Preparation method of high-purity climbazole
By intermittently adding chlorine and activated carbon for purification, the problems of environmental pollution and insufficient yield in the preparation of ganbaosu were solved, and the preparation of ganbaosu with high purity and high yield was achieved, reducing costs and purification difficulty.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- HEILONGJIANG BANGPU BIOTECHNOLOGY CO LTD
- Filing Date
- 2026-01-30
- Publication Date
- 2026-05-08
AI Technical Summary
In existing methods for preparing galbacin, the SO2 byproduct generated by the chlorination reaction of ether ketones causes environmental pollution, and the yield of galbacin is insufficient, affecting economic benefits.
Chlorine gas was added intermittently as a chlorinating agent, combined with activated carbon refining. The chlorination reaction was controlled in stages to avoid SO2 generation and improve the ether-ketone conversion rate. Activated carbon was used to adsorb and remove pigments and impurities from crude glycyrrhizin.
It improved the yield and purity of ganbaosu, reduced preparation costs, reduced environmental pollution, enhanced environmental friendliness, and reduced purification difficulty.
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Figure QLYQS_1
Abstract
Description
Technical Field
[0001] This invention relates to the field of synthetic chemistry technology, specifically to a method for preparing high-purity glycyrrhizin. Background Technology
[0002] Ganbaosu, also known as 1-(4-chlorophenoxy)-1-((1-imidazolyl)-3,3-dimethyl-2-butanone, is widely used in conditioning personal care products such as anti-itch and anti-dandruff shampoos and conditioners due to its broad-spectrum bactericidal properties. It can also be used in high-end detergents such as antibacterial soaps, shower gels, medicated toothpastes, and mouthwashes. When used in daily chemical products, the color and odor of Ganbaosu are subject to strict requirements. Pure Ganbaosu is a white or grayish-white crystal. If the purity is low, Ganbaosu will have poor color and an unpleasant odor, adversely affecting the quality of daily chemical products.
[0003] The preparation method of gamboglin generally involves first chlorinating pinacolone to obtain monochloropinacolone, then reacting monochloropinacolone with p-chlorophenol to obtain an ether ketone, followed by chlorination of the ether ketone to obtain a chloroether ketone, and finally reacting the chloroether ketone with imidazole to obtain gamboglin. Some studies have used sulfuryl chloride (SO2Cl2) as a chlorinating agent, but the SO2 byproduct generated by the ether ketone chlorination reaction pollutes the environment and is unsuitable for industrial production. Although the gamboglin obtained in this study had high purity, the yield was insufficient, meaning that more raw materials were wasted or converted into byproducts, increasing raw material costs. Furthermore, after scaling up production, the actual output would be far lower than expected, negatively impacting economic efficiency.
[0004] Therefore, how to develop a suitable ether-ketone chlorination method to reduce environmental pollution, solve the problem of insufficient yield of galbacon, and obtain galbacon with both high purity and high yield is worthy of our further exploration. Summary of the Invention
[0005] To address the aforementioned technical problems, this invention provides a method for preparing high-purity glycyrrhizin.
[0006] The objective of this invention can be achieved through the following technical solutions: A method for preparing high-purity glycyrrhizin includes the following steps: Step (1): Mix pinacolone and methanol, cool down, introduce chlorine gas, stir the reaction to obtain a reaction solution containing monochloropinacolone, and distill the reaction solution containing monochloropinacolone under reduced pressure and collect the fraction to obtain monochloropinacolone. Step (2): Mix toluene, p-chlorophenol and potassium carbonate, stir and heat, add monochloropinazone dropwise, heat and reflux and stir again, then cool and wash with water to obtain a reaction solution containing ether ketone; Step (3): Add chlorination reagent to the reaction solution containing ether ketone under stirring, heat and stir to obtain reaction solution containing chlorinated ether ketone, then heat and distill under reduced pressure on the reaction solution containing chlorinated ether ketone; cool down, keep warm, and centrifuge to obtain crude chlorinated ether ketone and centrifugation mother liquor 1. Dry the crude chlorinated ether ketone to obtain chlorinated ether ketone. Step (4): Mix toluene, imidazole, chloroether ketone, and N,N-dimethylbenzylamide, heat and reflux with stirring, add alkali solution to adjust pH, wash with water, cool the organic phase, keep it warm, and centrifuge to obtain centrifuged mother liquor 2 and crude galbacin; mix crude galbacin, toluene, and activated carbon, heat and reflux with stirring, cool and filter, continue to cool the filtrate and keep it warm, centrifuge to obtain refined product and centrifuged mother liquor 3, dry the refined product to obtain high-purity galbacin.
[0007] A method for preparing high-purity glycyrrhizin includes the following specific steps: Step (1): Mix pinacolone and methanol, cool to 0°C, introduce chlorine gas, and react at 0-5°C for 15-16 hours to obtain a reaction solution containing monochloropinacolone. Distill the reaction solution containing monochloropinacolone under reduced pressure by heating. First, collect the distillate at 40-55°C and seal it. Then, collect the fraction at 80-82°C to obtain monochloropinacolone. Furthermore, the ratio of pinacolone to methanol is 52-53g: 0.87-0.91g; Furthermore, the chlorine gas is added in stages; the stages are as follows: initially, chlorine gas is introduced at a rate of 0.8-1.0 L / min; in the middle stage, chlorine gas is introduced at a rate of 1.5-1.7 L / min; and in the later stage, chlorine gas is introduced at a rate of 0.5-0.7 L / min. The time ratio of the initial, middle, and later stages of chlorine gas introduction is 1:1.5:0.5. The total time of chlorine gas introduction is the reaction time at 0-5°C. Furthermore, the distillate at 40-55°C is methanol and unreacted pinacolone; In step (1), pinacolone reacts with chlorine to obtain monochloropinacolone; chlorine is added in stages, with a low flow rate in the early stage to prevent side reactions, an increased flow rate in the middle stage to maintain the reaction rate, and a decreased flow rate in the later stage to reduce residue. Step (2): Mix toluene, p-chlorophenol and potassium carbonate, stir and heat to 65-68℃, add monochloropinazone dropwise, heat to 115-120℃, reflux and stir for 6-7 hours, cool to 70-72℃, wash with water to obtain a reaction solution containing ether ketone. Further, the ratio of toluene, p-chlorophenol, potassium carbonate, and monochloropinazone is 1.9-2.1g: 43.0-44.0g: 23.3-23.8g: 47.0-48.0g; In step (2), p-chlorophenol reacts with monochloropinazone to obtain a reaction solution containing an ether ketone; Step (3): Add chlorination reagent to the reaction solution containing ether ketone under stirring at 30-35℃, and then stir at 35-37℃ for 1-1.2h to obtain the reaction solution containing chlorinated ether ketone. Then, heat the reaction solution containing chlorinated ether ketone and distill it under reduced pressure. First, collect the distillate at 75-90℃ and seal it. Cool the reaction solution containing chlorinated ether ketone after heating and reducing pressure distillation to 0℃ and keep it at that temperature for 1-1.2h. Centrifuge to obtain crude chlorinated ether ketone and centrifugal mother liquor 1. Heat the centrifugal mother liquor 1 and distill it under reduced pressure. Collect the distillate at 75-90℃ and seal it. Dry the crude chlorinated ether ketone at 48-50℃ for 5-6h to obtain chlorinated ether ketone. Furthermore, the chlorinating agent is added intermittently; the intermittent addition of chlorine gas is done by introducing chlorine gas at a rate of 0.8-1 L / min for 30-35 minutes, followed by a 3-5 minute pause; the total time for intermittent chlorine addition is 4.5-5 hours. In step (3), the ether ketone in the reaction solution containing ether ketone reacts with the chlorinating reagent to obtain chloroether ketone; the reaction is carried out by intermittently introducing chlorine gas, which is beneficial for efficient mixing and safe control; Step (4): Mix toluene, imidazole, chloroether ketone, and N,N-dimethylbenzylamide, heat to 115-120℃, reflux and stir for 12-12.5h, add alkali solution to adjust pH to 12-13, wash with water, cool the organic phase to 0℃, keep warm for 1-1.2h, centrifuge to obtain centrifugal mother liquor 2 and crude ganbaosu, heat centrifugal mother liquor 2 to reduce pressure and distill, collect the distillate at 75-90℃ and seal it; mix crude ganbaosu, toluene, and activated carbon, heat to 115-120℃, reflux and stir for 1-1.2h, cool to 75-77℃, filter, cool the filtrate to 0℃ and keep warm for 1-1.2h, centrifuge to obtain purified product and centrifugal mother liquor 3, heat centrifugal mother liquor 3 to reduce pressure and distill, collect the distillate at 75-90℃ and seal it, dry the purified product at 65-75℃ for 6-7h to obtain high-purity ganbaosu; Further, the ratio of toluene, imidazole, chloroether ketone, and N,N-dimethylbenzylamide is 2.3-2.5g: 24.0-24.5g: 91.5-92.5g: 4.5-5g; the alkaline solution is a sodium hydroxide solution with a mass fraction of 10-12%. Furthermore, the ratio of crude glycyrrhizin, toluene, and activated carbon is 1-1.5g: 13-15g: 75-85mg; In step (4), imidazole reacts with chloroether ketone to obtain crude gamboglin, which is then purified by activated carbon to adsorb and remove pigment molecules and organic impurities from the crude gamboglin. After filtration, crystallization, centrifugation and drying, high-purity gamboglin is obtained. Furthermore, the pressure used for heating and vacuum distillation in steps (1), (3), and (4) is all between -0.1 MPa and -0.08 MPa; Furthermore, the distillate at 75-90℃ mentioned in steps (3) and (4) is toluene.
[0008] The preparation process of the high-purity glycyrrhizin is as follows: .
[0009] The beneficial effects of this invention are: This invention discloses a method for preparing high-purity glycyrrhizin. The glycyrrhizin is obtained by reacting pinacolone with chlorine to obtain monochloropinacolone, reacting monochloropinacolone with p-chlorophenol to obtain ether ketone, chlorinating the ether ketone with a chlorinating reagent to obtain chloroether ketone, reacting the chloroether ketone with imidazole to obtain crude glycyrrhizin, and then refining the crude glycyrrhizin with activated carbon, filtering, crystallizing, centrifuging, and drying.
[0010] Using intermittently added chlorine gas as a chlorinating agent during the chlorination stage of ether ketone avoids excessively vigorous reactions and improves the selectivity of the reaction to convert ether ketone to chloroether ketone. This not only increases the yield of chloroether ketone but also avoids the generation of SO2 byproducts that pollute the environment, thus enhancing environmental friendliness, reducing raw material costs, and reducing the difficulty of purifying chloroether ketone. Consequently, it increases the yield of glycyrrhizin and reduces the difficulty of purifying crude glycyrrhizin.
[0011] In the purification stage of crude galbacin, the method of mixing crude galbacin, toluene, and activated carbon, heating and refluxing, followed by cooling, filtration, crystallization, and centrifugation can efficiently adsorb and remove pigment molecules and organic impurities in crude galbacin, thereby improving the purity of galbacin. The used activated carbon can be recycled and reused, reducing the preparation cost and avoiding the introduction of new impurities or reduction of the molecular structure stability of galbacin due to the use of alkali washing for purification, thus preventing galbacin degradation or yield reduction. Detailed Implementation
[0012] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0013] The following method is used to determine the yield of ganbaosu: The theoretical yield is calculated based on the amount of reactants fed and the stoichiometric relationship. The actual yield of ganbaosu is obtained by experimental measurement and is calculated as the ratio of the actual yield to the theoretical yield.
[0014] The purity of ganbaosu is determined using HPLC.
[0015] Example 1 A method for preparing high-purity glycyrrhizin includes the following steps: Step (1): Mix pinacolone and methanol, cool to 0°C, introduce chlorine gas, and react at 0°C for 15 hours to obtain a reaction solution containing monochloropinacolone. Distill the reaction solution containing monochloropinacolone under reduced pressure at -0.1 MPa. First, collect the distillate at 40°C and seal it. Then, collect the fraction at 80°C to obtain monochloropinacolone. The ratio of pinacolone to methanol is 52g:0.87g; chlorine gas is prepared by vaporizing liquid chlorine at 40℃ and then introducing it into a buffer tank, followed by staged addition via a flow meter; the staged addition involves introducing chlorine gas at a rate of 0.8L / min initially, 1.5L / min in the middle stage, and 0.5L / min in the later stage; the time ratio of chlorine gas introduction in the initial, middle, and later stages is 1:1.5:0.5; the total time for chlorine gas introduction is the reaction time at 0℃. Step (2): Mix toluene, p-chlorophenol, and potassium carbonate, stir and heat to 65°C, add monochloropinazone dropwise at a rate of 3 drops / s, and finish adding within 10 minutes. Then heat to 115°C, reflux and stir for 6 hours, cool to 70°C, and wash three times with water to obtain a reaction solution containing ether ketone. The ratio of toluene, p-chlorophenol, potassium carbonate, and monochloropinazone is 1.9g:43.0g:23.3g:47.0g. Step (3): Add chlorination reagent to the reaction solution containing ether ketone at 30°C and stir at 35°C for 1 hour to obtain the reaction solution containing chlorinated ether ketone. Then, distill the reaction solution containing chlorinated ether ketone under reduced pressure at -0.1 MPa. First, collect the distillate at 75°C and seal it. Cool the reaction solution containing chlorinated ether ketone after reduced pressure distillation to 0°C and keep it at that temperature for 1.1 hours. Centrifuge to obtain crude chlorinated ether ketone and centrifugal mother liquor 1. Distill the centrifugal mother liquor 1 under reduced pressure at -0.1 MPa. Collect the distillate at 75°C and seal it. Dry the crude chlorinated ether ketone at 48°C for 5 hours to obtain chlorinated ether ketone. The chlorination reagent is added by vaporizing liquid chlorine at 40°C and then introducing it into a buffer tank, followed by intermittent addition of chlorine gas via a flow meter. The intermittent addition of chlorine gas is carried out at a rate of 0.8 L / min for 30 minutes, followed by a 3-minute pause. The total time for intermittent addition of chlorine gas is 4.5 hours. Step (4): Mix toluene, imidazole, chloroether ketone, and N,N-dimethylbenzylamide, heat to 115°C, reflux and stir for 12 hours, add alkali solution to adjust pH to 12, wash with water, cool the organic phase to 0°C, keep warm for 1 hour, centrifuge to obtain centrifuged mother liquor 2 and crude ganbaosu, centrifuged mother liquor 2 is heated and distilled under reduced pressure at -0.1 MPa, collect the distillate at 75°C and seal it; mix crude ganbaosu, toluene, and activated carbon (supplier: Aladdin, item number C299105), heat to 115°C, reflux and stir for 1 hour, cool to 75°C, filter, cool the filtrate to 0°C, keep warm for 1 hour, centrifuge to obtain purified product and centrifuged mother liquor 3, centrifuged mother liquor 3 is heated and distilled under reduced pressure at -0.1 MPa, collect the distillate at 75°C and seal it, dry the purified product at 65°C for 6 hours to obtain high-purity ganbaosu; The ratio of toluene, imidazole, chloroether ketone, and N,N-dimethylbenzylamide was 2.3 g: 24.0 g: 91.5 g: 4.5 g; the alkali solution was a 10% sodium hydroxide solution; the ratio of crude glycyrrhizin, toluene, and activated carbon was 1 g: 13 g: 75 mg. The yield of the obtained glycyrrhizin was 95%, and the purity was 99.90%.
[0016] Example 2 A method for preparing high-purity glycyrrhizin includes the following steps: Step (1): Mix pinacolone and methanol, cool to 0°C, introduce chlorine gas, and react at 3°C for 15.5 h to obtain a reaction solution containing monochloropinacolone. Distill the reaction solution containing monochloropinacolone under reduced pressure at -0.09 MPa. First, collect the distillate at 49°C and seal it. Then, collect the fraction at 80°C to obtain monochloropinacolone. The ratio of pinacolone to methanol was 52.5g:0.89g; chlorine gas was prepared by vaporizing liquid chlorine at 40℃ and then introducing it into a buffer tank, followed by staged addition via a flow meter; the staged addition involved introducing chlorine gas at a rate of 0.9L / min initially, 1.6L / min in the middle stage, and 0.6L / min in the later stage; the time ratio of chlorine gas introduction in the initial, middle, and later stages was 1:1.5:0.5; the total time for introducing chlorine gas was the reaction time at 3℃. Step (2): Mix toluene, p-chlorophenol, and potassium carbonate, stir and heat to 67°C, add monochloropinazone dropwise at a rate of 3 drops / s, and finish adding within 10 minutes. Then heat to 118°C, reflux and stir for 6.5 hours, cool to 71°C, and wash three times with water to obtain a reaction solution containing ether ketone. The ratio of toluene, p-chlorophenol, potassium carbonate, and monochloropinazone is 2.0g:43.5g:23.5g:47.5g. Step (3): Add chlorination reagent to the reaction solution containing ether ketone at 33°C and stir at 36°C for 1.1 h to obtain the reaction solution containing chlorinated ether ketone. Then, distill the reaction solution containing chlorinated ether ketone under reduced pressure at -0.09 MPa. First, collect the distillate at 82°C and seal it. Cool the reaction solution containing chlorinated ether ketone after reduced pressure distillation to 0°C and keep it at that temperature for 1.1 h. Centrifuge to obtain crude chlorinated ether ketone and centrifugal mother liquor 1. Distill the centrifugal mother liquor 1 under reduced pressure at -0.09 MPa. Collect the distillate at 82°C and seal it. Dry the crude chlorinated ether ketone at 49°C for 5.5 h to obtain chlorinated ether ketone. The chlorination reagent is added by vaporizing liquid chlorine at 40°C and then introducing it into a buffer tank, followed by intermittent addition of chlorine gas via a flow meter. The intermittent addition of chlorine gas is carried out at a rate of 0.9 L / min for 33 minutes, followed by a 4-minute pause. The total time for intermittent addition of chlorine gas is 4.8 hours. Step (4): Mix toluene, imidazole, chloroether ketone, and N,N-dimethylbenzylamide, heat to 118℃, reflux and stir for 12.3h, add alkali solution to adjust pH to 12.5, wash with water, cool the organic phase to 0℃, keep warm for 1.1h, centrifuge to obtain centrifuged mother liquor 2 and crude glycyrrhizin, centrifuged mother liquor 2 is heated and distilled under reduced pressure at -0.09MPa, collect the distillate at 82℃ and seal it; the crude glycyrrhizin, toluene, Activated carbon (supplier: Aladdin, item number C299105) was mixed, heated to 118℃, refluxed and stirred for 1.1h, cooled to 76℃, filtered, and the filtrate was cooled to 0℃ and kept at that temperature for 1.1h. The purified product and centrifugal mother liquor 3 were obtained by centrifugation. The centrifugal mother liquor 3 was heated and distilled under reduced pressure at -0.09MPa. The distillate at 82℃ was collected and sealed. The purified product was dried at 70℃ for 6.5h to obtain high-purity ganbaosu. The ratio of toluene, imidazole, chloroether ketone, and N,N-dimethylbenzylamide was 2.4 g: 24.3 g: 92.0 g: 4.7 g; the alkali solution was an 11% sodium hydroxide solution; the ratio of crude glycyrrhizin, toluene, and activated carbon was 1.3 g: 14 g: 80 mg. The yield of the obtained glycyrrhizin was 95%, and the purity was 99.92%.
[0017] Example 3 A method for preparing high-purity glycyrrhizin includes the following steps: Step (1): Mix pinacolone and methanol, cool to 0°C, introduce chlorine gas, and react at 5°C for 16 hours to obtain a reaction solution containing monochloropinacolone. Distill the reaction solution containing monochloropinacolone under reduced pressure at -0.08 MPa. First, collect the distillate at 55°C and seal it. Then, collect the fraction at 80°C to obtain monochloropinacolone. The ratio of pinacolone to methanol is 53g:0.91g; chlorine gas is prepared by vaporizing liquid chlorine at 40℃ and then introducing it into a buffer tank, followed by staged addition via a flow meter; the staged addition involves introducing chlorine gas at a rate of 1.0L / min initially, 1.7L / min in the middle stage, and 0.7L / min in the later stage; the time ratio of chlorine gas introduction in the initial, middle, and later stages is 1:1.5:0.5; the total time for chlorine gas introduction is the reaction time at 5℃. Step (2): Mix toluene, p-chlorophenol, and potassium carbonate, stir and heat to 68°C, add monochloropinazone dropwise at a rate of 3 drops / s, and finish adding within 10 minutes. Then heat to 120°C, reflux and stir for 7 hours, cool to 72°C, and wash three times with water to obtain a reaction solution containing ether ketone. The ratio of toluene, p-chlorophenol, potassium carbonate, and monochloropinazone is 2.1g:44.0g:23.8g:48.0g. Step (3): Add chlorination reagent to the reaction solution containing ether ketone at 35°C and stir at 37°C for 1.2 h to obtain the reaction solution containing chlorinated ether ketone. Then, distill the reaction solution containing chlorinated ether ketone under reduced pressure at -0.08 MPa. First, collect the distillate at 90°C and seal it. Cool the reaction solution containing chlorinated ether ketone after reduced pressure distillation to 0°C and keep it at that temperature for 1.2 h. Centrifuge to obtain crude chlorinated ether ketone and centrifugal mother liquor 1. Distill the centrifugal mother liquor 1 under reduced pressure at -0.08 MPa. Collect the distillate at 90°C and seal it. Dry the crude chlorinated ether ketone at 50°C for 6 h to obtain chlorinated ether ketone. The chlorination reagent is added by vaporizing liquid chlorine at 40°C and then introducing it into a buffer tank, followed by intermittent addition of chlorine gas via a flow meter. The intermittent addition of chlorine gas is carried out at a rate of 1 L / min for 35 minutes, then stopped for 5 minutes. The total time for intermittent addition of chlorine gas is 5 hours. Step (4): Mix toluene, imidazole, chloroether ketone, and N,N-dimethylbenzylamide, heat to 120℃, reflux and stir for 12.5h, add alkali solution to adjust pH to 13, wash with water, cool the organic phase to 0℃, keep warm for 1.2h, centrifuge to obtain centrifuged mother liquor 2 and crude glycyrrhizin, centrifuged mother liquor 2 is heated and distilled under reduced pressure at -0.08MPa, collect the distillate at 90℃ and seal it; the crude glycyrrhizin, toluene, Activated carbon (supplier: Aladdin, item number C299105) was mixed, heated to 120℃, refluxed and stirred for 1.2h, cooled to 77℃, filtered, and the filtrate was cooled to 0℃ and kept at that temperature for 1.2h. The purified product and centrifugal mother liquor 3 were obtained by centrifugation. The centrifugal mother liquor 3 was heated and distilled under reduced pressure at -0.08MPa. The distillate at 90℃ was collected and sealed. The purified product was dried at 75℃ for 7h to obtain high-purity Ganbaosu. The ratio of toluene, imidazole, chloroether ketone, and N,N-dimethylbenzylamide was 2.5 g: 24.5 g: 92.5 g: 5 g; the alkali solution was a 12% sodium hydroxide solution; the ratio of crude glycyrrhizin, toluene, and activated carbon was 1.5 g: 15 g: 85 mg. The yield of the obtained glycyrrhizin was 96%, and the purity was 99.96%.
[0018] Comparative Example 1 Compared with Example 3, the addition of chlorinating reagent in step (3) was replaced with chlorine gas being introduced at a rate of 1 L / min, while the rest was exactly the same as in Example 3, to obtain high-purity glycyrrhizin. The yield of the obtained glycyrrhizin was 90%, and the purity was 98.96%.
[0019] Comparative Example 2 Compared with Example 3, in step (3), the addition of chlorination reagent was replaced by chlorine gas being introduced at a rate of 1 L / min for 35 min and then stopped for 10 min, while the rest was exactly the same as in Example 3, to obtain high-purity galangal. The yield of the obtained galangal was 92%, and the purity was 99.16%.
[0020] The above description is merely an example and illustration of the concept of the present invention. Those skilled in the art can make various modifications or additions to the specific embodiments described or use similar methods to replace them, as long as they do not deviate from the concept of the invention or exceed the scope defined in the claims, they should all fall within the protection scope of the present invention.
Claims
1. A method for preparing high-purity glycyrrhizin, characterized in that: Includes the following steps: Step (1): Mix pinacolone and methanol, cool down, introduce chlorine gas, stir the reaction to obtain a reaction solution containing monochloropinacolone, and distill the reaction solution containing monochloropinacolone under reduced pressure and collect the fraction to obtain monochloropinacolone. Step (2): Mix toluene, p-chlorophenol and potassium carbonate, stir and heat, add monochloropinazone dropwise, heat and reflux and stir again, then cool and wash with water to obtain a reaction solution containing ether ketone; Step (3): Add chlorination reagent to the reaction solution containing ether ketone under stirring, heat and stir to obtain the reaction solution containing chlorinated ether ketone, then heat and distill the reaction solution containing chlorinated ether ketone under reduced pressure; cool down, keep warm, and centrifuge to obtain crude chlorinated ether ketone and centrifugation mother liquor 1. Dry the crude chlorinated ether ketone to obtain chlorinated ether ketone. Step (4): Mix toluene, imidazole, chloroether ketone, and N,N-dimethylbenzylamide, heat and reflux with stirring, add alkali solution to adjust pH, wash with water, cool the organic phase, keep it warm, and centrifuge to obtain centrifuged mother liquor 2 and crude galbacin; mix crude galbacin, toluene, and activated carbon, heat and reflux with stirring, cool and filter, continue to cool the filtrate and keep it warm, centrifuge to obtain purified product and centrifuged mother liquor 3, heat centrifuged mother liquor 3 and distill under reduced pressure, dry the purified product to obtain high-purity galbacin.
2. The method for preparing high-purity glycyrrhizin according to claim 1, characterized in that: In step (1), the ratio of pinacolone to methanol is 52-53g: 0.87-0.91g.
3. The method for preparing high-purity glycyrrhizin according to claim 1, characterized in that: In step (1), the chlorine gas is added in stages; the staged addition is as follows: initially, chlorine gas is introduced at a rate of 0.8-1.0 L / min; in the middle stage, chlorine gas is introduced at a rate of 1.5-1.7 L / min; and in the later stage, chlorine gas is introduced at a rate of 0.5-0.7 L / min.
4. The method for preparing high-purity glycyrrhizin according to claim 3, characterized in that: The time ratio for introducing chlorine gas in the initial, middle, and later stages is 1:1.5:0.
5.
5. The method for preparing high-purity glycyrrhizin according to claim 1, characterized in that: In step (2), the ratio of the amount of toluene, p-chlorophenol, potassium carbonate and monochloropinazone is 1.9-2.1g: 43.0-44.0g: 23.3-23.8g: 47.0-48.0g.
6. The method for preparing high-purity glycyrrhizin according to claim 1, characterized in that: In step (3), the addition of chlorination reagent is done intermittently with chlorine gas; the intermittent addition of chlorine gas is done by introducing chlorine gas at a rate of 0.8-1 L / min for 30-35 min and then stopping for 3-5 min; the total time for intermittent addition of chlorine gas is 4.5-5 h.
7. The method for preparing high-purity glycyrrhizin according to claim 1, characterized in that: In step (4), the ratio of the amount of toluene, imidazole, chloroether ketone, and N,N dimethylbenzylamide is 2.3-2.5g: 24.0-24.5g: 91.5-92.5g: 4.5-5g.
8. The method for preparing high-purity glycyrrhizin according to claim 1, characterized in that: In step (4), the ratio of crude ganbaosu, toluene, and activated carbon is 1-1.5g: 13-15g: 75-85mg.
9. The method for preparing high-purity glycyrrhizin according to claim 1, characterized in that: The pressure used for heating and vacuum distillation in steps (1), (3), and (4) is between -0.1 MPa and -0.08 MPa.
10. The method for preparing high-purity glycyrrhizin according to claim 1, characterized in that: The preparation process of the high-purity glycyrrhizin is as follows: 。