Method for synthesizing dihydromyricetin

Abstract

According to the efficient and green dihydromyricetin synthesis method, myricetin and a Pd-PEG2000 catalyst are used as main raw materials, and a high-purity and high-content dihydromyricetin product is finally obtained through reactions such as a chemical reduction method and hydrogenation. The method is simple and convenient to operate and mild in reaction condition, and the prepared Pd-PEG2000 catalyst can be recycled for multiple times, is easy to recover and is suitable for industrial production of dihydromyricetin.

Description

Technical Field

[0001] The invention relates to a chemical synthesis method for a raw material for cosmetics, in particular to a method for synthesizing dihydromyricetin by one-step hydrogenation of myricetin catalyzed by Pd-polyethylene glycol. Background Art

[0002] Dihydromyricetin (DMY) is a natural flavonoid compound, generally found in rattan and other plants, with significant antioxidant, anti-inflammatory, alcohol detoxification, liver protection, immunity enhancement, blood lipid regulation and other effects. However, the traditional extraction and purification method is to use plant extraction to crush the rattan tea, then dissolve and filter it with a solvent, and purify it by crystallization, but there are a series of problems such as low efficiency and high cost. Summary of the invention

[0003] The present invention aims to overcome the above-mentioned defects and develop a method for one-step hydrogenation of myricetin using myricetin as a substrate and a high-efficiency catalyst, which has important industrial application value. Specifically, the present invention uses a Pd-polyethylene glycol catalyst to hydrogenate myricetin in one step to prepare dihydromyricetin.

[0004] The specific equation is as follows:

[0005]

[0006] This method achieves efficient hydrogenation reaction under mild conditions to prepare high-purity dihydromyricetin. It is easy to operate and suitable for large-scale production.

[0007] The invention provides a method for synthesizing dihydromyricetin, which specifically comprises: taking myricetin as a substrate and Pd-polyethylene glycol as a catalyst, catalyzing (polyethylene glycol is abbreviated as PEG, the catalyst is named Pd-PEG, and the PEG grafted macromolecule is selected from PEG200-6000) hydrogenation to synthesize dihydromyricetin in a hydrogen atmosphere.

[0008] Furthermore, the present invention provides a method for synthesizing dihydromyricetin, which also has the following characteristics: the polyethylene glycol in the above-mentioned Pd-polyethylene glycol is selected from one of the polyethylene glycols with an average molecular weight greater than 1000.

[0009] Furthermore, the present invention provides a method for synthesizing dihydromyricetin, which also has the following characteristics: the preparation method of the above-mentioned Pd-polyethylene glycol is: step 1. preparing a palladium source solution: dissolving Na2[PdCl4] or PdCl2 in deionized water to obtain a palladium ion solution; step 2. preparing a polyethylene glycol solution: dissolving polyethylene glycol in deionized water to obtain a polyethylene glycol solution; step 3. reducing palladium: slowly dropping the dissolved palladium source solution into the polyethylene glycol solution while stirring, and gradually adding NaBH4 solution to the reaction system at room temperature to reduce the palladium ions to form metallic palladium; step 4. separating the reaction from the precipitation and drying: continuing to stir the reaction mixture for 1-2 hours to ensure that the palladium is completely reduced and loaded onto the polyethylene glycol, and then obtaining Pd-polyethylene glycol after post-treatment.

[0010] Furthermore, the present invention provides a method for synthesizing dihydromyricetin, which also has the following characteristics: the reaction temperature is 25-55°C, the pressure is 1-5 MPa, and the reaction time is 1-5 hours to synthesize dihydromyricetin.

[0011] Furthermore, the present invention provides a method for synthesizing dihydromyricetin, which also has the following characteristics: the dosage of the above-mentioned catalyst is 1-5% of the quality of myricetin.

[0012] Furthermore, the method for synthesizing dihydromyricetin provided by the present invention also has the following characteristics: the flow rate of hydrogen is 0.1-1.0 L / min.

[0013] Furthermore, the method for synthesizing dihydromyricetin provided by the present invention also has the following characteristics: the reaction is carried out in a solvent environment, and the solvent is selected from alcohol. DETAILED DESCRIPTION

[0014] Example 1. Preparation of catalyst

[0015] Example 1.1. Pd-PEG2000 catalyst

[0016] (1) Preparation of palladium solution

[0017] Dissolve the palladium source: dissolve a certain amount of Na2[PdCl4] or PdCl2 in deionized water to obtain 1.0 mmol of palladium ion solution.

[0018] (2) Preparation of polyethylene glycol 2000 (PEG2000) solution

[0019] Take 1.0 g of PEG2000 and dissolve it in 10 ml of deionized water to obtain a PEG2000 solution.

[0020] (3) Reduction of Palladium

[0021] The dissolved palladium source solution is slowly added dropwise to the PEG2000 solution while stirring. At room temperature, a NaBH4 solution (e.g., 0.01 M, usually 2-3 times the amount of the palladium source) is gradually added to the reaction system to reduce palladium ions to form metallic palladium.

[0022] (4) Reaction, precipitation, separation and drying

[0023] Continue stirring the reaction mixture for 1 to 2 hours to ensure that the palladium is completely reduced and loaded onto PEG2000. If precipitation occurs, the insoluble matter can be removed by centrifugation or filtration, and then the unreacted reducing agent and solvent can be removed by washing. The excess solvent is removed by rotary evaporation or low-temperature vacuum drying to obtain the final Pd-PEG2000 catalyst.

[0024] Example 1.2. Pd-PEG200 catalyst

[0025] (1) Preparation of palladium solution

[0026] Dissolve the palladium source: dissolve a certain amount of Na2[PdCl4] or PdCl2 in deionized water to obtain 1.0 mmol of palladium ion solution.

[0027] (2) Preparation of polyethylene glycol 200 (PEG200) solution

[0028] Take 1.0 g of PEG200 and dissolve it in 10 ml of deionized water to obtain a PEG200 solution.

[0029] (3) Reduction of Palladium

[0030] The dissolved palladium source solution is slowly added dropwise to the PEG200 solution while stirring. At room temperature, a NaBH4 solution (e.g., 0.01 M, usually 2-3 times the amount of the palladium source) is gradually added to the reaction system to reduce palladium ions to form metallic palladium.

[0031] (4) Reaction, precipitation, separation and drying

[0032] Continue stirring the reaction mixture for 1 to 2 hours to ensure that the palladium is completely reduced and loaded onto PEG200. If precipitation occurs, the insoluble matter can be removed by centrifugation or filtration, and then the unreacted reducing agent and solvent can be removed by washing. The excess solvent is removed by rotary evaporation or low-temperature vacuum drying to obtain the final Pd-PEG200 catalyst.

[0033] Example 1.3. Pd-PEG1000 catalyst

[0034] (1) Preparation of palladium solution

[0035] Dissolve the palladium source: dissolve a certain amount of Na2[PdCl4] or PdCl2 in deionized water to obtain 1.0 mmol of palladium ion solution.

[0036] (2) Preparation of polyethylene glycol 1000 (PEG1000) solution

[0037] Take 1.0 g of PEG1000 and dissolve it in 10 ml of deionized water to obtain a PEG1000 solution.

[0038] (3) Reduction of Palladium

[0039] The dissolved palladium source solution is slowly added dropwise to the PEG1000 solution while stirring. At room temperature, a NaBH4 solution (e.g., 0.01 M, usually 2-3 times the amount of the palladium source) is gradually added to the reaction system to reduce palladium ions to form metallic palladium.

[0040] (4) Reaction, precipitation, separation and drying

[0041] Continue stirring the reaction mixture for 1 to 2 hours to ensure that the palladium is completely reduced and loaded onto PEG1000. If precipitation occurs, the insoluble matter can be removed by centrifugation or filtration, and then the unreacted reducing agent and solvent can be removed by washing. The excess solvent is removed by rotary evaporation or low-temperature vacuum drying to obtain the final Pd-PEG1000 catalyst.

[0042] Example 1.4. Pd-PEG5000 catalyst

[0043] (1) Preparation of palladium solution

[0044] Dissolve the palladium source: dissolve a certain amount of Na2[PdCl4] or PdCl2 in deionized water to obtain 1.0 mmol of palladium ion solution.

[0045] (2) Preparation of polyethylene glycol 5000 (PEG5000) solution

[0046] Take 1.0 g of PEG5000 and dissolve it in 10 ml of deionized water to obtain a PEG5000 solution.

[0047] (3) Reduction of Palladium

[0048] The dissolved palladium source solution is slowly added dropwise to the PEG5000 solution while stirring. At room temperature, a NaBH4 solution (eg, 0.01 M, usually 2-3 times the amount of the palladium source) is gradually added to the reaction system to reduce the palladium ions to form metallic palladium.

[0049] (4) Reaction, precipitation, separation and drying

[0050] Continue stirring the reaction mixture for 1 to 2 hours to ensure that the palladium is completely reduced and loaded onto PEG5000. If precipitation occurs, the insoluble matter can be removed by centrifugation or filtration, and then the unreacted reducing agent and solvent can be removed by washing. The excess solvent is removed by rotary evaporation or low-temperature vacuum drying to obtain the final Pd-PEG5000 catalyst.

[0051] Example 2. Catalytic hydrogenation reaction

[0052] In this embodiment, myricetin is used as a substrate, and Pd-polyethylene glycol prepared in Example 1 is used as a catalyst to synthesize dihydromyricetin by catalytic hydrogenation under a hydrogen atmosphere. The reaction temperature is 25-55° C., the pressure is 1-5 MPa, and the reaction time is 1-5 hours to synthesize dihydromyricetin. The amount of the catalyst is 1-5% of the quality of myricetin. The flow rate of hydrogen is 0.1-1.0 L / min. The reaction is carried out in an alcohol solvent environment.

[0053] Example 2.1. (Optimal conditions)

[0054] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG2000 catalyst, and introduce hydrogen, control the flow rate to 0.5 L / min (0.4 L / min, 0.6L / min, 0.7L / min have similar results). Control the reaction temperature at 45°C (50°C, 40°C have similar results), control the reaction pressure at 2 MPa (3MPa has similar results), and maintain the reaction time for 3 hours (more than 3 hours have similar results). Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin, with a yield of 76% and a purity of 91%. Use ethyl acetate and water for liquid-liquid distribution to remove insoluble impurities, and then purify by silica gel column chromatography to finally obtain dihydromyricetin with a purity greater than 98%.

[0055] 1 H-NMR (DMSO-d6, 500 MHz)δ: 4.88 (1H,d, J = 11Hz), 4.42 (1H, dd, J =11, 6.5Hz), 5.91 (1H,d,J=2.0 Hz), 5.84(1H, d, J=2.0Hz), 6.33 (1H, s), 6.38(1H,s); 13 C-NMR (DMSO-d6, 500MHz)δ:83.2, 71.5, 197.8, 163.2, 95.8, 166.8,94.7, 162.5, 100.4, 127.2, 106.9, 145.7, 133.1, 145.9, 106.9; m / z[M+H]+ :343.25.

[0056] Example 2.2. (lower catalyst dosage)

[0057] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 0.8g of 1% Pd-PEG2000 catalyst, and introduce hydrogen at a flow rate of 0.5 L / min. Control the reaction temperature at 45°C, the reaction pressure at 2 MPa, and maintain the reaction time for 3 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin with a yield of 57% and a purity of 73%.

[0058] Example 2.3. (Extremely low catalyst dosage)

[0059] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 0.5% 0.4g of Pd-PEG2000 catalyst, and introduce hydrogen, controlling the flow rate to 0.5 L / min. The reaction temperature was controlled at 45°C, the reaction pressure was controlled at 2 MPa, and the reaction time was maintained for 3 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin, with a yield of 27% and a purity of 35%. Use ethyl acetate and water for liquid-liquid distribution to remove insoluble impurities, and then purify by silica gel column chromatography, and the crude yield is reduced by half again.

[0060] Example 2.4 (higher catalyst dosage)

[0061] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 5% 4g of Pd-PEG2000 catalyst, and introduce hydrogen at a flow rate of 0.5 L / min. Control the reaction temperature at 45°C, the reaction pressure at 2 MPa, and maintain the reaction time for 3 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin with a yield of 53% and a purity of 79%.

[0062] Example 2.5 (Extremely high catalyst dosage)

[0063] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 8g of 10% Pd-PEG2000 catalyst, and introduce hydrogen, controlling the flow rate to 0.5 L / min. The reaction temperature was controlled at 45°C, the reaction pressure was controlled at 2 MPa, and the reaction time was maintained for 3 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin, with a yield of 50% and a purity of 64%. Ethyl acetate and water were used for liquid-liquid distribution to remove insoluble impurities, and then purified by silica gel column chromatography, and the crude product was reduced by one third again.

[0064] Example 2.6 (Selection of solvent)

[0065] Add 80g (0.25mol) of myricetin and 400ml of methanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG2000 catalyst, and introduce hydrogen at a flow rate of 0.5 L / min. Control the reaction temperature at 45°C, the reaction pressure at 2 MPa, and maintain the reaction time for 3 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin with a yield of 68% and a purity of 86%.

[0066] Example 2.7 (Selection of solvent)

[0067] Add 80g (0.25mol) of myricetin and 400ml of water to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG2000 catalyst, and introduce hydrogen at a flow rate of 0.5 L / min. Control the reaction temperature at 45°C and the reaction pressure at 2 MPa for 3 hours. No product.

[0068] Example 2.8 (Selection of solvent)

[0069] Add 80g (0.25mol) of myricetin and 400ml of DMSO to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG2000 catalyst, and introduce hydrogen, controlling the flow rate to 0.5 L / min. The reaction temperature was controlled at 45°C, the reaction pressure was controlled at 2 MPa, and the reaction time was maintained for 3 hours. Cool and filter to remove the catalyst, and evaporate the solvent under reduced pressure to obtain crude dihydromyricetin with a yield of 28% and a purity of 16%. Ethyl acetate and water were used for liquid-liquid distribution to remove insoluble impurities, and then purified by silica gel column chromatography.

[0070] Example 2.9 (high temperature)

[0071] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG2000 catalyst, and introduce hydrogen at a flow rate of 0.5 L / min. Control the reaction temperature at 55°C, the reaction pressure at 2 MPa, and maintain the reaction time for 3 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin with a yield of 25% and a purity of 72%.

[0072] Example 2.10 (low temperature)

[0073] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG2000 catalyst, and pass hydrogen at a flow rate of 0.5 L / min. The reaction temperature was controlled at 25°C, the reaction pressure was controlled at 2 MPa, and the reaction time was maintained for 3 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin with a yield of 12% and a purity of 44%. Use ethyl acetate and water for liquid-liquid distribution to remove insoluble impurities, and then purify by silica gel column chromatography, and the yield is reduced by half again.

[0074] Example 2.11 (low hydrogen flow rate)

[0075] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG2000 catalyst, and introduce hydrogen at a flow rate of 0.2 L / min. Control the reaction temperature at 45°C, the reaction pressure at 2 MPa, and maintain the reaction time for 3 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin with a yield of 29% and a purity of 67%.

[0076] Example 2.12 (hydrogen flow rate is too high)

[0077] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG2000 catalyst, and introduce hydrogen at a flow rate of 1 L / min. The reaction temperature was controlled at 45°C, the reaction pressure was controlled at 2 MPa, and the reaction time was maintained for 3 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin with a yield of 33% and a purity of 57%.

[0078] Example 2.13 (reaction pressure is low)

[0079] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG2000 catalyst, and introduce hydrogen at a flow rate of 0.5 L / min. Control the reaction temperature at 45°C, the reaction pressure at 1MPa, and maintain the reaction time for 3 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin with a yield of 48% and a purity of 73%.

[0080] Example 2.14 (Reaction pressure is high)

[0081] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG2000 catalyst, and introduce hydrogen at a flow rate of 0.5 L / min. Control the reaction temperature at 4°C, the reaction pressure at 5MPa, and maintain the reaction time for 3 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin with a yield of 57% and a purity of 81%.

[0082] Example 2.15 (short reaction time)

[0083] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG2000 catalyst, and introduce hydrogen, controlling the flow rate to 0.5 L / min. The reaction temperature was controlled at 45°C, the reaction pressure was controlled at 2MPa, and the reaction time was maintained for 1 hour. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin, with a yield of 45% and a purity of 84%. Use ethyl acetate and water for liquid-liquid distribution to remove insoluble impurities, and then purify by silica gel column chromatography, and the yield is reduced by one third again.

[0084] Example 2.16 (longer reaction time)

[0085] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG2000 catalyst, and introduce hydrogen at a flow rate of 0.5 L / min. Control the reaction temperature at 45°C, the reaction pressure at 2MPa, and maintain the reaction time for 5 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin with a yield of 70% and a purity of 89%.

[0086] Example 2.17 (Catalyst selected Pd-PEG200)

[0087] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG200 catalyst, and introduce hydrogen at a flow rate of 0.5 L / min. Control the reaction temperature at 45°C, the reaction pressure at 2 MPa, and maintain the reaction time for 3 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin with a yield of 16% and a purity of 46%.

[0088] Example 2.18 (Catalyst selected as Pd-PEG1000)

[0089] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG1000 catalyst, and introduce hydrogen at a flow rate of 0.5 L / min. Control the reaction temperature at 45°C, the reaction pressure at 2 MPa, and maintain the reaction time for 3 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin with a yield of 38% and a purity of 55%.

[0090] Example 2.19 (Catalyst selected Pd-PEG5000)

[0091] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-PEG5000 catalyst, and introduce hydrogen at a flow rate of 0.5 L / min. Control the reaction temperature at 45°C, the reaction pressure at 2 MPa, and maintain the reaction time for 3 hours. Cool down and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin with a yield of 29% and a purity of 48%.

[0092] Example 2.20 (Catalyst selected as Pd-C)

[0093] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-C catalyst, and introduce hydrogen at a flow rate of 0.5 L / min. Control the reaction temperature at 45°C, the reaction pressure at 2MPa, and maintain the reaction time for 3 hours. Cool down and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin, with a yield of 0%.

[0094] Example 2.21 (Catalyst selected Pd-C-PEG2000)

[0095] Add 80g (0.25mol) of myricetin and 400ml of ethanol to a 2L reactor, stir until dissolved, introduce 1.6g of 2% Pd-C-PEG2000 catalyst, and introduce hydrogen at a flow rate of 0.5 L / min. Control the reaction temperature at 45°C, the reaction pressure at 2 MPa, and maintain the reaction time for 3 hours. Cool and filter to remove the catalyst, evaporate the solvent to obtain crude dihydromyricetin with a yield of 5% and a purity of 22%.

[0096] Functions and effects of this embodiment:

[0097] This embodiment achieves efficient hydrogenation of myricetin by using catalysts such as Pd-PEG2000, with mild reaction conditions and reduced side reactions. The catalyst has good stability and recyclability and can be reused multiple times without affecting the reaction effect. The method is simple to operate, easy to industrialize, has high product purity and high yield, effectively reduces production costs, and has broad application prospects.

Claims

1. A method for synthesizing dihydromyricetin, characterized in that: Dihydromyricetin was synthesized by catalytic hydrogenation using myricetin as substrate and Pd-polyethylene glycol as catalyst in a hydrogen atmosphere.

2. A method for synthesizing dihydromyricetin as claimed in claim 1, characterized in that: The polyethylene glycol in the Pd-polyethylene glycol is selected from polyethylene glycols having an average molecular weight greater than 1000.

3. A method for synthesizing dihydromyricetin as claimed in claim 1, characterized in that: Step 1. Prepare a palladium source solution: dissolve Na2[PdCl4] or PdCl2 in deionized water to obtain a palladium ion solution; Step 2. Preparation of polyethylene glycol solution: dissolving polyethylene glycol in deionized water to obtain a polyethylene glycol solution; Step 3. Reduction of palladium: slowly drop the dissolved palladium source solution into the polyethylene glycol solution while stirring, and gradually add NaBH4 solution to the reaction system at room temperature to reduce the palladium ions to form metallic palladium; Step 4. Reaction and precipitation separation and drying: continue to stir the reaction mixture for 1-2 hours to ensure that the palladium is completely reduced and loaded onto the polyethylene glycol, and then post-treat to obtain Pd-polyethylene glycol.

4. A method for synthesizing dihydromyricetin as claimed in claim 1, characterized in that: The reaction temperature is 25-55°C, the pressure is 1-5 MPa, and the reaction time is 1-5 hours to synthesize dihydromyricetin.

5. A method for synthesizing dihydromyricetin as claimed in claim 1, characterized in that: The dosage of the catalyst is 1-5% of the quality of myricetin.

6. A method for synthesizing dihydromyricetin as claimed in claim 1, characterized in that: The flow rate of hydrogen was 0.1-1.0 L / min.

7. A method for synthesizing dihydromyricetin as claimed in claim 1, characterized in that: The reaction is carried out in a solvent environment, and the solvent is selected from alcohol.

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