CN114031534B - High-stability vitamin A and preparation method thereof - Google Patents
High-stability vitamin A and preparation method thereof Download PDFInfo
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Abstract
The application discloses a high-stability vitamin A and a preparation method thereof. The method comprises the steps of preparing vitamin A acetate crude oil by performing wittig reaction on a C15 phosphine salt mixture and pentacarbon aldehyde under the action of alkali liquor, and recrystallizing 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 0.1wt percent to 1wt percent
Description
Technical Field
The application relates to the field of vitamins, in particular to a vitamin A product and a preparation method thereof.
Technical Field
The C15 phosphine salt is an important intermediate for synthesizing vitamin A, carotenoid, aporate and the like by a wittig reaction. As mentioned in patent CN100455558C, a method for producing vitamin A acetate by reacting beta-vinyl ionol with triphenylphosphine in the presence of sulfuric acid to form C15 phosphine salt and then carrying out Wittig reaction with 4-acetoxy-2-methyl-but-2-enal, wherein the yield is about 90%, and the cis-trans isomer ratio is 7:3, has the advantages of less industrial three wastes, simple process flow, low operation cost and the like. However, the wittig reaction vitamin a synthesis process has the following pain points: firstly, in the reaction process, as the raw materials are complex, the side reactions are excessive, the conditions favorable for generating vitamin A are favorable for generating side product VA dimer impurities, so that VA selectivity is reduced, and the product yield is finally influenced; the second, by-product VA dimer contains a large number of conjugated structural chromogenic groups in its structure, whose presence severely affects the product color value of vitamin a acetate, making the product lose competitiveness in the food-grade vitamin a market. Thirdly, the VA dimer loses the bioavailability and is difficult to separate from the product as a heavy component, so that the production operation cost is increased, the stability of the vitamin A acetate is seriously influenced, and unnecessary economic loss is caused. Fourth, the formed dimer hinders the dispersion process of VA, so that the obtained crystals are easy to agglomerate, sticky and yellow, the size distribution of crystal particles is very uneven, and the use of downstream formulated products is seriously affected. Therefore, with the wittig reaction as the technical background, how to improve the selectivity of the target product VA acetate and reduce the generation of byproduct dimer has important commercial application significance for improving the market competitiveness of vitamin A.
The raw materials for preparing the C15 phosphine salt can inevitably generate substances with unstable structural properties through side reactions such as dehydration and the like in an acidic environment, on one hand, the structures of the impurities generally contain chromogenic groups with conjugated structures, and the high content of impurities seriously affects the chromaticity values of products of beta-carotene, aporate and vitamin A acetate generated by subsequent wittig reactions; on the other hand, high levels of impurities can also affect the side reactions of vitamin a acetate and thus the chemical stability of the vitamin a product. In order to remove impurities by performing wittig reaction as in patent CN101293863A, CN101544668A, pure C15 phosphonate is prepared by complex steps, but the purification process is complex in steps, long in flow, requires a lot of energy consumption and loss of multi-step superposition, and finally the yield of the obtained target compound is low. Experiments show that even if the wittig reaction is carried out after the pure C15 phosphonate product is obtained through a complicated purification step, a large amount of VA dimer is generated, because the VA dimer is generated under similar conditions to VA, and when the suitable conditions are favorable for the quick generation of VA, a large amount of VA dimer is generated. Therefore, how to control the proper conditions to quantitatively control the production of VA dimer is a key to improve VA market competitiveness.
Disclosure of Invention
The application provides a 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 crystal color and easy agglomeration after crystallization of vitamin A acetate are effectively solved.
In order to achieve the above object, the present application provides the following technical solutions:
a preparation method of high-stability vitamin A comprises the following steps:
(1) Dissolving a C15 phosphine salt raw material in a solvent a, and extracting with a solvent b under certain conditions to obtain a C15 phosphine salt mixture, wherein the content of a compound I and a compound II in the C15 phosphine salt mixture is controlled to be 0.1-1 wt%
(2) And (3) performing wittig reaction on the C15 phosphine salt mixture in the step (1) and pentacarbon aldehyde under the action of alkali liquor to prepare vitamin A acetate crude oil, and recrystallizing to obtain vitamin A crystals.
In the step (1) of the present application, the solvent a is one or more of methanol, ethanol, methylene chloride, 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 1-5:1.
in step (1) of the present application, 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 5.0wt%, preferably 0.5 to 1wt%. The polar solvent is one or more of dichloromethane, tetrahydrofuran, ethanol, ethyl acetate, methanol, water and the like, 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 preferably n-hexane. The mass ratio of the solvent b to the C15 phosphine salt is 0.5-10:1, preferably 1-3:1.
in step (1) of the present application, the extraction operation is carried out at a temperature of 0 to 80℃and preferably 30 to 50 ℃. The stirring speed of the extraction is 100-1000rpm, preferably 200-500rpm. The stirring time of the extraction is 5-300min, preferably 10-60min. The phase separation time of the extraction is 1-120min, preferably 10-60min.
In the step (2) of the present application, 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 percentage of the alkali liquor is 1-90 wt%, preferably 20-60 wt%.
The molar ratio of the C15 phosphine salt mixture to the pentacarbon aldehyde and the alkali is (0.5-5): 1 (0.5-5), preferably (1-2): 1 (1-2).
As a preferable scheme, in the step (2) of the application, the raw materials are added in the order of C15 phosphine salt mixture and pentacarbon aldehyde, and then alkali liquor is added dropwise.
In the step (2) of the present application, the reaction temperature is controlled to be 30 to 90 ℃, preferably 45 to 75 ℃.
In the step (2) of the present application, the reaction pressure is-0.09 to 5.0MPaG, preferably-0.05 to 1.0MPaG.
In the step (2) of the present application, the reaction time is 0.5 to 20 hours, preferably 1 to 5 hours.
In the step (2), the crude vitamin A acetate is dissolved in a crystallization reagent for crystallization, wherein the crystallization reagent is one or more of methanol, ethanol, isopropanol, ethylene glycol, n-butanol, isobutanol and the like, and the dosage of the crystallization reagent is 0.5-10 times, preferably 1-5 times, of the mass of the crude vitamin A acetate.
In the step (2) of the present application, the crystallization temperature is-15 to 30 ℃, preferably-5 to 20 ℃.
In the method for preparing vitamin A acetate, the existing reaction is shown as follows:
firstly reacting C15 phosphine salt with five-carbon aldehyde to generate vitamin A acetate; vitamin a acetate continues to react 2 to form VA dimer, noted as "by-product".
In the application, unexpectedly, the conversion rate of wittig reaction (reaction 1) can be effectively controlled by controlling the content of the compound I and the compound II in the raw material C15 phosphine salt within 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 are required 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 the C15 phosphine salt is too high, the conversion of the vitamin A acetate into the VA dimer is too much, and the by-products are too much, so that the chromaticity value and the stability of the product are affected. If the contents of the compound I and the compound II are too much, mass transfer and reaction of the C15 phosphine salt and the pentacarbon aldehyde are not facilitated, the wittig reaction rate is too slow, the average yield of the vitamin A acetate is low, the unit production cost is increased, and the excessive compounds I and II can also cause the increase of the chromaticity of the solution, so that the stability of the vitamin A product is reduced. Without being limited by any theory, the compounds I and II have similar structures and polarities with the vitamin A acetate, can be adsorbed on the surface of the vitamin A acetate product, prevent the contact between molecules of the vitamin A acetate and reduce the generation of dimers.
The technical scheme of the application has the beneficial effects that:
(1) The deterioration rate of the vitamin A product prepared by the method can be respectively reduced to 0.22%, 0.23% and 0.35% at 60 ℃ under the conditions of humidity and illumination, 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 the vitamin A product prepared by untreated C15 phosphine 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 VA dimer content in the obtained vitamin A acetate crude oil is less than 0.1 weight percent, the chromaticity value of the obtained VA crystal solution is less than 60Hazen, the average size of crystals is 100-200 mu m, and the problems of yellowing of crystals and easy agglomeration after the crystallization of the vitamin A acetate are effectively solved.
Drawings
Fig. 1 is a size distribution of vitamin a crystals under the laser particle sizer test of example 1.
Detailed Description
The technical scheme of the application is further described by the following specific embodiments. It will be apparent to those skilled in the art that the examples are merely to aid in understanding the application and are not to be construed as a specific limitation thereof.
Methanol, ethanol, carbonate, alkane solvents were all purchased from Shanghai Taitan technologies Co., ltd; pentacarbon aldehyde
Purchased from basf chemical company, inc;
c15 phosphine saltsFor self-made raw materials, the preparation method refers to the prior art, refers to CN109651150A, and is specifically shown as follows: after leak detection in the autoclave, triphenylphosphine (264.5 g,1.01 mol) and hydrochloric acid (96.8 g,38wt%,1.01 mol) were added thereto; by CO 2 After 3 times of replacement, CO is filled into a high-pressure reaction kettle 2 The gas is stirred and is started, the temperature is raised to enable the temperature in the high-pressure reaction kettle to be 45 ℃, the pressure in the high-pressure reaction kettle is kept to be 14MPa through a pressure regulating valve, 220g of (1 mol) vinyl-beta-ionol is pumped into the high-pressure reaction kettle through a advection pump to carry out salt forming reaction, and crude raw material C15 phosphine salt is prepared, wherein the content of the C15 phosphine salt is 95wt%, the content of the compound I is 2wt%, and the content of the compound II is 3wt%.
The chromaticity value of the product is that the product to be measured is prepared into 20% normal hexane solution, the chromaticity value is measured in a solution system, and the chromaticity unit is HAzen.
The crystal size was measured using a dandong baud BT-2900 dynamic image particle size meter.
The content and purity of each component are tested and calculated by an external standard method of a high performance liquid chromatograph (Shimadzu LC-20 AD), and the conversion rate is calculated based on the content of the product; the liquid chromatography conditions were as follows: chromatographic column: WAters XSelect HSS T3,4.6 μm×250mm; sample injection amount: 2-10 mu L, and performing fine adjustment according to the condition of the sample; column temperature: 40 ℃; flow rate: 1mL/min; a detector: an ultraviolet detector (UV) with a detection wavelength of 254-400 nm; mobile phase: acetonitrile/0.1% phosphoric acid in water; when in sample measurement, a liquid phase external standard curve is established by a pure product, and the mass fraction (content) of each detection substance is calculated by the linear relation of the concentration and the liquid phase peak area.
The deterioration rate of the product was tested by the following method: the three VA crystal samples are weighed respectively to obtain 10g (based on the actual weighing data, denoted as m 1 ) Storing at 60deg.C under nitrogen atmosphere, 25deg.C, RH90% + -5%, and illumination intensity 4500 lx+ -500 lx for 10 days, diluting the product after 10 days with solvent, and analyzing VA content (denoted as m) 2 ) Deterioration rate=100% × (m 1 -m 2 )/n×m 1 Where n represents the number of days of storage, n=10 in the following examples. Stability is measured as the inverse of the rate of deterioration.
Example 1:
52.74g of crude C15 phosphine salt is dissolved in 50.11g of water, the above aqueous solution is added into 50.11g of solvent b (99.5 wt% of n-hexane and 0.5wt% of methanol) at 30 ℃ and 200rpm, stirred for 15min, left stand for 15min for phase separation, and the raffinate phase composition (excluding solvent a water) is sampled and analyzed: the content of compound I was 540ppm, the content of compound II was 860ppm, and the content of C15 phosphine salt was 99.86%.
14.2g of pentacarbon aldehyde is added into the raffinate phase, after the temperature is raised to 45 ℃, 69g of K with the mass fraction of 20 percent is added dropwise 2 CO 3 The solution was reacted for 1 hour under a pressure of 50kPaA and a stirring speed of 200rpm to obtain a 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% by weight.
The obtained crude vitamin a oil was taken out and 33g of ethanol was added, crystallized at 0 c, filtered to obtain vitamin a crystals, and stability, chromaticity value and particle size were tested. The average deterioration rate of the vitamin A product in the nitrogen atmosphere at 60 ℃ is 0.29 percent/d, the average deterioration rate of the vitamin A product in the nitrogen atmosphere at 25 ℃ is 0.25 percent/d under the RH90 percent plus or minus 5 percent, and the average deterioration rate of the vitamin A product in the light intensity of 4500lx plus or minus 500lx is 0.47 percent/d. The purity of the obtained vitamin A crystal is 99.97%, the color of the vitamin A crystal tends to be white, the chromaticity 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 good dispersibility and no agglomeration phenomenon as shown in figure 1.
Example 2:
52.74g of crude C15 phosphine salt is dissolved in 100.22g of water, the above aqueous solution is added into 100.22g of solvent b (99.5 wt% of n-hexane and 0.5wt% of water) at 40 ℃ and a rotating speed of 300rpm, stirred for 30min, and left stand for 30min for phase separation, and the raffinate phase composition (excluding solvent a water) is sampled and analyzed: the content of compound I was 420ppm, the content of compound II was 780ppm, and the content of C15 phosphine salt was 99.88%.
14.2g of pentacarbon aldehyde is added into the raffinate phase, after the temperature is raised to 55 ℃, 92g of K with the mass fraction of 30% is added dropwise 2 CO 3 The solution was reacted for 2 hours under a pressure of 100kPaA and a stirring speed of 300rpm to obtain a crude vitamin A oil. The composition was determined by sampling and the conversion of C15 phosphine 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 the stability, chromaticity value and particle size. The average deterioration rate of the vitamin A product in the nitrogen atmosphere at 60 ℃ is 0.22 percent/d, the average deterioration rate of the vitamin A product in the nitrogen atmosphere at 25 ℃ is 0.23 percent/d under the RH90 plus or minus 5 percent conditions, and the average deterioration rate of the vitamin A product in the light intensity 4500lx plus or minus 500lx conditions is 0.35 percent/d. The purity of the obtained vitamin A crystal is 99.98%, the color of the vitamin A crystal tends to be white, the chromaticity value of the crystal solution is 39Hazen, the average size of the crystal is 100 mu m, the particles are uniformly distributed, the dispersibility is good, and the agglomeration phenomenon is avoided.
Example 3:
52.74g of crude C15 phosphine salt was dissolved in 150.33g of water, the above aqueous solution was added to 150.33g of solvent b (99 wt% n-hexane and 1wt% methanol) at 30℃and 400rpm, stirred for 45min and left standing for 45min for phase separation, and the raffinate phase composition was sampled and analyzed (excluding solvent a water): the content of compound I was 1200ppm, the content of compound II was 2100ppm, and the content of C15 phosphine salt was 99.67%.
7.1g of pentacarbon aldehyde is added into the raffinate phase, after the temperature is raised to 65 ℃, 18g of K with the mass fraction of 40% is added dropwise 2 CO 3 The solution was reacted for 3 hours under a pressure of 150kPaA and a stirring speed of 400rpm to obtain a crude vitamin A oil. The composition was determined by sampling and the conversion of C15 phosphine salt was 95.1%, the vitamin A selectivity was 99.2% and the vitamin A dimer content was 0.08%.
Taking out the obtained vitamin A crude oil, adding 99g of ethanol, crystallizing at 5 ℃, filtering to obtain vitamin A crystals, and testing the stability, the chromaticity value and the particle size. The average deterioration rate of the vitamin A product in the nitrogen atmosphere at 60 ℃ is 0.31 percent/d, the average deterioration rate of the vitamin A product in the nitrogen atmosphere at 25 ℃ is 0.29 percent/d under the RH90 plus or minus 5 percent conditions, and the average deterioration rate of the vitamin A product in the light intensity 4500lx plus or minus 500lx conditions is 0.51 percent/d. The purity of the obtained vitamin A crystal is 99.94%, the color of the vitamin A crystal tends to be white, the chromaticity value of the crystal solution is 49Hazen, the average size of the crystal is 125 mu m, the particles are uniformly distributed, the dispersibility is good, and the agglomeration phenomenon is avoided.
Example 4:
52.74g of crude C15 phosphine salt is dissolved in 200.44g of water, the above aqueous solution is added into 100.22g of solvent b (97 wt% of n-hexane and 3wt% of methanol) at 30 ℃ and 500rpm, stirred for 60min, and left stand for 60min for phase separation, and the raffinate phase composition (excluding solvent a water) is sampled and analyzed: the content of compound I was 3300ppm, that of compound II was 4700ppm, and that of the C15 phosphine salt was 99.2%.
7.1g of pentacarbon aldehyde is added into the raffinate phase, after the temperature is raised to 75 ℃, 28g of K with the mass fraction of 50% is added dropwise 2 CO 3 The solution was reacted for 4 hours under a pressure of 200kPaA and a stirring speed of 500rpm to obtain a crude vitamin A oil. The composition was determined by sampling to give a C15 phosphonate conversion of 94.6% and vitamin A selectivity of 99.0% and vitamin A dimer contentThe amount was 0.09%.
The obtained crude vitamin a oil was taken out and 132g of ethanol was added, crystallized at 10 ℃ and filtered to obtain vitamin a crystals, which were tested for stability, chromaticity value and particle size. The average deterioration rate of the vitamin A product in the nitrogen atmosphere at 60 ℃ is 0.37 percent/d, the average deterioration rate of the vitamin A product in the nitrogen atmosphere at 25 ℃ is 0.38 percent/d under the RH90 percent plus or minus 5 percent, and the average deterioration rate of the vitamin A product in the light intensity of 4500lx plus or minus 500lx is 0.56 percent/d. The purity of the obtained vitamin A crystal is 99.91%, the color of the vitamin A crystal tends to be white, the chromaticity value of the crystal solution is 57Hazen, the average size of the crystal is 145 mu m, the particles are uniformly distributed, the dispersibility is good, and the agglomeration phenomenon is avoided.
Comparative example 1:
52.74g of crude C15 phosphine salt is dissolved in 1002.2g of water, the above aqueous solution is added into 2004.4g of solvent b (n-hexane content 100%) under the conditions of 80 ℃ and 1000rpm, stirred for 600min, left stand for 600min for phase separation, and the raffinate phase composition (excluding solvent a water) is sampled and analyzed: the content of compound I was 80ppm, the content of compound II was 130ppm, and the content of C15 phosphine salt was 99.98%.
14.2g of pentacarbonaldehyde was added to the C15 phosphine salt solution, and after the temperature was raised to 55 ℃, 92g of K having a mass fraction of 30% was added dropwise 2 CO 3 The solution was reacted for 2 hours at a pressure of 100kPaA and a stirring speed of 300rpm to obtain a crude vitamin A oil. The composition was determined by sampling and the conversion of C15 phosphine 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 the stability, chromaticity value and particle size. The average deterioration rate of the vitamin A product in the nitrogen atmosphere at 60 ℃ is 0.82 percent/d, the average deterioration rate of the vitamin A product in the nitrogen atmosphere at 25 ℃ is 0.88 percent/d under the RH90 percent plus or minus 5 percent, and the average deterioration rate of the vitamin A product in the light intensity of 4500lx plus or minus 500lx is 1.03 percent/d. The purity of the obtained vitamin A crystal is 98.6%, the color is slightly yellowish, the chromaticity value of the crystal solution is 98Hazen, the average size of the crystal is 1000 mu m, and the phenomenon of partial agglomeration exists.
Comparative example 2:
52.74g of crude C15 phosphine salt are dissolved in 100.22g of water and the composition is analyzed by sampling (without solvent a water): the content of compound I was 20000ppm, the content of compound II was 30000ppm, and the content of C15 phosphine salt was 95%.
14.2g of pentacarbonaldehyde was added to the C15 phosphine salt solution, and after the temperature was raised to 55 ℃, 92g of K having a mass fraction of 30% was added dropwise 2 CO 3 The solution was reacted for 2 hours under a pressure of 100kPaA and a stirring speed of 300rpm to obtain a crude vitamin A oil. The composition was determined by sampling and the conversion of C15 phosphine 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 the stability, chromaticity value and particle size. The average deterioration rate of the vitamin A product in the nitrogen atmosphere at 60 ℃ is 0.99 percent/d, the average deterioration rate of the vitamin A product in the nitrogen atmosphere at 25 ℃ is 0.98 percent/d under the RH90 percent plus or minus 5 percent, and the average deterioration rate of the vitamin A product in the light intensity of 4500lx plus or minus 500lx is 1.32 percent/d. The purity of the obtained vitamin A crystal is 94.4%, the color of the vitamin A crystal is yellow, the chromaticity value of the crystal solution is 200Hazen, the average size of the crystal is 1200 mu m, and the vitamin A crystal has a partial agglomeration phenomenon.
Comparative example 3:
52.74g of crude C15 phosphine salt is dissolved in 100.22g of water, the above aqueous solution is added into 100.22g of solvent b (94 wt% of n-hexane and 6wt% of methanol) at 40 ℃ and a rotating speed of 300rpm, stirred for 30min, and kept stand for 30min for phase separation, and the raffinate phase composition (excluding solvent a water) is sampled and analyzed: the content of compound I was 8700ppm, the content of compound II was 10300ppm, and the content of the C15 phosphine salt was 98.1%.
14.2g of pentacarbon aldehyde is added into the raffinate phase, after the temperature is raised to 55 ℃, 92g of K with the mass fraction of 30% is added dropwise 2 CO 3 The solution was reacted for 2 hours under a pressure of 100kPaA and a stirring speed of 300rpm to obtain a crude vitamin A oil. The composition was determined by sampling and the conversion of C15 phosphine 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 the stability, chromaticity value and particle size. The average deterioration rate of the vitamin A product in the nitrogen atmosphere at 60 ℃ is 0.62 percent/d, the average deterioration rate of the vitamin A product in the nitrogen atmosphere at 25 ℃ is 0.75 percent/d under the RH90 percent plus or minus 5 percent, and the average deterioration rate of the vitamin A product in the light intensity 4500lx plus or minus 500lx is 0.91 percent/d. And the purity of the obtained vitamin A crystal is 98.5%, the color of the vitamin A crystal tends to be white, the chromaticity value of the crystal solution is 101Hazen, the average size of the crystal is 575 mu m, and the vitamin A crystal has a partial agglomeration phenomenon.
Claims (15)
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, and extracting with a solvent b under certain conditions to obtain a C15 phosphine salt mixture, wherein the content of a compound I and a compound II in the C15 phosphine salt mixture is controlled to be 0.1-1 wt%
(2) And (3) performing wittig reaction on the C15 phosphine salt mixture in the step (1) and pentacarbon aldehyde under the action of alkali liquor to prepare vitamin A acetate crude oil, and recrystallizing to obtain vitamin A crystals.
2. The method according to claim 1, wherein the solvent a is one or more of methanol, ethanol, methylene chloride, tetrahydrofuran, ethyl acetate and water.
3. The method according to claim 1, wherein the mass ratio of the solvent a to the C15 phosphine salt is 0.5-10:1.
4. the method according to claim 1, wherein the mass ratio of solvent a to C15 phosphine salt is 1-5:1.
5. the method according to any one of claims 1 to 4, wherein 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 5.0wt%.
6. The method according to claim 5, wherein the solvent b is a mixture of a polar solvent and a non-polar solvent, wherein the content of the polar solvent is 0.5-1wt%.
7. The method of claim 5, wherein the polar solvent is one or more of dichloromethane, tetrahydrofuran, ethanol, ethyl acetate, methanol, water; the nonpolar solvent is one or more of n-hexane, cyclohexane, n-heptane, petroleum ether, toluene, p-xylene and m-xylene.
8. The method according to claim 5, wherein the mass ratio of the solvent b to the C15 phosphine salt is 0.5 to 10:1.
9. the method according to claim 8, wherein the mass ratio of solvent b to C15 phosphine salt is 1-3:1.
10. the process according to any one of claims 1 to 4, wherein in step (1), the extraction operation is carried out at a temperature of 0 to 80 ℃; the stirring speed of the extraction is 100-1000rpm; the stirring time of the extraction is 5-300min; the phase separation time of the extraction is 1-120min.
11. The process of claim 10, wherein in step (1), the extraction operation is performed at a temperature of 30-50 ℃; the stirring speed of the extraction is 200-500rpm; the stirring time of the extraction is 10-60min; the phase separation time of the extraction is 10-60min.
12. The method according to any one of claims 1 to 4, wherein the molar ratio of the C15 phosphine salt mixture to the pentacarbonaldehyde and the base is (0.5 to 5) 1 (0.5 to 5); and/or, in the step (2), the reaction temperature is controlled to be 30-90 ℃.
13. The method according to claim 12, wherein the molar ratio of the C15 phosphine salt mixture to the pentacarbonaldehyde and the base is (1-2): 1 (1-2); and/or, in the step (2), the reaction temperature is controlled to be 45-75 ℃.
14. The method according to any one of claims 1 to 4, wherein in the step (2), the crude vitamin a acetate oil is dissolved in a crystallization agent for crystallization, wherein the crystallization agent is one or more of methanol, ethanol, isopropanol, ethylene glycol, n-butanol and isobutanol, and the amount of the crystallization agent is 0.5 to 10 times the mass of the crude vitamin a acetate oil; the crystallization temperature is-15-30 ℃.
15. The method according to claim 14, wherein in the step (2), the crystallization reagent is used in an amount of 1 to 5 times the mass of the crude vitamin a acetate; the crystallization temperature is-5-20 ℃.
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| CN202111384628.2A CN114031534B (en) | 2021-11-19 | 2021-11-19 | High-stability vitamin A and preparation method thereof |
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