Use of sulfonbenzamide derivatives

Abstract

The application belongs to the technical field of plant protection, and particularly relates to application of a sulfonbenzamide derivative. The application relates to application of the sulfonbenzamide derivative in preparation of an agricultural fungicide for plant pathogens. The sulfonbenzamide derivative is a chitin synthase inhibitor. The sulfonbenzamide derivative is a compound shown in formula I.

Description

Technical Field

[0001] This invention belongs to the field of plant protection technology, specifically relating to the application of a sulfonylbenzamide derivative. Background Technology

[0002] Chemical pesticides are the primary means of controlling plant diseases. However, due to the long-term irrational use of pesticides, many commercially available agents generally face the "3R" problem: resistance, pesticide residues, and the resurgence of harmful organisms. Therefore, developing novel fungicides with novel molecular structures and unique mechanisms of action has become an urgent need for the prevention and control of plant diseases in agriculture. [1] .

[0003] The rational design and discovery of novel active substances based on green selective targets is one of the important directions in the current creation of green pesticides. [2] Chitin is widely found in various organisms, including pathogens, algae, mollusks, and arthropods, and plays an important role in many physiological and biochemical processes such as growth, development, and metabolism. [3] Chitin is an important component of the cell wall of pathogenic bacteria, but it is absent in plants and mammals. [4] This characteristic allows for good selectivity and non-target biosafety when targeting key enzymes in the chitin biosynthesis pathway. Chitin synthase is a crucial enzyme catalyzing chitin synthesis; inhibiting its activity interferes with normal chitin synthesis, thereby hindering the formation and repair of pathogenic cell walls (fungi, oomycetes, and bacteria). Ultimately, this leads to abnormal cell structure and loss of infectivity in agricultural pathogens, achieving the goal of disease control while remaining safe and harmless to the host plant. [5] However, most existing chitin synthase inhibitors are pyrimidine nucleoside peptide inhibitors. These inhibitors have complex structures, high synthesis costs, significantly weaker in vivo activity than in vitro activity, are easily degraded by hydrolytic enzymes, and have poor permeability to fungal cell walls. Therefore, the design and discovery of highly efficient inhibitors targeting chitin synthase has become a cutting-edge research hotspot in the development of novel green fungicides, and has significant practical and economic value for promoting the creation of new pesticides in my country.

[0004] References: [1] Wu Jian, Song Baoan. Current status and reflections on green pesticide innovation and target research [J]. China Science Foundation, 2020, 34(4): 486-494. [2] Yang Guangfu. Chemical biology-guided molecular design of green pesticides [J]. China Science Foundation, 2020, 34(4): 495-501. [3] Li B, Shen Y, Wu H, et al. Design, synthesis and biological evaluation of novel 3,4-dihydro-2(1H)-quinolinone derivatives as potentialchitin synthase inhibitors and antifungal agents[J]. European Journal of Medicinal Chemistry, 2020, 195: 112278. [4] Shi X, Qiu S, Bao Y, et al. Screening and application of chitinsynthase inhibitors[J]. Processes, 2020, 8(9): 1029. [5] Cheng W, Lin M, Qiu M, et al. Chitin synthase is involved in invegetative growth, asexual reproduction and pathogenesis of Phytophthoracapsici and Phytophthora sojae[J]. Environmental Microbiology, 2019, 21(12):4537-4547. Summary of the Invention

[0005] The purpose of this invention is to provide an application of sulfonylbenzamide derivatives.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: Application of a sulfonylbenzamide derivative: its application in the preparation of fungicides for agricultural plant pathogens.

[0007] The sulfonylbenzamide derivatives are used as chitin synthase inhibitors.

[0008] The sulfonylbenzamide derivative is a compound of formula I: ;

[0009] In formula I, R 1 It is 1-methylpiperazine or 1,2,3,4-tetrahydroquinoline; R 2 For C1-C10 Alkyl, C1-C 10 Alkoxycarbonyl, cyano, halogen, or C1-C6 haloalkyl.

[0010] The sulfonylbenzamide derivatives are .

[0011] The agricultural plant pathogens mentioned are fungi, oomycetes, or bacteria.

[0012] The fungus includes rapeseed sclerotia ( Sclerotinia sclerotiorum , Ss ) or rice blast fungus ( Magnaporthe Rice , Mo ); The oomycetes include Phytophthora capsici ( Phytophthora capsicum , PC ) or fruit mold ( Pythium aphaniderm , Father ); The bacteria include *Cucumber angularis* (a bacterium that causes bacterial angular leaf spot). Pseudomonas syringae pv. lachrymans , Psl ).

[0013] The formulation of the bactericide is a pharmacodynamically acceptable formulation, including at least one of emulsifiable concentrates, wettable powders, suspension concentrates, powders, soluble powders, aqueous solutions, water-dispersible powders, fumigants, granules, and seed coating agents. Detailed Implementation

[0014] The present invention will now be described in further detail with reference to specific embodiments. The given embodiments are merely illustrative of the invention and not intended to limit its scope. The embodiments provided below can serve as a guide for further improvements by those skilled in the art and do not constitute a limitation on the invention in any way.

[0015] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Unless otherwise specified, the materials and reagents used in the following examples are commercially available.

[0016] Example 1 The series of target compounds were synthesized according to the following flowchart.

[0017] Taking target compound 15 as an example Synthesis of Intermediate I Weigh 1.1 g (11 mmol) of 1-methylpiperazine into a 50 mL round-bottom flask and dissolve it in 20 mL of ultra-dry dichloromethane (CH2Cl2). Then weigh 2.21 g (10 mmol) of p-nitrobenzenesulfonyl chloride and add it to 5 mL of ultra-dry dichloromethane (CH2Cl2), placing the solution in a constant-pressure dropping funnel. Slowly add the p-nitrobenzenesulfonyl chloride dichloromethane solution to the round-bottom flask under ice bath conditions. During the addition, the solution in the round-bottom flask changes from colorless and transparent to pale yellow. Stir at room temperature for 1 hour. After the reaction is complete, monitor the reaction by TLC [V(dichloromethane):V(methanol) = 10:1]. Filter the solution to obtain a white solid powder and a pale yellow filtrate. Wash the lower pale yellow filtrate three times with saturated sodium bicarbonate aqueous solution to neutralize the acidic byproducts generated during the hydrolysis reaction. Then extract the filtrate using a separatory funnel, collect the lower organic phase, and remove the solvent by vacuum distillation. The white solid powder and the rotary-dried solid were weighed together, and a total of 1.3 g of white solid powder was obtained, with a yield of 45.6%.

[0018] Synthesis of Intermediate II Weigh intermediate I (1.3 g, 4.6 mmol) into a 50 mL round-bottom flask and add 20 mL of anhydrous ethanol. Then add 5 eq of saturated ammonium chloride aqueous solution. Add iron powder (1.28 g, 23 mmol) in three portions. Heat and reflux at 60 °C with stirring. The reaction solution turns brownish-red. After the reaction is complete, monitor the reaction by TLC [V(dichloromethane):V(methanol) = 10:1]. Filter the solution, collect the pale yellow filtrate, remove the solvent by vacuum distillation, and dry to obtain 0.76 g of pale yellow solid powder, yield 65%.

[0019] Synthesis of target compound 15 Weigh 1 g (3.92 mmol) of intermediate II into a 50 mL round-bottom flask equipped with a stirrer, drying tube, and constant-pressure dropping funnel, and dissolve it in 20 mL of ultra-dry dichloromethane. Then add 3.92 mmol of triethylamine (1 eq). Under ice bath conditions, slowly add a mixture of p-toluenesulfonyl chloride (0.85 g, 4.31 mmol) and ultra-dry dichloromethane. Stir overnight at room temperature. After the reaction is complete, monitor the reaction by TLC [V(dichloromethane):V(methanol) = 10:1]. Wash the reaction solution three times with saturated sodium bicarbonate solution and three times with water. Column chromatography yielded 0.52 g of the target compound 15 as a white solid, with a yield of 31.7%.

[0020] 1: White solid; melting point 172.6-172.9℃; 1 H NMR (500 MHz, DMSO- d 6) δ 10.49 (s, 1H), 8.05 (d, J = 8.6 Hz, 2H), 7.97 (d,J = 8.6 Hz, 2H), 7.71 (d, J = 8.6 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.15 – 4.11 (m, 2H), 2.88 (s, 4H), 2.36 (s, 4H), 2.14(s, 3H), 1.36 (t, J = 6.9 Hz, 3H). HRMS Calcd. for C 20 H 25 N3O4S [M+H] + :404.1644, Found:404.1642. 2: Light orange solid, yield 37.2%; melting point 173.9-174.3℃; 1 H NMR (500 MHz, DMSO- d 6) δ10.75 (s, 1H), 7.99 (s, 2H), 7.72 (s, 2H), 7.51 (s, 1H), 7.42 (s, 1H), 7.32(s, 2H), 2.87 (s, 4H), 2.39 (s, 3H), 2.36 (s, 4H), 2.14 (s, 3H). 13 C NMR (126MHz, DMSO) δ 168.85, 143.96, 137.03, 135.89, 132.10, 131.11, 130.50, 129.24,127.81, 126.18, 119.82, 53.99, 46.21, 45.76, 19.77. HRMS Calcd. for C 19 H 23 N3O3S[M+H] + :374.1538, Found:374.1537. 3: Light orange solid, yield 35.6%; melting point 70.9-71.4℃; 1 H NMR (500 MHz, DMSO- d 6) δ10.62 (s, 1H), 8.07 (s, 2H), 7.79 (s, 2H), 7.73 (s, 2H), 7.45 (s, 2H), 2.88(s, 4H), 2.41 (s, 3H), 2.36 (s, 4H), 2.14 (s, 3H). 13C NMR (126 MHz, DMSO) δ166.72, 144.03, 138.31, 134.91, 133.06, 130.18, 129.36, 129.12, 128.74,125.49, 120.35, 53.98, 46.22, 45.76, 21.42. HRMS Calcd. for C 19 H 23 N3O3S [M+H] + :374.1538, Found:374.1537. 4: White solid, yield 45%; melting point 175.5-176.3℃; 1 H NMR (500 MHz, DMSO- d 6) δ 10.71 (s, 1H), 8.13 (d, J = 8.8 Hz, 2H), 7.93 (d, J = 8.1 Hz, 2H), 7.77 (d, J = 8.8 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 3.76 (s, 2H), 3.43 (s, 2H), 3.15 (s, 2H), 2.73 (s, 5H), 2.40 (s, 3H). 13 C NMR (126 MHz, DMSO) δ 166.49, 144.60, 142.66,131.94, 129.46, 129.19, 128.61, 128.45, 120.56, 51.96, 43.55, 42.32, 21.53.HRMS Calcd. for C 19 H 23 N3O3S [M+H] + :374.1538, Found:374.1535. 5: White solid, yield 30.1%; melting point 179.9-180.5℃; 1 H NMR (500 MHz, DMSO- d 6) δ 10.98 (s, 1H), 7.98 (d, J = 8.6 Hz, 2H), 7.73 (d, J= 8.7 Hz, 2H), 7.63 (s, 1H), 7.59 (s, 1H), 7.54 (s, 1H), 7.48 (s, 1H), 2.87 (s, 4H), 2.36 (s, 4H), 2.14(s, 3H). 13 C NMR (126 MHz, DMSO) δ 165.96, 143.51, 136.87, 131.93, 130.38,130.21, 129.70, 129.46, 129.34, 127.82, 119.85, 53.99, 46.21, 45.77. HRMSCalcd. for C 18 H 20 ClN3O3S [M+H] + :394.0992, Found:394.0993. 6: Light yellow solid, yield 39.3%; melting point 191.8-192.2℃; 1 H NMR (500 MHz, DMSO- d 6) δ 10.75 (s, 1H), 8.06 (d, J = 8.7 Hz, 2H), 8.04 (s, 1H), 7.94 (d, J = 7.7 Hz, 1H), 7.74 (d, J = 8.7 Hz, 2H), 7.71 (d, J = 8.0 Hz, 1H), 7.60 (t, J = 7.9 Hz, 1H), 2.89(s, 4H), 2.37 (s, 4H), 2.14 (s, 3H). 13 HRMS Calcd. for C 18 H 20 N3O3SCl [M+H] + :394.0992, Found:394.0991. 7: White solid, yield 42.0%; melting point 206.3-207.4℃; 1 H NMR (500 MHz, DMSO-d 6) δ10.71 (s, 1H), 8.07 – 8.04 (m, 2H), 8.02 – 7.99 (m, 2H), 7.74 (d, J = 8.9 Hz, 2H), 7.64 (d, J = 8.6 Hz, 2H), 2.89 (t, J = 4.8 Hz, 4H), 2.36 (t, J = 4.9 Hz, 4H), 2.14 (s, 3H). 13 C NMR (126 MHz, DMSO) δ 165.51, 143.78, 137.34, 133.58, 131.59,130.29, 129.61, 129.14, 120.47, 53.98, 46.22, 45.76. HRMS Calcd. forC 18 H 20 ClN3O3S [M+H] + :394.0992, Found:394.0991. 8: Light orange solid, yield 36.9%; melting point 109.9-110.3℃; 1 H NMR (500 MHz, DMSO- d 6) δ10.96 (s, 1H), 7.98 (s, 2H), 7.74 (s, 2H), 7.70 (s, 1H), 7.61 (s, 1H), 7.52(s, 1H), 7.46 (s, 1H), 2.88 (s, 4H), 2.39 (s, 4H), 2.16 (s, 3H). 13 C NMR (126MHz, DMSO) δ 166.84, 143.54, 139.03, 134.13, 133.27, 132.01, 130.92, 129.35,128.28, 119.85, 119.37, 53.95, 46.17, 45.70. HRMS Calcd. for C 18 H 20 BrN3O3S [M+H] + :438.0487, Found:438.0488. 9: Light orange solid, yield 46.3%; melting point 160.1-161.3℃; 1 H NMR (500 MHz, DMSO-d 6) δ10.50 (s, 1H), 8.08 (s, 2H), 8.01 (s, 2H), 7.73 – 7.71 (m, 2H), 7.11 (s, 2H), 3.86 (s, 3H), 2.89 (s, 4H), 2.36 (s, 4H), 2.14 (s, 3H). 13 C NMR (126 MHz, DMSO)δ 144.22, 131.80, 129.08, 126.85, 120.28, 114.25, 55.96, 53.97, 46.21, 45.74.HRMS Calcd. for C 19 H 23 N3O4S [M+H] + :390.1488, Found:390.1486. 10: White solid, yield 43.4%; melting point 222.6-223.4℃; 1 H NMR (500 MHz, DMSO- d 6) δ 10.88 (s, 1H), 8.12 (d, J = 8.2 Hz, 2H), 8.07 – 8.06 (m, 2H), 8.05 – 8.04 (m,2H), 7.75 (d, J = 8.6 Hz, 2H), 2.88 (s, 4H), 2.36 (s, 4H), 2.14 (s, 3H). 13 C NMR(126 MHz, DMSO) δ 165.27, 143.53, 138.92, 133.02, 129.93, 129.18, 120.56,118.72, 114.69, 53.98, 46.22, 45.77. HRMS Calcd. for C 19 H 20 N4O3S [M+H] + :385.1334, Found:385.1333. 11: White solid, yield 45.2%; melting point 100.1-101.2℃; 1 H NMR (500 MHz, DMSO- d 6) δ 11.04 (s, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.88 (d, J= 7.8 Hz, 1H), 7.82 (d, J = 7.0Hz, 1H), 7.77 (s, 1H), 7.75 (s, 2H), 7.73 (s, 1H), 2.89 (s, 4H), 2.40 (s,4H), 2.16 (s, 3H). 13 C NMR (126 MHz, DMSO) δ 166.60, 143.50, 133.18, 133.00,130.88, 129.95, 129.76, 129.36 (2C), 129.03, 126.92 (q, J=5.04 Hz), 125.28 (q, J=274.68 Hz), 119.89 (2C), 53.89 (2C), 46.10 (2C), 45.61. HRMS Calcd. forC 19 H 20 F3N3O3S [M+H] + :428.1256, Found:428.1254. 12: Light yellow solid, yield 38.3%; melting point 206.3-207.4℃; 1 H NMR (500 MHz, DMSO- d 6) δ 10.88 (s, 1H), 8.18 (d, J = 8.1 Hz, 2H), 8.08 (d, J = 8.8 Hz, 2H), 7.95 (d, J = 8.3Hz, 2H), 7.76 (d, J = 8.8 Hz, 2H), 2.89 (s, 4H), 2.37 (s, 4H), 2.14 (s, 3H). 13 CNMR (126 MHz, DMSO- d 6)δ165.47, 143.61, 138.72, 132.30 (q, J=32.76 Hz), 129.86,129.26 (2C), 129.17 (2C), 125.99 (q, J=3.78 Hz, 2C), 125.43 (q, J=273.42 Hz),120.55 (2C), 53.98 (2C), 46.22 (2C), 45.75. HRMS Calcd. for C 19 H 20 F3N3O3S [M+H]+ :428.1256, Found:428.1256. 13: White solid, yield 36.2%; melting point 169.1-170.4℃; 1 H NMR (500 MHz, DMSO- d 6) δ 10.49 (s, 1H), 8.06 (d, J = 8.8 Hz, 2H), 7.98 (d, J = 8.8 Hz, 2H), 7.71 (d, J = 8.7Hz, 2H), 7.08 (d, J = 8.8 Hz, 2H), 4.03 (t, J = 6.5 Hz, 2H), 2.88 (s, 4H), 2.36(s, 4H), 2.14 (s, 3H), 1.76 (q, J = 6.9 Hz, 2H), 1.00 (t, J = 7.4 Hz, 3H). 13 C NMR(126 MHz, DMSO) δ 165.89, 162.21, 144.23, 135.34, 130.34, 129.08, 126.64,120.27, 114.61, 69.75, 53.98, 46.22, 45.76, 22.42, 10.81. 14: White solid, yield 34.9%; melting point 105.4-106.3℃; 1 H NMR (500 MHz, DMSO- d 6) δ 10.59 (s, 1H), 8.08 (d, J = 8.7 Hz, 2H), 8.00 (d, J = 8.6 Hz, 2H), 7.71 (d, J = 8.7Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 4.07 (t, J = 6.4 Hz, 2H), 2.88 (s, 4H), 2.36(s, 4H), 2.14 (s, 3H), 1.75 – 1.70 (m, 2H), 1.46 (d, J = 7.5 Hz, 2H), 0.95 (t, J= 7.4 Hz, 3H). 13 C NMR (126 MHz, DMSO) δ 165.91, 162.19, 144.29, 130.38,129.05, 126.63, 120.30, 114.59, 67.98, 53.99, 46.23, 45.77, 31.09, 19.17,14.17. 15: White solid, yield 31.7%; melting point 107.5-108.4℃; 1 H NMR (500 MHz, DMSO- d 6) δ 10.59 (s, 1H), 8.06 (d, J = 8.8 Hz, 2H), 7.91 (d, J = 8.4 Hz, 2H), 7.72 (d, J = 8.7Hz, 2H), 7.57 (d, J = 8.3 Hz, 2H), 2.88 (s, 4H), 2.36 (s, 4H), 2.14 (s, 3H), 1.33 (s, 9H). 13 C NMR (126 MHz, DMSO) δ 166.55, 155.42, 144.09, 132.19, 129.12, 128.20, 125.75, 120.29, 53.98, 46.21, 45.75, 35.22, 31.38. 16: Light yellow solid, yield 41.2%; melting point 118.3-119.4℃; 1 H NMR (500 MHz, DMSO- d 6) δ10.57 (s, 1H), 7.94 (s, 2H), 7.73 (s, 2H), 7.63 (s, 1H), 7.60 (s, 2H), 7.43(s, 2H), 7.18 (dq, J = 8.3, 4.1 Hz, 1H), 7.08 (s, 2H), 3.78 (s, 2H), 2.46 (s, 2H), 2.40 (s, 3H), 1.62 (s, 2H). 13C NMR (126 MHz, DMSO) δ 166.71, 144.01,138.29, 136.90, 134.88, 133.48, 133.04, 130.94, 129.80, 128.84, 128.72,128.34, 126.70, 125.46, 125.17, 124.23, 120.34, 46.66, 26.52, 21.41. HRMSCalcd. for C 23 H 22 N₂O₃S [M+Na] + :429.1249, Found:429.1248. 17: Light yellow solid, yield 40.8%; melting point 171.3-171.8℃; 1 H NMR (500 MHz, DMSO- d 6) δ10.69 (s, 1H), 7.88 (s, 2H), 7.63 (d, J = 8.3 Hz, 1H), 7.60 (s, 2H), 7.49 –7.46 (m, 1H), 7.41 (td, J = 7.5, 1.4 Hz, 1H), 7.33 – 7.28 (m, 2H), 7.18 (ddd, J =8.6, 5.7, 3.3 Hz, 1H), 7.10 – 7.06 (m, 2H), 3.80 – 3.76 (m, 2H), 2.47 (d, J =6.6 Hz, 2H), 2.37 (s, 3H), 1.63 (s, 2H). 13 C NMR (126 MHz, DMSO) δ 168.81,143.93, 136.89, 135.90, 133.50, 131.10, 130.83, 130.50, 129.83, 128.47,127.82, 126.72, 126.16, 125.11, 124.05, 119.80, 46.69, 26.59, 21.62, 19.76.HRMS Calcd. for C 23 H 22 N₂O₃S [M+Na] + :429.1249, Found:429.1245. 18: Light yellow solid, yield 45.8%; melting point 189.7-190.3℃; 1 H NMR (500 MHz, DMSO- d 6) δ 10.51 (s, 1H), 7.93 (d, J = 8.8 Hz, 2H), 7.86 (d, J = 8.1 Hz, 2H), 7.62 (d, J = 8.2Hz, 1H), 7.58 (d, J = 8.7 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.19 (dt, J = 8.7, 4.5Hz, 1H), 7.08 (d, J = 4.3 Hz, 2H), 3.80 – 3.75 (m, 2H), 2.45 (t, J = 6.6 Hz, 2H),2.39 (s, 3H), 1.61 (p, J = 6.5 Hz, 2H). 13 C NMR (126 MHz, DMSO) δ 166.37, 144.04,142.63, 136.89, 133.38, 130.95, 129.80, 128.33, 126.70, 125.18, 124.24,120.34, 46.64, 26.51, 21.54. 19: Light yellow solid, yield 46.4%; melting point 172.3-173.4℃; 1 H NMR (500 MHz, DMSO- d 6) δ10.66 (s, 1H), 7.94 (s, 2H), 7.92 (s, 2H), 7.79 – 7.74 (m, 2H), 7.62 (dd, J =14.2, 8.6 Hz, 3H), 7.19 (ddd, J = 8.6, 5.2, 3.7 Hz, 1H), 7.10 – 7.05 (m, 2H), 3.78 (s, 2H), 2.45 (s, 2H), 1.62 (s, 2H). 13C NMR (126 MHz, DMSO) δ 165.61,143.77, 136.88, 133.91, 133.70, 131.96, 130.95, 130.43, 129.79, 128.35,126.70, 126.30, 125.19, 124.24, 120.48, 46.66, 26.51, 21.56. HRMS Calcd. forC 22 H 19 BrN2O3S [M+Na] + :493.0197, Found:493.0197. 20: White solid, yield 43.5%; 1 H NMR (500 MHz, DMSO- d 6) δ 10.43 (s, 1H), 7.93 (t, J = 8.2 Hz, 4H), 7.62 (d, J = 8.2 Hz, 1H), 7.57 (d, J = 8.8 Hz, 2H), 7.19 (dd, J = 8.6, 3.9 Hz, 1H), 7.08 – 7.06 (m, 3H), 7.04 (s, 1H), 4.12 (d, J = 7.0 Hz,2H), 3.78 – 3.76 (m, 2H), 2.45 (t, J = 6.6 Hz, 2H), 1.63 – 1.60 (m, 2H), 1.35(t, J = 7.0 Hz, 3H). 13 C NMR (126 MHz, DMSO) δ 165.88, 162.01, 144.19, 136.90,133.19, 130.93, 130.32, 129.80, 129.79, 128.30, 126.70, 126.60, 125.17,124.26, 120.26, 114.55, 63.91, 46.63, 26.49, 21.51, 14.98. HRMS Calcd. forC 24 H 24 N₂O₄S [M+Na] + :459.1354, Found:459.1356. 21: White solid, yield 38.9%; melting point 162.2-162.6℃; 1 H NMR (500 MHz, DMSO- d 6) δ10.52 (s, 1H), 7.92 (s, 2H), 7.88 (d, J = 8.1 Hz, 2H), 7.63 (d, J = 8.2 Hz, 1H), 7.58 (d, J = 8.8 Hz, 2H), 7.38 (d, J = 8.1 Hz, 2H), 7.21 – 7.17 (m, 1H), 7.08 (d, J = 4.3 Hz, 2H), 3.77 (d, J = 5.9 Hz, 2H), 2.69 (q, J = 7.6 Hz, 2H), 2.45 (t, J =6.6 Hz, 2H), 1.62 (q, J = 6.2 Hz, 2H), 1.21 (t, J = 7.6 Hz, 3H). 13 C NMR (126 MHz, DMSO) δ 166.46, 148.74, 144.05, 140.92, 136.89, 133.38, 132.28, 130.95,129.80, 128.42, 128.32, 126.70, 125.18, 124.23, 120.32, 46.65, 28.56, 26.51,21.55, 15.82. 22: Light yellow solid, yield 36.3%; melting point 87.9-88.7℃; 1 H NMR (500 MHz, DMSO- d 6) δ 10.52 (s, 1H), 7.93 (d, J = 8.8 Hz, 2H), 7.87 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 8.2Hz, 1H), 7.58 (d, J = 8.8 Hz, 2H), 7.41 (d, J = 8.2 Hz, 2H), 7.21 – 7.17 (m, 1H), 7.08 (d,J = 4.2 Hz, 2H), 3.79 – 3.76 (m, 2H), 2.97 (p, J = 6.9 Hz, 1H), 2.46 (t, J = 6.6 Hz, 2H), 1.63 – 1.60 (m, 2H), 1.23 (d, J = 6.9 Hz, 6H). 13 C NMR (126 MHz, DMSO) δ 165.88, 162.02, 144.20, 136.91, 133.21, 130.94, 130.32, 129.79,128.29, 126.69, 126.62, 125.16, 124.24, 120.27, 114.55, 63.93, 46.64, 26.51,21.55, 14.99. Example 2 The compound shown in Formula I exhibits inhibitory activity against plant pathogens. The compounds of Formula I prepared in the above embodiments were used to determine their in vitro antibacterial activity using the mycelial growth rate method. The tested fungi included rapeseed sclerotia ( Sclerotinia sclerotiorum , Ss ) and rice blast fungus ( Magnaporth Rice , Mo The tested oomycetes included *Phytophthora capsici* (…). Phytophthora capsicum , PC ) and Pythium spp. ( Pythium aphaniderm , Father The specific method is as follows: Weigh out the compounds shown in Formula I (compounds 1-22) and the control agents metalaxyl, dimethomorph, and prothioconazole, respectively, and prepare a stock solution with a concentration of 10000 μg / mL using dimethyl sulfoxide. Use a pipette to pipette the stock solution and add it to sterilized potato dextrose agar (PDA) medium cooled to approximately 55°C. After thorough mixing, pour approximately 15 mL of the culture medium containing the compounds into 9 cm diameter petri dishes. Use a blank control with an equal amount of dimethyl sulfoxide. Each treatment is repeated three times. After the culture medium in the dishes has cooled and solidified, prepare 5 mm diameter mycelial discs along the edge of the colonies and inoculate them into the center of the plates for each treatment. Invert the petri dishes and incubate them in the dark at 25°C. After the colonies in the blank control PDA plates have grown sufficiently, measure the colony diameter for each treatment using the cross-sectional method.

[0021] Calculate the mycelial growth inhibition rate using the following formula: Inhibition rate (%) = [(Control colony diameter - Treated colony diameter) / (Control colony diameter - 5mm)] × 100% The in vitro antibacterial activity data (50 μg / mL) of some compounds shown in Formula I are shown in Table 1.

[0022] Table 1. In vitro antibacterial activity data (50 μg / mL) of some compounds shown in Formula I

[0023] Note: " / " indicates that it has not been tested.

[0024] The results showed that the compounds in the examples recorded in Table 1 all had certain antibacterial effects against the tested plant pathogens. Compound 1, at a concentration of 50 μg / mL, showed an inhibition rate of 88.22% against *Phytophthora capsici*, comparable to the positive control agent metalaxyl. Compound 15 exhibited good in vitro antibacterial activity against *Phytophthora capsici*, *Sclerotinia sclerotiorum*, and *Pythium spp.*, with inhibition rates of 95.83%, 84.96%, and 89.51%, respectively, at a concentration of 50 μg / mL. Compound 18 showed an in vitro inhibition rate of 66.67% against *Bacillus oryzae* at a concentration of 50 μg / mL.

[0025] Example 3 The compounds shown in Formula I affect chitin synthase. Ps Chs1 inhibitory activity test The chitin synthase activity assay followed a published method with slight modifications. Microplates were coated with wheat germ lectin (50 μg / ml, Sigma) and then blocked with bovine serum albumin blocking buffer. The coated plates were stored at -20°C for later use. Before use, the liquid in the plates was drained by centrifugation. Then, 50 μl of reaction mixture (containing 1 mM UDP-GlcNAc, 50 mM Tris-HCl buffer, pH 7.5, 150 mM NaCl) was added to each well, followed by 50 μl of enzyme suspension, bringing the final volume to 100 μl. After incubation at 30°C for 1 hour, the plates were drained and washed three times. Then, 100 μl of wheat germ lectin-horseradish peroxidase (0.5 μg / ml, Sigma) was added, and incubation continued at 30°C for 30 minutes. The plates were drained by centrifugation and washed three times. Finally, 100 μl of peroxidase substrate reagent was added, and the absorbance was immediately measured at 652 nm over 5 minutes. Based on the standard curve prepared according to the same procedure, the GlcNAc content and chitin synthase activity after each treatment were calculated. Specific enzyme activity was expressed as the number of nanomoles of GlcNAc produced per microgram of protein per hour (nmol / μg protein / h). Each experiment was repeated three times.

[0026] The compounds shown in Formula I affect chitin synthase. PsThe inhibitory activity data of Chs1 are shown in Table 2.

[0027] The inhibitory activities of some compounds shown in Formula I on chitin synthase are shown in Table 2.

[0028] Table 2. Inhibitory activity data of the compounds shown in Formula I against chitin synthase.

[0029] Note: " / " indicates that it has not been tested.

[0030] The results of the chitin synthase inhibitory activity test showed that the compound of the present invention inhibits chitin synthase activity. Ps Chs1 exhibits certain inhibitory activity. Compound 1, at a concentration of 50 μM, shows inhibitory activity against... Ps The inhibition rate of Chs1 was 34%. Compound 15 inhibited... Ps Chs1 exhibited good enzyme inhibitory activity, with an inhibition rate of 73.48% at a concentration of 50 μg / mL. Compounds 18 and 19 showed similar inhibitory effects at a concentration of 50 μg / mL. Ps The inhibition rates of Chs1 were both greater than 50%, specifically 61.1% and 58.5%.

[0031] The compounds shown in Formula I affect chitin synthase. Ps Chs1 of K i Value test To evaluate enzyme kinetics, three different substrate (UDP-GlcNAc) concentrations (50, 250, and 500 μM) and different inhibitor concentrations were used for determination (Liu, Y., Liu, J., Xia, Y., Chen, W., Li, Y., He, X. and Yang, Q. (2025), Structure-based virtual screening of novel chitinsynthase inhibitors for the control of Phytophthora sojae. Pest Manag Sci,81: 777-785. https: / / doi.org / 10.1002 / ps.8480.). A solution containing 5 μg of... Ps The reaction mixture of Chs1, 0–30 μM compounds, and Buffer W containing 0.05% digitalis saponins was incubated with different concentrations of UDP-GlcNAc in a final volume of 100 μL. i Values ​​were determined using Dixon plot19 and data analysis was performed using PRISM software (GraphPad, San Diego, CA, USA).

[0032] The results showed that the K of compound 15 i =28.25±0.59μM.

[0033] Example 4 Determination of the inhibitory activity of some compounds shown in Formula I against plant pathogenic bacteria The inhibitory activity of the compound against plant pathogenic bacteria was determined using a 96-well plate turbidimetric method. The tested bacterial species was *Cucumber angularis* (a bacterium causing bacterial angular leaf spot). Pseudomonas syringae pv. lachrymans , Psl ).

[0034] Prepare stock solutions of 50 μg / mL for both the test compound and the control reagent containing sclerosin, and then add 2 μL per well to a 96-well plate. Four parallel wells are set up for each compound, along with negative control wells (containing a mixture of DMSO and water). Bacterial suspensions with activated OD values ​​between 0.8 and 1.0 are diluted 100-fold. In one of the four parallel wells for each compound, add 198 μL of sterile LB medium (as a blank control), and add 198 μL of LB medium containing bacteria to the remaining three wells. Place the 96-well plate in a shaker and incubate at 28°C and 180 rpm until the negative control wells show significant turbidity. Finally, measure the OD value of each well using a microplate reader at a wavelength of 598 nm.

[0035] Calculate the bacterial growth inhibition rate using the following formula:

[0036] Table 3 shows the in vitro bactericidal activity data (50 μg / mL) of some of the compounds shown in Formula I.

[0037] Table 3 shows some of the compounds in Formula I. Psl Results of in vitro bactericidal activity

[0038] The results showed that compounds 15 and 19 of Formula I, at a concentration of 50 μg / mL, were effective against *Cucumber angularis* (a bacterium that causes bacterial angular leaf spot). Psl The antibacterial rates were 100% and 82.5%, respectively.

[0039] The compounds shown in Formula I exhibit EC50 activity against plant pathogenic bacteria. 50 Value test The test method was the same as above (determination of the inhibitory screening activity of compounds against plant pathogenic bacteria). The concentration gradient of the test compounds was set as follows: 50, 25, 12.5, 6.25, 3.125, 1.5625, and 0.78125 μg / mL. Using the probability method, the corresponding probability values ​​were converted from the probability table, the concentrations were converted to logarithms, and a linear regression equation was fitted to calculate the EC50. 50 value.

[0040] The compounds shown in Formula I are effective against plant pathogenic bacteria (Cucumber bacterial angular leaf spot). Psl EC 50 The test results are shown in Table 4.

[0041] Table 4. Some compounds shown in Formula I show their effects on *Cucumber angular leaf spot* (…). Psl EC 50 Value measurement results

[0042] Test results showed that compounds 15 and 19 of Formula I were effective against *Cucumber angular leaf spot* (a pathogen that causes bacterial angular leaf spot). Psl EC 50 The values ​​were 13.91 and 1.56 μg / mL, respectively.

[0043] The present invention has been described in detail above. Those skilled in the art will recognize that the invention can be practiced in a wide range of ways with equivalent parameters, concentrations, and conditions without departing from its spirit and scope, and without requiring unnecessary experiments. While specific embodiments have been provided, it should be understood that further modifications can be made to the invention. In summary, according to the principles of the invention, this application is intended to include any changes, uses, or improvements to the invention, including changes made using conventional techniques known in the art that depart from the scope disclosed herein.

Claims

1. The application of a sulfonylbenzamide derivative, characterized in that: Application of sulfonylbenzamide derivatives in the preparation of fungicides for agricultural plant pathogens; The sulfonylbenzamide derivatives are , , , , , , ; The agricultural plant pathogen is rapeseed sclerotium. Sclerotinia sclerotiorum, Ss Rice blast fungus Magnaporthe Oryzae, Mo Phytophthora capsici Phytophthora capsici, Pc Fruit and vegetable mold Pythium aphanidermatum, Pa Bacterial angular leaf spot of cucumber Pseudomonas syringae pv. lachrymans, Psl .

2. The application of the sulfonylbenzamide derivative according to claim 1, characterized in that: Application of sulfonylbenzamide derivatives as chitin synthase inhibitors.

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