Thiadiazole-containing flavonol derivatives, and methods of making and using the same

Abstract

The application discloses a thiazole-containing flavonol derivative and a preparation method and application thereof, and belongs to the technical field of pesticide synthesis. A thiazole-containing flavonol derivative is generated by substitution reaction of 3-(bromoalkyloxy)-7-substituent-2-(4-substituent phenyl)-4H-chromone-4-ketone and 5-substituent-2-thiol-1,3,4-thiadiazole, and a structural formula is shown as formula Y: wherein n is 3 or 4; R1 is hydrogen or an amino group; R2 is hydrogen, an alkyl group or an alkoxy group; and R3 is hydrogen, a halogen, an alkyl group or an alkoxy group. The thiazole-containing flavonol derivative has good bacteriostatic activity and can be applied to the preparation of bacteriostatic medicaments.

Description

Technical Field

[0001] This invention belongs to the field of pesticide synthesis technology, specifically relating to a thiadiazole-containing flavonol derivative, its preparation method, and its application. Background Technology

[0002] Plant pathogen infections cause enormous economic losses to global agricultural production and pose a serious threat to human health and food safety. Currently, treating crops with antimicrobial agents is one of the most effective methods for controlling plant diseases. However, the long-term overuse of chemical antimicrobial agents has led to a continuous increase in the resistance of plant pathogens and has caused serious environmental pollution. Therefore, there is an urgent need to discover new, highly effective, and environmentally friendly antimicrobial agents to address this challenge. Flavonols, specifically 3-hydroxyflavones, are unique flavonoid compounds mainly found in dicotyledonous plants, especially in the flowers and leaves of some woody plants, such as tea, ginkgo, sea buckthorn, and locust flowers. As a natural active substance, flavonols possess a variety of beneficial physiological activities, are widely available, and have high safety profiles, making them a long-standing lead compound for drug and pesticide development. Furthermore, flavonols and their derivatives exhibit good antibacterial, antiviral, insecticidal, and anticancer biological activities, and have low toxicity, making them widely used in antimicrobial agents.

[0003] In 2017, Huang et al. (Huang, MG; Ruan, XH; Li, Q.; Zhang, JP; Zhong, XM; Wang, XB; Xie, Y.; Xiao, W.; Xue, W. Synthesis and antibacterial activity of novel phosphorylated flavonoid derivatives[J]. Phosphorus, Sulfu Silicon Relat. Elem., 2017, 192: 954-959.) synthesized a series of phosphate-containing flavonol derivatives and conducted bioactivity tests on all target compounds. Bioassay results showed that the target compounds exhibited good inhibitory activity against *Rhizoctonia solani*, *Rhizoctonia solani*, and *Rhizoctonia solani*.

[0004] 1,3,4-Thiadiazole and its derivatives are a class of five-membered heterocyclic compounds with good physicochemical properties. Their structural units contain a basic carbon, nitrogen, and sulfur framework, and chemical modification can yield bioactive derivatives with high efficiency and low toxicity. Among them, 1,3,4-thiadiazole, as a pharmaceutical synthesis intermediate, has antibacterial, antiviral, herbicidal, and insecticidal activities and has been widely used in pesticides.

[0005] To date, there have been no reports of introducing thiadiazole structures into flavonol derivatives and testing their inhibitory activity on plant bacteria and fungi. Summary of the Invention

[0006] The purpose of this invention is to provide a thiadiazole-containing flavonol derivative, its preparation method and application. By introducing an active thiadiazole intermediate into the structure of flavonol, a series of thiadiazole-containing flavonol derivatives with inhibitory activity against plant bacteria and plant fungi are synthesized.

[0007] To achieve the above objectives, the present invention provides the following technical solution:

[0008] One of the technical solutions of the present invention:

[0009] This invention provides a flavonol derivative containing thiadiazole, with the general structural formula shown in Formula Y:

[0010]

[0011] Where: n is 3 or 4; R1 is hydrogen or amino; R2 is hydrogen, alkyl or alkoxy; R3 is hydrogen, halogen, alkyl or alkoxy.

[0012] Furthermore, in the above-mentioned thiadiazole-containing flavonol derivatives: the alkyl group is a C1-C6 alkyl group; the alkoxy group is a C1-C6 alkoxy group; the halogen is fluorine, chlorine, or bromine. R3 is any ortho, meta, or para substitution on the benzene ring.

[0013] Further, the thiadiazole-containing flavonol derivatives are 3-(3-((5-amino-1,3,4-thiadiazole-2-yl)thio)propoxy)-2-(p-bromophenyl)-4H-chromone-4-one, 3-(3-((1,3,4-thiadiazole-2-yl)thio)propoxy)-2-(p-tolyl)-4H-chromone-4-one, 3-(3-((1,3,4-thiadiazole-2-yl)thio)propoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one, 3-(3-((1,3,4-thiadiazole-2-yl)thio)propoxy)-2-(p-methoxyphenyl)- 4H-Crotene-4-one, 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-chlorophenyl)-4H-Crotene-4-one, 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-fluorophenyl)-4H-Crotene-4-one, 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(m-fluorophenyl)-4H-Crotene-4-one or 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(o-methoxyphenyl)-4H-Crotene-4-one.

[0014] The second technical solution of the present invention:

[0015] This invention provides a method for preparing flavonol derivatives containing thiadiazole, comprising the following steps:

[0016] (1) Using substituted thiohydrazides and carbon disulfide (CS2) as raw materials and ethanol (EtOH) as solvent, 5-substituted-2-mercapto-1,3,4-thiadiazole was prepared under alkaline conditions. The reaction route is as follows:

[0017]

[0018] (2) Under conditions of ethanol as solvent and sodium hydroxide (NaOH) solution as acid-binding agent, substituted o-hydroxyacetophenone undergoes an aldol condensation reaction with substituted benzaldehyde to prepare 1-(2-hydroxy-4-substituted phenyl)-3-(substituted phenyl)prop-2-en-1-one. The reaction route is as follows:

[0019]

[0020] (3) 1-(2-hydroxy-4-substituted phenyl)-3-(substituted phenyl)prop-2-en-1-one was prepared by a ring-closing reaction under basic conditions to prepare 3-hydroxy-7-substituted-2-(substituted phenyl)-4H-chromone-4-one. The reaction route is as follows:

[0021]

[0022] (4) Under conditions of N,N-dimethylformamide (DMF) as solvent and K2CO3 as acid-binding agent, the 3-hydroxy-7-substituted-2-(substituted phenyl)-4H-chromone-4-one undergoes a nucleophilic substitution reaction with dibromoalkane to generate 3-(bromoalkoxy)-7-substituted-2-(4-substituted phenyl)-4H-chromone-4-one. The reaction route is as follows:

[0023]

[0024] (5) Under conditions where K2CO3 is used as an acid-binding agent and N,N-dimethylformamide is used as a solvent, the 3-(bromoalkoxy)-7-substituted-2-(4-substituted phenyl)-4H-chromone-4-one undergoes a substitution reaction with the 5-substituted-2-mercapto-1,3,4-thiadiazole to generate thiadiazole-containing flavonol derivatives. The reaction route is as follows:

[0025]

[0026] Furthermore, the preparation method of the 5-substituted-2-mercapto-1,3,4-thiadiazole is as follows:

[0027] Substituted thiohydrazide, K2CO3 and ethanol were mixed and stirred at room temperature for 15 min. Then carbon disulfide was added dropwise to the above reaction system, the temperature was raised to 60 °C and refluxed for 4-6 h. The reaction was monitored by TLC. After the reaction was completed, the mixture was cooled to room temperature, concentrated under reduced pressure, and then ice water was added. Hydrochloric acid was added dropwise, and a white solid precipitated. The solid was filtered under reduced pressure, the filter cake was washed with petroleum ether and dried to obtain 5-substituted-2-mercapto-1,3,4-thiadiazole.

[0028] The molar ratio of the substituted thiohydrazide, K2CO3 and carbon disulfide is (30-35):(45-50):(65-70), preferably 32.92:49.38:65.84.

[0029] Furthermore, the preparation method of 1-(2-hydroxy-4-substituted phenyl)-3-(substituted phenyl)prop-2-en-1-one is as follows:

[0030] The substituted o-hydroxyacetophenone, sodium hydroxide, and ethanol were mixed and stirred at room temperature for 30 min. Then, p-methylbenzaldehyde was added dropwise, and the reaction was carried out at room temperature for 14–18 h. The reaction was monitored by TLC. After the reaction was completed, the mixture was poured into an apparatus containing ice water. The pH was adjusted to 5–6 with hydrochloric acid solution, and the solid precipitated. The solid was filtered under reduced pressure and finally recrystallized from the ethanol / water system. The solid obtained was 1-(2-hydroxy-4-substituted phenyl)-3-(substituted phenyl)prop-2-en-1-one.

[0031] The molar ratio of the substituted o-hydroxyacetophenone, sodium hydroxide and substituted benzaldehyde to form a hydroxyaldehyde is (20-25):(85-90):(25-30), preferably 22.02:88.14:26.44.

[0032] Furthermore, the preparation method of the 3-hydroxy-7-substituted-2-(substituted phenyl)-4H-chromone-4-one is as follows:

[0033] 1-(2-hydroxy-4-substituted phenyl)-3-(substituted phenyl)prop-2-en-1-one (mmol) was mixed with methanol and stirred to dissolve. Then sodium hydroxide and H2O2 were added, and the mixture was stirred at room temperature for 10-14 h. The reaction was monitored by TLC. After the reaction was completed, the mixture was poured into a device containing ice water. The pH was adjusted to 5-6 with hydrochloric acid solution, and the solid precipitated. The solid was filtered under reduced pressure and finally recrystallized from the ethanol / water system. The obtained solid was 3-hydroxy-7-substituted 2-(substituted phenyl)-4H-chromone-4-one.

[0034] The molar ratio of 1-(2-hydroxy-4-substituted phenyl)-3-(substituted phenyl)prop-2-en-1-one, sodium hydroxide, and hydrogen peroxide is (10-15):(40-45):(75-80), preferably 12.59:44.06:75.54.

[0035] Furthermore, the preparation method of the 3-(bromoalkoxy)-7-substituted-2-(4-substituted phenyl)-4H-chromone-4-one is as follows:

[0036] 3-hydroxy-7-substituted-2-(substituted phenyl)-4H-chromone-4-one, K2CO3 and N,N-dimethylformamide were mixed and stirred at room temperature for 30 min. Then 1.21 mL of 1,3-dibromopropane was added dropwise and stirred at room temperature for 5-6 h. The reaction was monitored by TLC. After the reaction was completed, the mixture was concentrated under reduced pressure, extracted with ethyl acetate, and distilled under reduced pressure to obtain an oily substance. Finally, the mixture was stirred with petroleum ether / ethyl acetate to obtain a solid, which was 3-(bromoalkoxy)-7-substituted-2-(4-substituted phenyl)-4H-chromone-4-one.

[0037] The molar ratio of 3-hydroxy-7-substituted-2-(substituted phenyl)-4H-chromone-4-one, K2CO3 and 1,3-dibromopropane is (3.5-4):(10-15):(10-15), preferably 3.96:11.69:11.89.

[0038] Further, the method for the substitution reaction between the 3-(bromoalkoxy)-7-substituted-2-(4-substituted phenyl)-4H-chromone-4-one and the 5-substituted-2-mercapto-1,3,4-thiadiazole is as follows:

[0039] 5-Substituted-2-mercapto-1,3,4-thiadiazole, K2CO3 (mmol), and 40 mL of N,N-dimethylformamide were mixed and stirred to dissolve. Then, 3-(bromoalkoxy)-7-substituted-2-(4-substituted phenyl)-4H-chromone-4-one was added. The reaction was carried out at room temperature for 10–12 h, and the reaction was monitored by TLC. After the reaction was completed, the mixture was concentrated under reduced pressure, extracted with ethyl acetate, and distilled under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain a solid, which is the thiadiazole-containing flavonol derivative.

[0040] The molar ratio of the 5-substituted-2-mercapto-1,3,4-thiadiazole, K2CO3, and 3-(bromoalkoxy)-7-substituted-2-(4-substituted phenyl)-4H-chromone-4-one is (1.5-2):(2-2.5):(1-1.5), preferably 1.61:2.01:1.34.

[0041] The third technical solution of the present invention provides the application of the above-mentioned thiadiazole-containing flavonol derivatives in the preparation of drugs that inhibit the activity of plant bacteria or plant fungi.

[0042] Preferably, the plant bacteria are *Citrus canker pathogen*, *Actinidia chinensis*, *Bacillus thuringiensis*, and *Potato soft rot pathogen*; the plant fungi include *Gyromitra esculenta*, *Sclerotinia sclerotiorum*, *Black spot pathogen*, *Fusarium wilt*, *Anthracnose*, *Phytophthora*, *Rhizoctonia solani*, *Fusarium wilt*, *Fusarium wilt*, and *Pseudomonas stenophyllum*.

[0043] Compared with the prior art, the present invention has the following advantages and technical effects:

[0044] This invention involves a substitution reaction between 3-(bromoalkoxy)-7-substituted-2-(4-substituted phenyl)-4H-chromone-4-one and 5-substituted-2-mercapto-1,3,4-thiadiazole, which possesses excellent biological activity, to generate thiadiazole-containing flavonol derivatives. Furthermore, this invention uses substituted o-hydroxyacetophenone, substituted benzaldehyde, substituted thiohydrazide, carbon disulfide, etc., as raw materials to first prepare the above-mentioned compounds, which are then used in the preparation of thiadiazole-containing flavonol derivatives. All raw materials and reagents used in the entire preparation process are common, organic reagents and solvents are readily available, and the reaction conditions used in the preparation process are relatively mild, the post-processing is simple, and the yield is high, ranging from 37% to 92%.

[0045] Furthermore, the turbidimetric method and mycelial growth rate method were used to test the inhibitory activity of the synthesized derivatives against plant bacteria and fungi. It was found that some compounds of the present invention exhibit good inhibitory activity against plant bacteria and fungi, especially some target compounds which show good in vitro antibacterial activity against *Actinidia kiwifruit*, *Potamogeton crispus*, and *Citrus canker*, and can be considered as potential antibacterial agents. Additionally, some derivatives show good in vitro antifungal activity against *Botrytis cinerea*, *Rhizoctonia solani*, and *Pseudomonas stearans*, and can be considered as potential antifungal agents. Detailed Implementation

[0046] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0047] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0048] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0049] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be readily apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0050] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0051] In this embodiment of the invention, room temperature refers to 25±2℃.

[0052] The raw materials and reagents used in the embodiments of this invention were all purchased.

[0053] The technical solution of the present invention will be further illustrated by the following embodiments.

[0054] Example 1

[0055] The preparation of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-tolyl)-4H-chromone-4-one (target compound Y1) includes the following steps:

[0056] (1) Synthesis of 5-amino-2-mercapto-1,3,4-thiadiazole:

[0057] 3.0 g of aminothiourea (32.92 mmol), 6.82 g of K₂CO₃ (49.38 mmol), and 40 mL of ethanol were placed in a 100 mL round-bottom flask and stirred at room temperature for 15 min. Immediately afterwards, 3.95 mL of CS₂ (65.84 mmol) was slowly added dropwise to the reaction system. The temperature was raised to 60 °C, and the reaction was refluxed for 5 h. The reaction was monitored by TLC (dichloromethane:methanol = 8:1, v / v). After the reaction was complete, the reaction system was cooled to room temperature, concentrated under reduced pressure to remove some of the solvent, and then an appropriate amount of ice water was added. 10% (v / v) hydrochloric acid was added dropwise, resulting in the precipitation of a large amount of white solid. The solid was filtered under reduced pressure, washed with petroleum ether, dried, and stored for later use. The yield was 85%.

[0058] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(p-tolyl)propyl-2-en-1-one:

[0059] 3.0 g of o-hydroxyacetophenone (22.02 mmol), 3.53 g of sodium hydroxide (88.14 mmol), and 50 mL of ethanol were added to a round-bottom flask and stirred at room temperature for 30 min. Then, 3.18 g of p-methylbenzaldehyde (26.44 mmol) was slowly added dropwise, and the reaction was carried out at room temperature for 16 h. The reaction was monitored by TLC (petroleum ether:ethyl acetate = 4:1, v / v). After the reaction was completed, the reaction system was poured into a 500 mL beaker containing 200 mL of ice water. The pH was adjusted to 5-6 with 5% (v / v) dilute hydrochloric acid solution, and a large amount of yellow solid precipitated out. The solid was filtered under reduced pressure and recrystallized from the ethanol / water system to obtain the yellow solid, with a yield of 73%.

[0060] (3) Synthesis of 3-hydroxy-2-(p-tolyl)-4H-chromone-4-one:

[0061] 3.0 g (E)-1-(2-hydroxyphenyl)-3-(p-tolyl)propyl-2-en-1-one (12.59 mmol) and 45 mL methanol were added to a 100 mL round-bottom flask and stirred to dissolve. Then, 1.76 g sodium hydroxide (44.06 mmol) and 2.31 mL 30% (v / v) H₂O₂ (75.54 mmol) were slowly added. The mixture was stirred at room temperature for 12 h, and the reaction was monitored by TLC (petroleum ether:ethyl acetate = 4:1, v / v). After the reaction was complete, the reaction mixture was poured into a 500 mL beaker containing 200 mL of ice water. The pH was adjusted to 6 with 5% dilute hydrochloric acid solution, and a large amount of pale yellow solid precipitated out. The solid was filtered under reduced pressure and recrystallized from the ethanol / water system to obtain the pale yellow solid, with a yield of 69%.

[0062] (4) Synthesis of 3-(3-bromopropoxy)-2-(p-tolyl)-4H-chromone-4-one:

[0063] 1.0 g of 3-hydroxy-2-(p-tolyl)-4H-chromone-4-one (3.96 mmol), 1.64 g of K₂CO₃ (11.69 mmol), and 20 mL of N,N-dimethylformamide were added to a 50 mL round-bottom flask and stirred at room temperature for 30 min. Then, 1.21 mL of 1,3-dibromopropane (11.89 mmol) was slowly added dropwise, and the mixture was stirred at room temperature for 6 h. The reaction was monitored by TLC (petroleum ether:ethyl acetate = 3:1, v / v). After the reaction was complete, the solvent was removed by concentration under reduced pressure, followed by extraction with ethyl acetate and distillation under reduced pressure to remove the solvent, yielding a pale yellow oil. Finally, the oil was stirred with a petroleum ether / ethyl acetate system to obtain a white solid, with a yield of 73%.

[0064] (5) Synthesis of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-tolyl)-4H-chromone-4-one (target compound Y1):

[0065] 0.24 g of 5-amino-2-mercapto-1,3,4-thiadiazole (1.61 mmol), 0.28 g of K₂CO₃ (2.01 mmol), and 40 mL of N,N-dimethylformamide were added to a 50 mL round-bottom flask and stirred to dissolve. Then, 0.5 g of 3-(3-bromopropoxy)-2-(p-tolyl)-4H-chromone-4-one (1.34 mmol) was added, and the reaction was carried out at room temperature for 11 h. The reaction was monitored by TLC (petroleum ether:ethyl acetate = 2:1, V / V). After the reaction was completed, the reaction system was concentrated under reduced pressure to remove part of the solvent, and then extracted with ethyl acetate. The solvent was removed by distillation under reduced pressure to obtain the crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 5:1, V / V) to obtain the target compound Y1, a white solid, in 37% yield.

[0066] Example 2

[0067] The preparation of 3-(3-(5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one (target compound Y2) includes the following steps:

[0068] (1) Synthesis of 5-amino-2-mercapto-1,3,4-thiadiazole: Same as (1) in Example 1.

[0069] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(p-methoxyphenyl)prop-2-en-1-one: Compared with (2) of Example 1, the difference is that p-methoxybenzaldehyde is used as the raw material, while the other steps are the same.

[0070] (3) Synthesis of 3-hydroxy-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that p-(E)-1-(2-hydroxyphenyl)-3-(p-methoxyphenyl)prop-2-en-1-one is used as the raw material, and the other steps are the same.

[0071] (4) Synthesis of 3-(3-bromopropoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that p-3-hydroxy-2-(p-methoxyphenyl)-4H-chromone-4-one is used as the starting material, while the other steps are the same.

[0072] (5) Synthesis of 3-(3-(5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one is used as the starting material, and all other steps are the same, with a yield of 68%.

[0073] Example 3

[0074] The preparation of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(o-methoxyphenyl)-4H-chromone-4-one (target compound Y3) includes the following steps:

[0075] (1) Synthesis of 5-amino-2-mercapto-1,3,4-thiadiazole: Same as (1) in Example 1.

[0076] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(o-methoxyphenyl)prop-2-en-1-one: Compared with (2) of Example 1, the difference is that o-methoxybenzaldehyde is used as the raw material, while the other steps are the same.

[0077] (3) Synthesis of 3-hydroxy-2-(o-methoxyphenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxyphenyl)-3-(o-methoxyphenyl)prop-2-en-1-one is used as the raw material, and the other steps are the same.

[0078] (4) Synthesis of 3-(3-bromopropoxy)-2-(o-methoxyphenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that p-3-hydroxy-2-(o-methoxyphenyl)-4H-chromone-4-one is used as the starting material, and the other steps are the same.

[0079] (5) Synthesis of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(o-methoxyphenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-2-(o-methoxyphenyl)-4H-chromone-4-one is used as the starting material, and all other steps are the same, with a yield of 81%.

[0080] Example 4

[0081] The preparation of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-chlorophenyl)-4H-chromone-4-one (target compound Y4) includes the following steps:

[0082] (1) Synthesis of 5-amino-2-mercapto-1,3,4-thiadiazole: Same as (1) in Example 1.

[0083] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(p-chlorophenyl)prop-2-en-1-one: Compared with (2) of Example 1, the difference is that p-chlorobenzaldehyde is used as the raw material, while the other steps are the same.

[0084] (3) Synthesis of 3-hydroxy-2-(p-chlorophenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxyphenyl)-3-(p-chlorophenyl)prop-2-en-1-one is used as the raw material, and the other steps are the same.

[0085] (4) Synthesis of 3-(3-bromopropoxy)-2-(p-chlorophenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that p-3-hydroxy-2-(p-chlorophenyl)-4H-chromone-4-one is used as the starting material, while the other steps are the same.

[0086] (5) Synthesis of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-chlorophenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-2-(p-chlorophenyl)-4H-chromone-4-one is used as the starting material, and all other steps are the same, with a yield of 75%.

[0087] Example 5

[0088] The preparation of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-bromophenyl)-4H-chromone-4-one (target compound Y5) includes the following steps:

[0089] (1) Synthesis of 5-amino-2-mercapto-1,3,4-thiadiazole: Same as (1) in Example 1.

[0090] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(p-bromophenyl)prop-2-en-1-one: Compared with (2) of Example 1, the difference is that p-bromobenzaldehyde is used as the raw material, and all other steps are the same.

[0091] (3) Synthesis of 3-hydroxy-2-(p-bromophenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxyphenyl)-3-(p-bromophenyl)prop-2-en-1-one is used as the starting material, and the other steps are the same.

[0092] (4) Synthesis of 3-(3-bromopropoxy)-2-(p-bromophenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that p-3-hydroxy-2-(p-bromophenyl)-4H-chromone-4-one is used as the starting material, while the other steps are the same.

[0093] (5) Synthesis of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-bromophenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-2-(p-bromophenyl)-4H-chromone-4-one is used as the starting material; all other steps are the same, and the yield is 63%.

[0094] Example 6

[0095] The preparation of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-fluorophenyl)-4H-chromone-4-one (target compound Y6) includes the following steps:

[0096] (1) Synthesis of 5-amino-2-mercapto-1,3,4-thiadiazole: Same as (1) in Example 1.

[0097] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(p-fluorophenyl)prop-2-en-1-one: Compared with (2) of Example 1, the difference is that p-fluorobenzaldehyde is used as the raw material, while the other steps are the same.

[0098] (3) Synthesis of 3-hydroxy-2-(p-fluorophenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxyphenyl)-3-(p-fluorophenyl)prop-2-en-1-one is used as the raw material, and the other steps are the same.

[0099] (4) Synthesis of 3-(3-bromopropoxy)-2-(p-fluorophenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that p-3-hydroxy-2-(p-fluorophenyl)-4H-chromone-4-one is used as the starting material, while the other steps are the same.

[0100] (5) Synthesis of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-fluorophenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-2-(p-fluorophenyl)-4H-chromone-4-one is used as the starting material, and all other steps are the same, with a yield of 60%.

[0101] Example 7

[0102] The preparation of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(m-fluorophenyl)-4H-chromone-4-one (target compound Y7) includes the following steps:

[0103] (1) Synthesis of 5-amino-2-mercapto-1,3,4-thiadiazole: Same as (1) in Example 1.

[0104] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(m-fluorophenyl)prop-2-en-1-one: Compared with (2) of Example 1, the difference is that m-fluorobenzaldehyde is used as the raw material, while the other steps are the same.

[0105] (3) Synthesis of 3-hydroxy-2-(m-fluorophenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxyphenyl)-3-(m-fluorophenyl)prop-2-en-1-one is used as the raw material, and the other steps are the same.

[0106] (4) Synthesis of 3-(3-bromopropoxy)-2-(m-fluorophenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that p-3-hydroxy-2-(m-fluorophenyl)-4H-chromone-4-one is used as the starting material, and the other steps are the same.

[0107] (5) Synthesis of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(m-fluorophenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-2-(m-fluorophenyl)-4H-chromone-4-one is used as the starting material, and all other steps are the same, with a yield of 64%.

[0108] Example 8

[0109] The preparation of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(p-tolyl)-4H-chromone-4-one (target compound Y8) includes the following steps:

[0110] (1) Synthesis of 5-amino-2-mercapto-1,3,4-thiadiazole: Same as (1) in Example 1.

[0111] (2) Synthesis of (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(p-tolyl)prop-2-en-1-one: Compared with (2) of Example 1, the difference is that 2-hydroxy-4-methoxyacetophenone is used as the starting material, while the other steps are the same.

[0112] (3) Synthesis of 3-hydroxy-7-methoxy-2-(p-tolyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(p-tolyl)prop-2-en-1-one is used as the raw material, while the other steps are the same.

[0113] (4) Synthesis of 3-(3-bromopropoxy)-7-methoxy-2-(p-tolyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that p-3-hydroxy-7-methoxy-2-(p-tolyl)-4H-chromone-4-one is used as the starting material, and the other steps are the same.

[0114] (5) Synthesis of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(p-tolyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-7-methoxy-2-(p-tolyl)-4H-chromone-4-one is used as the starting material; all other steps are the same, and the yield is 81%.

[0115] Example 9

[0116] The preparation of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(p-methoxyphenyl)-4H-chromone-4-one (target compound Y9) includes the following steps:

[0117] (1) Synthesis of 5-amino-2-mercapto-1,3,4-thiadiazole: Same as (1) in Example 1.

[0118] (2) Synthesis of (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(p-methoxyphenyl)prop-2-en-1-one: Compared with (2) of Example 1, the difference is that 2-hydroxy-4-methoxyacetophenone and p-methoxybenzaldehyde are used as raw materials, while the other steps are the same.

[0119] (3) Synthesis of 3-hydroxy-7-methoxy-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(p-methoxyphenyl)prop-2-en-1-one is used as the starting material, while the other steps are the same.

[0120] (4) Synthesis of 3-(3-bromopropoxy)-7-methoxy-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that p-3-hydroxy-7-methoxy-2-(p-methoxyphenyl)-4H-chromone-4-one is used as the starting material, and the other steps are the same.

[0121] (5) Synthesis of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-7-methoxy-2-(p-methoxyphenyl)-4H-chromone-4-one is used as the starting material, and all other steps are the same, with a yield of 49%.

[0122] Example 10

[0123] The preparation of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(o-methoxyphenyl)-4H-chromone-4-one (target compound Y10) includes the following steps:

[0124] (1) Synthesis of 5-amino-2-mercapto-1,3,4-thiadiazole: Same as (1) in Example 1.

[0125] (2) Synthesis of (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(o-methoxyphenyl)prop-2-en-1-one: Compared with (2) of Example 1, the difference is that 2-hydroxy-4-methoxyacetophenone and o-methoxybenzaldehyde are used as raw materials, while the other steps are the same.

[0126] (3) Synthesis of 3-hydroxy-7-methoxy-2-(o-methoxyphenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(o-methoxyphenyl)prop-2-en-1-one is used as the starting material, while the other steps are the same.

[0127] (4) Synthesis of 3-(3-bromopropoxy)-7-methoxy-2-(o-methoxyphenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that p-3-hydroxy-7-methoxy-2-(o-methoxyphenyl)-4H-chromone-4-one is used as the starting material, and all other steps are the same.

[0128] (5) Synthesis of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(o-methoxyphenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-7-methoxy-2-(o-methoxyphenyl)-4H-chromone-4-one is used as the starting material, and all other steps are the same, with a yield of 77%.

[0129] Example 11

[0130] The preparation of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(p-fluorophenyl)-4H-chromone-4-one (target compound Y11) includes the following steps:

[0131] (1) Synthesis of 5-amino-2-mercapto-1,3,4-thiadiazole: Same as (1) in Example 1.

[0132] (2) Synthesis of (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(p-fluorophenyl)prop-2-en-1-one: Compared with (2) of Example 1, the difference is that 2-hydroxy-4-methoxyacetophenone and p-fluorobenzaldehyde are used as raw materials, while the other steps are the same.

[0133] (3) Synthesis of 3-hydroxy-7-methoxy-2-(p-fluorophenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(p-fluorophenyl)prop-2-en-1-one is used as the raw material, while the other steps are the same.

[0134] (4) Synthesis of 3-(3-bromopropoxy)-7-methoxy-2-(p-fluorophenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that p-3-hydroxy-7-methoxy-2-(p-fluorophenyl)-4H-chromone-4-one is used as the starting material, and the other steps are the same.

[0135] (5) Synthesis of 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(p-fluorophenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-7-methoxy-2-(p-fluorophenyl)-4H-chromone-4-one is used as the starting material, and all other steps are the same, with a yield of 62%.

[0136] Example 12

[0137] The preparation of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-tolyl)-4H-chromone-4-one (target compound Y12) includes the following steps:

[0138] (1) Synthesis of 1,3,4-thiadiazole-2-thiol: Compared with (1) of Example 1, the difference is that methylthionyl hydrazine is used as the raw material, while the other steps are the same.

[0139] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(p-tolyl)propyl-2-en-1-one: Same as (2) in Example 1.

[0140] (3) Synthesis of 3-hydroxy-2-(p-tolyl)-4H-chromone-4-one: Same as (3) in Example 1.

[0141] (4) Synthesis of 3-(3-bromopropoxy)-2-(p-tolyl)-4H-chromone-4-one: Same as (4) in Example 1.

[0142] (5) Synthesis of 3-(3-((1,3,4-thiadiazole-2-yl)thio)propoxy)-2-(p-tolyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 1,3,4-thiadiazole-2-thiol is used as the starting material, and all other steps are the same, with a yield of 81%.

[0143] Example 13

[0144] The preparation of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one (target compound Y13) includes the following steps:

[0145] (1) Synthesis of 1,3,4-thiadiazole-2-thiol: Compared with (1) of Example 1, the difference is that methylthionyl hydrazine is used as the raw material, while the other steps are the same.

[0146] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(p-methoxyphenyl)propyl-2-en-1-one: Compared with (2) of Example 1, the difference is that p-methoxybenzaldehyde is used as the raw material, while the other steps are the same.

[0147] (3) Synthesis of 3-hydroxy-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxyphenyl)-3-(p-methoxyphenyl)propyl-2-en-1-one is used as the raw material, and the other steps are the same.

[0148] (4) Synthesis of 3-(3-bromopropoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that 3-hydroxy-2-(p-methoxyphenyl)-4H-chromone-4-one is used as the starting material, and the other steps are the same.

[0149] (5) Synthesis of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one and 1,3,4-thiadiazol-2-thiol are used as raw materials, and all other steps are the same, with a yield of 59%.

[0150] Example 14

[0151] The preparation of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(o-methoxyphenyl)-4H-chromone-4-one (target compound Y14) includes the following steps:

[0152] (1) Synthesis of 1,3,4-thiadiazole-2-thiol: Compared with (1) of Example 1, the difference is that methylthionyl hydrazine is used as the raw material, while the other steps are the same.

[0153] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(o-methoxyphenyl)propyl-2-en-1-one: Compared with (2) of Example 1, the difference is that o-methoxybenzaldehyde is used as the raw material, while the other steps are the same.

[0154] (3) Synthesis of 3-hydroxy-2-(o-methoxyphenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxyphenyl)-3-(o-methoxyphenyl)propyl-2-en-1-one is used as the raw material, and the other steps are the same.

[0155] (4) Synthesis of 3-(3-bromopropoxy)-2-(o-methoxyphenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that 3-hydroxy-2-(o-methoxyphenyl)-4H-chromone-4-one is used as the starting material, and the other steps are the same.

[0156] (5) Synthesis of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(o-methoxyphenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-2-(o-methoxyphenyl)-4H-chromone-4-one and 1,3,4-thiadiazol-2-thiol are used as raw materials, and all other steps are the same, with a yield of 55%.

[0157] Example 15

[0158] The preparation of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-chlorophenyl)-4H-chromone-4-one (target compound Y15) includes the following steps:

[0159] (1) Synthesis of 1,3,4-thiadiazole-2-thiol: Compared with (1) of Example 1, the difference is that methylthionyl hydrazine is used as the raw material, while the other steps are the same.

[0160] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(p-chlorophenyl)propyl-2-en-1-one: Compared with (2) of Example 1, the difference is that p-chlorobenzaldehyde is used as the raw material, while the other steps are the same.

[0161] (3) Synthesis of 3-hydroxy-2-(p-chlorophenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxyphenyl)-3-(p-chlorophenyl)propyl-2-en-1-one is used as the raw material, and the other steps are the same.

[0162] (4) Synthesis of 3-(3-bromopropoxy)-2-(p-chlorophenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that 3-hydroxy-2-(p-chlorophenyl)-4H-chromone-4-one is used as the starting material, while the other steps are the same.

[0163] (5) Synthesis of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-chlorophenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-2-(p-chlorophenyl)-4H-chromone-4-one and 1,3,4-thiadiazol-2-thiol are used as raw materials, and all other steps are the same, with a yield of 73%.

[0164] Example 16

[0165] The preparation of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-bromophenyl)-4H-chromone-4-one (target compound Y16) includes the following steps:

[0166] (1) Synthesis of 1,3,4-thiadiazole-2-thiol: Compared with (1) of Example 1, the difference is that methylthionyl hydrazine is used as the raw material, while the other steps are the same.

[0167] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(p-bromophenyl)propyl-2-en-1-one: Compared with (2) of Example 1, the difference is that p-bromobenzaldehyde is used as the raw material, while the other steps are the same.

[0168] (3) Synthesis of 3-hydroxy-2-(p-bromophenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxyphenyl)-3-(p-bromophenyl)propyl-2-en-1-one is used as the starting material, and the other steps are the same.

[0169] (4) Synthesis of 3-(3-bromopropoxy)-2-(p-bromophenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that 3-hydroxy-2-(p-bromophenyl)-4H-chromone-4-one is used as the starting material, while the other steps are the same.

[0170] (5) Synthesis of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-bromophenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-2-(p-bromophenyl)-4H-chromone-4-one and 1,3,4-thiadiazol-2-thiol are used as raw materials, and all other steps are the same, with a yield of 71%.

[0171] Example 17

[0172] The preparation of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-fluorophenyl)-4H-chromone-4-one (target compound Y17) includes the following steps:

[0173] (1) Synthesis of 1,3,4-thiadiazole-2-thiol: Compared with (1) of Example 1, the difference is that methylthionyl hydrazine is used as the raw material, while the other steps are the same.

[0174] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(p-fluorophenyl)propyl-2-en-1-one: Compared with (2) of Example 1, the difference is that p-fluorobenzaldehyde is used as the raw material, while the other steps are the same.

[0175] (3) Synthesis of 3-hydroxy-2-(p-fluorophenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxyphenyl)-3-(p-fluorophenyl)propyl-2-en-1-one is used as the raw material, and the other steps are the same.

[0176] (4) Synthesis of 3-(3-bromopropoxy)-2-(p-fluorophenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that 3-hydroxy-2-(p-fluorophenyl)-4H-chromone-4-one is used as the starting material, while the other steps are the same.

[0177] (5) Synthesis of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-fluorophenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-2-(p-fluorophenyl)-4H-chromone-4-one and 1,3,4-thiadiazol-2-thiol are used as raw materials, and all other steps are the same, with a yield of 76%.

[0178] Example 18

[0179] The preparation of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(m-fluorophenyl)-4H-chromone-4-one (target compound Y17) includes the following steps:

[0180] (1) Synthesis of 1,3,4-thiadiazole-2-thiol: Compared with (1) of Example 1, the difference is that methylthionyl hydrazine is used as the raw material, while the other steps are the same.

[0181] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(m-fluorophenyl)propyl-2-en-1-one: Compared with (2) of Example 1, the difference is that m-fluorobenzaldehyde is used as the raw material, while the other steps are the same.

[0182] (3) Synthesis of 3-hydroxy-2-(m-fluorophenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxyphenyl)-3-(m-fluorophenyl)propyl-2-en-1-one is used as the raw material, and the other steps are the same.

[0183] (4) Synthesis of 3-(3-bromopropoxy)-2-(m-fluorophenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that 3-hydroxy-2-(m-fluorophenyl)-4H-chromone-4-one is used as the starting material, while the other steps are the same.

[0184] (5) Synthesis of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(m-fluorophenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-2-(m-fluorophenyl)-4H-chromone-4-one and 1,3,4-thiadiazol-2-thiol are used as raw materials, and all other steps are the same, with a yield of 52%.

[0185] Example 19

[0186] The preparation of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(p-tolyl)-4H-chromone-4-one (target compound Y19) includes the following steps:

[0187] (1) Synthesis of 1,3,4-thiadiazole-2-thiol: Compared with (1) of Example 1, the difference is that methylthionyl hydrazine is used as the raw material, while the other steps are the same.

[0188] (2) Synthesis of (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(p-tolyl)prop-2-en-1-one: Compared with (2) of Example 1, the difference is that 2-hydroxy-4-methoxyacetophenone is used as the starting material, while the other steps are the same.

[0189] (3) Synthesis of 3-hydroxy-7-methoxy-2-(p-tolyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(p-tolyl)prop-2-en-1-one is used as the raw material, while the other steps are the same.

[0190] (4) Synthesis of 3-(3-bromopropoxy)-7-methoxy-2-(p-tolyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that p-3-hydroxy-7-methoxy-2-(p-tolyl)-4H-chromone-4-one is used as the starting material, and the other steps are the same.

[0191] (5) Synthesis of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(p-tolyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-7-methoxy-2-(p-tolyl)-4H-chromone-4-one and 1,3,4-thiadiazol-2-thiol are used as raw materials, and all other steps are the same, with a yield of 77%.

[0192] Example 20

[0193] The preparation of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(p-methoxyphenyl)-4H-chromone-4-one (target compound Y20) includes the following steps:

[0194] (1) Synthesis of 1,3,4-thiadiazole-2-thiol: Compared with (1) of Example 1, the difference is that methylthionyl hydrazine is used as the raw material, while the other steps are the same.

[0195] (2) Synthesis of (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(p-methoxyphenyl)prop-2-en-1-one: Compared with (2) of Example 1, the difference is that 2-hydroxy-4-methoxyacetophenone and p-methoxybenzaldehyde are used as raw materials, while the other steps are the same.

[0196] (3) Synthesis of 3-hydroxy-7-methoxy-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(p-methoxyphenyl)prop-2-en-1-one is used as the starting material, while the other steps are the same.

[0197] (4) Synthesis of 3-(3-bromopropoxy)-7-methoxy-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that p-3-hydroxy-7-methoxy-2-(p-methoxyphenyl)-4H-chromone-4-one is used as the starting material, and the other steps are the same.

[0198] (5) Synthesis of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-7-methoxy-2-(p-methoxyphenyl)-4H-chromone-4-one and 1,3,4-thiadiazol-2-thiol are used as raw materials, and all other steps are the same, with a yield of 65%.

[0199] Example 21

[0200] The preparation of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(o-methoxyphenyl)-4H-chromone-4-one (target compound Y21) includes the following steps:

[0201] (1) Synthesis of 1,3,4-thiadiazole-2-thiol: Compared with (1) of Example 1, the difference is that methylthionyl hydrazine is used as the raw material, while the other steps are the same.

[0202] (2) Synthesis of (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(o-methoxyphenyl)prop-2-en-1-one: Compared with (2) of Example 1, the difference is that 2-hydroxy-4-methoxyacetophenone and o-methoxybenzaldehyde are used as raw materials, while the other steps are the same.

[0203] (3) Synthesis of 3-hydroxy-7-methoxy-2-(o-methoxyphenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(o-methoxyphenyl)prop-2-en-1-one is used as the starting material, while the other steps are the same.

[0204] (4) Synthesis of 3-(3-bromopropoxy)-7-methoxy-2-(o-methoxyphenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that p-3-hydroxy-7-methoxy-2-(o-methoxyphenyl)-4H-chromone-4-one is used as the starting material, and all other steps are the same.

[0205] (5) Synthesis of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(o-methoxyphenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-7-methoxy-2-(o-methoxyphenyl)-4H-chromone-4-one and 1,3,4-thiadiazol-2-thiol are used as raw materials, and all other steps are the same, with a yield of 46%.

[0206] Example 22

[0207] The preparation of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(p-fluorophenyl)-4H-chromone-4-one (target compound Y22) includes the following steps:

[0208] (1) Synthesis of 1,3,4-thiadiazole-2-thiol: Compared with (1) of Example 1, the difference is that methylthionyl hydrazine is used as the raw material, while the other steps are the same.

[0209] (2) Synthesis of (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(p-fluorophenyl)prop-2-en-1-one: Compared with (2) of Example 1, the difference is that 2-hydroxy-4-methoxyacetophenone and p-fluorobenzaldehyde are used as raw materials, while the other steps are the same.

[0210] (3) Synthesis of 3-hydroxy-7-methoxy-2-(p-fluorophenyl)-4H-chromone-4-one: Compared with (3) of Example 1, the difference is that (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(p-fluorophenyl)prop-2-en-1-one is used as the raw material, while the other steps are the same.

[0211] (4) Synthesis of 3-(3-bromopropoxy)-7-methoxy-2-(p-fluorophenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that p-3-hydroxy-7-methoxy-2-(p-fluorophenyl)-4H-chromone-4-one is used as the starting material, and the other steps are the same.

[0212] (5) Synthesis of 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(p-fluorophenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(3-bromopropoxy)-7-methoxy-2-(p-fluorophenyl)-4H-chromone-4-one and 1,3,4-thiadiazol-2-thiol are used as raw materials; all other steps are the same, and the yield is 82%.

[0213] Example 23

[0214] The preparation of 3-(4-((5-amino-1,3,4-thiadiazol-2-yl)thio)butoxy)-2-(p-tolyl)-4H-chromone-4-one (target compound Y23) includes the following steps:

[0215] (1) Synthesis of 5-amino-2-mercapto-1,3,4-thiadiazole: Same as (1) in Example 1.

[0216] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(p-tolyl)propyl-2-en-1-one: Same as (2) in Example 1.

[0217] (3) Synthesis of 3-hydroxy-2-(p-tolyl)-4H-chromone-4-one: Same as (3) in Example 1.

[0218] (4) Synthesis of 3-(4-bromobutoxy)-2-(p-tolyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that 1,4-dibromobutane is used as the starting material; the other steps are the same.

[0219] (5) Synthesis of 3-(4-((5-amino-1,3,4-thiadiazol-2-yl)thio)butoxy)-2-(p-tolyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(4-bromobutoxy)-2-(p-tolyl)-4H-chromone-4-one is used as the starting material; all other steps are the same, and the yield is 55%.

[0220] Example 24

[0221] The preparation of 3-(4-((5-amino-1,3,4-thiadiazol-2-yl)thio)butoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one (target compound Y24) includes the following steps:

[0222] (1) Synthesis of 5-amino-2-mercapto-1,3,4-thiadiazole: Same as (1) in Example 1.

[0223] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(p-methoxyphenyl)propyl-2-en-1-one: The difference from (2) of Example 1 is that p-methoxybenzaldehyde is used as the starting material; all other steps are the same.

[0224] (3) Synthesis of 3-hydroxy-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (2) of Example 1, the difference is that (E)-1-(2-hydroxyphenyl)-3-(p-methoxyphenyl)propyl-2-en-1-one is used as the starting material; all other steps are the same.

[0225] (4) Synthesis of 3-(4-bromobutoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that 1,4-dibromobutane is used as the starting material; all other steps are the same.

[0226] (5) Synthesis of 3-(4-((5-amino-1,3,4-thiadiazol-2-yl)thio)butoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(4-bromobutoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one is used as the starting material; all other steps are the same, and the yield is 57%.

[0227] Example 25

[0228] The preparation of 3-(4-((1,3,4-thiadiazol-2-yl)thio)butoxy)-2-(p-tolyl)-4H-chromone-4-one (target compound Y25) includes the following steps:

[0229] (1) Synthesis of 1,3,4-thiadiazole-2-thiol: Compared with (1) of Example 1, the difference is that methylthionyl hydrazine is used as the raw material, while the other steps are the same.

[0230] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(p-tolyl)propyl-2-en-1-one: Same as (2) in Example 1.

[0231] (3) Synthesis of 3-hydroxy-2-(p-tolyl)-4H-chromone-4-one: Same as (3) in Example 1.

[0232] (4) Synthesis of 3-(4-bromobutoxy)-2-(p-tolyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that 1,4-dibromobutane is used as the starting material; the other steps are the same.

[0233] (5) Synthesis of 3-(4-((1,3,4-thiadiazol-2-yl)thio)butoxy)-2-(p-tolyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(4-bromobutoxy)-2-(p-tolyl)-4H-chromone-4-one and 1,3,4-thiadiazol-2-thiol are used as raw materials; all other steps are the same, and the yield is 56%.

[0234] Example 26

[0235] The preparation of 3-(4-((1,3,4-thiadiazol-2-yl)thio)butoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one (target compound Y26) includes the following steps:

[0236] (1) Synthesis of 1,3,4-thiadiazole-2-thiol: Compared with (1) of Example 1, the difference is that methylthionyl hydrazine is used as the raw material, while the other steps are the same.

[0237] (2) Synthesis of (E)-1-(2-hydroxyphenyl)-3-(p-methoxyphenyl)propyl-2-en-1-one: Compared with (2) of Example 1, the difference is that p-methoxybenzaldehyde is used as the raw material, while the other steps are the same.

[0238] (3) Synthesis of 3-hydroxy-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (2) of Example 1, the difference is that (E)-1-(2-hydroxyphenyl)-3-(p-methoxyphenyl)propyl-2-en-1-one is used as the starting material, while the other steps are the same.

[0239] (4) Synthesis of 3-(4-bromobutoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (4) of Example 1, the difference is that 1,4-dibromobutane is used as the starting material, while the other steps are the same.

[0240] (5) Synthesis of 3-(4-((1,3,4-thiadiazol-2-yl)thio)butoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one: Compared with (5) of Example 1, the difference is that 3-(4-bromobutoxy)-2-(p-methoxyphenyl)-4H-chromone-4-one and 1,3,4-thiadiazol-2-thiol are used as raw materials, and all other steps are the same, with a yield of 73%.

[0241] The physicochemical properties and mass spectrometry data of the synthesized thiadiazole-containing flavonol derivatives are shown in Table 1, and the proton nuclear magnetic resonance spectra are also shown in Table 1. 1 H NMR and carbon spectroscopy (H NMR) 13 The C NMR data are shown in Table 2.

[0242] Table 1 Physicochemical properties and mass spectrometry analysis data of the target compound

[0243]

[0244] Table 2. NMR spectral data of the target compounds

[0245]

[0246]

[0247]

[0248]

[0249]

[0250] Experimental Example 1

[0251] Plant antibacterial activity test:

[0252] 1. Testing Method

[0253] The antibacterial activity of all 26 synthesized target compounds was tested using the turbidimetric method. *Actinidia kiwifruit canker* (Psa), *Xoo*, *Pcb*, and *Xac* were selected as experimental subjects, with commercially available thiabendazole copper (TC) as the control. The procedure is as follows:

[0254] 1.1 Preparation of Culture Medium

[0255] Nutrient Broth Medium (NB): Take 6g beef extract, 20g glucose, 10g peptone and 2g yeast powder, add them to a 5000mL beaker, add 2000mL distilled water, stir thoroughly to dissolve completely, then adjust the pH of the medium with 20% sodium hydroxide aqueous solution to maintain it at 7.2±0.2. Dispense the prepared medium into 250mL Erlenmeyer flasks, seal with breathable sealing film and store for later use.

[0256] Nutrient agar (NA): Place 100 mL of NB liquid medium into a 250 mL Erlenmeyer flask, add 1.8 g of agar powder, shake thoroughly to mix evenly, and seal with breathable sealing film for later use. Place the sealed NA and NB media in an autoclave and sterilize at 120°C for 20 minutes. After sterilization, store for later use.

[0257] 1.2 Bacterial Culture

[0258] Place 10 mL of NA medium into a bacterial culture dish, place it on a clean bench, and sterilize under UV light for 0.5 h. Use an inoculation loop to contact a single pathogenic bacterium and streak it onto the NA solid medium. After inoculation, quickly seal the dish with sealing film and place it in a 28°C incubator for activation. Use an inoculation loop to streak a portion of medium containing a suitable amount of single colony fragments onto sterilized NB medium, seal it with sealing film, and incubate it in a shaker until the logarithmic growth phase.

[0259] 1.3 Treatment of the drug

[0260] Weigh 8.0 mg of the compound and dissolve it in 160 μL of DMSO (dimethyl sulfoxide). Transfer 40 μL of the solution to sterile centrifuge tubes and add 4 mL of sterile 0.1 wt% Tween-20 to each centrifuge tube. Use 40 μL of DMSO and 4 mL of 0.1 wt% Tween-20 as blank control groups.

[0261] 1.4 Experimental Procedure for Antibacterial Activity

[0262] After sterilizing the ultraviolet-sterilized laminar flow hood for 0.5-1 h, add 1 mL of the prepared drug solution to a test tube containing sterilized NB medium. Transfer 200 μL of this solution to a 96-well plate, measure and record the OD value. Then, inoculate 40 μL of the bacterial culture into each test tube and incubate in a shaker for 24-48 h. The inhibition rate formula is as follows:

[0263] Corrected OD value = OD value of bacterial culture medium - OD value of sterile culture medium

[0264]

[0265] The results of the bioactivity test of plant-inhibiting bacteria are shown in Table 3.

[0266] Table 3. Inhibitory activity of the target compounds against four plant bacteria.

[0267]

[0268]

[0269] a: The average of three parallel tests. b: Using the commercially available thiabendazole copper as a positive control.

[0270] As shown in Table 3, some of the target compounds exhibit good antibacterial activity against *Xac* (citrus canker), *Psa* (kiwifruit canker), *Xoo* (rice bacterial blight), and *Pcb* (potato soft rot). At a concentration of 100 μg / mL, the inhibition rates of Y8, Y9, and Y21 against *Xac. citrus canker* were 62.8%, 70.1%, and 74.3%, respectively, all superior to thiabendazole copper (52.8%). The inhibition rates of Y19 and Y26 against *Psa. kiwifruit canker* were 60.4% and 73.9%, respectively, both superior to thiabendazole copper (52.8%). The inhibition rates of Y9, Y17, Y18, Y19, Y20, and Y21 against *Pcb. potato soft rot* were 88.9%, 78.8%, 71.3%, 69.4%, 88.8%, and 69.8%, respectively, all superior to thiabendazole copper (55.8%).

[0271] Experimental Example 2

[0272] Antifungal activity test:

[0273] 1. Testing Method

[0274] The mycelial growth rate method was used to test the inhibitory activities of 26 target compounds against *Botrytis cinerea* (Bc), *Sclerotinia sclerotiorum* (Ss), *Aureobasidium alb.* (Ab), *Fusarium wilt* (Fcu), *Anthracnose* (Cg), *Phytophthora* (Pc), *Sheath blight* (Rs), *Fusarium graminearum* (Fg), *Fusarium wilt* (Fca), and *Ps* (Ps). The specific operational steps are as follows:

[0275] 1.1 Preparation of Potato Dextrose Agar (PDA) Medium

[0276] Add 40g of potato dextrose agar to 1000mL of boiling distilled water, place it in a 2000mL beaker, measure 19.8mL of culture medium with a graduated cylinder, dispense it into 50mL Erlenmeyer flasks, seal them with breathable sealing film, and sterilize them in an autoclave at 121℃ for 20min.

[0277] 1.2 Fungal activation

[0278] Place the petri dish in a clean bench and sterilize it with ultraviolet light for 1 hour. Pour about 12 mL of sterilized PDA medium into the petri dish and let it cool. Place the frozen bacterial culture in a 28°C incubator for 2 hours. Use a sterilized needle to pick up the activated mycelium and place it in the center of the cooled medium. Seal it with sealing film and invert it into a 28°C constant temperature incubator for 3-5 days of activation.

[0279] 1.3 Treatment of the drug

[0280] Weigh 20.0 mg of the target compound, dissolve it in 2000 μL of DMSO, and prepare a solution with a concentration of 100 μg / mL.

[0281] 1.4 Experimental Procedures for Antifungal Activity

[0282] In a sterile laminar flow hood, 200 μL of the drug solution was added to sterile, warm PDA medium and shaken thoroughly to ensure even mixing. The drug concentration at this point was 100 μg / mL. 200 μL of DMSO was added to the sterile PDA medium as a blank control. After mixing, the mixture was evenly distributed into three 6 cm diameter petri dishes. Using a 5 mm diameter punch, mycelial pellets were collected from the activated mycelium-containing dishes and placed in the center of the dishes containing the drug solution and the blank control. The dishes were sealed with sealing film and inverted in a 28°C incubator for 2-5 days. Once the colonies in the blank control group reached a diameter of 4.0-5.0 cm, the diameter of the colonies in the drug solution was measured using the cross-sectional method. Each experiment was repeated three times. The inhibition rate formula is as follows:

[0283] Corrected diameter = Colony diameter in culture medium containing drug solution - Diameter of inoculated mycelial cake piece (5mm)

[0284]

[0285] The results of the bioactivity test for inhibiting plant fungi are shown in Table 4.

[0286] Table 4. Inhibitory activity of the target compounds against ten plant fungi. a

[0287]

[0288] a: The average of three parallel tests. b: Azoxystrobin (AZ) was used as a positive control.

[0289] As shown in Table 4, some of the target compounds exhibited good antifungal activity against *Botrytis cinerea* (Bc), *Sclerotinia sclerotiorum* (Ss), and *Ps* (Ps). Y12, Y13, Y17, and Y18 showed inhibition rates of 91.67%, 83.19%, 87.30%, and 92.34% against *Botrytis cinerea* (Bc), respectively, all superior to azoxystrobin (80.67%). Y14 showed an inhibition rate of 71.49% against *Sclerotinia sclerotiorum* (Ss), comparable to that of azoxystrobin (71.90%). Y5, Y14, Y15, Y17, Y18, and Y21 showed inhibition rates of 60.2%, 73.79%, 59.0%, 66.1%, 65.3%, and 72.80% against *Ps*, respectively, all superior to azoxystrobin (58.06%).

[0290] The above experimental activity data indicate that flavonol derivatives containing thiadiazole have a certain inhibitory effect on some plant bacteria and plant fungi. Among them, some target compounds show excellent activity in inhibiting plant bacteria and plant fungi and can be used as potential antibacterial drugs with good application prospects.

[0291] The antibacterial activity tests of the thiadiazole-containing flavonol derivatives described above showed that they had a significant inhibitory effect on blueberry gray mold.

[0292] The above are merely preferred embodiments of this application, but the scope of protection of this application is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in this application should be included within the scope of protection of this application. Therefore, the scope of protection of this application should be determined by the scope of the claims.

Claims

1. A thiazole-containing flavonol derivative, characterized by, The structural general formula is shown as formula Y: wherein: n is 3 or 4; R1 is hydrogen or amino; R2 is hydrogen, alkyl or alkoxy; R3 is hydrogen, halogen, alkyl or alkoxy; The alkyl is C1-C6 alkyl; the alkoxy is C1-C6 alkoxy; and the halogen is fluorine, chlorine or bromine.

2. The thiadiazole-containing flavonol derivative according to claim 1, characterized in that, The thiazolium-containing flavonol derivative is 3-(3-((5-amino-1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-bromophenyl)-4H-chromen-4-one, 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-tolyl)-4H-chromen-4-one, 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-methoxyphenyl)-4H-chromen-4-one, 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(o-methoxyphenyl)-4H-chromen-4-one, 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-chlorophenyl)-4H-chromen-4-one, 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(p-fluorophenyl)-4H-chromen-4-one, 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-2-(m-fluorophenyl)-4H-chromen-4-one or 3-(3-((1,3,4-thiadiazol-2-yl)thio)propoxy)-7-methoxy-2-(o-methoxyphenyl)-4H-chromen-4-one.

3. A method for preparing the thiazole-containing flavonol derivative according to any one of claims 1 to 2, characterized in that, The method comprises the following steps: 5-substituted-2-mercapto-1,3,4-thiadiazole is prepared from substituted thiohydrazine and carbon disulfide as raw materials and ethanol as solvent under alkaline conditions; 1-(2-hydroxy-4-substituted phenyl)-3-(substituted phenyl) propyl-2-en-1-one is prepared from substituted o-hydroxyacetophenone and substituted benzaldehyde through aldol condensation reaction under the condition that ethanol is used as solvent and sodium hydroxide solution is used as acid-binding agent; 3-hydroxy-7-substituted-2-(substituted phenyl)-4H-chromen-4-one is prepared from 1-(2-hydroxy-4-substituted phenyl)-3-(substituted phenyl) propyl-2-en-1-one through ring closure reaction under alkaline conditions; 3-(bromoalkoxy)-7-substituted-2-(4-substituted phenyl)-4H-chromen-4-one is generated from 3-hydroxy-7-substituted-2-(substituted phenyl)-4H-chromen-4-one through nucleophilic substitution reaction under the condition that N,N-dimethylformamide is used as solvent and K2CO3 is used as acid-binding agent; The thiazolium-containing flavonol derivative is generated from 3-(bromoalkoxy)-7-substituted-2-(4-substituted phenyl)-4H-chromen-4-one and 5-substituted-2-mercapto-1,3,4-thiadiazole through substitution reaction under the condition that K2CO3 is used as acid-binding agent and N,N-dimethylformamide is used as solvent.

4. The method of preparing thiazole-containing flavonol derivatives according to claim 3, characterized by, The preparation method of the 5-substituted-2-mercapto-1,3,4-thiadiazole is as follows: The substituted thiohydrazide, K2CO3 and ethanol are mixed, stirred at room temperature for 15 min, then carbon disulfide is added dropwise into the above reaction system, heated to 60 DEG C, refluxed for 4-6 h, the reaction is tracked by TLC, after the reaction is completed, cooled to room temperature, concentrated under reduced pressure, then add ice water, drop hydrochloric acid, precipitate white solid, reduced pressure filtration, the filter cake is washed with petroleum ether, dried to obtain 5-substituted-2-mercapto-1,3,4-thiadiazole; The molar ratio of the substituted thiohydrazide, K2CO3 and carbon disulfide is (30-35):(45-50):(65-70).

5. The method for preparing thiadiazole-containing flavonol derivatives according to claim 3, characterized in that, The preparation method of the 1-(2-hydroxy-4-substituted phenyl)-3-(substituted phenyl) propyl-2-en-1-ketone is as follows: The substituted o-hydroxyacetophenone, sodium hydroxide and ethanol are mixed, stirred at room temperature for 30 min, then the substituted benzaldehyde is added dropwise, reacted at room temperature for 14-18 h, the reaction is tracked by TLC, after the reaction is completed, poured into a device containing ice water, the pH is adjusted to 5-6 with hydrochloric acid solution, then the solid is precipitated, the solid is filtered under reduced pressure, finally recrystallized with an ethanol / water system, the obtained solid is 1-(2-hydroxy-4-substituted phenyl)-3-(substituted phenyl) propyl-2-en-1-ketone; The molar ratio of the substituted o-hydroxyacetophenone, sodium hydroxide and substituted benzaldehyde in the aldol reaction is (20-25):(85-90):(25-30).

6. The method for preparing thiadiazole-containing flavonol derivatives according to claim 4, characterized in that, The preparation method of the 3-hydroxy-7-substituted-2-(substituted phenyl)-4H-chromen-4-one is as follows: The 1-(2-hydroxy-4-substituted phenyl)-3-(substituted phenyl) propyl-2-en-1-ketone and methanol are mixed and stirred to dissolve, then sodium hydroxide and H2O2 are added, stirred at room temperature for 10-14 h, the reaction is tracked by TLC, after the reaction is completed, poured into a device containing ice water, the pH is adjusted to 5-6 with hydrochloric acid solution, then the solid is precipitated, the solid is filtered under reduced pressure, finally recrystallized with an ethanol / water system, the obtained solid is 3-hydroxy-7-substituted-2-(substituted phenyl)-4H-chromen-4-one; The molar ratio of the 1-(2-hydroxy-4-substituted phenyl)-3-(substituted phenyl) propyl-2-en-1-ketone, sodium hydroxide and hydrogen peroxide is (10-15):(40-45):(75-80).

7. The method for preparing thiadiazole-containing flavonol derivatives according to claim 3, characterized in that, The preparation method of the 3-(bromoalkoxy)-7-substituted-2-(4-substituted phenyl)-4H-chromen-4-one is as follows: The 3-hydroxy-7-substituted-2-(substituted phenyl)-4H-chromen-4-one, K2CO3 and N,N-dimethylformamide are mixed, stirred at room temperature for 30 min, then 1,3-dibromopropane is added dropwise, stirred at room temperature for 5-6 h, the reaction is tracked by TLC, after the reaction is completed, concentrated under reduced pressure, then extracted with ethyl acetate, distilled under reduced pressure to obtain an oil, finally stirred with petroleum ether / ethyl acetate, the obtained solid is 3-(bromoalkoxy)-7-substituted-2-(4-substituted phenyl)-4H-chromen-4-one; The molar ratio of the 3-hydroxy-7-substituent-2-(substituent phenyl)-4H-chromone-4-ketone, K2CO3 and 1,3-dibromopropane is (3.5-4):(10-15):(10-15).

8. The method for preparing thiadiazole-containing flavonol derivatives according to claim 3, characterized in that, The method for substituting the 3-(bromoalkoxy)-7-substituent-2-(4-substituent phenyl)-4H-chromone-4-ketone with the 5-substituent-2-thiol-1,3,4-thiadiazole is as follows: 5-substituent-2-thiol-1,3,4-thiadiazole, K2CO3 and 40 mL of N,N-dimethylformamide are mixed, stirred and dissolved, then 3-(bromoalkoxy)-7-substituent-2-(4-substituent phenyl)-4H-chromone-4-ketone is added, and the reaction is carried out at room temperature for 10-12 h, TLC is used to track the reaction, after the reaction is completed, vacuum concentration is carried out, then extraction is carried out with ethyl acetate, vacuum distillation is carried out, and the crude product is obtained, the crude product is purified by column chromatography to obtain a solid, which is a flavonol derivative containing thiadiazole; The molar ratio of the 5-substituent-2-thiol-1,3,4-thiadiazole, K2CO3 and 3-(bromoalkoxy)-7-substituent-2-(4-substituent phenyl)-4H-chromone-4-ketone is (1.5-2):(2-2.5):(1-1.5).

9. Use of the thiadiazole-containing flavonol derivative according to any one of claims 1 to 2 for the preparation of a medicament for the control of plant bacteria or plant fungi, characterized in that, The plant bacteria are Xanthomonas campestris, Xanthomonas citri, Xanthomonas oryzae or Pseudomonas solanacearum; The plant fungi are Botrytis cinerea, Sclerotinia sclerotiorum, Alternaria alternata, Fusarium oxysporum, Colletotrichum gloeosporioides, Phytophthora capsici, Rhizoctonia solani, Gibberella zeae, Fusarium oxysporum f. sp. cubense or Phomopsis sojae.

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