Application of tetra-n-butylammonium bromide as catalyst to catalysis of reaction of methoxy aromatic hydrocarbon and acyl bromide

Abstract

The invention provides an application of tetra-n-butylammonium bromide as a catalyst to catalyze reaction of methoxy aromatic hydrocarbon and acyl bromide, compared with the prior art, methoxy aromatic hydrocarbon and acyl bromide are used as raw materials, tetra-n-butylammonium bromide is used as the catalyst, esterification reaction is carried out under catalysis, and an esterification product is obtained. Wherein tetra-n-butylammonium bromide (TBAB) is dissociated into tetrabutylammonium cations (TBA < + >) and bromide ions (Br <->) in the reaction, and the tetrabutylammonium cations interact with oxygen atoms in the methoxy aromatic hydrocarbon, so that the oxygen atoms are polarized, and an intermediate I is obtained; taking bromine ions (Br <->) as a nucleophilic reagent, attacking sp3C-O bonds to form an intermediate II, carrying out nucleophilic substitution reaction on the intermediate II and acyl bromide to generate an esterification product, and regenerating tetra-n-butylammonium bromide; the tetra-n-butylammonium bromide can be circularly used for catalytic reaction. The raw materials used in the method are wide in source and low in cost, and the method has the advantages of atom economy and high yield and has a wide application prospect.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and particularly relates to the application of tetrabutylammonium bromide as a catalyst for catalyzing the reaction of methoxyarenes with acyl bromides. Background Art

[0002] Phenol esters are of great value in industries such as food, pharmaceuticals, agrochemicals, and natural products. They are usually synthesized by reacting phenols with acylating agents (such as acyl chlorides or acid anhydrides). However, in some syntheses, it is necessary to protect the hydroxyl group of phenols to prevent unnecessary side reactions. Subsequently, deprotection is required to expose the hydroxyl group for further functionalization. Therefore, directly converting the protected hydroxyl group of phenols without deprotection is highly desirable, because such protected structures, especially methoxyarenes, are common structures in biomass, pharmaceuticals, and natural products (Top. Curr. Chem. 2021, 379, 36.).

[0003] Traditional methods for the conversion of methoxyarenes usually involve a step-by-step process, first demethylation and then esterification with an acylating agent. In contrast, direct esterification of methoxyarenes is a more direct, atom- and step-economic method, but this method has been rarely explored. In 1999, the Singer research group reported that 1-ethyl-3-methylimidazolium iodide (emimI) and aluminum chloride could be used as effective solvents for the acylation of methoxyarenes (Tetrahedron Lett. 2000, 41, 1343.). Although this method has potential, it requires emimI and aluminum chloride as solvents and has a very low yield, mainly due to the formation of Friedel-Crafts compounds, resulting in high reaction costs and serious waste.

[0004] So far, no catalytic method for directly esterifying methoxyarenes with acyl compounds has been achieved. Summary of the Invention

[0005] The purpose of the present invention is to provide the application of tetrabutylammonium bromide as a catalyst for catalyzing the reaction of methoxyarenes with acyl bromides. Using methoxyarenes and acyl bromides as raw materials and tetrabutylammonium bromide as a catalyst, an esterification reaction is catalyzed to obtain an esterification product. The raw materials used in the present invention are widely sourced, low-cost, and have the advantages of atom economy and high yield, and have broad application prospects.

[0006] The specific technical solution of the present invention is as follows:

[0007] The application of tetrabutylammonium bromide as a catalyst for catalyzing the reaction of methoxyarenes with acyl bromides, wherein the molar ratio of tetrabutylammonium bromide, methoxyarenes, and acyl bromides is 0.02 - 0.04:1:1.2;

[0008] The structural formula of the methoxyarene is R 1 -R 6 is any one of H, C1-C4 straight-chain or branched hydrocarbon group, phenyl, phenoxy, halogen, trifluoromethyl, trifluoromethoxy or heteroaromatic ring;

[0009] wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 can be the same or different. Preferably, R 1 , R 2 , R 3 , R 4 , R 5 is H, R 6 is methyl;

[0010] Preferably, the methoxyarene is anisole, and the structural formula is

[0011] The structural formula of the acyl bromide is R 7 is any one of aryl, C1-C4 straight-chain hydrocarbon group or branched hydrocarbon group, benzene, heterocyclic ring, aromatic group;

[0012] Preferably, the C1-C4 straight-chain hydrocarbon group is any one of methyl, ethyl, propyl or tert-butyl; Preferably, the branched hydrocarbon group is isopropyl;

[0013] Catalyze the reaction of methoxyarene with acyl bromide, and the reaction is carried out under a protective atmosphere; the protective atmosphere is a nitrogen atmosphere;

[0014] The reaction conditions are: stirring at 80-120 °C for 10 hours;

[0015] The esterification product is prepared by the reaction, and the structural formula of the esterification product is wherein R 1 -R 5 is H, C1-C4 straight-chain or branched hydrocarbon group, phenyl or halogen;

[0016] R 7 is aryl, C1-C4 straight-chain hydrocarbon group or branched hydrocarbon group; the C1-C4 straight-chain hydrocarbon group is any one of methyl, ethyl, propyl or tert-butyl, and the branched hydrocarbon group is isopropyl;

[0017] Preferably, the specific application method is:

[0018] Under nitrogen conditions, mix tetrabutylammonium bromide, methoxyarene and acyl bromide, stir at 100 °C for 10 hours, cool to room temperature, purify and separate to obtain the esterification product;

[0019] The purification and separation are specifically as follows: after the reaction is completed, the mixture is cooled to room temperature and quenched with saturated aqueous NaHCO3. Then, the aqueous phase is extracted with dichloromethane DCM (3×5 mL), and the combined organic phases are dried over anhydrous Na2SO4. The filtrate is concentrated in vacuo to obtain the crude product, which is further purified by flash column chromatography on silica gel (ethyl acetate / hexane), and the target product is obtained by column chromatography separation after concentration.

[0020] Compared with the prior art, the present invention uses methoxyarene and acyl bromide as raw materials and tetrabutylammonium bromide as a catalyst to catalyze the esterification reaction to obtain an esterification product. Tetrabutylammonium bromide (TBAB) dissociates into tetrabutylammonium cation (TBA+) and bromide ion (Br-) in the reaction. The tetrabutylammonium cation interacts with the oxygen atom in methoxyarene to polarize the oxygen atom to obtain intermediate I; the bromide ion (Br-) acts as a nucleophile to attack the sp 3 C-O bond to form intermediate II, which undergoes a nucleophilic substitution reaction with acyl bromide to generate the esterification product and regenerate tetrabutylammonium bromide; tetrabutylammonium bromide can be recycled for the catalytic reaction. Description of the Drawings

[0021] Figure 1 1H NMR spectrum of the product of Example 1;

[0022] Figure 2 13C NMR spectrum of the product of Example 1;

[0023] Figure 3 1H NMR spectrum of the product of Example 2;

[0024] Figure 4 13C NMR spectrum of the product of Example 2;

[0025] Figure 5 1H NMR spectrum of the product of Example 3;

[0026] Figure 6 13C NMR spectrum of the product of Example 3;

[0027] Figure 7 1H NMR spectrum of the product of Example 4;

[0028] Figure 8 13C NMR spectrum of the product of Example 4;

[0029] Figure 9 1H NMR spectrum of the product of Example 5;

[0030] Figure 10 13C NMR spectrum of the product of Example 5;

[0031] Figure 111H NMR spectrum of the product of Example 6;

[0032] Figure 12 13C NMR spectrum of the product of Example 6;

[0033] Figure 13 1H NMR spectrum of the product of Example 7;

[0034] Figure 14 13C NMR spectrum of the product of Example 7;

[0035] Figure 15 1H NMR spectrum of the product of Example 8;

[0036] Figure 16 13C NMR spectrum of the product of Example 8;

[0037] Figure 17 1H NMR spectrum of the product of Example 9;

[0038] Figure 18 13C NMR spectrum of the product of Example 9;

[0039] Figure 19 1H NMR spectrum of the product of Example 10;

[0040] Figure 20 13C NMR spectrum of the product of Example 10;

[0041] Figure 21 1H NMR spectrum of the product of Example 11;

[0042] Figure 22 13C NMR spectrum of the product of Example 11;

[0043] Figure 23 1H NMR spectrum of the product of Example 12;

[0044] Figure 24 13C NMR spectrum of the product of Example 12;

[0045] Figure 25 1H NMR spectrum of the product of Example 13;

[0046] Figure 26 13C NMR spectrum of the product of Example 13;

[0047] Figure 27 1H NMR spectrum of the product of Example 14;

[0048] Figure 28 13C NMR spectrum of the product of Example 14;

[0049] Figure 29 1H NMR spectrum of the product of Example 15;

[0050] Figure 30 It is the carbon-13 NMR spectrum of the product of Example 15;

[0051] Figure 31 It is the proton NMR spectrum of the product of Example 16;

[0052] Figure 32 It is the carbon-13 NMR spectrum of the product of Example 16;

[0053] Figure 33 It is the proton NMR spectrum of the product of Example 17;

[0054] Figure 34 It is the carbon-13 NMR spectrum of the product of Example 17;

[0055] Figure 35 It is the proton NMR spectrum of the product of Example 18;

[0056] Figure 36 It is the carbon-13 NMR spectrum of the product of Example 18;

[0057] Figure 37 It is the reaction mechanism diagram taking anisole and propionyl bromide as examples. Detailed implementation manners

[0058] To make the objectives, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0059] The test materials and reagents used in the following embodiments, unless otherwise specified, can all be obtained from commercial channels.

[0060] For those not specifying specific techniques or conditions in the embodiments, they can all be carried out according to the techniques or conditions described in the literature in this field or according to the product specifications.

[0061] Example 1

[0062] The application of tetra-n-butylammonium bromide as a catalyst in the reaction of methoxyarene and acyl bromide for the preparation of phenylpropionate, and the reaction equation is as follows:

[0063]

[0064] The specific process is as follows:

[0065] In a nitrogen atmosphere, the following are successively added to the reaction flask nBu4NBr (6.4 mg, 0.02 mmol), 1a anisole (108 mg, 1 mmol), propionyl bromide (163.2 mg, 1.2 mmol), the reaction mixture was stirred at 100 ° C for 10 hours. Then the mixture was cooled to room temperature and quenched with saturated NaHCO3 aqueous solution. The aqueous phase was then extracted with dichloromethane DCM (3×5 mL), and the combined organic phase was dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to obtain a crude product, which was further purified by silica gel flash column chromatography (ethyl acetate / hexane) and concentrated to obtain the target product 3a (139.5 mg), an oily liquid, with a yield of 93%. 1 H NMR (400MHz, CDCl3) δ7.35 (t, J = 7.7Hz, 2H), 7.24–7.16 (m, 1H), 7.07 (d, J = 7.9Hz, 2H), 2.57 (q, J = 7.6Hz, 2H), 1.25 (t, J = 7.5Hz, 3H). 13 C NMR (100MHz, CDCl3) δ173.0,150.9,129.4,125.8,121.6,27.8,9.1.

[0066] Mechanism Figure 37 As shown: Using anisole and propionyl bromide as raw materials and tetrabutylammonium bromide as catalyst, the reaction mechanism is explained: the tetrabutylammonium cation polarizes the oxygen atom to generate intermediate I. At the same time, the bromine anion attacks the sp 3 C–O bond to form intermediate II. Subsequently, a nucleophilic substitution reaction with an acyl bromide occurs to generate the product and regenerate tetrabutylammonium bromide.

[0067] Example 2

[0068] The application of tetra-n-butylammonium bromide as a catalyst for the reaction of methoxy aromatics with acyl bromides is used to prepare 4-phenoxyphenyl propionate. The reaction equation is as follows:

[0069] The specific process is as follows: in a nitrogen atmosphere, add n Bu4NBr (6.4 mg, 0.02 mmol), 1b (200.1 mg, 1 mmol), propionyl bromide (163.2 mg, 1.2 mmol), the reaction mixture was stirred at 100 ° C for 10 hours. The mixture was then cooled to room temperature and quenched with saturated aqueous NaHCO3. The aqueous phase was then extracted with DCM (3×5 mL), and the combined organic phases were dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to obtain a crude product, which was further purified by silica gel flash column chromatography (ethyl acetate / hexane) and concentrated to obtain the target product 3b (210.6 mg) as a white solid with a yield of 87%.1 1H NMR (400 MHz, CDCl3) δ: 7.38 (t, J = 8.0 Hz, 2H), 7.18–7.12 (m, 1H), 7.13–6.95 (m, 6H), 2.63 (q, J = 7.6 Hz, 2H), 1.31 (t, J = 7.5 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ: 173.2, 157.3, 154.7, 146.3, 129.9, 123.4, 122.8, 119.7, 118.9, 27.8, 9.2。

[0070] Example 3

[0071] Use of tetrabutylammonium bromide as a catalyst for the reaction of methoxyarenes with acyl bromides for the preparation of 4-(trifluoromethoxy)phenyl propionate, and the reaction equation is as follows:

[0072]

[0073] The specific preparation process is as follows: Under a nitrogen atmosphere, Bu4NBr (6.4 mg, 0.02 mmol), 1c (192 mg, 1 mmol), and propionyl bromide (163.2 mg, 1.2 mmol) were successively added to the reaction flask, and the reaction mixture was stirred at 100 °C for 10 hours. Then the mixture was cooled to room temperature and quenched with saturated aqueous NaHCO3. Then the aqueous phase was extracted with DCM (3 × 5 mL), and the combined organic phases were dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to obtain a crude product, which was further purified by flash column chromatography on silica gel (ethyl acetate / hexane) to give the target product 3c (142.8 mg), an oily liquid, in a yield of 61%. n 1H NMR (400 MHz, CDCl3) δ: 7.20 (d, J = 8.6 Hz, 2H), 7.08 (d, J = 8.6 Hz, 2H), 2.56 (q, J = 7.5 Hz, 2H), 1.24 (t, J = 7.5 Hz, 3H). 1 13C NMR (100 MHz, CDCl3) δ: 172.7, 149.2, 146.5, 123.0, 122.1, 118.0 (q, J = 255 Hz), 27.6, 8.9. 13 19F NMR (376 MHz, CDCl3) δ -58.2。 19 19F NMR (376 MHz, CDCl3) δ -58.2。

[0074] Example 4

[0075] Use of tetrabutylammonium bromide as a catalyst for the reaction of methoxyarenes with acyl bromides for the preparation of 4-bromophenyl propionate, and the reaction equation is as follows:

[0076]

[0077] Specifically:

[0078] In a nitrogen atmosphere, add n Bu4NBr (6.4 mg, 0.02 mmol), 1d (186 mg, 1 mmol), propionyl bromide (163.2 mg, 1.2 mmol), the reaction mixture was stirred at 100 ° C for 10 hours. Then the mixture was cooled to room temperature and quenched with saturated NaHCO3 aqueous solution. The aqueous phase was then extracted with DCM (3×5 mL), and the combined organic phase was dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to obtain a crude product, which was further purified by silica gel flash column chromatography (ethyl acetate / hexane) and concentrated to obtain the target product 3d (196.1 mg), an oily liquid, with a yield of 86%. 1 H NMR (400MHz, CDCl3) δ7.46 (d, J = 8.3Hz, 2H), 6.96 (d, J = 8.4Hz, 2H), 2.56 (q, J = 7.6Hz, 2H), 1.23 (t, J = 7.6Hz, 3H). 13 C NMR (100MHz, CDCl3) δ172.6,149.8,132.4,123.4,123.4,118.8,27.7,9.0.

[0079] Example 5

[0080] The application of tetra-n-butylammonium bromide as a catalyst for the reaction of methoxy aromatics with acyl bromides is used to prepare 4-chlorophenyl propionate. The reaction equation is as follows:

[0081]

[0082] The specific preparation method is:

[0083] In a nitrogen atmosphere, add n Bu4NBr (6.4 mg, 0.02 mmol), 1e (142 mg, 1 mmol), propionyl bromide (163.2 mg, 1.2 mmol), the reaction mixture was stirred at 100 ° C for 10 hours. Then the mixture was cooled to room temperature and quenched with saturated NaHCO3 aqueous solution. The aqueous phase was then extracted with DCM (3×5 mL), and the combined organic phase was dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to obtain a crude product, which was further purified by silica gel flash column chromatography (ethyl acetate / hexane) and concentrated to obtain the target product 3e (161.9 mg), an oily liquid, with a yield of 88%. 11H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 8.8 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H), 2.57 (q, J = 7.5 Hz, 2H), 1.24 (t, J = 7.5 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 172.7, 149.3, 131.1, 129.5, 123.0, 27.7, 9.0。

[0084] Example 6

[0085] Application of tetrabutylammonium bromide as a catalyst in the reaction of methoxyarene with acyl bromide for the preparation of 4-fluorophenyl propionate, and the reaction equation is as follows:

[0086]

[0087] The specific preparation method is as follows:

[0088] Under a nitrogen atmosphere, Bu4NBr (6.4 mg, 0.02 mmol), 1f (126.1 mg, 1 mmol), and propionyl bromide (163.2 mg, 1.2 mmol) were successively added to the reaction flask, and the reaction mixture was stirred at 100 °C for 10 hours. Then the mixture was cooled to room temperature and quenched with saturated aqueous NaHCO3. Then the aqueous phase was extracted with DCM (3 × 5 mL), and the combined organic phases were dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to obtain a crude product, which was further purified by flash column chromatography on silica gel (ethyl acetate / hexane) to give the target product 3f (137.8 mg), an oily liquid, in a yield of 82%. n 1H NMR (400 MHz, CDCl3) δ 7.01 (d, J = 6.3 Hz, 4H), 2.62 (q, J = 7.6 Hz, 2H), 1.22 (t, J = 7.7 Hz, 3H). 1 13C NMR (100 MHz, CDCl3) δ 172.8, 160.1 (q, J = 242.2 Hz), 146.6 (q, J = 2.8 Hz), 122.9 (q, J = 8.4 Hz), 115.9 (q, J = 23.3 Hz), 27.5, 8.9. 13 19F NMR (376 MHz, CDCl3) δ -117.4。 19

[0089] Example 7

[0090] Application of tetrabutylammonium bromide as a catalyst in the reaction of methoxyarene with acyl bromide for the preparation of 4-(trifluoromethyl)phenyl propionate, and the reaction equation is as follows:

[0091]

[0092] The specific preparation method is as follows:

[0093] In a nitrogen atmosphere, the following are successively added to the reaction flask n Bu4NBr (6.4 mg, 0.02 mmol), 1 g (176 mg, 1 mmol), propionyl bromide (163.2 mg, 1.2 mmol). The reaction mixture is stirred at 100 °C for 10 hours. Then the mixture is cooled to room temperature and quenched with saturated aqueous NaHCO3. Then the aqueous phase is extracted with DCM (3 × 5 mL), and the combined organic phases are dried over anhydrous Na2SO4. The filtrate is concentrated in vacuo to obtain a crude product, which is further purified by flash column chromatography on silica gel (ethyl acetate / hexane). After purification by column chromatography of the concentrated product, the target product 3 g (115.6 mg), an oily liquid, is obtained with a yield of 53%. 1 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 8.7 Hz, 2H), 7.19 (d, J = 8.7 Hz, 2H), 2.59 (q, J = 7.6 Hz, 2H), 1.25 (t, J = 7.5 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 172.5, 153.4 (q, J = 1.1 Hz), 128.0 (q, J = 32.6 Hz), 126.8 (q, J = 3.8 Hz), 124.0 (q, J = 270.2 Hz), 122.2, 27.7, 8.8. 19 19F NMR (376 MHz, CDCl3) δ -62.37.

[0094] Example 8

[0095] Application of tetrabutylammonium bromide as a catalyst in the reaction of methoxyarene with acyl bromide for the preparation of [1,1'-biphenyl]-4-yl propionate, and the reaction equation is as follows:

[0096]

[0097] The specific preparation method is as follows:

[0098] In a nitrogen atmosphere, the following are successively added to the reaction flask nBu4NBr (6.4 mg, 0.02 mmol), 1h (184.1 mg, 1 mmol), propionyl bromide (163.2 mg, 1.2 mmol), the reaction mixture was stirred at 100 ° C for 10 hours. The mixture was then cooled to room temperature and quenched with saturated aqueous NaHCO3. The aqueous phase was then extracted with DCM (3×5 mL), and the combined organic phase was dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to obtain a crude product, which was further purified by silica gel flash column chromatography (ethyl acetate / hexane) and concentrated to obtain the target product 3h (210 mg) as a white solid with a yield of 93%. 1 H NMR (400MHz, CDCl3) δ7.61–7.52(m,4H),7.43(t,J=7.5Hz,2H),7.35(d,J=7.3Hz,1H),7.19–7.11(m,2H),2.62(q,J=7.6Hz,2H),1.29(t,J=7.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ173.2, 150.3, 140.5, 139.0, 128.9, 128.3, 127.4, 127.2, 122.0, 27.9, 9.2.

[0099] Example 9

[0100] The application of tetra-n-butylammonium bromide as a catalyst for the reaction of methoxy aromatics with acyl bromides is used to prepare 3-bromophenylpropionic acid ester. The reaction equation is as follows:

[0101] The specific preparation method is:

[0102] In a nitrogen atmosphere, add n Bu4NBr (6.4 mg, 0.02 mmol), 1i (186 mg, 1 mmol), propionyl bromide (163.2 mg, 1.2 mmol), the reaction mixture was stirred at 100 ° C for 10 hours. Then the mixture was cooled to room temperature and quenched with saturated aqueous NaHCO3. The aqueous phase was then extracted with DCM (3×5 mL), and the combined organic phase was dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to obtain a crude product, which was further purified by silica gel flash column chromatography (ethyl acetate / hexane) and concentrated to obtain the target product 3i (196.1 mg), an oily liquid, with a yield of 86%. 1H NMR (400MHz, CDCl3) δ7.34(d,J=8.1Hz,1H),7.28(s,1H),7.22(t,J=8.1Hz,1H),7.03(d,J=8.1Hz,1H),2.56(q,J=7.5Hz,2H),1.24(t,J=7.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ172.5,151.3,130.5,128.9,125.1,122.4,120.5,27.7,9.0.

[0103] Example 10

[0104] The application of tetra-n-butylammonium bromide as a catalyst for the reaction of methoxy aromatics with acyl bromides is used to prepare 2-bromophenylpropionic acid ester. The reaction equation is as follows:

[0105]

[0106] The specific preparation method is:

[0107] In a nitrogen atmosphere, add n Bu4NBr (6.4 mg, 0.02 mmol), 1i (186 mg, 1 mmol), propionyl bromide (163.2 mg, 1.2 mmol), the reaction mixture was stirred at 100 ° C for 10 hours. Then the mixture was cooled to room temperature and quenched with saturated aqueous NaHCO3. The aqueous phase was then extracted with DCM (3×5 mL), and the combined organic phase was dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to obtain a crude product, which was further purified by silica gel flash column chromatography (ethyl acetate / hexane) and concentrated to obtain the target product 3i (191.5 mg), an oily liquid, with a yield of 84%. 1 H NMR (400MHz, CDCl3) δ7.58(d,J=8.1Hz,1H),7.30(d,J=8.1Hz,1H),7.16–7.04(m,2H),2.64(q,J=7.5Hz,2H),1.29(t,J=7.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ172.0,148.3,133.3,128.5,127.3,123.8,116.3,27.6,9.1.

[0108] Embodiment 11

[0109] The application of tetra-n-butylammonium bromide as a catalyst for the reaction of methoxy aromatics with acyl bromides is used to prepare naphthalene-2-propionate. The reaction equation is as follows:

[0110]

[0111] The specific preparation method is:

[0112] In a nitrogen atmosphere, add n Bu4NBr (6.4 mg, 0.02 mmol), 1j (158.1 mg, 1 mmol), propionyl bromide (163.2 mg, 1.2 mmol), the reaction mixture was stirred at 100 ° C for 10 hours. Then the mixture was cooled to room temperature and quenched with saturated aqueous NaHCO3. The aqueous phase was then extracted with DCM (3×5 mL), and the combined organic phase was dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to obtain a crude product, which was further purified by silica gel flash column chromatography (ethyl acetate / hexane) and concentrated to obtain the target product 3j (182 mg) as a white solid with a yield of 91%. 1 H NMR(400MHz, CDCl3)δ7.83–7.76(m,3H),7.54(d,J=2.3Hz,1H),7.46–7.42(m, 2H), 7.21 (dd, J=8.8, 2.3Hz, 1H), 2.62 (q, J=7.5Hz, 2H), 1.28 (t, J=7.5Hz, 3H). 13 C NMR (100MHz, CDCl3) δ173.2,148.5,133.9,131.5,129.45,127.8,127.7,126.6,125.7,121.3,118.6,27.9,9.2.

[0113] Example 12

[0114] The application of tetra-n-butylammonium bromide as a catalyst for the reaction of methoxy aromatics with acyl bromides is used to prepare dibenzo[b,d]furan-3-yl propionate. The reaction equation is as follows:

[0115]

[0116] The specific preparation method is:

[0117] In a nitrogen atmosphere, add nBu4NBr (6.4 mg, 0.02 mmol), 1k (198 mg, 1 mmol), propionyl bromide (163.2 mg, 1.2 mmol). The reaction mixture was stirred at 100 °C for 10 h. Then the mixture was cooled to room temperature and quenched with saturated aqueous NaHCO3. The aqueous phase was then extracted with DCM (3 × 5 mL), and the combined organic phases were dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to give the crude product, which was further purified by flash column chromatography on silica gel (ethyl acetate / hexane) to afford the target product 3k (213.7 mg), a white solid, in 89% yield. 1 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 7.7 Hz, 1H), 7.64 (d, J = 2.4 Hz, 1H), 7.51 (dd, J = 8.6, 6.9 Hz, 2H), 7.41 (t, J = 7.7 Hz, 1H), 7.28 (t, J = 7.5 Hz, 1H), 7.12 (dd, J = 8.8, 2.5 Hz, 1H), 2.61 (q, J = 7.6 Hz, 2H), 1.28 (t, J = 7.6 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 173.5, 157.0, 153.6, 146.3, 127.6, 125.0, 124.0, 122.8, 120.9, 120.7, 113.6, 112.1, 111.8, 27.8, 9.2.

[0118] Example 13

[0119] Application of tetra-n-butylammonium bromide as a catalyst in the reaction of methoxyarenes with acyl bromides for the preparation of benzo[b]thiophen-6-yl propionate, and the reaction equation is as follows:

[0120]

[0121] The specific preparation method is as follows:

[0122] Under a nitrogen atmosphere, the following were successively added to the reaction flask n Bu4NBr (6.4 mg, 0.02 mmol), 1l (164 mg, 1 mmol), propionyl bromide (163.2 mg, 1.2 mmol). The reaction mixture was stirred at 100 °C for 10 h. Then the mixture was cooled to room temperature and quenched with saturated aqueous NaHCO3. The aqueous phase was then extracted with DCM (3 × 5 mL), and the combined organic phases were dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to give the crude product, which was further purified by flash column chromatography on silica gel (ethyl acetate / hexane) to afford the target product 3l (164.8 mg), a white solid, in 80% yield. 11H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.6 Hz, 1H), 7.49 (s, 1H), 7.42 (d, J = 5.4 Hz, 1H), 7.23 (d, J = 5.4 Hz, 1H), 7.03 (d, J = 8.7 Hz, 1H), 2.57 (q, J = 7.5 Hz, 2H), 1.24 (t, J = 7.5 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 173.4, 148.2, 140.4, 137.1, 128.2, 123.8, 123.2, 118.8, 116.0, 27.9, 9.2。

[0123] Example 14

[0124] Application of tetrabutylammonium bromide as a catalyst in the reaction of methoxyarene with acyl bromide for the preparation of 1,4-benzenedipropionate, and the reaction equation is as follows:

[0125]

[0126] The specific preparation method is as follows:

[0127] In a nitrogen atmosphere, Bu4NBr (12.8 mg, 0.04 mmol), 1m (138.1 mg, 1 mmol), and propionyl bromide (326.4 mg, 2.4 mmol) were successively added to a reaction flask, and the reaction mixture was stirred at 100 °C for 10 hours. Then the mixture was cooled to room temperature and quenched with saturated aqueous NaHCO3. Then the aqueous phase was extracted with DCM (3 × 5 mL), and the combined organic phases were dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to obtain a crude product, which was further purified by flash column chromatography on silica gel (ethyl acetate / hexane) to give the target product 3m (195.4 mg), a white solid, in 88% yield. n 1H NMR (400 MHz, CDCl3) δ 7.08 (s, 4H), 2.56 (d, J = 7.5 Hz, 4H), 1.25 (t, J = 7.6 Hz, 6H). 1 13C NMR (100 MHz, CDCl3) δ 172.9, 148.1, 122.4, 27.7, 9.1。 13

[0128] Example 15

[0129] Application of tetrabutylammonium bromide as a catalyst in the reaction of methoxyarene with acyl bromide for the preparation of phenyl benzoate, and the reaction equation is as follows:

[0130] ​

[0131] The specific preparation method is as follows:

[0132] In a nitrogen atmosphere, add successively to the reaction flask n Bu4NBr (12.8 mg, 0.04 mmol), 1a anisole (108 mg, 1 mmol), 2b (220.7 mg, 1.2 mmol), and stir the reaction mixture at 100 °C for 10 hours. Then cool the mixture to room temperature and quench with saturated aqueous NaHCO3. Then extract the aqueous phase with DCM (3 × 5 mL), and dry the combined organic phases with anhydrous Na2SO4. Concentrate the filtrate in vacuo to obtain the crude product, which is further purified by flash column chromatography on silica gel (ethyl acetate / hexane). After concentration, column chromatography separation gives the target product 4a (178.2 mg), a white solid, in 90% yield. 1 1H NMR (400 MHz, CDCl3) δ 8.25–8.11 (m, 2H), 7.68–7.59 (m, 1H), 7.51 (t, J = 7.8 Hz, 2H), 7.43 (t, J = 7.9 Hz, 2H), 7.31–7.14 (m, 3H). 13 13C NMR (100 MHz, CDCl3) δ 165.3, 151.1, 133.7, 130.3, 129.7, 129.6, 128.7, 126.0, 121.9.

[0133] Example 16

[0134] Application of tetrabutylammonium bromide as a catalyst in the reaction of methoxyarenes with acyl bromides for the preparation of phenyl furan-2-carboxylates, and the reaction equation is as follows:

[0135]

[0136] The specific preparation method is as follows:

[0137] In a nitrogen atmosphere, add successively to the reaction flask n Bu4NBr (12.8 mg, 0.04 mmol), 1a anisole (108 mg, 1 mmol), 2c (208.7 mg, 1.2 mmol), and stir the reaction mixture at 100 °C for 10 hours. Then cool the mixture to room temperature and quench with saturated aqueous NaHCO3. Then extract the aqueous phase with DCM (3 × 5 mL), and dry the combined organic phases with anhydrous Na2SO4. Concentrate the filtrate in vacuo to obtain the crude product, which is further purified by flash column chromatography on silica gel (ethyl acetate / hexane). After concentration, column chromatography separation gives the target product 4b (146.6 mg), a white solid, in 78% yield. 11H NMR (400 MHz, CDCl3) δ 7.62 (s, 1H), 7.44–7.32 (m, 3H), 7.25–7.13 (m, 3H), 6.53–6.52 (m, 1H). 13 13C NMR (100 MHz, CDCl3) δ 156.9, 150.1, 147.2, 143.9, 129.5, 126.0, 121.6, 119.4, 112.2。

[0138] Example 17

[0139] Application of tetrabutylammonium bromide as a catalyst in the reaction of methoxyarenes with acyl bromides for the preparation of phenyl 1-methyl-1H-indole-2-carboxylate, and the reaction equation is as follows:

[0140]

[0141] Specifically:

[0142] In a nitrogen atmosphere, Bu4NBr (12.8 mg, 0.04 mmol), 1a anisole (108 mg, 1 mmol), and 2d (284.4 mg, 1.2 mmol) were successively added to the reaction flask, and the reaction mixture was stirred at 100 °C for 10 hours. Then the mixture was cooled to room temperature and quenched with saturated aqueous NaHCO3. Then the aqueous phase was extracted with DCM (3 × 5 mL), and the combined organic phases were dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to obtain a crude product, which was further purified by flash column chromatography on silica gel (ethyl acetate / hexane) to give the target product 4c (165.7 mg), a white solid, in a yield of 66%. n 1H NMR (400 MHz, CDCl3) δ 7.67–7.62 (m, 1H), 7.47 (d, J = 4.0 Hz, 1H), 7.39–7.31 (m, 4H), 7.22–7.08 (m, 4H), 4.03 (s, 3H). 1 13C NMR (100 MHz, CDCl3) δ 160.8, 150.7, 140.3, 129.7, 126.9, 126.1, 125.7, 123.0, 122.0, 121.0, 111.8, 110.5, 31.8。 13

[0143] Example 18

[0144] Application of tetrabutylammonium bromide as a catalyst in the reaction of methoxyarenes with acyl bromides for the preparation of phenyl 2-(4-isobutylphenyl)propionate, and the reaction equation is as follows:

[0145] ​

[0146] The preparation method is specifically as follows:

[0147] In a nitrogen atmosphere, add n Bu4NBr (12.8 mg, 0.04 mmol), 1a anisole (108 mg, 1 mmol), 2e (321.7 mg, 1.2 mmol), the reaction mixture was stirred at 100 ° C for 10 hours. The mixture was then cooled to room temperature and quenched with saturated NaHCO3 aqueous solution. The aqueous phase was then extracted with DCM (3×5 mL), and the combined organic phase was dried over anhydrous Na2SO4. The filtrate was concentrated in vacuo to obtain a crude product, which was further purified by silica gel flash column chromatography (ethyl acetate / hexane) and concentrated to obtain the target product 4d (214.4 mg) as a white solid with a yield of 76%. 1 H NMR (400MHz, CDCl3) δ7.32–7.28(m,4H),7.18–7.09(m,3H),6.98(d,J=7.9Hz,2H),3.92(d,J=7.1H z,1H),2.46(d,J=7.2Hz,2H),1.92–1.79(m,1H),1.59(d,J=7.2Hz,3H),0.91(s,3H),0.90(s,3H). 13 C NMR (100MHz, CDCl3) δ173.3,151.0,140.9,137.4,129.6,129.4,127.4,125.8,121.5,45.4,30.3,22.5,22.5,18.7.

[0148] The description of the above embodiments is to facilitate the understanding and use of the invention by those skilled in the art. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative work. Therefore, the present invention is not limited to the above embodiments, and improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the present invention should be within the protection scope of the present invention.

Claims

1. The use of tetra-n-butylammonium bromide as a catalyst for the reaction of methoxy aromatics with acyl bromides, characterized in that: The structural formula of the methoxy aromatic hydrocarbon is R 1 -R 6 is H, C1-C4 straight or branched hydrocarbon or phenyl, phenoxy, halogen, trifluoromethyl, trifluoromethoxy or aromatic heterocycle; the acid bromide structural formula is R 7 It is any one of an aryl group, a C1-C4 straight chain hydrocarbon group or a branched chain hydrocarbon group, benzene, a heterocyclic ring or an aromatic group.

2. The use according to claim 1, characterized in that: The molar ratio of tetra-n-butylammonium bromide methoxy aromatic hydrocarbon and acyl bromide is 0.02-0.04:1:1.

2.

3. The use according to claim 1, characterized in that: In the structural formula of methoxy aromatic hydrocarbons, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 Can be the same or different.

4. The use according to claim 1 or 3, characterized in that: In the structural formula of methoxy aromatic hydrocarbons, R 1 , R 2 , R 3 , R 4 , R 5 H, R 6 It is methyl.

5. The use according to claim 1, characterized in that: In the acid bromide structural formula, the C1-C4 straight-chain hydrocarbon group is any one of methyl, ethyl, propyl or tert-butyl; and the branched hydrocarbon group is isopropyl.

6. The use according to claim 1, characterized in that: The catalytic reaction of methoxy aromatic hydrocarbon and acyl bromide is carried out under a protective atmosphere; the protective atmosphere is a nitrogen atmosphere.

7. The use according to claim 1 or 6, characterized in that: The reaction conditions are: stirring at 80-120°C for 10 hours.

8. The use according to claim 1 or 7, characterized in that: The reaction produces an esterification product, the structural formula of which is Where R 1 -R 5 is H, C1-C4 straight or branched hydrocarbon or phenyl or halogen; R 7 It is an aromatic group, a C1-C4 straight chain hydrocarbon group or a branched hydrocarbon group.

9. The use according to claim 1 or 2, characterized in that: The specific application method is: Under nitrogen conditions, tetra-n-butylammonium bromide, methoxy aromatic hydrocarbon and acyl bromide are mixed, stirred at 100° C. for 10 hours, cooled to room temperature, purified and separated to obtain an esterification product.

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