Coumarin derivatives containing substituted phenyl ether structures, their preparation methods and applications

Abstract

This invention relates to the fields of pesticide chemistry and medicinal chemistry, and in particular to a coumarin derivative containing a substituted phenyl ether structure, its preparation method, and its applications. This invention organically combines a coumarin structure with a substituted phenyl ether fragment to synthesize a novel class of coumarin derivatives containing a substituted phenyl ether structure. These compounds exhibit excellent antifungal activity and broad-spectrum activity, demonstrating superior inhibitory activity against *Agropyron cristatum*, *Sclerotinia sclerotiorum*, *Botrytis cinerea*, and *Tricholoma matsutake*. This invention provides a foundation for the development of novel fungicides using coumarin derivatives containing substituted phenyl ether structures as active ingredients.

Description

Technical Field

[0001] This invention relates to the fields of pesticide chemistry and pharmaceutical chemistry, and in particular to a coumarin derivative containing a substituted phenyl ether structure, its preparation method, and its application. Background Technology

[0002] Plant pathogenic fungi are a type of destructive parasite that can directly or indirectly cause a significant decline in crop yield and quality by secreting large amounts of toxins and harmful metabolites. It is estimated that global crop losses due to plant diseases and pests amount to approximately US$220 billion annually. Since the mid-20th century, the incidence and scope of fungal diseases have been increasingly severe, posing a serious threat to food security. Their impact extends beyond major food crops such as rice, corn, wheat, and soybeans, also affecting important economic crops such as coffee, bananas, and barley. Therefore, the prevention and control of plant fungal diseases is crucial in agricultural production.

[0003] For decades, traditional chemical fungicides have been widely used to control plant pathogenic fungi. However, many of these fungicides are not only toxic to humans but also harmful to beneficial insects and plant-promoting microorganisms. Long-term use of traditional fungicides has led to a series of problems, including slow degradation in the environment, adverse effects on non-target organisms, and the development of pathogen resistance. Therefore, the development of novel agricultural fungicides with novel mechanisms of action, environmental friendliness, and high efficiency has become an urgent need in this field.

[0004] Natural products, derived from the metabolic processes of animals, microorganisms, and plants, possess advantages such as good biocompatibility, structural diversity, specific target action, unique mechanisms of action, and low risk of drug resistance. Therefore, natural products have long been an important source for pharmaceutical and agrochemical research and development. Developing green and efficient fungicides using natural plant derivatives is an effective approach. Coumarins and their derivatives are widely found in natural plants of the Rutaceae, Fabaceae, Apiaceae, and Asteraceae families, possessing various biological activities including antiviral, antitumor, antioxidant, antibacterial, and herbicidal effects, and have important applications in both pesticides and pharmaceuticals. For example, the coumarin structure is widely used in anticoagulant rodenticides such as warfarin, cyhalothrin, and bromadiolone; in addition, the natural coumarin compound osthol has been reported to have insecticidal and antibacterial activities. Currently, among commercially available fungicides, only eugenol is a representative product containing a coumarin structure; however, as a methoxyacrylate fungicide, its mechanism of action is singular, and there is a potential risk of resistance. There is an urgent need to develop novel, highly efficient, and low-toxicity coumarin fungicides.

[0005] On the other hand, diphenyl ether structural units are widely found in bioactive natural products and drug molecules. These compounds possess a wide range of biological activities, such as anticancer, anti-inflammatory, antiviral, antibacterial, antimalarial, herbicidal, fungicidal, and insecticidal activities, making them an advantageous framework for drug development. Among existing fungicides, oxadiazon, chlorfenapyr, and chlorophenyl etheramide and fluphenyl etheramide developed by Central China Normal University all contain diphenyl ether structures. Therefore, modifying the coumarin structure by combining it with the diphenyl ether molecular skeleton to synthesize a new class of coumarin derivatives containing substituted phenyl ether structures, and studying their agricultural applications, is of great significance for developing pesticides with independent intellectual property rights. Summary of the Invention

[0006] The technical problem to be solved by this invention is to overcome the shortcomings of the prior art and provide a coumarin derivative containing a substituted phenyl ether structure, its preparation method, and its application. This invention organically combines the coumarin structure with the phenyl ether structure to synthesize a novel class of coumarin derivatives containing a substituted phenyl ether structure, with the aim of synthesizing compounds with highly efficient and broad-spectrum inhibitory activity against plant pathogens.

[0007] The technical solution adopted by this invention to solve its technical problem is: A coumarin derivative containing a substituted phenyl ether structure has the following general structural formula (I): ; Among them, R 1 It is hydrogen or halogen; R 2 The groups represented by hydrogen, halogen, amino, acylamino, hydroxyl, mercapto, acyl, ester, amide, aminoacyl, alkyl, alkoxy, haloalkyl, cyano, nitro, and their multiple substitution combinations at different positions; R 3 It is one of hydrogen, halogen, or alkyl.

[0008] Furthermore, the R 1 It is one of hydrogen, fluorine, chlorine, bromine, and iodine; R 2 The substitutions are hydrogen, fluorine, chlorine, bromine, iodine, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, cyano, nitro, and their multiple substitution combinations at different positions; R 3 It is one of hydrogen, fluorine, chlorine, bromine, iodine, and C1-C6 alkyl groups.

[0009] Furthermore, the coumarin derivatives containing substituted phenyl ether structures are preferably the following compounds:

[0010] .

[0011] A method for preparing coumarin derivatives containing substituted phenyl ether structures as described above, wherein the preparation method includes any one of the synthetic routes 1 to 5: Route 1: ; Route 2: ; Route 3: ; Route 4: ; Route 5: .

[0012] Furthermore, route 1 specifically includes the following steps: Step S11: Using substituted resorcinol (III) and substituted ethyl acetoacetate (IV) as raw materials, a Pechmann condensation reaction is carried out in a first acidic solvent to generate a 4-methyl-7-hydroxycoumarin compound corresponding to general formula (II). The obtained product is purified by column chromatography or recrystallization to obtain a pure product. The first acidic solvent is concentrated sulfuric acid or trifluoroacetic acid. Step S12: Using 4-methyl-7-hydroxycoumarin compound (II) and substituted phenylboronic acid (V) as raw materials, a coupling reaction is carried out in the first solvent using a copper catalyst to generate a coumarin derivative containing a substituted phenyl ether structure, i.e., general formula (I). The obtained product is purified by column chromatography to obtain a pure product; the first solvent is one of dichloromethane, methanol, and acetonitrile.

[0013] Furthermore, route 2 specifically includes the following steps: Step S21: Using substituted resorcinol (III) and substituted ethyl acetoacetate (IV) as raw materials, a Pechmann condensation reaction is carried out in a second acidic solvent to generate a 4-methyl-7-hydroxycoumarin compound corresponding to general formula (II). The obtained product is purified by column chromatography or recrystallization to obtain a pure product; the second acidic solvent is concentrated sulfuric acid or trifluoroacetic acid. Step S22: Using 4-methyl-7-hydroxycoumarin compound (II) and diaryliodonium tetrafluoroborate (VI) as raw materials, react with potassium tert-butoxide in a second solvent to generate a coumarin derivative containing o-fluorophenyl ether substitution, i.e., general formula (Ia). The obtained product is purified by column chromatography to obtain a pure product; the second solvent is tetrahydrofuran (THF) or acetonitrile.

[0014] Furthermore, route 3 specifically includes the following steps: Step S31: Using substituted m-halophenol (VIII) and substituted ethyl acetoacetate (IV) as raw materials, a Pechmann condensation reaction is carried out in a third acidic solvent to generate substituted 4-methyl-7-halocoumarin compounds corresponding to general formula (VII). The obtained product is purified by column chromatography or recrystallization to obtain a pure product; the third acidic solvent is concentrated sulfuric acid or trifluoroacetic acid. Step S32: Using substituted 4-methyl-7-halocoumarin compound (VII) and substituted phenol (IX) as raw materials, 1-naphthoic acid, cesium carbonate and a complex of copper trifluoromethanesulfonate and benzene are added, and the reaction is carried out in a third solvent to generate a coumarin derivative containing a substituted phenyl ether structure, i.e., general formula (I). The obtained product is purified by column chromatography to obtain a pure product; the third solvent is one of toluene, xylene, and N,N-dimethylformamide (DMF).

[0015] Furthermore, route 4 specifically includes the following steps: Step S41: Using substituted resorcinol (III) and substituted ethyl acetoacetate (IV) as raw materials, a Pechmann condensation reaction is carried out in a fourth acidic solvent to generate a 4-methyl-7-hydroxycoumarin compound corresponding to general formula (II). The obtained product is purified by column chromatography or recrystallization to obtain a pure product; the fourth acidic solvent is concentrated sulfuric acid or trifluoroacetic acid. Step S42: Using 4-methyl-7-hydroxycoumarin compound (II) and substituted halobenzene (X) as raw materials, potassium carbonate is added, and the mixture is reacted in a fourth solvent to generate a coumarin derivative containing a substituted phenyl ether structure, i.e., general formula (I). The obtained product is purified by column chromatography to obtain a pure product; the fourth solvent is N,N-dimethylformamide (DMF) or dimethyl sulfoxide.

[0016] Furthermore, route 5 specifically includes the following steps: Using substituted 4-methyl-7-phenylenecoumarin (Ib) as a starting material, it undergoes a halogenation reaction with N-bromosuccinimide (NBS) in a fifth solvent to generate a 3-bromosubstituted 4-methyl-7-phenylenecoumarin compound corresponding to general formula (Ic). The obtained product is purified by column chromatography or recrystallization to obtain a pure product; the fifth solvent is dichloromethane or chloroform.

[0017] An application of the coumarin derivative containing the substituted phenyl ether structure as described above involves applying the coumarin derivative containing the substituted phenyl ether structure to agricultural fungicides to prevent and control plant diseases caused by plant pathogenic fungi; wherein the plant pathogenic fungi are selected from the phyla Plasmomycota, Oomycota, Chytridiomycota, Zygomycota, Ascomycota, Basidiomycota, and Deuteromycota; more preferably, the plant pathogenic fungi are specifically Sclerotinia sclerotiorum, apple rot fungus, rice sheath blight fungus, grape gray mold fungus, and wheat take-all fungus.

[0018] The beneficial effects of this invention are as follows: This invention is rationally designed and has the following advantages: 1. A novel class of coumarin derivatives containing substituted phenyl ether structures was synthesized by organically combining the substituted phenyl ether structure with the natural structural fragment coumarin. Common plant fungi and oomycetes, such as Sclerotinia sclerotiorum of rapeseed, Pseudomonas macrantha of apple, Pseudomonas rhizogenes of rice, Botrytis cinerea of ​​grape, and Take-all fungus of wheat, were selected as targets for antibacterial activity determination. The results showed that this class of compounds exhibited broad-spectrum antibacterial activity against plant pathogenic fungi, especially showing excellent antibacterial activity against Pseudomonas macrantha of apple and Take-all fungus of wheat. 2. Structure-activity relationship analysis shows that the molecular skeleton phenyl ether and the substituent groups on coumarin in coumarin derivatives containing substituted phenyl ether structures play a crucial role in maintaining the high efficiency and broad spectrum antibacterial activity of this type of compound; 3. Coumarin derivatives containing substituted phenyl ether structures are structurally novel, simple to synthesize, and completely different from existing commercial bactericides. They are expected to be developed into new green bactericides that are highly efficient, safe, economical, and environmentally friendly. Detailed Implementation

[0019] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of this application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains.

[0020] It should be noted that the terminology used herein is for the purpose of describing particular implementations only and is not intended to limit the exemplary implementations according to this application. As used herein, the singular form includes the plural form unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this description, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0021] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0022] Example 1 Compound I-1 7-(2-fluorophenoxy)-4-methyl-2H-chromene-2-one According to Route 2, the preparation method of compound I-1 in this embodiment is as follows: In a 25 mL dry round-bottom flask, 4-methylumbelliferone (0.18 g, 1 mmol) was dissolved in 5 mL of THF, followed by the sequential addition of potassium tert-butoxide (0.11 g, 1.1 mmol) and diaryliodonium tetrafluoroborate (0.40 g, 1.1 mmol). The reaction was carried out in a 70 °C oil bath under magnetic stirring, and the reaction progress was monitored by TLC until the starting material disappeared. After the reaction system was cooled to room temperature, water (10 mL) was slowly added dropwise to quench the reaction. The aqueous phase was extracted with ethyl acetate (10 × 3 mL), and the organic phases were combined, washed with saturated sodium chloride solution (10 × 3 mL), dried over anhydrous magnesium sulfate, and the filtered organic phase was concentrated under reduced pressure using a rotary evaporator to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain compound I-1 as a white solid (0.12 g, yield 44%), mp = 124.4–129.8 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.54 (d, J = 8.8 Hz, 1H), 7.26 – 7.14 (m,4H), 6.94 (dd, J = 8.8, 2.5 Hz, 1H), 6.80 (d, J = 2.4 Hz), 6.25 – 6.11 (m,1H), 2.41 (d, J = 1.0 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 161.1, 160.9,155.1, 154.7 (d, J = 250.0 Hz), 152.4, 142.0 (d, J = 11.9 Hz), 126.7 (d, J = 7.0Hz), 126.0, 125.3 (d, J = 4.0 Hz), 123.3, 117.6 (d, J = 18.1 Hz), 115.4, 113.3,113.1, 104.2, 18.9; HRMS (ESI), m / z: calcd for C 16 H 12 FO3[M+H] + : 271.0765, found: 271.0771. Example 2 Compound I-2 7-(3-fluorophenoxy)-4-methyl-2H-chromene-2-one According to Route 1, the preparation method of compound I-2 in this embodiment is as follows: Under oxygen conditions, 4-methylumbelliferone (0.18 g, 1 mmol), 3-fluorophenylboronic acid (0.42 g, 3 mmol), anhydrous copper acetate (0.27 g, 1.5 mmol), 4-dimethylaminopyridine (0.24 g, 2 mmol), and 4Å molecular sieve (0.4 g) were added sequentially to a 10 mL dry reaction tube. Anhydrous dichloromethane (3 mL) was then injected, and the system was kept at 40 °C for 24 h. After the reaction was completed, the reaction was quenched with dichloromethane, and solid impurities were removed by diatomaceous earth filtration. The filtrate was concentrated under reduced pressure using a rotary evaporator to obtain the crude product. The crude product was purified by silica gel column chromatography (V(ethyl acetate):V(petroleum ether) = 1:5) to obtain compound I-2 as a white solid (0.14 g, yield 51%), mp = 104.4–106.2 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.56 (d, J = 8.7Hz, 1H), 7.34 (q, J = 8.1 Hz, 1H), 7.00 – 6.81 (m, 4H), 6.78 (d, J = 9.7 Hz,1H), 6.19 (s, 1H), 2.41 (s, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 163.6 (d, J =248.1 Hz), 160.9, 160.2, 156.8 (d, J = 10.5 Hz), 155.1, 152.3, 131.1 (d, J =9.6 Hz), 126.1, 115.9, 115.6 (d, J = 3.3 Hz), 114.8, 113.4, 111.8 (d, J = 21.1Hz), 107.8 (d, J = 24.2 Hz), 106.2, 18.9; HRMS (ESI), m / z: calcd for C 16 H 12 FO3[M+H] + : 271.0765, found: 271.0772. Example 3 Compound I-3 7-(4-fluorophenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-3 in this embodiment is as follows: The method described in Example 2 was used, except that 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 4-fluorophenylboronic acid (0.42 g, 3 mmol), and the other steps were the same as in Example 2. Compound I-3 was obtained as a white solid (0.16 g, yield 59%), mp = 113.2–116.5 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.54 (d, J = 8.8 Hz, 1H), 7.13 – 7.04 (m, 4H), 6.91 (dd, J = 8.8, 2.5 Hz, 1H), 6.82 (d, J = 2.4 Hz, 1H), 6.20 – 6.17 (m, 1H), 2.41 (d, J = 1.0Hz, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 161.4, 161.0, 159.9 (d, J = 243.9Hz), 155.1, 152.4, 151.1 (d, J = 2.8 Hz), 126.1, 122.0 (d, J = 8.5 Hz, 2C), 117.0 (d, J = 23.4 Hz, 2C), 115.3, 114.0, 113.1, 105.1, 18.9; HRMS (ESI), m / z:calcd for C 16 H 12 FO3[M+H] + : 271.0765, found: 271.0771. Example 4 Compound I-4 7-(2-Chlorophenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-4 in this embodiment is as follows: The method described in Example 2 was used, except that 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2-chlorophenylboronic acid (0.47 g, 3 mmol), and the other steps were the same as in Example 2. Compound I-4 was obtained as a white solid (0.06 g, yield 20%), mp = 122.9–131.8 °C. ¹H NMR (400 MHz, Chloroform- d ) δ 7.55 (d, J = 8.8 Hz, 1H), 7.51 (dd, J = 8.0, 1.5 Hz, 1H), 7.32(td, J = 7.8, 1.6 Hz, 1H), 7.22 (td, J = 7.8, 1.5 Hz, 1H), 7.15 (dd, J = 8.0, 1.5 Hz, 1H), 6.91 (dd, J = 8.8, 2.5 Hz, 1H), 6.75 (d, J = 2.5 Hz, 1H), 6.25 –6.03 (m, 1H), 2.41 (d, J = 1.0 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 161.0,160.6, 155.2, 152.4, 150.6, 131.4, 128.6, 127.2, 126.7, 126.1, 122.9, 115.4,113.5, 113.2, 104.5, 18.9; HRMS (ESI), m / z: calcd for C 16 H 12 ClO3[M+H] + :287.0469, found: 287.0476. Example 5 Compound I-5 7-(3-Chlorophenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-5 in this embodiment is as follows: The method described in Example 2 was used, except that 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 3-chlorophenylboronic acid (0.47 g, 3 mmol), and the other steps were the same as in Example 2. Compound I-5 was obtained as a white solid (0.11 g, yield 38%), mp = 125.3–129.5 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.56 (d, J = 8.7 Hz, 1H), 7.32 (t, J = 8.1 Hz, 1H), 7.19 (ddd, J =8.0, 1.9, 0.9 Hz, 1H), 7.07 (t, J = 2.1 Hz, 1H), 6.99 – 6.96 (m, 1H), 6.94 (dd, J = 8.7, 2.4 Hz, 1H), 6.89 (d, J = 2.4 Hz, 1H), 6.20 (d, J = 1.2 Hz, 1H), 2.42(d, J = 1.2 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.9, 160.2, 156.4,155.1, 152.3, 135.6, 131.0, 126.2, 125.1, 120.5, 118.3, 115.9, 114.7, 113.5,106.2, 18.9; HRMS (ESI), m / z: calcd for C 16 H 12 ClO3[M+H] + : 287.0469, found:287.0476. Example 6 Compound I-6 7-(4-Chlorophenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-6 in this embodiment is as follows: The method described in Example 2 was used, except that 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 4-chlorophenylboronic acid (0.47 g, 3 mmol), and the other steps were the same as in Example 2. Compound I-6 was obtained as a white solid (0.18 g, yield 64%), mp = 113.2–119.4 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.55 (d, J = 8.7 Hz, 1H), 7.41 – 7.34 (m, 2H), 7.05 – 6.99 (m,2H), 6.92 (dd, J = 8.7, 2.4 Hz, 1H), 6.87 (d, J = 2.4 Hz, 1H), 6.20 (s, 1H), 2.42(s, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.9, 160.7, 155.2, 154.1, 152.3,130.4 (2C), 130.3, 126.1, 121.6 (2C), 115.7, 114.4, 113.4, 105.8, 18.9; HRMS(ESI), m / z: calcd for C 16 H 12 ClO3[M+H] + : 287.0469, found: 287.0473. Example 7 Compound I-7 4-Methyl-7-(3-Tolyloxy)-2H-chromen-2-one The preparation method of compound I-7 in this embodiment is as follows: The method described in Example 2 was used, except that 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 3-methylphenylboronic acid (0.41 g, 3 mmol), and the other steps were the same as in Example 2. Compound I-7 was obtained as a white solid (0.08 g, yield 29%), mp = 74.0–75.0 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.53 (d, J = 8.8 Hz, 1H), 7.31 – 7.26 (m, 1H), 7.03 (d, J= 7.6Hz, 1H), 6.93 (dd, J = 8.8, 2.4 Hz, 1H), 6.88 (d, J = 8.6 Hz, 2H), 6.84 (d, J =2.4 Hz, 1H), 6.18 – 6.16 (m, 1H), 2.41 (d, J = 1.1 Hz, 3H), 2.36 (s, 3H); 13 CNMR (101 MHz, Chloroform- d ) δ 161.4, 161.1, 155.2, 155.1, 152.4, 140.6,130.0, 125.9, 125.9, 121.0, 117.3, 115.1, 114.4, 112.9, 105.4, 21.5, 18.9;HRMS (ESI), m / z: calcd for C 17 H 15 O3[M+H] + : 267.1016, found: 267.1020. Example 8 Compound I-8 4-Methyl-7-(4-Tolyloxy)-2H-Crownen-2-one The preparation method of compound I-8 in this embodiment is as follows: The method described in Example 2 was used, except that 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 4-methylphenylboronic acid (0.41 g, 3 mmol), and the other steps were the same as in Example 2. Compound I-8 was obtained as a white solid (0.14 g, yield 54%), mp = 117.5–120.5 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.51 (d, J = 8.8 Hz, 1H), 7.20 (d, J = 8.2 Hz, 2H), 6.97 (d, J =8.4 Hz, 2H), 6.92 (dd, J = 8.8, 2.4 Hz, 1H), 6.82 (d, J = 2.4 Hz, 1H), 6.16 (s,1H), 2.40 (s, 3H), 2.37 (s, 3H); 13C NMR (101 MHz, Chloroform- d ) δ 161.8,161.2, 155.2, 152.9, 152.4, 134.9, 130.8 (2C), 125.9, 120.4 (2C), 115.0,114.1, 112.9, 105.1, 21.0, 18.9. Example 9 Compound I-9 7-(2-Methoxyphenoxy)-4-methyl-2H-chromene-2-one According to route 3, the preparation method of compound I-9 in this embodiment is as follows: Under nitrogen protection, 7-bromo-4-methyl-2H-1-benzopyran-2-one (0.12 g, 0.5 mmol), guaiacol (0.18 g, 1.47 mmol), 1-naphthoic acid (0.25 g, 1.47 mmol), cesium carbonate (0.48 g, 1.47 mmol), copper(I)trifluoromethanesulfonate (0.09 g, 0.018 mmol), and 4Å molecular sieve (0.18 g) were added sequentially to a 10 mL dry reaction tube. Then, toluene (2 mL) and ethyl acetate (0.35 mg, 0.004 mmol) were added. The reaction was carried out in an oil bath at 110 °C for 24 h under magnetic stirring. The reaction progress was monitored by TLC until the starting material disappeared or no change occurred, indicating the end of the reaction. After the reaction was complete, the reaction was quenched by slowly adding 2N NaOH solution to the mixture. The aqueous phase was extracted with dichloromethane (10 × 3 mL), and the combined organic phases were washed with saturated sodium chloride solution (10 × 3 mL), dried over anhydrous magnesium sulfate, and filtered. The resulting organic phase was concentrated under reduced pressure using a rotary evaporator to obtain the crude product. The crude product was purified by silica gel column chromatography to give compound I-9 as a white solid (0.03 g, yield 19%), mp = 133.9–135.2 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.51 (d, J = 8.8 Hz, 1H), 7.26 – 7.20 (m,1H), 7.13 – 6.88 (m, 4H), 6.72 (d, J = 2.2 Hz, 1H, 6.15 (s, 1H), 3.79 (s, 3H), 2.40 (s, 3H); 13 C NMR (101 MHz, Chloroform- d) δ 161.7, 161.3, 155.1, 152.6,151.8, 143.0, 126.7, 125.8, 122.7, 121.5, 114.8, 113.3, 113.1, 112.6, 103.8,56.0, 18.9.HRMS (ESI), m / z: calcd for C 17 H 14 O4Na [M+Na] + : 305.0784, found:305.0790. Example 10 Compound I-10 4-Methyl-7-(2-(trifluoromethyl)phenoxy)-2H-chromene-2-one The preparation method of compound I-10 in this embodiment is as follows: The method described in Example 2 was used, except that 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2-trifluoromethylphenylboronic acid (0.57 g, 3 mmol), and the other steps were the same as in Example 2. Compound I-10 was obtained as a white solid (0.07 g, yield 21%), mp = 106.8–108.2 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.73 (d, J = 7.7 Hz, 1H), 7.56 (t, J = 7.7 Hz, 2H), 7.31 (t, J = 7.6 Hz, 1H), 7.09 (d, J = 8.2 Hz, 1H), 6.96 (dd, J = 8.7, 2.4 Hz, 1H), 6.85 (d, J = 2.4 Hz, 1H), 6.20 (s, 1H), 2.42 (s, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.9, 160.4, 155.0, 153.3 (q, J = 1.8 Hz), 152.3, 133.8,127.8 (q, J = 5.0 Hz), 126.2, 124.9, 123.2 (q, J = 272.7 Hz), 122.9 (q, J= 31.7Hz), 121.5, 115.9, 114.7, 113.5, 105.9, 18.9; HRMS (ESI), m / z: calcd forC 17 H 12 F3O3[M+H] + : 321.0733, found: 321.0736. Example 11 Compound I-11 4-Methyl-7-(3-(trifluoromethyl)phenoxy)-2H-chromene-2-one The preparation method of compound I-11 in this embodiment is as follows: The method described in Example 2 was used, except that 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 3-trifluoromethylphenylboronic acid (0.57 g, 3 mmol), and the other steps were the same as in Example 2. Compound I-11 was obtained as a white solid (0.10 g, yield 32%), mp = 139.2–146.3 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.58 (d, J = 8.7 Hz, 1H), 7.52 (t, J = 7.9 Hz, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.32 (s, 1H), 7.25 (d, J = 6.2 Hz, 1H), 6.95 (dd, J =8.7, 2.4 Hz, 1H), 6.88 (d, J = 2.4 Hz, 1H), 6.24 – 6.16 (m, 1H), 2.42 (d, J =1.1 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.8, 160.0, 156.0, 155.1,152.3, 132.8 (q, J = 32.9 Hz), 130.9, 126.3, 123.6 (q, J = 272.5 Hz), 123.2,121.5 (q, J = 3.8 Hz), 116.9 (q, J= 3.8 Hz), 116.1, 114.8, 113.6, 106.3, 18.9;HRMS (ESI), m / z: calcd for C 17 H 12 F3O3[M+H] + : 321.0733, found: 321.0740. Example 12 Compound I-12 6-Chloro-4-methyl-7-phenoxy-2H-chromene-2-one The preparation method of compound I-12 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with phenylboronic acid (0.37 g, 3 mmol). Other steps were the same as in Example 2. Compound I-12 was obtained as a white solid (0.12 g, yield 43%), mp = 134.4–135.7 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.66 (s, 1H), 7.45 – 7.39 (m, 2H), 7.26 (t, J = 3.7 Hz, 1H), 7.09 (d, J = 1.1 Hz, 1H), 7.07 (s, 1H), 6.75 (s, 1H), 6.21 (d, J = 1.1 Hz, 1H), 2.42 (d, J = 1.1 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d ) δ 160.4, 156.5, 155.0,153.2, 151.4, 130.5(2C), 126.2, 125.6, 120.5(2C), 120.1, 116.0, 114.1, 106.3,18.9; HRMS (ESI), m / z: calcd for C 16 H 12 ClO3[M+H] + : 287.0469, found: 287.0476. Example 13 Compound I-13 6-Chloro-7-(2-fluorophenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-13 in this embodiment is as follows: The method described in Example 1 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.2 g, 1 mmol), and the other steps were the same as in Example 1. Compound I-13 was obtained as a white solid (0.2 g, yield 70%), mp = 180.5–183.9 °C. 1 HNMR (400 MHz, Chloroform- d ) δ 7.67 (s, 1H), 7.30 – 7.26 (m, 1H), 7.24 (dq, J =4.6, 1.9 Hz, 1H), 7.22 – 7.14 (m, 2H), 6.65 (s, 1H), 6.22 – 6.19 (m, 1H), 2.41 (d, J = 1.1 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.3, 156.1, 154.3(d, J = 250.6 Hz), 153.2, 151.5, 141.7 (d, J = 11.9 Hz), 127.2 (d, J = 7.1 Hz), 126.2, 125.4 (d, J = 4.0 Hz), 123.0, 119.6, 117.8 (d, J = 17.9 Hz), 116.1,114.1, 104.6, 18.9. Example 14 Compound I-14 6-Chloro-7-(3-fluorophenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-14 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol), and the other steps were the same as in Example 2. Compound I-14 was obtained as white crystals (0.12 g, yield 41%), mp = 136.4–140.0 °C. 1 H NMR (400 MHz, Chloroform- d) δ 7.67 (s, 1H), 7.36 (td, J = 8.3, 6.5 Hz, 1H), 6.93 (tdd, J = 8.3, 2.5, 0.9 Hz, 1H), 6.85 (s, 2H), 6.77 (dt, J = 9.6, 2.4 Hz, 1H), 6.24 (d, J = 1.2 Hz, 1H), 2.42 (d, J = 1.2 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 163.7 (d, J = 248.6 Hz), 160.1, 156.5 (d, J = 10.6 Hz), 155.3,153.2, 151.3, 131.2 (d, J = 9.7 Hz), 126.4, 121.1, 116.9, 115.0 (d, J = 3.3Hz), 114.5, 112.1 (d, J = 21.1 Hz), 107.5, 107.3 (d, J = 24.7 Hz), 18.8. Example 15 Compound I-15 6-Chloro-7-(4-fluorophenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-15 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 4-fluorophenylboronic acid (0.42 g, 3 mmol). Other steps were the same as in Example 2. Compound I-15 was obtained as a white solid (0.13 g, yield 45%), mp = 124.0–127.4 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.65 (s, 1H), 7.24 – 7.08 (m, 2H), 7.05 (dd, J= 9.1, 4.5 Hz,2H), 6.69 (s, 1H), 6.20 (s, 1H), 2.41 (s, 3H); 13 C NMR (101 MHz, Chloroform- d )δ 160.2, 160.1 (d, J = 244.6 Hz), 156.6, 153.2, 151.4, 150.8 (d, J = 2.8 Hz), 126.2, 121.7 (d, J = 8.4 Hz, 2C), 120.2, 117.1 (d, J = 23.6 Hz, 2C), 116.1,114.1, 105.8. Example 16 Compound I-16 6-Chloro-7-(2-Chlorophenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-16 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2-chlorophenylboronic acid (0.47 g, 3 mmol). Other steps were the same as in Example 2. Compound I-16 was obtained as a pale yellow solid (0.07 g, yield 21%), mp = 148.0–149.5 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.68 (s, 1H), 7.53 (dd, J = 8.0, 1.5 Hz, 1H), 7.35 (td, J =7.8, 1.5 Hz, 1H), 7.27 (d, J = 1.5 Hz, 1H), 7.15 (dd, J = 8.0, 1.4 Hz, 1H), 6.56 (s, 1H), 6.21 (s, 1H), 2.42 (s, 3H); 13 C NMR (101 MHz, Chloroform- d) δ160.3, 155.8, 153.2, 151.5, 150.3, 131.5, 128.7, 127.2, 126.8, 126.3, 122.6,119.8, 116.1, 114.1, 105.0, 18.9; HRMS (ESI), m / z: calcd for C 16 H 11 Cl2O3[M+H] + :321.0080, found: 321.0089. Example 17 Compound I-17 6-Chloro-7-(3-Chlorophenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-17 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 3-chlorophenylboronic acid (0.47 g, 3 mmol). Other steps were the same as in Example 2. Compound I-17 was obtained as a white solid (0.13 g, yield 42%), mp = 141.0–143.0 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.68 (s, 1H), 7.34 (t, J = 8.1 Hz, 1H), 7.21 (ddd, J = 8.1,1.9, 0.9 Hz, 1H), 7.05 (t, J = 2.2 Hz, 1H), 6.95 (ddd, J = 8.3, 2.4, 1.0 Hz,1H), 6.84 (s, 1H), 6.24 (q, J = 1.3 Hz, 1H), 2.42 (d, J = 1.3 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d) δ 160.1, 156.1, 155.3, 153.2, 151.3, 135.7, 131.1,126.4, 125.4, 121.1, 119.9, 117.6, 116.9, 114.6, 107.5, 18.9; HRMS (ESI), m / z: calcd for C 16 H 11 Cl2O3[M+H] + : 321.0080, found: 321.0089. Example 18 Compound I-18 6-Chloro-7-(4-Chlorophenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-18 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 4-chlorophenylboronic acid (0.47 g, 3 mmol). Other steps were the same as in Example 2. Compound I-18 was obtained as a white solid (0.17 g, yield 53%), mp = 170.1–173.2 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.67 (s, 1H), 7.46 – 7.29 (m, 2H), 7.09 – 6.93 (m, 2H), 6.78 (s, 1H), 6.23 (s, 1H), 2.42 (d, J = 1.0 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d )δ 160.2, 155.8, 153.8, 153.2, 151.3, 130.6, 130.5 (2C), 126.4, 121.1 (2C),120.8, 116.6, 114.4, 106.8, 18.9. Example 19 Compound I-19 6-Chloro-4-methyl-7-(2-tolyloxy)-2H-chloro-2-one The preparation method of compound I-19 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2-methylphenylboronic acid (0.41 g, 3 mmol). Other steps were the same as in Example 2. Compound I-19 was obtained as a white solid (0.20 g, yield 68%), mp = 112.5–118.0 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.66 (s, 1H), 7.31 (d, J = 7.4 Hz, 1H), 7.25 (d, J = 8.0 Hz, 1H), 7.19 (t, J = 7.0 Hz, 1H), 7.00 (d, J = 7.8 Hz, 1H), 6.54 (s, 1H), 6.18 (s,1H), 2.41 (s, 3H), 2.19 (s, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.4,156.7, 153.4, 152.6, 151.5, 132.2, 130.3, 127.9, 126.2, 126.1, 120.9, 119.6,115.4, 113.7, 104.5, 18.9, 16.0; HRMS (ESI), m / z: calcd for C 17 H 14 ClO3[M+H] + :301.0626, found: 301.0633. Example 20 Compound I-20 6-Chloro-4-methyl-7-(3-tolyloxy)-2H-chloro-2-one The preparation method of compound I-20 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 3-methylphenylboronic acid (0.41 g, 3 mmol). Other steps were the same as in Example 2. Compound I-20 was obtained as a white solid (0.17 g, yield 57%), mp = 125.5–126.5 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.65 (s, 1H), 7.30 (t, J = 7.7 Hz, 1H), 7.06 (d, J = 7.5 Hz, 1H), 6.88 (d, J = 8.9 Hz, 2H), 6.75 (s, 1H), 6.20 (s, 1H), 2.41 (s, 3H), 2.37(s, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.4, 156.7, 154.9, 153.2, 151.5,140.8, 130.1, 126.3, 126.1, 120.7, 120.4, 117.1, 115.9, 114.0, 106.2, 21.5,18.9; HRMS (ESI), m / z: calcd for C 17 H 14 ClO3[M+H] + : 301.0626, found: 301.0632. Example 21 Compound I-21 6-Chloro-4-methyl-7-(4-tolyloxy)-2H-chloro-2-one The preparation method of compound I-21 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 4-methylphenylboronic acid (0.41 g, 3 mmol). Other steps were the same as in Example 2. Compound I-21 was obtained as a white solid (0.14 g, yield 47%), mp = 148.8–151.8 °C.1 H NMR (400 MHz, Chloroform- d ) δ 7.64 (s, 1H), 7.22 (d, J = 8.2 Hz, 2H), 6.97 (d, J = 8.4 Hz, 2H), 6.70 (s, 1H), 6.22 – 6.14 (m, 1H), 2.40 (s, 3H), 2.38 (s, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.4, 157.0, 153.2, 152.6, 151.5, 135.4, 130.9,130.3 (2C), 126.0, 120.1 (2C), 118.7, 113.8, 105.7, 21.0, 18.8. Example 22 Compound I-22 6-Chloro-7-(3-methoxyphenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-22 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 3-methoxyphenylboronic acid (0.46 g, 3 mmol). Other steps were the same as in Example 2. Compound I-22 was obtained as a white solid (0.11 g, yield 35%), mp = 142.5–144.0 °C. 1 H NMR (400MHz, Chloroform- d ) δ 7.66 (s, 1H), 7.31 (t, J = 8.2 Hz, 1H), 6.82 – 6.74 (m,2H), 6.64 (dd, J = 8.9, 1.4 Hz, 2H), 6.25 – 6.17 (m, 1H), 3.81 (s, 3H), 2.41(d, J = 1.1 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d) δ 161.4, 160.4, 156.3,156.1, 153.2, 151.4, 130.8, 126.1, 120.6, 116.1, 114.1, 111.9, 111.1, 106.6,106.1, 55.7, 18.9; HRMS (ESI), m / z: calcd for C 17 H 14 ClO4[M+H] + 317.0575, found: 317.0580. Example 23 Compound I-23 6-Chloro-7-(4-methoxyphenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-23 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 4-methoxyphenylboronic acid (0.46 g, 3 mmol). Other steps were the same as in Example 2. Compound I-23 was obtained as a pale yellow solid (0.07 g, yield 22%), mp = 173.0–174.8 °C. 1 H NMR (400MHz, Chloroform- d ) δ 7.63 (s, 1H), 7.09 – 6.97 (m, 2H), 6.98 – 6.89 (m, 2H), 6.65 (s, 1H), 6.17 (s, 1H), 3.83 (s, 3H), 2.40 (d, J = 1.1 Hz, 3H); 13 C NMR (101MHz, Chloroform- d ) δ 160.4, 157.5, 157.4, 153.3, 151.5, 148.0, 126.0, 121.7(2C), 119.7, 115.5 (2C), 115.4, 113.7, 104.9, 55.9, 18.8; HRMS (ESI), m / z:calcd for C 17 H 14 ClO4[M+H] + : 317.0575, found: 317.0586. Example 24 Compound I-24 6-Chloro-4-methyl-7-(2-(trifluoromethyl)phenoxy)-2H-chromene-2-one The preparation method of compound I-24 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2-trifluoromethylphenylboronic acid (0.57 g, 3 mmol). Other steps were the same as in Example 2. Compound I-24 was obtained as a pale yellow solid (0.06 g, yield 18%), mp = 130.5–132.8 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.76 (d, J = 7.7 Hz, 1H), 7.69 (s, 1H), 7.57 (t, J =7.6 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 7.01 (d, J = 8.2 Hz, 1H), 6.76 (s, 1H), 6.24 (s, 1H), 2.43 (s, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.1, 155.4,153.1, 152.9 (q, J = 1.8 Hz), 151.3, 133.9, 128.0 (q, J = 4.9 Hz), 126.4,125.2, 123.1 (q, J = 272.9 Hz), 122.5 (q, J = 31.9 Hz), 121.0, 120.5, 116.9,114.6, 107.0, 18.9. Example 25 Compound I-25 6-Chloro-4-methyl-7-(3-(trifluoromethyl)phenoxy)-2H-chromene-2-one The preparation method of compound I-25 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 3-trifluoromethylphenylboronic acid (0.57 g, 3 mmol). Other steps were the same as in Example 2. Compound I-25 was obtained as a white solid (0.11 g, yield 32%), mp = 104.8–107.2 °C. 1 H NMR (400MHz, Chloroform- d ) δ 7.7 (s, 1H), 7.6 – 7.4 (m, 2H), 7.3 (t, J = 2.0 Hz, 1H), 7.2 (d, J = 7.9 Hz, 1H), 6.8 (s, 1H), 6.3 (s, 1H), 2.4 (s, 3H); 13 C NMR (101MHz, Chloroform- d ) δ 160.1, 155.8, 155.0, 153.2, 151.2, 133.0 (q, J = 33.0Hz), 131.0, 126.5, 123.6 (q, J = 272.6 Hz), 122.5, 121.8 (q, J = 3.8 Hz),121.2, 117.1, 116.3 (q, J = 3.8 Hz), 114.7, 107.6, 18.9; HRMS (ESI), m / z:calcd for C 17 H 11 ClF3O3[M+H] + : 355.0343, found: 355.0351. Example 26 Compound I-26 6-Chloro-4-methyl-7-(4-(trifluoromethyl)phenoxy)-2H-chromene-2-one The preparation method of compound I-26 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 4-trifluoromethylphenylboronic acid (0.57 g, 3 mmol). Other steps were the same as in Example 2. Compound I-26 was obtained as a white solid (0.14 g, yield 40%), mp = 142.8–147.1 °C. 1 H NMR (400MHz, Chloroform- d ) δ 7.7 (s, 1H), 7.7 (d, J = 8.6 Hz, 2H), 7.1 (d, J = 8.5 Hz,2H), 6.9 (s, 1H), 6.3 (s, 1H), 2.4 (d, J = 1.2 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.0, 158.4, 154.4, 153.2, 151.2, 127.8 (q, J = 3.7 Hz, 2C), 127.0 (q, J = 32.9 Hz), 126.6, 124.0 (q, J = 271.8 Hz), 121.7, 118.8 (2C), 117.5, 114.9, 108.6, 18.9. Example 27 Compound I-27 7-(2,6-Dimethylphenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-27 in this embodiment is as follows: The method described in Example 2 was used, except that 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2,6-dimethylphenylboronic acid (0.45 g, 3 mmol), and the other steps were the same as in Example 2. Compound I-27 was obtained as a yellow solid (0.07 g, yield 28%), mp = 97.4–98.5 °C. 1 H NMR (400MHz, Chloroform- d ) δ 7.51 (d, J = 8.8 Hz, 1H), 7.11 (d, J= 1.2 Hz, 3H), 6.83(dd, J = 8.8, 2.5 Hz, 1H), 6.60 (d, J = 2.5 Hz, 1H), 6.14 (s, 1H), 2.40 (d, J =1.0 Hz, 3H), 2.12 (s, 6H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.2, 160.1,154.5, 151.6, 149.5, 130.2, 128.4 (2C), 125.1, 125.0, 113.5, 111.5, 111.2,101.6, 17.9, 15.3 (2C); HRMS (ESI), m / z: calcd for C 18 H 17 O3[M+H] + : 281.1172, found: 281.1181. Example 28 Compound I-28 7-(2,4-Dimethylphenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-28 in this embodiment is as follows: The method described in Example 2 was used, except that 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2,4-dimethylphenylboronic acid (0.45 g, 3 mmol), and the other steps were the same as in Example 2. Compound I-28 was obtained as a white solid (0.15 g, yield 56%), mp = 132.0–134.0 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.50 (d, J = 8.8 Hz, 1H), 7.09 (s, 1H), 7.03 (d, J =8.1 Hz, 1H), 6.95 – 6.78 (m, 2H), 6.69 (d, J = 2.5 Hz, 1H), 6.14 (s, 1H), 2.39(s, 3H), 2.34 (s, 3H), 2.13 (s, 3H); 13 C NMR (101 MHz, Chloroform- d) δ 161.9,161.2, 155.3, 152.5, 150.5, 135.4, 132.6, 130.3, 128.2, 125.9, 121.1, 114.6,113.1, 112.6, 103.8, 21.0, 18.9, 16.1; HRMS (ESI), m / z: calcd for C 18 H 17 O3[M+H] + : 281.1172, found: 281.1178. Example 29 Compound I-29 7-(2,4,6-trimethylphenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-29 in this embodiment is as follows: The method described in Example 2 was used, except that 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2,4,6-trimethylphenylboronic acid (0.49 g, 3 mmol), and the other steps were the same as in Example 2. Compound I-29 was obtained as a yellow liquid (0.06 g, yield 21%). 1 H NMR (400 MHz, Chloroform- d )δ 7.50 (d, J = 8.8 Hz, 1H), 6.92 (s, 2H), 6.83 (dd, J = 8.8, 2.4 Hz, 1H), 6.61(d, J = 2.5 Hz, 1H), 6.13 (s, 1H), 2.42 – 2.37 (m, 3H), 2.31 (s, 3H), 2.07 (s,6H); 13 C NMR (101 MHz, Chloroform- d ) δ 161.3, 161.3, 155.5, 152.6, 148.3,135.5, 130.7 (2C), 130.0 (2C), 126.1, 114.4, 112.4, 112.2, 102.6, 21.0, 18.9,16.2 (2C); HRMS (ESI), m / z: calcd for C 19 H 19 O3[M+H] + : 295.1334, found:295.1329. Example 30 Compound I-30 7-(2-Ethylphenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-30 in this embodiment is as follows: The method described in Example 2 was used, except that 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2-ethylphenylboronic acid (0.45 g, 3 mmol), and the other steps were the same as in Example 2. Compound I-30 was obtained as a white solid (0.10 g, yield 36%), mp = 72.0–76.9 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.52 (d, J = 8.8 Hz, 1H), 7.33 (dd, J = 7.1, 2.0 Hz, 1H), 7.22(td, J = 7.4, 1.6 Hz, 2H), 6.98 (dd, J = 7.5, 1.6 Hz, 1H), 6.89 (dd, J = 8.8, 2.4 Hz, 1H), 6.74 (d, J = 2.4 Hz, 1H), 6.15 (s, 1H), 2.58 (q, J = 7.6 Hz, 2H),2.40 (s, 3H), 1.17 (t, J = 7.6 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 161.9,161.2, 155.2, 152.5 (2C), 136.6, 130.4, 127.7, 126.0, 125.9, 121.2, 114.8,113.5, 112.7, 104.3, 23.2, 18.9, 14.5; HRMS (ESI), m / z: calcd for C 18 H 17 O3[M+H] + : 281.1178, found: 281.1180. Example 31 Compound I-31 7-(2-Isopropylphenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-31 in this embodiment is as follows: The method described in Example 2 was used, except that 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2-isopropylphenylboronic acid (0.49 g, 3 mmol), and the other steps were the same as in Example 2. Compound I-31 was obtained as a pale yellow liquid (0.15 g, yield 52%). 1 H NMR (400 MHz, Chloroform- d )δ 7.52 (d, J = 8.8 Hz, 1H), 7.44 – 7.34 (m, 1H), 7.25 – 7.18 (m, 2H), 7.00 –6.92 (m, 1H), 6.89 (dd, J = 8.8, 2.4 Hz, 1H), 6.75 (d, J = 2.4 Hz, 1H), 6.18 –6.12 (m, 1H), 3.15 (p, J = 6.9 Hz, 1H), 2.46 – 2.35 (m, 3H), 1.19 (d, J = 6.9Hz, 6H); 13 C NMR (101 MHz, Chloroform- d ) δ 162.1, 161.2, 155.3, 152.5, 151.9,141.0, 127.7, 127.4, 126.0 (2C), 121.3, 114.8, 113.5, 112.7, 104.3, 27.3,23.2 (2C), 18.9; HRMS (ESI), m / z: calcd for C 19 H 19 O3[M+H] + : 295.1329, found:295.1331. Example 32 Compound I-32 7-(2,4-bis(trifluoromethyl)phenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-32 in this embodiment is as follows: The method described in Example 2 was used, except that 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2,4-bis(trifluoromethyl)phenylboronic acid (0.77 g, 3 mmol), and the other steps were the same as in Example 2. Compound I-32 was obtained as a pale yellow solid (0.06 g, yield 16%), mp = 89.9 – 94.4 °C. 1HNMR (400 MHz, Chloroform- d ) δ 7.99 (s, 1H), 7.83 – 7.73 (m, 1H), 7.63 (d, J =8.6 Hz, 1H), 7.12 (d, J = 8.6 Hz, 1H), 7.06 – 6.92 (m, 2H), 6.26 (s, 1H), 2.44(s, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.5, 158.5, 156.8, 155.1, 152.1,130.9, 126.6 (q, J = 33.6 Hz), 126.6, 125.5, 123.4 (q, J = 271.9 Hz), 122.5 (q, J = 273.0 Hz), 122.7 (q, J = 32.7 Hz), 120.2, 117.1, 115.6, 114.3, 107.5,18.9. Example 33 Compound I-33 7-(4-chloro-2-(trifluoromethyl)phenoxy)-4-methyl-2H-benzopyran-2-one According to route 4, the preparation method of compound I-33 in this embodiment is as follows: Under nitrogen protection, 4-methylumbelliferone (0.18 g, 1.0 mmol), potassium carbonate (0.69 g, 5.0 mmol), and DMF (2 ml) were added sequentially to a 10 mL dry reaction tube. After stirring for 1 h, 5-chloro-2-fluorotrifluorotoluene (0.24 g, 1.2 mmol) dissolved in DMF was added. The reaction was carried out in an oil bath at 80 °C for 16 h under magnetic stirring. The reaction progress was monitored by TLC until the starting material disappeared or no change occurred, indicating the end of the reaction. After the reaction was completed, water was slowly added dropwise to quench the reaction. The aqueous phase was extracted with dichloromethane (10 × 3 mL). The combined organic phases were washed with saturated sodium chloride solution (10 × 3 mL), dried over anhydrous magnesium sulfate, and the filtered organic phase was concentrated under reduced pressure using a rotary evaporator to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain compound I-33 as a pale yellow solid (0.22 g, yield 61%), mp = 99.8–102.9 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.71 (d,J = 2.5 Hz, 1H), 7.58 (d, J = 8.7 Hz, 1H), 7.51 (dd, J = 8.8, 2.6 Hz, 1H), 7.03(d, J = 8.8 Hz, 1H), 6.94 (dd, J = 8.7, 2.4 Hz, 1H), 6.87 (d, J = 2.4 Hz, 1H), 6.22 (s, 1H), 2.42 (d, J = 1.2 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.6,159.8, 155.0, 152.1, 152.0 (d, J = 1.7 Hz), 133.7, 130.2, 127.9 (q, J = 5.1Hz), 126.3, 124.1 (q, J = 32.4 Hz), 122.6, 122.3 (q, J = 273.3 Hz), 116.3,114.6, 113.8, 106.2, 18.9. Example 34 Compound I-34 7-(4-bromo-2-(trifluoromethyl)phenoxy)-4-methyl-2H-benzopyran-2-one The preparation method of compound I-34 in this embodiment is as follows: The method described in Example 33 was used, except that 5-chloro-2-fluorotrifluorotoluene (0.24 g, 1.2 mmol) was replaced with 2-fluoro-5-bromotrifluorotoluene (0.29 g, 1.2 mmol), and the other steps were the same as in Example 33. Compound I-34 was obtained as a pale yellow solid (0.18 g, yield 44%), mp = 99.4–100.8 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.85 (d, J = 2.1 Hz, 1H), 7.66 (dd, J = 8.7, 2.3 Hz, 1H), 7.58 (d, J = 8.7 Hz, 1H), 6.95 (t, J= 8.3 Hz, 2H), 6.88(d, J = 2.3 Hz, 1H), 6.22 (s, 1H), 2.42 (s, 3H); 13 C NMR (101 MHz, Chloroform- d )δ 160.6, 159.6, 155.0, 152.6 (d, J = 1.7 Hz), 152.1, 136.7, 130.8 (q, J = 5.1Hz), 126.3, 124.4 (d, J = 32.3 Hz), 122.8, 122.2 (d, J = 273.4 Hz), 117.3,116.4, 114.7, 113.8, 106.3, 18.9. Example 35 Compound I-35 7-(4-iodo-2-(trifluoromethyl)phenoxy)-4-methyl-2H-benzopyran-2-one The preparation method of compound I-35 in this embodiment is as follows: The method described in Example 33 was used, except that 5-chloro-2-fluorotrifluorotoluene (0.24 g, 1.2 mmol) was replaced with 2-fluoro-5-iodotrifluorotoluene (0.35 g, 1.2 mmol), and the other steps were the same as in Example 33. Compound I-35 was obtained as a white solid (0.28 g, yield 62%), mp = 108.3–119.8 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 8.01 (d, J = 2.1 Hz, 1H), 7.84 (dd, J =8.6, 2.2 Hz, 1H), 7.58 (d, J = 8.7 Hz, 1H), 6.94 (dd, J = 8.7, 2.5 Hz, 1H), 6.89 (d, J = 2.4 Hz, 1H), 6.82 (d, J = 8.6 Hz, 1H), 6.22 (d, J = 1.2 Hz, 1H), 2.42 (d, J = 1.2 Hz, 3H); 13 C NMR (101 MHz, Chloroform-d ) δ 160.6, 159.5, 155.0,153.5 (d, J = 1.7 Hz), 152.1, 142.6, 136.5 (d, J = 5.0 Hz), 122.9, 126.3, 124.6(d, J = 31.9 Hz), 122.0 (d, J = 273.5 Hz), 116.4, 114.8, 113.8, 106.4, 87.2,18.9. Example 36 Compound I-36 4-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)-3-(trifluoromethyl)benzonitrile The preparation method of compound I-36 in this embodiment is as follows: The method described in Example 33 was used, except that 5-chloro-2-fluorotrifluorotoluene (0.24 g, 1.2 mmol) was replaced with 3-trifluoromethyl-4-fluorobenzonitrile (0.23 g, 1.2 mmol), and the other steps were the same as in Example 33. Compound I-36 was obtained as a white solid (0.08 g, yield 22%), mp = 183.3–184.5 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 8.02 (d, J = 2.0 Hz, 1H), 7.79 (dd, J = 8.6, 2.1 Hz, 1H), 7.66 (d, J = 9.3 Hz, 1H), 7.06 (d, J = 8.7 Hz, 1H), 7.02(dd, J = 4.6, 2.3 Hz, 2H), 6.28 (d, J = 1.4 Hz, 1H), 2.45 (d, J = 1.1 Hz, 3H); 13 CNMR (101 MHz, Chloroform- d ) δ 160.3, 157.9, 157.4, 155.0, 151.9, 137.5, 132.1(q, J = 5.1 Hz), 126.7, 122.8 (d, J = 32.8 Hz), 122.1 (d, J= 273.3 Hz), 119.6,117.6, 117.2, 116.0, 114.6, 108.3, 107.8, 18.9. Example 37 Compound I-37 2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)-3-(trifluoromethyl)benzonitrile The preparation method of compound I-37 in this embodiment is as follows: The method described in Example 33 was used, except that 5-chloro-2-fluorotrifluorotoluene (0.24 g, 1.2 mmol) was replaced with 2-fluoro-3-(trifluoromethyl)benzonitrile (0.23 g, 1.2 mmol), and the other steps were the same as in Example 33. Compound I-37 was obtained as a yellow solid (0.11 g, yield 32%), mp = 167.8–175.2 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 8.02 (d, J = 8.7 Hz, 1H), 7.93(d, J = 7.8 Hz, 1H), 7.63 – 7.52 (m, 2H), 6.98 (dd, J = 8.8, 2.6 Hz, 1H), 6.65(d, J = 2.5 Hz, 1H), 6.26 – 6.16 (m, 1H), 2.42 (d, J = 1.1 Hz, 3H); 13 C NMR (101MHz, Chloroform- d ) δ 160.6, 160.2, 155.0, 154.0 (d, J = 1.7 Hz), 152.2, 138.0,132.3 (q, J = 4.8 Hz), 126.6, 126.5, 126.2 (d, J = 32.7 Hz), 122.0 (d, J = 273.7Hz), 116.2, 113.7, 113.3, 109.8, 104.0, 18.9(2C). Example 38 Compound I-38 4-Methyl-7-(2-nitro-6-(trifluoromethyl)phenoxy)-2H-benzopyran-2-one The preparation method of compound I-38 in this embodiment is as follows: The method described in Example 33 was used, except that 5-chloro-2-fluorotrifluorotoluene (0.24 g, 1.2 mmol) was replaced with 2-fluoro-3-nitrotrifluorotoluene (0.21 g, 1.2 mmol), and the other steps were the same as in Example 33. Compound I-38 was obtained as a pale yellow solid (0.07 g, yield 19%), mp = 128.5 – 132.8 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 8.27 (d, J = 8.2 Hz, 1H), 8.07 (d, J =7.8 Hz, 1H), 7.59 (dd, J = 26.1, 8.5 Hz, 2H), 6.90 (dd, J = 8.8, 2.6 Hz, 1H), 6.64 (d, J = 2.5 Hz, 1H), 6.25 – 6.13 (m, 1H), 2.40 (d, J = 1.0 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.6, 160.2, 154.9, 152.2, 145.6, 143.6, 132.6 (q, J = 4.8 Hz), 130.1, 127.4 (q, J = 32.5 Hz), 126.6, 126.3, 122.0 (q, J = 274.2Hz), 116.1, 113.6, 112.6, 103.4, 18.8. Example 39 Compound I-39 6-Chloro-7-(2-ethylphenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-39 in this embodiment is as follows: The method described in Example 2 was used, except that 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol) was replaced with 4-methylumbelliferone (0.18 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2-ethylphenylboronic acid (0.45 g, 3 mmol). Other steps were the same as in Example 2. Compound I-39 was obtained as a white solid (0.08 g, yield 25%), mp = 110.0 – 111.0 °C.1 H NMR (400 MHz, Chloroform- d ) δ 7.66 (s, 1H), 7.34 (d, J = 8.9 Hz, 1H), 7.28 – 7.20 (m, 2H), 6.98 (d, J = 8.5 Hz, 1H), 6.58 (s, 1H), 6.18 (s, 1H), 2.57 (q, J = 7.5 Hz, 2H),2.41 (s, 3H), 1.19 (t, J = 7.6 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 160.5,157.0, 153.3, 152.2, 151.6, 136.2, 130.6, 127.8, 126.3, 126.1, 120.9, 119.6,115.4, 113.7, 104.6, 23.2, 18.9, 14.5. Example 40 Compound I-40 6-Chloro-7-(2-isopropylphenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-40 in this embodiment is as follows: The method described in Example 2 was used, except that 6-chloro-7-hydroxy-4-methylcoumarin (0.21 g, 1 mmol) was replaced with 4-methylumbelliferone (0.18 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2-isopropylphenylboronic acid (0.49 g, 3 mmol). Other steps were the same as in Example 2. Compound I-40 was obtained as a white solid (0.09 g, yield 29%), mp = 84.5 – 90.1 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.67 (s, 1H), 7.46 – 7.34 (m, 1H), 7.27 – 7.21 (m, 2H), 6.95(d, J = 9.3 Hz, 1H), 6.60 (s, 1H), 6.23 – 6.13 (m, 1H), 3.10 (p, J = 6.9 Hz, 1H), 2.41 (d, J = 1.1 Hz, 3H), 1.20 (s, 6H);13 C NMR (101 MHz, Chloroform- d ) δ160.5, 157.2, 153.3, 151.6, 151.6, 140.6, 127.9, 127.6, 126.4, 126.1, 120.8,119.7, 115.4, 113.7, 104.6, 27.5, 23.2(2C), 18.9. Example 41 Compound I-41 3-Fluoro-7-(2-isopropylphenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-41 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 3-fluoro-7-hydroxy-4-methyl-2H-1-benzopyran-2-one (0.19 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2-isopropylphenylboronic acid (0.49 g, 3 mmol). Other steps were the same as in Example 2. Compound I-41 was obtained as a white solid (0.08 g, yield 26%), mp = 89.0 – 90.7 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.49 (d, J = 8.8 Hz, 1H), 7.42 – 7.36 (m,1H), 7.25 – 7.15 (m, 2H), 7.00 – 6.89 (m, 2H), 6.78 (d, J = 2.4 Hz, 1H), 3.15(p, J = 6.9 Hz, 1H), 2.38 (d, J = 2.9 Hz, 3H), 1.18 (s, 6H); 13 C NMR (101 MHz, Chloroform- d ) δ 161.2 (d, J = 2.7 Hz), 155.4 (d, J = 30.1 Hz), 151.9, 151.8 (d, J = 2.3 Hz), 142.9 (d, J = 248.8 Hz), 141.0, 131.1 (d, J= 13.1 Hz), 127.7,127.5, 126.0, 125.9 (d, J = 6.2 Hz), 121.2, 114.4, 114.1 (d, J = 2.5 Hz),104.4, 27.3, 23.2(2C), 10.4; HRMS (ESI), m / z: calcd for C 19 H 18 FO3[M+H] + :313.1234, found: 313.1242. Example 42 Compound I-42 3-Chloro-7-(2-isopropylphenoxy)-4-methyl-2H-chromene-2-one The preparation method of compound I-42 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 3-chloro-7-hydroxy-4-methyl-2H-1-benzopyran-2-one (0.21 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2-isopropylphenylboronic acid (0.49 g, 3 mmol). Other steps were the same as in Example 2. Compound I-42 was obtained as a white solid (0.10 g, yield 31%), mp = 122.0 – 124.9 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.55 (d, J = 8.9 Hz, 1H), 7.43 – 7.36 (m,1H), 7.26 – 7.20 (m, 2H), 7.01 – 6.89 (m, 2H), 6.76 (d, J = 2.5 Hz, 1H), 3.13(p, J = 6.9 Hz, 1H), 2.56 (s, 3H), 1.19 (d, J = 6.9 Hz, 6H); 13 C NMR (101 MHz, Chloroform- d ) δ 162.0, 157.4, 153.1, 151.7, 147.9, 141.0, 127.7, 127.5,126.3, 126.2, 121.3, 118.6, 114.5, 114.1, 104.2, 27.3, 23.2(2C), 16.4. Example 43 Compound I-43 3-Bromo-7-(2-isopropylphenoxy)-4-methyl-2H-chromene-2-one According to route 5, the preparation method of compound I-43 in this embodiment is as follows: In a 10 mL dry reaction tube, 7-(2-isopropylphenoxy)-4-methyl-2H-chromene-2-one (0.15 g, 0.5 mmol) was dissolved in anhydrous dichloromethane (2 mL), and then N-bromosuccinimide (0.11 g, 0.6 mmol) was added. The reaction was carried out at room temperature for 4-6 h with magnetic stirring, and the reaction progress was monitored by TLC until the starting material disappeared or showed no change. After the reaction was completed, water (10 mL) was added to the mixture to quench the reaction, and the aqueous phase was extracted with ethyl acetate (10 × 3 mL). The combined organic phases were washed with saturated sodium chloride solution (10 × 3 mL), dried over anhydrous magnesium sulfate, and the obtained organic phase was concentrated under reduced pressure by rotary evaporator to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain compound I-43 as a pale yellow solid (0.26 g, yield 70%), mp = 129.9 – 131.2 ℃. 1 H NMR (400 MHz, Chloroform- d ) δ 7.58 (d, J = 8.9 Hz, 1H), 7.42 –7.37 (m, 1H), 7.26 – 7.17 (m, 2H), 6.99 – 6.90 (m, 2H), 6.75 (d, J = 2.5 Hz, 1H), 3.13 (p, J = 6.6 Hz, 1H), 2.60 (s, 3H), 1.19 (d, J = 6.9 Hz, 6H); 13 C NMR (101 MHz, Chloroform- d ) δ 162.2, 157.3, 153.5, 151.7, 151.1, 141.0, 127.7,127.5, 126.5, 126.2, 121.3, 114.6, 114.1, 110.5, 104.1, 27.3, 23.2(2C), 19.7. Example 44 Compound I-44 7-(2-Isopropylphenoxy)-3,4-Dimethyl-2H-chromene-2-one The preparation method of compound I-44 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 7-hydroxy-3,4-dimethyl-2H-1-benzopyran-2-one (0.19 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2-isopropylphenylboronic acid (0.49 g, 3 mmol). Other steps were the same as in Example 2. Compound I-44 was obtained as a white solid (0.10 g, yield 33%), mp = 87.5 – 89.0 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.52 (d, J = 8.8 Hz, 1H), 7.42 – 7.34 (m,1H), 7.25 – 7.17 (m, 2H), 6.99 – 6.92 (m, 1H), 6.88 (dd, J = 8.8, 2.5 Hz, 1H), 6.74 (d, J = 2.5 Hz, 1H), 3.17 (p, J = 6.9 Hz, 1H), 2.38 (s, 3H), 2.18 (s, 3H), 1.19 (d, J = 6.9 Hz, 6H); 13 C NMR (101 MHz, Chloroform- d ) δ 162.4, 160.9, 153.5,152.1, 146.2, 141.0, 127.6, 127.4, 125.8, 125.7, 121.2, 119.8, 115.4, 113.4,104.2, 27.2, 23.2(2C), 15.3, 13.4. Example 45 Compound I-45 3-Butyl-7-(2-isopropylphenoxy)-4-methyl-2H-chromen-2-one The preparation method of compound I-45 in this embodiment is as follows: The method described in Example 2 was used, except that 4-methylumbelliferone (0.18 g, 1 mmol) was replaced with 3-butyl-7-hydroxy-4-methyl-2H-1-benzopyran-2-one (0.23 g, 1 mmol), and 3-fluorophenylboronic acid (0.42 g, 3 mmol) was replaced with 2-isopropylphenylboronic acid (0.49 g, 3 mmol). Other steps were the same as in Example 2. Compound I-45 was obtained as a white solid (0.13 g, yield 38%), mp = 49.6 – 52.1 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.52 (d, J = 8.8 Hz, 1H), 7.41 – 7.34 (m,1H), 7.25 – 7.17 (m, 2H), 7.00 – 6.91 (m, 1H), 6.88 (dd, J = 8.8, 2.5 Hz, 1H), 6.72 (d, J = 2.5 Hz, 1H), 3.16 (p, J = 6.9 Hz, 1H), 2.68 – 2.58 (m, 2H), 2.38(s, 3H), 1.46 (ddq, J = 30.8, 15.1, 7.9, 7.0 Hz, 4H), 1.19 (d, J = 6.9 Hz, 6H), 0.94 (t, J = 7.2 Hz, 3H); 13 C NMR (101 MHz, Chloroform- d ) δ 162.0, 161.0, 153.6,152.1, 145.9, 141.0, 127.6, 127.4, 125.8, 125.8, 124.6, 121.2, 115.6, 113.4,104.1, 31.1, 27.5, 27.2, 23.2(2C), 23.0, 15.0, 14.1. Test case The inhibitory effects of the coumarin derivatives (compound numbers I-1 to I-45) synthesized in Examples 1 to 45 containing substituted phenyl ether structures on the pathogenic fungi of the tested plants.

[0023] 1. Experimental subjects The coumarin derivatives containing substituted phenyl ether structures synthesized in Examples 1 to 45 are compounds I-1 to I-45.

[0024] 2. Experimental Methods The linear mycelial growth rate method was used to determine the effects of compounds I-1 to I-45 on *Sclerotinia sclerotinia*, the causal agent of rapeseed rot (…). Sclerotinia sclerotiorum ), apple rot bacteria ( The waltz of evil Grape gray mold ( Botrytis gray Rice sheath blight pathogen ( Rhizoctonia solani ) and wheat total erosion ( Gaeumannomyces graminis The in vitro inhibitory activity of five tested plant pathogens was studied. The selected fungi were provided by the College of Plant Protection, Northwest A&F University.

[0025] Using 20 mg / L eugenol and oxadiazon solutions as positive controls and 5% DMSO aqueous solution as a blank control, the accurately weighed test compounds were completely dissolved in 5% DMSO (v / v) aqueous solution. The test solution or control solution was rapidly mixed with 150 mL of sterile PDA medium at 50 ℃ to obtain a drug-containing medium with a mass concentration of 20 mg / L. The medium was poured into sterilized petri dishes while hot, 10 mL per dish, and cooled for later use. The tested plant pathogens (cup diameter = 5 mm) were inoculated into the above petri dishes, with 3 replicates for each test group. After incubating in a constant temperature incubator at 25 ℃ for several hours, the colony diameter (mm) was measured using the cross-cross method, and the mycelial growth inhibition rate (IR) was calculated according to formula (1): ; Where: d0 is the diameter of the mushroom cake (5 mm), d c ds represents the average colony diameter (mm) of the blank control group, and ds represents the average colony diameter (mm) of the sample group.

[0026] 3. The experimental results are shown in Table 1. Table 1. Inhibitory effects (inhibition rate, %) of the coumarin derivatives synthesized in Examples 1 to 26 against plant pathogenic fungi at a concentration of 20 mg / L.

[0027] The data in the table is the average of three data points; Rs. . b for R. solani ; Ss c for S. sclerotiorum ; Bc d for B. cinerea ; Vm e for V. evil ; Gg f for G. graminis .

[0028] The antifungal activities of 26 synthesized compounds against *Rhizoctonia solani*, *Sclerotinia sclerotiorum*, *Botrytis cinerea*, *Fungiella vesicae*, and *Thunb. take-all* were determined at a concentration of 20 mg / L. Analysis of the structures of the compounds with superior activity revealed that compounds I-1 to I-26 showed higher overall inhibition rates against *Fungiella vesicae* than other fungi. Compound I-3 exhibited the best inhibition rate against *Fungiella vesicae*, reaching 100%. Compounds I-1, I-2, I-3, I-7, I-10, I-11, I-12, I-17, I-22, and I-25 showed inhibition rates exceeding 90% against *Fungiella vesicae*. When R... 1 When H is present, the overall activity of the compound is significantly better than that of R. 1 The compound is Cl; among them, compound I-10 has an inhibition rate of more than 80% against Sclerotinia sclerotiorum, Botrytis cinerea, Ophiopogonis macrantha, and Take-all fungus of wheat. Its inhibition rates against Sclerotinia sclerotiorum and Take-all fungus of wheat are 97.0% and 100%, respectively, which are superior to other compounds.

[0029] To further enhance the antifungal activity of the target compound, this invention further optimizes the compound structure based on the above results, fixing R... 1 For H, in R 2 Compounds I-27 to I-38 were synthesized by introducing polysubstituted groups including methyl, ethyl, isopropyl, chlorine, bromine, iodine, trifluoromethyl, cyano, and nitro. The antifungal activities of these 12 synthesized compounds against *Rhizoctonia solani*, *Sclerotinia sclerotiorum*, *Botrytis cinerea*, *Fungiella oleracea*, and *Tricholoma materia granatum* at a concentration of 20 mg / L were determined. The results are shown in Table 3. 2 For 2-Et and 2- i The activity of the -Pr compound was further enhanced, with inhibition rates of more than 85% against *Sclerotinia sclerotiorum*, *Botrytis cinerea*, *Ophiopogon japonicus*, and *Tricholoma materia rubra*. Therefore, further immobilization of R... 2 For 2-Et and 2- i When -Pr is used, investigate R 1 The activity of Cl was determined, and the results are shown in Table 2. The activity was not increased.

[0030] Table 2. Inhibitory effects (inhibition rate, %) of the coumarin derivatives synthesized in Examples 27–40 against plant pathogenic fungi at a concentration of 20 mg / L.

[0031] The data in the table is the average of three data points; Rs. . b for R.solani ; Ss c for S. sclerotiorum ; Bc d for B. cinerea ; Vm . e for V. evil ; Gg f for G. graminis .

[0032] Finally, fix the optimal configuration R. 1 For H, R 2 For 2- i -Pr, to explore R 3 The effect of substitution on the activity of compounds, in R 3 Five compounds were synthesized by introducing fluorine, chlorine, bromine, methyl, and butyl substituents. Their antifungal activities against *Rhizoctonia solani*, *Sclerotinia sclerotiorum*, *Botrytis cinerea*, *Fungiella asiatica*, and *Tricholoma materia granatum* at a concentration of 20 mg / L were determined. The results are shown in Table 3. 3 When the substituted group is fluorine, chlorine, bromine, methyl, or butyl, the antibacterial activity of the compound is not improved.

[0033] Table 3. Inhibitory effects (inhibition rate, %) of the coumarin derivatives synthesized in Examples 41-45 against plant pathogenic fungi at a concentration of 20 mg / L.

[0034] The data in the table is the average of three data points; Rs. b for R.solani ; Ss c for S. sclerotiorum ; Bc d for B. cinerea ; Vm e for V. evil ; Gg f for G. graminis .

[0035] In summary, the coumarin derivatives containing substituted phenyl ether structures prepared by chemical synthesis in this invention exhibit excellent antifungal activity, especially against Sclerotinia sclerotiorum, Botrytis cinerea, apple rot fungus, and wheat take-all fungus. Some compounds also exhibit broad-spectrum and high-efficiency activity. This lays the foundation for preparing fungicides with coumarin derivatives containing substituted phenyl ether structures as the main antifungal active ingredient.

[0036] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A coumarin derivative containing a substituted phenyl ether structure, characterized in that: Its general structural formula (I) is as follows: ； Among them, R 1 It is hydrogen or halogen; R 2 The groups represented by hydrogen, halogen, amino, acylamino, hydroxyl, mercapto, acyl, ester, amide, aminoacyl, alkyl, alkoxy, haloalkyl, cyano, nitro, and their multiple substitution combinations at different positions; R 3 It is one of hydrogen, halogen, or alkyl.

2. The coumarin derivative containing a substituted phenyl ether structure according to claim 1, characterized in that: The R 1 It is one of hydrogen, fluorine, chlorine, bromine, and iodine; R 2 The substitutions are hydrogen, fluorine, chlorine, bromine, iodine, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, cyano, nitro, and their multiple substitution combinations at different positions; R 3 It is one of hydrogen, fluorine, chlorine, bromine, iodine, and C1-C6 alkyl groups.

3. The coumarin derivative containing a substituted phenyl ether structure according to claim 1, characterized in that: The coumarin derivatives containing substituted phenyl ether structures are preferably the following compounds: 。 4. A method for preparing a coumarin derivative containing a substituted phenyl ether structure as described in any one of claims 1 to 3, characterized in that: The preparation method includes any one of the synthetic routes from route 1 to route 5: Route 1: ； Route 2: ； Route 3: ； Route 4: ； Route 5: 。 5. The method for preparing coumarin derivatives containing substituted phenyl ether structures according to claim 4, characterized in that: Route 1 specifically includes the following steps: Step S11: Using substituted resorcinol (III) and substituted ethyl acetoacetate (IV) as raw materials, a Pechmann condensation reaction is carried out in a first acidic reagent to generate a 4-methyl-7-hydroxycoumarin compound corresponding to general formula (II). The obtained product is purified by column chromatography or recrystallization to obtain a pure product. The first acidic reagent is concentrated sulfuric acid or trifluoroacetic acid. Step S12: Using 4-methyl-7-hydroxycoumarin compound (II) and substituted phenylboronic acid (V) as raw materials, a coupling reaction is carried out in the first solvent using a copper catalyst to generate a coumarin derivative containing a substituted phenyl ether structure, i.e., general formula (I). The obtained product is purified by column chromatography to obtain a pure product; the first solvent is one of dichloromethane, methanol, and acetonitrile.

6. The method for preparing coumarin derivatives containing substituted phenyl ether structures according to claim 4, characterized in that: Route 2 specifically includes the following steps: Step S21: Using substituted resorcinol (III) and substituted ethyl acetoacetate (IV) as raw materials, a Pechmann condensation reaction is carried out in a second acidic reagent to generate a 4-methyl-7-hydroxycoumarin compound corresponding to general formula (II). The obtained product is purified by column chromatography or recrystallization to obtain a pure product; the second acidic reagent is concentrated sulfuric acid or trifluoroacetic acid. Step S22: Using 4-methyl-7-hydroxycoumarin compound (II) and diaryliodonium tetrafluoroborate (VI) as raw materials, react with potassium tert-butoxide in a second solvent to generate a coumarin derivative containing o-fluorophenyl ether substitution, i.e., general formula (Ia). The obtained product is purified by column chromatography to obtain a pure product; the second solvent is tetrahydrofuran or acetonitrile.

7. The method for preparing coumarin derivatives containing substituted phenyl ether structures according to claim 4, characterized in that: Route 3 specifically includes the following steps: Step S31: Using substituted m-halophenol (VIII) and substituted ethyl acetoacetate (IV) as raw materials, a Pechmann condensation reaction is carried out in a third acidic reagent to generate a substituted 4-methyl-7-halocoumarin compound corresponding to general formula (VII). The obtained product is purified by column chromatography or recrystallization to obtain a pure product; the third acidic reagent is concentrated sulfuric acid or trifluoroacetic acid. Step S32: Using substituted 4-methyl-7-halocoumarin compound (VII) and substituted phenol (IX) as raw materials, 1-naphthoic acid, cesium carbonate and a complex of copper trifluoromethanesulfonate and benzene are added, and the reaction is carried out in a third solvent to generate a coumarin derivative containing a substituted phenyl ether structure, i.e., general formula (I). The obtained product is purified by column chromatography to obtain a pure product; the third solvent is one of toluene, xylene and N,N-dimethylformamide.

8. The method for preparing coumarin derivatives containing substituted phenyl ether structures according to claim 4, characterized in that: Route 4 specifically includes the following steps: Step S41: Using substituted resorcinol (III) and substituted ethyl acetoacetate (IV) as raw materials, a Pechmann condensation reaction is carried out in a fourth acidic reagent to generate a 4-methyl-7-hydroxycoumarin compound corresponding to general formula (II). The obtained product is purified by column chromatography or recrystallization to obtain a pure product; the fourth acidic reagent is concentrated sulfuric acid, trifluoroacetic acid, etc. Step S42: Using 4-methyl-7-hydroxycoumarin compound (II) and substituted halobenzene (X) as raw materials, potassium carbonate is added and reacted in a fourth solvent to generate a coumarin derivative containing a substituted phenyl ether structure, i.e., general formula (I). The obtained product is purified by column chromatography to obtain a pure product; the fourth solvent is N,N-dimethylformamide or dimethyl sulfoxide.

9. The method for preparing coumarin derivatives containing substituted phenyl ether structures according to claim 4, characterized in that: Route 5 specifically includes the following steps: Using substituted 4-methyl-7-phenylenecoumarin (Ib) as a starting material, it undergoes a halogenation reaction with N-bromosuccinimide in a fifth solvent to generate a 3-bromosubstituted 4-methyl-7-phenylenecoumarin compound corresponding to the general formula (Ic). The obtained product is purified by column chromatography or recrystallization to obtain a pure product; the fifth solvent is dichloromethane or chloroform.

10. The application of a coumarin derivative containing a substituted phenyl ether structure as described in any one of claims 1 to 3, characterized in that: The coumarin derivatives containing substituted phenyl ether structures are applied to agricultural fungicides to prevent and control plant diseases caused by plant pathogenic fungi. The plant pathogenic fungi are selected from the phyla Platycota, Oomycetes, Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetes, and Deuteromycetes.

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