Thiobenzoate compound containing trifluoromethyl oxadiazole fragment and preparation method and application thereof

Abstract

The invention relates to the technical field of agricultural chemicals and bactericides, and discloses a thiobenzoate compound containing a trifluoromethyl oxadiazole fragment as well as a preparation method and application of the thiobenzoate compound. The compound has a structure as shown in a formula I, and R1-R5 are 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, an amino group, a nitro group, a cyano group, a trifluoromethyl group and a trifluoromethoxy group. In the presence of a first solvent and a first alkali, 4-[5-(trifluoromethyl)-1, 2, 4-oxadiazole-3-yl] benzoyl chloride and a compound as shown in a formula II are subjected to a condensation reaction to obtain the thiobenzoate compound containing the trifluoromethyl oxadiazole fragment. The thiobenzoate compound containing the trifluoromethyl oxadiazole fragment provided by the invention is novel in structure, and a biological activity determination result shows that the compound has good bactericidal activity on soybean rust and wheat scab, and is suitable for large-scale popularization and application. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the technical field of agricultural chemicals and fungicides, and in particular to a benzoic acid thioester compound containing a trifluoromethyl oxadiazole fragment, and a preparation method and application thereof. Background Art

[0002] Soybean rust is caused by Psoralea pachyrhizi, which mainly infects the leaves, petioles and stems of soybeans. The disease starts from the lower leaves and gradually spreads to the upper parts. In the early stage of the disease, small brown spots appear on the leaves, and then the lesions gradually expand to form summer spores. When the lesions are dense, necrotic spots are formed that are limited by the leaf veins. In the late growth period, dark brown polygonal slightly raised winter spores are formed around the summer spores. After the disease occurs, it generally causes a 10% to 30% reduction in soybean production, and in severe cases, it even reduces production by more than 50%, which has a serious impact on soybean production.

[0003] 1,2,4-oxadiazole compounds play a very important role in the agricultural field because of their high efficiency, broad-spectrum biological activity and various changes in the substituents on the 1,2,4-oxadiazole ring. Their design, synthesis and biological activity research have always been one of the main directions of green pesticide creation research. Trifluoromethyl has a strong electron-withdrawing inductive effect. The introduction of this group into the molecule can significantly change the physical and chemical properties of the target molecule, prolong the action time of the drug in the body, and enhance the metabolic stability. In addition, the introduction of trifluoromethyl into the molecule can enhance the lipid solubility of the molecule, which is beneficial to the absorption and diffusion of drug molecules in the body. The introduction of trifluoromethyl groups into pesticides can enhance the efficacy of pesticides. In recent years, a series of 1,2,4-oxadiazole compounds containing trifluoromethyl substitution have been developed by researchers. A large amount of experimental data shows that this type of compound has a high inhibitory effect on plant pathogens such as soybean rust and wheat powdery mildew. At present, many large pesticide companies, such as Syngenta, BASF, DuPont, etc. are developing such compounds.

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

[0005]

[0006] In 2015, BASF developed a trifluoromethyloxadiazole fungicide Flufenoxadiazam. The results of biological activity tests showed that the drug has excellent activity against soybean rust and corn rust. The compound is a histone deacetylase (HDACs) inhibitor with a novel fungicide mechanism and no cross-resistance with the mainstream drugs on the market. It can be used as a lead compound for the development of soybean rust fungicides.

[0007] Summary of the invention

[0008] The purpose of the present invention is to provide a benzoic acid thioester compound containing a trifluoromethyl oxadiazole fragment and a preparation method and application thereof. The compound provided by the present invention has good fungicidal activity against soybean rust and wheat scab.

[0009] In order to achieve the above object, the first aspect of the present invention provides a benzoic acid thioester compound containing a trifluoromethyl oxadiazole fragment, wherein the compound has a structure shown in Formula I:

[0010]

[0011]

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

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

[0014]

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

[0016] The third aspect of the present invention provides the use of the benzoic acid thioester compound described in the first aspect or the benzoic acid thioester compound obtained by the preparation method described in the second aspect as a fungicide.

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

[0018] The benzoic acid thioester compound containing a trifluoromethyloxadiazole fragment provided by the present invention has a novel structure, and the biological activity test results show that the compound has good fungicidal activity against soybean rust and wheat scab, and is suitable for large-scale promotion and application. DETAILED DESCRIPTION

[0019] The endpoints and any values ​​of the ranges disclosed in this article 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 each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

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

[0021]

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

[0023] The present invention uses 5-trifluoromethyl-1,2,4-oxadiazole structure as active fragment, splices active substructures, uses Flufenoxadiazam as lead compound, replaces amide structure with thioester structure by bioisosteric principle, and finally obtains benzoic acid thioester compound containing trifluoromethyloxadiazole fragment. At a concentration as low as 4 mg / L, most compounds in this series of compounds have the same fungicidal activity as the lead compound Flufenoxadiazam against soybean rust. In the case that pathogenic fungi develop resistance to Flufenoxadiazam, the compounds of the present invention have the potential to replace Flufenoxadiazam for application in production. In addition, the compounds provided by the present invention show fungicidal activity against wheat scab that exceeds that of Flufenoxadiazam.

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

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

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

[0027] In some embodiments of the present invention, R 4One selected from the group consisting 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 is H;

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

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

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

[0034] Compound I-5: R 1 For H, R 2 For H, R 3 NO 2 , R 4 For H, R 5 is H;

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

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

[0037] Compound I-8: R 1 For H, R 2 For H, R 3 For Me, R 4 For H, R 5 is H;

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

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

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

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

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

[0043] Compound I-14: R 1 For H, R 2 NO 2 , R 3 For H, R 4 For H, R 5 is H;

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

[0045] Compound I-16: R 1 For H, R 2 OMe, R 3 For H, R 4 For H, R 5 is H;

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

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

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

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

[0050] Compound I-21: R 1 NO 2 , R 2 For H, R 3 For H, R 4 For H, R 5 is H;

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

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

[0053] Compound I-24: R1 For Me, R 2 For H, R 3 For H, R 4 For H, R 5 is H;

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

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

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

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

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

[0059] The second aspect of the present invention provides a method for preparing the compound of the first aspect, wherein the method comprises: in the presence of a first solvent and a first base, allowing 4-[5-(trifluoromethyl)-1,2,4-oxadiazole-3-yl]benzoyl chloride to undergo a condensation reaction with a compound of formula II to obtain a benzoic acid thioester compound containing a trifluoromethyloxadiazole 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 and 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 and 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 the compound of formula II and the first base in an ice-water bath.

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

[0068] In some embodiments of the present invention, the conditions of the condensation reaction include: the temperature is room temperature, and the time is 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 comprises the following steps:

[0070] (1) in the presence of a second solvent, a second base and 8-hydroxyquinoline, allowing 4-cyanobenzoic acid to undergo a first reaction with hydroxylamine hydrochloride to obtain 4-(N-hydroxycarbamimidoyl)benzoic acid;

[0071] (2) in the presence of a third solvent, allowing 4-(N-hydroxycarbamimidoyl)benzoic acid to undergo a second reaction with trifluoroacetic anhydride to obtain 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 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 mixed solvent of ethanol and water.

[0074] In some embodiments of the present invention, the second base 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 of the first reaction include: temperature of 85-87° C. and time of 5 h.

[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-hydroxycarbamimidoyl)benzoic acid to trifluoroacetic anhydride is 5:5-7, preferably 5:6.

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

[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 of the third reaction include: the temperature is room temperature, and the time is 1 hour.

[0085] The third aspect of the present invention provides the use of the benzoic acid thioester compound described in the first aspect or the benzoic acid thioester compound obtained by the preparation method described in the second aspect as a fungicide.

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

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

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

[0089] In the following examples and comparative examples, if no specific conditions are specified, the experiments were carried out under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used, if no manufacturer is specified, are all conventional products that can be obtained through commercial channels.

[0090] Example 1

[0091] This example is used to illustrate the preparation of compound I-1.

[0092]

[0093] (1) 4-Cyanobenzoic acid (17 mmol) was weighed into a dry round-bottom flask, and ethanol (20 mL) and water (10 mL) were added. Then, anhydrous sodium carbonate (25.8 mmol), hydroxylamine hydrochloride (31 mmol) and 8-hydroxyquinoline (0.85 mmol) were added. The mixture was placed in an oil bath at 85°C for reaction and heated under reflux for 5 h. The reaction was monitored by TLC (V 石油醚 :V 乙酸乙酯 =3:1), to clarify the reaction process; after the reaction is completed, after the reactant is cooled to room temperature, the ethanol solvent in the solution is removed by vacuum distillation, and the vacuum distillation is stopped after a large amount of solid is precipitated. The mixture is filtered using a sand core funnel, and then the pH value of the filtrate is adjusted to about 4. During the period, the filtrate is continuously stirred, and solids are precipitated after stirring. The filtrate is filtered again, and the solids filtered out are rinsed with distilled water for many times. Finally, the obtained white to light yellow solid is vacuum dried to obtain 4-(N-hydroxycarbamimidoyl)benzoic acid white solid 1, which is directly used in the next step reaction;

[0094] (2) Weigh 4-(N-hydroxycarbamimidoyl)benzoic acid (5 mmol) into a dry round-bottom flask, add ultra-dry tetrahydrofuran (30 mL) to dissolve, then weigh trifluoroacetic anhydride (6 mmol) and dissolve it in tetrahydrofuran (30 mL); under ice bath conditions, slowly add the trifluoroacetic anhydride dissolved in tetrahydrofuran to the tetrahydrofuran solution of 4-(N-hydroxycarbamimidoyl)benzoic acid, remove the ice bath, and continue the reaction for 5 h. The reaction was analyzed by TLC (V 石油醚 :V 乙酸乙酯=5:1) monitoring to determine the progress of the reaction; after the reaction, remove the ice bath, remove the solvent by distillation under reduced pressure, add distilled water to the obtained white solid, stir for 2 hours, and then filter the mixture with a sand core funnel, and vacuum dry the obtained solid to finally obtain 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoic acid as a white solid 2;

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

[0096] (4) Weigh thiophenol (4.6 mmol) and put it into another preheated and dried round-bottom flask, add 10 mL of ultra-dry dichloromethane to dissolve it, and add triethylamine (5 mmol); react under ice-water bath, slowly add 25 mL of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride solution (5 mmol) to the system, and the reaction produces a large amount of white smoke. When the white smoke is no longer produced, remove the ice bath and react at room temperature for 5 h. TLC (V 石油醚 :V 乙酸乙酯 =8:1) to monitor the reaction progress. After the reaction is completed, 20 mL of water is added to quench the reaction, and dichloromethane is used for extraction (15 mL × 3 times). The organic phase is collected, washed with saturated sodium chloride twice, and then dried with an appropriate amount of anhydrous sodium sulfate, filtered, and dried by spinning. 石油醚 :V 乙酸乙酯 =10:1 elution collection and spin drying 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 obtained).

[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 fungicidal activities of compounds I-1 to I-29 prepared in Examples 1-29 were verified as follows.

[0112] Test Example 1 Determination of fungicidal activity of compounds I-1 to I-29 against soybean rust pathogens

[0113] Take 10 mg of the sample of the test compound, dissolve it with 0.5 mL of acetone, prepare a 20000 mg / L mother solution, and prepare the test solution with concentrations of 400 mg / L, 200 mg / L, 40 mg / L, and 4 mg / L with water containing 0.1% Tween-80. Select two potted soybean seedlings in the true leaf stage and use the test solution for foliar spraying. Set the control agents Flufenoxadiazam and prothioconazole with the same concentration gradient. 24 hours after treatment, inoculate the pathogen with 3×10^5 spores / mL prepared. 12-15 days after spore inoculation, when the blank control has stable disease (lesions occupy more than 80% of the leaf area and the spore production is large), refer to the industry standard (the Agricultural Industry Standard of the People's Republic of China NY / T 1156.15-2008 Pesticide Indoor Bioassay Test Guidelines Fungicides Part 15: Pot Method for Control of Wheat Leaf Rust) to evaluate the control effect of the compound.

[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: control effect, %; CK: blank control disease index; PT: drug treatment disease index.

[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 can be seen from Table 3, the compounds of the present invention have good fungicidal activity against soybean rust pathogens. At a concentration of 400-40 mg / L, the activity is the same as that of the lead compound, and both can achieve 100% prevention effect. When the concentration is reduced to 4 mg / L, the activity of each compound is significantly reduced, but the activity of compound I-6 still maintains a prevention effect equivalent to that of the lead compound. The activity test results show that the compounds provided by the present invention can achieve a prevention effect equivalent to that of the lead compound Flufenoxadiazam in preventing and controlling soybean rust.

[0122] Test Example 2 Determination of fungicidal activity of compounds I-1 to I-29 against wheat scab pathogens

[0123] Take 10 mg of the sample of the compound to be tested, dissolve it in 0.5 mL of acetone, prepare a mother solution of 20,000 mg / L, and use water containing 0.1% Tween-80 to prepare a test solution with a concentration of 100 mg / L. Cut a wheat leaf about 8 cm high at the one-leaf and one-heart stage, soak it in a 10 mL centrifuge tube, start timing after soaking, use tweezers to clamp the leaf out after 30 seconds, and dry it. After 1 hour, divide the leaves with dried liquid into labeled 1% water agar test tubes, 8 leaves in each test tube, and repeat 3 times in one group. Set 100 mg / L fluopicolide as a positive control, and soak wheat leaves soaked in 0.1% Tween-80 pure water diluted acetone solution as a blank control, and repeat 3 times. Survey 6 days after the treatment of the agent, and measure the height of mycelial growth with the 1% water agar surface as the starting point.

[0124]

[0125] The fungicidal activities of compounds I-1 to I-29 against wheat fusarium scurf pathogens are shown in Table 4.

[0126] Table 4

[0127]

[0128]

[0129] It can be seen from Table 4 that all the compounds of the present invention are superior to Flufenoxadiazam in preventing and controlling wheat scab. The compounds provided by the present invention improve the prevention effect of the lead compound on wheat scab.

[0130] In summary, the compounds of the present invention have strong fungicidal activity against soybean rust and wheat scab, and therefore have good application prospects and development value.

[0131] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A benzoic acid thioester compound containing a trifluoromethyl oxadiazole fragment, characterized in that: The compound has a structure shown in Formula I: Among them, R 1 -R 5 Each is independently selected from one of 1-6 membered heterocyclic ring, alkyl group containing 1-12 carbon atoms, alkoxy group containing 1-12 carbon atoms, hydrogen, halogen, amino group, nitro group, cyano group, trifluoromethyl group and trifluoromethoxy group.

2. The compound according to claim 1, wherein R 1 One selected from the group consisting of hydrogen, fluorine, chlorine, bromine, nitro, trifluoromethyl, methyl and methoxy; Preferably, R 2 One selected from the group consisting of hydrogen, fluorine, chlorine, bromine, nitro, trifluoromethyl, methyl and methoxy; Preferably, R 3 One selected from the group consisting of hydrogen, fluorine, chlorine, bromine, nitro, trifluoromethyl, methyl, methoxy, ethyl and isopropyl; Preferably, R 4 One selected from the group consisting of hydrogen, fluorine and trifluoromethyl; Preferably, 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 is H; Compound I-2: R 1 For H, R 2 For H, R 3 For F, R 4 For H, R 5 is H; Compound I-3: R 1 For H, R 2 For H, R 3 Cl, R 4 For H, R 5 is H; Compound I-4: R 1 For H, R 2 For H, R 3 Br, R 4 For H, R 5 is H; Compound I-5: R 1 For H, R 2 For H, R 3 For NO2, R 4 For H, R 5 is H; Compound I-6: R 1 For H, R 2 For H, R 3 For CF3, R 4 For H, R 5 is H; Compound I-7: R 1 For H, R 2 For H, R 3 OMe, R 4 For H, R 5 is H; Compound I-8: R 1 For H, R 2 For H, R 3 For Me, R 4 For H, R 5 is H; Compound I-9: R 1 For H, R 2 For H, R 3 For Et, R 4 For H, R 5 is H; Compound I-10: R 1 For H, R 2 For H, R 3 i-Pr, R 4 For H, R 5 is H; Compound I-11: R 1 For H, R 2 For F, R 3 For H, R 4 For H, R 5 is H; Compound I-12: R 1 For H, R 2 Cl, R 3 For H, R 4 For H, R 5 is H; Compound I-13: R 1 For H, R 2 Br, R 3 For H, R 4 For H, R 5 is H; Compound I-14: R 1 For H, R 2 For NO2, R 3 For H, R 4 For H, R 5 is H; Compound I-15: R 1 For H, R 2 For CF3, R 3 For H, R 4 For H, R 5 is H; Compound I-16: R 1 For H, R 2 OMe, R 3 For H, R 4 For H, R 5 is H; Compound I-17: R 1 For H, R 2 For Me, R 3 For H, R 4 For H, R 5 is H; Compound I-18: R 1 For F, R 2 For H, R 3 For H, R 4 For H, R 5 is H; Compound I-19: R 1 Cl, R 2 For H, R 3 For H, R 4 For H, R 5 is H; Compound I-20: R 1 Br, R 2 For H, R 3 For H, R 4 For H, R 5 is H; Compound I-21: R 1 For NO2, R 2 For H, R 3 For H, R 4 For H, R 5 is H; Compound I-22: R 1 For CF3, R 2 For H, R 3 For H, R 4 For H, R 5 is H; Compound I-23: R 1 OMe, R 2 For H, R 3 For H, R 4 For H, R 5 is H; Compound I-24: R 1 For Me, R 2 For H, R 3 For H, R 4 For H, R 5 is H; Compound I-25: R 1 Cl, R 2 For H, R 3 Cl, R 4 For H, R 5 is H; Compound I-26: R 1 For H, R 2 Cl, R 3 Cl, R 4 For H, R 5 is H; Compound I-27: R 1 For F, R 2 For H, R 3 For F, R 4 For H, R 5 is H; Compound I-28: R 1 For H, R 2 For CF3, R 3 For H, R 4 For CF3, R 5 is H; Compound I-29: R 1 For F, R 2 For F, R 3 For F, R 4 For F, R 5 For F.

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

5. The method according to claim 4, wherein: The first solvent is selected from at least one of dichloromethane, dichloroethane, chloroform and toluene, preferably dichloromethane; Preferably, the first base is selected from at least one of triethylamine, pyridine, potassium tert-butoxide and potassium carbonate, preferably triethylamine; Preferably, the molar ratio of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride, the compound of formula II and the first base is 4-6:4-5:4-6; Preferably, the molar ratio of 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride, the compound of formula II and the first base is 5:4.6:5; Preferably, 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; Preferably, the conditions of the condensation reaction include: temperature of 0-30°C, time of 3-6h; Preferably, the conditions of the condensation reaction include: temperature is room temperature, and time is 5 hours.

6. The method according to claim 4 or 5, wherein: The preparation method of 4-[5-(trifluoromethyl)-1,2,4-oxadiazole-3-yl]benzoyl chloride comprises the following steps: (1) in the presence of a second solvent, a second base and 8-hydroxyquinoline, allowing 4-cyanobenzoic acid to undergo a first reaction with hydroxylamine hydrochloride to obtain 4-(N-hydroxycarbamimidoyl)benzoic acid; (2) in the presence of a third solvent, allowing 4-(N-hydroxycarbamimidoyl)benzoic acid to undergo a second reaction with trifluoroacetic anhydride to obtain 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 to obtain 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzoyl chloride.

7. The method according to claim 6, wherein: In the step (1), the second solvent is a mixed solvent of ethanol and water; Preferably, the second base is selected from at least one of anhydrous sodium carbonate, anhydrous potassium carbonate, sodium hydroxide and potassium hydroxide, preferably anhydrous sodium carbonate; Preferably, the molar ratio of 4-cyanobenzoic acid to hydroxylamine hydrochloride is 17:30-33, preferably 17:31; Preferably, 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; Preferably, the conditions of the first reaction include: temperature of 85-87° C. and time of 5 h.

8. The method according to claim 6 or 7, wherein: In the step (2), the third solvent is selected from at least one of tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide and 2-methyltetrahydrofuran, preferably tetrahydrofuran; Preferably, the molar ratio of 4-(N-hydroxycarbamimidoyl)benzoic acid to trifluoroacetic anhydride is 5:5-7, preferably 5:6; Preferably, the conditions of the second reaction include: temperature of 24-26° C. and time of 5 h.

9. The method according to any one of claims 6 to 8, wherein: In the step (3), the fourth solvent is selected from at least one of dichloromethane, dichloroethane, chloroform and toluene, preferably dichloromethane; Preferably, the catalyst is selected from at least one of N,N-dimethylformamide, N,N-dimethylacetamide and N,N-diethylformamide, preferably N,N-dimethylformamide; Preferably, 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; Preferably, the conditions of the third reaction include: temperature is room temperature, and time is 1 hour.

10. Use of the benzoic acid thioester compound according to any one of claims 1 to 3 or the benzoic acid thioester compound obtained by the preparation method according to any one of claims 4 to 9 as a fungicide; Preferably, the benzoic acid thioester compounds are used to prevent and control soybean rust and wheat fusarium head blight.

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