Preparation method of melanin precursor
By using dopamine hydrochloride and phenanthroline-Fe(II) catalysts and ferric ammonium sulfate oxidizer, the complexity and safety issues in the synthesis of melanin precursors are solved, and a low-cost, environmentally friendly large-scale production of melanin precursors is achieved.
Patent Information
- Application Number
- CN202510560615.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-30
- Publication Date
- 2025-07-25
AI Technical Summary
The existing melanin precursor synthesis methods have complex steps, harsh conditions, large safety hazards, high environmental costs, and difficult to achieve large-scale production.
Dopamine hydrochloride or its derivatives are used as raw materials, phenanthroline-Fe(II) is used as catalyst and ammonium ferric sulfate is used as oxidizing agent, and a series of reactions are carried out under a nitrogen atmosphere, including stirring, dropping addition, extraction and filtration to form a melanin precursor.
It has achieved efficient synthesis of melanin precursors, low raw material cost, short synthesis route, mild reaction conditions, simple post-processing, fewer three wastes, and easy to produce on a large scale.
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Figure CN120365203A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of hair dyes, and specifically relates to a method for preparing melanin precursors. Background Art
[0002] The dyeing effect of traditional hair dyes mainly depends on oxidative dyes such as p-phenylenediamine (PPD) and p-aminophenol (PAP). These compounds react with hydrogen peroxide to form stable pigment molecules, thereby achieving a long-lasting dyeing effect. However, such chemical components have obvious limitations. They can not only cause skin allergic reactions, but also increase the risk of teratogenesis with long-term or frequent use.
[0003] In contrast, the main active ingredient of melanin precursor hair dyes is 5,6-dihydroxyindole and its derivatives (melanin precursors). They have low sensitization and skin irritation, can produce a more natural pigment effect, have higher safety and lower overall toxicity, and these compounds have less impact on the environment and are more environmentally friendly. However, 5,6-dihydroxyindole and its derivatives are extremely sensitive to environmental factors such as oxygen, pH value, temperature, and light. Their synthesis and separation processes require strict control of reaction conditions, and storage also needs to be carried out in an anaerobic and low-temperature environment. Existing synthesis methods generally have problems such as complex steps and harsh conditions, which greatly limit their industrial production and application.
[0004] For example, using piperonal and vanillin as raw materials, 5,6-dihydroxyindole is obtained through nitration, deprotection, and reduction reactions. The reaction process is shown in the following formula:
[0005] The above preparation process needs to undergo a harsh demethylation process, and at the same time generates a large amount of wastewater. In addition, piperonal is listed as a first-class precursor chemical for drug manufacturing, and nitromethane is listed as an explosive precursor chemical. The use of piperonal and nitromethane is strictly controlled. Therefore, this process is not suitable for large-scale production.
[0006] There is also a preparation process in the prior art. It first cyclizes indole and then deprotects to obtain phenolic hydroxyl groups. The reaction process is shown in the following formula:
[0007] However, the reduction synthesis of indole requires the use of highly toxic hydrazine hydrate and flammable and explosive Raney nickel, and there are great safety hazards in the preparation process.
[0008] In addition, 5,6-dihydroxyindole can also be synthesized through the oxidation reaction of dopamine or L-DOPA. The reaction process is shown in the following formula:
[0009] This process is carried out in the aqueous phase and requires the use of potassium ferricyanide as a single-electron oxidant. A large amount of cyanide-containing wastewater is generated during the preparation process, and the treatment of cyanide-containing wastewater increases the environmental protection cost.
[0010] The above preparation methods of 5,6-dihydroxyindole all have various problems, which limit the large-scale production of 5,6-dihydroxyindole. Therefore, there is an urgent need in the prior art for a preparation method of 5,6-dihydroxyindole and its derivatives that is safe, environmentally friendly, and suitable for large-scale production. Summary of the Invention
[0011] The purpose of the present invention is to overcome the deficiencies existing in the prior art and provide a preparation method of a melanin precursor that is safe, environmentally friendly, and suitable for large-scale production.
[0012] The purpose of the present invention is achieved through the following technical solutions: A preparation method of a melanin precursor, comprising the following steps: (1) Under a nitrogen atmosphere, mix compound III with a deoxygenated solvent and dissolve it into a homogeneous solution A by stirring or ultrasonic treatment at 10 - 60 °C; (2) Under an inert gas atmosphere, dissolve compound I and a divalent iron salt in a complexing solvent, carry out a complexing reaction, and then evaporate the solvent under reduced pressure or add a poor solvent to precipitate compound II, and compound II is phenanthroline-Fe(II), as shown in the following formula; ; Among them, R 1 and R 2 are selected from H, methyl, ethyl, isopropyl, phenyl or substituted phenyl (such as 4-methoxyphenyl). Preferably, R 1 and R 2 are methyl; X is one of F, Cl, Br, CH3COO - , and preferably Cl; (3) Under a nitrogen atmosphere, dissolve ammonium ferric sulfate and a buffer in deoxygenated water and form a homogeneous solution B by stirring or ultrasonic treatment at 10 - 60 °C; (4) Add compound II as a catalyst to solution A, and form a mixed solution under a nitrogen atmosphere and continuous stirring; (5) At 10 - 60 °C, slowly drop solution B into the mixed solution obtained in step (4), stir and react for 2 - 10 h to prepare a reaction solution, as shown in the following formula: ; Among them, R 3 , R 4 are selected from one of H, methyl, ethyl, benzyl and tert-butoxycarbonyl, or R 3 and R 4 combine to form -CH2-; (6) Under a nitrogen atmosphere and with stirring, a reducing agent is added to the reaction solution to quench the excessive oxidizing agent, forming a reduced solution; (7) The reduced solution is subjected to anaerobic filtration through a pressure filter to obtain a clear filtrate; (8) An extractant is added to the filtrate under a nitrogen atmosphere, and extraction is carried out by mechanical stirring. After standing, it is layered, and the organic phase is separated. The aqueous phase is added with the extractant again to repeat the extraction operation; (9) After the organic phases are combined, water is removed by a desiccant, and filtration gives a secondary filtrate; (10) The secondary filtrate is concentrated under reduced pressure to remove the solvent, obtaining a crude solid; (11) The crude solid is redissolved with a good solvent, activated carbon is added for decolorization, and filtration gives a refined solution. The refined solution is concentrated and a poor solvent is added to precipitate the product. The precipitate is collected and dried under high vacuum to prepare a melanin precursor (5,6-dihydroxyindole or its derivative).
[0013] In the step (1), the solvent is one or a combination of two or more of water, tetrahydrofuran, methanol, ethanol, and tert-butanol, preferably water; the dissolution temperature is preferably 10 - 20 °C. The preferred solubilization method is mechanical stirring; the inert gas is nitrogen.
[0014] In the step (2), the inert gas is nitrogen or argon; the complexing solvent is one or a combination of two or more of tetrahydrofuran, dioxane, and ethylene glycol dimethyl ether, preferably tetrahydrofuran; the molar ratio of compound I to the divalent iron salt is 1:0.50 - 1.05, preferably 1:1; the poor solvent is one or a combination of two or more of ether, methyl tert-butyl ether, isopropyl ether, n-hexane, and n-heptane. The complexation reaction is carried out at 20 - 40 °C, and the complexation is complete in 1 - 5 h. After the complexation reaction is completed, the complexing solvent is removed by reduced pressure distillation, and the residue is washed with the above poor solvent, and the crystals of compound II are obtained by suction filtration; or the poor solvent is directly added to the reaction solution of the complexation reaction, cooled to 0 - 5 °C, and kept warm for crystallization, and the crystals of compound II are obtained by suction filtration.
[0015] In the step (3): the buffer is selected from one or a combination of two or more of sodium dihydrogen phosphate, potassium dihydrogen phosphate, ammonium dihydrogen phosphate, disodium hydrogen phosphate, and dipotassium hydrogen phosphate; the inert gas is nitrogen.
[0016] In the step (4): the molar ratio of compound II to compound III is 1:100 - 10, preferably 1:20.
[0017] In the step (5): the molar ratio of the compound III to ammonium ferric sulfate is 1:4 - 6, preferably 1:4.5; the reaction temperature is 40 - 50 °C, preferably 40 °C; the reaction time is 6 - 10 h, preferably 5 h.
[0018] In the step (6), the reducing agent is selected from one or more combinations of ascorbic acid, sodium dithionite and sodium sulfite, preferably sodium dithionite; the inert gas is nitrogen.
[0019] In the step (8), the extractant is selected from one or more combinations of ethyl acetate, butyl acetate, isobutyl acetate, methyl tert-butyl ether and isopropyl ether, preferably isopropyl ether; the inert gas is nitrogen.
[0020] In the step (9), the desiccant is selected from one or more combinations of sodium sulfate, magnesium sulfate and calcium chloride, preferably magnesium sulfate.
[0021] In the step (11): the good solvent is selected from one or more combinations of ethyl acetate, isopropyl ether, methyl tert-butyl ether and tetrahydrofuran, preferably ethyl acetate; the activated carbon has a specification of 100 - 300 mesh, preferably 200 mesh; the poor solvent is selected from one or more combinations of n-hexane, cyclohexane and n-heptane, preferably n-heptane.
[0022] The beneficial effects of the present invention are as follows: using dopamine hydrochloride or its derivatives as raw materials, phenanthroline-Fe(II) as the catalyst for single-electron oxidation reaction, and inexpensive ammonium ferric sulfate as the oxidant, the present invention realizes the efficient synthesis of melanin precursors. The present invention has low raw material cost, short synthesis route, mild reaction conditions, simple post-treatment, less three wastes, and is easy to realize large-scale production. Description of the Drawings
[0023] Figure 1 is the nuclear magnetic resonance hydrogen spectrum of 5,6-dihydroxyindole prepared in Example 1; Figure 2 is the nuclear magnetic resonance hydrogen spectrum of 5,6-dibenzyloxyindole prepared in Example 3. Detailed Embodiments
[0024] The present invention will be described in detail below with reference to the accompanying drawings.
[0025] Example 1 Preparation of 5,6-dihydroxyindole As a melanin precursor, the structure of 5,6-dihydroxyindole is shown as follows:
[0026] Prepare the compound II (catalyst) required for the reaction. The reaction formula is as follows:
[0027] Referring to the above formula, under nitrogen protection, 20.83 g of compound I (2,9-dimethyl-1,10-phenanthroline) and 12.67 g of anhydrous ferrous chloride were added to a 500 mL three-necked flask equipped with magnetic stirring. The flask was evacuated and purged with nitrogen three times, then 200 mL of deoxygenated tetrahydrofuran was added, and the mixture was stirred at 40 °C for 5 h. After the reaction was completed, 250 mL of anhydrous ether was added to the reaction system, and the three-necked flask was placed at 0 °C to stand for crystallization. The red crystals were collected by filtration and dried under vacuum to obtain 28.54 g of a red solid, which is compound II (2,9-dimethyl-1,10-phenanthroline-FeCl2), with a yield of 85.2%. The elemental analysis data is as follows: Anal. Calcd for C 14 H 12 Cl2FeN2: C, 50.19; H, 3.61; N, 8.63; Found: C,50.15; H, 3.69; N, 8.60。
[0028] Under nitrogen protection, 266.00 g of ammonium iron(III) sulfate dodecahydrate and 119.98 g of sodium dihydrogen phosphate were added to a 3 L reaction kettle equipped with mechanical stirring. The kettle was evacuated and purged with nitrogen three times, then 1 L of deoxygenated deionized water was added and stirred until dissolved to obtain a yellow ammonium iron(III) sulfate buffer solution.
[0029]
[0030] Referring to the above formula, under nitrogen protection, 18.96 g of Compound III (dopamine hydrochloride) was put into a 1 L three-necked flask equipped with a magnetic stirrer and a constant-pressure dropping funnel. The flask was evacuated and purged with nitrogen three times, and then 200 mL of deoxygenated deionized water was added and stirred until dissolved. 0.58 g of Compound II was added under a nitrogen atmosphere and stirred until dissolved. At room temperature and with continuous stirring, 450 mL of ammonium ferric sulfate buffer solution was added dropwise through the constant-pressure dropping funnel over a period of 2 h. After the addition was complete, stirring was continued for 5 h until the red color faded to form an inky blue solution. After determining by thin-layer chromatography that the raw materials and intermediate states were completely converted, 1.00 g of sodium dithionite powder was added to the solution, and continuous stirring was carried out for quenching the reaction until the blue color faded to form a brown suspension. Using diatomaceous earth as a padding material, the insoluble matter was removed by filtration through a nitrogen pressure filter to obtain a clear amber filtrate. The filtrate was transferred to a separatory funnel, 500 mL of methyl tert-butyl ether was added for extraction, and after liquid separation, the aqueous phase was extracted twice more with 100 mL of methyl tert-butyl ether. The organic phases from the three extractions were combined and dried over anhydrous magnesium sulfate. The dried organic phase was concentrated under reduced pressure to remove the solvent, yielding a brown oily crude product. The crude product was redissolved in 70 mL of deoxygenated ethyl acetate, 200-mesh activated carbon was added, and stirring was carried out for 30 minutes for decolorization, followed by filtration to obtain a light yellow solution. 200 mL of n-heptane was added to the filtrate, and the temperature was lowered to 0 °C and allowed to stand for crystallization. The off-white precipitate was collected by anaerobic filtration and the solvent was removed by vacuum drying to obtain 11.25 g of Compound IV (5,6-dihydroxyindole), with a yield of 75.4%. The prepared 5,6-dihydroxyindole was detected by proton nuclear magnetic resonance spectroscopy (see Figure 1 ) and the data obtained were as follows: 1 H NMR (400 MHz, DMSO- d6 ): δ (ppm) = 10.41 (s, 1H), 8.47 (s, 1H), 8.19 (s,1H), 7.00 - 6.97 (m, 1H), 6.81 (s, 1H), 6.74 (s, 1H), 6.13 - 6.11 (m, 1H).
[0031] Example 2 Preparation of 5,6-dihydroxyindole Compound II (catalyst) required for the preparation reaction, the reaction formula is as follows:
[0032] Referring to the above formula, under nitrogen protection, 18.21 g of Compound I (1,10-phenanthroline) and 12.66 g of anhydrous ferrous chloride were put into a 500 mL three-necked flask equipped with magnetic stirring. The flask was evacuated and purged with nitrogen three times, and then 200 mL of deoxygenated tetrahydrofuran was added. The mixture was stirred at 40 °C for 6 h. After the reaction was completed, 280 mL of anhydrous ether was added to the reaction system, and the three-necked flask was placed at 0 °C to stand for crystallization. The red crystals were collected by filtration and dried under vacuum to obtain 27.18 g of a red solid, which was Compound II (1,10-phenanthroline-FeCl2), with a yield of 88.5%. The elemental analysis data are as follows: Anal. Calcd forC 12 H8Cl2FeN2: C, 46.96; H, 2.63; N, 23.10; Found: C, 46.89; H, 2.69; N, 23.05。
[0033] Under nitrogen protection, 266.10 g of ammonium iron(III) sulfate dodecahydrate and 136.09 g of potassium dihydrogen phosphate were put into a 3 L reaction kettle equipped with mechanical stirring. The kettle was evacuated and purged with nitrogen three times, and then 1 L of deoxygenated deionized water was added and stirred until dissolved to obtain a yellow ammonium iron(III) sulfate buffer solution.
[0034]
[0035] Referring to the above formula, under nitrogen protection, 18.98 g of Compound III (dopamine hydrochloride) was added to a 1 L three-necked flask equipped with a magnetic stirrer and a constant-pressure dropping funnel. The flask was evacuated and purged with nitrogen three times, and then 200 mL of deoxygenated deionized water was added and stirred until dissolved. 1.51 g of Compound II was added under a nitrogen atmosphere and stirred until dissolved. At room temperature and with continuous stirring, 450 mL of ammonium ferric sulfate buffer solution was added dropwise through the constant-pressure dropping funnel over a period of 2 h. After the addition was complete, stirring was continued for 5 h until the red color faded and a dark blue solution was formed. After determining by thin-layer chromatography that the raw materials and intermediate states were completely converted, 1.00 g of sodium dithionite powder was added to the solution, and stirring was continued to quench the reaction until the blue color faded and a brown suspension was formed. Using diatomaceous earth as a padding material, the insoluble matter was removed by nitrogen pressure filtration to obtain a clear amber filtrate. The filtrate was transferred to a separatory funnel, and 500 mL of isopropyl ether was added for extraction. After liquid separation, the aqueous phase was extracted twice more with 100 mL of isopropyl ether, and the organic phases from the three extractions were combined and dried over anhydrous sodium sulfate. The dried organic phase was concentrated under reduced pressure to remove the solvent, obtaining a brown oily crude product. The crude product was redissolved in 70 mL of deoxygenated isopropyl ether, 300-mesh activated carbon was added, and the mixture was stirred for 30 minutes for decolorization, and then filtered to obtain a light yellow solution. 200 mL of n-hexane was added to the filtrate, and the temperature was lowered to 0 °C and allowed to stand for crystallization. The white precipitate was collected by anaerobic filtration and the solvent was removed under vacuum to obtain 10.25 g of off-white Compound IV (5,6-dihydroxyindole) with a yield of 68.8%.
[0036] Example 3 Preparation of 5,6-Dibenzyloxyindole As a melanin precursor, the structure of 5,6-dibenzyloxyindole is shown below:
[0037] In this example, the preparation methods of Compound II (catalyst) and ammonium ferric sulfate buffer solution were the same as those in Example 1.
[0038] The preparation reaction equation of 5,6-dibenzyloxyindole is shown below:
[0039] Referring to the above formula, under nitrogen protection, 37.00 g of Compound III (3,4-dibenzyloxy phenethylamine hydrochloride) was added to a 1 L three-necked flask equipped with a magnetic stirrer and a constant pressure dropping funnel. The flask was evacuated and purged with nitrogen three times, then 100 mL of deoxygenated deionized water and 100 mL of deoxygenated ethanol were added and stirred until dissolved. 0.58 g of Compound II was added under a nitrogen atmosphere and stirred until dissolved. At room temperature and with continuous stirring, 450 mL of ammonium ferric sulfate buffer solution was added dropwise through the constant pressure dropping funnel over a period of 2 h. After the addition was complete, stirring was continued for 10 h until the red color faded and a dark blue solution was formed. After determining by thin layer chromatography that the raw materials and intermediate states were completely converted, 1.00 g of sodium dithionite powder was added to the solution and stirring was continued to quench the reaction until the blue color faded to form a grayish-green suspension. Using diatomaceous earth as a padding material, the insoluble matter was removed by filtration through a nitrogen pressure filter to obtain a clear grayish-green filtrate. The filtrate was transferred to a separatory funnel, and 300 mL of ethyl acetate was added for extraction. After liquid separation, the aqueous phase was extracted twice more with 100 mL of ethyl acetate each time. The organic phases from the three extractions were combined and dried over anhydrous magnesium sulfate. The dried organic phase was concentrated under reduced pressure to remove the solvent, yielding a dark green oily crude product. The crude product was redissolved in 70 mL of deoxygenated ethyl acetate, 200-mesh activated carbon was added, and stirring was carried out for 50 minutes for decolorization. The mixture was filtered to obtain a dark green solution. 350 mL of n-heptane was added to the filtrate, and the temperature was lowered to 0 °C and allowed to stand for crystallization. The grayish-green precipitate was collected by anaerobic filtration and the solvent was removed by vacuum drying to obtain 25.68 g of grayish-green Compound IV (5,6-dibenzyloxyindole) with a yield of 88.0%. The prepared 5,6-dibenzyloxyindole was detected by 1H NMR spectroscopy (see Figure 2 ) and the data obtained were as follows: 1 1H NMR (400 MHz, CDCl3): δ δ (ppm) = 7.97 (br, 1H), 7.48 - 7.22 (m, 10H), 7.18 (s, 1H), 6.98 - 6.95 (m, 1H), 6.86 (s, 1H), 6.37 (s, 1H), 5.14 (s, 2H), 5.09 (s, 2H).
[0040] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than limiting the protection scope of the present invention. Any simple modification or equivalent replacement of the technical solution of the present invention by those of ordinary skill in the art shall not depart from the essence and scope of the technical solution of the present invention.
Claims
1. A method for preparing a melanin precursor, characterized in that It includes the following steps: (1) Under the atmosphere of an inert gas, mix Compound III with a deoxygenated solvent, and dissolve it into a homogeneous solution A by stirring or sonication at 10 - 60 °C; (2) Under an inert gas atmosphere, dissolve Compound I and a divalent iron salt in a complexing solvent, carry out a complexing reaction, and then evaporate the solvent under reduced pressure or add a poor solvent to precipitate Compound II, as shown in the following formula; ； Among them, R 1 and R 2 are selected from H, methyl, ethyl, isopropyl, phenyl or substituted phenyl, and X is one of F, Cl, Br, CH3COO - ; (3) Under the atmosphere of an inert gas, dissolve ammonium ferric sulfate and a buffer in deoxygenated water, and form a homogeneous solution B by stirring or sonication at 10 - 60 °C; (4) Add Compound II as a catalyst to Solution A, and form a mixed solution under a nitrogen atmosphere with continuous stirring; (5) At 10 - 60 °C, slowly add Solution B dropwise to the mixed solution obtained in step (4), stir and react for 2 - 10 h to prepare a reaction solution, as shown in the following formula: ； Among them, R 3 , R 4 is selected from one of H, methyl, ethyl, benzyl and tert-butoxycarbonyl, or R 3 and R 4 combine to form -CH2-; (6) Under an inert gas atmosphere and stirring conditions, add a reducing agent to the reaction solution to quench the excess oxidant and form a reduced solution; (7) Filter the reduced solution through a pressure filter under anaerobic conditions to obtain a clear filtrate; (8) Under an inert gas atmosphere, add an extractant to the filtrate, carry out an extraction operation by mechanical stirring, let it stand and separate into layers, separate out the organic phase, and add the extractant to the aqueous phase again to repeat the extraction operation; (9) After combining the organic phases, remove water through a desiccant and filter to obtain a secondary filtrate; (10) Remove the solvent from the secondary filtrate by vacuum distillation to obtain a crude solid; (11) Redissolve the crude solid with a good solvent, add activated carbon for decolorization, filter to obtain a refined solution, concentrate the refined solution and then add a poor solvent to precipitate the product, collect the precipitate, and dry it under high vacuum to prepare a melanin precursor.
2. The preparation method of a melanin precursor according to claim 1, characterized in that: In the above step (1), the solvent is one or a combination of two or more of water, tetrahydrofuran, methanol, ethanol, and tert-butanol; the dissolution temperature is 10 - 20 °C; the inert gas is nitrogen.
3. The preparation method of a melanin precursor according to the claim, characterized in that: In the above step (2), the inert gas is nitrogen or argon; the complexing solvent is one or a combination of two or more of tetrahydrofuran, dioxane, and ethylene glycol dimethyl ether; the molar ratio of Compound I to the divalent iron salt is 1:0.50 - 1.05; the poor solvent is one or a combination of two or more of ether, methyl tert-butyl ether, isopropyl ether, n-hexane, and n-heptane.
4. The preparation method of a melanin precursor according to claim 1, characterized in that: In the above step (3): the buffer is selected from one or a combination of two or more of sodium dihydrogen phosphate, potassium dihydrogen phosphate, ammonium dihydrogen phosphate, disodium hydrogen phosphate, and dipotassium hydrogen phosphate; the inert gas is nitrogen.
5. A method for preparing a melanin precursor according to claim 1, characterized in that: In the above step (4): the molar ratio of Compound II to Compound III is 1:100 - 10.
6. The preparation method of a melanin precursor according to claim 1, wherein: In the above step (5): the molar ratio of Compound III to ammonium ferric sulfate is 1:4 - 6; the reaction temperature is 40 - 50 °C; the reaction time is 6 - 10 h.
7. The preparation method of a melanin precursor according to claim 1, wherein: In the above step (6), the reducing agent is selected from one or a combination of two or more of ascorbic acid, sodium dithionite, and sodium sulfite; the inert gas is nitrogen.
8. The preparation method of a melanin precursor according to claim 1, characterized in that: In the step (8), the extractant is one or a combination of two or more of ethyl acetate, butyl acetate, isobutyl acetate, methyl tert-butyl ether, and isopropyl ether; the inert gas is nitrogen.
9. The preparation method of a melanin precursor according to claim 1, wherein: In the step (9), the desiccant is one or a combination of two or more of sodium sulfate, magnesium sulfate, and calcium chloride.
10. The preparation method of a melanin precursor according to claim 1, characterized in that: In the step (11): the good solvent is selected from one or a combination of two or more of ethyl acetate, isopropyl ether, methyl tert-butyl ether, and tetrahydrofuran; the activated carbon has a specification of 100-300 mesh; the poor solvent is selected from one or a combination of two or more of n-hexane, cyclohexane, and n-heptane.