Benzoic acid sulfenyl compounds containing a trifluoromethyl oxadiazole fragment, and methods of making and using the same

Abstract

The present application relates to the technical field of agrochemicals and fungicides, and discloses a benzoic acid sulfide compound containing a trifluoromethyl oxadiazole fragment as well as a preparation method and application thereof.The compound has a structure shown in formula I, wherein R 1 ‑R 5 Each is independently selected from one of a 1-6-membered heterocyclic ring, an alkyl group containing 1-12 carbon atoms, an alkoxy group containing 1-12 carbon atoms, hydrogen, halogen, amino, nitro, cyano, trifluoromethyl, and trifluoromethoxy.In the presence of a first solvent and a first base, 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride is subjected to a condensation reaction with a compound of formula II to obtain the benzoic acid sulfide compound containing a trifluoromethyl oxadiazole fragment.The benzoic acid sulfide compound containing a trifluoromethyl oxadiazole fragment provided by the present application has a novel structure, and the bioactivity determination result shows that the compound has good fungicidal activity on soybean rust and wheat scab, 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, specifically to a benzoic acid thioester compound containing a trifluoromethyloxadiazole fragment, its preparation method, and its application. Background Technology

[0002] Soybean rust is caused by the rust fungus *Tetranychus spp.*, primarily infecting the leaves, petioles, and stems of soybeans. The disease starts from the lower leaves and gradually spreads upwards. In the early stages, small brown spots appear on the leaves; these spots gradually enlarge, forming uredinia. When the lesions are dense, they form necrotic spots confined by the leaf veins. Later in the growth cycle, dark brown, polygonal, slightly raised telia form around the uredinia. After the disease occurs, it generally leads to a 10% to 30% reduction in soybean yield, and in severe cases, a reduction of more than 50%, seriously impacting soybean production.

[0003] 1,2,4-Oxadiazole compounds play a vital role in agriculture due to their high efficiency, broad-spectrum biological activity, and the variety of substituents on the 1,2,4-oxadiazole ring. Their design, synthesis, and bioactivity research have been a major focus of research in green pesticide creation. Trifluoromethyl groups possess strong electron-withdrawing inductive effects; introducing this group into the molecule can significantly alter the physicochemical properties of the target molecule, prolong the drug's duration of action in vivo, and enhance metabolic stability. Furthermore, introducing trifluoromethyl groups can enhance the lipophilicity of the molecule, facilitating drug absorption and diffusion in vivo. Introducing trifluoromethyl groups into pesticides can enhance their efficacy. In recent years, a series of 1,2,4-oxadiazole compounds containing trifluoromethyl substitutions have been developed by researchers, and extensive experimental data have shown that these compounds have high inhibitory effects on plant pathogens such as soybean rust and wheat powdery mildew. Currently, many large pesticide companies, such as Syngenta, BASF, and DuPont, are developing these compounds.

[0004] In 2023, Shenyang University of Chemical Technology designed and synthesized five 1,2,4-oxadiazole compounds using p-cyanobenzoic acid as a starting material. The target compounds exhibited high fungicidal activity against soybean rust.

[0005]

[0006] In 2015, BASF developed Flufenoxadiazam, a trifluoromethyloxadiazole fungicide. Bioactivity tests showed that this fungicide exhibits excellent activity against soybean and corn rust. This compound is a histone deacetylase (HDAC) inhibitor with a novel fungicidal mechanism and does not exhibit cross-resistance with currently available fungicides, making it a potential lead compound for the development of soybean rust fungicides.

[0007] Summary of the Invention

[0008] The purpose of this invention is to provide a benzoic acid thioester compound containing a trifluoromethyloxadiazole fragment, its preparation method, and its applications. The compound provided by this invention exhibits good fungicidal activity against soybean rust and wheat scab.

[0009] To achieve the above objectives, a first aspect of the present invention provides a benzoic acid thioester compound containing a trifluoromethyloxadiazole fragment, wherein the compound has the structure shown in Formula I:

[0010]

[0011]

[0012] Among them, R 1 -R 5 Each is independently selected from one of the following: 1-6 membered heterocycles, alkyl groups containing 1-12 carbon atoms, alkoxy groups containing 1-12 carbon atoms, hydrogen, halogen, amino, nitro, cyano, trifluoromethyl, and trifluoromethoxy.

[0013] The second aspect of the present invention provides a method for preparing the compound described in the first aspect, wherein the method comprises: in the presence of a first solvent and a first base, reacting 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride with a compound of formula II to obtain a benzoic acid thioester compound containing a trifluoromethyloxadiazol fragment;

[0014]

[0015] Among them, R 1 -R 5 As defined in the first aspect.

[0016] The third aspect of this invention provides the application of the benzoic acid thioester compounds described in the first aspect or the benzoic acid thioester compounds obtained by the preparation method described in the second aspect as bactericides.

[0017] The beneficial technical effects achieved by the present invention through the above technical solution are as follows:

[0018] The benzoic acid thioester compound containing the trifluoromethyloxadiazole fragment provided by this invention has a novel structure. The results of bioactivity assay show that the compound has good fungicidal activity against soybean rust and wheat scab, and is suitable for widespread application. Detailed Implementation

[0019] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0020] A first aspect of the present invention provides a benzoic acid thioester compound containing a trifluoromethyloxadiazole fragment, wherein the compound has the structure shown in Formula I:

[0021]

[0022] Among them, R 1 -R 5 Each is independently selected from one of the following: 1-6 membered heterocycles, alkyl groups containing 1-12 carbon atoms, alkoxy groups containing 1-12 carbon atoms, hydrogen, halogen, amino, nitro, cyano, trifluoromethyl, and trifluoromethoxy.

[0023] This invention uses the 5-trifluoromethyl-1,2,4-oxadiazole structure as the active fragment. Through the splicing of active substructures, with Flufenoxadiazam as the lead compound, and utilizing the principle of bioisosterism, the amide structure is replaced with a thioester structure, ultimately yielding benzoic acid thioester compounds containing the trifluoromethyloxadiazole fragment. At concentrations as low as 4 mg / L, most compounds in this series exhibit fungicidal activity comparable to that of the lead compound Flufenoxadiazam against soybean rust. In cases where pathogenic fungi have developed resistance to Flufenoxadiazam, the compounds of this invention have the potential to replace Flufenoxadiazam in production. Furthermore, the compounds provided by this invention demonstrate superior fungicidal activity against wheat scab compared to Flufenoxadiazam.

[0024] In some embodiments of the present invention, R 1 It is selected from one of hydrogen, fluorine, chlorine, bromine, nitro, trifluoromethyl, methyl, and methoxy.

[0025] In some embodiments of the present invention, R 2 It is selected from one of hydrogen, fluorine, chlorine, bromine, nitro, trifluoromethyl, methyl, and methoxy.

[0026] In some embodiments of the present invention, R 3 It is selected from one of hydrogen, fluorine, chlorine, bromine, nitro, trifluoromethyl, methyl, methoxy, ethyl and isopropyl.

[0027] In some embodiments of the present invention, R 4It is selected from one of hydrogen, fluorine, and trifluoromethyl.

[0028] In some embodiments of the present invention, R 5 Selected from hydrogen or fluorine.

[0029] In some embodiments of the present invention, the compound is selected from one of the following compounds:

[0030] Compound I-1: R 1 For H, R 2 For H, R 3 For H, R 4 For H, R 5 For H;

[0031] Compound I-2: R 1 For H, R 2 For H, R 3 For F, R 4 For H, R 5 For H;

[0032] Compound I-3: R 1 For H, R 2 For H, R 3 For Cl, R 4 For H, R 5 For H;

[0033] Compound I-4: R 1 For H, R 2 For H, R 3 For Br, R 4 For H, R 5 For H;

[0034] Compound I-5: R 1 For H, R 2 For H, R 3 For NO2, R 4 For H, R 5 For H;

[0035] Compound I-6: R 1 For H, R 2 For H, R 3 For CF3, R 4 For H, R 5 For H;

[0036] Compound I-7: R 1 For H, R 2 For H, R 3 For OMe, R 4 For H, R 5 For H;

[0037] Compound I-8: R1 For H, R 2 For H, R 3 For Me, R 4 For H, R 5 For H;

[0038] Compound I-9: R 1 For H, R 2 For H, R 3 For Et, R 4 For H, R 5 For H;

[0039] Compound I-10: R 1 For H, R 2 For H, R 3 For i-Pr, R 4 For H, R 5 For H;

[0040] Compound I-11: R 1 For H, R 2 For F, R 3 For H, R 4 For H, R 5 For H;

[0041] Compound I-12: R 1 For H, R 2 For Cl, R 3 For H, R 4 For H, R 5 For H;

[0042] Compound I-13: R 1 For H, R 2 For Br, R 3 For H, R 4 For H, R 5 For H;

[0043] Compound I-14: R 1 For H, R 2 For NO2, R 3 For H, R 4 For H, R 5 For H;

[0044] Compound I-15: R 1 For H, R 2 For CF3, R 3 For H, R 4 For H, R 5 For H;

[0045] Compound I-16: R 1 For H, R 2 For OMe, R3 For H, R 4 For H, R 5 For H;

[0046] Compound I-17: R 1 For H, R 2 For Me, R 3 For H, R 4 For H, R 5 For H;

[0047] Compound I-18: R 1 For F, R 2 For H, R 3 For H, R 4 For H, R 5 For H;

[0048] Compound I-19: R 1 For Cl, R 2 For H, R 3 For H, R 4 For H, R 5 For H;

[0049] Compound I-20: R 1 For Br, R 2 For H, R 3 For H, R 4 For H, R 5 For H;

[0050] Compound I-21: R 1 For NO2, R 2 For H, R 3 For H, R 4 For H, R 5 For H;

[0051] Compound I-22: R 1 For CF3, R 2 For H, R 3 For H, R 4 For H, R 5 For H;

[0052] Compound I-23: R 1 For OMe, R 2 For H, R 3 For H, R 4 For H, R 5 For H;

[0053] Compound I-24: R 1 For Me, R 2 For H, R 3 For H, R 4 For H, R5 For H;

[0054] Compound I-25: R 1 For Cl, R 2 For H, R 3 For Cl, R 4 For H, R 5 For H;

[0055] Compound I-26: R 1 For H, R 2 For Cl, R 3 For Cl, R 4 For H, R 5 For H;

[0056] Compound I-27: R 1 For F, R 2 For H, R 3 For F, R 4 For H, R 5 For H;

[0057] Compound I-28: R 1 For H, R 2 For CF3, R 3 For H, R 4 For CF3, R 5 For H;

[0058] Compound I-29: R 1 For F, R 2 For F, R 3 For F, R 4 For F, R 5 It is F.

[0059] The second aspect of the present invention provides a method for preparing the compound described in the first aspect, wherein the method comprises: in the presence of a first solvent and a first base, reacting 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride with a compound of formula II to obtain a benzoic acid thioester compound containing a trifluoromethyloxadiazol fragment;

[0060]

[0061] Among them, R 1 -R 5 As defined in the first aspect.

[0062] In some embodiments of the present invention, the first solvent is selected from at least one of dichloromethane, dichloroethane, chloroform and toluene, preferably dichloromethane.

[0063] In some embodiments of the present invention, the first base is selected from at least one of triethylamine, pyridine, potassium tert-butoxide, and potassium carbonate, preferably triethylamine.

[0064] In some embodiments of the present invention, the molar ratio of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride, the compound of formula II, to the first base is 4-6:4-5:4-6.

[0065] In some embodiments of the present invention, the molar ratio of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride, the compound of formula II, to the first base is 5:4.6:5.

[0066] In some embodiments of the present invention, 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride is mixed with a compound of formula II and a first base under ice-water bath conditions.

[0067] In some embodiments of the present invention, the conditions for the condensation reaction include: a temperature of 0-30°C and a time of 3-6 hours.

[0068] In some embodiments of the present invention, the conditions for the condensation reaction include: a temperature of room temperature and a time of 5 hours.

[0069] In some embodiments of the present invention, the preparation method of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride includes the following steps:

[0070] (1) In the presence of a second solvent, a second base and 8-hydroxyquinoline, 4-cyanobenzoic acid is reacted with hydroxylamine hydrochloride in a first reaction to give 4-(N-hydroxymethylamidine)benzoic acid;

[0071] (2) In the presence of a third solvent, 4-(N-hydroxymethylammonium)benzoic acid is reacted with trifluoroacetic anhydride in a second reaction to give 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid;

[0072] (3) In the presence of a fourth solvent and a catalyst, 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid is reacted with oxalyl chloride in a third reaction to obtain 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride.

[0073] In some embodiments of the present invention, in step (1), the second solvent is a mixture of ethanol and water.

[0074] In some embodiments of the present invention, the second alkali is selected from at least one of anhydrous sodium carbonate, anhydrous potassium carbonate, sodium hydroxide, and potassium hydroxide, preferably anhydrous sodium carbonate.

[0075] In some embodiments of the present invention, the molar ratio of 4-cyanobenzoic acid to hydroxylamine hydrochloride is 17:30-33, preferably 17:31.

[0076] In some embodiments of the present invention, the molar ratio of 4-cyanobenzoic acid, the second base and 8-hydroxyquinoline is 17:25-30:0.8-1, preferably 17:25.8:0.85.

[0077] In some embodiments of the present invention, the conditions for the first reaction include: a temperature of 85-87°C and a time of 5 hours.

[0078] In some embodiments of the present invention, in step (2), the third solvent is selected from at least one of tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide and 2-methyltetrahydrofuran, preferably tetrahydrofuran.

[0079] In some embodiments of the present invention, the molar ratio of 4-(N-hydroxymethylammonium)benzoic acid to trifluoroacetic anhydride is 5:5-7, preferably 5:6.

[0080] In some embodiments of the present invention, the conditions for the second reaction include: a temperature of 24-26°C and a time of 5 hours.

[0081] In some embodiments of the present invention, in step (3), the fourth solvent is selected from at least one of dichloromethane, dichloroethane, chloroform and toluene, preferably dichloromethane.

[0082] In some embodiments of the present invention, the catalyst is selected from at least one of N,N-dimethylformamide, N,N-dimethylacetamide and N,N-diethylformamide, preferably N,N-dimethylformamide.

[0083] In some embodiments of the present invention, the molar ratio of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid, oxalyl chloride and catalyst is 5:5.4:6.48.

[0084] In some embodiments of the present invention, the conditions for the third reaction include: a temperature of room temperature and a time of 1 hour.

[0085] The third aspect of this invention provides the application of the benzoic acid thioester compounds described in the first aspect or the benzoic acid thioester compounds obtained by the preparation method described in the second aspect as bactericides.

[0086] In some embodiments of the present invention, the benzoic acid thioester compounds are used to prevent and control soybean rust and wheat scab.

[0087] In this invention, the benzoic acid thioester compound containing the trifluoromethyloxadiazole fragment has fungicidal activity against the pathogenic fungi of soybean rust and wheat scab, and can be used for the prevention and control of these diseases.

[0088] The present invention will be described in detail below through embodiments.

[0089] Unless otherwise specified in the following examples and comparative examples, all conditions were performed under standard conditions or conditions recommended by the manufacturer. Reagents or instruments used, unless otherwise specified, are all commercially available products.

[0090] Example 1

[0091] This example illustrates the preparation of compound I-1.

[0092]

[0093] (1) Weigh 17 mmol of 4-cyanobenzoic acid into a dry round-bottom flask, add 20 mL of ethanol and 10 mL of water, then add 25.8 mmol of anhydrous sodium carbonate, 31 mmol of hydroxylamine hydrochloride and 0.85 mmol of 8-hydroxyquinoline. Place the flask in an oil bath and react at 85 °C. Heat under reflux for 5 h and monitor the reaction by TLC (VL). 石油醚 :V 乙酸乙酯 =3:1), clarify the reaction process; after the reaction is completed, after the reactants are cooled to room temperature, the ethanol solvent in the solution is removed by vacuum distillation. After a large amount of solid precipitates, the vacuum distillation is stopped, and the mixture is filtered using a sintered glass funnel. Then the pH of the filtrate is adjusted to about 4, and the filtrate is stirred continuously. After stirring, solid precipitates, and it is filtered again. The filtered solid is washed multiple times with distilled water. Finally, the white to pale yellow solid obtained is dried under vacuum to obtain 4-(N-hydroxymethylamidine)benzoic acid white solid 1, which is directly used in the next reaction.

[0094] (2) Weigh 5 mmol of 4-(N-hydroxymethylamidine)benzoic acid into a dry round-bottom flask, add 30 mL of ultra-dry tetrahydrofuran to dissolve it, and then weigh 6 mmol of trifluoroacetic anhydride and dissolve it in 30 mL of tetrahydrofuran. Under ice bath conditions, slowly add the trifluoroacetic anhydride dissolved in tetrahydrofuran to the tetrahydrofuran solution of 4-(N-hydroxymethylamidine)benzoic acid. Remove the ice bath and continue the reaction for 5 h. Analyze the reaction by TLC (V 石油醚 :V 乙酸乙酯=5:1) Monitoring to determine the reaction progress; after the reaction is completed, the ice bath is removed, the solvent is removed by vacuum distillation, distilled water is added to the obtained white solid, and the mixture is stirred for 2 hours. Then the mixture is filtered with a sintered glass funnel, and the obtained solid is dried under vacuum to finally obtain 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid white solid 2.

[0095] (3) Weigh 5 mmol of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid and use 25 mL of ultra-dry dichloromethane as solvent. Add 6.48 mmol of N,N-dimethylformamide as catalyst and slowly add 5.4 mmol of oxaloyl chloride under ice bath conditions, releasing a large amount of gas. After the gas release is no longer intense, remove the ice bath and react at room temperature for 1 h. The resulting mixed solution is the 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride solution.

[0096] (4) Weigh 4.6 mmol of thiophenol and place it in another preheated and dried round-bottom flask. Dissolve it in 10 mL of ultra-dry dichloromethane and add triethylamine (5 mmol). React under ice-water bath conditions. Slowly add 25 mL of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride solution (5 mmol) to the system. The reaction produces a large amount of white fumes. When the white fumes no longer occur, remove the ice bath and react at room temperature for 5 h. TLC (V 石油醚 :V 乙酸乙酯 =8:1) Monitor the reaction progress. After the reaction is complete, add 20 mL of water to quench and stop the reaction. 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 The product was collected by elution at a ratio of 10:1 and evaporated to dryness to obtain the target product: compound I-1.

[0097] Example 2-29

[0098] Compounds I-2 to I-29 were prepared according to the method of Example 1, except that the thiophenol in step (4) was replaced accordingly.

[0099] The physicochemical data of compounds I-1 to I-29 prepared in Examples 1-29 are shown in Table 1 (from which the compounds of formula II used can be identified).

[0100] Table 1

[0101]

[0102]

[0103] Compounds I-1 to I-29 1 H NMR, 13 The C NMR and HRMS data are shown in Table 2.

[0104] Table 2

[0105]

[0106]

[0107]

[0108]

[0109]

[0110]

[0111] The bactericidal activity of compounds I-1 to I-29 prepared in Examples 1-29 was verified as follows.

[0112] Test Example 1: Determination of the fungicidal activity of compounds I-1 to I-29 against soybean rust pathogen.

[0113] Take 10 mg of the test compound sample, dissolve it in 0.5 mL of acetone to prepare a stock solution of 20000 mg / L. Prepare test solutions with concentrations of 400 mg / L, 200 mg / L, 40 mg / L, and 4 mg / L using water containing 0.1% Tween-80. Select two true-leaf stage potted soybean seedlings and spray the leaves with the test solutions. Use the same concentration gradient for the control agents Flufenoxadiazam and Prothioconazole. Inoculate with the prepared solution at 3 × 10^5 spores / mL 24 hours after treatment. 12-15 days after inoculation, when the blank control shows stable disease development (lesions covering more than 80% of the leaf area and high spore production), evaluate the control efficacy of the compound according to the industry standard (People's Republic of China Agricultural Industry Standard NY / T 1156.15-2008 Pesticide Indoor Bioassay Test Guidelines Fungicides Part 15: Control of Wheat Leaf Rust Test - Pot Method).

[0114]

[0115] X: Disease index; Ni: Disease leaf index at each level; i: Relative level value; N: Total number of leaves surveyed.

[0116]

[0117] P: Prevention and control effect, %; CK: Disease index of blank control; PT: Disease index of drug treatment.

[0118] The fungicidal activities of compounds I-1 to I-29 against soybean rust pathogens are shown in Table 3.

[0119] Table 3

[0120]

[0121] As shown in Table 3, the compounds of this invention exhibit good fungicidal activity against soybean rust pathogens. At concentrations of 400-40 mg / L, their activity is the same as the lead compound, achieving 100% control efficacy. When the concentration is reduced to 4 mg / L, the activity of each compound decreases significantly, but compounds I-6 still maintain control efficacy comparable to the lead compound. The activity test results indicate that the compounds provided by this invention can achieve control efficacy comparable to the lead compound Flufenoxadiazam in controlling soybean rust.

[0122] Test Example 2: Determination of the fungicidal activity of compounds I-1 to I-29 against wheat scab pathogen.

[0123] Take 10 mg of the test compound sample, dissolve it in 0.5 mL of acetone to prepare a stock solution of 20000 mg / L, and prepare a test solution of 100 mg / L using water containing 0.1% Tween-80. Cut wheat leaves approximately 8 cm tall at the one-leaf-one-heart stage, immerse them in 10 mL centrifuge tubes, and start timing after immersion. After 30 seconds, remove the leaves with tweezers and air-dry them. After 1 hour, aliquot the dried leaves into labeled 1% water agar tubes, 8 leaves per tube, with 3 replicates per group. A 100 mg / L fluopyram solution is used as a positive control, and wheat leaves immersed in an acetone solution diluted with 0.1% Tween-80 in purified water serve as a blank control, with 3 replicates per group. An investigation is conducted 6 days after treatment, measuring the mycelial growth height starting from the 1% water agar surface.

[0124]

[0125] The fungicidal activities of compounds I-1 to I-29 against the pathogen of wheat scab are shown in Table 4.

[0126] Table 4

[0127]

[0128]

[0129] As shown in Table 4, all compounds of this invention outperform Flufenoxadiazam in controlling wheat scab. The compounds provided by this invention improve the efficacy of the lead compound against wheat scab.

[0130] In summary, the compounds of this invention exhibit strong fungicidal activity against soybean rust and wheat scab, thus demonstrating promising application prospects and development value.

[0131] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A benzoate thioester compound containing a trifluoromethyloxadiazole fragment, characterized in that, The compound has the structure shown in Formula I: Formula I Among them, R 1 -R 5 Each is independently selected from one of 1-6 membered heterocycles, alkyl groups containing 1-12 carbon atoms, alkoxy groups containing 1-12 carbon atoms, hydrogen, halogen, amino, nitro, trifluoromethyl, and trifluoromethoxy.

2. The compound according to claim 1, wherein, R 1 It is selected from one of hydrogen, fluorine, chlorine, bromine, nitro, trifluoromethyl, methyl, and methoxy; And / or, R 2 It is selected from one of hydrogen, fluorine, chlorine, bromine, nitro, trifluoromethyl, methyl, and methoxy; And / or, R 3 Selected from one of hydrogen, fluorine, chlorine, bromine, nitro, trifluoromethyl, methyl, methoxy, ethyl, and isopropyl; And / or, R 4 Selected from one of hydrogen, fluorine, and trifluoromethyl; And / or, R 5 Selected from hydrogen or fluorine.

3. The compound according to claim 1 or 2, wherein, The compound is selected from one of the following compounds: Compound I-1: R 1 For H, R 2 For H, R 3 For H, R 4 For H, R 5 For H; Compound I-2: R 1 For H, R 2 For H, R 3 For F, R 4 For H, R 5 For H; Compound I-3: R 1 For H, R 2 For H, R 3 For Cl, R 4 For H, R 5 For H; Compound I-4: R 1 For H, R 2 For H, R 3 For Br, R 4 For H, R 5 For H; Compound I-5: R 1 For H, R 2 For H, R 3 For NO2, R 4 For H, R 5 For H; Compound I-6: R 1 For H, R 2 For H, R 3 For CF3, R 4 For H, R 5 For H; Compound I-7: R 1 For H, R 2 For H, R 3 For OMe, R 4 For H, R 5 For H; Compound I-8: R 1 For H, R 2 For H, R 3 For Me, R 4 For H, R 5 For H; Compound I-9: R 1 For H, R 2 For H, R 3 For Et, R 4 For H, R 5 For H; Compound I-10: R 1 For H, R 2 For H, R 3 for i -Pr,R 4 For H, R 5 For H; Compound I-11: R 1 For H, R 2 For F, R 3 For H, R 4 For H, R 5 For H; Compound I-12: R 1 For H, R 2 For Cl, R 3 For H, R 4 For H, R 5 For H; Compound I-13: R 1 For H, R 2 For Br, R 3 For H, R 4 For H, R 5 For H; Compound I-14: R 1 For H, R 2 For NO2, R 3 For H, R 4 For H, R 5 For H; Compound I-15: R 1 For H, R 2 For CF3, R 3 For H, R 4 For H, R 5 For H; Compound I-16: R 1 For H, R 2 For OMe, R 3 For H, R 4 For H, R 5 For H; Compound I-17: R 1 For H, R 2 For Me, R 3 For H, R 4 For H, R 5 For H; Compound I-18: R 1 For F, R 2 For H, R 3 For H, R 4 For H, R 5 For H; Compound I-19: R 1 For Cl, R 2 For H, R 3 For H, R 4 For H, R 5 For H; Compound I-20: R 1 For Br, R 2 For H, R 3 For H, R 4 For H, R 5 For H; Compound I-21: R 1 For NO2, R 2 For H, R 3 For H, R 4 For H, R 5 For H; Compound I-22: R 1 For CF3, R 2 For H, R 3 For H, R 4 For H, R 5 For H; Compound I-23: R 1 For OMe, R 2 For H, R 3 For H, R 4 For H, R 5 For H; Compound I-24: R 1 For Me, R 2 For H, R 3 For H, R 4 For H, R 5 For H; Compound I-25: R 1 For Cl, R 2 For H, R 3 For Cl, R 4 For H, R 5 For H; Compound I-26: R 1 For H, R 2 For Cl, R 3 For Cl, R 4 For H, R 5 For H; Compound I-27: R 1 For F, R 2 For H, R 3 For F, R 4 For H, R 5 For H; Compound I-28: R 1 For H, R 2 For CF3, R 3 For H, R 4 For CF3, R 5 For H; Compound I-29: R 1 For F, R 2 For F, R 3 For F, R 4 For F, R 5 It is F.

4. A method for preparing a compound according to any one of claims 1-3, characterized in that, The method comprises: in the presence of a first solvent and a first base, reacting 4-[5-(trifluoromethyl)-1,2,4-oxadiazole-3-yl]benzoyl chloride with a compound of formula II to obtain a benzoic acid thioester compound containing a trifluoromethyloxadiazole fragment; Formula II Among them, R 1 -R 5 As defined in any one of claims 1-3.

5. The method according to claim 4, wherein, The first solvent is selected from at least one of dichloromethane, dichloroethane, chloroform, and toluene; And / or, the first base is selected from at least one of triethylamine, pyridine, potassium tert-butoxide, and potassium carbonate; And / or, the molar ratio of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride, the compound of formula II, to the first base is 4-6:4-5:4-6; And / or, 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride is mixed with the compound of formula II and the first base under ice-water bath conditions; And / or, the conditions for the condensation reaction include: a temperature of 0-30 °C and a time of 3-6 h.

6. The method according to claim 4, wherein, The first solvent is dichloromethane; And / or, the first base is triethylamine; And / or, the molar ratio of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride, the compound of formula II, to the first base is 5:4.6:5; And / or, the conditions for the condensation reaction include: a temperature of room temperature and a time of 5 h.

7. The method according to claim 4 or 5, wherein, The preparation method of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride includes the following steps: (1) In the presence of a second solvent, a second base and 8-hydroxyquinoline, 4-cyanobenzoic acid is reacted with hydroxylamine hydrochloride in a first reaction to give 4-(N-hydroxymethylamidine)benzoic acid; (2) In the presence of a third solvent, 4-(N-hydroxymethylammoni)benzoic acid is reacted with trifluoroacetic anhydride in a second reaction to give 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid; (3) In the presence of a fourth solvent and a catalyst, 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid is reacted with oxalyl chloride in a third reaction to obtain 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride.

8. The method according to claim 7, wherein, In step (1), the second solvent is a mixture of ethanol and water; And / or, the second base is selected from at least one of anhydrous sodium carbonate, anhydrous potassium carbonate, sodium hydroxide, and potassium hydroxide; And / or, the molar ratio of 4-cyanobenzoic acid to hydroxylamine hydrochloride is 17:30-33; And / or, the molar ratio of 4-cyanobenzoic acid, the second base, and 8-hydroxyquinoline is 17:25-30:0.8-1; And / or, the conditions for the first reaction include: a temperature of 85-87 °C and a time of 5 h.

9. The method according to claim 7, wherein, The second alkali is anhydrous sodium carbonate; And / or, the molar ratio of 4-cyanobenzoic acid to hydroxylamine hydrochloride is 17:31; And / or, the molar ratio of 4-cyanobenzoic acid, the second base and 8-hydroxyquinoline is 17:25.8:0.

85.

10. The method according to claim 7, wherein, In step (2), the third solvent is selected from at least one of tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide and 2-methyltetrahydrofuran; And / or, the molar ratio of 4-(N-hydroxymethylamidine)benzoic acid to trifluoroacetic anhydride is 5:5-7; And / or, the conditions for the second reaction include: a temperature of 24-26 °C and a time of 5 h.

11. The method according to claim 7, wherein, The third solvent is tetrahydrofuran; And / or, the molar ratio of 4-(N-hydroxymethylamino)benzoic acid to trifluoroacetic anhydride is 5:

6.

12. The method according to claim 7, wherein, In step (3), the fourth solvent is selected from at least one of dichloromethane, dichloroethane, chloroform, and toluene; And / or, the catalyst is selected from at least one of N,N-dimethylformamide, N,N-dimethylacetamide and N,N-diethylformamide; And / or, the molar ratio of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid, oxalyl chloride and catalyst is 5:5.4:6.48; And / or, the conditions for the third reaction include: a temperature of room temperature and a time of 1 h.

13. The method according to claim 7, wherein, The fourth solvent is dichloromethane; And / or, the catalyst is N,N-dimethylformamide.

14. The use of the benzoic acid thioester compound according to any one of claims 1-3 or the benzoic acid thioester compound obtained by the preparation method according to any one of claims 4-13 as a bactericide; in, The benzoic acid thioester compounds are used to control wheat scab.

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