Preparation method of high-purity Vc-2-sodium monophosphate

Abstract

The invention belongs to the technical field of synthesis and purification of organic phosphorus-containing compounds, and particularly relates to a preparation method of high-purity Vc-2-sodium monophosphate. Pre-treating the esterification reaction liquid by using acidic resin, neutralizing and concentrating, and then carrying out a decoloration and alcohol precipitation impurity removal process to obtain a crude product; and dissolving the crude product, decolorizing, removing impurities, and recrystallizing to obtain a high-purity Vc-2-sodium monophosphate finished product. In the implementation process, the esterification reaction liquid is pretreated by using acidic resin before column exchange, and only less water is needed for dilution, so that the problems of dilution and dissolution before resin exchange are solved, the water for dilution and dissolution is reduced, and the production cost of concentration is reduced; in addition, the concentrated solution is subjected to decoloration and impurity removal through a decoloration and alcohol precipitation impurity removal method before alcohol precipitation crystallization, so that a finished product which is whiter in appearance and higher in purity is obtained.

Description

Technical Field

[0001] The present invention relates to the technical field of synthesis and purification of organophosphorus compounds, and particularly relates to a method for preparing sodium Vc-2-monophosphate with high purity. Background Art

[0002] L-ascorbic acid (vitamin C, also known as Vc) and its salts are widely used in medicine, food, cosmetics and animal feed. However, due to the presence of unstable groups in the molecular structure of L-ascorbic acid, it is sensitive to temperature and oxidation itself, resulting in easy thermal or oxidative decomposition during manufacturing, storage and use. By converting it into the form of phosphate salt, antioxidant decomposition and thermal decomposition can be achieved, and the stability is greatly improved. Sodium Vc-2-monophosphate is designed to address the above problems. The unstable groups of L-ascorbic acid (Vc) are protected by phosphate groups, so that it has both the active function of Vc and can resist antioxidant decomposition and thermal decomposition during normal use.

[0003] So far, in the prior art of the present field, sodium trimetaphosphate is used as a phosphorylation reagent to react with sodium L-ascorbate under alkaline conditions to prepare Vc-2-phosphate salt (see Chinese patents CN1491952A and CN105481895B). In the above two methods, Vc-2-phosphate salt is obtained by reacting L-ascorbic acid (or its salt) with sodium trimetaphosphate, sodium hydroxide and calcium hydroxide. After the reaction solution is subjected to resin exchange and neutralized with sodium hydroxide solution, sodium L-ascorbate-2-phosphate is obtained after alcohol precipitation. In practical applications, the reaction solution is a mixture of calcium and sodium salts of Vc-2-phosphate, and contains a certain amount of calcium and sodium salts of Vc-dimer and trimer phosphate. Even if diluted many times with water, the calcium salt of Vc-phosphate cannot be well dissolved. On the one hand, a lot of water is wasted. On the other hand, during resin exchange, the undissolved calcium salt will accumulate above the resin column, which not only clogs the resin, reduces the resin exchange capacity, but also reduces the yield of the final product. Diluting and dissolving with too much water also increases the cost during subsequent concentration. After the exchange solution is neutralized and concentrated, the original invention directly obtains the finished product by alcohol precipitation without a good impurity removal process. The obtained sodium L-ascorbate-2-monophosphate finished product has a deep color and a purity generally around 95%-97%. Summary of the Invention

[0004] In view of the above problems occurring in the preparation process, the present invention aims to provide an optimized method for preparing high-purity sodium L-ascorbic acid-2-monophosphate, aiming to solve the dilution and dissolution problems before resin exchange, reduce the water used for dilution and dissolution, and lower the production cost of concentration; and through a unique process of decolorization and alcohol precipitation for impurity removal, obtain a finished product with a whiter appearance and higher purity. The present invention is essentially an optimization and reinvention of the authorized invention CN105481895B of this unit. The two innovative points of the present invention are the addition of an acidic resin pretreatment process before exchange and the addition of a decolorization and alcohol precipitation for impurity removal process before alcohol precipitation crystallization.

[0005] In the present invention, before the exchange into the column, the esterification reaction solution is pretreated with an acidic resin, and only a small amount of water is needed for dilution to make the reaction solution completely clear. This not only significantly saves the water consumption for dilution, but also saves the corresponding concentration cost in the subsequent concentration. On the other hand, when the clarified solution enters the column for exchange, it will not block the resin column, and after the calcium salt is dissolved, it will not affect the yield of the final product. Therefore, it has significant economic benefits.

[0006] After the exchange solution is neutralized with sodium hydroxide and concentrated, the present invention creatively proposes a decolorization and alcohol precipitation for impurity removal process. By adding a certain amount of alcohol during the activated carbon decolorization process, a part of the impurities are precipitated during the decolorization process. After filtering out the activated carbon and impurities, alcohol precipitation is carried out to obtain the crude product. After the crude product is dissolved, it is decolorized and purified again, and recrystallized to obtain a product with a whiter color. The purity of the obtained sodium Vc-2-monophosphate finished product exceeds 99%.

[0007] The present invention provides a method for preparing high-purity sodium Vc-2-phosphate. Dissolve sodium ascorbate in water, add sodium trimetaphosphate and calcium hydroxide for phosphorylation reaction. The molar ratio of sodium ascorbate, sodium trimetaphosphate and calcium hydroxide is (3.30 - 3.45):1:(1.65 - 1.75). Control the reaction temperature and pH of the system. After adding calcium hydroxide, continue the reaction for 2 - 5 hours to make the reaction more complete. After the esterification solution is diluted, add an acidic resin for stirring pretreatment, and then carry out ion exchange with a strongly acidic cation resin. Preferably, the pH of the clarified solution is controlled at 1.5 - 3.0. The exchange solution is neutralized with a concentrated sodium hydroxide solution and then concentrated. The concentrated solution is filtered by decolorization and alcohol precipitation, and then methanol is used to precipitate crystals, centrifuged and washed with a water-methanol solution to obtain the crude sodium Vc-2-monophosphate; after the crude product is dissolved, it is decolorized, alcohol-precipitated and filtered again. After alcohol precipitation, it is centrifuged, washed with crystals and dried to obtain a high-purity sodium Vc-2-monophosphate finished product.

[0008] Mix sodium L-ascorbate with water to form a suspension, add a suspension of calcium hydroxide thereto, adjust the pH value of the mixed solution to 9.0 - 10.5, add sodium tripolyphosphate, slowly add the calcium hydroxide suspension to control the reaction, keep the pH value of the mixed solution at 9.0 - 10.5, and gradually raise the reaction temperature to 50 - 65 °C. After the addition of calcium hydroxide is completed, continue the reaction for 3 hours and then terminate the reaction.

[0009] The reaction solution for preparing Vc-2-phosphate salt mentioned above is a mixture of Vc-2-phosphate calcium salt and sodium salt. Due to the solubility of Vc-polyphosphate calcium salt in water, even if diluted many times with water, the Vc-phosphate calcium salt cannot be well dissolved. On the one hand, a lot of water is wasted. On the other hand, during resin exchange, the undissolved calcium salt will accumulate above the resin column, which not only clogs the resin, reduces the resin exchange capacity, but also reduces the yield of the final product and increases the cost in subsequent concentration. The inventor creatively uses an acidic resin as a pretreatment agent during the dilution process of the reaction solution. By acidifying and exchanging the Vc-2-phosphate calcium salt in the reaction solution, the problem of poor solubility of Vc-2-phosphate calcium in the reaction solution is well solved, and 50% of the water used for dilution and dissolution can be saved.

[0010] Preferably, the reaction solution is diluted with 4 - 6 times of water, an acidic resin is added and stirred, and the pH of the diluted solution is adjusted to 2.0 - 3.0 to make the reaction solution clear.

[0011] The clear liquid enters the column, is exchanged with an acidic resin, the acidic exchange liquid is collected, the exchange liquid is neutralized and concentrated with sodium hydroxide solution, so that the content of Vc-2-phosphate sodium in the concentrated liquid is 10 - 15%, and the neutralized and concentrated liquid is obtained.

[0012] The inventor noticed that in the authorized patent CN105481895B applied by this unit, the subsequent treatment method of the neutralized and concentrated liquid (referred to as the concentrated liquid) is to directly obtain Vc-2-monophosphate sodium through alcohol precipitation, without other impurity removal processes in the middle. The appearance color of the obtained Vc-2-monophosphate sodium is poor, and even after recrystallization, it cannot be significantly improved, all with obvious yellow or light yellow color. The inventor creatively proposes to decolorize and remove impurities from the concentrated liquid by a decolorizing alcohol precipitation and impurity removal method before alcohol precipitation crystallization. This not only well solves the problem of the yellowish appearance color of the Vc-2-monophosphate sodium finished product, but also through detection, it is found that the content and purity have been significantly improved, and the quality of the finished product has been significantly improved.

[0013] The decolorization and impurity removal method of the present invention is characterized in that decolorization and impurity removal are carried out simultaneously and synergistically. The basic principle of the decolorization and impurity removal method of the present invention is that adding activated carbon can adsorb pigments, and adding a certain amount of methanol can cause the sodium salt of Vc and Vc-2-dimer and polyphosphate sodium salt in the concentrated solution to precipitate in advance. The viscous Vc-2-dimer and polyphosphate sodium salt adhere to the activated carbon together, which is convenient to filter out together during filtration. The alcohols for alcohol precipitation are not limited to methanol or ethanol.

[0014] The experimental results show that the decolorization and alcohol precipitation impurity removal method of the present invention well solves the problem of the yellowish appearance color of the finished product of sodium Vc-2-monophosphate, and at the same time effectively improves the content and purity of the finished product.

[0015] The preferred method of the present invention is to add 0.3-1.0‰ of activated carbon in the concentrated solution based on the concentrated solution, and add 0.5-1.0 times of methanol in the concentrated solution for decolorization and alcohol precipitation for 30 minutes. During the decolorization process, a part of the impurities precipitate by alcohol precipitation. After filtering out the activated carbon and impurities, alcohol precipitation is carried out again to obtain the crude product. After the crude product is dissolved, it is decolorized and purified by alcohol precipitation again. After alcohol precipitation and recrystallization, a product with better color is obtained, and the purity of the obtained product sodium Vc-2-monophosphate exceeds 99%.

[0016] Compared with the method described in the authorized invention CN105481895B of the present unit, after the reaction is completed, the reaction solution is diluted with a large amount of water, then resin exchange is carried out, and the exchange solution is neutralized and concentrated and then directly subjected to alcohol precipitation and crystallization.

[0017] The present invention creatively pretreats the esterification reaction solution with an acidic resin before entering the column for exchange. Only a small amount of water is needed for dilution to make the reaction solution completely clear. This not only significantly saves the dilution water consumption, but also saves the corresponding concentration cost in the subsequent concentration. On the other hand, the clarified solution enters the column for exchange and will not block the resin column. After the calcium salt is dissolved, it will not affect the yield of the final product. Therefore, it has significant economic benefits.

[0018] After the exchange solution is neutralized with sodium hydroxide and concentrated, the present invention creatively proposes a decolorization and alcohol precipitation impurity removal process. By adding a certain amount of alcohol during the activated carbon decolorization process, a part of the impurities precipitate during the decolorization process. After filtering out the activated carbon and impurities, alcohol precipitation is carried out to obtain the crude product. After the crude product is dissolved, it is decolorized, purified and recrystallized to obtain a product with a whiter color. The purity of the obtained finished product of sodium Vc-2-monophosphate is higher, and the purity detected by HPLC is greater than 99%. Description of the Drawings

[0019] Figure 1 It is a process flow chart for the preparation of high-purity sodium Vc-2-monophosphate. Detailed Embodiments

[0020] Example 1: Add 280 ml of deionized water to a 1000-ml beaker. While stirring, add 556 g of sodium L-ascorbate to form a suspension. Slowly add a 30% calcium hydroxide suspension to it until the pH value reaches 9.5. Then slowly add 260 g of sodium tripolyphosphate. At the same time, use a 30% calcium hydroxide suspension to control the pH value of the reaction solution within the range of 9.0 - 10.5, and gradually raise the temperature of the reaction solution to 60°C. After all the calcium hydroxide is added, continue the reaction for 3 hours, which is the end point of the reaction. Stir and dilute the reaction mixture with 6 times the amount of deionized water, and adjust the pH to 2.48 with an acidic resin, and the reaction solution becomes clear. Pass the reaction solution through an acidic resin column for exchange and collect the acidic exchange solution. Neutralize the exchange solution to pH 10.5 with a 30% sodium hydroxide solution; concentrate the neutralized solution. Then add 28 g of activated carbon to the concentrated solution, and add 4 L of methanol and stir for 30 minutes for decolorization and impurity removal by alcohol precipitation. After pressure filtration, add 5 L of methanol dropwise to the decolorized solution for crystallization. Centrifuge and wash the crystals with water and methanol to obtain the crude product of sodium Vc-2-monophosphate. Dissolve the crude product in 3.4 kg of deionized water with stirring, add 25 g of activated carbon, then add 3 L of methanol, and stir for 30 minutes for the second decolorization and impurity removal by alcohol precipitation. After pressure filtration, add 4 L of methanol dropwise to the decolorized solution for crystallization. Centrifuge and wash the crystals with methanol to obtain the refined wet product. Dry the wet product to obtain 487.26 g of the finished product of sodium Vc-2-monophosphate. The dry content of sodium Vc-2-monophosphate detected by HPLC is 98.74%, and the purity is 99.32%.

[0021] Example 2: Add 5 liters of deionized water into a 30 L glass reactor. While stirring, add 1 kg of sodium L-ascorbate to form a suspension. Slowly add a 30% calcium hydroxide suspension thereto until the pH value reaches 9.7. Then slowly add 4.7 kg of sodium tripolyphosphate. At the same time, control the pH value of the reaction solution within the range of 9.0 - 10.5 with the 30% calcium hydroxide suspension, and gradually increase the temperature of the reaction solution to 60°C. After all the calcium hydroxide is added, continue the reaction for 3 hours, which is the reaction end point. Stir and dilute the reaction mixture with 4 times the amount of deionized water, and adjust the pH to 2.36 with an acidic resin, and the reaction solution becomes clear. Pass the reaction solution through an acidic resin column for exchange and collect the acidic exchange solution. Neutralize the exchange solution to pH 10.5 with a 30% sodium hydroxide solution. After the neutralized solution is concentrated by a nanofiltration membrane, add 500 g of activated carbon to the concentrated solution, and add 70 L of methanol and stir for 30 minutes for decolorization, alcohol precipitation and impurity removal. After pressure filtration, add 90 L of methanol dropwise to the decolorized solution for crystallization. After centrifugation, wash the crystals with water and methanol to obtain the crude product of sodium Vc-2-monophosphate. Dissolve the crude product in 62 kg of deionized water with stirring, add 380 g of activated carbon, then add 54 L of methanol, and stir for 30 minutes for the second decolorization, alcohol precipitation and impurity removal. After filtration, add 70 L of methanol dropwise to the decolorized solution for crystallization. After centrifugation, wash the crystals with methanol to obtain the refined wet product. Dry the wet product to obtain 7.9 kg of the finished product of sodium Vc-2-monophosphate. By HPLC detection, the dry content of sodium Vc-2-monophosphate in it is 99.05%, and the purity is 99.35%.

Claims

1. A preparation method of high-purity sodium ascorbyl-2-monophosphate, characterized in that: It includes the following process steps: Dissolve sodium ascorbate in water, add sodium trimetaphosphate and calcium hydroxide for phosphorylation reaction. After diluting the esterification solution, add acidic resin for pretreatment, then conduct ion exchange with strongly acidic cation resin. The exchange solution is neutralized with concentrated sodium hydroxide solution and then concentrated. The concentrated solution is decolorized, alcohol-precipitated and filtered, and then crystals are precipitated with an alcohol solvent, centrifuged and washed with a water-methanol solution to obtain crude Vc-2-monophosphate sodium; the crude product is dissolved and then decolorized, alcohol-precipitated and filtered again. After alcohol precipitation, it is centrifuged, washed with crystals and dried to obtain high-purity Vc-2-monophosphate sodium finished product.

2. The preparation method of a high-purity sodium Vc-2-monophosphate according to claim 1, characterized in that: Add sodium trimetaphosphate and calcium hydroxide for phosphorylation reaction. The molar ratio of sodium ascorbate, sodium trimetaphosphate and calcium hydroxide is (3.30 - 3.45):1:(1.65 - 1.75). Control the reaction temperature and pH of the system. After adding calcium hydroxide, continue the reaction for 2 - 5 hours to make the reaction more complete.

3. The preparation method of a high-purity sodium Vc-2-monophosphate according to claim 1, wherein: After diluting the esterification solution, add acidic resin and stir for pretreatment to obtain a clear solution, and then conduct ion exchange with strongly acidic cation resin.

4. The preparation method of a high-purity sodium ascorbyl-2-monophosphate according to claim 3, characterized in that: The pH of the said clear solution is controlled at 1.5 - 3.

0.

5. The preparation method of a high-purity sodium Vc-2-monophosphate according to claim 1, characterized in that: Decolorize, alcohol-precipitate, remove impurities and filter the neutralized concentrated solution. Decolorization, alcohol precipitation and impurity removal are carried out simultaneously. The decolorization and alcohol precipitation scheme is to add powdered activated carbon to the concentrated solution and add methanol for alcohol precipitation during stirring, stir for 30 minutes to precipitate impurities.

6. The preparation method of a high-purity Vc-2-monophosphate sodium according to claim 5, characterized in that: The weight of the added powdered activated carbon is 0.3 - 1.0‰ of the decolorized solution.

7. The preparation method of a high-purity sodium Vc-2-monophosphate according to claim 5, characterized in that: The usage amount of the alcohol solvent for decolorization and alcohol precipitation is 0.5 - 1.0 times that of the decolorized solution.

8. A method for preparing high-purity sodium ascorbyl-2-monophosphate according to claim 5, characterized in that: The alcohol solvent for alcohol precipitation uses methanol or ethanol.

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