1, 3, 4-oxadiazole compound as well as preparation method and application thereof

Abstract

The invention relates to the technical field of pesticide chemistry, and provides a 1, 3, 4-oxadiazole compound as well as a preparation method and application thereof. The invention provides a novel 1, 3, 4-oxadiazole compound, the antibacterial activity of the novel 1, 3, 4-oxadiazole compound is tested, and it is shown that the novel 1, 3, 4-oxadiazole compound has obvious antibacterial activity on botrytis cinerea. The skeleton of the 1, 3, 4-oxadiazole compound provided by the invention is different from that of traditional commercially available bactericides, and the 1, 3, 4-oxadiazole compound is novel in structure and good in antibacterial activity, can be applied to agriculture and solve the problem of drug resistance, provides a new choice for research, development and application of agricultural chemicals, and has a wide application prospect.

Description

Technical Field

[0001] This invention relates to the field of pesticide chemistry, and in particular to a 1,3,4-oxadiazole compound, its preparation method, and its application. Background Technology

[0002] Plant pathogens, as one of the major threats to agricultural production, encompass various types such as fungi, bacteria, and oomycetes. They can widely infect various cultivated crops such as vegetables, fruits, and grains, leading not only to reduced crop yields and decreased quality, but also, in severe cases, crop failure, thus imposing an economic burden on growers and hindering the sustainable development of the agricultural industry.

[0003] Currently, chemical control remains the core method for controlling plant pathogenic diseases in the field. Agricultural antimicrobial agents, as key substances in chemical control, play an irreplaceable role in emergency disease control and reducing yield losses. However, existing agricultural antimicrobial agents are outdated and have a limited structural framework. Current mainstream products are mostly copper-based formulations, a few agricultural antibiotics, and traditional heterocyclic compounds. Long-term reliance on a single type of agent leads to pathogen resistance, significantly reduces the efficacy of pesticides, and forces an increase in pesticide dosage.

[0004] To address the aforementioned issues, the agricultural sector has an increasingly urgent need for the research and development of novel agricultural antibacterial agents. Developing antibacterial agents with novel structural frameworks is a pressing problem that needs to be solved. Summary of the Invention

[0005] In view of this, the present invention provides a 1,3,4-oxadiazole compound, its preparation method, and its application. The 1,3,4-oxadiazole compound provided by the present invention has a novel structure and good antibacterial activity, which is of great significance for solving the problem of plant pathogens.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution: A 1,3,4-oxadiazole compound having the structure shown in Formula I: Formula I; In Formula I: R is selected from any of the following structures: , , , ; Wherein, R1 is selected from one or more of C1~C5 alkyl, halogen, C1~C5 haloalkyl, phenyl, C3~C6 cycloalkyl and C1~C3 alkoxy, and n takes the value of 1~3; R2 is halogen, and m takes the value of 0~2.

[0007] Preferably, in R1, the C1-C5 alkyl group is selected from one or more of methyl, ethyl and isobutyl, the halogen is selected from one or more of F, Cl and Br, the C1-C5 haloalkyl group is selected from one or two of trifluoromethyl and monobromomethyl, the C3-C6 cycloalkyl group is cyclohexyl, and the C1-C3 alkoxy group is methoxy; in R2, the halogen is selected from one or more of F, Cl and Br.

[0008] Preferably, R in formula I can be any of the following structures: .

[0009] This invention also provides a method for preparing the 1,3,4-oxadiazole compounds described above, comprising the following steps: The compound with the structure shown in Formula 1, hydrazine hydrate, and ethanol were mixed and subjected to a first reaction to obtain the compound with the structure shown in Formula 2. The compound with the structure shown in Formula 2, methanol, carbon disulfide and potassium hydroxide were mixed and subjected to a second reaction to obtain the compound with the structure shown in Formula 3. The compound with the structure shown in Formula 4, SO2Cl2 and haloalkane were mixed and subjected to a third reaction to obtain the compound with the structure shown in Formula 5. The compound with the structure shown in Formula 3, the compound with the structure shown in Formula 5, acetone and potassium carbonate are mixed and subjected to a fourth reaction to obtain the compound with the structure shown in Formula 6. The compound with the structure shown in Formula 6, sulfonyl chloride, 4-dimethylaminopyridine, triethylamine, and haloalkane were mixed and subjected to a fifth reaction to obtain a 1,3,4-oxadiazole compound with the structure shown in Formula I; the structure of the sulfonyl chloride is shown in Formula 7. Formula 1 Formula 2 Formula 3 Formula 4 Formula 5 Formula 6; Formula 7.

[0010] Preferably, the molar ratio of the compound with the structure shown in Formula 1 to hydrazine hydrate is 1:8~12; the first reaction is carried out under reflux conditions for 3~6 hours.

[0011] Preferably, the molar ratio of the compound with the structure shown in Formula 2, carbon disulfide, and potassium hydroxide is 1:4~6:1~1.5; the temperature of the second reaction is 65~75℃, and the reaction time is 100~120h.

[0012] Preferably, the molar ratio of the compound with the structure shown in Formula 4 to SO2Cl2 is 1:1 to 1.5; the temperature of the third reaction is 30 to 50°C, and the reaction time is 2 to 5 hours.

[0013] Preferably, the molar ratio of the compound with the structure shown in Formula 3, the compound with the structure shown in Formula 5, and potassium carbonate is 1:1~1.5:1~1.5; the temperature of the fourth reaction is 50~80℃, and the reaction time is 1~5h.

[0014] Preferably, the molar ratio of the compound with the structure shown in Formula 6, sulfonyl chloride, 4-dimethylaminopyridine, and triethylamine is 1:1~1.5:0.1~0.3:1~1.5; the temperature of the fifth reaction is 15~25°C, and the reaction time is 3~8 hours.

[0015] The present invention also provides the application of the 1,3,4-oxadiazole compounds described above in the preparation of antibacterial agents.

[0016] This invention provides a 1,3,4-oxadiazole compound with the structural formula shown in Formula I. This invention provides a novel 1,3,4-oxadiazole compound and has tested its antibacterial activity, demonstrating its effectiveness against *Botrytis cinerea* (…). Botrytis cinerea It exhibits significant antibacterial activity. The 1,3,4-oxadiazole compounds provided by this invention have a different skeleton from traditional commercially available fungicides, featuring a novel structure and good antibacterial activity. They can be applied in agriculture and solve the problem of drug resistance, providing a new option for the research and application of agricultural chemicals and showing broad application prospects. Attached Figure Description

[0017] Figure 1 This is a route diagram for the synthesis of 1,3,4-oxadiazole compounds according to the present invention. Detailed Implementation

[0018] This invention provides a 1,3,4-oxadiazole compound having the structure shown in Formula I: Formula I; In Formula I: R is selected from any of the following structures: , , , ; Wherein, R1 is selected from one or more of C1~C5 alkyl, halogen, C1~C5 haloalkyl, phenyl, C3~C6 cycloalkyl and C1~C3 alkoxy, and n takes the value of 1~3; R2 is halogen, and m takes the value of 0~2.

[0019] In this invention, the value of n can be 1, 2 or 3, indicating that the number of R1 groups can be 1, 2 or 3. When the number of R1 groups is greater than 1, the types of multiple R1 groups can be the same or different.

[0020] In this invention, the value of m can be 0, 1, or 2, indicating that the number of R2 groups can be 0, 1, or 2. When there are 0 R2 groups, that is, R is a thiophene group. When there are 2 R2 groups, the two R2 groups can be of the same type or different types. In this invention, in R1, the C1-C5 alkyl group is selected from one or more of methyl, ethyl and isobutyl, the halogen is selected from one or more of F, Cl and Br, the C1-C5 haloalkyl group is selected from one or two of trifluoromethyl and monobromomethyl, the C3-C6 cycloalkyl group is cyclohexyl, and the C1-C3 alkoxy group is methoxy; in R2, the halogen is selected from one or more of F, Cl and Br.

[0021] In this invention, R in Formula I is preferably any one of the following structures: .

[0022] This invention also provides a method for preparing the 1,3,4-oxadiazole compounds described above, comprising the following steps: The compound with the structure shown in Formula 1, hydrazine hydrate, and ethanol were mixed and subjected to a first reaction to obtain the compound with the structure shown in Formula 2. The compound with the structure shown in Formula 2, methanol, carbon disulfide and potassium hydroxide were mixed and subjected to a second reaction to obtain the compound with the structure shown in Formula 3. The compound with the structure shown in Formula 4, SO2Cl2 and haloalkane were mixed and subjected to a third reaction to obtain the compound with the structure shown in Formula 5. The compound with the structure shown in Formula 3, the compound with the structure shown in Formula 5, acetone and potassium carbonate are mixed and subjected to a fourth reaction to obtain the compound with the structure shown in Formula 6. The compound with the structure shown in Formula 6, sulfonyl chloride, 4-dimethylaminopyridine, triethylamine, and haloalkane were mixed and subjected to a fifth reaction to obtain a 1,3,4-oxadiazole compound with the structure shown in Formula I; the structure of the sulfonyl chloride is shown in Formula 7. Formula 1 Formula 2 Formula 3 Formula 4 Formula 5 Formula 6 Formula 7.

[0023] In this invention, the synthetic route of the 1,3,4-oxadiazole compounds is as follows: Figure 1 As shown below, in conjunction with Figure 1 Please provide a detailed explanation.

[0024] In this invention, a compound with the structure shown in Formula 1, hydrazine hydrate, and ethanol are mixed and subjected to a first reaction to obtain a compound with the structure shown in Formula 2. In this invention, the molar ratio of the compound with the structure shown in Formula 1 to hydrazine hydrate is preferably 1:8 to 12, specifically 1:10; the first reaction is preferably carried out under reflux conditions, and the reaction time is preferably 3 to 6 hours, specifically 4 hours. After the reaction is completed, the resulting product is preferably recrystallized to obtain a compound with the structure shown in Formula 2.

[0025] After obtaining the compound with the structure shown in Formula 2, the present invention mixes the compound with the structure shown in Formula 2, methanol, carbon disulfide, and potassium hydroxide to carry out a second reaction to obtain the compound with the structure shown in Formula 3. In the present invention, the molar ratio of the compound with the structure shown in Formula 2, carbon disulfide, and potassium hydroxide is preferably 1:4~6:1~1.5, specifically 1:5:1.2; the temperature of the second reaction is preferably 65~75℃, and the reaction time is preferably 100~120h; after the second reaction is completed, the present invention preferably purifies the obtained product by column chromatography to obtain the compound having the structure shown in Formula 3; the eluent used for the column chromatography purification is preferably petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate during column chromatography elution is changed from 10:1 to 3:1.

[0026] In this invention, a compound with the structure shown in Formula 4, SO2Cl2, and a haloalkane are mixed and subjected to a third reaction to obtain a compound with the structure shown in Formula 5. In this invention, the haloalkane is preferably trichloromethane; the molar ratio of the compound with the structure shown in Formula 4 to SO2Cl2 is preferably 1:1 to 1.5, specifically 1:1.2; the temperature of the third reaction is preferably 30 to 50°C, specifically 36°C; and the reaction time is preferably 2 to 5 hours, specifically 3 hours. After the third reaction is completed, the product is preferably purified by column chromatography. The eluent used in the column chromatography purification is preferably petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate during column chromatography elution is changed from 100:1 to 30:1.

[0027] After obtaining the compounds with the structures shown in Formula 3 and Formula 5, the present invention mixes the compounds with the structures shown in Formula 3 and Formula 5, acetone, and potassium carbonate to carry out a fourth reaction to obtain the compound with the structure shown in Formula 6. In the present invention, the molar ratio of the compounds with the structures shown in Formula 3, Formula 5, and potassium carbonate is preferably 1:1~1.5:1~1.5, specifically 1:1.2:1.2; the temperature of the fourth reaction is preferably 50~80℃, specifically 60℃, and the reaction time is preferably 1~5h, specifically 2h. After the fourth reaction is completed, the present invention preferably purifies the obtained product by column chromatography. The eluent used in the column chromatography purification is preferably petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate during column chromatography elution is changed from 10:1 to 7:1.

[0028] After obtaining the compound with the structure shown in Formula 6, the present invention mixes the compound with the structure shown in Formula 6, sulfonyl chloride, 4-dimethylaminopyridine (DMAP), triethylamine, and a haloalkane to carry out a fifth reaction to obtain a 1,3,4-oxadiazole compound with the structure shown in Formula I; the structure of the sulfonyl chloride is shown in Formula 7. In the present invention, the molar ratio of the compound with the structure shown in Formula 6, sulfonyl chloride, 4-dimethylaminopyridine, and triethylamine is preferably 1:1~1.5:0.1~0.3:1~1.5, specifically 1:1.2:0.1:1.2; the temperature of the fifth reaction is preferably 15~25℃, and the reaction time is preferably 3~8h, specifically 4h. After the fifth reaction is completed, the present invention preferably purifies the obtained product by column chromatography, and the eluent used for column chromatography purification is preferably petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate during column chromatography elution is changed from 20:1 to 10:1.

[0029] This invention also provides the application of the 1,3,4-oxadiazole compounds described in the above scheme in the preparation of antibacterial agents; in this invention, the antibacterial agent is specifically an agricultural antibacterial agent; the fungus is a plant pathogen, specifically Botrytis cinerea.

[0030] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0031] Example 1 Preparation of compound I-1 In a round-bottom flask, 0.1 mol of compound 1 was dissolved in 20 mL of ethanol, and then 1 mol of hydrazine hydrate was added. After stirring under reflux for 4 h, recrystallization was performed to obtain compound 2. White crystals, yield 75%.

[0032] In a round-bottom flask, 0.01 mol of compound 2 was dissolved in 20 mL of methanol, followed by the addition of 0.05 mmol of CS2 and 0.012 mol of KOH. After reacting for 5 days, the mixture was purified by column chromatography using petroleum ether and ethyl acetate as eluents. The volume ratio of petroleum ether to ethyl acetate during column chromatography was varied from 10:1 to 3:1. Compound 3 was obtained as white crystals in 52% yield.

[0033] In a round-bottom flask, 0.01 mol of compound 4 was dissolved in 10 mL of CHCl3, and then 0.012 mol of SO2Cl2 was added dropwise. After reacting at 36 °C for 3 h, the mixture was purified by column chromatography using petroleum ether and ethyl acetate as eluents. The volume ratio of petroleum ether to ethyl acetate during column chromatography was changed from 100:1 to 30:1 to obtain compound 5.

[0034] In a 100 mL round-bottom flask, 1 mmol of compound 3 and 1.2 mmol of compound 5 were dissolved in acetone, and 1.2 mmol of potassium carbonate was added. After reacting at 60 °C for 2 h, the mixture was purified by column chromatography using petroleum ether and ethyl acetate as eluents. The volume ratio of petroleum ether to ethyl acetate during column chromatography was changed from 10:1 to 7:1 to obtain compound 6.

[0035] In a 100 mL round-bottom flask, 1 mmol of compound 6, 1.2 mmol of sulfonyl chloride (p-methylbenzenesulfonyl chloride), 0.1 mmol of DMAP, and 1.2 mmol of triethylamine were dissolved in 10 mL of dichloromethane. After reacting for 4 h, the mixture was purified by column chromatography using petroleum ether and ethyl acetate as eluents. The volume ratio of petroleum ether to ethyl acetate was varied from 20:1 to 10:1 during column chromatography to give compound I-1. The structural identification data are as follows: 1 H NMR (400 MHz, Acetone- d 6) δ 7.99 – 7.92 (m, 2H), 7.89 (d, J = 1.9 Hz, 1H), 7.70 (t, J = 0.9 Hz, 1H), 7.56 – 7.49 (m, 2H), 7.06 (d, J = 1.9 Hz, 1H), 4.89 (d, J = 0.9 Hz, 2H). HRMS (m / z) calcd for C 17H 12 BrClN4O3S3[MH] + : 530.9016;found: 530.9009. Examples 2-30: Preparation of compounds I-2-I-30 The preparation method is the same as in Example 1, except that the structure of sulfonyl chloride is changed to prepare compounds I-2 to I-30. The structure and identification data of the obtained products are as follows: Compound I-2 1 H NMR (400 MHz, CDCl3) δ 7.75 – 7.70 (m, 1H), 7.70 – 7.60 (m, 1H), 7.58 – 7.50 (m, 1H), 7.13 – 7.03 (m, 2H), 6.95 (d, J = 2.0 Hz, 1H), 4.61 (s,2H). HRMS (m / z) calcd for C 16 H8BrClF2N4O3S3[MH] + : 552.8671; found: 552.8663. Compound I-3 1 H NMR (600 MHz, Acetone- d 6) δ 8.26 – 8.20 (m, 1H), 7.92 – 7.82 (m,2H), 7.58 – 7.50 (m, 1H), 7.09 (d, J = 1.9 Hz, 1H), 4.73 (d, J = 0.9 Hz, 2H).HRMS (m / z) calcd for C 16 H7BrCl4N4O3S3[MH] + : 640.7510; found: 640.7496. Compound I-4 1 H NMR (400 MHz, Chloroform- d) δ 7.80 – 7.75 (m, 1H), 7.51 (s, 2H),7.26 (s, 1H), 6.96 (d, J = 1.9 Hz, 1H), 4.59 (s, 2H). HRMS (m / z) calcd forC 16 H7BrCl4N4O3S3[M-H] + : 618.7691; found: 618.7694. Compound I-5 1 1H NMR (400 MHz, Chloroform- d ) δ 8.26 (d, J = 8.5 Hz, 1H), 7.79 (d, J =1.9 Hz, 1H), 7.54 (s, 1H), 7.53 – 7.47 (m, 2H), 6.96 (d, J = 1.9 Hz, 1H), 4.60(s, 2H). HRMS (m / z) calcd for C 16 H8BrCl3N4O3S3[M-H] + : 584.8080; found: 584.8084. Compound I-6 1 1H NMR (400 MHz, Chloroform- d ) δ 8.26 (d, J = 8.5 Hz, 1H), 7.79 (d, J =1.9 Hz, 1H), 7.54 (s, 1H), 7.53 – 7.47 (m, 2H), 6.96 (d, J = 1.9 Hz, 1H), 4.60(s, 2H). HRMS (m / z) calcd for C 16 H9BrClFN4O3S3[M-H] + : 534.8765; found:534.8768. Compound I-7 11H NMR (400 MHz, Chloroform- d ) δ 7.80 (t, J J = 6.0 Hz, 2H), 7.63 – 7.47(m, 2H), 6.91 (d, J J = 1.9 Hz, 1H), 4.66 (d, J J = 0.9 Hz, 2H). HRMS (m / z) calcd forC 16 17H7BrClF3N4O3S3[M-H] + :592.8396; found: 592.8396. Compound I-8 1 1H NMR (400 MHz, Chloroform- d ) δ 8.27 (d, J J = 2.5 Hz, 1H), 7.79 (d, J J =2.0 Hz, 1H), 7.62 – 7.52 (m, 2H), 7.44 (d, J J = 8.5 Hz, 1H), 6.98 (d, J J = 1.9 Hz,1H), 4.61 (d, J J = 0.9 Hz, 2H). HRMS (m / z) calcd for C 16 18H8BrCl3N4O3S3[M-H] + :584.8080; found:584.8094. Compound I-9 1 1H NMR (400 MHz, Acetone- d d6) δ 7.87 – 7.80 (m, 2H), 7.75 (d, J J = 1.9 Hz,1H), 7.55 (d, J J = 1.0 Hz, 1H), 7.43 – 7.36 (m, 2H), 6.91 (d, J J = 1.9 Hz, 1H),4.74 (d, J J = 0.9 Hz, 2H), 2.62 (q, J= 7.6 Hz, 2H), 1.09 (t, J = 7.6 Hz, 3H). HRMS(m / z) calcd for C 18 H 14 BrClN4O3S3[M-H] + : 544.9173; found: 544.9178. Compound I-10 1 H NMR (400 MHz, Chloroform- d ) δ 8.18 (td, J = 8.5, 5.9 Hz, 1H), 7.70(t, J = 2.1 Hz, 1H), 7.55 (s, 1H), 7.12 (ddt, J = 9.8, 7.1, 1.5 Hz, 1H), 6.96(ddd, J = 10.6, 8.3, 2.5 Hz, 1H), 6.92 (d, J = 1.9 Hz, 1H), 4.62 (s, 2H). HRMS(m / z) calcd for C 16 H8BrClF2N4O3S3[M-H] + : 552.8671; found: 552.8672. Compound I-11 1 H NMR (400 MHz, Chloroform- d ) δ 8.00 (dd, J = 8.6, 7.5 Hz, 1H), 7.70(t, J = 2.1 Hz, 1H), 7.59 – 7.52 (m, 2H), 7.41 (dd, J = 9.4, 1.8 Hz, 1H), 6.92(d, J = 2.0 Hz, 1H), 4.62 (d, J = 0.9 Hz, 2H). HRMS (m / z) calcd forC 16 H8Br2ClFN4O3S3[M-H] +: 612.7871; found: 612.7880. Compound I-12 1 H NMR (400 MHz, Acetone- d 6) δ 8.14 – 8.05 (m, 2H), 7.94 (d, J = 1.9 Hz, 1H), 7.81 (dd, J = 8.6, 2.0 Hz, 2H), 7.70 (d, J = 0.9 Hz, 1H), 7.10 (d, J = 1.8 Hz, 1H), 4.89 (d, J = 0.9 Hz, 2H), 4.86 (s, 2H). HRMS (m / z) calcd forC 17 H 11 Br2ClN4O3S3[MH] + : 608.8121; found: 608.8121. Compound I-13 1 H NMR (400 MHz, Acetone- d 6) δ 8.08 – 7.97 (m, 2H), 7.86 – 7.74 (m,3H), 7.64 – 7.57 (m, 2H), 7.55 (d, J = 1.0 Hz, 1H), 7.42 – 7.28 (m, 3H), 6.94(d, J = 1.9 Hz, 1H), 4.74 (s, 2H). HRMS (m / z) calcd for C 22 H 14 BrClN4O3S3[MH] + :592.9173; found: 592.9175. Compound I-14 1 H NMR (400 MHz, Acetone- d 6) δ 7.85 – 7.82 (m, 2H), 7.76 (d,J = 1.9 Hz, 1H), 7.55 (d, J = 0.9 Hz, 1H), 7.44 – 7.40 (m, 2H), 6.91 (d, J = 1.9 Hz, 1H), 4.74 (d, J = 0.9 Hz, 2H), 2.54 (tt, J = 11.6, 3.0 Hz, 1H), 1.71 – 1.67 (m, 4H), 1.30 (dddd, J = 16.5, 14.8, 9.2, 2.8 Hz, 4H), 1.23 – 1.01 (m, 2H). HRMS (m / z) calcd for C 22 H 20 BrClN4O3S3[M-H] + : 598.9642; found: 598.9648. Compound I-15 1 H NMR (400 MHz, Acetone- d 6) δ 7.88 – 7.82 (m, 2H), 7.76 (d, J = 1.9 Hz, 1H), 7.66 – 7.57 (m, 2H), 7.55 (d, J = 1.0 Hz, 1H), 6.91 (d, J = 1.9 Hz, 1H), 4.74 (d, J = 0.9 Hz, 2H), 1.20 (s, 9H). HRMS (m / z) calcd for C 20 H 18 BrClN4O3S3[M-H] + : 572.9486; found: 572.9489. Compound I-16 1 H NMR (400 MHz, Acetone- d 6) δ 8.41 (dd, J = 8.6, 1.0 Hz, 1H), 8.24 (dt, J= 8.3, 1.3 Hz, 1H), 8.15 (dd, J = 7.5, 1.2 Hz, 1H), 8.03 – 7.95 (m, 2H), 7.64(ddd, J = 8.6, 6.9, 1.4 Hz, 1H), 7.60 – 7.48 (m, 3H), 6.90 (d, J = 1.9 Hz, 1H),4.64 (d, J = 1.0 Hz, 2H). HRMS (m / z) calcd for C 20 H 12 BrClN4O3S3[M-H] + : 566.9016;found: 566.9024. Compound I-17 1 H NMR (400 MHz, Acetone- d 6) δ 8.60 (d, J = 2.0 Hz, 1H), 8.04 (dd, J =8.3, 3.7 Hz, 2H), 7.96 – 7.89 (m, 1H), 7.88 – 7.80 (m, 2H), 7.69 – 7.56 (m,2H), 7.53 (s, 1H), 6.91 (d, J = 1.9 Hz, 1H), 4.71 (d, J = 0.9 Hz, 2H). HRMS (m / z)calcd for C 20 H 12 BrClN4O3S3[M-H] + : 566.9016; found: 566.9023. Compound I-18 1 H NMR (400 MHz, Acetone- d 6) δ 7.80 (dd, J = 8.0, 1.7 Hz, 1H), 7.69 (d, J = 1.9 Hz, 1H), 7.68 – 7.61 (m, 1H), 7.51 (d, J= 0.9 Hz, 1H), 7.14 (dd, J = 8.5, 1.0 Hz, 1H), 7.10 – 7.03 (m, 1H), 6.90 (d, J = 1.9 Hz, 1H), 4.69 (d, J = 0.9 Hz, 2H), 3.80 (s, 3H). HRMS (m / z) calcd for C 17 H 12 BrClN4O4S3[M-H] + : 546.8965; found: 546.8969. Compound I-19 1 H NMR (400 MHz, Acetone- d 6) δ 8.06 – 7.92 (m, 2H), 7.78 (d, J = 1.9 Hz, 1H), 7.66 – 7.58 (m, 2H), 7.55 (d, J = 0.9 Hz, 1H), 6.96 (d, J = 1.9 Hz, 1H), 4.74 (d, J = 0.9 Hz, 2H). HRMS (m / z) calcd for C 16 H9BrCl2N4O3S3[M-H] + : 550.8470; found: 550.8470. Compound I-20 1 H NMR (400 MHz, Acetone- d 6) δ 7.95 – 7.86 (m, 1H), 7.84 – 7.77 (m, 1H), 7.76 (t, J = 2.1 Hz, 1H), 7.53 (d, J = 1.0 Hz, 1H), 7.43 (td, J = 7.8, 1.1 Hz, 1H), 7.35 (ddd, J = 10.8, 8.4, 1.1 Hz, 1H), 7.02 (d, J= 1.9 Hz, 1H), 4.71 (d, J =0.9 Hz, 2H). HRMS (m / z) calcd for C 16 H9BrClFN4O3S3[M-H] + : 534.8765; found:534.8772. Compound I-21 1 H NMR (400 MHz, Acetone- d 6) δ 7.84 – 7.74 (m, 3H), 7.66 (td, J = 8.1,5.3 Hz, 1H), 7.55 (d, J = 0.9 Hz, 1H), 7.50 (tdd, J = 8.4, 2.6, 0.9 Hz, 1H), 6.97(d, J = 1.9 Hz, 1H), 4.75 (d, J = 0.9 Hz, 2H). HRMS (m / z) calcd forC 16 H9BrClFN4O3S3[M-H] + : 534.8765; found:534.8767. Compound I-22 1 H NMR (400 MHz, Acetone- d 6) δ 8.24 – 8.09 (m, 1H), 8.06 – 7.97 (m,1H), 7.94 (d, J = 1.9 Hz, 1H), 7.79 – 7.70 (m, 1H), 7.69 (d, J = 2.2 Hz, 1H),7.12 (d, J = 1.9 Hz, 1H), 4.87 (s, 2H). HRMS (m / z) calcd for C 16 H8BrClF2N4O3S3[M-H] + : 552.8671; found: 552.8674. Compound I-23 1 H NMR (400 MHz, Acetone- d 6) δ 8.36 (dd, J J = 6.6, 2.4 Hz, 1H), 8.22 – 8.14 (m, 1H), 7.98 (d, J J = 1.9 Hz, 1H), 7.75 – 7.66 (m, 2H), 7.14 (d, J J = 1.9 Hz,1H), 4.91 (d, J J = 0.9 Hz, 2H). HRMS (m / z) calcd for C 16 H8BrCl2FN4O3S3[M-H] + : 568.8376; found: 568.8376. Compound I-24 1 H NMR (400 MHz, Acetone- d 6) δ 8.03 – 7.97 (m, 1H), 7.90 (tt, J J = 7.8,1.1 Hz, 1H), 7.81 (td, J J = 7.8, 1.4 Hz, 1H), 7.77 (d, J J = 1.9 Hz, 1H), 7.71 (dd, J J = 8.1, 1.2 Hz, 1H), 7.47 (d, J J = 1.0 Hz, 1H), 7.10 (dd, J J = 9.1, 1.6 Hz, 1H),4.62 (d, J J = 0.9 Hz, 2H). HRMS (m / z) calcd for C 17 H9BrClF3N4O3S3[M-H] + : 584.8734;found: 584.8738. Compound I-25 1 H NMR (400 MHz, Acetone- d6) δ 8.23 – 8.13 (m, 2H), 7.96 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 1.8 Hz, 1H), 7.54 (d, J = 1.0 Hz, 1H), 6.99 (d, J = 1.9 Hz, 1H), 4.74 (d, J = 0.9 Hz, 2H). HRMS (m / z) calcd for C 17 H9BrClF3N4O3S3[M-H] + : 584.8734; found: 584.8733. Compound I-26 1 H NMR (400 MHz, Acetone- d 6) δ 8.75 – 8.70 (m, 2H), 8.46 – 8.41 (m, 1H), 7.97 (d, J = 1.9 Hz, 1H), 7.56 (d, J = 0.9 Hz, 1H), 7.04 (d, J = 1.9 Hz, 1H), 4.77 (d, J = 0.9 Hz, 2H). HRMS (m / z) calcd for C 18 H8BrClF6N4O3S3[M-H] + : 652.7770; found: 652.7774. Compound I-27 1 H NMR (400 MHz, Acetone- d 6) δ 8.45 (d, J = 2.4 Hz, 1H), 8.30 (dd, J = 8.6, 2.4 Hz, 1H), 7.94 (d, J = 8.6 Hz, 1H), 7.88 (d, J = 1.9 Hz, 1H), 7.56 (d, J = 0.9 Hz, 1H), 7.02 (d,J = 1.9 Hz, 1H), 4.77 (d, J = 0.9 Hz, 2H). HRMS (m / z) calcdfor C 17 H8BrCl2F3N4O3S3[M-H] + : 618.8344; found: 618.8340. Compound I-28 1 H NMR (400 MHz, Acetone- d 6) δ 8.07 (dd, J = 5.0, 1.4 Hz, 1H), 7.91 (dd, J = 3.9, 1.4 Hz, 1H), 7.73 (d, J = 1.9 Hz, 1H), 7.59 – 7.52 (m, 1H), 7.19 (dd, J =5.0, 3.9 Hz, 1H), 6.95 (d, J = 1.9 Hz, 1H), 4.76 (d, J = 0.9 Hz, 2H). HRMS (m / z)calcd for C 14 H8BrClN4O3S4[M-H] + : 522.8424; found: 522.8426. Compound I-29 1 H NMR (400 MHz, Acetone- d 6) δ 7.77 (d, J = 4.2 Hz, 1H), 7.73 (d, J = 1.9Hz, 1H), 7.56 (d, J = 1.0 Hz, 1H), 7.29 (d, J = 4.2 Hz, 1H), 6.99 (d, J = 1.9 Hz,1H), 4.76 (d, J = 0.9 Hz, 2H). HRMS (m / z) calcd for C14H7Br2ClN4O3S4 [M-H] +:600.7529; found: 600.7529. Compound I-30 1 H NMR (400 MHz, Acetone- d 6) δ 7.80 (d, J = 1.9 Hz, 1H), 7.55 (d, J = 1.0Hz, 1H), 7.32 (t, 1H), 7.07 (d, J = 1.8 Hz, 1H), 4.75 (d, J = 0.9 Hz, 2H). HRMS(m / z) calcd for C 14 H6BrC l3 N4O3S4[MH] + : 590.7644; found: 590.7648. Antibacterial activity test: Botrytis cinerea was cultured in potato dextrose broth for 3 days, followed by antibacterial experiments. In 96-well plates, the compound was prepared at concentrations of 128, 64, 32, 16, 8, and 4 mg / L using a two-fold dilution method. 5 μL of the target bacterial culture was then added, and the plates were incubated at 28°C for 3 days. The OD values ​​at 600 nm were measured using a microplate reader, and a standard curve was plotted based on the OD values. The EC50 was then calculated. 50 Prunol was used as a positive control. The test results are shown in Table 1.

[0036] Table 1. Anti-Botrytis cinerea activity of compounds I-1 to I-30

[0037] As can be seen from the data in Table 1, the 1,3,4-oxadiazole compounds provided by this invention have good antibacterial activity against Botrytis cinerea, among which compounds I-3, I-4, I-5, I-8, I-26, I-27, I-28, I-29 and I-30 have antibacterial activity exceeding that of the positive control tau phenol.

[0038] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A 1,3,4-oxadiazole compound, characterized in that, It has the structure shown in Equation I: Equation I; In Formula I: R is selected from any of the following structures: , , , ; Wherein, R1 is selected from one or more of C1~C5 alkyl, halogen, C1~C5 haloalkyl, phenyl, C3~C6 cycloalkyl and C1~C3 alkoxy, and n takes the value of 1~3; R2 is halogen, and m takes the value of 0~2.

2. The 1,3,4-oxadiazole compound according to claim 1, characterized in that, In R1, the C1-C5 alkyl group is selected from one or more of methyl, ethyl and isobutyl, the halogen is selected from one or more of F, Cl and Br, the C1-C5 haloalkyl group is selected from one or two of trifluoromethyl and monobromomethyl, the C3-C6 cycloalkyl group is cyclohexyl, and the C1-C3 alkoxy group is methoxy; in R2, the halogen is selected from one or more of F, Cl and Br.

3. The 1,3,4-oxadiazole compound according to claim 1 or 2, characterized in that, In Equation I, R can be any of the following structures: 。 4. The method for preparing the 1,3,4-oxadiazole compound according to any one of claims 1 to 3, characterized in that, Includes the following steps: The compound with the structure shown in Formula 1, hydrazine hydrate, and ethanol were mixed and subjected to a first reaction to obtain the compound with the structure shown in Formula 2. The compound with the structure shown in Formula 2, methanol, carbon disulfide and potassium hydroxide were mixed and subjected to a second reaction to obtain the compound with the structure shown in Formula 3. The compound with the structure shown in Formula 4, SO2Cl2, and haloalkane were mixed and subjected to a third reaction to obtain the compound with the structure shown in Formula 5. The compound with the structure shown in Formula 3, the compound with the structure shown in Formula 5, acetone and potassium carbonate are mixed and subjected to a fourth reaction to obtain the compound with the structure shown in Formula 6. The compound with the structure shown in Formula 6, sulfonyl chloride, 4-dimethylaminopyridine, triethylamine, and haloalkane were mixed and subjected to a fifth reaction to obtain a 1,3,4-oxadiazole compound with the structure shown in Formula I; the structure of the sulfonyl chloride is shown in Formula 7. Formula 1 Formula 2 Formula 3 Formula 4 Formula 5 Formula 6; Formula 7.

5. The preparation method according to claim 4, characterized in that, The molar ratio of the compound with the structure shown in Formula 1 to hydrazine hydrate is 1:8~12; the first reaction is carried out under reflux conditions for 3~6 hours.

6. The preparation method according to claim 4, characterized in that, The molar ratio of the compound with the structure shown in Formula 2, carbon disulfide, and potassium hydroxide is 1:4~6:1~1.5; the temperature of the second reaction is 65~75℃, and the reaction time is 100~120h.

7. The preparation method according to claim 4, characterized in that, The molar ratio of the compound with the structure shown in Formula 4 to SO2Cl2 is 1:1 to 1.5; the temperature of the third reaction is 30 to 50°C, and the reaction time is 2 to 5 hours.

8. The preparation method according to claim 4, characterized in that, The molar ratio of the compound with the structure shown in Formula 3, the compound with the structure shown in Formula 5, and potassium carbonate is 1:1~1.5:1~1.5; the temperature of the fourth reaction is 50~80℃, and the reaction time is 1~5h.

9. The preparation method according to claim 4, characterized in that, The molar ratio of the compound with the structure shown in Formula 6, sulfonyl chloride, 4-dimethylaminopyridine, and triethylamine is 1:1~1.5:0.1~0.3:1~1.5; the temperature of the fifth reaction is 15~25℃, and the reaction time is 3~8h.

10. The use of the 1,3,4-oxadiazole compounds according to any one of claims 1 to 3 in the preparation of antibacterial agents.

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