CN114656478B - Preparation method of ellagic acid - Google Patents

Preparation method of ellagic acid Download PDF

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Publication number
CN114656478B
CN114656478B CN202011539220.3A CN202011539220A CN114656478B CN 114656478 B CN114656478 B CN 114656478B CN 202011539220 A CN202011539220 A CN 202011539220A CN 114656478 B CN114656478 B CN 114656478B
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acid
ellagic acid
reaction
ellagic
liquid
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CN114656478A (en
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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
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Wufeng Chicheng Biotech Co ltd
Research Institute of Resource Insects of Chinese Academy of Forestry
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Wufeng Chicheng Biotech Co ltd
Research Institute of Resource Insects of Chinese Academy of Forestry
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/06—Peri-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
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Abstract

The invention discloses a preparation method of ellagic acid, which comprises the steps of repeatedly mixing alkaline solution of tannic acid with air under the action of a jet pump, and carrying out oxidation treatment to prepare ellagic acid. The ellagic acid prepared by the method has high yield and purity, and the thermal stability of the ellagic acid is improved.

Description

Preparation method of ellagic acid
Technical Field
The invention relates to a preparation method of natural products, 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 C 14 H 6 O 8 Is a plant multiple Phenolic flavonoids are widely found in fruits, nuts and other plant tissues, such as pomegranates, strawberries, walnuts, and the like. Research at home and abroad shows that EA has various biological activities such as oxidation resistance, inflammation resistance, bacteriostasis, tumor resistance, toxicity resistance and the like, and has potential prevention and treatment effects on chronic diseases such as cardiovascular and cerebrovascular diseases, diabetes, neuropathy and the like. The brucines cancer institute in the united states called "ellagic acid" is the only natural variety of anticancer products for the last decade. In recent years, the development and application of natural ellagic acid have become a hot spot for scientific research, and have wide application prospects.
Currently, the preparation methods of ellagic acid mainly include direct extraction, chemical synthesis, chemical degradation and natural product degradation. 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 uses gallic acid (ester) or its derivative as raw material, and uses the oxidation coupling under the catalysis of enzyme to produce ellagic acid, its yield can be up to 20% -30%, but its cost is high; the chemical degradation method, namely the oxidation method of gallnut tannins, is that the gallnut tannins are aerated under alkaline condition to prepare ellagic acid, the operation is carried out under normal temperature and normal pressure, and the production cost is low; the natural product degradation method mainly utilizes microorganisms such as aspergillus niger and aspergillus xylophilus to decompose ellagitannins to prepare ellagic acid, but the separation and purification of the ellagic acid are difficult, and the method is only suitable for laboratory preparation. The method for preparing ellagic acid really realizes industrialization by a 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 the aspects of high purity, color and luster and the like of 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 a gas-carrying and air-charging device, high-speed jet generated by a nozzle after the working liquid is pressurized pumps 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 level to escape, and the liquid is pressurized again to the liquid-gas jet reactor for circulation. The method determines the preferable technological parameters of the preparation of the ellagic acid by examining the influence of four single factors such as metal ions, tannic acid mass concentration, reaction time, reaction temperature and the like on the yield and purity of the ellagic acid crude product. In order to obtain ellagic acid with higher purity, 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 explored on the basis of preparation, a purification method suitable for the ellagic acid is sought, 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 biological medicine and cosmetology.
Disclosure of Invention
The invention aims to provide a method for preparing, purifying and refining ellagic acid, which aims at solving 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 prior 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 tannic acid reaction liquid with air under the action of a jet pump, and carrying out oxidation treatment.
Wherein the oxidation treatment time is 5-8h, preferably 6h; the reaction temperature is 10 to 50℃and preferably 20 ℃.
In particular, the number of mixing of the reaction liquid with air during the oxidation reaction is 20 to 40 times/h, preferably 30 to 40 times/h, and more preferably 30 to 32 times/h.
In particular, the tannic acid reaction solution is prepared according to the following method: mixing tannic acid with waterAdding alkaline compound after forming tannic acid water solution, and adjusting pH value of tannic acid water solution to 8.0-9.0; then NaHCO is added 3 Stirring and dissolving to prepare the tannic acid reaction solution.
In particular, the aqueous tannic acid solution has a mass-to-volume concentration of 10-100g/L, preferably 10-50g/L.
In particular, the NaHCO 3 The addition amount of (2) is that 12-126g NaHCO is added into every 4L tannic acid water solution 3 。
In particular, 63g of NaHCO is added to an aqueous tannic acid solution having a value of 8.0 to 9.0 per 4. 4L, pH 3 A solid.
In particular, the method further comprises the step of purifying the crude ellagic acid product obtained by the oxidation treatment, wherein the purification treatment comprises the following steps:
Adding ellagic acid prepared by oxidation treatment into NaOH solution, stirring and dissolving to obtain ellagic acid crude product preparation solution; then adding acidic substances to adjust the pH of the crude ellagic acid preparation solution to 4-6, and precipitating ellagic acid by acid precipitation; and then filtering to obtain the purified ellagic acid.
Wherein the mass volume concentration of the ellagic acid crude product preparation solution is 5-20g/L, preferably 10g/L, namely 5-20g, preferably 10g of ellagic acid prepared by oxidation treatment is added into each 1LNaOH solution.
In particular, the NaOH solution has a mass percentage of 1-2%, preferably 1.2%.
Wherein the acidic substance is 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 further comprises the step of drying the filtered ellagic acid, wherein the drying temperature is 40-60 ℃, preferably 50 ℃; the drying treatment time is at least 24 hours, preferably 24-36 hours.
In particular, it further comprises subjecting the purified ellagic acid to a refining treatment, wherein the refining treatment comprises the steps of: adding purified ellagic acid into the washing liquid, heating while stirring, and washing the purified ellagic acid; and then filtering, and obtaining a filter cake, namely the refined ellagic acid.
Wherein the washing liquid 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), namely the feed liquid ratio of purified ellagic acid to washing liquid is 1: (50-300), preferably 1: (100-200), further preferably 1:200, i.e. 50-300ml of washing liquid, preferably 100-200ml, more preferably 200ml, is added per 1g of purified ellagic acid.
Wherein, the temperature of the washing is 25-85 ℃, preferably 55-65 ℃ and more preferably 65 ℃ by heating and stirring; stirring for 1-2h, preferably 1h; the stirring rate is 300-1000rpm, preferably 500rpm.
In particular, the method further comprises the step of drying the filtered ellagic acid, wherein the drying temperature is 40-60 ℃, preferably 50 ℃; the drying treatment time is at least 24 hours, preferably 24-36 hours.
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 water solution, adding alkaline compound, and regulating pH value of tannic acid water solution to 8.0-9.0; then NaHCO is added 3 Stirring and dissolving to prepare tannic acid reaction solution;
2) Placing tannic acid reaction liquid into a reaction container, flowing out the tannic acid reaction liquid from the lower part of the reaction container under the action of a fluid pump, filtering the tannic acid reaction liquid by a filter, and conveying filtrate to a jet pump after flowing through the fluid pump through a pipeline, wherein the tannic acid reaction liquid and air are subjected to oxidation reaction under the action of the jet pump;
3) The mixed solution after the oxidation reaction flows back into the reaction container, gas floats upwards to the surface of the liquid to overflow, 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 solution, is filtered by a filter and is trapped 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 are subjected to oxidation reaction under the action of the jet pump;
4) Repeating the step 3) until the oxidation reaction is carried out for 5-8h, stopping the fluid pump and the jet pump, and refluxing the reaction mixed solution into the reaction container to stop the oxidation reaction;
5) Adding acidic substances into the reaction container, adjusting the pH value of the reaction mixed solution to 4-5, and carrying out acid precipitation and precipitation on ellagic acid dissolved in the reaction mixed solution; then filtering the mixed solution 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 with the ellagic acid precipitate trapped by filtering 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 is preferably NaOH; the pH value of the tannic acid aqueous solution is adjusted to 8.5; the NaHCO 3 The addition amount of (2) is that 12-126g NaHCO is added into every 4L tannic acid water solution 3 A solid.
In particular, the aqueous tannic acid solution has a mass-volume concentration of 10 to 100g/L, preferably 10 to 50g/L, and more preferably 25g/L.
Wherein 63g NaHCO is added into tannic acid water solution with a value of 8.0-9.0 per 4. 4L, pH 3 A solid.
In particular, 63g NaHCO was added to an aqueous tannic acid solution having a value of 8.5 per 4. 4L, pH 3 A solid.
Wherein, the reactor in the step 2) and the step 3) is communicated with the atmosphere, the reaction liquid is required to pass through a filter before passing through a fluid pump, and the tannic acid reaction liquid treated by the fluid pump is fully mixed with air.
In particular, the number of mixing times of the reaction liquid and the gas treated by the jet pump during the oxidation reaction in steps 2), 3) and 4) is 20 to 40 times/h, preferably 30 to 40 times/h, and more preferably 30 to 32 times/h.
The mixing times of the reaction liquid and the gas, namely the mixing times of the liquid and the gas (the circulation times of the reaction liquid) are the mixing times of all the reaction liquid and the air in unit time, and all the reaction liquid flows through a jet pump to be completely mixed with the air and is recorded as the mixing times of the liquid and the gas (namely the circulation times are 1 time and the liquid exchanging times are 1 time).
The liquid-gas mixing frequency is the frequency of liquid exchange, the frequency of the reaction liquid in the reaction container in unit time returning to the reaction container after all the reaction liquid passes through the filter, the fluid pump and the jet pump from the reaction container, and the frequency of the periodical change is completed
In particular, the time for mixing liquid and gas for 1 time (i.e. circulating the reaction liquid for 1 time) is 1.5-3min, the liquid exchange frequency is 1.5-3 min/time, i.e. the circulating times per hour is 20-40 times.
In particular, the lift range of the fluid pump is 10-100 m, and the flow is 1-200m 3 /h。
In particular, the number of mixing times 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 tannic acid reaction liquid passes through a jet pump, high-speed jet flow is generated at a nozzle of the jet pump, a negative pressure area is formed at an outlet of the nozzle of the jet pump, ambient normal pressure air is sucked into a suction chamber of the jet pump, and liquid/gas phases are fully mixed in a mixing pipe of the jet pump. 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-liquid two phases is increased, the mixing of the gas-liquid is effectively promoted, the mass transfer process of the gas-liquid is enhanced, 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 tannic acid reaction liquid and air, gas floats upwards to overflow to the surface of the liquid, 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; the filtrate is pressurized under the action of a fluid pump and then is conveyed to a jet pump through a pipeline, and tannic acid in the filtrate and air sucked in the environment are subjected to oxidation reaction under the action of the jet pump;
Wherein, in step 4), the treatment of step 3) is repeated 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 intercepts the ellagic acid generated in the reaction process, so that the ellagic acid is prevented from being excessively oxidized with air through a jet pump, and peroxide byproducts are generated.
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 selected from one or more of glacial acetic acid, hydrochloric acid, phosphoric acid, sulfuric acid, formic acid, lactic acid, citric acid, tartaric acid or malic acid, preferably glacial acetic acid.
In particular, step 6) further comprises washing the combined ellagic acid with pure water 3-5 times (usually until the washing effluent is neutral), followed by drying to obtain the crude ellagic acid.
In particular, the drying treatment temperature is 40-60 ℃, preferably 50 ℃; the drying treatment is carried out for at least 24 hours, preferably 24-36 hours, until the water content of the crude ellagic acid is below 10%, preferably 2-10%.
In particular, the method also comprises the step 7) of purification treatment, and NaOH solution is added into the crude ellagic acid product prepared in the step 6), and stirred and dissolved to prepare crude ellagic acid product preparation liquid; adding acidic substances into the preparation solution to adjust the pH value of the preparation solution to 4-6, and carrying out acid precipitation on ellagic acid; and then filtering to obtain the purified ellagic acid.
Wherein the concentration of the NaOH solution in the step 7) is 1-2% by mass, and preferably 1.2% by mass.
In particular, the crude ellagic acid preparation has a mass/volume concentration of 5-20g/L, preferably 10g/L, i.e. 5-20g, preferably 10g of crude ellagic acid is added per 1LNaOH solution.
Wherein the acidic substance in step 7) is selected from glacial acetic acid, hydrochloric acid, citric acid, tartaric acid or malic acid, preferably glacial acetic acid.
Wherein the pH of the preparation in step 7) is adjusted to 4-5, preferably 4.5.
In particular, it also comprises a step of standing for at least 2 hours and then carrying out the filtration treatment.
In particular, the method further comprises washing the filtered ellagic acid precipitate with pure water for 3-5 times, and drying to obtain the purified ellagic acid. Washing with pure water until the washing effluent is neutral.
In particular, the drying treatment temperature is 40-60 ℃, preferably 50 ℃; the drying treatment time is at least 24 hours, preferably 24-36 hours, and the water content of ellagic acid is lower than 10%, preferably 2-10%.
In particular, the method also comprises a step 8) of refining treatment, wherein the purified ellagic acid prepared in the step 7) is added into the washing liquid, and is heated and simultaneously stirred; and then filtering, and obtaining a filter cake, namely the refined ellagic acid.
Wherein the washing liquid is absolute methanol or absolute ethanol, preferably absolute methanol.
In particular, 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. 1g of purified ellagic acid per 1g of purified ellagic acid is added to 50-300ml of washing liquid with stirring, preferably 1: (100-200).
In particular, during the refining treatment, the washing temperature is controlled to be 25-85 ℃, preferably 55-65 ℃, and more preferably 65 ℃; the number of washing is 1 to 2, preferably 1; the washing time is 1-2h, preferably 1h; the stirring rate is 300-1000rpm, preferably 500rpm.
Particularly, deionized water is adopted to wash the filtered filter cake until the washing effluent is neutral; and then drying the washed filter cake until the water content of the filter cake is lower 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 examines the influence of metal ions, tannic acid mass concentration, reaction temperature and reaction time on ellagic acid yield and purity. The influence of a solvent method and a crystallization method on the recovery rate and the purity of the ellagic acid is further explored, and the high-purity sample of the ellagic acid is characterized by high performance liquid chromatography, infrared spectrum, ultraviolet-visible spectrum and thermogravimetry. The obtained preferable process conditions are as follows: introducing metal ion Na into tannic acid solution with mass concentration of 25g/L + (namely NaOH) adjusts the pH value of the reaction solution to 8.5, the reaction temperature is 20 ℃, the reaction time is 6 hours, and the yield of the ellagic acid prepared under the condition is 46.72% after alkali dissolution and acid precipitation, and the purity is 84.55%; the methanol solvent washing method is selected to treat for 1h at 65 ℃, the purity of the ellagic acid reaches 98.13%, the recovery rate is 75.03%, and the heat of the ellagic acid is improvedStability.
Compared with the prior art, the invention has the following advantages and benefits:
(1) The yield of the ellagic acid purified by the method is high and reaches more than 46%, the purity of the ellagic acid is high and reaches more than 84%, particularly, the ellagic acid is reacted for 6 hours by adopting a liquid-gas jet technology under the conditions of pH=8.5, tannic acid concentration of 25g/L and 20 ℃, the yield of the ellagic acid obtained by an alkali-dissolution acid precipitation (sodium hydroxide dissolution and glacial acetic acid acidification to pH 4.5) purification method is 46.72%, and the purity is 84.55%, and compared with the prior art, the reaction time of the ellagic acid is obviously shortened by adopting the liquid-gas jet technology.
(2) The method for preparing the ellagic acid has high reaction speed, remarkably shortens the time for oxidizing the tannic acid to generate the ellagic acid, improves the preparation efficiency of the ellagic acid, and has the oxidation reaction time of less than 8 hours, usually 5-8 hours, and the time for preparing the ellagic acid in the prior art is 18-36 hours.
(3) After the ellagic acid prepared by the method is purified, the purity of the ellagic acid is obviously improved to more than 98 percent. Comparing the purification methods of ellagic acid, determining that the solvent washing method is suitable by comprehensively considering factors such as efficiency and the like, and preparing ellagic acid with different purities by adjusting the ratio of feed to liquid, wherein the purification conditions of the ellagic acid with the purity of 95 percent are as follows: ellagic acid and methanol feed liquid ratio is 1:100 (g/mL), stirring for 1h at 65 ℃, and washing for 1 time; the other conditions are fixed, and ellagic acid with the purity of 98% can be obtained only when the feed liquid ratio is changed 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 tannic acid mass concentration on ellagic acid crude yield and purity;
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 ellagic acid crude product;
FIG. 5 is a graph showing the effect of acid type, 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 refining;
FIG. 7 is a graph showing the effect of the number of solvent washes on ellagic acid recovery and purity during the refining process;
FIG. 8 is a graph showing the effect of feed liquid comparison on ellagic acid recovery and purity during refining;
FIG. 9 is a graph showing the results of Lab colorimetric measurements for different ellagic acid samples;
FIG. 10a is a liquid chromatogram of different ellagic acid samples;
FIG. 10b is an infrared spectrum of different ellagic acid samples;
FIG. 10c is a graph of the UV-visible spectrum 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. a 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 catheter.
Detailed Description
The invention will be further described with reference to specific embodiments, and advantages and features of the invention will become apparent from the description. These examples are merely exemplary and do not limit the scope of the invention in any way. It will be understood by those skilled in the art that various changes and substitutions of details and forms of the technical solution of the present invention may be made without departing from the spirit and scope of the present invention, but these changes and substitutions fall within the scope of the present invention.
Reagents and apparatus
Tannic acid (TA, gallnut tannic acid, mass fraction (purity) 92.07%), food grade, five-peak red sincery biotechnology, inc; ellagic acid (EA, 99.7% mass fraction (purity)), standard, sigma aldrich (shanghai) trade limited; methanol (volume fraction is more than or equal to 99.5%), absolute ethyl alcohol, sodium hydroxide, potassium hydroxide, ammonia water (weight percentage concentration is 25-28%), concentrated hydrochloric acid (mass percentage concentration is 36%), analytically pure, tianjin wind-driven vessel chemical reagent technology Co., ltd; n-methylpyrrolidone (NMP), sodium bicarbonate, glacial acetic acid (volume percent concentration is greater than or equal to 99.5%), N-butanol, ethyl acetate, acetone, analytically pure, guangdong Guanghua technology Co., ltd; methanol, acetonitrile, phosphoric acid, chromatographic grade, sigma aldrich (Shanghai) trade limited.
A Tensor27 fourier transform infrared spectrometer (FTIR), bruk spectroscopy instruments, germany; agilent Cary type ultraviolet-visible spectrophotometer, agilent1200 type high performance liquid chromatograph, agilent technologies inc; STA2500 type synchronous thermal analyzer, germany, chi-resistant scientific instruments; NH300 color difference meter, sanhen science and technology Co., ltd; CPC505 conductivity meter, style, germany; 2004-21 type constant temperature water bath, national Limited.
Referring to fig. 1, a tannic acid reaction solution 10 is stored in a reaction vessel 1, a reaction solution outlet 11 is arranged at the bottom of the reaction vessel and is communicated with a conduit 5, a valve 12 is arranged at the outlet, and the outflow of the reaction solution in the reaction vessel is controlled or stopped by opening and closing the valve. When the valve is opened, the reaction liquid in the reaction vessel is led out through the guide pipe. A reaction liquid inlet 13 is provided on the side wall (generally, the middle lower portion) of the reaction vessel, the reaction liquid inlet is provided at a higher level than the outlet, and the reaction liquid inlet is connected to a 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 guide pipe, and flows back into the reaction container from the reaction liquid inlet. The reaction liquid in the reaction container is circulated and repeatedly flowed under the action of the fluid pump, so that tannic acid in the reaction container and air in the environment are subjected to oxidation reaction until the tannic acid is completely oxidized into ellagic acid, the ellagic acid generated by oxidation is intercepted by the filter, filtered liquid is circulated and repeatedly flowed under the action of the fluid pump, and the tannic acid in the reaction liquid is fully contacted with the air in the environment inhaled by the jet pump, so that the ellagic acid is generated by oxidation reaction.
EXAMPLE 1 preparation of ellagic acid
1. Preparing tannic acid reaction liquid
100g of tannic acid (58.78 mmol) which is accurately weighed is dissolved in 4L of deionized water to prepare a tannic acid water solution (the mass volume concentration is 25 g/L); then adding alkaline solution (NaOH solution) to adjust the pH value of the tannic acid water solution to 8.5 (usually 8.0-9.0); then 63g (0.75 mol) of NaHCO are added 3 Preparing tannic acid reaction liquid;
in the embodiment of the invention, the concentration of the tannic acid aqueous solution is exemplified by 25g/L, and other concentrations of 20-30g/L are also applicable; by the introduction of NaHCO 3 The purpose of (2) 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 can not change greatly. NaHCO (NaHCO) 3 To a tannic acid solution having an addition amount of 8.5 per 4. 4L, pH, 12-126g (preferably 63 g) NaHCO is added 3 The solid was dissolved with stirring.
In the specific embodiment of the invention, an alkaline compound (usually an alkaline solution such as NaOH, KOH, ammonia solution) is added to adjust the pH of the aqueous tannic acid solution to 8-9.
2. Oxidation treatment
Referring to fig. 1, a tannic acid reaction solution is placed in a reactor 1, the reaction solution flows through a filter from the bottom of the reactor through a valve by a conduit 5, the filtered reaction solution flows through a fluid pump 3 by the conduit 5, the reaction solution is pressurized by the fluid pump and then flows through a jet pump 4 by the conduit, air in the environment is pumped to a mixing pipe and a diffusion pipe (not shown) of the jet pump by high-speed jet generated by a nozzle (not shown) of the jet pump, the pumped 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 tannic acid reaction solution flows into the reactor 1 from an inlet of the reaction solution, the bubbles react with oxygen in the air, the bubbles float to escape, tannic acid and tannic acid generated by oxidation of the oxygen flow out from the lower part of the reactor in the reaction solution, the reaction solution is filtered again, the fluid pump pressurizes, the jet pump sucks the air again, and the liquid is uniformly mixed with the air Spraying the gas into a reactor for cyclic reciprocation, fully reacting tannic acid with oxygen in the air, oxidizing to generate ellagic acid until the tannic acid is completely converted to generate ellagic acid, wherein when the reaction liquid flows through a filter, ellagic acid solids generated in the reaction liquid are intercepted by the filter, excessive oxidation of the ellagic acid to generate peroxide and impurities is avoided, and cyclic reciprocation is carried out for 8 hours (usually 5-8 hours) of oxidation reaction time; the mixing ratio of the reaction liquid to the air volume is 1:1 (usually 1:1-2) in the process of mixing the reaction liquid through a jet pump; the liquid-gas mixing times are 30 times/h (20-40 times/h); the oxidation reaction temperature is 20 ℃ (usually 10-50 ℃); the pump lift of the fluid pump is 25 meters (typically 10-100 m); flow rate of 2m 3 /h (generally 1-200m 3 /h)。
The oxidation reaction in the present invention is a continuous reaction, and in this example, the reaction liquid (4L): the number of liquid-gas mixing times 1 represents that the mixing of 4L of the reaction liquid with the gas is recorded as 1 time (namely, the flow rate of 4L of the reaction liquid is 1 time when the reaction liquid is mixed with the gas through a jet pump), and 1 cycle is completed for about 120 seconds (1 time is completed for 90-180 seconds).
The most critical 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 all the reaction liquid and air in unit time. The liquid-gas mixing times (i.e. circulation times) are that all the reaction liquid flows through the jet pump to be completely mixed with air, and the liquid-gas mixing is recorded as 1 time (i.e. circulation 1 time). The cycle time is from 90 to 180s, preferably from 113 to 120s, i.e. from 20 to 40 cycles per hour, preferably from 30 to 32 cycles per hour.
If the volume of the reaction liquid is increased, the fluid pump is replaced by a high-flow fluid pump, and the flow and the pipe diameter of the jet pump are matched with those of the fluid pump so as to meet the circulation requirement of the reaction liquid; if the volume of the reaction liquid is large in the industrial production process, the reactor is also large, and a plurality of groups of fluid pumps and jet devices can be added in parallel at the same time so as to meet the requirement of the circulation of all the reaction liquid. According to the volume of the reaction liquid and the mixing times of liquid and gas, the volume of the liquid to be processed of the fluid pump or the jet pump in unit time is calculated, and the specification and the number of the fluid pumps are selected according to the volume flow of the liquid to be processed and the resistance of a pipeline system. The size and the number of the jet pumps are matched with those of the fluid pumps.
The jet pump is used as a gas-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, the reaction liquid is repeatedly circulated under the action of the fluid pump and the jet pump, tannic acid fully reacts with oxygen in the air, and ellagic acid is generated by oxidation; the ellagic acid generated by the oxidation of tannic acid has low solubility, the filter intercepts and filters the supersaturated part of the ellagic acid generated by the oxidation in the reactor, and the filtered reaction solution has low content of the product ellagic acid, so that the oxidation of tannic acid can be accelerated, and the conversion efficiency is improved.
3. Acid precipitation
After the oxidation reaction is carried out for 8 hours in a circulating and reciprocating way, the valve is closed, the reaction liquid flows back into the reaction container, then glacial acetic acid is added into the reaction container, the pH value of the compound in the container is regulated to be 4.5 (usually 4-5), acid precipitation treatment is carried out, and ellagic acid dissolved in the reaction liquid is separated out; and then the mixed solution after the acid precipitation treatment is sent to a filter for filtering, the precipitated ellagic acid is trapped, and the liquid is discharged as waste liquid and is treated separately.
4. Drying treatment
Combining ellagic acid collected in the reaction process and ellagic acid generated by acid precipitation treatment after the reaction, and washing a filter cake with pure water until the pH of the washing effluent is neutral, wherein the washing of the filter cake is usually carried out 3-5 times; the washed cake is then dried in an oven at 50 ℃ (typically 40-60 ℃) for at least 24 hours to a cake moisture 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 according to a formula (1), preparing the prepared crude ellagic acid into a crude ellagic acid methanol solution with the mass concentration of 1g/L, and measuring the purity of the ellagic acid product by adopting a liquid chromatography, wherein:
yield of ellagic acid crude (%) = (ellagic acid crude mass/tannic acid mass) ×100 (1)
Preparing ellagic acid methanol solution with the mass concentration of 1g/L from the crude ellagic acid, measuring the purity by adopting a liquid phase external standard method, preparing ellagic acid standard substance solution (the mass concentration range is 0.05-0.25 g/L), and carrying out liquid chromatography detection, wherein the detection conditions are as follows: the chromatographic column is Agilent ZORBAX SB-C18 (4.6 mm multiplied by 250mm,5 μm), the temperature is 30 ℃, the flow rate is 1mL/min, the mobile phase is washed in a gradient way, the V (acetonitrile) is 0min, the V (volume fraction of 0.2% phosphoric acid aqueous solution) =20:80, the V (acetonitrile) is 0-5 min, the V (volume fraction of 0.2% phosphoric acid aqueous solution) =40:60, the V (acetonitrile) is 5-10 min, the V (volume fraction of 0.2% phosphoric acid aqueous solution) =100:0, the sample injection amount is 10 μL, and the wavelength of the UV detector is 266nm. 3 replicates per sample. Measurement results: the yield of the crude ellagic acid is 52.10 percent and the purity is 60.11 percent.
Example 1A
An ellagic acid crude product (26.92 g) was produced in the same manner as in example 1, except that the alkaline solution added to the "formulated tannic acid reaction solution" in step 1 was a KOH solution and the pH of the tannic acid aqueous solution was adjusted to 8.5.
The yield of the crude ellagic acid is 26.92%, and the purity is 31.11%.
Example 1B
An ellagic acid crude product (18.32 g) was produced in the same manner as in example 1, except that the alkaline solution added to the "formulated tannic acid reaction solution" in step 1) 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 examples 1, 1A, 1B, the order of influence of metal ions on the yield of ellagic acid crude product was Na in order + >K + >NH 4 + Wherein Na is + While participating in the reaction, the yield of the crude ellagic acid product is 52.10 percent, and K is introduced + The yield is reduced to 26.92%, which is about Na + 1/2 of (2), NH 4 + The yield of ellagic acid produced by the introduction was 18.32%. Therefore, the invention selects Na + (NaOH) preparation of ellagic acid.
Example 1C
1. Preparing tannic acid reaction liquid
Respectively and precisely weighed tannic acid (40, 200, 280, 400 g) is dissolved in 4L deionized water to prepare tannic acid water solution (mass volume concentration is 10, 50, 75, 100 g/L)) The method comprises the steps of carrying out a first treatment on the surface of the Then adding alkaline solution (NaOH solution) to adjust the pH value of the tannic acid water solution to 8.5 (usually 8.0-9.0); then 63g (0.75 mol) of NaHCO are added 3 Preparing tannic acid reaction liquid;
2. oxidation treatment
The tannic acid reaction liquids are respectively added into the reaction containers to respectively carry out cyclic oxidation reactions, wherein the treatment liquid-gas mixing times in the oxidation reaction process are 30 times/h, and the rest is the same as the step 2) of the example 1.
3. Acid precipitation
The same as in step 3) of example 1.
4. Drying treatment
The amounts of the crude ellagic acid produced in the same manner as in step 3) of example 1 were 22.57g, 90.16g, 70.42g and 84.16g, respectively, for the tannic acid aqueous solutions having concentrations of 10, 50, 75 and 100 g/L.
And (3) respectively calculating the crude ellagic acid yield prepared by the tannic acid reaction solutions with different concentrations according to a formula (1), and respectively measuring the purity of the ellagic acid product by adopting a liquid chromatography. The yield and purity of crude ellagic acid with different tannic acid concentrations are shown in figure 2. As can be seen from fig. 2, the yield of ellagic acid crude product decreased with increasing tannic acid mass concentration, and the yield of ellagic acid crude product decreased from 56.43% to 52.10% when tannic acid mass concentration increased from 10g/L to 25 g/L; when the tannic acid mass concentration was further increased to 100g/L, the yield of the ellagic acid crude product was 21.04%, which was only 37.29% of 10g/L (tannic acid mass concentration).
The ellagic acid purity tends to decrease firstly and then to be stable along with the increase of the mass concentration of the tannic acid, and when the mass concentration of the tannic acid is 10g/L, the ellagic acid purity is relatively high and is 71.65%; the purity of ellagic acid was reduced to 60.11% when the tannic acid concentration was increased to 25g/L, and the effect of the tannic acid concentration on the ellagic acid purity was not great if the tannic acid concentration was further increased.
The possible reason is that the tannic acid molecules have a large number of phenolic hydroxyl groups and benzene rings, and the tannic acid solution is in a molecular aggregation state and exists in a colloid form to cause incomplete reaction, so that the yield and purity of ellagic acid are affected as the concentration of tannic acid increases and the hydrogen bond and the hydrophobic effect of the tannic acid cause intermolecular association.
Although the tannic acid mass concentration is 10g/L, the yield and purity of the ellagic acid crude product are high, but the actual production efficiency is not high due to the low concentration. Thus, in combination, the concentration of the aqueous tannic acid solution is usually selected to be 10 to 50g/L, preferably 25g/L.
Example 1D
1. Preparing tannic acid reaction liquid
The procedure of step 1) of example 1 was followed except that 9 parts of tannic acid (100 g each) was accurately weighed and dissolved in 4L of deionized water, respectively.
2. Oxidation treatment
9 parts of tannic acid reaction solution are respectively added into a reaction container, and respectively subjected to cyclic reciprocating oxidation treatment, and the steps are the same as those in step 2) of the example 1 except that the oxidation reaction time of the tannic acid reaction solution is 1, 2, 3, 4, 5, 6, 7, 8 and 9 hours respectively, and the liquid-gas mixing frequency is 40 times/hour.
3. Acid precipitation
The procedure was the same as in step 3) of example 1, except that the oxidation time was 1 to 9 hours, respectively.
4. Drying treatment
The same as in step 3) of example 1.
9 samples of 1-9h of the cyclic oxidation reaction are respectively prepared into 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 according to a formula (1), and measuring the purity of the ellagic acid by adopting a liquid phase external standard method. The yield and purity of the crude ellagic acid prepared by different oxidation treatment times of tannic acid are shown in figure 3. As can be seen from fig. 3, the yield of the crude ellagic acid product tended to rise and then stabilize with the increase in the reaction time, while the purity of ellagic acid increased and then decreased.
When the reaction time is 6 hours, the purity of the crude ellagic acid product reaches 60.06 percent to the maximum, and the yield is 55.11 percent; the reaction time is further prolonged and the yield of the crude ellagic acid product is further increased until an equilibrium is reached for 8 hours, but the purity is reduced with it, probably due to oxidation of the ellagic acid produced under alkaline conditions, and the duration of the oxidation treatment of ellagic acid is comprehensively considered to be 5-8 hours, preferably 6 hours.
Compared with shaking table or air stirring technology and factory existing technology (ventilating tannic acid liquid by using an air compressor and reacting for at least 36 h) adopted by researchers, the reaction time of the ellagic acid prepared by the liquid-air jet technology is shortened to 5-8h from 16h and 24h respectively, and the reaction efficiency is obviously improved. The working liquid is pressurized by the fluid pump, then high-speed jet flow is generated by the liquid-gas jet device, external air is sucked according to the Bernoulli principle, and the gas is broken into tiny bubbles and dispersed in the liquid-phase fluid under the shearing action of the working liquid, so that the contact area of gas-liquid two phases is increased, the gas-liquid mixing and mass and heat transfer processes are effectively promoted, the chemical reaction rate is accelerated, and the high-flux interface oxidation benefit of tannic acid is realized.
Example 1E
1. Preparing tannic acid reaction liquid
The procedure of step 1) of example 1 was followed except that 5 parts of tannic acid (100 g each) was accurately weighed and dissolved in 4L of deionized water, respectively.
2. Oxidation treatment
The procedure of step 2) of example 1 was the same as that of step 2) of example 1 except that 5 parts of tannic acid reaction solution was respectively added to the reaction vessels, the oxidation treatment was respectively carried out in a cyclic manner, and the oxidation reaction temperatures in the reaction vessels were controlled to be 10, 20, 30, 40, 50 ℃ during the oxidation reaction of 5 parts of tannic acid reaction solution.
3. Acid precipitation
The procedure was the same as in step 3) of example 1, except for the reaction for 6 h.
4. Drying treatment
The same as in step 3) of example 1.
5 parts of tannic acid reaction liquid react at the oxidation reaction temperatures of 10, 20, 30, 40 and 50 ℃ respectively to obtain 53.89g, 53.27g, 57.39g, 62.20g and 56.18g of crude ellagic acid.
Calculating the yield of crude ellagic acid according to formula (1), measuring the purity of ellagic acid by liquid phase external standard method, and performing different oxidation reactionsThe crude ellagic acid yield and purity over time are shown in figure 4. As is clear from FIG. 4, metal ions Na were introduced into the aqueous tannic acid solution at a mass concentration of 25g/L + When the reaction time is 6 hours, the yield of the crude ellagic acid product is in a trend of rising and then falling along with the rising of the reaction temperature;
The purity of ellagic acid is always in a decreasing trend, and when the reaction temperature is raised to 40 ℃, the yield reaches a maximum value 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, other by-products being formed; the reaction rate is correspondingly slowed down under the low temperature condition, but the reaction can be effectively controlled, and the yield is not high, but the purity of the ellagic acid is much higher than that under the high temperature condition, for example, the purity of the ellagic acid at 10 ℃ is 3.97 times of that at 40 ℃, but the yield is not greatly changed and the purity is 5.63% different from that of the ellagic acid at 20 ℃. Therefore, in view of time efficiency and energy consumption, the oxidation reaction temperature is preferably 20℃and usually 10 to 30℃while ensuring the yield and purity of the crude ellagic acid product as much as possible.
Example 2
1. Preparing tannic acid reaction liquid
100g of tannic acid (58.78 mmol) which was precisely weighed was dissolved in 4L of deionized water to prepare an aqueous tannic acid solution; then adding alkaline solution (NaOH solution) to adjust the pH value of the tannic acid water solution to 8.5 (usually 8.0-9.0); then 0.75mol NaHCO is added 3 Preparing tannic acid reaction liquid;
2. Oxidation treatment
Except that the oxidation reaction time is 6 hours, the reaction temperature is 25 ℃; the procedure of step 2) of example 1 was repeated except that the number of liquid-gas mixture was 32 times/h;
3. acid precipitation
The procedure was the same as in step 3) of example 1, except for reaction 6 h.
4. Drying treatment
Crude ellagic acid (55.11 g) was obtained in the same manner as in step 4) of example 1;
5. purification treatment
Accurately weighing 50g of the crude ellagic acid product prepared in the step 4) under stirring, adding into a NaOH solution, stirring and dissolving to prepare a crude ellagic acid product preparation solution (5L), wherein the concentration of the NaOH solution is 1.2 percent (usually 1-2 percent) by mass; the mass volume concentration of the ellagic acid crude product preparation solution 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 was 10:1 (generally (5-20): 1, i.e. 5-20g, preferably 10g of crude ellagic acid are dissolved in 1 liter of NaOH solution.
Dividing the ellagic acid product preparation solution into 5 parts, adding glacial acetic acid into each part of ellagic acid crude product preparation solution respectively, adjusting the pH value of the ellagic acid crude product preparation solution to be 4.0, 4.5, 5.0, 5.5 and 6.0 (usually 4.0-6.0), separating out ellagic acid, and precipitating;
after standing, carrying out suction filtration treatment respectively, and washing filter cakes with deionized water respectively until washing effluent is neutral; the filter cake was then placed in an oven and dried at 50 c (typically 40-60 c) for at least 24 hours until the water content of the filter cake was 5% (typically less than 10%, preferably 2-10%) to yield 5 parts of purified ellagic acid (8.95 g, 9.23g, 8.82g, 8.94g, 8.90 g), respectively.
Preparing purified ellagic acid into purified ellagic acid methanol solution with the mass concentration of 1g/L, and measuring the purity of the purified ellagic acid by adopting a liquid phase external standard method, wherein the prepared ellagic acid standard solution (with the mass concentration range of 0.05-0.25 g/L) is prepared, and the liquid phase chromatographic conditions are the same as those of the purity measurement of the example 1. Calculating the yield of purified ellagic acid according to formula (2); the measurement results of 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 same as in example 2 was conducted, except that in the "purification treatment" in step 5), concentrated hydrochloric acid (36% by mass) was added to each of the crude ellagic acid preparation solutions, and the pH values of the 5 parts of 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 9.20g, 9.21g, 8.17g, 8.20g and 8.24g, respectively.
Measuring 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 measurement results of 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 at pH 4.5, the yield and purity of glacial acetic acid acidified ellagic acid were 46.72% and 84.55%, respectively, and at continuing to decrease pH to 4.0, the yield (46.36%) and purity (84.13%) of ellagic acid tended to be smooth. The purity of the glacial acetic acid-acidified ellagic acid is slightly higher than that of the concentrated hydrochloric acid-acidified sample, the yield is approximately equal to that of the concentrated hydrochloric acid-acidified sample, and the color of the glacial acetic acid-acidified ellagic acid is relatively yellow compared with that of the hydrochloric acid-treated ellagic acid.
Hydrochloric acid is used for replacing glacial acetic acid for acidic precipitation, when the mass percent concentration of the hydrochloric acid is more than 10 percent and the pH value is lower than 4.0, the ellagic acid becomes grey or grey, and becomes an unqualified product, in the actual production process, if hydrochloric acid with the mass concentration lower than 10 percent is used for acidification, a large amount of industrial wastewater can be generated, and the pH value of the reaction solution for acid precipitation is difficult to control due to the fact that the concentrated hydrochloric acid is too strong, the ellagic acid becomes grey, so that the economic value of the ellagic acid is influenced. Therefore, the invention adopts weak acid glacial acetic acid to adjust the pH of the 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 hydrochloric acid acidified ellagic acid are higher than those of acetic acid, and when the pH is less than 5.0, the yield of the glacial acetic acid acidified ellagic acid is approximately equal to that of a concentrated hydrochloric acid acidified sample, and the purity is slightly different, but the concentrated hydrochloric acid is stronger than the glacial acetic acid, so that the acid amount is locally excessive in the acidification process, and the ellagic acid product becomes grey black. Currently, ellagic acid is mainly used in the cosmetic industry, and grey-black products influence 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 tannic acid reaction liquid
The procedure of step 1) of example 2 was followed except that 4 parts of 100g tannic acid each was precisely weighed and dissolved in 4L of deionized water;
2. oxidation treatment
The rest is the same as the step 2) of the embodiment 2 except that the number of the treatment liquid exchange times is 30;
3. acid precipitation
The same as in step 3) of example 2.
4. Drying treatment
The same as in step 4) of example 2, and 4 parts of the prepared crude ellagic acid were combined together to give 223.4g total, with a purity of 64.26% as determined by liquid chromatography.
Example 3A
5. Purification treatment
110g of the crude ellagic acid prepared in example 3 was precisely weighed, added into 11L of NaOH solution, stirred and dissolved to prepare crude ellagic acid preparation solution (11L), wherein the concentration of the NaOH solution is 1.2% (usually 1-2%) by mass; the mass volume concentration of the ellagic acid crude product preparation solution is 10g/L (usually 5-20 g/L);
then adding glacial acetic acid into the ellagic acid crude product preparation liquid, regulating the pH value of the ellagic acid crude product preparation liquid to be 4.5, and separating out the ellagic acid to generate a precipitate;
standing, performing suction filtration, and washing a filter cake with deionized water until washing effluent is neutral; drying the filter cake in an oven at 50deg.C (typically 40-60deg.C) for at least 24h until the water content of the filter cake is 5% (typically 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
Respectively accurately weighing 12 parts of purified ellagic acid (5 g each, 16.54 mmol) and respectively adding the 12 parts of purified ellagic acid into a certain amount of washing liquid (absolute methanol and absolute ethanol), wherein the feed liquid ratio (m: v) of the purified ellagic acid to the washing liquid is 1:200 (g/mL), namely the ratio of the mass (g) of the purified ellagic acid to the volume (mL) of the washing liquid is 1:200 (g/mL); then stirring at different temperatures, washing and purifying ellagic acid for 1h (usually 1-2 h), wherein in the washing process adopting anhydrous methanol, the stirring and washing temperature is 25, 35, 45, 55 and 65 ℃; in the washing process by adopting absolute ethyl alcohol, the stirring washing temperature is 25, 35, 45, 55, 65, 75 and 85 ℃; the stirring rate is 500rpm (typically 300-1000 rpm); respectively suction-filtering, respectively placing the filter cakes in an oven, drying at 50deg.C (40-60deg.C) for at least 24h until the water content of the filter cakes is 5% (usually less than 10%, preferably 2-10%), to obtain refined ellagic acid, and respectively measuring the quality of the refined ellagic acid;
the prepared refined ellagic acid is respectively prepared into refined ellagic acid methanol solutions with the mass concentration of 1g/L, the purity of the refined ellagic acid is measured by adopting a liquid chromatography external standard method, wherein the prepared ellagic acid standard solution (with the mass concentration range of 0.05-0.25 g/L) is prepared, and the liquid chromatography conditions are the same as those of the purity measurement of the example 1. Calculating the yield of refined ellagic acid according to 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 is anhydrous methanol, the change in the washing temperature has little effect on the recovery rate of ellagic acid. The possible reason is that, as the temperature increases, although the recovery quality of the ellagic acid sample decreases, the impurities of the ellagic acid are also dissolved by the detergent during the washing process, increasing the purity of the ellagic acid from 90.95% (purity of purified ellagic acid at 25 ℃) to 98.13% (purity of purified ellagic acid at 65 ℃), the quality loss being offset by the purity increase, resulting in a smooth recovery of ellagic acid. When the detergent is ethanol, the recovery rate and the purity of the ellagic acid show a trend of rising and then falling along with the rising of the temperature, and when the temperature is 65 ℃, the recovery rate and the purity of the ellagic acid reach the maximum, respectively 78.93 percent and 96.22 percent. In summary, at 65 ℃, the purity of the methanol washing ellagic acid is higher than that of ethanol, so that the methanol is selected as a solvent, and the subsequent experiment is carried out at 65 ℃.
In the ellagic acid refining treatment process of the invention, methanol is preferably used as a detergent, and the washing temperature is 55-65 ℃, preferably 65 ℃.
Example 3B
5. Purification treatment
Purified ellagic acid (100.96 g) 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 precisely weighed and added to 11L of NaOH solution, and stirred and dissolved to prepare a crude ellagic acid preparation solution (11L), and the purity of the purified ellagic acid was 84.8% as determined by a liquid chromatography external standard method;
6. Refining treatment
5g of purified ellagic acid (16.54 mmol) is respectively and accurately weighed and 5 parts of purified ellagic acid are respectively added into a certain amount of washing liquid (anhydrous methanol), wherein the feed liquid ratio of the purified ellagic acid to the methanol is 1:200 (g/mL), namely the ratio of the mass (g) of the purified ellagic acid to the volume (mL) of the washing liquid (anhydrous methanol) is 1:200 (g/mL); followed by stirring at 65℃for 1h (usually 1-2 h), and a first washing; then suction filtering, and respectively placing the filter cakes in a baking oven with the temperature of 50 ℃ (usually 40-60 ℃) and drying for at least 24 hours until the water content of the filter cakes is 5%, thus preparing the first washing ellagic acid;
adding 4 parts of the dried first-time washing ellagic acid into a certain amount of washing liquid (anhydrous methanol), wherein the liquid-to-material ratio m (ellagic acid): V (methanol) =1:200 (g/mL); followed by stirring at 65℃for 1h (usually 1-2 h) and a second wash; then suction filtering, and respectively placing the filter cakes in a baking oven with the temperature of 50 ℃ (usually 40-60 ℃) and drying for at least 24 hours until the water content of the filter cakes is 5%, thus obtaining the second washing ellagic acid;
adding 3 parts of the dried second washing ellagic acid into a certain amount of washing liquid (anhydrous methanol), wherein the liquid-to-material ratio m (ellagic acid): V (methanol) =1:200 (g/mL); followed by stirring at 65℃for 1h (usually 1-2 h) and a third wash; then suction filtering, and respectively placing the filter cakes in a baking oven with the temperature of 50 ℃ (usually 40-60 ℃) and drying for at least 24 hours until the water content of the filter cakes is 5%, thus obtaining the washing ellagic acid for the third time;
Adding 2 parts of the dried ellagic acid subjected to the third washing into a certain amount of washing liquid (anhydrous methanol), wherein the liquid-to-material ratio m (ellagic acid): V (methanol) =1:200 (g/mL); followed by stirring at 65℃for 1h (usually 1-2 h) and a fourth wash; then suction filtering, and respectively placing the filter cakes in a baking oven with the temperature of 50 ℃ (usually 40-60 ℃) and drying for at least 24 hours until the water content of the filter cakes is 5%, thus obtaining the fourth washing ellagic acid;
adding 1 part of the dried fourth washing ellagic acid into a certain amount of washing liquid (anhydrous methanol), wherein the liquid-to-material ratio m (ellagic acid): V (methanol) =1:200 (g/mL); followed by stirring at 65℃for 1h (usually 1-2 h), and a fifth washing; then suction filtering, and respectively placing the filter cakes in a baking oven with the temperature of 50 ℃ (usually 40-60 ℃) and drying for at least 24 hours until the water content of the filter cakes is 5%, thus obtaining the fifth washing ellagic acid;
during the first to fifth washing, the stirring rate was 500rpm (typically 300-1000 rpm).
The mass of each of the first to fifth washing ellagic acid was measured, and the first to fifth washing ellagic acid was dissolved in methanol, respectively, to prepare washing ellagic acid methanol solutions having a mass concentration of 1g/L, and purity was measured by liquid chromatography external standard method, and then recovery rate of purified ellagic acid after purification treatment was calculated, and the measurement result is shown in FIG. 7. As can be seen from fig. 7: under the conditions of 65 ℃ and liquid-to-material ratio m (ellagic acid): V (methanol) =1:200 (g/mL) and treatment time of 1h, the purity of the ellagic acid is only increased from 98.03% to 98.57% when the washing times of the solvent are increased, the recovery rate of the ellagic acid is reduced from 75.03% to 67.89%, and the comprehensive consideration of the washing times is more suitable for 1 time.
Example 3C
6. Refining treatment
Precisely weighing 5 parts of purified ellagic acid prepared in step 5) "purification treatment" of example 3B, each 5g (16.54 mmol) of the purified ellagic acid, respectively, and adding the 5 parts to a certain amount of washing liquid (anhydrous methanol), wherein the feed liquid ratio of the purified ellagic acid to the washing liquid is 1:50, 1:100, 1:150, 1:200, 1:300 (g/mL), respectively, i.e. the ratio of the mass (g) of the purified ellagic acid to the volume (mL) of the washing liquid anhydrous methanol is 1:50, 1:100, 1:150, 1:200, 1:300 (g/mL), respectively; followed by stirring at 65℃for 1h (usually 1-2 h); then suction filtering, respectively placing the filter cakes in a baking oven with the temperature of 50 ℃ (usually 40-60 ℃) and drying for at least 24 hours until the water content of the filter cakes is 5%, obtaining refined ellagic acid, and respectively measuring the quality of the refined ellagic acid;
dissolving the prepared refined ellagic acid in methanol to prepare refined ellagic acid methanol solution with the mass concentration of 1g/L respectively, measuring the purity by adopting a liquid chromatography external standard method, and calculating the yield of the refined ellagic acid according to a formula (3); the measurement results of the purity and yield of purified ellagic acid are shown in FIG. 8.
As is clear from FIG. 8, at a temperature (65 ℃) and the number of times of washing (1 time), the purity of ellagic acid increases as the feed liquid ratio decreases at 1h, and the recovery rate of ellagic acid is inversely related to the feed liquid ratio, and when the feed liquid ratio is 1:100 (g/mL), the recovery rate and purity of ellagic acid are 86.01% and 95.93%, respectively, and when the feed liquid ratio increases to 1:200 (g/mL), the purity of ellagic acid is 97.98%, and the recovery rate decreases to 75.03%, so that the feed liquid ratio in the ellagic acid refining treatment of the present invention is 1:100-200 (g/mL).
Comparative example
The purification treatment of the purified ellagic acid can be carried out by adopting a crystallization method, an alkali dissolution acid precipitation method, an antisolvent method and the like which are commonly used in the field besides solvent washing, so that the purity of the ellagic acid is further improved.
The purified ellagic acid obtained in the purification treatment of the example 3B is respectively and precisely weighed 5 parts (16.54 mmol) of the purified ellagic acid remained after the purification treatment of the example 3B and the example 3C, 250mL of absolute methanol solution is respectively added into each part, reflux is carried out for 4 hours in a water bath at 80 ℃, hot filtration is carried out, deionized water with different volumes is respectively added into filtrate to enable the volume fractions of methanol to be respectively 10%, 25%, 50%, 75% and 90%, the filtrate is placed in an environment at 5 ℃ to be crystallized for 24 hours, suction filtration is carried out, the filtrate is washed by deionized water for 3 times, and the filtrate is dried in an oven at 50 ℃ for 24 hours until the water content of a filter cake is 5%, thus obtaining 2.31g, 2.18g, 3.29g, 3.41g and 1.56g of purified ellagic acid respectively; the purity was measured by liquid chromatography external standard method and was 93.25%, 97.16%, 97.66%, 98.04% and 98.81%, respectively.
Example 4
1. Preparing tannic acid reaction liquid
The same as in step 1) of example 2;
2. oxidation treatment
The same as in step 2) of example 2;
3. acid precipitation
The same as in step 3) of example 2.
4. Drying treatment
Crude ellagic acid (55.42 g) was obtained in the same manner as in step 4) of example 2;
5. purification treatment
The procedure of step 5) of example 3A was repeated except that 50g of the crude ellagic acid prepared in step 4) was precisely weighed, added to 5L of NaOH solution, and stirred and dissolved to prepare a crude ellagic acid preparation solution (5L), thereby preparing purified ellagic acid (EA purified product, 46.15 g);
accurately weighing purified ellagic acid, adding the purified ellagic acid into methanol to prepare a ellagic acid methanol solution with the mass concentration of 1g/L, and measuring the purity of the purified ellagic acid by adopting a liquid phase external standard method, wherein the purity of the purified ellagic acid is 83.95%;
6. refining treatment
Adding all the purified ellagic acid into a washing solution (methanol), wherein the feed liquid ratio of the purified ellagic acid to the washing solution is 1:100 (g/mL), namely the feed liquid ratio m (ellagic acid): V (methanol) =1:100 (g/mL); stirring at 65deg.C for 1 hr (usually 1-2 hr), suction filtering, and drying the filter cake in oven at 50deg.C (usually 40-60deg.C) for at least 24 hr to obtain refined ellagic acid (EA refined product, 34.99 g);
accurately weighing refined ellagic acid, adding into methanol, preparing refined ellagic acid methanol solution with mass concentration of 1g/L, and measuring purity by liquid phase external standard method to obtain refined ellagic acid purity of 96%.
Example 4A
The procedure of step 6) of example 4 was repeated except that the liquid-to-material ratio m (ellagic acid): V (methanol) =1:200 (g/mL) in the "refining treatment" step of step 6) was changed to 65 ℃.
Refined ellagic acid (29.83 g) was obtained, the purity of which was 97.94%.
Example 4B
The procedure of step 6) of example 4 was repeated except that the number of times of stirring and washing in the "refining treatment" step was 2. Refined ellagic acid (25.49 g) was obtained, the purity of which was 98.30%.
Test example 1 determination of the color value of ellagic acid
Lab color values of commercially available ellagic acid (EA-commercially available), purified ellagic acid (EA-purified) obtained by the purification treatment of step 5) in example 4, and purified ellagic acid (EA-purified) obtained by the purification treatment of step 6) were measured by using a Sanin NH300 color difference meter, and the measurement results are shown in FIG. 9.
The color change can be understood by measuring Lab color value of ellagic acid product. Wherein, the L value represents the brightness degree 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), ranging from-128 to 128; the value b represents the change in color from blue (-b) to yellow (+b), ranging from-128 to 128.
Lab color values for the different ellagic acid samples are shown in FIG. 9. As can be seen from FIG. 9, the L value is EA-marketed < EA purification < EA-purification, wherein the L value of EA-purification reaches 72.35, which is 53.09% higher than EA-marketed, and the ellagic acid prepared by the method of the present invention has higher brightness than commercially available samples; the values of a of EA-commercial, EA purification and EA-purification 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, and positive values indicated that the sample was yellowish. In summary, the L values of EA-commercially available, EA-purified and EA-purified have a greater influence on the color of the sample, and the higher the purity of the ellagic acid sample, the greater the L value thereof.
Test example 2 determination of properties of ellagic acid
Taking the purified ellagic acid (purified ellagic acid sample) obtained by the "purification treatment" of step 5 "in example 4, respectively; and 6), respectively carrying out liquid chromatography, infrared spectrum, ultraviolet-visible spectrum and thermogravimetric analysis on the refined ellagic acid (ellagic acid high purity sample) and the ellagic acid standard substance obtained by the refining treatment, wherein:
infrared spectroscopic analysis (FTIR): FTIR test of ellagic acid standard, purified ellagic acid sample and high purity ellagic acid sample by potassium bromide tablettingScanning range: 4000 cm to 400 cm -1 Resolution is 4 cm -1 ；
Ultraviolet-visible spectrophotometry (UV-Vis): methanol is used as a solvent to prepare a sample with the mass concentration of 4mg/L, and an ellagic acid standard substance, an ellagic acid purified sample and an ellagic acid high-purity sample are subjected to ultraviolet-visible light full-wavelength scanning, and the wavelength ranges are: 800-200 nm;
thermogravimetric analysis (TG): sample 3-5 mg is taken in an alumina ceramic crucible, thermogravimetric analysis is carried out at the temperature rising speed of 10 ℃/min within 35-800 ℃, the purging and the protective atmosphere are both high-purity nitrogen (volume fraction is more than or equal to 99.99%), and the flow rates are respectively 50 mL/min and 20mL/min.
The test results are shown in FIGS. 10a-d, the purified ellagic acid sample was purified ellagic acid; the ellagic acid high purity sample is refined ellagic acid.
As shown in fig. 10a, under the same liquid phase analysis conditions, the peak time of ellagic acid standard, purified ellagic acid and purified ellagic acid were all 5.5min, and only the peak area was different in size, the order of standard > high purity sample > purified sample, indicating only the difference in purity between samples.
As shown in FIG. 10b, the infrared spectra of purified ellagic acid and refined ellagic acid were substantially identical to those of the standard, 3475cm -1 The position is the expansion vibration absorption peak of O-H, 1720cm -1 At C=O, there are the telescopic vibration absorption peaks, 1617, 1581, 1509, 1449cm -1 The telescopic vibration absorption peak of C=C on the benzene ring is the characteristic absorption peak of ellagic acid.
As shown in fig. 10c, the peak positions of the purified, refined ellagic acid and the standard were the same (254, 360 nm), but the absorbance values of the purified ellagic acid were lower than those of the refined 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 ℃ respectively, which are higher than the initial pyrolysis temperature of 200 ℃ of tannic acid, which indicates that no tannic acid residue exists in the ellagic acid sample, and after the ellagic acid sample is washed and refined by the solvent method of the invention, the inflection point of the ellagic acid TG is raised from 483.9 ℃ of the purified sample to 498.7 ℃ and is close to 502.8 ℃ of the standard, and the inflection point of the ellagic acid TG can be gradually raised with the increase of the purity. From the above-described performance characterization results, it was found that the purification of ellagic acid by solvent washing method improved the purity and thermal stability of 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 and substitutions of details and forms of the technical solution of the present invention may be made without departing from the spirit and scope of the present invention, but these changes and substitutions fall within the scope of the present invention.

Claims (7)

1. A method for preparing ellagic acid, which is characterized by comprising the following steps in sequence:
1) Mixing tannic acid with water to obtain tannic acid water solution, adding alkaline compound, and regulating pH value of tannic acid water solution to 8.0-9.0; then NaHCO is added 3 Stirring and dissolving to prepare tannic acid reaction solution;
2) Placing tannic acid reaction liquid into a reaction container, flowing out the tannic acid reaction liquid from the lower part of the reaction container under the action of a fluid pump, filtering the tannic acid reaction liquid by a filter, and conveying filtrate to a jet pump after flowing through the fluid pump through a pipeline, wherein the tannic acid reaction liquid and air are subjected to oxidation reaction under the action of the jet pump;
3) The mixed solution after the oxidation reaction flows back into the reaction container, gas floats upwards to the surface of the liquid to overflow, the ellagic acid generated by the reaction is separated out, the separated ellagic acid flows out from the lower part of the reaction container along with the mixed solution, the separated ellagic acid is filtered by a filter, and the separated ellagic acid is trapped in the filter, so that the excessive oxidation of the separated ellagic acid and air is avoided; the filtrate flows through a fluid pump through a pipeline and then is conveyed to a jet pump, and the filtrate and air are subjected to oxidation reaction under the action of the jet pump;
4) Repeating the step 3), wherein the ellagic acid separated out by the oxidation reaction is trapped in a filter, so that excessive oxidation of the separated ellagic acid and air is avoided; the filtrate is conveyed to a jet pump through a pipeline and a fluid pump, and is subjected to oxidation reaction with air, the fluid pump and the jet pump are stopped after the oxidation reaction is carried out for 5-8 hours, and the reaction mixed solution flows back to a reaction container to stop the oxidation reaction;
5) Adding acidic substances into the reaction container, regulating the pH value of the reaction mixed solution to 4-5, and carrying out acid precipitation and precipitation on ellagic acid dissolved in the reaction mixed solution; then filtering the mixed solution 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 with the ellagic acid precipitate trapped by filtering in the step (5) to obtain a crude ellagic acid product.
2. The method of claim 1, wherein the basic compound in step 1) is selected from one or more of NaOH, KOH, or ammonia; the NaHCO 3 The addition amount of (2) is that 12-126g NaHCO is added into every 4L tannic acid water solution 3 A solid.
3. The method of claim 1 or 2, wherein the aqueous tannic acid solution of step 1) has a mass-to-volume concentration of 10-100g/L.
4. The method according to claim 1 or 2, wherein the number of mixing times of the reaction liquid and the gas treated by the jet pump during the oxidation reaction in steps 2), 3) and 4) is 20 to 40 times/h.
5. The method of claim 1 or 2, wherein the acidic material in step 5) is selected from glacial acetic acid, or one or more of hydrochloric acid, phosphoric acid, sulfuric acid, formic acid, lactic acid, citric acid, tartaric acid, or malic acid.
6. The method according to claim 1 or 2, further comprising the step of 7) purifying, wherein a NaOH solution is added to the crude ellagic acid product prepared in step 6), and the solution is stirred and dissolved to prepare a crude ellagic acid product preparation; adding acidic substances into the preparation solution to adjust the pH value of the preparation solution to 4-6, and carrying out acid precipitation on ellagic acid; and then filtering to obtain the purified ellagic acid.
7. The method according to claim 6, further comprising the step of 8) refining, wherein the purified ellagic acid prepared in the step 7) is added to the washing solution, and the heating and the stirring treatment are performed at the same time; and then filtering, and obtaining a filter cake, namely the refined ellagic acid.
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Publication number Priority date Publication date Assignee Title
EP0390107A2 (en) * 1989-03-29 1990-10-03 Kikkoman Corporation Process for producing ellagic acid
CN104341431A (en) * 2014-09-30 2015-02-11 桂林三宝生物科技有限公司 Method for extracting ellagic acid from pomegranate peel
CN105175427A (en) * 2015-08-10 2015-12-23 五峰赤诚生物科技有限公司 Method and device for preparation of ellagic acid from gall flowers
CN106279199A (en) * 2016-08-18 2017-01-04 贵阳单宁科技有限公司 A kind of synthetic method of ellagic acid

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0390107A2 (en) * 1989-03-29 1990-10-03 Kikkoman Corporation Process for producing ellagic acid
CN104341431A (en) * 2014-09-30 2015-02-11 桂林三宝生物科技有限公司 Method for extracting ellagic acid from pomegranate peel
CN105175427A (en) * 2015-08-10 2015-12-23 五峰赤诚生物科技有限公司 Method and device for preparation of ellagic acid from gall flowers
CN106279199A (en) * 2016-08-18 2017-01-04 贵阳单宁科技有限公司 A kind of synthetic method of ellagic acid

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