CN114031534A - High-stability vitamin A and preparation method thereof - Google Patents
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Abstract
The invention discloses a high-stability vitamin A and a preparation method thereof. According to the method, a C15 phosphonium salt mixture and pentanal are subjected to wittig reaction under the action of alkali liquor to prepare vitamin A acetate crude oil, and the crude oil is recrystallized to obtain vitamin A crystals. By controlling the content of the compound I and the compound II in the C15 phosphine salt mixture to be 0.1 to 1 weight percent
Description
Technical Field
The invention relates to the field of vitamins, in particular to a vitamin A product and a preparation method thereof.
Technical Field
The C15 phosphonium salt is an important intermediate for synthesizing vitamin A, carotenoid, apo ester and the like by wittig reaction. For example, patent CN100455558C discloses a method for producing vitamin A acetate by reacting beta-vinyl ionol with triphenylphosphine in the presence of sulfuric acid to generate C15 phosphonium salt, and then carrying out Wittig reaction with 4-acetoxy-2-methyl-but-2-enal, wherein the yield is about 90%, the ratio of cis-trans isomers is 7:3, and the method has the advantages of less industrial three wastes, simple process flow, low operation cost and the like. However, the wittig reaction process for synthesizing vitamin a has the following pain points: firstly, in the reaction process, due to the complex raw materials and excessive side reactions, the condition which is favorable for the generation of vitamin A is also favorable for the generation of a by-product VA dimer impurity, so that the VA selectivity is reduced, and the product yield is finally influenced; secondly, the structure of the byproduct VA dimer contains a large number of chromogenic groups with conjugated structures, and the chromogenic groups seriously affect the product chromatic value of the vitamin A acetate, so that the product loses competitiveness in the market of food-grade vitamin A. Thirdly, the VA dimer loses the bioavailability and is difficult to separate from the product as a heavy component, thereby not only increasing the production and operation cost, but also seriously influencing the stability of the vitamin A acetate and causing unnecessary economic loss. Fourthly, the generated dimer obstructs the dispersing process of VA, so that the obtained crystal is easy to agglomerate, sticky and yellow, the size distribution of crystal particles is extremely uneven, and the use of downstream formulated products is seriously influenced. Therefore, with wittig reaction as the technical background, how to improve the selectivity of the target product VA acetic ester and reduce the generation of by-product dimers has important commercial application significance for improving the market competitiveness of vitamin A.
The raw material for preparing the C15 phosphonium salt inevitably generates substances with unstable structural properties through side reactions such as dehydration and the like in an acid environment, on one hand, the structures of the impurities generally contain chromogenic groups with conjugated structures, and the high-content impurities seriously influence the chromatic values of products of beta-carotene, apo ester and vitamin A acetate generated by the subsequent wittig reaction; on the other hand, high levels of impurities can also affect the side reactions of vitamin a acetate, which in turn can affect the chemical stability of the vitamin a product. For example, in patent CN101293863A and CN101544668A, the wittig reaction is carried out to remove impurities, and a pure product of C15 phosphonium salt is prepared by complicated steps, but the purification process has complicated steps, long flow path, large energy consumption and loss due to multi-step superposition, and the yield of the target compound finally obtained is low. It was found experimentally that even when the wittig reaction is carried out after obtaining pure C15 phosphine salt through a complicated purification step, a large amount of VA dimer is produced, because the conditions for producing VA dimer are similar to those of VA, and when suitable conditions favor the rapid production of VA, a large amount of VA dimer is often accompanied. Therefore, how to control the appropriate conditions to quantitatively control the production of VA dimer is the key to improve VA market competitiveness.
Disclosure of Invention
The invention provides high-stability vitamin A and a preparation method thereof, which can greatly improve the chemical stability of VA products. In addition, the problems of yellowing of crystals and easy agglomeration after the vitamin A acetate is crystallized are effectively solved.
In order to achieve the purpose, the invention provides the following technical scheme:
a preparation method of high-stability vitamin A comprises the following steps:
(1) dissolving a C15 phosphine salt raw material in a solvent a, extracting with a solvent b under certain conditions to obtain a C15 phosphine salt mixture, and controlling the content of a compound I and a compound II in the C15 phosphine salt mixture to be 0.1-1 wt%
(2) And (2) performing wittig reaction on the C15 phosphonium salt mixture in the step (1) and pentanal under the action of alkali liquor to prepare vitamin A acetate crude oil, and recrystallizing to obtain a vitamin A crystal.
In step (1) of the present invention, the solvent a is one or more of methanol, ethanol, dichloromethane, tetrahydrofuran, ethyl acetate and water, preferably water. The mass ratio of the solvent a to the C15 phosphine salt is 0.5-10: 1, preferably 1 to 5: 1.
in step (1) of the present invention, the solvent b is a mixture of a polar solvent and a non-polar solvent, wherein the content of the polar solvent is 0.1 to 5.0 wt%, preferably 0.5 to 1 wt%. The polar solvent is one or more of dichloromethane, tetrahydrofuran, ethanol, ethyl acetate, methanol, water and the like, and preferably methanol. The nonpolar solvent in the solvent b is one or more of n-hexane, cyclohexane, n-heptane, petroleum ether, toluene, p-xylene, m-xylene and the like, and n-hexane is preferred. The mass ratio of the solvent b to the C15 phosphine salt is 0.5-10: 1, preferably 1 to 3: 1.
in step (1) of the present invention, the temperature of the extraction operation is 0 to 80 ℃, preferably 30 to 50 ℃. The stirring speed of the extraction is 100-1000rpm, preferably 200-500 rpm. The stirring time for extraction is 5-300min, preferably 10-60 min. The phase separation time of the extraction is 1-120min, preferably 10-60 min.
In step (2) of the present invention, the alkali solution of the wittig reaction is a metal inorganic salt or alkali, such as one or more of sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium methoxide, etc., preferably potassium carbonate. The alkali liquor is an aqueous solution, and the mass percent of the alkali liquor is 1-90 wt%, preferably 20-60 wt%.
The molar ratio of the C15 phosphine salt mixture to the pentanal and the alkali is (0.5-5) to 1 (0.5-5), preferably (1-2) to 1 (1-2).
As a preferable scheme, in the step (2) of the invention, the raw materials are added into the reaction kettle in the sequence of C15 phosphine salt mixture and pentanal, and then the alkali liquor is added dropwise.
In the step (2), the reaction temperature is controlled to be 30-90 ℃, and preferably 45-75 ℃.
In the step (2), the reaction pressure is-0.09-5.0 MPaG, preferably-0.05-1.0 MPaG.
In the step (2), the reaction time is 0.5-20 h, preferably 1-5 h.
In the step (2) of the present invention, the vitamin a acetate crude oil is dissolved in a crystallization reagent to perform crystallization, wherein the crystallization reagent is one or more of methanol, ethanol, isopropanol, ethylene glycol, n-butanol, isobutanol, etc., and the amount of the crystallization reagent is 0.5 to 10 times, preferably 1 to 5 times, the mass of the vitamin a acetate crude oil.
In the step (2), the crystallization temperature is-15 to 30 ℃, preferably-5 to 20 ℃.
In the process for preparing vitamin A acetate according to the invention, the reactions present are schematically as follows:
In the invention, surprisingly, the conversion rate of wittig reaction (reaction 1) can be effectively controlled by controlling the contents of the compound I and the compound II in the phosphine salt of the raw material C15 in a certain range, and the formation of VA dimer is inhibited, so that the selectivity of vitamin A acetate is improved, the formation of VA dimer is reduced, the stability of the obtained product is improved, the crystal size is uniform, and the color reaches the standard.
According to the technical scheme, the contents of the compound I and the compound II need to be controlled, if the contents of the compound I and the compound II are too small, the wittig reaction rate is too high, the conversion rate of C15 phosphonium salt is too high, the conversion rate of vitamin A acetate to VA dimer is too much, and the chromatic value and the stability of the product are influenced. If the content of the compound I and the compound II is too large, the mass transfer and the reaction of the C15 phosphonium salt and the pentanal are not facilitated, the wittig reaction rate is too slow, the average yield of the vitamin A acetate is lower, the unit production cost is increased, and the excessive compound I and the excessive compound II can also cause the solution color to increase and reduce the stability of the vitamin A product. Without being bound by any theory, compounds I and II have similar structure and polarity to vitamin a acetate, and can adsorb to the surface of the vitamin a acetate product, preventing contact between vitamin a acetate molecules, and reducing dimer formation.
The technical scheme of the invention has the beneficial effects that:
(1) the deterioration rate of the prepared vitamin A product can be respectively reduced to 0.22%, 0.23% and 0.35% under the conditions of humidity and illumination at 60 ℃, and the deterioration rate of the vitamin A product which is not treated by the method is respectively 0.99%, 0.98% and 1.32%; compared with a vitamin A product prepared by untreated C15 phosphonium salt, the heat stability can be improved by 3.5 times, the humidity stability can be improved by 3.3 times, the illumination stability can be improved by 2.8 times, and the chemical stability of the vitamin A product is greatly improved.
(2) The content of VA dimer in the obtained crude oil of vitamin A acetate is less than 0.1 wt%, the chromatic value of the obtained VA crystal solution is less than 60Hazen, the average size of the crystal is 100-200 mu m, and the problems of yellow color and easy agglomeration of the crystal after the vitamin A acetate is crystallized are effectively solved.
Drawings
FIG. 1 is a graph of the size distribution of vitamin A crystals as measured by the laser particle sizer of example 1.
Detailed Description
The technical solution of the present application is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present application and should not be construed as a specific limitation of the present application.
Methanol, ethanol, carbonate and alkane solvents are all purchased from Shanghai Tantake technologies, Inc.; five carbon aldehyde
c15 phosphonium salts
For self-made raw materials, the preparation method refers to the prior art and CN109651150A, and is concretely as follows: after the leak detection of the autoclave, triphenylphosphine (264.5g, 1.01mol) and hydrochloric acid (96.8g, 38 wt%, 1.01mol) were added thereto; with CO2After 3 times of replacement, CO is filled into the high-pressure reaction kettle2And (2) starting gas and stirring, raising the temperature to ensure that the temperature in the high-pressure reaction kettle is 45 ℃, maintaining the pressure in the kettle at 14MPa through a pressure regulating valve, pumping (220g, 1mol) of vinyl-beta-ionol into the high-pressure reaction kettle through an advection pump to carry out salt forming reaction, and preparing a crude raw material C15 phosphonium salt, wherein the content of the C15 phosphonium salt is 95 wt%, the content of the compound I is 2 wt%, and the content of the compound II is 3 wt%.
The colorimetric value of the product is that the product to be measured is prepared into a 20 percent normal hexane solution, and colorimetric value measurement is carried out on the solution system, wherein the colorimetric unit is HAzen.
The crystal size was measured using a Dandongbaut BT-2900 dynamic image grain size determinator.
The content and purity of each component are obtained by testing and calculating through an external standard method of a high performance liquid chromatograph (Shimadzu LC-20AD), and the conversion rate is obtained by calculating based on the content of the product; the liquid chromatography conditions were as follows: a chromatographic column: WAters xselectricity HSS T3, 4.6 μm × 250 mm; sample introduction amount: 2-10 mu L, and fine adjustment is carried out according to the sample condition; column temperature: 40 ℃; flow rate: 1 mL/min; a detector: an ultraviolet detector (UV) with a detection wavelength of 254-400 nm; mobile phase: acetonitrile/0.1% phosphoric acid aqueous solution; when the sample is measured, a liquid phase external standard curve is established by using the pure product, and the mass fraction (content) of each detected substance is calculated by using the linear relation between the concentration and the liquid phase peak area.
The rate of deterioration of the product was tested using the following method: respectively weighing 10g of VA crystal sample (based on actual weighing data, recording as m)1) Storing the mixture in nitrogen atmosphere at 60 deg.C, RH 90% +/-5% at 25 deg.C, and illumination intensity of 4500lx + -500 lx for 10 days, diluting the product after 10 days storage with solvent, and analyzing VA content (denoted as m) with high performance liquid chromatography2) The rate of change of the strain is 100% × (m)1-m2)/n×m1Where n denotes the number of days of storage, in the following example n is 10. Stability is measured as the inverse of the rate of deterioration.
Example 1:
52.74g of the crude material C15 phosphine salt was dissolved in 50.11g of water, the above aqueous solution was added to 50.11g of solvent b (99.5 wt% n-hexane and 0.5 wt% methanol) at 30 ℃ and 200rpm, the mixture was stirred for 15min, left to stand for 15min for phase separation, and sampled for analysis of the composition of the raffinate phase (excluding solvent a water): the content of the compound I is 540ppm, the content of the compound II is 860ppm, and the content of the C15 phosphine salt is 99.86%.
Adding 14.2g of pentanal into raffinate, heating to 45 ℃, and dropwise adding 69g of 20 mass percent K2CO3Solution under pressure of50kPaA, stirring and reacting for 1h at the rotating speed of 200rpm to obtain crude vitamin A oil. The composition was determined by sampling, and the conversion of C15 phosphine salt was 95.2%, the vitamin A selectivity was 99.3%, and the vitamin A dimer content was 0.05 wt%.
And taking out the obtained vitamin A crude oil, adding 33g of ethanol, crystallizing at 0 ℃, filtering to obtain vitamin A crystals, and testing stability, chromatic value and particle size. The vitamin A product has an average deterioration rate of 0.29%/d in a nitrogen atmosphere at 60 ℃, an average deterioration rate of 0.25%/d at 25 ℃ and RH 90% + -5%, and an average deterioration rate of 0.47%/d at a light intensity of 4500lx +/-500 lx. And the purity of the obtained vitamin A crystal is 99.97%, the color is nearly white, the chromatic value of the crystal solution is 43Hazen, the average size of the crystal is 120 mu m, the particles are uniformly distributed, and the vitamin A crystal has better dispersibility and no agglomeration phenomenon as shown in figure 1.
Example 2:
52.74g of the crude material C15 phosphine salt was dissolved in 100.22g of water, and the above aqueous solution was added to 100.22g of solvent b (99.5 wt% n-hexane and 0.5 wt% water) at 40 ℃ and 300rpm, stirred for 30min, left to stand for 30min for phase separation, and sampled for analysis of the composition of the raffinate phase (excluding solvent a water): the content of the compound I is 420ppm, the content of the compound II is 780ppm, and the content of the C15 phosphine salt is 99.88%.
Adding 14.2g of pentanal into raffinate, heating to 55 ℃, and dropwise adding 92g of 30 mass percent K2CO3And reacting the solution for 2 hours at the pressure of 100kPaA and the stirring speed of 300rpm to obtain crude vitamin A oil. The composition was determined by sampling, and the conversion of C15 phosphonium salt was 95.4%, the vitamin A selectivity was 99.4%, and the vitamin A dimer content was 0.04%.
Taking out the obtained vitamin A crude oil, adding 66g of ethanol, crystallizing at-5 ℃, filtering to obtain vitamin A crystals, and testing stability, chromatic value and particle size. The vitamin A product has an average deterioration rate of 0.22%/d in a nitrogen atmosphere at 60 ℃, an average deterioration rate of 0.23%/d at 25 ℃ and RH 90% + -5%, and an average deterioration rate of 0.35%/d at a light intensity of 4500lx +/-500 lx. The purity of the obtained vitamin A crystal is 99.98%, the color of the obtained vitamin A crystal tends to be white, the chromatic value of the crystal solution is 39Hazen, the average size of the crystal is 100 mu m, the particle distribution is uniform, the dispersibility is good, and the agglomeration phenomenon is avoided.
Example 3:
52.74g of crude material C15 phosphine salt is dissolved in 150.33g of water, the aqueous solution is added into 150.33g of solvent b (99 wt% of normal hexane and 1 wt% of methanol) under the conditions of 30 ℃ and 400rpm, the mixture is stirred for 45min, kept stand for 45min for phase separation, and a sample is taken for analyzing the composition of a raffinate phase (not containing solvent a water): the content of the compound I was 1200ppm, the content of the compound II was 2100ppm, and the content of the C15 phosphine salt was 99.67%.
Adding 7.1g of pentanal into the raffinate, heating to 65 ℃, and dropwise adding 18g of 40 mass percent K2CO3And reacting the solution for 3 hours under the pressure of 150kPaA and the stirring speed of 400rpm to obtain crude vitamin A oil. The composition was determined by sampling, and the conversion of C15 phosphonium salt was 95.1%, the vitamin A selectivity was 99.2%, and the vitamin A dimer content was 0.08%.
And taking out the obtained vitamin A crude oil, adding 99g of ethanol, crystallizing at 5 ℃, filtering to obtain vitamin A crystals, and testing stability, chromatic value and particle size. The vitamin A product has an average deterioration rate of 0.31%/d in a nitrogen atmosphere at 60 ℃, an average deterioration rate of 0.29%/d at 25 ℃ and RH 90% + -5%, and an average deterioration rate of 0.51%/d at a light intensity of 4500lx +/-500 lx. The purity of the obtained vitamin A crystal is 99.94%, the color of the obtained vitamin A crystal tends to be white, the chromatic value of the crystal solution is 49Hazen, the average size of the crystal is 125 mu m, the particle distribution is uniform, the dispersibility is good, and the agglomeration phenomenon is avoided.
Example 4:
52.74g of crude material C15 phosphine salt is dissolved in 200.44g of water, the aqueous solution is added into 100.22g of solvent b (97 wt% of n-hexane and 3 wt% of methanol) at 30 ℃ and 500rpm, the mixture is stirred for 60min, kept stand for 60min for phase separation, and a sample is taken for analysis of the composition of a raffinate phase (not containing solvent a water): the content of the compound I is 3300ppm, the content of the compound II is 4700ppm, and the content of the C15 phosphine salt is 99.2%.
Adding 7.1g of pentanal into the raffinate, heating to 75 ℃, and dropwise adding 28g of 50% K2CO3And reacting the solution for 4 hours under the pressure of 200kPaA and the stirring speed of 500rpm to obtain crude vitamin A oil. The composition was determined by sampling, and the conversion of C15 phosphonium salt was 94.6%, the vitamin A selectivity was 99.0%, and the vitamin A dimer content was 0.09%.
Taking out the obtained vitamin A crude oil, adding 132g of ethanol, crystallizing at 10 ℃, filtering to obtain vitamin A crystals, and testing stability, chromatic value and particle size. The vitamin A product has an average deterioration rate of 0.37%/d in a nitrogen atmosphere at 60 ℃, an average deterioration rate of 0.38%/d at 25 ℃ and RH 90% + -5%, and an average deterioration rate of 0.56%/d at a light intensity of 4500lx + -500 lx. And the purity of the obtained vitamin A crystal is 99.91%, the color of the obtained vitamin A crystal tends to be white, the chromatic value of the crystal solution is 57Hazen, the average size of the crystal is 145 mu m, the particle distribution is uniform, the dispersibility is good, and the agglomeration phenomenon is avoided.
Comparative example 1:
52.74g of crude raw material C15 phosphonium salt is dissolved in 1002.2g of water, the aqueous solution is added into 2004.4g of solvent b (normal hexane content is 100%) under the conditions of 80 ℃ and 1000rpm of rotation speed, the mixture is stirred for 600min, kept stand for 600min for phase separation, and sampled to analyze the composition of raffinate phase (not containing solvent a water): the content of the compound I is 80ppm, the content of the compound II is 130ppm, and the content of the C15 phosphine salt is 99.98 percent.
Adding 14.2g of pentanal into the C15 phosphonium salt solution, heating to 55 ℃, and dropwise adding 92g of 30 mass percent K2CO3And reacting the solution for 2 hours at the pressure of 100kPaA and the stirring speed of 300rpm to obtain crude vitamin A oil. The composition was determined by sampling, and the conversion of C15 phosphonium salt was 98.9%, the vitamin A selectivity was 96.6%, and the vitamin A dimer content was 1.36%.
Taking out the obtained vitamin A crude oil, adding 66g of ethanol, crystallizing at-5 ℃, filtering to obtain vitamin A crystals, and testing stability, chromatic value and particle size. The vitamin A product has an average deterioration rate of 0.82%/d in a nitrogen atmosphere at 60 ℃, an average deterioration rate of 0.88%/d at 25 ℃ and RH 90% + -5%, and an average deterioration rate of 1.03%/d at a light intensity of 4500lx +/-500 lx. And the purity of the obtained vitamin A crystal is 98.6%, the color is slightly yellowish, the chromatic value of the crystal solution is 98Hazen, the average size of the crystal is 1000 mu m, and partial agglomeration phenomenon exists.
Comparative example 2:
52.74g of the crude C15 phosphine salt was dissolved in 100.22g of water and sampled for analysis of its composition (excluding solvent a water): the content of the compound I is 20000ppm, the content of the compound II is 30000ppm, and the content of the C15 phosphine salt is 95%.
Adding 14.2g of pentanal into the C15 phosphonium salt solution, heating to 55 ℃, and dropwise adding 92g of 30 mass percent K2CO3And (3) reacting the solution for 2 hours under the pressure of 100kPaA and the stirring speed of 300rpm to obtain crude vitamin A oil. The composition was determined by sampling, and the conversion of C15 phosphonium salt was 82.3%, the vitamin A selectivity was 74.7%, and the vitamin A dimer content was 5.85%.
Taking out the obtained vitamin A crude oil, adding 66g of ethanol, crystallizing at-5 ℃, filtering to obtain vitamin A crystals, and testing stability, chromatic value and particle size. The vitamin A product has an average deterioration rate of 0.99%/d in a nitrogen atmosphere at 60 ℃, an average deterioration rate of 0.98%/d at 25 ℃ and RH 90% + -5%, and an average deterioration rate of 1.32%/d at a light intensity of 4500lx +/-500 lx. And the purity of the obtained vitamin A crystal is 94.4%, the color is yellow, the chromatic value of the crystal solution is 200Hazen, the average size of the crystal is 1200 mu m, and partial agglomeration phenomenon exists.
Comparative example 3:
52.74g of the crude material C15 phosphine salt was dissolved in 100.22g of water, and the above aqueous solution was added to 100.22g of solvent b (94 wt% n-hexane and 6 wt% methanol) at 40 ℃ and 300rpm, stirred for 30min, allowed to stand for 30min for phase separation, and sampled for analysis of the composition of the raffinate phase (excluding solvent a water): the content of the compound I is 8700ppm, the content of the compound II is 10300ppm, and the content of the C15 phosphine salt is 98.1%.
Adding 14.2g of pentanal into raffinate, heating to 55 ℃, and dropwise adding 92g of 30 mass percent K2CO3And reacting the solution for 2 hours at the pressure of 100kPaA and the stirring speed of 300rpm to obtain crude vitamin A oil. The composition was determined by sampling and the conversion of C15 phosphonium salt was 90.4%, the vitamin A selectivity was 88.6%, and the vitamin A dimer content was 1.59%.
Taking out the obtained vitamin A crude oil, adding 66g of ethanol, crystallizing at-5 ℃, filtering to obtain vitamin A crystals, and testing stability, chromatic value and particle size. The vitamin A product has an average deterioration rate of 0.62%/d in a nitrogen atmosphere at 60 ℃, an average deterioration rate of 0.75%/d at 25 ℃ and RH 90% + -5%, and an average deterioration rate of 0.91%/d at a light intensity of 4500lx +/-500 lx. The purity of the obtained vitamin A crystal is 98.5%, the color of the obtained vitamin A crystal tends to be white, the chromatic value of the crystal solution is 101Hazen, the average size of the crystal is 575 mu m, and the partial agglomeration phenomenon exists.
Claims (10)
1. A preparation method of high-stability vitamin A comprises the following steps:
(1) dissolving a C15 phosphine salt raw material in a solvent a, extracting with a solvent b under certain conditions to obtain a C15 phosphine salt mixture, and controlling the content of a compound I and a compound II in the C15 phosphine salt mixture to be 0.1-1 wt%
(2) And (2) performing wittig reaction on the C15 phosphonium salt mixture in the step (1) and pentanal under the action of alkali liquor to prepare vitamin A acetate crude oil, and recrystallizing to obtain a vitamin A crystal.
2. The process according to claim 1, wherein the solvent a is one or more of methanol, ethanol, dichloromethane, tetrahydrofuran, ethyl acetate and water, preferably water.
3. The process according to claim 1 or 2, wherein the mass ratio of the solvent a to the C15 phosphine salt is 0.5-10: 1, preferably 1 to 5: 1.
4. a process according to any one of claims 1 to 3, characterised in that the solvent b is a mixture of a polar solvent and a non-polar solvent, wherein the polar solvent is present in an amount of 0.1 to 5.0 wt.%, preferably 0.5 to 1 wt.%.
5. The process according to claim 4, wherein the polar solvent is one or more of dichloromethane, tetrahydrofuran, ethanol, ethyl acetate, methanol, water, preferably methanol; the nonpolar solvent is one or more of n-hexane, cyclohexane, n-heptane, petroleum ether, toluene, p-xylene and m-xylene, and n-hexane is preferred.
6. The method according to claim 4 or 5, wherein the mass ratio of the solvent b to the C15 phosphine salt is 0.5-10: 1, preferably 1 to 3: 1.
7. the process according to any one of claims 1 to 6, wherein in step (1), the temperature of the extraction operation is 0 to 80 ℃, preferably 30 to 50 ℃; the stirring speed of the extraction is 100-1000rpm, preferably 200-500 rpm; the stirring time for extraction is 5-300min, preferably 10-60 min; the phase separation time of the extraction is 1-120min, preferably 10-60 min.
8. The method according to any one of claims 1 to 7, wherein the molar ratio of the C15 phosphine salt mixture to the pentanal and the base is (0.5-5): 1 (0.5-5), preferably (1-2): 1 (1-2); and/or in the step (2), the reaction temperature is controlled to be 30-90 ℃, preferably 45-75 ℃.
9. The method according to any one of claims 1 to 8, wherein in the step (2), the vitamin A acetate crude oil is dissolved in a crystallization reagent, the crystallization reagent is one or more of methanol, ethanol, isopropanol, ethylene glycol, n-butanol and isobutanol, and the amount of the crystallization reagent is 0.5 to 10 times, preferably 1 to 5 times, of the mass of the vitamin A acetate crude oil; the crystallization temperature is-15 to 30 ℃, preferably-5 to 20 ℃.
10. The highly stable vitamin A prepared by the method of any one of claims 1 to 9, wherein the solution of VA crystals has a color value of less than 60Hazen and the average size of the crystals is 100 to 200 μm.
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|---|---|---|---|---|
| JP2003238528A (en) * | 2002-02-14 | 2003-08-27 | Sumitomo Chem Co Ltd | Method for producing vitamin a |
| DE10359433A1 (en) * | 2003-12-17 | 2005-07-21 | Basf Ag | Process for the preparation of vitamin A acetate |
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