A method for preparing 3-aryl / alkyl-beta-naphthyl ether compounds

Abstract

The application provides a preparation method of 3-aryl / alkyl-beta-naphthyl ether compounds, and the preparation method comprises the following steps: reacting trimethyl orthoformate with 1,3-diaromatic propyl ketone compounds or 1-aryl-3-alkyl ketone compounds to obtain 3-aryl-beta-naphthyl ether compounds or 3-alkyl-beta-naphthyl ether compounds. The reaction condition of the application is mild, trimethyl orthoformate is cheap and easy to obtain, can be used as a methylation reagent and a carbon source for extending a carbon chain at the same time, the range of reaction substrates is wide, and 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 application is suitable for large-scale industrial production; the complex substrate prepared in advance in the traditional reaction is avoided, the metal catalyst necessary for the traditional reaction is not needed, the binaftyl alcohol precursor compounds can be prepared with high chemical selectivity, and a more simple and efficient route is provided for the olefin hydroformylation / hydroformyl esterification reaction for synthesizing bidentate ligands.

Description

Technical Field

[0001] This invention belongs to the field of organic compound synthesis technology, and relates to the preparation of a 3-aryl / alkyl-β-naphthyl methyl ether compound. Background Technology

[0002] 3-Aryl / alkyl-β-naphthyl ether compounds represent an important class of skeletal structures among numerous organic functional molecules. They hold significant promise for applications in the synthesis of natural products, bioactive drugs, organic materials, ligands, and catalysts.

[0003] Because naphthalene ethers have important applications, the synthesis of various functionalized naphthalene ethers is of great significance. For example, the traditional method for synthesizing 3-aryl-β-naphthalene ethers mainly utilizes transition metal-catalyzed aryl halides, arylboronic acids, aryl Grignard reagents, etc., to achieve C-C coupling reactions with functionalized naphthalene ethers, as shown in the reaction flow below.

[0004]

[0005] Although the aforementioned synthetic methods offer high conversion rates and selectivity, demonstrating potential value in drug synthesis, they often require the use of complex ligands / catalysts and involve linear, multi-step synthesis of pre-functionalized naphthyl ether compounds. Sometimes, the use of substrates with moisture- or oxygen-sensitive functional groups further complicates the process. Because the variety of functionalized naphthyl ethers is very limited, these methods can only synthesize structurally simple 3-aryl-β-naphthyl ethers.

[0006] Literature review reveals that alkyne cyclization has become an important and efficient method for synthesizing carbocyclic compounds due to the ease of obtaining alkyne-containing substrates and the economical nature of the synthetic steps. In recent years, only a few studies have reported the direct synthesis of naphthalene ether derivatives via alkyne cyclization, for example:

[0007] (1) In 2014, Balamurugan's group reported a novel reaction for the synthesis of polysubstituted α-naphthyl methyl ethers via an intramolecular cyclization reaction catalyzed by trifluoromethanesulfonic acid, using trimethyl orthoformate as a carbon source. In this tandem reaction, the alkynyl ketone and trimethyl orthoformate first undergo a trifluoromethanesulfonic acid-catalyzed acetalization reaction, elongating the carbon atom in situ to generate an intermediate. Then, an intramolecular cyclization reaction is performed to generate polysubstituted α-naphthyl methyl ethers:

[0008]

[0009] (2) In 2021, Balamurugan's research group reported that polysubstituted α-naphthyl methyl ethers can be synthesized from alkynyl groups and alkynones via intramolecular cyclization under silver tetrafluoroborate catalysis. In this method, the carbonyl group in the substrate reacts in situ with trimethyl orthoformate to generate a ketal intermediate. Then, the alkyne is activated by silver and undergoes cyclization and aromatization reactions to obtain polysubstituted α-naphthyl methyl ethers.

[0010]

[0011] (3) In 2022, Zhou's research group reported that cuprous iodide can catalyze the cyclization reaction between terminal alkynes and o-bromoacetophenone to generate α-naphthyl ether derivatives. This method is the first to achieve ketone-catalyzed cyclization coupling reaction between 2-bromoaryl ketones and terminal alkynes, yielding functionalized α-naphthyl ethers in moderate to excellent yields. The reaction involves 6-endo-dig cyclization and C(sp... 2 The )-O coupling reaction is a novel method for the one-step synthesis of multifunctional substituted naphthyl ethers from simple starting materials:

[0012]

[0013] 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-naphthalene ethers and are difficult to synthesize β-naphthalene ethers. Summary of the Invention

[0014] In view of the shortcomings of the prior art, the purpose of this invention is to provide a method for preparing 3-aryl / alkyl-β-naphthyl methyl ether compounds.

[0015] To achieve this objective, the present invention adopts the following technical solution:

[0016] On one hand, the present invention provides a method for preparing 3-aryl / alkyl-β-naphthyl methyl ether compounds, the method comprising the following steps:

[0017] Trimethyl orthoformate reacts with 1,3-diarylacetone or 1-aryl-3-alkyl ketone compounds to give 3-aryl-β-naphthyl methyl ethers or 3-alkyl-β-naphthyl methyl ethers.

[0018] In this invention, the " / " in 3-aryl / alkyl-β-naphthyl methyl ether compounds represents "or", meaning that the substituent at the 3-position is aryl or alkyl.

[0019] Preferably, the molar ratio of the trimethyl orthoformate to the 1,3-diarylacetone compound or the 1-aryl-3-alkyl ketone 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.

[0020] Preferably, the structure of the 1,3-diarylacetone compound is as follows:

[0021] R1 and R2 are independently selected from hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, and C6-C12 aryl; R1 and R2 exist independently or form a cyclic structure with the benzene ring in which they are located.

[0022] Preferably, the cyclic structure is a benzene ring.

[0023] Preferably, the 1,3-diarylacetone compound is selected from...

[0024] Any one of them.

[0025] Preferably, the structure of the 1-aryl-3-alkyl ketone compound is as follows:

[0026] R3 and R4 are independently selected from hydrogen, C1-C5 alkyl, or C1-C5 alkoxy.

[0027] Preferably, the 1-aryl-3-alkyl ketone compound is selected from... Any one of them.

[0028] Preferably, the reaction is carried out in the presence of an acidic reagent.

[0029] Preferably, the acidic reagent is at least one of sulfonic acid compounds.

[0030] 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.

[0031] 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.

[0032] Preferably, the reaction is carried out in an organic solvent.

[0033] Preferably, the organic solvent is selected from at least one of chloroalkanes, aromatic hydrocarbons, nitrile compounds, or trimethyl orthoformate or trifluoromethanesulfonic acid.

[0034] 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.

[0035] Preferably, the reaction is carried out in an air atmosphere.

[0036] 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 0.5h-12h, for example 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 11h or 12h.

[0037] As a preferred embodiment of the present invention, the preparation method of the 3-aryl / alkyl-β-naphthyl methyl ether compound includes the following steps:

[0038] Trimethyl orthoformate reacts with 1,3-diarylacetone or 1-aryl-3-alkyl ketone in an organic solvent at 15-100°C for 0.5-12 h in the presence of an acidic sulfonic acid compound to yield a 3-aryl-β-naphthyl methyl ether compound or a 3-alkyl-β-naphthyl methyl 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, chloroform, acetonitrile, toluene, trimethyl orthoformate, or trifluoromethanesulfonic acid; the molar ratio of the trimethyl 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.

[0039] Compared with the prior art, the present invention has the following beneficial effects:

[0040] The reaction conditions of this invention are mild, and trimethyl orthoformate is inexpensive and readily available. It can simultaneously serve as a methylating agent and a carbon source for extending one carbon chain. It has a broad substrate range and good functional group tolerance. The reaction is highly efficient and selective, with simple post-processing and easy operation, making it suitable for large-scale industrial production. It avoids the need for the pre-preparation of complex substrates in traditional reactions and eliminates the need for metal catalysis required in traditional reactions. It can prepare naphthol precursor compounds with high chemoselectivity, providing a simpler and more efficient route for the synthesis of bidentate ligands through olefin hydroformylation / hydroformyl esterification reactions. Detailed Implementation

[0041] 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.

[0042] The data and purity of the new compounds presented in the following examples were determined by nuclear magnetic resonance.

[0043] Example 1

[0044] Preparation of 3-phenyl-β-naphthyl methyl ether:

[0045]

[0046] In a 25 mL reaction tube, 1,3-diphenylacetone (105 mg, 0.5 mmol), trimethyl orthoformate (165 μL, 159 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.

[0047] 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 85% yield.

[0048] The 1H NMR spectrum data of the obtained product are as follows:

[0049] 1 HNMR (400MHz, CDCl3): δ7.93-7.90 (m, 3H), 7.77 (s, 2H), 7.59-7.50 (m, 5H), 7.35-7.34 (m, 1H), 4.02 (s, 3H).

[0050] The carbon NMR spectrum data of the obtained product are as follows:

[0051] 13 CNMR (100MHz, CDCl3): δ155.2, 138.3, 133.9, 132.3, 129.9, 129.7(2C), 128.8, 127.9(2C), 127.6, 127.2, 126.3(2C), 123.8, 105.6, 55.4.

[0052] It is evident that the product obtained is 3-phenyl-β-naphthyl methyl ether.

[0053] Example 2

[0054] Preparation of 6-methyl-3-(4-tolyl)-β-naphthyl methyl ether:

[0055]

[0056] In a 25 mL reaction tube, 1,3-bis(4-tolyl)acetone (119 mg, 0.5 mmol), trimethyl orthoformate (165 μL, 159 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.

[0057] 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 82% yield.

[0058] The 1H NMR spectrum data of the obtained product are as follows:

[0059] 1 HNMR (400MHz, CDCl3): δ7.66-7.63 (m, 2H), 7.53 (s, 1H), 7.50-7.47 (m, 2H), 7.27-7.22 (m, 3H), 7.15 (s, 1H), 3.87 (s, 3H), 2.47 (s, 3H), 2.40 (s, 3H).

[0060] The carbon NMR spectrum data of the obtained product are as follows:

[0061] 13CNMR (100MHz, CDCl3): δ154.7, 136.8, 135.6, 133.3, 132.3, 132.0, 129.6 (2 C), 129.1, 129.0, 128.7 (2C), 128.4, 126.6, 126.2, 105.5, 55.4, 21.5, 21.2.

[0062] The high-resolution mass spectrometry data of the obtained product are as follows:

[0063] HRMS (APCI): C 19 H 19 O + [M+H] + Calculated value: 263.1431; Test value: 263.1431.

[0064] It is evident that the product obtained is 6-methyl-3-(4-tolyl)-β-naphthyl methyl ether.

[0065] Example 3

[0066] Preparation of 6-methoxy-3-(4-methoxyphenyl)-β-naphthyl methyl ether:

[0067]

[0068] In a 25 mL reaction tube, 1,3-bis(4-methoxyphenyl)acetone (135 mg, 0.5 mmol), trimethyl orthoformate (165 μL, 159 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.

[0069] 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 69% yield.

[0070] The 1H NMR spectrum data of the obtained product are as follows:

[0071] 1 HNMR (400MHz, CDCl3): δ7.65-7.62 (m, 2H), 7.56-7.52 (m, 2H), 7.14-7.09 (m, 3H), 6.98-6.95 (m, 2H), 3.87 (s, 3H), 3.86 (s, 3H), 3.83 (s, 3H).

[0072] The carbon NMR spectrum data of the obtained product are as follows:

[0073] 13 CNMR (100MHz, CDCl3): δ158.9, 156.3, 153.8, 132.3, 130.8 (3C), 129.6, 128.9, 128.4, 127.8, 118.6, 113.5 (2C), 105.9, 105.8, 55.5, 55.3, 55.2.

[0074] The high-resolution mass spectrometry data of the obtained product are as follows:

[0075] HRMS (APCI): C 19 H 19 O3 + [M+H] + Calculated value: 295.1329; Test value: 295.1331.

[0076] It is evident that the product obtained is 6-methoxy-3-(4-methoxyphenyl)-β-naphthyl methyl ether.

[0077] Example 4

[0078] Preparation of 6-fluoro-3-(4-fluorophenyl)-β-naphthyl methyl ether:

[0079]

[0080] In a 25 mL reaction tube, 1,3-bis(4-fluorophenyl)acetone (123 mg, 0.5 mmol), trimethyl orthoformate (165 μL, 159 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 6 hours.

[0081] 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 57% yield.

[0082] The 1H NMR spectrum data of the obtained product are as follows:

[0083] 1HNMR (400MHz, CDCl3): δ7.72-7.68 (m, 1H), 7.61 (s, 1H), 7.56-7.51 (m, 2H), 7.38-7.34 (s, 1H), 7.24-7.18 (m, 2H), 7.14-7.08 (m, 2H), 3.88 (s, 3H).

[0084] The carbon NMR spectrum data of the obtained product are as follows:

[0085] 13 CNMR (100MHz, CDCl3): δ162.3 (d, J=245Hz), 159.6 (d, J=242Hz), 154.4, 133.9 (d, J=3.8Hz), 132.4, 131.2 (d, J=7.6Hz, 2C), 130.8, 129.1 (d, J=9.5Hz), 129.0 (d, J=4.7Hz), 128.4 (d, J=8.6Hz), 116.5 (d, J=24.8Hz), 114.9 (d, J=20.9Hz, 2C), 110.8, (d, J=20.9Hz), 105.9, 55.5.

[0086] The high-resolution mass spectrometry data of the obtained product are as follows:

[0087] HRMS (APCI): C 17 H 13 F2O + [M+H] + Calculated value: 271.0929; Test value: 271.0924.

[0088] It is evident that the product obtained is 6-fluoro-3-(4-fluorophenyl)-β-naphthyl methyl ether.

[0089] Example 5

[0090] Preparation of 6-chloro-3-(4-chlorophenyl)-β-naphthyl methyl ether:

[0091]

[0092] In a 25 mL reaction tube, 1,3-bis(4-chlorophenyl)acetone (139 mg, 0.5 mmol), trimethyl orthoformate (165 μL, 159 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.

[0093] 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.

[0094] The 1H NMR spectrum data of the obtained product are as follows:

[0095] 1 HNMR (400MHz, CDCl3): δ7.73-7.72 (m, 1H), 7.68-7.65 (m, 1H), 7.59 (s, 1H), 7.51-7.48 (m, 2H), 7.41-7.35 (m, 3H), 7.16 (s, 1H), 3.89 (s, 3H).

[0096] The carbon NMR spectrum data of the obtained product are as follows:

[0097] 13 CNMR (100MHz, CDCl3): δ155.2, 136.2, 133.5, 132.3, 132.2, 130.9(2C), 129.5, 129.3, 128.9, 128.2(2C), 127.9, 127.3, 126.3, 106.7, 55.6.

[0098] The high-resolution mass spectrometry data of the obtained product are as follows:

[0099] HRMS (APCI): C 17 H 13 Cl2O + [M+H] + Calculated value: 303.0338; Test value: 303.0349.

[0100] It is evident that the product obtained is 6-chloro-3-(4-chlorophenyl)-β-naphthyl methyl ether.

[0101] Example 6

[0102] Preparation of 6-bromo-3-(4-bromophenyl)-β-naphthyl methyl ether:

[0103]

[0104] In a 25 mL reaction tube, 1,3-bis(4-bromophenyl)acetone (183 mg, 0.5 mmol), trimethyl orthoformate (165 μL, 159 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.

[0105] 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 59% yield.

[0106] The 1H NMR spectrum data of the obtained product are as follows:

[0107] 1 HNMR (400MHz, CDCl3): δ7.73-7.72 (m, 1H), 7.68-7.65 (m, 1H), 7.59 (s, 1H), 7.51-7.48 (m, 2H), 7.41-7.35 (m, 3H), 7.16 (s, 1H), 3.89 (s, 3H).

[0108] The carbon NMR spectrum data of the obtained product are as follows:

[0109] 13 CNMR (100MHz, CDCl3): δ155.2, 136.2, 133.5, 132.3, 132.2, 130.9(2C), 129.5, 129.3, 128.9, 128.2(2C), 127.9, 127.3, 126.3, 106.7, 55.6.

[0110] The high-resolution mass spectrometry data of the obtained product are as follows:

[0111] HRMS (APCI): C 17 H 12 Br2O + [M+H] + Calculated value: 389.9255; Test value: 389.9252.

[0112] It is evident that the product obtained is 6-bromo-3-(4-bromophenyl)-β-naphthyl methyl ether.

[0113] Example 7

[0114] Preparation of 3-(naphthyl)-2-methoxyphenanthrene:

[0115]

[0116] In a 25 mL reaction tube, 1,3-bis(naphthyl)acetone (155 mg, 0.5 mmol), trimethyl orthoformate (165 μL, 159 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.

[0117] 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.

[0118] The 1H NMR spectrum data of the obtained product are as follows:

[0119] 1 HNMR (400MHz, CDCl3): δ8.66 (s, 1H), 8.60-8.57 (m, 1H), 8.09 (s, 1H), 7.91-7.77 (m, 5H ), 7.72-7.65(m, 2H), 7.60-7.55(m, 1H), 7.52-7.45(m, 3H), 7.30(s, 1H), 3.91(s, 3H).

[0120] The carbon NMR spectrum data of the obtained product are as follows:

[0121] 13 CNMR (100MHz, CDCl3): δ155.8, 136.4, 133.5, 132.9, 132.6, 131.4, 131.2, 130.4, 128.6, 128.4, 128. 3, 128.2, 127.6, 127.5, 127.2, 126.7, 126.1, 126.0, 125.9, 125.6, 125.5, 124.5, 122.2, 107.9, 55.6.

[0122] The high-resolution mass spectrometry data of the obtained product are as follows:

[0123] HRMS (APCI): C 25 H 19 O + [M+H] + Calculated value: 335.1431; Test value: 335.1431.

[0124] It can be seen that the product obtained is 3-(naphthyl)-2-methoxyphenanthrene.

[0125] Example 8

[0126] Preparation of 3-methyl-β-naphthyl methyl ether:

[0127]

[0128] 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.

[0129] 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.

[0130] The 1H NMR spectrum data of the obtained product are as follows:

[0131] 1 HNMR (400MHz, CDCl3): δ7.70-7.66 (m, 2H), 7.55 (s, 1H), 7.38-7.34 (m, 1H), 7.31-7.26 (m, 1H), 7.05 (s, 1H), 3.91 (s, 3H), 2.36 (s, 3H).

[0132] The carbon NMR spectrum data of the obtained product are as follows:

[0133] 13 CNMR (100MHz, CDCl3): δ156.8, 133.4, 128.8, 128.7, 128.4, 126.8, 126.3, 125.3, 123.4, 104.4, 55.2, 16.9.

[0134] It is evident that the product obtained is 3-methyl-β-naphthyl methyl ether.

[0135] Example 9

[0136] Preparation of 3-propyl-β-naphthyl methyl ether:

[0137]

[0138] 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.

[0139] 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 46% yield.

[0140] The 1H NMR spectrum data of the obtained product are as follows:

[0141] 1 HNMR (400MHz, CDCl3): δ7.72-7.69(m, 2H), 7.55(s, 1H), 7.39-7.34(m, 1H), 7.32-7.27(m, 1H ), 7.08 (s, 1H), 3.92 (s, 3H), 2.73 (t, J = 7.2Hz, 2H), 1.73-1.66 (m, 2H), 0.99 (t, J = 7.2Hz, 3H).

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

[0143] 13 CNMR (100MHz, CDCl3): δ156.6, 133.3, 132.8, 128.8, 128.1, 127.0, 126.2, 125.4, 123.4, 106.7, 55.1, 32.8, 22.8, 14.1.

[0144] The high-resolution mass spectrometry data of the obtained product are as follows:

[0145] HRMS (APCI): C 14 H 17 O + [M+H] + Calculated value: 201.1274; Test value: 201.1277.

[0146] Example 10

[0147] Preparation of 7-methoxy-β-naphthyl methyl ether:

[0148]

[0149] In a 25 mL reaction tube, 1-(3-methoxyphenyl)acetone (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.

[0150] 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.

[0151] The 1H NMR spectrum data of the obtained product are as follows:

[0152] 1 HNMR (400MHz, CDCl3): δ7.64 (s, 1H), 7.62 (s, 1H), 7.04-7.03 (m, 2H), 7.00-6.99 (m, 1H), 6.98-6.96 (m, 1H), 3.87 (s, 6H).

[0153] The carbon NMR spectrum data of the obtained product are as follows:

[0154] 13 CNMR (100MHz, CDCl3): δ158.2(2C), 135.9, 129.0(2C), 124.3, 116.0(2C), 105.3(2C), 55.2(2C).

[0155] It is evident that the product obtained is 7-methoxy-β-naphthyl methyl ether.

[0156] In Examples 1 to 10, dichloromethane was used as the reaction solvent. Experiments showed that, in addition to dichloromethane, other suitable reaction solvents include chloroalkanes such as 1,2-dichloroethane and chloroform, aromatic hydrocarbons such as toluene, nitrile solvents such as acetonitrile, and organic solvents such as trimethyl orthoformate and trifluoromethanesulfonic acid.

[0157] (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.

[0158] (2) Aromatic hydrocarbons include, but are not limited to, benzene, toluene, chlorobenzene, o-dichlorobenzene and xylene.

[0159] (3) Acetonitrile, benzonitrile, trimethyl orthoformate and trifluoromethanesulfonic acid can all be used as reaction solvents in this invention.

[0160] Examples 11 to 20

[0161] Except for the different reaction solvents, Examples 11 to 20 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:

[0162] Table 1

[0163]

[0164]

[0165] From the table above (where NR indicates no reaction), we can see that:

[0166] (1) When using a nonprotic solvent, the reaction yield is high, especially when using halogenated hydrocarbons as the reaction solvent. Among them, the reaction is best in dichloromethane (Example 1), with a separation yield of 85%.

[0167] (2) When other protic solvents are used, the reaction is poor or even non-reacting.

[0168] Taking all factors into consideration, dichloromethane is the best reaction solvent.

[0169] In Examples 1 to 10, trifluoromethanesulfonic acid was used as the acid. Tests showed that hydrochloric acid, trifluoroacetic acid, methanesulfonic acid, fluorosulfonic acid, and Lewis acid BF3 were also suitable. . Neither Et2O nor FeCl3 can effectively replace trifluoromethanesulfonic acid in this invention.

[0170] Examples 21 to 26

[0171] Except for the different acids, Examples 21 to 26 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:

[0172] Table 2

[0173]

[0174]

[0175] From the table above (where NR indicates no reaction), we can see that:

[0176] (1) Other organic acids, inorganic acids, and Lewis acids cannot effectively replace trifluoromethanesulfonic acid in catalytic reactions; (2) Trifluoromethanesulfonic acid has a unique ability to catalyze substrate-selective reactions. Considering all factors, trifluoromethanesulfonic acid is the best acid.

[0177] In Examples 1 to 26:

[0178] 1. The optimal molar ratio of trimethyl orthoformate to 1,3-diarylacetone or 1-aryl-3-alkylacetone is 3:1, and other ratios are not limited to this.

[0179] 2. The optimal molar ratio of trifluoromethanesulfonic acid to 1,3-diarylacetone or 1-aryl-3-alkylacetone is 4:1, and other ratios are not limited to this.

[0180] 3. The reaction temperature can be adjusted appropriately within the range of 15-100℃, and the corresponding reaction time can be adjusted appropriately within the range of 0.5-12h.

[0181] 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 a 3-aryl / alkyl-β-naphthyl methyl ether compound, characterized in that, The preparation method includes the following steps: Trimethyl orthoformate reacts with 1,3-diarylacetone or 1-aryl-3-alkyl ketone compounds to give 3-aryl-β-naphthyl methyl ethers or 3-alkyl-β-naphthyl methyl ethers; 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, trimethyl orthoformate, or trifluoromethanesulfonic acid. The molar ratio of the trimethyl orthoformate to the 1,3-diarylacetone compound or the 1-aryl-3-alkyl ketone compound is 3-9:1; 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.

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; R1 and R2 exist independently or form a cyclic structure with the benzene ring in which they are located.

3. The preparation method according to claim 2, characterized in that, The cyclic structure is a benzene ring.

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

5. 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.

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

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

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

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

10. The preparation method according to claim 1, characterized in that, The reaction temperature is 15-100℃, and the reaction time is 0.5h-12h.

11. The preparation method according to claim 1, characterized in that, The preparation method of the 3-aryl / alkyl-β-naphthyl methyl ether compound includes the following steps: Trimethyl orthoformate reacts with 1,3-diarylacetone or 1-aryl-3-alkyl ketone in an organic solvent at 15-100°C for 0.5-12 h in the presence of an acidic sulfonic acid compound to yield a 3-aryl-β-naphthyl methyl ether compound or a 3-alkyl-β-naphthyl methyl 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 trimethyl 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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