Environment-friendly and energy-saving glycyrrhetinic acid preparation process

Abstract

The invention provides an environment-friendly and energy-saving glycyrrhetinic acid preparation process, and relates to the technical field of chemical processes, and the environment-friendly and energy-saving glycyrrhetinic acid preparation process comprises the following steps: S1, preparing coarse crystal mother liquor dry powder, S2, carrying out acetylation reaction, S3, separating an acetylated glycyrrhetinic acid crude product, S4, washing the crude product, and S5, drying. Effective components and most impurities in the raw materials are well separated, acetylglycyrrhizic acid with certain purity is obtained under mild conditions, the initiator is moved forward, production cost is reduced, conditions are mild, the reaction is carried out under normal pressure, energy consumption and potential safety hazards of high-pressure production are reduced, reaction time is short, and the method is suitable for industrial production. The reaction process is completed within less than one hour, so that the production cycle is shortened, the energy consumption is reduced, the production cost is low, the initial raw materials are cheap, the production process is simplified, the production cost is greatly reduced, and the pollution is small because chloroform is involved in the production, so that the pollution of an organic solvent to the environment and the harm to a human body are reduced.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical processes, and more specifically, particularly relates to an environmentally friendly and energy-saving process for preparing glycyrrhetinic acid. Background Art

[0002] Glycyrrhetinic acid has a very significant anti-inflammatory effect and is widely used in various aspects of medicine and chemical industry. The preparation process of this product is roughly as follows: using glycyrrhizic acid monoammonium salt as raw material, it is cleaved under high pressure and high temperature for a long time to remove two molecules of glucuronic acid and convert it into glycyrrhetinic acid. Then it is extracted with chloroform, the chloroform layer is separated, and concentrated to obtain the crude product of glycyrrhetinic acid, and finally crystallized and recrystallized with ethanol;

[0003] The glycyrrhetinic acid produced by this process has good quality, but it also has the following problems:

[0004] 1. The starting material is monoammonium glycyrrhizinate, and the production cost is relatively high;

[0005] 2. The reaction is carried out under high pressure, which places high demands on equipment;

[0006] 3. Long-term high temperature and high pressure, energy consumption is also large;

[0007] 4. Using chloroform as a solvent will cause certain environmental pollution. Summary of the invention

[0008] In order to solve the above technical problems, the present invention provides an environmentally friendly and energy-saving process for preparing glycyrrhetinic acid to solve the above problems.

[0009] An environmentally friendly and energy-saving process for preparing glycyrrhetinic acid comprises the following steps:

[0010] S1: preparing coarse crystal mother liquor dry powder;

[0011] S2: acetylation reaction;

[0012] S3: separation of crude acetylated glycyrrhetinic acid;

[0013] S4: washing crude product;

[0014] S5: Dry.

[0015] Preferably, S1 comprises the following steps:

[0016] S11: concentrating the crude crystal mother liquor in the preparation of glycyrrhizic acid monoammonium salt under reduced pressure to recover most of the ethanol;

[0017] S12: Continue to concentrate the residual liquid until the Baume is 16-18, and spray dry it to obtain a coarse crystal mother liquor dry powder.

[0018] Preferably, S2 comprises the following steps:

[0019] S21: Take 100g of mother liquor powder, put it into a reaction bottle, and add 350ml of acetic acid;

[0020] S22: Add 20 g of concentrated sulfuric acid, stir, and slowly heat to a slightly boiling state, the temperature is about 110° C., react for 30 minutes, and then cool.

[0021] Preferably, S3 is to place the reaction solution in a Buchner funnel and filter it to obtain a wet product of acetylated glycyrrhetinic acid.

[0022] Preferably, in S3, centrifugal separation or plate and frame filtration can be used in production, and the acetic acid in the mother liquor can be recovered and reused.

[0023] Preferably, S4 is to wash the wet acetylated glycyrrhetinic acid product repeatedly with ethanol in small amounts for multiple times until the color becomes noticeably lighter.

[0024] Preferably, S5 specifically comprises: placing the washed wet acetylated glycyrrhetinic acid product in a vacuum oven for drying at a temperature of 50-60° C. for about 4 hours.

[0025] Preferably, the concentration of acetic acid in S2 is 70%-80%.

[0026] Preferably, the concentration of ethanol in S4 is 80%.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] In the present invention, the raw material is cheap and easily available, and the raw material used is the mother liquor of the production of monoammonium salt. Moving the starting material forward is beneficial to reducing the production cost.

[0029] In the present invention, the conditions are relatively mild and the reaction is carried out under normal pressure, thus reducing the energy consumption and safety hazards of high-pressure production.

[0030] In the present invention, the reaction time is short and the reaction process is completed in less than one hour, thereby shortening the production cycle and reducing energy consumption.

[0031] In the present invention, the production cost is low, the starting raw materials are cheap, the production process is simplified, and the production cost is greatly reduced.

[0032] The present invention has low pollution because chloroform is not involved in the production, thereby reducing the pollution of the environment and the harm to the human body caused by the organic solvent. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 It is the influence of different reaction times on the product yield in the present invention;

[0034] Figure 2 The influence of different solvent concentrations on the product yield in the present invention;

[0035] Figure 3 It is the effect of washing with different concentrations of ethanol on the product in the present invention;

[0036] Figure 4 It is a schematic diagram of a series of experiments in the present invention for determining the yield of crude product. DETAILED DESCRIPTION

[0037] The following embodiments of the present invention are described in further detail in conjunction with the accompanying drawings and examples. The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention.

[0038] See also Figure 1-Figure 4 The present invention provides an environmentally friendly and energy-saving process for preparing glycyrrhetinic acid, comprising the following steps:

[0039] S1: Preparation of coarse crystal mother liquor dry powder: In the production process of monoammonium glycyrrhizinate, a large amount of coarse crystal mother liquor is produced. First, these coarse crystal mother liquors are introduced into the vacuum concentration device. By reducing the pressure in the device, ethanol can be evaporated quickly at a relatively low temperature, thereby recovering most of the ethanol. In this process, the changes in pressure and temperature need to be closely monitored to ensure the efficiency and safety of the concentration process;

[0040] When most of the ethanol is recovered, continue to concentrate the residual liquid. At this time, it is necessary to gradually increase the concentration temperature and pressure to increase the concentration of the residual liquid. Use a Baume hydrometer to measure the concentration of the residual liquid in real time until the Baume degree reaches 16-18, then stop the concentration operation;

[0041] Subsequently, the concentrated residual liquid is sent to the spray drying equipment. During the spray drying process, the liquid is atomized into fine droplets through a special nozzle, and hot air is introduced at the same time to evaporate the water in the droplets quickly, thereby obtaining a dry powdery substance, that is, coarse-crystalline mother liquor dry powder. In order to ensure the drying effect and product quality, the parameters of the spray drying equipment such as the inlet temperature, outlet temperature, and spray pressure need to be precisely controlled.

[0042] S2: Acetylation reaction: Accurately weigh 100g of the prepared coarse crystal mother liquor powder and carefully put it into a clean reaction bottle. Then, add 350ml of 70%-80% acetic acid to the reaction bottle. During the addition of acetic acid, pour slowly to avoid splashing of the solution. Then, add 20g of concentrated sulfuric acid;

[0043] Be especially careful when adding concentrated sulfuric acid, as it is highly corrosive. Add it in small amounts in batches and stir constantly during the addition process to ensure the uniformity and safety of the reaction system.

[0044] After stirring evenly, start to slowly heat the reaction bottle. You can use an oil bath or electric heating jacket to heat it, so that the temperature in the reaction bottle gradually rises to a slightly boiling state, and keep the temperature at around 110°C. During the heating process, continue to stir to ensure that the reaction proceeds evenly;

[0045] After the reaction has been carried out for 30 minutes, the heating is stopped and the reaction system is allowed to cool naturally to room temperature. During the cooling process, stirring must be continued to prevent local overheating or overcooling.

[0046] S3: Separation of crude acetylated glycyrrhetinic acid: After the reaction solution is cooled to room temperature, it is transferred to a Buchner funnel for suction filtration. During the suction filtration process, filter paper or filter cloth is used to filter the reaction solution to separate the solid crude acetylated glycyrrhetinic acid from the liquid;

[0047] In order to improve the separation efficiency and effect, the filter paper or filter cloth can be properly pre-treated before filtration, such as wetting and compacting. At the same time, the vacuum degree and filtration speed of the filtration should be controlled to avoid poor separation effect caused by too fast or too slow filtration.

[0048] In actual production, if conditions permit, centrifugal separation or plate and frame filter pressing can be used instead of suction filtration. Centrifugal separation uses centrifugal force to separate solids and liquids, which has the advantages of fast separation speed and good effect. Plate and frame filter pressing achieves solid-liquid separation by applying pressure to make the liquid pass through the filter plate, which is suitable for large-scale production.

[0049] In addition, the acetic acid in the mother liquor produced during the separation process can be recovered and reused through an appropriate recovery process to reduce production costs and reduce environmental pollution.

[0050] S4: Washing the crude product: Put the separated acetylated glycyrrhetinic acid crude product into a container and wash it with 100 ml of 75% ethanol. When washing, add ethanol slowly in small amounts and multiple times while stirring continuously to allow the ethanol to fully contact with the crude product.

[0051] After each addition of ethanol, let it stand for a while to allow the ethanol to fully penetrate and dissolve the impurities, then pour out the ethanol solution containing impurities, and repeat this process until the color of the crude product becomes significantly lighter, indicating that the impurities have been fully removed;

[0052] During the washing process, attention should be paid to controlling the amount of ethanol used and the number of washes to ensure that impurities are fully removed while avoiding product loss due to excessive washing.

[0053] S5: Drying: Spread the washed wet acetylated glycyrrhetinic acid product evenly on the tray of the vacuum oven, set the oven temperature to 50-60°C, start the vacuum system, create a negative pressure environment to reduce the evaporation temperature of water and speed up the drying speed;

[0054] During the drying process, the degree of dryness of the product should be checked regularly. This can be determined by sampling to test the moisture content or observing the appearance and texture of the product. Generally speaking, the drying time is about 4 hours, but the specific time may vary depending on the moisture content of the product and the performance of the oven;

[0055] When the product reaches a predetermined degree of dryness, the oven is closed and the product is taken out after being cooled to room temperature to obtain a dry acetylated glycyrrhetinic acid product.

[0056] Through a series of experiments, the effects of different reaction times and solvent concentrations on the experimental results were compared. The reaction time and solvent concentration were determined.

[0057] 1. Effect of reaction time on product yield:

[0058] In addition to reaction time and solvent concentration, reaction temperature is also an important factor affecting acetylation reaction. Therefore, we designed a set of experiments to explore the effect of different reaction temperatures on product yield and quality. The effect of different reaction times on product yield is shown in Figure 1 .

[0059] 2. Effect of different acetic acid concentrations on reaction results:

[0060] Take 100g of the coarse crystal mother liquor dry product, 4 portions, operate according to the above scheme, the acetic acid concentration is 70%, 75%, 80%, 85%, separate the reaction product, dry and weigh it, the effect of different solvent concentrations on the product yield is shown in Figure 2 .

[0061] 3. Effects of different concentrations of ethanol washing on the product:

[0062] Take 100g of the coarse crystal mother liquor dry product, 3 portions, operate according to the above scheme, the ethanol concentration is 70%, 75%, 80% respectively, separate the reaction product, dry and weigh it, the effect of different concentrations of ethanol washing on the product is shown in Figure 3 .

[0063] 4. Comprehensively consider various factors, determine the reaction time, acetylated acetic acid concentration, washing ethanol concentration, arrange a series of experiments, and determine the crude product yield. Figure 4 .

[0064] This process separates the active ingredients from most impurities through acetylation of the dry powder of the mother liquor produced by monoammonium glycyrrhizinate, and obtains acetylglycyrrhizic acid of a certain purity under relatively mild conditions. Its advantages are cheap and easy to obtain raw materials, relatively mild conditions, short reaction time, low production cost and little pollution.

[0065] The embodiments of the present invention are given for the purpose of illustration and description, and are not intended to be exhaustive or to limit the invention to the disclosed forms. Many modifications and variations will be apparent to those of ordinary skill in the art. The embodiments are selected and described in order to better illustrate the principles and practical applications of the present invention and to enable those of ordinary skill in the art to understand the present invention and thereby design various embodiments with various modifications suitable for specific uses.

Claims

1. An environmentally friendly and energy-saving process for preparing glycyrrhetinic acid, characterized in that: The following steps are involved: S1: preparing coarse crystal mother liquor dry powder; S2: acetylation reaction; S3: separation of crude acetylated glycyrrhetinic acid; S4: washing crude product; S5: Dry.

2. The environmentally friendly and energy-saving process for preparing glycyrrhetinic acid according to claim 1, characterized in that: S1 includes the following steps: S11: concentrating the crude crystal mother liquor in the preparation of glycyrrhizic acid monoammonium salt under reduced pressure to recover most of the ethanol; S12: Continue to concentrate the residual liquid until the Baume is 16-18, and spray dry it to obtain a coarse crystal mother liquor dry powder.

3. The environmentally friendly and energy-saving process for preparing glycyrrhetinic acid according to claim 1, characterized in that: S2 includes the following steps: S21: Take 100g of mother liquor powder, put it into a reaction bottle, and add 350ml of acetic acid; S22: Add 20 g of concentrated sulfuric acid, stir, and slowly heat to a slightly boiling state, the temperature is about 110° C., react for 30 minutes, and then cool.

4. The environmentally friendly and energy-saving process for preparing glycyrrhetinic acid according to claim 1, characterized in that: S3 is to place the reaction solution in a Buchner funnel, filter it with suction, and obtain a wet product of acetylated glycyrrhetinic acid.

5. The environmentally friendly and energy-saving process for preparing glycyrrhetinic acid as claimed in claim 1, characterized in that: In S3, centrifugal separation or plate and frame filtration can be used in production, and the acetic acid in the mother liquor can be recovered and reused.

6. The environmentally friendly and energy-saving process for preparing glycyrrhetinic acid according to claim 1, characterized in that: S4 specifically involves repeatedly washing the wet product of acetylated glycyrrhetinic acid with ethanol in small amounts for multiple times until the color becomes noticeably lighter.

7. The environmentally friendly and energy-saving process for preparing glycyrrhetinic acid according to claim 1, characterized in that: S5 specifically comprises: placing the washed wet acetylated glycyrrhetinic acid product into a vacuum oven for drying at a temperature of 50-60° C. for about 4 hours.

8. The environmentally friendly and energy-saving process for preparing glycyrrhetinic acid as claimed in claim 1, characterized in that: The concentration of acetic acid in S2 is 70%-80%.

9. The environmentally friendly and energy-saving process for preparing glycyrrhetinic acid as claimed in claim 1, characterized in that: The concentration of ethanol in S4 is 80%.

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