Preparation method and application of indole C2-position derivative containing 1, 3, 4-oxadiazole and thioether structure

Abstract

The invention discloses a preparation method and application of an indole C2-position derivative containing a 1, 3, 4-oxadiazole and thioether structure. The compound can be used for effectively preventing and treating bacterial diseases such as kiwi fruit canker pathogen, citrus canker pathogen and rice bacterial blight pathogen. Wherein the EC50 value of the compound 2-((2-fluorophenyl) sulfo)-5-(1H-indol-2-yl)-1, 3, 4-oxadiazole on pathogenic bacteria of the kiwifruit canker is 27.35 mu g / mL, and the prevention and treatment effect is the best; the EC50 values of the compound 2-(1H-indole-2-yl)-5-((4-trifluoromethoxy-phenyl) sulfo)-1, 3, 4-oxadiazole on pathogenic bacteria of citrus canker and pathogenic bacteria of rice bacterial blight are 32.94 mu g / mL and 49.52 mu g / mL respectively, and the control effect is the most ideal. The pesticide composition is obviously superior to control pesticides such as bismerthiazol and thiediazole copper. The indole C2-site derivative containing the 1, 3, 4-oxadiazole and thioether structure can be applied to prevention and treatment of bacterial diseases of crops, and is simple in structure, convenient in preparation process, low in production cost and wide in application prospect.

Description

Technical Field

[0001] The present invention relates to the field of chemical engineering technology, specifically to indole C2 derivatives containing 1,3,4-oxadiazole and thioether structures, and also to a preparation method of indole C2 derivatives containing 1,3,4-oxadiazole and thioether structures, and an application of the indole C2 derivatives containing 1,3,4-oxadiazole and thioether structures in the preparation of drugs for preventing and treating plant bacterial diseases. Background Art

[0002] Plant bacterial diseases are diseases caused by bacteria infecting plants. For example, kiwifruit canker, citrus canker and rice bacterial blight are all globally important bacterial diseases, which are characterized by rapid onset, great harm and wide distribution. So far, there is no effective control agent.

[0003] At present, using chemical agents to control kiwifruit canker, citrus canker and rice bacterial blight is still a commonly used method. However, the long-term use of traditional chemical pesticides will also bring many problems: such as cross-resistance, killing beneficial microorganisms, etc. This series of problems also force people to continuously increase the use of chemical pesticides. In this way, the ecological environment is damaged more and more seriously.

[0004] Natural products have been proven to be a valuable resource in the new chemical field, providing inspiration for the discovery of new pesticides with unique structures and mechanisms of action. Indole and its derivatives are a highly regarded heterocyclic skeleton, which are widely present in naturally occurring substances and various bioactive compounds. This unique structural motif plays a crucial role in the fields of organic chemistry and biochemistry. Many compounds containing an indole skeleton in their structural framework have been firmly proven to have a wide range of biological activities. These activities cover a variety of important biological functions. Notably, they include anti-cancer, antibacterial, antifungal, antioxidant and antiviral properties.

[0005] The 1,3,4-oxadiazole group, as a specific heterocyclic compound with two nitrogen atoms and one oxygen atom, plays an important role as a basic building block in the fields of natural products and drug molecules. Its unique structural features endow it with a wide range of biological activities, including antioxidant activity, insecticidal activity, antiviral activity, herbicidal activity, antibacterial activity and antifungal activity. At the same time, thioether compounds, as a class of interesting organic compounds, are characterized by forming a thioether bond by connecting two alkyl or aryl groups through a sulfur atom. Thioethers have diverse chemical properties and reaction activities, and thus are used as important intermediates in many synthesis processes.

[0006] Based on the previous work of our research group, this invention mainly uses 5-substituted indole-2-carboxylic acid as the raw material to design and synthesize a series of novel indole C2-position derivatives containing 1,3,4-oxadiazole and thioether structures. The turbidimetry method was used to determine the in vitro biological activities of the target compounds against Pseudomonas syringae pv. actinidiae, Xanthomonas axonopodis pv. citri, and Xanthomonas oryzae pv. oryzae. Among them, the EC 50 value of compound 2-((2-fluorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (5c) against the pathogen of kiwifruit canker is 27.35 μg / mL, and the control effect is the best; the EC 50 values of compound 2-(1H-indol-2-yl)-5-((4-trifluoromethoxyphenyl)thio)-1,3,4-oxadiazole (5o) against the pathogens of citrus canker and rice bacterial blight are 32.94 μg / mL and 49.52 μg / mL respectively, and the control effect is the most ideal, which is significantly better than the control agents bismerthiazol and thiodiazole copper. SUMMARY OF THE INVENTION

[0007] Aiming at the deficiencies of the prior art, the purpose of this invention is to provide indole C2-position derivatives containing 1,3,4-oxadiazole and thioether structures, as well as their applications in the preparation of drugs for preventing and treating bacterial diseases such as kiwifruit canker, citrus canker, and rice bacterial blight.

[0008] The technical solution adopted in this invention is an indole C2-position derivative containing 1,3,4-oxadiazole and thioether structures, which has the following general formula:

[0009]

[0010] In formula (I): R 1 The substituent is hydrogen, chlorine, R 2 The substituent is phenyl, 2-methylphenyl, 2-fluorophenyl, 2-chlorophenyl, 3-methylphenyl, 3-methoxyphenyl, 3-fluorophenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 3,4-dimethylphenyl, 3,5-dimethoxyphenyl, 3,4-dichlorophenyl;

[0011] The specific compounds are:

[0012] Compound 5a: 2-benzylthio-5-(1H-indol-2-yl)-2-1,3,4-oxadiazole;

[0013] Compound 5b: 2-(1H-indol-2-yl)-5-((2-methylphenyl)thio)-1,3,4-oxadiazole;

[0014] Compound 5c: 2-((2-fluorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole;

[0015] Compound 5d: 2-((2-chlorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole;

[0016] Compound 5e: 2-(1H-indol-2-yl)-5-((3-methylphenyl)thio)-1,3,4-oxadiazole;

[0017] Compound 5f: 2-(1H-indol-2-yl)-5-((3-methoxyphenyl)thio)-1,3,4-oxadiazole;

[0018] Compound 5g: 2-((3-fluorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole;

[0019] Compound 5h: 2-(1H-indol-2-yl)-5-((4-methylphenyl)thio)-1,3,4-oxadiazole;

[0020] Compound 5i: 2-((4-tert-butylphenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole;

[0021] Compound 5j: 2-(1H-indol-2-yl)-5-((4-methoxyphenyl)thio)-1,3,4-oxadiazole;

[0022] Compound 5k: 2-((4-fluorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole;

[0023] Compound 5l: 2-((4-chlorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole;

[0024] Compound 5m: 2-((4-bromophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole;

[0025] Compound 5n: 4-(((5-(1H-indol-2-yl)-1,3,4-oxadiazol-2-yl)thio)methyl)-benzonitrile;

[0026] Compound 5o: 2-(1H-indol-2-yl)-5-((4-(trifluoromethyl)phenyl)thio)-1,3,4-oxadiazole;

[0027] Compound 5p: 2-((3,4-dimethylphenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole;

[0028] Compound 5q: 2-((3,4-dichlorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole;

[0029] Compound 5r: 2-((3,5-dimethoxyphenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole;

[0030] Compound 5s: 2-(5-chloro-1H-indol-2-yl)-5-((4-chlorophenyl)thio)-1,3,4-oxadiazole;

[0031] Compound 5t: 2-(5-chloro-1H-indol-2-yl)-5-((3,4-dichlorophenyl)thio)-1,3,4-oxadiazole.

[0032] The synthetic route of the above-mentioned indole C2-position derivatives containing 1,3,4-oxadiazole and thioether structures is as follows:

[0033]

[0034] The preparation method of the indole C2-position derivatives containing 1,3,4-oxadiazole and thioether structures for preventing and controlling crop bacterial diseases according to the present invention, and the preparation steps of the indole C2-position derivatives containing 1,3,4-oxadiazole and thioether structures are as follows:

[0035] (1) Synthesis of intermediate 5-substituted-2-methyl indole-2-carboxylate (2):

[0036] Add an appropriate amount of substituted indole-2-carboxylic acid to a flask containing methanol, and add a small amount of concentrated sulfuric acid as a catalyst thereto. React at 75 - 80 °C in an oil bath for 3 - 4 h. After the reaction is completed, distill off methanol under reduced pressure, and recrystallize the residue with methanol to obtain intermediate 2;

[0037] (2) Synthesis of intermediate 5-substituted-2-formylhydrazide indole (3):

[0038] Add an appropriate amount of intermediate 2, hydrazine hydrate and methanol to a beaker in sequence, and reflux for 5 - 7 h. After the reaction is completed, cool the reaction solution to room temperature to precipitate a solid, filter by suction, and recrystallize the filter cake with anhydrous methanol to obtain intermediate 3;

[0039] (3) Synthesis of intermediate 5-substituted-2-(5-mercapto-1,3,4-oxadiazol-2-yl)-indole (4):

[0040] Add appropriate amounts of intermediate 3, potassium hydroxide, absolute ethanol and water into a flask in sequence, stir at room temperature, wait until the solid is completely dissolved, then slowly add an appropriate amount of carbon disulfide, and then heat to reflux for 6 - 8 h. Monitor the reaction by TLC. After the reaction is completed, remove the solvent ethanol under reduced pressure, adjust to pH = 1 or so with 5% dilute hydrochloric acid to obtain a white solid. Filter by suction and dry, and then recrystallize with absolute ethanol to obtain intermediate 4;

[0041] (4) Synthesis of the target compound 5 - substituted - 2 - (5 - substituted mercapto - 1,3,4 - oxadiazol - 2 - yl) - indole (5):

[0042] Add appropriate amounts of intermediate 4, ethanol and triethylamine into a flask in sequence, stir at room temperature for 30 min. After the solid is completely dissolved, add an appropriate amount of RCH2X, and continue to stir at room temperature for 3 - 5 h. Monitor the reaction by TLC. After the reaction is completed, pour the reaction into an appropriate amount of ice water, filter by suction and dry, and then recrystallize with absolute ethanol to obtain the target compound 5.

[0043] The substituted indole - 2 - carboxylic acid described in the present invention is indole - 2 - carboxylic acid and 5 - chloroindole - 2 - carboxylic acid.

[0044] The R described in the present invention 2 CH2X is benzyl chloride, 2 - methylbenzyl chloride, 2 - fluorobenzyl chloride, 2 - chlorobenzyl chloride, 3 - methylbenzyl chloride, 3 - methoxybenzyl chloride, 3 - fluorobenzyl chloride, 4 - methylbenzyl chloride, 4 - tert - butylbenzyl chloride, 4 - methoxybenzyl chloride, 4 - fluorobenzyl chloride, 4 - chlorobenzyl chloride, 4 - bromobenzyl chloride, 4 - cyanobenzyl chloride, 4 - trifluoromethylbenzyl chloride, 3,4 - dimethylbenzyl chloride, 3,5 - dimethoxybenzyl chloride, 3,4 - dichlorobenzyl chloride.

[0045] The application of the indole C2 - position derivative containing 1,3,4 - oxadiazole and thioether structures in the present invention in the preparation of drugs for preventing and treating plant bacterial diseases, and the plant bacterial diseases are kiwifruit canker, citrus canker and rice bacterial blight.

[0046] The present invention uses substituted indole - 2 - carboxylic acid as a raw material to synthesize a series of indole C2 - position derivatives containing 1,3,4 - oxadiazole and thioether structures, and uses the turbidity method to determine their in vitro biological activities against the pathogens of kiwifruit canker, citrus canker and rice bacterial blight. The results of biological activity determination show that: most of the compounds have good in vitro biological activities against the pathogens of kiwifruit canker, citrus canker and rice bacterial blight. Among them, the EC of the compound 2 - ((2 - fluorophenyl)thio) - 5 - (1H - indol - 2 - yl) - 1,3,4 - oxadiazole against the pathogen of kiwifruit canker 50The value is 27.35 ug / mL, and the control effect is the best; the EC of compound 2-(1H-indol-2-yl)-5-((4-trifluoromethoxyphenyl)thio)-1,3,4-oxadiazole against the pathogen of citrus canker and the pathogen of rice bacterial blight 50 values are 32.94 ug / mL and 49.52 ug / mL respectively, and the control effect is the most ideal, significantly better than the control agents bismerthiazol and thiodiazole copper. Specific implementation manners

[0047] Example 1:

[0048] Taking compound 2-benzylthio-5-(1H-indol-2-yl)-2-1,3,4-oxadiazole (compound 5a) of the present invention as an example to illustrate the preparation of the target compound, and referring to the synthesis of other different substituents by this example.

[0049] The preparation method of 2-benzylthio-5-(1H-indol-2-yl)-2-1,3,4-oxadiazole (compound 5a) includes the following steps:

[0050] (1) Synthesis of intermediate methyl indole-2-carboxylate (2):

[0051] Add 10 mmol of indole-2-carboxylic acid to a 100 mL flask containing 50 mL of methanol, and add 1 mL of concentrated sulfuric acid as a catalyst thereto. React at 75 °C in an oil bath for 4 h. After the reaction is completed, distill off methanol under reduced pressure. The residue is recrystallized with methanol to obtain the intermediate methyl indole-2-carboxylate;

[0052] (2) Synthesis of intermediate indole-2-carbohydrazide (3):

[0053] Add 10 mmol of intermediate methyl indole-2-carboxylate, 15 mmol of hydrazine hydrate and 10 mL of methanol to a 100 mL beaker in sequence, and reflux for 5 h. After the reaction is completed, cool the reaction solution to room temperature to precipitate a solid, filter by suction, and recrystallize the filter cake with anhydrous methanol to obtain the intermediate indole-2-carbohydrazide;

[0054] (3) Synthesis of intermediate 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-indole (4):

[0055] In a 100 mL flask, 10 mmol of the intermediate indole-2-carbohydrazide, 15 mmol of potassium hydroxide, 10 mL of absolute ethanol and 4 mL of water were successively added. Stir at room temperature until the solid is completely dissolved. Then, 20 mmol of carbon disulfide was slowly added dropwise, and the temperature was raised to reflux for 8 h. The reaction was monitored by TLC. After the reaction was completed, the solvent ethanol was removed under reduced pressure, and the pH was adjusted to about 1 with 5% dilute hydrochloric acid to obtain a white solid. The solid was filtered by suction, dried, and then recrystallized with absolute ethanol to obtain the intermediate 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-indole;

[0056] (4) Synthesis of the target compound 2-benzylthio-5-(1H-indol-2-yl)-2-1,3,4-oxadiazole (5):

[0057] In a 100 mL flask, 10 mmol of the intermediate 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-indole, 30 mL of ethanol and 13 mmol of triethylamine were successively added. Stir at room temperature for 30 min. After the solid was completely dissolved, 12 mmol of benzyl chloride was added, and the reaction was continued to stir at room temperature for 3 h. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was poured into an appropriate amount of ice water, filtered by suction, dried, and then recrystallized with absolute ethanol to obtain the target compound 2-benzylthio-5-(1H-indol-2-yl)-2-1,3,4-oxadiazole (Compound 5a).

[0058] Example 2:

[0059] The preparation method of 2-(1H-indol-2-yl)-5-((2-methylphenyl)thio)-1,3,4-oxadiazole (Compound 5b) includes the following steps;

[0060] Compound 5b can be obtained by modifying the corresponding reactants and reaction parameters according to the steps of Example 1.

[0061] Example 3:

[0062] The preparation method of 2-((2-fluorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (Compound 5c) includes the following steps;

[0063] Compound 5c can be obtained by modifying the corresponding reactants and reaction parameters according to the steps of Example 1.

[0064] Example 4:

[0065] The preparation method of 2-((2-chlorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (Compound 5d) includes the following steps;

[0066] Compound 5d can be obtained by modifying the corresponding reactants and reaction parameters according to the steps of Example 1.

[0067] Example 5:

[0068] A method for preparing 2-(1H-indol-2-yl)-5-((3-methylphenyl)thio)-1,3,4-oxadiazole (Compound 5e), comprising the following steps;

[0069] Compound 5e can be obtained by modifying the corresponding reactants and reaction parameters according to the steps of Example 1.

[0070] Example 6:

[0071] A method for preparing 2-(1H-indol-2-yl)-5-((3-methoxyphenyl)thio)-1,3,4-oxadiazole (Compound 5f), comprising the following steps;

[0072] Compound 5f can be obtained by modifying the corresponding reactants and reaction parameters according to the steps of Example 1.

[0073] Example 7:

[0074] A method for preparing 2-((3-fluorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (Compound 5g), comprising the following steps;

[0075] Compound 5g can be obtained by modifying the corresponding reactants and reaction parameters according to the steps of Example 1.

[0076] Example 8:

[0077] A method for preparing 2-(1H-indol-2-yl)-5-((4-methylphenyl)thio)-1,3,4-oxadiazole (Compound 5h), comprising the following steps;

[0078] Compound 5h can be obtained by modifying the corresponding reactants and reaction parameters according to the steps of Example 1.

[0079] Example 9:

[0080] A method for preparing 2-((4-tert-butylphenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (Compound 5i), comprising the following steps;

[0081] Compound 5i can be obtained by modifying the corresponding reactants and reaction parameters according to the steps of Example 1.

[0082] Example 10:

[0083] Preparation method of 2-(1H-indol-2-yl)-5-((4-methoxyphenyl)thio)-1,3,4-oxadiazole (Compound 5j), comprising the following steps;

[0084] Compound 5j can be obtained by modifying the corresponding reactants and reaction parameters with reference to the steps of Example 1.

[0085] Example 11:

[0086] Preparation method of 2-((4-fluorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (Compound 5k), comprising the following steps;

[0087] Compound 5k can be obtained by modifying the corresponding reactants and reaction parameters with reference to the steps of Example 1.

[0088] Example 12:

[0089] Preparation method of 2-((4-chlorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (Compound 5l), comprising the following steps;

[0090] Compound 5l can be obtained by modifying the corresponding reactants and reaction parameters with reference to the steps of Example 1.

[0091] Example 13:

[0092] Preparation method of 2-((4-bromophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (Compound 5m), comprising the following steps;

[0093] Compound 5m can be obtained by modifying the corresponding reactants and reaction parameters with reference to the steps of Example 1.

[0094] Example 14:

[0095] Preparation method of 4-(((5-(1H-indol-2-yl)-1,3,4-oxadiazol-2-yl)thio)methyl)benzonitrile (Compound 5n), comprising the following steps;

[0096] Compound 5n can be obtained by modifying the corresponding reactants and reaction parameters with reference to the steps of Example 1.

[0097] Example 15:

[0098] Preparation method of 2-(1H-indol-2-yl)-5-((4-(trifluoromethyl)phenyl)thio)-1,3,4-oxadiazole (Compound 5o), comprising the following steps;

[0099] Compound 5o can be obtained by modifying the corresponding reactants and reaction parameters with reference to the steps of Example 1.

[0100] Example 16:

[0101] A preparation method of 2-((3,4-dimethylphenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (Compound 5p) comprises the following steps;

[0102] Compound 5p can be obtained by modifying the corresponding reactants and reaction parameters with reference to the steps of Example 1.

[0103] Example 17:

[0104] A preparation method of 2-((3,4-dichlorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (Compound 5q) comprises the following steps;

[0105] Compound 5q can be obtained by modifying the corresponding reactants and reaction parameters with reference to the steps of Example 1.

[0106] Example 18:

[0107] A preparation method of 2-((3,5-dimethoxyphenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (Compound 5r) comprises the following steps;

[0108] Compound 5r can be obtained by modifying the corresponding reactants and reaction parameters with reference to the steps of Example 1.

[0109] Example 19:

[0110] A preparation method of 2-(5-chloro-1H-indol-2-yl)-5-((4-chlorophenyl)thio)-1,3,4-oxadiazole (Compound 5s) comprises the following steps;

[0111] Compound 5s can be obtained by modifying the corresponding reactants and reaction parameters with reference to the steps of Example 1.

[0112] Example 20:

[0113] A preparation method of 2-(5-chloro-1H-indol-2-yl)-5-((3,4-dichlorophenyl)thio)-1,3,4-oxadiazole (Compound 5t) comprises the following steps;

[0114] Compound 5t can be obtained by modifying the corresponding reactants and reaction parameters with reference to the steps of Example 1.

[0115] The structural formulas, physicochemical properties and spectral information of the target compounds prepared in the above Examples 1-20 are as follows:

[0116]

[0117] 2-Benzylthio-5-(1H-indol-2-yl)-1,3,4-oxadiazole (5a). White solid; yield 86%, melting point 158.8 - 159.1 °C; 1 H NMR (400 MHz, DMSO-d6) δ 12.24 (s, 1H), 7.68 (d, J = 9.1 Hz, 1H), 7.52–7.46 (m, 3H), 7.36 (t, J = 7.3 Hz, 2H), 7.33–7.24 (m, 2H), 7.19 (s, 1H), 7.11 (t, J = 7.5 Hz, 1H), 4.61 (s, 2H); 13 C NMR (101 MHz, DMSO-d6) δ 163.0, 161.0, 138.2, 137.0, 129.5, 129.1, 128.3, 127.7, 124.8, 122.0, 121.1, 120.9, 112.7, 105.5, 36.5; HRMS (ESI, m / z): Mass calcd. for C 17 H 14 N3OS + [M + H] + 308.0852, found 308.0850.

[0118]

[0119] 2-(1H-Indol-2-yl)-5-((2-methylphenyl)thio)-1,3,4-oxadiazole (5b). White solid; yield 80%, melting point 122.0 - 122.7 °C; 1 HNMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 8.3 Hz, 1H), 7.42 (d, J = 7.4 Hz, 1H), 7.30–7.15 (m, 5H), 7.14–7.08 (m, 1H), 4.62 (s, 2H), 2.42 (s, 3H); 13 CNMR (101 MHz, DMSO-d6) δ 162.8, 161.1, 138.2, 137.4, 134.2, 131.0, 130.5, 128.8, 127.7, 126.6, 124.8, 122.0, 121.1, 120.9, 112.7, 105.5, 35.2, 19.2; HRMS (ESI, m / z): Mass calcd. for C 18 H 16 N3OS + [M + H] +322.1009, found 322.1006.

[0120]

[0121] 2-Benzylthio-5-(1H-indol-2-yl)-1,3,4-oxadiazole (5c). White solid; yield 90%, melting point 97.5 - 98.3 °C; 1 HNMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 7.68 (d, J = 7.9 Hz, 1H), 7.58 (t, J = 7.7 Hz, 1H), 7.49 (d, J = 8.5 Hz, 1H), 7.42–7.33 (m, 1H), 7.31–7.15 (m, 4H), 7.11 (t, J = 7.0 Hz, 1H), 4.63 (s, 2H); 13 CNMR (101 MHz, DMSO-d6) δ 162.1, 161.3, 161.1 (d, J = 284.8 Hz), 138.3, 131.9 (d, J = 3.5 Hz), 130.8 (d, J = 8.2 Hz), 127.7, 125.2, 125.1, 124.8, 124.0 (d, J = 14.5 Hz), 122.0, 121.0 (d, J = 17.5 Hz), 116.0 (d, J = 21.0 Hz), 112.8, 105.6, 30.5; 19 FNMR (377 MHz, DMSO-d6) δ -116.90; HRMS (ESI, m / z): Mass calcd. for C 17 H 13 FN3OS + [M + H] + 326.0758, found 326.0761.

[0122]

[0123] 2-((2-Chlorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (5d). White solid; yield 84%, melting point 170.5 - 171.6 °C; 1 HNMR (400 MHz, DMSO-d6) δ 12.26 (s, 1H), 7.70–7.62 (m, 2H), 7.55–7.46 (m, 2H), 7.40–7.32 (m, 2H), 7.27 (t, J = 8.2 Hz, 1H), 7.20 (s, 1H), 7.11 (t, J = 7.0 Hz, 1H), 4.68 (s, 2H); 13 CNMR(101 MHz, DMSO-d6) δ 162.48, 161.28, 138.27, 134.31, 133.83, 132.06, 130.53, 130.15, 128.02, 127.71, 124.82, 121.99, 121.06, 120.89, 112.76, 105.60, 34.93; HRMS(ESI, m / z): Mass calcd. for C 17 H 13 ClN3OS + [M + H] + 342.0462, found 342.0465.

[0124]

[0125] 2-(1H-Indol-2-yl)-5-((3-methylphenyl)thio)-1,3,4-oxadiazole 5e: White solid; yield 81%, melting point 246.1 - 246.7 °C; 1 1H NMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 7.68 (d, J = 8.1 Hz, 1H), 7.49 (d, J = 9.3 Hz, 1H), 7.32–7.18 (m, 5H), 7.14–7.07 (m, 2H), 4.57 (s, 2H), 2.28 (s, 3H); 13 13C NMR (101 MHz, DMSO-d6) δ 163.0, 161.0, 138.3, 138.2, 136.7, 130.1, 129.0, 129.0, 127.7, 126.6, 124.8, 121.9, 121.1, 120.9, 112.7, 105.5, 36.6, 21.4; HRMS(ESI, m / z): Mass calcd. for C 18 H 16 N3OS + [M + H] + 322.1009, found 322.1007.

[0126]

[0127] 2-(1H-Indol-2-yl)-5-((3-methoxyphenyl)thio)-1,3,4-oxadiazole (5f). White solid; yield 82%, melting point 108.1 - 108.7 °C; 11H NMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 7.68 (d, J = 7.0 Hz, 1H), 7.49 (d, J = 7.3 Hz, 1H), 7.30–7.24 (m, 2H), 7.20 (s, 1H), 7.14–7.04 (m, 3H), 6.87 (d, J = 10.8 Hz, 1H), 4.58 (s, 2H), 3.73 (s, 3H); 13 13C NMR (101 MHz, DMSO-d6) δ 163.0, 161.0, 159.8, 138.4, 138.2, 130.2, 127.7, 124.8, 122.0, 121.7, 121.1, 120.9, 115.2, 113.8, 112.7, 105.5, 55.5, 36.5; HRMS (ESI, m / z): Mass calcd. for C 18 H 16 N3O2S + [M + H] + 338.0958, found 338.0957.

[0128]

[0129] 2-((3-Fluorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (5 g) White solid; Yield 81%, melting point 138.4 - 139.3 °C; 1 1H NMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.3 Hz, 1H), 7.39 (dt, J = 22.1, 8.1 Hz, 3H), 7.28 (t, J = 7.0 Hz, 1H), 7.21–7.08 (m, 3H), 4.63 (s, 2H); 13 13C NMR (101 MHz, DMSO-d6) δ 163.7, 162.1 (d, J = 158.4 Hz), 161.1, 140.0 (d, J = 7.7 Hz), 138.3, 131.1, 131.0, 127.7, 125.7 (d, J = 2.6 Hz), 124.8, 122.0, 121.0 (d, J = 19.8 Hz), 116.3 (d, J = 22.2 Hz), 115.1 (d, J = 20.6 Hz), 112.8, 105.5, 35.8; 19 19F NMR (377 MHz, DMSO-d6) δ -112.94; HRMS (ESI, m / z): Mass calcd. for C 17 H13 FN3OS + [M+H] + 326.0758, found 326.0758.

[0130]

[0131] 2-(1H-Indol-2-yl)-5-((4-methylphenyl)thio)-1,3,4-oxadiazole (5h). White solid; yield 76%, melting point 171.2 - 172.3 °C; 1 H NMR (400 MHz, DMSO-d6) δ 12.24 (s, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 8.1 Hz, 1H), 7.37 (d, J = 8.0 Hz, 2H), 7.27 (t, J = 8.3 Hz, 1H), 7.22–7.14 (m, 3H), 7.11 (t, J = 8.0 Hz, 1H), 4.56 (s, 2H), 2.27 (s, 3H); 13 C NMR (101 MHz, DMSO-d6) δ 163.0, 161.0, 138.2, 137.6, 133.8, 129.7, 129.5, 127.7, 124.8, 122.0, 121.1, 120.9, 112.7, 105.5, 36.4, 21.2; HRMS (ESI, m / z): Mass calcd. for C 18 H 16 N3OS + [M+H] + 344.0828, found 344.0819.

[0132]

[0133] 2-((4-tert-Butylphenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (5i). White solid; yield 83%, melting point 105.8 - 106.1 °C; 1 H NMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 7.67 (d, J = 7.0 Hz, 1H), 7.49 (d, J = 9.2 Hz, 1H), 7.44–7.35 (m, 4H), 7.27 (t, J = 7.0 Hz, 1H), 7.19 (s, 1H), 7.11 (t, J = 7.5 Hz, 1H), 4.58 (s, 2H), 1.25 (s, 9H); 1313C NMR (101 MHz, DMSO-d6) δ 163.1, 161.0, 150.8, 138.2, 133.8, 129.3, 127.7, 125.9, 124.8, 121.9, 121.1, 120.9, 112.7, 105.5, 36.2, 34.7, 31.5; HRMS (ESI, m / z): Mass calcd. for C 21 H 22 N3OS + [M + H] + 386.1298, found 386.1297.

[0134]

[0135] 2-(1H-Indol-2-yl)-5-((4-methoxyphenyl)thio)-1,3,4-oxadiazole (5j). White solid; yield 80%, melting point 100.5 - 101.8 °C; 1 1H NMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 7.68 (d, J = 8.1 Hz, 1H), 7.49 (d, J = 7.2 Hz, 1H), 7.42 (d, J = 8.7 Hz, 2H), 7.27 (t, J = 7.7 Hz, 1H), 7.20 (s, 1H), 7.11 (t, J = 7.5 Hz, 1H), 6.91 (d, J = 8.7 Hz, 2H), 4.56 (s, 2H), 3.73 (s, 3H); 13 13C NMR (101 MHz, DMSO-d6) δ 163.1, 161.0, 159.4, 138.2, 130.9, 128.6, 127.7, 124.8, 122.0, 121.1, 120.9, 114.5, 112.7, 105.5, 55.6, 36.3; HRMS (ESI, m / z): Mass calcd. for C 18 H 15 N3O2SNa + [M + Na] + 360.0777, found 360.0775.

[0136]

[0137] 2-((4-Fluorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (5k). White solid; yield 78%, melting point 144.1 - 144.3 °C; 11H NMR (400 MHz, DMSO-d6) δ 12.26 (s, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.59–7.48 (m, 3H), 7.31–7.25 (m, 1H), 7.20 (t, J = 8.9 Hz, 3H), 7.12 (t, J = 7.5 Hz, 1H), 4.61 (s, 2H); 13 13C NMR (101 MHz, DMSO-d6) δ 163.4, 162.0 (d, J = 186.9 Hz), 160.9, 138.3, 133.3 (d, J = 3.0 Hz), 131.6 (d, J = 8.3 Hz), 127.7, 124.8, 122.0, 121.0 (d, J = 22.5 Hz), 115.9 (d, J = 21.7 Hz), 112.7, 105.5, 35.7; 19 19F NMR (377 MHz, DMSO-d6) δ -114.27; HRMS (ESI, m / z): Mass calcd. for C 17 H 13 FN3OS + [M + H] + 326.0758, found 326.0758.

[0138]

[0139] 2-((4-Chlorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (5l). White solid; yield 75%, melting point 160.8 - 161.3 °C; 1 1H NMR (400 MHz, DMSO-d6) δ 12.22 (s, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 8.5 Hz, 2H), 7.47 (d, J = 9.3 Hz, 1H), 7.42 (d, J = 8.5 Hz, 2H), 7.27 (t, J = 7.6 Hz, 1H), 7.18 (s, 1H), 7.11 (t, J = 7.0 Hz, 1H), 4.60 (s, 2H); 13 13C NMR (101 MHz, DMSO-d6) δ 162.8, 161.1, 138.2, 136.3, 132.9, 131.4, 129.1, 127.7, 124.8, 122.0, 121.0, 120.9, 112.7, 105.5, 35.7; HRMS (ESI, m / z): Mass calcd. for C 17 H 13 ClN3OS + [M + H]+ 342.0462, found 342.0454.

[0140]

[0141] 2-((4-Bromophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (5m). White solid; yield 76%, melting point 133.7 - 134.7 °C; 1 H NMR (400 MHz, DMSO-d6) δ 12.22 (s, 1H), 7.67 (d, J = 6.9 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.50–7.43 (m, 3H), 7.29–7.24 (m, 1H), 7.18 (s, 1H), 7.11 (t, J = 8.0 Hz, 1H), 4.58 (s, 2H); 13 C NMR (101 MHz, DMSO-d6) δ 162.8, 161.1, 138.2, 136.7, 132.0, 131.7, 127.7, 124.8, 122.0, 121.5, 121.0, 120.9, 112.7, 105.5, 35.7; HRMS (ESI, m / z): Mass calcd. for C 17 H 13 BrN3OS + [M + H] + 385.9957, found 385.9961.

[0142]

[0143] 4-(((5-(1H-Indol-2-yl)-1,3,4-oxadiazol-2-yl)-thio)-methyl)-benzonitrile (5n). White solid; yield 79%, melting point 103.4 - 104.7 °C; 1 H NMR (400 MHz, DMSO-d6) δ 12.23 (s, 1H), 7.84 (d, J = 8.4 Hz, 2H), 7.69 (dd, J = 13.1, 8.2 Hz, 3H), 7.48 (d, J = 8.3 Hz, 1H), 7.27 (t, J = 7.0 Hz, 1H), 7.18 (s, 1H), 7.11 (t, J = 7.0 Hz, 1H), 4.68 (s, 2H); 13¹³C NMR (101 MHz, DMSO-d₆) δ 162.7, 161.2, 143.2, 138.2, 133.0, 130.5, 127.7, 124.8, 122.0, 121.0, 120.9, 119.1, 112.7, 111.0, 105.9, 35.9; HRMS (ESI, m / z): Mass calcd. for C 18 H 13 N₄OS + [M + H] + 333.0805, found 333.0801.

[0144]

[0145] 2-(1H-Indol-2-yl)-5-((4-(trifluoromethoxy)phenyl)thio)-1,3,4-oxadiazole (5o). White solid; yield 73%, melting point 106.4 - 107.1 °C; 1 ¹H NMR (400 MHz, DMSO-d₆) δ 12.23 (s, 1H), 7.74 (s, 4H), 7.67 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 8.1 Hz, 1H), 7.27 (t, J = 7.7 Hz, 1H), 7.17 (s, 1H), 7.11 (t, J = 7.5 Hz, 1H), 4.70 (s, 2H); 13 ¹³C NMR (101 MHz, DMSO-d₆) δ 162.7, 161.1, 142.3, 138.2, 130.3, 127.7, 126.0 (q, J = 4.2, 3.8 Hz), 124.8, 121.9, 121.0, 120.9, 112.7, 105.6, 35.7; HRMS (ESI, m / z): Mass calcd. for C 18 H 13 F₃N₃OS + [M + H] + 376.0726, found 376.0724.

[0146]

[0147] 2-((3,4-Dimethylphenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (5p). White solid; yield 86%, melting point 129.1 - 129.7 °C; 11H NMR (400 MHz, DMSO-d6) δ 12.24 (s, 1H), 7.68 (d, J = 8.1 Hz, 1H), 7.49 (d, J = 8.3 Hz, 1H), 7.30–7.23 (m, 2H), 7.19 (s, 2H), 7.14–7.06 (m, 2H), 4.53 (s, 2H), 2.18 (d, J = 3.6 Hz, 6H); 13 13C NMR (101 MHz, DMSO-d6) δ 163.0, 161.1, 138.2, 136.9, 135.1, 134.0, 130.6, 130.2, 127.7, 127.0, 124.8, 122.0, 120.9, 112.7, 105.5, 36.4, 19.8, 19.5; HRMS (ESI, m / z): Mass calcd. for C 19 H 17 N3OSNa + [M+Na] + 358.0985, found 358.0983.

[0148]

[0149] 2-((3,4-Dichlorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (5q). White solid; yield 85%, melting point 159.1 - 159.3 °C; 1 1H NMR (400 MHz, DMSO-d6) δ 12.24 (s, 1H), 7.81 (d, J = 2.1 Hz, 1H), 7.65 (dd, J = 17.5, 8.2 Hz, 2H), 7.50 (dd, J = 12.5, 8.2 Hz, 2H), 7.27 (t, J = 7.6 Hz, 1H), 7.18 (s, 1H), 7.11 (t, J = 7.5 Hz, 1H), 4.60 (s, 2H); 13 13C NMR (101 MHz, DMSO-d6) δ 162.7, 161.2, 138.7, 138.2, 131.6, 131.4, 131.2, 130.9, 129.9, 127.7, 124.8, 122.0, 121.0, 120.9, 112.7, 105.6, 35.1; HRMS (ESI, m / z): Mass calcd. for C 17 H 12 Cl2N3OS + [M+H] + 376.0073, found 376.0066.

[0150]

[0151] 2-((3,5-Dimethoxyphenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole (5r). White solid; yield 84%, melting point 136.3 - 136.5 °C; 1 H NMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 7.68 (d, J = 9.1 Hz, 1H), 7.49 (d, J = 9.3 Hz, 1H), 7.27 (t, J = 8.2 Hz, 1H), 7.20 (s, 1H), 7.11 (t, J = 7.5 Hz, 1H), 6.67 (d, J = 2.3 Hz, 2H), 6.44 (t, J = 2.3 Hz, 1H), 4.53 (s, 2H), 3.72 (s, 6H); 13 C NMR (101 MHz, DMSO-d6) δ 163.0, 161.0, 161.0, 139.1, 138.2, 127.7, 124.8, 121.9, 121.1, 120.9, 112.7, 107.5, 105.5, 100.0, 55.6, 36.7; HRMS (ESI, m / z): Mass calcd. for C 19 H 18 N3O3S + [M + H] + 368.1063, found 368.1064.

[0152]

[0153] 2-(5-Chloro-1H-indol-2-yl)-5-((4-chlorophenyl)thio)-1,3,4-oxadiazole (5s). White solid; yield 84%, melting point 136.3 - 136.5 °C; 1 H NMR (400 MHz, DMSO-d6) δ 12.46 (s, 1H), 7.75 (s, 1H), 7.53 (d, J = 8.5 Hz, 2H), 7.49 (d, J = 8.7 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.7 Hz, 1H), 7.17 (s, 1H), 4.61 (s, 2H); 1313C NMR (101 MHz, DMSO-d6) δ 163.2, 160.7, 136.6, 136.2, 132.9, 131.4, 129.1, 128.8, 125.4, 124.9, 122.6, 121.0, 114.3, 105.0, 35.7; HRMS (ESI, m / z): Mass calcd. for C 17 H 12 Cl2N3OS + [M + H] + 376.0073, found 376.0056.

[0154]

[0155] 2-(5-Chloro-1H-indol-2-yl)-5-((3,4-dichlorophenyl)thio)-1,3,4-oxadiazole (5t). White solid; yield 84%, melting point 136.3 - 136.5 °C; 1 HNMR (400 MHz, DMSO-d6) δ 12.45 (s, 1H), 7.81 (s, 1H), 7.74 (s, 1H), 7.63 (d, J = 8.3 Hz, 1H), 7.50 (t, J = 8.5 Hz, 2H), 7.27 (d, J = 8.7 Hz, 1H), 7.16 (s, 1H), 4.60 (s, 2H); 13 13C NMR (101 MHz, DMSO-d6) δ 163.1, 160.8, 138.6, 136.6, 131.6, 131.4, 131.2, 130.9, 129.9, 128.7, 125.4, 124.9, 122.6, 121.0, 114.3, 105.0, 35.1; HRMS (ESI, m / z): Mass calcd. for C 17 H 11 Cl3N3OS+ [M + H] + 409.9683, found 409.9674。

[0156] Experimental Example 1: Determination of the indoor antibacterial activity of the target compounds prepared in Examples 1 - 20

[0157] Kiwi canker pathogen, citrus canker pathogen and rice bacterial blight pathogen will be streaked on NA (beef extract: 3 g, peptone: 5 g, yeast extract: 1 g, glucose: 10 g, agar: 20 g, secondary water: 1 L; adjust the pH to about 7 with 5 mol / L NaOH solution, sterilize at 121 °C for 20 min) solid medium, and cultured at 30 °C until single colonies grow. Pick the single colonies of kiwi canker pathogen, citrus canker pathogen and rice bacterial blight pathogen on the NA solid medium into NB liquid medium (beef extract: 3 g, peptone: 5 g, yeast extract: 1 g, glucose: 10 g, agar: 20 g, secondary water: 1 L; adjust the pH to about 7 with 5 mol / L NaOH solution, sterilize at 121 °C for 20 min), and culture with constant shaking at 28 °C and 180 rpm in a constant temperature shaker until the logarithmic growth phase for standby.

[0158] The target compounds prepared in Examples 1 - 20 and the commercial control agents are respectively formulated into medicated NB liquid media with concentrations of 100 and 50 μg / mL. Add 40 μL of the above-prepared NB liquid medium containing kiwi canker pathogen, citrus canker pathogen and rice bacterial blight pathogen, and culture with constant shaking at 30 °C and 180 rpm in a constant temperature shaker for 24 - 48 h. Measure the OD value (OD 595 ) of the bacterial liquid at each concentration on an enzyme-linked immunosorbent assay (ELISA) reader. Additionally, measure the OD values of the NB liquid media of the agents with concentrations of 100 and 50 μg / mL and the commercial control agent, and correct the OD values caused by the agents themselves. The calculation formulas for the corrected OD value and the inhibition rate are as follows:

[0159] Corrected OD value = OD value of the bacteria-containing medium - OD value of the sterile medium;

[0160] Inhibition rate (%) = (OD value of the bacterial liquid in the corrected control medium - OD value of the bacterial liquid in the corrected toxic medium) / OD value of the bacterial liquid in the corrected control medium × 100;

[0161] Measure the inhibitory activities of the target compounds prepared in Examples 1 - 20 according to the above method, and the results are shown in Tables 1 - 2.

[0162] Table 1 Inhibitory activities of the target compounds prepared in Examples 1 - 20 against kiwi canker pathogen, citrus canker pathogen and rice bacterial blight pathogen

[0163]

[0164] Table 2 EC of the target compounds prepared in Examples 1 - 20 against kiwi canker pathogen, citrus canker pathogen and rice bacterial blight pathogen 50 value

[0165]

[0166] As can be seen from Table 1 and Table 2: Most of the compounds have good in vitro biological activities against the pathogens of kiwifruit canker, citrus canker and rice bacterial blight. Among them, the EC 50 value of the compound 2-((2-fluorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole against the pathogen of kiwifruit canker is 27.35 μg / mL, and the control effect is the best; the EC 50 values of the compound 2-(1H-indol-2-yl)-5-((4-trifluoromethoxyphenyl)thio)-1,3,4-oxadiazole against the pathogens of citrus canker and rice bacterial blight are 32.94 μg / mL and 49.52 μg / mL respectively, and the control effect is the most ideal, which is significantly better than the control agents bismerthiazol and thiodiazole copper. Since the indole C2-position derivatives containing 1,3,4-oxadiazole and thioether structures in the present invention have very similar structures, it can be predicted that other compounds also have certain effects on inhibiting the pathogens of kiwifruit canker, citrus canker and rice bacterial blight.

Claims

1. An indole C2 derivative containing 1,3,4-oxadiazole and thioether structures, characterized in that, Has the following general formula: In formula (I): R 1 The substituent is hydrogen, chlorine, R 2 The substituent is phenyl, 2-methylphenyl, 2-fluorophenyl, 2-chlorophenyl, 3-methylphenyl, 3-methoxyphenyl, 3-fluorophenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 3,4-dimethylphenyl, 3,5-dimethoxyphenyl, 3,4-dichlorophenyl; The specific compounds are as follows: Compound 5a: 2-Benzylthio-5-(1H-indol-2-yl)-1,3,4-oxadiazole; Compound 5b: 2-(1H-Indol-2-yl)-5-((2-methylphenyl)thio)-1,3,4-oxadiazole; Compound 5c: 2-((2-Fluorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole; Compound 5d: 2-((2-Chlorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole; Compound 5e: 2-(1H-Indol-2-yl)-5-((3-methylphenyl)thio)-1,3,4-oxadiazole; Compound 5f: 2-(1H-Indol-2-yl)-5-((3-methoxyphenyl)thio)-1,3,4-oxadiazole; Compound 5g: 2-((3-Fluorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole; Compound 5h: 2-(1H-Indol-2-yl)-5-((4-methylphenyl)thio)-1,3,4-oxadiazole; Compound 5i: 2-((4-tert-Butylphenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole; Compound 5j: 2-(1H-Indol-2-yl)-5-((4-methoxyphenyl)thio)-1,3,4-oxadiazole; Compound 5k: 2-((4-Fluorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole; Compound 5l: 2-((4-Chlorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole; Compound 5m: 2-((4-Bromophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole; Compound 5n: 4-(((5-(1H-Indol-2-yl)-1,3,4-oxadiazol-2-yl)thio)methyl)-benzonitrile; Compound 5o: 2-(1H-Indol-2-yl)-5-((4-(trifluoromethyl)phenyl)thio)-1,3,4-oxadiazole; Compound 5p: 2-((3,4-Dimethylphenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole; Compound 5q: 2-((3,4-Dichlorophenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole; Compound 5r: 2-((3,5-Dimethoxyphenyl)thio)-5-(1H-indol-2-yl)-1,3,4-oxadiazole; Compound 5s: 2-(5-Chloro-1H-indol-2-yl)-5-((4-chlorophenyl)thio)-1,3,4-oxadiazole; Compound 5t: 2-(5-Chloro-1H-indol-2-yl)-5-((3,4-dichlorophenyl)thio)-1,3,4-oxadiazole.

2. The preparation method of an indole C2 derivative containing 1,3,4-oxadiazole and thioether structures as described in claim 1, characterized in that, The synthetic route is as follows: R 1 and R 2 As shown in claim 1: R 2 CH2X is benzyl chloride, 2-methylbenzyl chloride, 2-fluorobenzyl chloride, 2-chlorobenzyl chloride, 3-methylbenzyl chloride, 3-methoxybenzyl chloride, 3-fluorobenzyl chloride, 4-methylbenzyl chloride, 4-tert-butylbenzyl chloride, 4-methoxybenzyl chloride, 4-fluorobenzyl chloride, 4-chlorobenzyl chloride, 4-bromobenzyl chloride, 4-cyanobenzyl chloride, 4-trifluoromethylbenzyl chloride, 3,4-dimethylbenzyl chloride, 3,5-dimethoxybenzyl chloride, 3,4-dichlorobenzyl chloride.

3. The preparation method of the indole C2-position derivative containing 1,3,4-oxadiazole and thioether structures according to claim 2, wherein, The preparation steps of indole C2-position derivatives containing 1,3,4-oxadiazole and thioether structures are as follows: (1) Synthesis of intermediate 5-substituted-2-methyl indole-3-carboxylate (2): Add an appropriate amount of substituted indole-2-carboxylic acid into a flask containing methanol, and add a small amount of concentrated sulfuric acid as a catalyst thereto. React at 75-80 °C in an oil bath for 3-4 h. After the reaction is completed, distill off methanol under reduced pressure. The residue is recrystallized with methanol to obtain intermediate 2; (2) Synthesis of intermediate 5-substituted-2-formylhydrazinoindole (3): Add an appropriate amount of intermediate 2, hydrazine hydrate and methanol into a beaker in sequence, and reflux for 5-7 h. After the reaction is completed, cool the reaction solution to room temperature to precipitate a solid. Filter by suction, and recrystallize the filter cake with anhydrous methanol to obtain intermediate 3; (3) Synthesis of intermediate 5-substituted-2-(5-mercapto-1,3,4-oxadiazol-2-yl)-indole (4): Add an appropriate amount of intermediate 3, potassium hydroxide, absolute ethanol and water into a flask in sequence, stir at room temperature until the solid is completely dissolved, then slowly add an appropriate amount of carbon disulfide and heat to reflux for 6-8 h. Monitor the reaction by TLC. After the reaction is completed, remove the solvent ethanol under reduced pressure, adjust to pH = about 1 with 5% dilute hydrochloric acid to obtain a white solid. Filter by suction, dry, and then recrystallize with absolute ethanol to obtain intermediate 4; (4) Synthesis of target compound 2-benzylthio-5-(1H-indol-2-yl)-2-1,3,4-oxadiazole (5): Add an appropriate amount of intermediate 4, ethanol and triethylamine into a flask in sequence, stir at room temperature for 30 min. After the solid is completely dissolved, add an appropriate amount of RCH2X, and continue to stir at room temperature for 3-5 h. Monitor the reaction by TLC. After the reaction is completed, pour the reaction into an appropriate amount of ice water, filter by suction, dry, and then recrystallize with absolute ethanol to obtain target compound 5.

4. The preparation method of the indole C2-position derivative containing 1,3,4-oxadiazole and thioether structures according to claim 2, characterized in that, The substituted indole-2-carboxylic acid is indole-2-carboxylic acid and 5-chloroindole-2-carboxylic acid.

5. Use of the indole C2-position derivative containing 1,3,4-oxadiazole and thioether structures as described in claim 1 in the preparation of a drug for preventing and treating plant bacterial diseases.

6. Use of the indole C2 derivative containing 1,3,4-oxadiazole and thioether structures as claimed in claim 5 in the preparation of a drug for preventing and treating plant bacterial diseases, characterized in that, The plant bacterial diseases are kiwifruit canker, citrus canker and rice bacterial blight.

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