3-hydroxy-2, 3-dihydrobenzofuran derivative with antibacterial activity as well as preparation method and application of 3-hydroxy-2, 3-dihydrobenzofuran derivative

Abstract

The invention discloses a 3-hydroxy-2, 3-dihydrobenzofuran derivative with antibacterial activity and a preparation method and application thereof, and the method comprises the following steps: step 1, taking a compound I, a compound II and a catalyst, adding into an organic solvent, fully stirring at normal temperature, and carrying out alkylation aldol condensation cascade reaction to obtain a compound III; removing the organic solvent in the crude product through reduced pressure rotary evaporation to obtain a crude product; the compound I is salicylaldehyde or a salicylaldehyde derivative, and the compound II is a 1-bromobenzalacetone derivative; and step 2, removing the catalyst, unreacted raw materials and other impurities by using column chromatography to obtain the 3-hydroxy-2, 3-dihydrobenzofuran derivative with antibacterial activity. The preparation method has the advantages of being simple, low in price and high in yield, and the prepared compound has a good bacteriostatic effect.

Description

Technical Field

[0001] The invention relates to dihydrobenzofuran compounds, in particular to 3-hydroxy-2,3-dihydrobenzofuran derivatives with antibacterial activity and a preparation method and application thereof. Background Art

[0002] 2,3-Dihydrobenzofuran is a class of heterocyclic compounds with good biological activity and low molecular weight. It is widely used in agriculture, medicine, chemical industry and other fields and has great application value. Studies have reported that dihydrobenzofuran (DHBs) is a necessary structural unit for the biological activity of various non-natural products such as polyether ion carrier antibiotics and macrolide drugs. It is also the basic structural unit of many important natural products such as plant lignin and red sandalwood. In addition, it is worth noting that compounds with dihydrobenzofuran structure are also used to treat 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], 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.], insecticide [Wangjin X, Diajing 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.], etc. 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 reaction substrate, inorganic base K2CO3 as the reaction catalyst, and acetone as the reaction solvent. Under heating reflux conditions, an intramolecular ring-closure reaction occurred, and finally a 2,3-dihydrobenzofuran structure was constructed. 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 catalytically activate intramolecular hydrogen bonds, and in situ generated enamines attacked the α, β-unsaturated double bonds, resulting in an intramolecular nucleophilic reaction. After ring closure, a chiral 2,3-dihydrobenzofuran structure was constructed. The reaction formula is as follows:

[0006]

[0007] In 2024, Feng Miao et al. [Feng Miao, Lv Lanlan, Guo Yijia, et al. Organic Chemistry, 2024, 1-12.] reported the silver-catalyzed 5-exo-dig cyclization of o-hydroxyphenylpropargyl alcohol with isonitrile as ligand, and constructed a series of 2-methylene-2,3-dihydrobenzofuran-3-ol compounds with moderate to excellent yields. The reaction formula is as follows:

[0008]

[0009] However, to date, the conditions required for the synthesis of 2,2,3-dihydrobenzofuran derivatives are relatively harsh. In most cases, precious metals are used, which are costly and not environmentally friendly. Therefore, there is an urgent need to explore a new method to synthesize new 2,3-dihydrobenzofuran derivatives. Summary of the invention

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

[0011] In order to achieve the above object, the present invention adopts the following technical solutions:

[0012] A 3-hydroxy-2,3-dihydrobenzofuran and its derivatives having antibacterial activity, the structural formula of which is as follows:

[0013]

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

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

[0016] Step 1: Compound I, Compound II and a catalyst are added to an organic solvent, stirred sufficiently at room temperature, and subjected to alkylation aldol condensation cascade reaction, and then the organic solvent in the crude product is removed by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows:

[0017]

[0018] The compound I is salicylaldehyde or a salicylaldehyde derivative, and the compound II is a 1-bromobenzylideneacetone derivative;

[0019] Step 2: Using column chromatography to remove the catalyst, unreacted raw materials and other impurities to obtain 3-hydroxy-2,3-dihydrobenzofuran derivatives 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] Furthermore, the 1-bromobenzylideneacetone derivative is 1-bromo-4-phenyl-3-butene-2-one, 1-bromo-4(4-bromophenyl)-3-butene-2-one, 1-bromo-4(4-chlorophenyl)-3-butene-2-one or 1-bromo-4(4-methoxyphenyl)-3-butene-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] A 3-hydroxy-2,3-dihydrobenzofuran derivative with antibacterial activity is used as an antibacterial agent.

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

[0028] The present invention uses cheap salicylaldehyde or salicylaldehyde derivatives or 1-bromobenzylideneacetone derivatives as raw materials, and in the presence of a catalyst, in an organic solvent, alkylation aldol condensation tandem reaction is used to simply and quickly prepare 3-hydroxy-2,3-dihydrobenzofuran derivatives. After conventional vacuum rotary evaporation and column chromatography purification, the product purity reaches more than 98%, and the yield reaches 53% to 93%; in addition, the prepared 3-hydroxy-2,3-dihydrobenzofuran derivatives have a certain inhibitory effect on apple rot bacteria, potato stem wilt bacteria, rapeseed black leg bacteria and tomato gray mold bacteria. In short, the present invention not only has the advantages of simple operation steps, low cost, green and mild reaction conditions, simple post-treatment, and high yield, and is suitable for industrial production, but also the prepared compounds have good antibacterial effects, and thus have potential social and economic benefits. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1-2 : Nuclear magnetic resonance spectrum of compound 3aa prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0030] The specific contents of the present invention are further explained in detail below in conjunction with embodiments.

[0031] Example 1

[0032] Step 1: Add 1 mmol of salicylaldehyde, 2 mmol of 1-bromo-4-phenyl-3-butene-2-one and 1.2 mmol of potassium carbonate to 2 mL of tetrahydrofuran, stir for 3 h at room temperature, and track by TLC until the reaction of the raw materials is complete. Then, remove the tetrahydrofuran by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows:

[0033]

[0034] Step 2: petroleum ether and ethyl acetate were mixed in a volume ratio of 40:1 as an eluent, and 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 by nuclear magnetic resonance and high-resolution mass spectrometry using an AVANCE NEO 600M nuclear magnetic resonance spectrometer produced by Bruker, Germany. Figure 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: (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-bromosalicylaldehyde, 2 mmol of 1-bromo-4-phenyl-3-butene-2-one and 1.2 mmol of potassium carbonate to 2 mL of tetrahydrofuran, stir for 3 h at room temperature, track by TLC until the reaction of the raw materials is complete, and then remove tetrahydrofuran by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows:

[0038]

[0039] Step 2: petroleum ether and ethyl acetate were mixed in a volume ratio of 30:1 as an eluent, and potassium 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-phenylprop-2-en-1-one with antibacterial activity, denoted as 3ba, with a yield of 90%.

[0040] The structure of compound 3ba was identified by nuclear magnetic resonance and high-resolution mass spectrometry using the AVANCE NEO 600M nuclear magnetic resonance spectrometer produced by Bruker, Germany. 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, found368.1813. 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-butene-2-one and 1.2 mmol of potassium carbonate to 2 mL of tetrahydrofuran, stir for 3 h at room temperature, track by TLC until the reaction of the raw materials is complete, and then remove tetrahydrofuran by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows:

[0043]

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

[0045] The structure of compound 3ca was identified by nuclear magnetic resonance and high-resolution mass spectrometry using the AVANCE NEO 600M nuclear magnetic resonance spectrometer produced by Bruker, Germany. 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-butene-2-one and 1.2 mmol of potassium carbonate to 2 mL of tetrahydrofuran, stir for 3 h at room temperature, track by TLC until the reaction of the raw materials is complete, and then remove tetrahydrofuran by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows:

[0048]

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

[0050] The structure of compound 3ab was identified by nuclear magnetic resonance and high-resolution mass spectrometry using the AVANCE NEO 600M nuclear magnetic resonance spectrometer produced by Bruker, Germany. 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-butene-2-one and 1.2 mmol of potassium carbonate to 2 mL of tetrahydrofuran, stir for 3 h at room temperature, track by TLC until the reaction of the raw materials is complete, and then remove tetrahydrofuran by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows:

[0053]

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

[0055] The structure of compound 3ac was identified by nuclear magnetic resonance and high-resolution mass spectrometry using the AVANCE NEO 600M nuclear magnetic resonance spectrometer produced by Bruker, Germany. 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-butene-2-one and 1.2 mmol of potassium acetate to 2 mL of dioxane, stir for 3 h at room temperature, track by TLC until the reaction of the raw materials is complete, and then remove the dioxane by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows:

[0058]

[0059] Step 2: petroleum ether and ethyl acetate were mixed in a volume ratio of 40:1 as an eluent, and 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 by nuclear magnetic resonance and high-resolution mass spectrometry using the AVANCE NEO 600M nuclear magnetic resonance spectrometer produced by Bruker, Germany. 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 5-bromosalicylaldehyde, 2 mmol 1-bromo-4 (4-bromophenyl) -3-butene-2-one and 1.2 mmol sodium carbonate to 2 mL dioxane, stir for 3 h at room temperature, track by TLC until the reaction of the raw materials is complete, and then remove the dioxane by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows:

[0063]

[0064] Step 2: petroleum ether and ethyl acetate were mixed in a volume ratio of 30:1 as an eluent, and 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 by nuclear magnetic resonance and high-resolution mass spectrometry using the AVANCE NEO 600M nuclear magnetic resonance spectrometer produced by Bruker, Germany. 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, indicating 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 mycelium 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 the activity of 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 azoxystrobin were set to 50 μg / mL, and the 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 azoxystrobin

[0068]

[0069] As can be seen from Table 1, although all compounds have certain inhibitory effects on apple rot pathogen (Valsa mali, VM), potato stem wilt pathogen (Fusarium solani, FS), rapeseed black leg pathogen (Leptosphaeria biglobosa, LB) and tomato gray mold pathogen (Botrytis cinerea, BC), the same compound at the same concentration has different inhibitory effects on the growth of mycelium of different plant-derived pathogenic fungi, and different compounds have different inhibitory effects on the growth of mycelium of the same plant-derived pathogenic fungi. Most of the 2,3-dihydrobenzofuran compound derivatives synthesized in Examples 1 to 7 have no inhibitory effects on apple rot pathogen (Valsa mali, VM). mali, VM) and rape black shank pathogen (Leptosphaeria biglobosa, LB). In particular, the compound 3ab synthesized in Example 4 had a growth inhibition rate of 75.53% on apple rot pathogen (Valsamali, VM) and a growth inhibition rate of 82.80% on rape black shank pathogen (Leptosphaeria biglobosa, LB). The antibacterial effect was much higher than the inhibition rate of the positive drug azoxystrobin in the control group.

Claims

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

2. The method for preparing the 3-hydroxy-2,3-dihydrobenzofuran derivative having antibacterial activity according to claim 1, characterized in that: The steps include: Step 1: Compound I, Compound II and a catalyst are added to an organic solvent, stirred sufficiently at room temperature, and subjected to alkylation aldol condensation cascade reaction, and then the organic solvent in the crude product is removed by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows: The compound I is salicylaldehyde or a salicylaldehyde derivative, and the compound II is a 1-bromobenzylideneacetone derivative; Step 2: Using column chromatography to remove the catalyst, unreacted raw materials and other impurities to obtain 3-hydroxy-2,3-dihydrobenzofuran derivatives with antibacterial activity.

3. The method for preparing the 3-hydroxy-2,3-dihydrobenzofuran derivative having antibacterial activity according to claim 2, characterized in that: The ratio of the 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 having 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 having antibacterial activity according to claim 2, characterized in that: The 1-bromobenzylideneacetone derivative is 1-bromo-4-phenyl-3-butene-2-one, 1-bromo-4(4-bromophenyl)-3-butene-2-one, 1-bromo-4(4-chlorophenyl)-3-butene-2-one or 1-bromo-4(4-methoxyphenyl)-3-butene-2-one.

6. The method for preparing the 3-hydroxy-2,3-dihydrobenzofuran derivative having antibacterial activity according to claim 2, characterized in that: The organic solvent is tetrahydrofuran or dioxane.

7. The method for preparing the 3-hydroxy-2,3-dihydrobenzofuran derivative having antibacterial activity according to claim 2, characterized in that: The catalyst is potassium carbonate, sodium carbonate or potassium acetate.

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

1.

9. Use of the 3-hydroxy-2,3-dihydrobenzofuran derivative having antibacterial activity according to claim 1 as an antibacterial agent.

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