A method for preparing a functionalized beta-naphthyl ether compound

Abstract

The application provides a preparation method of a functionalized beta-naphthyl ether compound, and the preparation method comprises the following steps: triethyl orthoformate is reacted with a 1,3-diarylpropanone compound or a 1-aryl-3-alkyl ketone compound to obtain a 3-substituted-beta-naphthyl ether compound. The reaction condition is mild, the triethyl orthoformate is cheap and easy to obtain, can be simultaneously used as an ethylation reagent and a carbon source for extending a carbon chain, the reaction substrate range is wide, the functional group tolerance is good, the reaction is efficient, the selectivity is high, the post-treatment is simple, the operation is simple, and the method is suitable for large-scale industrial production; the method avoids the pre-preparation of complex substrates in traditional reactions, does not need metal catalysis which is necessary in traditional reactions, can be applied to synthesis of ligands, and simplifies a synthesis route of a hydroformylation reaction ligand.

Description

Technical Field

[0001] This invention belongs to the field of organic compound synthesis technology, and relates to a method for preparing functionalized β-naphthyl ethyl ether compounds. Background Technology

[0002] Binaphthols have significant application prospects in the synthesis of natural products, pharmaceuticals, organic light-emitting materials, ligands, and catalysts, and are widely used in ligands and chiral phosphoric acid catalysts (e.g., (S)-binaphthol ligands and chiral phosphoric acid catalysts). Among these, the conversion of functionalized β-naphthyl ethers to binaphthol via coupling reactions is the simplest and most efficient method, thus the efficient synthesis of functionalized β-naphthyl ethers is of great significance.

[0003]

[0004] Given the importance of substituted naphthyl ether compounds in applications such as biomedical materials, chemists have developed various methods for their synthesis. Currently, a commonly used method is synthesis via transition metal-catalyzed coupling reactions. For example, 3-aryl-substituted naphthyl ethers can be synthesized using functionalized naphthyl ethers (halogens or boric acids) and aryl compounds (boric acids, halogens, borate esters, or Grignard reagents, etc.) as reactants, with palladium or nickel as catalysts. The reaction process is as follows:

[0005]

[0006] However, the above methods often face problems such as the pre-introduction of functional groups, complicated substrate synthesis, high cost, use of precious metal catalysts, complex ligand design, and harsh operating conditions.

[0007] Based on literature review, the following reaction process is used in existing technologies to prepare 3-aryl-substituted naphthyl ethers:

[0008]

[0009] When functionalized naphthyl ether is directly used for coupling reaction under metal catalysis, it is difficult to synthesize naphthyl ether compounds with substituents on the A ring due to the influence of the substituents on the A ring of naphthyl ether, thus limiting the diversity of functional groups of substituted naphthyl ether.

[0010] Due to the readily available availability of alkynyl substrates and the economical nature of the synthetic steps, new carbocyclic skeletons can be formed through intramolecular or intermolecular cyclization, directly introducing an aromatic ring at the C3- position. Since this method is not limited by the substituents on the A ring of naphthalene ethers, cyclization reactions of alkynes have become an important and efficient method for synthesizing carbocyclic compounds. For example:

[0011] (1) In 2014, Balamurugan’s group reported a new reaction for the preparation of polysubstituted α-naphthyl ethers via an intramolecular cyclization reaction catalyzed by triethyl orthoformate as a carbon source:

[0012]

[0013] (2) In 2021, Balamurugan's research group reported that polysubstituted α-naphthyl ethers can be prepared by intramolecular cyclization of alkynyl groups and alkynones under silver tetrafluoroborate catalysis.

[0014]

[0015] However, most of these synthetic methods have many drawbacks, such as cumbersome experimental operations, complicated pre-preparation of substrates, numerous side reactions, and poor tolerance to functional groups. Furthermore, they are limited to synthesizing α-naphthyl ethyl ether, and it is difficult to synthesize β-naphthyl ethyl ether. Summary of the Invention

[0016] In view of the shortcomings of the prior art, the purpose of this invention is to provide a method for preparing functionalized β-naphthyl ethyl ether compounds.

[0017] To achieve this objective, the present invention adopts the following technical solution:

[0018] On one hand, the present invention provides a method for preparing functionalized β-naphthyl ethyl ether compounds, the preparation method comprising the following steps:

[0019] Triethyl orthoformate reacts with 1,3-diarylacetone or 1-aryl-3-alkyl ketone compounds to give 3-substituted β-naphthyl ether compounds.

[0020] In this invention, the triethyl orthoformate is an ethylating agent. Preferably, the molar ratio of the triethyl orthoformate to the 1,3-diarylacetone compound or the 1-aryl-3-alkylketone compound is 1-9:1, for example, 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 7:1, 7.5:1, 8:1, 8.5:1 or 9:1.

[0021] Preferably, the structure of the 1,3-diarylacetone compound is as follows:

[0022] R1 and R2 are independently selected from hydrogen, halogen, C1-C4 (e.g., C1, C2, C3 or C4) alkyl, C1-C4 (e.g., C1, C2, C3 or C4) alkoxy, C6-C12 aryl; m and n are integers from 0 to 4 (e.g., 0, 1, 2, 3 or 4).

[0023] Preferably, the 1,3-diarylacetone compound is selected from... Any one of them.

[0024] Preferably, the structure of the 1-aryl-3-alkyl ketone compound is as follows:

[0025] R3 and R4 are independently selected from hydrogen, C1-C5 (e.g., C1, C2, C3, C4 or C5) alkyl or C1-C5 (e.g., C1, C2, C3, C4 or C5) alkoxy, and p is an integer from 0 to 5 (e.g., 0, 1, 2, 3, 4 or 5).

[0026] Preferably, the 1-aryl-3-alkyl ketone compound is selected from... Any one of them.

[0027] Preferably, the reaction is carried out in the presence of an acidic reagent.

[0028] Preferably, the acidic reagent is at least one of sulfonic acid compounds.

[0029] Preferably, the acidic reagent is selected from at least one of trifluoromethanesulfonic acid, methanesulfonic acid, fluorosulfonic acid, or bis(trifluoromethanesulfonyl)imide, and is preferably trifluoromethanesulfonic acid.

[0030] Preferably, the molar ratio of the acidic reagent to the 1,3-diarylacetone compound or the 1-aryl-3-alkylketone compound is 0.2-5:1, for example 0.2:1, 0.5:1, 0.8:1, 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1 or 5:1.

[0031] Preferably, the reaction is carried out in an organic solvent.

[0032] Preferably, the organic solvent is selected from at least one of chloroalkanes, aromatic hydrocarbons, nitrile compounds, or trimethyl orthoformate or trifluoromethanesulfonic acid.

[0033] Preferably, the organic solvent is selected from at least one of 1,2-dichloroethane, dichloromethane, trichloromethane, acetonitrile, toluene, benzonitrile, trimethyl orthoformate, or trifluoromethanesulfonic acid, with dichloromethane being the most preferred.

[0034] Preferably, the reaction is carried out in an air atmosphere.

[0035] Preferably, the reaction temperature is 15-100℃, for example 15℃, 20℃, 25℃, 30℃, 35℃, 40℃, 50℃, 60℃, 70℃, 80℃, 90℃ or 100℃, and the reaction time is 1h-24h, for example 1h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 11h, 12h, 14h, 16h, 18h, 20h, 22h or 24h.

[0036] As a preferred embodiment of the present invention, the preparation method of the functionalized β-naphthyl ether compound includes the following steps:

[0037] In an air atmosphere, triethyl orthoformate reacts with a 1,3-diarylacetone compound or a 1-aryl-3-alkyl ketone compound in an organic solvent at 15-100°C for 1-24 hours in the presence of an acidic sulfonic acid compound to yield a 3-substituted β-naphthyl ether compound. The sulfonic acid compound is selected from at least one of trifluoromethanesulfonic acid, methanesulfonic acid, fluorosulfonic acid, or bis(trifluoromethanesulfonyl)imide. The organic solvent is selected from at least one of 1,2-dichloroethane, dichloromethane, trichloromethane, acetonitrile, toluene, trimethyl orthoformate, or trifluoromethanesulfonic acid. The molar ratio of triethyl orthoformate to the 1,3-diarylacetone compound or the 1-aryl-3-alkyl ketone compound is 1-9:1, and the molar ratio of the acidic reagent to the 1,3-diarylacetone compound or the 1-aryl-3-alkyl ketone compound is 0.2-5:1.

[0038] Compared with the prior art, the present invention has the following beneficial effects:

[0039] This invention utilizes mild reaction conditions, readily available and inexpensive triethyl orthoformate, which can simultaneously serve as an ethylating agent and a carbon source for extending a single carbon chain. It exhibits a broad substrate range, good functional group tolerance, high efficiency and selectivity, simple post-processing, and convenient operation, making it suitable for large-scale industrial production. It avoids the need for complex pre-preparation of substrates in traditional reactions and eliminates the metal catalysis required in conventional reactions. It can be applied to ligand synthesis, simplifying the ligand synthesis route for hydroformylation reactions. By introducing the aromatic ring skeleton at the C3-position of naphthol, it can regulate electrons and steric hindrance in the synthesis of bidentate phosphorus ligands for olefin hydroformylation. Suitable for large-scale industrial production, it provides a novel synthetic route for the efficient and rapid synthesis of this type of compound. Detailed Implementation

[0040] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0041] The data and purity of the new compounds presented in the following examples were determined by nuclear magnetic resonance.

[0042] Example 1

[0043] Preparation of 3-phenyl-β-naphthyl ethyl ether:

[0044]

[0045] In a 25 mL reaction tube, 1,3-diphenylacetone (105 mg, 0.5 mmol), triethyl orthoformate (249 μL, 222 mg, 1.5 mmol), and dichloromethane (2 mL) were added sequentially. Then, trifluoromethanesulfonic acid (177 μL, 300 mg, 2 mmol) was added. After sealing the reaction tube, the mixture was stirred thoroughly. The reaction process was monitored by thin-layer chromatography, and the reaction was completed after 4 hours.

[0046] After the reaction was complete, dichloromethane (10 mL) was first added to the reaction tube to dilute the reaction solution, and then triethylamine (0.5 mL) was added dropwise to quench the reaction. The mixture was stirred for another 10 min, and then the organic solvent was removed by rotary evaporation. The residue was purified by column chromatography (petroleum ether / ethyl acetate = 30 / 1) to give a white solid in 63% yield.

[0047] The 1H NMR spectrum data of the obtained product are as follows:

[0048] 1 HNMR (400MHz, CDCl3): δ7.79-7.71(m, 3H), 7.65-7.62(m, 2H), 7.45-7.40(m, 3H ), 7.38-7.33 (m, 2H), 7.20 (s, 1H), 4.15 (q, J=6.8Hz, 2H), 1.41 (t, J=6.8Hz, 3H).

[0049] The carbon NMR spectrum data of the obtained product are as follows:

[0050] 13 CNMR (100MHz, CDCl3): δ54.5, 138.4, 134.0, 132.5, 130.0, 129.8(2C), 128.8, 127.8(2C), 127.7, 127.0, 126.3, 126.2, 123.8, 106.7, 63.8, 14.6.

[0051] The high-resolution mass spectrometry data of the obtained product are as follows:

[0052] HRMS (APCI): C 18 H 17 O + [M+H] +Calculated value: 249.1274; Test value: 249.1278.

[0053] It is evident that the product obtained is 3-phenyl-β-naphthyl ethyl ether.

[0054] Example 2

[0055] Preparation of 6-methyl-3-(4-tolyl)-β-naphthyl ethyl ether:

[0056]

[0057] In a 25 mL reaction tube, 1,3-bis(4-tolyl)acetone (119 mg, 0.5 mmol), triethyl orthoformate (249 μL, 222 mg, 1.5 mmol), and dichloromethane (2 mL) were added sequentially. Then, trifluoromethanesulfonic acid (177 μL, 300 mg, 2 mmol) was added. After sealing the reaction tube, the mixture was stirred thoroughly. The reaction process was monitored by thin-layer chromatography, and the reaction was completed after 4 hours.

[0058] After the reaction was complete, dichloromethane (10 mL) was first added to the reaction tube to dilute the reaction solution, and then triethylamine (0.5 mL) was added dropwise to quench the reaction. The mixture was stirred for another 10 min, and then the organic solvent was removed by rotary evaporation. The residue was purified by column chromatography (petroleum ether / ethyl acetate = 30 / 1) to give a white solid in 66% yield.

[0059] The 1H NMR spectrum data of the obtained product are as follows:

[0060] 1 HNMR (400MHz, CDCl3): δ7.66 (s, 1H), 7.63-7.60 (m, 1H), 7.54-7.52 (m, 3H), 7.26-7.21 (m, 3H), 7.14 (s, 1H), 4.11 (q, J=6.8Hz, 2H), 2.46 (s, 3H), 2.40 (s, 3H), 1.39 (t, J=6.8Hz, 3H).

[0061] The carbon NMR spectrum data of the obtained product are as follows:

[0062] 13 CNMR (100MHz, CDCl3): δ154.0, 136.6, 135.6, 133.1, 132.3, 132.0, 129.6 (2C), 129.1, 129.0, 128.6 (2C), 128.3, 126.6, 126.1, 106.5, 63.7, 21.5, 21.2, 14.6.

[0063] The high-resolution mass spectrometry data of the obtained product are as follows:

[0064] HRMS (APCI): C 20 H 20 O + [M+H] + Calculated value: 277.1587; Test value: 277.1591.

[0065] It can be seen that the product obtained is 6-methyl-3-(4-tolyl)-β-naphthyl ethyl ether.

[0066] Example 3

[0067] Preparation of 6-methoxy-3-(4-methoxyphenyl)-β-naphthyl ethyl ether:

[0068]

[0069] In a 25 mL reaction tube, 1,3-bis(4-methoxyphenyl)acetone (135 mg, 0.5 mmol), triethyl orthoformate (249 μL, 222 mg, 1.5 mmol), and dichloromethane (2 mL) were added sequentially. Then, trifluoromethanesulfonic acid (177 μL, 300 mg, 2 mmol) was added. After sealing the reaction tube, the mixture was stirred thoroughly. The reaction process was monitored by thin-layer chromatography, and the reaction was completed after 4 hours.

[0070] After the reaction was complete, dichloromethane (10 mL) was first added to the reaction tube to dilute the reaction solution, and then triethylamine (0.5 mL) was added dropwise to quench the reaction. The mixture was stirred for another 10 min, and then the organic solvent was removed by rotary evaporation. The residue was purified by column chromatography (petroleum ether / ethyl acetate = 30 / 1) to give a white solid in 54% yield.

[0071] The 1H NMR spectrum data of the obtained product are as follows:

[0072] 1 HNMR (400MHz, CDCl3): δ7.64-7.56 (m, 4H), 7.14 (s, 1H), 7.12-7.08 (m, 2H), 6.98-6 .95 (m, 2H), 4.10 (q, J=7.2Hz, 2H), 3.88 (s, 3H), 3.85 (s, 3H), 1.39 (t, J=7.6Hz, 3H).

[0073] The carbon NMR spectrum data of the obtained product are as follows:

[0074] 13CNMR (100MHz, CDCl3): δ158.8, 156.3, 153.1, 132.4, 130.9, 130.8 (2C), 129.7, 129.0, 128.4, 127.7, 118.6, 113.3(2C), 107.1, 105.9, 63.9, 55.3, 55.2, 14.7.

[0075] The high-resolution mass spectrometry data of the obtained product are as follows:

[0076] HRMS (APCI): C 20 H 21 O3 + [M+H] + Calculated value: 309.1485; Test value: 309.1484.

[0077] It is evident that the product obtained is 6-methoxy-3-(4-methoxyphenyl)-β-naphthyl ether.

[0078] Example 4

[0079] Preparation of 6-fluoro-3-(4-fluorophenyl)-β-naphthyl ethyl ether:

[0080]

[0081] In a 25 mL reaction tube, 1,3-bis(4-fluorophenyl)acetone (123 mg, 0.5 mmol), triethyl orthoformate (249 μL, 222 mg, 1.5 mmol), and dichloromethane (2 mL) were added sequentially. Then, trifluoromethanesulfonic acid (177 μL, 300 mg, 2 mmol) was added. After sealing the reaction tube, the mixture was stirred thoroughly. The reaction process was monitored by thin-layer chromatography, and the reaction was completed after 10 h.

[0082] After the reaction was complete, dichloromethane (10 mL) was first added to the reaction tube to dilute the reaction solution, and then triethylamine (0.5 mL) was added dropwise to quench the reaction. The mixture was stirred for another 10 min, and then the organic solvent was removed by rotary evaporation. The residue was purified by column chromatography (petroleum ether / ethyl acetate = 30 / 1) to give a white solid in 61% yield.

[0083] The 1H NMR spectrum data of the obtained product are as follows:

[0084] 1HNMR (400MHz, CDCl3): δ7.71-7.67 (m, 1H), 7.64 (s, 1H), 7.60-7.55 (m, 2H), 7.40-7.36 (s, 1H), 7 .24-7.20 (m, 1H), 7.18 (s, 1H), 7.13-7.08 (m, 2H), 4.12 (q, J=6.8Hz, 2H), 1.40 (t, J=6.8Hz, 3H).

[0085] The carbon NMR spectrum data of the obtained product are as follows:

[0086] 13 CNMR (100MHz, CDCl3): δ162.3 (d, J=245Hz), 159.5 (d, J=245Hz), 153.8, 134.0 (d, J=2.8Hz), 132.5, 131.3 (d, J=7.7Hz, 2C), 130.8, 129.1 (d, J=8.6Hz), 129.0 (d, J=4.8Hz), 128.4 (d, J=8.6Hz), 116.4 (d, J=24.8Hz), 114.8 (d, J=21.0Hz, 2C), 110.7, (d, J=21.0Hz), 106.8, 63.9, 14.6.

[0087] The high-resolution mass spectrometry data of the obtained product are as follows:

[0088] HRMS (APCI): C 18 H 14 F2O + [M] + Calculated value: 284.1013; Test value: 284.1011.

[0089] It is evident that the product obtained is 6-fluoro-3-(4-fluorophenyl)-β-naphthyl ethyl ether.

[0090] Example 5

[0091] Preparation of 6-chloro-3-(4-chlorophenyl)-β-naphthyl ethyl ether:

[0092]

[0093] In a 25 mL reaction tube, 1,3-bis(4-chlorophenyl)acetone (139 mg, 0.5 mmol), triethyl orthoformate (249 μL, 222 mg, 1.5 mmol), and dichloromethane (2 mL) were added sequentially. Then, trifluoromethanesulfonic acid (177 μL, 300 mg, 2 mmol) was added. After sealing the reaction tube, the mixture was stirred thoroughly. The reaction process was monitored by thin-layer chromatography, and the reaction was completed after 4 hours.

[0094] After the reaction was complete, dichloromethane (10 mL) was first added to the reaction tube to dilute the reaction solution, and then triethylamine (0.5 mL) was added dropwise to quench the reaction. The mixture was stirred for another 10 min, and then the organic solvent was removed by rotary evaporation. The residue was purified by column chromatography (petroleum ether / ethyl acetate = 30 / 1) to give a white solid in 49% yield.

[0095] The 1H NMR spectrum data of the obtained product are as follows:

[0096] 1 HNMR (400MHz, CDCl3): δ7.73-7.72(m, 1H), 7.65-7.60(m, 2H), 7.54-7.51(m, 2H ), 7.41-7.34 (m, 3H), 7.15 (s, 1H), 4.13 (q, J=6.8Hz, 2H), 1.40 (t, J=6.8Hz, 3H).

[0097] The carbon NMR spectrum data of the obtained product are as follows:

[0098] 13 CNMR (100MHz, CDCl3): δ154.5, 136.4, 133.3, 132.3, 132.2, 131.0 (2C), 129.4, 129.2, 128.8, 128.1 (2C), 127.8, 127.2, 126.3, 106.6, 64.0, 14.5.

[0099] The high-resolution mass spectrometry data of the obtained product are as follows:

[0100] HRMS (APCI): C 18 H 14 Cl2O + [M+H] + Calculated value: 317.0495; Test value: 317.0495.

[0101] It is evident that the product obtained is 6-chloro-3-(4-chlorophenyl)-β-naphthyl ether.

[0102] Example 6

[0103] Preparation of 6,7-dimethoxy-3-(3,4-dimethoxyphenyl)-β-naphthalene ethyl ether:

[0104]

[0105] In a 25 mL reaction tube, 1,3-bis(3,4-dimethoxyphenyl)acetone (183 mg, 0.5 mmol), triethyl orthoformate (249 μL, 222 mg, 1.5 mmol), and dichloromethane (2 mL) were added sequentially. Then, trifluoromethanesulfonic acid (177 μL, 300 mg, 2 mmol) was added. After sealing the reaction tube, the mixture was stirred thoroughly. The reaction process was monitored by thin-layer chromatography, and the reaction was completed after 10 h.

[0106] After the reaction was complete, dichloromethane (10 mL) was first added to the reaction tube to dilute the reaction solution, and then triethylamine (0.5 mL) was added dropwise to quench the reaction. The mixture was stirred for another 10 min, and then the organic solvent was removed by rotary evaporation. The residue was purified by column chromatography (petroleum ether / ethyl acetate = 30 / 1) to give a white solid in 65% yield.

[0107] The 1H NMR spectrum data of the obtained product are as follows:

[0108] 1 HNMR (400MHz, CDCl3): δ7.63 (s, 1H), 7.27-7.25 (m, 1H), 7.20-7.16 (m, 1H), 7.12 (s, 1H), 7.09 (s, 1H), 7.06 (s, 1H), 6 .96-6.93 (m, 1H), 4.12 (q, J=6.8Hz, 2H), 4.00 (s, 3H), 3.98 (s, 3H), 3.93 (s, 3H), 3.92 (s, 3H), 1.43 (t, J=6.8Hz, 3H).

[0109] The carbon NMR spectrum data of the obtained product are as follows:

[0110] 13 CNMR (100MHz, CDCl3): δ153.5, 149.8, 148.1, 148.0, 147.9, 131.4, 129.8, 129.4, 1 28.1, 124.0, 121.8, 113.3, 110.8, 106.4(2C), 105.3, 63.8, 55.9, 55.8(2C), 14.8.

[0111] The high-resolution mass spectrometry data of the obtained product are as follows:

[0112] HRMS (APCI): C 22 H 25 O5 + [M+H] + Calculated value: 369.1697; Test value: 369.1693.

[0113] It can be seen that the product obtained is 6,7-dimethoxy-3-(3,4-dimethoxyphenyl)-β-naphthalene ethyl ether.

[0114] Example 7

[0115] Preparation of 3-methyl-β-naphthylethyl ether:

[0116]

[0117] In a 25 mL reaction tube, 1-phenylbutanone (74 mg, 0.5 mmol) and trimethyl orthoformate (1 mL, 4.5 mmol) were added sequentially. Then, trifluoromethanesulfonic acid (177 μL, 300 mg, 2 mmol) was added. After sealing the reaction tube, the mixture was stirred thoroughly. The reaction process was monitored by thin-layer chromatography, and the reaction was completed after 4 hours.

[0118] After the reaction was complete, dichloromethane (10 mL) was first added to the reaction tube to dilute the reaction solution, and then triethylamine (0.5 mL) was added dropwise to quench the reaction. The mixture was stirred for another 10 min, and then the organic solvent was removed by rotary evaporation. The residue was purified by column chromatography (petroleum ether / ethyl acetate = 30 / 1) to give a white solid in 55% yield.

[0119] The 1H NMR spectrum data of the obtained product are as follows:

[0120] 1 HNMR (400MHz, CDCl3): δ7.67-7.64(m, 2H), 7.54(s, 1H), 7.37-7.32(m, 1H), 7.29-7 .24 (m, 1H), 7.02 (s, 1H), 4.10 (q, J=6.8Hz, 2H), 2.36 (s, 3H), 1.46 (t, J=6.8Hz, 3H).

[0121] The carbon NMR spectrum data of the obtained product are as follows:

[0122] 13 CNMR (100MHz, CDCl3): δ156.2, 133.4, 128.7, 128.6 (2C), 126.8, 126.3, 125.2, 123.3, 105.1, 63.3, 16.9, 14.8.

[0123] The high-resolution mass spectrometry data of the obtained product are as follows:

[0124] HRMS (APCI): C 13 H 15 O + [M+H] + Calculated value: 187.1118; Test value: 187.1117.

[0125] It is evident that the product obtained is 3-methyl-β-naphthyl ethyl ether.

[0126] Example 8

[0127] Preparation of 3-propyl-β-naphthyl ethyl ether:

[0128]

[0129] In a 25 mL reaction tube, 1-phenylhexanone (88 mg, 0.5 mmol) and trimethyl orthoformate (1 mL, 4.5 mmol) were added sequentially. Then, trifluoromethanesulfonic acid (177 μL, 300 mg, 2 mmol) was added. After sealing the reaction tube, the mixture was stirred thoroughly. The reaction process was monitored by thin-layer chromatography, and the reaction was completed after 4 hours.

[0130] After the reaction was complete, dichloromethane (10 mL) was first added to the reaction tube to dilute the reaction solution, and then triethylamine (0.5 mL) was added dropwise to quench the reaction. The mixture was stirred for another 10 min, and then the organic solvent was removed by rotary evaporation. The residue was purified by column chromatography (petroleum ether / ethyl acetate = 30 / 1) to obtain a colorless oily liquid in 45% yield.

[0131] The 1H NMR spectrum data of the obtained product are as follows:

[0132] 1 HNMR (400MHz, CDCl3): δ7.70-7.65 (m, 2H), 7.54 (s, 1H), 7.37-7.33 (m, 1H), 7.30-7.26 (m, 1H), 7.05 (s, 1H), 4 .12 (q, J=7.6Hz, 2H), 2.74 (t, J=7.6Hz, 2H), 1.75-1.65 (m, 2H), 1.47 (t, J=7.6Hz, 3H), 0.98 (t, J=7.2Hz, 3H).

[0133] The carbon NMR spectrum data of the obtained product are as follows:

[0134] 13 CNMR (100MHz, CDCl3): δ156.0, 133.3, 133.0, 128.7, 128.0, 127.0, 126.2, 125.3, 123.3, 105.4, 63.3, 32.8, 22.9, 14.8, 14.1.

[0135] The high-resolution mass spectrometry data of the obtained product are as follows:

[0136] HRMS (APCI): C 15 H19 O + [M+H] + Calculated value: 215.1431; Test value: 215.1430.

[0137] Example 9

[0138] Preparation of 4,5-dimethoxy-β-naphthyl ether:

[0139]

[0140] In a 25 mL reaction tube, 3,4-dimethoxyphenylacetone (82 mg, 0.5 mmol) and trimethyl orthoformate (1 mL, 4.5 mmol) were added sequentially. Then, trifluoromethanesulfonic acid (177 μL, 300 mg, 2 mmol) was added. After sealing the reaction tube, the mixture was stirred thoroughly. The reaction process was monitored by thin-layer chromatography, and the reaction was completed after 4 hours.

[0141] After the reaction was complete, dichloromethane (10 mL) was first added to the reaction tube to dilute the reaction solution, and then triethylamine (0.5 mL) was added dropwise to quench the reaction. The mixture was stirred for another 10 min, and then the organic solvent was removed by rotary evaporation. The residue was purified by column chromatography (petroleum ether / ethyl acetate = 30 / 1) to give a white solid in 50% yield.

[0142] The 1H NMR spectrum data of the obtained product are as follows:

[0143] 1 HNMR (400MHz, CDCl3): δ7.49-7.46 (m, 1H), 6.96-6.90 (m, 4H), 4.01 (q, J=6.8Hz, 2H), 3.88 (s, 3H), 3.86 (s, 3H), 1.36 (t, J=6.8Hz, 3H).

[0144] The carbon NMR spectrum data of the obtained product are as follows:

[0145] 13 CNMR (100MHz, CDCl3): δ155.9, 147.8, 147.6, 130.1, 127.6, 123.9, 116.3, 106.4, 106.3, 105.5, 63.3, 55.6 (2C), 14.8.

[0146] It is evident that the product obtained is 4,5-dimethoxy-β-naphthyl ether.

[0147] In Examples 1 to 9, dichloromethane was used as the reaction solvent. Experiments showed that, in addition to dichloromethane, other organic solvents that can be used as the reaction solvent include 1,2-dichloroethane, chloroform and other chloroalkanes, acetonitrile, toluene, trimethyl orthoformate, and trifluoromethanesulfonic acid.

[0148] (1) The halogenated hydrocarbon can be either primary carbon or secondary carbon, preferably dichloromethane, which is a primary carbon. Chlorinated alkanes include, but are not limited to, chloroform, carbon tetrachloride and 1,2-dichloroethane.

[0149] (2) Aromatic hydrocarbons include, but are not limited to, benzene, toluene, chlorobenzene, o-dichlorobenzene and xylene.

[0150] (3) Acetonitrile, benzonitrile, trimethyl orthoformate and trifluoromethanesulfonic acid can all be used as reaction solvents in this invention.

[0151] Examples 10 to 19

[0152] Except for the different reaction solvents, Examples 10 to 19 were identical to Example 1 in all other operations. The organic solvents used in each example and the yields of the corresponding products are shown in Table 1 below:

[0153] Table 1

[0154]

[0155]

[0156] From the table above (NR indicates no reaction), we can see that:

[0157] (1) When using aprotic solvents, the reaction yield is high, especially when using halogenated hydrocarbons as reaction solvents. Among them, the reaction is best in dichloromethane (Example 1), with a separation yield of 63%.

[0158] (2) When other protic solvents are used, the reaction is poor or even non-reacting.

[0159] Taking all factors into consideration, dichloromethane is the best reaction solvent.

[0160] In Examples 1 to 9, trifluoromethanesulfonic acid was the preferred acid. Experiments showed that hydrochloric acid, trifluoroacetic acid, p-toluenesulfonic acid, fluorosulfonic acid, and Lewis acid BF3 were also suitable. . Neither Et2O nor FeCl3 can efficiently replace trifluoromethanesulfonic acid in this invention.

[0161] Examples 20 to 25

[0162] Except for the different acids, Examples 20 to 25 were identical to Example 1 in all other operations. The acids used in each example and the yields of the corresponding products are shown in Table 2 below:

[0163] Table 2

[0164]

[0165]

[0166] From the table above (NR indicates no reaction), we can see that:

[0167] (1) Other organic acids, inorganic acids, and Lewis acids cannot efficiently replace trifluoromethanesulfonic acid in catalytic reactions;

[0168] (2) Trifluoromethanesulfonic acid has a unique function of catalyzing substrate-selective reactions.

[0169] Taking all factors into consideration, trifluoromethanesulfonic acid is the best acid.

[0170] In Examples 1 to 25:

[0171] (1) The optimal molar ratio of trimethyl orthoformate to 1,3-diarylacetone / 1-aryl-3-alkyl ketone is 3:1, and other ratios are not limited to this; (2) The optimal molar ratio of trifluoromethanesulfonic acid to 1,3-diarylacetone / 1-aryl-3-alkyl ketone is 4:1, and other ratios are not limited to this; (3) The reaction temperature can be adjusted appropriately within the range of 15-100℃, and the reaction time can be adjusted appropriately within the range of 1-24h.

[0172] The applicant declares that the preparation method of the present invention is illustrated by the above embodiments, but the present invention is not limited to the above embodiments, that is, it does not mean that the present invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. A method for preparing functionalized β-naphthalene ethyl ether compounds, characterized in that, The preparation method includes the following steps: Triethyl orthoformate reacts with 1,3-diarylacetone or 1-aryl-3-alkyl ketone compounds to give 3-substituted-β-naphthyl ether compounds; The reaction is carried out in the presence of an acidic reagent, namely trifluoromethanesulfonic acid. The reaction is carried out in an organic solvent; the organic solvent is selected from at least one of chloroalkanes, aromatic hydrocarbons, nitrile compounds, or trimethyl orthoformate or trifluoromethanesulfonic acid. The molar ratio of triethyl orthoformate to 1,3-diarylacetone or 1-aryl-3-alkyl ketone is 3-9:1; the molar ratio of the acidic reagent to 1,3-diarylacetone or 1-aryl-3-alkyl ketone is 2-5:

1.

2. The preparation method according to claim 1, characterized in that, The structure of the 1,3-diarylacetone compound is shown below: R1 and R2 are independently selected from hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, and C6-C12 aryl; m and n are integers from 0 to 4.

3. The preparation method according to claim 2, characterized in that, The 1,3-diarylacetone compound is selected from... , , , , or Any one of them.

4. The preparation method according to claim 1, characterized in that, The structure of the 1-aryl-3-alkyl ketone compound is shown below: R3 and R4 are independently selected from hydrogen, C1-C5 alkyl or C1-C5 alkoxy, and p is an integer from 0 to 5.

5. The preparation method according to claim 4, characterized in that, The 1-aryl-3-alkyl ketone compound is selected from... , or Any one of them.

6. The preparation method according to claim 1, characterized in that, The organic solvent is selected from at least one of 1,2-dichloroethane, dichloromethane, chloroform, acetonitrile, toluene, benzonitrile, trimethyl orthoformate, or trifluoromethanesulfonic acid.

7. The preparation method according to claim 6, characterized in that, The organic solvent is dichloromethane.

8. The preparation method according to claim 1, characterized in that, The reaction takes place in an air atmosphere.

9. The preparation method according to claim 1, characterized in that, The reaction temperature is 15-100℃, and the reaction time is 1h-24h.

10. The preparation method according to claim 1, characterized in that, The preparation method includes the following steps: In an air atmosphere, triethyl orthoformate reacts with a 1,3-diarylacetone compound or a 1-aryl-3-alkyl ketone compound in an organic solvent at 15-100°C for 1-24 hours in the presence of an acidic sulfonic acid compound to yield a 3-substituted β-naphthyl ether compound. The sulfonic acid compound is trifluoromethanesulfonic acid. The organic solvent is selected from at least one of 1,2-dichloroethane, dichloromethane, trichloromethane, acetonitrile, toluene, trimethyl orthoformate, or trifluoromethanesulfonic acid. The molar ratio of triethyl orthoformate to the 1,3-diarylacetone compound or the 1-aryl-3-alkyl ketone compound is 3-9:1, and the molar ratio of the acidic reagent to the 1,3-diarylacetone compound or the 1-aryl-3-alkyl ketone compound is 2-5:1.

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