CN113583017B - Method for selectively extracting and separating artemisinin/arteannuin by using hydrophilic ionic liquid - Google Patents

Abstract

The invention relates to a method for selective extraction and separation of artemisinin/artemisinin by hydrophilic ionic liquid. The specific process is as follows: mixing an aqueous solution of ionic liquid and an organic solvent solution of artemisinin/artemisinin, shaking at a constant temperature, and standing , respectively take the ionic liquid phase and the organic solvent phase, constant volume with methanol, detect the concentrations of artemisinin and artemisinin in the raffinate phase (organic solvent phase) and the extraction phase (ionic liquid phase), and obtain the separation selectivity. The ionic liquid aqueous solution can extract artemisinin from crude artemisinin with high selectivity, and then the raffinate phase is directly cooled and crystallized to obtain artemisinin products. The invention is applicable to the removal of low-content artemisinin, has simple and green operation, and can realize high-selectivity separation of artemisinin/artemisinin.

Description

A method for selective extraction and separation of artemisinin/artemisinin by hydrophilic ionic liquid

technical field

The invention relates to the field of purification and separation of natural products, in particular to a method for selectively extracting and separating artemisinin/artemisinin with a hydrophilic ionic liquid.

Background technique

Artemisinin is the most effective antimalarial drug recognized by the World Health Organization. It also has pharmacological activities such as antiparasitic, antifungal, anti-inflammatory, anticancer, and treatment of lupus erythematosus. It is mainly derived from Artemisia annua. This natural plant contains hundreds of components, including artemisinin, artemether, dihydroartemisinin, deoxyartemisinin and other substances that are very similar in structure to artemisinin.

The industry mainly adopts column chromatography-recrystallization purification to obtain artemisinin products, but studies have shown that it is difficult to effectively remove artemisinin with existing technologies. The structures of artemisinin and artemisinin are shown in Figure 1. There is only one C=C bond difference between the two, and their physical and chemical properties are very close. The presence of artemisinin can cause serious side effects, such as allergies, decreased drug effectiveness, etc. Therefore, the highly selective separation of artemisinin from artemisinin is one of the most challenging problems in obtaining high-quality artemisinin products.

Patent CN107746407 A discloses a method for reducing artemisinin in artemisinin. First, the petroleum ether extract of Artemisia annua is prepared and passed through a silica gel column, and then the silica gel column is eluted with a mixture of petroleum ether and ethyl acetate. Finally, the eluate is crystallized and recrystallized to achieve the purpose of separating artemisinin and artemisinin, which can reduce the content of artemisinin to 0.93-1.96%, but the process is complicated and time-consuming, so new methods need to be developed Obtain high quality artemisinin. Media innovation is the key to developing a new process for the selective separation of artemisinin and artemisinene. Ionic liquid is a special material with adjustable structure and performance. By changing the anion and/or cation structure and introducing specific functional groups, suitable Functionalized ionic liquids for a certain requirement. It has been reported that ionic liquids can identify and separate homologs with high selectivity through hydrogen bonding and π-π interactions, and are widely used in the separation of alkanes/alkenes, natural active homologues, metal ions, etc., and their separation efficiency is better than that of traditional media. For example, Liang et al. used 7 organic solvents and 11 ionic liquids to extract and separate vitamin D3 and tachysterol 3 with different double bond positions, and found that the separation selectivity of the ionic liquid system was higher than that of organic solvents, and the separation effect of sulfolane in organic solvents was the best. , the separation selectivity of vitamin D3 and tachysterol 3 is 1.44, while the selectivity of ionic liquid system can reach 1.77.

The present invention uses ionic liquid aqueous solution as the medium to separate artemisinin/artemisinene, can selectively extract artemisinin (even if the content of artemisinene is lower than 0.9%, this method is also applicable) to the ionic liquid phase, and cool and crystallize the organic solvent High-quality artemisinin products can be obtained in this phase. Compared with the traditional separation method, the method of the present invention is simple and efficient, reduces the consumption of organic solvents, and reduces the stripping process at the same time, and is a high-efficiency, green and environment-friendly process.

Contents of the invention

The purpose of the present invention is to provide an efficient, green, and environmentally friendly method for purifying artemisinin, which utilizes the strong interaction between ionic liquid and artemisinin to extract and remove artemisinin from crude artemisinin with high selectivity. Get high quality artemisinin products.

For reaching this purpose, the present invention adopts following technical scheme:

Mix the ionic liquid aqueous solution with the organic solvent solution of artemisinin/artemisinin, shake at a constant temperature, stand and separate to obtain a two-phase solution, and use high performance liquid chromatography to measure the concentrations of artemisinin and artemisinin in the two phases respectively, Calculate the separation selectivity.

As a preferred technical solution of the present invention, the ionic liquid is trimethylamine hydrochloride, triethylamine hydrochloride, choline chloride, allyl trimethyl ammonium chloride, diallyl dimethyl One or more of the ammonium chlorides, relying on the hydrophobic interaction and π-π complexation between the ionic liquid and the artemisinin to selectively extract and separate the artemisinin into the ionic liquid aqueous solution.

As a preferred technical solution of the present invention, the content of artemisinin in the crude artemisinin product is 0.8-7.5%.

As a preferred technical solution of the present invention, the volume ratio of the ionic liquid aqueous solution to the organic solvent solution containing artemisinin/artemisinin is 0.25:1-4:1.

As a preferred technical solution of the present invention, the organic solvent is one or both of cyclohexane and petroleum ether.

As a preferred technical solution of the present invention, the shaking temperature is 30-60° C., the time is 0.5-7 hours, and the two-phase solution is obtained by standing at the shaking temperature for 4 hours, and the extraction phase (ionic liquid phase) and extraction phase are respectively taken. The remaining phase (organic solvent phase) was 0.5 mL each, and the volume was adjusted to 5 mL with methanol, and the concentrations of artemisinin and artemisinin in the two phases were measured by high performance liquid chromatography, and the separation selectivity was obtained by calculation.

As a preferred technical solution of the present invention, the ionic liquid aqueous solution and the crude artemisinin organic solvent solution containing 0.8-7.5% artemisinin are mixed according to the volume ratio of 0.25:1-4:1, and shake at a constant temperature of 30-60°C 0.5～7h, shake the temperature and stand for 4h to separate the layers to obtain a two-phase solution, take 0.5mL of the extract phase (ionic liquid phase) and raffinate phase (organic solvent phase) respectively, dilute to 5mL with methanol, and use high performance liquid chromatography Determine the concentration of artemisinin and artemisinin in the two phases, and calculate the partition coefficient and separation selectivity.

The invention provides a method for selective extraction and separation of artemisinin/artemisinin by hydrophilic ionic liquid, the ionic liquid used is not volatile, biodegradable, and can identify artemisinic molecules with high selectivity, and at the same time, it is comparable to traditional methods Compared with the present invention, the operation is simple, the amount of organic solvent can be reduced, and it is an efficient and green purification and separation method.

Description of drawings

Figure 1 shows the structure of artemisinin.

Figure 2 shows the structure of artemisinin.

Detailed ways

In order to make the object, technical solution and advantages of the present invention clearer, the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the specific embodiments described here are only used to explain the present invention, not to limit the present invention.

comparative example

1) Mix equal volumes of pure water and cyclohexane solution containing artemisinin/artemisinin (artemisinin content: 4.9%), shake at 50°C for 5h, stand at 50°C for 4h, and separate to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (aqueous phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and use high-performance liquid chromatography to determine the content of artemisinin and artemisinin in the two phases, respectively. concentration, the calculated separation selectivity was 4.53.

Example 1

1) Mix an equal volume of 5% allyltrimethylammonium chloride aqueous solution (mole fraction) with a cyclohexane solution containing artemisinin/artemisinin (artemisinin content 4.9%), shake at 50°C for 5h , Stand at 50°C for 4h, and separate the layers to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 6.45.

Example 2

1) Mix equal volumes of 5% triethylamine hydrochloride aqueous solution (mole fraction) and cyclohexane solution containing artemisinin/artemisinin (artemisinin content 4.9%), shake at 50°C for 5h, and 50°C After standing for 4h, the layers were separated to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 5.97.

Example 3

1) Mix equal volumes of 5% allyltrimethylammonium chloride aqueous solution (mole fraction) with cyclohexane solution containing artemisinin/artemisinin (artemisinin content 5%), shake at 50°C for 0.5 h, stand at 50°C for 4h, and separate the layers to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 4.67.

Example 4

1) Mix an equal volume of 5% allyltrimethylammonium chloride aqueous solution (mole fraction) with a cyclohexane solution containing artemisinin/artemisinin (artemisinin content 4.5%), shake at 50°C for 1h , Stand at 50°C for 4h, and separate the layers to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 6.61.

Example 5

1) Mix an equal volume of 5% allyltrimethylammonium chloride aqueous solution (mole fraction) with a cyclohexane solution containing artemisinin/artemisinin (5% artemisinin content), shake at 50°C for 4h , Stand at 50°C for 4h, and separate the layers to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 4.74.

Example 6

1) Mix 5% allyltrimethylammonium chloride aqueous solution (mole fraction) with cyclohexane solution containing artemisinin/artemisinin (artemisinin content 5%) in equal volume, shake at 30°C for 1h , Stand at 30°C for 4h, and separate the layers to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 5.63.

Example 7

1) Mix equal volumes of 5% allyltrimethylammonium chloride aqueous solution (mole fraction) with cyclohexane solution containing artemisinin/artemisinin (4.5% artemisinin content), shake at 40°C for 1h , Stand at 40°C for 4h, and separate the layers to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 5.77.

Example 8

1) Mix an equal volume of 5% allyltrimethylammonium chloride aqueous solution (mole fraction) with a cyclohexane solution containing artemisinin/artemisinin (artemisinin content 5.1%), shake at 60°C for 1h , Stand at 60°C for 4h, and separate the layers to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 4.16.

Example 9

1) Mix 10% allyltrimethylammonium chloride aqueous solution (mole fraction) with cyclohexane solution containing artemisinin/artemisinin (artemisinin content 4.2%) in equal volume, shake at 40°C for 1h , Stand at 40°C for 4h, and separate the layers to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 8.49.

Example 10

1) Mix equal volumes of 40% allyltrimethylammonium chloride aqueous solution (mole fraction) and cyclohexane solution containing artemisinin/artemisinin (artemisinin content 4.3%), shake at 40°C for 1h , Stand at 40°C for 4h, and separate the layers to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 11.41.

Example 11

1) Mix equal volumes of 35% allyltrimethylammonium chloride aqueous solution (mole fraction) with cyclohexane solution containing artemisinin/artemisinin (artemisinin content 4.4%), shake at 40°C for 0.5 h, stand at 40°C for 4h, and separate the layers to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 10.70.

Example 12

1) Mix equal volumes of 25% allyltrimethylammonium chloride aqueous solution (mole fraction) and petroleum ether solution containing artemisinin/artemisinin (artemisinin content 1.7%), shake at 40°C for 1h, After standing at 40°C for 4h, the layers were separated to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 10.18.

Example 13

1) Mix equal volumes of 25% allyltrimethylammonium chloride aqueous solution (mole fraction) and cyclohexane solution containing artemisinin/artemisinin (artemisinin content 3.5%), shake at 40°C for 1h , Stand at 40°C for 4h, and separate the layers to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 9.11.

Example 14

1) Mix 25% allyltrimethylammonium chloride aqueous solution (mole fraction) with cyclohexane solution containing artemisinin/artemisinin (artemisinin content 2.9%) according to the volume ratio of 0.25:1. Shake at 40°C for 1h, stand at 40°C for 4h, and separate the layers to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 7.29.

Example 15

3) Mix 25% diallyldimethylammonium chloride aqueous solution (mole fraction) with cyclohexane solution containing artemisinin/artemisinin (artemisinin content 3.7%) according to the volume ratio of 1:1, Shake at 40°C for 1h, stand at 40°C for 4h, and separate the layers to obtain a two-phase solution.

4) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 6.87.

Example 16

1) Mix 25% allyltrimethylammonium chloride aqueous solution (mole fraction) with cyclohexane solution containing artemisinin/artemisinin (0.8% artemisinin content) according to the volume ratio of 1:1. Shake at 40°C for 1h, stand at 40°C for 4h, and separate the layers to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 12.23.

Example 17

1) Mix 25% allyltrimethylammonium chloride aqueous solution (mole fraction) with cyclohexane solution containing artemisinin/artemisinin (artemisinin content 7.5%) according to the volume ratio of 1:1. Shake at 40°C for 1h, stand at 40°C for 4h, and separate the layers to obtain a two-phase solution.

2) Take 0.5 mL each of the extract phase (ionic liquid phase) and the raffinate phase (organic solvent phase) with a syringe, dilute to 5 mL with methanol, and determine artemisinin and artemisinin in the two phases by high performance liquid chromatography. concentration, the calculated separation selectivity was 10.03.

Use high performance liquid chromatography (High Performance Liquid Chromatography, HPLC) to measure the concentration of artemisinin/artemisinin in the extract phase (e)/raffinate phase (r), and calculate the partition coefficient of artemisinin and artemisinin according to the following formula (D) and separation selectivity (S).

The above are only the specific implementation steps of the present invention, but the scope of protection of the present invention is not limited thereto. Any changes or substitutions that can be easily imagined by anyone familiar with the technical field within the technical scope of the disclosure of the present invention are all Should be covered within the protection scope of the present invention.

Claims (1)

1. A method for selectively extracting and separating artemisinin/arteannuin by using a hydrophilic ionic liquid is characterized by firstly mixing an artemisinin crude product containing arteannuin with an organic solvent according to a certain proportion to obtain a uniform organic phase, then adding an ionic liquid aqueous solution according to a certain proportion, shaking at a constant temperature, and finally standing for layering to obtain a two-phase solution, wherein the ionic liquid aqueous solution can be used for extracting arteannuin from the artemisinin crude product at a high selectivity, and then directly cooling and crystallizing the residual phase to obtain an artemisinin product, wherein the mass content of arteannuin in the artemisinin crude product is 0.8 to 7.5%; the ionic liquid is one or a mixture of two or more of triethylamine hydrochloride, allyl trimethyl ammonium chloride and diallyl dimethyl ammonium chloride; the organic solvent is one or a mixture of cyclohexane and petroleum ether; the mass fraction of ionic liquid substances in the ionic liquid aqueous solution is 5% -40%; the volume ratio of the ionic liquid aqueous solution to the organic solution is 0.25 to 1; the temperature of constant temperature oscillation is 30 to 60 ℃, and the time is 0.5 to 7h.

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