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

Abstract

The invention discloses a 3-oxopropyl-2, 3-dihydrobenzofuran derivative with antibacterial activity and a preparation method and application thereof.The method comprises the steps that 1, a compound I, a compound II and a catalyst are taken and added into an organic solvent, sufficient stirring is conducted at the normal temperature, an alkylation Michael addition cascade reaction is conducted, and a compound III is obtained; removing the organic solvent in the crude product through reduced pressure rotary evaporation to obtain a crude product; the compound I is o-hydroxy benzalacetone or an o-hydroxy benzalacetone derivative, and the compound II is a 1-bromobenzalacetone derivative; and step 2, removing the catalyst, unreacted raw materials and other impurities by utilizing column chromatography to obtain the 3-oxopropyl-2, 3-dihydrobenzofuran derivative with the 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-oxopropyl-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 2011, Kan et al. [Wakimoto T, Miyata K, Ohuchi H, et al. Organic Letters 2011, 13 (10), 2789-2791.] reported a rhodium-catalyzed enantioselective synthesis of cis-2-amide-3-aryl-2,3-dihydrobenzofuran. The reaction process is as follows:

[0004]

[0005] In 2017, the Li and Xu groups [Li Y, Tang Y, He X, et al. Chemistry (Weinheim an der Bergstrasse, Germany), 2017, 23(31): 7453-7457.] synthesized a series of novel 2,3-dihydrobenzofuran compounds by cyclooxygenation of 1,1-disubstituted olefins with anisole compounds based on the metal rhodium (III)-catalyzed CH bond activation strategy. The reaction process is as follows:

[0006]

[0007] In 2021, Professor Xu Minghua's research group [Zhu DX, Liu JG, Xu MH. Journal of the American Chemical Society, 2021, 143(23): 8583-8589.] used a one-pot method to synthesize a series of chiral benzodihydrofuran compounds in a stereodivergent manner using quinine-derived thiourea catalyst and rhodium (I) metal catalyst for synergistic catalysis. They cleverly utilized the OH in the reaction substrate and the α,β-unsaturated ester structure generated during the reaction to undergo an intramolecular oxa-Michael tandem reaction, constructing a chiral benzodihydrofuran skeleton and obtaining compounds corsifuran A and corsifuran B. The reaction process is as follows:

[0008]

[0009] 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 reaction of o-hydroxyphenyl propargyl 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 process is as follows:

[0010]

[0011] However, the synthesis of 2,3-dihydrobenzofuran derivatives to date usually involves complex substrates, long steps, high costs, and is environmentally unfriendly. Therefore, there is an urgent need to explore a new method to synthesize new 2,3-dihydrobenzofuran derivatives. Summary of the invention

[0012] In view of the shortcomings of the prior art, the purpose of the present invention is to provide a 3-oxopropyl-2,3-dihydrobenzofuran derivative with antibacterial activity and 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.

[0013] In order to achieve the above object, the present invention adopts the following technical solutions:

[0014] A 3-oxopropyl-2,3-dihydrobenzofuran derivative with antibacterial activity, the structural formula of which is as follows:

[0015]

[0016] In the formula, R 1 and R 2 is hydrogen, chlorine, bromine or methoxy.

[0017] A method for preparing a 3-oxopropyl-2,3-dihydrobenzofuran derivative having antibacterial activity comprises the following steps:

[0018] Step 1: Compound I, Compound II and a catalyst are added to an organic solvent, stirred sufficiently at room temperature, and subjected to an alkylation Michael addition 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:

[0019]

[0020] The compound I is o-hydroxybenzylideneacetone or an o-hydroxybenzylideneacetone derivative, and the compound II is a 1-bromobenzylideneacetone derivative;

[0021] Step 2: Using column chromatography to remove the catalyst, unreacted raw materials and other impurities, to obtain 3-oxopropyl-2,3-dihydrobenzofuran derivatives with antibacterial activity.

[0022] Furthermore, the ratio of compound I, compound II, catalyst and organic solvent is 1 mmol: 2 mmol: 1.2 mmol: 2 mL.

[0023] Furthermore, the o-hydroxybenzylideneacetone derivative is 5-bromo-o-hydroxybenzylideneacetone, 5-chloro-o-hydroxybenzylideneacetone or 4-methoxy-o-hydroxybenzylideneacetone.

[0024] 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.

[0025] Furthermore, the organic solvent is tetrahydrofuran or dioxane.

[0026] Furthermore, the catalyst is potassium carbonate, potassium acetate or sodium carbonate.

[0027] 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.

[0028] A 3-oxopropyl-2,3-dihydrobenzofuran derivative with antibacterial activity is used as an antibacterial agent.

[0029] Compared with the prior art, the present invention has the following technical effects:

[0030] The present invention uses cheap and readily available o-hydroxybenzylideneacetone or o-hydroxybenzylideneacetone derivatives and 1-bromobenzylideneacetone derivatives as raw materials, and in the presence of a catalyst, in an organic solvent, alkylation Michael addition tandem reaction is used to simply and quickly prepare 3-oxopropyl-2,3-dihydrobenzofuran derivatives. After conventional vacuum rotary evaporation and column chromatography purification, the product purity reaches more than 99%, and the yield reaches 60% to 84%. In addition, the prepared 3-oxopropyl-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

[0031] Figure 1(a) to Figure 1(b) : Nuclear magnetic resonance spectrum of compound 3aa prepared in Example 1 of the present invention;

[0032] Figure 2(a) to Figure 2(b) : Nuclear magnetic resonance spectrum of compound 3bb prepared in Example 2 of the present invention. DETAILED DESCRIPTION

[0033] The specific contents of the present invention are further explained in detail below in conjunction with embodiments.

[0034] Example 1

[0035] Step 1: Add 1 mmol of o-hydroxybenzylideneacetone, 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 tetrahydrofuran from the crude product by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows:

[0036]

[0037] 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-oxopropyl-2,3-dihydrobenzofuran derivative with antibacterial activity, denoted as 3aa, with a yield of 72%.

[0038] 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(a) to Figure 1(b) As shown: 1 H NMR (600MHz, CDCl3) δ7.78(d,J=16.0Hz,1H),7.60(dd,J=7.0,1.8Hz,2H),7.39(d,J=6.4Hz,3H),7.28(s,1H),7.25(s,1H),7.19(d,J= 7.6Hz,1H),7.14(d,J=7.4Hz,1H),6.97-6.87(m,2H),4.92(d,J=5.8Hz,1H),4.09(d,J=6.4Hz,1H),2.97(d,J=6.9Hz,2H),2.23(s,3H); 13 C NMR (151MHz, CDCl3) δ206.3,196.9,158.9,145.2,134.5,130.9,129.0,128.9,1 28.8,128.6,124.8,121.5,120.6,110.0,89.9,49.1,40.9,30.3; HRMS(ESI)m / z Calcd for C 20 H 18 O3[M+Na] + 329.1148, found 329.1154. This indicates that the 3-oxopropyl-2,3-dihydrobenzofuran synthesized in Example 1 has the structure shown in structural formula 3aa.

[0039] Example 2

[0040] Step 1: Add 1 mmol of 5-bromo-o-hydroxybenzylideneacetone, 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 from the crude product by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows:

[0041]

[0042] 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-oxopropyl-2,3-dihydrobenzofuran derivative with antibacterial activity, denoted as 3bb, with a yield of 70%.

[0043] The structure of compound 3bb was identified by nuclear magnetic resonance and high-resolution mass spectrometry using AVANCE NEO 600M nuclear magnetic resonance spectrometer produced by Bruker, Germany. Figure 2(a) to Figure 2(b) As shown: 1 H NMR (400MHz, CDCl3) δ7.70(d,J=16.0Hz,1H),7.53(d,J=8.5Hz,2H),7.46(d,J=8.5Hz,2H),7.29(dd,J=8.5,2.0Hz,1H),7.26 -7.19(m,2H),6.81(d,J=8.5Hz,1H),4.93(d,J=5.7Hz,1H),4.05(dd,J=12.8,6.6Hz,1H),2.96(d,J=6.9Hz,2H),2.23(s,3H); 13 C NMR (101MHz, CDCl3) δ206.1,196.0,158.0,144.0,133.2,132.2,131.8,131.0,1 30.1,127.9,125.4,120.9,113.4,111.5,90.1,48.8,40.6,30.2; HRMS(ESI)m / z Calcd for C 20 H 16 Br2O3[M+Na] + 484.9358, found 484.9359. This indicates that the 3-oxopropyl-2,3-dihydrobenzofuran derivative synthesized in Example 2 has the structure shown in Structural Formula 3bb.

[0044] Example 3

[0045] Step 1: Add 1 mmol of 5-chloro-o-hydroxybenzylideneacetone, 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 from the crude product by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows:

[0046]

[0047] 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-oxopropyl-2,3-dihydrobenzofuran derivative with antibacterial activity, denoted as 3ca, with a yield of 84%.

[0048] 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: 1 H NMR (600MHz, CDCl3) δ7.77(d,J=16.0Hz,1H),7.58(dd,J=7.4,1.7Hz,2H),7.38(d,J=6.8Hz,3H),7.22(d,J=16.0Hz,1H),7. 12(dd,J=10.6,2.1Hz,2H),6.83(d,J=8.4Hz,1H),4.94(d,J=5.8Hz,1H),4.13-4.01(m,1H),2.99-2.89(m,2H),2.20(s,3H); 13 C NMR (151MHz, CDCl3) δ206.0,196.1,157.5,145.4,134.3,131.0,128.9,128 .8,128.8,126.2,125.0,120.4,110.8,90.2,48.7,40.6,30.; HRMS(ESI)m / z Calcd for C 20 H 17 ClO3[M+Na] + 363.0758, found 363.0759. This indicates that the 3-oxopropyl-2,3-dihydrobenzofuran derivative synthesized in Example 3 has the structure shown in structural formula 3ca.

[0049] Example 4

[0050] Step 1: Add 1 mmol of 4-methoxy-o-hydroxybenzylideneacetone, 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 from the crude product by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows:

[0051]

[0052] 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-oxopropyl-2,3-dihydrobenzofuran derivative with antibacterial activity, denoted as 3da, with a yield of 73%.

[0053] The structure of compound 3da 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: 1 H NMR (600MHz, CDCl3) δ7.78(d,J=15.9Hz,1H),7.63-7.56(m,2H),7.39(d,J=5.9Hz,3H),7.23(s,1H),7.02(d,J=8.3Hz,1H),6.53(d,J=2.2 Hz,1H),6.44(dd,J=8.3,2.1Hz,1H),4.93(d,J=5.5Hz,1H),4.00(dd,J=12.6,6.6Hz,1H),3.78(s,3H),2.93(d,J=6.9Hz,2H),2.21(s,3H); 13 CNMR (151MHz, CDCl3) δ206.6,196.9,161.0,160.2,145.1,134.5,130.9,128.9 ,128.8,124.9,120.5,107.2,96.5,90.7,55.6,49.4,40.4,30.3; HRMS(ESI)m / z Calcd for C 21 H 20 O4[M+Na] + 359.1254, found359.1255. This indicates that the 3-oxopropyl-2,3-dihydrobenzofuran derivative synthesized in Example 4 has the structure shown in structural formula 3da.

[0054] Example 5

[0055] Step 1: Add 1 mmol of o-hydroxybenzylideneacetone, 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 from the crude product by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows:

[0056]

[0057] 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-oxopropyl-2,3-dihydrobenzofuran derivative with antibacterial activity, denoted as 3ab, with a yield of 80%.

[0058] 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: 1 H NMR (400MHz, CDCl3) δ7.69(d,J=15.9Hz,1H),7.51(d,J=8.5Hz,2H),7.44(d,J=8.5Hz,2H),7.25-7.07(m,3H), 6.91(dd,J=18.7,7.8Hz,2H),4.91(d,J=5.7Hz,1H),4.07(q,J=6.5Hz,1H),2.96(d,J=6.9Hz,2H),2.22(s,2H); 13 C NMR (101MHz, CDCl3) δ206.5,196.6,158.8,143.6,133.3,132.2,131.3,130.0,1 29.0,128.4,124.7,121.6,121.1,109.9,89.8,49.0,40.7,30.2; HRMS(ESI)m / z CalcdforC 20 H 17 BrO3[M+Na] + 384.0361, found 384.0363. This indicates that the 3-oxopropyl-2,3-dihydrobenzofuran derivative synthesized in Example 5 has the structure shown in Structural Formula 3ab.

[0059] Example 6

[0060] Step 1, add 1 mmol of o-hydroxybenzylideneacetone, 2 mmol of 1-bromo-4 (4-chlorophenyl) -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 in the crude product by vacuum rotary evaporation to obtain a crude product, the reaction formula is as follows:

[0061]

[0062] 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-oxopropyl-2,3-dihydrobenzofuran derivative with antibacterial activity, denoted as 3ac, with a yield of 72%.

[0063] 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: 1 H NMR (400MHz, CDCl3) δ7.72(d,J=16.0Hz,1H),7.52(d,J=8.5Hz,2H),7.36(d,J=8.5Hz,2H),7.23-7.11(m,3H) ,6.96-6.87(m,2H),4.91(d,J=5.7Hz,1H),4.07(dd,J=12.8,6.5Hz,1H),2.96(d,J=6.9Hz,2H),2.22(s,3H); 13 CNMR(151MHz,CDCl3)δ205.9,197.4,158.7,143.3,137.1,132.8,131.9,129.9,129 .3,129.0,128.4,124.7,121.9,121.6,110.0,87.6,44.5,40.0,30.5; HRMS(ESI)m / z Calcdfor C 20 H 17 ClO3[M+Na] + 363.0758, found 363.0758. This indicates that the 3-oxopropyl-2,3-dihydrobenzofuran derivative synthesized in Example 6 has the structure shown in Structural Formula 3ac.

[0064] Example 7

[0065] Step 1: Add 1 mmol of o-hydroxybenzylideneacetone, 2 mmol of 1-bromo-4 (4-methoxyphenyl) -3-butene-2-one and 1.2 mmol of sodium carbonate 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 in the crude product by vacuum rotary evaporation to obtain a crude product. The reaction formula is as follows:

[0066]

[0067] 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-oxopropyl-2,3-dihydrobenzofuran derivative with antibacterial activity, denoted as 3ad, with a yield of 60%.

[0068] 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: 1 H NMR (600MHz, CDCl3) δ7.72(d,J=15.9Hz,1H),7.53(d,J=8.5Hz,2H),7.20(t,J=7.7Hz,1H),7.13(t,J=6.9Hz,1H),6.97-6.87(m,5H),5. 35(d,J=9.6Hz,1H),4.35(dd,J=15.9,7.8Hz,1H),3.85(s,3H),2.78(dd,J=18.0,6.4Hz,1H),2.66(dd,J=18.0,7.9Hz,1H),2.09(s,3H); 13 C NMR (151MHz, CDCl3) δ205.1,197.5,160.8,160.6,144.2,135.1,131.2,127.6, 127.9,123.8,121.2,106.9,97.6,91.6,57.8,50.3,41.1,31.5.HRMS(ESI)m / z Calcd for C 21 H 20 O4[M+Na]+359.1254,found359.1255.HRMS(ESI)m / z Calcd for C 20 H 18 O3[M+Na] + 329.1148, found329.1154. This indicates that the 3-oxopropyl-2,3-dihydrobenzofuran derivative synthesized in Example 7 has the structure shown in structural formula 3ad.

[0069] The mycelium growth rate method was used to test the inhibitory effects of the 3-oxopropyl-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-oxopropyl-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.

[0070] Table 1 Antibacterial results of 3-oxopropyl-2,3-dihydrobenzofuran derivatives and azoxystrobin

[0071]

[0072] 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), rape 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 3-oxopropyl-2,3-dihydrobenzofuran compound derivatives synthesized in Examples 1 to 7 have relatively obvious inhibitory effects on apple rot pathogen (Valsa mali, VM) and rape black leg pathogen (Leptosphaeria biglobosa, LB), especially, compound 3aa synthesized in Example 1, compound 3da synthesized in Example 4 and compound 3ab synthesized in Example 5 have relatively obvious inhibitory effects on apple rot pathogen (Valsa mali, VM). mali, VM) reached a growth inhibition rate of more than 70%, and the antibacterial effect was significantly higher than that of the positive drug azoxystrobin in the control group.

Claims

1. A 3-oxopropyl-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-oxopropyl-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 an alkylation Michael addition 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 o-hydroxybenzylideneacetone or an o-hydroxybenzylideneacetone 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-oxopropyl-2,3-dihydrobenzofuran derivatives with antibacterial activity.

3. The method for preparing the 3-oxopropyl-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-oxopropyl-2,3-dihydrobenzofuran derivative having antibacterial activity according to claim 2, characterized in that: The o-hydroxybenzylidene acetone derivative is 5-bromo-o-hydroxybenzylidene acetone, 5-chloro-o-hydroxybenzylidene acetone or 4-methoxy-o-hydroxybenzylidene acetone.

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

8. The method for preparing the 3-oxopropyl-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-oxopropyl-2,3-dihydrobenzofuran derivative having antibacterial activity according to claim 1 as an antibacterial agent.

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