylaniline (13.5 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and nicotinic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS001 (17.2 g), with a yield of 92% and a purity of 98.9%.

[0032] NMR and MS of CS001:

[0033] 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).

[0034] 13 C NMR (125 MHz, DMSO-d6) δ 166.88, 156.31, 151.40, 151.22, 149.32,139.03, 135.57, 132.75, 131.42, 129.72, 124.45, 123.62, 119.45, 115.20,29.52, 23.43.

[0035] ESI-MS m / z: 375 [M+H] + .

[0036] Example 2

[0037] This embodiment provides the preparation of compound CS002:

[0038]

[0039] 4-Phenoxy-2,6-diisopropylaniline (13.5 g, 50.0 mmol) was dissolved in tetrahydrofuran (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and pyrazinic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with tetrahydrofuran (20 mL) and dried to give a white solid compound CS002 (16.3 g), with a yield of 87% and a purity of 99.0%.

[0040] NMR and MS of CS002:

[0041] 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).

[0042] 13 C NMR (125 MHz, DMSO-d6) δ 163.29, 156.31, 151.40, 147.73, 146.21,144.81, 144.59, 139.17, 131.48, 129.72, 124.45, 119.45, 115.20, 29.58, 23.43.

[0043] ESI-MS m / z: 376 [M+H] + .

[0044] Example 3

[0045] This embodiment provides the preparation of compound CS003:

[0046]

[0047] 4-Phenoxy-2,6-diisopropylaniline (13.5 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and 2-pyridinecarboxylic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS003 (17.2 g), with a yield of 92% and a purity of 98.6%.

[0048] NMR and MS of CS003:

[0049] 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).

[0050] 13 C NMR (125 MHz, DMSO-d6) δ 163.24, 156.31, 151.40, 150.48, 148.79,139.18, 137.81, 131.33, 129.72, 126.43, 124.45, 123.30, 119.45, 115.20,29.58, 23.43.

[0051] ESI-MS m / z: 375 [M+H] + .

[0052] Example 4

[0053] This embodiment provides the preparation of compound CS004:

[0054]

[0055] 4-Phenoxy-2,6-diisopropylaniline (13.5 g, 50.0 mmol) was dissolved in ethyl acetate (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and valeric acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with ethyl acetate (20 mL) and dried to give a white solid compound CS004 (16.3 g), with a yield of 92% and a purity of 98.0%.

[0056] NMR and MS of CS004:

[0057] 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).

[0058] 13 C NMR (125 MHz, DMSO-d6) δ 173.05, 156.31, 151.39, 138.27, 131.24,129.72, 124.45, 119.45, 115.12, 36.13, 29.55, 26.90, 23.43, 21.77, 13.82.

[0059] ESI-MS m / z: 354 [M+H] + .

[0060] Example 5

[0061] This embodiment provides the preparation of compound CS005:

[0062]

[0063] 4-Phenoxy-2,6-diisopropylaniline (13.5 g, 50.0 mmol) was dissolved in 1,4-dioxane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and acetic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with 1,4-dioxane (20 mL) and dried to give a white solid compound CS005 (13.2 g), with a yield of 85% and a purity of 98.5%.

[0064] NMR and MS of CS005:

[0065] 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).

[0066] 13 C NMR (125 MHz, DMSO-d6) δ 169.87, 156.31, 151.38, 138.26, 132.06,129.72, 124.45, 119.45, 115.11, 29.55, 23.43, 22.91.

[0067] ESI-MS m / z: 312 [M+H] + .

[0068] Example 6

[0069] This embodiment provides the preparation of compound CS006:

[0070]

[0071] 4-Phenoxy-2,6-Diisopropylaniline (13.5 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and propionic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS006 (9.0 g), with a yield of 55% and a purity of 98.3%.

[0072] NMR and MS of CS006:

[0073] 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).

[0074] 13 C NMR (125 MHz, DMSO-d6) δ 174.00, 156.31, 151.39, 138.27, 131.29,129.72, 124.45, 119.45, 115.12, 29.55, 29.34, 23.43, 9.59.

[0075] ESI-MS m / z: 326 [M+H] + .

[0076] Example 7

[0077] This embodiment provides the preparation of compound CS007:

[0078]

[0079] 4-Phenoxy-2,6-Diisopropylaniline (13.5 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and butyric acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS007 (14.4 g), with a yield of 85% and a purity of 98.1%.

[0080] NMR and MS of CS007:

[0081] 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).

[0082] 13 C NMR (125 MHz, DMSO-d6) δ 172.70, 156.31, 151.39, 138.27, 131.24,129.72, 124.45, 119.45, 115.12, 38.11, 29.55, 23.43, 19.01, 13.82.

[0083] ESI-MS m / z: 340 [M+H] + .

[0084] Example 8

[0085] This embodiment provides the preparation of compound CS008:

[0086]

[0087] 4-Phenoxy-2,6-diisopropylaniline (13.5 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and hexanoic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS008 (14.7 g), with a yield of 80% and a purity of 98.4%.

[0088] NMR and MS of CS008:

[0089] 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).

[0090] 13 C NMR (125 MHz, DMSO-d6) δ 173.02, 156.31, 151.39, 138.27, 131.24,129.72, 124.45, 119.45, 115.12, 36.46, 32.55, 29.55, 24.80, 23.43, 23.33,13.98.

[0091] ESI-MS m / z: 368 [M+H] + .

[0092] Example 9

[0093] This embodiment provides the preparation of compound CS009:

[0094]

[0095] 4-(2-pyridinoxy)-2,6-diisopropylaniline (13.5 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and nicotinic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed that the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS009 (15.6 g), with a yield of 83% and a purity of 97.0%.

[0096] NMR and MS of CS009:

[0097] 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).

[0098] 13 C NMR (125 MHz, DMSO-D6) δ 166.88, 163.38, 151.22, 151.03, 149.32,147.94, 139.63, 139.59, 135.57, 132.08, 131.42, 123.62, 118.83, 117.17,116.67, 29.52, 23.43.

[0099] ESI-MS m / z: 376 [M+H] + .

[0100] Example 10

[0101] This embodiment provides the preparation of compound CS010:

[0102]

[0103] 4-(3-trifluoromethylphenoxy)-2,6-diisopropylaniline (16.9 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and acetic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS010 (14.2 g), with a yield of 75% and a purity of 98.0%.

[0104] NMR and MS of CS010:

[0105] 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).

[0106] 13 C NMR (125 MHz, DMSO-D6) δ 169.87, 156.53, 156.51, 156.50, 156.48,151.42, 138.26, 133.05, 132.79, 132.54, 132.28, 132.06, 130.86, 130.85,130.83, 130.82, 126.95, 124.80, 122.66, 121.26, 121.23, 121.19, 121.16,120.52, 119.95, 115.83, 115.80, 115.77, 115.73, 115.11, 29.55, 23.43, 22.91.

[0107] ESI-MS m / z: 380 [M+H] + .

[0108] Example 11

[0109] This embodiment provides the preparation of compound CS011:

[0110]

[0111] 4-(3-fluorophenoxy)-2,6-diisopropylaniline (14.4 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and acetic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS011 (14.0 g), with a yield of 85% and a purity of 98.0%.

[0112] NMR and MS of CS011:

[0113] 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).

[0114] 13 C NMR (125 MHz, DMSO-D6) δ 169.87, 164.11, 162.09, 158.02, 157.96,151.42, 138.26, 132.06, 130.10, 130.03, 115.54, 115.51, 115.11, 110.98,110.81, 107.87, 107.71, 29.55, 23.43, 22.91.

[0115] ESI-MS m / z: 330 [M+H] + .

[0116] Example 12

[0117] This embodiment provides the preparation of compound CS012:

[0118]

[0119] 4-(3-Chlorophenoxy)-2,6-diisopropylaniline (15.2 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and acetic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS012 (14.0 g), with a yield of 81% and a purity of 98.9%.

[0120] NMR and MS of CS012:

[0121] 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).

[0122] 13 C NMR (125 MHz, DMSO-D6) δ 169.87, 156.79, 151.45, 138.26, 134.57,132.06, 130.69, 124.91, 118.91, 117.42, 115.11, 29.55, 23.43, 22.91.

[0123] ESI-MS m / z: 346 [M+H] + .

[0124] Example 13

[0125] This embodiment provides the preparation of compound CS013:

[0126]

[0127] 4-(2-pyrazinoxy)-2,6-diisopropylaniline (13.6 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and nicotinic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed that the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS013 (16.0 g), with a yield of 85% and a purity of 97.6%.

[0128] NMR and MS of CS013:

[0129] 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), 8.45 (dd, J = 3.5, 0.9 Hz, 1H), 8.28 (dt, J = 7.9, 2.4 Hz, 1H), 8.24 (d, J = 3.5 Hz, 1H), 8.03 (d, J = 0.9Hz, 1H), 7.50 (dd, J = 7.9, 4.8 Hz, 1H), 7.08 (s, 2H), 3.20 – 3.08 (m, 2H),1.28 (d, J = 6.5 Hz, 12H).

[0130] 13 C NMR (125 MHz, DMSO-D6) δ 166.88, 158.20, 151.22, 150.89, 149.32,142.73, 139.58, 136.74, 135.99, 135.57, 132.08, 131.42, 123.62, 117.10,29.52, 23.43.

[0131] ESI-MS m / z: 377 [M+H] + .

[0132] Example 14

[0133] This embodiment provides the preparation of compound CS014:

[0134]

[0135] 4-Phenoxy-2,6-Dicyclopropylaniline (13.3 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and nicotinic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS014 (15.7 g), with a yield of 85% and a purity of 98.0%.

[0136] NMR and MS of CS014:

[0137] 1 H NMR (500 MHz, DMSO-D6) δ 9.17 (dd, J = 2.3, 1.6 Hz, 1H), 9.10 (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), 7.39 – 7.32 (m, 2H), 7.10 (tt, J = 7.3, 1.3Hz, 1H), 7.03 – 6.97 (m, 2H), 6.72 (s, 2H), 2.74 – 2.66 (m, 2H), 1.03 – 0.90(m, 8H).

[0138] 13 C NMR (125 MHz, DMSO-D6) δ 166.88, 156.31, 151.22, 150.80, 149.32,135.57, 134.77, 134.73, 131.42, 129.72, 124.45, 123.62, 119.45, 115.80,15.51, 8.20.

[0139] ESI-MS m / z: 371 [M+H] + .

[0140] Example 15

[0141] This embodiment provides the preparation of compound CS015:

[0142]

[0143] 4-(4-trifluoromethylphenoxy)-2,6-dicyclopropylaniline (16.7 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and nicotinic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS015 (19.7 g), with a yield of 90% and a purity of 98.5%.

[0144] NMR and MS of CS015:

[0145] 1 H NMR (500 MHz, DMSO-D6) δ 9.17 (dd, J = 2.3, 1.6 Hz, 1H), 9.10 (s,1H), 8.73 (ddd, J = 4.5, 2.6, 1.6 Hz, 1H), 8.28 (dt, J = 7.9, 2.4 Hz, 1H),7.68 – 7.63 (m, 2H), 7.50 (dd, J = 7.9, 4.8 Hz, 1H), 7.16 – 7.10 (m, 2H),6.72 (s, 2H), 2.74 – 2.66 (m, 2H), 1.03 – 0.90 (m, 8H).

[0146] 13 C NMR (125 MHz, DMSO-D6) δ 166.88, 159.60, 151.22, 150.85, 149.32,135.57, 134.77, 134.73, 131.42, 127.46, 127.43, 127.40, 127.36, 127.12,125.23, 124.98, 124.72, 124.47, 123.62, 122.83, 120.69, 118.88, 118.86,118.85, 118.83, 115.80, 15.51, 8.20.

[0147] ESI-MS m / z: 439 [M+H] + .

[0148] Example 16

[0149] This embodiment provides the preparation of compound CS016:

[0150]

[0151] 4-Isopropoxy-2,6-dicyclopropylaniline (11.6 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and nicotinic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS016 (15.9 g), with a yield of 95% and a purity of 98.2%.

[0152] NMR and MS of CS016:

[0153] 1 H NMR (500 MHz, DMSO-D6) δ 8.76 (s, 1H), 7.99 – 7.92 (m, 2H), 7.56 –7.49 (m, 1H), 7.49 – 7.42 (m, 2H), 6.66 (s, 2H), 4.68 (hept, J = 5.7 Hz, 1H), 2.72 – 2.64 (m, 2H), 1.32 (d, J = 5.7 Hz, 6H), 1.03 – 0.90 (m, 8H).

[0154] 13 C NMR (125 MHz, DMSO-D6) δ 167.04, 153.63, 136.28, 134.94, 134.82, 132.22, 128.98, 128.04, 113.33, 72.41, 21.96, 15.48, 8.20.

[0155] ESI-MS m / z: 336 [M+H] + .

[0156] Example 17

[0157] This embodiment provides the preparation of compound CS017:

[0158]

[0159] 4-Isobutoxy-2,6-dicyclopropylaniline (12.3 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and benzoic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS017 (14.3 g), with a yield of 82% and a purity of 98.2%.

[0160] NMR and MS of CS017:

[0161] 1 H NMR (500 MHz, DMSO-D6) δ 8.76 (s, 1H), 7.95 (dt, J = 8.0, 1.2 Hz,2H), 7.56 – 7.49 (m, 1H), 7.49 – 7.42 (m, 2H), 6.71 (s, 2H), 4.34 (qt, J =6.4, 4.8 Hz, 1H), 2.72 – 2.64 (m, 2H), 1.77 – 1.58 (m, 2H), 1.27 (d, J = 6.3Hz, 3H), 0.99 (d, J = 7.9 Hz, 3H), 0.98 – 0.90 (m, 8H).

[0162] 13 C NMR (125 MHz, DMSO-D6) δ 167.04, 153.82, 136.15, 135.15, 134.82,132.22, 128.98, 128.04, 113.62, 76.41, 28.90, 16.53, 15.48, 12.71, 8.20.

[0163] ESI-MS m / z: 350 [M+H] + .

[0164] Example 18

[0165] This embodiment provides the preparation of compound CS018:

[0166]

[0167] 4-Isobutoxy-2,6-dipropylaniline (12.6 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and acetic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS018 (16.9 g), with a yield of 96% and a purity of 96.9%.

[0168] NMR and MS of CS018:

[0169] 1 H NMR (500 MHz, DMSO-D6) δ 8.89 (s, 1H), 7.95 (dt, J = 8.0, 1.2 Hz,2H), 7.56 – 7.49 (m, 1H), 7.49 – 7.42 (m, 2H), 6.58 (s, 2H), 4.33 (ddddq, J =7.9, 6.2, 4.8, 3.2, 1.6 Hz, 1H), 2.67 (td, J = 6.3, 1.0 Hz, 4H), 1.77 – 1.63(m, 2H), 1.63 – 1.55 (m, 4H), 1.27 (d, J = 6.3 Hz, 3H), 1.01 – 0.93 (m, 9H).

[0170] 13 C NMR (125 MHz, DMSO-D6) δ 167.07, 151.34, 135.19, 134.82, 132.22,131.19, 128.98, 128.04, 116.32, 76.41, 34.13, 28.90, 22.41, 16.53, 14.22,12.71.

[0171] ESI-MS m / z: 354 [M+H] + .

[0172] Example 19

[0173] This embodiment provides the preparation of compound CS019:

[0174]

[0175] 4-Propoxy-2,6-diisopropylaniline (11.8 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and propionic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS019 (13.8 g), with a yield of 95% and a purity of 98.6%.

[0176] NMR and MS of CS019:

[0177] 1 H NMR (500 MHz, DMSO-D6) δ 8.02 (s, 1H), 6.72 (s, 2H), 3.99 (t, J =5.4 Hz, 2H), 3.13 – 3.02 (m, 2H), 2.37 (q, J = 7.1 Hz, 2H), 1.87 – 1.77 (m,2H), 1.27 (d, J = 6.6 Hz, 12H), 1.18 (t, J = 7.1 Hz, 3H), 1.07 (t, J = 7.8Hz, 3H).

[0178] 13 C NMR (125 MHz, DMSO-D6) δ 174.00, 153.43, 139.88, 130.89, 111.72, 70.15, 29.56, 29.34, 23.44, 22.59, 10.47, 9.59.

[0179] ESI-MS m / z: 292 [M+H] + .

[0180] Example 20

[0181] This embodiment provides the preparation of compound CSO20:

[0182]

[0183] 4-Isobutoxy-2,6-diisopropylaniline (12.5 g, 50.0 mmol) was dissolved in dichloromethane (70 mL). EDCI (11.5 g, 60.0 mmol), HOBt (8.11 g, 60.0 mmol), and propionic acid (50.0 mmol) were added sequentially at room temperature, and the reaction was carried out for 18 h. TLC showed the reaction was complete. The reaction solution was cooled to 15 °C, and a white solid was filtered off. The filter cake was washed with dichloromethane (20 mL) and dried to give a white solid compound CS013 (13.7 g), with a yield of 90% and a purity of 97.6%.

[0184] NMR and MS of CS013:

[0185] 1 H NMR (500 MHz, DMSO-D6) δ 8.02 (s, 1H), 6.69 (s, 2H), 3.87 (d, J =5.1 Hz, 2H), 3.13 – 3.02 (m, 2H), 2.37 (q, J = 7.1 Hz, 2H), 2.03 (ddt, J =14.5, 7.2, 5.1 Hz, 1H), 1.27 (d, J = 6.6 Hz, 12H), 1.18 (t, J = 7.1 Hz, 3H), 1.05 (d, J = 7.1 Hz, 6H).

[0186] 13 C NMR (125 MHz, DMSO-D6) δ 174.00, 153.57, 139.74, 131.02, 112.11, 75.04, 29.56, 29.34, 28.22, 23.44, 19.27, 9.59.

[0187] ESI-MS m / z: 306 [M+H] + .

[0188] Test Example 1: Activity Test

[0189] Test insect: Greenhouse whitefly (Trialeurodes vaporariorum Westwood), reared indoors using successive generations of tomato plants. Rearing conditions: 16 hours of light, 8 hours of darkness, temperature 26℃, and air humidity 70%.

[0190] Host plant: Select intact tomato seedlings (12-15cm tall, 4-5 true leaves, and free of pesticide residues).

[0191] 1. Preparation of the medicinal solution

[0192] Concentration gradient settings: A total of 6 concentration gradients were set up, using water containing 0.5% acetone and 0.1% Tween-80 as solvents to prepare drug solutions of 0.5 μg / mL, 2 μg / mL, 5 μg / mL, 10 μg / mL, 20 μg / mL and 30 μg / mL.

[0193] Control group: Water containing 0.5% acetone and 0.1% Tween-80.

[0194] 2. Handling Method

[0195] (1) Arrange the planted tomato pots in order, then select fresh leaves from each tomato plant and spray the test sample solution onto the back of the leaves with a spray bottle. The spray volume is 0.5 mL / plant.

[0196] (2) Place the tested whiteflies in a 4°C refrigerator, take them out after 10 min, and use a suction tube to suck 10 greenhouse whiteflies onto the underside of the leaves. Each treatment has 3 replicates.

[0197] 3. Observation and Recording

[0198] Observe the mortality symptoms at 24h, 48h, and 72h after treatment, and count the number of dead insects.

[0199] If an adult insect is gently touched with a soft brush and its antennae do not move, its legs do not have the ability to crawl, and its wings do not tremble, it is considered dead.

[0200] Count the number of dead insects in each box, and calculate the actual mortality rate and the corrected mortality rate (repeat the experiment if the mortality rate in the control group is >10%):

[0201] Actual mortality rate (%) = (Number of dead insects / Total number of insects introduced) × 100;

[0202] Corrected mortality rate (%) = [(treatment group mortality rate - control group mortality rate) / (1 - control group mortality rate)] × 100.

[0203] EC of compounds CS001-CS020 50 The test results (μg / mL) are shown in Table 1 below.

[0204] Table 1

[0205]

[0206] The results showed that the compounds provided by the present invention all had good insecticidal activity, among which CS005, CS006, CS007, CS011 and CS015 had better insecticidal activity, and CS005 and CS011 showed even better insecticidal activity.

[0207] Test Example 2: Field Control Efficacy Test

[0208] Overview of the test site

[0209] 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 Linyi thin-skinned chili peppers were planted. The experiment was conducted from July 20 to 27, 2025, when the plants were in the flowering stage.

[0210] Test reagent preparation method

[0211] The test reagents and dosages are shown in Table 1 below.

[0212] Preparation method: Dissolve the technical grade drug (CS001~CS020) 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 crops using an electric sprayer (Guangnong brand 3WBD-16 model, working pressure 0.15~0.4MPa). The effective content is 15g / ha.

[0213] Before applying the pesticide, the initial population of adult whiteflies was investigated. One day and three days after application, the number of live adult whiteflies was investigated. Five samples were taken from each plot, with two seedlings fixed at each point. One leaf from the top, middle and bottom of each seedling was taken and tagged.

[0214] The data was compiled using Excel software, and the formula for calculating the insect population decline rate is as follows:

[0215] Insect population reduction rate (%) = (Number of insects before application - Number of insects after application) / Number of insects before application × 100.

[0216] The activity test results of compounds CS001-CS008 against whiteflies are shown in Table 2 below.

[0217] Table 2

[0218]

[0219] The results showed that the compounds provided by this invention all had a certain inhibitory effect on whiteflies. At the same concentration of active ingredient, the tested compounds CS005, CS006, CS007, CS008, CS011, CS012, and CS015 all showed significant control effects. Among them, the short-chain candidate compounds CS005 and CS011 were particularly outstanding, not only with high rapid action but also with a significantly longer duration of action than other compounds.

[0220] 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 4-(aryl / alkoxy)-2,6-dialkylaniline derivative, characterized in that, Specifically, it is one of the following compounds. 。 2. A composition, characterized in that, Contains the 4-(aryl / alkoxy)-2,6-dialkylaniline derivative as described in claim 1 and a pharmaceutically acceptable pharmaceutical carrier and / or excipient.

3. The composition according to claim 2, characterized in that, The weight percentage of the 4-(aryl / alkoxy)-2,6-dialkylaniline derivative is 0.1-99.5%.

4. The use of the 4-(aryl / alkoxy)-2,6-dialkylaniline derivative of claim 1 or the composition of claim 2 in the preparation of an anti-whitefly drug.

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