CN116178359A - Heterocyclic substitution-based disulfide derivative, preparation method and application thereof - Google Patents

Heterocyclic substitution-based disulfide derivative, preparation method and application thereof Download PDF

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CN116178359A
CN116178359A CN202310272800.8A CN202310272800A CN116178359A CN 116178359 A CN116178359 A CN 116178359A CN 202310272800 A CN202310272800 A CN 202310272800A CN 116178359 A CN116178359 A CN 116178359A
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bacterial leaf
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李建专
蔡佳
昝宁宁
曾露
伍思凯
王建
陈菲菲
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Guizhou University
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    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
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    • A—HUMAN NECESSITIES
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
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Abstract

The application relates to a disulfide derivative based on heterocyclic substitution, a preparation method and application thereof, and a structural formula is shown as a formula V:
Figure DDA0004135266290000011
the method comprises the steps of carrying out a first treatment on the surface of the The test of plant bacterial inhibition activity of the disulfide derivative containing heterocyclic substitution proves that the disulfide derivative containing heterocyclic substitution has good antibacterial activity on plant bacterial diseases, can be applied to preparation of plant bacterial inhibition medicaments, and has simple structure and preparation process and low production cost.

Description

Heterocyclic substitution-based disulfide derivative, preparation method and application thereof
Technical Field
The application relates to the field of pesticide synthesis, in particular to a disulfide derivative based on heterocyclic substitution, a preparation method and application thereof.
Background
The bacterial diseases of major plants such as bacterial leaf blight of rice, bacterial leaf streak of rice, citrus canker and the like seriously endanger the yield and quality of grain crops and cash crops in China, and cause huge economic loss to agricultural production in China every year. However, the current agricultural chemical varieties for preventing and treating bacterial diseases in China are very limited, the quantity of the agricultural chemical varieties is about 280, and the agricultural chemical varieties only account for 2.6% of the total quantity of registered products of the domestic bactericides, and the agricultural chemical varieties mainly comprise copper preparations, antibiotics bactericides, zinc thiazole, and metconazole, and the like, and the problems of serious resistance, poor prevention effect, environmental pollution and the like are caused. Thus, there is a need to develop new, efficient, low risk, and mechanism of action unique green bactericides.
Benzofuran derivatives and analogues thereof are widely found in natural products as a typical representative of a class of oxygen-containing heterocyclic compounds. Many compounds containing benzofuran structures have antibacterial, anti-HIV, anti-tumor, and cardiovascular aging delaying effects. To date, more than 30 natural benzofurans have been used clinically, and more than 3000 benzopyrans have been found in natural products in humans and are ready for clinical screening. The benzofuran compounds are extracted from medicinal plants and marine organisms, and can be separated from a plurality of bacteria and fungus metabolites. Along with continuous researches, different functional groups are introduced into each substitution position of benzofuran to form a series of derivatives with practical value, and the derivatives are continuously developed and applied to the field of medicines, so that the derivatives have important significance for the treatment of diseases and the development of human beings.
The derivatives containing 1,3, 4-oxadiazole structure, which are independently developed from the subject in recent years, are bactericides with novel structure and broad-spectrum activity, and have broad-spectrum and high-efficiency antibacterial activity on various plant pathogenic bacteria, such as: the sulfone compounds such as the methanesulfonyl bacteria oxazole, the dichloro bacteria oxazole and the fluorobenze oxazole sulfone have excellent antibacterial activity. However, these compounds are susceptible to degradation by light due to instability of their sulfone-based structure, which is easily decomposed or inactivated in field applications, resulting in photodegradation, which limits their popularization and popularity as commercial bactericides. Therefore, the improvement of the stability of the sulfone compounds is the key for further developing the sulfone compounds into agricultural bactericides.
Furthermore, allicin is a natural thiosulfinate salt, isolated from garlic in 1944 and found to have antibacterial activity against a variety of gram negative and gram positive bacteria, and mechanism studies have shown that the antibacterial activity of allicin is associated with its thiol group, which can react with a variety of enzymes such as: alcohol dehydrogenase, thioredoxin reductase, RNA polymerase, and the like. Although allicin has various biological activities, its chemical and thermal instability has prompted efforts to develop new drugs for therapeutic use. Disulfide bonds (S-S bonds) are an important chemical functional group in allicin, and are also present in various natural small molecule compounds and biological protein structures. Some small molecule compounds containing disulfide bond have been reported in literature to show antibacterial, antiviral, antitumor and other biological activities, and have green and low toxicity in vivo. In view of this, in order to find disulfide derivatives with novel structure, broad spectrum, high efficiency, low toxicity and high activity, 1,3, 4-oxadiazole is taken as a main skeleton, allicin disulfide groups with excellent antibacterial activity are introduced by methods such as active substructure splicing and the like, a series of novel disulfide derivatives containing heterocycle substitution are synthesized, the antibacterial activity of the compounds in agriculture is evaluated, and development of novel agricultural bactericides with broad spectrum, high efficiency, green and pollution-free sustainable development is expected.
In 2017, yang et al (Fong, j.; yuan, m.; jakobsen, t.h.; mortensen, k.t.; delos Santos, m.m.s.; chua, s.l.; yang, l.; tan, c.h.; nielsen, t.e.; givskov, m.Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa)Journal ofMedicinal chemistry.2017, 60, (1), 215-227.) after quantitative structure-activity relationship (SAR) studies, 25 disulfide-containing analogs were synthesized and tested for QS inhibitory activity. SAR studies have shown that allyl groups can be substituted with other substituents, with benzothiazole derivatives having the highest activity (IC 50 =0.56 μm). These compounds were able to reduce QS-regulated virulence factors (elastase, rhamnolipid and suppurative blue) and successfully inhibit pseudomonas aeruginosa infection in the relevant mouse model.
2021, ouyang Gui (Ouyang Guiping, zhu Mei, wang Zhenchao, li Yan, fan Sai, tao Shilin. A preparation method of 6-fluoroquinazoline derivatives containing disulfide structure and application thereof [ P ]. CN113754595A,2021 ]) takes 6-fluoroquinazoline as parent structure, and introduces disulfide (heterocycle) structure into the system, so as to synthesize a series of 6-fluoroquinazoline derivatives containing disulfide structure, and the in vitro experimental result shows that: wherein, the compounds 1-6, 8-10, 13 and 17 can still realize the inhibition effect of more than 90% at a lower concentration of 25ppm, and the inhibition rate of the metconazole at the same concentration is only about 30%.
In 2022, ouyang Gui et al (Zhu, m.; li, y.; long, x.; wang, c.; ouyang, g.; wang, z. Antibacterial Activity of Allicin-Inspired Disulfide Derivatives against Xanthomonas axonopodis pv. Citri. International Journal of Molecular sciences.2022, 23, (19), 11947.;) authors found that compound 1 exhibited significant anti-Xac activity semi-Effective Concentrations (EC) in vitro 50 ) 2.6. Mu.g/mL, while the positive control, thiabendazole (EC 50 ) 57. Mu.g/mL and metconazole (EC) 50 ) At 68 μg/mL, the compound has excellent anti-citrus ulcer activity.
In 2022, before Liu Ying and the like (before Liu Ying, li Weiguo, wangru, chunhua, zhang Zhijun, an Junxia, ma Yue. A disulfide bond compound, a preparation method thereof and application thereof in antibiosis [ P ]. CN114773261A,2022 ]) 32 disulfide bond compounds are synthesized, antibacterial activity screening of 32 target compounds is tested, 17 compounds have good inhibition effect on bacterial blight bacteria (Xoo) of paddy rice, MIC=1.56-100 ug/mL, wherein MIC values of the compounds S5, S6 and S7 are respectively 1.56, 6.25 and 12.5ug/mL, which are superior to that of positive control drug thiamycocopper (MIC=100 ug/mL); the 8 compounds have better inhibition effect on citrus canker (Xac), wherein MIC=6.25-100 ug/mL, wherein MIC values of the compounds S6 and S7 are 6.25 ug/mL and 12.5ug/mL respectively, which are superior to those of the positive control drug and the thiabendazole copper (MIC=100 ug/mL);
disulfide bonds (S-S bonds) are an important chemical functional group in allicin, and are also present in various natural small molecule compounds and biological protein structures. Some small molecular compounds containing disulfide bonds are reported to show biological activities such as antibiosis, anti-tumor and the like and have low toxicity in vivo, so that the disulfide bonds are introduced into a 1,3, 4-oxadiazole structure in the study to achieve better sterilization effect.
Disclosure of Invention
The object of the present application is to provide a preparation method and application of disulfide derivatives based on heterocyclic substitution, wherein a series of disulfide derivatives containing 1,3, 4-oxadiazole with plant bacteria inhibiting activity are synthesized by introducing active disulfide bonds into a 1,3, 4-oxadiazole structure.
In order to achieve the above purpose, the present application provides the following technical solutions:
a disulfide derivative containing 1,3, 4-oxadiazole, which has the following structural formula:
Figure BDA0004135266270000031
wherein: r is R 1 Hydrogen, methyl, methoxy, halogen (chlorine, bromine, fluorine), and the like. R is R 2 Ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, cyclohexyl, n-butyl, 2-propenyl, heterocycles, and the like.
A disulfide derivative comprising 1,3, 4-oxadiazole as described above, wherein: r is R 1 Hydrogen, methyl, methoxy, halogen (chlorine, bromine, fluorine), and the like. R is R 2 Is ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl,Cyclohexyl, n-butyl, 2-propenyl, heterocycle, and the like.
The application also provides a preparation method of the disulfide derivative containing 1,3, 4-oxadiazole, which has the following synthetic route:
(1) The salicylaldehyde I containing the substituent groups is taken as a raw material, is put into a three-mouth bottle, is subjected to reflux reaction with ethyl bromoacetate to form a ring, and is purified by column chromatography (PE: EA=10:1) to obtain the benzofuran ethyl formate II containing the substituent groups.
Figure BDA0004135266270000032
(2) The II and hydrazine hydrate undergo hydrazinolysis reaction to obtain benzofurancarbohydrazide III containing each substituent group
Figure BDA0004135266270000033
(3) And (3) after the reflux reaction of III and carbon disulfide under alkaline conditions, adjusting the PH=3-4 by using 5% diluted hydrochloric acid to generate benzofuran-1, 3, 4-oxadiazole-2-thiol III containing various substituents.
Figure BDA0004135266270000034
(4) III reacts with each substituted mercaptan under the catalysis of 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) to obtain a target compound V series through column chromatography (PE: EA=10:1).
Figure BDA0004135266270000035
The application further provides the application of the heterocyclic substituted disulfide derivative in inhibiting plant bacteria.
The beneficial technical effects of the application are as follows:
the method takes salicylaldehyde, ethyl bromoacetate and the like containing substituent groups as raw materials to prepare benzofurancarboxylic acid ethyl ester with each substituent group; the benzofuran ethyl formate and hydrazine hydrate of each substituent are taken as raw materials, hydrazinolysis reaction is carried out to obtain benzofuran formylhydrazine containing each substituent, PH=3-4 is regulated by using 5% diluted hydrochloric acid after reflux reaction with carbon disulfide under alkaline condition to generate benzofuran-1, 3, 4-oxadiazole-2-thiol containing each substituent, and the benzofuran-1, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) is reacted with each substituted thiol under the catalysis of 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) to obtain a target compound V series. Disulfide groups with excellent activity are introduced into the structure of 1,3, 4-oxadiazole. A series of disulfide derivatives containing 1,3, 4-oxadiazole are synthesized, and the compounds of the application have excellent plant bacterial inhibition activity through testing the plant bacterial inhibition activity of the synthesized disulfide derivatives containing 1,3, 4-oxadiazole, so that the compounds can be used for preparing medicaments for inhibiting plant pathogens.
Drawings
FIG. 1 shows the therapeutic activity of compounds V1-V4 at 200. Mu.g/mL for bacterial leaf blight of rice;
FIG. 2 shows the protective activity of the compounds V1-V4 against bacterial leaf blight of rice at 200. Mu.g/mL.
Examples
Various exemplary embodiments of the present application will now be described in detail, which should not be considered as limiting the application, but rather as more detailed description of certain aspects, features and embodiments of the present application. It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application. All the starting materials and solvents used in the examples were commercially available products of the corresponding purity.
Example 1
A process for the preparation of 2- (benzofuran-2-yl) -5- (ethyldithio) -1,3, 4-oxadiazole (target compound V1) comprising the steps of:
(1) Preparation of benzofuran-2-carboxylic acid ethyl ester (intermediate 1):
salicylaldehyde (1 g,4.4 mmol) was dissolved in acetonitrile (20 ml), followed by the addition of ethyl bromoacetate (660 μl,6.6 mmol) and potassium carbonate (3.0 g,22 mmol) and reflux for 48 hours. After the reaction was completed, the reaction product was poured into ice water, extracted with ethyl acetate, the organic phases were combined, washed three times with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel chromatography (petroleum ether: ethyl acetate=10:1) to give oily liquid intermediate 1, yield: 86%.
(2) Preparation of benzofuran-2-carboxylic acid hydrazide (intermediate 2):
5mL of 80% hydrazine hydrate was slowly added to ethanol (30 mL) containing 0.5g (2.63 mmol) of benzofuran-2-carboxylic acid ethyl ester. After heating and refluxing for 6 hours, cooling to room temperature, filtering under reduced pressure, and recrystallizing the crude product in ethanol to obtain white intermediate 2 with a yield of 74%.
(3) Preparation of 5- (benzofuran-2-yl) -1,3, 4-oxadiazole-2-thiol (intermediate 3):
benzofuran-2-carboxylic acid hydrazide (3.04 g,10 mmol) was accurately weighed into a 100mL three-necked flask, potassium hydroxide (0.84 g,15 mmol) was added to the system, and 50mL ethanol was added as solvent. Stirring at room temperature to fully dissolve, slowly adding carbon disulfide after dissolving, heating and refluxing for 10 hours, concentrating under reduced pressure to remove part of solvent, and pouring the obtained reaction mixture into ice water to adjust the pH to be 3-4 by dilute hydrochloric acid. The resulting solid was collected by suction filtration, washed with water and petroleum ether, and then recrystallized from EtOH/DMF to give intermediate 3, a 1,3, 4-oxadiazole derivative in 76% yield.
(4) Preparation of 2- (benzofuran-2-yl) -5- (ethyldithio) -1,3, 4-oxadiazole (target compound V1):
0.15g (504. Mu. Mol) of 5- (benzofuran-2-yl) -1,3, 4-oxadiazole-2-thiol was weighed accurately into a 50mL flask under ice bath conditions, 10mL of acetone was added as a solvent, and 57. Mu.L (757. Mu. Mol) of ethanethiol was slowly added dropwise to the system after dissolution. Then, 0.12g (504. Mu. Mol) of 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) was slowly added to the system, and the reaction was continued with stirring. The progress of the reaction was monitored by TLC, after completion of the reaction, a small amount of water was added to find out a solid precipitated, and the obtained solid was purified by column chromatography (PE/ea=10:1) under reduced pressure and suction to give the objective compound V1, yield: 68%.
Example 2
A process for the preparation of 2- (5-bromobenzofuran-2-yl) -5- (ethyldithio) -1,3, 4-oxadiazole (target compound V2) comprising the steps of:
(1) Preparation of ethyl 5-bromobenzofuran-2-carboxylate (intermediate 1):
step (1) of example 1 was followed, except that salicylaldehyde was replaced with an equimolar amount of 4-bromosalicylaldehyde.
(2) Preparation of 5-bromobenzofuran-2-carboxylic acid hydrazide (intermediate 2):
step (2) of example 1 was followed, except that benzofuran-2-carboxylic acid ethyl ester was replaced with an equimolar amount of 5-bromobenzofuran-2-carboxylic acid ethyl ester.
(3) Preparation of 5- (5-bromobenzofuran-2-yl) -1,3, 4-oxadiazole-2-thiol (intermediate 3):
step (3) of example 1 is followed, except that benzofuran-2-carboxylic acid hydrazide is replaced with an equimolar amount of 5-bromobenzofuran-2-carboxylic acid hydrazide.
(4) Preparation of 2- (5-bromobenzofuran-2-yl) -5- (ethyldisulfide) -1,3, 4-oxadiazole (target compound V2):
step (4) as in example 1, except that 5- (benzofuran-2-yl) -1,3, 4-oxadiazole-2-thiol is replaced with an equimolar amount of 5- (5-bromobenzofuran-2-yl) -1,3, 4-oxadiazole-2-thiol, yield: 63%.
Example 3
A process for the preparation of 2- (5-chlorobenzofuran-2-yl) -5- (ethyldithio) -1,3, 4-oxadiazole (target compound V3) comprising the steps of:
(1) Preparation of 5-chlorobenzofuran-2-carboxylic acid ethyl ester (intermediate 1):
step (1) of example 1 was followed, except that salicylaldehyde was replaced with an equimolar amount of 4-chlorosalicylaldehyde.
(2) Preparation of 5-chlorobenzofuran-2-carboxylic acid hydrazide (intermediate 2):
step (2) of example 1 was repeated except that benzofuran-2-carboxylic acid ethyl ester was replaced with an equimolar amount of 5-chlorobenzofuran-2-carboxylic acid ethyl ester.
(3) Preparation of 5- (5-chlorobenzofuran-2-yl) -1,3, 4-oxadiazole-2-thiol (intermediate 3):
step (3) of example 1 was followed, except that benzofuran-2-carboxylic acid hydrazide was replaced with an equimolar amount of 5-chlorobenzofuran-2-carboxylic acid hydrazide.
(4) Preparation of 2- (5-chlorobenzofuran-2-yl) -5- (ethyldithio) -1,3, 4-oxadiazole (target compound V3):
step (4) as in example 1, except that 5- (benzofuran-2-yl) -1,3, 4-oxadiazole-2-thiol is replaced with an equimolar amount of 5- (5-chlorobenzofuran-2-yl) -1,3, 4-oxadiazole-2-thiol, yield: 67%.
Example 4
A process for the preparation of 2- (5-fluorobenzofuran-2-yl) -5- (ethyldithio) -1,3, 4-oxadiazole (target compound V4) comprising the steps of:
(1) Preparation of ethyl 5-fluorobenzofuran-2-carboxylate (intermediate 1):
step (1) of example 1 is followed, except that salicylaldehyde is replaced with an equimolar amount of 4-fluoro salicylaldehyde.
(2) Preparation of 5-fluorobenzofuran-2-carboxamide (intermediate 2):
step (2) of example 1 was followed, except that benzofuran-2-carboxylic acid ethyl ester was replaced with an equimolar amount of 5-fluorobenzofuran-2-carboxylic acid ethyl ester.
(3) Preparation of 5- (5-fluorobenzofuran-2-yl) -1,3, 4-oxadiazole-2-thiol (intermediate 3):
step (3) of example 1 is followed, except that benzofuran-2-carboxylic acid hydrazide is replaced with an equimolar amount of 5-fluorobenzofuran-2-carboxylic acid hydrazide.
(4) Preparation of 2- (5-fluorobenzofuran-2-yl) -5- (ethyldithio) -1,3, 4-oxadiazole (target compound V4):
step (4) as in example 1, except that 5- (benzofuran-2-yl) -1,3, 4-oxadiazole-2-thiol is replaced with an equimolar amount of 5- (5-fluorobenzofuran-2-yl) -1,3, 4-oxadiazole-2-thiol, yield: 58%.
Example 5
A process for the preparation of 2- (benzofuran-2-yl) -5- (propyldithio) -1,3, 4-oxadiazole (target compound V5) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) are described in example 1.
(4) Preparation of 2- (benzofuran-2-yl) -5- (propyldisulfide) -1,3, 4-oxadiazole (target compound V5): step (4) of example 1, except that ethanethiol was replaced with equimolar amount of propanethiol, yield: 59%.
Example 6
A process for the preparation of 2- (5-bromobenzofuran-2-yl) -5- (propyldisulfide) -1,3, 4-oxadiazole (target compound V6) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 2.
(4) Preparation of 2- (5-bromobenzofuran-2-yl) -5- (propyldisulfide) -1,3, 4-oxadiazole (target compound V6): step (4) of example 2, except that ethanethiol was replaced with equimolar propanethiol, yield: 63%.
Example 7
A process for the preparation of 2- (5-chlorobenzofuran-2-yl) -5- (propyldithio) -1,3, 4-oxadiazole (target compound V7) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 3.
(4) Preparation of 2- (5-chlorobenzofuran-2-yl) -5- (propyldisulfide) -1,3, 4-oxadiazole (target compound V7): step (4) as in example 3, except that ethanethiol was replaced with equimolar propanethiol, yield: 61%.
Example 8
A process for the preparation of 2- (5-fluorobenzofuran-2-yl) -5- (propyldithio) -1,3, 4-oxadiazole (target compound V8) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 4.
(4) Preparation of 2- (5-fluorobenzofuran-2-yl) -5- (propyldisulfide) -1,3, 4-oxadiazole (target compound V8): step (4) as in example 4, except that ethanethiol was replaced with equimolar propanethiol, yield: 59%.
Example 9
A process for the preparation of 2- (benzofuran-2-yl) -5- (isopropyldithio) -1,3, 4-oxadiazole (target compound V9) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) are described in example 1.
(4) Preparation of 2- (benzofuran-2-yl) -5- (isopropyldithio) -1,3, 4-oxadiazole (target compound V9): step (4) as in example l, except that ethanethiol was replaced with equimolar isopropyl thiol, yield: 61%.
Example 10
A process for the preparation of 2- (5-bromobenzofuran-2-yl) -5- (isopropyldithio) -1,3, 4-oxadiazole (target compound V10) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 2.
(4) Preparation of 2- (5-bromobenzofuran-2-yl) -5- (isopropyldithio) -1,3, 4-oxadiazole (target compound V10): step (4) of example 2, except that ethanethiol was replaced with equimolar isopropyl thiol, yield: 57%.
Example 11
A process for the preparation of 2- (5-chlorobenzofuran-2-yl) -5- (isopropyldithio) -1,3, 4-oxadiazole (target compound V11) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 3.
(4) Preparation of 2- (5-chlorobenzofuran-2-yl) -5- (isopropyldithio) -1,3, 4-oxadiazole (target compound V11): step (4) of example 3, except that ethanethiol was replaced with equimolar isopropyl thiol, yield: 56%.
Example 12
A process for the preparation of 2- (5-fluorobenzofuran-2-yl) -5- (isopropyldithio) -1,3, 4-oxadiazole (target compound V12) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 4.
(4) Preparation of 2- (5-fluorobenzofuran-2-yl) -5- (isopropyldithio) -1,3, 4-oxadiazole (target compound V12): step (4) of example 4, except that ethanethiol was replaced with equimolar isopropyl thiol, yield: 65%.
Example 13
A process for the preparation of 2- (benzofuran-2-yl) -5- (butyldisulpho) -1,3, 4-oxadiazole (target compound V13), comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) are described in example 1.
(4) Preparation of 2- (benzofuran-2-yl) -5- (butyldithio) -1,3, 4-oxadiazole (target compound V13): step (4) of example 1, except that ethanethiol was replaced with equimolar butanethiol, yield: 57%.
Example 14
A process for the preparation of 2- (5-bromobenzofuran-2-yl) -5- (butyldisulpho) -1,3, 4-oxadiazole (target compound V14), comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 2.
(4) Preparation of 2- (5-bromobenzofuran-2-yl) -5- (butyldisulfide) -1,3, 4-oxadiazole (target compound V14): step (4) of example 2, except that ethanethiol was replaced with equimolar butanethiol, yield: 61%.
Example 15
A process for the preparation of 2- (5-chlorobenzofuran-2-yl) -5- (butyldisulpho) -1,3, 4-oxadiazole (target compound V15), comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 3.
(4) Preparation of 2- (5-chlorobenzofuran-2-yl) -5- (butyldithio) -1,3, 4-oxadiazole (target compound V15): step (4) of example 3, except that ethanethiol was replaced with equimolar butanethiol, yield: 67%.
Example 16
A process for the preparation of 2- (5-fluorobenzofuran-2-yl) -5- (butyldisulpho) -1,3, 4-oxadiazole (target compound V16), comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 4.
(4) Preparation of 2- (5-fluorobenzofuran-2-yl) -5- (butyldisulpho) -1,3, 4-oxadiazole (target compound V16): step (4) of example 4, except that ethanethiol was replaced with equimolar butanethiol, yield: 59%.
Example 17
A process for the preparation of 2- (benzofuran-2-yl) -5- (isobutyldithio) -1,3, 4-oxadiazole (target compound V17) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) are described in example 1.
(4) Preparation of 2- (benzofuran-2-yl) -5- (isobutyldithio) -1,3, 4-oxadiazole (target compound V17): step (4) of example 1, except that ethanethiol was replaced with equimolar isobutanethiol, yield: 53%.
Example 18
A process for the preparation of 2- (5-bromobenzofuran-2-yl) -5- (isobutyldithio) -1,3, 4-oxadiazole (target compound V18) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 2.
(4) Preparation of 2- (5-bromobenzofuran-2-yl) -5- (isobutyldisulfide) -1,3, 4-oxadiazole (target compound V18): step (4) of example 2, except that ethanethiol was replaced with equimolar isobutanethiol, yield: 58%.
Example 19
A process for the preparation of 2- (5-chlorobenzofuran-2-yl) -5- (isobutyldithio) -1,3, 4-oxadiazole (target compound V19) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 3.
(4) Preparation of 2- (5-chlorobenzofuran-2-yl) -5- (isobutyldithio) -1,3, 4-oxadiazole (target compound V19): step (4) of example 3, except that ethanethiol was replaced with equimolar isobutanethiol, yield: 57%.
Example 20
A process for the preparation of 2- (5-fluorobenzofuran-2-yl) -5- (isobutyldithio) -1,3, 4-oxadiazole (target compound V20) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 4.
(4) Preparation of 2- (5-fluorobenzofuran-2-yl) -5- (isobutyldithio) -1,3, 4-oxadiazole (target compound V20): step (4) of example 4, except that ethanethiol was replaced with equimolar isobutanethiol, yield: 64%.
Example 21
A process for the preparation of 2- (benzofuran-2-yl) -5- (sec-butyldithio) -1,3, 4-oxadiazole (target compound V21), comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) are described in example 1.
(4) Preparation of 2- (benzofuran-2-yl) -5- (sec-butyldithio) -1,3, 4-oxadiazole (target compound V21): step (4) of example 1 was followed, except that ethanethiol was replaced with equimolar sec-butanethiol, yield: 55%.
Example 22
A process for the preparation of 2- (5-bromobenzofuran-2-yl) -5- (sec-butyldithio) -1,3, 4-oxadiazole (target compound V22) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 2.
(4) Preparation of 2- (5-bromobenzofuran-2-yl) -5- (sec-butyldithio) -1,3, 4-oxadiazole (target compound V22): step (4) of example 2 was followed, except that ethanethiol was replaced with equimolar sec-butanethiol, yield: 58%.
Example 23
A process for the preparation of 2- (5-chlorobenzofuran-2-yl) -5- (sec-butyldithio) -1,3, 4-oxadiazole (target compound V23) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 3.
(4) Preparation of 2- (5-chlorobenzofuran-2-yl) -5- (sec-butyldithio) -1,3, 4-oxadiazole (target compound V23): step (4) of example 3 was followed, except that ethanethiol was replaced with equimolar sec-butanethiol, yield: 63%.
Example 24
A process for the preparation of 2- (5-fluorobenzofuran-2-yl) -5- (sec-butyldithio) -1,3, 4-oxadiazole (target compound V24) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 4.
(4) Preparation of 2- (5-fluorobenzofuran-2-yl) -5- (sec-butyldithio) -1,3, 4-oxadiazole (target compound V24): step (4) of example 4, except that ethanethiol was replaced with equimolar sec-butanethiol, yield: 67%.
Example 25
A process for the preparation of 2- (benzofuran-2-yl) -5- (tert-butyldisulpho) -1,3, 4-oxadiazole (target compound V25), comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) are described in example 1.
(4) Preparation of 2- (benzofuran-2-yl) -5- (tert-butyldisulpho) -1,3, 4-oxadiazole (target compound V25): step (4) of example 1, except that ethanethiol was replaced with equimolar tert-butanethiol, yield: 53%.
Example 26
A process for the preparation of 2- (5-bromobenzofuran-2-yl) -5- (tert-butyldisulpho) -1,3, 4-oxadiazole (target compound V26), comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 2.
(4) Preparation of 2- (5-bromobenzofuran-2-yl) -5- (tert-butyldisulpho) -1,3, 4-oxadiazole (target compound V26): step (4) of example 2, except that ethanethiol was replaced with equimolar tert-butanethiol, yield: 59%.
Example 27
A process for the preparation of 2- (5-chlorobenzofuran-2-yl) -5- (tert-butyldisulpho) -1,3, 4-oxadiazole (target compound V27), comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 3.
(4) Preparation of 2- (5-chlorobenzofuran-2-yl) -5- (tert-butyldisulpho) -1,3, 4-oxadiazole (target compound V27): step (4) of example 3, except that ethanethiol was replaced with equimolar tert-butanethiol, yield: 52%.
Example 28
A process for the preparation of 2- (5-fluorobenzofuran-2-yl) -5- (tert-butyldisulpho) -1,3, 4-oxadiazole (target compound V28), comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 4.
(4) Preparation of 2- (5-fluorobenzofuran-2-yl) -5- (tert-butyldisulpho) -1,3, 4-oxadiazole (target compound V28): step (4) of example 4, except that ethanethiol was replaced with equimolar tert-butanethiol, yield: 61%.
Example 29
A process for the preparation of 2- (benzofuran-2-yl) -5- (pentyldithio) -1,3, 4-oxadiazole (target compound V29) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) are described in example 1.
(4) Preparation of 2- (benzofuran-2-yl) -5- (pentyldithio) -1,3, 4-oxadiazole (target compound V29): step (4) of example 1, except that ethanethiol was replaced with equimolar amyl thiol, yield: 51%.
Example 30
A process for the preparation of 2- (5-bromobenzofuran-2-yl) -5- (pentyldithio) -1,3, 4-oxadiazole (target compound V30) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 2.
(4) Preparation of 2- (5-bromobenzofuran-2-yl) -5- (pentyldithio) -1,3, 4-oxadiazole (target compound V30): step (4) of example 2, except that ethanethiol was replaced with equimolar amyl thiol, yield: 58%.
Example 31
A process for the preparation of 2- (5-chlorobenzofuran-2-yl) -5- (pentyldithio) -1,3, 4-oxadiazole (target compound V31) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 3.
(4) Preparation of 2- (5-chlorobenzofuran-2-yl) -5- (pentyldithio) -1,3, 4-oxadiazole (target compound V31): step (4) of example 3, except that ethanethiol was replaced with equimolar amyl thiol, yield: 55%.
Example 32
A process for the preparation of 2- (5-fluorobenzofuran-2-yl) -5- (pentyldithio) -1,3, 4-oxadiazole (target compound V32) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 4.
(4) Preparation of 2- (5-fluorobenzofuran-2-yl) -5- (pentyldithio) -1,3, 4-oxadiazole (target compound V32): step (4) of example 4, except that ethanethiol was replaced with equimolar amyl thiol, yield: 63%.
Example 33
A process for the preparation of 2- (benzofuran-2-yl) -5- (cyclohexyldisulfide) -1,3, 4-oxadiazole (target compound V33), comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) are described in example 1.
(4) Preparation of 2- (benzofuran-2-yl) -5- (cyclohexyldisulfide) -1,3, 4-oxadiazole (target compound V33): step (4) of example 1, except that ethanethiol was replaced with equimolar cyclohexyl thiol, yield: 61%.
Example 34
A process for the preparation of 2- (5-bromobenzofuran-2-yl) -5- (cyclohexyldisulfide) -1,3, 4-oxadiazole (target compound V34) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 2.
(4) Preparation of 2- (5-bromobenzofuran-2-yl) -5- (cyclohexyldisulfide) -1,3, 4-oxadiazole (target compound V34): step (4) of example 2, except that ethanethiol was replaced with equimolar cyclohexyl thiol, yield: 57%.
Example 35
A process for the preparation of 2- (5-chlorobenzofuran-2-yl) -5- (cyclohexyldisulfide) -1,3, 4-oxadiazole (target compound V35) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 3.
(4) Preparation of 2- (5-chlorobenzofuran-2-yl) -5- (cyclohexyldisulfide) -1,3, 4-oxadiazole (target compound V35): step (4) of example 3, except that ethanethiol was replaced with equimolar cyclohexyl thiol, yield: 57%.
Example 36
A process for the preparation of 2- (5-fluorobenzofuran-2-yl) -5- (cyclohexyldisulfide) -1,3, 4-oxadiazole (target compound V36) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 4.
(4) Preparation of 2- (5-fluorobenzofuran-2-yl) -5- (cyclohexyldisulfide) -1,3, 4-oxadiazole (target compound V36): step (4) of example 4, except that ethanethiol was replaced with equimolar cyclohexyl thiol, yield: 62%.
Example 37
A process for the preparation of 2- (benzofuran-2-yl) -5- ((3-methylbutan-2-yl) dithio) -1,3, 4-oxadiazole (target compound V37) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) are described in example 1.
(4) Preparation of 2- (benzofuran-2-yl) -5- ((3-methylbutan-2-yl) disulfide) -1,3, 4-oxadiazole (target compound V37): step (4) as in example 1. The difference is that the ethanethiol is replaced by equimolar 3-methylbutan-2-yl thiol, yield: 62%.
Example 38
A process for the preparation of 2- (5-bromobenzofuran-2-yl) -5- ((3-methylbutan-2-yl) disulfide) -1,3, 4-oxadiazole (target compound V38) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 2.
(4) Preparation of 2- (5-bromobenzofuran-2-yl) -5- ((3-methylbutan-2-yl) disulfide) -1,3, 4-oxadiazole (target compound V38): step (4) of example 2 was followed, except that ethanethiol was replaced with equimolar 3-methylbutan-2-yl-thiol, yield: 58%.
Example 39
A process for the preparation of 2- (5-chlorobenzofuran-2-yl) -5- ((3-methylbutan-2-yl) dithio) -1,3, 4-oxadiazole (target compound V39) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 3.
(4) Preparation of 2- (5-chlorobenzofuran-2-yl) -5- ((3-methylbutan-2-yl) disulfide) -1,3, 4-oxadiazole (target compound V39): step (4) of example 3 was followed, except that ethanethiol was replaced with equimolar 3-methylbutan-2-yl-thiol, yield: 51%.
Example 40
A process for the preparation of 2- (5-chlorobenzofuran-2-yl) -5- ((3-methylbutan-2-yl) dithio) -1,3, 4-oxadiazole (target compound V40) comprising the steps of:
(1) Preparation of- (3): steps (1) - (3) as in example 4.
(4) A process for the preparation of 2- (5-chlorobenzofuran-2-yl) -5- ((3-methylbutan-2-yl) dithio) -1,3, 4-oxadiazole (target compound V40): step (4) as in example 4, except that ethanethiol was replaced with equimolar 3-methylbutan-2-yl thiol, yield: 61%.
Physicochemical properties of the heterocyclic substituted disulfide derivatives prepared in examples 1 to 40 are shown in Table 1, hydrogen nuclear magnetic resonance spectrum [ ] 1 H NMR, carbon spectrum 13 C NMR) and fluorine Spectroscopy 19 F NMR) data are shown in table 2.
TABLE 1 physicochemical Properties of heterocyclic substituted disulfide derivatives prepared in examples 1 to 40
Figure BDA0004135266270000121
/>
Figure BDA0004135266270000131
TABLE 2 Nuclear magnetic resonance Spectroscopy data for heterocyclic substituted disulfide derivatives prepared in examples 1-40
Figure BDA0004135266270000132
/>
Figure BDA0004135266270000141
/>
Figure BDA0004135266270000151
/>
Figure BDA0004135266270000161
/>
Figure BDA0004135266270000171
/>
Figure BDA0004135266270000181
/>
Figure BDA0004135266270000191
Activity test example 1
Plant bacteria inhibition activity test:
(1) Test method
The in vitro activity test of the target compound on rice bacterial blight bacteria (Xoo), rice bacterial leaf spot bacteria (Xoc) and citrus canker bacteria (Xac) is carried out by adopting a nephelometry at the concentration of 100 and 50 mug/mL, and the control medicaments in the experiment are zinc thiazole and copper thiabendazole. The 3 germs are cultivated on NA solid medium, and then are cultivated in a constant temperature bacteria incubator at 28 ℃ until single colony is grown. Selecting single colony, placing it in NB liquid culture medium, shake culturing at 28deg.C in 180r/min constant temperature shaking table to logarithmic phase for use. Preparing 100 and 50 μg/mL concentration of compound and control medicament into drug-containing NB culture medium, taking three groups of 200 μl drug-containing NB culture medium into 96-well plates as blank control, taking three groups of 190 μl drug-containing NB culture medium into tubes in the 96-well plates as experimental group, and weighing 10 μl of strain containing the 5 coloniesNB liquid culture medium was added to the experimental group well plate and cultured for 24h at a constant temperature of 28℃and 180r/min with shaking. OD of the sterile NB liquid medium dosed at 595nm wavelength was determined on a spectrophotometer 595 Value, simultaneously measuring bacterial liquid OD of each concentration 595 Values.
Correcting OD 595 Value = fungus-containing medium OD 595 Sterile Medium OD 595
Inhibition (%) = (after correction control medium bacterial liquid OD 595 Correction of the OD of the drug-containing Medium 595 ) After correction, the OD value of the control culture medium is multiplied by 100%.
(2) The results of the biological activity test of the plant-inhibiting bacteria are shown in Table 3
The EC of V1-V40 target compounds against bacterial blight of rice (Xoo), bacterial leaf spot of rice (Xoc) and Uyghur disease of citrus (Xac) were tested by nephelometry at five concentrations of 25, 12.5, 6.25, 3.125 and 1.5625. Mu.g/mL 50 Values, activity data are shown in tables 3,4 and 5. The activity results show that the target compounds V1-V40 are superior to zinc thiazole (12.72 mu g/mL) and copper thiabendazole (66.41 mu g/mL) for rice bacterial blight bacteria (Xoo). EC of target compounds V1-V40 against Rice bacterial Pyricularia (Xoc) 50 Is superior to both zinc thiazole (29.07 mug/mL) and copper thiabendazole (78.49 mug/mL). EC of target Compounds V1-V40 against Ulmaria tangutica (Xac) 50 All are superior to copper thiabendazole (120.36 mug/mL), wherein most of the target compounds have EC against citrus canker (Xac) 50 Is superior to zinc thiazole (41.00 mug/mL).
TABLE 3 EC of target Compounds V1-V40 on Xoo 50 Value of
Figure BDA0004135266270000192
/>
Figure BDA0004135266270000201
/>
Figure BDA0004135266270000211
Note that: TZ: zinc thiazole; TC: thiabendazole copper;
TABLE 4 EC of target compounds V1-V40 against Xoc 50 Value of
Figure BDA0004135266270000212
/>
Figure BDA0004135266270000221
/>
Figure BDA0004135266270000231
Note that: TZ: zinc thiazole; TC: thiabendazole copper;
TABLE 5 EC of target compounds V1-V40 on Xac 50 Value of
Figure BDA0004135266270000232
/>
Figure BDA0004135266270000241
/>
Figure BDA0004135266270000251
Note that: TZ: zinc thiazole; TC: thiabendazole copper;
the treatment (FIG. 1) and protective activity (FIG. 2) of the V1-V4 target compounds against bacterial blight of rice (Xoo) were tested at 200 μg/mL using the leaf-cutting method.
The therapeutic activity is shown in the results of Table 6: the treatment effect of the compound V1 (60.08%) on rice bacterial leaf blight bacteria (Xoo) is equivalent to that of thiabendazole copper (60.10%).
The protective activity is shown in the results of Table 7: the protection effect of the compounds V3 (47.55%) and V4 (42.21%) on rice bacterial blight bacteria (Xoo) is better than that of thiabendazole copper (28.80%).
TABLE 6 in vivo therapeutic Activity of target Compounds V1-V4 against Xoo
Figure BDA0004135266270000261
Note that: TC: thiabendazole copper;
TABLE 7 in vivo protective Activity of target Compounds V1-V4 against Xoo
Figure BDA0004135266270000262
Note that: TC: thiabendazole copper;
the above embodiments are merely preferred embodiments of the present application, and the scope of the present application is not limited to the above embodiments, and any simple modification, equivalent variation and modification made to the above embodiments according to the technical matter of the present application shall fall within the protection scope defined by the claims of the present application.

Claims (8)

1. A heterocyclic-substituted-based disulfide derivative or a stereoisomer thereof, or a salt thereof or a solvate thereof, wherein the compound has a structure represented by formula V:
Figure FDA0004135266260000011
wherein the method comprises the steps of
R 1 Independently selected from one or more of hydrogen, halogen, nitro, hydroxy, amino;
R 2 independently selected from one or more of hydrogen, halogen, alkyl, cycloalkyl, alkoxy, aryl.
2. The heterocycle-substituted disulfide derivative or stereoisomer thereof, or a salt or solvate thereof, as claimed in claim 1, wherein the compound is selected from the group consisting of:
R 1 independently selected from one or more of hydrogen, halogen;
R 2 independently selected from one or more of hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, isopentyl, neopentyl, cyclobutyl.
3. The heterocycle-substituted disulfide derivative or stereoisomer thereof, or a salt or solvate thereof, as claimed in claim 1, wherein the compound is selected from the group consisting of: selected from the following specific compounds:
Figure FDA0004135266260000012
/>
Figure FDA0004135266260000021
4. a heterocycle-based substituted disulfide derivative according to any one of claims 1 to 3, characterized by comprising the steps of:
(4) IV reacting with each substituted thiol under the catalysis of 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ);
Figure FDA0004135266260000022
further comprises:
(3) III, carrying out reflux reaction with carbon disulfide under alkaline conditions to generate IV;
Figure FDA0004135266260000031
further comprises:
(2) Carrying out hydrazinolysis reaction on II and hydrazine hydrate to obtain III;
Figure FDA0004135266260000032
further comprises:
(1) The salicylaldehyde I containing substituent is taken as a raw material and reacts with ethyl bromoacetate flow to generate II
Figure FDA0004135266260000033
5. A composition comprising a heterocyclic-substituted disulfide derivative or a stereoisomer thereof, or a salt thereof or a solvate thereof as claimed in claim 1, and an agriculturally acceptable adjuvant or fungicide, insecticide or herbicide; preferably, the formulation of the composition is selected from the group consisting of Emulsifiable Concentrates (EC), powders (DP), wettable Powders (WP), granules (GR), aqueous Solutions (AS), suspensions (SC), ultra low volume sprays (ULV), soluble Powders (SP), microcapsules (MC), smoke agents (FU), aqueous Emulsions (EW), water dispersible granules (WG).
6. Use of a heterocyclic substituted disulfide derivative or stereoisomer thereof, or a salt thereof or a solvate thereof as claimed in claim 1, or a composition as claimed in claim 5, for controlling an agricultural pest, preferably a plant bacterial or fungal disease; more preferably, the agricultural pest is a plant leaf blight and a plant canker; most preferably, the agricultural pest is bacterial leaf blight of rice, bacterial leaf spot of rice, citrus canker, bacterial leaf blight of cucumber, bacterial leaf blight of konjak, bacterial canker of grape, bacterial canker of tomato, bacterial canker of kiwifruit, bacterial canker of apple, bacterial leaf blight of cucumber, bacterial leaf blight of pepper, bacterial sclerotium of rape, bacterial leaf spot of wheat, bacterial leaf spot of potato, bacterial leaf spot of blueberry.
7. A method for controlling agricultural plant diseases and insect pests, which is characterized by comprising the following steps: allowing the heterocycle-based substituted disulfide derivative or stereoisomer thereof, or salt thereof or solvate thereof, or the composition of claim 5 to act on a pest or living environment thereof; preferably, the agricultural pest is a bacterial or fungal plant disease; more preferably, the agricultural pest is bacterial leaf blight of rice, bacterial leaf spot of citrus, bacterial leaf spot of cucumber, bacterial leaf spot of konjak, bacterial leaf spot of grape, bacterial leaf spot of tomato, bacterial leaf spot of kiwi, bacterial leaf spot of apple, bacterial leaf spot of cucumber, bacterial leaf spot of pepper, bacterial leaf spot of rape, bacterial leaf spot of wheat, bacterial leaf spot of potato, bacterial leaf spot of blueberry.
8. A method for protecting a plant from an agricultural pest comprising the method step wherein the plant is contacted with a heterocycle-based substituted disulfide derivative of claim 1 or a stereoisomer thereof, or a salt thereof or a solvate thereof, or a composition of claim 5; the agricultural plant diseases and insect pests are rice bacterial leaf blight bacteria, rice bacterial leaf spot bacteria, citrus canker bacteria, cucumber bacterial leaf spot bacteria, konjak bacterial leaf spot bacteria, grape canker bacteria, tomato canker bacteria, kiwi fruit canker bacteria, apple canker bacteria, cucumber gray mold bacteria, pepper fusarium wilt bacteria, rape sclerotium bacteria, wheat red mold bacteria, potato late blight bacteria and blueberry root rot bacteria.
CN202310272800.8A 2023-03-20 2023-03-20 Heterocyclic substitution-based disulfide derivative, preparation method and application thereof Pending CN116178359A (en)

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