Phenoxypyridine compound containing acylthiourea and heterocyclic structure as well as preparation method and application of phenoxypyridine compound

Abstract

The invention discloses a phenoxypyridine compound with acylthiourea and a heterocyclic structure as well as a preparation method and application of the phenoxypyridine compound. The invention belongs to the field of herbicides. The invention aims to solve the technical problem that the existing herbicide cannot give consideration to both herbicidal activity and use safety. The phenoxypyridine compound containing the acylthiourea and the heterocyclic structure, provided by the invention, has good inhibitory activity on PPO (Poly-p-phenylene Oxide). The herbicidal composition has especially excellent herbicidal activity on weeds such as morning glory, dog tail grass, chenopodium quinoa and abutilon fiber, and especially has an excellent effect on dicotyledonous weeds, and the control effect is even superior to that of some commercial herbicides sold in the market. The compound can be used as a PPO inhibitor. The weeding composition can also be prepared into a weeding agent for preventing and controlling crop weeds.

Description

Technical Field

[0001] The invention belongs to the field of herbicides, and in particular relates to a phenoxypyridine compound containing acylthiourea and a heterocyclic structure, and a preparation method and application thereof. Background Art

[0002] The production of food is threatened by natural factors such as diseases, insects, and weeds. Among them, weed damage can reduce crop yields by nearly 11%. Weed damage not only competes with field crops for resources necessary for plant growth, but also makes the breeding and spread of diseases and insect pests more serious. Therefore, effective control of weeds in crop fields is very important for food production. The use of herbicides is a relatively economical, time-saving and labor-saving method. With the increasing use of herbicides year by year, it brings some negative effects such as environmental pollution, resistant weeds, drug damage, and residues. In order to solve the problems of herbicide damage and the increasingly serious weed resistance, it is very necessary to develop new herbicides with ultra-high activity, low residue, low toxicity and selectivity.

[0003] Protoporphyrinogen oxidase (PPO) is an important target in the research of green herbicides. Currently, PPO herbicides are mainly divided into eight categories of products. Among them, diphenyl ethers are the earliest discovered PPO herbicides. This type of herbicide has a broad spectrum of weed control, fast weed control, low dosage and is not easy to produce resistance. It has broad application prospects. However, due to long-term unreasonable use, environmental pollution, resistant weeds, pesticide damage, residues and other problems have occurred.

[0004] At present, there are also many problems in commercial diphenyl ether PPO herbicides. For example, trifluorfen can effectively control broadleaf weeds in soybean fields, but when the spraying dosage is inappropriate or the soil is dry, the control effect is poor and slight phytotoxicity occurs, showing symptoms such as yellowing, shrinking, and browning of soybean leaves; due to the physical and chemical properties of flufenacet, it is easy to stay on the soil surface, the residual period is relatively long, and it causes phytotoxicity to subsequent crops. In addition, flufenacet remaining in the soil is washed by rainwater, thereby polluting surface water such as rivers, lakes, and reservoirs, as well as groundwater; oxyfluorfenacet needs to be sprayed on sunny days when used in rice fields. If heavy rain occurs after application and the water submerges the seedling core, the seedlings will die due to phytotoxicity. Therefore, the study of new diphenyl ether derivative PPO inhibitor herbicides is of great significance for finding highly active and safe lead compounds. Summary of the invention

[0005] In order to overcome the above technical defects, the present invention provides a phenoxypyridine compound containing acylthiourea and a heterocyclic structure, and a preparation method and application thereof.

[0006] The technical solution of the present invention is as follows:

[0007] One of the purposes of the present invention is to provide a phenoxypyridine compound containing an acylthiourea and a heterocyclic structure, wherein the general structural formula of the compound is shown in the following formula (I) or formula (II):

[0008]

[0009] Wherein R1 is at least one selected from H, Cl, Br, NO2 or CF3; X is O or S; R2 is H or Cl.

[0010] The second object of the present invention is to provide a method for preparing a phenoxypyridine compound containing acylthiourea and a heterocyclic structure, the method being carried out according to the following steps:

[0011] Step 1: Dissolve 4-aminophenol or 3-aminophenol and an acid-binding agent in an organic solvent 1, then add compound a. After the reaction is completed, cool to room temperature, add distilled water, extract, wash, dry and concentrate to obtain intermediate d or intermediate e. The structural formula of compound a is:

[0012]

[0013] Step 2: Compound f and potassium thiocyanate are dissolved in organic solvent 2 to obtain respective organic solutions, and then the two organic solutions are mixed. After the reaction is completed, the mixture is cooled and filtered to obtain a solution containing intermediate h; the structural formula of compound f is:

[0014]

[0015] Step 3: adding intermediate d or intermediate e to a solution containing intermediate h to react. After the reaction is completed, adding a poor solvent to the reaction solution, allowing it to stand, filtering, collecting insoluble matter, and recrystallizing to obtain a phenoxypyridine compound (I) or (II) containing acylthiourea and a heterocyclic structure;

[0016] In compound a and compound f, R1, X and R2 are as defined above.

[0017] In further limitation, in step 1, the organic solvent 1 is N,N-dimethylformamide or dimethyl sulfoxide, preferably dimethyl sulfoxide.

[0018] It is further defined that the acid binding agent in step 1 is cesium carbonate or potassium carbonate, preferably cesium carbonate.

[0019] It is further defined that in step 1, the molar ratio of compound a to 4-aminophenol or 3-aminophenol and the acid-binding agent is 1:1:(1-3), preferably 1:1:2.

[0020] It is further defined that the reaction temperature in step 1 is 80-100°C, preferably 90°C.

[0021] It is further defined that the organic solvent 2 in step 2 is acetone or acetonitrile, preferably acetonitrile.

[0022] It is further defined that the molar ratio of compound f to potassium thiocyanate in step 2 is less than 1.

[0023] It is further defined that the reaction temperature in step 2 is 25-70°C, preferably 70°C.

[0024] It is further defined that in step three, the molar ratio of intermediate d or intermediate e to intermediate h is less than 1.

[0025] It is further defined that the reaction temperature in step 3 is 20-40°C, preferably 25-30°C.

[0026] It is further defined that the poor solvent in step 3 is distilled water or a NaHCO3 solution with a pH of 8-9, preferably a NaHCO3 solution with a pH of 8-9.

[0027] It is further defined that the solvent used for recrystallization in step 3 is acetonitrile-water.

[0028] The third object of the present invention is to provide a phenoxypyridine compound containing acylthiourea and a heterocyclic structure for use as a protoporphyrinogen oxidase (PPO) inhibitor.

[0029] A fourth object of the present invention is to provide a phenoxypyridine compound containing acylthiourea and a heterocyclic structure for use in preventing and controlling weeds in crops.

[0030] It is further defined that the weeds are monocotyledonous weeds or dicotyledonous weeds.

[0031] It is further specified that the weeds are at least one of crabgrass, foxtail grass, barnyard grass, morning glory, Amaranthus retroflexus, and velvetleaf.

[0032] It is further limited that the crop is wheat, rice, corn, cotton, soybean or peanut.

[0033] A fifth object of the present invention is to provide a phenoxypyridine compound containing acylthiourea and a heterocyclic structure for use as an active ingredient in the preparation of a weed killer drug.

[0034] It is further defined that the active ingredient in the formulation is applied at a concentration of 37.5-300 g ai / ha.

[0035] Compared with the prior art, the present invention has the following advantages:

[0036] The present invention provides a phenoxypyridine compound containing acylthiourea and a heterocyclic structure, and a preparation method and application thereof. The compound of the present invention has high safety to crops while maintaining high herbicidal activity.

[0037] The phenoxypyridine compounds containing acylthiourea and heterocyclic structures provided by the present invention have good inhibitory activity against PPO. The phenoxypyridine compounds containing acylthiourea and heterocyclic structures provided by the present invention have particularly excellent herbicidal activity against weeds such as morning glory, foxtail grass, quinoa, and chrysanthemum, especially against dicotyledonous weeds, and the control effect is even better than some commercial herbicides on the market. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 The present invention provides a synthetic route for the phenoxypyridine compounds containing acylthiourea and heterocyclic structures;

[0039] Figure 2 This is a diagram showing the herbicidal activity effect of I-12 at different application rates in Application Example 1;

[0040] Figure 3 This is a diagram showing the crop safety effect of I-12 at an application rate of 300 g ai / ha in Application Example 3. DETAILED DESCRIPTION

[0041] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0042] The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials, reagents, methods and instruments used are conventional materials, reagents, methods and instruments in the art unless otherwise specified, and can be obtained through commercial channels by those skilled in the art.

[0043] The structures of the compounds in the following examples were confirmed by nuclear magnetic resonance (NMR) and mass spectrometry (MS).

[0044] Embodiment 1, (combination Figure 1 Preparation of N-[(4-(pyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide (I-1)

[0045] Step 1: Preparation of intermediate d

[0046] In a round-bottom flask, add 20.0mmol 4-aminophenol and 40mmol cesium carbonate, then add 40mL dimethyl sulfoxide and stir at room temperature for 30 minutes. Add 20.05mmol 2-chloropyridine, then heat to 90°C, stir the reaction, and use thin layer chromatography (TLC) to monitor the progress of the reaction until 4-aminophenol reacts completely. Cool to room temperature, filter under reduced pressure, and collect the filtrate. Add 80mL of distilled water to the filtrate and stir for 10 minutes. Extract with ethyl acetate, collect the organic phase, and wash with saturated brine. Add anhydrous sodium sulfate to the organic phase and dry for 24 hours. Filter and remove ethyl acetate by rotary evaporation to obtain a viscous liquid, which is intermediate d.

[0047] Step 2: Preparation of intermediate h

[0048] In a round-bottom flask containing 50 mL of acetonitrile, add 5 mmol of potassium thiocyanate and stir until completely dissolved. Add dropwise 40 mL of acetonitrile solution containing 4 mmol of furanyl chloride. Heat to 70°C and stir for 50 minutes. Cool to room temperature and filter to obtain an acetonitrile solution containing intermediate h.

[0049] Step 3: Preparation of N-[(4-(pyridine-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (I-1)

[0050] Place all the acetonitrile solution containing intermediate h in step 2 in a round-bottom flask, and add 3 mmol of intermediate d synthesized in step 1. Stir at room temperature for 2 hours, and use TLC to monitor the reaction until the reaction is complete. Pour the reaction solution into a sodium bicarbonate solution (pH = 8), the solution becomes turbid, and is placed in a 4°C environment and allowed to stand overnight. Filter and collect the solid to obtain a crude product. The crude product is recrystallized (acetonitrile-water, v / v = 1 / 8) to obtain N-[(4-(pyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide. Gray solid, yield 87%.

[0051] The product detection data are as follows: mp: 134.2-135.1°C; 1 H NMR (600MHz, CDCl3) δ12.31(s,1H),9.20(s,1H),8.20(ddd,J=5.0,2.0,0.8Hz,1H),7.77-7.68(m,3H),7.63(dd,J=1.8,0.9Hz,1H),7.3 9(dd,J=3.6,0.8Hz,1H),7.21-7.16(m,2H),7.01(ddd,J=7.2,5.0,1.0Hz,1H),6.94(dt,J=8.3,0.9Hz,1H),6.64(dd,J=3.6,1.7Hz,1H); 13C NMR (151MHz, CDCl3) δ177.94,163.45,156.75,152.47,147.67,146.49,144 .93,139.60,134.03,125.45,121.53,119.01,118.74,113.45,111.69; HRMS calcd for[M+H+]C 17 H 13 N3O3S,340.0756,found340.0754.

[0052] After characterization, the structure of the obtained product is:

[0053] Example 2 Preparation of N-[(4-(5-bromopyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide (I-2)

[0054] The difference between this example and Example 1 is that 2-chloropyridine in step 1 is replaced by 5-bromo-2-chloropyridine. The other steps and parameters are the same as those in Example 1. N-[(4-(5-bromopyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. Pink solid, yield 82%.

[0055] The product test data are as follows: mp: 170.0-171.0°C; 1 H NMR (600MHz, CDCl3) δ12.32(s,1H),9.20(s,1H),8.22(dd,J=2.6,0.7Hz,1H),7.78(dd,J=8.7,2.6Hz,1H),7.76-7.72(m,2H),7.6 3(dd,J=1.7,0.8Hz,1H),7.40(dd,J=3.6,0.8Hz,1H),7.20-7.15(m,2H),6.87(dd,J=8.7,0.7Hz,1H),6.64(dd,J=3.6,1.8Hz,1H); 13 C NMR (151MHz, CDCl3) δ178.01,162.31,156.78,152.03,148.36,146.53,144 .93,142.08,134.39,125.49,121.56,119.07,113.81,113.48,113.22; HRMS calcd for[M+H+]C 17 H 12 BrN3O3S,417.9861,found417.9859.

[0056] After characterization, the structure of the obtained product is:

[0057] Example 3 Preparation of N-[(4-(3-chloropyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide (I-3)

[0058] The difference between this example and Example 1 is that 2-chloropyridine in step 1 is replaced by 2,3-dichloropyridine. The other steps and parameters are the same as those in Example 1. N-[(4-(3-chloropyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. A purple solid is obtained with a yield of 93%.

[0059] The product detection data are as follows: mp: 132.4-133.2°C; 1 H NMR (600MHz, CDCl3) δ12.33(s,1H),9.23(s,1H),8.03(dd,J=4.8,1.7Hz,1H),7.80-7.72(m,3H),7.66-7.60 (m,1H),7.40(d,J=3.6Hz,1H),7.25-7.18(m,2H),6.98(dd,J=7.7,4.8Hz,1H),6.64(dd,J=3.6,1.7Hz,1H); 13 C NMR (151MHz, CDCl3) δ178.03,158.86,156.80,151.87,146.53,145.14,144 .94,139.43,134.44,125.38,121.85,119.52,119.23,119.04,113.45; HRMS calcd for[M+H+]C 17 H 12 ClN3O3S,374.0366, found 374.0367.

[0060] After characterization, the structure of the obtained product is:

[0061] Example 4 Preparation of N-[(4-(5-chloropyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide (I-4)

[0062] The difference between this example and Example 1 is that 2-chloropyridine in step 1 is replaced by 2,5-dichloropyridine. The other steps and parameters are the same as those in Example 1. N-[(4-(5-chloropyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. A pink solid is obtained with a yield of 83%.

[0063] The product test data are as follows: mp: 165.3-165.5°C; 1H NMR (600MHz, CDCl3) δ12.32(s,1H),9.21(s,1H),8.19-8.08(m,1H),7.79-7.71(m,2H),7.69-7.60(m ,2H),7.39(dd,J=3.6,0.8Hz,1H),7.21-7.13(m,2H),6.95-6.87(m,1H),6.64(dd,J=3.6,1.8Hz,1H); 13 C NMR (151MHz, CDCl3) δ178.02,161.86,156.79,152.13,146.54,146.06,144 .92,139.38,134.35,126.11,125.51,121.54,119.07,113.48,112.63; HRMS calcd for[M+H+]C 18 H 11 ClF3N3O2S2,374.0366, found 374.0374.

[0064] After characterization, the structure of the obtained product is:

[0065] Example 5 Preparation of N-[(4-(3,5-dichloropyridine-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (I-5)

[0066] The difference between this example and Example 1 is that 2-chloropyridine in step 1 is replaced by 2,3,5-trichloropyridine. The other steps and parameters are the same as those in Example 1. N-[(4-(3,5-dichloropyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. A pink solid is obtained with a yield of 95%.

[0067] The product test data are as follows: mp: 143.4-144.0°C; 1 H NMR (600MHz, CDCl3) δ12.28(s,1H),9.14(s,1H),7.90(d,J=2.3Hz,1H),7.73-7.68(m,3H),7.56(d d,J=1.7,0.8Hz,1H),7.33(dd,J=3.6,0.8Hz,1H),7.15-7.09(m,2H),6.58(dd,J=3.6,1.7Hz,1H); 13C NMR (151MHz, DMSO) δ179.40,158.02,157.53,151.38,148.96,145.18,144. 19,139.80,135.51,126.43,125.78,121.94,119.16,119.10,113.16; HRMS calcd for[M+H+]C 17 H 11 Cl2N3O3S,407.9976,found 407.9970.

[0068] After characterization, the structure of the obtained product is:

[0069] Example 6 Preparation of N-[(4-(3-nitropyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide (I-6)

[0070] The difference between this example and Example 1 is that 2-chloropyridine in step 1 is replaced by 2-chloro-3-nitropyridine. The other steps and parameters are the same as those in Example 1. N-[(4-(3-nitropyridine-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide is obtained. An orange solid is obtained with a yield of 74%.

[0071] The product test data are as follows: mp: 162.6-163.3°C; 1 H NMR (600MHz, CDCl3) δ12.37(s,1H),9.21(s,1H),8.40-8.32(m,2H),7.84-7.77(m,2H),7.64(dd,J=1.7,0.8Hz ,1H),7.40(dd,J=3.6,0.8Hz,1H),7.26-7.22(m,2H),7.17(dd,J=7.9,4.8Hz,1H),6.65(dd,J=3.6,1.8Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.99,156.79,155.67,151.72,150.70,146.57,144 .91,135.53,135.14,134.57,125.31,122.20,119.09,118.56,113.48; HRMS calcd for[M+H+]C 17 H 12 N4O5S,385.0607,found 385.0601.

[0072] After characterization, the structure of the obtained product is:

[0073] Example 7 Preparation of N-[(4-(4-nitropyridine-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (I-7)

[0074] The difference between this example and example 1 is that 2-chloropyridine in step 1 is replaced by 2-chloro-4-nitropyridine. The other steps and parameters are the same as those in example 1. N-[(4-(4-nitropyridine-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide is obtained. A pink solid is obtained with a yield of 93%.

[0075] The product detection data are as follows: mp: 166.2-166.9°C; 1 H NMR (600MHz, CDCl3) δ12.39(s,1H),9.22(s,1H),8.25(d,J=5.7Hz,1H),7.85-7.77(m,2H),7.64(dd,J=1.8,0.8Hz,1H),7.4 1(dd,J=3.6,0.8Hz,1H),7.15-7.11(m,2H),6.87(d,J=2.2Hz,1H),6.83(dd,J=5.8,2.2Hz,1H),6.66(dd,J=3.6,1.7Hz,1H); 13 C NMR (151MHz, CDCl3) δ178.15,166.25,156.83,152.79,151.62,150.75,146 .64,144.82,135.34,126.03,121.17,119.24,113.54,112.13,111.48; HRMS calcd for[M+H+]C 17 H 12 N4O5S,385.0607,found 385.0605.

[0076] After characterization, the structure of the obtained product is:

[0077] Example 8 Preparation of N-[(4-(5-nitropyridine-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (I-8)

[0078] The difference between this example and example 1 is that 2-chloropyridine in step 1 is replaced by 2-chloro-5-nitropyridine. The other steps and parameters are the same as those in example 1. N-[(4-(5-nitropyridine-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide is obtained. Yellow solid, yield 86%.

[0079] The product detection data are as follows: mp: 167.7-138.5°C;1 H NMR (600MHz, CDCl3) δ12.39(s,1H),9.23(s,1H),9.04(d,J=2.7Hz,1H),8.49(dd,J=9.0,2.8Hz,1H),7.85-7.7 8(m,2H),7.64(s,1H),7.41(d,J=3.5Hz,1H),7.24-7.18(m,2H),7.07(d,J=9.1Hz,1H),6.66(d,J=2.0Hz,1H); 13 C NMR (151MHz, CDCl3) δ176.19,164.72,154.91,148.92,144.69,143.04,142 .94,138.56,133.38,133.09,123.65,120.09,117.26,111.60,109.57; HRMS calcd for[M+H+]C 17 H 12 N4O5S,385.0607,found 385.0607.

[0080] After characterization, the structure of the obtained product is:

[0081] Example 9 Preparation of N-[(4-(3-trifluoromethylpyridin-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (I-9)

[0082] The difference between this example and Example 1 is that 2-chloropyridine in step 1 is replaced by 2-chloro-3-(trifluoromethyl)pyridine. The other steps and parameters are the same as those in Example 1. N-[(4-(3-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. A pink solid is obtained with a yield of 73%.

[0083] The product test data are as follows: mp: 194.5-195.3°C; 1 H NMR (600MHz, CDCl3) δ12.34(s,1H),9.20(s,1H),8.30(dd,J=5.0,1.9Hz,1H),8.00(dd,J=7.6,1.9Hz,1H),7.79-7.74(m,2H),7.63(d d,J=1.7,0.8Hz,1H),7.40(dd,J=3.6,0.8Hz,1H),7.25-7.20(m,2H),7.11(ddd,J=7.6,5.0,0.8Hz,1H),6.64(dd,J=3.6,1.8Hz,1H); 13C NMR (151MHz, CDCl3) δ178.00,160.18,156.77,151.33,150.84,146.51,144.95,137.10(q,J FC =4.5Hz),134.71,125.32,122.72(q,J FC =271.8Hz),122.11,119.03,117.99,114.44(q,J FC =33.2Hz),113.45; HRMScalcd for[M+H+]C 18 H 12 F3N3O3S,408.0630,found 408.0625.

[0084] After characterization, the structure of the obtained product is:

[0085] Example 10 Preparation of N-[(4-(4-trifluoromethylpyridin-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (I-10)

[0086] The difference between this example and Example 1 is that 2-chloropyridine in step 1 is replaced by 2-chloro-4-(trifluoromethyl)pyridine. The other steps and parameters are the same as those in Example 1. N-[(4-(4-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. A pink solid with a yield of 90%.

[0087] The product test data are as follows: mp: 200.1-200.9°C; 1 H NMR (600MHz, CDCl3) δ12.35(s,1H),9.21(s,1H),8.32(d,J=5.2Hz,1H),7.81-7.76(m,2H),7.63(d d,J=1.8,0.8Hz,1H),7.40(dd,J=3.6,0.8Hz,1H),7.23-7.18(m,4H),6.65(dd,J=3.6,1.7Hz,1H); 13 C NMR (151MHz, CDCl3) δ178.01,163.97,156.79,151.53,148.93,146.53,144.93,141.82(q,J FC =37.7Hz),134.70,125.48,122.47(q,J FC =273.3Hz),121.84,119.06,114.24(q,J FC=3.0Hz),113.47,108.15(q,J FC =4.5Hz); HRMS calcd for[M+H+]C 18 H 12 F3N3O3S,408.0630,found406.0626.

[0088] After characterization, the structure of the obtained product is:

[0089] Example 11 Preparation of N-[(4-(5-trifluoromethylpyridin-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (I-11)

[0090] The difference between this example and Example 1 is that 2-chloropyridine in step 1 is replaced by 2-chloro-5-(trifluoromethyl)pyridine. The other steps and parameters are the same as those in Example 1. N-[(4-(5-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. White solid, yield 86%.

[0091] The product detection data are as follows: mp: 111.1-111.3°C; 1 H NMR (600MHz, CDCl3) δ12.36(s,1H),9.22(s,1H),8.44(d,J=2.6Hz,1H),7.91(dd,J=8.7,2.5Hz,1H),7.81-7.73(m,2H ),7.64(d,J=1.7Hz,1H),7.40(d,J=3.6Hz,1H),7.23-7.17(m,2H),7.05(d,J=8.7Hz,1H),6.65(dd,J=3.6,1.7Hz,1H); 13 C NMR (151MHz, CDCl3) δ178.05,165.60,156.80,151.35,146.56,145.46(q,J FC =4.5Hz),144.90,136.82(q,J FC =3.0Hz),134.83,125.53,123.67(q,J FC =271.8Hz),121.96,121.79(q,J FC =33.2Hz),119.11,113.49,111.48; HRMS calcd for[M+H+]C 18 H 12 F3N3O3S,408.0630,found 408.0627.

[0092] After characterization, the structure of the obtained product is:

[0093] Example 12 Preparation of N-[(4-(6-trifluoromethylpyridin-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (I-12)

[0094] The difference between this example and Example 1 is that 2-chloropyridine in step 1 is replaced by 2-chloro-6-(trifluoromethyl)pyridine. The other steps and parameters are the same as those in Example 1. N-[(4-(6-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. A pink solid with a yield of 96%.

[0095] The product test data are as follows: mp: 126.7-127.0°C; 1 H NMR (600MHz, CDCl3) δ12.35(s,1H),9.20(s,1H),7.85(t,J=7.9Hz,1H),7.78-7.73(m,2H),7.63(d,J= 1.7Hz,1H),7.43-7.37(m,2H),7.25-7.20(m,2H),7.07(d,J=8.4Hz,1H),6.64(dd,J=3.6,1.7Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.98,163.16,156.76,151.62,146.53,144.92,146.32(q,J FC =36.2Hz),140.69,134.47,125.37,121.36,120.99(q,J FC =274.8Hz),119.08,115.22(q,J FC =3.0Hz),114.60,113.48; HRMS calcd for[M+H+]C 18 H 12 F3N3O3S,408.0630,found408.0630.

[0096] After characterization, the structure of the obtained product is:

[0097] Example 13 Preparation of N-[(4-(4-trifluoromethylpyridin-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide (I-13)

[0098] The difference between this example and Example 1 is that 2-chloropyridine in step 1 is replaced by 2-chloro-4-(trifluoromethyl)pyridine. In step 2, furanoyl chloride is replaced by thiophenecarboxylic acid chloride. The other steps and parameters are the same as those in Example 1. N-[(4-(4-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide is obtained. Gray solid, yield 93%.

[0099] The product test data are as follows: mp: 168.1-169.0°C; 1 H NMR (600MHz, CDCl3) δ12.43(s,1H),8.95(s,1H),8.33(d,J=5.2Hz,1H),7.76(dd,J=22.0,6.5Hz,4H),7.23-7.16(m,5H); 13 CNMR(151MHz,CDCl3)δ178.06,163.96,161.16,151.57,148.93,141.89(q,J FC =37.7Hz),135.90,134.66,134.41,130.82,128.59,125.47,122.47(q,J FC =273.3Hz),121.84,114.25(q,J FC =3.0Hz),108.18(q,J FC =4.5Hz); HRMS calcd for[M+H+]C 18 H 12 F3N3O2S2,424.0401,found 424.0400.

[0100] After characterization, the structure of the obtained product is:

[0101] Example 14 Preparation of N-[(4-(5-trifluoromethylpyridin-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide (I-14)

[0102] The difference between this example and Example 13 is that 2-chloro-4-(trifluoromethyl)pyridine in step 1 is replaced by 2-chloro-5-(trifluoromethyl)pyridine. The other steps and parameters are the same as those in Example 13. N-[(4-(5-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide is obtained. Pink solid, yield 77%.

[0103] The product test data are as follows: mp: 127.6-127.9°C; 1H NMR (600MHz, CDCl3) δ12.44(s,1H),8.95(s,1H),8.45(dt,J=2.8,1.0Hz,1H),7.92( dd,J=8.7,2.5Hz,1H),7.81-7.71(m,4H),7.24-7.18(m,3H),7.05(d,J=8.7Hz,1H); 13 C NMR (151MHz, CDCl3) δ178.15,165.58,161.22,151.40,145.46(q,J FC =214.2Hz),136.81(q,J FC =3.0Hz),135.90,134.80,134.44,130.86,128.59,125.53,123.66(q,J FC =271.8Hz),121.95,121.82(q,J FC =33.2Hz),111.48; HRMS calcd for[M+H+]C 18 H 12 F3N3O2S2,424.0401,found 424.0399.

[0104] After characterization, the structure of the obtained product is:

[0105] Example 15 Preparation of N-[(4-(6-trifluoromethylpyridin-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide (I-15)

[0106] The difference between this example and Example 13 is that 2-chloro-4-(trifluoromethyl)pyridine in step 1 is replaced by 2-chloro-6-(trifluoromethyl)pyridine. The other steps and parameters are the same as those in Example 13. N-[(4-(6-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide is obtained. Yellow solid, yield 75%.

[0107] The product detection data are as follows: mp: 158.5-159.3°C; 1 H NMR (600MHz, CDCl3) δ12.43 (s, 1H), 8.95 (s, 1H), 7.85 (t, J = 8.0Hz, 1H), 7.78-7.72 (m, 4H), 7 .40(d,J=7.3Hz,1H),7.26-7.22(m,2H),7.20(dd,J=5.0,3.9Hz,1H),7.08(d,J=8.4Hz,1H); 13C NMR (151MHz, CDCl3) δ178.02,163.14,161.14,151.66,146.32(q,J FC =34.7Hz),140.69,135.88,134.43,134.40,130.83,128.58,125.35,121.36,120.99(q,J FC =273.3Hz),115.23(q,J FC =3.0Hz),114.62; HRMS calcd for[M+H+]C 18 H 12 F3N3O2S2,424.0401,found424.0394.

[0108] After characterization, the structure of the obtained product is:

[0109] Example 16 Preparation of 5-chloro-N-[(4-((4-trifluoromethylpyridin-2-oxy)phenyl)carbamothioyl]thiophene-2-carboxamide (I-16)

[0110] The difference between this example and Example 13 is that the thiophenecarbonyl chloride in step 2 is replaced by 5-chloro-2-thiophene chloride. The other steps and parameters are the same as those in Example 13. 5-Chloro-N-[(4-((4-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide is obtained. White solid, yield 89%.

[0111] The product test data are as follows: mp: 199.7-200.4°C; 1 H NMR (600MHz, CDCl3) δ12.30 (s, 1H), 8.88 (s, 1H), 8.33 (d, J = 5.2Hz, 1H), 7.78- 7.72(m,2H),7.53(d,J=4.1Hz,1H),7.23-7.19(m,4H),7.03(d,J=4.1Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.80,163.93,160.04,151.64,148.92,141.88(q,J FC =33.2Hz),140.18,134.54,134.33,130.09,127.93,125.47,122.46(q,J FC =273.3Hz),121.86,114.28(q,J FC =4.5Hz),108.19(q,J FC=4.5Hz); HRMS calcdfor[M+H+]C 18 H 11 ClF3N3O2S2,458.0012, found 458.0007.

[0112] After characterization, the structure of the obtained product is:

[0113] Example 17 Preparation of 5-chloro-N-[(4-((5-trifluoromethylpyridin-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide (I-17)

[0114] The difference between this example and Example 14 is that the thiophenecarbonyl chloride in step 2 is replaced by 5-chloro-2-thiophene chloride. The other steps and parameters are the same as those in Example 14. 5-Chloro-N-[(4-((5-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide is obtained. White solid, yield 96%.

[0115] The product test data are as follows: mp: 195.0-195.8°C; 1 H NMR (600MHz, CDCl3) δ12.30(s,1H),8.85(s,1H),8.44(s,1H),7.92(dd,J=8.6,2.7Hz,1H ),7.76(d,J=8.2Hz,2H),7.52(d,J=4.1Hz,1H),7.21(d,J=8.3Hz,2H),7.08-7.00(m,2H); 13 C NMR (151MHz, CDCl3) δ177.79,165.55,160.03,151.46,145.46(q,J FC =4.5Hz),140.20,136.82(q,J FC =3.0Hz),134.67,134.30,130.09,127.94,125.48,123.66(q,J FC =271.8Hz),121.96,121.85(q,J FC =34.2Hz),111.51; HRMS calcd for[M+H+]C 18 H 11 ClF3N3O2S2,458.0012, found 458.0008.

[0116] After characterization, the structure of the obtained product is:

[0117] Example 18 Preparation of N-[(3-(pyridine-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (II-1)

[0118] The difference between this example and example 1 is that in step 1, 4-aminophenol is replaced by 3-aminophenol to obtain intermediate e. The other steps and parameters are the same as those in example 1. N-[(3-(pyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. White solid, yield 91%.

[0119] The product test data are as follows: mp: 140.2-141.0°C; 1 H NMR (600MHz, CDCl3) δ12.37(s,1H),9.17(s,1H),8.21(dd,J=5.2,2.0Hz,1H),7.73-7.68(m,1H),7.67-7.60(m,2H),7.52(dd,J=8.1,2.0Hz,1H),7.42 (t,J=8.1Hz,1H),7.38(d,J=3.6Hz,1H),7.06(dd,J=8.1,2.3Hz,1H),7.02(dd,J=7.2,5.0Hz,1H),6.95(d,J=8.3Hz,1H),6.63(dd,J=3.6,1.7Hz,1H); 13 CNMR (151MHz, CDCl3) δ177.73,163.28,156.68,154.36,147.69,146.50,144.87,139 .64,138.76,129.81,120.01,119.45,119.06,118.81,116.78,113.45,111.78; HRMS calcd for[M+H+]C 17 H 13 N3O3S,340.0756,found 340.0751.

[0120] After characterization, the structure of the obtained product is:

[0121] Example 19 Preparation of N-[(3-(3-chloropyridine-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (II-2)

[0122] The difference between this example and example 3 is that in step 1, 4-aminophenol is replaced by 3-aminophenol to obtain intermediate e. The other steps and parameters are the same as those in example 3. N-[(3-(3-chloropyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. White solid, yield 80%.

[0123] The product detection data are as follows: mp: 146.1-146.9°C; 1 H NMR (600MHz, CDCl3) δ12.40(s,1H),9.17(s,1H),8.05(dd,J=4.8,2.3Hz,1H),7.81-7.74(m,1H),7.69(d,J=2.3Hz,1H),7.62(d,J=2.2Hz,1H),7.57(dd ,J=8.1,2.1Hz,1H),7.44(t,J=8.2Hz,1H),7.38(d,J=3.2Hz,1H),7.09(dd, J=8.4,2.2Hz,1H),6.98(ddd,J=7.4,4.9,2.3Hz,1H),6.63(t,J=2.3Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.64,158.70,156.69,153.78,146.50,145.19,144.87,139.42 ,138.71,129.68,120.35,119.68,119.56,119.30,119.06,116.93,113.46; HRMScalcd for[M+H+]C 17 H 12 ClN3O3S,374.0366,found 374.0362.

[0124] After characterization, the structure of the obtained product is:

[0125] Example 20 Preparation of N-[(3-(5-chloropyridine-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (II-3)

[0126] The difference between this example and example 4 is that in step 1, 4-aminophenol is replaced by 3-aminophenol to obtain intermediate e. The other steps and parameters are the same as those in example 4. N-[(3-(5-chloropyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. White solid, yield 98%.

[0127] The product detection data are as follows: mp: 159.4-159.5°C; 1H NMR (600MHz, CDCl3) δ12.39(s,1H),9.17(s,1H),8.14(t,J=2.3Hz,1H),7.71-7.64(m,2H),7.62(dd,J=1.9,0.9Hz,1H),7.50(ddd,J=8.2,2.3,1 .1Hz,1H),7.43(t,J=8.2Hz,1H),7.40-7.36(m,1H),7.05(ddd,J=8.1,2.4,1.1Hz,1H),6.92(dd,J=8.7,1.8Hz,1H),6.64(dt,J=3.4,1.7Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.77,161.70,156.71,154.07,146.53,146.12,144.89,139 .40,138.85,129.87,126.19,120.25,119.34,119.09,116.71,113.47,112.69; HRMS calcd for[M+H+]C 17 H 12 ClN3O3S,374.0366, found 374.0361.

[0128] After characterization, the structure of the obtained product is:

[0129] Example 21 Preparation of N-[(3-(3,5-dichloropyridine-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (II-4)

[0130] The difference between this example and example 5 is that in step 1, 4-aminophenol is replaced by 3-aminophenol to obtain intermediate e. The other steps and parameters are the same as those in example 5. N-[(3-(3,5-dichloropyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. White solid, yield 97%.

[0131] The product detection data are as follows: mp: 138.2-138.9°C; 1H NMR (600MHz, CDCl3) δ12.43(s,1H),9.18(s,1H),7.99(d,J=2.4Hz,1H),7.78(d,J=2.4Hz,1H),7.72(t,J=2.2Hz,1H),7.63(s,1H), 7.55(dd,J=8.1,2.1Hz,1H),7.44(t,J=8.1Hz,1H),7.39(d,J=3.4Hz,1H),7.07(dd,J=8.2,2.3Hz,1H),6.64(dd,J=3.5,1.8Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.66,157.29,156.71,153.44,146.54,144.84,143.55,142.23,138 .92,138.77,129.75,125.92,120.57,119.67,119.55,119.12,117.22,116.85,113.48; HRMS calcd for[M+H+]C 17 H 11 Cl2N3O3S,407.9976,found407.9973.

[0132] After characterization, the structure of the obtained product is:

[0133] Example 22 Preparation of N-[(3-(3-nitropyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide (II-5)

[0134] The difference between this example and Example 6 is that in step 1, 4-aminophenol is replaced by 3-aminophenol to obtain intermediate e. The other steps and parameters are the same as those in Example 6. N-[(3-(3-nitropyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. Yellow solid, yield 93%.

[0135] The product detection data are as follows: mp: 171.2-171.5°C; 1 H NMR (600MHz, CDCl3) δ12.45(s,1H),9.17(s,1H),8.46-8.26(m,2H),7.78(t,J=2.1Hz,1H),7.65-7.57(m,2H),7.47(t,J= 8.1Hz,1H),7.39(d,J=3.6Hz,1H),7.18(dd,J=7.9,4.8Hz,1H),7.11(dd,J=8.2,2.3Hz,1H),6.64(dd,J=3.6,1.7Hz,1H);13 C NMR (151MHz, CDCl3) δ177.66,156.73,155.53,152.71,151.77,146.56,144.86,138 .86,135.53,134.60,129.79,120.95,119.92,119.13,118.61,117.25,113.48; HRMS calcd for[M+H+]C 17 H 12 N4O5S,385.0607 found 385.0605.

[0136] After characterization, the structure of the obtained product is:

[0137] Example 23 Preparation of N-[(3-(4-nitropyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide (II-6)

[0138] The difference between this example and Example 7 is that in step 1, 4-aminophenol is replaced by 3-aminophenol to obtain intermediate e. The other steps and parameters are the same as those in Example 7. N-[(3-(4-nitropyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. Pink solid, yield 96%.

[0139] The product test data are as follows: mp: 142.8-143.2°C; 1 H NMR (600MHz, CDCl3) δ12.45(s,1H),9.20(s,1H),8.25(d,J=5.8Hz,1H),7.75(t,J=2.1Hz,1H),7.63(dd,J=1.8,0.8Hz,1H),7.50-7.43(m,2H ),7.40(dd,J=3.6,0.8Hz,1H),7.01(dt,J=7.0,2.2Hz,1H),6.92(d,J=2.2Hz,1H),6.85(dd,J=5.8,2.2Hz,1H),6.65(dd,J=3.6,1.7Hz,1H); 13 C NMR (151MHz, CDCl3) δ178.05,165.99,156.79,153.61,152.82,150.78,146.66,144 .77,139.43,130.56,121.06,119.29,118.80,116.54,113.54,112.25,111.53; HRMS calcd for[M+H+]C 17 H 12N4O5S,385.0607,found 385.0616.

[0140] After characterization, the structure of the obtained product is:

[0141] Example 24 Preparation of N-[(3-(3-trifluoromethylpyridin-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide (II-7)

[0142] The difference between this example and Example 9 is that in step 1, 4-aminophenol is replaced by 3-aminophenol to obtain intermediate e. The other steps and parameters are the same as those in Example 9. N-[(3-(3-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide (II-7) is obtained as a white solid with a yield of 77%.

[0143] The product detection data are as follows: mp: 160.9-161.8°C; 1 H NMR (600MHz, CDCl3) δ12.42(s,1H),9.19(s,1H),8.31(dd,J=4.9,1.9Hz,1H),8.00(dd,J=7.7,1.9Hz,1H),7.68(t,J=2.1Hz ,1H),7.65-7.58(m,2H),7.45(t,J=8.1Hz,1H),7.39(dd,J=3.6,0.8Hz,1H),7.15-7.06(m,2H),6.64(dd,J=3.6,1.7Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.69,160.02,156.71,153.23,150.89,146.53,144.83,138.72,137.12(q,J FC =4.5Hz),129.71,122.69(q,J FC =271.8Hz),120.70,119.96,119.11,118.05,117.27,114.44(q,J FC =33.2Hz),113.47; HRMScalcd for[M+H+]C 18 H 12 F3N3O3S,408.0630,found408.0634.

[0144] After characterization, the structure of the obtained product is:

[0145] Example 25 Preparation of N-[(3-(4-trifluoromethylpyridin-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (II-8)

[0146] The difference between this example and Example 10 is that in step 1, 4-aminophenol is replaced by 3-aminophenol to obtain intermediate e. The other steps and parameters are the same as those in Example 10. N-[(3-(4-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide (II-8) is obtained. It is a yellow solid with a yield of 98%.

[0147] The product detection data are as follows: mp: 152.7-153.2°C; 1 H NMR (600MHz, CDCl3) δ12.42(s,1H),9.18(s,1H),8.34(d,J=5.2Hz,1H),7.74(t,J=2.2Hz,1H),7.62(dd,J=1.8,0.8Hz,1H),7.53(ddd,J=8.1,2.2, 1.0Hz,1H),7.45(t,J=8.1Hz,1H),7.39(dd,J=3.6,0.8Hz,1H),7.24-7.19(m,2H),7.08(ddd,J=8.1,2.3,1.0Hz,1H),6.64(dd,J=3.6,1.7Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.77,163.81,156.72,153.44,148.97,146.55,144.84,141.86(q,J FC =34.7Hz),138.90,129.93,122.46(q,J FC =273.3Hz),120.61,119.62,119.13,117.02,114.31(q,J FC =3.0Hz),113.49,108.19(q,J FC =4.5Hz); HRMS calcd for[M+H+]C 18 H 12 F3N3O3S,408.0630,found408.0626.

[0148] After characterization, the structure of the obtained product is:

[0149] Example 26 Preparation of N-[(3-(5-trifluoromethylpyridin-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (II-9)

[0150] The difference between this example and Example 11 is that in step 1, 4-aminophenol is replaced by 3-aminophenol to obtain intermediate e. The other steps and parameters are the same as those in Example 11. N-[(3-(5-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. White solid, yield 97%.

[0151] The product test data are as follows: mp: 111.4-112.3°C; 1 H NMR (600MHz, CDCl3) δ12.43(s,1H),9.18(s,1H),8.46(s,1H),7.92(dd,J=8.7,2.8Hz,1H),7.75(d,J=2.3Hz,1H),7.63(s, 1H),7.54(d,J=8.1Hz,1H),7.46(t,J=8.1Hz,1H),7.39(t,J=2.6Hz,1H),7.07(dd,J=15.0,8.4Hz,2H),6.67-6.61(m,1H); 13 C NMR (151MHz, CDCl3) δ177.81,165.47,156.74,153.30,146.56,145.52(q,J FC =4.5Hz),144.86,138.94,136.84(q,J FC =3.0Hz),129.95,123.68(q,J FC =271.8Hz),121.85(q,J FC =33.2Hz),120.75,119.74,119.15,117.16,113.49,111.49; HRMS calcd for[M+H+]C 18 H 12 F3N3O3S,408.0630,found408.0623.

[0152] After characterization, the structure of the obtained product is:

[0153] Example 27 N-[(3-(6-trifluoromethylpyridin-2-oxy)phenyl)carbamothioyl]furan-2-carboxamide (II-10)

[0154] The difference between this example and Example 12 is that in step 1, 4-aminophenol is replaced by 3-aminophenol to obtain intermediate e. The other steps and parameters are the same as those in Example 12. N-[(3-(6-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]furan-2-carboxamide is obtained. White solid, yield 76%.

[0155] The product test data are as follows: mp: 104.0-104.9°C; 1 H NMR (600MHz, CDCl3) δ12.41(s,1H),9.19(s,1H),7.85(t,J=7.9Hz,1H),7.74(t,J=2.2Hz,1H),7.62(d,J=1 .9Hz,1H),7.50(dd,J=8.0,2.1Hz,1H),7.47-7.37(m,3H),7.16-7.05(m,2H),6.64(dt,J=3.0,1.5Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.84,163.09,156.74,153.55,146.56,146.39(q,J FC =34.7Hz),144.84,140.75,138.87,129.88,121.00(q,J FC =273.3Hz),120.39,119.31,119.16,116.66,115.31(q,J FC =3.0Hz),114.56,113.49; HRMS calcd for[M+H+]C 18 H 12 F3N3O3S,408.0630,found 408.0628.

[0156] After characterization, the structure of the obtained product is:

[0157] Example 28 Preparation of N-[(3-(pyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide (II-11)

[0158] The difference between this example and Example 18 is that in step 2, furanoyl chloride is replaced by thiophenecarboxylic acid chloride to obtain intermediate e. The other steps and parameters are the same as those in Example 18. N-[(3-(pyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide is obtained. Yellow solid, yield 97%.

[0159] The product test data are as follows: mp: 170.9-171.5°C; 1H NMR (600MHz, CDCl3) δ12.45(s,1H),8.92(s,1H),8.22(ddd,J=5.0,2.1,0.8H z,1H),7.74-7.67(m,3H),7.64(t,J=2.2Hz,1H),7.52(ddd,J=8.0,2.2,0.9Hz ,1H),7.42(t,J=8.1Hz,1H),7.18(dd,J=4.9,3.9Hz,1H),7.07(ddd,J=8.1,2. 3,1.0Hz,1H),7.02(ddd,J=7.2,5.0,1.0Hz,1H),6.95(dt,J=8.3,0.9Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.77,163.28,161.07,154.40,147.71,139.64,138.74,135 .87,134.37,130.79,129.81,128.55,119.97,119.47,118.83,116.76,111.80; HRMS calcd for[M+H+]C 17 H 13 N3O2S2,356.0527,found 356.0526.

[0160] After characterization, the structure of the obtained product is:

[0161] Example 29 Preparation of N-[(3-(5-chloropyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide (II-12)

[0162] The difference between this example and Example 20 is that in step 2, furanoyl chloride is replaced by thiophenecarboxylic acid chloride to obtain intermediate e. The other steps and parameters are the same as those in Example 20. N-[(3-(5-chloropyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide is obtained. White solid, yield 99%.

[0163] The product test data are as follows: mp: 199.2-199.8°C; 1H NMR (600MHz, DMSO) δ12.51(s,1H),11.65(s,1H),8.39(d,J=3.9Hz,1H),8.24(d,J=2.8Hz,1H),8.06(dd,J=4.0,2.3Hz,1H),7 .99(dp,J=8.2,2.2Hz,1H),7.68(s,1H),7.54-7.43(m,2H),7.29-7.23(m,1H),7.14(d,J=8.6Hz,1H),7.06(d,J=8.0Hz,1H); 13 C NMR (151MHz, DMSO) δ179.08,162.45,161.93,153.99,146.13,140.51,139.69,137. 10,135.90,133.25,130.19,129.24,125.95,121.00,119.35,117.16,113.65; HRMS calcd for[M+H+]C 17 H 12 ClN3O2S2,390.0138,found390.0133.

[0164] After characterization, the structure of the obtained product is:

[0165] Example 30 Preparation of N-[(3-(3,5-dichloropyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide (II-13)

[0166] The difference between this example and Example 21 is that in step 2, furanoyl chloride is replaced by thiophenecarboxylic acid chloride to obtain intermediate e. The other steps and parameters are the same as those in Example 21. N-[(3-(3,5-dichloropyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide is obtained. White solid, yield 96%.

[0167] The product detection data are as follows: mp: 139.05-140.01°C; 1 H NMR (600MHz, CDCl3) δ12.51(s,1H),8.90(s,1H),7.99(d,J=2.3Hz,1H),7.78(d,J=2.3Hz,1H),7.72(dt,J=8.0 ,3.6Hz,3H),7.55(d,J=8.2Hz,1H),7.44(td,J=8.1,1.9Hz,1H),7.19(q,J=3.2Hz,1H),7.07(d,J=8.1Hz,1H); 13C NMR (151MHz, CDCl3) δ177.68,161.09,157.27,153.45,143.55,138.93,138.72,135 .79,134.46,130.80,129.76,128.58,125.93,120.55,119.68,119.57,116.84; HRMS calcd for[M+H+]C 17 H 11 Cl2N3O2S2,423.9748,found 423.9750.

[0168] After characterization, the structure of the obtained product is:

[0169] Example 31 Preparation of N-[(3-(3-nitropyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide (II-14)

[0170] The difference between this example and Example 22 is that in step 2, furanoyl chloride is replaced by thiophenecarboxylic acid chloride to obtain intermediate e. The other steps and parameters are the same as those in Example 22. N-[(3-(3-nitropyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide is obtained. Yellow solid, yield 80%.

[0171] The product test data are as follows: mp: 169.9-170.9°C; 1 H NMR (600MHz, CDCl3) δ12.45(s,1H),9.17(s,1H),8.46-8.26(m,2H),7.78(t,J=2.1Hz,1H),7.65-7.57(m,2H),7.47(t,J= 8.1Hz,1H),7.39(d,J=3.6Hz,1H),7.18(dd,J=7.9,4.8Hz,1H),7.11(dd,J=8.2,2.3Hz,1H),6.64(dd,J=3.6,1.7Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.66,156.73,155.53,152.71,151.77,146.56,144.86,138 .86,135.53,134.60,129.79,120.95,119.92,119.13,118.61,117.25,113.48; HRMS calcd for[M+H+]C 17 H 12 N4O5S,385.0607 found 385.0605.

[0172] After characterization, the structure of the obtained product is:

[0173] Example 32 Preparation of N-[(3-(4-nitropyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide (II-15)

[0174] The difference between this example and Example 23 is that in step 2, furanoyl chloride is replaced by thiophenecarboxylic acid chloride to obtain intermediate e. The other steps and parameters are the same as those in Example 23. N-[(3-(4-nitropyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide is obtained. White solid, yield 96%.

[0175] The product detection data are as follows: mp: 142.8-143.4°C; 1 H NMR (600MHz, CDCl3) δ12.54(s,1H),8.95(s,1H),8.26(d,J=5.7Hz,1H),7.80-7.71(m,3H),7.50-7.45(m,2H) ,7.20(dd,J=4.9,3.9Hz,1H),7.01(dt,J=6.2,2.5Hz,1H),6.92(d,J=2.2Hz,1H),6.86(dd,J=5.8,2.2Hz,1H); 13 C NMR (151MHz, CDCl3) δ178.11,166.01,161.21,153.60,152.78,150.74,139.40,135 .68,134.63,130.96,130.60,128.64,121.07,118.84,116.54,112.27,111.55; HRMS calcd for[M+H+]C 17 H 12 N4O4S2,401.0378,found401.0372.

[0176] After characterization, the structure of the obtained product is:

[0177] Example 33 Preparation of N-[(3-(3-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide (II-16)

[0178] The difference between this example and Example 24 is that in step 2, furanoyl chloride is replaced by thiophenecarboxylic acid chloride to obtain intermediate e. The other steps and parameters are the same as those in Example 24. N-[(3-(3-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide is obtained. Yellow solid, yield 75%.

[0179] The product detection data are as follows: mp: 148.8-150.6°C; 1 H NMR (600MHz, CDCl3) δ12.51(s,1H),8.93(s,1H),8.31(dd,J=4.9,2.0Hz,1H),8.00(dd,J=7.6,2.1Hz,1H),7.73(t,J=4.6Hz,2 H),7.68(t,J=2.1Hz,1H),7.61(dd,J=8.1,2.2Hz,1H),7.46(dd,J=8.9,7.5Hz,1H),7.19(t,J=4.3Hz,1H),7.14-7.07(m,2H); 13 C NMR (151MHz, CDCl3) δ177.72,161.11,160.02,153.24,150.89,138.68,137.12(q,J FC =4.5Hz),135.81,134.46,130.80,129.73,128.58,122.69(q,J FC =271.8Hz),120.67,119.99,118.06,117.27,114.45(q,J FC =33.2Hz); HRMS calcd for[M+H+]C 18 H 12 F3N3O2S2,424.0401,found424.0407.

[0180] After characterization, the structure of the obtained product is:

[0181] Example 34 Preparation of N-[(3-(4-trifluoromethylpyridin-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide (II-17)

[0182] The difference between this example and Example 25 is that in step 2, furanoyl chloride is replaced by thiophenecarboxylic acid chloride to obtain intermediate e. The other steps and parameters are the same as those in Example 25. N-[(3-(4-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide is obtained. Yellow solid, yield 76%.

[0183] The product detection data are as follows: mp: 131.0-131.5°C; 1H NMR (600MHz, CDCl3) δ12.50(s,1H),8.90(s,1H),8.35(dt,J=5.3,0.7Hz,1H),7.79-7.68(m,3H),7.54(d dd,J=8.2,2.1,0.9Hz,1H),7.46(t,J=8.1Hz,1H),7.24-7.18(m,3H),7.08(ddd,J=8.1,2.3,1.0Hz,1H); 13 CNMR(151MHz,CDCl3)δ177.80,163.82,161.10,153.48,148.99,141.88(q,J FC =34.7Hz),138.87,135.82,134.45,130.82,129.94,128.58,122.47(q,J FC =273.3Hz),120.58,119.64,117.00,,114.33(q,J FC =3.0Hz),108.20(q,J FC =4.5Hz); HRMS calcd for[M+H+]C 18 H 12 F3N3O2S2,424.0401,found 424.0404.

[0184] After characterization, the structure of the obtained product is:

[0185] Example 35 Preparation of N-[(3-(5-trifluoromethylpyridin-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide (II-18)

[0186] The difference between this example and Example 26 is that in step 2, furanoyl chloride is replaced by thiophenecarboxylic acid chloride to obtain intermediate e. The other steps and parameters are the same as those in Example 26. N-[(3-(5-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide is obtained. White solid, yield 98%.

[0187] The product detection data are as follows: mp: 136.2-137.2°C; 1H NMR (600MHz, CDCl3) δ12.51(s,1H),8.91(s,1H),8.46(d,J=2.6Hz,1H),7.92(dd,J=8.7,2.4Hz,1H),7.7 8-7.69(m,3H),7.54(dd,J=7.8,2.1Hz,1H),7.46(t,J=8.1Hz,1H),7.22-7.16(m,1H),7.11-7.01(m,2H); 13 CNMR(151MHz,CDCl3)δ177.83,165.45,161.12,153.30,145.52(q,J FC =4.5Hz),138.90,136.84(q,J FC =3.0Hz),135.80,134.48,130.84,129.96,128.59,124.67(q,J FC =271.8Hz),121.86(q,J FC =33.2Hz),120.72,119.76,117.15,111.50; HRMS calcd for[M+H+]C 18 H 12 F3N3O2S2,424.0401,found 424.0398.

[0188] After characterization, the structure of the obtained product is:

[0189] Example 36 Preparation of N-[(3-(6-trifluoromethylpyridin-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide (II-19)

[0190] The difference between this example and Example 27 is that in step 2, furanoyl chloride is replaced by thiophenecarboxylic acid chloride to obtain intermediate e. The other steps and parameters are the same as those in Example 27. N-[(3-(6-trifluoromethylpyridine-2-oxy)phenyl)thiocarbamoyl]thiophene-2-carboxamide is obtained. White solid, yield 82%.

[0191] The product detection data are as follows: mp: 101.2-101.3°C; 1H NMR (600MHz, CDCl3) δ12.51(s,1H),8.99(s,1H),7.86(dt,J=11.5,5.3Hz,1H),7.74(q,J=4.5Hz,3H) ,7.49(d,J=8.1Hz,1H),7.43(ddd,J=18.5,7.7,3.5Hz,2H),7.19(p,J=4.1Hz,1H),7.15-7.07(m,2H); 13 C NMR (151MHz, CDCl3) δ177.92,163.09,161.17,153.57,146.39(q,J FC =34.7Hz),140.76,138.84,135.82,134.48,130.88,129.90,128.59,121.00(q,J FC =274.8Hz),120.38,119.34,116.66,115.32(d,J FC =3.0Hz),114.58; HRMS calcd for[M+H+]C 18 H 12 F3N3O2S2,424.0401,found424.0407.

[0192] After characterization, the structure of the obtained product is:

[0193] Example 37 Preparation of 5-chloro-N-[(3-pyridine-2-oxy)phenylthiocarbamoyl]thiophene-2-carboxamide (II-20)

[0194] The difference between this example and Example 28 is that in step 2, the thiophenecarbonyl chloride is replaced by 5-chloro-2-chlorothiophene to obtain intermediate e. The other steps and parameters are the same as those in Example 28. 5-chloro-N-[(3-pyridine-2-oxy)phenylthiocarbamoyl]thiophene-2-carboxamide is obtained. Yellow solid, yield 82%.

[0195] The product detection data are as follows: mp: 138.9-139.4°C; 1H NMR (600MHz, CDCl3) δ12.32(s,1H),8.82(s,1H),8.28-8.16(m,1H),7.75-7.68(m,1H),7.62(t,J=2.1Hz,1H),7. 50(d,J=4.6Hz,2H),7.42(t,J=8.1Hz,1H),7.07(dd,J=8.2,2.2Hz,1H),7.05-6.98(m,2H),6.95(d,J=8.3Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.50,163.26,159.95,154.42,147.72,140.11,139.64,138 .63,134.32,130.07,129.83,127.91,119.96,119.55,118.85,116.76,111.83; HRMS calcd for[M+H+]C 17 H 12 ClN3O2S2,390.0138,found 390.0136.

[0196] After characterization, the structure of the obtained product is:

[0197] Example 38 Preparation of 5-chloro-N-[(3,5-dichloropyridine-2-oxy)phenylthiocarbamoyl]thiophene-2-carboxamide (II-21)

[0198] The difference between this example and Example 30 is that in step 2, the thiophenecarbonyl chloride is replaced by 5-chloro-2-chlorothiophene to obtain intermediate e. The other steps and parameters are the same as those in Example 30. 5-chloro-N-[(3,5-dichloropyridine-2-oxy)phenylthiocarbamoyl]thiophene-2-carboxamide is obtained. White solid, yield 98%.

[0199] The product detection data are as follows: mp: 173.2-173.7°C; 1 H NMR (600MHz, CDCl3) δ12.37(s,1H),8.83(s,1H),7.99(d,J=2.6Hz,1H),7.78(d,J=2.4Hz,1H),7.69(t,J= 2.3Hz,1H),7.52(dd,J=15.2,6.0Hz,2H),7.44(t,J=8.3Hz,1H),7.11-7.05(m,1H),7.01(d,J=3.8Hz,1H); 13C NMR(151MHz,DMSO)δ178.27,160.63,156.77,152.93,143.69,139.26,139.07,137.15 ,135.65,132.84,129.60,128.90,125.37,120.85,118.95,118.68,116.67; HRMScalcd for[M+H+]C 17 H 10 Cl3N3O2S2,457.9358, found 459.9357.

[0200] After characterization, the structure of the obtained product is:

[0201] Example 39 Preparation of 5-chloro-N-[(3-nitropyridine-2-oxy)phenylthiocarbamoyl]thiophene-2-carboxamide (II-22)

[0202] The difference between this example and Example 31 is that in step 2, the thiophenecarbonyl chloride is replaced by 5-chloro-2-chlorothiophene to obtain intermediate e. The other steps and parameters are the same as those in Example 31. 5-chloro-N-[(3-nitropyridine-2-oxy)phenylthiocarbamoyl]thiophene-2-carboxamide is obtained. Yellow solid, yield 93%.

[0203] The product test data are as follows: mp: 195.2-195.6°C; 1 H NMR (600MHz, DMSO) δ12.36(s,1H),11.75(s,1H),8.60(dd,J=8.0,1.8Hz,1H),8.45(dd,J=4.8,1.8Hz,1H),8.29(d,J=4.2Hz,1H),7.73(t,J= 2.2Hz,1H),7.60-7.53(m,1H),7.49(t,J=8.1Hz,1H),7.41(dd,J=8.0,4.8Hz,1H),7.32(d,J=4.2Hz,1H),7.15(ddd,J=8.1,2.3,1.0Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.43,159.99,155.50,152.69,151.77,140.24,138.69,135 .57,134.57,134.22,130.11,129.84,127.94,120.96,120.05,118.64,117.28; HRMS calcd for[M+H+]C 17 H 11ClN4O4S2,434.9988,found 434.9991.

[0204] After characterization, the structure of the obtained product is:

[0205] Example 40 Preparation of 5-chloro-N-[(4-nitropyridine-2-oxy)phenylthiocarbamoyl]thiophene-2-carboxamide (II-23)

[0206] The difference between this example and Example 32 is that in step 2, the thiophenecarbonyl chloride is replaced by 5-chloro-2-chlorothiophene to obtain intermediate e. The other steps and parameters are the same as those in Example 32. 5-chloro-N-[(4-nitropyridine-2-oxy)phenylthiocarbamoyl]thiophene-2-carboxamide is obtained. White solid, yield 97%.

[0207] The product detection data are as follows: mp: 174.9-175.3°C; 1 H NMR (600MHz, CDCl3) δ12.40(s,1H),8.84(s,1H),8.26(d,J=5.8Hz,1H),7.73(q,J=1.6Hz,1H),7.52(d, J=4.2Hz,1H),7.50-7.44(m,2H),7.05-6.99(m,2H),6.92(d,J=2.2Hz,1H),6.86(dd,J=5.8,2.2Hz,1H); 13 CNMR(151MHz,CDCl3)δ177.83,166.01,160.05,153.62,152.77,150.73,140.44,139 .29,134.09,130.63,130.19,127.98,121.07,118.93,116.54,112.27,111.56; HRMS calcd for[M+H+]C 17 H 11 ClN4O4S2,434.9988, found 434.9984.

[0208] After characterization, the structure of the obtained product is:

[0209] Example 41 Preparation of 5-chloro-N-[(4-trifluoromethylpyridin-2-oxy)phenylthiocarbamoyl]thiophene-2-carboxamide (II-24)

[0210] The difference between this example and Example 34 is that in step 2, the thiophenecarbonyl chloride is replaced by 5-chloro-2-chlorothiophene to obtain intermediate e. The other steps and parameters are the same as those in Example 34. 5-chloro-N-[(4-trifluoromethylpyridine-2-oxy)phenylthiocarbamoyl]thiophene-2-carboxamide is obtained. White solid, yield 98%.

[0211] The product detection data are as follows: mp: 137.4-138.4°C; 1 H NMR (600MHz, CDCl3) δ12.38(s,1H),8.88(s,1H),8.34(d,J=5.2Hz,1H),7.70(t,J=2.2Hz,1H),7.51(dd,J=7.1, 2.5Hz,2H),7.45(t,J=8.1Hz,1H),7.23-7.18(m,2H),7.08(ddd,J=8.1,2.3,1.0Hz,1H),7.01(d,J=4.1Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.57,163.77,160.02,153.43,148.97,141.86(q,J FC =34.7Hz),140.24,138.71,134.23,130.12,129.97,127.94,122.44(q,J FC =273.3Hz),120.62,119.76,117.05,114.34(q,J FC =3.0Hz),108.2(q,J FC =4.5Hz); HRMS calcd for[M+H+]C 18 H 11 ClF3N3O2S2,458.0012,found 458.0016.

[0212] After characterization, the structure of the obtained product is:

[0213] Example 42 Preparation of 5-chloro-N-[(5-trifluoromethylpyridin-2-oxy)phenylthiocarbamoyl]thiophene-2-carboxamide (II-25)

[0214] The difference between this example and Example 35 is that in step 2, the thiophenecarbonyl chloride is replaced by 5-chloro-2-chlorothiophene to obtain intermediate e. The other steps and parameters are the same as those in Example 35. 5-chloro-N-[(5-trifluoromethylpyridine-2-oxy)phenylthiocarbamoyl]thiophene-2-carboxamide is obtained. White solid, yield 97%.

[0215] The product detection data are as follows: mp: 176.6-177.3°C; 1 H NMR (600MHz, CDCl3) δ12.37(s,1H),8.81(s,1H),8.46(s,1H),7.92(d,J=8.5Hz,1H),7.72 (d,J=2.8Hz,1H),7.56-7.43(m,3H),7.07(dd,J=18.4,8.4Hz,2H),7.02(t,J=3.2Hz,1H); 13 C NMR (151MHz, CDCl3) δ177.55,165.43,159.98,153.32,145.52(q,J FC =4.5Hz),140.27,138.78,136.85(q,J FC =3.0Hz),134.23,130.09,129.98,127.94,123.66(q,J FC =271.8Hz),121.89(q,J FC =33.2Hz),120.71,119.86,117.16,111.52; HRMS calcd for[M+H+]C 18 H 11 ClF3N3O2S2,458.0012,found458.0009.

[0216] After characterization, the structure of the obtained product is:

[0217] Application Example 1 Test for determination of herbicidal activity of the compounds of Examples 1-42

[0218] In order to explore the control effect of compounds on weeds, common weeds were selected for experiments: barnyard grass, crabgrass, foxtail grass, morning glory, quinoa and ramie.

[0219] Weed planting method: Fill a small flower pot (r = 4cm, h = 8cm) with about 6cm deep flower soil, soak it with water, put in the weed seeds used for testing, cover the top with about 2cm of flower soil, spray the surface with a spray bottle, and place it in an artificial waiting room to wait for it to grow. The temperature is 25-30℃, the humidity is 60-70%, and the light and dark cycles are 12h each.

[0220] Preparation of target compound emulsion: Weigh 10 mg of the target compound of Examples 1-42, dissolve each in 1 mL of N,N-dimethylformamide, add 1 drop of Tween-80 (T-80) as an emulsifier, and dilute to volume in a 10 mL volumetric flask with distilled water to obtain an emulsion with a target compound concentration of 1 g / L. A commercial PPO herbicide oxyfluorfen was selected as a control, and an aqueous solution containing only T-80 and DMF without the target compound was used as a blank control.

[0221] When monocotyledonous weeds grew to the single-leaf stage and dicotyledonous weeds grew to the two-leaf stage, the stems and leaves of the weeds were sprayed at concentrations of 37.5g ai / ha, 75g ai / ha and 150g ai / ha, respectively. The commercial PPO herbicide oxyfluorfen was used as the control group. Most weed plants showed obvious symptoms of water loss, leaf curling, burning and yellowing 12 hours after the spraying, and bleaching and death occurred 48 hours later.

[0222] As shown in Table 1, most of the target compounds have better inhibitory ability against dicotyledonous weeds than monocotyledonous weeds, and also have higher inhibitory ability against monocotyledonous weed foxtail grass. Most of the target compounds showed more than 80% inhibitory activity against weeds at an application dose of 150g ai / ha, and even at a low application dose of 37.5g ai / ha, some compounds still had higher weed inhibitory ability. According to the results in Table 1, the compounds containing the group CF3 on the pyridine ring have stronger inhibitory ability against weeds, especially when the group CF3 is located at the 4th and 6th positions of pyridine, the herbicidal effect is better. In addition, the herbicidal effect of the compound whose five-membered heterocyclic ring is furan is better than that of thiophene. In addition, when the five-membered heterocyclic ring contains an electron-withdrawing group (Cl), the electron cloud density on the five-membered ring is reduced, resulting in a weakened herbicidal effect. Compounds I-10, I-12, II-8, and II-10 showed excellent weed inhibitory ability, which was equivalent to or slightly better than oxyfluorfen.

[0223] Application Example 2 Test of the inhibitory activity of Examples 1-42 on PPO

[0224] Plant tissue sample processing method: Take barnyard grass leaves and rinse them in 5mL ice-cold PBS, and wipe them dry with filter paper. Add 9 times the volume of homogenization medium in a homogenization tube at a ratio of weight (g): volume (mL) = 1:9, cut the tissue pieces into pieces under ice water bath conditions, grind them thoroughly, and make a 10% homogenate. Centrifuge the prepared 10% homogenate at 6000rmin in a high-speed refrigerated centrifuge for 15 minutes, and take the supernatant for determination.

[0225] Homogenization medium: Tris-HCl phosphate buffer (PBS), wherein the concentration of Tris-HCl is 0.05 mol / L, and the pH of the phosphate buffer is 7.4.

[0226] The PPO enzyme concentration was determined using a plant protoporphyrinogen oxidase (PPOX) ELISA kit. The results are shown in Table 1. By measuring the inhibitory ability of the compounds on the PPO enzyme, it was found that the herbicidal activity results of the target compounds were almost consistent with the in vitro PPO inhibitory activity results.

[0227] Table 1 Greenhouse herbicidal activity of compounds

[0228]

[0229]

[0230]

[0231]

[0232]

[0233]

[0234] Note: Grading scale of herbicidal activity (inhibition percentage): ++++, ≥90%; +++, 80-89%; ++, 60-79%; +, 50-59%; -, <50%.

[0235] Application Example 3 Crop Safety Test

[0236] This example is used to illustrate the safety of the phenoxypyridine compounds containing acylthiourea and heterocyclic structure of the present invention to crops. Test target crops: wheat, corn, rice, soybean, cotton and peanut.

[0237] Planting method of crops: Wheat, corn, rice, soybean and peanut seeds should be soaked in warm water for 12 hours before planting, and germinated in a 25℃ environment for 24 hours. Then select 8 uniform and well-germinated crop seeds, fill a small flower pot (r=4cm, h=8cm) with about 6cm deep flower soil, soak it with water, put the seeds used for testing, cover the top layer with about 2cm of flower soil, spray the surface with a watering can, and place it in an artificial climate room to wait for it to grow. Humidity 60-70%, light and dark for 12 hours each cycle.

[0238] Preparation of target compound emulsion: Weigh 10 mg of the target compounds of Example 12 and Example 25, dissolve each in N,N-dimethylformamide, add 1 drop of Tween-80 (T-80) as an emulsifier, and make up to volume in a 10 mL volumetric flask with distilled water to obtain an emulsion with a target compound concentration of 1 g / L.

[0239] When the crops grew to the 3-leaf stage, they were sprayed with pesticides at concentrations of 150 g ai / ha and 300 g ai / ha, respectively, and a commercial PPO herbicide oxyfluorfen was used as a control crop. After spraying, the growth of the crops was continuously observed.

[0240] It can be seen from the results shown in Table 2 that the above compounds can be used as herbicides. When the application dose is 300 g ai / ha, cotton and wheat show high tolerance to compounds I-12 and II-8, and the crop safety is much higher than that of the commercial herbicide oxyfluorfen.

[0241] Table 2 Safety of compounds I-12, II-8 and oxyfluorfen to crops

[0242]

[0243] The above are only preferred specific embodiments of the present invention, which are all different implementations based on the overall concept of the present invention, and the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. A phenoxypyridine compound containing acylthiourea and a heterocyclic structure, characterized in that: The general structural formula of the compound is shown in the following formula (I) or formula (II): Wherein R1 is at least one selected from H, Cl, Br, NO2 or CF3; X is O or S; R2 is H or Cl.

2. The method for preparing the compound according to claim 1, characterized in that: The method: Step 1: Dissolve 4-aminophenol or 3-aminophenol and an acid-binding agent in an organic solvent 1, then add compound a. After the reaction is completed, cool to room temperature, add distilled water, extract, wash, dry and concentrate to obtain intermediate d or intermediate e. The structural formula of compound a is: Step 2: Compound f and potassium thiocyanate are dissolved in organic solvent 2 to obtain respective organic solutions, and then the two organic solutions are mixed. After the reaction is completed, the mixture is cooled and filtered to obtain a solution containing intermediate h; the structural formula of compound f is: Step 3: adding intermediate d or intermediate e to a solution containing intermediate h to react. After the reaction is completed, adding a poor solvent to the reaction solution, allowing it to stand, filtering, collecting insoluble matter, and recrystallizing to obtain a phenoxypyridine compound (I) or (II) containing acylthiourea and a heterocyclic structure; In compound a and compound f, R1, X and R2 are as defined in claim 1.

3. The method according to claim 2, characterized in that In step 1, the organic solvent 1 is N,N-dimethylformamide or dimethyl sulfoxide, the acid-binding agent is cesium carbonate or potassium carbonate, the molar ratio of compound a to 4-aminophenol or 3-aminophenol and the acid-binding agent is 1:1:(1-3), and the reaction temperature is 80-100°C.

4. The method according to claim 2, characterized in that: In step 2, the organic solvent 2 is acetone or acetonitrile, the molar ratio of compound f to potassium thiocyanate is less than 1, and the reaction temperature is 25-70°C.

5. The method according to claim 2, characterized in that: In step 3, the molar ratio of intermediate d or intermediate e to intermediate h is less than 1, the reaction temperature is 20-40° C., the poor solvent is distilled water or NaHCO 3 solution with a pH of 8-9, and the solvent used for recrystallization is acetonitrile-water.

6. Use of the compound according to claim 1 as a PPO inhibitor.

7. Use of the compound according to claim 1 in controlling weeds in crops.

8. The use according to claim 7, characterized in that: The weeds are monocotyledonous weeds or dicotyledonous weeds, and the crops are wheat, rice, corn, cotton, soybean or peanut.

9. Use of the compound according to claim 1 as an active ingredient in the preparation of herbicidal agents.

10. The use according to claim 9, characterized in that: The active ingredient in the agent is applied at a concentration of 37.5-300 gai / ha.

Images