ARYL SULFIDE COMPRISING BENZYLAMINE, SYNTHESIS METHOD AND APPLICATION THEREOF

Abstract

The invention belongs to the technical field of pesticides and specifically relates to an aryl sulfide containing a benzylamine structure, a synthesis method therefor, and an application thereof. The aryl sulfide is denoted as compound I. Also provided is an agriculturally acceptable salt of the aryl sulfide. The compound represented by formula I shows excellent effects on various harmful organisms, especially spider mites represented by Tetranychus cinnabarinus, Tetranychus urticae, Tetranychus Kanzawai Kishida, Panonychus citri, etc., and can be used for controlling all kinds of harmful mites.

Claims

1. An aryl sulfide comprising benzylamine, being represented by formula I, or an agriculturally acceptable salt thereof; ##STR00042## wherein: n is 0, 1 or 2; X and Y at each occurrence represent hydrogen, fluorine, chlorine, bromine, iodine, a cyano group, a C.sub.1-4 alkyl, a C.sub.1-4 haloalkyl, a C.sub.1-4 alkoxy, or a C.sub.1-4 haloalkoxy; R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 at each occurrence represent hydrogen, fluorine, chlorine, bromine, iodine, a cyano group, nitro, amino, hydroxymethyl, carboxyl, hydroxyl, sulphydryl, C.sub.1-10 alkyl, C.sub.1-10 haloalkyl, C.sub.1-10 alkoxy, haloalkoxy, alkoxycarbonyl, C.sub.1-10 haloalkoxycarbonyl, C.sub.1-10 alkylsulfonyloxy, alkylsulfonyl, alkylthiol, C.sub.1-10 haloalkylthiol, C.sub.2-10 ethoxycarbonyl, C.sub.1-10 alkyl carbonyl, amino carbonyl, C.sub.1-10 N-alkyl carbonyl, N, N-dimethylcarbonyl, N, N-dimethylthiocarbonyl, C.sub.1-10 N-alkyl thiocarbonyl, 2-oxoprooxycarbonyl, or methoxymethoxycarbonyl; and R.sub.6 represents C.sub.1-6 haloalkyl, C.sub.2-6 alkynyl, C.sub.2-6 alkenyl, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, or C.sub.3-6 epoxy alkyl.

2. The aryl sulfide of claim 1, wherein in formula I, n is 0 or 1; X is fluorine, chlorine, or methyl; Y is chlorine or methyl; R.sub.1 is hydrogen, fluorine, chlorine, bromine, hydroxyl, nitro, hydroxymethyl, a cyano group, trifluoromethyl, C.sub.1-3 alkyl, C.sub.1-4 alkoxycarbonyl, acetyl, propionyl, C.sub.1-3 alkoxy, ethylthio, 2-fluoroethanothioxy, 2-chloroethanothioxy, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, propylthio, 2,2,2-trifluoroethylsulfinyl, vinyloxycarbonyl, 2,2, 2-trifluoroethoxycarbonyl, or N-methylcarbonyl; R.sub.2 is hydrogen, fluorine, or chlorine; R.sub.3 is hydrogen, fluorine, chlorine, bromine, or a cyano group; R.sub.4 and R.sub.5 at each occurrence represent hydrogen; and R.sub.6 is N-propyl or 2,2,2-trifluoroethyl.

3. The aryl sulfide of claim 2, wherein n is 0 or 1; X is fluorine; Y is chlorine or methyl; R.sub.1 is methoxycarbonyl, ethoxycarbonyl, ethylthio, or 2,2,2-trifluoroethylthio; R.sub.2, R.sub.4, and R.sub.5 at each occurrence represent hydrogen; R.sub.3 is hydrogen, fluorine, chlorine, or a cyano group; and R.sub.6 is 2,2,2-trifluoroethyl.

4. The aryl sulfide of claim 1, wherein the formula I comprises: ##STR00043##

5. A method for preparing the aryl sulfide of claim 1, the method having the following synthesis route: ##STR00044## the method comprising: heating a mixture of a nitro compound II and chlorosulfonic acid to yield a sulfonyl chloride compound III; reducing the sulfonyl chloride compound III to yield a disulfide compound IV; reducing the disulfide compound IV with hydrogen or a metal to yield an amino compound V; contacting the amino compound V with an electrophilic reagent under alkaline conditions to yield an intermediate VI; contacting the intermediate VI with substituted benzyl bromide to yield a first compound I-A; and contacting the first compound I-A with m-chloroperoxybenzoic acid or hydrogen peroxide for oxidation reaction to yield a second compound I-B.

6. A method for preparing the aryl sulfide of claim 1, the method having the following synthesis route: ##STR00045## the method comprising: preparing a benzylamine intermediate XIII from an intermediate VII; contacting the benzylamine intermediate XIII with sulfonyl chloride, followed by reduction reaction and substitution reaction, to yield a first compound I-A; and contacting the first compound I-A with m-chloroperoxybenzoic acid or hydrogen peroxide for oxidation reaction to yield a second compound I-B.

7. A method of control of mites, the method comprising applying the aryl sulfide of claim 1 or a salt thereof.

8. A method of control of nematodes, the method comprising applying the aryl sulfide of claim 1 or a salt thereof.

9. An agricultural composition, comprising the aryl sulfide of claim 1, an agricultural salt and at least one liquid or solid carrier.

10. A method for control of an invertebrate pest, the method comprising treating the invertebrate pest, a food chain thereof, a habitat or breeding place, or a plant and soil where the invertebrate pest grows with the aryl sulfide of claim 1 and an agricultural salt thereof.

11. The method of claim 10, comprising treating the plant with an insecticidally effective dose of a compound represented by formula I and an agricultural salt thereof.

Description

DETAILED DESCRIPTION

[0077] To further illustrate the disclosure, embodiments detailing an aryl sulfide comprising benzylamine and preparation method thereof are described below. It should be noted that the following embodiments are intended to describe and not to limit the disclosure.

Example 1

Preparation of N-(4-chloro-3-fluorobenzyl)-2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (Compound 249)

S1. Preparation of 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride

[0078] ##STR00010##

[0079] At room temperature, chlorosulfonic acid (34.95 g, 30 mmol) was added into a 250 mL round bottom flask, and 2-fluoro-4-methylnitrobenzene (15.5 g, 10 mmol) was slowly added into the flask in four batches. The reaction solution was exothermic obviously. Thereafter, the reaction flask was heated at 60° C., and 2 hours later, the reaction was detected to be basically completed. The reaction solution was added into 500 mL of ice-water mixture, and 400 mL of dichloromethane was added for extraction and liquid separation. 300 mL of water was added to the organic phase. After extraction and separation, the organic phase was evaporated in a rotary evaporator and extracted by silica gel column chromatography, to obtain 16.5 g of a light yellow solid (yield of 64.45%).

S2. Preparation of 1,2-bis (4-fluoro-2-methyl-5-nitrophenyl) disulfide

[0080] ##STR00011##

[0081] Under the protection of nitrogen, 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (12.7 g, 5 mmol) was dissolved in 200 mL of acetic acid. 40 mL concentrated hydrochloric acid was added, and the reaction solution was heated to reflux. An iron powder (11.2 g, 20 mmol) was slowly added into the reaction solution in 4 batches within 1 hour. 1.5 hours later, 20 mL of concentrated salt acid was added and stirred for an hour. Thereafter, most acetic acid in the reaction solution was evaporated, and 300 mL of ethyl acetate and 300 mL of water were added to the reaction solution for extraction and liquid separation. 150 mL of ethyl acetate was added to the water layer for extraction and liquid separation again. The organic layers were combined and washed with 50 mL of saturated sodium chloride solution, dried over 10 g of anhydrous sodium sulfate for 10 min, evaporated in a rotary evaporator, and purified by silica gel column chromatography, to obtain 7.4 g of a light brown solid (yield of 79.56%).

S3. Preparation of 5,5′-disulfide (2-fluoro-4-methylaniline)

[0082] ##STR00012##

[0083] Method 1:

[0084] 1,2-bis (4-fluoro-2-methyl-5-nitrophenyl) disulfide (3.72 g, 1 mmol) was added to 30 mL of 20% hydrochloric acid. The reaction solution was heated at 60° C., and zinc powder (1.30 g, 2 mmol) was slowly added in batches and stirred for 1 hour under heating. Most of acetic acid was removed by vacuum rotary evaporation, and 100 mL of saturated sodium carbonate solution and 100 mL ethyl acetate were added to the residue for extraction and separation. The organic layer was dried over 5 g of anhydrous sodium sulfate, evaporated in a rotary evaporator, and purified by silica gel column chromatography, to yield 2.45 g of an off-white solid (yield of 78.52%).

[0085] Method 2:

[0086] 1,2-bis (4-fluoro-2-methyl-5-nitrophenyl) disulfide (1.86 g, 0.5 mmol) was dissolved in 30 mL of anhydrous ethanol. The air in the reaction flask was replaced with nitrogen, and 0.3 g of palladium carbon (containing 50% water) with 10% palladium was added. The gas in the reaction flask was replaced with hydrogen, and the reaction solution was stirred in 20 atmospheric pressure in the hydrogen atmosphere at 65° C. for 10 hours. After the reaction, the palladium carbon was removed by vacuum filtration, and the reaction solution was evaporated in a rotary evaporator to obtain 1.50 g of a light brown solid (yield of 96.2%).

S4. Preparation of 2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline

[0087] ##STR00013##

[0088] Method 1:

[0089] 5,5′-disulfide (2-fluoro-4-methylaniline) (1.56 g, 5 mmol) was dissolved in 30 mL of N, N-dimethylformamide (DMF). 50 mL of sodium dihydrogen phosphate (5.0 g, 41.7 mmol) aqueous solution was added to the reaction solution. The air in the reaction flash was purged by nitrogen, and sodium hydrosulfite (2.5 g, 14.4 mmol) was added. The reaction flask was heated at 60° C. for 2 hours, and then 2,2-trifluoroethyltrifluoromethane sulfonate (3.48 g, 14.4 mmol) was added and stirred for 1 hour. Thereafter, the reaction solution was added into 300 mL of water, and 200 mL of ethyl acetate was added for extraction and liquid separation. The organic layer was washed with water four times, 300 mL of water each time. After washing, the organic layer was evaporated in a rotary evaporator, and purified by silica gel column chromatography, to yield to obtain 1.68 g of light brown liquid (yield 70.29%).

[0090] .sup.1H-NMR (400 MHz, d6-DMSO): δ=7.01 (m, 2H, Ar—H), 5.12 (s, 2H, N—H), 3.76 (dd, J=21.2, 10.4 Hz, 2H, CH.sub.2), 2.30 (s, 3H, CH.sub.3).

[0091] Method 2:

[0092] 5,5′-disulfide (2-fluoro-4-methylaniline) (1.56 g, 5 mmol) was dissolved in 30 mL of N, N-dimethylformamide (DMF). Sodium carbonate (0.53 g, 5 mmol) and sodium hydroxymethylsulfinate (0.67 g, 5 mmol) were added, and then 2,2,2-trifluoroioethane (3.15 g, 15 mmol) was added and stirred for 1 hour. Thereafter, the reaction solution was added into 300 mL of water, and 200 mL of ethyl acetate was added for extraction and liquid separation. The organic layer was washed with water four times, 300 mL of water each time. After washing, the organic layer was evaporated in a rotary evaporator, and purified by silica gel column chromatography, to yield to obtain 1.77 g of light brown liquid (yield of 74.06%).

[0093] .sup.1H-NMR (400 MHz, d6-DMSO): δ=7.01 (m, 2H, Ar—H), 5.12 (s, 2H, N—H), 3.76 (dd, J=21.2, 10.4 Hz, 2H, CH.sub.2), 2.30 (s, 3H, CH.sub.3).

S5. Preparation of N-(4-chloro-3-fluorobenzyl)-2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (Compound 249)

[0094] 2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (239 mg, 1 mmol) was added to DMF (5 mL), and then potassium carbonate (138 mg, 1 mmol) and 4-bromomethyl-1-chloro-2-fluorobenzene (223 mg, 1 mmol) were added sequentially. The reaction solution was stirred at room temperature for 5 hours, added into 100 mL of water, and extracted twice with 100 mL of ethyl acetate. The organic phase was washed with water, dried over anhydrous sodium sulfate, vacuum concentrated, and purified with column chromatography to yield 252 mg of a colorless viscous liquid. The yield was 66.0%.

[0095] .sup.1H-NMR (500 MHz, CDCl.sub.3): δ=7.21-7.34 (m, 2H), 7.00-7.04 (m, 1H), 6.79-6.88 (m, 2H), 4.44 (d, J=8.0 Hz, 2H), 3.17 (q, J=7.5 Hz, 2H), 2.36 (d, J=21.5 Hz, 3H).

[0096] MS (m/z, ESI): 382.04 (m+H).

Example 2

Preparation of 2-fluoro-N-(3-fluorobenzyl)-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (compound 229)

S1. Preparation of 4-fluoro-2-methyl-5-nitrophenylthiophenol

[0097] 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (0.15 mol, 38.0 g) was placed in a 250 mL single mouthed flask, and 80 mL of hydroiodate was added. The reaction solution turned black, and was stirred at room temperature for 1 hour. Thereafter, 80 mL of saturated sodium sulfite solution was slowly added, and a yellow powdery solid appeared in the reaction solution. The yellow powdery solid was vacuum filtered and washed with water, to yield 28.0 g of a light yellow powder with a yield of 100%.

S2. Preparation of 4-fluoro-2-methyl-5-aminothiophenol

[0098] 4-fluoro-2-methyl-5-nitrobenzene thiophenol (0.15 mol, 28.0 g) was dissolved in anhydrous ethanol (280 mL), and 10% palladium carbon (1.0 g, 50% water content) was added. The gas in the reaction flask was replaced by hydrogen three times, and the reaction solution was stirred overnight at room temperature under normal pressure in the hydrogen atmosphere. The reaction solution was filtered under reduced pressure to remove palladium carbon, and concentrated to dryness under reduced pressure to remove ethanol. 23.2 g of a gray white solid was obtained with a yield of 98.7%. 1H-NMR (400 MHz, d6-DMSO): δ=6.93 (m, 2H, Ar—H), 5.12 (s, 2H, N—H), 3.35 (br, 0.5H, S—H), 2.15 (s, 3H, CH3).

S3. Preparation of 2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl) thio) aniline

[0099] 4-fluoro-2-methyl-5-aminothiophenol (25 mmol, 3.9 g) was dissolved in anhydrous DMF (50 mL), and then sodium carbonate (50 mmol, 5.3 g, 2 eq) and sodium hydroxymethyl sulfite (25 mmol, 3.4 g, 1 eq) were added successively. Thereafter, trifluoroethane (27.5 mmol, 5.8 G, 1.1 eq) was added under ice bath. The reaction solution was stirred at room temperature for 2 hours until the reaction was complete. The reaction solution was poured into water, and extracted and separated with ethyl acetate. The organic layer was washed with water for three times, and then washed with saturated salt water once. After separation, the organic layer was dried over anhydrous sodium sulfate, and dried under reduced pressure to yield a light brown oily liquid. The light brown oily liquid was purified by column chromatography with a mobile phase of petroleum ether:ethyl acetate=10:1, to yield 4.2 g of a yellow oily product with a yield of 71.2%.

[0100] 1H-NMR (400 MHz, d6-DMSO): δ=7.01 (m, 2H, Ar—H), 5.12 (s, 2H, N—H), 3.76 (dd, J=21.2, 10.4 Hz, 2H, CH2), 2.30 (s, 3H, CH3).

S4. Preparation of 2-fluoro-N-(3-fluorobenzyl)-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (Compound 229)

[0101] ##STR00014##

[0102] The operations are the same as that in S5 of Example 1.

[0103] .sup.1H-NMR (500 MHz, CDCl.sub.3): δ=7.28-7.33 (m, 1H), 7.05-7.14 (m, 2H), 6.94-6.99 (m, 1H), 6.85 (d, J=15.0 Hz, 1H), 6.75 (d, J=10.5 Hz, 1H), 4.36 (d, J=7.0 Hz, 2H), 3.17 (q, J=12.0 Hz, 2H), 2.35 (d, J=6.0 Hz, 3H).

[0104] MS (m/z, ESI): 388.07 (m+H).

Example 3

Preparation of 2-fluoro-N-(3-methoxybenzyl)-4-methyl-5-(2,2,2-trifluoroethyl) thio) aniline (Compound 239)

S1: Preparation of N-(2-fluoro-4-methylphenyl) acetamide

[0105] ##STR00015##

[0106] 2-fluoro-4-methylaniline (125 g, 1 mol) was dissolved in dichloromethane (1 L), and triethylamine (111 g, 1.1 mol) was added. The mixture solution was cooled in an ice salt bath until the internal temperature thereof was 0° C. Acetic anhydride (102 g, 1 mol) was added slowly. Thereafter, the reaction solution was stirred for reaction at room temperature for 3 hours. 2 L of water was added to the reaction solution for extraction and separation. The organic phase was dried over anhydrous sodium sulfate, and evaporated in a rotary evaporator, to yield 162 g of a white solid, with a yield of 97.0%.

S2: Preparation of 5-acetamino-4-fluoro-2-methylbenzenesulfonyl chloride

[0107] ##STR00016##

[0108] N-(2-fluoro-4-methylphenyl) acetamide (145 g, 868 mmol) was added to a 1 L round bottom flask, and a tail gas absorption device was disposed on the round bottom flask. Chlorosulfonic acid (302 g, 2.60 mol) was slowly added and electrically stirred. Thereafter, the mixed solution was heated until the internal temperature thereof was 60° C. 3 hours later, the temperature was reduced to room temperature. The reaction liquid was stirred and slowly added to 2 kg of ice, and extracted twice with 500 mL of ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and evaporated in a rotary evaporator, to yield 175.2 g of an off-white solid, with a yield of 76.2%.

S3: Preparation of N-(2-fluoro-5-mercapto-4-methylphenyl) acetamide

[0109] ##STR00017##

[0110] 5-acetamino-4-fluoro-2-methylbenzenesulfonyl chloride (174.6 g, 660 mmol) was added to acetic acid (700 mL), and red phosphorus (50 g, 1.61 mol) and iodine (2 g) were added sequentially. The reaction liquid was heated to a reflux state and stirred for 3 hours. The reaction liquid was concentrated under reduced pressure to remove acetic acid. 1.5 L of water and 1 L of ethyl acetate were added for extraction and liquid separation. 500 mL of ethyl acetate was added to the aqueous phase to separate the liquid. The organic phases were combined, washed with sodium carbonate solution, separated and evaporated in a rotary evaporator to yield 103.4 g of a light brown solid with a yield of 78.4%.

S4: Preparation of 5-amino-4-fluoro-2-methylthiophenol

[0111] ##STR00018##

[0112] N-(2-fluoro-5-mercapto-4-methylphenyl) acetamide (101 g, 507 mmol) was added to 10% sodium hydroxide aqueous solution (1 L), heated and refluxed for 5 hours. The pH of the reaction solution was adjusted to 7 with dilute hydrochloric acid, and then the reaction solution was extracted with ethyl acetate. The organic phase was dried with anhydrous sodium sulfate and concentrated under reduced pressure. 62.7 g of an off-white solid was obtained with a yield of 78.8%.

S5: Preparation of 2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline

[0113] ##STR00019##

[0114] 5-amino-4-fluoro-2-methylthiophene (15.72 g, 0.1 mol) was dissolved in DMF (100 mL), and then potassium hydroxide (5.6 g, 0.1 mol), sodium formaldehyde bisulfite (15.4 g, 0.1 mol) and trifluoro iodoethane (20.9 g, 0.1 mol) were successively added. The reaction solution was stirred at room temperature for 5 hours, and then added into 500 mL of water. 500 mL of ethyl acetate extract was added for extraction and liquid separation. 200 mL of ethyl acetate was added to the aqueous phase to extract and separate the liquid. The organic layers were combined, washed with 500 mL of water twice. The organic phase was separated, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and then purified by column chromatography. 16.6 g of a light brown liquid was obtained with a yield of 69.45%.

S6: Preparation of 2-fluoro-N-(3-methoxybenzyl)-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (Compound 239)

[0115] ##STR00020##

[0116] The operations are the same as that in S5 of Example 1.

[0117] .sup.1H-NMR (500 MHz, CDCl.sub.3): δ=7.24-7.28 (m, 1H), 6.76-6.98 (m, 5H), 4.30 (d, J=16.5 Hz, 2H), 3.75 (s, 3H), 3.15 (q, J=12.0 Hz, 2H), 2.35 (s, 3H).

[0118] MS (m/z, ESI): 360.09 (m+H).

Example 4

Preparation of 2-fluoro-4-methyl-n-(3-nitrobenzyl)-5-((2,2,2-trifluoroethyl) thio) aniline (Compound 241)

[0119] ##STR00021##

[0120] The operations are the same as that in S5 of Example 1.

[0121] .sup.1H-NMR (500 MHz, CDCl.sub.3): δ=8.10 (d, J=10.0 Hz, 1H), 7.58-7.60 (m, 2H), 7.44-7.47 (m, 1H), 6.87 (d, J=14.5 Hz, 1H), 6.68 (d, J=11.0 Hz, 1H), 4.75 (d, J=8.0 Hz, 2H), 3.15 (q, J=12.0 Hz, 2H), 2.35 (s, 3H).

[0122] MS (m/z, ESI): 375.06 (m+H).

Example 5

Preparation of N-(3,4-dichlorobenzyl)-2-fluoro-4-methyl-5-(2,2,2-trifluoroethyl) thio) aniline (Compound 247)

[0123] ##STR00022##

[0124] The operations are the same as that in S5 of Example 1.

[0125] .sup.1H-NMR (500 MHz, CDCl.sub.3): δ=7.34-7.45 (m, 2H), 7.19 (dd, J.sub.1=3.0 Hz, J.sub.2=10.5 Hz, 1H), 6.73 (d, J=10.5 Hz, 1H), 6.55 (d, J=10.5 Hz, 1H), 4.31 (d, J=6.5 Hz, 2H), 3.17 (q, J=12.5 Hz, 2H), 2.36 (d, J=14.0 Hz, 3H).

[0126] MS (m/z, ESI): 398.01 (m+H).

Example 6

Preparation of 2-(((2-fluoro-4-methyl-5-((2,2, 2-trifluoroethyl) thio) phenyl) amino) methyl) benzoate (Compound 53)

[0127] ##STR00023##

[0128] The operations are the same as that in S5 of Example 1.

[0129] .sup.1H-NMR (500 MHz, CDCl.sub.3): δ=7.98 (d, J=9.5 Hz, 1H), 7.46-7.48 (m, 2H), 7.31-7.34 (m, 1H), 6.80-6.84 (m, 2H), 4.68 (s, 2H), 3.92 (s, 3H), 3.18 (q, J=12.0 Hz, 3H), 2.32 (s, 3H).

[0130] MS (m/z, ESI): 388.06 (m+H).

Example 7

Preparation of N-(3-bromobenzyl)-2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (Compound 233)

[0131] ##STR00024##

[0132] The operations are the same as that in S5 of Example 1.

[0133] .sup.1H-NMR (500 MHz, CDCl.sub.3): δ=7.51 (s, 1H), 7.38-7.42 (m, 1H), 7.23-7.40 (m, 2H), 6.85-6.88 (m, 1H), 6.76 (d, J=11.0 Hz, 1H), 4.34 (s, 2H), 3.17 (q, J=12.0 Hz, 2H), 2.36 (d, J=10.0 Hz, 3H).

[0134] MS (m/z, ESI): 408.00 (m+H).

Example 8

Preparation of 2-fluoro-N-(4-iodobenzyl)-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (Compound 707)

[0135] ##STR00025##

[0136] The operations are the same as that in S5 of Example 1.

[0137] .sup.1H-NMR (500 MHz, CDCl.sub.3): δ=7.72 (s, 1H), 7.62 (d, J=9.5 Hz, 1H), 7.29-7.32 (m, 1H), 7.08-7.12 (m, 1H), 6.87 (d, J=15.5 Hz, 1H), 6.76 (d, J=11.0 Hz, 1H), 4.32 (s, 2H), 3.17 (q, J=12.0 Hz, 2H), 2.33 (d, J=21.5 Hz, 3H).

[0138] MS (m/z, ESI): 455.87 (m+H).

Example 9

Preparation of N-(3-bromo-5-fluorobenzyl)-2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (Compound 251)

[0139] ##STR00026##

[0140] The operations are the same as that in S5 of Example 1.

[0141] .sup.1H-NMR (500 MHz, CDCl.sub.3): δ=7.19-7.27 (m, 3H) 6.78-6.87 (m, 2H), 4.37 (d, J=7.0 Hz, 2H), 3.21 (q, J=12.0 Hz, 2H), 2.34-2.36 (m, 3H).

[0142] MS (m/z, ESI): 325.98 (m+H).

Example 10

Preparation of 2-fluoro-n-(4-fluorobenzyl)-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (Compound 709)

[0143] ##STR00027##

[0144] The operations are the same as that in S5 of Example 1.

[0145] .sup.1H-NMR (500 MHz, CDCl.sub.3): δ=7.30-7.34 (m, 2H), 6.96-7.06 (m, 2H), 6.82 (d, J=11.5 Hz, 1H), 6.76 (d, J=11.0 Hz, 1H), 4.31 (d, J=7.0 Hz, 2H), 3.22 (q, J=12.5 Hz, 2H), 2.34-2.36 (m, 3H).

[0146] MS (m/z, ESI): 348.07 (m+H).

Example 11

Preparation of N-(4-chlorobenzyl)-2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (Compound 711)

[0147] ##STR00028##

[0148] The operations are the same as that in S5 of Example 1.

[0149] .sup.1H-NMR (500 MHz, CDCl3): δ=7.35 (s, 1H), 7.22-7.28 (m, 3H), 6.87 (d, J=15.0 Hz, 1H), 6.76 (d, J=11.0 Hz, 1H), 4.31 (d, J=7.0 Hz, 2H), 3.21 (q, J=12.0 Hz, 2H), 2.34-2.37 (m, 3H).

[0150] MS (m/z, ESI): 364.05 (m+H).

Example 12

Preparation of N-benzyl-2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (Compound 1105)

[0151] ##STR00029##

[0152] The operations are the same as that in S5 of Example 1.

[0153] .sup.1H-NMR (500 MHz, CDCl3): δ=7.18-7.28 (m, 6H), 6.73-6.82 (m, 2H), 4.26 (s, 2H), 3.06-3.16 (m, 2H), 2.27 (s, 3H).

[0154] MS (m/z, ESI): 330.09 (m+H).

Example 13

Preparation of 4-((2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl) thio) phenyl) amino) methyl) benzylnitrile (Compound 721)

[0155] ##STR00030##

[0156] The operations are the same as that in S5 of Example 1.

[0157] .sup.1H-NMR (500 MHz, CDCl3): δ=7.64 (d, J=10.0 Hz, 2H), 7.46 (d, J=10.5 Hz, 2H), 6.88 (d, J=18.5 Hz, 1H), 6.66 (d, J=11.0 Hz, 1H), 4.44 (s, 2H), 3.14 (q, J=7.0 Hz, 2H), 2.36 (s, 3H).

[0158] MS (m/z, ESI): 355.08 (m+H).

Example 14

Preparation of methyl 4-((2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl) thio) phenyl) amino) methyl benzoate (Compound 739)

[0159] ##STR00031##

[0160] The operations are the same as that in S5 of Example 1.

[0161] .sup.1H-NMR (500 MHz, CDCl3): δ=7.94 (d, J=10.5 Hz, 2H), 7.34 (d, J=10.0 Hz, 2H), 6.77 (d, J=15.5 Hz, 1H), 6.68 (d, J=10.5 Hz, 1H), 4.34 (s, 2H), 3.83 (s, 3H), 3.07 (q, J=12.0 Hz, 2H), 2.27 (s, 3H).

[0162] MS (m/z, ESI): 388.06 (m+H).

Example 15

Preparation of 2-fluoro-N-(4-methoxybenzyl)-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (Compound 1131)

[0163] ##STR00032##

[0164] The operations are the same as that in S5 of Example 1.

[0165] .sup.1H-NMR (500 MHz, CDCl3): δ=7.20-7.26 (m, 2H), 7.67-7.84 (m, 4H), 5.07 (s, 1H), 4.20 (s, 2H), 3.69 (s, 3H), 3.13 (q, J=12.0 Hz, 2H), 2.28 (s, 3H).

[0166] MS (m/z, ESI): 360.09 (m+H).

Example 16

Preparation of 2-((2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl) thio) phenyl) amino) methyl) benzylnitrile (Compound 33)

[0167] ##STR00033##

[0168] The operations are the same as that in S5 of Example 1.

[0169] .sup.1H-NMR (500 MHz, CDCl3): δ=7.68 (d, J=9.5 Hz, 1H), 7.50-7.55 (m, 2H), 7.35-7.37 (m, 1H), 6.85 (d, J=8.5 Hz, 1H), 6.74 (d, J=10.5 Hz, 1H), 3.18 (q, J=12.0 Hz, 2H), 2.35 (s, 3H).

[0170] MS (m/z, ESI): 355.08 (m+H).

Example 17

Preparation of 2-fluoro-4-methyl-N-(4-nitrobenzyl)-5-((2,2,2-trifluoroethyl) thio) aniline (Compound 755)

[0171] ##STR00034##

[0172] The operations are the same as that in S5 of Example 1.

[0173] .sup.1H-NMR (500 MHz, CDCl3): δ=7.68 (d, J=9.5 Hz, 1H), 7.50-7.55 (m, 2H), 7.35-7.37 (m, 1H), 6.85 (d, J=8.5 Hz, 1H), 6.74 (d, J=10.5 Hz, 1H), 4.49 (s, 2H), 3.18 (q, J=12.0 Hz, 2H), 2.35 (s, 3H).

[0174] MS (m/z, ESI): 375.06 (m+H).

Example 18

Preparation of 2-fluoro-N-(2-iodobenzyl)-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (Compound 31)

[0175] ##STR00035##

[0176] The operations are the same as that in S5 of Example 1.

[0177] .sup.1H-NMR (500 MHz, CDCl3): δ=7.86 (d, J=10.0 Hz, 1H), 7.30-7.33 (m, 2H), 6.95-7.00 (m, 1H), 6.85 (d, J=8.5 Hz, 1H), 6.73 (d, J=11.0 Hz, 1H), 4.34 (s, 2H), 3.20 (q, J=12.0 Hz, 2H), 2.35 (s, 3H).

[0178] MS (m/z, ESI): 455.87 (m+H).

Example 19

Preparation of 2-fluoro-4-methyl-5-((2,2,2-trifluoroethyl) thio)-N-(2-(trifluoromethoxy) benzyl) aniline (Compound 1107)

[0179] ##STR00036##

[0180] The operations are the same as that in S5 of Example 1.

[0181] .sup.1H-NMR (500 MHz, CDCl3): δ=7.30-7.53 (m, 4H), 6.85 (d, J=16.5 Hz, 1H), 6.73 (d, J=10.5 Hz, 1H), 4.44 (s, 2H), 3.17 (q, J=12.0 Hz, 2H), 2.36 (s, 3H).

[0182] MS (m/z, ESI): 413.95 (m+H).

Example 20

Preparation of 2-fluoro-n-(4-fluorobenzyl)-4-methyl-5-((2,2,2-trifluoroethyl) sulfinyl) aniline (Compound 710)

[0183] ##STR00037##

[0184] 2-fluoro-N-(4-fluorobenzyl)-4-methyl-5-((2,2,2-trifluoroethyl) thio) aniline (347 mg, 1 mmol) was dissolved in chloroform (5 mL). m-chloroperoxybenzoic acid (172 mg, 1 mmol) was added under an ice bath. The reaction solution was stirred for 1 hour, and 50 mL of ethyl acetate and 50 mL of water were added for extraction and liquid separation. 50 mL of ethyl acetate was added to the aqueous phase. The organic phases were combined, washed with 50 mL of saturated salt water, evaporated in a rotary evaporator and purified by silica gel column chromatography, to obtain 288 mg of a white solid, with a yield of 79.3%.

[0185] .sup.1H-NMR (500 MHz, CDCl3): δ=7.30-7.34 (m, 2H), 6.96-7.06 (m, 2H), 6.85 (d, J=11.5 Hz, 1H), 6.56 (d, J=11.0 Hz, 1H), 4.31 (d, J=7.0 Hz, 2H), 3.22 (q, J=12.5 Hz, 2H), 2.26 (s, 3H).

[0186] MS (m/z, ESI): 364.07 (m+H).

Example 21

Preparation of 2-((((2-Fluoro-4-methyl-5-((2,2, 2-trifluoroethyl) sulfonyl) phenyl) amino) methyl) benzoate (Compound 54)

[0187] ##STR00038##

[0188] The operations are the same as that in S5 of Example 1 and Example 20.

[0189] 1H-NMR (500 MHz, CDCl3): δ=7.94-8.04 (m, 1H), 7.45-7.48 (m, 2H), 7.25-7.28 (m, 2H), 6.82 (d, J=14.5 Hz, 1H), 4.73 (s, 2H), 3.94 (s, 3H), 3.29 (q, J=18.0 Hz, 2H), 2.23 (s, 3H).

[0190] MS (m/z, ESI): 404.1 (m+H), 424.1 (m+Na).

Example 22

Preparation of 5-Fluoro-2-((((2-Fluoro-4-methyl-5-(2,2, 2-trifluoroethyl) thio) phenyl) amino) methyl) benzoate (Compound 303)

[0191] ##STR00039##

[0192] The operations are the same as that in S5 of Example 1.

[0193] 1H-NMR (500 MHz, CDCl3): δ=7.68 (dd, J.sub.1=3.5 Hz, J.sub.2=11.5 Hz, 1H), 7.45 (dd, J.sub.1=7.0 Hz, J.sub.2=10.5 Hz, 1H), 7.16 (t, J=10 Hz, 1H), 6.81 (dd, J.sub.1=10.5 Hz, J.sub.2=17.5 Hz, 2H), 4.65 (s, 2H), 3.92 (s, 3H), 3.19 (q, J=7.5 Hz, 2H), 2.33 (s, 3H).

[0194] MS (m/z, ESI): 406.5 (m+H).

Example 23

Preparation of 2-((((4-chloro-2-fluoro-5-((2,2, 2-trifluoroethyl) thio) phenyl) amino) methyl) benzoate (Compound 1202)

[0195] ##STR00040##

[0196] The operations are the same as that in S5 of Example 1.

[0197] 1H-NMR (500 MHz, CDCl3): δ=8.00 (dd, J.sub.1=1.5 Hz, J.sub.2=9.5 Hz, 1H), 7.43-7.50 (m, 2H), 7.33-7.38 (m, 1H), 7.05 (d, J=14 Hz, 1H), 6.91 (d, J=6.0 Hz, 1H), 4.69 (s, 2H), 3.92 (s, 3H), 3.32 (q, J=14.0 Hz, 2H).

[0198] MS (m/z, ESI): 408.5 (m+H), 430.5 (m+Na).

Example 24

Preparation of 2-Fluoro-N-(4-Fluoro-Benzyl)-4-methyl-5-((2,2, 2-trifluoroethyl) sulfide) aniline (hydrochloride of Compound 709)

[0199] ##STR00041##

[0200] 2-fluoro-N-(4-fluoro-benzyl)-4-methyl-5-((2,2, 2-trifluoroethyl) sulfide) aniline (347 mg, 1 mmol) was dissolved in methanol (5 mL), and 30% hydrogen chloride methanol solution (5 mL) was added. The mixed solution was stirred at room temperature for 1 hour, and distilled under reduced pressure to remove the solvent and hydrogen chloride. 384 mg of a white solid was obtained with a yield of 100%.

[0201] .sup.1H-NMR (500 MHz, DMSO): δ=7.11-7.28 (m, 6H), 6.75-6.85 (m, 2H), 4.58 (d, J=7.0 Hz, 2H), 3.22 (q, J=12.5 Hz, 2H), 2.34-2.36 (m, 3H).

[0202] MS (m/z, ESI): 348.07 (m+H).

Example of Preparation 1

[0203] Emulsifiable Concentrate Comprising 8% of Compound 709

[0204] 8 parts of the compound 709 were dissolved in a mixture of 10 parts of methylnaphthalene, 2 parts of methylpyrrolidone and 20 parts of methyl oleate 1169. The mixture was stirred, and 8 parts of calcium dodecyl benzene sulfonate and 4 parts of tristyrene phenol polyoxyethylene polyoxypropylene ether were added. The balance was aromatic solvent oil until the total weight was 100 parts. The mixed solution was stirred to yield an emulsifiable concentrate comprising 8% of the compound 709.

Example of Preparation 2

[0205] Suspension Agent Comprising 20% of Compound 710

[0206] 20 parts of the compound 71, 1 part of magnesium aluminum silicate and 0.3 parts of benzoic acid were mixed for use. 3 parts of ammonium tristyrylphenol polyoxyethylene ether sulfate, 3 parts of a block polyether, 5 parts of ethylene glycol and water were sheared and mixed in a high-speed shear machine. Then, the sheared additives were added to the solid mixture, stirred and sheared, and then ground in a grinder for 3 hours. Thereafter, the glass beads were filtered out to obtain a suspending agent comprising 20% of the compound 710.

Example of Preparation 3

[0207] Wettable Powders Comprising 20% of Compound 53

[0208] 20 parts of the compound 53 was added to a mixture of 2 parts of sodium lauryl sulfate, 4 parts of sodium lignosulfonate, 20 parts of silica hydrate and 54 parts of clay. The mixture was fully stirred to yield wettable powders comprising 20% of the compound 53.

Example of Preparation 4

[0209] Granules Comprising 5% of Compound 53

[0210] 2 parts of sodium dodecylbenzene sulfonate, 10 parts of bentonite and 83 parts of clay were added to 5 parts of the compound 53. The mixture was stirred fully, and appropriate amount of water was added. The mixture was continuously stirred, granulated with a granulator, and air dried to yield granules comprising 5% of the compound 53.

Example of Preparation 5

[0211] Dry Flowable Comprising 30% of Compound 53

[0212] 30 parts of the compound 53, 20 parts of sodium lignosulfonate, 2 parts of a wetting agent, and 2 parts of white carbon black were mixed, and Kaolin was added until the total weight was 100 parts. The mixture was mixed with water, smashed and homogenized with a shearing machine, ground in a sand mill, and spray dried to yield a dry flowable comprising 30% of the compound 53.

Example of Use

[0213] Activity Test of Tetranychus cinnabarinus

[0214] The compound under test was dissolved in acetone and diluted to desired concentration with 0.1% Tween 80 solution with acetone content not exceeding 5%.

[0215] One true leaf was removed from the bean seedlings having two true leaves. Tanyanychus cinarinus was inoculated and the cardinal number thereof investigated. The whole plant was sprayed with a handheld sprayer, and each treatment was repeated for 3 times. After treatment, the bean seedlings were cultured in a constant temperature room. 72 hours later, the number of live mites was investigated and the mortality rate was calculated. The number of Tetranychus cinnabarinus was 100-200 per inoculation.

Mortality=(number of inoculated mites−number of live mites after treatment)×number of inoculated mites×100%.

[0216] In this test, the following compounds showed a lethal rate of over 90% against mites at 100 ppm (100 mg/L): Nos 1, 2, 3, 4, 5, 6, 25, 26, 27, 28, 29, 30, 33, 34, 39, 40, 41, 42, 43, 44, 53, 54, 55, 56, 57, 58, 67, 68, 71, 72, 95, 96, 97, 98, 99, 100, 108, 109, 110, 111, 139, 140, 141, 142, 153, 154, 155, 156, 167, 168, 169, 170, 229, 230, 231, 232, 247, 248, 249, 250, 253, 254, 255, 256, 257, 258, 275, 276, 277, 278, 283, 284, 285, 286, 289, 290, 291, 292, 293, 294, 303, 304, 305, 306, 307, 308, 317, 318, 321, 322, 331, 332, 355, 356, 357, 358, 366, 367, 368, 369, 423, 424, 425, 426, 507, 508, 509, 510, 523, 524, 535, 536, 537, 538, 577, 578, 619, 620, 635, 636, 647, 648, 649, 650, 805, 806, 807, 808, 817, 818, 819, 820, 929, 930, 931, 932, 957, 958, 1029, 1030, 1031, 1032, 1043, 1044, 1045, 1046, 1071, 1072, 1113, 1114, 1115, 1116, 1117, 1118, 1125, 1126, 1165, 1166, 1167, 1168, 1177, 1178, 1202, 1203, 1204, 1205, 1216, 1217, 1256, 1257, 1264, 1265, 1266, 1267, 1268, 1269, 1270, 1271, 1274, 1275, 1282, 1283, 1284, 1285, 1286, 1287, 1288, 1289, 1292, 1293, 1300, 1301, 1302, 1303, 1304, 1305, 1306, 1307, 1310, 1311, 1318, 1319, 1320, 1321, 1322, 1323, 1324, 1325, 1328, 1329.

[0217] In this test, the following compounds showed a lethal rate of more than 90% against mites at 25 ppm (25 mg/L): Nos 53, 54, 55, 56, 108, 109, 303, 304, 305, 306, 366, 367, 535, 536, 1165, 1166, 1167, 1168, 1177, 1178, 1202, 1203, 1264, 1265, 1282, 1283, 1300, 1301, 1318, 1319.

[0218] In this test, the following compounds showed a lethal rate of more than 90% against mites at 6.25 ppm (6.25 mg/L): Nos 53, 54, 303, 304, 1165, 1166, 1202, 1203.

[0219] According to the above method, the compound Nos 53, 54, 303, 304, 1165, 1166, 1202 and 1203 of the disclosure were selected to carry out the acaricidal parallel test with bifenazate and cyflumetofen. The test results are shown in Table 2 below:

TABLE-US-00002 TABLE 2 Test data Compound No: Concentration (ppm) Mortality % 53 3.12 99 54 3.12 100 303 3.12 99 304 3.12 98 1165 3.12 99 1166 3.12 98 1202 3.12 97 1203 3.12 98 Bifenazate 3.12 85 Cyflumetofen 3.12 72

[0220] It will be obvious to those skilled in the art that changes and modifications may be made, and therefore, the aim in the appended claims is to cover all such changes and modifications.