A stilbene compound containing a sulfonamide fragment, and a preparation method and application thereof

Abstract

The application belongs to the technical field of agricultural chemicals and fungicides, and specifically discloses a stilbene compound containing a sulfonamide fragment, a preparation method and application thereof. The compound is prepared by the following steps: firstly, benzyl bromide is reacted with triphenylphosphine; then, the reaction product is reacted with potassium tert-butoxide; and then, the product is reacted with 4-nitrobenzaldehyde to obtain (E)-4-nitro-diphenyl ethylene; (E)-4-nitro-diphenyl ethylene is reacted with tetrahydroxydiboron and 4,4'-bipyridine to obtain (E)-4-amino-diphenyl ethylene; cyclohexanone is reacted with sulfur trioxide-dioxane adduct; then, the product is mixed with oxalyl chloride and a catalyst to obtain 2-oxocyclohexylsulfonyl chloride; and 2-oxocyclohexylsulfonyl chloride is mixed with (E)-4-amino-diphenyl ethylene and triethylamine to obtain the stilbene compound containing a sulfonamide fragment. The compound has good fungicidal activity and is suitable for wide range of popularization and application.

Description

Technical Field

[0001] This invention relates to the field of agricultural chemicals and fungicides, and in particular to a stilbene compound containing a sulfonamide fragment, its preparation method, and its application. Background Technology

[0002] Stilbene compounds are an important class of natural products. These compounds are widely distributed, found in traditional Chinese medicines such as rhubarb, polygonum cuspidatum, he shou wu, and veratrum nigrum; fruits of plants such as grapes, peanuts, and mulberries; and secondary metabolites of microorganisms such as Streptomyces, yeasts, and bacteria. Natural ( E Stilbene compounds have wide applications in the biological and pharmaceutical fields. For example, resveratrol, paclitaxel, and pterostilbene all possess medicinal activities such as anticancer, antibacterial, antioxidant, blood pressure-lowering, and cardiovascular protection. Studies have found that... E )-Stilbene compounds can also inhibit the spore germination of *Botrytis cinerea* and *Bacillus oryzae*, and have a good inhibitory effect on plant pathogenic fungi such as *Botrytis cinerea*, *Downy mildew*, *Anthracnose fungus*, and *Pythium spp.*. However, these compounds are present in extremely low amounts in plants and their sources are limited. Meanwhile, natural ( E )-Stilbene derivatives are easily oxidized and chemically unstable, resulting in low bioavailability and severely limiting their application and development in the field of plant protection.

[0003] The sulfonamide group is an important pharmacophore in many pharmaceutical and pesticide molecules, and sulfonamide compounds exhibit excellent activity in both pharmaceutical and pesticide fields. Introducing sulfonamide fragments into drug molecules is expected to effectively enhance the interaction between the compound and its target, improve bioavailability, and thus improve and enhance the compound's biological activity.

[0004] Therefore, how to disclose a stilbene compound containing a sulfonamide fragment, its preparation method, and its applications, to solve the problem of natural ( E )-Stilbene derivatives are easily oxidized, chemically unstable, and have low bioavailability. Summary of the Invention

[0005] In view of this, the present invention provides a stilbene compound containing a sulfonamide fragment, a method for its preparation and its application. The synthesized compound has good bactericidal activity and antifungal activity against a variety of fungi.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: A stilbene compound containing a sulfonamide fragment has the structure shown in Formula 1:

[0007] Formula 1

[0008] R 2 ~R 6 It is an independent group consisting of one of alkyl, alkoxy, hydrogen, halogen, and sulfonamide groups with 1 to 12 carbon atoms.

[0009] Another object of the present invention is to provide a method for preparing stilbene compounds containing sulfonamide fragments, comprising the following steps: 1) Compound 1 was reacted with triphenylphosphine to give benzyltriphenylphosphine bromide; 2) The benzyltriphenylphosphine bromide obtained in step 1) is reacted with tert-butoxide, and after the reaction is complete, it is mixed with 4-nitrobenzaldehyde to obtain ( E) -4-Nitro-diphenylethylene; 3) Take the result obtained in step 2) E) A mixture of -4-nitro-diphenylethylene, tetrahydroxydiboron, and 4,4'-bipyridine reacts to yield ( E) -4-Amino-diphenylethylene; 4) Cyclohexanone was reacted with sulfur trioxide-dioxane adduct to give 2-oxocyclohexyl sulfonate; 5) The 2-oxocyclohexyl sulfonate obtained in step 4) is mixed with oxalyl chloride and catalyst, and reacted to obtain 2-oxocyclohexyl sulfonyl chloride; 6) 2-Oxocyclohexylsulfonyl chloride and ( E) -4-amino-diphenylethylene and triethylamine are mixed and reacted to obtain stilbene compounds containing sulfonamide fragments; Among them, 2-oxocyclohexylsulfonyl chloride and ( E) There is no specific order in the preparation of 4-amino-diphenylethylene; The structure of compound 1 is as follows: ;R 2 ~R 6 It is an independent group consisting of one of alkyl, alkoxy, hydrogen, halogen, and sulfonamide groups with 1 to 12 carbon atoms.

[0010] Preferably, in step 1), the molar ratio of benzyl bromide to triphenylphosphine is 35:30; The reaction temperature in step 1) is 60~110℃, and the reaction time is 2~12h.

[0011] Preferably, in step 2), the molar ratio of benzyltriphenylphosphine bromide to tert-butoxide is 5:6.5, the reaction temperature of benzyltriphenylphosphine bromide and tert-butoxide is 0°C, and the reaction time is 30 min. The tert-butoxide salt includes potassium tert-butoxide and / or sodium tert-butoxide.

[0012] Preferably, in step 2), the molar ratio of benzyltriphenylphosphine bromide to 4-nitrobenzaldehyde is 5:5; and the reaction time during the reaction with 4-nitrobenzaldehyde is 2~20h.

[0013] Preferably, in step 3) ( E) The molar ratio of -4-nitro-diphenylethylene, tetrahydroxydiboron and 4,4'-bipyridine is 5:15:0.25; The reaction time in step 3) is 15 minutes.

[0014] Preferably, in step 4), the molar ratio of cyclohexanone to sulfur trioxide-dioxane adduct is 50:60; The reaction temperature in step 4) is 0℃, and the reaction time is 2h.

[0015] Preferably, in step 5), the molar volume ratio of 2-oxocyclohexyl sulfonate, oxalyl chloride, and catalyst is 10 mmol: 10 mmol: 0.5~1 mL; The reaction time in step 5) is 3-4 hours; The catalyst in step 5) is N,N-dimethylformamide.

[0016] Preferably, in step 6), 2-oxocyclohexylsulfonyl chloride reacts with ( E) The molar ratio of 4-amino-diphenylethylene to triethylamine is 6:5:7; The reaction time in step 6) is 3~24h.

[0017] Another object of the present invention is to provide an application of the stilbene compound containing a sulfonamide fragment prepared by the above preparation method in a bactericide.

[0018] As can be seen from the above technical solution, compared with the prior art, the present invention has the following beneficial effects: This invention synthesizes stilbene compounds containing sulfonamide fragments. Bioactivity assays show that the synthesized compounds have good bactericidal activity. The stilbene compounds containing sulfonamide fragments obtained in this invention have shown good application effects in inhibiting fungi such as rapeseed sclerotinia, gray mold, rice sheath blight, and Fusarium oxysporum, and are suitable for widespread application. Detailed Implementation

[0019] This invention provides a stilbene compound containing a sulfonamide fragment, having the structure shown in Formula 1:

[0020] Formula 1

[0021] R2 ~R 6 Independently, it is one of the following: an alkyl group with 1 to 12 carbon atoms, an alkoxy group with 1 to 12 carbon atoms, a hydrogen group, a halogen group, and a sulfonamide group; R 1 Group is .

[0022] This invention also provides a method for preparing stilbene compounds containing sulfonamide fragments, comprising the following steps: 1) Compound 1 was reacted with triphenylphosphine to give benzyltriphenylphosphine bromide; 2) The benzyltriphenylphosphine bromide obtained in step 1) is reacted with tert-butoxide, and after the reaction is complete, it is mixed with 4-nitrobenzaldehyde to obtain ( E) -4-Nitro-diphenylethylene; 3) Take the result obtained in step 2) E) A mixture of -4-nitro-diphenylethylene, tetrahydroxydiboron, and 4,4'-bipyridine reacts to yield ( E) -4-Amino-diphenylethylene; 4) Cyclohexanone was reacted with sulfur trioxide-dioxane adduct to give 2-oxocyclohexyl sulfonate; 5) The 2-oxocyclohexyl sulfonate obtained in step 4) is mixed with oxalyl chloride and catalyst, and reacted to obtain 2-oxocyclohexyl sulfonyl chloride; 6) 2-Oxocyclohexylsulfonyl chloride and ( E) -4-amino-diphenylethylene and triethylamine are mixed and reacted to obtain stilbene compounds containing sulfonamide fragments; Among them, 2-oxocyclohexylsulfonyl chloride and ( E) There is no specific order in the preparation of 4-amino-diphenylethylene; The structure of compound 1 is as follows: ;R 2 ~R 6 It is an independent group consisting of one of alkyl, alkoxy, hydrogen, halogen, and sulfonamide groups with 1 to 12 carbon atoms.

[0023] In this invention, the ( E) -4-Nitro-diphenylethylene is trans-4-nitro-diphenylethylene; E) -4-Amino-diphenylethylene is trans-4-amino-diphenylethylene.

[0024] In this invention, the molar ratio of benzyl bromide to triphenylphosphine in step 1) is 35:30.

[0025] In this invention, the reaction temperature in step 1) is 60~110℃, specifically 70℃, 80℃, 90℃, or 100℃; the reaction time is 2~12h, specifically 4h, 5h, 6h, 8h, or 10h.

[0026] In this invention, the molar ratio of benzyltriphenylphosphine bromide to tert-butoxide in step 2) is 5:6.5, the reaction temperature of benzyltriphenylphosphine bromide and tert-butoxide is 0°C, and the reaction time is 30 min.

[0027] In this invention, the tert-butoxide salt includes potassium tert-butoxide and / or sodium tert-butoxide.

[0028] In this invention, the tert-butoxide salt in step 2) is preferably added in batches, and the number of batches is preferably 3-6 times, specifically 3 times, 4 times, 5 times, or 6 times; the batches are preferably added in equal batches.

[0029] In this invention, the molar ratio of benzyltriphenylphosphine bromide to 4-nitrobenzaldehyde in step 2) is 5:5; the reaction time during the reaction with 4-nitrobenzaldehyde is 2~20h, specifically 4h, 5h, 6h, 8h, 10h, 12h, 15h, 16h, or 18h.

[0030] In this invention, the reaction in step 2) is preferably carried out under an inert atmosphere, which includes one or more of nitrogen atmosphere and rare gas atmosphere.

[0031] In this invention, 4-nitrobenzaldehyde in step 2) is preferably added in batches, preferably 3-6 times, specifically 3 times, 4 times, 5 times, or 6 times; the batches are preferably of equal quality.

[0032] In this invention, in step 3) ( E) The molar ratio of -4-nitro-diphenylethylene, tetrahydroxydiboron and 4,4'-bipyridine is 5:15:0.25.

[0033] In this invention, the reaction time in step 3) is 15 minutes.

[0034] In this invention, the molar ratio of cyclohexanone and sulfur trioxide-dioxane adduct in step 4) is 50:60; In this invention, the reaction temperature in step 4) is 0°C and the reaction time is 2 hours.

[0035] In this invention, the molar volume ratio of 2-oxocyclohexyl sulfonate, oxalyl chloride and catalyst in step 5) is 10 mmol: 10 mmol: 0.5~1 mL.

[0036] In this invention, the 2-oxocyclohexyl sulfonate, oxalyl chloride and catalyst are preferably mixed in an ice bath.

[0037] In this invention, the reaction time in step 5) is 3-4 hours.

[0038] In this invention, the catalyst in step 5) is N,N-dimethylformamide.

[0039] In this invention, in step 6), 2-oxocyclohexylsulfonyl chloride reacts with ( E) The molar ratio of 4-amino-diphenylethylene to triethylamine is 6:5:7; In this invention, 2-oxocyclohexylsulfonyl chloride and ( E) When 4-amino-diphenylethylene and triethylamine are mixed, it is preferable to mix them in an ice bath.

[0040] In this invention, the reaction time in step 6) is 3 to 24 hours, specifically 5 hours, 8 hours, 10 hours, 12 hours, 15 hours, 18 hours, or 20 hours.

[0041] In this invention, the reactions in steps 1) to 6) are preferably carried out independently in an organic solvent.

[0042] The present invention also provides the application of stilbene compounds containing sulfonamide fragments prepared by the above preparation method in bactericides.

[0043] In this invention, the stilbene compounds containing sulfonamide fragments have inhibitory effects on pathogenic fungi such as rapeseed sclerotium, gray mold, rice sheath blight, and Fusarium oxysporum, and can be used for the prevention and control of their diseases.

[0044] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0045] Example 1

[0046] The specific preparation process of compound I-3 is shown below:

[0047] The specific preparation process is as follows: Benzyl bromide (35 mmol) and triphenylphosphine (30 mmol) were weighed into a dry round-bottom flask, toluene (75 mL) was added, and the mixture was placed in an oil bath and refluxed at 80°C for 8 h. The reaction was monitored by TLC (VL). 石油醚 V 乙酸乙酯= 3:1), to clarify the reaction process. After completion, after the reactants cooled to room temperature, the mixture was filtered through a sintered glass funnel. The obtained solid was washed twice with toluene and once with n-hexane, and then dried under vacuum to obtain benzyltriphenylphosphine bromide white solid 1, which was directly used in the next reaction. Weigh 5 mmol of benzyltriphenylphosphine bromide into a preheated two-necked flask and dissolve it in 20 mL of ultra-dry tetrahydrofuran. The reaction should be carried out under nitrogen protection and an ice bath. Potassium tert-butoxide (6.5 mmol) is added slowly in four equal batches, reacting for 30 min each time. The mixture is then placed in an ice bath, and 5 mmol of 4-nitrobenzaldehyde is added in four equal batches, reacting at room temperature for 10 h. The reaction is then monitored by TLC (V1). 石油醚 V 乙酸乙酯 = 5:1) Monitoring was used to determine the reaction progress. After the reaction was completed, the reaction was quenched with 10 mL of water, extracted with ethyl acetate (15 mL × 3 times), the organic phase was collected, washed twice with saturated sodium chloride solution, dried with an appropriate amount of anhydrous sodium sulfate, filtered, evaporated to dryness, and column-fed. 石油醚 V 乙酸乙酯 Elute at a ratio of 5:1, collect, and evaporate to dryness to obtain the target product. Since the product is... Z , E The mixed product with different configurations was therefore recrystallized in a petroleum ether-ethyl acetate mixed solvent to obtain... E Type 2 target product, yellow solid compound 2; Weigh E 5 mmol of 4-nitro-diphenylethylene, 15 mmol of tetrahydroxydiboron, and 0.25 mmol of 4,4'-bipyridine were placed in a round-bottom flask, and 25 mL of the solution was used. N , N - Dimethylformamide was used as a solvent. The reaction mixture was stirred at room temperature for 15 minutes. The volume was measured by TLC (V2). 石油醚 V 乙酸乙酯 = 3:1) Monitor the reaction progress. After the reaction is complete, add 10 mL of water to quench the reaction mixture. Extract three times with dichloromethane, wash three times with saturated NaCl, dry with an appropriate amount of anhydrous sodium sulfate, filter, and evaporate to dryness before column chromatography. Use V 石油醚 V 乙酸乙酯 Elute at a ratio of 3:1, collect, and evaporate to dryness to give a yellow solid compound 3; Weigh 50 mmol of cyclohexanone into a dry three-necked flask and add 250 mL of dry 1,2-dichloroethane. Under nitrogen protection, slowly add 60 mmol of sulfur trioxide-dioxane adduct and react the mixture at 0°C for two hours. After the reaction is complete, add 250 mL of distilled water to the mixture and slowly add solid calcium carbonate while stirring to adjust the pH of the mixture to 6-7. Filter the mixture and separate the aqueous phase through a separatory funnel. Slowly add solid potassium carbonate to adjust the pH to 8-9. After filtration and rotary evaporation, the target product, crude potassium sulfonate, is obtained as a yellow solid compound 4. Weigh 10 mmol of 2-oxocyclohexyl sulfonate and place it in a dry round-bottom flask. Dissolve it in 10 mL of ultra-dry dichloromethane, and then add 0.5 mL of [unspecified ingredient]. N , N Using dimethylformamide as a catalyst, 10 mmol of oxaloyl chloride was slowly added under ice bath conditions, releasing a large amount of gas. After the gas release ceased to be vigorous, the ice bath was removed, and the reaction was allowed to proceed at room temperature for 3 hours. The resulting mixed solution is the 2-oxocyclohexylsulfonyl chloride solution. Weigh the raw material ( E) 5 mmol of 4-amino-diphenylethylene was placed in another dry round-bottom flask and dissolved in 10 mL of ultra-dry dichloromethane. Under nitrogen protection, 7 mmol of triethylamine was added. The reaction was carried out in an ice bath. A solution of 6 mmol of 2-oxocyclohexylsulfonyl chloride in dichloromethane was slowly added dropwise, producing a large amount of white fumes. Once the white fumes ceased to be produced, the ice bath was removed, and the reaction was allowed to proceed at room temperature for 12 h. TLC (V1) was then performed. 石油醚 V 乙酸乙酯 = 3:1) Monitor the reaction progress. After the reaction is complete, quench with 10 mL of 1 mol / L hydrochloric acid, extract with dichloromethane (15 mL × 3 times), collect the organic phase, wash twice with saturated sodium chloride, dry with an appropriate amount of anhydrous sodium sulfate, filter, evaporate to dryness, and use V 石油醚 V 乙酸乙酯 = 3:1 elution, collection, and rotary drying to obtain the target product I-3.

[0048] The physicochemical data of compounds I-1 to I-30 obtained according to the preparation method of Example 1 are shown in Table 1 below; 1 The H NMR and MS data are shown in Table 2.

[0049] Table 1 Physicochemical data of compounds I-1 to I-30

[0050] Table 2. Compounds I-1 to I-30 1 H NMR,13 C NMR and HRMS data

[0051] The bactericidal activity of compounds I-1 to I-30 obtained in Examples was verified: 1. Determination of the fungicidal activity of compounds I-1 to I-30 against various plant pathogens: The fungicidal activity of compounds against various plant pathogens was determined using the mycelial growth rate method, as follows: Compounds I-1 to I-30 were weighed and dissolved in acetone, then diluted to a final volume to prepare a 5000 mg / L test reagent. This reagent was stored in a low-temperature refrigerator for activity assays. Under aseptic conditions, 0.3 mL of the 5000 mg / L test reagent was mixed thoroughly with 30 mL of melted (60±5 ℃) PDA medium to prepare 30 mL of a 50 mg / L toxic medium. This 30 mL of toxic medium was then evenly poured into three 9 cm diameter petri dishes, 10 mL per dish. Cyclosulfuron-methyl, carbendazim, iprodione, and cyclohexylsulfonamide were used as control agents for *Botrytis cinerea*, *Rhizoctonia solani*, *Fusarium oxysporum*, and *Sclerotinia sclerotinia*. Acetone was used as a blank control at a concentration of 50 mg / L. After the toxic medium in the petri dishes had solidified, 0.5 cm diameter pathogenic bacteria blocks were inoculated into each dish. The dishes were then incubated at 28 ℃. After the colonies in the blank control had grown sufficiently, the colony diameter of each treatment was measured using the cross-sectional method, and the average value was taken. The inhibition rate was calculated based on the average colony diameter of the corrected blank control and treatment groups. The fungicidal activities of compounds I-1 to I-30 against various plant pathogens are shown in Table 3 below.

[0052]

[0053] Table 3. Fungicidal activity of compounds I-1 to I-30 against various plant pathogens.

[0054] Table 3 shows that compounds I-3, 4, and 17 have good inhibitory effects on *Sclerotinia sclerotinia*, with inhibition rates of 93.86%, 98.32%, and 90.49%, respectively. Compound I-4 showed the highest activity, exceeding that of commercial fungicides such as iprodione and carbendazim, and comparable to that of boscalid. Compounds I-8, 11, 12, and 23 showed the best effects against *Botrytis cinerea* 5055, approaching the levels of commercial fungicides such as iprodione, carbendazim, and boscalid. Against *Botrytis cinerea* AS-06, 21 compounds showed activity exceeding that of boscalid, with compounds I-11, 12, 26, and 30 showing the best effects and exceeding the control fungicide iprodione. Compound I-12 exceeded that of carbendazim. Compounds I-8, 12, and 28 showed the best inhibitory effects against *Fusarium oxysporum*, exceeding that of iprodione and boscalid. Compounds I-8 and 12 showed similar activity to carbendazim. Compounds I-1, 3, 8, and 11 showed the best control effects against Rhizoctonia solani. Among them, compounds I-1, 3, and 11 had higher activity than cyazofamid and were close to the activity of carbendazim and cyazofamid.

[0055] 2. The median concentration (EC50) of the compound inhibiting *Rhizoctonia solani*, *Sclerotinia sclerotiorum*, and *Botrytis cinerea*. 50 The determination of ) The fungicidal activity of the compound against *Rhizoctonia solani*, *Sclerotinia sclerotiorum*, and *Botrytis cinerea* was determined using the mycelial growth rate method, as follows: The compounds were weighed and dissolved in acetone, and the solution was brought to a final volume to prepare a 5000 mg / L test reagent. Then, using a dilution method, test reagents with concentrations of 5000, 1250, 312.5, 78, and 19.5 mg / L were prepared and stored in a low-temperature refrigerator for activity assays. Under aseptic conditions, 0.3 mL of the 5000 mg / L reagent was mixed thoroughly with 30 mL of melted (60±5 ℃) PDA medium to prepare 30 mL of a 50 mg / L toxic medium. This 30 mL toxic medium was then evenly poured into three 9 cm diameter petri dishes, 10 mL per dish. This process was repeated to prepare four concentration gradients of toxic medium: 50, 12.5, 3.125, 0.78, and 0.195 mg / L. Using iprodione, boscalid, and cyclohexylsulfamethoxam as control agents, and acetone as a blank control, the concentration gradients were 50, 12.5, 3.125, 0.78, and 0.195 mg / L. After the toxic culture medium in the dishes solidified, pathogenic bacterial blocks with a diameter of 0.5 cm were inoculated. The dishes were incubated at 28 ℃. After the colonies in the blank control had fully grown, the colony diameter of each treatment was measured using the cross-sectional method, and the average value was recorded. The inhibition rate was calculated using the corrected average colony diameter of the blank control and the treatments. The inhibitory activity of each compound against *Sclerotinia sclerotiorum* was determined using the mycelial growth rate method, and the EC50 of the corresponding compounds was calculated.50 The EC50 values ​​were calculated in triplicate for each compound and control reagent. 50 The measurement results are shown in Table 4:

[0056] Table 4. Toxicity of some compounds

[0057] For rice sheath blight pathogens, compounds I-1, I-3, I-8, I-12, and EC... 50 The values ​​were 13.36 mg·L. -1 15.18 mg·L -1 19.41 mg·L -1 7.97 mg·L -1 All were higher than the control agent cyclohexylsulfamethoxam, but lower than boscalid. For Sclerotinia sclerotinia, compounds I-3, I-4, I-17, and I-19, EC... 50 The values ​​were 3.91 mg·L⁻¹ -1 3.97 mg·L -1 10.80 mg·L -1 13.52 mg·L -1 All were higher than those of cyclohexylsulfamethoxam (13.58 mg·L⁻¹). -1 ), lower than that of boscalid (0.13 mg·L⁻¹). -1 ), iprodione (0.16 mg·L) -1 For gray mold, the EC50 of compounds I-11, I-12, and I-29 50 The values ​​were 24.58 mg·L. -1 21.79 mg·L -1 25.87 mg·L -1 All were higher than the control agent cyclohexylsulfamethoxam (27.41 mg·L⁻¹). -1 ), but lower than iprodione (3.91 mg·L⁻¹). -1 ) and boscalid (6.9 mg·L) -1 ).

[0058] 3. The bactericidal activity of the compounds was determined using the rapeseed leaf method and the tomato pot method.

[0059] (1) Rapeseed live leaf method: Mix 20 mg of the compound with 15 mg of Tween-20, dissolve in 0.1 mL of acetone, then mix with 7.5 mg of agricultural emulsion 500 and 30 mg of agricultural emulsion 600, dissolve in 0.4 mL of dimethyl sulfoxide, and finally add dimethyl sulfoxide to make up to 1 mL, to prepare a solution containing a compound with a mass concentration of 2 mg·L⁻¹. -1 The emulsifiable concentrate was diluted with water to a concentration of 500 mg·L⁻¹. -1 The test solution of the reagent was prepared by preparing a 2 mg·L⁻¹ solution of iprodione technical. -1 Procymidone and boscalid technical grade were formulated to a 2 mg·L⁻¹ solution. -1 Cyclosulfuron-methyl EC was used as a control, with a blank control consisting of an EC solution without the target compound. When rapeseed seedlings had four cotyledons, the solution was sprayed evenly. After the solution air-dried, 5 mm diameter Sclerotinia sclerotiorum var. sclerotiorum were inoculated into the center of each cotyledon. The inoculated seedlings were placed in an intelligent artificial climate chamber and cultured in darkness for 12 h at 26±1 ℃ and relative humidity above 90%, followed by 12 h under light. Once the blank control showed full disease development, the diameter of the lesions was measured, and the control effect was assessed by the inhibition rate. Each treatment had five replicates.

[0060]

[0061] (2) Tomato pot cultivation method: Botrytis cinerea, iprodione, and cyclohexanesulfonamide were used as control agents, and acetone was used as a blank control. The test strain was tomato gray mold AS-06, and the screening concentration was 200 mg·L⁻¹. -1 First, the prepared test solution was evenly sprayed onto three pots of tomato seedlings. After 24 hours, once the solution had completely evaporated, the mycelial suspension was evenly sprayed onto the tomato seedlings in all treatment groups. The humidity inside the cultivation rack was maintained above 80%, and the temperature between 20-25 ℃. After the control group had fully developed disease, data was collected and recorded using a tiered survey method. The fungicidal activity of compound I-1-I-30 against *Sclerotinia sclerotiorum* and *Botrytis cinerea* is shown in Table 5.

[0062]

[0063] Table 5. Bactericidal activity of compounds against Sclerotinia sclerotiorum.

[0064] As can be seen from Table 5, at 200 mg·L -1At the specified concentrations, the target compounds demonstrated good in vivo control efficacy against *Sclerotinia sclerotinia*, the causal agent of rapeseed rot. Among the 30 tested compounds, 20 showed greater protective activity against *Sclerotinia sclerotinia* than cyclohexylsulfamate (32.27%). Compound I-24 exhibited the highest inhibition rate at 61.49%, slightly lower than the commercially available fungicide iprodione (72.34%). Pot experiments on tomatoes also showed good in vivo protective effects against *Botrytis cinerea*, the causal agent of gray mold. Eighteen compounds showed better control efficacy than cyclohexylsulfamate (56.74%), 25 were better than the control fungicide iprodione (51.39%), and three were better than the control fungicide botrytisc (84.98%), namely compounds I-25 (90.92%), I-27 (88.28%), and I-30 (89.51%). Therefore, this series of compounds provides good in vivo protection against *Sclerotinia sclerotinia* and *Botrytis cinerea*.

[0065] 4. The bactericidal activity of the compound was determined using the strawberry in vivo test method.

[0066] Using commercially available pesticides such as boscalid, iprodione, and cyclohexylsulfonamide as control agents, acetone as a blank control, and tomato gray mold AS-06 as the test strain, at 400 mg·L⁻¹... -1 To evaluate the in vivo protective activity of the compound at the desired concentration, uniformly sized strawberries were disinfected with 75% alcohol in a clean bench. After the alcohol had completely evaporated, the prepared test solution was evenly sprayed onto three strawberries. After 24 hours, once the solution had evaporated, mycelial cakes were collected using an inoculation needle and placed in the center of each strawberry. The humidity in the culture tray was maintained above 80%, and the temperature was kept between 20-25 °C. Data were collected at 48 and 72 hours, and the calculation formula is as follows:

[0067] The fungicidal activity of compound I-1-I-30 against Botrytis cinerea is shown in Table 6.

[0068] Table 6. Fungicidal activity of compounds against gray mold.

[0069] As can be seen from Table 6, at 400 mg·L -1At the specified concentrations, the target compounds showed good in vivo control efficacy against gray mold. Of the 30 tested compounds, 17 showed better control efficacy than the control agent cyclohexylsulfamethoxam (56.74%); 25 compounds were better than the control agent iprodione (51.39%); and 5 compounds were better than the control agent boscalid (84.98%), namely compounds I-9 (97.04%), I-10 (86.59%), I-11 (92.81%), I-13 (86.81%), and I-15 (91.60%).

[0070] In summary, this series of compounds exhibits strong fungicidal activity. Several compounds demonstrate fungicidal activity against *Botrytis cinerea* and *Sclerotinia sclerotinia*, comparable to commercially available agents such as iprodione and boscalid. Some compounds show even higher activity than commercial agents and possess strong protective activity, indicating significant application and development potential.

[0071] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0072] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A stilbene compound containing a sulfonamide fragment, characterized in that, It has the structure shown in Equation 1 below: Formula 1 R 2 ~R 6 It is an independent group consisting of one of alkyl, alkoxy, hydrogen, halogen, and sulfonamide groups with 1 to 12 carbon atoms.

2. The method for preparing a stilbene compound containing a sulfonamide fragment as described in claim 1, characterized in that, Includes the following steps: 1) Compound 1 was reacted with triphenylphosphine to give benzyltriphenylphosphine bromide; 2) The benzyltriphenylphosphine bromide obtained in step 1) is reacted with tert-butoxide, and after the reaction is completed, it is mixed with 4-nitrobenzaldehyde to obtain E-4-nitro-diphenylethylene; 3) Mix E-4-nitro-diphenylethylene, tetrahydroxydiboron and 4,4'-bipyridine obtained in step 2) and react to obtain E-4-amino-diphenylethylene; 4) Cyclohexanone was reacted with sulfur trioxide-dioxane adduct to give 2-oxocyclohexyl sulfonate; 5) The 2-oxocyclohexyl sulfonate obtained in step 4) is mixed with oxalyl chloride and catalyst, and reacted to obtain 2-oxocyclohexyl sulfonyl chloride; 6) 2-Oxocyclohexylsulfonyl chloride was mixed with E-4-amino-diphenylethylene and triethylamine and reacted to obtain stilbene compounds containing sulfonamide fragments; There is no specific order in which 2-oxocyclohexylsulfonyl chloride and E-4-amino-diphenylethylene are prepared. The structure of compound 1 is as follows: ;R 2 ~R 6 It is an independent group consisting of one of alkyl, alkoxy, hydrogen, halogen, and sulfonamide groups with 1 to 12 carbon atoms.

3. The method for preparing a stilbene compound containing a sulfonamide fragment according to claim 2, characterized in that, In step 1), the molar ratio of benzyl bromide to triphenylphosphine is 35:30; The reaction temperature in step 1) is 60~110℃, and the reaction time is 2~12h.

4. The method for preparing a stilbene compound containing a sulfonamide fragment according to claim 3, characterized in that, In step 2), the molar ratio of benzyltriphenylphosphine bromide to tert-butoxide is 5:6.5, the reaction temperature of benzyltriphenylphosphine bromide and tert-butoxide is 0℃, and the reaction time is 30 min. The tert-butoxide salt includes potassium tert-butoxide and / or sodium tert-butoxide.

5. The method for preparing a stilbene compound containing a sulfonamide fragment according to claim 4, characterized in that, In step 2), the molar ratio of benzyltriphenylphosphine bromide to 4-nitrobenzaldehyde is 5:5; the reaction time during the reaction with 4-nitrobenzaldehyde is 2~20h.

6. A method for preparing a stilbene compound containing a sulfonamide fragment according to any one of claims 2 to 5, characterized in that, In step 3), the molar ratio of E-4-nitro-diphenylethylene, tetrahydroxydiboron, and 4,4'-bipyridine is 5:15:0.

25. The reaction time in step 3) is 15 minutes.

7. The method for preparing a stilbene compound containing a sulfonamide fragment according to claim 6, characterized in that, In step 4), the molar ratio of cyclohexanone and sulfur trioxide-dioxane adduct is 50:60; The reaction temperature in step 4) is 0℃, and the reaction time is 2h.

8. The method for preparing a stilbene compound containing a sulfonamide fragment according to claim 7, characterized in that, In step 5), the molar volume ratio of 2-oxocyclohexyl sulfonate, oxalyl chloride, and catalyst is 10 mmol: 10 mmol: 0.5~1 mL. The reaction time in step 5) is 3-4 hours; The catalyst in step 5) includes N,N-dimethylformamide.

9. A method for preparing a stilbene compound containing a sulfonamide fragment according to claim 7 or 8, characterized in that, In step 6), the molar ratio of 2-oxocyclohexylsulfonyl chloride to E-4-amino-diphenylethylene and triethylamine is 6:5:

7. The reaction time in step 6) is 3~24h.

10. The use of stilbene compounds containing sulfonamide fragments prepared by the preparation method according to any one of claims 2 to 9 in the preparation of bactericides.

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