Coumarin derivative containing Schiff base structure as well as preparation method and application of coumarin derivative in resisting plant pathogenic fungi

Abstract

The invention discloses a coumarin derivative containing a Schiff base structure as well as a preparation method and application of the coumarin derivative in resisting plant pathogenic fungi, and belongs to the field of medicinal chemistry. The coumarin derivative containing the Schiff base structure is generated by taking coumarin as a parent and reacting with the Schiff base containing an azomethyl characteristic functional group, and is used for preventing plant fungal infectious diseases. The coumarin derivative containing the Schiff base structure, provided by the invention, has a good inhibition effect on botrytis cinerea, alternaria solani, fusarium oxysporum and alternaria alternata, and can be used as a lead compound for creating a novel agricultural bactericide.

Description

Technical Field

[0001] The invention belongs to the field of medicinal chemistry and relates to a coumarin derivative containing a Schiff base structure, a preparation method thereof and an application thereof in resisting plant pathogenic fungi. Background Art

[0002] In agricultural production, plant pathogenic fungi can cause a variety of epidemic diseases, posing a serious threat to the yield and quality of food and cash crops. Among them, several important soil-borne fungi, including Botrytis cinerea, Alternaria, and Fusarium, have attracted much attention due to the typical infectious disease symptoms they cause. For example, Botrytis cinerea can cause gray mold in grapes, which is characterized by sunken, necrotic lesions on the plant, often accompanied by brown spots, seriously affecting grape yield and quality. To reduce the damage caused by plant pathogenic fungi, chemical fungicides are widely used. However, many chemical fungicides are toxic to humans, insects, and microorganisms that benefit plant growth. Therefore, the discovery and development of new, eco-friendly, and highly effective agricultural fungicides with novel mechanisms of action is a pressing research focus in this field.

[0003] Coumarins are a class of natural secondary metabolites with a benzo-α-pyrone structure, found widely in plants such as the Atractylodes family, Umbelliferae family, and Solanaceae family. Due to their unique heterocyclic structure, coumarin skeletons interact with numerous non-covalent receptors in organisms, resulting in a wide range of pharmacological properties (including antibacterial, antiviral, anticancer, antioxidant, and anti-inflammatory properties), leading to their extensive research and application in the pharmaceutical, pesticide, and food sectors. Furthermore, coumarins exhibit low toxicity, a unique mode of action, resistance to drug resistance, and multiple modification sites, making them common lead compounds in agricultural product research and development.

[0004] Schiff bases are a class of compounds containing a characteristic azomethyl functional group (-C=N-) and are prepared through the nucleophilic condensation reaction of aldehydes or ketones with primary amines. As the most common and widely used organic compound, Schiff bases have been widely used in various fields due to their antifungal, antitumor and anti-inflammatory activities. Schiff bases are synthesized into new compounds by combining drugs or introducing effective groups. These compounds have different connection modes and modes of action, thus showing activity complementarity, reducing drug resistance and enhancing bactericidal effects. Therefore, hybridizing Schiff bases and coumarin into a single molecule provides an important basis for the future development of agricultural chemicals. Summary of the Invention

[0005] To address the above-mentioned technical problems and deficiencies, the present invention provides a coumarin derivative containing a Schiff base structure, a preparation method thereof, and its application against plant pathogenic fungi. The present invention uses coumarin as a matrix and introduces a Schiff base structure to obtain a coumarin derivative containing a Schiff base structure. These Schiff base-containing coumarin derivatives exhibit excellent antifungal activity against Botrytis cinerea and Fusarium oxysporum, opening up new areas for the prevention and treatment of various plant fungal diseases and possessing broad potential for development and application.

[0006] In a first aspect, the present invention provides a coumarin derivative containing a Schiff base structure, having a structure as shown in general formula (I),

[0007]

[0008] wherein R1 is Br;

[0009] R2 is selected from any one of CH3, Cl, F, OCH3;

[0010] R3 is selected from any one of CH3, Br, and F.

[0011] Furthermore, the coumarin derivatives containing a Schiff base structure provided by the present invention have the following structure:

[0012]

[0013]

[0014] In a second aspect, the present invention provides a method for preparing coumarin derivatives containing a Schiff base structure, comprising: dissolving 3-amino-7-hydroxycoumarin in anhydrous methanol or anhydrous ethanol; after heating, adding a methanol or ethanol solution of an aldehyde compound to the 3-amino-7-hydroxycoumarin solution, then adding 1 to 2 drops of glacial acetic acid or acetic acid, and heating to reflux for reaction; after the reaction is completed, collecting the suspended matter, washing, and obtaining a compound.

[0015] Furthermore, in the preparation method of coumarin derivatives containing a Schiff base structure provided by the present invention, the aldehyde compound is selected from any one of 2-hydroxy-5-methylbenzaldehyde, 2-hydroxy-4-methylbenzaldehyde, 4-chloro-2-hydroxybenzaldehyde, 5-fluoro-2-hydroxybenzaldehyde, 4-fluoro-2-hydroxybenzaldehyde, 2-hydroxy-4-methoxybenzaldehyde, 5-bromo-2-hydroxybenzaldehyde, and 3-bromo-2-hydroxybenzaldehyde.

[0016] Furthermore, in the method for preparing coumarin derivatives containing a Schiff base structure provided by the present invention, the molar ratio of the 3-amino-7-hydroxycoumarin to the aldehyde compound is 1:1.5.

[0017] Furthermore, in the method for preparing coumarin derivatives containing a Schiff base structure provided by the present invention, the heating temperature is 40°C.

[0018] Furthermore, in the method for preparing coumarin derivatives containing a Schiff base structure provided by the present invention, the conditions for the heating reflux reaction include: a temperature of 79° C. and a reaction time of 8 hours.

[0019] In a third aspect, the present invention provides a method for controlling plant pathogenic fungi, comprising a coumarin derivative containing a Schiff base structure.

[0020] Furthermore, in the method for controlling plant pathogenic fungi provided by the present invention, the plant pathogenic fungi are Botrytis cinerea or Fusarium oxysporum.

[0021] In a fourth aspect, the present invention provides the use of coumarin derivatives containing a Schiff base structure in the preparation of drugs for preventing and treating gray mold of Korla fragrant pear.

[0022] Compared with the prior art, the technical solution provided by the present invention has at least the following beneficial effects or advantages:

[0023] The present invention generates a series of coumarin derivatives containing a Schiff base structure by reacting coumarin with a Schiff base, which are used in the preparation of antibacterial drugs. The coumarin derivatives containing a Schiff base structure are targeted at fungi including Botrytis cinerea, which causes gray mold in strawberries and tomatoes; Alternaria solani, which causes early blight in tomatoes; Fusarium oxysporum, which causes crop wilt; and Alternaria solani, which causes black mold in tomatoes. The coumarin derivatives containing a Schiff base structure exhibit excellent inhibitory activity against Botrytis cinerea, Alternaria solani, Fusarium oxysporum, and Alternaria solani, and can serve as lead compounds for the development of new agricultural fungicides. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The inhibitory effects of compound 3m and azoxystrobin on Botrytis cinerea.

[0025] Figure 2 The control effect of compound 3m and myclobutanil on gray mold of Korla pear. DETAILED DESCRIPTION

[0026] The technical solutions of the present invention are described below with reference to the following examples. However, the present invention is not limited to the following examples. The experimental methods and detection methods described in each example are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0027] Preparation Example

[0028] This preparation example provides the synthesis methods of some intermediates and compounds. The synthesis methods of the remaining intermediates and compounds are similar and can be easily synthesized. The specific synthesis routes are shown below.

[0029] Compound 3 is 3-amino-7-hydroxycoumarin. The H NMR spectrum of compound 3 is ( 1 H NMR) characterization results are: 1 H NMR (600MHz, Methanol-d4): δ7.19 (d, J = 8.5 Hz, 1H), 6.80 (s, 1H), 6.72 (dd, J = 8.5, 2.4 Hz, 1H), 6.67 (d, J = 2.4 Hz, 1H).

[0030] The C NMR spectrum of compound 3 ( 13 C NMR) characterization results are: 13 C NMR (150MHz, Methanol-d4): δ161.69, 158.27, 151.53, 131.23, 127.19, 115.21, 114.32, 113.71, 103.09.

[0031] Synthesis of compound 3a ((E)-7-hydroxy-3-((2-hydroxy-5-methylphenylene)amino)coumarin):

[0032]

[0033] Using ultrasound, 0.1770 g (1 mmol) of 3-amino-7-hydroxycoumarin was dissolved in 20 mL of anhydrous methanol. At 40°C, 0.2041 g (1.5 mmol) of 2-hydroxy-5-methylbenzaldehyde dissolved in 10 mL of anhydrous methanol was added dropwise to the 3-amino-7-hydroxycoumarin solution in a round-bottom flask. 0.05 mL of glacial acetic acid was then added, and the mixture was stirred and refluxed at 79°C for 8 hours. The reaction progress was monitored by TLC, during which the solution turned from colorless to orange and solid precipitated. The reaction was stopped, cooled to room temperature, and the product was washed with methanol, filtered, and dried to obtain the pure product, an orange solid, (E)-7-hydroxy-3-((2-hydroxy-5-methylphenylene)amino)coumarin, with a yield of 65.45% and a melting point of 242-245°C.

[0034] The H NMR spectrum of compound 3a ( 1 H NMR) characterization results are: 1H NMR (400MHz, DMSO-d6): δ12.58(s,1H),10.62(s,1H),9.17(s,1H),8.02(s,1H),7.56(d,J=8.5Hz,1H),7 .40(d,J=2.2Hz,1H),7.22(dd,J=8.3,2.0Hz,1H),6.88–6.82(m,2H),6.77(d,J=2.2Hz,1H),2.27(s,3H).

[0035] The C NMR spectrum of compound 3a ( 13 C NMR) characterization results are: 13 C NMR (101MHz, DMSO-d6): δ163.82,161.08,158.20,158.05,153.80,134.37,131.93 ,131.61,129.92,129.41,127.86,119.08,116.60,113.75,111.67,101.96,19.89.

[0036] The synthesis of compound 3b ((E)-7-hydroxy-3-((2-hydroxy-4-methylphenylene)amino)coumarin) was based on the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced by 2-hydroxy-4-methylbenzaldehyde; anhydrous methanol was replaced by anhydrous ethanol; and glacial acetic acid was replaced by acetic anhydride.

[0037] The structure of compound 3b is:

[0038] The H NMR spectrum of compound 3b ( 1 H NMR) characterization results are: 1 H NMR (400MHz, DMSO-d6): δ12.93(s,1H),10.60(s,1H),9.17(s,1H),8.01(s,1H),7.55(d,J=8.5Hz,1H),7.4 8(d,J=8.1Hz,1H), 6.83(dd,J=8.5,2.3Hz,1H), 6.79(d,J=7.7Hz,2H), 6.77(d,J=2.2Hz,1H), 2.31(s,3H).

[0039] The C NMR spectrum of compound 3b ( 13 C NMR) characterization results are: 13C NMR (101MHz, DMSO-d6): δ163.72,161.01,160.49,158.11,153.75,144.39,132.26 ,131.24,131.21,129.85,129.31,120.42,117.00,113.73,111.68,101.96,21.47.

[0040] The synthesis of compound 3c ((E)-7-hydroxy-3-((5-chloro-2-hydroxybenzylidene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 5-chloro-2-hydroxybenzaldehyde.

[0041] The structure of compound 3c is

[0042] The H NMR spectrum of compound 3c ( 1 H NMR) characterization results are: 1 H NMR (600MHz, DMSO-d6): δ12.73(s,1H),10.68(s,1H),9.26(s,1H),8.07(s,1H),7.74(d,J=2.8Hz,1H),7.59(d,J= 8.5Hz, 1H), 7.44 (dd, J=8.8, 2.7Hz, 1H), 7.00 (d, J=8.8Hz, 1H), 6.85 (dd, J=8.5, 2.3Hz, 1H), 6.78 (d, J=2.3Hz, 1H).

[0043] The C NMR spectrum of compound 3c ( 13 C NMR) characterization results are: 13 C NMR (151MHz, DMSO-d6): δ161.91,161.35,158.87,157.90,153.95,132.95,132 .78,130.34,130.11,128.97,122.75,120.97,118.76,113.84,111.61,102.00.

[0044] The synthesis of compound 3d ((E)-7-hydroxy-3-((4-chloro-2-hydroxybenzylidene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 4-chloro-2-hydroxybenzaldehyde.

[0045] The structure of compound 3d is

[0046] The H NMR spectrum of compound 3d ( 1 H NMR) characterization results are:1 H NMR (400MHz, DMSO-d6): δ13.25(s,1H),10.66(s,1H),9.26(s,1H),8.08(s,1H),7.67(d,J=8.2Hz, 1H),7.58(d,J=8.6Hz,1H),7.05–7.02(m,2H),6.85(dd,J=8.5,2.3Hz,1H),6.78(d,J=2.2Hz,1H).

[0047] The C NMR spectrum of compound 3d ( 13 C NMR) characterization results are: 13 C NMR (101MHz, DMSO-d6) δ162.58,161.28,161.16,157.95,153.89,137.70,133. 37,132.27,130.05,128.80,119.58,118.59,116.63,113.83,111.60,102.00.

[0048] The synthesis of compound 3e ((E)-7-hydroxy-3-((5-chloro-2,4-dihydroxyphenylene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 5-chloro-2,4-dihydroxybenzaldehyde.

[0049] The structure of compound 3e is

[0050] The H NMR spectrum of compound 3e ( 1 H NMR) characterization results are: 1 H NMR (600MHz, DMSO-d6): δ10.87(s,1H),10.60(s,1H),9.97(s,1H),9.05(s,1H),7.94(s,1H),7.5 9(s,1H),7.23(d,J=8.4Hz,1H),6.83(dd,J=8.5,2.3Hz,1H),6.77(d,J=2.2Hz,1H),6.58(s,1H).

[0051] The C NMR spectrum of compound 3e ( 13 C NMR) characterization results are: 13C NMR (151MHz, DMSO-d6): δ161.41,160.00,159.06,156.18,153.66,149.37,132 .75,130.29,129.77,125.80,116.07,113.76,113.01,112.28,103.57,101.89.

[0052] The synthesis of compound 3f ((E)-7-hydroxy-3-((5-fluoro-2-hydroxyphenylene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 5-fluoro-2-hydroxybenzaldehyde.

[0053] The structure of compound 3f is

[0054] The H NMR spectrum of compound 3f ( 1 H NMR) characterization results are: 1 H NMR (600MHz, DMSO-d6): δ12.47(s,1H),10.68(s,1H),9.26(s,1H),8.06(s,1H),7.59(d,J=8.5Hz,1H),7.51(dd,J=9.0, 3.2Hz, 1H), 7.28 (td, J = 8.7, 3.2Hz, 1H), 6.98 (dd, J = 9.0, 4.5Hz, 1H), 6.84 (dd, J = 8.5, 2.3Hz, 1H), 6.78 (d, J = 2.2Hz, 1H).

[0055] The C NMR spectrum of compound 3f ( 13 C NMR) characterization results are: 13 C NMR (151MHz, DMSO-d6): δ162.19,161.35,159.06,157.94,156.51,156.16,155.84,153.95,149.36,132.90, 130.29,130.13,129.00,125.79,118.20,118.15,116.47,116.32,113.86,113.00,111.67,109.86,102.02.

[0056] The synthesis of compound 3g ((E)-7-hydroxy-3-((4-fluoro-2-hydroxyphenylene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 4-fluoro-2-hydroxybenzaldehyde.

[0057] The structure of compound 3g is

[0058] The H NMR spectrum of compound 3g ( 1 H NMR) characterization results are: 1 H NMR (400MHz, DMSO-d6): δ13.51(s,1H),10.64(s,1H),9.23(s,1H),8.05(s,1H),7.73–7.67(m,1H),7.56 (d, J = 8.5 Hz, 1H), 6.84 (dd, J = 5.6, 2.8 Hz, 1H), 6.82 (d, J = 3.2 Hz, 1H), 6.79 (s, 1H), 6.77 (d, J = 2.3 Hz, 1H).

[0059] The C NMR spectrum of compound 3g ( 13 C NMR) characterization results are: 13 C NMR (101MHz, DMSO-d6): δ166.41,163.91,162.95,162.68,161.18,158.01,153.83,134.49,131 .77,131.74,129.95,128.81,116.58,113.80,111.59,107.12,106.89,103.82,103.60,101.99.

[0060] The synthesis of compound 3h ((E)-7-hydroxy-3-((2-hydroxy-4-methoxyphenylene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced by 2-hydroxy-4-methoxybenzaldehyde.

[0061] The structure of compound 3h is

[0062] H NMR spectrum of compound 3h ( 1 H NMR) characterization results are: 1 H NMR (400MHz, DMSO-d6): δ13.47(s,1H),10.57(s,1H),9.10(s,1H),7.97(s,1H),7.54(d,J=8.5Hz,1H),7.49(d,J=8.7Hz, 1H), 6.82 (dd, J = 8.5, 2.3Hz, 1H), 6.76 (d, J = 2.2Hz, 1H), 6.55 (dd, J = 8.7, 2.4Hz, 1H), 6.48 (d, J = 2.4Hz, 1H), 3.80 (s, 3H).

[0063] The C NMR spectrum of compound 3h ( 13 C NMR) characterization results are: 13C NMR (101MHz, DMSO-d6): δ163.95,163.35,163.10,160.81,158.20,153.59,134.01 ,130.30,129.68,129.22,113.70,113.03,111.73,107.14,101.98,100.91,55.52.

[0064] The synthesis of compound 3i ((E)-7-hydroxy-3-((5-bromo-2-hydroxybenzylidene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 5-bromo-2-hydroxybenzaldehyde.

[0065] The structure of compound 3i is

[0066] The H NMR spectrum of compound 3i ( 1 H NMR) characterization results are: 1 H NMR (400MHz, DMSO-d6): δ12.73(s,1H),10.66(s,1H),9.24(s,1H),8.04(s,1H),7.84(d,J=2.6Hz,1H),7.57(d,J= 8.6Hz, 1H), 7.53 (dd, J=8.8, 2.6Hz, 1H), 6.93 (d, J=8.8Hz, 1H), 6.84 (dd, J=8.5, 2.2Hz, 1H), 6.77 (d, J=2.2Hz, 1H).

[0067] The C NMR spectrum of compound 3i ( 13 C NMR) characterization results are: 13 C NMR (101MHz, DMSO-d6): δ161.78,161.34,159.26,157.89,153.94,135.69,133 .28,132.71,130.09,128.96,121.58,119.17,113.83,111.60,110.13,102.00.

[0068] The synthesis of compound 3j ((E)-7-hydroxy-3-((2,5-dihydroxybenzylidene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced by 2,5-dihydroxybenzaldehyde.

[0069] The structure of compound 3j is

[0070] The H NMR spectrum of compound 3j ( 1 H NMR) characterization results are:1 H NMR (600MHz, DMSO-d6) δ12.04(s,1H),10.62(s,1H),9.13(s,1H),9.11(s,1H),8.01(s,1H),7.56(d,J=8.4Hz,1H),6.99 (d, J=3.0Hz, 1H), 6.87 (dd, J=8.8, 3.0Hz, 1H), 6.83 (dd, J=8.5, 2.2Hz, 1H), 6.80 (d, J=8.8Hz, 1H), 6.77 (d, J=2.2Hz, 1H).

[0071] The C NMR spectrum of compound 3j ( 13 C NMR) characterization results are: 13 C NMR(151MHz,DMSO-d6)δ163.52,161.02,158.14,153.81,153.26,149.72,131. 19,129.89,129.80,121.55,119.42,117.41,116.33,113.75,111.72,102.00.

[0072] The synthesis of compound 3k ((E)-7-hydroxy-3-((5-chloro-2-(trifluoromethyl)phenylene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 5-chloro-2-(trifluoromethyl)benzaldehyde.

[0073] The structure of compound 3k is

[0074] H NMR spectrum of compound 3k ( 1 H NMR) characterization results are: 1 H NMR (600MHz, DMSO-d6): δ10.66(s,1H),9.24(s,1H),8.07(s,1H),7.71(dd,J=8.4,6.7Hz,1 H),7.57(d,J=8.5Hz,1H),6.84(t,J=2.8Hz,1H),6.78(d,J=2.4Hz,1H),6.70–6.64(m,2H).

[0075] The C NMR spectrum of compound 3k ( 13 C NMR) characterization results are: 13C NMR(151MHz,DMSO-d6)δ163.44,161.64,159.48,158.50,156.60,154.30,132.22, 130.72,130.44,129.30,126.22,114.28,113.43,112.07,110.30,102.48,102.31.

[0076] The synthesis of compound 31 ((E)-7-hydroxy-3-((4-bromo-2-hydroxybenzylidene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced by 4-bromo-2-hydroxybenzaldehyde.

[0077] The structure of compound 31 is

[0078] The H NMR spectrum of compound 3l ( 1 H NMR) characterization results are: 11 H NMR (400MHz, DMSO-d6): δ9.24 (s, 1H), 8.06 (s, 1H), 7.57 (t, J = 8.4Hz, 2H), 7.18–7.14 (m, 2H), 6.83 (dd, J = 8.5, 2.3Hz, 1H), 6.76 (d, J = 2.2Hz, 1H).

[0079] The C NMR spectrum of compound 3l ( 13 C NMR) characterization results are: 13 C NMR (101MHz, DMSO-d6): δ162.62,161.31,161.06,157.94,153.90,133.40,132 .33,130.06,128.81,126.63,122.44,119.60,118.88,113.85,111.61,102.01.

[0080] The synthesis of compound 3m ((E)-7-hydroxy-3-((3-bromo-2-hydroxybenzylidene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 3-bromo-2-hydroxybenzaldehyde.

[0081] The structure of compound 3m is

[0082] H NMR spectrum of compound 3m ( 1 H NMR) characterization results are: 1H NMR (400MHz, DMSO-d6): δ10.71(s,1H),9.28(s,1H),8.18(s,1H),7.72(dd,J=7.9,1.5Hz,1H),7.62(dd,J=7.8 ,1.6Hz,1H),7.58(d,J=8.5Hz,1H),6.94(t,J=7.8Hz,1H),6.86(dd,J=8.5,2.3Hz,1H),6.78(d,J=2.2Hz,1H).

[0083] The C NMR spectrum of compound 3m ( 13 C NMR) characterization results are: 13 C NMR (101MHz, DMSO-d6) δ163.46,161.54,157.87,157.45,154.01,136.30,132. 80,132.35,130.20,127.57,120.23,120.04,113.94,111.48,110.13,102.07.

[0084] The synthesis of compound 3n ((E)-7-hydroxy-3-((2-chloro-4-fluorophenylene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 2-chloro-4-fluorobenzaldehyde.

[0085] The structure of compound 3n is

[0086] The H NMR spectrum of compound 3n ( 1 H NMR) characterization results are: 1 H NMR (400MHz, DMSO-d6): δ10.63(s,1H),9.47(s,1H),8.19(dd,J=8.9,6.4Hz,1H),7.96(s,1H),7.5 9 (d, J = 8.6 Hz, 2H), 7.37 (td, J = 8.5, 2.6 Hz, 1H), 6.82 (dd, J = 8.5, 2.3 Hz, 1H), 6.75 (d, J = 2.2 Hz, 1H).

[0087] The C NMR spectrum of compound 3n ( 13 C NMR) characterization results are: 13C NMR (101MHz, DMSO-d6): δ165.39,162.87,161.72,158.19,156.87,154.24,136.72,136.61,135 .87,130.71,130.49,130.33,130.23,117.92,117.67,116.02,115.80,114.15,112.32,102.29.

[0088] The synthesis of compound 3o ((E)-7-hydroxy-3-((2-bromo-4-fluorophenylene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the starting material 2-hydroxy-5-methylbenzaldehyde was replaced with 2-bromo-4-fluorobenzaldehyde.

[0089] The structure of compound 3o is

[0090] The H NMR spectrum of compound 3o ( 1 H NMR) characterization results are: 1 H NMR (400MHz, DMSO-d6): δ10.63(s,1H),9.44(s,1H),8.17(dd,J=8.9,6.4Hz,1H),7.96(s,1H),7.73(dd,J=8 .6, 2.6Hz, 1H), 7.60 (d, J = 8.6Hz, 1H), 7.44–7.39 (m, 1H), 6.83 (dd, J = 8.5, 2.3Hz, 1H), 6.76 (d, J = 2.2Hz, 1H).

[0091] The C NMR spectrum of compound 3o ( 13 C NMR) characterization results are: 13 C NMR: (101MHz, DMSO-d6): δ161.29,158.72,157.73,153.80,135.67,131.19,131 .15,130.14,130.06,120.52,120.27,115.94,115.72,113.71,111.89,101.85.

[0092] The synthesis of compound 3p ((E)-7-hydroxy-3-((4-bromo-2-chlorophenylene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 4-bromo-2-chlorobenzaldehyde.

[0093] The structure of compound 3p is

[0094] The H NMR spectrum of compound 3p ( 1H NMR) characterization results are: 1 H NMR (600MHz, DMSO-d6): δ10.67(s,1H),9.49(s,1H),8.05(d,J=8.5Hz,1H),8.00(s,1H),7.88(d,J=1. 9Hz, 1H), 7.70–7.67 (m, 1H), 7.60 (d, J = 8.5Hz, 1H), 6.82 (dd, J = 8.5, 2.3Hz, 1H), 6.75 (d, J = 2.2Hz, 1H).

[0095] The C NMR spectrum of compound 3p ( 13 C NMR) characterization results are: 13 C NMR (151MHz, DMSO-d6): δ161.47,157.72,156.51,153.91,132.39,131.26, 131.14,131.01,130.22,129.23,125.78,125.56,113.80,111.93,101.89.

[0096] The synthesis of compound 3q ((E)-7-hydroxy-3-((4-bromo-2-fluorophenylene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the starting material 2-hydroxy-5-methylbenzaldehyde was replaced with 4-bromo-2-fluorobenzaldehyde.

[0097] The structure of compound 3q is

[0098] The H NMR spectrum of compound 3q ( 1 H NMR) characterization results are: 1 H NMR (400MHz, DMSO-d6): δ10.64(s,1H),9.31(s,1H),8.03–7.97(m,2H),7.74(dd,J=10 .2,1.9Hz,1H),7.61–7.56(m,2H),6.83(dd,J=8.5,2.3Hz,1H),6.76(d,J=2.3Hz,1H).

[0099] The C NMR spectrum of compound 3q ( 13 C NMR) characterization results are: 13 C NMR (101MHz, DMSO-d6): δ163.06,161.28,160.50,157.71,153.81,135.08,130 .06,128.63,128.40,123.08,122.99,119.80,119.56,113.72,111.86,101.85.

[0100] The synthesis of compound 3r ((E)-7-hydroxy-3-((3-bromo-4-fluorobenzylidene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 3-bromo-4-fluorobenzaldehyde.

[0101] The structure of compound 3r is

[0102] The H NMR spectrum of compound 3r ( 1 H NMR) characterization results are: 1 H NMR (600MHz, DMSO-d6) δ10.61(s,1H),9.04(s,1H),8.23(dd,J=6.9,2.1Hz,1H),7.96(ddd,J=8.6,5.0,2.1Hz,1H ), 7.89 (s, 1H), 7.56 (d, J = 8.5Hz, 1H), 7.54 (t, J = 8.6Hz, 1H), 6.83 (dd, J = 8.5, 2.3Hz, 1H), 6.76 (d, J = 2.3Hz, 1H).

[0103] The C NMR spectrum of compound 3r ( 13 C NMR) characterization results are: 13 C NMR(151MHz,DMSO-d6)δ161.04,160.94,159.41,157.81,153.75,134.31,133.49,133. 17,130.96,130.23,129.85,117.52,117.37,113.68,111.83,109.03,108.88,101.90.

[0104] The synthesis of compound 3s ((E)-7-hydroxy-3-((3-chloro-4-fluorophenylene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the starting material 2-hydroxy-5-methylbenzaldehyde was replaced with 3-chloro-4-fluorobenzaldehyde.

[0105] The structure of compound 3s is

[0106] The H NMR spectrum of compound 3s ( 1 H NMR) characterization results are: 1H NMR (400MHz, DMSO-d6): δ9.05(s,1H),8.10(dd,J=7.4,2.0Hz,1H),7.93(ddd,J=8.7,4.9,2.1Hz,1H),7.8 8(s,1H),7.58(d,J=7.3Hz,1H),7.55(d,J=1.8Hz,1H),6.82(dd,J=8.5,2.3Hz,1H),6.76(d,J=2.2Hz,1H).

[0107] The C NMR spectrum of compound 3s ( 13 C NMR) characterization results are: 13 C NMR (101MHz, DMSO-d6) δ161.04,160.28,159.46,157.76,153.73,134.00,133.61,130. 86,130.19,129.83,129.54,120.57,120.38,117.71,117.49,113.66,111.80,101.87.

[0108] The synthesis of compound 3t ((E)-7-hydroxy-3-((3-chloro-4-(1H-imidazol-1-yl)phenylene)amino)coumarin) was similar to that of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 3-chloro-4-(1H-imidazol-1-yl)benzaldehyde.

[0109] The structure of compound 3t is

[0110] The H NMR spectrum of compound 3t ( 1 H NMR) characterization results are: 1 H NMR (600MHz, DMSO-d6) δ10.66(s,1H),9.19(s,1H),8.21(d,J=2.0Hz,1H),7.98(s,1H),7.71(d,J=8.2Hz,1H),7.60( d,J=8.5Hz,1H),7.23(d,J=8.4Hz,1H),7.16(s,2H),6.85(dd,J=8.5,2.3Hz,1H),6.78(d,J=2.3Hz,1H),6.69(s,1H).

[0111] The C NMR spectrum of compound 3t ( 13 C NMR) characterization results are: 13C NMR(151MHz,DMSO-d6)δ159.03,156.14,149.34,137.74,131.56,130.26,130.03, 129.13,128.90,128.83,125.76,120.79,113.54,112.98,109.85,101.92,101.86.

[0112] The synthesis of compound 3u ((E)-7-hydroxy-3-(((5-phenylthiophen-2-yl)methylene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 5-phenylthiophene-2-carboxaldehyde.

[0113] The structure of compound 3u is

[0114] The H NMR spectrum of compound 3u ( 1 H NMR) characterization results are: 1 H NMR (400MHz, DMSO-d6): δ10.58(s,1H),9.28(s,1H),7.88(s,1H),7.77(d,J=7.0Hz,2H),7.72(d,J=3.9Hz,1H),7.64(d,J=3.9H z, 1H), 7.57 (d, J = 8.6Hz, 1H), 7.47 (t, J = 7.5Hz, 2H), 7.39 (t, J = 7.4Hz, 1H), 6.83 (dd, J = 8.5, 2.3Hz, 1H), 6.76 (d, J = 2.2Hz, 1H).

[0115] The C NMR spectrum of compound 3u ( 13 C NMR) characterization results are: 13 C NMR (101MHz, DMSO-d6): δ160.91,157.90,155.05,153.50,148.20,141.93,135.24,135.21,134 .04,133.99,133.09,130.28,129.74,129.28,128.77,125.79,124.88,113.63,112.07,101.82.

[0116] The synthesis of compound 3v ((E)-7-hydroxy 3-(((5-methylthiophen-2-yl)methylene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 5-methylthiophene-2-carboxaldehyde.

[0117] The structure of compound 3v is

[0118] H NMR spectrum of compound 3v ( 1 H NMR) characterization results are: 1 H NMR (600MHz, DMSO-d6): δ10.52(s,1H),8.35(s,1H),8.01(s,1H),7.88(d,J=2.5Hz,1H),7.02(dd,J=3 .7, 1.3Hz, 1H), 6.72 (t, J = 3.3Hz, 1H), 6.36 (dd, J = 8.7, 2.4Hz, 1H), 6.27 (d, J = 2.4Hz, 1H), 3.15 (s, 3H).

[0119] The C NMR spectrum of compound 3v ( 13 C NMR) characterization results are: 13 C NMR (151MHz, DMSO-d6): δ164.76,162.38,158.97,157.40,140.78,139.16 ,138.96,128.19,120.37,116.60,115.85,114.16,108.90,103.36,23.30.

[0120] The synthesis of compound 3w ((E)-7-hydroxy 3-(((5-bromothiophen-2-yl)methylene)amino)coumarin) was carried out with reference to the synthesis of compound 3a, except that the raw material 2-hydroxy-5-methylbenzaldehyde was replaced with 5-bromothiophene-2-carboxaldehyde.

[0121] The structure of compound 3w is

[0122] The H NMR spectrum of compound 3w ( 1 H NMR) characterization results are: 1 H NMR (600MHz, DMSO-d6): δ9.03(s,1H),7.70(d,J=1.3Hz,1H),7.67(s,1H),7.52(d,J= 1.5Hz, 1H), 7.36 (d, J = 8.5Hz, 1H), 6.60 (dd, J = 8.5, 2.3Hz, 1H), 6.54 (d, J = 2.2Hz, 1H).

[0123] The C NMR spectrum of compound 3w ( 13 C NMR) characterization results are: 13C NMR (151MHz, DMSO-d6): δ161.34,158.04,154.26,153.85,144.04,135.31,134.98,130.19,129.96,129.16,113.96,112.11,110.05,102.03.

[0124] Compound 8 is 4-methyl-7-hydroxy-8-aldehyde coumarin. The H NMR spectrum of compound 8 is ( 1 H NMR) characterization results are: 1 H NMR (600MHz, Chloroform-d): δ12.20 (s, 1H), 10.60 (s, 1H), 7.72 (d, J = 9.0 Hz, 1H), 6.90 (d, J = 9.0 Hz, 1H), 6.20 (s, 1H), 2.42 (s, 3H).

[0125] The C NMR spectrum of compound 8 ( 13 C NMR) characterization results are: 13 C NMR (151MHz, Chloroform-d): δ193.55, 165.40, 159.35, 156.28, 152.80, 133.04, 114.42, 112.20, 108.80, 105.29, 19.09.

[0126] Synthesis of compound 8a ((E)-7-hydroxy-4-methyl-8-((o-toluimido)methyl)coumarin):

[0127]

[0128] Using ultrasound, 0.2448 g (1.2 mmol) of 4-methyl-7-hydroxy-8-formylcoumarin was dissolved in 20 mL of anhydrous methanol. At 40°C, 0.1071 g (1 mmol) of o-methylaniline dissolved in 10 mL of anhydrous methanol was added dropwise to the 4-methyl-7-hydroxy-8-formylcoumarin solution in a round-bottom flask. 0.05 mL of acetic acid was then added, and the mixture was stirred and refluxed at 79°C for 8 hours. The reaction progress was monitored by TLC, during which the solution changed from colorless to orange with the precipitation of solids. The reaction was terminated, cooled to room temperature, and the product was washed with methanol, filtered, and dried to obtain the pure orange product, (E)-7-hydroxy-4-methyl-8-((o-toluylimino)methyl)coumarin, with a yield of 76.88% and a melting point of 169-171°C.

[0129] H NMR spectrum of compound 8a ( 1 H NMR) characterization results are: 1H NMR (600MHz, Chloroform-d): δ15.45(s,1H),9.32(s,1H),7.58(dd,J=9.0,2.0Hz,1H),7.30(d,J=4.3Hz,2H),7.27(d,J=8 .1Hz,1H),7.25–7.21(m,1H),6.91(dd,J=9.0,2.0Hz,1H),6.13(d,J=2.0Hz,1H),2.46–2.42(m,3H),2.42(d,J=1.8Hz,3H).

[0130] The C NMR spectrum of compound 8a ( 13 C NMR) characterization results are: 13 C NMR (151MHz, Chloroform-d): δ167.63,160.41,155.97,154.71,153.43,145.16,132.28, 131.07,129.50,127.82,127.38,118.12,115.37,110.96,110.90,107.03,19.11,18.35.

[0131] The synthesis of compound 8b ((E)-7-hydroxy-4-methyl-8-(((2-methoxyphenyl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with o-anisidine.

[0132] The structure of compound 8b is

[0133] The H NMR spectrum of compound 8b ( 1 H NMR) characterization results are: 1 H NMR (400MHz, Chloroform-d): δ9.35 (s, 1H), 7.55 (d, J = 7.4Hz, 1H), 7.46 (dd, J = 7.9, 1.5Hz, 1H), 7.30 (t, J = 7.7Hz, 1H),7.08–7.02(m,1H),7.01(dd,J=8.2,1.2Hz,1H),6.81(d,J=8.2Hz,1H),6.06(s,1H),3.96(s,3H),2.39(s,3H).

[0134] The C NMR spectrum of compound 8b ( 13 C NMR) characterization results are: 13C NMR (101MHz, Chloroform-d): δ162.36,160.67,156.31,153.65,153.56,152.44,132 .40,129.88,124.27,121.29,118.63,114.39,113.88,111.95,110.19,56.18,19.14.

[0135] The synthesis of compound 8c ((E)-7-hydroxy-4-methyl-8-(((2,3-dimethylphenyl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with 2,3-dimethylaniline.

[0136] The structure of compound 8c is

[0137] H NMR spectrum of compound 8c ( 1 H NMR) characterization results are: 1 H NMR (400MHz, DMSO-d6): δ9.69(s,1H),9.17(s,1H),7.76(d,J=9.0Hz,1H),7.17(d,J=7.9Hz,1H),6.9 1(d,J=1.6Hz,1H),6.88(d,J=2.0Hz,1H),6.22(d,J=1.3Hz,1H),2.40(d,J=1.2Hz,3H),2.15(s,3H).

[0138] The C NMR spectrum of compound 8c ( 13 C NMR) characterization results are: 13 C NMR (101MHz, Chloroform-d): δ167.85,160.44,156.26,154.72,153.43,145.33,138.18,130 .52,129.34,128.69,126.64,118.71,116.33,115.46,110.90,110.80,20.47,19.10,14.18.

[0139] The synthesis of compound 8d ((E)-7-hydroxy-4-methyl-8-(((3-hydroxy-2-methylphenyl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with 3-hydroxy-2-methylaniline.

[0140] The structure of compound 8d is

[0141] The H NMR spectrum of compound 8d ( 1H NMR) characterization results are: 1 H NMR (400MHz, DMSO-d6): δ9.65(s,1H),9.10(d,J=1.7Hz,1H),7.76(d,J=9.0Hz,1H),7.12(t,J=8.0Hz,1H),6.9 1(d,J=4.6Hz,1H),6.89(d,J=5.9Hz,1H),6.82(d,J=8.0Hz,1H),6.21(s,1H),2.40–2.36(m,3H),2.17(s,3H).

[0142] The C NMR spectrum of compound 8d ( 13 C NMR) characterization results are: 113 C NMR (101MHz, DMSO-d6): δ166.34,159.16,156.06,155.99,154.11,154.04,146.07,13 0.53,127.08,117.97,114.51,113.96,110.59,110.25,109.08,106.15,18.39,10.28.

[0143] The synthesis of compound 8e ((E)-7-hydroxy-4-methyl-8-(((3-hydroxy-4-methylphenyl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with 3-hydroxy-4-methylaniline.

[0144] The structure of compound 8e is

[0145] The H NMR spectrum of compound 8e ( 1 H NMR) characterization results are: 1 H NMR (400MHz, DMSO-d6): δ9.69(s,1H),9.17(s,1H),7.76(d,J=9.0Hz,1H),7.17(d,J=7.9Hz,1H),6.9 1(d,J=1.6Hz,1H),6.88(d,J=2.0Hz,1H),6.22(d,J=1.3Hz,1H),2.40(d,J=1.2Hz,3H),2.15(s,3H).

[0146] The C NMR spectrum of compound 8e ( 13 C NMR) characterization results are: 13C NMR (101MHz, DMSO-d6): δ166.00,159.18,156.25,154.92,154.06,154.02,144.28,13 1.40,130.34,124.28,114.43,112.45,110.67,110.18,106.33,106.02,18.35,15.74.

[0147] The synthesis of compound 8f ((E)-7-hydroxy-4-methyl-8-(((3-chloro-4-methylphenyl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with 3-chloro-4-methylaniline.

[0148] The structure of compound 8f is

[0149] The H NMR spectrum of compound 8f ( 1 H NMR) characterization results are: 1 H NMR (600MHz, Chloroform-d): δ14.77(s,1H),9.31(s,1H),7.58(d,J=8.8Hz,1H),7.38(d,J=2.2Hz,1H),7.28 (d,J=8.0Hz,1H),7.18(dd,J=8.1,2.2Hz,1H),6.91(d,J=8.8Hz,1H),6.14(s,1H),2.41(s,3H),2.40(s,3H).

[0150] The C NMR spectrum of compound 8f ( 13 C NMR) characterization results are: 13 C NMR (151MHz, Chloroform-d): δ166.07,160.30,156.80,154.54,153.33,145.88,135.72, 135.33,131.76,129.45,122.08,119.76,114.80,111.43,111.26,107.04,19.89,19.09.

[0151] The synthesis of compound 8g ((E)-7-hydroxy-4-methyl-8-(((3-fluoro-4-methylphenyl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with 3-fluoro-4-methylaniline.

[0152] The structure of compound 8g is

[0153] The H NMR spectrum of compound 8g ( 1H NMR) characterization results are: 1 H NMR (400MHz, Chloroform-d): δ9.32(s,1H),7.58(d,J=8.8Hz,1H),7.23(d,J=8.0Hz,1H),7.10–7.0 6 (m, 2H), 6.92 (d, J = 8.9 Hz, 1H), 6.14 (d, J = 1.4 Hz, 1H), 2.42 (d, J = 1.2 Hz, 3H), 2.31 (d, J = 2.0 Hz, 3H).

[0154] The C NMR spectrum of compound 8g ( 13 C NMR) characterization results are: 13 C NMR (101MHz, Chloroform-d): δ168.20,160.52,154.75,154.71,153.49,142.12,137.96, 132.19,131.85,129.36,127.96,117.70,115.61,110.78,110.66,106.98,21.17,18.28.

[0155] The synthesis of compound 8h ((E)-7-hydroxy-4-methyl-8-(((2,4-dimethylphenyl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with 2,4-dimethylaniline.

[0156] The structure of compound 8h is

[0157] H NMR spectrum of compound 8h ( 1 H NMR) characterization results are: 1 H NMR (400MHz, Chloroform-d): δ9.31(s,1H),7.56(d,J=9.0Hz,1H),7.24(d,J=8.7Hz,1H),7.10(d ,J=6.5Hz,2H),6.90(d,J=9.0Hz,1H),6.12(d,J=1.3Hz,1H),2.41(d,J=1.5Hz,6H),2.36(s,3H).

[0158] The C NMR spectrum of compound 8h ( 13 C NMR) characterization results are: 13C NMR (101MHz, Chloroform-d): δ162.80,160.15,156.57,154.43,153.18,146.10,132.07,132 .01,129.27,124.56,124.38,116.79,114.71,111.10,108.46,108.22,18.94,14.37,14.34.

[0159] The synthesis of compound 8i ((E)-7-hydroxy-4-methyl-8-(((2-chloro-4-methylphenyl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with 2-chloro-4-methylaniline.

[0160] The structure of compound 8i is

[0161] H NMR spectrum of compound 8i ( 1 H NMR) characterization results are: 1 H NMR (400MHz, Chloroform-d): δ9.39(s,1H),7.60(d,J=8.9Hz,1H),7.37(d,J=8.2Hz,1H),7.33(d,J=1.0Hz ,1H),7.19–7.15(m,1H),6.96(d,J=8.9Hz,1H),6.15(d,J=1.3Hz,1H),2.43(d,J=1.2Hz,3H),2.38(s,3H).

[0162] The C NMR spectrum of compound 8i ( 13 C NMR) characterization results are: 13 C NMR (101MHz, Chloroform-d): δ166.21,160.40,156.11,154.61,153.42,141.29,139.32, 130.84,129.84,129.49,128.76,118.93,114.99,111.38,111.19,107.24,21.08,19.13.

[0163] The synthesis of compound 8j ((E)-7-hydroxy-4-methyl-8-(((2-chloro-4-fluorophenyl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with 2-chloro-4-fluoroaniline.

[0164] The structure of compound 8j is

[0165] The H NMR spectrum of compound 8j (1 H NMR) characterization results are: 1 H NMR (400MHz, Chloroform-d): δ9.35(s,1H),7.61(d,J=8.9Hz,1H),7.43(dd,J=8.9,5.3Hz,1H),7.28–7.25(m ,1H),7.10(ddd,J=9.0,7.7,2.8Hz,1H),6.96(d,J=8.9Hz,1H),6.15(d,J=1.3Hz,1H),2.43(d,J=1.2Hz,3H).

[0166] The C NMR spectrum of compound 8j ( 13 C NMR) characterization results are: 13 C NMR (101MHz, Chloroform-d): δ165.54,162.82,160.22,157.17,154.60,153.35,140.89,140.85,131.06, 130.95,129.72,120.33,120.24,117.86,117.61,115.37,115.15,114.74,111.62,111.44,107.19,19.12.

[0167] The synthesis of compound 8k ((E)-7-hydroxy-4-methyl-8-((m-toluimido)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with m-toluidine.

[0168] The structure of compound 8k is

[0169] H NMR spectrum of compound 8k ( 1 H NMR) characterization results are: 1 H NMR(600MHz,Chloroform-d)δ15.67(d,J=2.7Hz,1H),9.31(d,J=2.5Hz,1H),7.58(d,J=9.0Hz,1H),7.17–7.14(m, 2H), 7.05 (dd, J=7.8, 1.8Hz, 1H), 6.90 (d, J=9.0Hz, 1H), 6.13 (d, J=1.4Hz, 1H), 2.42 (d, J=1.3Hz, 3H), 2.40 (s, 3H).

[0170] The C NMR spectrum of compound 8k ( 13 C NMR) characterization results are: 13C NMR(151MHz,Chloroform-d)δ168.42,160.61,155.33,154.78,153.57,144.34,137.28, 130.94,129.54,129.13,128.66,118.53,115.74,110.77,110.64,106.94,21.15,17.88.

[0171] The synthesis of compound 81 ((E)-7-hydroxy-4-methyl-8-((p-toluylimino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced by p-methylaniline.

[0172] The structure of compound 81 is:

[0173] H NMR spectrum of compound 81 ( 1 H NMR) characterization results are: 1 H NMR (600MHz, Chloroform-d): δ15.36(d,J=2.1Hz,1H),9.34(d,J=1.4Hz,1H),7.56(d,J=9.0Hz,1H),7.31–7.29 (m,2H),7.25(d,J=8.2Hz,2H),6.90(d,J=8.9Hz,1H),6.13(d,J=1.4Hz,1H),2.41(d,J=1.2Hz,3H),2.40(s,3H).

[0174] The C NMR spectrum of compound 81 ( 13 C NMR) characterization results are: 13 C NMR(151MHz,Chloroform-d)δ167.41,160.52,155.38,154.62,153.48,143.61, 138.06,130.32,129.27,121.21,115.35,110.92,110.91,106.94,21.27,19.12.

[0175] The synthesis of compound 8m ((E)-7-hydroxy-4-methyl 8-((((2,5-dimethylphenyl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with 2,5-dimethylaniline.

[0176] The structure of compound 8m is

[0177] H NMR spectrum of compound 8m ( 1 H NMR) characterization results are:1 H NMR(600MHz,Chloroform-d)δ15.51(d,J=2.4Hz,1H),9.28(d,J=2.0Hz,1H),7.58(d,J=9.0Hz,1H),7.19(t,J=7.7Hz,1H),7 .13(dd,J=12.3,7.3Hz,2H),6.92(d,J=9.0Hz,1H),6.13(d,J=1.4Hz,1H),2.42(d,J=1.2Hz,3H),2.35(s,3H),2.34(s,3H).

[0178] The C NMR spectrum of compound 8m ( 13 C NMR) characterization results are: 13 C NMR(151MHz,Chloroform-d)δ167.82,160.47,156.32,154.73,153.45,145.38,138.20,130 .55,129.47,129.35,126.66,116.36,115.46,110.90,110.83,107.04,20.49,19.12,14.21.

[0179] The synthesis of compound 8n ((E)-7-hydroxy-4-methyl-8-(((5-chloro-2-hydroxyphenyl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with 5-chloro-2-hydroxyaniline.

[0180] The structure of compound 8n is

[0181] H NMR spectrum of compound 8n ( 1 H NMR) characterization results are: 1 H NMR (600MHz, DMSO-d6) δ15.59(d,J=3.4Hz,1H),10.46(s,1H),9.33(d,J=3.2Hz,1H),7.75(d,J=9.0Hz,1H),7.72(d,J=2 .5Hz, 1H), 7.21 (dd, J = 8.6, 2.5Hz, 1H), 6.99 (d, J = 8.7Hz, 1H), 6.84 (d, J = 9.0Hz, 1H), 6.21 (d, J = 1.4Hz, 1H), 2.40 (s, 3H).

[0182] The C NMR spectrum of compound 8n ( 13 C NMR) characterization results are: 13C NMR(151MHz,DMSO-d6)δ168.28,159.31,155.54,154.45,154.15,149.73,133.03, 130.72,128.09,123.33,119.60,117.76,115.49,109.85,109.81,106.08,18.42.

[0183] The synthesis of compound 8o ((E)-7-hydroxy-4-methyl-8-(((2-hydroxy-5-(trifluoromethyl)phenyl)imino)methyl)coumarin) was similar to that of compound 8a, except that the raw material o-methylaniline was replaced with 2-hydroxy-5-(trifluoromethyl)aniline.

[0184] The structure of compound 8o is

[0185] The H NMR spectrum of compound 8o ( 1 H NMR) characterization results are: 1 H NMR (600MHz, DMSO-d6) δ15.53(s,1H),11.06(s,1H),9.39(s,1H),7.95(d,J=2.2Hz,1H),7.76(d,J=9.0Hz,1H),7.5 2 (dd, J = 8.6, 2.2 Hz, 1H), 7.15 (d, J = 8.5 Hz, 1H), 6.85 (d, J = 9.0 Hz, 1H), 6.21 (d, J = 1.4 Hz, 1H), 2.39 (d, J = 1.3 Hz, 3H).

[0186] The C NMR spectrum of compound 8o ( 13 C NMR) characterization results are: 13 C NMR(151MHz,DMSO-d6)δ168.35,159.76,156.93,154.87,154.58,154.39,133.07,131.18,125 .87,125.85,124.01,120.63,117.97,117.94,117.23,115.76,110.45,110.34,106.57,18.86.

[0187] The synthesis of compound 8p ((E)-7-hydroxy-4-methyl-8-(((2-hydroxy-5-methylphenyl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with 2-hydroxy-5-methylaniline.

[0188] The structure of compound 8p is

[0189] The H NMR spectrum of compound 8p ( 1 H NMR) characterization results are: 1 H NMR (600MHz, DMSO-d6) δ16.08(d,J=5.1Hz,1H),10.23(s,1H),9.32(d,J=4.9Hz,1H),7.72(d,J=9.1Hz,1H),7.52(d,J=8.1Hz,1H),6 .82(d,J=1.8Hz,1H),6.78(d,J=9.1Hz,1H),6.75(dd,J=8.2,1.8Hz,1H),6.17(d,J=1.4Hz,1H),2.39(d,J=1.2Hz,3H),2.27(s,3H).

[0190] The C NMR spectrum of compound 8p ( 13 C NMR) characterization results are: 13 C NMR (151MHz, DMSO-d6) δ170.69,152.94,150.81,139.25,130.87,128.52,121.15,119.79,117.39,116.82,109.62,109.39,106.18,21.40,18.91.

[0191] The synthesis of compound 8q ((E)-7-hydroxy-4-methyl-8-(((5-fluoro-2-hydroxyphenyl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with 5-fluoro-2-hydroxyaniline.

[0192] The structure of compound 8q is

[0193] The H NMR spectrum of compound 8q ( 1 H NMR) characterization results are: 1 H NMR (600MHz, DMSO-d6) δ15.69(d,J=3.7Hz,1H),10.19(s,1H),9.33(d,J=3.6Hz,1H),7.75(d,J=9.1Hz,1H),7.58(dd,J=9.8,3.0Hz ,1H),7.03(td,J=8.6,3.0Hz,1H),6.97(dd,J=8.9,5.2Hz,1H),6.83(d,J=9.0Hz,1H),6.20(d,J=1.4Hz,1H),2.40(d,J=1.2Hz,3H).

[0194] The C NMR spectrum of compound 8q ( 13 C NMR) characterization results are:13 C NMR(151MHz,DMSO-d6)δ168.71,159.31,156.50,155.21,154.94,154.50,154.17,147.16,147.15,132.12, 132.06,130.74,117.08,117.02,115.69,114.94,114.79,109.72,109.69,106.65,106.49,106.01,18.43.

[0195] The synthesis of compound 8r ((E)-7-hydroxy-4-methyl-8-(((4-hydroxypyridin-2-yl)imino)methyl)coumarin) was similar to that of compound 8a, except that the raw material o-methylaniline was replaced with 2-amino-4-hydroxypyridine.

[0196] The structure of compound 8r is

[0197] The H NMR spectrum of compound 8r ( 1 H NMR) characterization results are: 1 H NMR (600MHz, DMSO-d6) δ14.95–14.87(m,1H),11.09(s,1H),9.91(s,1H),8.27(d,J=5.7Hz,1H),7.82(d,J=9. 0Hz, 1H), 6.91 (d, J = 9.0Hz, 1H), 6.87 (s, 1H), 6.81–6.78 (m, 1H), 6.25 (d, J = 1.4Hz, 1H), 2.41 (d, J = 1.2Hz, 3H).

[0198] The synthesis of compound 8s ((E)-7-hydroxy-4-methyl-8-(((4-fluoropyridin-2-yl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with 2-amino-4-fluoropyridine.

[0199] The structure of compound 8s is

[0200] The H NMR spectrum of compound 8s ( 1 H NMR) characterization results are: 1H NMR (600MHz, DMSO-d6) δ14.79(d,J=2.1Hz,1H),9.99(s,1H),8.40(d,J=5.6Hz,1H),7.85(d,J=9.0Hz,1H),7 .22(d,J=2.4Hz,1H),7.01–6.99(m,1H),6.95(d,J=8.9Hz,1H),6.27(d,J=1.4Hz,1H),2.42(d,J=1.2Hz,3H).

[0201] The synthesis of compound 8t ((E)-7-hydroxy-4-methyl-8-(((4-methoxypyridin-2-yl)imino)methyl)coumarin) was carried out with reference to the synthesis of compound 8a, except that the raw material o-methylaniline was replaced with 2-amino-4-methoxypyridine.

[0202] The structure of compound 8t is

[0203] The H NMR spectrum of compound 8t ( 1 H NMR) characterization results are: 1 H NMR(400MHz,Chloroform-d)δ10.08(s,1H),8.33(d,J=5.6Hz,1H),7.59(d,J=9.0Hz,1H),6.88(d,J=9 .1Hz,1H),6.81(d,J=2.2Hz,1H),6.78(d,J=5.6Hz,1H),6.15–6.10(m,1H),3.91(s,3H),2.41(s,3H).

[0204] The C NMR spectrum of compound 8t ( 13 C NMR) characterization results are: 13 C NMR(101MHz,Chloroform-d)δ168.91,167.66,160.16,158.52,157.20,155.43,153. 06,150.09,130.25,115.68,110.88,110.63,109.50,106.70,104.49,55.49,18.91.

[0205] Example 1

[0206] This example provides the antibacterial effect of coumarin derivatives containing a Schiff base structure on plant fungi.

[0207] 1. Fungi used in the experiment

[0208] The fungi used in the experiment are shown in Table 1.

[0209] Table 1 Fungal names and sources

[0210] name Latin name English abbreviation Alternaria Alternaria alternata A. alternata Alternaria solani Alternaria solani A.solani Botrytis cinerea Botrytis cinerea B. cinerea Fusarium oxysporum Fusarium oxysporum F.oxysporum

[0211] The above strains are all provided by the Chemical Ecology Laboratory of the Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, and can also be purchased directly through Gary Chemical Network, Shanghai Bo Ke Biotechnology Co., Ltd., etc.

[0212] 2. Preparation of PDA Medium

[0213] Fresh potatoes are prepared according to a specific ratio: 1000 mL of distilled water is added for every 200 g of potatoes. First, the potatoes are peeled and cut into long strips. Then, they are added to distilled water and cooked until soft but not mushy. While still hot, the cooked potatoes are filtered through 6 to 8 layers of gauze. The residue is discarded, and distilled water is added to bring the filtrate to a total volume of 1000 mL. The potato liquid is then heated to 80°C, and glucose (20 g / 1000 mL) and agar powder (20 g / 1000 mL) are added. After adding the glucose and agar powder, constant stirring is required to ensure complete dissolution. Finally, the prepared culture medium is carefully transferred into a conical flask and sealed. The flask is sterilized in an autoclave at 120°C for 20 minutes to obtain PDA culture medium.

[0214] 3. Preparation of mother liquor solution of coumarin derivatives containing Schiff base structure

[0215] 12 mg of compounds 3a-3w and compounds 8a-8t were weighed and dissolved in 1200 μL of dimethyl sulfoxide. The mixture was shaken evenly to completely dissolve the drugs, to obtain a mother solution to be tested with a concentration of 10 mg / mL.

[0216] 4. Determination of the inhibitory effect of coumarin derivatives containing Schiff base structure on mycelial growth

[0217] The in vitro antifungal activity of the prepared compounds was evaluated by the mycelial linear growth rate method. Two fungicides, thiophanate-methyl and myclobutanil, were selected as positive controls. Dimethyl sulfoxide (DMSO) solvent was used as a blank control. 100 μL of liquid was drawn from the mother liquor to be tested and added to 10 mL of PDA medium so that the concentration of the compound in the PDA medium was 100 μg / mL. The injected compound was shaken evenly to obtain a semi-solid culture medium. Next, a fungal cake with a diameter of 7 mm was inoculated into the center of the PDA culture medium and cultured in the dark at 25°C. The root growth of the mycelium was measured using diameters in different directions, and the data were statistically analyzed. The mycelial growth was recorded for 48, 72, and 96 hours. Each treatment was repeated three times, and the average of the three data was taken. The formula for in vitro growth inhibition rate is as follows:

[0218] Inhibition rate (%) = [(d c -d0)-(d s -d0)] / (d c -d0)×100%

[0219] Wherein, d0 is the diameter of the fungal cake (7 mm), dc is the diameter of the fungus in the medium treated with dimethyl sulfoxide, and ds is the diameter of the fungus in the medium treated with the compound.

[0220] For compounds with an inhibition rate of more than 70% at a concentration of 100 μg / mL, dimethyl sulfoxide solution was used as the solvent and further tested at five concentrations (100 μg / mL, 50 μg / mL, 25 μg / mL, 12.5 μg / mL and 6.25 μg / mL) to determine their maximum effect concentration (EC 50 ). EC 50 The values ​​and their 95% confidence intervals (CI) were calculated by nonlinear regression analysis embedded in the IBM SPSS Statistics 27 program.

[0221] 5. Determination of the fungal inhibitory effects of coumarin derivatives containing Schiff base structures

[0222] The inhibitory effects of compounds 3a-3w and 8a-8t against four plant pathogenic fungi (Alternaria alternata, Alternaria solanacearum, Botrytis cinerea, and Fusarium oxysporum) were determined, and the commercial fungicides chlorothalonil and azoxystrobin, as well as the natural product osthole, were selected as positive controls.

[0223] Table 2 Inhibition rate of compounds 3a-3w, compounds 8a-8t, chlorothalonil, azoxystrobin and osthole against plant pathogenic fungi in 48 h

[0224]

[0225]

[0226] Table 3 Inhibition rate of compounds 3a-3w, compounds 8a-8t, chlorothalonil, azoxystrobin and osthole against plant pathogenic fungi at 72 h

[0227]

[0228]

[0229] Table 4 Inhibition rate of compounds 3a-3w, compounds 8a-8t, chlorothalonil, azoxystrobin and osthole against plant pathogenic fungi in 96 h

[0230]

[0231]

[0232] The inhibitory effects of compounds 3a-3w, 8a-8t, chlorothalonil, azoxystrobin, and osthole on plant pathogens at 48 h are shown in Table 2. The inhibitory effects of compounds 3a-3w, 8a-8t, chlorothalonil, azoxystrobin, and osthole on plant pathogens at 72 h are shown in Table 3. The inhibitory effects of compounds 3a-3w, 8a-8t, chlorothalonil, azoxystrobin, and osthole on plant pathogens at 96 h are shown in Table 4. Most of the target compounds showed moderate to excellent inhibitory activity against the four plant pathogens, especially against Botrytis cinerea and Fusarium oxysporum. At 48 h, the introduction of the Schiff base moiety enhanced the inhibitory activity of most compounds against Alternaria alternata compared to the parent compounds 3 and 8. Compounds 3r and 8t exhibited inhibition rates exceeding 60% against Alternaria alternata, while the inhibition rates of the other compounds were mostly between 10% and 50%, lower than those of the positive controls chlorothalonil and azoxystrobin. Against Alternaria solani, most compounds exhibited inhibition rates between 10% and 50%, showing varying degrees of increase compared to the parent compounds. Against Botrytis cinerea, the inhibition rates of the compounds were significantly increased, particularly compounds 3b, 3g, 3h, 3j, 3l, 3m, and 3v, which achieved inhibition rates exceeding 95% and even 100% at a concentration of 100 μg / mL, representing 40% to 50% higher inhibition rates than the positive control. For Fusarium oxysporum, the inhibition rates of compounds 3g, 3h and 3m can reach more than 95%, especially compounds 3g and 3h, with an inhibition rate of 100%, which is significantly better than the commercially available fungicides chlorothalonil (65.45%) and azoxystrobin (70.37%).

[0233] At 72 hours, the inhibitory effects of most compounds on plant fungi were comparable to those at 48 hours, with no significant changes. For Alternaria alternata, only compound 3r achieved an inhibition rate of over 60%, which was superior to the positive control chlorothalonil. For Alternaria solani, compound 3w and compound 8m had an inhibition rate of around 40%, comparable to that at 48 hours. For Botrytis cinerea, the inhibition rate of most compounds decreased by about 5% to 10% compared to that at 48 hours, but still remained between 60% and 80%, with 3g and 3m achieving an inhibition rate of up to 99%. For Fusarium oxysporum, compound 3g achieved an inhibition rate of 100%, while compound 3m and 3h achieved inhibition rates of over 90%.

[0234] At 96 hours, the inhibition rates of all compounds against Alternaria alternata decreased to varying degrees, with compound 3r alone achieving a 65.07% inhibition rate, exceeding that of the positive control, chlorothalonil. Against Alternaria solani, the inhibition rates of the compounds decreased by an average of approximately 5% compared to those observed at 72 hours, with most compounds ranging from 10% to 40%. This represented an improvement over the parent compound's inhibitory effect, but lower than that of the positive controls, osthole and azoxystrobin. Against Botrytis cinerea, most compounds exhibited inhibition rates exceeding 50%, exceeding those of the parent compounds, 3-amino-7-hydroxycoumarin and 8-formyl-7-hydroxy-4-methylcoumarin. Compounds 3a, 3f, 3g, 3h, and 3m were particularly outstanding, achieving inhibition rates of 89.32%, 87.52%, 92.46%, 94.57%, and 97.50%, respectively. This was superior to the positive controls, osthole, thiophanate-methyl, and azoxystrobin, which exhibited inhibition rates of 46.18%, 56.77%, and 61.75%, respectively. Against Fusarium oxysporum, most compounds exhibited inhibition rates that decreased by 5% to 10% compared to those observed at 48 and 72 hours, but remained between 50% and 80%. Compounds 3g, 3h, and 3m exhibited the highest inhibition rates, exceeding those of the positive controls, osthole, thiophanate-methyl, and azoxystrobin, by 40% to 60%.

[0235] Analysis of the inhibition rates in Tables 2, 3, and 4 revealed structure-activity relationships (SARs) for the compounds. First, the SARs showed that compounds derived from 3-amino-7-hydroxycoumarin were generally more active than those derived from 4-methyl-7-hydroxy-8-formylcoumarin. The target compounds exhibited better inhibitory effects against Botrytis cinerea than against Alternaria alternata, Alternaria solanacearum, and Fusarium oxysporum. Second, the antifungal activity of the compounds was closely related to the substitution type and position of the benzene ring. When a halogen atom (F, Cl, or Br) was introduced at the ortho, meta, or para position of the benzene ring, and the substituent at the ortho position was an electron-donating group, the antifungal activity of the compounds was significantly improved. Similar patterns were observed for p-methoxy and m-(p-)methyl compounds. The antifungal activity trend of 3-amino-7-hydroxycoumarin derivatives (3m > 3j (3i)) indicated that electron-withdrawing groups at the C-3 position were more effective than those at the C-4, C-5, or C-6 positions. At the para position, fluorine (3g) and bromine (3j) were beneficial for the activity, whereas more polar or bulky substituents (3k, 3l, and 3p-3s) resulted in decreased antifungal performance, indicating that electronegativity and substituent size are crucial for antifungal performance.

[0236] The initial antifungal screening was performed at a compound concentration of 100 μg / mL. For compounds with an inhibition rate of more than 70% at 100 μg / mL for 72 h, they were further tested at five concentrations (100, 50, 25, 12.5, and 6.25 μg / mL) using dimethyl sulfoxide solution as the solvent to determine their half-maximal effective concentration (EC 50 ). EC 50 The values ​​and their 95% confidence intervals (CIs) were calculated by nonlinear regression analysis embedded in the IBM SPSS Statistics 27 program. 50 The results are shown in Table 5.

[0237] Table 5 Antifungal EC values ​​of compounds 50 (μg / mL) value

[0238]

[0239]

[0240] In order to more clearly and intuitively understand the inhibitory effect of coumarin derivatives containing Schiff base structure on plant pathogenic fungi, the EC values ​​of compounds with inhibition rate exceeding 70% at a concentration of 100 μg / mL were determined. 50 The results showed that the EC values ​​of most compounds were 50 The values ​​were close to or better than the positive control, EC 50The values ​​were all below 40 μg / mL. In particular, compounds 3m and 3g had excellent antifungal properties against Botrytis cinerea and Fusarium oxysporum. The EC values ​​of 3m and 3g against Botrytis cinerea were 50 The values ​​were 1.621 μg / mL and 6.179 μg / mL, respectively, and the EC values ​​against Fusarium oxysporum were 50 The values ​​were 2.495 μg / mL and 6.033 μg / mL, respectively. In addition, some compounds also showed good antifungal properties against Fusarium oxysporum. The EC values ​​of compounds 3d and 3h against Fusarium oxysporum were 50 The values ​​were 9.775μg / mL and 12.219μg / mL, respectively, which were significantly better than chlorothalonil (31.810μg / mL), azoxystrobin (63.431μg / mL) and osthole (124.965μg / mL). Compound 3q had excellent antifungal activity against Alternaria alternata, with EC 50 The value was 19.788 μg / mL, which was better than the positive control chlorothalonil (124.965 μg / mL). Compound 3m showed good antifungal activity against both Botrytis cinerea and Fusarium oxysporum. Figure 1 Figure 2 shows the antifungal effects of compound 3m and azoxystrobin at various concentrations against Botrytis cinerea. Compound 3m exhibited significantly enhanced antifungal activity with increasing concentration, and was therefore selected for further investigation. Furthermore, all coefficients of determination (R²) were greater than 0.9, indicating a good correlation between concentration and antifungal activity.

[0241] 6. The control effect of coumarin derivatives containing Schiff base structure on gray mold of Korla fragrant pear. The in vivo antifungal activity of compound 3m was tested on fragrant pear, and Botrytis cinerea was selected as the target plant pathogenic fungus. Figure 2 Table 6 shows the control effect of compound 3m and azoxystrobin on gray mold of Korla fragrant pear at concentrations of 400 μg / mL, 200 μg / mL and 100 μg / mL. Table 7 shows the average inhibition rate of compound 3m and azoxystrobin on gray mold of Korla fragrant pear. Figure 2 As shown in the results, compared with the blank control and azoxystrobin, compound 3m can effectively protect the fragrant pear from the plant pathogenic fungus Botrytis cinerea. At a concentration of 100 μg / mL, compound 3m has excellent inhibitory performance against Botrytis cinerea, with an inhibition rate of 67.7%, which is much higher than the inhibition rate of 46.3% of azoxystrobin. 50 The compound 3m has the potential to be developed into a new fungicide.

[0242] Table 6 Average inhibition rate of compound 3m and azoxystrobin on gray mold of Korla pear

[0243]

[0244] As described above, the basic principles, main features and advantages of the present invention are well described. The above embodiments and descriptions are merely descriptions of preferred embodiments of the present invention, and the present invention is not limited to the above embodiments. Various changes and improvements made to the technical solutions of the present invention by those skilled in the art without departing from the spirit and scope of the present invention should fall within the scope of protection determined by the present invention.

Claims

1. A coumarin derivative containing a Schiff base structure, characterized in that: Having a structure as shown in general formula (I), wherein R1 is Br; R2 is selected from any one of CH3, Cl, F, OCH3; R3 is selected from any one of CH3, Br, and F.

2. The coumarin derivative containing a Schiff base structure according to claim 1, characterized in that: Has the following structure, 3. A method for preparing a coumarin derivative containing a Schiff base structure, characterized in that: include: 3-amino-7-hydroxycoumarin is dissolved in anhydrous methanol or anhydrous ethanol; after heating, an anhydrous methanol or anhydrous ethanol solution of an aldehyde compound is added dropwise to the 3-amino-7-hydroxycoumarin solution, and then 1 to 2 drops of glacial acetic acid or acetic anhydride are added dropwise, and the mixture is heated under reflux for reaction; after the reaction is completed, the suspended matter is collected and washed to obtain a compound.

4. The preparation method according to claim 3, characterized in that The aldehyde compound is selected from any one of 2-hydroxy-5-methylbenzaldehyde, 2-hydroxy-4-methylbenzaldehyde, 4-chloro-2-hydroxybenzaldehyde, 5-fluoro-2-hydroxybenzaldehyde, 4-fluoro-2-hydroxybenzaldehyde, 2-hydroxy-4-methoxybenzaldehyde, 5-bromo-2-hydroxybenzaldehyde, and 3-bromo-2-hydroxybenzaldehyde.

5. The preparation method according to claim 3, characterized in that The molar ratio of the 3-amino-7-hydroxycoumarin to the aldehyde compound is 1:1.

5.

6. The preparation method according to claim 3, characterized in that The heating temperature is 40°C.

7. The preparation method according to claim 3, characterized in that The conditions for the heating reflux reaction include: temperature of 79° C. and time of 8 h.

8. A method for preventing and controlling plant pathogenic fungi, characterized in that: The method comprises using the coumarin derivative having a Schiff base structure according to any one of claims 1 to 2.

9. The method according to claim 8, characterized in that The plant pathogenic fungus is Botrytis cinerea or Fusarium oxysporum.

10. Use of the coumarin derivative containing a Schiff base structure according to any one of claims 1 to 2 in the preparation of a drug for preventing and treating gray mold of Korla fragrant pear.

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