Phenyl-1, 3, 4-oxadiazole-thiopropionate derivative as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of organic synthesis and pesticides, and particularly discloses a phenyl-1, 3, 4-oxadiazole-thiopropionate derivative as well as a preparation method and application thereof. The phenyl-1, 3, 4-oxadiazole-thiopropionate compound provided by the invention has a structural general formula as shown in a formula I in the specification, wherein Rx is one or more of H, CH3, Br, Cl or F. The phenyl-1, 3, 4-oxadiazole-thiopropionate compound provided by the invention has excellent herbicidal activity, and has the advantages of high safety, small dosage, low cost and the like. The invention also provides a preparation method and application of the compound.

Description

Technical Field

[0001] This invention relates to the fields of organic synthesis and pesticide technology, and in particular to a phenyl-1,3,4-oxadiazole-thiopropionate derivative, its preparation method and uses. Background Technology

[0002] In agricultural production, weeds compete with crops for nutrients, water, and sunlight, leading to reduced yields and economic losses. Herbicides, as the primary means of weed control, are widely used in farmland worldwide. Existing herbicides mainly include sulfonylureas, imidazolinones, and triazines, which achieve weed control by inhibiting the enzyme activity or growth processes of weeds. However, with long-term use, weeds have developed widespread resistance to these herbicides, resulting in reduced weed control efficiency. Furthermore, many traditional herbicides suffer from long environmental residues, high ecotoxicity, and damage to non-target crops, limiting their sustainable application.

[0003] Therefore, there is an urgent need to develop new herbicides to solve the problem of weed resistance. Summary of the Invention

[0004] This invention aims to at least solve one of the technical problems existing in the prior art. To this end, this invention provides a class of phenyl-1,3,4-oxadiazole-thiopropionate derivatives with excellent biological activity to overcome the shortcomings of insufficient activity or poor selectivity of compounds in the prior art. The phenyl-1,3,4-oxadiazole-thiopropionate compounds provided by this invention exhibit excellent herbicidal activity and show significant control effects against dicotyledonous amaranthaceae weeds and monocotyledonous grass weeds.

[0005] In a first aspect, the present invention provides a phenyl-1,3,4-oxadiazole-thiopropionate compound having the general structural formula shown in Formula I: ; Wherein, Rx is one or more of H, CH3, Br, Cl or F.

[0006] According to some embodiments of the present invention, its structural formula includes any one of the following formulas II to XII: , , , , , , , , , , .

[0007] According to some preferred embodiments of the present invention, its structural formula includes any one of Formula II, Formula III or Formula V.

[0008] The preferred compounds of formula II, III, or V of this invention exhibit more significant control effects against dicotyledonous Amaranthaceae weeds and monocotyledonous Gramineae weeds, and toxicity test results show that their EC50 content is significantly higher than that of other compounds. 50 The values ​​were significantly lower, and field trial results showed that its control efficacy against total weeds and fresh weight was significantly better, with advantages of lower cost and environmental friendliness. The selected compound achieved a fresh weight control efficacy of at least 92.7% against amaranth rotundifolia 7 days after application, which was comparable to the positive control agent 2,4-D (95.7%); and a fresh weight control efficacy of at least 74.1% against barnyardgrass 7 days after application, which was better than the positive control agent 2,4-D (72.6%).

[0009] A second aspect of the present invention provides a method for preparing the phenyl-1,3,4-oxadiazole-thiopropionate compound as described in any one of claims 1 to 3, comprising the following steps: Compound X was dissolved in a solvent, and an acid-binding agent and compound 1 were added. The mixture was heated and stirred to carry out the reaction. After the reaction was completed, compound 2 was obtained by extraction, washing, and drying. The synthetic route is as follows: ; The molar ratio of compound X to compound 1 is (0.8~3):1.

[0010] This invention explores and selects methyl 2-bromopropionate as a synthetic raw material. By introducing the key methyl propionate group into the target compound, the herbicidal activity of the target compound can be enhanced.

[0011] According to some preferred embodiments of the present invention, the molar ratio of compound X to compound 1 is (1~2):1.

[0012] According to some embodiments of the present invention, the molar ratio of compound 1 to the acid-binding agent is 1:(1~4); preferably, the molar ratio of compound 1 to the acid-binding agent is 1:(2~3).

[0013] According to some embodiments of the present invention, the solvent is at least one selected from N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, acetone, tetrahydrofuran, or chloroform.

[0014] According to some embodiments of the present invention, the acid-binding agent is at least one of sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate, or triethylamine.

[0015] According to some embodiments of the present invention, the heating and stirring conditions are: temperature 50~90℃, stirring speed 500~600rpm, time 4~8h, and thin-layer chromatography is used for monitoring during the reaction.

[0016] According to some embodiments of the present invention, the extraction is performed using dichloromethane.

[0017] According to some embodiments of the present invention, the washing is performed by washing with salt water 2 to 5 times.

[0018] According to some embodiments of the present invention, the drying is performed using magnesium sulfate; prior to the drying, the material is further subjected to filtration and solvent evaporation.

[0019] A third aspect of the invention provides the use of phenyl-1,3,4-oxadiazole-thiopropionate compounds as described in the first aspect of the invention in the preparation of herbicides.

[0020] According to some embodiments of the present invention, the herbicide includes herbicides for annual and perennial weeds.

[0021] A fourth aspect of the present invention provides a herbicidal composition comprising the phenyl-1,3,4-oxadiazole-thiopropionate compound as described in any one of claims 1 to 3.

[0022] The beneficial effects of this invention are: The 1,3,4-oxadiazole-phenyl-thiopropionate compounds provided by this invention exhibit excellent herbicidal activity, showing significant control effects against dicotyledonous amaranthaceae weeds and monocotyledonous grasses. Specifically, the fresh weight control efficacy against *Amaranthus retroflexus* reaches at least 92.7% seven days after application, and against *Barnyardgrass* at least 74.1% seven days after application. It also demonstrates good control efficacy against barnyardgrass resistant to cyhalofop-butyl, with low residue levels in later crops and safety for non-target bees. This compound requires low dosage, is low in cost, and has a short residual period, mitigating the potential environmental threat of pesticides. Furthermore, its synthesis method is simple and economical, making it a suitable lead compound for developing highly effective and low-toxicity novel herbicides.

[0023] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention. Attached Figure Description

[0024] The present invention will be further described below with reference to the accompanying drawings and embodiments, wherein: Figure 1 This is a schematic diagram of the synthetic route of phenyl-1,3,4-oxadiazole-thiopropionate compounds according to an embodiment of the present invention. Detailed Implementation

[0025] The following will describe the concept and technical effects of the present invention clearly and completely with reference to embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention.

[0026] Unless otherwise specified in the examples, the procedures should be performed under standard conditions or conditions recommended by the manufacturer. Reagents or instruments whose manufacturers are not specified are all commercially available products. Example 1

[0027] This embodiment prepares a phenyl-1,3,4-oxadiazole-thiopropionate compound: methyl 2-((5-(2-tolyl)-1,3,4-oxadiazole-2-yl)thio)propionate. A schematic diagram of the synthetic route is shown below. Figure 1 As shown, the specific preparation steps are as follows: 1.92 g (10 mmol) of compound A was dissolved in a 100 mL round-bottom flask containing 25 mL of N,N-dimethylformamide. After dissolution, 4.15 g of sodium carbonate (30 mmol) was added as an acid-binding agent, followed by 1.67 g (10 mmol) of compound 1. The mixture was slowly heated to 60 °C and stirred at 550 rpm for 5 h. Once the starting material spot disappeared as monitored by TLC, the mixture was cooled to room temperature, and then 50 mL of dichloromethane was added for extraction twice. The mixture was washed three times with brine, dried with anhydrous magnesium sulfate, filtered, and the solvent was evaporated by rotary evaporation. After drying, the product weighed 2.421 g, and the yield was calculated to be 87.0%.

[0028] The synthetic route for the above reaction is as follows: .

[0029] The target compound obtained in this embodiment was characterized by NMR and high-resolution mass spectrometry, and the results are as follows: Yellow solid 1 H NMR (400 MHz, CHCl3- d 6 , δ ppm): 7.87 (d, J= 6.4 Hz, 1H, Ar-H), 7.42-7.39 (m, 1H, Ar-H), 7.34-7.29 (m, 2H, Ar-H), 4.54-4.49 (m, 1H, Ar-H), 3.79 (s, 3H, OCH3-H), 2.69 (s, 3H, CH3-H ), 1.75 (d, J= 7.2 Hz, 3H, CH3-H). 13 C10 NMR (100 MHz, CHCl3-) d 6, δ ppm): 171.37, 166.31, 162.20, 138.35, 131.76,131.33, 128.75, 126.19, 122.48, 53.13, 44.47, 22.09, 18.20. HRMS (ESI)C 13 H 14 N₂O₃S [M+H] + :calcd. 279.0798, found 270.0797. Example 2

[0030] This embodiment prepares a phenyl-1,3,4-oxadiazole-thiopropionate compound: methyl 2-((5-(3,4-dimethylphenyl)-1,3,4-oxadiazole-2-yl)thio)propionate. The specific preparation steps are as follows: 2.06 g (10 mmol) of compound B was dissolved in a 100 mL round-bottom flask containing 25 mL of N,N-dimethylformamide. After dissolution, 4.15 g of sodium carbonate (30 mmol) was added as an acid-binding agent, followed by 1.67 g (10 mmol) of compound 1. The mixture was slowly heated to 60 °C and stirred at 550 rpm for 5 h. After the TLC monitoring showed that the starting material spot disappeared, the mixture was cooled to room temperature, and then dichloromethane (50 mL) was added for extraction twice. The mixture was washed three times with brine, dried with anhydrous magnesium sulfate, filtered, the solvent was rotary evaporated, dried, and weighed 2.371 g. The yield was calculated to be 81.1%.

[0031] The synthetic route for the above reaction is as follows: .

[0032] The target compound obtained in this embodiment was characterized by NMR and high-resolution mass spectrometry, and the results are as follows: Yellow solid 1 H NMR (400 MHz, CHCl3- d 6 , δ ppm): 7.62 (s, 2H, Ar-H), 4.54-4.48 (m, 1H, Ar-H), 3.79 (s, 3H, OCH3-H), 2.38 (s, 6H, CH3-H), 1.75 (d, J= 7.2Hz, 3H, CH3-H). 13 C10 NMR (100 MHz, CHCl3-) d 6, δ ppm): 171.41, 166.48, 162.13,138.86, 133.60, 124.48, 123.20, 53.12, 44.53, 21.22, 18.22. HRMS (ESI)C 14 H 16 N₂O₃S [M+H] + :calcd. 293.0956, found 293.0955.

[0033] Example 3 This embodiment prepares a phenyl-1,3,4-oxadiazole-thiopropionate compound: methyl 2-((5-(3-chlorophenyl)-1,3,4-oxadiazole-2-yl)thio)propionate. The specific preparation steps are as follows: 2.13 g (10 mmol) of compound C was dissolved in a 100 mL round-bottom flask containing 25 mL of N,N-dimethylformamide. After dissolution, 4.15 g of sodium carbonate (30 mmol) was added as an acid-binding agent, followed by 1.67 g (10 mmol) of compound 1. The mixture was slowly heated to 60 °C and stirred at 550 rpm for 5 h. After the TLC monitoring showed that the starting material spot disappeared, the mixture was cooled to room temperature, and then 50 mL of dichloromethane was added for extraction twice. The mixture was washed three times with brine, dried with anhydrous magnesium sulfate, filtered, and the solvent was evaporated by rotary evaporation. After drying, the product weighed 2.501 g, and the yield was calculated to be 83.7%.

[0034] The synthetic route for the above reaction is as follows: .

[0035] The target compound obtained in this embodiment was characterized by NMR and high-resolution mass spectrometry, and the results are as follows: Yellow solid 1 H NMR (400 MHz, CHCl3- d 6 , δ ppm): 8.00 (s, 1H, Ar-H), 7.90(d, J= 6.0 Hz, 1H, Ar-H), 7.52-7.50 (m, 1H, Ar-H ), 7.45 (t, J= 8.0 Hz, 1H, Ar-H), 4.56-4.51 (m, 1H, Ar-H), 3.80 (s, 3H, OCH3-H), 1.76 (d, J= 7.2 Hz, 3H, CH3-H). 13 C NMR (100 MHz, CHCL3-d 6 , δ ppm): 171.28, 164.94, 135.26, 131.89,130.49, 126.73, 125.07, 124.83, 53.20, 44.61, 18.20. HRMS (ESI) C 12 H 11 ClN2O3S[M+H] + :calcd 299.0252, found 299.0251. Example 4

[0036] This embodiment prepares a phenyl-1,3,4-oxadiazole-thiopropionate compound: methyl 2-((5-(2,3-dichlorophenyl)-1,3,4-oxadiazole-2-yl)thio)propionate. The specific preparation steps are as follows: 2.47 g (10 mmol) of compound D was dissolved in a 100 mL round-bottom flask containing 25 mL of N,N-dimethylformamide. After dissolution, 4.15 g of sodium carbonate (30 mmol) was added as an acid-binding agent, followed by 1.67 g (10 mmol) of compound 1. The mixture was slowly heated to 60 °C and stirred at 550 rpm for 5 h. After the TLC monitoring showed that the starting material spot disappeared, the mixture was cooled to room temperature, and then dichloromethane (50 mL) was added for extraction twice. The mixture was washed three times with brine, dried with anhydrous magnesium sulfate, filtered, the solvent was rotary evaporated, dried, and weighed 2.813 g. The yield was calculated to be 84.4%.

[0037] The synthetic route for the above reaction is as follows: .

[0038] The target compound obtained in this embodiment was characterized by NMR and high-resolution mass spectrometry, and the results are as follows: Yellow solid 1 H NMR (400 MHz, CHCl3- d 6 , δ ppm): 7.86-7.83 (m, 1H, Ar-H), 7.67-7.64 (m, 1H, Ar-H), 7.46 (t, J= 8.0 Hz, 1H, Ar-H), 4.57-7.51 (m, 1H, Ar-H), 3.80 (s, 3H, OCH3-H), 1.77 (d, J= 7.2 Hz, 3H, CH3-H). 13 C NMR (100 MHz, CHCL3-) d6 , δ ppm): 171.19, 163.90, 163.59, 135.09, 133.31, 131.60, 129.37,127.66, 124.89, 53.21, 44.62, 36.51, 18.23. HRMS (ESI) C 12 H 10 Cl2N2O3S [M+H] + :calcd 332.9862, found 332.9860.

[0039] Example 5 This embodiment prepares a phenyl-1,3,4-oxadiazole-thiopropionate compound: methyl 2-((5-(3,4-dichlorophenyl)-1,3,4-oxadiazole-2-yl)thio)propionate. The specific preparation steps are as follows: 2.47 g (10 mmol) of compound E was dissolved in a 100 mL round-bottom flask containing 25 mL of N,N-dimethylformamide. After dissolution, 4.15 g of sodium carbonate (30 mmol) was added as an acid-binding agent, followed by 1.67 g (10 mmol) of compound 1. The mixture was slowly heated to 60 °C and stirred at 550 rpm for 5 h. Once the TLC monitoring showed that the starting material had disappeared, the mixture was cooled to room temperature, and then 50 mL of dichloromethane was added for extraction twice. The mixture was washed three times with brine, dried with anhydrous magnesium sulfate, filtered, and the solvent was rotary evaporated. After drying, the product weighed 2.719 g, and the yield was calculated to be 81.6%.

[0040] The synthetic route for the above reaction is as follows: .

[0041] The target compound obtained in this embodiment was characterized by NMR and high-resolution mass spectrometry, and the results are as follows: Yellow solid 1 H NMR (400 MHz, CHCl3- d 6 , δ ppm): 8.09 (d, J= 6.0 Hz, 1H, Ar-H), 7.86-7.83 (m, 1H, Ar-H), 7.59 (d, J= 8.4 Hz, 1H, Ar-H), 4.57-4.51 (m, 1H, Ar-H), 3.80 (s, 3H, OCH3-H), 1.76 (d, J= 7.2 Hz, 3H, CH3-H). 13C NMR (100 MHz, CHCL3- d 6 , δ ppm): 171.19, 164.22, 163.30, 136.31, 133.74, 131.32, 128.41,125.72, 123.22, 53.21, 44.65, 18.19. HRMS (ESI) C 12 H 10 Cl2N2O3S [M+H] + : calcd332.9862, found 332.9860. Example 6

[0042] This embodiment prepares a phenyl-1,3,4-oxadiazole-thiopropionate compound: methyl 2-((5-(3,5-dichlorophenyl)-1,3,4-oxadiazole-2-yl)thio)propionate. The specific preparation steps are as follows: 2.47 g (10 mmol) of compound F was dissolved in a 100 mL round-bottom flask containing 25 mL of N,N-dimethylformamide. After dissolution, 4.15 g of sodium carbonate (30 mmol) was added as an acid-binding agent, followed by 1.67 g (10 mmol) of compound 1. The mixture was slowly heated to 60 °C and stirred at 550 rpm for 5 h. Once the TLC monitoring showed that the starting material had disappeared, the mixture was cooled to room temperature, and then 50 mL of dichloromethane was added for extraction twice. The mixture was washed three times with brine, dried with anhydrous magnesium sulfate, filtered, and the solvent was evaporated by rotary evaporation. After drying, the product weighed 2.959 g, and the yield was calculated to be 88.8%.

[0043] The synthetic route for the above reaction is as follows: .

[0044] The target compound obtained in this embodiment was characterized by NMR and high-resolution mass spectrometry, and the results are as follows: Yellow solid 1 H NMR (400 MHz, CHCl3- d 6 , δ ppm): 7.90 (d, J= 1.6 Hz, 2H, Ar-H), 7.52 (t, J= 2.0 Hz, 1H, Ar-H), 4.58-4.52 (m, 1H, Ar-H), 3.80 (s, 3H, OCH3-H), 1.77 (d, J= 7.2 Hz, 3H, CH3-H). 13C10 NMR (100 MHz, CHCl3-) d 6 , δ ppm): 171.18,163.88, 163.66, 136.07, 135.37, 131.69, 128.27, 126.03, 124.97, 53.23, 44.67,18.19. HRMS (ESI) C 12 H 10 Cl2N2O3S [M+H] + :calcd 332.9862, found 332.9860. Example 7

[0045] This embodiment prepares a phenyl-1,3,4-oxadiazole-thiopropionate compound: methyl 2-((5-(2,3-difluorophenyl)-1,3,4-oxadiazole-2-yl)thio)propionate. The specific preparation steps are as follows: 2.14 g (10 mmol) of compound G was dissolved in a 100 mL round-bottom flask containing 25 mL of N,N-dimethylformamide. After dissolution, 4.15 g of sodium carbonate (30 mmol) was added as an acid-binding agent, followed by 1.67 g (10 mmol) of compound 1. The mixture was slowly heated to 60 °C and stirred at 550 rpm for 5 h. After the TLC monitoring showed that the starting material spot disappeared, the mixture was cooled to room temperature, and then 50 mL of dichloromethane was added for extraction twice. The mixture was washed three times with brine, dried with anhydrous magnesium sulfate, filtered, and the solvent was evaporated by rotary evaporation. After drying, the product weighed 2.148 g, and the yield was calculated to be 71.5%.

[0046] The synthetic route for the above reaction is as follows: .

[0047] The target compound obtained in this embodiment was characterized by NMR and high-resolution mass spectrometry, and the results are as follows: Yellow solid 1 H NMR (400 MHz, CHCl3- d 6 , δ ppm): 7.81-7.77 (m, 1H, Ar-H),7.40-7.34 (m, 1H, Ar-H), 7.29-7.22 (m, 1H, Ar-H ), 4.56-4.51 (m, 1H, Ar-H), 3.80 (s, 3H, OCH3-H), 1.76 (d, J= 7.2 Hz, 3H, CH3-H). 13C NMR (100 MHz, CHCL3- d 6 , δ ppm): 171.19, 165.53, 161.98, 161.94, 152.44, 152.33, 149.96, 149.85,149.70, 147.11, 146.97, 124.93, 124.88, 124.86, 124.81, 124.14, 124.10,120.65, 120.48, 113.99, 113.91, 53.18, 44.59, 18.16. HRMS (ESI) C 12 H 10 F2N2O3S[M+H] + : calcd. 300.1038, found 300.1034. Example 8

[0048] This embodiment prepares a phenyl-1,3,4-oxadiazole-thiopropionate compound: methyl 2-((5-(3,5-difluorophenyl)-1,3,4-oxadiazole-2-yl)thio)propionate. The specific preparation steps are as follows: 2.14 g (10 mmol) of compound H was dissolved in a 100 mL round-bottom flask containing 25 mL of N,N-dimethylformamide. After dissolution, 4.15 g of sodium carbonate (30 mmol) was added as an acid-binding agent, followed by 1.67 g (10 mmol) of compound 1. The mixture was slowly heated to 60 °C and stirred at 550 rpm for 5 h. Once the TLC monitoring showed that the starting material had disappeared, the mixture was cooled to room temperature, and then 50 mL of dichloromethane was added for extraction twice. The mixture was washed three times with brine, dried with anhydrous magnesium sulfate, filtered, and the solvent was rotary evaporated. After drying, the product weighed 2.24 g, and the yield was calculated to be 74.6%.

[0049] The synthetic route for the above reaction is as follows: .

[0050] The target compound obtained in this embodiment was characterized by NMR and high-resolution mass spectrometry, and the results are as follows: Yellow solid 1 H NMR (400 MHz, CHCl3- d 6, δ ppm): 7.57-7.53 (m, 2H, Ar-H), 7.02-6.97 (m, 1H, Ar-H), 4.58-4.52 (m, 1H, Ar-H), 3.81 (s, 3H, OCH3-H), 1.76(d, J= 6.4 Hz, 3H, CH3-H). 13 C NMR (100 MHz, CHCL3- d 6 , δ ppm): 171.16, 164.54,164.41, 164.21, 163.57, 162.05, 161.92, 126.20, 126.10, 125.99, 110.05,109.97, 109.85, 109.77, 107.53, 107.28, 107.03, 53.21, 44.64, 18.17. HRMS(ESI) C 12 H 10 F2N2O3S [M+H] + : calcd. 300.1038, found 300.1034. Example 9

[0051] This embodiment prepares a phenyl-1,3,4-oxadiazole-thiopropionate compound: methyl 2-((5-(2-bromophenyl)-1,3,4-oxadiazole-2-yl)thio)propionate. The specific preparation steps are as follows: 2.57 g (10 mmol) of compound I was dissolved in a 100 mL round-bottom flask containing 25 mL of N,N-dimethylformamide. After dissolution, 4.15 g of sodium carbonate (30 mmol) was added as an acid-binding agent, followed by 1.67 g (10 mmol) of compound 1. The mixture was slowly heated to 60 °C and stirred at 550 rpm for 5 h. TLC monitoring until the starting material spot disappeared, cooling to room temperature, then adding dichloromethane (50 mL) for extraction twice, washing three times with brine, drying with anhydrous magnesium sulfate, filtering, rotary evaporating the solvent, drying, weighing 2.550 g, and calculating the yield as 74.3%.

[0052] The synthetic route for the above reaction is as follows: .

[0053] The target compound obtained in this embodiment was characterized by NMR and high-resolution mass spectrometry, and the results are as follows: Yellow solid 1 H NMR (400 MHz, CHCl3-d 6 , δ ppm): 7.90-7.88 (m, 1H, Ar-H), 7.76-7.74 (m, 1H, Ar-H), 7.47-7.43 (m, 1H, Ar-H), 7.41-7.36 (m, 1H, Ar-H), 4.56-4.51 (m, 1H, Ar-H), 3.80 (s, 3H, OCH3-H), 1.76 (d, J= 7.2 Hz, 3H, CH3-H). 13 C NMR (100 MHz, CHCL3- d 6 , δ ppm): 171.24, 164.91, 163.20, 134.61, 132.61,131.44, 127.65, 124.82, 121.50, 53.18, 44.60, 18.27. HRMS (ESI) C 12 H 11 BrN2O3S[M+H] + : calcd. 342.9747, found 342.9750. Example 10

[0054] This embodiment prepares a phenyl-1,3,4-oxadiazole-thiopropionate compound: methyl 2-((5-(4-bromo-3-chlorophenyl)-1,3,4-oxadiazole-2-yl)thio)propionate. The specific preparation steps are as follows: 2.92 g (10 mmol) of compound J was dissolved in a 100 mL round-bottom flask containing 25 mL of N,N-dimethylformamide. After dissolution, 4.15 g of sodium carbonate (30 mmol) was added as an acid-binding agent, followed by 1.67 g (10 mmol) of compound 1. The mixture was slowly heated to 60 °C and stirred at 550 rpm for 5 h. After the TLC monitoring showed that the starting material spot disappeared, the mixture was cooled to room temperature, and then 50 mL of dichloromethane was added for extraction twice. The mixture was washed three times with brine, dried with anhydrous magnesium sulfate, filtered, the solvent was rotary evaporated, dried, and weighed 3.202 g. The yield was calculated to be 84.8%.

[0055] The synthetic route for the above reaction is as follows: .

[0056] The target compound obtained in this embodiment was characterized by NMR and high-resolution mass spectrometry, and the results are as follows: Yellow solid 1H NMR (400 MHz, CHCl3-d6, δ ppm): 8.08 (s, 1H, Ar-H), 7.76 (s, 2H, Ar-H), 4.57-4.52 (m, 1H, Ar-H), 3.80 (s, 3H, OCH3-H), 1.76 (d, J=7.2Hz, 3H, CH3-H). 13 C NMR (100 MHz, CHCl3-d6, δ ppm): 171.20, 164.32, 163.34,135.73, 134.63, 128.14, 126.54, 125.71, 123.88, 53.22, 44.65, 18.19. HRMS(ESI) C 12 H 10 BrN2O3S [M+H]+: calcd. 376.9357, found 376.9360. Example 11

[0057] This embodiment prepares a phenyl-1,3,4-oxadiazole-thiopropionate compound: methyl 2-((5-(4-chloro-2-methylphenyl)-1,3,4-oxadiazole-2-yl)thio)propionate. The specific preparation steps are as follows: 2.27 g (10 mmol) of compound K was dissolved in a 100 mL round-bottom flask containing 25 mL of N,N-dimethylformamide. After dissolution, 4.15 g of sodium carbonate (30 mmol) was added as an acid-binding agent, followed by 1.67 g (10 mmol) of compound 1. The mixture was slowly heated to 60 °C and stirred at 550 rpm for 5 h. After the TLC monitoring showed that the starting material spot disappeared, the mixture was cooled to room temperature, and then dichloromethane (50 mL) was added for extraction twice. The mixture was washed three times with brine, dried with anhydrous magnesium sulfate, filtered, the solvent was rotary evaporated, dried, and weighed 2.415 g. The yield was calculated to be 77.2%.

[0058] The synthetic route for the above reaction is as follows: .

[0059] The target compound obtained in this embodiment was characterized by NMR and high-resolution mass spectrometry, and the results are as follows: Yellow solid 1H NMR (400 MHz, CHCl3-d6, δ ppm): 7.84 (d, J=8.4 Hz, 1H,Ar-H), 7.54 (s, 1H, Ar-H), 7.46 (d, J=6.0 Hz, 2H, Ar-H), 4.61-4.56 (m, 1H,Ar-H), 3.79 (s, 3H, OCH3-H), 2.58 (s, 3H, CH3-H), 1.63 (d, J=7.6 Hz, 3H, CH3-H). 13 C NMR (100 MHz, DMSO-d6, δ ppm): 171.32, 165.49, 161.90, 140.42, 136.63,131.83, 130.75, 127.04, 121.43, 53.35, 44.25, 21.60, 18.26. HRMS (ESI)C 13 H 13 ClN2O3S [M+H]+: calcd. 313.0409, found 313.0408. Example 12

[0060] In this embodiment, the foliar spray method (NY / T 1155.4-2006) was used to conduct indoor toxicity tests on the phenyl-1,3,4-oxadiazole-thiopropionate compounds prepared in Examples 1 to 11.

[0061] Test reagents: (a) Example 1; (b) Example 2; (c) Example 3; (d) Example 4; (e) Example 5; (f) Example 6; (g) Example 7; (h) Example 8; (i) Example 9; (j) Example 10; (k) Example 11; (l) Positive control (2,4-dichlorophenoxyacetic acid, 2,4-D); (m) Water control.

[0062] Test materials: barnyard grass and reverse-branch amaranth.

[0063] After soaking and germinating barnyard grass and amaranth retroflexus seeds, 20 seeds were sown in 0.25 m² plastic pots filled with soil. The seeds were then cultured in a greenhouse until the seedlings reached the 2-leaf stage before treatment. The herbicide was applied using a handheld compressor sprayer (3NY-1.2) at the designed concentration gradient (15 g / ha, 30 g / ha, 40-45 g / ha, 60 g / ha, 75 g / ha, 90 g / ha), with a spray volume of 50 mL per treatment. The soil was kept moist after treatment. Each treatment was repeated four times. Twenty days after treatment, the fresh weight of the aboveground parts of each treatment was measured, and the fresh weight control efficacy (%) was calculated using the following formula: E = 100 × (CT) / C; In the formula, E represents the fresh weight efficacy; C represents the fresh weight of the control aboveground parts; and T represents the fresh weight of the treated aboveground parts.

[0064] The experimental results are shown in Tables 1 and 2.

[0065]

[0066]

[0067] As can be seen from Tables 1 and 2, most herbicides have an EC50 effect on barnyardgrass. 50 Concentrated at 65–115 g / ha, of which agent a (EC) 50 =69.29 g / ha), Agent b (EC 50 =66.58 g / ha) and agent d (EC 50 =68.17 g / ha) has a strong efficacy; agent c (EC 50 =113.33) and Agent i (EC 50 =107.23) is the least toxic. For *Amaranthus retroflexus* (Table 2), EC... 50 The concentrations were in the range of 54–94 g / ha, generally lower than those in Table 1, indicating that most agents had a more significant inhibitory effect on Amaranthus retroflexus. Example 13

[0068] This embodiment tests the bee safety of the phenyl-1,3,4-oxadiazole-thiopropionate compounds prepared in Examples 1-11.

[0069] Test reagents: (a) Example 1; (b) Example 2; (c) Example 3; (d) Example 4; (e) Example 5; (f) Example 6; (g) Example 7; (h) Example 8; (i) Example 9; (j) Example 10; (k) Example 11; (l) Sugar water control.

[0070] Test material: Italian honeybee.

[0071] Healthy, uniformly weighted Italian honeybees, typically worker bees, were selected. The test substance was prepared as a 40,000 ppm stock solution using acetone, and then diluted with 50% sucrose solution to six concentrations: 50, 100, 200, 400, 800, and 1600 ppm. The bees' responses were assessed by feeding them sugar solutions containing different concentrations of the test substance. Typically, 20 worker bees were placed in a feeding cage, and the experiment was repeated three times. The medicated sugar solution was provided as the sole food source, and each concentration was tested three times. The mortality rate was observed after a period of time (72 hours). Temperature, humidity, and light should be kept stable (e.g., 25℃ ± 2℃, relative humidity 50%-70%). Other environmental stressors or sources of pollution should be avoided to prevent interference with the bees. The experimental results were analyzed using SPSS to calculate the dose that would kill half of the bees.

[0072] The results showed that Examples 2, 3, 5, 7, and 8 had an LD50 effect on the Chinese honeybee. 50 The concentration of the median lethal dose (the dose that would kill half of the bees) was greater than 800 ppm, and the rest were greater than 200 ppm (greater than 200 ppm is considered low toxicity for bees).

[0073] Test results show that the compounds in each embodiment are of low toxicity to non-target bees. Example 14

[0074] This embodiment presents a field test of the phenyl-1,3,4-oxadiazole-thiopropionate compounds prepared in Examples 1-11.

[0075] The phenyl-1,3,4-oxadiazole-thiopropionate compounds prepared in Examples 1-11 were applied to control annual and perennial weeds in cornfields. In Examples 1-11, the phenyl-1,3,4-oxadiazole-thiopropionate compounds were diluted with water and sprayed at a concentration of 150 g / ha. Seven days after application, the plant control efficacy of the compounds in Examples 1-11 against total weeds was 89.85%, 91.56%, 75.67%, 92.14%, 83.25%, 82.56%, 83.68%, 85.88%, 78.96%, 80.64%, and 81.63%, respectively. The fresh weight control efficacy was 90.56%, 90.33%, 78.55%, 91.68%, 85.69%, 85.32%, 83.64%, 87.62%, 80.37%, 82.53%, and 82.58%, respectively.

[0076] The results above show that the phenyl-1,3,4-oxadiazole-thiopropionate compounds provided by this invention have significant effects on the control of annual and perennial weeds in cornfields, and the weed control spectrum has been further broadened. They not only have the potential to be developed into herbicides, but also have the advantages of low cost and environmental protection.

[0077] The embodiments of the present invention have been described in detail above. However, the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of the present invention. Furthermore, the embodiments of the present invention and the features thereof can be combined with each other unless otherwise specified.

Claims

1. A phenyl-1,3,4-oxadiazole-thiopropionate compound, characterized in that, Its general structural formula is shown in Formula I: ； Wherein, Rx is one or more of H, CH3, Br, Cl or F.

2. The phenyl-1,3,4-oxadiazole-thiopropionate compound according to claim 1, characterized in that, Its structural formula includes any one of the following formulas II to XII: 。 3. The phenyl-1,3,4-oxadiazole-thiopropionate compound according to claim 2, characterized in that, Its structural formula includes any one of the formulas shown in Formula II, Formula III, or Formula V.

4. A method for preparing the phenyl-1,3,4-oxadiazole-thiopropionate ester compound as described in any one of claims 1 to 3, characterized in that, Includes the following steps: Compound X was dissolved in a solvent, and an acid-binding agent and compound 1 were added. The mixture was heated and stirred to carry out the reaction. After the reaction was completed, compound 2 was obtained by extraction, washing, and drying. The synthetic route is as follows: ； The molar ratio of compound X to compound 1 is (0.8~3):

1.

5. The preparation method according to claim 4, characterized in that, The molar ratio of compound 1 to the acid-binding agent is 1:(1~3).

6. The preparation method according to claim 4, characterized in that, The solvent is at least one of N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, acetone, tetrahydrofuran, or chloroform; the acid-binding agent is at least one of sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate, or triethylamine.

7. The preparation method according to claim 4, characterized in that, The heating and stirring conditions are: temperature 50~90℃, stirring speed 500~600rpm, time 4~8h, and thin-layer chromatography is used for monitoring during the reaction.

8. The preparation method according to claim 4, characterized in that, The extraction is performed using dichloromethane; the washing is performed using brine 2-5 times; the drying is performed using magnesium sulfate; and the material is further treated by filtration and solvent evaporation before drying.

9. The use of the phenyl-1,3,4-oxadiazole-thiopropionate compound as described in any one of claims 1 to 3 in the preparation of herbicides.

10. A herbicidal composition, characterized in that, Includes the phenyl-1,3,4-oxadiazole-thiopropionate compounds as described in any one of claims 1 to 3.

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