Preparation method of aryl substituted ester

Abstract

The invention provides a preparation method of aryl substituted ester, which comprises the following steps of: performing alkylation reaction on different substituted alpha-bromo-aryl ethanone as shown in a formula 1 and different substituted phenol as shown in a formula 2 or 3 which are used as raw materials under the catalysis of a catalyst to generate aryl substituted ester as shown in a formula 4 or 5. Firstly, a series of aryl substituted esters are synthesized, and a relatively good yield is obtained; secondly, the route provided by the invention has remarkable green chemical characteristics, and environment-friendly acetonitrile is used as a reaction solvent; and thirdly, the route realizes high stereoselectivity of the reaction by optimizing the reaction conditions, reduces the generation of byproducts, and realizes oxidation reduction economy and atom economy. According to the method, the aryl substituted ester synthesized through efficient alkylation reaction has potential physiological activity, and an important material basis is provided for related drug development and biological activity research.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis technology, and specifically relates to a method for preparing aryl substituted esters. Background Technology

[0002] Alkylation is an important class of organic chemical reactions, essentially involving the transfer of alkyl groups from one molecule to another. The core of alkylation is the introduction of alkyl groups (such as methyl and ethyl) into a compound molecule. Based on reaction type and mechanism, this reaction can be mainly classified into electrophilic alkylation, nucleophilic alkylation, and transition metal-catalyzed cross-coupling reactions. Alkylation plays a crucial role in chemical production. In petroleum production, isoalkanes and low-molecular-weight olefins can be converted into alkylates through alkylation, thereby producing high-octane gasoline. The alkylation products of isobutane and C3-C5 olefins are ideal components for clean gasoline, possessing multiple advantages such as high octane number, low vapor pressure, sulfur-free, olefin-free, and aromatic-free. In fine chemicals and pharmaceutical synthesis, alkylation is a key method for constructing molecular skeletons. Most drug molecules contain alkyl chains or alkyl-substituted cyclic structures, and alkylation is indispensable in the synthesis of these structures. For example, the critical alkylation step is essential in the synthesis of the analgesic ibuprofen. Meanwhile, in pesticide production, the synthesis of herbicides, insecticides, and fungicides widely relies on alkylation reactions to introduce specific functional groups. Furthermore, the production of fine chemicals such as dyes, fragrances, and surfactants also depends on alkylation reactions.

[0003] With increasing environmental awareness, the drawbacks of traditional alkylation processes (using highly corrosive liquid acids) and reagents (such as halogenated alkanes) have become apparent. Research has shifted towards developing environmentally friendly solid acid catalysts (such as molecular sieves and heteropoly acids) and greener alkylating reagents (such as alcohols and alkenes). In the field of pharmaceutical synthesis, asymmetric alkylation technology has seen significant development, enabling the highly selective synthesis of single chiral molecules and becoming an indispensable tool in modern organic synthesis.

[0004] The Williamson reaction, also known as the Williamson synthesis or Williamson ether synthesis, is an important method for preparing symmetrical or asymmetrical ethers. This reaction is achieved through the reaction of an alcohol with a base and a haloalkane. The alcohol is deprotonated by the base to form an alkoxide, which then undergoes nucleophilic substitution (S1) with the haloalkane. N 2) The reaction yields the corresponding ether and metal halide. In recent years, the Williamson reaction has become an attractive strategy for synthesizing oxygen-containing heterocyclic scaffolds by cyclizing halogenated compounds into five-membered ring structures. The Williamson reaction is typically carried out in the presence of a base, using various inorganic bases such as CH3COONa, KF, NaOH, and KOH. However, these inorganic base conditions are not compatible with all functional groups and usually require reflux heating and a relatively long reaction time.

[0005] In summary, how to obtain an alkylation preparation process that is environmentally friendly, has stable preparation technology, and high yield is a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0006] To address the shortcomings of existing technologies, the present invention adopts the following technical solution:

[0007] The first aspect of this invention provides a method for preparing aryl substituted esters, comprising the following steps: using different substituted α-bromoaryl ethyl ketones as shown in Formula 1 and different substituted phenols as shown in Formula 2 or 3 as raw materials, an alkylation reaction is carried out under the catalysis of a catalyst to generate aryl substituted esters as shown in Formula 4 or 5, the specific reaction route of which is shown in Formula (I) below:

[0008]

[0009] Wherein, R1 is selected from H,

[0010] R2 is selected from any one or more of H, -CF3, and -OCH3;

[0011] R3 is selected from any one or more of H and -OCH3;

[0012] R4 is selected from any one or more of H and -CF3;

[0013] R5 is selected from Any one or more of them;

[0014] Furthermore, the reaction catalyst is N,N-diisopropylethylamine (i.e., DIPEA);

[0015] Furthermore, the reaction solvent is selected from any one or more of acetonitrile, methanol, acetone, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide, dichloromethane, 1,4-dioxane, n-hexane, ethyl acetate, and chloroform.

[0016] Furthermore, the reaction condition is reflux heating; even further, the reflux heating temperature is 60–80°C;

[0017] Furthermore, the molar ratio of the different substituted α-bromoaryl ethyl ketones shown in Formula 1, the different substituted phenols shown in Formula 2 or 3, and the catalyst is 1:1:1 to 3.

[0018] Furthermore, the molar ratio of the different substituted α-bromoaryl ethyl ketones shown in Formula 1, the different substituted phenols shown in Formula 2 or 3, and the catalyst is 1:1:2;

[0019] Furthermore, the specific structure of the aryl substituted esters shown in Formula 4 or 5 is selected from any one or more of Formulas 3-1 to 3-12:

[0020]

[0021]

[0022] The present invention has the following beneficial effects:

[0023] First, the synthetic route of this invention uses phenols with different substituents and α-bromoaryl ethyl ketones with different substituents as raw materials, and DIPEA as a catalyst, to conduct a reflux heating reaction, synthesizing a series of aryl substituted esters through alkylation with good yields. Second, this route exhibits significant green chemistry characteristics, using environmentally friendly acetonitrile as the reaction solvent and avoiding the use of highly toxic reagents, strong acids and bases, and highly flammable reagents. Third, this route achieves high stereoselectivity and reduces the formation of byproducts through optimized reaction conditions. The method achieves redox economy and atom economy through the operation without protecting groups. Furthermore, systematic experiments have demonstrated that DIPEA is the optimal base for alkylation reactions, possessing good value for industrial production and application. In addition, the aryl substituted esters synthesized through this method via a highly efficient alkylation reaction possess potential physiological activities, providing an important material basis for related drug development and bioactivity research. Attached Figure Description

[0024] Figure 1 For compound 3-1 1 1H NMR spectrum (400MHz CDCl3);

[0025] Figure 2 For compound 3-1 13 C10 NMR spectrum (101MHz CDCl3);

[0026] Figure 3 For compound 3-2 1 1H NMR spectrum (400MHz CDCl3);

[0027] Figure 4 For compound 3-2 13 C10 NMR spectrum (101MHz CDCl3);

[0028] Figure 5 For compound 3-3 1 1H NMR spectrum (400MHz CDCl3);

[0029] Figure 6 For compound 3-3 13C10 NMR spectrum (101MHz CDCl3);

[0030] Figure 7 For compounds 3-4 1 1H NMR spectrum (400MHz CDCl3);

[0031] Figure 8 For compounds 3-4 13 C10 NMR spectrum (101MHz CDCl3);

[0032] Figure 9 For compounds 3-5 1 1H NMR spectrum (400MHz CDCl3);

[0033] Figure 10 For compounds 3-5 13 C10 NMR spectrum (101MHz CDCl3);

[0034] Figure 11 For compounds 3-6 1 1H NMR spectrum (400MHz CDCl3);

[0035] Figure 12 For compounds 3-6 13 C10 NMR spectrum (101MHz CDCl3);

[0036] Figure 13 For compounds 3-7 1 1H NMR spectrum (400MHz CDCl3);

[0037] Figure 14 For compounds 3-7 13 C10 NMR spectrum (101MHz CDCl3);

[0038] Figure 15 For compounds 3-8 1 1H NMR spectrum (400MHz acetone-d6);

[0039] Figure 16 For compounds 3-8 13 C10 NMR spectrum (101 MHz acetone-d6);

[0040] Figure 17 For compounds 3-9 1 1H NMR spectrum (400MHz acetone-d6);

[0041] Figure 18 For compounds 3-9 13C10 NMR spectrum (101 MHz acetone-d6);

[0042] Figure 19 For compounds 3-10 1 1H NMR spectrum (400MHz acetone-d6);

[0043] Figure 20 For compounds 3-10 13 C10 NMR spectrum (101 MHz acetone-d6);

[0044] Figure 21 For compound 3-11 1 1H NMR spectrum (400MHz acetone-d6);

[0045] Figure 22 For compound 3-11 13 C10 NMR spectrum (101 MHz acetone-d6);

[0046] Figure 23 For compound 3-12 1 1H NMR spectrum (400MHz acetone-d6);

[0047] Figure 24 For compound 3-12 13 C10 NMR spectrum (101 MHz acetone-d6). Detailed Implementation

[0048] The following embodiments are intended to enable those skilled in the art to more fully understand the present invention, but are not intended to limit the invention to the scope of the embodiments described.

[0049] Example 1: Preparation of 2-phenoxy-1-phenylethanol-1-one

[0050]

[0051] Under nitrogen protection, a magnetic stir bar was added to a round-bottom flask. 2-Bromoacetophenone 1-1 (60 mg, 0.3 mmol, 1.0 eq.) and phenol 2-1 (28.2 mg, 0.3 mmol, 1.0 eq.) were dissolved in acetonitrile (0.2 M). After the substrates were completely dissolved, DIPEA (105 μL, 0.6 mmol, 2.0 eq.) was added. The reaction mixture was then heated at 70 °C. The reaction was considered complete when the starting material disappeared, as monitored by TLC. After the reaction was complete, the reaction solution was allowed to cool naturally to room temperature and quenched with distilled water. The reaction solution was transferred to a separatory funnel and extracted with ethyl acetate. The mixture was washed successively with water and saturated NaCl solution, followed by extraction with ethyl acetate. The combined organic phases were dried over anhydrous Na₂SO₄, filtered, and the solvent was removed under vacuum to obtain a crude residue. This residue was further purified by column chromatography to obtain a white solid (35.7 mg, 56%).

[0052] Structural characterization data of compound 3-1 (2-phenoxy-1-phenylethanol-1-one): 1 H NMR (400MHz, CDCl3) δ8.05~7.94(m,2H),7.67~7.58(m,1H),7.56~7.46(m,2H),7.34~7.24(m,2H),6.99(td,J=6.9,6.4,1.1Hz,1H),6.95(dt ,J=7.9,1.0Hz,2H),5.29(s,2H);13CNMR(101MHz,CDCl3)δ194.65,158.07,134.65,134.04,129.72,128.98,128.26,121.78,114.89,70.86.

[0053] Example 2: Preparation of 1-phenyl-2-(p-tolyloxy)ethane-1-one

[0054]

[0055] Under nitrogen protection, a magnetic stir bar was added to a round-bottom flask. 2-Bromoacetophenone 1-1 (60 mg, 0.3 mmol, 1.0 eq.) and p-cresol 2-2 (32.5 mg, 0.3 mmol, 1.0 eq.) were dissolved in acetonitrile (0.2 M). After the substrate was completely dissolved, DIPEA (105 μL, 0.6 mmol, 2.0 eq.) was added, and the reaction mixture was heated at 70 °C. The reaction was considered complete when the starting material disappeared, as monitored by TLC. After the reaction was complete, the reaction solution was allowed to cool naturally to room temperature and quenched with distilled water. The reaction solution was transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed sequentially with water and saturated NaCl aqueous solution, and then extracted sequentially with ethyl acetate. After combining the organic phases, the mixture was dried with anhydrous Na2SO4, filtered, and the solvent was removed under vacuum to obtain a crude residue. The residue was further purified by column chromatography (PE:EA = 50:1) to obtain a white solid (40.0 mg, 59%).

[0056] Structural characterization data of compound 1-phenyl-2-(p-tolyloxy)ethane-1-one: 1 H NMR (400MHz, CDCl3) δ8.05~7.97(m,2H),7.67~7.57(m,1H),7.55~7.45(m,2H),7.12~7.03(m,2H),6.90~6.81(m,2H),5.26(s,2H),2.28(s,3H); 13 C NMR (101MHz, CDCl3) δ194.85,155.99,134.69,133.98,131.08,130.14,128.95,128.25,114.76,71.10,20.64.

[0057] Example 3: Preparation of 2-(4-methoxyphenoxy)-1-phenylethane-1-one

[0058]

[0059]

[0060] Under nitrogen protection, a magnetic stir bar was added to a round-bottom flask. 2-Bromoacetophenone 1-1 (60 mg, 0.3 mmol, 1.0 eq.) and 4-methoxyphenol 2-3 (37.2 mg, 0.3 mmol, 1.0 eq.) were dissolved in acetonitrile (0.2 M). After the substrates were completely dissolved, DIPEA (105 μL, 0.6 mmol, 2.0 eq.) was added, and the reaction mixture was heated at 70 °C. The reaction was considered complete when the starting material disappeared, as monitored by TLC. After the reaction was complete, the reaction solution was allowed to cool naturally to room temperature and quenched with distilled water. The reaction solution was transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed sequentially with water and saturated NaCl aqueous solution, and then extracted sequentially with ethyl acetate. After combining the organic phases, the mixture was dried with anhydrous Na2SO4, filtered, and the solvent was removed under vacuum to obtain a crude residue. The residue was further purified by column chromatography (PE:EA = 50:1) to obtain a white solid (43.7 mg, 60%).

[0061] Structural characterization data of compound 2-(4-methoxyphenoxy)-1-phenylethane-1-one: 1 H NMR (400MHz, CDCl3) δ8.04~7.96(m,2H),7.66~7.57(m,1H),7.50(t,J=7.8Hz,2H),6.94~6.86(m,2H),6.86~6.79(m,2H),5.23(s,2H),3.76(s,3H); 13 C NMR (101MHz, CDCl3) δ194.95,154.52,152.26,134.66,133.97,128.94,128.21,116.05,114.77,71.80,55.79.

[0062] Example 4: Preparation of 2-(4-nitrophenoxy)-1-phenylethane-1-one

[0063]

[0064] Under nitrogen protection, a magnetic stir bar was added to a round-bottom flask. 2-Bromoacetophenone 1-1 (60 mg, 0.3 mmol, 1.0 eq.) and 4-nitrophenol 2-4 (41.7 mg, 0.3 mmol, 1.0 eq.) were dissolved in acetonitrile (0.2 M). After the substrates were completely dissolved, DIPEA (105 μL, 0.6 mmol, 2.0 eq.) was added, and the reaction mixture was heated at 70 °C. The reaction was considered complete when the starting material disappeared, as monitored by TLC. After the reaction was complete, the reaction solution was allowed to cool naturally to room temperature and quenched with distilled water. The reaction solution was transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed sequentially with water and saturated NaCl aqueous solution, and then extracted sequentially with ethyl acetate. After combining the organic phases, the mixture was dried with anhydrous Na2SO4, filtered, and the solvent was removed under vacuum to obtain a crude residue. The residue was further purified by column chromatography (PE:EA = 50:1) to obtain a pale yellow solid (76.4 mg, 99%).

[0065] Structural characterization data of compound 2-(4-nitrophenoxy)-1-phenylethane-1-one: 1 H NMR (400MHz, CDCl3) δ8.25~8.16(m,2H),8.03~7.94(m,2H),7.71~7.62(m,1H),7.54(dd,J=8.4,7.1Hz,2H),7.03~6.94(m,2H),5.44(s,2H); 13 C NMR (101MHz, CDCl3) δ192.89,163.00,142.19,134.55,134.05,129.21,128.12,126.09,114.90,70.70.

[0066] Example 5: Preparation of 2-(4-acetylphenoxy)-1-phenylethane-1-one

[0067]

[0068] Under nitrogen protection, a magnetic stir bar was added to a round-bottom flask. 2-Bromoacetophenone 1-1 (60 mg, 0.3 mmol, 1.0 eq.) and 1-(4-hydroxyphenyl)ethane-1-one 2-5 (40.8 mg, 0.3 mmol, 1.0 eq.) were dissolved in acetonitrile (0.2 M). After the substrate was completely dissolved, DIPEA (105 μL, 0.6 mmol, 2.0 eq.) was added, and the reaction mixture was heated at 65 °C. The reaction was considered complete when the starting material disappeared, as monitored by TLC. After the reaction was complete, the reaction solution was allowed to cool naturally to room temperature and quenched with distilled water. The reaction solution was transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed sequentially with water and saturated NaCl aqueous solution, and then extracted sequentially with ethyl acetate. After combining the organic phases, the mixture was dried with anhydrous Na2SO4, filtered, and the solvent was removed under vacuum to obtain a crude residue. The residue was further purified by column chromatography (PE:EA = 50:1) to obtain a pale yellow solid (64.1 mg, 84%).

[0069] Structural characterization data of compound 2-(4-acetylphenoxy)-1-phenylethane-1-one: 1 H NMR (400MHz, CDCl3) δ8.03~7.95(m,2H),7.97~7.88(m,2H),7.69~7.57(m,1H),7.52(t,J=7.7Hz,2H),7.01~6.92(m,2H),5.37(s,2H),2.54(s,3H); 13 C NMR (101MHz, CDCl3) δ196.92,193.61,161.85,134.29,131.10,130.74,129.08,128.14,114.51,70.48,26.53.

[0070] Example 6: Preparation of 4-(2-oxo-2-phenoxy)benzaldehyde

[0071]

[0072] Under nitrogen protection, a magnetic stir bar was added to a round-bottom flask. 2-Bromoacetophenone 1-1 (60 mg, 0.3 mmol, 1.0 eq.) and 4-hydroxybenzaldehyde 2-6 (36.6 mg, 0.3 mmol, 1.0 eq.) were dissolved in acetonitrile (0.2 M). After the substrates were completely dissolved, DIPEA (105 μL, 0.6 mmol, 2.0 eq.) was added, and the reaction mixture was heated at 75 °C. The reaction was considered complete when the starting material disappeared, as monitored by TLC. After the reaction was complete, the reaction solution was allowed to cool naturally to room temperature and quenched with distilled water. The reaction solution was transferred to a separatory funnel and extracted with ethyl acetate. The aqueous phase was washed sequentially with water and saturated NaCl aqueous solution, and then extracted sequentially with ethyl acetate. The organic phases were combined, dried with anhydrous Na2SO4, filtered, and the solvent was removed under vacuum to obtain a crude residue. The residue was further purified by column chromatography (PE:EA = 8:1) to obtain a pale yellow solid (60.6 mg, 84%).

[0073] Structural characterization data of compound 4-(2-oxo-2-phenoxy)benzaldehyde: 1 H NMR (400MHz, CDCl3) δ9.89 (s, 1H), 8.05 ~ 7.95 (m, 2H), 7.89 ~ 7.78 (m, 2H), 7.70 ~ 7.60 (m, 1H), 7.53 (t, J = 7.7Hz, 2H), 7.08 ~ 6.99 (m, 2H), 5.41 (s, 2H); 13 C NMR (101MHz, CDCl3) δ193.36,190.90,162.96,134.39,134.23,132.14,130.70,129.14,128.16,115.13,70.53.

[0074] Example 7: Preparation of 3-(2-oxo-2-phenoxy)benzaldehyde

[0075]

[0076] Under nitrogen protection, a magnetic stir bar was added to a round-bottom flask. 2-Bromoacetophenone 1-1 (60 mg, 0.3 mmol, 1.0 eq.) and 3-hydroxybenzaldehyde 2-7 (36.6 mg, 0.3 mmol, 1.0 eq.) were dissolved in acetonitrile (0.2 M). After the substrates were completely dissolved, DIPEA (105 μL, 0.6 mmol, 2.0 eq.) was added, and the reaction mixture was heated at 70 °C. The reaction was considered complete when the starting material disappeared, as monitored by TLC. After the reaction was complete, the reaction solution was allowed to cool naturally to room temperature and quenched with distilled water. The reaction solution was transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed sequentially with water and saturated NaCl aqueous solution, and then extracted sequentially with ethyl acetate. After combining the organic phases, the mixture was dried with anhydrous Na2SO4, filtered, and the solvent was removed under vacuum to obtain a crude residue. The residue was further purified by column chromatography (PE:EA = 8:1) to obtain a yellow solid (58.7 mg, 81%).

[0077] Structural characterization data of compound 3-(2-oxo-2-phenoxy)benzaldehyde: 1 H NMR (400MHz, CDCl3) δ9.95 (s, 1H), 8.03 ~ 7.96 (m, 2H), 7.68 ~ 7.59 (m, 1H), 7.52 (d, J = 7.9Hz, 2H), 7.49(s,1H),7.45(d,J=7.5Hz,1H),7.39(dd,J=2.9,1.3Hz,1H),7.31~7.23(m,1H),5.38(s,2H); 13 C NMR (101MHz, CDCl3) δ193.63,192.04,158.65,137.83,134.31,134.22,130.39,129.05,128.08,124.54,122.33,112.89,70.53.

[0078] Example 8: Preparation of 6-(2-oxo-2-phenoxy)benzofuran-3(2H)-one

[0079]

[0080] Under nitrogen protection, a magnetic stir bar was added to a round-bottom flask. 2-Bromoacetophenone 1-1 (60 mg, 0.3 mmol, 1.0 eq.) and 6-hydroxybenzofuran-3(2H)-one 2-8 (45.1 mg, 0.3 mmol, 1.0 eq.) were dissolved in acetonitrile (0.2 M). After the substrates were completely dissolved, DIPEA (105 μL, 0.6 mmol, 2.0 eq.) was added, and the reaction mixture was heated at 70 °C. The reaction was considered complete when the starting material disappeared, as monitored by TLC. After the reaction was complete, the reaction solution was allowed to cool naturally to room temperature and quenched with distilled water. The reaction solution was transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed sequentially with water and saturated NaCl aqueous solution, and then extracted sequentially with ethyl acetate. After combining the organic phases, the mixture was dried with anhydrous Na2SO4, filtered, and the solvent was removed under vacuum to obtain a crude residue. The residue was further purified by column chromatography (PE:EA = 4:1) to obtain a pale yellow solid (73.2 mg, 91%).

[0081] Structural characterization data of compound 6-(2-oxo-2-phenoxy)benzofuran-3(2H)-one: 1 H NMR (400MHz, Acetone-d6) δ8.13~8.04(m,2H),7.75~7.66(m,1H),7.53(dd,J=8.3,0.7Hz,1H),6.84~6.76(m,2H),5.75(s,2H),4.65(s,2H); 13 C NMR (101MHz, Acetone-d6) δ197.47,193.65,176.86,167.57,135.48,134.66,129.68,128.77,125.36,115.59,112.48,98.38,76.13,71.43.

[0082] Example 9: Preparation of 2-((1H-indol-4-yl)oxy)-1-phenylethane-1-one

[0083]

[0084] Under nitrogen protection, a magnetic stir bar was added to a round-bottom flask. 2-Bromoacetophenone 1-1 (60 mg, 0.3 mmol, 1.0 eq.) and 1H-indole-4-ol 2-9 (40 mg, 0.3 mmol, 1.0 eq.) were dissolved in acetonitrile (0.2 M). After the substrates were completely dissolved, DIPEA (105 μL, 0.6 mmol, 2.0 eq.) was added, and the reaction mixture was heated at 70 °C. The reaction was considered complete when the starting material disappeared, as monitored by TLC. After the reaction was complete, the reaction solution was allowed to cool naturally to room temperature and quenched with distilled water. The reaction solution was transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed sequentially with water and saturated NaCl aqueous solution, and then extracted sequentially with ethyl acetate. The organic phases were combined, dried with anhydrous Na2SO4, filtered, and the solvent was removed under vacuum to obtain crude residue. The residue was further purified by column chromatography (PE:EA = 50:1) and (PE:EA = 6:1) to obtain a black solid (47.6 mg, 63%).

[0085] Structural characterization data of compound 2-((1H-indol-4-yl)oxy)-1-phenylethane-1-one: 1 H NMR (400MHz, Acetone-d6) δ10.29(s,1H),8.16~8.08(m,2H),7.67(ddq,J=8.8,6.8,1.3Hz,1H),7.61~7.51(m,2H),7.24(t,J=2.8Hz,1H ),7.06(dp,J=8.2,0.8Hz,1H),6.98(td,J=7.9,1.1Hz,1H),6.60(dtt,J=3.1,2.2,0.9Hz,1H),6.50(dd,J=7.6,0.8Hz,1H),5.55(s,2H); 13 C NMR (101MHz, Acetone-d6) δ195.44,152.73,138.78,136.01,134.32,129.57,128.93,124.08,122.70,119.82,106.08,101.14,99.80,71.45.

[0086] Example 10: Preparation of (Z)-2-(4-(2-(4-methoxyphenyl)-2-oxoethoxy)benzyl)benzofuran-3(2H)-one

[0087]

[0088] Under nitrogen protection, a magnetic stir bar was added to a round-bottom flask. 2-Bromo-1-(4-methoxyphenyl)ethane-1-one 1-2 (69 mg, 0.3 mmol, 1.0 eq.) and (Z)-2-(4-hydroxybenzyl)benzofuran-3(2H)-one 2-10 (71.5 mg, 0.3 mmol, 1.0 eq.) were dissolved in acetonitrile (0.2 M). After the substrates were completely dissolved, DIPEA (105 μL, 0.6 mmol, 2.0 eq.) was added, and the reaction mixture was heated at 70 °C. The reaction was considered complete when the starting material disappeared, as monitored by TLC. After the reaction was complete, the reaction solution was allowed to cool naturally to room temperature and quenched with distilled water. The reaction solution was transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed sequentially with water and saturated NaCl aqueous solution, and then extracted sequentially with ethyl acetate. The organic phases were combined, dried with anhydrous Na2SO4, filtered, and the solvent was removed under vacuum to obtain a crude residue. The residue was further purified by column chromatography (PE:EA = 2:1) to obtain a yellow solid (103.1 mg, 89%).

[0089] Structural characterization data of compound (Z)-2-(4-(2-(4-methoxyphenyl)-2-oxoethoxy)benzyl)benzofuran-3(2H)-one: 1 H NMR (400MHz, Acetone-d6) δ8.10~8.06(m,2H),8.03~7.98(m,2H),7.81~7.76(m,2H),7.5 0(dt,J=8.2,0.9Hz,1H),7.35~7.29(m,1H),7.15~7.07(m,4H),6.85(s,1H),3.92(s,3H); 13 C NMR (101MHz, Acetone-d6) δ192.73,184.25,166.61,164.97,160.94,146.62,137.80,134.13,1 31.13,128.55,126.18,124.87,124.50,122.52,116.15,114.83,113.89,112.95,70.88,56.01.

[0090] Example 11: Preparation of 7-(2-(3,5-bis(trifluoromethyl)phenyl)-2-oxoethoxy)-4-methyl-2H-chromen-2-one

[0091]

[0092] Under nitrogen protection, a magnetic stir bar was added to a round-bottom flask. 1-(3,5-bis(trifluoromethyl)phenyl)-2-bromoethane-1-one 1-3 (101 mg, 0.3 mmol, 1.0 eq.) and 7-hydroxy-4-methyl-2H-methylene-2-one 2-11 (53 mg, 0.3 mmol, 1.0 eq.) were dissolved in acetonitrile (0.2 M). After the substrates were completely dissolved, DIPEA (105 μL, 0.6 mmol, 2.0 eq.) was added, and the reaction mixture was heated at 70 °C. The reaction was considered complete when the starting material disappeared, as monitored by TLC. After the reaction was complete, the reaction solution was allowed to cool naturally to room temperature and quenched with distilled water. The reaction solution was transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed sequentially with water and saturated NaCl aqueous solution, and then extracted sequentially with ethyl acetate. The organic phases were combined, dried with anhydrous Na2SO4, filtered, and the solvent was removed under vacuum to obtain a crude residue. The residue was further purified by column chromatography (PE:EA = 4:1) to obtain a white solid (86.5 mg, 67%).

[0093] Structural characterization data of compound 7-(2-(3,5-bis(trifluoromethyl)phenyl)-2-oxoethoxy)-4-methyl-2H-chromene-2-one: 1 H NMR (400MHz, Acetone-d6) δ8.71~8.65(m,2H),8.40(dt,J=1.8,0.9Hz,1H),7.71(d,J=8.9Hz,1H),7.07( dd,J=8.8,2.6Hz,1H),7.03(d,J=2.5Hz,1H),6.15(d,J=1.3Hz,1H),5.96(s,2H),2.45(d,J=1.2Hz,3H); 13 C NMR (101MHz, Acetone-d6) δ192.43,162.04,160.74,156.11,153.65,137.51,132.59(q,J=33.7Hz ), 129.41, 127.59, 127.11, 124.08 (d, J = 272.4Hz), 114.83, 113.33, 112.67, 102.37, 71.66, 18.54.

[0094] Example 12: Preparation of 5-(4-hydroxybenzyl)-3-(2-(3-methoxyphenyl)-2-oxoethyl)thiazolidin-2,4-dione

[0095]

[0096] Under nitrogen protection, a magnetic stir bar was added to a round-bottom flask. 2-Bromo-1-(3-methoxyphenyl)ethane-1-one 1-4 (69 mg, 0.3 mmol, 1.0 eq.) and 5-(4-hydroxybenzyl)thiazolidin-2,4-dione 2-12 (67 mg, 0.3 mmol, 1.0 eq.) were dissolved in acetonitrile (0.2 M). After the substrates were completely dissolved, DIPEA (105 μL, 0.6 mmol, 2.0 eq.) was added, and the reaction mixture was heated at 70 °C. The reaction was considered complete when the starting material disappeared, as monitored by TLC. After the reaction was complete, the reaction solution was allowed to cool naturally to room temperature and quenched with distilled water. The reaction solution was transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed sequentially with water and saturated NaCl aqueous solution, and then extracted sequentially with ethyl acetate. The organic phases were combined, dried with anhydrous Na2SO4, filtered, and the solvent was removed under vacuum to obtain a crude residue. The residue was further purified by column chromatography (PE:EA = 4:1) to obtain a yellow solid (100.3 mg, 90%).

[0097] Structural characterization data of compound 5-(4-hydroxybenzyl)-3-(2-(3-methoxyphenyl)-2-oxoethyl)thiazolidin-2,4-dione: 1 H NMR (400MHz, Acetone-d6) δ8.44(s,1H),7.75~7.66(m,1H),7.58(dd,J=2.7,1.6Hz,1H),7.51(t,J=8.0Hz,1H),7.27(ddd,J=8.3,2.7,0.9Hz,1H),7.23 ~7.15(m,2H),6.89~6.78(m,2H),5.12(s,2H),4.90(dd,J=10.0,4.2Hz,1H) ,3.89(s,3H),3.54(dd,J=14.1,4.2Hz,1H),3.06(dd,J=14.1,10.0Hz,1H); 13 C NMR (101MHz, Acetone-d6) δ191.31,174.34,171.33,161.01,157.61,136.59,131. 20,130.96,128.28,121.40,121.25,116.28,113.28,55.86,52.88,48.27,38.53.

[0098] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art may make various modifications and alterations without departing from the spirit and scope of the present invention, and all such modifications and alterations shall be within the protection scope of the present invention.

Claims

1. A method for preparing an aryl-substituted ester, characterized in that, Includes the following steps: Using different substituted α-bromoaryl ethyl ketones as shown in Formula 1 and different substituted phenols as shown in Formula 2 or 3 as raw materials, an alkylation reaction is carried out under the catalysis of a catalyst to generate aryl substituted esters as shown in Formula 4 or 5. The specific reaction route is shown in Formula (I) below: Wherein, R1 is selected from H, R2 is selected from any one or more of H, -CF3, and -OCH3; R3 is selected from any one or more of H and -OCH3; R4 is selected from any one or more of H and -CF3; R5 is selected from Any one or more of them.

2. The method for preparing aryl-substituted esters according to claim 2, characterized in that, The reaction catalyst is N,N-diisopropylethylamine (i.e., DIPEA).

3. The method for preparing aryl-substituted esters according to claim 1, characterized in that, The reaction solvent is selected from any one or more of acetonitrile, methanol, acetone, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide, dichloromethane, 1,4-dioxane, n-hexane, ethyl acetate, and chloroform.

4. The method for preparing aryl-substituted esters according to claim 1, characterized in that, The reaction conditions are reflux heating.

5. The method for preparing the aryl-substituted ester according to claim 5, characterized in that, The reflux heating temperature is 60–80°C.

6. The method for preparing aryl-substituted esters according to claim 1, characterized in that, The molar ratio of the different substituted α-bromoaryl ethyl ketones shown in Formula 1, the different substituted phenols shown in Formula 2 or 3, and the catalyst is 1:1:1 to 3.

7. The method for preparing aryl-substituted esters according to claim 6, characterized in that, The molar ratio of the different substituted α-bromoaryl ethyl ketones shown in Formula 1, the different substituted phenols shown in Formula 2 or 3, and the catalyst is 1:1:

2.

8. The method for preparing aryl-substituted esters according to claim 1, characterized in that, The specific structure of the aryl substituted esters shown in Formula 4 or 5 is selected from any one or more of Formulas 3-1 to 3-12:

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