A method for visible light photocatalytic cleavage of β-O-4 type lignin model compounds

Abstract

This invention discloses a method for visible light-catalyzed cleavage of β-O-4 type lignin model compounds, comprising: mixing a photosensitizer, a β-O-4 type lignin model compound of formula I, a protic acid, an amine, and a solvent under an inert atmosphere, and reacting the mixture under visible light irradiation and at 25–45°C for 6–48 h; subsequently, the reaction solution is post-treated to obtain aromatic ketone compounds of formula II and phenolic compounds of formula III, respectively. This method is mild, efficient, green, and economical, and suitable for scale-up production.

Description

Technical Field

[0001] This invention relates to a method for catalytically cleaving lignin-type compounds, specifically a method for catalytically cleaving β-O-4 type lignin model compounds under visible light to obtain value-added small molecule products. Background Technology

[0002] The increasing demand for energy in modern society means that the use of traditional energy sources not only depletes fossil resources but also severely pollutes the environment. Biomass is a recognized promising alternative to fossil fuels. Lignin is the most abundant natural phenolic polymer, accounting for approximately 20%–30% of the total mass of biomass. Lignin's unique aromatic structure gives it a distinct advantage in the catalytic conversion into high-value aromatic chemicals. The β-O-4 bond accounts for 43%–62% of the bonds in natural lignin. Depolymerizing the large lignin molecules by cleaving the β-O-4 bonds in its structure yields smaller, value-added products. The reaction formula is as follows:

[0003]

[0004] Lignin molecules undergo photocatalytic cleavage of intramolecular β-O-4 bonds to yield value-added aromatic small molecule compounds.

[0005] Based on this, researchers have developed various strategies for catalytic cleavage of lignin-type compounds over the past few decades. Among these, Song et al. used AuNPs / Li-Al LDH catalysts to oxidatively depolymerize organic solvent lignin and sulfate lignin (see Chemical Science., 2018, 9(42), 8127-8133.). Sales et al. reported the catalytic oxidation of lignin using a Pd / γ-Al2O3 catalyst under oxygen, obtaining a series of aromatic aldehydes by breaking C / C bonds during the reaction (see Chemical Engineering Science., 2007, 62(18-20), 5386-5391.). Dabral et al. developed a TEMPO / DAIB catalytic system, obtaining 15% organic components from the oxidation of lignin by breaking β-O-4 and C / C bonds (see Chemsuschem., 2017, 10(13), 2707-2713.). Lin et al. selected CrCl3 and Pd / C as bifunctional catalysts, which synergistically promoted the cleavage and hydrogenation of β-O-4 bonds, preventing the polymerization of reaction intermediates and yielding 19.2 wt.% aromatic monomers (see Journal of the Energy Institute., 2020, 93(2), 784-791.). Gong et al. used Bi and Pt co-modified TiO2 to oxidatively depolymerize lignin sulfonates under sunlight irradiation (see Applied Catalysis B: Environmental., 2017, 204, 296-303.). Luo et al. reported the use of a DPA-BP / NHPI / O2 photocatalytic system for the aerobic oxidation of β-O-4 lignin model compounds (see Journal of Organic Chemistry., 2016, 81(19), 9131-9137.).

[0006] Unfortunately, the aforementioned methods for catalytic cleavage of lignin-type compounds all suffer from drawbacks to varying degrees, including harsh reaction conditions, expensive and difficult-to-obtain catalysts, low yields of target products, and cumbersome operations. In 2019, Gabriel's research group achieved the co-catalytic cleavage of β-O-4 type lignin model compounds using blue LED light irradiation and [Ir(ppy)2(dtbbpy)]PF6 at room temperature (see ACS Catalysis., 2019, 9, 2252-2260.). Although this method offers mild reaction conditions and high conversion rates of target products, it still suffers from limitations such as insufficient substrate universality, the high cost and difficulty in obtaining the precious metal Ir as a catalyst, and poor economic practicality. Therefore, finding an economical, green, mild, and efficient method for catalytic cleavage of β-O-4 type lignin model compounds is particularly important. Summary of the Invention

[0007] To address the limitations of current catalytic cracking technologies, this invention provides a method for the visible light catalytic cracking of β-O-4 type lignin model compounds.

[0008] In this invention, oxidized β-O-4 type lignin model compounds undergo intramolecular CO bond homolytic cleavage under photocatalytic conditions to yield multiplied small molecule phenolic and aromatic ketone compounds; the photocatalytic conditions are visible light irradiation and the addition of a photosensitizer, amine, and protic acid. This method is mild, efficient, green, and economical, and suitable for scale-up production.

[0009] The technical solution of the present invention is as follows:

[0010] A method for visible light photocatalytic cleavage of β-O-4 type lignin model compounds, comprising:

[0011] Under an inert atmosphere, a photosensitizer, a β-O-4 type lignin model compound of Formula I, a protic acid, an amine and a solvent are mixed and reacted under visible light irradiation and at 25-45°C (preferably 30°C) for 6-48 hours (preferably 16 hours). The reaction solution is then post-treated to obtain aromatic ketone compounds of Formula II and phenolic compounds of Formula III, respectively.

[0012] in,

[0013] The molar ratio of the β-O-4 type lignin model compound, amine, protic acid, and photosensitizer shown in Formula I is 1:1.5-3:0.01-0.15:0.02-0.1, preferably 1:2.5:0.1:0.05;

[0014] The photosensitizer is selected from at least one of copper-based photosensitizer PS1, copper-based photosensitizer PS2, copper-based photosensitizer PS3, copper-based photosensitizer PS4, copper-based photosensitizer PS5, and organic photosensitizer PS6; copper-based photosensitizer PS2 is preferred.

[0015] The structural formula of the photosensitizer is as follows:

[0016]

[0017] The protic acid is selected from hydrochloric acid, nitric acid, formic acid, or acetic acid, with formic acid being preferred;

[0018] The amine is selected from triethylamine, tetramethylethylenediamine, or diisopropylethylamine, preferably diisopropylethylamine;

[0019] The solvent is selected from toluene, acetonitrile, diethyl ether, dichloromethane, ethyl acetate, dimethyl sulfoxide, 1,2-dichloroethane, 1,4-dioxane, methanol, ethanol or tetrahydrofuran, preferably tetrahydrofuran;

[0020] The volume molar ratio of the solvent to the β-O-4 type lignin model compound shown in Formula I is 10–25:1, mL / mmol; preferably 20:1, mL / mmol.

[0021] The visible light source is a blue LED, which can be a 10W blue LED, a 15W blue LED, or a 30W blue LED, with a 15W blue LED being preferred. In a specific embodiment of the present invention, the Schlenk reaction tube containing the reaction solution is placed 2 to 8 cm away from the blue LED light source.

[0022] The specific post-processing method is as follows: After the reaction is completed, 100-200 mesh silica gel for column chromatography is added to the reaction solution and the solvent is removed by vacuum distillation. The crude product is dry-loaded for column chromatography separation. Gradient elution is performed using petroleum ether / ethyl acetate volume ratio of 20-10:1 as the eluent. The target compound eluent is obtained by TLC detection and evaporated to dryness under reduced pressure to obtain the aromatic ketone compounds shown in Formula II and the phenolic compounds shown in Formula III, respectively.

[0023] The reaction formula is as follows:

[0024]

[0025] In Equations I to III,

[0026] R 1 It is H, 4-methoxy, 3,4-dimethoxy or 3,4,5-trimethoxy, preferably 4-methoxy or 3,4-dimethoxy;

[0027] R 2 The radical is H, 2-methoxy, 3-methoxy, 4-methoxy, chlorine, bromine, phenyl, cyclohexyl, 3,5-dimethyl, 3,5-dimethoxy, 2,6-dimethoxy, acetyl, tert-butyl, cyano, or nitro, preferably phenyl, methoxy, dimethoxy, cyclohexyl, or acetyl.

[0028] Specifically, the β-O-4 type lignin model compound represented by Formula I is one of the following:

[0029]

[0030] The β-O-4 type lignin model compound described in this invention can be prepared by those skilled in the art based on methods disclosed in existing literature.

[0031] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0032] 1) The β-O-4 type lignin template substrate used in this technical solution can be obtained by combining inexpensive and multi-fragmented commercially available drugs through simple chemical reactions. Therefore, the substrate is simple and readily available, and has a variety of functional groups.

[0033] 2) This technical solution obtains value-added small molecule phenols and aromatic ketones by photocatalytic cleavage of β-O-4 type lignin model compounds. The reaction conditions are mild, the substrate is universal, there are few side reactions, and the yield of the target product is high.

[0034] 3) This technical solution uses inexpensive copper complexes as photosensitizers to replace expensive and hard-to-obtain precious metals Ir as catalysts for catalytic cracking of lignin template substrates. The reaction operation is simple and economical. Attached Figure Description

[0035] Figure 1 The reaction mechanism involved in the photocatalytic reaction of this invention. Detailed Implementation

[0036] The present invention is further described below through specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0037] The β-O-4 type lignin template substrate used in this invention can be prepared according to literature, and the typical steps are as follows:

[0038]

[0039] Weigh 12 mmol (1.2 equiv.) of phenolic compound S2 and add it dropwise to a round-bottomed flask fitted with a magnetic flask. Then, pour 50 mL of acetone into the flask to dissolve it. Weigh 15 mmol (1.5 equiv.) of potassium carbonate and add it to the solution, stirring for 30 min. Separately, weigh 10 mmol (1.0 equiv.) of α-bromoacetophenone compound S1 in a beaker and add 20 mL of acetone, stirring to dissolve it. Slowly add the S1 solution dropwise to the round-bottomed flask. After the addition is complete, heat the suspension under reflux at 70 °C with stirring overnight.

[0040] After the reaction, the solvent was removed from the resulting suspension by vacuum distillation, and then water was added and shaken to dissolve the solid. The resulting solution was extracted with ethyl acetate (3 × 50 mL), and the organic phases were combined and dried over anhydrous Na₂SO₄ and filtered. 100-200 mesh silica gel was added to the filtrate and the solvent was removed by vacuum distillation. The crude product was then subjected to column chromatography with petroleum ether / ethyl acetate at a ratio of 10:1 as the eluent to obtain the β-O₄-type lignin template substrate S3.

[0041] β-O-4 type lignin model compounds (I) are all known compounds, and their 1 The H NMR characterization results are consistent with those reported in the literature.

[0042] The photosensitizer PS2 used in the following examples is synthesized as follows:

[0043] Synthesis of photosensitizer PS2:

[0044]

[0045] Take a 50 mL three-necked flask and add a magnetic stir bar. Add 4,7-diphenyl-1,10-phenanthroline (1.5 mmol, 1.0 equiv.) to the flask, replace the flask with argon gas three times, and then dry it by blowing it with a hot air gun for 20 min under vacuum. Add 15 mL of redistilled toluene, and then add isopropyllithium (6 mL, 4.0 equiv., 1 M in Hexane) dropwise under ice bath conditions. Stir the reaction at room temperature for 16 hours. After the reaction is complete, remove the toluene by rotary evaporation, then dissolve it in dichloromethane. Add activated manganese dioxide (15 mmol, 10.0 equiv.) to the reaction solution, stir overnight at room temperature, and finally separate the yellow ligand 2,9-diisopropyl-4,7-diphenylphenanthroline (1 mmol, 1.0 equiv.) by column chromatography (PE:EA = 20:1), with a yield of 67%.

[0046] Take a 50 mL three-necked flask, add a magnetic stir bar and connect a reflux condenser. Add Cu(MeCN)4PF6 (1 mmol, 1.0 equiv.) and 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene) (1 mmol, 1.0 equiv.) to the flask, purging with argon gas three times, and then add redistilled and dried dichloromethane (30 mL). Heat and stir at 35 °C for 4 hours, then slowly add a solution of 2,9-diisopropyl-4,7-diphenylphenanthroline (1 mmol, 1.0 equiv.) in dichloromethane (10 mL) at room temperature. After the addition is complete, continue heating and stirring at 35 °C for 3 hours. After the reaction is complete, cool to room temperature, and slowly add the reaction solution dropwise to vigorously stirred n-hexane (150 mL) to precipitate the crude product. Filter and wash the filter cake with n-hexane (3 × 30 mL). The obtained filter cake is the photosensitizer PS2, with a yield of 1 mmol and a yield of 100%.

[0047] Examples of catalytic cleavage of β-O-4 type lignin model compounds:

[0048] Example 1

[0049]

[0050] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%), 2-(2-methoxyphenoxy)-1-acetophenone (0.2 mmol, 48 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products acetophenone and guaiacol were purified by column chromatography (eluting PE / EA = 20:1-10:1) to obtain the corresponding products. These substances were white crystals and a yellow liquid, respectively, with yields of 15.8 mg and 15.3 mg, representing 66% and 62%, respectively.

[0051] Characterization data: Acetophenone 1 H NMR (400MHz, CDCl3) δ8.01-7.89(m,2H),7.60-7.53(m,1H),7.50-7.42(m,2H),2.61(s,3H). 13 C NMR (101MHz, CDCl3) δ 198.16, 137.14, 133.11, 128.58, 128.32, 26.62. Guaiacin 1H NMR (400MHz, CDCl3) δ6.97-6.94(m,1H),6.90(dd,J=5.6,3.6Hz,1H),6.88-6.86(m,2H),5.69(br,1H),3.89(s,3H). 13 C NMR (101MHz, CDCl3) δ146.7,145.8,121.6,120.3,114.7,110.9,56.0.

[0052] Example 2

[0053]

[0054] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethyl ketone (0.2 mmol, 54 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products, hawthorn ketone and guaiacol, were purified by column chromatography (eluting PE / EA = 20:1-10:1) to obtain the corresponding products. These substances were white crystals and a yellow liquid, respectively, with yields of 23.1 mg and 18.8 mg, representing 77% and 76%, respectively.

[0055] Characterization data: Hawthorn flower ketone 1 H NMR (400MHz, CDCl3) δ7.94 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 2.56 (s, 3H). 13 C NMR (101MHz, CDCl3) δ 196.9, 163.6, 130.7 (2C), 130.5, 113.8 (2C), 55.6, 26.5. Guaiacin 1 H NMR (400MHz, CDCl3) δ6.96-6.93(m,1H),6.89(dd,J=5.6,3.6Hz,1H),6.87-6.85(m,2H),5.68(br,1H),3.88(s,3H). 13 C NMR (101MHz, CDCl3) δ146.8,145.7,121.5,120.2,114.6,110.8,55.9.

[0056] Example 3

[0057]

[0058] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(3-methoxyphenoxy)-1-(4-methoxyphenyl)ethyl ketone (0.2 mmol, 54 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products, hawthorn ketone and 3-methoxyphenol, were purified by column chromatography (eluting PE / EA = 20:1-10:1). These substances were white crystals and red liquid, respectively, with yields of 21.9 mg and 17.6 mg, representing 73% and 71% yields, respectively.

[0059] Characterization data: Hawthorn flower ketone 1 H NMR (400MHz, CDCl3) δ7.96 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 2.58 (s, 3H). 13 C10 NMR (101 MHz, CDCl3) δ 196.8, 163.5, 130.6 (2C), 130.4, 113.7 (2C), 55.5, 26.4 3-Methoxyphenol 1 H NMR (400MHz, CDCl3) δ7.15 (t, J = 8.4Hz, 1H), 6.54 (dd, J = 1.6Hz, 7.6Hz, 1H), 6.48-6.44 (m, 2H), 5.72 (br-s, 1H), 3.79 (s, 3H). 13 CNMR (125MHz, CDCl3) δ161.10,156.83,130.28,107.86,106.58,101.62,55.41.

[0060] Example 4

[0061]

[0062] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(4-methoxyphenoxy)-1-(4-methoxyphenyl)ethyl ketone (0.2 mmol, 54 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products, hawthorn ketone and 4-methoxyphenol, were purified by column chromatography (eluting PE / EA = 20:1-10:1). Both substances were white crystals, with yields of 24 mg and 18.9 mg, respectively, representing yields of 75% and 76%.

[0063] Characterization data: Hawthorn flower ketone 1 H NMR (400MHz, CDCl3) δ7.94 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 2.56 (s, 3H). 13 C10 NMR (101 MHz, CDCl3) δ 196.9, 163.6, 130.7 (2C), 130.5, 113.8 (2C), 55.6, 26.5 4-Methoxyphenol 1 H NMR (400MHz, CDCl3) δ7.03-6.53(m,4H),4.60(s,1H),3.77(s,3H). 13 C NMR (125MHz, CDCl3) δ153.79,149.47,116.07,113.86,57.83.

[0064] Example 5

[0065]

[0066] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(2-bromophenoxy)-1-(4-methoxyphenyl)ethyl ketone (0.2 mmol, 64 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products, hawthorn ketone and o-bromophenol, were purified by column chromatography (eluting PE / EA = 20:1-10:1). These substances were white crystals and colorless liquids, respectively, with yields of 24.9 mg and 26.6 mg, representing yields of 83% and 77%, respectively.

[0067] Characterization data: Hawthorn flower ketone 1 H NMR (400MHz, CDCl3) δ7.96 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 2.58 (s, 3H). 13 C10 NMR (101 MHz, CDCl3) δ 196.8, 163.5, 130.6 (2C), 130.4, 113.7 (2C), 55.5, 26.4. o-Bromophenol 1 H NMR (400MHz, CDCl3) δ7.47(dd,J=8.0,1.6Hz,1H),7.23(td,J=7.7,1.6Hz,1H),7.03(dd,J=8.2,1.6Hz,1H),6.81(td,J=7.7,1.6Hz,1H). 13 C NMR (101MHz, CDCl3) δ152.37,132.15,129.33,121.96,116.27,110.39.

[0068] Example 6

[0069]

[0070] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(3-chlorophenoxy)-1-(4-methoxyphenyl)ethyl ketone (0.2 mmol, 64 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products, hawthorn ketone and m-chlorophenol, were purified by column chromatography (eluting PE / EA = 20:1-10:1). These substances were white crystals and white solids, respectively, with yields of 26.4 mg and 21.3 mg, representing yields of 88% and 83%, respectively.

[0071] Characterization data: Hawthorn flower ketone 1 H NMR (400MHz, CDCl3) δ7.94 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 2.56 (s, 3H). 13 C10 NMR (101 MHz, CDCl3) δ 196.9, 163.6, 130.7 (2C), 130.5, 113.8 (2C), 55.6, 26.5. m-Chlorophenol 1 H NMR (400MHz, CDCl3) δ6.20-6.16 (t, J = 8Hz, 1H), 6.95-6.89 (m, 2H), 6.77-6.74 (m, 1H), 5.49 (s, br, 1H). 13 C NMR (101MHz, CDCl3) δ156.37,134.89,130.50,121.01,115.96,113.85.

[0072] Example 7

[0073]

[0074] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(biphenyl-4-oxy)-1-(4-methoxyphenyl)ethyl ketone (0.2 mmol, 63.6 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products, hawthorn ketone and 4-hydroxybiphenyl, were purified by column chromatography (eluting PE / EA = 20:1-10:1). These substances were white crystals and white solids, respectively, with yields of 23.1 mg and 24.5 mg, representing 77% and 72%, respectively.

[0075] Characterization data: Hawthorn flower ketone 1 H NMR (400MHz, CDCl3) δ7.95 (d, J = 8.8 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 2.57 (s, 3H). 13 C10 NMR (101 MHz, CDCl3) δ 196.8, 163.5, 130.6 (2C), 130.4, 113.7 (2C), 55.5, 26.4 4-Hydroxybiphenyl 1 H NMR (400MHz, CDCl3) δ7.55 (t, J = 8.3Hz, 2H), 7.49 (q, J = 11.3Hz, 2H), 7.44-7.40 (m, 2H), 7.33-7.21 (m, 1H), 6.91 (d, J = 8.6Hz, 2H), 4.81 (s, br, 1H). 13 C NMR (101MHz, CDCl3) δ154.86,140.57,133.86,128.57,128.24,126.56,115.46.

[0076] Example 8

[0077]

[0078] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(cyclohexyl-4-phenoxy)-1-(4-methoxyphenyl)ethyl ketone (0.2 mmol, 64.8 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon gas three times. Then, diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products, hawthorn ketone and 4-cyclohexylphenol, were purified by column chromatography (eluting PE / EA = 20:1-10:1). The substance was a white crystalline solid and a white solid, with yields of 21 mg and 23.9 mg, respectively, and yields of 70% and 68%.

[0079] Characterization data: Hawthorn flower ketone 1 H NMR (400MHz, CDCl3) δ7.96 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 2.58 (s, 3H). 13 C10 NMR (101 MHz, CDCl3) δ 196.82, 163.53, 130.61 (2C), 130.42, 113.71 (2C), 55.51, 26.42 4-Cyclohexylphenol 1 H NMR (400MHz, CDCl3) δ7.07(d,J=8.4Hz,2H),6.75(d,J=8.4Hz,2H),4.70(br,1H),2.43(tt,J=8.4,3.6Hz ,1H),1.93-1.79(m,4H),1.73(dd,J=12.4,3.2,1.6Hz,1H),1.62(m,1H),1.37(m,3H),1.29-1.16(m,1H). 13 CNMR (101MHz, CDCl3) δ153.5,140.5,127.8,115.0,43.7,34.7,27.0,26.2.

[0080] Example 9

[0081]

[0082] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(3,5-dimethylphenoxy)-1-(4-methoxyphenyl)ethyl ketone (0.2 mmol, 54 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products, hawthorn ketone and 3,5-dimethylphenol, were purified by column chromatography (eluting PE / EA = 20:1–10:1). These substances were white crystals and white solids, respectively, with yields of 21.6 mg and 17 mg, representing 72% and 70%, respectively.

[0083] Characterization data: Hawthorn flower ketone 1 H NMR (400MHz, CDCl3) δ7.95 (d, J = 8.8 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 2.57 (s, 3H). 13 C10 NMR (101 MHz, CDCl3) δ 196.84, 163.53, 130.61 (2C), 130.42, 113.72 (2C), 55.51, 26.43, 3,5-dimethylphenol 1 H NMR (400MHz, CDCl3) δ6.60(s,1H),6.48(s,2H),2.28(s,6H). 13 C NMR (101MHz, CDCl3) δ155.48,139.67,122.70,113.19,21.36.

[0084] Example 10

[0085]

[0086] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-phenoxy-1-acetophenone (0.2 mmol, 42 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products acetophenone and phenol were purified by column chromatography (eluting PE / EA = 20:1-10:1). These substances were white crystals and colorless crystals, respectively, with yields of 13.4 mg and 10 mg, and percentages of 56% and 52%, respectively.

[0087] Characterization data: Acetophenone 1 H NMR (400MHz, CDCl3) δ8.02-7.88(m,2H),7.61-7.54(m,1H),7.51-7.43(m,2H),2.62(s,3H). 13 C NMR (101MHz, CDCl3) δ 198.15, 137.16, 133.15, 128.59, 128.33, 26.64. Phenol 1 H NMR (400MHz, CDCl3) δ7.30-7.22(m,2H),6.95(tt,J=7.3,1.1Hz,1H),6.89-6.79(m,2H),4.90-4.60(m,1H). 13 C NMR (101MHz, CDCl3) δ155.42,129.71,120.87,115.30.

[0088] Example 11

[0089]

[0090] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%), 2-(2,6-dimethoxyphenoxy)-1-(3,4-dimethoxyphenyl)ethyl ketone (0.2 mmol, 66.4 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon gas three times. Then, diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products 3,4-dimethoxyacetophenone and 2,6-dimethoxyphenol were purified by column chromatography (eluting PE / EA = 20:1-10:1). The substance was a colorless crystal and a white solid, with yields of 28.4 mg and 24.2 mg, respectively, and yields of 79% and 77%.

[0091] Characterization data: 3,4-Dimethoxyacetophenone 1 H NMR (400MHz, CDCl3) δ7.57(dd,J=8.3,1.9Hz,1H),7.52(d,J=1.9Hz,1H),6.88(d,J=8.3Hz,1H),3.94(s,3H),3.93(s,3H),2.56(s,3H). 13 CNMR (101MHz, CDCl3) δ 196.9, 153.4, 149.1, 130.6, 123.4, 110.2, 110.1, 56.2, 56.1, 26.3, 2, 6-dimethoxyphenol 1 H NMR (400MHz, CDCl3) δ6.80 (t, J = 8.4Hz, 1H), 6.59 (d, J = 8.4Hz, 2H), 5.51 (br, 1H), 3.89 (s, 6H). 13 C NMR (101MHz, CDCl3) δ147.3(2C),134.9,119.1,104.9(2C),56.3(2C).

[0092] Example 12

[0093]

[0094] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%), 2-(3,5-dimethoxyphenoxy)-1-(3,4-dimethoxyphenyl)ethyl ketone (0.2 mmol, 66.4 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon gas three times. Then, diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products 3,4-dimethoxyacetophenone and 3,5-dimethoxyphenol were purified by column chromatography (eluting PE / EA = 20:1-10:1). Both substances were colorless crystals, with yields of 27 mg and 22.1 mg, respectively, and yields of 75% and 72%.

[0095] Characterization data: 3,4-Dimethoxyacetophenone 1 H NMR (400MHz, CDCl3) δ7.54(dd,J=8.3,1.9Hz,1H),7.49(d,J=1.9Hz,1H),6.85(d,J=8.3Hz,1H),3.91(s,3H),3.89(s,3H),2.53(s,3H). 13 CNMR (101 MHz, CDCl3) δ 196.9, 153.4, 149.1, 130.6, 123.4, 110.2, 110.1, 56.2, 56.1, 26.3, 3,5-Dimethoxyphenol 1 H NMR (400MHz, CDCl3) δ6.04 (t, J = 2.0Hz, 1H), 6.02 (d, J = 2.0Hz, 2H), 4.73 (br, s, 1H), 3.71 (s, 6H). 13 C NMR (101MHz, CDCl3) δ161.5,157.6,94.3,92.9,55.3.

[0096] Example 13

[0097]

[0098] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%), 2-(2-methoxyphenoxy)-1-(3,4,5-trimethoxyphenyl)ethyl ketone (0.2 mmol, 66.4 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon gas three times. Then, diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products 3,4,5-trimethoxyacetophenone and guaiacol were purified by column chromatography (eluting PE / EA = 20:1-10:1) to obtain the corresponding products 3,4,5-trimethoxyacetophenone and guaiacol. The substance was a white crystalline solid and a yellow liquid, with yields of 37 mg and 20.3 mg, respectively, and yields of 89% and 82%.

[0099] Characterization data: 3,4,5-trimethoxyacetophenone 1 H NMR (400MHz, CDCl3) δ2.60 (s, 3H), 3.93 (d, J = 2.5Hz, 9H), 7.22 (s, 2H). 13 C NMR (101 MHz, CDCl3) δ 26.4, 56.3, 60.9, 105.9, 132.5, 143.1, 153.1, 196.9. Guaiacin 1 H NMR (400MHz, CDCl3) δ6.96-6.93(m,1H),6.89(dd,J=5.6,3.6Hz,1H),6.87-6.85(m,2H),5.68(br,1H),3.88(s,3H). 13 C NMR (101MHz, CDCl3) δ146.8,145.7,121.5,120.2,114.6,110.8,55.9.

[0100] Example 14

[0101]

[0102] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(4-acetylphenoxy)-1-(4-methoxyphenyl)ethyl ketone (0.2 mmol, 59.6 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products, hawthorn ketone and p-hydroxyacetophenone, were purified by column chromatography (eluting PE / EA = 20:1-10:1). Both substances were white solids, with yields of 20.4 mg and 19.8 mg, respectively, representing yields of 68% and 73%.

[0103] Characterization data: Hawthorn flower ketone 1 H NMR (400MHz, CDCl3) δ7.95 (d, J = 8.8 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 2.57 (s, 3H). 13 C10 NMR (101 MHz, CDCl3) δ 196.8, 163.5, 130.6 (2C), 130.4, 113.7 (2C), 55.5, 26.4. p-Hydroxyacetophenone 1 H NMR (400MHz, CDCl3) δ7.91 (d, J = 8.6 Hz, 2H), 6.89 (d, J = 8.6 Hz, 2H), 5.73 (br, 1H), 2.57 (br, 3H). 13 C NMR (101MHz, CDCl3) δ198.2,161.0,131.3(2C),130.1,115.6(2C),26.5.

[0104] Example 15

[0105]

[0106] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(4-acetylphenoxy)-1-(3,4-dimethoxyphenyl)ethyl ketone (0.2 mmol, 65.6 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon gas three times. Then, diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products 3,4-dimethoxyacetophenone and p-hydroxyacetophenone were purified by column chromatography (eluting PE / EA = 20:1-10:1). Both substances were white solids, with yields of 25.2 mg and 20.2 mg, respectively, and yields of 70% and 74%.

[0107] Characterization data: 3,4-Dimethoxyacetophenone 1 H NMR (400MHz, CDCl3) δ7.57(dd,J=8.3,1.9Hz,1H),7.52(d,J=1.9Hz,1H),6.88(d,J=8.3Hz,1H),3.94(s,3H),3.93(s,3H),2.56(s,3H). 13 CNMR (101MHz, CDCl3) δ 196.9, 153.4, 149.1, 130.6, 123.4, 110.2, 110.1, 56.2, 56.1, 26.3. p-Hydroxyacetophenone 1 H NMR (400MHz, CDCl3) δ7.92 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.6 Hz, 2H), 5.74 (br, 1H), 2.58 (br, 3H). 13 C NMR (101MHz, CDCl3) δ198.21,161.02,131.32(2C),130.14,115.62(2C),26.53.

[0108] Example 16

[0109]

[0110] In a dry Schlenk reaction tube, photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(4-acetylphenoxy)-1-acetophenone (0.2 mmol, 50.8 mg, 1.0 equiv.) were added. The tube was purged with argon three times, and then diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products acetophenone and p-hydroxyacetophenone were purified by column chromatography (eluting PE / EA = 20:1-10:1). Both were white solids, with yields of 15.4 mg and 17.9 mg, respectively, representing yields of 64% and 66%.

[0111] Characterization data: Acetophenone 1 H NMR (400MHz, CDCl3) δ8.02-7.88(m,2H),7.61-7.54(m,1H),7.51-7.43(m,2H),2.62(s,3H). 13 C NMR (101 MHz, CDCl3) δ 198.15, 137.16, 133.15, 128.59, 128.33, 26.64. p-Hydroxyacetophenone 1 H NMR (400MHz, CDCl3) δ7.94 (d, J = 8.6 Hz, 2H), 6.92 (d, J = 8.6 Hz, 2H), 5.76 (br, 1H), 2.60 (br, 3H). 13 C NMR (101MHz, CDCl3) δ198.25,161.03,131.32(2C),130.14,115.62(2C),26.52.

[0112] Example 17

[0113]

[0114] In a dry Schlenk reaction tube, photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(4-methoxyphenoxy)-1-acetophenone (0.2 mmol, 48.4 mg, 1.0 equiv.) were added. The tube was purged with argon three times, and then diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products acetophenone and p-methoxyphenol were purified by column chromatography (eluting PE / EA = 20:1-10:1). Both substances were white solids, with yields of 16.8 mg and 16.9 mg, respectively, representing yields of 70% and 68%.

[0115] Characterization data: Acetophenone 1 H NMR (400MHz, CDCl3) δ8.01-7.90(m,2H),7.63-7.50(m,1H),7.53-7.43(m,2H),2.60(s,3H). 13 C NMR (101 MHz, CDCl3) δ 198.14, 137.18, 133.12, 128.60, 128.34, 26.65 4-Methoxyphenol 1 H NMR (400MHz, CDCl3) δ7.01-6.52(m,4H),4.63(s,1H),3.78(s,3H). 13 C NMR (125MHz, CDCl3) δ153.77,149.49,116.03,113.82,57.86.

[0116] Example 18

[0117]

[0118] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(4-tert-butylphenoxy)-1-(4-methoxyphenyl)ethyl ketone (0.2 mmol, 59.6 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products, hawthorn ketone and p-tert-butylphenol, were purified by column chromatography (eluting PE / EA = 20:1-10:1). Both substances were white solids, with yields of 22.5 mg and 21.9 mg, respectively, representing yields of 75% and 73%.

[0119] Characterization data: Hawthorn flower ketone 1 H NMR (400MHz, CDCl3) δ7.95 (d, J = 8.8 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 2.57 (s, 3H). 13 C10 NMR (101 MHz, CDCl3) δ 196.81, 163.52, 130.62 (2C), 130.41, 113.74 (2C), 55.52, 26.41. p-tert-Butylphenol 1 H NMR (400MHz, CDCl3) δ7.29-7.21(m,2H),6.80-6.74(m,2H),1.29(s,9H). 13 C NMR (101MHz, CDCl3) δ31.6, 34.1, 114.8, 126.4, 143.5, 153.2.

[0120] Example 19

[0121]

[0122] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(2-nitrophenoxy)-1-(4-methoxyphenyl)ethyl ketone (0.2 mmol, 57.4 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon three times, and then diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products, hawthorn ketone and o-nitrophenol, were purified by column chromatography (eluting PE / EA = 20:1-10:1). These substances were white and yellow solids, respectively, with yields of 23.7 mg and 21.4 mg, representing 79% and 77% yields, respectively.

[0123] Characterization data: Hawthorn flower ketone 1 H NMR (400MHz, CDCl3) δ7.96 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 2.58 (s, 3H). 13 C10 NMR (101 MHz, CDCl3) δ 196.82, 163.53, 130.61 (2C), 130.42, 113.71 (2C), 55.51, 26.42. o-Nitrophenol 1 H NMR (400MHz, CDCl3) δ10.59(br,1H),8.11(d,J=8.4Hz,1H),7.59(t,J=7.7Hz,1H),7.16(d,J=8.4Hz,1H),6.99(t,J=7.8Hz,1H). 13 CNMR (101MHz, CDCl3) δ155.26,137.67,133.84,125.21,120.35,120.11.

[0124] Example 20

[0125]

[0126] Photosensitizer PS2 (0.01 mmol, 12 mg, 5 mol%) and 2-(4-cyanophenoxy)-1-(4-methoxyphenyl)ethyl ketone (0.2 mmol, 53.4 mg, 1.0 equiv.) were added to a dry Schlenk reaction tube. The tube was purged with argon gas three times. Then, diisopropylethylamine (0.5 mmol, 65 mg, 2.5 equiv.), HCOOH (0.02 mmol, 81 mg, 0.1 equiv.), and tetrahydrofuran (4 mL) were added dropwise. The reaction tube was placed 3 cm away from a 15W blue LED light source and reacted at 30 °C for 16 hours. After the reaction was complete, the solvent was removed by rotary evaporation, and the products, hawthorn ketone and p-cyanophenol, were purified by column chromatography (eluting PE / EA = 20:1-10:1). Both substances were white crystals, with yields of 21 mg and 16.2 mg, respectively, representing yields of 70% and 68%.

[0127] Characterization data: Hawthorn flower ketone 1 H NMR (400MHz, CDCl3) δ7.94 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 2.55 (s, 3H). 13 C10 NMR (101 MHz, CDCl3) δ 196.83, 163.52, 130.61 (2C), 130.42, 113.71 (2C), 55.53, 26.42. p-Cyanophenol 1 H NMR (400MHz, CDCl3) δ7.55 (d, J = 8.4Hz, 2H), 6.95 (d, J = 8.4Hz, 2H), 6.84 (br, s, 1H). 13 C NMR (101MHz, CDCl3) δ160.4, 134.5, 119.4, 116.6, 103.0.

Claims

1. A method of photocatalytic cleavage of a visible light of a β-0-4 type lignin model compound, characterized by, The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The photosensitizer is a copper-based photosensitizer The method comprises the following steps: The structural formula of the photosensitizer is as follows: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: R 1 is H, 4-methoxy, 3,4-dimethoxy or 3,4,5-trimethoxy; R 2 is H, 2-methoxy, 3-methoxy, 4-methoxy, chloro, bromo, phenyl, cyclohexyl, 3,5- dimethyl, 3,5-dimethoxy, 2,6-dimethoxy, acetyl, t-butyl, cyano, or nitro.

2. The method of photocatalytic cleavage of visible light of β-0-4 type lignin model compounds according to claim 1, characterized in that, The method comprises the following steps:

3. The method of claim 1, wherein the β-0-4 type lignin model compound is visible light catalytically cleaved, and the method is characterized by, The method comprises the following steps:

4. The method of photocatalytic cleavage of visible light of β-0-4 type lignin model compounds according to claim 1, characterized in that, The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following

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