Derivatives of 3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one, and their preparation and application

Abstract

The present invention relates to a new class of compounds and their preparation methods and applications, in particular to ( E )-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one derivatives and their preparation methods and applications. E The structural formula of )-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one is shown in Formula I, wherein R is selected from the group consisting of chlorine, bromine, methyl, methoxy, 2,3,4-trimethoxy, ethoxy, nitro, and 2,4-dichloro. Experiments have shown that the compounds of the present invention are particularly effective against Botrytis cinerea ( Botryosphaeria dothidea )、Pythium aphanidermatum( Pythium aphanidermatum ) showed good antifungal activity, with some drugs showing comparable activity to the marketed drug fluopyram. The compounds of this invention will provide more options for the development of antifungal drugs and have broad application prospects. #imgabs0#

Description

Technical Field

[0001] The present invention relates to a new class of compounds, preparation methods and applications thereof, and specifically to derivatives of (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one, preparation methods and applications thereof. Background Art

[0002] Chalcone has a wide range of pharmacological activities, such as antibacterial, antimalarial, antiprotozoal, antituberculosis, anticancer, and antifungal. Studies have found that the reactive α,β-unsaturated ketone group in chalcone is the reason for its biological activity. Deepa Gupta et al. described the antifungal activity of newly synthesized chalcone derivatives against the fungus Microsporum gypseum, and the results were superior to ketoconazole. Among them, the 4-chloro derivative (1) and the unsubstituted derivative of chalcone (2) showed antifungal activity superior to ketoconazole (J. Adv. Pharm. Technol. Res., 2015, 6, 114-7). Aimei et al. evaluated the in vitro and in vivo antifungal activity of quinoline derivatives related to the chalcone moiety against Candida albicans. Mechanistic studies demonstrated that PK-10 combined with FLC inhibited the formation of Candida albicans hyphae, induced the accumulation of reactive oxygen species (ROS), the destruction of mitochondrial membrane potential, and the decrease of intracellular ATP content, leading to mitochondrial dysfunction, indicating that they are new drugs for the treatment of drug-resistant Candida albicans infections (Eur. J. Med. Chem., 2023, 260).

[0003]

[0004] Furthermore, the structure of chalcone also has great potential value in drug synthesis and its application in antifungal applications. Chinese Patent CN116478032A discloses 2',3,4',5,6'-pentahydroxy-3'-isopentenyl chalcone analogs and their applications, demonstrating that 2',3,4',5,6'-pentahydroxy-3'-isopentenyl chalcone can significantly inhibit the major postharvest pathogens of citrus: Citric acid green mold, Citric acid penicillium, and Citric acid rot fungus. Chinese Patent CN118490668A discloses the use of 2,6,2',4'-tetrahydroxy-6'-methoxy chalcone in the preparation of antibacterial and / or anti-inflammatory drugs. Chinese Patent CN110655464A discloses a chalcone compound containing an oxyacetic acid structure and its antibacterial application, demonstrating that the compound has certain activity against Escherichia coli, Staphylococcus aureus, and Salmonella, and has great potential value in the development of antibacterial drugs.

[0005] Therefore, it is of great significance to develop a new derivative containing a chalcone skeleton and explore its antibacterial uses. Summary of the Invention

[0006] One of the purposes of the present invention is to provide a new derivative containing a chalcone skeleton: a derivative of 3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-trifluoromethylpropenone.

[0007] A second object of the present invention is to provide a method for preparing the above-mentioned 3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-trifluoromethylpropenone derivatives.

[0008] The second object of the present invention is to provide the application of the above-mentioned 3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-trifluoromethylpropenone derivatives.

[0009] In order to achieve the above object, the present invention adopts the following technical solutions:

[0010] Derivatives of (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one represented by chemical structural formula I:

[0011]

[0012] Wherein, R is selected from the group consisting of chlorine, bromine, methyl, methoxy, 2,3,4-trimethoxy, ethoxy, nitro, and 2,4-dichloro.

[0013] Preferably, the derivative of (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one is selected from: compounds E1, E2, E3, E4, E5, E6, E7, E8 or E9; wherein E1 is (E)-3-(4-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0014] E2 is (E)-3-(2-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0015] E3 is (E)-3-(4-bromophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0016] E4 is (E)-3-(4-methylphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0017] E5 is (E)-3-(2-methoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E6 is (E)-3-(2,3,4-trimethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0018] E7 is (E)-3-(4-ethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E8 is (E)-3-(4-nitrophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E9 is (E)-3-(2,4-dichlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one.

[0019] The preparation method of the above-mentioned (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one derivative is as follows:

[0020]

[0021] Wherein, R is selected from the group consisting of chlorine, bromine, methyl, methoxy, 2,3,4-trimethoxy, ethoxy, nitro, and 2,4-dichloro.

[0022] The present invention also provides the use of the above-mentioned (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one derivatives in the preparation of antifungal preparations.

[0023] Preferably, the plant fungus is Botryosphaeria dothidea or Pythium aphanidermatum.

[0024] Preferably, the (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one is selected from compounds E1, E3, E4, E5, E6, E7 or E8, wherein

[0025] E1 is (E)-3-(4-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0026] E3 is (E)-3-(4-bromophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0027] E4 is (E)-3-(4-methylphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0028] E5 is (E)-3-(2-methoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E6 is (E)-3-(2,3,4-trimethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0029] E7 is (E)-3-(4-ethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E8 is (E)-3-(4-nitrophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one.

[0030] The beneficial effects of the present invention are:

[0031] This invention provides a new class of chalcone-based derivatives: 3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-trifluoromethylpropenone derivatives, as well as their preparation methods and applications. Experiments have shown that these compounds exhibit particularly strong antifungal activity against Botryosphaeria dothidea and Pythium aphanidermatum, with some showing comparable activity to the marketed drug flupyrosaccharide. These compounds will provide more options for the development of antifungal drugs and have broad application prospects. DETAILED DESCRIPTION

[0032] The present invention will be further described below with reference to the following examples. The following examples are only for illustration and are not intended to limit the scope of protection of the present invention in any way.

[0033] The processes and methods not described in detail in the following examples are conventional methods known in the art. The reagents used in the examples are all analytically pure or chemically pure and are commercially available or prepared by methods well known to those skilled in the art. The following examples all achieve the objectives of the present invention.

[0034] Example 1

[0035] Synthesis of 7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran (B):

[0036]

[0037] To a single-necked flask, 6.0 g (37 mmol) of furanol, 0.24 g (1.5 mmol) of potassium iodide, and 7.58 g (55 mmol) of potassium carbonate were added, using anhydrous ethanol as the solvent. The mixture was stirred at 45°C for approximately 30 min, followed by the addition of 7.79 g (55 mmol) of methyl iodide. The reaction was monitored by TLC until completion. The reaction solution was rotary evaporated to remove the solvent, redissolved in dichloromethane, and filtered to remove the potassium carbonate. The solution was then poured into ice water, whereupon a large amount of solid precipitated. After filtration and drying, brown crystals B were obtained with a yield of 80.7%.

[0038] Example 2

[0039] Synthesis of 1-(7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-1-ethanone (C):

[0040]

[0041] Under ice-bath conditions, a three-necked flask was charged with 1,2-dichloroethane as the reaction solvent. 5.86 g (44 mmol) of anhydrous zinc chloride was then added dropwise using a dropping funnel. Acetyl chloride (3.68 g (47 mmol)) was then added dropwise using a dropping funnel. The reaction was stirred for approximately 30 minutes. Six g (34 mmol) of compound B, fully dissolved in 1,2-dichloroethane, was then added dropwise using a dropping funnel. The initial reaction solution was light blue, but gradually turned dark purple after the addition of compound B. The reaction lasted approximately 6 hours, and TLC confirmed the reaction was complete. After completion, the mixture was poured into 0.1 mol / L glacial hydrochloric acid while stirring. The organic phase was collected, dried, and the solvent removed. Recrystallization from anhydrous ethanol or column chromatography was performed to obtain C, a white solid in a 57.2% yield.

[0042] Example 3

[0043] Synthesis of (E)-3-(4-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D1):

[0044]

[0045] To a single-necked flask, add 0.4 g (1.8 mol) of compound C, 0.33 g (2.4 mmol) of p-chlorobenzaldehyde, and an appropriate amount of sodium hydroxide. A mixture of water and anhydrous ethanol (volume ratio of water to anhydrous ethanol approximately 1:3) was used as the solvent. The reaction was stirred at room temperature for 3 hours, with TLC monitoring during the reaction. A yellow precipitate formed during the reaction, which was the product. Filter the solution, wash the filter cake with water and a small amount of anhydrous ethanol, dry it, and weigh it to obtain a pale yellow solid, D1, in a yield of 50.6%.

[0046] Example 4

[0047] Synthesis of (E)-3-(2-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D2):

[0048]

[0049] To a single-necked flask, add 0.2 g (0.9 mmol) of compound C, 0.2 g (1.0 mmol) of o-chlorobenzaldehyde, and an appropriate amount of sodium hydroxide. A mixture of water and anhydrous ethanol (volume ratio of water to anhydrous ethanol approximately 1:3) was used as the solvent. The reaction was stirred at room temperature for 3 hours, with TLC monitoring during the reaction. After the reaction, the solution was yellow-green. The pH was adjusted to neutral, and the product was extracted with ethyl acetate. The upper organic phase was removed from the solvent, purified by column chromatography, dried, and weighed to yield a green oil, D2, in a 49.1% yield.

[0050] Example 5

[0051] Synthesis of (E)-3-(4-bromophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D3):

[0052]

[0053] The preparation method was the same as that in Example 3. The reaction was carried out at room temperature for 3 h to obtain D3 with an overall yield of 51.1%.

[0054] Example 6

[0055] Synthesis of (E)-3-(4-methylphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D4):

[0056]

[0057] The preparation method was the same as that in Example 3. The reaction was carried out at room temperature for 3 h to obtain D4 with an overall yield of 76.7%.

[0058] Example 7

[0059] Synthesis of (E)-3-(2-methoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D5):

[0060]

[0061] The preparation method was the same as that of Example 4. The reaction was carried out at room temperature for 3 h to obtain D5 with an overall yield of 69.1%.

[0062] Example 8

[0063] Synthesis of (E)-3-(2,3,4-trimethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D6):

[0064]

[0065] The preparation method was the same as that in Example 4. The reaction was carried out at room temperature for 3 h to obtain D6 with a total yield of 88.9%.

[0066] Example 9

[0067] Synthesis of (E)-3-(4-ethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D7):

[0068]

[0069] The preparation method was the same as that in Example 3. The reaction was carried out at room temperature for 3 h to obtain D7 with a total yield of 90.8%.

[0070] Example 10

[0071] Synthesis of (E)-3-(4-nitrophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D8):

[0072] The preparation method was the same as that in Example 3. The reaction was carried out at room temperature for 3 h to obtain D8 with an overall yield of 31.2%.

[0073] Example 11

[0074] Synthesis of (E)-3-(2,4-dichlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D9):

[0075]

[0076] The preparation method was the same as that in Example 3. The reaction was carried out at room temperature for 3 h to obtain D9 with a total yield of 69.6%.

[0077] Example 12

[0078] Synthesis of (E)-3-(4-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E1):

[0079]

[0080] To a single-necked flask, 0.3 g (0.88 mmol) of compound D1 was added, followed by 0.42 g (1.3 mmol) of Togni reagent and 0.0835 g (0.62 mmol) of CuI. An appropriate amount of DMF was added as solvent, and the air in the flask was evacuated. Nitrogen was used as a protective gas and the reaction was carried out at 80°C for 3 days. TLC confirmed the completion of the reaction. After the reaction, DMF was extracted with water, and the organic layer was extracted with ethyl acetate. The solvent was removed by vortexing, and the product was purified by column chromatography, dried, and weighed to obtain a pale yellow oil, E1, in a yield of 24.6%.

[0081] E1: yellow oily substance, 1 H NMR (600MHz, CDCl3) δ1.45(s,6H,2×CH3),2.92(s,2H,CH2),3.81(s,3H,CH3),7.16(q,J=8.3Hz,4H,C6H4 2,3,5,6-H),7.26(s,2H,C6H2 2,6-H),7.35(s,1H,C=CH).HRMS:HR-MS(ESI):m / z calcd for C 21 H 18 ClF3O3([M+Na] + )433.0789,found433.0796.

[0082] Example 13

[0083] Synthesis of (E)-3-(2-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E2):

[0084]

[0085] The preparation method was the same as compound E1, and the reaction was carried out at room temperature for 3 h to obtain E2 with a total yield of 19.3%.

[0086] E2: yellow oily substance, 1H NMR (600MHz, CDCl3) δ1.47(s,6H,2×CH3),2.95(s,2H,CH2),3.84(s,3H,CH3),7.04(t,J=7.6Hz,1H,C6H4 4-H),7.17(t,J=7.8Hz,1H,C6H4 5-H),7.22(d,J=7.6Hz,1H,C6H4 3-H),7.26(s,2H,C6H4 5-H,C6H2 6-H),7.31(s,1H,C6H2 2-H),7.72(s,1H,C=CH).HRMS: HR-MS(ESI):m / z calcd for C 21 H 18 ClF3O3([M+H] + )411.0969,found411.0979.

[0087] Example 14

[0088] Synthesis of (E)-3-(4-bromophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E3):

[0089]

[0090] The preparation method was the same as compound E1, and the reaction was carried out at room temperature for 3 h to obtain E3 with an overall yield of 17.9%.

[0091] E3: yellow oily substance, 1 H NMR (600MHz, CDCl3) δ1.50(s,6H,2×CH3),2.98(s,2H,CH2),3.87(s,3H,CH3),7.16(d,J=8.5Hz,2H,C6H4 2,6-H),7.31(m,2H,C6H2 2,6-H),7.36(d,J=8.5Hz,2H,C6H4 3,5-H),7.41(s,1H,C=CH).HRMS:HR-MS(ESI):m / z calcd for C 21 H 18 BrF3O3([M+H] + )455.0464,found 455.0474.

[0092] Example 15

[0093] Synthesis of (E)-3-(4-methylphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E4):

[0094]

[0095] The preparation method was the same as compound E1, and the reaction was carried out at room temperature for 3 h to obtain E4 with an overall yield of 19.8%.

[0096] E4: yellow oily substance, 1 H NMR (600MHz, CDCl3) δ1.41(s,6H,2×CH3),2.18(s,3H,C6H4-CH3),2.88(s,2H,CH2),3.77(s,3H,CH3),6.94(d,J=8.0Hz,2H,C6H4 3,5-H),7.09(d,J=8.1Hz,2H,C6H4 2,6-H),7.27(d,J=11.3Hz,2H,C6H2 2,6-H),7.35(s,1H,C=CH).HRMS: HR-MS(ESI):m / z calcd for C 22 H 21 F3O3([M+H] + )391.1516, found 391.1526.

[0097] Example 16

[0098] Synthesis of (E)-3-(2-methoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E5):

[0099]

[0100] The preparation method was the same as compound E1, and the reaction was carried out at room temperature for 3 h to obtain E5 with an overall yield of 49.9%.

[0101] E5: yellow oily substance, 1 H NMR (600MHz, CDCl3) δ1.47(s,6H,2×CH3),2.93(s,2H,CH2),3.82(s,3H,CH3),3.83(s,3H,C6H4-OCH3),6.71(t,J=7.5Hz,1H,C6H4-H),6.78(d,J=8 .3Hz, 1H, C6H4-H), 7.13 (d, J=7.5Hz, 1H, C6H4-H), 7.21 (t, J=7.9Hz, 1H, C6H4-H), 7.33 (d, J=3.4Hz, 2H), 7.74 (s, 1H, C=CH). HRMS: HR-MS (ESI): m / z calcd for C 22 H 21 F3O4([M+H]+ )407.1465, found 407.1475.

[0102] Example 17

[0103] Synthesis of (E)-3-(2,3,4-trimethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E6):

[0104]

[0105] The preparation method was the same as compound E1, and the reaction was carried out at room temperature for 3 h to obtain E6 with an overall yield of 33.5%.

[0106] E6: yellow oily substance, 1 H NMR (600MHz, CDCl3) δ1.48(s,6H,2×CH3),2.95(s,2H,CH2),3.77(d,J=4.0Hz,6H,C6H2 OCH3,C6H4 4-OCH3),3.84(s,3H,C6H4 3-OCH3),3.92(s,3H,C6H42-OCH3),6.41(d,J=8.8Hz,1H,C6H4 5-H),6.87(d,J=8.8Hz,1H,C6H4 6-H),7.35(d,J=23.6Hz,2H,C6H2 2,6-H),7.62(s,1H,C=CH).HRMS:HR-MS(ESI):m / z calcd for C 24 H 25 F3O6([M+H] + )467.1676, found 467.1684.

[0107] Example 18

[0108] Synthesis of (E)-3-(4-ethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E7):

[0109]

[0110] The preparation method was the same as compound E1, and the reaction was carried out at room temperature for 3 h to obtain E7 with an overall yield of 32.7%.

[0111] E7: yellow oily substance, 1H NMR(600MHz, CDCl3)δ1.36(t,J=7.0Hz,3H,C6H4-CH3),1.50(s,6H,2×CH3),2.97(s,2 H,CH2),3.85(s,3H,CH3),3.96(q,J=7.0Hz,2H,C6H4-CH2),6.72(d,J=8.7Hz,2H,C6H4 3,5-H),7.21(d,J=8.6Hz,2H,C6H4 2,6-H),7.30(s,1H,C6H2 6-H),7.37(s,1H,C6H2 2-H),7.43(s,1H,C=CH).HRMS: HR-MS(ESI):m / z calcd for C 23 H 23 F3O4([M+H] + )421.1627, found 421.1632.

[0112] Example 19

[0113] Synthesis of (E)-3-(4-nitrophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E8):

[0114]

[0115] The preparation method was the same as compound E1, and the reaction was carried out at room temperature for 3 h to obtain E8 with an overall yield of 23.5%.

[0116] E8: yellow oily substance, 1 H NMR (600MHz, CDCl3) δ1.43(s,6H,2×CH3),2.91(s,2H,CH2),3.81(s,3H,CH3),7.23(s,1H,C6H2 6-H),7.34(d,J=8.9Hz,2H,C=CH,C6H2 2-H),7.41(d,J=8.7Hz,2H,C6H4 2,6-H),8.03(d,J=8.7Hz,2H,C6H4 3,5-H).HRMS: HR-MS(ESI):m / zcalcd for C 21 H 18 F3NO5([M+H] + )422.1210, found 422.1219.

[0117] Example 20

[0118] Synthesis of (E)-3-(2,4-dichlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E9):

[0119]

[0120] The preparation method was the same as compound E1, and the reaction was carried out at room temperature for 3 h to obtain E9 with an overall yield of 11.6%.

[0121] E9: yellow oily substance, 1 H NMR (600MHz, CDCl3) δ1.49(s,6H,2×CH3),2.97(s,2H,CH2),3.85(s,3H,CH3),7.03(dd,J=8.4,1.9Hz,1H,C6H4 5-H),7.17(d,J=8.4Hz,1H,C6H4 3-H), 7.26 (s, 1H, C6H2 6-H), 7.29 (s, 1H, C6H24 2-H), 7.35 (d, J=1.9Hz, 1H, C6H4 6-H), 7.61 (s, 1H, C=CH). HRMS: HR-MS (ESI): m / z calcd for C 21 H 17 Cl2F3O3([M+H] + )445.0580,found445.0590.

[0122] Example 21

[0123] Determination of Antifungal Activity of 3-Aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-trifluoromethylpropenone Derivatives

[0124] 1. Antifungal activity test method

[0125] The plant fungi used in this experiment were laboratory-grown strains of Botryosphaeria dothidea and Pythium aphanidermatum, both of which have been stored at 4°C. The culture medium used was potato agar-dextrose medium (PDA). The PDA medium recipe consists of: 200g potatoes, 20g glucose, 15g agar, and 1000mL distilled water. Preparation: Wash and peel 200g of potatoes, cut into small pieces, and boil until soft (boil for 20-30 minutes, until punctured by a glass rod). Filter through eight layers of gauze into a beaker. Add 15-20g agar and 20g glucose, depending on the experiment's needs. Stir thoroughly, dissolve thoroughly, and cool slightly. Add water to 1000mL, aliquot, and sterilize at 121°C for 30 minutes. Cool and set aside.

[0126] 2. Bactericidal activity (in vitro) test method: The growth rate method was used, including the following steps:

[0127] (1) First, culture the above plant fungi on a PDA plate at 25°C for about 3-6 days before use;

[0128] (2) Heat and melt the PDA culture medium, cool it to 45-50°C, add 10 μl of 20 mg / mL concentration of the test compound to make a culture medium containing 100 μg / mL of the drug solution, and pour it into the culture dish to cool. Fuzoxanil is used as a positive control.

[0129] (3) Using aseptic operation procedures, use a punch to punch a circular bacterial cake (0.50 cm in diameter) at the edge of the hyphae of each strain after 6 days of culture (growth conditions should be as consistent as possible), then use an inoculation needle to pick it into the center of the drug-containing plate, and then place the culture plate upside down in the incubator for culture;

[0130] (4) Observe and measure the growth of mycelium at different times after treatment, measure the diameter using the cross-cross method, process the data, and calculate the inhibition rate;

[0131]

[0132] Each treatment was repeated 3 times.

[0133] Sample: Derivative of (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one:

[0134]

[0135] Wherein, R is selected from the group consisting of chlorine, bromine, methyl, methoxy, 2,3,4-trimethoxy, ethoxy, and nitro.

[0136] Table 1 Inhibition rate of some compounds of the present invention against Pythium aphanidermatum and Pythium aphanidermatum (%)

[0137]

[0138] The results in Table 1 show that when the test compound concentration is 100 μg / mL, the compounds of the present invention exhibit different degrees of inhibitory activity against Botrytis cinerea and have universal inhibitory activity against the pathogen. The compounds of the present invention have potential significance for inhibiting plant pathogenic fungi.

Claims

1. Chemical structural formula Ⅰ shown in ( E )-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one derivatives: ； in, R is selected from the group consisting of: chlorine, bromine, methyl, methoxy, 2,3,4-trimethoxy, ethoxy, nitro, and 2,4-dichloro.

2. According to claim 1 ( E )-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one derivatives, characterized in that The E )-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one derivatives are selected from: compounds E1, E2, E3, E4, E5, E6, E7, E8 or E9; wherein, E1 is ( E )-3-(4-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E2 is ( E )-3-(2-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E3 is ( E )-3-(4-bromophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E4 is ( E )-3-(4-methylphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E5 is ( E )-3-(2-methoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E6 is ( E )-3-(2,3,4-trimethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E7 is ( E )-3-(4-ethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E8 is ( E )-3-(4-nitrophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E9 is ( E )-3-(2,4-dichlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one.

3. The ( E The method for preparing a derivative of )-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one is characterized in that: The reaction formula is as follows: ； Wherein, R is defined as in claim 1.

4. The method according to claim 1 or 2 ( E )-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one derivatives in the preparation of anti-plant fungal preparations; the plant fungus is Botrytis cinerea ( Botryosphaeria dothidea ) or Pythium aphanidermatum ( Pythium aphanidermatum ).

5. The use according to claim 4, characterized in that The ( E The derivative of )-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one is selected from compounds E1, E3, E4, E5, E6, E7 or E8, wherein the definitions of E1, E3, E4, E5, E6, E7, and E8 are as described in claim 2.

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