Method for preparing 6-methoxy-1-tetralone through photocatalytic oxidation

Abstract

The invention belongs to the technical field of organic synthesis, and discloses a method for preparing 6-methoxy-1-tetralone through photocatalytic oxidation, which comprises the following steps: placing a 6-methoxy-1, 2, 3, 4-tetrahydronaphthalene solution under illumination and aerobic conditions, and catalyzing the 6-methoxy-1, 2, 3, 4-tetrahydronaphthalene solution through a photosensitive manganese catalyst as shown in a formula I and / or a formula II to prepare the 6-methoxy-1-tetralone, and X is one or two of-OTf or-OAc. According to the method, under the catalysis of the photosensitive manganese catalyst I or II, benzyl methylene at the naphthalene ring C1 position can be selectively oxidized, and the method has the advantages of being good in selectivity, high in conversion rate, mild in reaction condition and the like.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology and relates to a method for preparing 6-methoxy-1-naphthoone by photocatalytic oxidation. Specifically, it relates to a method for preparing 6-methoxy-1-naphthoone by photocatalysis, using oxygen as an oxidant and with high regioselectivity of 6-methoxy-1,2,3,4-tetrahydronaphthalene. Background Technology

[0002] Naphthone compounds are a class of high-value organic synthetic intermediates with cyclic ketone structures. Their unique reactivity makes them widely used in pharmaceuticals, pesticides, and functional materials. Among them, 6-methoxy-3,4-dihydro-2H-naphth-1-one (i.e., 6-methoxy-1-naphthone) is a key intermediate in the synthesis of steroidal oral contraceptives for women (such as 18-methylnorethindrone and trienolone).

[0003] Currently, the main methods for synthesizing 6-methoxy-1-naphthoquinone include the following three categories: (1) Stoichiometric oxidation method: using 6-methoxy-1,2,3,4-tetrahydronaphthalene as raw material, oxidizing with stoichiometric oxidants such as CrO3 and MnO2. Since both C1 and C4 positions in the molecule are benzylic methylene groups with similar reactivity, this method has poor regioselectivity and low yield of the target product (see Research on Synthesis of 6-methoxy-1-naphthoquinone, Zhejiang Chemical Industry, 2013, 44, 17-19). (2) Friedel-Crafts acylation or cyclization: such as cyclization with ethyl 3-methoxyphenylbutyrate (see Mechanical metal activation for Ni-catalyzed, Mn-mediated cross-electrophile coupling between aryl and alkyl bromides, New J. Chem., 2021, 45, 11269-11274), or the construction of a naphthone skeleton by Friedel-Crafts acylation of anisole and 4-chlorobutyryl chloride (see Chinese Patent CN111333494, invention name: Synthesis Method of 6-methoxy-1-naphthone). Both methods require the use of stoichiometric Lewis acid catalysts (such as AlCl3), generating a large amount of aluminum-containing waste, and 4-chlorobutyryl chloride is highly toxic and corrosive, posing environmental pollution and safety issues. (3) Reduction method: Chinese patent CN117088765, entitled "Method for preparing 6-methoxy-1-naphthoone using a microchannel reactor," discloses a method for preparing 6-hydroxynaphthoone from 1,6-dihydroxynaphthalene as a starting material via catalytic reduction, followed by methylation synthesis to obtain 6-methoxy-1-naphthoone. This method requires sophisticated reaction equipment, using high-pressure hydrogen and palladium catalysts, and the reaction requires a pressure of 1-3 MPa. The operation is cumbersome, and the reaction conditions are harsh.

[0004] In recent years, although new methods such as photocatalysis and transition metal catalysis for C–H oxidation have made progress, existing catalytic systems still struggle to achieve efficient and selective oxidation at the C1 position when dealing with substrates such as 6-methoxy-1,2,3,4-tetrahydronaphthalene, which have multiple similar reaction sites, resulting in limited product yield and purity.

[0005] In summary, existing synthetic methods generally suffer from insufficient regioselectivity, use of toxic or hazardous reagents, harsh reaction conditions, and significant environmental pollution. Therefore, there is an urgent need to develop a novel catalytic strategy that utilizes mild conditions, employs a green oxidant (such as oxygen), and possesses high regioselectivity for oxidizing the C1 methylene group, in order to achieve the safe, efficient, and environmentally friendly synthesis of 6-methoxy-1-naphthone. Summary of the Invention

[0006] To address the aforementioned problems in the existing technology, this invention provides a method for preparing 6-methoxy-1-naphthoone by photocatalytic oxidation, using 6-methoxy-1,2,3,4-tetrahydronaphthalene as raw material, and obtaining 6-methoxy-1-naphthoone with high selectivity through aerobic catalysis by a photosensitive manganese catalyst.

[0007] This invention discloses a method for preparing 6-methoxy-1-naphthoone by photocatalytic oxidation. The reaction formula is shown below. A 6-methoxy-1,2,3,4-tetrahydronaphthalene solution is placed under light and aerobic conditions and catalyzed by a photosensitive manganese catalyst as shown in Formula I and / or Formula II to obtain 6-methoxy-1-naphthoone, wherein X is one or both of -OTf and -OAc.

[0008]

[0009]

[0010] In one embodiment of the present invention, the amount of the photosensitive manganese catalyst is preferably 0.5 to 5 mol of 6-methoxy-1,2,3,4-tetrahydronaphthalene.

[0011] In one embodiment of the present invention, the preferred illumination conditions are: illumination power of 1W to 45W and wavelength of 360 to 460nm.

[0012] In one embodiment of the present invention, the reaction solvent used in the reaction is preferably one or more of ethyl acetate, acetonitrile, toluene or dichloromethane. During the reaction, the raw material 6-methoxy-1,2,3,4-tetrahydronaphthalene is first dissolved in the reaction solvent to obtain a 6-methoxy-1,2,3,4-tetrahydronaphthalene solution, and then a selective oxidation reaction is carried out.

[0013] In one embodiment of the present invention, the reaction solvent used in the reaction is preferably a mixed solvent composed of ethyl acetate and acetonitrile, ethyl acetate and toluene, or ethyl acetate and dichloromethane.

[0014] In one embodiment of the present invention, the preferred reaction temperature is 0–45°C and the reaction time is 2–24 hours.

[0015] In one embodiment of the present invention, the reaction temperature is preferably room temperature.

[0016] In one embodiment of the invention, a post-processing step is also included, comprising removing the solvent by vacuum distillation and separating by column chromatography (eluent is ethyl acetate: n-hexane = 1:20, v / v) to obtain 6-methoxy-1-naphthoone.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0018] This invention discloses a method for the photocatalytic oxidation of 6-methoxy-1-naphthoquinone. Using 6-methoxy-1,2,3,4-tetrahydronaphthalene as a raw material, the method involves catalysis with a photosensitive manganese catalyst as shown in Formula I and / or Formula II under light and aerobic conditions. This method, catalyzed by photosensitive manganese catalyst I or II, selectively oxidizes the benzylic methylene group at the C1 position of the naphthalene ring, avoiding the problems of poor selectivity, low yield, and low purity associated with traditional oxidants. Furthermore, it utilizes readily available and inexpensive 6-methoxy-1,2,3,4-tetrahydronaphthalene as a raw material, achieving the desired result in a one-step oxidation reaction. The reaction steps are short, resulting in high atom economy, and the reaction conditions are mild, allowing for the preparation of 6-methoxy-1-naphthoquinone at room temperature under aerobic and light-induced conditions. Therefore, this method for preparing 6-methoxy-1-naphthoquinone has advantages such as good selectivity, high conversion rate, and mild reaction conditions. Attached Figure Description

[0019] Figure 1 The 6-methoxy-1-naphthone of Example 1 of this invention 1 H NMR spectrum;

[0020] Figure 2 The 6-methoxy-1-naphthone of Example 1 of this invention 13 C-NMR spectrum. Detailed Implementation

[0021] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

[0022] Numerous specific details are set forth in the following description to provide a full understanding of the invention. However, the invention can be practiced in many other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0023] Unless otherwise specified, all raw materials used in this invention are commercially available. The photosensitive manganese catalyst, as shown in Formula I and / or Formula II, can be prepared according to the method described in Chinese Patent CN120554420, entitled "A Photosensitive Manganese Catalyst and Its Preparation Method and Application". The photosensitive manganese catalyst I or II of this invention is shown below.

[0024]

[0025]

[0026] When using the above-mentioned photosensitive manganese catalyst I or II for the oxidation of 6-methoxy-1,2,3,4-tetrahydronaphthalene, theoretically one or more of catalysts IA, IIA, IB, and IIB can be added to the reaction system, such as adding two of catalysts IA and IIA simultaneously, or adding three of catalysts IIA, IB, and IIB simultaneously, or adding four of catalysts IA, IIA, IB, and IIB simultaneously, etc. However, in order to keep the reaction system simple and the product easy to separate, in the embodiments of the present invention, it is preferable to use only one catalyst for the photocatalytic synthesis of 6-methoxy-1-naphthoquinone.

[0027] Example 1: Synthesis of 6-methoxy-1-naphthone

[0028]

[0029] Compound 1a (81.1 mg, 0.5 mmol) and photosensitive manganese catalyst IIA (4.8 mg, 5.0 μmol) were dissolved in 2 mL of an organic mixed solvent (ethyl acetate: acetonitrile = 4:1). The reaction was carried out under an oxygen atmosphere and at room temperature under 25 W blue light (λmax = 360-370 nm) for 5 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 72 mg of 6-methoxy-1-naphthoquinone 2a, in 82% yield.

[0030] Characterization of 6-methoxy-1-naphthone 2a by 1H NMR, 1C NMR, and mass spectrometry: (e.g.) Figure 1 As shown, 1HNMR(600MHz, CDCl3) δ8.03(d,J=9.0Hz,1H),6.84(dd,J=8.4,2.4Hz,1H),6.72(d,J =2.4Hz,1H),3.87(s,3H),2.94(t,J=6.0Hz,2H),2.62(t,J=6.0,2H),2.13(m,2H). Such as Figure 2 As shown, 13 C NMR (100MHz, CDCl3) δ197.23,163.55,146.97,129.65,126.34,113.05,112.62,55.43,38.91,30.18,23.39.HRMS-ESI(m / z):calcd for C11H13O2[M+H]+:177.0911,found 177.0915.

[0031] Example 2: Synthesis of 6-methoxy-1-naphthone

[0032]

[0033] Compound 1a (81.1 mg, 0.5 mmol) and the photosensitive manganese catalyst IA (4.3 mg, 5.0 μmol) were dissolved in 2 mL of an organic mixed solvent (ethyl acetate: acetonitrile = 4:1). The reaction was carried out under an oxygen atmosphere and at room temperature under 25 W blue light (λmax = 360-370 nm) for 6 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 61 mg of 6-methoxy-1-naphthoquinone 2a, in 69% yield.

[0034] Example 3: Synthesis of 6-methoxy-1-naphthone

[0035]

[0036] Compound 1a (81.1 mg, 0.5 mmol) and the photosensitive manganese catalyst IB (3.4 mg, 5.0 μmol) were dissolved in 2 mL of an organic mixed solvent (ethyl acetate: acetonitrile = 4:1). The reaction was carried out under an oxygen atmosphere and at room temperature under 25 W blue light (λmax = 360-370 nm) for 7 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 59 mg of 6-methoxy-1-naphthoanone 2a, in 67% yield.

[0037] Example 4: Synthesis of 6-methoxy-1-naphthone

[0038]

[0039] Compound 1a (81.1 mg, 0.5 mmol) and photosensitive manganese catalyst IIB (3.9 mg, 5.0 μmol) were dissolved in 2 mL of an organic mixed solvent (ethyl acetate: acetonitrile = 4:1). The reaction was carried out under an oxygen atmosphere and at room temperature under 25 W blue light (λmax = 360-370 nm) for 5 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 71 mg of 6-methoxy-1-naphthoquinone 2a, in 80% yield.

[0040] Example 5: Synthesis of 6-methoxy-1-naphthone

[0041]

[0042] Compound 1a (81.1 mg, 0.5 mmol) and photosensitive manganese catalyst IIA (2.4 mg, 2.5 μmol) were dissolved in 2 mL of an organic mixed solvent (ethyl acetate: acetonitrile = 4:1). The reaction was carried out under an oxygen atmosphere and at room temperature under 25 W blue light (λmax = 360-370 nm) for 5 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 69 mg of 6-methoxy-1-naphthoanone 2a, in 78% yield.

[0043] Example 6: Synthesis of 6-methoxy-1-naphthone

[0044]

[0045] Compound 1a (81.1 mg, 0.5 mmol) and photosensitive manganese catalyst IIA (24.0 mg, 25.0 μmol) were dissolved in 2 mL of an organic mixed solvent (ethyl acetate: acetonitrile = 4:1). The reaction was carried out under an oxygen atmosphere and at room temperature under 25 W blue light (λmax = 360-370 nm) for 5 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 71 mg of 6-methoxy-1-naphthoquinone 2a, in 81% yield.

[0046] Example 7: Synthesis of 6-methoxy-1-naphthone

[0047]

[0048] Compound 1a (81.1 mg, 0.5 mmol) and photosensitive manganese catalyst IIA (4.8 mg, 5.0 μmol) were dissolved in 2 mL of an organic mixed solvent (ethyl acetate: toluene = 4:1). The reaction was carried out under an oxygen atmosphere and at room temperature under 25 W blue light (λmax = 360-370 nm) for 5 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 62 mg of 6-methoxy-1-naphthoquinone 2a, in 70% yield.

[0049] Example 8: Synthesis of 6-methoxy-1-naphthoone

[0050]

[0051] Compound 1a (81.1 mg, 0.5 mmol) and photosensitive manganese catalyst IIA (4.8 mg, 5.0 μmol) were dissolved in 2 mL of an organic mixed solvent (ethyl acetate: dichloromethane = 4:1). The reaction was carried out under an oxygen atmosphere and at room temperature under 25 W blue light (λmax = 360-370 nm) for 5 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 64 mg of 6-methoxy-1-naphthoanone 2a, in 73% yield.

[0052] Example 9: Synthesis of 6-methoxy-1-naphthone

[0053]

[0054] Compound 1a (16.2 mg, 0.1 mmol) and photosensitive manganese catalyst IIA (1.0 mg, 1.0 μmol) were dissolved in 2 mL of an organic mixed solvent (ethyl acetate: acetonitrile = 4:1). The reaction was carried out under an oxygen atmosphere and at room temperature under 1 W blue light (λmax = 360-370 nm) for 24 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 12 mg of 6-methoxy-1-naphthoquinone 2a, in 70% yield.

[0055] Example 10: Synthesis of 6-methoxy-1-naphthone

[0056]

[0057] Compound 1a (81.1 mg, 0.5 mmol) and photosensitive manganese catalyst IIA (4.8 mg, 5.0 μmol) were dissolved in 2 mL of an organic mixed solvent (ethyl acetate: acetonitrile = 4:1). The reaction was carried out under an oxygen atmosphere and at room temperature under 35 W blue light (λmax = 360-370 nm) for 8 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 69 mg of 6-methoxy-1-naphthoquinone 2a, in 78% yield.

[0058] Example 11: Synthesis of 6-methoxy-1-naphthone

[0059]

[0060] Compound 1a (1.3 g, 8.0 mmol) and photosensitive manganese catalyst IIA (76.9 mg, 80.0 μmol) were dissolved in 10 mL of an organic mixed solvent (ethyl acetate: acetonitrile = 4:1). The reaction was carried out under an oxygen atmosphere and at room temperature under 45 W blue light (λmax = 360-370 nm) for 20 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 902.2 mg of 6-methoxy-1-naphthoanone 2a, in 64% yield.

[0061] Example 12: Synthesis of 6-methoxy-1-naphthone

[0062]

[0063] Compound 1a (81.1 mg, 0.5 mmol) and photosensitive manganese catalyst IIA (4.8 mg, 5.0 μmol) were dissolved in 2 mL of an organic mixed solvent (ethyl acetate: acetonitrile = 4:1). The reaction was carried out under an oxygen atmosphere and at room temperature under 25 W blue light (λmax = 450-460 nm) for 8 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 63 mg of 6-methoxy-1-naphthoanone 2a, in 72% yield.

[0064] Example 13: Synthesis of 6-methoxy-1-naphthone

[0065]

[0066] Compound 1a (81.1 mg, 0.5 mmol) and photosensitive manganese catalyst IIA (4.8 mg, 5.0 μmol) were dissolved in 2 mL of an organic mixed solvent (ethyl acetate: acetonitrile = 4:1). The reaction was carried out under an oxygen atmosphere and at 0 °C under 25 W blue light (λmax = 360-370 nm) for 4 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 62 mg of 6-methoxy-1-naphthoanone 2a, in 70% yield.

[0067] Example 14: Synthesis of 6-methoxy-1-naphthone

[0068]

[0069] Compound 1a (81.1 mg, 0.5 mmol) and photosensitive manganese catalyst IIA (4.8 mg, 5.0 μmol) were dissolved in 2 mL of an organic mixed solvent (ethyl acetate: acetonitrile = 4:1). The reaction was carried out under an oxygen atmosphere and at 35 °C under 25 W blue light (λmax = 360-370 nm) for 2 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 71 mg of 6-methoxy-1-naphthoquinone 2a, in 81% yield.

[0070] Example 15: Synthesis of 6-methoxy-1-naphthone

[0071]

[0072] Compound 1a (81.1 mg, 0.5 mmol) and photosensitive manganese catalyst IIA (4.8 mg, 5.0 μmol) were dissolved in 2 mL of an organic mixed solvent (ethyl acetate: acetonitrile = 4:1). The reaction was carried out under an oxygen atmosphere and at 45 °C under 25 W blue light (λmax = 360-370 nm) for 2 hours. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give 64 mg of 6-methoxy-1-naphthoanone 2a, in 73% yield.

[0073] The preferred embodiments of the present invention disclosed above are merely illustrative of the invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the invention to the specific implementations described. Clearly, many modifications and variations can be made based on the content of this specification. This specification selects and specifically describes these embodiments to better explain the principles and practical applications of the invention, thereby enabling those skilled in the art to better understand and utilize the invention. The invention is limited only by the claims and their full scope and equivalents.

Claims

1. A method for preparing 6-methoxy-1-naphthone by photocatalytic oxidation, characterized in that, The reaction is shown below. 6-Methoxy-1,2,3,4-Tetrahydronaphthalene solution is placed under light and aerobic conditions and catalyzed by a photosensitive manganese catalyst as shown in Formula I and / or Formula II to prepare 6-methoxy-1-naphthoone, wherein X is one or both of -OTf and -OAc.

2. The method for preparing 6-methoxy-1-naphthone by photocatalytic oxidation according to claim 1, characterized in that, The amount of the photosensitive manganese catalyst used is 0.5 to 5 mol of 6-methoxy-1,2,3,4-tetrahydronaphthalene.

3. The method for preparing 6-methoxy-1-naphthone by photocatalytic oxidation according to claim 1, characterized in that, The illumination conditions are as follows: illumination power of 1W to 45W and wavelength of 360 to 460nm.

4. The method for preparing 6-methoxy-1-naphthone by photocatalytic oxidation according to claim 1, characterized in that, The reaction solvent used is one or more of ethyl acetate, acetonitrile, toluene, or dichloromethane.

5. The method for preparing 6-methoxy-1-naphthone by photocatalytic oxidation according to claim 4, characterized in that, The reaction solvent used is a mixture of ethyl acetate and acetonitrile, ethyl acetate and toluene, or ethyl acetate and dichloromethane.

6. The method for preparing 6-methoxy-1-naphthone by photocatalytic oxidation according to claim 1, characterized in that, The reaction temperature is 0–45℃; the reaction time is 2–24 hours.

7. The method for preparing 6-methoxy-1-naphthone by photocatalytic oxidation according to claim 6, characterized in that, The reaction temperature was room temperature.

8. The method for preparing 6-methoxy-1-naphthone by photocatalytic oxidation according to claim 1, characterized in that, It also includes post-processing steps, including removing the solvent by vacuum distillation and separating by column chromatography (eluting ethyl acetate: n-hexane = 1:20, v / v) to obtain 6-methoxy-1-naphthoone.

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