A preparation method of high-purity Vc-2-monophosphate sodium

Abstract

The present invention belongs to the technical field of synthesis and purification of organic phosphorus-containing compounds, and in particular to a method for preparing high-purity sodium monophosphate of Vc-2. The esterification reaction liquid is pretreated with an acidic resin, and after neutralization and concentration, a decolorization alcohol precipitation and impurity removal process is used to obtain a crude product; after the crude product is dissolved, a high-purity sodium monophosphate finished product of Vc-2 is obtained after decolorization, impurity removal and recrystallization. During implementation, the esterification reaction liquid is pretreated with an acidic resin before the exchange column, and only needs to be diluted with less water, the purpose of which is to solve the dilution and dissolution problem before resin exchange, reduce the dilution and dissolution water and reduce the production cost of concentration; in addition, the present invention carries out a process of decolorizing and removing impurities on the concentrated solution by a decolorization alcohol precipitation and impurity removal method before alcohol precipitation and crystallization, so as to obtain a finished product with a whiter appearance and higher purity.

Description

Technical Field

[0001] The present invention relates to the technical field of synthesis and purification of organic phosphorus-containing compounds, and in particular to a method for preparing high-purity sodium Vc-2-monophosphate. 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 its molecular structure, L-ascorbic acid is sensitive to temperature and oxidation, making it susceptible to thermal or oxidative decomposition during manufacturing, storage, and use. Forming it into a phosphate salt can resist oxidative decomposition and thermal decomposition, significantly improving its stability. Sodium Vc-2-monophosphate addresses this issue by protecting the unstable groups of L-ascorbic acid (Vc) with phosphate groups. This allows it to retain the activity of Vc while resisting oxidative and thermal decomposition during normal use.

[0003] To date, prior art uses sodium trimetaphosphate as a phosphorylating agent to react with sodium L-ascorbate under alkaline conditions to prepare Vc-2-phosphate (see Chinese Patents CN1491952A and CN105481895B). In both methods, L-ascorbic acid (or its salt) reacts with sodium trimetaphosphate, sodium hydroxide, and calcium hydroxide to produce Vc-2-phosphate. The reaction solution is then subjected to resin exchange, neutralized with sodium hydroxide solution, and alcohol precipitation to yield the finished product, sodium L-ascorbic acid-2-phosphate. In practical applications, the reaction solution is a mixture of calcium and sodium salts of Vc-2-phosphate, containing a certain amount of calcium and sodium salts of Vc dimer and tripolyphosphates. Even when diluted many times with water, the calcium salt of Vc phosphate does not dissolve well. On the one hand, a lot of water is wasted. On the other hand, during resin exchange, undissolved calcium salts accumulate above the resin column, clogging the resin and reducing its exchange capacity, which in turn reduces the final product yield. Excessive water dilution and dissolution also increases costs during subsequent concentration. After neutralization and concentration of the exchange solution, the original invention directly uses alcohol precipitation to obtain the finished product, without a thorough impurity removal process. The resulting sodium L-ascorbic acid-2-monophosphate product is dark in color and generally has a purity of around 95%-97%. Summary of the Invention

[0004] In response to the above-mentioned problems arising during the preparation process, the present invention aims to provide an optimized method for preparing high-purity sodium L-ascorbic acid-2-monophosphate, with the aim of solving the dilution and dissolution problem before resin exchange, reducing the amount of water used for dilution and dissolution, and lowering the production cost of concentration; and through a unique decolorization and alcohol precipitation and impurity removal process, a finished product with a whiter appearance and higher purity is obtained. The present invention is essentially an optimization and reinvention of the invention CN105481895B authorized by this unit. The addition of an acidic resin pretreatment process before exchange and the addition of a decolorization and alcohol precipitation and impurity removal process before alcohol precipitation crystallization are the two major innovations of the present invention.

[0005] By creatively pretreating the esterification reaction liquid with an acidic resin before exchange into the column, the present invention allows complete clarification of the reaction liquid with only a small amount of water for dilution. This not only significantly reduces the amount of dilution water but also eliminates the corresponding concentration costs during subsequent concentration. Furthermore, the exchange of the clarified liquid into the column does not clog the resin column, and the dissolution of the calcium salt does 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 innovatively proposes a decolorization and alcohol precipitation process. By adding a certain amount of alcohol during the activated carbon decolorization process, some impurities are precipitated during the decolorization process. After filtering out the activated carbon and impurities, alcohol precipitation is performed to obtain a crude product. After the crude product is dissolved, decolorization and impurity removal, followed by recrystallization, a whiter product is obtained. The resulting sodium Vc-2-monophosphate product has a purity exceeding 99%.

[0007] The present invention provides a method for preparing high-purity sodium vitamin C-2-phosphate. Sodium vitamin C salt is dissolved in water, and sodium trimetaphosphate and calcium hydroxide are added to carry out a phosphoesterification reaction. The molar ratio of sodium vitamin C salt, sodium trimetaphosphate, and calcium hydroxide is (3.30-3.45):1:(1.65-1.75). The reaction temperature and pH of the system are controlled. After the addition of calcium hydroxide, the reaction is continued for 2-5 hours to ensure a more complete reaction. The esterification solution is diluted, and then pre-treated with an acidic resin and stirred. Ion exchange is then performed with a strong acidic cationic resin. The pH of the clear solution is preferably controlled between 1.5 and 3.0. The exchange solution is neutralized with a concentrated sodium hydroxide solution and concentrated. The concentrate is decolorized and filtered through alcohol precipitation. Crystals are then precipitated with methanol, centrifuged, and washed with a methanol solution to obtain a crude sodium vitamin C-2-monophosphate. The crude product is dissolved, decolorized, filtered through alcohol precipitation, centrifuged, and washed with a methanol solution to obtain a high-purity sodium vitamin C-2-monophosphate product.

[0008] Sodium L-ascorbate is mixed with water to form a suspension, a calcium hydroxide suspension is added thereto, the pH value of the mixture is adjusted to 9.0-10.5, sodium trimetaphosphate is added, and the calcium hydroxide suspension is slowly added to control the reaction. The pH value of the mixed solution is 9.0-10.5, and the reaction temperature is gradually increased to 50-65°C. After the addition of calcium hydroxide is completed, the reaction is continued for 3 hours and then terminated.

[0009] The reaction solution for preparing the above-mentioned Vc-2-phosphate salt 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, Vc phosphate calcium salt cannot be dissolved well. On the one hand, a lot of water is wasted. On the other hand, when exchanged with resin, undissolved calcium salt will gather above the resin column, not only blocking the resin and reducing the resin exchange capacity, but also reducing the final product yield and increasing the cost in subsequent concentration. The inventors creatively use acidic resin as a pre-treating agent in the reaction solution dilution process. By acidifying and exchanging the Vc-2-phosphate calcium salt in the reaction solution, the problem of the difficult dissolution of Vc-2-phosphate calcium in the reaction solution is well solved, and 50% of the dilution and dissolution water can be saved.

[0010] Preferably, the reaction solution is diluted with 4-6 times water, and acidic resin is added and stirred, and the pH of the dilution solution is adjusted to 2.0-3.0, so that the reaction solution can be clarified.

[0011] The clear liquid enters the column and is exchanged with an acidic resin. The acidic exchange liquid is collected, and the exchange liquid is neutralized with a sodium hydroxide solution and concentrated to make the Vc-2-sodium phosphate content in the concentrated liquid 10-15%, thereby obtaining a neutralized concentrated liquid.

[0012] The inventors noted that in the CN105481895B patent application filed by this unit, the subsequent treatment of the neutralized concentrate (hereinafter referred to as the concentrate) involves direct alcohol precipitation to obtain sodium Vc-2-monophosphate, without any intermediate impurity removal process. The resulting sodium Vc-2-monophosphate exhibited poor color, which was not significantly improved even after recrystallization, resulting in a distinct yellow or pale yellow hue. The inventors creatively proposed decolorizing and removing impurities from the concentrate using a decolorization and alcohol precipitation method prior to crystallization. This not only effectively addressed the yellowing issue of the finished sodium Vc-2-monophosphate, but also, through testing, significantly improved its content and purity, significantly enhancing the quality of the finished product.

[0013] The decolorization and impurity removal method of the present invention is characterized by simultaneous decolorization and impurity removal, achieving a coordinated effect. The basic principle of the decolorization and impurity removal method of the present invention is that the addition of activated carbon can adsorb pigments, and the addition of a certain amount of methanol can cause the Vc sodium salt and Vc-2-dimer and polyphosphate sodium salt in the concentrate to precipitate in advance. The sticky Vc-2-dimer and polyphosphate sodium salt adhere to the activated carbon, making it convenient to filter them out together during filtration. The alcohol used for alcohol precipitation is not limited to methanol or ethanol.

[0014] The experimental results show that the decolorization and alcohol separation impurity removal method of the present invention effectively solves the problem of yellowing of the appearance of the finished product of sodium Vc-2-monophosphate, and also effectively improves the content and purity of the finished product.

[0015] The preferred method of the present invention comprises the following steps: adding 0.3-1.0‰ activated carbon to the concentrate, and adding 0.5-1.0 times the amount of methanol to the concentrate for decolorization and alcohol precipitation for 30 minutes; precipitating a portion of impurities through alcohol precipitation during the decolorization process; filtering out the activated carbon and impurities; and then performing alcohol precipitation to obtain a crude product; dissolving the crude product and then performing decolorization and alcohol precipitation to remove impurities; and then performing alcohol precipitation and recrystallization to obtain a product with better color. The purity of the obtained product, sodium Vc-2-monophosphate, exceeds 99%.

[0016] Compared with the method described in the invention CN105481895B authorized by this unit, after the reaction is completed, the reaction solution is diluted with a large amount of water, and then exchanged with resin. After the exchange liquid is neutralized and concentrated, it is directly crystallized through alcohol precipitation.

[0017] By creatively pretreating the esterification reaction liquid with an acidic resin before exchange into the column, the present invention allows complete clarification of the reaction liquid with only a small amount of water for dilution. This not only significantly reduces the amount of dilution water but also eliminates the corresponding concentration costs during subsequent concentration. Furthermore, the exchange of the clarified liquid into the column does not clog the resin column, and the dissolution of the calcium salt does 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 process. By adding a certain amount of alcohol during the activated carbon decolorization process, some impurities are precipitated during the decolorization process. After filtering out the activated carbon and impurities, alcohol precipitation is performed to obtain a crude product. After the crude product is dissolved, decolorization and impurity removal are performed, followed by recrystallization to obtain a whiter product. The resulting sodium Vc-2-monophosphate product has a higher purity, with a purity exceeding 99% as determined by HPLC. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is a process flow chart for the preparation of high-purity sodium Vc-2-monophosphate. DETAILED DESCRIPTION

[0020] Example 1: 280 ml of deionized water was added to a 1000 ml beaker, and 556 g of sodium L-ascorbate was added under stirring to form a suspension. A 30% calcium hydroxide suspension was slowly added thereto until the pH reached 9.5. 260 g of sodium trimetaphosphate was then slowly added. The pH of the reaction solution was simultaneously controlled within the range of 9.0-10.5 using the 30% calcium hydroxide suspension. The temperature of the reaction solution was gradually raised to 60°C. After the calcium hydroxide had been completely added, the reaction was continued for 3 hours, which was the end point of the reaction. The reaction mixture was diluted with 6 times the amount of deionized water, stirred, and adjusted to pH 2.48 with an acidic resin. The reaction solution was clarified. The reaction solution was subjected to an acidic resin column exchange, and the acidic exchange solution was collected and neutralized with 30% sodium hydroxide solution to a pH of 10.5. After concentrating the neutralized solution, 28 grams of activated carbon was added to the concentrate, and 4 liters of methanol were added and stirred for 30 minutes to decolorize and remove impurities. After pressure filtration, 5 liters of methanol were added to the decolorized solution for crystallization. The solution was centrifuged and the crystals were washed with methanol to obtain a crude sodium Vc-2-monophosphate. The crude product was added to 3.4 kilograms of deionized water and stirred to dissolve. 25 grams of activated carbon and then 3 liters of methanol were added. The solution was stirred for 30 minutes to decolorize and remove impurities. After pressure filtration, 4 liters of methanol were added to the decolorized solution for crystallization. The solution was centrifuged and washed with methanol to obtain a refined wet product. The wet product was dried to obtain 487.26 grams of finished sodium Vc-2-monophosphate. HPLC analysis showed a dry content of 98.74% and a purity of 99.32%.

[0021] Example 2: 5 liters of deionized water were added to a 30-liter glass reactor. 1 kg of sodium L-ascorbate was added under stirring to form a suspension. A 30% calcium hydroxide suspension was slowly added to the suspension until the pH reached 9.7. Then, 4.7 kg of sodium trimetaphosphate was slowly added. The pH of the reaction solution was simultaneously controlled within the range of 9.0-10.5 using the 30% calcium hydroxide suspension. The temperature of the reaction solution was gradually raised to 60°C. After all the calcium hydroxide had been added, the reaction was continued for 3 hours. This was the end point of the reaction. The reaction mixture was diluted with 4 times the amount of deionized water, stirred, and adjusted to pH 2.36 with an acidic resin. The reaction solution was clarified. The reaction solution was then passed through an acidic resin column for exchange, and the acidic exchanged solution was collected and neutralized with 30% sodium hydroxide solution to a pH of 10.5. After the neutralization solution is concentrated through a nanofiltration membrane, 500 grams of activated carbon are added to the concentrated solution, and 70 liters of methanol are added and stirred for 30 minutes to carry out decolorization and alcohol separation and impurity removal. After the filter press, 90 liters of methanol are added to the decolorization solution for crystallization. After centrifugation, the crystals are washed with methanol to obtain a crude Vc-2-monophosphate sodium product. The crude product is added to 62 kilograms of deionized water for stirring and dissolving, 380 grams of activated carbon are added, and then 54 liters of methanol are added and stirred for 30 minutes to carry out decolorization and alcohol separation and impurity removal for the second time. After filtering, 70 liters of methanol are added to the decolorization solution for crystallization. After centrifugation, the crystals are washed with methanol to obtain a refined wet finished product. The wet finished product is dried to obtain 7.9 kilograms of Vc-2-monophosphate sodium finished product, which has a dry content of 99.05% and a purity of 99.35% as determined by HPLC.

Claims

1. A method for preparing high-purity sodium Vc-2-monophosphate, characterized in that: The method comprises the following steps: dissolving vitamin C sodium salt in water, adding sodium trimetaphosphate and calcium hydroxide to carry out phosphating reaction, diluting the esterified solution, adding an acidic resin for pretreatment, then carrying out ion exchange with a strong acidic cationic resin, neutralizing the exchange solution with a concentrated sodium hydroxide solution and concentrating the solution, decolorizing, alcohol precipitation and filtering the concentrated solution, then using an alcohol solvent to precipitate crystals, centrifuging and washing the crystals with a methanol solution to obtain a crude product of sodium VC-2-monophosphate; dissolving the crude product, decolorizing, alcohol precipitation and filtering once, centrifuging after alcohol precipitation, washing the crystals and drying to obtain a high-purity sodium VC-2-monophosphate product; In the phosphating reaction, the molar ratio of sodium vitamin C salt, sodium trimetaphosphate, and calcium hydroxide is (3.30-3.45):1:(1.65-1.75). The reaction temperature and pH of the system are controlled. After adding calcium hydroxide, the reaction is continued for 2-5 hours to ensure a more complete reaction. The decolorization, alcohol precipitation and filtration process of the concentrated liquid also includes an impurity removal step, and the decolorization, alcohol precipitation and impurity removal steps are carried out simultaneously. The specific method is to add powdered activated carbon to the concentrated liquid, and add methanol for alcohol precipitation during stirring, stirring for 30 minutes to precipitate impurities; the weight of the added powdered activated carbon is 0.3-1.0‰ of the decolorized liquid; the amount of alcohol solvent used in the decolorization and alcohol precipitation is 0.5-1.0 times that of the decolorized liquid.

2. The method for preparing high-purity sodium Vc-2-monophosphate according to claim 1, wherein: After the esterification liquid is diluted, an acidic resin is added and stirred for pretreatment to obtain a clear liquid, and then ion exchange is performed using a strong acidic cationic resin.

3. The method for preparing high-purity Vc-2-monophosphate sodium according to claim 2, wherein: The pH of the clear liquid is controlled at 1.5-3.

0.

4. The method for preparing high-purity sodium Vc-2-monophosphate according to claim 1, wherein: The alcohol solvent used in the alcohol precipitation is methanol or ethanol.

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