阅读说明：本技术 含二苯醚基的5-三氟甲基取代噁二唑类化合物的制备方法与应用 (Preparation method and application of diphenyl ether group-containing 5-trifluoromethyl substituted oxadiazole compound ) 是由 谷文 杨子辉 刘青松 孙月 王石发 孙雪宝 孙露 陈霖霖 于 2021-09-30 设计创作，主要内容包括：本发明公开了含二苯醚基的5-三氟甲基取代噁二唑类化合物的制备方法与应用,所述化合物包括式Ⅰ的化合物：其中,R基团为4-H、4-F、4-Cl、-NH-(2)和4-OCH-(3)中的一种,本发明所述含二苯醚基的5-三氟甲基取代噁二唑类化合物,分子结构新颖,均为新化合物；化学结构特征鲜明,结构式中含有二苯醚基团,其中二苯醚基团与5-三氟甲基噁二唑苯甲酸通过酰胺键相连接,对于防治油菜菌核病、小麦赤霉病和番茄早疫病显示出较好的效果。(The invention discloses a preparation method and application of a diphenyl ether group-containing 5-trifluoromethyl substituted oxadiazole compound, wherein the compound comprises a compound shown in a formula I: wherein, R group is 4-H, 4-F, 4-Cl or-NH 2 And 4-OCH 3 In the invention, the diphenyl ether group-containing 5-trifluoromethyl substituted oxadiazole compound has a novel molecular structure and is a new compound; the chemical structure is characterized in that the structural formula contains diphenyl ether group, wherein the diphenyl ether group is connected with 5-trifluoromethyl oxadiazole benzoic acid through amido bond, and the compound shows better effects on preventing and treating sclerotinia rot of colza, wheat scab and early blight of tomatoThe effect of (1).)

1. A5-trifluoromethyl substituted oxadiazole compound containing diphenyl ether group is characterized in that: the compounds include compounds of formula i:

wherein, R group is 4-H, 4-F, 4-Cl or-NH₂And 4-OCH₃One kind of (1).

2. The method for producing a diphenyl ether-based 5-trifluoromethyl-substituted oxadiazole compound according to claim 1, comprising: comprises the steps of (a) preparing a mixture of a plurality of raw materials,

4-cyanobenzoic acid reacts with hydroxylamine hydrochloride and triethylamine to synthesize an intermediate 1;

the intermediate 1 reacts with trifluoroacetic anhydride to synthesize an intermediate 2, namely 4- [5- (trifluoromethyl) -1,2, 4-oxadiazole-3-yl ] benzoic acid;

4- [5- (trifluoromethyl) -1,2, 4-oxadiazole-3-yl ] benzoic acid and 4-substituted phenoxyaniline react in one step under the condition that 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride EDCI, 4-dimethylaminopyridine DMAP and dichloromethane are used as solvents to synthesize the 5-trifluoromethyl substituted oxadiazole compound.

3. The method for producing a diphenyl ether-based 5-trifluoromethyl-substituted oxadiazole compound according to claim 2, comprising: the intermediate 2 is synthesized by a specific process comprising,

dissolving 4-cyanobenzoic acid in dry tetrahydrofuran and N, N-dimethylformamide, adding triethylamine and hydroxylamine hydrochloride while stirring, heating the reaction solution to a reflux temperature for reaction, monitoring by TLC (thin layer chromatography) that the raw materials are completely reacted, cooling to room temperature to obtain an intermediate 1, then dropwise adding trifluoroacetic anhydride, heating the reaction solution again to the reflux temperature for reaction for 0.5h, cooling, pouring the reaction solution into water, and separating out a solid while stirring to obtain an intermediate 2.

4. The method for producing a diphenyl ether-based 5-trifluoromethyl-substituted oxadiazole compound according to claim 3, comprising: the molar use ratio of the 4-cyanobenzoic acid to the hydroxylamine hydrochloride is 1: 1.0-2.0.

5. The method for producing a diphenyl ether-based 5-trifluoromethyl-substituted oxadiazole compound according to claim 3, comprising: the molar use ratio of the 4-cyanobenzoic acid to the triethylamine is 1: 2.0-3.0.

6. The method for producing a diphenyl ether-based 5-trifluoromethyl-substituted oxadiazole compound according to claim 3, comprising: the reaction temperature is 60-80 ℃, and the total time is 2-5 h.

7. The method for producing a diphenyl ether-based 5-trifluoromethyl-substituted oxadiazole compound according to claim 2, comprising: the molar use ratio of the 4-substituted phenoxyaniline to the 4- [5- (trifluoromethyl) -1,2, 4-oxadiazole-3-yl ] benzoic acid is 1: 1.0-1.3, and the reaction time is 6-10 h.

8. The use of the diphenyl ether-based 5-trifluoromethyl substituted oxadiazole compound according to claim 1 for controlling agricultural or forestry plant fungi.

9. The use of claim 8, wherein: the plant fungi include Botrytis cinerea, Sclerotinia sclerotiorum and Phytophthora solani.

Technical Field

The invention belongs to the technical field of pesticide synthesis, and particularly relates to a preparation method and application of a diphenyl ether group-containing 5-trifluoromethyl substituted oxadiazole compound.

Background

The soybean rust belongs to worldwide, airborne and obligate parasitic diseases, is one of main diseases of soybeans, is widely prevalent in the world from the 20 th century, and is increasingly rampant in recent decades, and the damage range of the soybean rust is spread in countries and regions such as Asia, Africa, Europe, America, oceania and the like.

At present, commonly used medicaments for preventing and treating soybean rust mainly comprise triazoles, methoxy acrylates, SDHI and the like; however, with the increasing use of a large number of repeated drug administration modes, the problem of resistance of the existing bactericides is highlighted. It has been reported that in brazil, the control effect of prothioconazole has been reduced from the first 100% to around 80%; the control effect of the strobilurin pesticide is generally reduced, the azoxystrobin and the pyraclostrobin are even reduced to 30-40%, and the field performance is almost ineffective; the new variety of the SDHI benzovindiflupyr has greatly reduced drug effect and is no longer a life-saving drug for farmers.

Therefore, the search of a novel compound with high efficiency, low toxicity, environmental friendliness and a brand-new action mechanism to replace the existing soybean rust high-resistance variety is a long-standing great problem. Wheat powdery mildew, which is an important disease in wheat producing areas, also needs to find varieties with high and new targets.

Disclosure of Invention

This section is for the purpose of summarizing some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. In this section, as well as in the abstract and the title of the invention of this application, simplifications or omissions may be made to avoid obscuring the purpose of the section, the abstract and the title, and such simplifications or omissions are not intended to limit the scope of the invention.

The present invention has been made keeping in mind the above and/or other problems occurring in the prior art.

Accordingly, it is an object of the present invention to overcome the deficiencies of the prior art and to provide a class of 1,2, 4-oxadiazole biphenylcarboxamides containing a diphenyl ether group. In order to solve the technical problems, the invention provides the following technical scheme: comprises 5-trifluoromethyl substituted oxadiazole compounds containing diphenyl ether group, which is characterized in that: the compounds include compounds of formula i:

wherein, R group is 4-H, 4-F, 4-Cl or-NH₂And 4-OCH₃One kind of (1).

It is a further object of the present invention to overcome the deficiencies of the prior art by providing a process for preparing 1,2, 4-oxadiazole biphenylcarboxamides containing a diphenyl ether group comprising,

4-cyanobenzoic acid reacts with hydroxylamine hydrochloride and triethylamine to synthesize an intermediate 1;

the intermediate 1 reacts with trifluoroacetic anhydride to synthesize an intermediate 2, namely 4- [5- (trifluoromethyl) -1,2, 4-oxadiazole-3-yl ] benzoic acid;

4- [5- (trifluoromethyl) -1,2, 4-oxadiazole-3-yl ] benzoic acid and 4-substituted phenoxyaniline react in one step under the condition that 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride EDCI, 4-dimethylaminopyridine DMAP and dichloromethane are used as solvents to synthesize the 5-trifluoromethyl substituted oxadiazole compound.

As a preferable embodiment of the preparation method of the diphenyl ether group-containing 1,2, 4-oxadiazole biphenyl carboxamide compound, the invention is that: the intermediate 2 is synthesized by a specific process comprising,

dissolving 4-cyanobenzoic acid in dry tetrahydrofuran and N, N-dimethylformamide, adding triethylamine and hydroxylamine hydrochloride while stirring, heating the reaction solution to a reflux temperature for reaction, monitoring by TLC (thin layer chromatography) that the raw materials are completely reacted, cooling to room temperature to obtain an intermediate 1, then dropwise adding trifluoroacetic anhydride, heating the reaction solution again to the reflux temperature for reaction for 0.5h, cooling, pouring the reaction solution into water, and separating out a solid while stirring to obtain an intermediate 2.

As a preferable embodiment of the preparation method of the diphenyl ether group-containing 1,2, 4-oxadiazole biphenyl carboxamide compound, the invention is that: the molar use ratio of the 4-cyanobenzoic acid to the hydroxylamine hydrochloride is 1: 1.0-2.0.

As a preferable embodiment of the preparation method of the diphenyl ether group-containing 1,2, 4-oxadiazole biphenyl carboxamide compound, the invention is that: the molar use ratio of the 4-cyanobenzoic acid to the triethylamine is 1: 2.0-3.0.

As a preferable embodiment of the preparation method of the diphenyl ether group-containing 1,2, 4-oxadiazole biphenyl carboxamide compound, the invention is that: the reaction temperature is 60-80 ℃, and the total time is 2-5 h.

As a preferable embodiment of the preparation method of the diphenyl ether group-containing 1,2, 4-oxadiazole biphenyl carboxamide compound, the invention is that: the molar use ratio of the 4-substituted phenoxyaniline to the 4- [5- (trifluoromethyl) -1,2, 4-oxadiazole-3-yl ] benzoic acid is 1: 1.0-1.3, and the reaction time is 6-10 h.

The invention further aims to overcome the defects in the prior art and provide the application of diphenyl ether-based 5-trifluoromethyl substituted oxadiazole compounds in preventing and treating agricultural or forestry plant fungi.

As a preferable embodiment of the application of the diphenyl ether group-containing 1,2, 4-oxadiazole biphenyl carboxamide compound of the invention, wherein: the plant fungi include Botrytis cinerea, Sclerotinia sclerotiorum and Phytophthora solani.

The invention has the beneficial effects that:

(1) the diphenyl ether group-containing 5-trifluoromethyl substituted oxadiazole compound has a novel molecular structure, and is a new compound; the chemical structure is characterized in that the structural formula contains diphenyl ether group, wherein the diphenyl ether group is connected with 5-trifluoromethyl oxadiazole benzoic acid through amido bond, and the compound has good effect on preventing and treating sclerotinia rot of colza, wheat scab and early blight of tomato.

(2) The preparation method of the compound is simple and convenient, the raw materials are easy to obtain, and the reaction conditions are easy to control. Especially in the step of synthesizing the diphenyl ether group-containing 5-trifluoromethyl substituted oxadiazole compound, the product can be obtained by column chromatography.

(3) The compound of the invention is a medicament for preventing and treating plant fungi in the agricultural or forestry field, and the medicament has better effect on preventing and treating sclerotinia rot of colza, wheat scab and early blight of tomato.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without inventive exercise. Wherein:

FIG. 1 is a schematic diagram of a preparation method of a diphenyl ether group-containing 5-trifluoromethyl substituted oxadiazole compound in an embodiment of the invention;

FIG. 2 is a schematic diagram of the in vitro assay (plate) of Compound I-4 against Sclerotinia sclerotiorum in the example of the present invention (from left to right concentrations are 5mg/L,1.25mg/L,0.3125mg/L,0.0781mg/L and 0.0195mg/L in this order);

FIG. 3 is a schematic diagram of in vivo experiments on Botrytis cinerea (tomato plant method) by the compound I-5 in the example of the present invention.

Detailed Description

In order to make the aforementioned objects, features and advantages of the present invention more comprehensible, specific embodiments thereof are described in detail below with reference to examples of the specification.

In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described and will be readily apparent to those of ordinary skill in the art without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.

Furthermore, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.

The preparation method of the diphenyl ether group-containing 5-trifluoromethyl substituted oxadiazole compound in the embodiment of the invention is shown in figure 1.

Example 1

Preparation of diphenyl ether group-containing 5-trifluoromethyl substituted oxadiazole compound:

4-cyanobenzoic acid (0.017mol) is dissolved in 30ml of dry tetrahydrofuran and 10ml of N, N-dimethylformamide, triethylamine (0.0425mol) and hydroxylamine hydrochloride (0.0255mol) are added under stirring, and the reaction solution is heated to the reflux temperature for reaction for 2 hours. TLC (thin layer chromatography) is used for monitoring the complete reaction of the raw materials, then the raw materials are cooled to room temperature, trifluoroacetic anhydride (0.0408mol) is dripped, the reaction liquid is heated again to the reflux temperature for reaction for 0.5h, the reaction liquid is cooled, the reaction liquid is poured into 200mL water, solid is separated out under stirring, and white solid 4- [5- (trifluoromethyl) -1,2, 4-oxadiazole-3-yl is obtained after suction filtration and drying]Benzoic acid, white solid, yield 72%, m.p.169-171 ℃.¹H NMR(600MHz,DMSO)δ13.39(s,1H),8.21–8.19(m,2H),8.17-8.15(m,2H).¹³C NMR(150MHz,DMSO)δ167.9,166.4,165.3(q,J＝43.5Hz),134.2,130.3,129.4,127.6,115.7(q,J＝271.5Hz,)..

The intermediate 4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl is added to a dry 25ml single-neck flask]Benzoic acid (1.2mmol), 4-aminodiphenyl ether (1.0mmol), EDCI (1.2mmol), 4-dimethylaminopyridine (0.2mmol) and CH₂Cl₂(10mL), after dissolving and clarifying with stirring, the reaction was carried out at room temperature for 6-10 h. TLC to monitor the completion of the reaction, washing the organic layer with water (10 ml. times.3), washing with saturated brine (10 ml. times.3), drying, filtering under reduced pressure, concentrating under reduced pressure to remove dichloromethane to obtain crude product, and purifying with silica gel column chromatography (eluent CH)₂Cl₂MeOH 20:1) to obtain the target compound I-1,

white solid with a yield of 83 percent, m.p.206.5-208.1 ℃,¹H NMR(600MHz,DMSO)δ10.51(s,1H),8.24–8.23(m,2H),8.19–8.17(m,2H),7.83-7.80(m,2H),7.40–7.38(m,2H),7.13(t,J＝7.4Hz),7.07–7.05(m,2H),7.01-6.99(m,2H).¹³C NMR(150MHz,DMSO)δ167.9,165.2(t,J＝43.0Hz,),164.3,157.2,152.4,138.3,134.5,130.0,128.8,127.4,127.0,123.1,122.2,119.2,118.0,115.7(t,J＝270.1Hz).

example 2

The intermediate 4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl is added to a dry 25ml single-neck flask]Benzoic acid (1.2mmol),4- (4-fluorophenoxy) aniline (1.0mmol), EDCI (1.2mmol), 4-dimethylaminopyridine (0.2mmol) and CH₂Cl₂(10mL), after dissolving and clarifying with stirring, the reaction was carried out at room temperature for 6-10 h. TLC to monitor the completion of the reaction, washing the organic layer with water (10 ml. times.3), washing with saturated brine (10 ml. times.3), drying, filtering under reduced pressure, concentrating under reduced pressure to remove dichloromethane to obtain crude product, and purifying with silica gel column chromatography (eluent CH)₂Cl₂MeOH 20:1) gave the title compound I-2 as a white solid in 80% yield, m.p.201.1-202.5 ℃.¹HNMR(600MHz,DMSO)δ10.51(s,1H),8.24(d,J＝8.5Hz,2H),8.19(d,J＝8.5Hz,2H),7.81(d,J＝9.0Hz,2H),7.25–7.22(m,2H),7.07–7.04(m,4H).¹³C NMR(150MHz,DMSO)δ168.4,165.7(t,J＝43.9Hz),164.8,158.5(d,J＝237.6Hz),153.6,153.4,138.8,135.1,129.3,127.9,127.5,122.7,120.5(d,J＝8.5Hz),119.2,116.9(d,J＝23.2Hz),116.2(t,J＝271.6Hz).

Example 3

Adding the intermediate 4-[5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl]Benzoic acid (1.2mmol),4- (4-chlorophenoxy) aniline (1.0mmol), EDCI (1.2mmol), 4-dimethylaminopyridine (0.2mmol) and CH₂Cl₂(10mL), after dissolving and clarifying with stirring, the reaction was carried out at room temperature for 6-10 h. TLC to monitor the completion of the reaction, washing the organic layer with water (10 ml. times.3), washing with saturated brine (10 ml. times.3), drying, filtering under reduced pressure, concentrating under reduced pressure to remove dichloromethane to obtain crude product, and purifying with silica gel column chromatography (eluent CH)₂Cl₂MeOH 20:1) to give the title compound I-3 in 71% yield, m.p.205.8-207.1 deg.c,¹H NMR(600MHz,DMSO)δ10.53(s,1H),8.23(d,J＝8.4Hz,2H),8.18(d,J＝8.4Hz,2H),7.83(d,J＝9.0Hz,2H),7.43(d,J＝8.9Hz,2H),7.09(d,J＝9.0Hz,2H),7.02(d,J＝8.9Hz,2H).¹³C NMR(150MHz,DMSO)δ168.4,164.9,156.7,152.4,138.7,135.6,130.3,129.3,127.9,127.4(d,J＝33.9Hz),122.7,122.0,120.1,120.0,118.1(d,J＝245Hz).

example 4

The intermediate 4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl is added to a dry 25ml single-neck flask]Benzoic acid (1.2mmol),4- (4-aminophenoxy) aniline (1.0mmol), EDCI (1.2mmol), 4-dimethylaminopyridine (0.2mmol) and CH₂Cl₂(10mL), after dissolving and clarifying with stirring, the reaction was carried out at room temperature for 6-10 h. TLC to monitor the completion of the reaction, washing the organic layer with water (10 ml. times.3), washing with saturated brine (10 ml. times.3), drying, filtering under reduced pressure, concentrating under reduced pressure to remove dichloromethane to obtain crude product, and purifying with silica gel column chromatography (eluent CH)₂Cl₂MeOH 20:1) to give the title compound I-4 as a white solid, yield 50%, m.p.170-171.6 deg.c,¹HNMR(600MHz,DMSO)δ10.41(s,1H),8.21(d,J＝8.5Hz,2H),8.16(d,J＝8.5Hz,2H),7.70(d,J＝9.0Hz,2H),6.88(d,J＝9.0Hz,2H),6.77–6.75(m,2H),6.59(d,J＝8.8Hz,2H),4.97(s,2H)；¹³C NMR(150MHz,DMSO)δ165.2,161.7,152.6,151.4,150.9,145.3,142.2(d,J＝39.3Hz),133.1,128.8,127.4,126.9,122.1,120.5,118.9,116.8,114.8(d,J＝13.9Hz),114.7(q,J＝267.5Hz).

example 5

The intermediate 4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl is added to a dry 25ml single-neck flask]Benzoic acid (1.2mmol),4- (4-methoxyphenoxy) aniline (1.0mmol), EDCI (1.2mmol), 4-dimethylaminopyridine (0.2mmol) and CH₂Cl₂(10mL), after dissolving and clarifying with stirring, the reaction was carried out at room temperature for 6-10 h. TLC to monitor the completion of the reaction, washing the organic layer with water (10 ml. times.3), washing with saturated brine (10 ml. times.3), drying, filtering under reduced pressure, concentrating under reduced pressure to remove dichloromethane to obtain crude product, and purifying with silica gel column chromatography (eluent CH)₂Cl₂MeOH ═ 20:1) gave the title compound I-5 as a white solid in 70% yield, m.p.201-203.1 ℃.¹H NMR(600MHz,DMSO)δ10.46(s,1H),8.22(d,J＝8.4Hz,2H),8.18(d,J＝8.4Hz,2H),7.76(d,J＝9.0Hz,2H),7.00-6.96(m,5H),3.75(s,3H).¹³C NMR(150MHz,DMSO)δ168.4,164.7,155.9,154.4,150.4,138.8,134.4,129.3,129.0,127.9(,127.4,122.6,120.7,118.3,112.5(J＝265.1Hz),55.9

Example 6

The third step of the synthetic route, namely the reaction condition of the condensation reaction, is studied, and different types of catalysts and condensing agents are selected. Taking the example of the synthesis of compound I-1, the intermediate 4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] was added to a dry 25ml single-neck flask]Benzoic acid (1.2mmol), 4-phenoxyaniline (1.0mmol), condensing agent (1.2mmol), catalyst (0.2mmol) and CH₂Cl₂(10mL), the reaction mixture was dissolved with stirring and clarified, and then the reaction mixture was reacted at room temperature and monitored by TLC.

TABLE 1 examination of condensation reaction conditions

Note "-" untreated

Four reaction conditions were investigated, with 1-ethyl- (3-dimethylaminopropyl) carbonyldiimine hydrochloride (EDCI) as the condensing agent and 1-hydroxybenzotriazole (Hobt) as the catalyst, the conversion of 4-phenoxyaniline as the starting material was lower than when 4-Dimethylaminopyridine (DMAP) was used as the catalyst; dicyclohexylcarbodiimide (DCC) has stronger condensation capacity than EDCI, but impurities are generated in the reaction process, a byproduct Dicyclohexylurea (DCU) is difficult to completely remove by column chromatography, and the separation yield is low (45%); when 2- (7-azabenzotriazole) -N, N, N ', N' -tetramethyluronium Hexafluorophosphate (HATU) is used as a condensing agent, TLC monitors that only a small amount of 4-phenoxyaniline as a raw material is converted, and the conversion rate is low. The preferred condensation reaction conditions are EDCI as the condensing agent and DMAP as the catalyst.

Example 7

Bactericidal activity (in vitro) test

The plant fungi used in the experiment are strains stored at 4 ℃ in a laboratory, are rhizoctonia solani (ACCC 38870), botrytis cinerea (ACCC 36027), sclerotinia sclerotiorum (ACCC 30096), early blight of tomato (ACCC 36110) and gibberella zeae (ACCC 31060), and are all purchased from the Chinese agricultural microbial strain preservation management center (ACCC). The adopted culture medium is a potato agar glucose culture medium (PDA for short). The PDA culture medium formula comprises 200g of potato (peeled), 20g of glucose, 15g of agar and 1000mL of distilled water, and the preparation method comprises the following steps: cleaning and peeling potatoes, weighing 200g of potatoes, cutting the potatoes into small pieces, adding water, boiling the potatoes thoroughly (boiling for 20-30 minutes and being capable of being punctured by a glass rod), filtering the potatoes in a beaker by eight layers of gauze, adding 15-20g of agar according to experimental requirements, adding 20g of glucose, stirring the mixture evenly, slightly cooling the mixture after the mixture is fully dissolved, supplementing water to 1000mL, sterilizing the mixture for 30 minutes at 121 ℃ after split charging, and cooling the mixture for later use.

The experimental method comprises the following steps: a growth rate method is used.

(1) Firstly, 5 plant fungi are cultured on a PDA flat plate at 25 ℃ for about 3-6 days for later use;

(2) heating PDA culture medium to melt, cooling to 45-50 deg.C, adding 100 μ L of 10g/L to-be-tested compound to obtain culture medium containing 20mg/L medicinal liquid, and respectively pouring into culture dish for cooling, and using boscalid (boscalid) as positive control;

(3) taking a circular fungus cake (diameter is 0.50cm) from the edge of each strain hypha cultured for 6d (growth conditions are consistent as much as possible) by using a puncher in an aseptic operation procedure, picking the circular fungus cake to the center of a drug-containing flat plate by using an inoculating needle, and then placing the culture dish in an incubator (28 ℃) for culture;

(4) observing and measuring the growth condition of hyphae at different time after treatment, measuring the diameter by adopting a cross method, processing data and calculating the inhibition rate;

(5) inhibition (%) × (control hypha diameter-treated hypha diameter)/(control hypha diameter-0.5) × 100;

(6) each treatment was repeated 3 times.

TABLE 2 inhibitory Activity test results of Diphenyl ether group-containing 5-trifluoromethyl substituted oxadiazole Compounds against five agricultural pathogenic fungi

Note a three replicates for each treatment in the experiment and the data in the table is the average of the three replicates.

EC of part of the Compounds of Table 3₅₀Value of

The results of the bactericidal activity measurements of the experimental groups I-1 to I-5 and the control medicament boscalid are shown in tables 2 and 3. As can be seen from the results in tables 2 and 3, at a concentration of 20mg/L, the compounds I-1 to I-5 showed different degrees of bacteriostatic activity against 5 plant fungi, some of the compounds showed relatively good bacteriostatic activity against early blight of tomato and gibberellic disease of wheat, and the respective compounds showed comparable inhibitory rates against sclerotinia sclerotiorum and botrytis cinerea as the control medicament boscalid.

FIG. 2 is a schematic diagram of the in vitro assay (plate) of Compound I-4 against Sclerotinia sclerotiorum in the present example (from left to right concentrations are 5mg/L,1.25mg/L,0.3125mg/L,0.0781mg/L and 0.0195mg/L in this order).

As part of the target compounds have better inhibitory activity on three pathogenic bacteria, namely sclerotinia sclerotiorum, fusarium graminearum, early blight of tomato and botrytis cinerea, the EC of part of the compounds with higher inhibition rate is tested₅₀The value is obtained. As can be seen from Table 3, the EC of Compound I-5 against Botrytis cinerea₅₀EC with value superior to boscalid₅₀A value; the inhibitory activity of the compound I-4 on sclerotinia sclerotiorum is slightly higher than that of EC of boscalid₅₀The value is obtained. In addition, Compound I-5 has EC against Phytophthora solani₅₀And the compound is equivalent to boscalid and has the potential of developing antifungal agents.

Example 8

Sterilization in vivo experiment

Tomato plants were used for in vivo testing. The well grown Botrytis cinerea cake was inoculated and dissolved in 0.5% (v/v) to make a spore suspension. When the tomato plants grow to 30 leaves, the prepared compound I-5 solution and boscalid (boscalid) solution are uniformly sprayed on the plants, and after air drying, the spore suspension is uniformly sprayed on the plant leaves. Culturing in a greenhouse at 24 +/-1 ℃ and 80% relative humidity, observing for several days, and after blank control is sufficiently ill, investigating disease indexes of the tomato plants to be tested.

TABLE 4 test of inhibitory Activity of Compound I-5 against Botrytis cinerea (tomato plant Living body)

FIG. 3 is a schematic diagram of in vivo experiments on Botrytis cinerea (tomato plant method) by the compound I-5 in the example of the present invention.

The control effect of the compound on botrytis cinerea is 77.55%, which is close to boscalid (80.31%), and the result shows that the compound I-5 can be further developed as a lead compound.

The diphenyl ether group-containing 5-trifluoromethyl substituted oxadiazole compound has obvious structural difference and distinct chemical structural characteristics, and has good effects on preventing and treating sclerotinia rot of colza, fusarium graminearum and early blight of tomato. The compound can be used for preventing and treating agricultural or forestry plant fungal diseases, and has the advantages of simple preparation method, high yield and stable product property.

It should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.