3-hydroxy-2,3-dihydrobenzofuran derivatives having antibacterial activity, processes for their preparation and use

Abstract

The application discloses a 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity and a preparation method and application thereof. The method comprises the following steps: in step 1, compounds I, compound II and a catalyst are added into an organic solvent, fully stirred at normal temperature, subjected to an alkylated hydroxy aldehyde condensation series reaction, and then the organic solvent in a crude product is removed through rotary evaporation under reduced pressure to obtain the crude product; the compound I is salicylaldehyde or a salicylaldehyde derivative, and the compound II is a 1-bromobenzylidene propionone derivative; in step 2, column chromatography is used to remove the catalyst, unreacted raw materials and other impurities to obtain the 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity. The application has the advantages of simple preparation method, low price and high yield, and the prepared compound has good bacteriostatic effect.

Description

Technical Field

[0001] This invention relates to dihydrobenzofuran compounds, specifically 3-hydroxy-2,3-dihydrobenzofuran derivatives with antibacterial activity, their preparation methods, and applications. Background Technology

[0002] 2,3-Dihydrobenzofurans are a class of low-molecular-weight heterocyclic compounds with good biological activity, widely used in agriculture, medicine, and chemical industries, and have great application value. Studies have reported that dihydrobenzofurans (DHBs) are essential structural units for the biological activity of various non-natural products such as polyether ion-carrier antibiotics and macrolide drugs, and are also basic structural units of many important natural products such as plant lignin and sandalwood. Furthermore, it is noteworthy that compounds with the dihydrobenzofuran structure also have applications in treating cancer [Tistechok S, Stierhof M, Myronovskyi M, et al. Furaquinocins K and L:. Antibiotics, 2022, 11(11):1587.], insomnia [Takagi S, Sugihara G, Takahashi H, et al.. Frontiers in Neurology, 2023, 14:1280131], and antibacterial [Mehdi SH, Hashim R, Ghalib RM, et al. Journal] of Molecular Structure, 2011, 1006(1-3):318-323.], anti-inflammatory [Closse A, Haefliger W, Hauser D, et al. Journal of Medicinal Chemistry, 1981, 24(12):1465-1471.], insecticidal [Wangjin X, Dianjing S, Xiaojun C, et al. Environmental Science and Pollution Research, 2023, 30:106047-106058.] and antioxidant [Shaw CY, Chen CC, Tsai Y C.. Journal of Natural Products, 2002, 65(5):740-741.], therefore, the synthesis of benzodihydrofuran compounds has always been a hot topic in medicinal chemistry research, for example:

[0003] In 1991, Nichols et al. [Nichols DE, Snyder SE, Oberlender R, et al. Journal of Medicinal Chemistry, 1991, 34(1): 276-281.] used 2-(2-bromomethyl)benzene-1,4-diol as the substrate, inorganic base K2CO3 as the catalyst, and acetone as the solvent. Under reflux conditions, an intramolecular ring-closure reaction was carried out, ultimately constructing the 2,3-dihydrobenzofuran structure. The reaction formula is as follows:

[0004]

[0005] In 2016, Barrios et al. [Barrios Antúnez DJ, Greenhalgh MD, Fallan C, et al. Organic & Biomolecular Chemistry, 2016, 14(30): 7268-7274.] used a chiral thiourea bifunctional catalyst to catalyze the activation of intramolecular hydrogen bonds, thereby generating an enamine in situ that attacks the α,β-unsaturated double bond, resulting in an intramolecular nucleophilic reaction. After ring closure, a chiral 2,3-dihydrobenzofuran structure was constructed, as shown in the following reaction formula:

[0006]

[0007] In 2024, Feng Miao et al. [Feng Miao, Lü Lanlan, Guo Yijia, et al. Organic Chemistry, 2024, 1-12.] reported a silver-catalyzed 5-exo-dig cyclization reaction of o-hydroxyphenylpropynyl alcohol with isonitrile as ligand, constructing a series of 2-methylene-2,3-dihydrobenzofuran-3-ol compounds in moderate to excellent yields. The reaction formulas are as follows:

[0008]

[0009] However, the conditions required for synthesizing 22,3-dihydrobenzofuran derivatives are quite demanding, and most of the time precious metals are used, which is costly and environmentally unfriendly. Therefore, it is urgent to explore a new method to synthesize novel 2,3-dihydrobenzofuran derivatives. Summary of the Invention

[0010] In view of the shortcomings of the existing technology, the purpose of this invention is to provide a 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity, as well as its preparation method and application. It not only has the advantages of simple preparation method, low price and high yield, but also the prepared compound has good antibacterial effect.

[0011] To achieve the above objectives, the present invention employs the following technical solution:

[0012] A 3-hydroxy-2,3-dihydrobenzofuran and its derivatives with antibacterial activity have the following structural formula:

[0013]

[0014] In the formula, R 1 and R 2 It can be hydrogen, chlorine, bromine, or methoxy.

[0015] A method for preparing a 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity includes the following steps:

[0016] Step 1: Compound I, Compound II, and the catalyst are added to an organic solvent and stirred thoroughly at room temperature. The mixture undergoes a series alkylation aldol condensation reaction. The organic solvent is then removed from the crude product by rotary evaporation under reduced pressure to obtain the crude product. The reaction formula is as follows:

[0017]

[0018] Compound I is salicylaldehyde or a salicylaldehyde derivative, and compound II is a 1-bromobenzylacetone derivative;

[0019] Step 2: Remove the catalyst, unreacted raw materials and other impurities by column chromatography to obtain a 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity.

[0020] Furthermore, the ratio of compound I, compound II, catalyst, and organic solvent is 1 mmol: 2 mmol: 1.2 mmol: 2 mL.

[0021] Furthermore, the salicylaldehyde derivative is 5-bromosalicylaldehyde or 5-chlorosalicylaldehyde.

[0022] Further, the 1-bromobenzylacetone derivative is 1-bromo-4-phenyl-3-buten-2-one, 1-bromo-4(4-bromophenyl)-3-buten-2-one, 1-bromo-4(4-chlorophenyl)-3-buten-2-one or 1-bromo-4(4-methoxyphenyl)-3-buten-2-one.

[0023] Furthermore, the organic solvent is tetrahydrofuran or dioxane.

[0024] Furthermore, the catalyst is potassium carbonate, potassium acetate, or sodium carbonate.

[0025] Furthermore, the eluent used in the column chromatography is a mixture of petroleum ether and ethyl acetate in a volume ratio of (20-40):1.

[0026] Application of a 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity as an antibacterial agent.

[0027] Compared with the prior art, the present invention has the following technical effects:

[0028] This invention uses inexpensive salicylaldehyde or salicylaldehyde derivatives, or 1-bromobenzylacetone derivatives, as raw materials to prepare 3-hydroxy-2,3-dihydrobenzofuran derivatives via a simple and rapid alkylation aldol condensation tandem reaction in an organic solvent under the action of a catalyst. After conventional purification by vacuum rotary evaporation and column chromatography, the product purity reached over 98%, and the yield reached 53%–93%. Furthermore, the prepared 3-hydroxy-2,3-dihydrobenzofuran derivatives exhibited certain inhibitory effects against apple rot fungus, potato wilt fungus, rapeseed black shank fungus, and tomato gray mold fungus. In short, this invention not only has the advantages of simple operation steps, low cost, green and mild reaction conditions, simple post-processing, and high yield, making it suitable for industrial production, but also the prepared compound has good antibacterial activity, thus possessing potential socio-economic benefits. Attached Figure Description

[0029] Figures 1-2 The nuclear magnetic resonance spectrum of compound 3aa prepared in Example 1 of this invention. Detailed Implementation

[0030] The specific content of the present invention will be further explained in detail below with reference to the embodiments.

[0031] Example 1

[0032] Step 1: Add 1 mmol of salicylaldehyde, 2 mmol of 1-bromo-4-phenyl-3-buten-2-one, and 1.2 mmol of potassium carbonate to 2 mL of tetrahydrofuran. Stir at room temperature for 3 h. Monitor the reaction by TLC until the reactants are completely reacted. Then remove the tetrahydrofuran by rotary evaporation under reduced pressure to obtain the crude product. The reaction formula is as follows:

[0033]

[0034] Step 2: Petroleum ether and ethyl acetate were mixed at a volume ratio of 40:1 as the eluent. Potassium carbonate, unreacted raw materials, and other impurities were removed by column chromatography to obtain a 3-hydroxy-2,3-dihydrobenzofuran derivative (E)-1-(3-hydroxy-2,3-dihydrobenzofuran-2-yl)-3-phenylprop-2-en-1-one with antibacterial activity, denoted as 3aa, with a yield of 79%.

[0035] The structure of compound 3aa was identified using an AVANCE NEO 600M nuclear magnetic resonance spectrometer manufactured by Bruker, Germany, via nuclear magnetic resonance and high-resolution mass spectrometry. The results are as follows: Figures 1-2 As shown: 1 H NMR(600MHz, CDCl3)δ7.78(dd,J=16.0,5.3Hz,1H),7.64-7.54(m,2H),7.49-7.28(m, 5H),7.24(d,J=16.8Hz,1H),7.14-6.93(m,2H),5.66-5.47(m,1H),5.19-5.12(m,1H); 13 C NMR (151MHz, CDCl3) δ196.0,159.6,144.8,131.2,128.9,128.9,127.1,126.0,121.9,120.4,110.9,93.3,89.6,75.7,73.3; HRMS (ESI) m / z Calcd for C 17 H 14 O3[M+Na] + 289.0833, found 289.0833. This indicates that the 3-hydroxy-2,3-dihydrobenzofuran derivative synthesized in Example 1, the derivative: (E)-1-(3-hydroxy-2,3-dihydrobenzofuran-2-yl)-3-phenylprop-2-en-1-one, has the structure shown in structural formula 3aa.

[0036] Example 2

[0037] Step 1: Add 1 mmol of 5-bromosalicylic acid, 2 mmol of 1-bromo-4-phenyl-3-buten-2-one, and 1.2 mmol of potassium carbonate to 2 mL of tetrahydrofuran. Stir at room temperature for 3 h. Monitor the reaction by TLC until the reactants are completely reacted. Then remove the tetrahydrofuran by rotary evaporation under reduced pressure to obtain the crude product. The reaction formula is as follows:

[0038]

[0039] Step 2: Petroleum ether and ethyl acetate were mixed at a volume ratio of 30:1 as the eluent. Potassium carbonate, unreacted raw materials, and other impurities were removed by column chromatography to obtain a 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity, (E)-1-(5-bromo-3-hydroxy-2,3-dihydrobenzofuran-2-yl)-3-phenylprop-2-en-1-one, denoted as 3ba, with a yield of 90%.

[0040] The structure of compound 3ba was identified using a Bruker AVANCE NEO 600M nuclear magnetic resonance spectrometer (manufactured in Germany) via nuclear magnetic resonance and high-resolution mass spectrometry. The results are as follows: 1H NMR(400MHz, CDCl3) δ7.80(d,J=15.9Hz,1H),7.65-7.49(m,3H),7.48-7.36(m,4H),7.22(d,J=16.0H z,1H),7.09(d,J=16.0Hz,1H),6.92(d,J=8.6Hz,1H),5.56(d,J=31.9Hz,1H),5.17(d,J=6.5Hz,1H); 13 C NMR(101MHz, CDCl3)δ193.6,155.4,141.1,136.7,132.1,130.1,129.0,127.0,125.9,121.1,120.6109.2,92.2,88.9,72.6.HRMS(ESI)m / z Calcd for C 17 H 13 BrO3[M+Na] + 368.1812, found 368.1813. This indicates that the 3-hydroxy-2,3-dihydrobenzofuran derivative (E)-1-(5-bromo-3-hydroxy-2,3-dihydrobenzofuran-2-yl)-3-phenylprop-2-en-1-one synthesized in Example 2 has the structure shown in structural formula 3ba.

[0041] Example 3

[0042] Step 1: Add 1 mmol of 5-chlorosalicylaldehyde, 2 mmol of 1-bromo-4-phenyl-3-buten-2-one, and 1.2 mmol of potassium carbonate to 2 mL of tetrahydrofuran. Stir at room temperature for 3 h. Monitor the reaction by TLC until the reactants are completely reacted. Then remove the tetrahydrofuran by rotary evaporation under reduced pressure to obtain the crude product. The reaction formula is as follows:

[0043]

[0044] Step 2: Petroleum ether and ethyl acetate were mixed at a volume ratio of 25:1 as the eluent. Potassium carbonate, unreacted raw materials, and other impurities were removed by column chromatography to obtain a 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity, (E)-1-(5-chloro-3-hydroxy-2,3-dihydrobenzofuran-2-yl)-3-phenylprop-2-en-1-one, denoted as 3ca, with a yield of 93%.

[0045] The structure of compound 3ca was identified using an AVANCE NEO 600M nuclear magnetic resonance spectrometer (manufactured by Bruker, Germany) via nuclear magnetic resonance and high-resolution mass spectrometry. The results are as follows: 1H NMR(600MHz, CDCl3) δ7.79(d,J=16.0Hz,1H),7.64-7.57(m,2H),7.48-7.35(m,5H),7.28(dd,J=8.5,2 .0Hz,1H),7.22(d,J=15.9Hz,1H),6.95(d,J=8.6Hz,1H),5.61(d,J=6.6Hz,1H),5.18(d,J=6.6Hz,1H); 13 C NMR (151MHz, CDCl3) δ195.7,158.1,145.2,134.2,131.2,131.1,129.0,129.0,128.7,126.6,126.1,121.4,112.0,90.1,73.0; HRMS (ESI) m / z Calcd for C 17 H 13 ClO3[M+Na] + 368.323.7272, found323.7274. This indicates that the 3-hydroxy-2,3-dihydrobenzofuran derivative (E)-1-(5-chloro-3-hydroxy-2,3-dihydrobenzofuran-2-yl)-3-phenylprop-2-en-1-one synthesized in Example 3 has the structure shown in structural formula 3ca.

[0046] Example 4

[0047] Step 1: Add 1 mmol of salicylaldehyde, 2 mmol of 1-bromo-4-(4-bromophenyl)-3-buten-2-one, and 1.2 mmol of potassium carbonate to 2 mL of tetrahydrofuran. Stir at room temperature for 3 h. Monitor the reaction by TLC until the reactants are completely reacted. Then remove the tetrahydrofuran by rotary evaporation under reduced pressure to obtain the crude product. The reaction formula is as follows:

[0048]

[0049] Step 2: Petroleum ether and ethyl acetate were mixed at a volume ratio of 20:1 as the eluent. Potassium carbonate, unreacted raw materials, and other impurities were removed by column chromatography to obtain a 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity, (E)-3-(4-bromophenyl)-1-(3-hydroxy-2,3-dihydrobenzofuran-2-yl)prop-2-en-1-one, denoted as 3ab, with a yield of 90%.

[0050] The structure of compound 3ab was identified using an AVANCE NEO 600M nuclear magnetic resonance spectrometer (manufactured by Bruker, Germany) via nuclear magnetic resonance and high-resolution mass spectrometry. The results are as follows: 1H NMR (400MHz, CDCl3) δ7.72(dd,J=16.0,7.2Hz,1H),7.53(d,J=8.3Hz,2H),7.51-7.39(m,3H),7.35(q,J=7.4Hz,1 H),7.23(s,1H),7.10(d,J=16.0Hz,1H),7.02(dd,J=15.0,7.6Hz,2H),5.58(d,J=33.7Hz,1H),5.19-5.11(m,1H); 13 C NMR (151MHz, CDCl3) δ158.5,146.1,133.9,131.3,129.1,128.9,128.7,120.2,112.5,93.5,77.2,77.0,76.8,75.3; HRMS (ESI) m / z Calcd for C 17 H 13 BrO3[M+Na] + 366.9940, found 366.9943. This indicates that the 3-hydroxy-2,3-dihydrobenzofuran derivative (E)-3-(4-bromophenyl)-1-(3-hydroxy-2,3-dihydrobenzofuran-2-yl)prop-2-en-1-one synthesized in Example 4 has the structure shown in structural formula 3ab.

[0051] Example 5

[0052] Step 1: Add 1 mmol of salicylaldehyde, 2 mmol of 1-bromo-4-(4-chlorophenyl)-3-buten-2-one, and 1.2 mmol of potassium carbonate to 2 mL of tetrahydrofuran. Stir at room temperature for 3 h. Monitor the reaction by TLC until the reactants are completely reacted. Then remove the tetrahydrofuran by rotary evaporation under reduced pressure to obtain the crude product. The reaction formula is as follows:

[0053]

[0054] Step 2: Petroleum ether and ethyl acetate were mixed at a volume ratio of 30:1 as the eluent. Potassium carbonate, unreacted raw materials, and other impurities were removed by column chromatography to obtain a 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity, (E)-3-(4-chlorophenyl)-1-(3-hydroxy-2,3-dihydrobenzofuran-2-yl)prop-2-en-1-one, denoted as 3ac, with a yield of 85%.

[0055] The structure of compound 3ac was identified using an AVANCE NEO 600M nuclear magnetic resonance spectrometer (manufactured by Bruker, Germany) via nuclear magnetic resonance and high-resolution mass spectrometry. The results are as follows: 1H NMR(400MHz, CDCl3) δ7.73(dd,J=16.0,5.9Hz,1H),7.52(dd,J=14.4,8.5Hz,2H),7.43(dd,J=17.6,7.2Hz,1H),7 .35(dd,J=11.3,8.1Hz,3H),7.22(d,J=16.0Hz,1H),7.11-6.96(m,3H),5.64-5.50(m,1H),5.13(d,J=6.7Hz,1H); 13 C NMR(101MHz, CDCl3)δ195.9,159.6,143.2,137.0,131.3,130.0,129.3,127.1,126.0,122.0,120.9,110.0,93.3,89.7,73.4.HRMS(ESI)m / z Calcd for C 17 H 13 ClO3[M+Na] + 323.7272, found 323.7274. This indicates that the 3-hydroxy-2,3-dihydrobenzofuran derivative (E)-3-(4-chlorophenyl)-1-(3-hydroxy-2,3-dihydrobenzofuran-2-yl)prop-2-en-1-one synthesized in Example 5 has the structure shown in structural formula 3ac.

[0056] Example 6

[0057] Step 1: Add 1 mmol of salicylaldehyde, 2 mmol of 1-bromo-4-(4-methoxyphenyl)-3-buten-2-one, and 1.2 mmol of potassium acetate to 2 mL of dioxane. Stir at room temperature for 3 h. Monitor the reaction by TLC until the starting material reacts completely. Then remove the dioxane by rotary evaporation under reduced pressure to obtain the crude product. The reaction formula is as follows:

[0058]

[0059] Step 2: Petroleum ether and ethyl acetate were mixed at a volume ratio of 40:1 as the eluent. Potassium acetate, unreacted raw materials, and other impurities were removed by column chromatography to obtain a 3-hydroxy-2,3-dihydrobenzofuran derivative (E)-1-(3-hydroxy-2,3-dihydrobenzofuran-2-yl)-3-(4-methoxyphenyl)prop-2-en-1-one with antibacterial activity, denoted as 3ad, with a yield of 53%.

[0060] The structure of compound 3ad was identified using an AVANCE NEO 600M nuclear magnetic resonance spectrometer (manufactured by Bruker, Germany) via nuclear magnetic resonance and high-resolution mass spectrometry. The results are as follows: 1H NMR (400MHz, CDCl3) δ7.77(dd,J=15.9,9.6Hz,1H),7.55(dd,J=15.5,8.7Hz,2H),7.43(dd,J=20.6,7.4Hz,1H),7.33 (q,J=7.5Hz,1H),7.14(d,J=15.9Hz,1H),7.07-6.84(m,5H),5.56(d,J=36.1Hz,1H),5.18-5.11(m,1H),3.84(s,3H); 13 C NMR (101MHz, CDCl3) δ195.9,162.2,162.1,159.6,144.8,131.1,130.8,126. 0,121.8,119.3,117.9,114.4,110.9,93.3,89.6,73.3,55.4; HRMS(ESI)m / z Calcdfor C 18 H 16 NaO4[M+Na] + 319.3112, found 368.319.3110. This indicates that the 3-hydroxy-2,3-dihydrobenzofuran derivative (E)-1-(3-hydroxy-2,3-dihydrobenzofuran-2-yl)-3-(4-methoxyphenyl)prop-2-en-1-one synthesized in Example 6 has the structure shown in structural formula 3ad.

[0061] Example 7

[0062] Step 1: Add 1 mmol of 5-bromosalicylic acid, 2 mmol of 1-bromo-4-(4-bromophenyl)-3-buten-2-one, and 1.2 mmol of sodium carbonate to 2 mL of dioxane. Stir at room temperature for 3 h. Monitor the reaction by TLC until the reactants are completely reacted. Then remove the dioxane by rotary evaporation under reduced pressure to obtain the crude product. The reaction formula is as follows:

[0063]

[0064] Step 2: Petroleum ether and ethyl acetate were mixed at a volume ratio of 30:1 as the eluent. Sodium carbonate, unreacted raw materials, and other impurities were removed by column chromatography to obtain a 3-hydroxy-2,3-dihydrobenzofuran derivative (E)-1-(5-bromo-3-hydroxy-2,3-dihydrobenzofuran-2-yl)-3-(4-bromophenyl)prop-2-en-1-one with antibacterial activity, denoted as 3bb, with a yield of 63%.

[0065] The structure of compound 3bb was identified using an AVANCE NEO 600M nuclear magnetic resonance spectrometer (manufactured by Bruker, Germany) via nuclear magnetic resonance and high-resolution mass spectrometry. The results are as follows: 1H NMR(600MHz, CDCl3)δ7.72(dd,J=16.0,5.4Hz,1H),7.57-7.50(m,3H),7.50-7.40(m,3H),7.21(d,J=15.9Hz,1H) ,7.07(d,J=16.0Hz,1H),6.91(dd,J=8.6,5.4Hz,1H),5.58(dd,J=27.1,21.3Hz,1H),5.16(dd,J=9.3,5.1Hz,1H); 13 C NMR (151MHz, CDCl3) δ194.5,157.5,142.4,133.0,128.7,128.5,128.1,127.8,120.6,119.6 112.1,111.4,92.1,88.7,74.1,71.2.HRMS(ESI)m / z Calcd for C 17 H 12 Br2O3[M+Na] + 447.0772, found 447.0773, indicates that the 3-hydroxy-2,3-dihydrobenzofuran derivative (E)-1-(5-bromo-3-hydroxy-2,3-dihydrobenzofuran-2-yl)-3-(4-bromophenyl)prop-2-en-1-one synthesized in Example 7 has the structure shown in structural formula 3bb.

[0066] The mycelial growth rate method was used to test the inhibitory effects of the 3-hydroxy-2,3-dihydrobenzofuran derivatives synthesized in Examples 1 to 7 on four plant-derived fungi. The specific process was as follows: the concentrations of the 3-hydroxy-2,3-dihydrobenzofuran derivatives and the existing antibacterial drug pyraclostrobin were both set at 50 μg / mL, and antibacterial tests were performed on the four plant-derived fungi respectively. The results are shown in Table 1.

[0067] Table 1. Antibacterial results of 3-hydroxy-2,3-dihydrobenzofuran derivatives and pyraclostrobin.

[0068]

[0069] As shown in Table 1, although all compounds exhibited some inhibitory effects against *Valsa mali* (VM), *Fusarium solani* (FS), *Leptosphaeria biglobosa* (LB), and *Botrytis cinerea* (BC), the inhibitory activity of the same compound at the same concentration against the mycelial growth of different plant-derived pathogenic fungi varied. Furthermore, different compounds showed varying inhibitory effects on the mycelial growth of the same plant-derived pathogenic fungi. Most of the 2,3-dihydrobenzofuran derivatives synthesized in Examples 1–7 showed inhibitory effects against *Valsa mali* (VM), *Fusarium solani* (FS), *Leptosphaeria biglobosa* (LB), and *Botrytis cinerea* (BC). The compound 3ab synthesized in Example 4 showed significant inhibitory effects on Valsamali (VM) and Leptosphaeria biglobosa (LB), the causal agent of black shank in rapeseed. In particular, the growth inhibition rate of Valsamali (VM) reached 75.53%, and the growth inhibition rate of Leptosphaeria biglobosa (LB) reached 82.80%, which is much higher than the inhibition rate of the control group positive control drug pyraclostrobin.

Claims

1. A 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity, characterized in that, The structure is as follows: In the formula, R 1 and R 2 It can be hydrogen, chlorine, bromine, or methoxy.

2. The method for preparing the 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity according to claim 1, characterized in that, Includes the following steps: Step 1: Compound I, Compound II, and the catalyst are added to an organic solvent and stirred thoroughly at room temperature. The mixture undergoes a series alkylation aldol condensation reaction. The organic solvent is then removed from the crude product by rotary evaporation under reduced pressure to obtain the crude product. The reaction formula is as follows: Compound I is salicylaldehyde or a salicylaldehyde derivative, and compound II is a 1-bromobenzylacetone derivative; The organic solvent is tetrahydrofuran or dioxane; The catalyst is potassium carbonate, sodium carbonate, or potassium acetate. Step 2: Remove the catalyst, unreacted raw materials and other impurities by column chromatography to obtain a 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity.

3. The method for preparing the 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity according to claim 2, characterized in that, The ratio of compound I, compound II, catalyst, and organic solvent is 1 mmol: 2 mmol: 1.2 mmol: 2 mL.

4. The method for preparing the 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity according to claim 2, characterized in that, The salicylaldehyde derivative is 5-bromosalicylaldehyde or 5-chlorosalicylaldehyde.

5. The method for preparing the 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity according to claim 2, characterized in that, The 1-bromobenzylacetone derivative is 1-bromo-4-phenyl-3-buten-2-one, 1-bromo-4(4-bromophenyl)-3-buten-2-one, 1-bromo-4(4-chlorophenyl)-3-buten-2-one or 1-bromo-4(4-methoxyphenyl)-3-buten-2-one.

6. The method for preparing the 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity according to claim 2, characterized in that, The eluent used in the column chromatography was a mixture of petroleum ether and ethyl acetate in a volume ratio of (20-40):

1.

7. The application of the 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity as described in claim 1 as an antibacterial agent for plant-derived fungi.

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