A method for preparing 19-formyl-4-androstene-3,17-dione by electrocatalytic oxidation of a carbonaceous volcano-shaped catalyst

Abstract

The invention discloses a method for preparing 19-formyl-4-androstene-3,17-dione by electrocatalytic oxidation of a carbonaceous volcano-shaped catalyst. The method adopts a continuous flow type electrolyzer for reaction, wherein the carbonaceous volcano-shaped catalyst is used as a working electrode in the anode chamber, 19-hydroxymethyl-4-androstene-3,17-dione is dissolved in an organic alkaline solution as an anode solution, and nitroxide free radicals are added as a medium; in the cathode chamber, nickel foam is used as a counter electrode, and an alkaline solution is used as a cathode solution, and 19-formyl-4-androstene-3,17-dione is obtained by reaction under one condition. The present invention uses ACT as a medium for electrocatalytic alcohol oxidation reaction, avoids the use of heavy metals such as manganese and chromium, and the process is green, environmentally friendly, simple and efficient; the crater-shaped catalyst used has a large specific surface area, can anchor ACT on the electrode surface, and activate free radicals faster to reduce concentration polarization, improve mass transfer efficiency and catalytic activity, thereby improving reaction efficiency, and has a short production cycle and high time-space yield.

Description

Technical Field

[0001] The invention relates to a method for synthesizing an organic chemical product, and in particular to a method for preparing 19-formyl-4-androstene-3,17-dione by electrocatalytic oxidation of a carbonaceous volcano-shaped catalyst. Background Art

[0002] Steroid hormone carbonyl intermediates are an important class of steroid drug intermediates, which can be used to prepare drugs such as tibolone, hydrocortisone, mifepristone, dienogest, norethindrone, etc. The method for preparing steroid hormone carbonyl intermediates in the prior art usually uses sterol as a raw material, and obtains steroid hormone carbonyl intermediates through Jones reagent oxidation, such as the synthesis of 19-formyl-4-androstene-3,17-dione and 7α-methyl-19-aldehyde-4-androstene-3,17-dione. Using 19-hydroxymethyl-4-androstene-3,17-dione as a raw material, the product 19-formyl-4-androstene-3,17-dione is obtained through Jones reagent oxidation. At present, heavy metal chromium oxidants are used for sterol oxidation. The chromium oxidation process conditions are strict, the reaction feed amount must be excessive, and there are problems such as poor oxidation selectivity, heavy metal chromium pollution of the environment, and difficulty in chromium treatment.

[0003] Therefore, the development of green, highly selective and efficient alcohol oxidation methods has attracted more and more attention. The key to achieving efficient and highly selective oxidation of alcohols lies in catalysts. There are many reports on corresponding catalyst research, including various catalytic fields such as homogeneous, heterogeneous, biological and enzyme-mimicking. Among them, 4-acetylamino-2,2,6,6-tetramethylpiperidin-1-nitrogen oxide free radical (ACT) is eye-catching as an organic small molecule catalyst. ACT is a stable N-oxyl free radical and is now available as an industrial commodity. ACT catalyzes alcohol oxidation reactions, which are simple to operate, fast, mild in conditions, and show near-quantitative selectivity for aldehydes or ketones, and have been successfully applied in industrial production. Although ACT shows good catalytic activity and selectivity, the reaction of ACT as a medium is affected by concentration polarization, and has disadvantages such as poor solubility and weak mass transfer. At the same time, ACT is expensive and difficult to recover after the reaction, which has become a bottleneck for the widespread application of ACT catalytic alcohol oxidation reactions. Summary of the invention

[0004] In view of the above problems existing in the prior art, the present invention provides a method for preparing 19-formyl-4-androstene-3,17-dione by electrocatalytic oxidation of 19-hydroxymethyl-4-androstene-3,17-dione using a carbonaceous volcano-shaped catalyst. The process uses ACT as a medium for the electrocatalytic alcohol oxidation reaction, avoiding the use of heavy metals such as manganese and chromium. The process is green, environmentally friendly, simple and efficient. The pure carbon material used in the catalyst is a good electrode material, while avoiding the consumption of precious metal raw materials. The unique crater shape has a large specific surface area, and can better anchor the nitrogen oxide free radicals on the electrode surface, activate ACT faster, reduce concentration polarization, improve mass transfer efficiency and catalytic activity, and thus improve reaction efficiency. The carbonaceous volcano-shaped catalyst exhibits the advantages of low production cost, high reaction efficiency, high product yield, short production cycle, and high space-time yield during the reaction process.

[0005] The present invention defines a method for preparing 19-formyl-4-androstene-3,17-dione by electrocatalytic oxidation of a carbonaceous volcano-shaped catalyst, wherein a constant current meter is used to control the reaction current, a continuous flow type electrolytic cell is used to carry out the reaction, a cathode chamber and an anode chamber are separated by an ion exchange membrane, a carbonaceous volcano-shaped catalyst is used as a working electrode in the anode chamber, a solution obtained by dissolving the reaction substrate 19-hydroxymethyl-4-androstene-3,17-dione shown in formula (1a) in a mixed solvent is used as an anode solution, and nitroxide free radicals are used as a medium; in the cathode chamber, nickel foam is used as a counter electrode, and 0.1-2.0 mol / L sodium carbonate solution is used as the cathode solution, and the reaction is carried out in a constant temperature water bath. The electrocatalytic oxidation reaction is carried out at 20-60°C under the reaction current of 0.5-1.5A and the cell voltage of 1-20V. After the reaction time of 30-70 minutes, the reaction solution is cooled, extracted with an organic solvent, and the organic layer is distilled at normal pressure to obtain 19-formyl-4-androstene-3,17-dione shown in formula (1b). The reaction equation is as follows:

[0006]

[0007] Furthermore, the present invention also defines that the volume of the cathode chamber and the anode chamber are both 50-250 mL; the volume usage of the anode solvent is 10-20 mmol / L based on the amount of 19-hydroxymethyl-4-androstene-3,17-dione.

[0008] Furthermore, the present invention also defines that the mixed solvent of the anode chamber is divided into a main solvent and a secondary solvent, the main solvent is a 0.1-2.0 mol / L sodium carbonate aqueous solution; the secondary solvent is one of tetrahydrofuran, dichloromethane, acetonitrile or acetone; the feed volume ratio of the main solvent and the secondary solvent is 3:7-7:3, and the pH of the mixed solvent is 9.0-12.0.

[0009] Furthermore, the present invention also defines the nitroxide free radical as 4-acetylamino-2,2,6,6-tetramethylpiperidin-1-nitroxide free radical (also known as ACT), and the concentration of the nitroxide free radical in the anode mixed solution is 0.1-2 mmol / L.

[0010] Furthermore, the present invention also limits the concentration of the sodium carbonate solution in the cathode chamber to 0.1-1.0 mol / L.

[0011] Furthermore, the present invention also limits the organic solvent used for extraction to toluene, dichloromethane, chloroform or ethyl acetate.

[0012] Furthermore, the present invention further defines that the carbonaceous volcano-shaped catalyst is composed of a carrier carbon felt and a carbonaceous nano-volcano crater supported on the carbon felt, and the loading amount of the carbonaceous nano-volcano crater on the carbon felt is 5-30 mg / cm 3 .

[0013] Furthermore, the present invention also defines the size of the carbonaceous volcano-shaped catalyst as 3×3 cm 2 .

[0014] Furthermore, the present invention also defines that the preparation method of the carbonaceous volcano-shaped catalyst comprises the following steps:

[0015] 1) According to the feed ratio, surfactant and carbon precursor molecules are respectively dissolved in 30-100 mL of water and ultrasonically dispersed at room temperature, which is called solution A. The surfactant is a mixture of P123 and sodium oleate; the carbon precursor molecule is ribose;

[0016] 2) placing the solution A and the carbon felt carrier in step 1) into a hydrothermal kettle for hydrothermal carbonization, and performing a hydrothermal reaction at 120-180° C. for 6-36 hours. After the reaction is completed, the carbon felt carrier is cooled to room temperature, and the carbon felt carrier is taken out, and repeatedly washed with distilled water and ethanol, and then vacuum dried at 60° C. to obtain a supported carbonaceous volcano-like catalyst;

[0017] 3) placing the supported catalyst dried in step 2) in a tubular furnace for high-temperature carbonization, and calcining it in an atmosphere of high-purity gas at a temperature of 400-900° C. for 2-6 hours. After the reaction is completed, the carbonaceous volcano-shaped catalyst is obtained.

[0018] Furthermore, the present invention also defines that the dual surfactants in step 1) are P123 and sodium oleate, the feed ratio is 16:1, and the carbon precursor molecule is ribose; the hydrothermal temperature in step 2) is 160-180°C, and the hydrothermal time is 6-24 hours; the high-purity gas introduced in step 3) is nitrogen or argon, the calcination temperature is 600-900°C, and the calcination time is 4-6 hours.

[0019] By adopting the above technology, compared with the prior art, the present invention has the following beneficial effects:

[0020] (1) The present invention uses 19-hydroxymethyl-4-androstene-3,17-dione as a raw material, and the target product is 19-formyl-4-androstene-3,17-dione, with substantially no by-products produced;

[0021] (2) The present invention better anchors ACT on the electrode surface through the carbonaceous crater catalyst, greatly improving the mass transfer efficiency and reaction efficiency. At the same time, compared with other catalysts, the amount of ACT used is reduced, which greatly reduces the production cost;

[0022] (3) The present invention adopts electrocatalysis to carry out oxidation reaction, and anodic oxidation produces 19-formyl-4-androstene-3,17-dione, and hydrogen is the only product of the cathode. The reaction process is at normal temperature and pressure, the reaction conditions are mild and controllable, and the reaction process is green and environmentally friendly;

[0023] (4) Compared with the noble metal catalysts such as Au and Pd commonly used in the prior art, the present invention uses pure carbon materials and free radical media, which has low overall cost and avoids the consumption of noble metal raw materials;

[0024] (5) The present invention adopts a specific process method, the raw material conversion rate reaches 100%, the selectivity of 19-formyl-4-androstene-3,17-dione reaches more than 99%, the product yield reaches more than 99%, the reaction time is short, and the time-space yield is high. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1a is a SEM image of the HOCFs / GF catalyst of Example 1 at 1 μm;

[0026] Figure 1b is a SEM image of the HOCFs / GF catalyst of Example 1 at 200 nm;

[0027] Figure 2 This is a graph showing the relative concentration changes of raw materials and products during the reaction of Example 1. DETAILED DESCRIPTION

[0028] The technical solution of the present invention is further described in detail below through specific embodiments in conjunction with the accompanying drawings.

[0029] Example 1: Synthesis of HOCFs / GF-V1 catalyst and electrocatalytic oxidation of 19-hydroxymethyl-4-androstene-3,17-dione to produce 19-formyl-4-androstene-3,17-dione

[0030] (1) According to the feed ratio, 0.12 mmol sodium oleate, 0.0075 mmol P123 and 3 g ribose were dissolved in 100 mL water and ultrasonically dispersed at room temperature for 30 minutes, which was called solution A.

[0031] (2) Solution A in step (1) and a carbon felt carrier (size about 3×3 cm) were added to the mixture. 2 ) was added to a hydrothermal reactor and subjected to hydrothermal reaction at 160°C for 12 hours, then cooled to room temperature, the carbon felt was taken out, washed twice with distilled water and ethanol, and then vacuum dried at 60°C to obtain a supported catalyst. The loading amount of the carbonaceous volcano-like catalyst on the carbon felt was 15 mg / cm 3 ;

[0032] (3) The catalyst dried in step (2) is placed in a crucible and placed in a nitrogen furnace, and the temperature is increased to 600° C. at a heating rate of 10° C. / min and kept constant for 1 hour, and then the temperature is increased to 900° C. at a heating rate of 5° C. / min and kept constant for 1 hour, and then cooled to room temperature to obtain the carbonaceous volcano-shaped catalyst, which is marked as HOCFs / GF-V1. Its SEM scanning electron microscope image is as follows: Figure 1a and 1b. Figure 1a , Figure 1b It can be found that the HOCFs / GF catalyst has a crater morphology and is evenly distributed, with an opening size of about 300-850nm.

[0033] The catalytic performance of the HOCFs / GF catalyst prepared in Example 1 was tested, and the specific method was as follows:

[0034] The reaction current was controlled by a constant current meter, and the reaction was carried out in a continuous flow electrolyzer. In the anode chamber, the HOCFs / GF catalyst was cut into pieces of about 3×3 cm 2 The size of the cathode chamber is 100 mL, and the two electrode chambers are separated by an ion exchange membrane.

[0035] S1: Take 20mmol / L 19-hydroxymethyl-4-androstene-3,17-dione (denoted as 1a) as the reaction substrate and dissolve it in 100mL of a mixed solvent as the anode solution, wherein the main solvent is 1 mol / L sodium carbonate aqueous solution, the secondary solvent is acetonitrile, the volume ratio is 5:5, and 2mmol / L 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-nitroxide free radical (ACT) is added as the medium; the cathode solution uses 100mL 1mol / L sodium carbonate aqueous solution;

[0036] S2: Place the entire electrolytic cell in a constant temperature water bath, control the temperature of the reaction system to 30°C, and stir magnetically, control the pH to 11.0, the current to 1A, the voltage to 0.6-1.5 V, and react for 30 minutes;

[0037] S3: After cooling the electrolytic solution in the anode chamber of step S2 to room temperature, extracting and stratifying with ethyl acetate, evaporating and separating the ethyl acetate phase, 19-formyl-4-androstene-3,17-dione (denoted as 1b) is obtained. Figure 2 As shown, with the increase of reaction time, the raw material 19-hydroxymethyl-4-androstene-3,17-dione is gradually decreasing, and the main product 19-formyl-4-androstene-3,17-dione is gradually increasing. Among them, when the reaction reaches 30 minutes, the conversion rate of 19-hydroxymethyl-4-androstene-3,17-dione is 99.92%, the selectivity of 19-formyl-4-androstene-3,17-dione is 99.95%, and the calculated space-time yield can reach 16.47.

[0038] Example 2: Electrocatalytic oxidation of 19-hydroxymethyl-4-androstene-3,17-dione to produce 19-formyl-4-androstene-3,17-dione using HOCFs / GF-V2 catalyst

[0039] (1) According to the feed ratio, 0.12 mmol sodium oleate, 0.0075 mmol P123 and 3 g ribose were dissolved in 80 mL water and ultrasonically dispersed at room temperature for 30 min, which was called solution A.

[0040] (2) Solution A in step (1) and a carbon felt carrier (size about 3×3 cm) were added to the mixture. 2 ) was added to a hydrothermal reactor and subjected to hydrothermal reaction at 160°C for 24 hours, then cooled to room temperature, the carbon felt was taken out, washed twice with distilled water and ethanol, and then vacuum dried at 60°C to obtain a supported catalyst. The loading amount of the carbonaceous volcano-shaped catalyst on the carbon felt was 30 mg / cm 3 ;

[0041] (3) The catalyst dried in step (2) is placed in a crucible and placed in a nitrogen furnace. The temperature is increased to 700° C. at a heating rate of 10° C. / min and kept constant for 1 hour. Then, the temperature is increased to 900° C. at a heating rate of 5° C. / min and kept constant for 1 hour. The crucible is cooled to room temperature to obtain the carbonaceous volcano-shaped catalyst, which is labeled as HOCFs / GF-V2.

[0042] The catalytic performance of the HOCFs / GF catalyst prepared in Example 2 was tested, and the specific method was as follows:

[0043] The reaction current was controlled by a constant current meter, and the reaction was carried out in a continuous flow electrolyzer. In the anode chamber, the HOCFs / GF catalyst was cut into pieces of about 3×3 cm 2 The size of the cathode chamber is 150 mL, and the two electrode chambers are separated by an ion exchange membrane.

[0044] S1: Take 20mmol / L 19-hydroxymethyl-4-androstene-3,17-dione as the reaction substrate and dissolve it in 150mL of a mixed solvent as the anode solution, wherein the main solvent is 0.5mol / L sodium carbonate aqueous solution, the secondary solvent is dichloromethane, the volume ratio is 3:7, and 1.5mmol / L 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-nitroxide free radical (ACT) is added as the medium; the cathode solution uses 150mL 0.5mol / L sodium carbonate aqueous solution;

[0045] S2: Place the entire electrolytic cell in a constant temperature water bath, control the temperature of the reaction system to 40°C, and stir magnetically, control the pH to 10.0, the current to 1.5A, the voltage to 0.5-1.2V, and react for 40 minutes;

[0046] S3: After cooling the electrolytic solution in the anode chamber of step S2 to room temperature, extract and decompose the solution with toluene, and separate the toluene phase by evaporation to obtain the 19-formyl-4-androstene-3,17-dione product. As the reaction time increases, the raw material 19-hydroxymethyl-4-androstene-3,17-dione gradually decreases, and the main product 19-formyl-4-androstene-3,17-dione gradually increases. Among them, when the reaction reaches 30 minutes, the conversion rate of 19-hydroxymethyl-4-androstene-3,17-dione is 90.92%, the selectivity of 19-formyl-4-androstene-3,17-dione is 99.51%, and the calculated time-space yield can reach 12.12.

[0047] Example 3: Electrocatalytic oxidation of 19-hydroxymethyl-4-androstene-3,17-dione to produce 19-formyl-4-androstene-3,17-dione using HOCFs / GF-V3 catalyst

[0048] (1) According to the feed ratio, 0.12 mmol sodium oleate, 0.0075 mmol P123 and 3 g ribose were dissolved in 50 mL water and ultrasonically dispersed at room temperature for 30 minutes, which was called solution A.

[0049] (2) Solution A in step (1) and a carbon felt carrier (size about 3×3 cm) were added. 2) was added to a hydrothermal reactor and subjected to hydrothermal reaction at 170°C for 18 hours. The mixture was cooled to room temperature, and the carbon felt was taken out. The carbon felt was washed twice with distilled water and ethanol, and then vacuum dried at 60°C to obtain a supported catalyst. The loading amount of the carbonaceous volcano-shaped catalyst on the carbon felt was 25 mg / cm 3 ;

[0050] (3) The catalyst dried in step (2) is placed in a crucible, and placed in a nitrogen furnace, and the temperature is increased to 800° C. at a heating rate of 5° C. / min, and then cooled to room temperature after being kept at the constant temperature for 2 hours to obtain the carbonaceous volcano-shaped catalyst, which is marked as HOCFs / GF-V3.

[0051] The catalytic performance of the HOCFs / GF catalyst prepared in Example 3 was tested, and the specific method was as follows:

[0052] The reaction current was controlled by a constant current meter, and the reaction was carried out in a continuous flow electrolyzer. In the anode chamber, the HOCFs / GF catalyst was cut into pieces of about 3×3 cm 2 The cathode chamber and anode chamber have a volume of 200 mL each, and the two electrode chambers are separated by an ion exchange membrane.

[0053] S1: Take 15mmol / L 19-hydroxymethyl-4-androstene-3,17-dione as the reaction substrate and dissolve it in 200mL of a mixed solvent as the anode solution, wherein the main solvent is 2mol / L sodium carbonate aqueous solution, the secondary solvent is acetone, the volume ratio is 4:6, and 1mmol / L 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-nitroxide free radical (ACT) is added as the medium; the cathode solution uses 200mL of 2mol / L sodium carbonate aqueous solution;

[0054] S2: Place the entire electrolytic cell in a constant temperature water bath, control the temperature of the reaction system to 60°C, and stir magnetically, control the pH to 10.0, the current to 1A, the voltage to 0.6-1.5 V, and react for 45 minutes;

[0055] S3: After cooling the electrolytic solution in the anode chamber of step S2 to room temperature, extract and separate the layers with dichloromethane, and evaporate and separate the dichloromethane phase to obtain the 19-formyl-4-androstene-3,17-dione product. As the reaction time increases, the raw material 19-hydroxymethyl-4-androstene-3,17-dione gradually decreases, and the main product 19-formyl-4-androstene-3,17-dione gradually increases. Among them, when the reaction reaches 30 minutes, the conversion rate of 19-hydroxymethyl-4-androstene-3,17-dione is 84.14%, the selectivity of 19-formyl-4-androstene-3,17-dione is 97.94%, and the calculated time-space yield can reach 9.81.

[0056] Example 4: Electrocatalytic oxidation of 19-hydroxymethyl-4-androstene-3,17-dione to produce 19-formyl-4-androstene-3,17-dione using HOCFs / GF-V4 catalyst

[0057] (1) According to the feed ratio, 0.12 mmol sodium oleate, 0.0075 mmol P123 and 3 g ribose were dissolved in 40 mL water and ultrasonically dispersed at room temperature for 30 minutes, which was called solution A.

[0058] (2) Solution A in step (1) and a carbon felt carrier (size about 3×3 cm) were added. 2 ) was added to a hydrothermal reactor and subjected to hydrothermal reaction at 180°C for 12 hours, then cooled to room temperature, the carbon felt was taken out, washed twice with distilled water and ethanol, and then vacuum dried at 60°C to obtain a supported catalyst. The loading amount of the carbonaceous volcano-like catalyst on the carbon felt was 10 mg / cm 3 ;

[0059] (3) The catalyst dried in step (2) is placed in a crucible, and then placed in a nitrogen furnace, and the temperature is increased to 600° C. at a heating rate of 5° C. / min, and then cooled to room temperature after being kept at the constant temperature for 2 hours to obtain the carbonaceous volcano-shaped catalyst, which is marked as HOCFs / GF-V4.

[0060] The catalytic performance of the HOCFs / GF catalyst prepared in Example 4 was tested, and the specific method was as follows:

[0061] The reaction current was controlled by a constant current meter, and the reaction was carried out in a continuous flow electrolyzer. In the anode chamber, the HOCFs / GF catalyst was cut into pieces of about 3×3 cm 2 The size of the cathode chamber is 250 mL, and the two electrode chambers are separated by an ion exchange membrane.

[0062] S1: Take 10mmol / L 19-hydroxymethyl-4-androstene-3,17-dione as the reaction substrate and dissolve it in 250mL of a mixed solvent as the anode solution, wherein the main solvent is 2mol / L sodium carbonate aqueous solution, the secondary solvent is tetrahydrofuran, the volume ratio is 6:4, and 0.5mmol / L 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-nitroxide free radical (ACT) is added as the medium; the cathode solution uses 250mL of 2mol / L sodium carbonate aqueous solution;

[0063] S2: Place the entire electrolytic cell in a constant temperature water bath, control the temperature of the reaction system to 50°C, and stir magnetically, control the pH to 12.0, the current to 0.5A, the voltage to 0.8-1.5V, and react for 65 minutes;

[0064] S3: After cooling the electrolytic solution in the anode chamber of step S2 to room temperature, extract and separate the layers with chloroform, and separate the chloroform phase by evaporation to obtain the 19-formyl-4-androstene-3,17-dione product. As the reaction time increases, the raw material 19-hydroxymethyl-4-androstene-3,17-dione gradually decreases, and the main product 19-formyl-4-androstene-3,17-dione gradually increases. Among them, when the reaction reaches 30 minutes, the conversion rate of 19-hydroxymethyl-4-androstene-3,17-dione is 80.56%, the selectivity of 19-formyl-4-androstene-3,17-dione is 96.36%, and the calculated time-space yield is 6.40.

[0065] Example 5: Electrocatalytic oxidation of 19-hydroxymethyl-4-androstene-3,17-dione to produce 19-formyl-4-androstene-3,17-dione using HOCFs / GF-V5 catalyst

[0066] (1) According to the feed ratio, 0.12 mmol sodium oleate, 0.0075 mmol P123 and 3 g ribose were dissolved in 30 mL water and ultrasonically dispersed at room temperature for 30 min, which was called solution A.

[0067] (2) Solution A in step (1) and a carbon felt carrier (size about 3×3 cm) were added to the mixture. 2 ) was added to a hydrothermal kettle, and the reaction was carried out at 180°C for 6 hours, then cooled to room temperature, the carbon felt was taken out, and washed twice with distilled water and ethanol, and then vacuum dried at 60°C to obtain a supported catalyst. The loading amount of the carbonaceous volcano-shaped catalyst on the carbon felt was 5 mg / cm 3 ;

[0068] (3) The catalyst dried in step (2) is placed in a crucible, and then placed in a nitrogen furnace, and the temperature is increased to 400° C. at a heating rate of 5° C. / min, and then cooled to room temperature after being kept at the constant temperature for 2 hours to obtain the carbonaceous volcano-shaped catalyst, which is marked as HOCFs / GF-V5.

[0069] The catalytic performance of the HOCFs / GF catalyst prepared in Example 5 was tested, and the specific method was as follows:

[0070] The reaction current was controlled by a constant current meter, and the reaction was carried out in a continuous flow electrolyzer. In the anode chamber, the HOCFs / GF catalyst was cut into pieces of about 3×3 cm 2The size of the cathode chamber is 50 mL, and the two electrode chambers are separated by an ion exchange membrane.

[0071] S1: Take 10mmol / L 19-hydroxymethyl-4-androstene-3,17-dione as the reaction substrate and dissolve it in 50mL of a mixed solvent as the anode solution, wherein the main solvent is 0.1mol / L sodium carbonate aqueous solution, the secondary solvent is acetone, the volume ratio is 7:3, and 0.1mmol / L 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-nitroxide free radical (ACT) is added as the medium; the cathode solution uses 50mL 0.1mol / L sodium carbonate aqueous solution;

[0072] S2: Place the entire electrolytic cell in a constant temperature water bath, control the temperature of the reaction system to 20°C, and stir magnetically, control the pH to 12.0, the current to 0.5A, the voltage to 0.9-1.5V, and react for 70 minutes;

[0073] S3: After cooling the electrolytic solution in the anode chamber of step S2 to room temperature, extract and separate the layers with dichloromethane, and evaporate and separate the dichloromethane phase to obtain the 19-formyl-4-androstene-3,17-dione product. As the reaction time increases, the raw material 19-hydroxymethyl-4-androstene-3,17-dione gradually decreases, and the main product 19-formyl-4-androstene-3,17-dione gradually increases. Among them, when the reaction reaches 30 minutes, the conversion rate of 19-hydroxymethyl-4-androstene-3,17-dione is 78.58%, the selectivity of 19-formyl-4-androstene-3,17-dione is 96.14%, and the calculated time-space yield is 5.78.

[0074] Example 6: GF electrocatalytic oxidation of 19-hydroxymethyl-4-androstene-3,17-dione to produce 19-formyl-4-androstene-3,17-dione

[0075] The reaction current was controlled by a constant current meter, and the reaction was carried out in a continuous flow electrolytic cell. In the anode chamber, the GF was cut into pieces of about 3×3 cm 2 The size of the cathode chamber is directly used as the working electrode; in the cathode chamber, the nickel foam is used as the counter electrode. The volume of the cathode chamber and the anode chamber is 100mL, and the two electrode chambers are separated by an ion exchange membrane.

[0076] S1: Take 20mmol / L 19-hydroxymethyl-4-androstene-3,17-dione as the reaction substrate and dissolve it in 100mL of a mixed solvent as the anode solution, wherein the main solvent is 1mol / L sodium carbonate aqueous solution, the secondary solvent is acetonitrile, the volume ratio is 6:4, and 2mmol / L 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-nitroxide free radical (ACT) is added as the medium; the cathode solution uses 100mL 1mol / L sodium carbonate aqueous solution;

[0077] S2: Place the entire electrolytic cell in a constant temperature water bath, control the temperature of the reaction system to 30°C, and stir magnetically, control the pH to 10.0, the current to 0.5A, the voltage to 0.6-1.2V, and react for 70 minutes;

[0078] S3: After cooling the electrolytic solution in the anode chamber of step S2 to room temperature, extract and separate the layers with ethyl acetate, and evaporate and separate the ethyl acetate phase to obtain the 19-formyl-4-androstene-3,17-dione product. The conversion rate of 19-hydroxymethyl-4-androstene-3,17-dione is 69.97%, the selectivity of 19-formyl-4-androstene-3,17-dione is 85.37%, and the calculated space-time yield is 4.57.

[0079] For the electrocatalytic oxidation of 19-hydroxymethyl-4-androstene-3,17-dione to produce 19-formyl-4-androstene-3,17-dione, the conversion rate, selectivity and Faraday efficiency of the two catalysts (HOCFs / GF, GF) prepared above at different ACT contents were compared. The results are shown in Table 1.

[0080] Table 1 Conversion rate, selectivity and Faraday efficiency of catalysts at different ACT contents

[0081]

[0082] As can be seen from Table 1, in the presence of 2mmol / L 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-nitroxide free radical (ACT), when the reaction lasts for 30 minutes, the conversion rate of 19-hydroxymethyl-4-androstene-3,17-dione is 99.92%, the selectivity of 19-formyl-4-androstene-3,17-dione is 99.95%, and the Faraday efficiency can reach 99.87%. In the reaction of electrocatalytic alcohol oxidation with low concentration (0.1mmol / L or 0.5mmol / L) of ACT as a medium, the conversion rate, selectivity and space-time yield of a series of catalysts such as HOCFs / GF are still higher than those of GF catalyst. Compared with GF catalyst, HOCFs / GF catalyst has good electrocatalytic activity, which may be due to the confinement effect of the unique nano-carbon crater shape, which makes it easier for nitroxide free radicals to anchor on the active electrode surface. In the reaction of GF electrocatalytic oxidation, ACT free in the solution has a large mass transfer resistance and cannot be activated faster on the electrode surface. The ACT anchored on the active electrode surface through the nanocarbon craters can be activated more easily and quickly for the next reaction, reducing the mass transfer resistance of the reaction and greatly improving the reaction efficiency.

[0083] The above description is only part of the embodiments of the present invention and is not intended to limit the present invention. All equivalent changes and modifications made according to the content of the present invention are within the protection scope of the present invention.

Claims

1. A method for preparing 19-formyl-4-androstene-3,17-dione by electrocatalytic oxidation of a carbonaceous volcano-shaped catalyst, wherein a constant current meter is used to control the reaction current, a continuous flow electrolytic cell is used for the reaction, and the cathode chamber and the anode chamber are separated by an ion exchange membrane, characterized in that In the anode chamber, a carbonaceous volcano-shaped catalyst is used as a working electrode, a solution obtained by dissolving the reaction substrate 19-hydroxymethyl-4-androstene-3,17-dione shown in formula (1a) in a mixed solvent is used as an anode solution, and a nitroxide free radical is used as a medium; in the cathode chamber, a nickel foam is used as a counter electrode, and a 0.1-2.0 mol / L sodium carbonate solution is used as a cathode solution. The reaction is carried out in a constant temperature water bath, and an electrocatalytic oxidation reaction is carried out at 20-60°C at a reaction current of 0.5-1.5 A and a cell voltage of 1-20 V. After the reaction for 30-70 minutes, the reaction solution is cooled, extracted with an organic solvent, and the organic layer is distilled at atmospheric pressure to obtain 19-formyl-4-androstene-3,17-dione shown in formula (1b). The reaction equation is as follows: ； The carbonaceous volcano-shaped catalyst is composed of a carrier carbon felt and carbonaceous nano-volcano craters supported on the carbon felt. The preparation method of the carbonaceous volcano-shaped catalyst comprises the following steps: 1) According to the feed ratio, surfactant and carbon precursor molecules are dissolved in 30-100 mL of water respectively and dispersed by ultrasonic at room temperature, which is called solution A. The surfactant is a mixture of P123 and sodium oleate; the carbon precursor molecule is ribose; 2) placing the solution A and the carbon felt carrier in step 1) into a hydrothermal kettle for hydrothermal carbonization, and performing a hydrothermal reaction at 120-180° C. for 6-36 hours. After the reaction is completed, the carbon felt carrier is cooled to room temperature, and the carbon felt carrier is taken out, and repeatedly washed with distilled water and ethanol, and then vacuum dried at 60° C. to obtain a supported carbonaceous volcano-like catalyst; 3) placing the supported catalyst dried in step 2) in a tubular furnace for high-temperature carbonization, and calcining in an atmosphere of high-purity gas at a temperature of 400-900° C. for 2-6 hours. After the reaction is completed, the carbonaceous volcano-shaped catalyst is obtained.

2. The method for preparing 19-formyl-4-androstene-3,17-dione by electrocatalytic oxidation of a carbonaceous volcano-shaped catalyst according to claim 1, characterized in that The volumes of the cathode chamber and the anode chamber are both 50-250 mL; the volume of the anode solvent is 10-20 mmol / L based on the amount of 19-hydroxymethyl-4-androstene-3,17-dione.

3. The method for preparing 19-formyl-4-androstene-3,17-dione by electrocatalytic oxidation of a carbonaceous volcano-shaped catalyst according to claim 1, characterized in that The mixed solvent in the anode chamber is divided into a main solvent and a secondary solvent, the main solvent is a 0.1-2.0 mol / L sodium carbonate aqueous solution; the secondary solvent is one of tetrahydrofuran, dichloromethane, acetonitrile or acetone; the volume ratio of the main solvent to the secondary solvent is 3:7-7:3, and the pH of the mixed solvent is 9.0-12.

0.

4. The method for preparing 19-formyl-4-androstene-3,17-dione by electrocatalytic oxidation of a carbonaceous volcano-shaped catalyst according to claim 1, characterized in that The nitroxide free radical is 4-acetylamino-2, 2, 6, 6-tetramethylpiperidin-1-nitroxide free radical, and the concentration of the nitroxide free radical in the anode mixed solution is 0.1-2 mmol / L.

5. The method for preparing 19-formyl-4-androstene-3,17-dione by electrocatalytic oxidation of a carbonaceous volcano-shaped catalyst according to claim 1, characterized in that The concentration of the sodium carbonate solution in the cathode chamber is 0.1-1.0 mol / L.

6. The method for preparing 19-formyl-4-androstene-3,17-dione by electrocatalytic oxidation of a carbonaceous volcano-shaped catalyst according to claim 1, characterized in that The organic solvent used for extraction is toluene, dichloromethane, chloroform or ethyl acetate.

7. The method for preparing 19-formyl-4-androstene-3,17-dione by electrocatalytic oxidation of a carbonaceous volcano-shaped catalyst according to claim 1, characterized in that The carbon nano-volcano loading on the carbon felt is 5-30 mg / cm 3 .

8. The method for preparing 19-formyl-4-androstene-3,17-dione by electrocatalytic oxidation of a carbonaceous volcano-shaped catalyst according to claim 1, characterized in that The size of the carbonaceous volcano catalyst is 3 × 3 cm 2 .

9. The method for preparing 19-formyl-4-androstene-3,17-dione by electrocatalytic oxidation of a carbonaceous volcano-shaped catalyst according to claim 1, characterized in that In step 2), the hydrothermal temperature is 160-180°C, and the hydrothermal time is 6-24 hours; in step 3), the high-purity gas introduced is nitrogen or argon, the calcination temperature is 600-900°C, and the calcination time is 4-6 hours.

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