CN114656478A

CN114656478A - Preparation method of ellagic acid

Info

Publication number: CN114656478A
Application number: CN202011539220.3A
Authority: CN
Inventors: 徐涓; 张弘; 陈赤清; 李坤; 李凯; 张雯雯; 毛业富; 刘义稳; 张品德; 陈清龙
Original assignee: Wufeng Chicheng Biotech Co ltd; Research Institute of Resource Insects of Chinese Academy of Forestry
Current assignee: Wufeng Chicheng Biotech Co ltd; Research Institute of Resource Insects of Chinese Academy of Forestry
Priority date: 2020-12-23
Filing date: 2020-12-23
Publication date: 2022-06-24
Anticipated expiration: 2040-12-23
Also published as: CN114656478B

Abstract

The invention discloses a preparation method of ellagic acid, which comprises the steps of repeatedly mixing an alkaline solution of the ellagic acid with air under the action of a jet pump, and carrying out oxidation treatment to prepare the ellagic acid. The method has the advantages that the ellagic acid prepared by the method is high in yield and purity, the thermal stability of the ellagic acid is improved, the method combines a liquid-gas jet oxidation method and a solvent washing method to prepare the ellagic acid, the preparation time of the ellagic acid is greatly shortened, the purity of the ellagic acid is obviously improved, the production efficiency of the ellagic acid in industrial production is obviously improved, the method is suitable for large-scale industrial production of the ellagic acid, and the application of the ellagic acid in the fields of medicines and cosmetics is widened.

Description

Preparation method of ellagic acid

Technical Field

The invention relates to a preparation method of a natural product, in particular to a method for preparing ellagic acid by a chemical method, and belongs to the fields of food technology and biotechnology.

Background

Ellagic Acid (EA) is a dimeric derivative of gallic acid, and has a molecular formula of C₁₄H₆O₈It is a plant polyphenol flavone substance widely existing in fruits, nuts and other plant tissues, such as pomegranate, strawberry, walnut, etc. Domestic and foreign researches show that EA has multiple biological activities of oxidation resistance, inflammation resistance, bacteriostasis, tumor resistance, toxicity resistance and the like, and has potential effects of preventing and treating chronic diseases such as cardiovascular and cerebrovascular diseases, diabetes, neuropathy and the like. The brugkins cancer institute in the united states that "ellagic acid is the only natural variety of anticancer preparations in the last decade. In recent years, the development and application of natural ellagic acid have become the hot points of scientific research, and have wide application prospects.

At present, the preparation method of ellagic acid mainly comprises a direct extraction method, a chemical synthesis method, a chemical degradation method and a natural product degradation method. The direct extraction method is limited by the content of ellagic acid in the raw materials, the industrial process is relatively complex, and the significance of actual production is not great; the chemical synthesis method takes gallic acid (ester) or derivatives thereof as raw materials, and the gallic acid (ester) or the derivatives thereof are oxidized and coupled under enzyme catalysis to generate the ellagic acid, the yield can reach 20 to 30 percent, but the cost is higher; the chemical degradation method, namely the oxidation method of the gallnut tannin, is to introduce air or oxygen into the gallnut tannin under the alkaline condition to prepare the ellagic acid, the operation is carried out at normal temperature and normal pressure, and the production cost is lower; the natural product degradation method mainly utilizes microorganisms such as aspergillus niger and aspergillus kawachii to decompose ellagitannin to prepare ellagic acid, but the separation and purification of ellagic acid are difficult, and the method is only suitable for laboratory preparation. The method for preparing ellagic acid really realizes industrialization and is a Chinese gall Tannic Acid (TA) oxidation method, but the problems of long time consumption (24-36 h), low purity (80% -90%) and the like still exist in actual production. The quality requirements of the fields of beauty cosmetics, medicines and the like on high purity, color and luster and the like of the ellagic acid limit the application of the ellagic acid in the fields.

In order to solve the problems, the invention adopts the liquid-gas jet reactor to replace an air compressor as an air carrying and charging device, after the working liquid is pressurized, the high-speed jet generated by a nozzle pumps the ambient air to a mixing pipe and a diffusion pipe, the sucked air is dispersed into tiny bubbles due to the shearing action of the high-speed liquid and is fully mixed with the working liquid, and finally the tiny bubbles are sprayed into the reactor, the bubbles float to the liquid surface and escape, and the liquid is pressurized again to the liquid-gas jet reactor for circulation. The method determines the better process parameters of the preparation by observing the influence of four single factors such as metal ions, tannin mass concentration, reaction time, reaction temperature and the like on the yield and purity of the crude ellagic acid product. In order to obtain higher-purity ellagic acid, on the basis of preparation, the influence of a solvent washing method, a crystallization method, an alkali-dissolution acid-precipitation method and an anti-solvent method on the purity of the ellagic acid is further researched, a purification method suitable for the ellagic acid is sought, the high-purity ellagic acid is obtained, and a new technical scheme is provided for improving the commercial value of the ellagic acid and expanding the application of the ellagic acid in the fields of biomedicine and cosmetics.

Disclosure of Invention

The invention aims to provide a method for preparing, purifying and refining ellagic acid, aiming at the technical problems of long time consumption, low production efficiency, low product purity, color difference of ellagic acid and the like in the actual production process of the existing ellagic acid.

In order to achieve the purpose of the invention, the invention provides a preparation method of ellagic acid, which comprises the steps of repeatedly mixing tannin reaction liquid and air under the action of a jet pump, and carrying out oxidation treatment.

Wherein the oxidation treatment time is 5-8h, preferably 6 h; the reaction temperature is 10 to 50 ℃ and preferably 20 ℃.

Particularly, the mixing frequency of the reaction liquid and air in the oxidation reaction process is 20 to 40 times/h, preferably 30 to 40 times/h, and more preferably 30 to 32 times/h.

In particular, the tannin reaction solution is prepared by the following method: mixing tannic acid and water to prepare a tannic acid aqueous solution, adding an alkaline compound, and adjusting the pH value of the tannic acid aqueous solution to 8.0-9.0; then NaHCO is added₃Stirring and dissolving to prepare the tannic acid reaction solution.

Particularly, the mass volume concentration of the tannic acid aqueous solution is 10-100g/L, preferably 10-50 g/L.

In particular, said NaHCO₃The addition amount of the compound is 12-126g of NaHCO added into 4L of tannic acid aqueous solution₃。

In particular, 63g of NaHCO was added to an aqueous solution of tannic acid having a value of 8.0 to 9.0, 4L, pH₃And (3) solid.

In particular, the method also comprises the step of purifying the crude ellagic acid obtained by the oxidation treatment, wherein the purification treatment comprises the following steps:

adding ellagic acid obtained by oxidation treatment into NaOH solution, stirring and dissolving to obtain ellagic acid crude product preparation solution; then adding an acidic substance to adjust the pH of the ellagic acid crude product preparation solution to 4-6, and performing acid precipitation on ellagic acid; then filtering to obtain the purified ellagic acid.

Wherein the mass volume concentration of the crude ellagic acid preparation liquid is 5-20g/L, preferably 10g/L, namely 5-20g, preferably 10g of ellagic acid prepared by oxidation treatment is added into 1LNaOH solution.

In particular, the NaOH solution is present in an amount of 1 to 2% by mass, preferably 1.2% by mass.

Wherein the acidic substance is selected from glacial acetic acid or hydrochloric acid, preferably glacial acetic acid; the pH of the preparation is adjusted to 4-5, preferably 4.5.

In particular, the method also comprises the step of drying the filtered ellagic acid, wherein the drying temperature is 40-60 ℃, and preferably 50 ℃; the drying treatment time is at least 24 hours, preferably 24-36 hours.

In particular, the method also comprises the step of refining the purified ellagic acid, wherein the refining treatment comprises the following steps: adding the purified ellagic acid into a washing solution, heating while stirring, and washing the purified ellagic acid; then filtering is carried out, and the filter cake is the refined ellagic acid.

Wherein the washing solution is absolute methanol or/and absolute ethanol.

In particular, the ratio of the mass of purified ellagic acid to the volume of the washing liquid (m/v) is 1: (50-300) (g/ml), i.e. the feed-to-liquor ratio of purified ellagic acid to washing liquor is 1: (50-300), preferably 1: (100-200), more preferably 1:200, that is, 50 to 300ml of washing solution, preferably 100 to 200ml, and more preferably 200ml, per 1g of purified ellagic acid.

Wherein, the heating and stirring are carried out, and the washing temperature is 25-85 ℃, preferably 55-65 ℃, and further preferably 65 ℃; stirring for 1-2h, preferably 1 h; the stirring rate is 300-1000rpm, preferably 500 rpm.

In another aspect, the present invention provides a method for preparing ellagic acid, comprising the steps of, in order:

1) mixing tannic acid with water to obtain tannic acid aqueous solution, adding alkaline compound, and adjusting pH of the tannic acid aqueous solution to 8.0-9.0; then NaHCO is added₃Stirring and dissolving to prepare a tannic acid reaction solution;

2) placing the tannic acid reaction liquid in a reaction container, then under the action of a fluid pump, enabling the tannic acid reaction liquid to flow out of the lower part of the reaction container and be filtered by a filter, enabling filtrate to flow through the fluid pump through a pipeline and then be conveyed to a jet pump, and enabling the tannic acid reaction liquid to be subjected to oxidation reaction with air under the action of the jet pump;

3) refluxing the mixed solution after the oxidation reaction into the reaction container, floating the gas to the liquid surface to overflow, separating out the ellagic acid generated by the reaction, allowing the separated ellagic acid to flow out of the lower part of the reaction container along with the mixed solution, filtering by a filter, and trapping in the filter; the filtrate flows through a fluid pump through a pipeline and then is conveyed to a jet pump, and the filtrate and air undergo oxidation reaction under the action of the jet pump;

4) repeating the step 3) until the oxidation reaction lasts for 5-8h, stopping the fluid pump and the jet pump, refluxing the reaction mixed solution into the reaction container, and stopping the oxidation reaction;

5) adding an acidic substance into the reaction container, adjusting the pH value of the reaction mixed solution to 4-5, and carrying out acid precipitation and precipitation on the ellagic acid dissolved in the reaction mixed solution; then filtering the mixed liquid in the reaction vessel;

6) and (3) combining the ellagic acid precipitate obtained by filtering the reaction liquid in the oxidation reaction process in the step 3-4) through a filter and the ellagic acid precipitate intercepted in the step 5) to obtain a crude ellagic acid product.

Wherein, the alkaline compound in the step 1) is selected from NaOH, KOH and ammonia water, and NaOH is preferred; the pH value of the tannic acid aqueous solution is adjusted to 8.5; said NaHCO₃The addition amount of the compound is 12-126g of NaHCO added into 4L of tannic acid aqueous solution₃And (3) solid.

Particularly, the mass volume concentration of the aqueous tannic acid solution is 10 to 100g/L, preferably 10 to 50g/L, and more preferably 25 g/L.

Wherein 63g NaHCO is added to the aqueous solution of tannic acid with a value of 8.0-9.0 of 4L, pH₃And (3) a solid.

In particular, 63g NaHCO was added to an aqueous solution of tannic acid having a value of 8.5, 4L, pH₃And (3) a solid.

Wherein, the reactor in the step 2) and the step 3) is communicated with the atmosphere, the reaction liquid needs to pass through a filter before flowing through the fluid pump, and the tannin reaction liquid treated by the fluid pump is fully mixed with the air.

Particularly, the mixing frequency of the reaction liquid and the gas treated by the jet pump in the oxidation reaction process in the steps 2), 3) and 4) is 20-40 times/h, preferably 30-40 times/h, and more preferably 30-32 times/h.

Wherein, the mixing frequency of the reaction liquid and the gas, namely the liquid-gas mixing frequency (the circulation frequency of the reaction liquid), is the mixing frequency of all the reaction liquid and the air in unit time, and the complete mixing of all the reaction liquid and the air through the jet pump is marked as liquid-gas mixing for 1 time (namely circulation for 1 time and liquid change for 1 time).

The frequency of liquid-gas mixing, i.e. the frequency of liquid change, and the frequency of the reaction liquid in the reaction container returning to the reaction container after passing through the filter, the fluid pump and the jet pump in unit time

Particularly, the time of mixing liquid and gas for 1 time (namely, the reaction liquid circulates for 1 time) is 1.5 to 3min, and the liquid changing frequency is 1.5 to 3 min/time, namely, the circulation frequency per hour is 20 to 40 times.

In particular, the fluid pump has a head in the range of 10-100m and a flow rate of 1-200m³/h。

In particular, the mixing frequency of the tannic acid reaction solution with air is in the range of 20 to 40 times/h, preferably 30 to 40 times/h, and more preferably 30 to 32 times/h.

The tannin reaction liquid passes through the jet pump, high-speed jet flow is generated at the nozzle of the jet pump, a negative pressure area is formed at the nozzle outlet of the jet pump, ambient atmospheric air is sucked into the jet pump suction chamber, and liquid/gas phases are fully mixed in a jet pump mixing pipe. Under the shearing action of the high-speed jet flow of the reaction liquid, the sucked air is broken into tiny bubbles, the tannic acid reaction liquid is dispersed into tiny liquid flow, the contact area of gas phase and liquid phase is increased, the gas-liquid mixing is effectively promoted, the mass transfer process is strengthened, the chemical reaction rate is accelerated, and the oxidation reaction of the tannic acid reaction liquid and the air is promoted and accelerated;

because of the density difference between the tannic acid reaction liquid and the air, the gas floats upwards to the liquid surface and overflows, the ellagic acid generated by the reaction is separated out, and the separated ellagic acid flows out from the lower part of the reaction container along with the reaction mixed liquid, is filtered by a filter and is trapped in the filter; pressurizing the filtrate under the action of a fluid pump, conveying the filtrate to a jet pump through a pipeline, and carrying out oxidation reaction on tannic acid in the filtrate and air sucked in the environment under the action of the jet pump;

wherein, the step 3) is repeated in the step 4) for 5 to 8 hours, preferably 6 hours; the oxidation reaction temperature is 10 to 50 ℃, preferably 10 to 30 ℃, and more preferably 20 to 25 ℃.

In the oxidation reaction process, the filter traps the ellagic acid generated in the reaction process, and the ellagic acid is prevented from being excessively oxidized with air through the jet pump to generate a peroxide byproduct.

Wherein the pH of the reaction mixture in the step 5) is adjusted to 4.5.

In particular, the acidic substance in step 5) is one or more selected from glacial acetic acid, hydrochloric acid, phosphoric acid, sulfuric acid, formic acid, lactic acid, citric acid, tartaric acid or malic acid, and is preferably glacial acetic acid.

In particular, the step 6) also comprises washing the combined ellagic acid with pure water for 3-5 times (usually washing until the washing effluent is neutral), and then drying to obtain the crude ellagic acid.

In particular, the drying treatment temperature is 40-60 ℃, preferably 50 ℃; the drying treatment time is at least 24h, preferably 24-36h, and the drying is carried out until the water content of the ellagic acid crude product is less than 10%, preferably 2-10%.

Particularly, the method also comprises the step 7) of purification treatment, namely adding NaOH solution into the ellagic acid crude product prepared in the step 6), stirring and dissolving to prepare ellagic acid crude product preparation liquid; adding an acidic substance into the prepared solution to adjust the pH of the prepared solution to 4-6, and performing acid precipitation on ellagic acid; then filtering to obtain the purified ellagic acid.

Wherein, the mass percentage concentration of the NaOH solution in the step 7) is 1-2%, and is preferably 1.2%.

In particular, the mass volume concentration of the ellagic acid crude product preparation liquid is 5-20g/L, preferably 10g/L, namely 5-20g, preferably 10g of ellagic acid crude product is added into 1LNaOH solution.

Wherein, the acidic substance in the step 7) is selected from glacial acetic acid, hydrochloric acid, citric acid, tartaric acid or malic acid, and preferably glacial acetic acid.

Wherein, the pH of the preparation solution is adjusted to 4-5, preferably 4.5 in the step 7).

In particular, the method also comprises standing for at least 2 hours and then performing the filtration treatment.

Particularly, the method also comprises the steps of washing the filtered ellagic acid precipitate for 3-5 times by pure water, and then drying to obtain the purified ellagic acid. Washing with pure water until the washing effluent is neutral.

Particularly, the drying treatment temperature is 40-60 ℃, and preferably 50 ℃; the drying treatment time is at least 24h, preferably 24-36h, and the drying is carried out until the water content of ellagic acid is less than 10%, preferably 2-10%.

Particularly, the method also comprises a step 8) of refining treatment, wherein the purified ellagic acid prepared in the step 7) is added into a washing solution, and heating and stirring treatment are carried out simultaneously; then filtering is carried out, and a filter cake is the refined ellagic acid.

Wherein the washing solution is absolute methanol or absolute ethanol, and preferably absolute methanol.

Particularly, the feed-liquid ratio in the refining treatment process is 1: (50-300) (g/ml), i.e. the ratio of the mass of purified ellagic acid to the volume of the washing liquid is 1: (50-300), i.e. every 1g of purified ellagic acid is added to 50-300ml of washing liquor for stirring treatment, preferably 1: (100-200).

Particularly, in the refining treatment process, the washing temperature is controlled to be 25-85 ℃, preferably 55-65 ℃, and further preferably 65 ℃; the number of washing is 1-2, preferably 1; the washing time is 1-2h, preferably 1 h; the stirring rate is 300-1000rpm, preferably 500 rpm.

Particularly, washing the filtered filter cake by deionized water until the washing effluent liquid is neutral; the washed filter cake is then dried until the water content of the filter cake is less than 10%, preferably 2-10%.

In particular, the drying treatment temperature is 40-60 ℃, preferably 50 ℃; the drying treatment time is at least 24 hours, preferably 24-36 hours.

The invention inspects the influence of metal ions, the mass concentration of tannic acid, the reaction temperature and the reaction time on the yield and the purity of the ellagic acid. Further exploring the influence of a solvent method and a crystallization method on the recovery rate and the purity of the ellagic acid, and characterizing the high-purity ellagic acid sample by high performance liquid chromatography, infrared spectrum, ultraviolet-visible light spectrum and thermogravimetry. The preferred process conditions obtained are: metallic ion Na is introduced into tannic acid solution with mass concentration of 25g/L⁺Adjusting the pH value of the reaction solution to 8.5 by (namely NaOH), the reaction temperature is 20 ℃, the reaction time is 6h, and the yield of the ellagic acid prepared by the conditions is 46.72 percent and the purity is 84.55 percent after the ellagic acid is subjected to alkali-dissolving and acid-precipitating; a methanol solvent washing method is selected to treat the ellagic acid for 1 hour at 65 ℃, the purity of the ellagic acid reaches 98.13%, the recovery rate is 75.03%, and the thermal stability of the ellagic acid is improved.

Compared with the prior art, the invention has the following advantages and benefits:

(1) the ellagic acid purified by the method has high yield of more than 46 percent and high purity of more than 84 percent, particularly, the ellagic acid is reacted for 6 hours under the conditions of pH 8.5, tannic acid concentration of 25g/L and 20 ℃, and the ellagic acid obtained by the purification method of alkali solution and acid precipitation (sodium hydroxide dissolution and glacial acetic acid acidification to pH 4.5) has the yield of 46.72 percent and the purity of 84.55 percent, compared with the prior art, the liquid-gas jet technology obviously shortens the reaction time.

(2) The method for preparing the ellagic acid has the advantages of being high in reaction speed, remarkably shortening the time for generating the ellagic acid by oxidizing the tannic acid, and improving the preparation efficiency of the ellagic acid, and the ellagic acid prepared by the method has the oxidation reaction time of less than 8 hours, usually 5-8 hours, and the oxidation reaction time of 18-36 hours in the prior art.

(3) The purity of the ellagic acid prepared by the method is obviously improved to more than 98% after the ellagic acid is purified. Compared with the re-purification method of the ellagic acid, the solvent washing method is suitable for determining by comprehensively considering factors such as efficiency and the like, and the ellagic acid with different purities can be prepared by adjusting the material-liquid ratio, wherein the purification conditions for obtaining the ellagic acid with the purity of 95 percent are as follows: the ratio of ellagic acid to methanol is 1:100(g/mL), stirring for 1h at 65 ℃, and washing for 1 time; fixing the rest conditions, and obtaining the ellagic acid with the purity of 98% only by changing the feed-liquid ratio to 1:200 (g/mL).

Drawings

FIG. 1 is a schematic diagram of an ellagic acid production apparatus;

FIG. 2 is a graph showing the effect of the mass concentration of tannic acid on the yield and purity of crude ellagic acid;

FIG. 3 is a graph showing the effect of oxidation treatment time on the yield and purity of ellagic acid crude product;

FIG. 4 is a graph showing the effect of oxidation treatment temperature on the yield and purity of crude ellagic acid products;

FIG. 5 is a graph showing the effect of acid type and pH on ellagic acid yield and purity during purification treatment;

FIG. 6 is a graph showing the effect of temperature on ellagic acid recovery and purity during the refining process;

FIG. 7 is a graph showing the effect of the number of solvent washes on the recovery and purity of ellagic acid during the refining process;

FIG. 8 is a graph showing the effect of feed liquid ratio on ellagic acid recovery rate and purity during refining treatment;

FIG. 9 is a graph of the Lab colorimetric values of different ellagic acid samples;

FIG. 10a is a liquid chromatogram of different ellagic acid samples;

FIG. 10b is a graph of the infrared spectra of different ellagic acid samples;

FIG. 10c is a chart of UV-Vis spectra of different ellagic acid samples;

FIG. 10d is a thermogravimetric analysis of different ellagic acid samples.

Description of the reference numerals

1. A reactor; 10. reaction solution; 11. an outlet; 12. a valve; 13. an inlet; 2. a filter; 3. a fluid pump; 4. a liquid-gas jet pump; 5. a conduit.

Detailed Description

The invention will be further described with reference to specific embodiments, and the advantages and features of the invention will become apparent as the description proceeds. These examples are illustrative only and do not limit the scope of the present invention in any way. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.

Reagent and apparatus

Tannic acid (TA, gallnut tannic acid, mass fraction (purity) 92.07%), food grade, wufeng houcheng biotechnology limited; ellagic acid (EA, 99.7% by mass (purity)), standard, sigma aldrich trade ltd; methanol (volume fraction is more than or equal to 99.5 percent), absolute ethyl alcohol, sodium hydroxide, potassium hydroxide, ammonia water (weight percentage concentration is 25-28 percent), concentrated hydrochloric acid (mass percentage concentration is 36 percent), analytically pure, Tianjin, Wenyu chemical reagent science and technology Limited; n-methylpyrrolidone (NMP), sodium bicarbonate, glacial acetic acid (the volume percentage concentration is more than or equal to 99.5%), N-butanol, ethyl acetate and acetone, and the analytical reagent is pure, Guangdong Guanghua science and technology, Inc.; methanol, acetonitrile, phosphoric acid, chromatography grade, sigma aldrich trade ltd.

Tensor27 type Fourier transform Infrared Spectroscopy (FTIR), Bruker instruments, Germany; agilent Cary type ultraviolet-visible spectrophotometer, Agilent1200 type high performance liquid chromatograph, Agilent technologies ltd; STA2500 type synchronous thermal analyzer, German Chinesemeter; NH300 colorimeter, san en shi technologies ltd; conductivity meter model CPC505, semester germany; model 2004-21 constant temperature water bath, guohio ltd.

As shown in FIG. 1, a tannin reaction solution 10 is stored in a reaction vessel 1, a reaction solution outlet 11 is provided at the bottom of the reaction vessel, the outlet is communicated with a conduit 5, a valve 12 is provided at the outlet, and the outflow or stop of the reaction solution in the reaction vessel is controlled by opening or closing the valve. When the valve is opened, the reaction liquid in the reaction container is led out through the guide pipe. A reaction liquid inlet 13 is provided on the side wall (usually, the middle lower portion) of the reaction vessel, the height of the reaction liquid inlet is set higher than that of the outlet, and the reaction liquid inlet is connected to the jet pump through a conduit. A conduit 5 is connected between the reaction liquid outlet and the inlet, and a filter 2, a fluid pump 3 and a jet pump 4 are sequentially arranged on the conduit from the reaction liquid outlet to the inlet, wherein the filter, the fluid pump and the jet pump are sequentially connected through the conduit.

The tannic acid reaction liquid stored in the reaction container flows out from the reaction liquid outlet, sequentially flows through the filter, the fluid pump and the jet pump through the conduit, and flows back into the reaction container from the reaction liquid inlet. The reaction liquid in the reaction container circularly and repeatedly flows under the action of the fluid pump, so that the tannic acid in the reaction container and the air in the environment are subjected to oxidation reaction until the tannic acid is completely oxidized into the ellagic acid, the ellagic acid generated by oxidation is intercepted by the filter, the filtered liquid circularly and repeatedly flows under the action of the fluid pump, the tannic acid in the reaction liquid is fully contacted with the air in the environment sucked by the jet pump, and the oxidation reaction is carried out to generate the ellagic acid.

EXAMPLE 1 preparation of ellagic acid

1. Preparing reaction liquid of tannic acid

Accurately weighing 100g of tannic acid (58.78mmol) and dissolving in 4L of deionized water to obtain a tannic acid aqueous solution (the mass volume concentration is 25 g/L); then adding an alkaline solution (NaOH solution) to adjust the pH value of the tannic acid aqueous solution to 8.5 (usually 8.0-9.0); then 63g (0.75mol) NaHCO were added₃Preparing a tannic acid reaction solution;

in the embodiment of the invention, the concentration of the tannic acid aqueous solution is 25g/L, and other concentrations of 20-30g/L are also applicable; NaHCO is added₃The purpose of the method is to form a buffer system with sodium hydroxide, so as to ensure that the pH value of the tannic acid reaction solution is basically kept stable in the reaction process and cannot be changed greatly. NaHCO 2₃In an amount of 12 to 126g (preferably 63g) NaHCO per 4L, pH of 8.5 tannic acid solution₃Solid, stirring to dissolve.

In one embodiment of the invention, an alkaline compound (usually an alkaline solution, such as NaOH, KOH, aqueous ammonia) is added to adjust the pH of the aqueous solution of tannic acid to 8 to 9.

2. Oxidation treatment

As shown in FIG. 1, a tannic acid reaction solution is placed in a reactor 1, and the reaction solution passes through the bottom of the reactor through a conduit 5The valve flows through the filter, the filtered reaction solution flows through the fluid pump 3 through the conduit 5, the reaction solution is pressurized by the fluid pump and then flows through the jet pump 4 through the conduit, the air in the environment is sucked to the mixing pipe and the diffusion pipe (not shown in the figure) of the jet pump through the high-speed jet flow generated by the nozzle (not shown in the figure) of the jet pump, the sucked air is dispersed into tiny bubbles due to the shearing action of the high-speed liquid and is fully mixed with the tannic acid reaction solution, finally the tiny bubbles flow into the reactor 1 from the reaction solution inlet, the tannic acid reaction solution reacts with the oxygen in the air, the bubbles float to the liquid surface and escape, the tannic acid generated by oxidation of the tannic acid and the oxygen is mixed in the reaction solution and flows out from the lower part of the reactor, then the reaction solution is filtered again, pressurized by the fluid pump, the jet pump sucks the air again and sprays the liquid and the air into the reactor again for circulation, the tannic acid fully reacts with oxygen in the air, and is oxidized to generate the ellagic acid until the tannic acid is completely converted to generate the ellagic acid, wherein when the reaction liquid flows through the filter, ellagic acid solids generated in the reaction liquid are intercepted by the filter, so that the phenomenon that the ellagic acid is excessively oxidized to generate peroxide and generate impurities is avoided, the circulation is repeated, and the oxidation reaction time is 8h (usually 5-8 h); the mixing ratio of the reaction liquid to the air in the process of mixing the reaction liquid by flowing through the jet pump is 1:1 (usually 1: 1-2); the liquid-gas mixing times are 30 times/h (20-40 times/h); the oxidation reaction temperature is 20 ℃ (usually 10-50 ℃); the fluid pump head is 25 meters (typically 10-100 m); the flow rate is 2m³H (typically 1-200 m)³/h)。

The oxidation reaction in the present invention is a continuous reaction, and the reaction solution (4L): the number of liquid-gas mixing times of 1 was recorded as 1 (i.e., 1 liquid-gas mixing was performed at a flow rate of 4L per jet pump), and about 120 seconds was performed for 1 cycle (90-180 seconds for 1).

The most important point in the invention is to control the liquid-gas mixing times (namely the circulation times of the reaction liquid) in unit time, namely the mixing times of the whole reaction liquid and air in unit time. The liquid-gas mixing times (namely the circulation times) are that all reaction liquid flows through the jet pump and is completely mixed with air and recorded as liquid-gas mixing for 1 time (namely circulation for 1 time). The time for 1 cycle is 90-180s, preferably 113-120s, i.e. the number of cycles per hour is 20-40, preferably 30-32.

If the volume of the reaction liquid is increased, the fluid pump is replaced by a large-flow fluid pump, and the flow and the pipe diameter of the jet pump are matched with the fluid pump so as to meet the requirement of reaction liquid circulation; if the volume of the reaction liquid in the industrial production process is large, the reactor is also large, and a plurality of groups of fluid pumps and ejectors can be added in parallel at the same time so as to meet the requirement of the circulation of all the reaction liquid. Calculating the volume of liquid to be treated by the fluid pump or the jet pump in unit time according to the volume of the reaction liquid and the liquid-gas mixing times, and selecting the specification and the number of the fluid pumps according to the volume flow of the liquid to be treated and the resistance of a pipeline system. The specification and the number of the jet pumps are matched with those of the fluid pumps.

The jet pump is used as an air-carrying and air-charging device, air and liquid are fully mixed in the jet pump through jet flow and are returned to the reactor through a pipeline system, reaction liquid is repeatedly circulated under the action of the fluid pump and the jet pump, and tannic acid fully reacts with oxygen in the air and is oxidized to generate ellagic acid; the ellagic acid generated by oxidation of the tannic acid has low solubility, the supersaturated part of the ellagic acid generated by oxidation in the reactor is intercepted and filtered by the filter, and the ellagic acid content of the product in the filtered reaction liquid is low, so that the oxidation of the tannic acid can be accelerated, and the conversion efficiency is improved.

3. Acid precipitation of precipitate

After the oxidation reaction is carried out for 8 hours in a circulating and reciprocating manner, a valve is closed, the reaction liquid flows back to the reaction container, glacial acetic acid is added into the reaction container, the pH value of the compound in the container is adjusted to be 4.5 (usually 4-5), acid precipitation and precipitation treatment are carried out, and ellagic acid dissolved in the reaction liquid is precipitated; and then sending the mixed liquid after the acidification and precipitation treatment into a filter for filtering, intercepting the precipitated ellagic acid, and discharging the liquid as waste liquid for further treatment.

4. Drying treatment

Combining ellagic acid collected during the reaction with ellagic acid produced by the post-reaction acidification precipitation treatment, and washing the filter cake with pure water until the pH of the washing effluent is neutral, typically washing the filter cake 3-5 times; the washed filter cake is then dried in an oven at 50 deg.C (typically 40-60 deg.C) for at least 24h to a water content of 5% (typically less than 10%, preferably 2-10%) to produce crude ellagic acid (59.08 g).

Calculating the yield of the crude ellagic acid product according to the formula (1), preparing the prepared crude ellagic acid product into a methanol solution of the crude ellagic acid product with the mass concentration of 1g/L, and measuring the purity of the ellagic acid product by adopting a liquid chromatography, wherein:

yield (%) of crude ellagic acid (crude ellagic acid mass/tannic acid mass) × 100 (1)

Preparing an ellagic acid methanol solution with the mass concentration of 1g/L from the crude ellagic acid, performing purity determination by adopting a liquid-phase external standard method, preparing an ellagic acid standard solution (with the mass concentration range of 0.05-0.25 g/L), and performing liquid chromatography detection, wherein the detection conditions are as follows: the chromatographic column is Agilent ZORBAX SB-C18(4.6mm multiplied by 250mm, 5 μm), the temperature is 30 ℃, the flow rate is 1mL/min, the mobile phase is washed in a gradient way, 0min V (acetonitrile) is that V (volume fraction 0.2% phosphoric acid aqueous solution) is 20:80, 0-5 min V (acetonitrile) is that V (volume fraction 0.2% phosphoric acid aqueous solution) is 40:60, 5-10 min V (acetonitrile) is that V (volume fraction 0.2% phosphoric acid aqueous solution) is 100:0, the sample injection amount is 10 μ L, and the wavelength of the UV detector is 266 nm. 3 replicates per sample. And (3) measuring results: the yield of the crude ellagic acid is 52.10%, and the purity is 60.11%.

Example 1A

The same procedure as in example 1 was repeated except that the alkaline solution added in the step 1) "preparation of a tannic acid reaction solution" was a KOH solution, and the pH of the aqueous tannic acid solution was adjusted to 8.5, to obtain a crude ellagic acid product (26.92 g).

The yield of the crude ellagic acid is 26.92%, and the purity is 31.11%.

Example 1B

Crude ellagic acid (18.32g) was obtained in the same manner as in example 1 except that the alkaline solution added in the step 1) "preparation of the reaction solution of tannic acid" was an aqueous ammonia solution and the pH of the aqueous tannic acid solution was adjusted to 8.5.

The yield of the crude ellagic acid is 18.32%, and the purity is 25.55%.

Based on example 1,1A and 1B, the influence sequence of the metal ions on the yield of the ellagic acid crude product is sequentially Na⁺>K⁺>NH₄ ⁺In which Na⁺The yield of the crude ellagic acid product is 52.10% when the reaction is carried out, and K is introduced⁺The yield is reduced to 26.92 percent and is about Na ⁺1/2, NH₄ ⁺The yield of ellagic acid produced by the introduction of (2) was 18.32%. Therefore, the invention selects Na⁺(NaOH) ellagic acid was prepared.

Example 1C

1. Preparing reaction liquid of tannic acid

Respectively and accurately weighing tannic acid (40, 200, 280 and 400g) and dissolving in 4L deionized water to obtain tannic acid aqueous solution (with mass volume concentration of 10, 50, 75 and 100 g/L); then adding alkaline solution (NaOH solution) to adjust pH of the tannic acid aqueous solution to 8.5 (usually 8.0-9.0); then 63g (0.75mol) NaHCO were added₃Preparing a tannic acid reaction solution;

2. oxidation treatment

The tannic acid reaction solutions are respectively added into reaction vessels to respectively carry out the cyclic oxidation reaction, wherein the rest is the same as the step 2) of the embodiment 1 except that the treatment solution and the treatment gas are mixed for 30 times/h in the oxidation reaction process.

3. Acid precipitation of precipitate

Same as in step 3) of example 1.

4. Drying treatment

The amounts of crude ellagic acid obtained by using 10, 50, 75 and 100g/L aqueous tannic acid solution were 22.57g, 90.16g, 70.42g and 84.16g, respectively, in this order, as in step 3) of example 1.

Respectively calculating the yield of crude ellagic acid products prepared from the tannic acid reaction solution with different concentrations according to the formula (1), and respectively determining the purity of the ellagic acid products by adopting liquid chromatography. The yield and purity of ellagic acid crude product with different tannin concentrations are shown in figure 2. As can be seen from FIG. 2, the yield of the crude ellagic acid product decreases with the increase of the tannin mass concentration, and when the tannin mass concentration increases from 10g/L to 25g/L, the yield of the crude ellagic acid product decreases from 56.43% to 52.10%; when the tannin mass concentration is continuously increased to 100g/L, the yield of the crude ellagic acid product is 21.04%, which is only 37.29% of 10g/L (tannin mass concentration).

The ellagic acid purity tends to be stable after being reduced along with the increase of the tannin mass concentration, and when the tannin mass concentration is 10g/L, the ellagic acid purity is relatively high and is 71.65%; when the concentration of the tannin is increased to 25g/L, the purity of the ellagic acid is reduced to 60.11%, and if the concentration of the tannin is continuously increased, the purity of the ellagic acid is not greatly influenced.

The possible reason is that a large amount of phenolic hydroxyl groups and benzene rings exist in the molecules of the tannic acid, intermolecular association occurs due to hydrogen bonds and hydrophobic interaction of the tannic acid along with the increase of the concentration of the tannic acid, and the tannic acid solution is in a molecular aggregation state and exists in the solution in a colloid form, so that the reaction is incomplete, and the yield and the purity of the ellagic acid are influenced.

Although the mass concentration of tannic acid is 10g/L, the yield and the purity of the ellagic acid crude product are high, the practical production efficiency is not high due to the low concentration. Therefore, the concentration of the aqueous tannic acid solution is generally 10 to 50g/L, preferably 25g/L, in view of the combination.

Example 1D

1. Preparing reaction liquid of tannic acid

The procedure of step 1) of example 1 was repeated, except that 9 parts of tannic acid (100 g each) was accurately weighed and dissolved in 4L of deionized water.

2. Oxidation treatment

9 parts of the tannic acid reaction solution were charged into the reaction vessel, and the oxidation treatment was carried out in a cyclic reciprocating manner, and the same procedure as in 2) of example 1, except that the oxidation reaction time of the 9 parts of the tannic acid reaction solution was 1, 2, 3, 4, 5, 6, 7, 8, and 9 hours, and the number of liquid-gas mixing times was 40 times/hour.

3. Acid precipitation of precipitate

The same procedure as in step 3) of example 1 was repeated, except that the oxidation time was 1 to 9 hours, respectively.

4. Drying treatment

Same as in step 3) of example 1.

9 samples of the cyclic oxidation reaction for 1 to 9 hours respectively obtain 8.71g, 21.60g, 34.85g, 45.22g, 50.87g, 55.11g, 57.98g, 59.08g and 59.28g of crude ellagic acid.

And (3) calculating the yield of the crude ellagic acid product according to the formula (1), and determining the purity of the ellagic acid by adopting a liquid-phase external standard method. The yield and purity of ellagic acid crude product prepared by different oxidation treatment time of tannic acid are shown in figure 3. As can be seen from FIG. 3, the yield of the crude ellagic acid product tends to increase and then to be stable as the reaction time increases, while the purity of ellagic acid increases and then decreases.

When the reaction time is 6 hours, the purity of the ellagic acid crude product reaches 60.06 percent at most, and the yield is 55.11 percent; the reaction time is continuously prolonged, the yield of the crude ellagic acid product is continuously increased until the crude ellagic acid product reaches the equilibrium for 8 hours, but the purity is reduced along with the increase of the crude ellagic acid product, probably due to the oxidation of the ellagic acid generated under the alkaline condition, and the oxidation treatment time of the ellagic acid is 5-8 hours, preferably 6 hours in comprehensive consideration.

Compared with a shaking table or air-blowing stirring technology adopted by researchers and a factory existing technology (air compressor is used for ventilating the tannic acid solution for at least 36 hours), the liquid-air jet technology for preparing the ellagic acid shortens the reaction time from 16 hours and 24 hours to 5-8 hours respectively, and obviously improves the reaction efficiency. The reason is that after the working liquid is pressurized by the fluid pump, high-speed jet flow is generated by the liquid-gas jet device, outside air is sucked in according to the Bernoulli principle, and gas is broken into fine bubbles and dispersed in liquid phase fluid under the shearing action of the working liquid, so that the contact area of gas and liquid phases is increased, the gas-liquid mixing and mass and heat transfer processes are effectively promoted, the chemical reaction rate is accelerated, and the tannin high-flux interface oxidation benefit is realized.

Example 1E

1. Preparing reaction liquid of tannic acid

The procedure of step 1) of example 1 was repeated, except that 5 parts of tannic acid (100 g each) was accurately weighed and dissolved in 4L of deionized water.

2. Oxidation treatment

The same procedure as in 2) of example 1 was repeated except that 5 parts of the tannin reaction solutions were charged into the reaction vessels, respectively, and the oxidation treatment was carried out in a cyclic manner, and the oxidation reaction temperatures in the reaction vessels were controlled to 10, 20, 30, 40, and 50 ℃ during the oxidation reaction of 5 parts of the tannin reaction solutions.

3. Acid precipitation of precipitate

The procedure was followed in step 3) of example 1, except that the reaction time was 6 hours.

4. Drying treatment

Same as in step 3) of example 1.

5 parts of tannic acid reaction liquid are reacted at the oxidation reaction temperature of 10 ℃, 20 ℃, 30 ℃, 40 ℃ and 50 ℃ respectively to prepare 53.89g, 53.27g, 57.39g, 62.20g and 56.18g of crude ellagic acid.

The yield of crude ellagic acid is calculated according to formula (1), the purity of ellagic acid is determined by liquid phase external standard method, and the yield and purity of crude ellagic acid at different oxidation reaction time are shown in FIG. 4. As can be seen from FIG. 4, in the aqueous solution of tannic acid having a mass concentration of 25g/L, metal ion Na was introduced⁺When the reaction time is 6 hours, the yield of the ellagic acid crude product shows a trend of increasing firstly and then decreasing along with the increase of the reaction temperature;

the purity of ellagic acid is always in a downward trend, and when the reaction temperature is increased to 40 ℃, the yield reaches a maximum of 62.20%, but the purity is only 18.07%. Probably due to the accelerated oxidation of ellagic acid under high temperature and alkaline conditions, with the formation of other by-products; under the condition of low temperature, the reaction rate is correspondingly slowed down, but the reaction can be effectively controlled, although the yield is not high, the purity of the ellagic acid is much higher than that under the condition of high temperature, for example, the purity of the ellagic acid at 10 ℃ is 3.97 times of that at 40 ℃, but the yield is not changed greatly and the purity is different by 5.63 percent compared with that at 20 ℃. Therefore, from the viewpoint of time efficiency and energy consumption, the reaction is allowed to proceed at normal temperature as much as possible while ensuring the yield and purity of the crude ellagic acid product, and the oxidation reaction temperature is preferably 20 ℃ and usually 10 to 30 ℃.

Example 2

1. Preparing reaction liquid of tannic acid

Accurately weighing 100g of tannic acid (58.78mmol) and dissolving in 4L of deionized water to obtain tannic acid aqueous solution; followed by the addition of alkalinityA solution (NaOH solution) to adjust the pH of the aqueous tannic acid solution to 8.5 (typically 8.0-9.0); then 0.75mol of NaHCO is added₃Preparing a tannic acid reaction solution;

2. oxidation treatment

Except that the oxidation reaction time is 6h, the reaction temperature is 25 ℃; the same procedure as in step 2) of example 1 was repeated except that the number of liquid-gas mixing cycles was 32 times/hour;

3. acid precipitation of precipitate

Same as step 3) of example 1 except that the reaction was carried out for 6 h.

4. Drying treatment

In the same manner as in step 4) of example 1, a crude ellagic acid product (55.11g) was obtained;

5. purification treatment

Accurately weighing 50g of the ellagic acid crude product prepared in the step 4) under stirring, adding into NaOH solution, stirring and dissolving to obtain ellagic acid crude product preparation solution (5L), wherein the mass percentage concentration of the NaOH solution is 1.2% (usually 1-2%); the mass volume concentration of the ellagic acid crude product preparation liquid is 10g/L (usually 5-20 g/L); the ratio of the mass of the crude ellagic acid to the volume of the NaOH solution is 10: 1 (usually (5-20): 1, i.e. 5-20g, preferably 10g, of crude ellagic acid dissolved in 1 liter of NaOH solution.

Then dividing the ellagic acid product preparation solution into 5 parts, each part being 1L, respectively adding glacial acetic acid into each part of ellagic acid crude product preparation solution, adjusting pH of ellagic acid crude product preparation solution to 4.0, 4.5, 5.0, 5.5, 6.0 (usually 4.0-6.0), respectively, separating out ellagic acid, and precipitating;

after standing, respectively carrying out suction filtration treatment, and respectively washing filter cakes by deionized water until washing effluent liquid is neutral; the filter cake is then placed in an oven and dried at 50 ℃ (typically 40-60 ℃) for at least 24 hours until the water content of the filter cake is 5% (typically less than 10%, preferably 2-10%) to obtain 5 parts of purified ellagic acid (8.95g, 9.23g, 8.82g, 8.94g, 8.90g), respectively.

Preparing the prepared purified ellagic acid into a purified ellagic acid methanol solution with the mass concentration of 1g/L, and performing purity determination on the purified ellagic acid by adopting a liquid-phase external standard method, wherein an ellagic acid standard solution (the mass concentration range is 0.05-0.25 g/L) is prepared, and the liquid-phase chromatographic condition is the same as that of the purity determination in example 1. Calculating the yield of purified ellagic acid according to formula (2); the purity and yield of purified ellagic acid are shown in FIG. 5.

The purity of tannic acid in the formula (2) is 92.07%

Example 2A

The procedure of example 2 was repeated, except that concentrated hydrochloric acid (36% by mass) was added to each of the crude ellagic acid preparation solutions in the step 5) "purification treatment", and the pH values of the 5 crude ellagic acid preparation solutions were adjusted to 4.0, 4.5, 5.0, 5.5, and 6.0, respectively, to obtain 5 parts of purified ellagic acid (9.20 g, 9.21g, 8.17g, 8.20g, and 8.24g, respectively).

Determining the purity of the purified ellagic acid by adopting a liquid chromatography external standard method, and calculating the yield of the purified ellagic acid according to a formula (2); the purity and yield of purified ellagic acid are shown in FIG. 5. As can be seen from fig. 5, the yield and purity of ellagic acid increased with decreasing pH, and when pH 4.5, the yield and purity of glacial acetic acid acidulated ellagic acid were 46.72% and 84.55%, respectively, and when pH was further decreased to 4.0, the yield (46.36%) and purity (84.13%) of ellagic acid tended to level off. The purity of the ellagic acid acidified by glacial acetic acid is slightly higher than that of the concentrated hydrochloric acid acidified sample, the yield of the ellagic acid acidified by glacial acetic acid is approximately equivalent to that of the concentrated hydrochloric acid acidified sample, and the color of the ellagic acid acidified by glacial acetic acid is yellowish relative to that of the ellagic acid treated by hydrochloric acid.

And the hydrochloric acid is used for replacing glacial acetic acid to perform ellagic acid acidic precipitation, when the mass percentage concentration of the hydrochloric acid is more than 10% and the pH value is lower than 4.0, the ellagic acid is changed into grey and even grey, and becomes an unqualified product, and in the actual production process, if the hydrochloric acid with the mass concentration of lower than 10% is adopted for acidification, a large amount of industrial wastewater can be generated, and the pH value of the reaction liquid acid precipitation is difficult to control due to too strong acidity of the concentrated hydrochloric acid, so that the ellagic acid is changed into grey, and the economic value of the ellagic acid is influenced. Therefore, the weak acid glacial acetic acid is selected to adjust the pH value of acid precipitation, and the acidification pH value is 4-5, preferably 4.5.

As can be seen from FIG. 5, when the pH is not less than 5.0, the yield and purity of the ellagic acid acidified by hydrochloric acid are higher than those of the ellagic acid acidified by acetic acid, and when the pH is less than 5.0, the yield of the ellagic acid acidified by glacial acetic acid is approximately equal to that of the ellagic acid acidified by concentrated hydrochloric acid, and the purity is slightly different, but the concentrated hydrochloric acid is stronger than the glacial acetic acid, so that the local excess of the acid amount is caused in the acidification process, and the ellagic acid product is grayish black. At present, ellagic acid is mainly used in the cosmetic industry, and a gray black product can affect the sensory quality of cosmetics, so that ellagic acid with yellow color is more acceptable in the development of cosmetic products.

Example 3

1. Preparing reaction liquid of tannic acid

The procedure of example 2 was repeated except that 4 parts of 100g of tannic acid was accurately weighed and dissolved in 4L of deionized water, respectively;

2. oxidation treatment

The procedure of example 2 was repeated except that the number of times of changing the liquid was changed 30 times;

3. acid precipitation of precipitate

Same as in step 3) of example 2.

4. Drying treatment

Same as in step 4) of example 2, and 4 parts of the prepared crude ellagic acid were combined, total 223.4g, and purity by liquid chromatography was 64.26%.

Example 3A

5. Purification treatment

Precisely weighing 110g of the ellagic acid crude product prepared in example 3, adding the weighed 110g of ellagic acid crude product into 11L of NaOH solution, and stirring to dissolve, thereby preparing a crude ellagic acid preparation solution (11L), wherein the mass percentage concentration of the NaOH solution is 1.2% (usually 1-2%); the mass volume concentration of the crude ellagic acid preparation liquid is 10g/L (usually 5-20 g/L);

adding glacial acetic acid into the ellagic acid crude product preparation solution, adjusting the pH value of the ellagic acid crude product preparation solution to 4.5, and separating out ellagic acid to generate a precipitate;

standing, performing suction filtration, and washing a filter cake with deionized water until the washing effluent is neutral; drying the filter cake in an oven at 50 deg.C (usually 40-60 deg.C) for at least 24 hr until the water content of the filter cake is 5% (usually less than 10%, preferably 2-10%) to obtain purified ellagic acid (101.53 g);

the purity of the purified ellagic acid is determined to be 85.25% by adopting a liquid chromatography external standard method;

6. refining treatment

Accurately weighing 12 parts of purified ellagic acid (5 g of each part, 16.54mmol) respectively, and adding into a certain amount of washing solution (anhydrous methanol, anhydrous ethanol) respectively, wherein the material-to-solution ratio (m: v) of the purified ellagic acid to the washing solution is 1:200(g/mL), i.e. the ratio of the mass (g) of the purified ellagic acid to the volume (mL) of the washing solution is 1:200 (g/mL); then stirring at different temperatures, washing the purified ellagic acid for 1h (usually 1-2h), wherein in the washing process with anhydrous methanol, the stirring washing temperature is 25, 35, 45, 55, 65 ℃; in the washing process by adopting absolute ethyl alcohol, the stirring and washing temperatures are 25, 35, 45, 55, 65, 75 and 85 ℃; the stirring rate is 500rpm (typically 300 and 1000 rpm); respectively performing suction filtration, respectively placing the filter cakes in an oven, drying at 50 deg.C (usually 40-60 deg.C) for at least 24 hr until the water content of the filter cakes is 5% (usually less than 10%, preferably 2-10%), preparing refined ellagic acid, and respectively determining the quality of the refined ellagic acid;

the prepared refined ellagic acid is prepared into refined ellagic acid methanol solutions with the mass concentration of 1g/L respectively, and the purity of the refined ellagic acid is measured by adopting a liquid chromatography external standard method, wherein an ellagic acid standard solution (the mass concentration range is 0.05-0.25 g/L) is prepared, and the liquid chromatography conditions are the same as those of the purity measurement in example 1. Calculating the yield of the refined ellagic acid according to the formula (3); the measurement results of the purity and yield of purified ellagic acid are shown in FIG. 6.

As can be seen from fig. 6, when the detergent was absolute methanol, the change in washing temperature had little effect on the recovery rate of ellagic acid. The reason is probably that, although the recovery quality of the ellagic acid sample is lowered with the increase in temperature, impurities of ellagic acid are also dissolved by the detergent during washing, so that the purity of ellagic acid is increased from 90.95% (the purity of purified ellagic acid at 25 ℃) to 98.13% (the purity of purified ellagic acid at 65 ℃), and the quality loss and the purity increase are balanced, so that the recovery rate of ellagic acid tends to be smooth. When the detergent is ethanol, the recovery rate and the purity of the ellagic acid tend to increase and then decrease along with the increase of the temperature, and when the temperature is 65 ℃, the recovery rate and the purity of the ellagic acid reach the maximum, and are respectively 78.93% and 96.22%. In conclusion, the purity of the ellagic acid washed by the methanol is higher than that of the ethanol at the temperature of 65 ℃, so that the subsequent experiments are carried out at the temperature of 65 ℃ by using the methanol as a solvent.

Methanol is preferably used as a detergent in the refining treatment process of the ellagic acid, and the washing temperature is 55-65 ℃, and is preferably 65 ℃.

Example 3B

5. Purification treatment

Purified ellagic acid (100.96g) was obtained in the same manner as in step 5) of example 3A except that 110g of the crude ellagic acid prepared in example 3 was accurately weighed out and added to 11L of NaOH solution, and dissolved with stirring to prepare a crude ellagic acid preparation solution (11L), and the purity of the purified ellagic acid was determined to be 84.8% by a liquid chromatography external standard method;

6. refining treatment

Accurately weighing 5g of purified ellagic acid (16.54mmol)5 parts respectively, and adding into a certain amount of washing solution (anhydrous methanol) respectively, wherein the material-to-liquid ratio of the purified ellagic acid to the methanol is 1:200(g/mL), i.e. the ratio of the mass (g) of the purified ellagic acid to the volume (mL) of the anhydrous methanol in the washing solution is 1:200 (g/mL); followed by a first wash at 65 ℃ with stirring for 1h (usually 1-2 h); then, carrying out suction filtration, and respectively placing filter cakes in drying ovens with 50 ℃ (usually 40-60 ℃) for drying for at least 24 hours until the water content of the filter cakes is 5% to prepare first washing ellagic acid;

adding 4 parts of the dried first washing ellagic acid into a certain amount of washing liquid (anhydrous methanol), wherein the liquid-to-material ratio m (ellagic acid) V (methanol) is 1:200 (g/mL); followed by a second wash with stirring at 65 ℃ for 1h (typically 1-2 h); then, carrying out suction filtration, and respectively placing filter cakes in drying ovens with 50 ℃ (usually 40-60 ℃) for drying for at least 24 hours until the water content of the filter cakes is 5% to prepare second washing ellagic acid;

adding 3 parts of dried second washing ellagic acid into a certain amount of washing liquid (anhydrous methanol), wherein the liquid-to-material ratio m (ellagic acid) to V (methanol) is 1:200 (g/mL); followed by a third wash with stirring at 65 ℃ for 1h (typically 1-2 h); then, carrying out suction filtration, and respectively placing filter cakes in drying ovens with 50 ℃ (usually 40-60 ℃) for drying for at least 24 hours until the water content of the filter cakes is 5% to prepare washed ellagic acid for the third time;

adding 2 parts of dried third washing ellagic acid into a certain amount of washing liquid (anhydrous methanol), wherein the liquid-to-material ratio m (ellagic acid) V (methanol) is 1:200 (g/mL); followed by a fourth wash at 65 ℃ with stirring for 1h (typically 1-2 h); then, carrying out suction filtration, and respectively placing filter cakes in drying ovens with 50 ℃ (usually 40-60 ℃) for drying for at least 24 hours until the water content of the filter cakes is 5% to prepare the fourth washing ellagic acid;

adding 1 part of the dried fourth washing ellagic acid into a certain amount of washing liquid (absolute methanol), wherein the liquid-to-material ratio m (ellagic acid) to V (methanol) is 1:200 (g/mL); followed by a fifth wash with stirring at 65 ℃ for 1h (typically 1-2 h); then, carrying out suction filtration, and respectively placing filter cakes in ovens with 50 ℃ (usually 40-60 ℃) for drying for at least 24 hours until the water content of the filter cakes is 5% to prepare fifth washing ellagic acid;

during the first to fifth washings, the stirring rate was 500rpm (typically 300-1000 rpm).

The mass of each part of the first-fifth washing ellagic acid is respectively measured, the first-fifth washing ellagic acid is respectively dissolved in methanol to respectively prepare washing ellagic acid methanol solution with the mass concentration of 1g/L, the purity is measured by adopting a liquid chromatography external standard method, then the recovery rate of the ellagic acid after the purification treatment of the purified ellagic acid is calculated, and the measurement result is shown in figure 7. As can be seen from fig. 7: under the conditions of 65 ℃ of temperature, 1:200(g/mL) of liquid-material ratio m (ellagic acid) V (methanol) and 1h of treatment time, the purity of the ellagic acid is improved from 98.03% to 98.57% by increasing the washing times of the solvent, while the recovery rate of the ellagic acid is reduced from 75.03% to 67.89%, and the washing times are preferably 1.

Example 3C

6. Refining treatment

Accurately weighing 5 parts of the purified ellagic acid prepared in step 5) "purification treatment" of example 3B, each 5g (16.54mmol) of the purified ellagic acid being added to a certain amount of washing solution (anhydrous methanol), wherein the material-to-solution ratios of the purified ellagic acid to the washing solution are 1:50, 1:100, 1:150, 1:200, and 1:300(g/mL), respectively, i.e., the ratios of the mass (g) of the purified ellagic acid to the volume (mL) of the anhydrous methanol in the washing solution are 1:50, 1:100, 1:150, 1:200, and 1:300(g/mL), respectively; followed by stirring at 65 ℃ for 1h (typically 1-2 h); then, carrying out suction filtration, respectively placing filter cakes in ovens with 50 ℃ (usually 40-60 ℃) for drying for at least 24 hours until the water content of the filter cakes is 5%, preparing refined ellagic acid, and respectively measuring the quality of the refined ellagic acid;

dissolving the prepared refined ellagic acid in methanol, respectively preparing refined ellagic acid methanol solutions with mass concentration of 1g/L, performing purity determination by adopting a liquid chromatography external standard method, and calculating the yield of the refined ellagic acid according to formula (3); the measurement results of the purity and yield of purified ellagic acid are shown in FIG. 8.

As can be seen from fig. 8, at a temperature (65 ℃) and the number of washing times (1), the washing time is 1h, the ellagic acid purity is increased along with the decrease of the feed-liquid ratio, the recovery rate of ellagic acid is in negative correlation with the feed-liquid ratio, the recovery rate and purity of ellagic acid are 86.01% and 95.93% respectively when the feed-liquid ratio is 1:100(g/mL), the purity of ellagic acid is 97.98% and the recovery rate is 75.03% when the feed-liquid ratio is increased to 1:200(g/mL), therefore, the feed-liquid ratio in the process of ellagic acid refining according to the present invention is 1: 100-.

Comparative example

The purified ellagic acid can be refined by solvent washing, crystallization, alkali-soluble acid precipitation, and antisolvent method, which are commonly used in the art, to further improve the purity of ellagic acid.

Accurately weighing 5 parts of purified ellagic acid which is obtained by purifying the purified ellagic acid in the example 3B and is remained after refining the purified ellagic acid in the examples 3B and 3C, adding 250mL of anhydrous methanol solution into each 5g (16.54mmol), refluxing in 80 ℃ water bath for 4h, performing heat filtration, adding deionized water with different volumes into filtrate to ensure that the volume fractions of methanol are respectively 10%, 25%, 50%, 75% and 90%, crystallizing in 5 ℃ environment for 24h, performing suction filtration, washing for 3 times by deionized water, and drying in a 50 ℃ oven for 24h until the water content of a filter cake is 5%, thus respectively preparing 2.31g, 2.18g, 3.29g, 3.41g and 1.56g of the purified ellagic acid; the purity of the product is 93.25%, 97.16%, 97.66%, 98.04% and 98.81% respectively by liquid chromatography external standard method.

Example 4

1. Preparing reaction liquid of tannic acid

Same as in step 1) of example 2;

2. oxidation treatment

Same as step 2) of example 2;

3. acid precipitation of precipitate

Same as in step 3) of example 2.

4. Drying treatment

In the same manner as in step 4) of example 2, a crude ellagic acid product (55.42g) was prepared;

5. purification treatment

Purified ellagic acid (EA purified product, 46.15g) was obtained in the same manner as in step 5) of example 3A except that 50g of the crude ellagic acid prepared in step 4) was accurately weighed, added to 5L of NaOH solution, and dissolved with stirring to prepare a crude ellagic acid preparation solution (5L);

accurately weighing purified ellagic acid, adding into methanol, preparing 1g/L ellagic acid methanol solution, and performing purity determination by liquid phase external standard method to obtain purified ellagic acid with purity of 83.95%;

6. refining treatment

Adding all the purified ellagic acid into a washing solution (methanol), wherein the material-to-liquid ratio of the purified ellagic acid to the washing solution is 1:100(g/mL), namely the material-to-liquid ratio m (ellagic acid) and V (methanol) is 1:100 (g/mL); stirring at 65 deg.C for 1h (usually 1-2h), filtering, and drying the filter cake in 50 deg.C (usually 40-60 deg.C) oven for at least 24h to obtain refined ellagic acid (EA refined product, 34.99 g);

accurately weighing refined ellagic acid, adding into methanol, preparing a refined ellagic acid methanol solution with a mass concentration of 1g/L, and performing purity determination by adopting a liquid phase external standard method, wherein the determination result is that the purity of the refined ellagic acid is 96%.

Example 4A

The procedure was carried out in the same manner as in step 6) of example 4 except that in the "purification treatment" step of step 6, the liquid-to-liquid ratio m (ellagic acid): V (methanol): 1:200(g/mL) was changed, and the washing temperature with stirring was 65 ℃.

Purified ellagic acid (29.83g) was obtained, and the purity of purified ellagic acid was 97.94%.

Example 4B

The procedure was carried out in the same manner as in step 6) of example 4 except that the number of washing with stirring in the "purification treatment" step of step 6 was 2. Refined ellagic acid (25.49g) was obtained, and the purity of the refined ellagic acid was 98.30%.

Test example 1 measurement of color value of ellagic acid

Lab colorimetric values of ellagic acid (EA-commercially available) purchased in the market, purified ellagic acid (EA-purified) obtained by the purification treatment in step 5) in example 4, and purified ellagic acid (EA-purified) obtained by the purification treatment in step 6) were measured by a Sanyne NH300 colorimeter, and the measurement results are shown in FIG. 9.

The color change of the ellagic acid product can be known by measuring the Lab colorimetric value of the ellagic acid product. Wherein the L value represents the brightness of the color, and the value range is 0-100 (0: pure black, 100: pure white); the value a represents the change of color from green (-a) to red (+ a), and ranges from-128 to 128; the b value represents the change of color from blue (-b) to yellow (+ b), and ranges from-128 to 128.

The Lab color values of the different ellagic acid samples are shown in FIG. 9. As can be seen from FIG. 9, the L values are EA-commercially available < EA purification < EA-refinement, wherein the L value of the EA-refinement reaches 72.35, which is 53.09% higher than that of EA-commercially available, and the brightness of the ellagic acid prepared by the method of the present invention is higher than that of the commercially available sample; the values of a of EA-commercially available, EA purified and EA-refined are negative values of-2.13, -3.91 and-2.35 respectively, which indicates that the sample is greenish; the b values were 11.70, 13.73 and 12.13, respectively, all positive values indicating a yellowish sample. In conclusion, the L values of EA-commercial, EA-purified and EA-refined have a greater influence on the color of the sample, and the higher the purity of the ellagic acid sample is, the greater the L value thereof is.

Test example 2 determination of characteristic of ellagic acid

Purified ellagic acid (purified sample of ellagic acid) prepared by the "purification treatment" of step 5 in example 4 was taken, respectively; and (6) respectively carrying out liquid chromatography, infrared spectroscopy, ultraviolet-visible spectroscopy and thermogravimetric analysis on the refined ellagic acid (high-purity ellagic acid sample) prepared by the step 6) refining treatment and the ellagic acid standard substance, wherein:

infrared spectroscopic analysis (FTIR): performing FTIR test on ellagic acid standard substance, ellagic acid purified sample and ellagic acid high-purity sample by using a potassium bromide tabletting method, wherein the scanning range is as follows: 4000-400 cm^-1Resolution of 4 cm^-1；

Ultraviolet-visible spectrophotometric analysis (UV-Vis): preparing a sample with the mass concentration of 4mg/L by using methanol as a solvent, and performing ultraviolet-visible light full-wavelength scanning on an ellagic acid standard substance, an ellagic acid purified sample and an ellagic acid high-purity sample, wherein the wavelength ranges are as follows: 800-200 nm;

thermogravimetric analysis (TG): 3-5 mg of a sample is taken and put in an alumina ceramic crucible, thermogravimetric analysis is carried out at the temperature rise speed of 10 ℃/min within 35-800 ℃, the purging and protective atmosphere are high-purity nitrogen (the volume fraction is more than or equal to 99.99%), and the flow rate is 50 mL/min and 20mL/min respectively.

The test results are shown in FIGS. 10a-d, and the purified sample of ellagic acid is purified ellagic acid; the high-purity ellagic acid sample is refined ellagic acid.

As shown in fig. 10a, under the same liquid phase analysis conditions, the peak emergence time of the ellagic acid standard, the purified ellagic acid and the purified ellagic acid are all 5.5min, and only the peak areas are different in size, and the sequence is standard > high purity sample > purified sample, which indicates that only the purity difference exists between the samples.

As shown in FIG. 10b, the infrared spectra of purified ellagic acid and refined ellagic acid are substantially identical to that of a standard, wherein 3475cm^-1At the position of 1720cm, which is the absorption peak of O-H stretching vibration^-1The position (A) is a stretching vibration absorption peak of C ═ O, 1617, 1581, 1509 and 1449cm^-1The position (A) is a stretching vibration absorption peak of C ═ C on a benzene ring, and the stretching vibration absorption peaks all have characteristic absorption peaks of ellagic acid.

As shown in fig. 10c, the peak positions of the purified and purified ellagic acid are the same as those of the standard (254, 360nm), but the absorbance value of the purified ellagic acid is lower than that of the purified ellagic acid at the same concentration due to the higher impurity content of the purified ellagic acid.

As shown in FIG. 10d, the initial pyrolysis temperatures of the ellagic acid standard, the purified sample and the high-purity sample are 484.1, 468.40 and 481.6 ℃ which are 200 ℃ higher than the initial pyrolysis temperature of tannic acid, respectively, which indicates that there is no tannic acid residue in the ellagic acid sample, and after the solvent method washing and refining treatment by the method of the present invention, the inflection point of ellagic acid TG is increased from 483.9 ℃ of the purified sample to 498.7 ℃, which is close to 502.8 ℃ of the standard, and it can be seen that the inflection point TG of ellagic acid is gradually increased along with the increase of the purity. According to the performance characterization results, the purification of the ellagic acid by the solvent washing method improves the purity and the thermal stability of the ellagic acid.

The above-described embodiments of the present invention are merely exemplary and do not limit the scope of the present invention in any way. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.

Claims

1. A method for preparing ellagic acid is characterized in that under the action of a jet pump, a tannic acid reaction solution and air are repeatedly mixed for oxidation treatment.

2. The method according to claim 1, characterized in that the oxidation treatment time is 5-8h, preferably 6 h.

3. The method as set forth in claim 1 or2, wherein the tannin reaction solution is prepared by: mixing tannic acid with water to obtain tannic acid aqueous solution, adding alkaline compound, and adjusting pH of the tannic acid aqueous solution to 8.0-9.0; then NaHCO is added₃Stirring and dissolving to prepare theThe tannic acid reaction solution of (1).

4. A preparation method of ellagic acid is characterized by comprising the following steps of:

1) mixing tannic acid and water to prepare a tannic acid aqueous solution, adding an alkaline compound, and adjusting the pH value of the tannic acid aqueous solution to 8.0-9.0; then NaHCO is added₃Stirring and dissolving to prepare a tannic acid reaction solution;

5. The method as set forth in claim 4, wherein in the step 1), the basic compound is one or more selected from NaOH, KOH and ammonia; said NaHCO₃The addition amount of the compound is 12-126g of NaHCO added into 4L of tannic acid aqueous solution₃And (3) a solid.

6. The method as set forth in claim 4 or 5, wherein the mass volume concentration of the aqueous solution of tannic acid in the step 1) is 10 to 100 g/L.

7. The method as set forth in claim 4 or 5, wherein the number of times of mixing the reaction liquid and the gas treated by the jet pump during the oxidation reaction in the steps 2), 3), 4) is 20 to 40 times/h.

8. A process according to claim 4 or 5, wherein in step 5) the acidic substance is selected from glacial acetic acid, or one or more of hydrochloric acid, phosphoric acid, sulphuric acid, formic acid, lactic acid, citric acid, tartaric acid or malic acid.

9. The method according to claim 4 or 5, further comprising a step 7) of purification treatment of adding NaOH solution to the crude ellagic acid prepared in step 6), and stirring to dissolve to prepare a crude ellagic acid preparation solution; adding an acidic substance into the prepared solution to adjust the pH of the prepared solution to 4-6, and performing acid precipitation on ellagic acid; then filtering to obtain the purified ellagic acid.

10. The method according to claim 9, further comprising a step 8) of refining, wherein the purified ellagic acid prepared in the step 7) is added to the washing solution, heated while stirring; then filtering is carried out, and the filter cake is the refined ellagic acid.