Method for reducing yellow chromaticity of vitamin A acetate

Abstract

The invention provides a method for reducing yellow chromaticity of vitamin A acetate. The method comprises the following steps: decoloring a vitamin A acetate crude product and activated carbon in the presence of a solvent, filtering the activated carbon, and removing the solvent from filtrate to obtain the vitamin A acetate with obviously reduced color. By controlling the key indexes of the activated carbon, the VA loss rate in the activated carbon decoloration process is lower than 5%, and the problem of low yield in the VA decoloration process is effectively solved.

Description

Technical Field

[0001] The invention belongs to the field of chemical intermediate synthesis, and particularly relates to a method for reducing the yellow chroma of vitamin A acetate. Background Art

[0002] Vitamin A acetate is one of the 13 essential vitamins for humans and animals, and is widely used in the fields of feed and food. At present, the main methods for industrial production of vitamin A acetate include the C14+C6 route represented by DSM and Xinhecheng and the C15+C5 route represented by manufacturers such as BASF and Zhejiang Medicine. These process production processes involve multi-step chemical synthesis reactions. Especially in the final reaction of synthesizing crude vitamin A acetate, due to the instability of the structure of vitamin A acetate and the harsh reaction conditions, a large number of side reactions are involved in the reaction. The main by-products include various cis isomers, VA alcohol and various vitamin A impurities. As a result, the crude vitamin A acetate produced has a relatively low purity and a yellowish color (b value>60), while vitamin A acetate used in the food field requires a very light yellow chroma (b value<40), so the crude product needs further post-treatment to remove the color. The common means of removing the color in the industry is crystallization.

[0003] The crystallization process mainly utilizes the different solubilities of impurities and all-trans vitamin A acetate in solvents. VA is precipitated from the crystallization liquid by cooling, and then a product with higher purity and lighter color is obtained by filtering. However, due to the relatively high impurity content and many types of impurities in crude vitamin A, some of which are solubilizing impurities, will inhibit the precipitation of all-trans vitamin A acetate during the crystallization process, resulting in a decrease in the crystallization yield. In the industry, the crystallization yield of crude VA is generally only about 90%, resulting in a large loss of VA. In addition, the crystallization process often cannot remove some color-developing impurities with similar solubility to VA, such as VA oligomers with a molecular weight of less than 1000, resulting in the vitamin A acetate product obtained by the crystallization process having a b value generally between 30 and 35, which is not suitable for some scenarios in the food field that have high requirements for product color.

[0004] Therefore, it is of great significance to develop a method for decolorizing vitamin A acetate with high efficiency and low loss rate. Summary of the invention

[0005] The object of the present invention is to provide a method for reducing the yellow chromaticity of vitamin A acetate with high efficiency and low loss rate.

[0006] To achieve the above-mentioned object of the invention, the technical solution of the present invention is as follows:

[0007] A method for reducing the yellow chromaticity of vitamin A acetate, comprising the steps of decolorizing crude vitamin A acetate and activated carbon in the presence of an organic solvent, filtering and separating the activated carbon, and removing the organic solvent from the filtrate to obtain vitamin A acetate with significantly reduced color;

[0008] The activated carbon is weakly alkaline, which is specifically characterized by: the pH range of the aqueous solution obtained by fully stirring 10g of activated carbon in 100g of water is 7-8.5, and the pore size range of the activated carbon is 1-20nm.

[0009] In a specific embodiment, the crude vitamin A acetate comprises all-trans vitamin A acetate isomer, 11-cis vitamin A acetate isomer, 13-cis vitamin A acetate isomer, 9-cis vitamin A acetate isomer and retinoid impurities.

[0010] In a preferred embodiment, the crude vitamin A acetate contains, by mass percentage, 60-95% all-trans vitamin A acetate isomer content, 0-1% 11-cis vitamin A acetate isomer content, 0-3% 13-cis vitamin A acetate isomer content, 0-5% 9-cis vitamin A acetate isomer content, and 5-40% retinoid impurity content.

[0011] In a specific embodiment, the organic solvent is selected from one or more of acetonitrile, N,N-dimethylformamide, hexane, pentane, heptane, benzene, toluene, methyl tert-butyl ether, tetrahydrofuran, ethanol, methanol, isopropanol, n-propanol and butanol, preferably acetonitrile.

[0012] In a preferred embodiment, the mass ratio of the organic solvent to the crude vitamin A acetate is (1-10):1, preferably (2-4):1.

[0013] In a specific embodiment, the activated carbon is selected from one or more of fruit shell activated carbon, coconut shell activated carbon and wood activated carbon, preferably wood activated carbon.

[0014] In a preferred embodiment, the pH of the aqueous solution obtained by fully stirring 10 g of activated carbon in 100 g of water is in the range of 7.2-7.5; and the pore size of the activated carbon is in the range of 5-8 nm.

[0015] In a preferred embodiment, the mass ratio of the activated carbon to the crude vitamin A acetate is (0.01-0.3):1, preferably (0.05-0.1):1.

[0016] In a specific embodiment, the reaction temperature of the decolorization treatment is 20-60°C, preferably 30-40°C; and / or the reaction time is 0.1-2h, preferably 0.5-1h.

[0017] In a specific embodiment, the temperature for removing the organic solvent from the filtrate is 30-60°C, preferably 40-50°C.

[0018] Compared with the prior art, the present invention has the following positive effects:

[0019] The present invention, through in-depth research on activated carbon and vitamin A acetate, has invented a method for decolorizing vitamin A acetate with high efficiency and low loss rate. The decolorization yield is ≥95%, which is more than 5% higher than the yield of the traditional crystallization process. It is a very meaningful industrial application method. DETAILED DESCRIPTION

[0020] The technical solution of the present invention is further described below, but is not limited thereto. Any modification or equivalent replacement of the technical solution of the present invention without departing from the scope of the technical solution of the present invention should be included in the protection scope of the present invention.

[0021] The present invention discloses a method for reducing the yellow chromaticity of vitamin A acetate, comprising decolorizing crude vitamin A acetate and activated carbon in the presence of a solvent for a period of time, filtering and separating the activated carbon, and removing the solvent from the filtrate to obtain vitamin A acetate with significantly reduced color;

[0022] Wherein, the activated carbon is weakly alkaline, specifically characterized by that the pH range of the aqueous solution obtained by fully stirring every 10g of activated carbon in 100g of water is 7-8.5, for example, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, etc., preferably 7.2-7.5; the pore size range of the activated carbon is 1-20nm, for example, 2nm, 3nm, 4nm, 5nm, 6nm, 7nm, 8nm, 9nm, 10nm, 11nm, 12nm, 13nm, 14nm, 15nm, 16nm, 17nm, 18nm, 19nm, 20nm, etc., preferably 5-8nm.

[0023] Due to the particularity of the molecular structure of vitamin A, the synthesis of vitamin A acetate in the industry is generally made by splicing two molecular fragments through chemical reactions. The process conditions in the splicing reaction are generally harsh, involving medium-strong bases such as sodium alcohol, sodium hydroxide, sodium carbonate, or strong acids such as hydrochloric acid and sulfuric acid. Under these conditions, vitamin A acetate will generate a large number of vitamin A-like impurities such as double bond isomerization, chain scission, dehydration, and VA low molecular weight polymers. These impurities will cause the color of the crude vitamin A to deepen significantly, among which VA oligomers with a molecular weight of less than 1000 are the main coloring substances. Through research, it is found that VA oligomers can be adsorbed by activated carbon, but at the same time, activated carbon will also produce indiscriminate adsorption of product VA, resulting in product loss. Through detailed research on color impurities and activated carbon, especially the investigation of activated carbon acidity, alkalinity, pore size and other indicators, we found that by controlling these key indicators, the coloring VA low molecular weight polymer can be selectively adsorbed, so that the loss rate of the product VA acetate can be reduced to less than 5%.

[0024] In the present invention, the crude vitamin A acetate contains a certain amount of all-trans vitamin A acetate isomer, 11-cis vitamin A acetate isomer, 13-cis vitamin A acetate isomer, 9-cis vitamin A acetate isomer and retinoid impurities.

[0025] In the present invention, the crude vitamin A acetate product contains, by weight percentage, 60-95% of all-trans vitamin A acetate isomers, 0-1% of 11-cis vitamin A acetate isomers, 0-3% of 13-cis vitamin A acetate isomers, 0-5% of 9-cis vitamin A acetate isomers, and 5-40% of retinoid impurities.

[0026] In the present invention, the decolorization process is carried out in the presence of an organic solvent, and the organic solvent is selected from one or more of acetonitrile, N,N-dimethylformamide, hexane, pentane, heptane, benzene, toluene, methyl tert-butyl ether, tetrahydrofuran, ethanol, methanol, isopropanol, n-propanol and butanol, preferably acetonitrile.

[0027] Wherein, the mass ratio of the organic solvent to the reaction substrate is (1-10):1, for example, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, etc., preferably (2-4):1.

[0028] In the present invention, the activated carbon used is selected from one or more of fruit shell activated carbon, coconut shell activated carbon and wood activated carbon, preferably wood activated carbon; the mass ratio of activated carbon to crude vitamin A acetate is (0.01-0.3):1, for example, 0.02:1, 0.03:1, 0.05:1, 0.06:1, 0.08:1, 0.1:1, 0.12:1, 0.15:1, 0.18:1, 0.2:1, 0.25:1, 0.3:1, etc., preferably (0.05-0.1):1.

[0029] In the present invention, the reaction temperature of the decolorization process is 20-60°C, for example, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, etc., preferably 30-40°C; the reaction time is 0.1-2h, for example, 0.5h, 1h, 1.5h, etc., preferably 0.5-1h.

[0030] In the present invention, the temperature for removing the solvent from the decolorized filtrate is 30-60°C, for example, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, etc., preferably 40-50°C.

[0031] There is no particular limitation on the decolorization, filtration separation, solvent removal and other operations in the present invention, and they can all be carried out according to conventional techniques in the art, such as stirring and mixing, centrifugal filtration, flash evaporation and the like.

[0032] The present invention is further explained below by more specific examples, but does not constitute any limitation.

[0033] Liquid chromatography analysis: Agilent 1260 liquid chromatograph, chromatographic column Sphersorb C18 column UV-visible spectrophotometer Hitachi L7420, chromatographic workstation data processing system Chomatopac C-RIA, stationary phase Zorbax-SIL. Chromatographic conditions: mobile phase is methanol / acetonitrile = 10 / 1 (v / v) mixture, detection temperature is 45°C, flow rate is 0.8mL / min, wavelength is 455nm. Qualitative and quantitative analysis of product composition was performed.

[0034] Color number analysis: Hangzhou Color Spectrum Desktop Spectrophotometer DS-39D, the characterization method is Lab value. The Lab color model is composed of three elements: illuminance (L) and a and b related to color. L represents luminosity, which is equivalent to brightness. a represents the range from red to green, and b represents the range from blue to yellow. The value range of L is from 0 to 100. When L=50, it is equivalent to 50% black. The value ranges of a and b are both from +120 to -120, where +120a is red, and gradually transitions to -120a to turn green. By the same principle, +120b is yellow and -120b is blue. All colors are composed of the interactive changes of these three values. The present invention mainly focuses on the b value.

[0035] Specifications and sources of some reagents in the examples and comparative examples

[0036] Reagent name Reagent Specifications Manufacturer Crude Vitamin A Acetate Industrial Grade Wanhua Chemical Activated carbon AR Revel Purification Acetonitrile, n-hexane, ethanol AR Maclean

[0037] Example 1

[0038] 100g of crude vitamin A acetate (all-trans isomer content 60.0%, 9-cis isomer content 4.0%, VA-like impurities 36.0%, sample b value 95) and 200g of acetonitrile were added to a 500mL three-necked flask equipped with a magnetic stirrer. The mixture was replaced with nitrogen three times. The reaction solution was heated to 30°C. 5g of activated carbon (fruit shell activated carbon, pH = 7.2, pore size 1-5nm) was added under nitrogen protection. The mixture was stirred for 0.1h. After the reaction was completed, the mixture was filtered while hot. The filtrate was freed from the solvent using a rotary evaporator at a water bath temperature of 40°C. The product yield was 96.0% and the b value was 21.

[0039] Example 2

[0040] 100g of crude vitamin A acetate (all-trans isomer content 95.0%, 11-cis isomer content 0.2%, 13-cis isomer content 1.1%, VA-like impurities 3.7%, sample b value 69) and 400g of heptane were added to a 1000mL three-necked flask equipped with a magnetic stirrer, and the mixture was replaced with nitrogen three times. The reaction solution was heated to 40°C, and 1g of activated carbon (coconut shell activated carbon, pH = 7.5, pore size 5-8nm) was added under nitrogen protection. The mixture was stirred for 0.5h and filtered while hot after the reaction. The filtrate was desolventized using a rotary evaporator at a water bath temperature of 50°C. The product yield was 97% and the b value was 25.

[0041] Example 3

[0042] 100 g of crude vitamin A acetate (all-trans isomer content 80.2%, 11-cis isomer content 0.5%, 9-cis isomer content 5.0%, 13-cis isomer content 2.5%, VA-like impurities 11.8%, sample b value 78) and 100 g of ethanol were added to a 2000 mL three-necked flask equipped with a magnetic stirrer. The mixture was replaced with nitrogen three times. The reaction solution was maintained at 20° C. 10 g of activated carbon (wood activated carbon, pH=7.0, pore size 8-10 nm) was added under nitrogen protection. The mixture was stirred for 2.0 h. After the reaction was completed, the mixture was filtered while hot. The filtrate was desolventized using a rotary evaporator at a water bath temperature of 30° C. The product yield was 98.1% and the b value was 19.

[0043] Example 4

[0044] 100g of crude vitamin A acetate (all-trans isomer content 89.6%, 11-cis isomer content 1.0%, 9-cis isomer content 1.4%, 13-cis isomer content 3.0%, VA-like impurities 5.0%, sample b value 71) and 1000g of acetonitrile were added to a 500mL three-necked flask equipped with a magnetic stirrer. The mixture was replaced with nitrogen three times. The reaction solution was heated to 60°C. 30g of activated carbon (fruit shell activated carbon, pH = 8.5, pore size 10-20nm) was added under nitrogen protection. The mixture was stirred for reaction for 1.0h. After the reaction was completed, the mixture was filtered while hot. The filtrate was desolventized using a rotary evaporator at a water bath temperature of 60°C. The product yield was 98.8% and the b value was 24.

[0045] Comparative Example 1

[0046] 100g of crude vitamin A acetate (all-trans isomer content 60%, 9-cis isomer content 4%, VA-like impurities 36%, sample b value 95) and 200g of acetonitrile were added to a 500mL three-necked flask equipped with a magnetic stirrer. The mixture was replaced with nitrogen three times. The reaction solution was heated to 30°C. 5g of activated carbon (fruit shell activated carbon, pH = 6.5, pore size 1-5nm) was added under nitrogen protection. The mixture was stirred for 0.1h. After the reaction was completed, the mixture was filtered while hot. The filtrate was desolventized using a rotary evaporator at a water bath temperature of 40°C. The product yield was 92.1% and the b value was 37.

[0047] Compared with Example 1, the reaction conditions and the raw materials only had the pH of the activated carbon below the limit, resulting in a product b value higher than 30 and a significant decrease in product yield.

[0048] Comparative Example 2

[0049] 100g of crude vitamin A acetate (all-trans isomer content 60%, 9-cis isomer content 4%, VA-like impurities 36%, sample b value 95) and 200g of acetonitrile were added to a 500mL three-necked flask equipped with a magnetic stirrer. The mixture was replaced with nitrogen three times. The reaction solution was heated to 30°C. 5g of activated carbon (fruit shell activated carbon, pH = 9.0, pore size 1-5nm) was added under nitrogen protection. The mixture was stirred for 0.1h. After the reaction was completed, the mixture was filtered while hot. The filtrate was desolventized using a rotary evaporator at a water bath temperature of 40°C. The product yield was 91.7% and the b value was 45.

[0050] Compared with Example 1, the reaction conditions and the raw materials only had the pH of the activated carbon higher than the limit, resulting in a product b value higher than 30 and a significant decrease in the product yield.

[0051] Comparative Example 3

[0052] 100g of crude vitamin A acetate (all-trans isomer content 60%, 9-cis isomer content 4%, VA-like impurities 36%, sample b value 95) and 200g of acetonitrile were added to a 500mL three-necked flask equipped with a magnetic stirrer. The mixture was replaced with nitrogen three times. The reaction solution was heated to 30°C. 5g of activated carbon (fruit shell activated carbon, pH = 7.2, pore size 0.5-0.8nm) was added under nitrogen protection. The mixture was stirred for 0.1h. After the reaction was completed, the mixture was filtered while hot. The filtrate was desolventized using a rotary evaporator at a water bath temperature of 40°C. The product yield was 94.1% and the b value was 39.

[0053] Compared with Example 1, among the reaction conditions and the raw materials, only the pore size is below the limit, and as a result, the b value of the product is higher than 30, and the product yield is also greatly reduced.

[0054] Comparative Example 4

[0055] 100g of crude vitamin A acetate (all-trans isomer content 60%, 9-cis isomer content 4%, VA-like impurities 36%, sample b value 95) and 200g of acetonitrile were added to a 500mL three-necked flask equipped with a magnetic stirrer. The mixture was replaced with nitrogen three times. The reaction solution was heated to 30°C. 5g of activated carbon (fruit shell activated carbon, pH = 7.2, pore size 22-25nm) was added under nitrogen protection. The mixture was stirred for 0.1h. After the reaction was completed, the mixture was filtered while hot. The filtrate was desolventized using a rotary evaporator at a water bath temperature of 40°C. The product yield was 92.7% and the b value was 44.

[0056] Compared with Example 1, only the pore size among the reaction conditions and the raw materials is higher than the limit value, resulting in a product b value higher than 30 and a significant decrease in product yield.

Claims

1. A method for reducing the yellow chromaticity of vitamin A acetate, characterized in that: The method comprises the steps of decolorizing crude vitamin A acetate and activated carbon in the presence of an organic solvent, filtering to separate the activated carbon, and removing the organic solvent from the filtrate to obtain vitamin A acetate with significantly reduced color; The activated carbon is weakly alkaline, which is specifically characterized by: the pH range of the aqueous solution obtained by fully stirring 10g of activated carbon in 100g of water is 7-8.5, and the pore size range of the activated carbon is 1-20nm.

2. The method according to claim 1, characterized in that The crude vitamin A acetate contains all-trans vitamin A acetate isomers, 11-cis vitamin A acetate isomers, 13-cis vitamin A acetate isomers, 9-cis vitamin A acetate isomers and retinoid impurities.

3. The method according to claim 2, characterized in that Calculated by mass percentage, the crude vitamin A acetate contains 60-95% of all-trans vitamin A acetate isomers, 0-1% of 11-cis vitamin A acetate isomers, 0-3% of 13-cis vitamin A acetate isomers, 0-5% of 9-cis vitamin A acetate isomers, and 5-40% of retinoid impurities.

4. The method according to any one of claims 1 to 3, characterized in that: The organic solvent is selected from one or more of acetonitrile, N,N-dimethylformamide, hexane, pentane, heptane, benzene, toluene, methyl tert-butyl ether, tetrahydrofuran, ethanol, methanol, isopropanol, n-propanol and butanol, preferably acetonitrile.

5. The method according to claim 4, characterized in that The mass ratio of the organic solvent to the crude vitamin A acetate is (1-10):1, preferably (2-4):

1.

6. The method according to any one of claims 1 to 5, characterized in that: The activated carbon is selected from one or more of fruit shell activated carbon, coconut shell activated carbon and wood activated carbon, preferably wood activated carbon.

7. The method according to any one of claims 1 to 6, characterized in that: The pH of the aqueous solution obtained by fully stirring 10g of activated carbon in 100g of water is in the range of 7.2-7.5; the pore size of the activated carbon is in the range of 5-8nm.

8. The method according to claim 7, characterized in that The mass ratio of the activated carbon to the crude vitamin A acetate is (0.01-0.3):1, preferably (0.05-0.1):

1.

9. The method according to any one of claims 1 to 8, characterized in that The reaction temperature of the decolorization treatment is 20-60°C, preferably 30-40°C; and / or the reaction time is 0.1-2h, preferably 0.5-1h.

10. The method according to any one of claims 1 to 6, characterized in that: The temperature of the filtrate for removing the organic solvent is 30-60°C, preferably 40-50°C.