A method for reducing the yellow color of vitamin a acetate

Abstract

The present application provides a method for reducing the yellow color of vitamin A acetate, comprising the steps of decolorizing crude vitamin A acetate and activated carbon in the presence of a solvent, filtering the activated carbon, and removing the solvent from the filtrate to obtain vitamin A acetate with significantly reduced color. By controlling the key indicators of activated carbon, the present application achieves a VA loss rate of less than 5% during the activated carbon decolorization process, effectively solving the problem of low yield during VA decolorization.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of chemical intermediates synthesis, and particularly relates to a method for reducing the yellow color of vitamin A acetate. BACKGROUND

[0002] Vitamin A acetate is one of the 13 vitamins essential for humans and animals, and is widely used in the fields of feed and food. At present, the main methods for producing vitamin A acetate in industry include C14+C6 route represented by Desman and Xinhecheng and C15+C5 route represented by BASF and Zhejiang Pharmaceutical. These processes involve multiple chemical synthesis reactions, especially in the 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, and the main by-products include various cis-isomers, VA alcohol and various vitamin A impurities. The crude vitamin A acetate produced has low purity and yellow color (b value > 60), while vitamin A acetate used in the food field requires very light yellow color (b value < 40), so the crude product needs further post-treatment for color removal. The common method for removing 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, and the VA is precipitated from the crystallization solution by cooling, and then the product with higher purity and lighter color is obtained by filtration. However, due to the high content of impurities in the crude vitamin A, there are many types of impurities, some of which are solubility-promoting impurities, which can inhibit the precipitation of all-trans vitamin A acetate during crystallization, resulting in a decrease in crystallization yield. The crystallization yield of the crude VA in the industry is generally only about 90%, resulting in a large loss of VA. Moreover, some color-developing impurities similar to VA in solubility, such as VA oligomers with a molecular weight less than 1000, cannot be removed by the crystallization process, resulting in a b value of the vitamin A acetate product obtained by the crystallization process generally between 30-35, which is not suitable for some scenarios in the food field that require high product color.

[0004] Therefore, it is very meaningful to develop an efficient and low-loss vitamin A acetate decolorization method. SUMMARY

[0005] The purpose of the present application is to provide an efficient and low-loss method for reducing the yellow color of vitamin A acetate.

[0006] To achieve the above-mentioned purposes, the technical solutions of the present application are as follows:

[0007] A method for reducing the yellow color of vitamin A acetate, comprising the steps of: subjecting crude vitamin A acetate to a decolorization treatment in the presence of an organic solvent, and then separating activated carbon by filtration, and removing the organic solvent from the filtrate to obtain vitamin A acetate with significantly reduced color;

[0008] In the present application, the activated carbon is weakly alkaline, and is characterized by a pH range of 7-8.5 in a water solution obtained by fully stirring 10 g of the activated carbon in 100 g of water, and a pore size range of 1-20 nm.

[0009] In a specific embodiment, 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 vitamin A-like impurities.

[0010] In a preferred embodiment, 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 vitamin A-like impurities, in terms of mass percentage.

[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 nutshell activated carbon, coconut shell activated carbon, and wood-based activated carbon, preferably wood-based activated carbon.

[0014] In a preferred embodiment, the pH range of a water solution obtained by fully stirring 10 g of the activated carbon in 100 g of water is 7.2-7.5, and the pore size range of the activated carbon is 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 decoloring treatment is 20-60℃, preferably 30-40℃; 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℃, preferably 40-50℃.

[0018] Compared with the prior art, the positive effects of the present application are:

[0019] The present application is a high-efficiency, low-loss-rate method for decoloring vitamin A acetate, with a decoloring yield of ≥95%, which is 5% or more higher than the product yield of the traditional crystallization process, and is a very meaningful industrial application method. DETAILED DESCRIPTION

[0020] The technical solutions of the present application are further described below, but are not limited thereto, and any modification or equivalent replacement to the technical solutions of the present application without departing from the scope of the technical solutions of the present application shall be encompassed in the protection scope of the present application.

[0021] The method for reducing the yellow color of vitamin A acetate of the present application decolors crude vitamin A acetate and active carbon in the presence of a solvent for a period of time, then separates the active carbon by filtration, and removes the solvent from the filtrate to obtain vitamin A acetate with significantly reduced color;

[0022] The active carbon is weakly alkaline, specifically characterized in that, the pH of the aqueous solution obtained by fully stirring 10g of the active carbon in 100g of water is in the range of 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., and is preferably in the range of 7.2-7.5; the pore size of the active carbon is in the range of 1-20nm, for example, 2nm, 3nm, 4nm, 5nm, 6nm, 7nm, 8nm, 9nm, 10nm, 11nm, 12nm, 13nm, 14nm, 15nm, 16nm, 17nm, 18nm, 19nm, 20nm, etc., and is preferably in the range of 5-8nm.

[0023] Due to the particularity of the molecular structure of vitamin A, the synthetic vitamin A acetate in the industry is generally spliced by two molecular fragments through chemical reaction. In the splicing reaction, the process conditions are generally harsh, which may involve strong bases such as sodium alcoholate, sodium hydroxide, sodium carbonate, or strong acids such as hydrochloric acid and sulfuric acid. Under these conditions, a large amount of vitamin A acetate will generate double bond isomerization, chain breaking, dehydration, VA low molecular weight polymer and other vitamin A-like impurities. These impurities will cause the color of the crude vitamin A to darken significantly, and the VA oligomer with a molecular weight of less than 1000 is the main coloring substance. Through research, it is found that the VA oligomer can be adsorbed by activated carbon, but at the same time, activated carbon will also non-discriminately adsorb product VA, resulting in product loss. Through detailed research on coloring impurities and activated carbon, especially the investigation of indicators such as the acidity and basicity of activated carbon and pore size, it is found that by controlling these key indicators, the coloring VA low molecular weight polymer can be selectively adsorbed, and the loss rate of product VA acetate can be reduced to less than 5%.

[0024] In the present application, the crude vitamin A acetate contains a certain amount of 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 vitamin A-like impurities.

[0025] In the present application, the content of all-trans vitamin A acetate isomers in the crude vitamin A acetate is 60-95% by mass percentage, the content of 11-cis vitamin A acetate isomers is 0-1%, the content of 13-cis vitamin A acetate isomers is 0-3%, the content of 9-cis vitamin A acetate isomers is 0-5%, and the content of vitamin A-like impurities is 5-40%.

[0026] In the present application, the decolorization process is carried out in the presence of an organic solvent 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] 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 application, 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 application, the reaction temperature of the decolorization treatment process is 20-60℃, for example 25℃, 30℃, 35℃, 40℃, 45℃, 50℃, 55℃, 60℃, etc., preferably 30-40℃; the reaction time is 0.1-2h, for example 0.5h, 1h, 1.5h, etc., preferably 0.5-1h.

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

[0031] In the present application, the decolorization treatment, filtration separation, removal of solvent and the like are not particularly limited and can be carried out according to conventional techniques in the art, for example stirring and mixing, centrifugal filtration, flash evaporation and the like.

[0032] The present application is further explained and illustrated by more specific examples below, but without any limitation.

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

[0034] Color analysis: Hangzhou color spectrum table spectrophotometer DS-39D, characterization means for Lab value, Lab color model is composed of illumination (L) and three elements related to color a, b. L represents illumination (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, and L = 50 is equivalent to 50% black; the value range of a and b is from +120 to -120, wherein +120a is red, and gradually transitions to -120a to become green; similarly, +120b is yellow, and -120b is blue. All colors are composed of the three values, and the present application mainly focuses on the b value.

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

[0036] Reagent name Reagent specification Manufacturer Vitamin A acetate crude Industrial grade Wanhua Chemical Activated carbon AR Revel Purification Acetonitrile, n-hexane, ethanol AR Macklin

[0037] Example 1

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

[0039] Example 2

[0040] A 1000 mL three-necked flask with magnetic stirring was charged with 100 g 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 impurity 3.7%, sample b value 69) and 400 g of heptane, replaced with nitrogen three times, the reaction liquid was heated to 40°C, 1 g of activated carbon (coconut shell activated carbon, pH = 7.5, pore size 5-8 nm) was added under nitrogen protection, and the reaction was stirred for 0.5 h. After the reaction was completed, it was filtered hot, and the filtrate was removed by rotary evaporator at water bath temperature 50°C. The product yield was 97%, and the b value was 25.

[0041] Example 3

[0042] A 2000 mL three-necked flask equipped with magnetic stirring was charged with 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, and the reaction solution was replaced with nitrogen three times. The reaction solution was kept at 20°C, and 10 g of activated carbon (wood-based activated carbon, pH = 7.0, pore size 8-10 nm) was added under nitrogen protection. The reaction was stirred for 2.0 h, and after the reaction was completed, the reaction solution was filtered while hot. The filtrate was subjected to solvent removal 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] A 500 mL three-necked flask equipped with magnetic stirring was charged with 100 g 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 1000 g of acetonitrile, and the reaction solution was replaced with nitrogen three times. The reaction solution was heated to 60°C, and 30 g of activated carbon (shell-based activated carbon, pH = 8.5, pore size 10-20 nm) was added under nitrogen protection. The reaction was stirred for 1.0 h, and after the reaction was completed, the reaction solution was filtered while hot. The filtrate was subjected to solvent removal 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] A 500 mL three-necked flask equipped with magnetic stirring was charged with 100 g of crude vitamin A acetate (all-trans isomer content 60%, 9-cis isomer content 4%, VA-like impurities 36%, sample b value 95) and 200 g of acetonitrile, and the reaction solution was replaced with nitrogen three times. The reaction solution was heated to 30°C, and 5 g of activated carbon (shell-based activated carbon, pH = 6.5, pore size 1-5 nm) was added under nitrogen protection. The reaction was stirred for 0.1 h, and after the reaction was completed, the reaction solution was filtered while hot. The filtrate was subjected to solvent removal 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] In comparison with Example 1, only the pH of the activated carbon in the reaction conditions and raw materials was lower than the limit value, and as a result, the b value of the product was higher than 30, and the product yield was also greatly reduced.

[0048] Comparative Example 2

[0049] Into a 500 mL three-necked flask equipped with magnetic stirring, 100 g of crude vitamin A acetate (60% of all-trans isomer, 4% of 9-cis isomer, 36% of VA-like impurities, sample b value 95) and 200 g of acetonitrile were introduced, and the reaction solution was heated to 30°C under nitrogen protection. Then 5 g of activated carbon (shell activated carbon, pH = 9.0, pore size 1-5 nm) was added under stirring for 0.1 h. After the reaction was completed, the reaction solution was filtered while hot, and the filtrate was concentrated by rotary evaporation 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, only the pH of the activated carbon in the reaction conditions and raw materials was higher than the limit value, and the b value of the product was higher than 30, and the product yield was also greatly reduced.

[0051] Comparative Example 3

[0052] Into a 500 mL three-necked flask equipped with magnetic stirring, 100 g of crude vitamin A acetate (60% of all-trans isomer, 4% of 9-cis isomer, 36% of VA-like impurities, sample b value 95) and 200 g of acetonitrile were introduced, and the reaction solution was heated to 30°C under nitrogen protection. Then 5 g of activated carbon (shell activated carbon, pH = 7.2, pore size 0.5-0.8 nm) was added under stirring for 0.1 h. After the reaction was completed, the reaction solution was filtered while hot, and the filtrate was concentrated by rotary evaporation 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, only the pore size of the activated carbon in the reaction conditions and raw materials was lower than the limit value, and the b value of the product was higher than 30, and the product yield was also greatly reduced.

[0054] Comparative Example 4

[0055] Into a 500 mL three-necked flask equipped with magnetic stirring, 100 g of crude vitamin A acetate (60% of all-trans isomer, 4% of 9-cis isomer, 36% of VA-like impurities, sample b value 95) and 200 g of acetonitrile were introduced, and the reaction solution was heated to 30°C under nitrogen protection. Then 5 g of activated carbon (shell activated carbon, pH = 7.2, pore size 22-25 nm) was added under stirring for 0.1 h. After the reaction was completed, the reaction solution was filtered while hot, and the filtrate was concentrated by rotary evaporation 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 of the activated carbon in the reaction conditions and raw materials was higher than the limit value, and the b value of the product was higher than 30, and the product yield was also greatly reduced.

Claims

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

2. The method as described in claim 1, characterized in that, The crude vitamin A acetate contains 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 vitamin A-like impurities.

3. The method as described in claim 2, characterized in that, Based on mass percentage, the crude vitamin A acetate contains 60-95% all-trans vitamin A acetate isomer, 0-1% 11-cis vitamin A acetate isomer, 0-3% 13-cis vitamin A acetate isomer, 0-5% 9-cis vitamin A acetate isomer, and 5-40% vitamin A-like impurities.

4. The method according to any one of claims 1-3, 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.

5. The method as described in claim 4, characterized in that, The organic solvent is selected from acetonitrile.

6. The method as described in claim 4, characterized in that, The mass ratio of the organic solvent to the crude vitamin A acetate is (1-10):

1.

7. The method as described in claim 6, characterized in that, The mass ratio of the organic solvent to the crude vitamin A acetate is (2-4):

1.

8. The method according to any one of claims 1-3, 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.

9. The method as described in claim 8, characterized in that, The activated carbon is selected from wood-based activated carbon.

10. The method according to any one of claims 1-3, characterized in that, The pH range of the aqueous solution obtained by thoroughly stirring 10g of activated carbon in 100g of water is 7.2-7.5; the pore size of the activated carbon ranges from 5-8nm.

11. The method as described in claim 10, characterized in that, The mass ratio of activated carbon to crude vitamin A acetate is (0.01-0.3):

1.

12. The method as described in claim 11, characterized in that, The mass ratio of activated carbon to crude vitamin A acetate is (0.05-0.1):

1.

13. The method according to any one of claims 1-3, characterized in that, The reaction temperature for the decolorization treatment is 20-60℃; and / or, the reaction time is 0.1-2h.

14. The method as described in claim 13, characterized in that, The decolorization treatment is carried out at a temperature of 30-40℃ and / or for a reaction time of 0.5-1h.

15. The method according to any one of claims 1-3, characterized in that, The temperature for removing organic solvents from the filtrate is 30-60℃.

16. The method as described in claim 15, characterized in that, The temperature for removing organic solvents from the filtrate is 40-50℃.