Coumarin compound containing 7-N / O acethydrazide as well as preparation method and application of coumarin compound

Abstract

The invention discloses a coumarin compound of 7-N / O acethydrazide as well as a preparation method and application of the coumarin compound. The preparation method of the coumarin compound of 7-N / O acethydrazide is simple to operate, no precious metal participates in the reaction, and the reaction is efficient. The novel coumarin compound of 7-N / O acethydrazide disclosed by the invention has good fungicidal activity, and the novel coumarin compound of 7-N / O acethydrazide shows efficient and / or broad-spectrum bacteriostatic activity. The novel coumarin compound of 7-N / O acethydrazide disclosed by the invention has good herbicidal activity. The weeding composition can be effectively applied to prevention and control of pathogenic fungi of crops and common field weeds.

Description

Technical Field

[0001] The invention belongs to the technical field of compounds, and in particular relates to a coumarin compound containing 7-N / O acetylhydrazine and a preparation method and application thereof. Background Art

[0002] Coumarin compounds, as secondary metabolites of phenylpropanoids synthesized by plants, have good environmental compatibility, unique physiological activity and strong structural plasticity. In the agricultural field, coumarin has antifungal, antibacterial, antiviral and herbicidal biological activities, which have attracted extensive attention from pesticide developers.

[0003] As an important nitrogen-containing structure, the hydrazide unit is widely present in compounds with antifungal, insecticidal and herbicidal biological activities. Compared with the common amide skeleton, the hydrazide skeleton has better flexibility and can more effectively bind to active enzymes in the body. Therefore, the development of 7-N / O acetylhydrazide compounds with natural coumarin as the skeleton has positive significance and extremely important value.

[0004] Currently, new coumarin compounds of 7-N / O acetylohydrazide and their synthesis routes, antibacterial and herbicidal activities have not been reported. Summary of the invention

[0005] Purpose of the invention: The technical problem to be solved by the present invention is to adopt the strategy of substructure splicing of active units, use ethyl bromoacetate as a connecting bridge, introduce the phenylhydrazide fragment into the coumarin skeleton, and construct a series of new coumarin compounds of 7-N / O acetohydrazide with antibacterial and antifungal activity and herbicidal activity.

[0006] The technical problem that the present invention needs to solve is to provide a preparation method for a series of novel coumarin compounds of 7-N / O acetylhydrazine.

[0007] The technical problem that the present invention also aims to solve is to provide the use of coumarin compounds of 7-N / O acetylhydrazine in the preparation of products for inhibiting or killing pathogens.

[0008] The final technical problem to be solved by the present invention is to provide a series of novel coumarin compounds of 7-N / O acetylhydrazine for use in weed control.

[0009] Technical solution: In order to solve the above technical problems, the first aspect of the present invention provides a coumarin compound of 7-N / O acetylhydrazine, the structure of which is shown in Formula III:

[0010]

[0011] wherein R1 is selected from Me, Et, Pr or CF3; R2 is selected from H or Cl; R3 is selected from H or Me; R′ is selected from 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 4-Br, 2-CH3O, 3-CH3O, 4-CH3O, 3,4-diCH3, 2,3-diCl, 2,4-diCl, 2,5-diCl, 2,6-diCl, 3,4-diCl, 3,5-diCl, 2,3,6-trCl, 2,4,6-trCl, 2,4-diF, 3,4-diF, and preferably, R′ is selected from 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 4-Cl, 2-Br, 4-Br, 4-CH3O, 3,4-diCH3 or 2,4,6-trCl; and X is selected from N or O.

[0012] Wherein, the structure of the compound is shown in Formula I:

[0013]

[0014] Wherein, R1 is selected from Me, Et, Pr, CF3; R′ is selected from one or more of 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 4-Br, 2-CH3O, 3-CH3O, 4-CH3O, 3,4-diCH3, 2,3-diCl, 2,4-diCl, 2,5-diCl, 2,6-diCl, 3,4-diCl, 3,5-diCl, 2,3,6-trCl, 2,4,6-trCl, 2,4-diF, 3,4-diF, and preferably, R′ is selected from 2-F, 3-F, 4-F, 2-Cl, 4-Cl, 4-CF3;

[0015] Wherein, the structure of the compound is shown in Formula II:

[0016]

[0017] R1 is selected from Me and CF3; R2 is selected from H and Cl; R3 is selected from H and Me; R′ is selected from one or more of 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 4-Br, 2-CH3O, 3-CH3O, 4-CH3O, 3,4-diCH3, 2,3-diCl, 2,4-diCl, 2,5-diCl, 2,6-diCl, 3,4-diCl, 3,5-diCl, 2,3,6-trCl, 2,4,6-trCl, 2,4-diF and 3,4-diF, and preferably, R′ is selected from 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 2-Br, 4-Br, 4-CH3O, 3,4-diCH3 and 2,4,6-trCl.

[0018] The second aspect of the present invention provides a method for preparing a coumarin compound of 7-N-acetylhydrazine, comprising the following steps:

[0019] (1) Using 3-aminophenol as a raw material, EA, sodium bicarbonate and phenyl chloroformate are added in sequence to prepare N-(3-hydroxyphenyl)phenyl carbamate;

[0020] (2) N-(3-hydroxyphenyl)carbamic acid phenyl ester reacts with concentrated sulfuric acid solution, and then β-keto acid ester is added to react to prepare substituted coumarin amino acid phenyl ester;

[0021] (3) adding potassium hydroxide solution to the substituted coumarin amino acid phenyl ester, dissolving and stirring, and then heating and stirring to react, thereby preparing an intermediate substituted 7-aminocoumarin;

[0022] (4) adding acetonitrile solution to substituted 7-aminocoumarin, N,N-diisopropylethylamine DIEA and sodium iodide to dissolve them, and then adding ethyl bromoacetate dropwise in a reactor to react, thereby preparing an intermediate ethyl 2-((2-nitro-4-(substituted)-2H-coumarin-7-yl)amino)acetate;

[0023] (5) dissolving the intermediate ethyl 2-((2-nitrogen-4-(substituted)-2H-coumarin-7-yl)amino)acetate in ethanol, adding sodium hydroxide solution and stirring at room temperature, and monitoring the reaction progress by TLC. After the reaction is complete, adjusting the pH value of the aqueous phase to prepare the intermediate 2-((2-nitrogen-4-(substituted)-2H-coumarin-7-yl)amino)acetic acid;

[0024] (6) Acetonitrile solution was added to the intermediate 2-((2-nitro-4-(substituted)-2H-coumarin-7-yl)amino)acetic acid and substituted phenylhydrazine to fully dissolve them, and then O-benzotriazole-N,N,N′,N′-tetramethyluronium tetrafluoroborate was added, followed by dropwise addition of triethylamine. The reaction was stirred at room temperature and the progress of the reaction was monitored by TLC to prepare a series of target compounds 7-N-acetylhydrazine coumarin.

[0025] Furthermore, the preparation method of 7-N-acetylhydrazine coumarin compounds of the present invention specifically comprises:

[0026] Using 3-aminophenol (1) as a raw material, a 7-N-acetylhydrazine coumarin compound shown in formula I is obtained through protection reaction, cyclization reaction, deprotection reaction, substitution reaction, deprotection reaction, and condensation reaction, comprising the following steps:

[0027] Step (1), add 3-aminophenol (1) to a flask, then add EA:H2O=2:1 as solvent, sonicate for 1 min to completely dissolve the raw materials, then add sodium bicarbonate and stir in an ice bath for 5 min, and slowly add phenyl chloroformate. Monitor the reaction process by TLC. Wait until the reaction is finished. Pour the reaction solution into a separatory funnel and let it stand for stratification, collect the organic layer, add water and saturated brine to wash three times respectively, then concentrate the organic phase, and dry it by rotary evaporation to obtain a white solid N-(3-hydroxyphenyl)phenyl carbamate (2); wherein the molar ratio of 3-aminophenol (1) to phenyl chloroformate is 1:1.2.

[0028] Step (2), take N-(3-hydroxyphenyl) phenyl carbamate (2) and add it to a round-bottom flask, take anhydrous ethanol and pour it into a small beaker, slowly pour the concentrated sulfuric acid solution into the beaker containing anhydrous ethanol, and stir with a glass rod at the same time. After the diluted concentrated sulfuric acid ethanol solution is cooled, pour it into the above round-bottom flask and stir for 15 minutes to fully dissolve the raw materials. Then slowly add β-keto ester dropwise, and after the addition is complete, stir at room temperature for 4-6 hours. TLC monitors the reaction process. After the reaction is completed, slowly pour the reaction solution into ice water, and a large amount of gray solid precipitates. After suction filtration, wash the filter cake with a small amount of ethanol and dry it to obtain a gray powder substituted coumarin amino acid phenyl ester (4); wherein the molar ratio of N-(3-hydroxyphenyl) phenyl carbamate (2) to β-keto ester is 1:1.

[0029] Step (3), add substituted coumarin amino acid phenyl ester (4) to a round-bottom flask, then add 45% potassium hydroxide solution (w:w) to the round-bottom flask, dissolve and stir, then heat to 100°C, stir and react for about 1 hour. Monitor the reaction process by TLC until the reaction is complete. Pour the reaction solution into ice water, add concentrated hydrochloric acid dropwise to adjust the pH value to 1 to 2, then add ammonia water to adjust the pH value to 4 to 5, solid is generated, filter, and recrystallize from ethanol to obtain the intermediate substituted 7-aminocoumarin (5).

[0030] Step (4), add substituted 7-aminocoumarin (5), N, N-diisopropylethylamine DIEA and sodium iodide to a flask, add acetonitrile solution to dissolve it, stir it magnetically for about 5 minutes, add ethyl bromoacetate dropwise to the reaction flask, adjust the heating device to 95°C, reflux for 24 hours, and detect the reaction progress by TLC. When the reaction is complete, remove the heating device, pour the reaction solution into ice water while stirring while hot, and let it stand overnight to obtain a large amount of gray-brown solid. Then, filter the mixed solution, wash the upper solid with a small amount of ethanol, and dry it to obtain the intermediate 2-((2-nitrogen-4-(substituted)-2H-coumarin-7-yl)amino)ethyl acetic acid (6); wherein the molar ratio of substituted 7-aminocoumarin (5) to sodium iodide and ethyl bromoacetate is 1:1.2:1.2.

[0031] Step (5), the intermediate ethyl 2-((2-nitrogen-4-(substituted)-2H-coumarin-7-yl)amino)acetate (6), is added to a round-bottom flask, dissolved with ethanol, and stirred with a magnetic force for about 15 minutes to fully dissolve it. A 10% sodium hydroxide solution is added to the reaction flask, stirred at room temperature for about 4 hours, and the reaction progress is monitored by TLC. After the reaction is complete, the ethanol solution is removed by vacuum distillation, the resulting residue is poured into a beaker, distilled water is added, and 15% dilute hydrochloric acid is taken to adjust the pH value of the aqueous phase to 2-3. A large amount of gray-brown solid is precipitated. The mixed solution is filtered, the upper solid is washed with a small amount of ethanol, and dried to obtain the intermediate 2-((2-nitrogen-4-(substituted)-2H-coumarin-7-yl)amino)acetic acid (7).

[0032] Step (6), the intermediate 2-((2-azino-4-(substituted)-2H-coumarin-7-yl)amino)acetic acid (7) and substituted phenylhydrazine were added to a round-bottom flask, and acetonitrile solution was added to fully dissolve. Weigh O-benzotriazole-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU) and add it to a reaction flask, then dropwise add triethylamine, stir at room temperature for about 3 hours, monitor the reaction progress by TLC, if solid precipitates after the reaction, filter it, and wash the upper solid with a small amount of dichloromethane; if no solid precipitates, extract it with ethyl acetate and combine the organic phases, remove the solvent in the obtained organic phase by vacuum concentration, and purify it by column chromatography using a dry loading method, and use a petroleum ether / ethyl acetate system as the eluent to obtain a series of target compounds 7-N-acetylhydrazine coumarin; wherein the molar ratio of substituted 2-((2-nitrogen-4-(substituted)-2H-coumarin-7-yl)amino)acetic acid (7) to substituted phenylhydrazine, TBTU, and triethylamine is 1:1:1:1.

[0033] The third aspect of the present invention provides a method for preparing a coumarin compound of 7-O acetylhydrazine, comprising the following steps:

[0034] (1) Using substituted meta-diphenol as a raw material, adding concentrated sulfuric acid ethanol solution and β-keto acid ester in sequence to react to prepare substituted 7-hydroxycoumarin;

[0035] (2) adding acetonitrile solution to substituted 7-hydroxycoumarin, N,N-diisopropylethylamine DIEA and sodium iodide to dissolve them, and then dropping ethyl bromoacetate in a reactor to react, to prepare an intermediate ethyl 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetate;

[0036] (3) dissolving ethyl 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetate in ethanol, adding sodium hydroxide solution, stirring at room temperature, and monitoring the reaction progress by TLC. After the reaction is complete, adjusting the pH value of the aqueous phase to prepare the intermediate 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetic acid;

[0037] (4) Acetonitrile solution was added to the intermediate 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetic acid and substituted phenylhydrazine to fully dissolve, and then O-benzotriazole-N,N,N′,N′-tetramethyluronium tetrafluoroborate was added, followed by dropwise addition of triethylamine. The reaction was stirred at room temperature and the progress of the reaction was monitored by TLC to prepare a series of target compounds 7-O acetylhydrazine coumarin.

[0038] Wherein, the molar ratio of the 3-aminophenol to phenyl chloroformate is 1:1-3; preferably, the molar ratio of the N-(3-hydroxyphenyl)phenyl carbamate to β-keto acid ester is 1:0.8-3; preferably, the molar ratio of the substituted 7-aminocoumarin to sodium iodide and ethyl bromoacetate is 1:1-3:1-3; preferably, the molar ratio of the substituted 2-((2-nitro-4-(substituted)-2H-coumarin-7-yl)amino)acetic acid to substituted phenylhydrazine, TBTU and triethylamine is 1: 1~2.5:1~2.5:1~2.5; preferably, the molar ratio of the substituted meta-diphenol to β-keto acid ester is 1:0.8~3; preferably, the molar ratio of the substituted 7-hydroxycoumarin to sodium iodide and ethyl bromoacetate is 1:1~3:1~3; preferably, the molar ratio of the 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetic acid to substituted phenylhydrazine, TBTU and triethylamine is 1:1~2.5:1~2.5:1~2.5.

[0039] Furthermore, the preparation method of the coumarin compound of 7-O acetylhydrazine specifically comprises:

[0040] Using substituted meta-diphenol (9) as a raw material, a 7-O-acetylhydrazine coumarin compound shown in formula II is obtained through cyclization reaction, substitution reaction, deprotection reaction, and condensation reaction, comprising the following steps:

[0041] Step (1), substituted meta-diphenol (9) is added to a round-bottom flask, anhydrous ethanol is poured into a small beaker, concentrated sulfuric acid solution is slowly poured into the beaker containing anhydrous ethanol, and stirred with a glass rod at the same time. After the diluted concentrated sulfuric acid ethanol solution is cooled, it is poured into the above round-bottom flask and stirred for 15 minutes to fully dissolve the raw materials. Subsequently, β-keto ester is slowly added dropwise, and after the addition is completed, the reaction is stirred at room temperature for 4-6 hours. TLC monitors the reaction process. After the reaction is completed, the reaction solution is slowly poured into ice water, and a large amount of gray solid is precipitated. After suction filtration, the filter cake is washed with a small amount of ethanol and dried to obtain substituted 7-hydroxycoumarin (10); wherein the molar ratio of substituted meta-diphenol (9) to β-keto ester is 1:1.

[0042] Step (2), add substituted 7-hydroxycoumarin (10), N, N-diisopropylethylamine DIEA and sodium iodide to a flask, add acetonitrile solution to dissolve it, stir it magnetically for about 5 minutes, add ethyl bromoacetate dropwise to the reaction flask, adjust the heating device to 95°C, reflux for 24 hours, and detect the reaction progress by TLC. When the reaction is complete, remove the heating device, pour the reaction solution into ice water while stirring while hot, and let it stand overnight to obtain a large amount of solid. Then, filter the mixed solution, wash the upper solid with a small amount of ethanol, and dry it to obtain the intermediate ethyl 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetate (11); wherein the molar ratio of substituted 7-hydroxycoumarin (10) to sodium iodide and ethyl bromoacetate is 1:1.2:1.2.

[0043] Step (3), the intermediate ethyl 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetate (11) was added to a round-bottom flask, dissolved with ethanol, and stirred with a magnetic force for about 15 minutes to fully dissolve it. A 10% sodium hydroxide solution was added to the reaction flask, stirred at room temperature for about 4 hours, and the reaction progress was monitored by TLC. After the reaction was complete, the ethanol solution was removed by vacuum distillation, and the resulting residue was poured into a beaker, distilled water was added, and 15% dilute hydrochloric acid was taken to adjust the pH value of the aqueous phase to 2-3. A large amount of solid precipitated, and the mixed solution was filtered, and the upper solid was washed with a small amount of ethanol and dried to obtain the intermediate 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetic acid (12).

[0044] Step (4), the intermediate 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetic acid (12) and substituted phenylhydrazine were added to a round-bottom flask, and acetonitrile solution was added to fully dissolve. O-benzotriazole-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU) was weighed and added to a reaction flask, followed by dropwise addition of triethylamine, and the mixture was stirred at room temperature for about 3 hours. The reaction progress was monitored by TLC. If solid precipitated after the reaction, it was filtered and the upper solid was washed with a small amount of dichloromethane. If no solid precipitated, it was extracted with ethyl acetate and the organic phases were combined. The solvent in the obtained organic phase was removed by vacuum concentration. The dry loading method was used for column chromatography purification. The eluent was petroleum ether / ethyl acetate system to obtain a series of target compounds 7-O acetylhydrazine coumarin. The molar ratio of 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetic acid (12) to substituted phenylhydrazine, TBTU and triethylamine was 1:1:1:1.

[0045] The method for preparing the coumarin compounds of 7-N / O acetylhydrazine of the present invention also includes purification of the target compound. There is no special requirement for the purification method. Those skilled in the art can adopt various conventional purification methods, for example, extraction with an extractant, drying with a desiccant, and impurity removal by column chromatography and the like to obtain a high-purity target compound.

[0046] The fourth aspect of the present invention provides the use of the coumarin compounds of 7-N / O acetylhydrazine in the preparation of products for inhibiting or killing pathogens.

[0047] The pathogens include but are not limited to pathogenic fungi of crops, and the pathogenic fungi of crops include but are not limited to one or more of Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, Altemaria solani, Colletotrichum orbiculare or Alternaria alternata.

[0048] The fifth aspect of the present invention provides the use of the coumarin compounds of 7-N / O acetylhydrazine in weeding. Preferably, the weeding includes but is not limited to the removal of field weeds.

[0049] The field weeds include but are not limited to one or more of barnyard grass (Echinochloa crus-galli), crabgrass (Digitaria sanguinalis (L.) Scop.), velvetleaf (Abutilon theophrasti Medicus) or amaranth (Amaranthus retroflexus L.).

[0050] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages:

[0051] 1. The present invention uses various unsubstituted 3-aminophenols, various substituted β-ketoesters, ethyl bromoacetate, and various substituted or unsubstituted phenylhydrazines as starting materials, and a novel coumarin compound of 7-N acetylhydrazine can be obtained through six simple steps of reaction. The preparation method of the novel coumarin compound of 7-N acetylhydrazine of the present invention is simple to operate, does not involve precious metals in the reaction, and has high reaction efficiency.

[0052] 2. The present invention uses various substituted or unsubstituted meta-diphenols, various substituted β-ketoesters, ethyl bromoacetate, and various substituted or unsubstituted phenylhydrazines as starting materials, and a novel coumarin compound of 7-O acetohydrazide can be obtained through four simple reactions. The preparation method of the novel coumarin compound of 7-O acetohydrazide of the present invention is simple to operate, does not involve precious metals in the reaction, and has high reaction efficiency.

[0053] 3. The novel coumarin compounds of 7-N / O acetohydrazide of the present invention have good fungicidal activity, and the novel coumarin compounds of 7-N / O acetohydrazide show high efficiency and / or broad-spectrum antibacterial activity. The novel coumarin compounds of 7-N / O acetohydrazide of the present invention have good herbicidal activity. They can be effectively applied to the prevention and control of pathogenic fungi of crops and common field weeds. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Figure 1 The graph is the protective effect of compounds 43, 22 and trifluorfen on Amaranthus retroflexus after treatment for 14 days at 100 μg / mL;

[0055] Figure 2 The graph shows the protective effect of compounds 43, 22 and trifluorfen on velvetleaf after 14 days of treatment at 100 μg / mL;

[0056] Figure 3 The graph is the control effect of compounds 43, 22 and clethodim on barnyard grass at 100 μg / mL for 14 days;

[0057] Figure 4 The graph shows the protective effect of compounds 43, 22 and clethodim on crabgrass at 100 μg / mL for 14 days. DETAILED DESCRIPTION

[0058] The technical solution of the present invention is further described below in conjunction with the accompanying drawings.

[0059] The technical scheme of the present invention is described in detail through examples. In the examples, unless otherwise specified, all the raw materials used are purchased from commercial sources (Table 1), and their purity levels are all analytically pure, without expiration, moisture absorption, or deterioration. The room temperature is 25°C.

[0060] Table 1. List of main reagents

[0061]

[0062]

[0063] Me represents a methyl group, Et represents an ethyl group, and Pr represents a propyl group.

[0064] Example 1 Preparation of Novel Coumarin Compounds of 7-N-Acetylhydrazine

[0065]

[0066] Wherein, R1 is selected from Me, Et, Pr, CF3; R′ is selected from 2-F, 3-F, 4-F, 2-Cl, 4-Cl, 4-CF3.

[0067] The specific steps are as follows:

[0068] 1. Protection reaction: 6.5 g of 3-aminophenol (1) was added to a 250 mL two-necked flask, followed by 100 mL of ethyl acetate (EA) and 50 mL of water. The raw materials were completely dissolved by ultrasonication for 1 min, and then 5 g (60 mmol) of sodium bicarbonate was added and stirred in an ice bath for 5 min. 9.4 g (60 mmol) of phenyl chloroformate was slowly added dropwise. The reaction process was monitored by TLC. After the reaction was completed, the reaction solution was poured into a separating funnel and allowed to stand for stratification. The organic layer was collected and washed three times with water and saturated brine respectively. The organic phase was then concentrated and dried by rotary evaporation to obtain a white solid N-(3-hydroxyphenyl)phenylcarbamate (2).

[0069] 2. Cyclization reaction: 8.35 g (50 mmol) of N-(3-hydroxyphenyl)carbamic acid phenyl ester (2) was added to a round-bottom flask, 6 mL of anhydrous ethanol was poured into a small beaker, and 14 mL of concentrated sulfuric acid solution was slowly poured into the beaker containing anhydrous ethanol, while stirring with a glass rod. After the diluted concentrated sulfuric acid ethanol solution was cooled, it was poured into the round-bottom flask and stirred for 15 min to fully dissolve the raw materials. Subsequently, 50 mmol of β-keto acid ester (3) was slowly added dropwise, and after the addition was completed, the reaction was stirred at room temperature for 4-6 h. The reaction process was monitored by TLC. After the reaction was completed, the reaction solution was slowly poured into 200 mL of ice water, and a large amount of gray solid precipitated. After suction filtration, the filter cake was washed with a small amount of ethanol and dried to obtain a gray powder of substituted coumarin amino acid phenyl ester (4).

[0070] 3. Deprotection reaction: Add substituted coumarin amino acid phenyl ester (4) to a 50 mL round-bottom flask, then add 10 mL 45% potassium hydroxide solution (w:w) to the round-bottom flask, dissolve and stir, then heat to 100°C, and stir to react for about 1 hour. Monitor the reaction process by TLC. After the reaction is completed, pour the reaction solution into ice water, add concentrated hydrochloric acid dropwise to adjust the pH value to 1 to 2, then add ammonia water to adjust the pH value to 4 to 5. If solids are generated, filter and recrystallize from ethanol to obtain the intermediate substituted 7-aminocoumarin (5).

[0071] 4. Substitution reaction: substituted 7-aminocoumarin (5) (10 mmol), N,N-diisopropylethylamine DIEA (10 mmol) and 1.8 g (12 mmol) of sodium iodide were added to a flask, 20 mL of acetonitrile solution was added to dissolve it, magnetic stirring was performed for 5 min, 12 mmol of ethyl bromoacetate was added dropwise to the reaction flask, the heating device was adjusted to 95°C, refluxed for 24 hours, and the reaction progress was monitored by TLC. When the reaction was complete, the heating device was removed, and the reaction solution was poured into 100 mL of ice water while stirring while hot, and allowed to stand overnight to obtain a large amount of gray-brown solid. The mixed solution was then filtered, and the upper solid was washed with a small amount of ethanol, and dried to obtain the intermediate ethyl 2-((2-nitrogen-4-(substituted)-2H-coumarin-7-yl)amino)acetate (6).

[0072] 5. Deprotection reaction: The intermediate ethyl 2-((2-nitrogen-4-(substituted)-2H-coumarin-7-yl)amino)acetate (6) was added to a 250 mL round-bottom flask, dissolved with 100 mL ethanol, and fully dissolved by magnetic stirring for 15 min. 15 mL of 10% sodium hydroxide solution was added to the reaction flask, stirred at room temperature for about 4 h, and the reaction progress was monitored by TLC. After the reaction was complete, the ethanol solution was removed by vacuum distillation, the residue was poured into a beaker, 20 mL of distilled water was added, and 15% dilute hydrochloric acid was taken to adjust the pH value of the aqueous phase to 2-3. A large amount of gray-brown solid precipitated. The mixed solution was filtered, the upper solid was washed with a small amount of ethanol, and dried to obtain the intermediate 2-((2-nitrogen-4-(substituted)-2H-coumarin-7-yl)amino)acetic acid (7).

[0073] 6. Condensation reaction: 3.00 mmol of the intermediate 2-((2-azino-4-(substituted)-2H-coumarin-7-yl)amino)acetic acid (7) and 3.00 mmol of substituted phenylhydrazine (8) were added to a 50 mL round-bottom flask, and 25 mL of acetonitrile solution was added to fully dissolve. 3.00mmol O-benzotriazole-N,N,N′,N′-tetramethyluronium tetrafluoroboric acid (TBTU) was weighed and added to the reaction flask, followed by dropwise addition of 6.00mmol triethylamine, and stirred at room temperature for 3h. The reaction progress was monitored by TLC. If solid precipitated after the reaction, it was filtered and a small amount of dichloromethane was used to wash the upper solid. If no solid precipitated, it was extracted with ethyl acetate and the organic phases were combined. The solvent in the obtained organic phase was removed by reduced pressure concentration. The dry loading method was used for column chromatography purification. The eluent was petroleum ether / ethyl acetate system to obtain a series of target compounds 7-N acetylhydrazine coumarin 1 to 12. The substituent groups of each compound are shown in Table 2. The 7-N acetylhydrazine coumarin compounds shown in Formula I are shown in Table 2.

[0074] Table 2. 7-N-acetylhydrazine coumarin compounds

[0075]

[0076] The structural characterization data of the target compounds 7-N-acetylhydrazine coumarin 1 to 12 are as follows:

[0077] Compound 1: N'-(4-fluorophenyl)-2-((4-methyl-2-oxo-2H-coumarin-7-yl)amino)acetylhydrazine:

[0078] White solid, yield: 47.5%, mp: 163.5-164.5℃, 1H NMR (400MHz, DMSO-d6) δ9.93(d,J=3.0Hz,1H),7.74(d,J=2.9Hz,1H),7.47(d,J=8.7Hz,1H),6.98(t,J=6.2Hz,1H),6.94(t,J=8.9Hz,2H),6.7 3(d,J=4.6Hz,1H),6.71(d,J=4.6Hz,1H),6.68(dd,J=8.8,2.2Hz,1H),6.45(d,J=2.3Hz,1H),5.96(s,1H),3.90(d,J=6.2Hz,2H),2.33(s,3H). 13 C NMR (125MHz, DMSO-d6) δ170.01,161.25,155.95,154.32,152.62,146.28,127.90,126.41,125.08,115.58 (d,J=22.5Hz),114.00(d,J=8.5Hz),110.01(d,J=29.0Hz),108.50,97.47.45.05,18.55.HR-MS(ESI):m / z calcd for C 18 H 17 FN3O3([M+H] + )342.1248,Found342.1254.

[0079] Compound 2: 2-((4-ethyl-2-oxo-2H-coumarin-7-yl)amino)-N′-(3-fluorophenyl)acetylhydrazine:

[0080] White solid, yield: 65.8%, mp: 161.8-162.5℃, 1 H NMR (500MHz, DMSO-d6) δ9.93(d,J=3.6Hz,1H),8.06(s,1H),7.47(dd,J=8.8,4.2Hz,1H),7.06(dt,J=12.3,6.0Hz,1H),6.97(d,J=5.2Hz,1H),6.69–6 .61(m,1H),6.54–6.47(m,1H),6.46–6.33(m,3H),5.89(d,J=4.0Hz,1H),3 .90(t,J=5.2Hz,2H),2.67(dt,J=11.6,6.0Hz,2H),1.15(t,J=7.2Hz,3H). 13C NMR (125MHz, DMSO-d6) δ170.12, 164.69, 162.78, 161.52, 159.20, 156.15, 152.44, 151.97 (d, J = 10.0Hz), 130.72 (d, J = 10.0Hz), 125. 96,111.32,108.92(d,J=31.0Hz),106.69,105.10(d,J=21.0Hz),99.23(d,J=25.0Hz),97.73,45.08,24.55,13.11.HR-MS(ESI):m / z calcd for C 19 H 19 FN3O3([M+H] + )356.1405,Found 356.1414.

[0081] Compound 3: 2-((4-ethyl-2-oxo-2H-coumarin-7-yl)amino)-N'-(4-fluorophenyl)acetylhydrazine:

[0082] White solid, yield: 44.8%, mp: 162.7-163.5℃, 1 H NMR (400 MHz, DMSO-d6) 1 H NMR (400MHz, DMSO-d6) δ9.94(d,J=3.0Hz,1H),7.76(d,J=2.9Hz,1H),7.52(d,J=8.8Hz,1H),7.00(t,J=6.4Hz,1H),6.95(t,J=8.8Hz,2H),6.73(dd,J= 8.9,4.5Hz,2H),6.68(dd,J=8.8,2.3Hz,1H),6.46(d,J=2.3Hz,1H),5.94( s,1H),3.91(d,J=6.2Hz,2H),2.73(q,J=7.5Hz,2H),1.21(t,J=7.4Hz,3H). 13 C NMR (125MHz, DMSO-d6) δ169.98,161.52,159.30,157.29,156.13,155.43,152.50,146.32,126.01,115 .58(d,J=22.5Hz),113.97(d,J=7.5Hz),108.97,106.64,97.66,45.01,24.55,13.16.HR-MS(ESI):m / z calcd forC 19 H 19 FN3O3([M+H] +)356.1405,Found 356.1415.

[0083] Compound 4: N'-(2-chlorophenyl)-2-((4-ethyl-2-oxo-2H-coumarin-7-yl)amino)acetylhydrazine:

[0084] White solid, yield: 48.4%, mp: 163.4-164.1℃, 1 H NMR(500MHz,DMSO-d6)δ10.15–10.03(m,1H),7.50(d,J=8.8Hz,2H),7.26(d, J=7.8Hz,1H),7.09(t,J=7.7Hz,1H),7.02(t,J=6.2Hz,1H),6.81(d,J=8.0Hz ,1H),6.75–6.71(m,1H),6.71–6.68(m,1H),6.49(d,J=2.2Hz,1H),5.92(s,1 H), 3.96 (d, J = 6.1Hz, 2H), 2.70 (q, J = 10.6, 8.9Hz, 2H), 1.19 (t, J = 7.2Hz, 3H). 13 C NMR(125MHz,DMSO-d6)δ170.01,161.53,159.24,156.15,152.47,145.12,129.69,128.11,125.9 5,120.07,117.72,113.55,111.39,109.02,106.67,97.74,45.04,24.56,13.14.HR-MS(ESI):m / z calcd for C 19 H 19 ClN3O3([M+H] + )372.1109,Found372.1105.

[0085] Compound 5: N'-(4-chlorophenyl)-2-((4-ethyl-2-oxo-2H-coumarin-7-yl)amino)acetylhydrazine:

[0086] White solid, yield: 51.5%, mp: 163.9-164.6℃, 1H NMR (400MHz, DMSO-d6) δ9.96(d,J=2.3Hz,1H),7.97(s,1H),7.52(d,J=8.8Hz,1H),7.13(d,J=8.9Hz,2H),7.00(t,J=6.2Hz,1H),6.77–6.68( m,2H),6.67(dd,J=8.8,2.3Hz,1H),6.46(d,J=2.3Hz,1H),5.93(s,1H),3.92(d,J=6.1Hz,2H),2.72(q,J=7.5Hz,2H),1.20(t,J=7.4Hz,3H). 13 C NMR(126MHz,DMSO-d6)δ169.53,161.02,158.81,155.65,152.00,148.27,128.45,125.54,1 21.86,113.76,110.82,108.51,106.18,97.19,44.51,24.07,12.68.HR-MS(ESI):m / zcalcd for C 19 H 19 ClN3O3([M+H] + )372.1109,Found 372.1111.

[0087] Compound 6: N'-(2-fluorophenyl)-2-((2-oxo-4-propyl-2H-coumarin-7-yl)amino)acetylhydrazine:

[0088] White solid, yield: 49.5%, mp: 165.9-166.6℃, 1 H NMR(500MHz,DMSO-d6)δ9.98(s,1H),7.73(s,1H),7.52(dd,J=8.9,2.6Hz,1H),7.11–6.99(m,2H),6.92(t,J=7.7Hz,1H),6.79(t,J=8.5Hz,1H),6. 74–6.65(m,2H),6.46(s,1H),5.92(s,1H),3.92(d,J=5.8Hz,2H),2.66(t ,J=7.5Hz,2H),1.61(td,J=14.5,6.9Hz,2H),0.95(td,J=7.4,2.6Hz,3H). 13CNMR(126MHz,DMSO-d6)δ169.54,160.86,157.30,155.79,152.02,149.20,136.83,125.69,124.38,118.73, 114.87(d,J=17.6Hz),113.69,110.88,108.59,107.10,97.21,44.49,32.89,21.65,13.75.HR-MS(ESI):m / z calcd for C 20 H 21 FN3O3([M+H] + )370.1561,Found370.1564.

[0089] Compound 7: N'-(4-fluorophenyl)-2-((2-oxo-4-propyl-2H-coumarin-7-yl)amino)acetylhydrazine:

[0090] White solid, yield: 39.8%, mp: 164.8-165.6℃, 1 H NMR (500MHz, DMSO-d6) δ9.96(d,J=4.6Hz,1H),7.78(s,1H),7.51(t,1H),7.02(d,J=5.8Hz,1H),6.96–6.91(m,2H),6.76–6.71(m,2H),6.70–6. 65(m,1H),6.46(d,J=2.8Hz,1H),5.92(d,J=4.1Hz,1H),3.92(s,2H),2.65(q,J=7.8,6.8Hz,2H),1.60(h,J=7.0Hz,2H),0.95(d,J=6.9Hz,3H). 13 C NMR(126MHz, DMSO-d6)δ169.51,160.89,157.30,155.89(d,J=233.5Hz),155.79,152.02,145.85,125.70,115.09 (d,J=22.3Hz),113.51(d,J=7.8Hz),110.85,108.60,107.11,97.22,44.55,32.90,21.64,13.74.HR-MS(ESI):m / z calcd for C 20 H 21 FN3O3([M+H] + )370.1561,Found 370.1563.

[0091] Compound 8: 2-((2-oxo-4-propyl-2H-coumarin-7-yl)amino)-N'-(4-(trifluoromethyl)phenyl)acetylhydrazine:

[0092] White solid, yield: 40.0%, mp: 165.4-166.0℃, 1 H NMR (500MHz, DMSO-d6) δ10.10(s,1H),8.46(s,1H),7.52(d,J=8.5Hz,1H),7.42(d,J=7.5Hz,2H),7.04(s,1H),6.84(d,J=7.5Hz,2H),6.69(d, J=8.9Hz,1H),6.49(s,1H),5.92(d,J=2.9Hz,1H),3.97(d,J=3.3Hz,2H),2.80–2.57(m,2H),1.61(q,J=7.3,6.8Hz,2H),0.95(t,J=7.1Hz,3H). 13 C NMR (126MHz, DMSO-d6) δ169.71,160.89,157.27,155.81,152.47,152.02,126.12,125.73,123.98(q,J=63.1Hz ),118.39(q,J=32.0Hz),111.64,110.83,108.69,107.20,97.34,44.59,32.93,21.66,13.71.HR-MS(ESI):m / z calcd for C 21 H 21 F3N3O3([M+H] + )420.1530,Found 420.1540.

[0093] Compound 9: N'-(4-chlorophenyl)-2-((2-oxo-4-propyl-2H-coumarin-7-yl)amino)acetylhydrazine:

[0094] White solid, yield: 33.0%, mp: 164.1-165.0℃, 1H NMR(500MHz,DMSO-d6)δ9.98(d,J=3.2Hz,1H),7.98(t,J=7.0Hz,1H),7.59–7.49 (m,1H),7.47–7.37(m,1H),7.19–7.06(m,2H),6.73(dd,J=9.1,3.2Hz,2H),6.68( dt,J=9.1,3.0Hz,1H),6.46(d,J=3.0Hz,1H),5.93(d,J=4.5Hz,1H),3.92(s,2H) ,2.66(q,J=6.9,5.8Hz,2H),1.61(dq,J=14.4,7.4Hz,2H),0.96(t,J=7.2Hz,3H). 13 C NMR(126MHz,DMSO-d6)δ169.57,160.90,157.34,155.78,152.02,148.29,128.46,125.75,1 21.90,119.21,113.79,108.63,107.14,97.26,44.57,32.92,21.67,13.76.HR-MS(ESI):m / z calcd for C 20 H 21 ClN3O3([M+H] + )386.1266,Found386.1265.

[0095] Compound 10: N'-(3-fluorophenyl)-2-((2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)amino)acetylhydrazine:

[0096] White solid, yield: 35.0%, mp: 167.5-168.2℃, 1 H NMR (400MHz, DMSO-d6) δ9.98(d,J=2.4Hz,1H),8.10(d,J=2.4Hz,1H),7.41(q,J=7.2,6.0Hz,3H),7.12(q,J= 7.6Hz,1H),6.79(dd,J=9.2,2.4Hz,1H),6.62–6.50(m,3H),6.43(d,J=13.6Hz,2H),4.00(d,J=13.2Hz,1H). 13C NMR (125MHz, DMSO-d6) δ169.71, 164.71, 162.79, 159.85, 157.11, 153.50, 151.95 (d, J = 10.5Hz), 140.71 (q, J = 31.5Hz), 130.73 (d, J = 9.5 Hz),127.81,125.84,110.12,108.75(d,J=16.5Hz),105.11(d,J=21.5Hz),102.86,99.22(d,J=25.5Hz),98.00,44.81.HR-MS(ESI):m / z calcd for C 18 H 14 F4N3O3([M+H] + )396.0966,Found396.0961.

[0097] Compound 11: N'-(4-fluorophenyl)-2-((2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)amino)acetylhydrazine:

[0098] White solid, yield: 44.0%, mp: 167.8-168.4℃, 1 H NMR(500MHz,DMSO-d6)δ9.99(s,1H),7.80(s,1H),7.46–7.33(m,2H),6.95(t,J=8.4H z,2H),6.75(dt,J=9.3,6.0Hz,3H),6.57(s,1H),6.49(s,1H),3.97(d,J=6.0Hz,2H). 13 C NMR (126MHz, DMSO-d6) δ173.15,169.17,159.43,156.89,156.65,155.03,153.05,145.81,140.25(q,J=32.0Hz),125.36, 122.01(q,J=275.2Hz),115.14(d,J=22.2Hz),113.55(d,J=7.6Hz),108.21(d,J=5.2Hz),102.37,44.33.HR-MS(ESI):m / z calcd for C 18 H 14 F4N3O3([M+H] + )396.0966,Found396.0967.

[0099] Compound 12: N′-(4-chlorophenyl)-2-((2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)amino)acetylhydrazine:

[0100] White solid, yield: 50.8%, mp: 169.1-170.0℃, 1 H NMR (500MHz, DMSO-d6) δ10.00(s,1H),8.00(s,1H),7.40(s,2H),7.14(d,J=8.3Hz,2H),6.84–6.67(m,3H),6.54(d,J=27.3Hz,2H),3.98(s,2H). 13 C NMR (126MHz, DMSO-d6) δ169.14, 159.39, 156.62, 153.02, 148.22, 140.21 (q, J = 31.8Hz), 128.47, 125.37 ,121.99(q,J=276.1Hz),121.92,113.76,109.65,108.24,102.36,97.47,44.27.HR-MS(ESI):m / zcalcd for C 18 H 14 ClF3N3O3([M+H] + )411.0670,Found 411.0675.

[0101] Example 2 Preparation of Novel Coumarin Compounds of 7-O-Acetylhydrazine

[0102]

[0103] wherein R1 is selected from Me and CF3; R2 is selected from H and Cl; R3 is selected from H and Me; R 、 Selected from 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 2-Br, 4-Br, 4-CH3O, 3,4-diCH3, 2,4,6-trCl.

[0104] 1. Cyclization reaction: 50 mmol of substituted or unsubstituted resorcinol (9) is added to a round-bottom flask, 6 mL of anhydrous ethanol is poured into a small beaker, 14 mL of concentrated sulfuric acid solution is slowly poured into the beaker containing anhydrous ethanol, and stirred with a glass rod. After the diluted concentrated sulfuric acid ethanol solution is cooled, it is poured into a 100 mL round-bottom flask and stirred for 15 min to fully dissolve the raw materials. Subsequently, 50 mmol of β-ketoester (3) is slowly added dropwise, and after the addition is complete, the reaction is stirred at room temperature for 4-6 hours. The reaction process is monitored by TLC. After the reaction is completed, the reaction solution is slowly poured into 200 mL of ice water, and a large amount of gray solid is precipitated. After suction filtration, the filter cake is washed with a small amount of ethanol and dried to obtain substituted 7-hydroxycoumarin (10).

[0105] 2. Substitution reaction: 10 mmol of substituted 7-hydroxycoumarin (10), 10 mmol of N,N-diisopropylethylamine DIEA and 1.8 g (12 mmol) of sodium iodide were added to a 50 mL flask, 20 mL of acetonitrile solution was added to dissolve, magnetic stirring was performed for about 5 min, 12 mmol of ethyl bromoacetate was added dropwise to the reaction flask, the heating device was adjusted to 95°C, refluxed for 24 hours, and the reaction progress was monitored by TLC. When the reaction was complete, the heating device was removed, and the reaction solution was poured into ice water while stirring while hot, and allowed to stand overnight to obtain a large amount of solid. The mixed solution was then filtered, and the upper solid was washed with a small amount of ethanol and dried to obtain the intermediate ethyl 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetate (11).

[0106] 3. Deprotection reaction: The intermediate ethyl 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetate (11) was added to a 250 mL round-bottom flask, dissolved with 100 mL ethanol, and fully dissolved by magnetic stirring for about 15 min. 15 mL of 10% sodium hydroxide solution was added to the reaction flask, stirred at room temperature for about 4 h, and the reaction progress was monitored by TLC. After the reaction was complete, the ethanol solution was removed by vacuum distillation, and the resulting residue was poured into a 50 mL beaker, 20 mL of distilled water was added, and 15% dilute hydrochloric acid was taken to adjust the pH value of the aqueous phase to 2-3. A large amount of solid precipitated. The mixed solution was filtered, and the upper solid was washed with a small amount of ethanol and dried to obtain the intermediate 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetic acid (12).

[0107] 4. Condensation reaction: 3.00 mmol of the intermediate 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetic acid (12) and 3.00 mmol of substituted phenylhydrazine (8) were added to a 50 mL round-bottom flask, and 25 mL of acetonitrile solution was added to fully dissolve. O-benzotriazole-N,N,N′,N′-tetramethyluronium tetrafluoroboric acid (TBTU) was weighed and added to the reaction flask, followed by dropwise addition of 6.00 mmol of triethylamine. The mixture was stirred at room temperature for about 3 h, and the reaction progress was monitored by TLC. If solid precipitated after the reaction, it was filtered and the upper solid was washed with a small amount of dichloromethane; if no solid precipitated, it was extracted with ethyl acetate and the organic phases were combined. The solvent in the obtained organic phase was removed by reduced pressure concentration, and column chromatography was used for purification by dry loading method. The eluent was petroleum ether / ethyl acetate system to obtain a series of target compounds 7-O acetylhydrazine coumarin 13-53. The substituent groups of each compound are shown in Table 3. The 7-O acetylhydrazine coumarin shown in Formula II is shown in Table 3.

[0108] Table 3. 7-O-acetylhydrazine coumarin

[0109]

[0110]

[0111] The structural characterization data of the target compound 7-O acetylhydrazine coumarin 13-53 are as follows:

[0112] Compound 13: N′-(2-fluorophenyl)-2-((4-methyl-2-oxo-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0113] White solid, yield: 67.8%, mp: 131.3-131.7℃, 1 H NMR (400MHz, DMSO-d6) δ10.20 (s, 1H), 7.78 (s, 1H), 7.73 (d, J = 8.8Hz, 1H), 7.11-7.01 (m, 3H) ,6.96(t,J=7.7Hz,1H),6.79(dd,J=12.3,4.5Hz,1H),6.25(s,1H),4.83(s,2H),2.41(s,3H). 13 C NMR (126MHz, DMSO-d6) δ167.40,160.89,160.35,154.6,153.63,136.79,126.67,124.64,119. 12,113.90,113.79,112.84,111.61,101.78,66.56,45.65,18.33,8.64.HR-MS(ESI):m / zcalcd for C 18 H 15 FN2O4([M+H] + )343.1089, found 343.1092.

[0114] Compound 14: N'-(3-fluorophenyl)-2-((4-methyl-2-oxo-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0115] White solid, yield: 64.1%, mp: 159.1-160.1℃, 1 H NMR (400MHz, DMSO-d6) δ10.06(d,J=3.3Hz,1H),7.73(d,J=8.8Hz,1H),7.51(d,J=3.3Hz,1H), 7.05(dd,J=8.8,2.5Hz,1H),7.01(d,J=2.4Hz,1H),6.71(dd,J=21.1,9.1Hz,4H),4.77(s,2H). 13C NMR (100MHz, DMSO-d6) δ167.32, δ163.30 (d, J = 241.1Hz), 160.81, 160.22, 154.63, 153.52, 151.42 (d, J = 10.5Hz), 130.39 (d, J = 9.8 Hz),126.65,113.79,112.77,111.60,108.44,104.78(d,J=21.4Hz),101.76,98.83(d,J=25.7Hz),66.50,18.30.HR-MS(ESI):m / z calcd forC 18 H 15 FN2O4([M+H] + )343.1089, found 343.1092.

[0116] Compound 15: N′-(4-fluorophenyl)-2-((4-methyl-2-oxo-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0117] White solid, yield: 84.1%, mp: 119.0-119.8℃, 1 H NMR (400MHz, DMSO-d6) δ10.12(d,J=2.9Hz,1H),7.82(d,J=2.8Hz,1H),7.74(d,J=8.8Hz,1H),7.06(dd,J=8.8,2.5Hz,1H), 7.02(d,J=2.4Hz,1H),6.97(t,J=8.9Hz,2H),6.76-6.68(m,2H),6.26(d,J=1.1Hz,1H),4.80(s,2H),2.42(d,J=0.9Hz,3H). 13 C NMR(126MHz,DMSO-d6)δ167.35,160.88,160.39,155.21,154.68,153.69,145.79,126 .70,115.44,115.26,113.80,112.81,111.65,101.79,66.59,18.34.HR-MS(ESI):m / z calcd for C 18 H 15 FN2O4([M+H] + )343.1089,found343.1089.

[0118] Compound 16: N′-(2-chlorophenyl)-2-((4-methyl-2-oxo-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0119] White solid, yield: 81.6%, mp: 145.9-146.7℃, 1 H NMR (400MHz, DMSO-d6) δ10.23(s,1H),7.74(d,J=8.7Hz,1H),7.57(d,J=1.2Hz,1H),7.28(dt,J=13.7,6.8H z,1H),7.13(t,J=7.7Hz,1H),7.09-7.03(m,2H),6.83-6.68(m,2H),6.25(s,1H),4.83(s,2H),2.42(s,3H). 13 C NMR (126MHz, DMSO-d6) δ167.72,161.13,160.76,154.97,154.06,144.85,129.71,128.20,127 .03,120.27,117.76,114.20,113.49,113.22,111.94,102.12,66.85,18.66.HR-MS(ESI):m / z calcd for C 18 H 15 ClN2O4([M+H] + )359.0793, found 359.0795.

[0120] Compound 17: N′-(3-chlorophenyl)-2-((4-methyl-2-oxo-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0121] White solid, yield: 79.5%, mp: 133.7-134.4℃, 1 H NMR (400MHz, DMSO-d6) δ10.16(s,1H),8.14(d,J=2.1Hz,1H),7.74(d,J=8.8Hz,1H),7.13(t,J=8.0Hz,1 H),7.09-7.01(m,2H),6.73-6.64(m,2H),6.61(t,J=1.9Hz,1H),6.25(s,1H),4.84(s,2H),2.41(s,3H). 13C NMR(126MHz,DMSO-d6)δ167.56,160.84,160.43,154.74,153.72,150.85,133.79,130.60,126 .81,118.39,114.01,112.92,111.73,111.59,111.29,101.84,66.63,18.40.HR-MS(ESI):m / z calcd for C 18 H 15 ClN2O4([M+H] + )359.0793,found359.0796.

[0122] Compound 18: N'-(2-bromophenyl)-2-((4-methyl-2-oxo-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0123] White solid, yield: 76.2%, mp: 142.4-142.7℃, 1 H NMR (400MHz, DMSO-d6) δ10.27(s,1H),7.74(d,J=8.7Hz,1H),7.45(dd,J=7.9,1.2Hz,1H),7.34(s,1H),7.17(t,J =7.7Hz,1H),7.12-7.02(m,2H),6.78(d,J=8.2Hz,1H),6.73-6.67(m,1H),6.26(s,1H),4.83(s,2H),2.42(s,3H). 13 C NMR(126MHz,DMSO-d6)δ167.36,160.86,160.40,154.71,153.70,145.57,132.61,128.51,126.74,1 20.64,113.91,113.50,112.92,111.69,107.22,101.87,66.61,18.39(d,J=1.3Hz).HR-MS(ESI):m / z calcd for C 18 H 15 BrN2O4([M+H] + )403.0288, found 403.0291.

[0124] Compound 19: N'-(4-bromophenyl)-2-((4-methyl-2-oxo-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0125] White solid, yield: 80.7%, mp: 145.5-146.3℃,1 H NMR (400MHz, DMSO-d6) δ10.15(s,1H),8.05(d,J=1.9Hz,1H),7.73(d,J=8.7Hz,1H),7.27(d,J=8.8Hz,2H),7.0 5(dd,J=8.8,2.4Hz,1H),7.02(d,J=2.3Hz,1H),6.69(d,J=8.8Hz,2H),6.25(s,1H),4.81(s,2H),2.41(s,3H). 13 C NMR(126MHz,DMSO-d6)δ167.50,160.87,160.47,154.70,153.70,148.66,131.58,126 .73,114.59,113.91,112.85,111.70,109.87,101.83,66.60,18.42.HR-MS(ESI):m / z calcd for C 18 H 15 BrN2O4([M+H] + )403.0288, found 403.0291.

[0126] Compound 20: N′-(4-methoxyphenyl)-2-((4-methyl-2-oxo-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0127] White solid, yield: 87.6%, mp: 158.0-158.7℃, 1 H NMR (400MHz, DMSO-d6) δ10.07(d,J=3.3Hz,1H),7.74(d,J=8.8Hz,1H),7.51(d,J=3.3Hz,1H),7.06(dd,J=8.8,2.5Hz,1H),7 .02(d,J=2.4Hz,1H),6.71(dd,J=21.1,9.1Hz,4H),6.26(d,J=1.1Hz,1H),4.78(s,2H),3.65(s,3H),2.42(d,J=0.9Hz,3H). 13 C NMR(126MHz,DMSO-d6)δ167.91,161.18,161.12,154.96,154.38,153.47,143.24,127 .13,114.77,114.61,114.27,113.37,111.90,102.07,66.85,18.72.HR-MS(ESI):m / z calcd for C 19 H 18N2O5([M+H] + )355.1289, found355.1289.

[0128] Compound 21: N'-(3,4-dimethylphenyl)-2-((4-methyl-2-oxo-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0129] White solid, yield: 77.3%, mp: 127.5-128.1℃, 1 H NMR (400MHz, DMSO-d6) δ10.03(d,J=3.0Hz,1H),7.73(d,J=8.7Hz,1H),7.57(d,J=3.0Hz,1H),7.06(dd,J=8.8,2.4Hz,1H) ,7.02(d,J=2.4Hz,1H),6.87(d,J=8.8Hz,1H),6.47(d,J=5.8Hz,2H),6.25(s,1H),4.79(s,2H),2.41(s,3H),2.07(s,6H). 13 C NMR(126MHz,DMSO-d6)δ167.32,160.88,160.30,154.70,153.54,147.25,136.37,129.80,126.65,1 26.37,114.02,112.89,111.64,110.28,101.76,66.59,19.76,18.63,18.30.HR-MS(ESI):m / zcalcd for C 20 H 20 N2O4([M+H] + )353.1496, found 353.1499.

[0130] Compound 22: 2-((4-methyl-2-oxo-2H-coumarin-7-yl)oxy)-N′-(2,4,6-trichlorophenyl)acetylhydrazine:

[0131] White solid, yield: 74.3%, mp: 148.4-148.5℃, 1 H NMR (400MHz, DMSO-d6) δ10.39(d,J=1.3Hz,1H),7.69(d,J=8.8Hz,1H),7.49(s,2H),7.45(d,J=1.2Hz,1H),7 .00(dd,J=8.8,2.5Hz,1H),6.95(d,J=2.4Hz,1H),6.23(d,J=0.9Hz,1H),4.70(s,2H),2.40(d,J=0.6Hz,3H).13 C NMR(126MHz,DMSO-d6)δ166.77,160.89,160.31,154.66,153.62,140.79,128.68,126 .63,125.36,124.47,113.79,112.78,111.61,101.66,65.82,18.34.HR-MS(ESI):m / z calcd for C 18 H 13 Cl3N2O4([M+H] + )427.0013, found 427.0018.

[0132] Compound 23: N'-(2-fluorophenyl)-2-((2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0133] White solid, yield: 67.8%, mp: 168.4-168.9℃, 1 H NMR (400MHz, DMSO-d6) δ10.16(s,1H),7.78(s,1H),7.68(d,J=7.6Hz,1H),7.21-7.14(m,2H),7.06(dd,J=12.6,3 .5Hz,1H),6.97(t,J=7.5Hz,1H),6.91(s,1H),6.81(t,J=8.0Hz,1H),6.73(dd,J=11.9,6.9Hz,1H),4.86(s,2H). 13 C NMR(100MHz,DMSO-d6)δ167.17(s),161.67(s),158.92(s),155.81(s),151.57(s) ),149.19(s),139.62(q,J=31.5Hz),136.72(d,J=10.7Hz),126.13(s),124.67(d, J=3.2Hz),121.90(d,J=275.2Hz),119.18(d,J=6.6Hz),115.10(d,J=17.7Hz),11 4.08(s),113.89(s),107.15(s),102.77(s),66.64(s).HR-MS(ESI):m / zcalcdfor C 18 H 12 F4N2O4([M+H] + )397.0806, found 397.0803.

[0134] Compound 24: N′-(3-fluorophenyl)-2-((2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0135] White solid, yield: 69.6%, mp: 165.1-165.7℃, 67.8%, 1 H NMR (400MHz, DMSO-d6) δ10.15(d,J=2.2Hz,1H),8.13(d,J=1.7Hz,1H),7.68(d,J=7.4Hz,1H),7.20–7.09(m,3H), 6.90(s,1H),6.55(dd,J=8.2,1.4Hz,1H),6.48(td,J=8.3,2.0Hz,1H),6.41(dt,J=11.7,2.2Hz,1H),4.88(s,2H). 13 C NMR(126MHz,DMSO-d6)δ167.35,163.49(d,J=240.5Hz),161.73,159.00,155.8 7,151.49(d,J=10.4Hz),139.79(q,J=31.3Hz),130.62(d,J=10.0Hz),126.26,1 21.96(d,J=275.5Hz),114.15,113.86(d,J=5.6Hz),108.66(d,J=2.1Hz),107. 25,105.10(d,J=21.3Hz),102.86,99.02(d,J=25.9Hz),66.72.HR-MS(ESI):m / z calcd for C 18 H 12 F4N2O4([M+H] + )397.0806, found 397.0804.

[0136] Compound 25: N′-(4-fluorophenyl)-2-((2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0137] White solid, yield: 64.1%, mp: 189.2-189.8℃, 1H NMR (400MHz, DMSO-d6) δ10.14(d,J=2.5Hz,1H),7.83(d,J=2.6Hz,1H),7.67(d,J=8.5Hz,1H),7.16(d d,J=12.8,2.3Hz,2H),6.98(t,J=8.8Hz,2H),6.89(s,1H),6.75(dd,J=8.8,4.6Hz,2H),4.85(s,2H). 13 C NMR(100MHz,DMSO-d6)δ167.06,161.64,158.88,157.28,155.78,154.95,145.74,139.56(d,J=32.1Hz ),126.09,115.31(d,J=22.3Hz),114.00,113.71(d,J=7.5Hz),107.09,102.71,66.64.HR-MS(ESI):m / z calcd for C 18 H 12 F4N2O4([M+H] + )397.0806, found397.0809.

[0138] Compound 26: N′-(2-chlorophenyl)-2-((2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0139] White solid, yield: 66.7%, mp: 190.1-190.6℃, 1 H NMR (400MHz, DMSO-d6) δ10.25(s,1H),7.68(d,J=7.2Hz,1H),7.57(s,1H),7.29(dd,J=7.9,1.3 Hz,1H),7.17(ddd,J=16.6,10.1,4.8Hz,3H),6.91(s,1H),6.83-6.72(m,2H),4.88(s,2H).13C NMR (100MHz, DMSO-d6) δ167.21, 161.70, 158.96, 155.85, 144.61, 139.71 (d, J = 30.7Hz), 129.45, 127. 95,126.17,123.30,120.60,119.99,117.51,114.13,113.27,107.18,102.83,66.69.HR-MS(ESI):m / z calcd for C 18 H 12 ClF3N2O4([M+H] +)413.0511,found413.0513.

[0140] Compound 27: N′-(3-chlorophenyl)-2-((2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0141] White solid, yield: 74.1%, mp: 199.5-199.9℃, 1 H NMR (400MHz, DMSO-d6) δ10.17(d,J=2.1Hz,1H),8.15(d,J=2.1Hz,1H),7.68(d,J=7.9Hz,1 H),7.22-7.09(m,3H),6.89(s,1H),6.74-6.67(m,2H),6.62(t,J=1.9Hz,1H),4.89(s,2H). 13 C NMR(100MHz,DMSO-d6)δ167.13,160.16(d,J=279.5Hz),158.77,155.74,150.76,139.55(d,J=32.2Hz),133.65,130 .46,126.08,120.46,118.23,114.01,113.79(d,J=5.9Hz),111.46,111.17,107.12,102.67,66.62.HR-MS(ESI):m / z calcd for C 18 H 12 ClF3N2O4([M+H] + )413.0511,found413.0513.

[0142] Compound 28: N′-(2-bromophenyl)-2-((2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0143] White solid, yield: 76.5%, mp: 196.7-197.2℃, 1 H NMR (400MHz, DMSO-d6) δ10.30(s,1H),7.68(d,J=8.8Hz,1H),7.45(dd,J=7.9,1.3Hz,1H),7.34(d,J=1.6Hz, 1H),7.21-7.15(m,3H),6.91(s,1H),6.80(dd,J=8.1,1.2Hz,1H),6.71(td,J=7.7,1.4Hz,1H),4.88(s,2H). 13C NMR (126MHz, DMSO-d6) δ171.19,167.19,161.70,158.97,155.84,145.57,139.7(q,J=31.5Hz),132.6 3,128.55,126.19,123.02,120.70,114.13,113.55,107.25,107.18,102.84,66.66.HR-MS(ESI):m / z calcd for C 18 H 12 BrF3N2O4([M+H] + )457.0005,found457.0008.

[0144] Compound 29: N'-(4-bromophenyl)-2-((2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0145] White solid, yield: 80.2%, mp: 190.6-191.4℃, 1 H NMR (400MHz, DMSO-d6) δ10.16(d,J=2.4Hz,1H),8.05(d,J=2.3Hz,1H),7.68(dd,J=8.6,1.3Hz,1H), 7.28(d,J=8.8Hz,2H),7.16(dt,J=8.9,2.4Hz,2H),6.90(s,1H),6.70(d,J=8.8Hz,2H),4.86(s,2H). 13 C NMR(100MHz,DMSO-d6)δ167.35,161.89,159.14,156.05,148.86,139.67(q,J=32.0Hz),131.77, 126.38,122.16(d,J=276.0Hz),114.74,114.27,109.97,107.39,103.00,66.89.HR-MS(ESI):m / z calcd for C 18 H 12 BrF3N2O4([M+H] + )457.0005,found 457.0001.

[0146] Compound 30: N'-(4-cyanophenyl)-2-((2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0147] White solid, yield: 70.9%, mp: 167.5-168.4℃, 1H NMR (400MHz, DMSO-d6) δ10.29(s,1H),8.72(s,1H),7.69(d,J=7.3Hz,1H),7.55(d,J=8.6Hz,2H) ,7.19(d,J=2.4Hz,1H),7.16(d,J=9.1Hz,1H),6.91(s,1H),6.80(d,J=8.8Hz,2H),4.90(s,2H). 13 C NMR(100MHz,DMSO-d6)δ167.34,161.64,159.02,155.86,152.86,139.69(q,J=32.0Hz),133.69, 126.27,123.33,120.60,120.31,114.07,112.12,107.27,102.81,99.43,66.64.HR-MS(ESI):m / z calcd for C 19 H 12 F3N3O4([M+H] + )404.0853,found404.0851.

[0148] Compound 31: N'-(4-methoxyphenyl)-2-((2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0149] White solid, yield: 80.0%, mp: 193.2-193.9℃, 1 H NMR (400MHz, DMSO-d6) δ10.08(d,J=3.3Hz,1H),7.67(d,J=7.3Hz,1H),7.51(d,J=3.3Hz ,1H),7.18-7.13(m,2H),6.90(s,1H),6.72(q,J=9.1Hz,4H),4.83(s,2H),3.65(s,3H). 13 C NMR (100MHz, DMSO-d6) δ166.80,161.62,158.78,155.72,152.87,142.96,139.64(q,J=32.0H z),126.01,114.68,114.26,113.98,113.93,107.01,102.65,66.62,55.33.HR-MS(ESI):m / z calcd forC 19 H 15 F3N2O5([M+H] + )409.1005, found 409.1008

[0150] Compound 32: N'-(3,4-dimethylphenyl)-2-((2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0151] White solid, yield: 64.1%, mp: 201.5-201.9℃, 1 H NMR (400MHz, DMSO-d6) δ10.04(s,1H),7.68(d,J=8.2Hz,1H),7.57(s,1H),7.16(d, J=7.7Hz,2H),6.94-6.83(m,2H),6.47(d,J=8.6Hz,2H),4.84(s,2H),2.08(s,6H). 13 C NMR (126MHz, DMSO-d6) δ166.96,161.70,158.87,155.79,147.20,139.62(q,J=31.5Hz),136.37,129.81,127 .44,126.40,126.12,123.00,114.09,113.98,110.28,107.11,102.71,66.65,19.79,18.64.HR-MS(ESI):m / z calcd for C 20 H 17 F3N2O4([M+H] + )407.1213, found 407.1211. Compound 33: 2-((2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)-N'-(2,4,6-trichlorophenyl)acetylhydrazide:

[0152] White solid, yield: 50.5%, mp: 164.1-164.4℃, 1 H NMR (400MHz, DMSO-d6) δ10.38(s,1H),7.60(d,J=4.2Hz,1H),7.46(d,J=0.8Hz,2H),7.41(s,1H),7.06(s,2H),6.85(s,1H),4.70(s,2H). 13C NMR(100MHz,DMSO-d6)δ166.60,161.69,158.89,155.78,140.78,139.62(q,J=31.5Hz),128.69,12 6.03,125.44,124.54,113.99,113.78(d,J=4.8Hz),107.07,102.63,65.92,45.91.HR-MS(ESI):m / z calcd for C 18 H9Cl4F3N2O4([M+H] + )516.9314, found 516.9310.

[0153] Compound 34: 2-((6-chloro-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)-N′-(2-fluorophenyl)acetylhydrazine:

[0154] White solid, yield: 67.6%, mp: 145.1-145.4℃, 1 H NMR(400MHz,DMSO-d6)δ10.11(s,1H),7.82(s,1H),7.65(s,1H),7.34(s,1H),7.09-7.04(m ,1H),7.02-6.97(m,2H),6.89(t,J=8.0Hz,1H),6.74(dd,J=11.9,6.7Hz,1H),5.02(s,2H). 13 C NMR(100MHz,DMSO-d6)δ166.97(s),158.76(s),157.16(s),154.53(s),151.82 (s),149.44(s),138.89(q,J=31.1Hz),136.83(d,J=10.6Hz),125.24(s),124.9 4(d,J=3.1Hz),121.84(d,J=276.0Hz),119.64(d,J=6.8Hz),119.28(s),115.3 8(d,J=17.7Hz),114.18(s),107.73(s),103.31(s),67.26(s).HR-MS(ESI):m / z calcd for C 18 H 11 ClF4N2O4([M+H] + )431.0416,found431.0420.

[0155] Compound 35: 2-((6-chloro-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)-N′-(3-fluorophenyl)acetylhydrazine:

[0156] White solid, yield: 70.5%, mp: 155.9-156.3℃, 1 H NMR(400MHz,DMSO-d6)δ10.09(d,J=1.9Hz,1H),8.17(s,1H),7.66(s,1H),7.37(s,1H),7.15 (dd,J=15.1,8.1Hz,1H),7.00(s,1H),6.62-6.56(m,1H),6.49(t,J=8.5Hz,2H),5.02(s,2H). 13 C NMR (126MHz, DMSO-d6) δ166.70,164.40,162.49,158.45,156.98,154.35,151.37(d,J=10.5Hz),138.60(q,J=32.76Hz),130.54(d,J=11.6H z),125.00,119.05,115.24,108.55(d,J=2.7Hz),107.49,105.04(d,J=21.6Hz),103.12,98.97(d,J=26.0Hz),67.15.HR-MS(ESI):m / zcalcd for C 18 H 11 ClF4N2O4([M+H] + )431.0416, found 431.0418.

[0157] Compound 36: 2-((6-chloro-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)-N'-(4-fluorophenyl)acetylhydrazine:

[0158] White solid, yield: 56.7%, mp: 152.3-152.9℃, 1 H NMR (400MHz, DMSO-d6) δ10.07(d,J=2.7Hz,1H),7.85(d,J=2.6Hz,1H),7.65(s, 1H),7.34(s,1H),6.99(dd,J=11.5,6.2Hz,3H),6.81-6.73(m,2H),4.99(s,2H). 13C NMR (126MHz, DMSO-d6) δ167.06, 161.64, 158.87, 157.04, 155.77, 155.19, 145.72 (d, J = 2.0Hz), 139.56 (q, J = 31.5 Hz),126.09,115.31(d,J=22.5Hz),114.00,113.71(d,J=7.7Hz),107.09,102.70,99.67,66.64.HR-MS(ESI):m / z calcd for C 18 H 11 ClF4N2O4([M+H] + )431.0416,found431.0419.

[0159] Compound 37: 2-((6-chloro-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)-N′-(2-chlorophenyl)acetylhydrazine:

[0160] White solid, yield: 73.4%, mp: 112.7-113.5℃, 1 H NMR (400MHz, DMSO-d6) δ10.19(s,1H),7.66(d,J=1.2Hz,1H),7.60(s,1H),7.35(s,1H),7.31-7.26(m,1H),7.1 6(dd,J=11.3,4.1Hz,1H),7.00(s,1H),6.89(dd,J=8.2,1.2Hz,1H),6.76(dd,J=7.8,1.4Hz,1H),5.03(s,2H). 13 C NMR (126MHz, DMSO-d6) δ170.40(s), 166.50(s), 158.36(s), 157.57(d, J=62. 7Hz),156.89(s),154.26(s),145.44(s),144.66(s),138.42(d,J=33.1Hz),1 32.49(d,J=13.2Hz),128.40(d,J=33.7Hz),124.79(d,J=17.0Hz),122.68(s ),120.50(s),118.88(s),107.41(s),107.07(s),66.98(s).HR-MS(ESI):m / z calcd for C 18 H 11 Cl2F3N2O4([M+H] + )447.0121, found 447.0127.

[0161] Compound 38: 2-((6-chloro-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)-N'-(3-chlorophenyl)acetylhydrazine:

[0162] White solid, yield: 76.9%, mp: 136.1-136.6℃, 1 H NMR (400MHz, DMSO-d6) δ10.18(s,1H),7.66(d,J=1.3Hz,1H),7.60(s,1H),7.36(s,1H),7.29(dt,J=9.4,2.8H z,1H),7.21-7.10(m,1H),7.00(s,1H),6.89(dd,J=8.2,1.3Hz,1H),6.77(td,J=7.8,1.4Hz,1H),5.03(s,2H). 13 C NMR (126MHz, DMSO-d6) δ166.89, 158.75, 157.25, 154.63, 144.83, 144.03, 138.78 (q, J = 32.76Hz), 129.69, 128.19, 125. 19(dd,J=4.7,2.0Hz),121.95(d,J=279.0Hz),120.19,119.25,117.69,113.50,107.82,103.50,67.37.HR-MS(ESI):m / z calcdfor C 18 H 11 Cl2F3N2O4([M+H] + )447.0121, found 447.0118.

[0163] Compound 39: N'-(2-bromophenyl)-2-((6-chloro-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0164] White solid, yield: 64.3%, mp: 153.3-154.2℃, 1 H NMR (400MHz, DMSO-d6) δ10.23(s,1H),7.66(s,1H),7.45(d,J=7.8Hz,1H),7.36(d,J=4.8Hz,2H) ,7.20(t,J=7.6Hz,1H),7.00(s,1H),6.88(d,J=8.1Hz,1H),6.71(dd,J=7.5Hz,1H),5.03(s,2H). 13C NMR (100MHz, DMSO-d6) δ 166.47, 158.33, 156.87, 154.24, 145.42, 144.64, 138.42 (d, J = 33.4Hz), 132. 48,128.38,124.78,120.50,118.87,115.22,113.41,107.40,107.07,103.12,66.98.HR-MS(ESI):m / z calcd for C 18 H 11 BrClF3N2O4([M+H] + )492.9595,found492.9596.

[0165] Compound 40: N′-(4-bromophenyl)-2-((6-chloro-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0166] White solid, yield: 75.2%, mp: 188.4-189.1℃, 1 H NMR(400MHz,DMSO-d6)δ10.09(d,J=2.1Hz,1H),8.08(s,1H),7.66(s,1H),7.34(s ,1H),7.30(s,1H),7.28(s,1H),7.01(s,1H),6.73(d,J=8.8Hz,2H),5.00(s,2H). 13 C NMR (126MHz, DMSO-d6) δ166.51,158.34,156.87,154.24,148.46,147.63,138.40(d,J=29.3Hz),131.57,131.31(d ,J=1.0Hz),124.82(d,J=10.0Hz),121.59(d,J=274.1Hz),118.87,114.37,109.70,107.40,67.01.HR-MS(ESI):m / z calcd for C 18 H 11 BrClF3N2O4([M+H] + )492.9595, found 492.9599.

[0167] Compound 41: 2-((6-chloro-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)-N'-(4-cyanophenyl)acetohydrazide:

[0168] White solid, yield: 67.7%, mp: 169.1-170.0℃,1 H NMR (400MHz, DMSO-d6) δ10.40(s,1H),7.65(d,J=8.4Hz,2H),7.49(d,J=8.7Hz,3H),7.25(s,1H),7.00(s,1H),4.90(s,2H). 13 C NMR(126MHz,DMSO-d6)δ166.78,158.52,156.94,154.35,152.77,138.56(d,J=32.4Hz),133.63, 128.71,125.00,124.74,120.24,119.00,112.08,107.57,103.10,99.44,67.01.HR-MS(ESI):m / z calcd for C 19 H 11 ClF3N3O4([M+H] + )438.0463, found 438.0467.

[0169] Compound 42: 2-((6-chloro-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)-N'-(3,4-dimethylphenyl)acetylhydrazine:

[0170] White solid, yield: 76.5%, mp: 158.4-158.9℃, 1 H NMR (400MHz, DMSO-d6) δ9.98(d,J=2.8Hz,1H),7.66(s,1H),7.61(d,J=2.7Hz,1H),7.33(s,1H),7.00(d,J=5 .4Hz,1H),6.89(d,J=8.0Hz,1H),6.54(s,1H),6.51(d,J=8.0Hz,1H),4.98(s,2H),2.11(s,3H),2.08(s,3H). 13 C NMR (126MHz, DMSO-d6) δ166.91,158.83,157.23,154.56,147.28,146.39,139.05(q,J=31.5Hz),136.93,13 0.23,127.14,125.32,119.47,115.32,114.37,110.68,107.74,103.20,67.43,20.08,18.92.HR-MS(ESI)cd for C 20 H 16 ClF3N2O4([M+H] +)441.0824, found 441.0826.

[0171] Compound 43: 2-((6-chloro-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)-N'-(2,4,6-trichlorophenyl)acetylhydrazine:

[0172] White solid, yield: 70.0%, mp: 189.7-190.2℃, 1 H NMR (400MHz, DMSO-d6) δ10.41 (s, 1H), 7.64 (d, J = 5.7Hz, 2H), 7.49 (s, 2H), 7.24 (s, 1H), 6.99 (s, 1H), 4.90 (s, 2H). 13 C NMR(126MHz,DMSO-d6)δ166.12,158.46,157.49,156.87,154.30,140.73,138.60(q,J=32.76Hz),128 .70,125.94(q,J=277.2Hz),125.85,125.68,124.76,118.96,107.48,103.03,66.40.HR-MS(ESI):m / z calcd for C 18 H9Cl4F3N2O4([M+H] + )516.9314,found516.9310.

[0173] Compound 44: N′-(2-fluorophenyl)-2-((8-methyl-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0174] White solid, yield: 77.6%, mp: 179.6-180.2℃, 1 H NMR (400MHz, DMSO-d6) δ10.08(d,J=1.6Hz,1H),7.78(s,1H),7.58(d,J=8.2Hz,1H),7.16-7.04(m,2H),6.97(t ,J=7.5Hz,1H),6.89(s,1H),6.86-6.79(m,1H),6.75(ddd,J=15.3,10.1,4.4Hz,1H),4.90(s,2H),2.31(s,3H). 13C NMR (126MHz, DMSO-d6) δ171.27,167.29,159.41,155.91(d,J=740.6Hz),151.28,149.38,139.81(q,J=31.5Hz),136.73,136.65,124.58(d, J=3.3Hz),123.14,119.07(d,J=6.6Hz),115.02(d,J=17.4Hz),114.43,113.88(d,J=3.3Hz),109.44,107.20,66.90,8.44.HR-MS(ESI):m / z calcd for C 19 H 14 F4N2O4([M+H] + )411.0963, found 411.0961.

[0175] Compound 45: N'-(3-fluorophenyl)-2-((8-methyl-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0176] White solid, yield: 54.1%, mp: 150.4-150.7℃, 1 H NMR (400MHz, DMSO-d6) δ10.06(d,J=2.2Hz,1H),8.13(d,J=1.5Hz,1H),7.58(d,J=8.2Hz,1H),7.17- 7.09(m,2H),6.90(s,1H),6.55(dd,J=8.2,1.4Hz,1H),6.51-6.38(m,2H),4.91(s,2H),2.31(s,3H). 13 C NMR(126MHz,DMSO-d6)δ168.02,164.59,162.66,159.56,159.45,153.17,151.40(d,J=9.3Hz),14 0.33(dd,J=34.4,27.4Hz),123.48,120.97,114.88,107.54,100.00,67.02,8.99.HR-MS(ESI):m / z calcd for C 19 H 14 F4N2O4([M+H] + )411.0963, found 411.0961.

[0177] Compound 46: N'-(4-fluorophenyl)-2-((8-methyl-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0178] White solid, yield: 70.2%, mp: 193.3-194.2℃, 1 H NMR (400MHz, DMSO-d6) δ10.04(d,J=19.4Hz,1H),7.79(d,J=19.4Hz,1H),7.56(d,J=11.1Hz,1H),7 .12-7.05(m,1H),6.97-6.83(m,3H),6.70(s,2H),4.86(d,J=21.6Hz,2H),2.28(d,J=21.8Hz,3H). 13 C NMR (126MHz, DMSO-d6) δ167.33,159.48,158.94,157.09,155.23,153.01,145.75(d,J=1.8Hz),139.92(dd,J=62.7,32 .3Hz),123.2,115.31(d,J=22.3Hz),114.48,113.77(d,J=7.6Hz),109.45,107.23,66.94,8.77.HR-MS(ESI):m / zcalcd for C 19 H 14 F4N2O4([M+H] + )411.0963, found 411.0962.

[0179] Compound 47: N'-(2-chlorophenyl)-2-((8-methyl-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0180] White solid, yield: 65.4%, mp: 157.9-158.4℃, 1 H NMR (400MHz, DMSO-d6) δ10.17 (s, 1H), 7.62-7.53 (m, 2H), 7.29 (d, J = 7.2Hz, 1H), 7.13(t,J=8.3Hz,2H),6.89(s,1H),6.83-6.73(m,2H),4.91(s,2H),2.31(s,3H). 13C NMR(126MHz,DMSO-d6)δ167.32,159.97,159.45,158.95,153.01,145.54,139.90(q,J=31.9Hz),132.58, 128.56,123.20,123.08,120.66,114.50,113.54,109.50,107.28,107.22,66.92,8.52.HR-MS(ESI):m / z calcd forC 19 H 14 ClF3N2O4([M+H] + )427.0667, found 427.0664.

[0181] Compound 48: N′-(3-chlorophenyl)-2-((8-methyl-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0182] White solid, yield: 67.9%, mp: 154.8-155.2℃, 1 H NMR (400MHz, DMSO-d6) δ10.09(d,J=1.7Hz,1H),8.14(d,J=1.7Hz,1H),7.56(t,J=13.8Hz,1H),7 .13(t,J=8.0Hz,2H),6.88(s,1H),6.69(ddd,J=16.2,8.5,1.6Hz,3H),4.91(s,2H),2.31(s,3H). 13 C NMR (126MHz, DMSO-d6) δ167.46,159.42,158.92,153.05,150.83,139.99(q,J=31.5Hz),133.79,130.56,123.2 8,120.88,118.39,114.55,113.55(d,J=7.3Hz),111.60,111.32,109.32,107.30,66.97,8.50.HR-MS(ESI):m / z calcd for C 19 H 14 ClF3N2O4([M+H] + )427.0667, found 427.0670.

[0183] Compound 49: N′-(2-bromophenyl)-2-((8-methyl-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0184] White solid, yield: 74.2%, mp: 149.9-150.4℃, 1 H NMR (400MHz, DMSO-d6) δ10.20(s,1H),7.58(d,J=7.9Hz,1H),7.45(dd,J=7.9,1.3Hz,1H),7.32(s,1H),7.16(d d,J=15.6,8.2Hz,2H),6.90(s,1H),6.81-6.76(m,1H),6.71(td,J=7.7,1.4Hz,1H),4.91(s,2H),2.32(s,3H). 13 C NMR (126MHz, DMSO-d6) δ167.60,159.74,159.23,153.30,145.82,140.19(q,J=32.2Hz),132.87,128.78,123.51(d ,J=2.6Hz),123.36,120.95,114.79,113.84,109.86,107.56,107.51,100.00,67.22,8.80.HR-MS(ESI):m / zcalcd forC 19 H 14 BrF3N2O4([M+H] + )471.0162, found 471.0163.

[0185] Compound 50: N'-(2-bromophenyl)-2-((8-methyl-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0186] White solid, yield: 80.0%, mp: 143.9-144.2℃, 1 H NMR (400MHz, DMSO-d6) δ10.08(d,J=2.3Hz,1H),8.04(d,J=2.2Hz,1H),7.58(d,J=7.9Hz,1H),7.27(d ,J=8.8Hz,2H),7.11(d,J=9.1Hz,1H),6.89(s,1H),6.68(d,J=8.9Hz,2H),4.89(s,2H),2.30(s,3H). 13CNMR(126MHz,DMSO-d6)δ167.19,159.35,158.79,152.93,148.54,139.76(q,J=31.5Hz),131 .39,123.13,122.99,114.40,114.36,109.59,109.33,107.15,66.83,8.62.HR-MS(ESI):m / z calcd for C 19 H 14 BrF3N2O4([M+H] + )471.0162, found 471.0158.

[0187] Compound 51: N'-(4-methoxyphenyl)-2-((8-methyl-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0188] White solid, yield: 79.1%, mp: 187.5-187.1℃, 1 H NMR (400MHz, DMSO-d6) δ9.99(d,J=3.3Hz,1H),7.58(d,J=7.5Hz,1H),7.51(d,J=3.2Hz,1H),7.11(d,J=9 .1Hz,1H),6.89(s,1H),6.71(dd,J=23.3,9.0Hz,4H),4.86(s,2H),3.66(s,3H),2.32(d,J=10.9Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ167.22(s),159.53(s),159.02(s),153.02(s),143.03(s),140.44(q,J=32.3Hz),123.2 6(s),114.54(s),114.39(s),114.09(s),109.53(s),107.30(s),67.03(s),55.47(s),8.54(s).HR-MS(ESI):m / z calcd for C 20 H 17 F3N2O5([M+H] + )423.1162, found 423.1160.

[0189] Compound 52: N'-(3,4-dimethylphenyl)-2-((8-methyl-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)acetylhydrazine:

[0190] White solid, yield: 72.1%, mp: 180.8-181.3℃, 1 H NMR(400MHz,DMSO-d6)δ9.97(d,J=3.0Hz,1H),7.61-7.53(m,2H),7.12(d,J=9.1Hz,1H), 6.91-6.83(m,2H),6.50-6.42(m,2H),4.87(s,2H),2.31(s,3H),2.10(t,J=10.4Hz,6H). 13 C NMR (126MHz, DMSO-d6) δ171.39,167.19,159.50,158.96,153.04,147.22,136.37,129.81,126.4 2,123.20,114.52,113.99,110.34,109.40,107.26,67.00,19.80,18.65,8.77.HR-MS(ESI):m / z calcd forC 21 H 19 F3N2O4([M+H] + )421.1370, found 421.1367.

[0191] Compound 53: 2-((8-methyl-2-oxo-4-(trifluoromethyl)-2H-coumarin-7-yl)oxy)-N′-(2,4,6-trichlorophenyl)acetylhydrazine:

[0192] White solid, yield: 80.1%, mp: 190.4-191.0℃, 1 H NMR (400MHz, DMSO-d6) δ10.38(d,J=1.9Hz,1H),7.51(s,2H),7.43(d,J=1.9Hz,1H),7.05(d,J=9.1Hz,1H),6.88(s,1H),4.78(s,2H),2.26(s,2H). 13 C NMR (126MHz, DMSO-d6) δ167.08, 159.73, 159.23, 153.30, 141.11, 140.18 (q, J = 32.2Hz), 128.98, 125.8 5,124.96,123.37,114.67,113.90(d,J=6.4Hz),109.71,107.51,100.02,66.50,8.74.HR-MS(ESI):m / z calcd for C 19 H 12 Cl3F3N2O4([M+H] +)494.9888 found 494.9892.

[0193] Example 3 Detection of antibacterial activity of target compound

[0194] Six common agricultural plant pathogenic fungi, including strawberry gray mold (Botrytis cinerea), tomato early blight (Altemaria solani), rice sheath blight (Rhizoctonia solani), wheat head blight (Fusarium graminearum), cucumber anthracnose (Colletotrichum orbiculare) and apple spot (Alternaria alternata), were used as experimental objects, and the mycelium growth rate method was used to preliminarily screen the antibacterial activity of the target compounds. Commonly used commercial antibacterial agents for the prevention and control of corresponding crop diseases and commercial antibacterial agents carbendazim, boscalid and osthole, which have a certain degree of structural similarity with the target compounds, were selected as control agents.

[0195] Experiment: culture dish (Haimen Chuangxin Consumables Co., Ltd.), high pressure sterilizer (TOMY SX-700), electric constant temperature biochemical incubator (Shanghai Jinghong Experimental Equipment Co., Ltd.), eppendrof pipette, double-sided clean workbench (Suzhou Purification Equipment Co., Ltd.), hole puncher, turbidity meter, etc.

[0196] Experimental methods:

[0197] (I) Preliminary screening of the antifungal activity of 53 target compounds using the mycelium growth rate method

[0198] Preparation of potato dextrose agar (PDA) medium: Peel the potatoes, weigh 200 g, slice them, put them into 1000 mL of water and cook for about 30 minutes. At this time, the potatoes are cooked but not mushy. Filter them into a measuring cylinder with 2 layers of gauze, remove the residue, add water to 1000 mL, add 18 g of agar to the filtrate, cook until melted, add 20 g of glucose, stir evenly, divide them into Erlenmeyer flasks, and sterilize them at 121°C and 1 MPa for 20 minutes.

[0199] Preparation of drug-containing culture medium: accurately weigh 25 mg of the test compound (53 target compounds, commercial drug carbendazim (purchased from Maclean, CAS No.: 10605-21-7), boscalid (purchased from Maclean, CAS No.: 188425-85-6), osthole (purchased from Maclean, CAS No.: 484-12-8)), dissolve in 1 mL DMSO to prepare a 25 mg / mL drug solution, draw 0.1 mL of the drug solution, add it to 50 mL of sterile PDA culture medium (DMSO final concentration is about 0.2%), shake well, prepare a drug-containing culture medium with a concentration of 50 μg / mL, and pour it evenly into 3 sterile culture dishes with a diameter of 9 cm. The culture medium prepared by adding an equal amount of DMSO (0.1 mL) is used as the blank group.

[0200] EC 50 Toxicity assay: according to the initial screening activity test data, a concentration gradient was set, and 10 mg of the compound to be tested was weighed. After dissolving in DMSO, half of the amount was gradiently diluted into 5 concentrations (10 μg / mL, 5 μg / mL, 2.5 μg / mL, 1.25 μg / mL, 0.625 μg / mL). Drug-containing plates were prepared, and the inhibition rate at each concentration was calculated after inoculation and culture. The linear equation and EC were obtained by the statistical software DPS. 50 Values ​​and confidence intervals.

[0201] A medication group and a blank group were set up, and the treatment method and the amount of solvent added were the same as those of the medication group. The specific experimental data are shown in Table 4.

[0202] Bacteria inoculation and activity determination: The preserved bacteria: Botrytis cinerea, Altemaria solani, Rhizoctonia solani, Fusarium graminearum, Colletotrichum orbiculare and Alternaria alternata (donated by the College of Plant Protection, Nanjing Agricultural University) were taken out of a 4°C refrigerator and activated twice in fresh sterile PDA medium before use. A hole was punched at the edge of a normally growing colony with a hole puncher (inner diameter 0.5 cm) to prepare a bacterial cake, and the bacterial cake was inoculated into the center of the drug-containing medium plate or the blank medium plate with an inoculation needle (mycelium facing up), and cultured in an incubator at 25°C. When the colonies on the culture medium of the blank group grow to about 2 / 3 of the plate diameter (i.e., the colony diameter is 6.5 cm), measure the colony diameter, measure each colony diameter twice by the cross method, and calculate the average value (unit: cm). Three replicates were set for each treatment. The growth inhibition rate after drug treatment was calculated as follows:

[0203] Inhibition rate (%) = (blank group colony diameter - drug group colony diameter) / (blank group colony diameter - 0.5) × 100%

[0204] Table 4. Preliminary screening results of the antifungal activity of the target compounds [inhibition rate η (%)] (test concentration 50 μg / mL)

[0205]

[0206]

[0207] Table 4 shows the results of the antibacterial test on common agricultural fungi, and the following conclusions can be drawn:

[0208] 1. 7-N / O acetylhydrazine coumarin compounds showed certain antibacterial activity against common agricultural fungi, with some inhibition effects reaching 100%, and the inhibitory activity against some fungi was significantly higher than that of commercial pesticides (carbendazim, boscalid, and osthole).

[0209] 2. The mycelium growth rate method was used to measure that compounds 1-53 had significant inhibitory activity against rice sheath blight, apple spot pathogen, tomato early blight pathogen, cucumber anthracnose pathogen and strawberry gray mold pathogen. The inhibition rate of most compounds against rice sheath blight pathogen exceeded 80% at 50 μg / mL.

[0210] 3. Overall, when the substituent on the benzene ring of the hydrazine part is a halogen atom, it has a better antibacterial effect on rice sheath blight, apple spot pathogen, tomato early blight pathogen, cucumber anthracnose pathogen and strawberry gray mold pathogen.

[0211] 4. By comparing the activity results of Formula I and Formula II, the compound after N is replaced by O still has high antibacterial activity and the synthesis cost is reduced.

[0212] For compounds with an inhibition rate of more than 70% in the initial in vitro activity screening, the EC values ​​against the tested pathogens were further determined at a concentration gradient of 10, 5, 2.5, 1.25, and 0.625 μg / mL. 50 The obtained data were calculated using the DPS data processing system, EC 50 The values ​​are shown in Table 5-10.

[0213] Table 5. EC of some compounds against Rhizoctonia solani 50 (μg / mL) Results

[0214]

[0215]

[0216] Table 6. Antibacterial activity of some compounds against strawberry gray mold EC50 (μg / mL) Results

[0217]

[0218] Table 7. Antibacterial activity of some compounds against tomato early blight pathogen EC 50 (μg / mL) Results

[0219]

[0220]

[0221] Table 8. Antibacterial activity of some compounds against wheat fusarium sphaeroides EC 50 (μg / mL) Results

[0222]

[0223] Table 9. Antibacterial activity of some compounds against cucumber anthracnose pathogen EC 50 (μg / mL) Results

[0224]

[0225] Table 10. Antibacterial activity of some compounds against apple leaf spot pathogen EC 50 (μg / mL) Results

[0226]

[0227]

[0228] From the test results of common agricultural fungi in Table 5-10, we can draw the following conclusions:

[0229] 1. The introduction of an electron-withdrawing group at the R1 position of coumarin is beneficial to the improvement of the inhibitory activity of the compound against rice sheath blight. For example, the EC of compound 25 (R1 = CF3, R' = 4-F) against rice sheath blight is 50 The value was 0.36 μg / mL, compound 15 (R1=Me, R′=4-F; anti-R.solani EC 50 value=1.06μg / mL).

[0230] 2. The introduction of electron-withdrawing groups at the benzene ring of the hydrazide fragment is beneficial to the improvement of the inhibitory activity of the compound against rice sheath blight. For example, the EC of the inhibitory activity of compound 23-29 (R1 = CF3, R' = 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 2-Br) against rice sheath blight is 50The values ​​were 0.49, 1.26, 0.36, 0.43, 0.60, and 0.40 μg / mL, respectively, which were superior to compound 31 (R1=CF3; R'=4-OMe anti-R.solani EC 50 value = 3.70 μg / mL).

[0231] Example 4 Detection of herbicidal activity of target compound

[0232] Four common field weeds, Echinochloa crus-galli, Digitaria sanguinalis (L.) Scop., Abutilon theophrasti Medicus, and Amaranthus retroflexus L., were used as experimental objects. The small cup method was used to conduct a preliminary screening of the target compounds for their herbicidal activity. Commonly used commercial herbicides, clethodim and trifluorfen, for controlling the corresponding weeds were selected as control agents.

[0233] Experimental methods:

[0234] The weed seeds for the test (including barnyard grass, crabgrass, ramie, and Amaranthus retroflexus) were evenly sown in small flower pots filled with culture soil, the culture soil ratio was matrix soil: black soil: foamed coconut brick = 1:1:1, and the flower pot size was 10×10 cm. 10 seeds of ramie were sown per pot, and 15 seeds of the other weeds were sown per pot. When the weeds grew to the 3-leaf stage, 5 weed seedlings with consistent growth were retained in each pot for standby use. The target compound to be tested, the commercial herbicide clethodim and trifluorfen prepared by the present invention were dissolved in 0.1 mL DMSO, respectively, and diluted to a concentration of 100 mg / L with a Tween-80 aqueous solution (0.1% v / v) for standby use. The weed seedlings for the test were placed on a conveyor belt (the conveyor belt speed was 10 m / min) for application. A fan-shaped nozzle (DL-5) was used, the spray pressure was set to 0.4MPa, the spray radiation range was 0.6m, the flow rate was 0.54L / min, the amount of liquid applied per hectare was 900L, and the amount of active ingredient was 90g / ha. The blank control group used Tween-80 aqueous solution (0.1% v / v). Each treatment was repeated twice. After the application of the pesticide, the test weeds were placed in a greenhouse for routine management and provided with natural light. After 14 days of cultivation, the ineffective or poorly effective treatments were eliminated by visual inspection. The above-ground parts of the remaining samples of each treatment were cut, and the fresh weight was weighed to calculate the fresh weight control effect.

[0235] The calculation formula is as follows:

[0236]

[0237] Where: Cw is the fresh weight of control weeds; Pw is the fresh weight of treated weeds.

[0238] Table 11. Control effects of some target compounds on four weeds at a concentration of 100 μg / mL (90 g / ha)

[0239]

[0240]

[0241] From Table 11 and Figures 1 to 4 The test results of common field weeds can draw the following conclusions:

[0242] 1. At a concentration of 100 μg / mL, some compounds showed certain inhibitory activity against dicotyledonous weeds Amaranthus retroflexus and Abutilon velvetleaf.

[0243] 2. According to the control effect of the compounds on Amaranthus retroflexus, replacing the halogen atom on the benzene ring of the hydrazine part has a better control effect. The substituents on the coumarin ring have the least effect on the activity.

[0244] 3. At a concentration of 100 μg / mL, the control efficacy of compound 22 on dicotyledonous weeds Amaranthus retroflexus and Abelmoschus velutipes was comparable to that of the control drug acifluorfen, both of which were 100%.

[0245] 4. At a concentration of 100 μg / mL, compound 43 had a better control effect on the monocotyledonous weed Digitaria tangutica than the control drug Clethodim, with a control effect of 100%.

Claims

1. 7-N / O acetic acid hydrazide coumarin compound, the structure of the compound is shown in formula III: in, R1 is selected from Me, Et, Pr or CF3; R2 is selected from H or Cl; R3 is selected from H or Me; R′ is selected from one or more of 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 4-Br, 2-CH3O, 3-CH3O, 4-CH3O, 3,4-diCH3, 2,3-diCl, 2,4-diCl, 2,5-diCl, 2,6-diCl, 3,4-diCl, 3,5-diCl, 2,3,6-trCl, 2,4,6-trCl, 2,4-diF or 3,4-diF; X is selected from N or O.

2. The novel coumarin compound of 7-N / O acetic acid hydrazide according to claim 1, wherein the structure of the compound is as shown in Formula I: in, R1 is selected from Me, Et, Pr, CF3; R′ is selected from one or more of 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 4-Br, 2-CH3O, 3-CH3O, 4-CH3O, 3,4-diCH3, 2,3-diCl, 2,4-diCl, 2,5-diCl, 2,6-diCl, 3,4-diCl, 3,5-diCl, 2,3,6-trCl, 2,4,6-trCl, 2,4-diF or 3,4-diF, and preferably, R′ is selected from 2-F, 3-F, 4-F, 2-Cl, 4-Cl or 4-CF3.

3. The novel coumarin compound of 7-N / O acetic acid hydrazide according to claim 1, wherein the structure of the compound is shown in Formula II: R1 is selected from Me, CF3; R2 is selected from H, Cl; R3 is selected from H, Me; R′ is selected from one or more of 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 4-Cl, 2-Br, 3-Br, 4-Br, 2-CH3O, 3-CH3O, 4-CH3O, 3,4-diCH3, 2,3-diCl, 2,4-diCl, 2,5-diCl, 2,6-diCl, 3,4-diCl, 3,5-diCl, 2,3,6-trCl, 2,4,6-trCl, 2,4-diF or 3,4-diF, and preferably, R′ is selected from 2-F, 3-F, 4-F, 2-Cl, 3-Cl, 2-Br, 4-Br, 4-CH3O, 3,4-diCH3 or 2,4,6-trCl.

4. The method for preparing the coumarin compounds of 7-N / O acetylhydrazine according to claim 2, characterized in that: The method for preparing the coumarin compound of 7-N-acetylhydrazine comprises the following steps: (1) Using 3-aminophenol as a raw material, ethyl acetate EA, sodium bicarbonate and phenyl chloroformate are added in sequence to prepare N-(3-hydroxyphenyl)phenyl carbamate; (2) N-(3-hydroxyphenyl)carbamic acid phenyl ester is added to a concentrated sulfuric acid solution, and then β-keto acid ester is added to react to prepare substituted coumarin amino acid phenyl ester; (3) adding potassium hydroxide solution to the substituted coumarin amino acid phenyl ester, dissolving and stirring, and then heating and stirring to react, thereby preparing an intermediate substituted 7-aminocoumarin; (4) adding acetonitrile solution to substituted 7-aminocoumarin, N,N-diisopropylethylamine DIEA and sodium iodide to dissolve them, and then adding ethyl bromoacetate dropwise in a reactor to react, thereby preparing an intermediate ethyl 2-((2-nitro-4-(substituted)-2H-coumarin-7-yl)amino)acetate; (5) dissolving the intermediate ethyl 2-((2-nitrogen-4-(substituted)-2H-coumarin-7-yl)amino)acetate in ethanol, adding sodium hydroxide solution and stirring at room temperature, and monitoring the reaction progress by TLC. After the reaction is complete, adjusting the pH value of the aqueous phase to prepare the intermediate 2-((2-nitrogen-4-(substituted)-2H-coumarin-7-yl)amino)acetic acid; (6) Acetonitrile solution was added to the intermediate 2-((2-nitro-4-(substituted)-2H-coumarin-7-yl)amino)acetic acid and substituted phenylhydrazine to fully dissolve them, and then O-benzotriazole-N,N,N′,N′-tetramethyluronium tetrafluoroborate was added, followed by dropwise addition of triethylamine. The reaction was stirred at room temperature and the progress of the reaction was monitored by TLC to prepare a series of target compounds 7-N-acetylhydrazine coumarin.

5. The method for preparing the coumarin compounds of 7-N / O acetylhydrazine according to claim 3, characterized in that: The method for preparing the coumarin compound of 7-O acetylhydrazine comprises the following steps: (1) Using substituted meta-diphenol as a raw material, adding concentrated sulfuric acid ethanol solution and β-keto acid ester in sequence to react to prepare substituted 7-hydroxycoumarin; (2) adding acetonitrile solution to substituted 7-hydroxycoumarin, N,N-diisopropylethylamine DIEA and sodium iodide to dissolve them, and then dropping ethyl bromoacetate in a reactor to react, to prepare an intermediate ethyl 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetate; (3) dissolving ethyl 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetate in ethanol, adding sodium hydroxide solution, stirring at room temperature, and monitoring the reaction progress by TLC. After the reaction is complete, adjusting the pH value of the aqueous phase to prepare the intermediate 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetic acid; (4) Acetonitrile solution was added to the intermediate 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetic acid and substituted phenylhydrazine to fully dissolve, and then O-benzotriazole-N,N,N′,N′-tetramethyluronium tetrafluoroborate was added, followed by dropwise addition of triethylamine. The reaction was stirred at room temperature and the progress of the reaction was monitored by TLC to prepare a series of target compounds 7-O acetylhydrazine coumarin.

6. The preparation method according to claim 4 or 5, characterized in that: The molar ratio of the 3-aminophenol to phenyl chloroformate is 1:1-3; preferably, the molar ratio of the N-(3-hydroxyphenyl)phenyl carbamate to β-keto acid ester is 1:0.8-3; preferably, the molar ratio of the substituted 7-aminocoumarin to sodium iodide and ethyl bromoacetate is 1:1-3:1-3; preferably, the molar ratio of the substituted 2-((2-nitro-4-(substituted)-2H-coumarin-7-yl)amino)acetic acid to substituted phenylhydrazine, TBTU and triethylamine is 1:1 ~2.5:1~2.5:1~2.5; preferably, the molar ratio of the substituted meta-diphenol to β-keto acid ester is 1:0.8~3; preferably, the molar ratio of the substituted 7-hydroxycoumarin to sodium iodide and ethyl bromoacetate is 1:1~3:1~3; preferably, the molar ratio of the 2-((2-oxo-4-(substituted)-2H-coumarin-7-yl)oxy)acetic acid to substituted phenylhydrazine, TBTU and triethylamine is 1:1~2.5:1~2.5:1~2.

5.

7. Use of the coumarin compound of 7-N / O acetylhydrazine according to any one of claims 1 to 4 in the preparation of a product for inhibiting or killing pathogens.

8. The use according to claim 7, wherein the pathogens include crop pathogenic fungi, and the crop pathogenic fungi include one or more of rice sheath blight (Rhizoctonia solani), strawberry gray mold (Botrytis cinerea), wheat head blight (Fusarium graminearum), tomato early blight (Altemaria solani), cucumber anthracnose (Colletotrichum orbiculare) or apple spot (Alternaria alternata).

9. Use of the coumarin compound of 7-N / O acetylhydrazine according to any one of claims 1 to 4 in weeding, preferably, the weeding includes the removal of field weeds, preferably, the use includes the preparation of pesticide formulations for common field weeds.

10. The use according to claim 9, characterized in that: The field weeds include one or more of barnyard grass (Echinochloacrus-galli), crabgrass (Digitaria sanguinalis (L.) Scop.), velvetleaf (Abutilon theophrastiMedicus) or amaranth (Amaranthus retroflexus L.).

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