阅读说明：本技术 一种维生素a棕榈酸酯的制备方法 (Preparation method of vitamin A palmitate ) 是由 罗朝辉 林龙 翟文超 张弈宇 王嘉辉 高洪坤 于 2021-01-15 设计创作，主要内容包括：本发明提供了一种维生素A棕榈酸酯的制备方法,该方法采用金属氰化物改性碱金属硫化物,得到了一种用于维生素A棕榈酸酯的固体碱催化剂,并以VA醋酸酯和棕榈酸为原料,一步法合成维生素A棕榈酸酯,具有反应条件温和,选择性高,无副产物生成等优势,反应所得产品在低温下更能稳定保存且易结晶析出,收率高；解决了传统维生素A棕榈酸酯合成中固体酸催化体系中存在的设备腐蚀问题,工艺绿色环保。(The invention provides a preparation method of vitamin A palmitate, which adopts metal cyanide to modify alkali metal sulfide to obtain a solid base catalyst for the vitamin A palmitate, and adopts VA acetate and palmitic acid as raw materials to synthesize the vitamin A palmitate by a one-step method, so that the preparation method has the advantages of mild reaction conditions, high selectivity, no byproduct generation and the like, and the product obtained by the reaction can be more stably stored at low temperature, is easy to crystallize and separate out, and has high yield; solves the problem of equipment corrosion in a solid acid catalytic system in the traditional vitamin A palmitate synthesis, and has green and environment-friendly process.)

1. A preparation method of vitamin A palmitate is characterized in that: the vitamin A acetate and palmitic acid are subjected to ester exchange reaction under the action of a solid base catalyst to prepare the vitamin A acetate.

2. The method of claim 1, wherein: the preparation method of the solid base catalyst comprises the following steps:

(1) adding silicon dioxide powder into an acid solution for soaking, adding high molecular polymer nano-sphere particles into the acid solution, violently stirring the mixture to uniformly mix the mixture, filtering the mixture, and drying the mixture for later use;

(2) dissolving metal sulfide in the first mixed solvent, adding the carrier prepared in the step (1) after uniform dispersion, stirring for a certain time at a certain temperature, heating to a certain temperature, adding metal cyanide, stirring, filtering, taking out, and roasting to obtain the solid base catalyst.

3. The method of claim 1, wherein: the acid solution in the step (1) is one or more of aqueous solutions of sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid and hydrobromic acid, preferably an aqueous solution of hydrochloric acid;

preferably, in step (1), the high molecular polymer is one or more of polyol of polyoxyalkylene, polystyrene, water-soluble polyester, polyether ester, polyether modified polysiloxane, preferably nano-particle ball of polystyrene; preferably, the mass ratio of the high molecular polymer to the silicon dioxide is 1:0.5-1:10, preferably 1:1-1: 5;

preferably, in the step (1), the soaking time of the silicon dioxide in the acid solution is 1-20h, preferably 2-12 h; the impregnation temperature is 20 to 400 ℃, preferably 50 to 250 ℃.

4. The method of claim 1, wherein: the addition amount of the carrier prepared in the step (1) is as follows: adding 5-100g of high molecular polymer modified silicon dioxide, preferably 10-50 g, into each mole of metal sulfide;

preferably, in the step (2), the molar ratio of the metal cyanide compound to the metal sulfide compound is 0.1: 1-5: 1, preferably 0.5: 1-2: 1.

5. The method of claim 1, wherein: in the step (2), the mixed solvent I is a mixed solution of water and an organic solvent I, preferably water/ethylene glycol, water/glycerol, water/isopropanol, water/n-butanol, water/acetone and water/butanol, more preferably water/n-butanol, wherein the mass ratio of the water to the organic solvent I is 0.05: 1-1: 1, preferably 0.1: 1-0.5: 1;

preferably, in the step (2), the stirring time after the carrier is added is 5-40h, preferably 8-16 h; the stirring temperature is 50-400 ℃, and preferably 50-150 ℃;

preferably, in the step (2), the roasting temperature of the catalyst is 50-600 ℃, and preferably 100-300 ℃; the time for roasting the catalyst is 1-20 hours, preferably 5-10 hours.

6. The method of claim 1, wherein: the VA acetate is dissolved in an organic solvent III, the organic solvent III for dissolving the VA acetate comprises one or more of petroleum ether, n-hexane, n-heptane, acetonitrile, dichloromethane, trichloromethane and chloroform, and the n-hexane is preferred;

preferably, the feed molar flow ratio of VA acetate to palmitic acid is 1: 1.05-1: 1.5, preferably 1: 1.15-1: 1.35;

preferably, the mass space velocity of the VA acetic ester is 1-200h^-1Preferably 5 to 150h^-1；

Preferably, the reaction temperature is 10-60 ℃, preferably 20-30 ℃; the residence time of the mixed reaction liquid is 0.2-20 min, preferably 1-10 min; the reaction pressure is 0.005MPa to 0.08MPa, preferably 0.01MPa to 0.03 MPa.

7. The method of claim 1, wherein: the extractant is one or more of toluene, m-xylene, o-xylene, p-xylene, acetone, ethyl acetate and the like, and toluene is preferred; the flow rate of the extracting agent is 0.5 to 5 times, preferably 1 to 3 times of the mass flow rate of the raw material VA acetic ester;

preferably, the crystallization reagent is one or more of methanol, ethanol, isopropanol, n-butanol, n-propanol, ethylene glycol and the like, preferably ethanol; the flow rate of the crystallization reagent is 1-10 times, preferably 2-4 times of the mass flow rate of the raw material VA acetate; the crystallization temperature is-2 to 20 ℃, preferably 0 to 10 ℃.

Technical Field

The invention belongs to the technical field of chemical synthesis, and particularly relates to a preparation method of vitamin A palmitate.

Background

Vitamin a, also known as retinol, is a natural fat-soluble vitamin, one of the essential nutrients for the human body. However, vitamin a is irritant to the skin and relatively active in chemical properties, and is easily destroyed by acid, air, oxidant, high temperature or ultraviolet rays, and vitamin a ester derivatives are relatively stable and non-irritant, so that commercial vitamin a is provided to the market in the form of ester. Among vitamin a ester series products, the market occupation of vitamin a acetate and vitamin a palmitate is the largest, and VA palmitate has long carbon chain, low melting point and good oil solubility, so VA palmitate is widely applied to food, medicine and cosmetics and becomes the most common additive in food or cosmetics.

The VA palmitate is mainly prepared by a chemical synthesis method and a biological enzyme method. The chemical synthesis mainly takes VA acetate as a raw material, hydrolysis reaction is carried out to generate VA alcohol, and palmitoyl chloride is added to carry out acylation reaction to generate VA palmitate. The synthesis process is complex, the reaction conditions are harsh, the number of byproducts is large, and the separation is difficult. The biological enzyme method mainly takes VA acetate as a raw material, and the VA palmitate is generated by esterification or ester exchange reaction in the presence of lipase.

Patent JP62248495 discloses an enzymatic synthesis of VA palmitate with a yield of only 80% at 30 ℃ for 12h, but the enzymatic method has to be carried out at a lower concentration, the production capacity is lower, the reaction product contains lipase making the subsequent separation difficult, there is no cost advantage and the product quality is affected.

Patent CN104673870A discloses that VA acetate and organic alcohol are firstly prepared into VA alcohol in the presence of immobilized esterase e. The reaction process is complicated, and the steps are complicated and are filtered for many times. In addition, VA alcohol is easily deteriorated by heat during the process of distilling out excess organic alcohol under reduced pressure, which affects the quality of the product. Therefore, the development of a novel preparation method of VA palmitate is of great importance to industrial production.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention provides a preparation method of vitamin A palmitate, which adopts a solid base catalyst to catalyze the reaction of vitamin A acetate and palmitic acid to obtain a product with high selectivity, basically no by-product, high low-temperature stability and easy storage.

In order to achieve the purpose, the technical scheme of the invention is as follows:

a preparation method of vitamin A palmitate comprises the following steps: the preparation method comprises the following steps: the vitamin A acetate and palmitic acid are subjected to ester exchange reaction under the action of a solid base catalyst to prepare the vitamin A acetate.

The preparation method of the solid base catalyst comprises the following steps:

(1) adding silicon dioxide powder into acid solution for dipping, adding high molecular polymer nano-sphere particles into the acid solution, violently stirring the mixture to uniformly mix the mixture, filtering the mixture, and drying the mixture for later use.

(2) Dissolving metal sulfide in the first mixed solvent, adding the carrier prepared in the step (1) after uniform dispersion, and stirring for a certain time at a certain temperature. Heating to a certain temperature, then adding metal cyanide, stirring, filtering, taking out, and roasting to obtain the solid base catalyst.

In the invention, the acid solution in the step (1) is one or more of aqueous solutions of sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid and hydrobromic acid, preferably an aqueous solution of hydrochloric acid, wherein the mass percent of the hydrochloric acid is 1-36 wt%, preferably 5-15 wt%. The purpose of the impregnation with the acid solution is to homogenize the pore size of the silica powder.

In the present invention, in step (1), the high molecular polymer is one or more of polyol of polyoxyalkylene, polystyrene, water-soluble polyester, polyether ester, polyether modified polysiloxane, and is preferably a nanoparticle sphere of polystyrene. The mass ratio of the high molecular polymer to the silicon dioxide is 1:0.5-1:10, preferably 1:1-1: 5.

The purpose of adding the polymer is to increase the hydrophilicity of the inorganic nonmetal carrier silicon dioxide so as to adsorb more reactants and increase the catalytic performance; and secondly, the surface of the silicon dioxide is modified, so that more space is provided for loading of an active center, and the catalytic performance is improved.

In the invention, in the step (1), the soaking time of the silicon dioxide in the acid solution is 1-20h, preferably 2-12 h; the impregnation temperature is 20 to 400 ℃, preferably 50 to 250 ℃.

The surface of the silica carrier is modified by adopting a high molecular polymer, so that the hydrophilicity of the inorganic nonmetal carrier silica is increased, more reactants are adsorbed, and the catalytic performance is improved; and secondly, the surface of the silicon dioxide is modified, so that more space is provided for loading of an active center, and the catalytic performance is improved.

In the invention, in the step (1), after filtration, drying is carried out for 1-20h at 10-200 ℃, the drying temperature is preferably 50-120 ℃, and the drying time is preferably 5-12 h.

In the invention, in the step (2), the mixed solvent I is a mixed solution of water and an organic solvent I, such as water/ethylene glycol, water/glycerol, water/isopropanol, water/n-butanol, water/acetone, water/butanol and the like, preferably water/n-butanol, wherein the mass ratio of the water to the organic solvent I is 0.05: 1-1: 1, preferably 0.1: 1-0.5: 1;

in step (2) of the present invention, the addition amount of the carrier prepared in step (1) is: 5 to 100g, preferably 10 to 50g, of the high molecular polymer-modified silica is added per mole of the metal sulfide.

In step (2) of the present invention, the metal sulfide includes one or more of alkali metal and alkaline earth metal sulfides, such as sodium sulfide, lithium sulfide, potassium sulfide, magnesium sulfide, calcium sulfide, etc., preferably sodium sulfide; the metal cyanide includes one or more of sodium cyanate, potassium cyanate, silver cyanate, ammonium cyanate, sodium hexacyanocobaltate, potassium ferricyanide, potassium hexacyanocobaltate, etc., preferably potassium ferricyanide.

In the invention, in the step (2), the stirring time is 5-40h, preferably 8-16h after the carrier is added; the stirring temperature is 50-400 ℃, and preferably 50-150 ℃; the metal hydride is added in a dropwise manner, the time for dropwise adding the metal cyanide is 0.5-10 hours, preferably 1-2.5 hours, and the temperature during dropwise adding is 100-800 ℃, preferably 250-450 ℃.

In the present invention, in the step (2), the metal cyanide is dissolved in the second organic solvent and then added dropwise, wherein the second organic solvent is one or more of methanol, ethanol, propanol, isopropanol, butanol, pentanol, hexanol, tetrahydrofuran, acetonitrile and chloroalkane, preferably methanol. The molar ratio of the metal cyanide to the metal sulfide is 0.1:1 to 5:1, preferably 0.5:1 to 2: 1.

The addition of the metal cyanide can be compounded with the inorganic metal salt, and firstly, the catalyst is adjusted to be in proper alkalinity, namely, the selectivity of the reaction is controlled; secondly, the lipophilicity of the catalyst is increased, namely the catalytic performance is improved; thirdly, the adsorption performance of the inorganic base on the polymer modified carrier is increased, namely, the mechanical strength is improved.

In the invention, in the step (2), the carrier is added and stirred for a certain time, and then nitrogen is used for gas stripping, wherein the volume flow of the nitrogen gas stripping is 10-500 mL/min, preferably 50-250 mL/min, and the purpose of the nitrogen gas stripping is to enable the alkali metal sulfide to be uniformly adsorbed on the carrier.

In the invention, in the step (2), the roasting temperature of the catalyst is 50-600 ℃, preferably 100-300 ℃; the time for roasting the catalyst is 1-20 hours, preferably 5-10 hours.

In some preferred embodiments of the present invention, the preparation method of the present invention comprises the steps of:

in the invention, the VA acetate is dissolved in the organic solvent III, the organic solvent III for dissolving the VA acetate comprises one or more of petroleum ether, n-hexane, n-heptane, acetonitrile, dichloromethane, trichloromethane and chloroform, and the n-hexane is preferred. The mass fraction of the VA acetate in the organic solvent III is 1 to 40 weight percent, and preferably 10 to 20 weight percent.

In the present invention, the molar flow rate ratio of the feed of VA acetate to palmitic acid is 1:1.05 to 1:1.5, preferably 1:1.15 to 1: 1.35.

The mass space velocity of VA acetic ester is 1-200h^-1Preferably 5 to 150h^-1。

In the invention, the reaction temperature is 10-60 ℃, preferably 20-30 ℃; the residence time of the mixed reaction liquid is 0.2-20 min, preferably 1-10 min; the reaction pressure is 0.005MPa to 0.08MPa, preferably 0.01MPa to 0.03 MPa.

After the reaction is finished, the reaction liquid is contacted with an extracting agent for extraction and separation to obtain VA palmitate, the VA palmitate is separated out in a crystallization reagent after being concentrated, product crystals are collected, and the low-temperature stability of the product crystals is measured.

In the invention, the extractant is one or more of toluene, m-xylene, o-xylene, p-xylene, acetone, ethyl acetate and the like, and toluene is preferred. The flow rate of the extracting agent is 0.5-5 times, preferably 1-3 times of the mass flow rate of the raw material VA acetic ester.

In the present invention, the crystallization reagent is one or more selected from methanol, ethanol, isopropanol, n-butanol, n-propanol, ethylene glycol, etc., preferably ethanol. The flow rate of the crystallization reagent is 1-10 times, preferably 2-4 times of the mass flow rate of the raw material VA acetate. The low-temperature crystallization temperature is-2-20 ℃, and preferably 0-10 ℃.

Compared with the traditional VA palmitate exchange synthesis process, the method has the following beneficial effects:

(1) the invention provides a solid base catalyst of metal hydride modified alkali metal sulfide, which has high mechanical strength, high catalytic activity, good selectivity, mild reaction condition and no byproduct generation, and is used for the reaction of VA acetic ester and palmitic acid.

(2) The reaction condition for synthesizing VA palmitate by using the solid base catalyst is milder, and the product obtained by the reaction can be stored more stably at low temperature and is easy to crystallize and separate out.

(3) The solid base catalysis system is adopted to solve the problem of equipment corrosion in the traditional solid acid catalysis system, and the process is green and environment-friendly.

(4) The solid base catalyst provided by the invention has few by-products in the process of synthesizing VA palmitate, can greatly reduce the contents of succinic acid, methyl ether and vitamin A dimer, has high selectivity and low catalyst consumption, and has good cyclic utilization rate.

Detailed Description

Potassium ferricyanide, methanol and sodium sulfide were purchased from Shanghai Tantake technologies, Inc., and polystyrene nanoparticles were purchased from Nanjing Xiancheng science and technology, Inc. The solid acid catalyst amberlyst45 was purchased from south university synthetic catalyst, inc.

Example 1

20g of silicon dioxide is placed in 200mL of 5 wt% hydrochloric acid, dipped for 2h at 50 ℃, 20g of polystyrene powder is rapidly added under stirring, filtered after vigorous stirring to obtain a white solid, dried for 5h at 50 ℃ and ground for standby. Dropwise adding 1mol of sodium sulfide into 500mL of a mixed solvent of butanol and water, wherein the volume ratio of the water to the butanol is 0.1: weighing 10g of the solid powder, and pouring sulfur into the solid powderStirring the sodium chloride solution at 50 ℃ for 8h, then blowing 50mL/min nitrogen into the system, heating the system to 250 ℃ under reflux, and stopping introducing the nitrogen. And (3) dropwise adding the prepared 0.5mol/L and 1L of potassium ferricyanide methanol solution, and controlling the dropwise adding flow rate to ensure that the dropwise adding time is 1 h. After the dropwise addition, the obtained solid is filtered and taken out, and is roasted for 5 hours at the temperature of 100 ℃ in the nitrogen atmosphere to obtain the catalyst Na₂S-K₃[Fe(CN)₆]@P-SiO₂。

A normal hexane solution of VA acetate with the mass fraction of 10 wt% is preheated to 20 ℃ and then enters from the upper part of a fixed bed reactor at the flow rate of 2.46 kg/min. Palmitic acid was preheated to 20 ℃ and fed at a flow rate of 221.2g/min from the lower part of the fixed bed reactor. The fixed bed reactor is filled with 5.01g of catalyst, the reaction material is contacted with the filled catalyst on the bed layer, the residence time of the material VA acetic ester is 2.5min, and the reaction is carried out at 20 ℃ and the system pressure of 0.01 MPa. After the reaction is finished, the reaction liquid is extracted and separated by 0.246kg/min toluene to obtain a product liquid, and the content of VA palmitate is 97.63%, the content of vitamin A dimer is 1.12%, the content of succinic acid is 0.89%, and the content of dimethyl ether is 0.36% in liquid phase analysis. The recovery rate of the toluene solvent after reduced pressure distillation and concentration is 96.6 percent, then 0.492kg/min of absolute ethyl alcohol is introduced into the concentrated solution containing VA palmitate, the VA palmitate is rapidly crystallized and separated out at 10 ℃, and the recovery rate of crystals is 95.3 percent. The VA palmitate crystals are stored for 10 days at 10 ℃ in a nitrogen-sealed mode, and the deterioration rate of the VA palmitate crystals is only 0.02%.

Example 2

20g of silicon dioxide is put into 200mL of hydrochloric acid with 10 wt%, dipped for 6h at 100 ℃, 60g of polystyrene powder is rapidly added under stirring, filtered after vigorous stirring, dried for 8h at 80 ℃ and ground for standby. Dropwise adding 1mol of sodium sulfide into 500mL of a mixed solvent of butanol and water, wherein the volume ratio of the water to the butanol is 0.25: weighing 20g of the solid powder, adding the solid powder into a sodium sulfide solution, stirring at 100 ℃ for 12h, blowing 100mL/min of nitrogen into the system, heating the system to 300 ℃ under reflux, and stopping introducing the nitrogen. Dissolving prepared 1.0mol/L, 1L sodium hexacyanocobaltate (III) in methanolDropping the mixture into the reactor, and controlling the dropping flow rate to ensure that the dropping time is 1.5 h. After the dropwise addition, the obtained solid is filtered and taken out, and is roasted for 8 hours at the temperature of 200 ℃ in the nitrogen atmosphere to obtain the catalyst Na₂S-Na₃[Co(CN)₆]@P-SiO₂。

A normal hexane solution of VA acetate with the mass fraction of 20 wt% is heated to 25 ℃ and then enters from the upper part of a fixed bed reactor at the flow rate of 1.314 kg/min. Palmitic acid was preheated to 25 ℃ and fed at a flow rate of 246g/min from the lower part of the fixed bed reactor. The fixed bed reactor is filled with 5.11g of catalyst, the reaction material is contacted with the filled catalyst on the bed layer, the residence time of the material VA acetic ester in the reactor is 6.5min, and the reaction is carried out at 25 ℃ and the system pressure of 0.02 MPa. After the reaction is finished, the reaction solution is extracted and separated by 0.657kgmin toluene to obtain a product solution, and the content of VA palmitate is 98.63%, the content of vitamin A dimer is 0.85%, the content of succinic acid is 0.45%, and the content of methyl ether is 0.07% in liquid phase analysis. The recovery rate of the toluene solvent after reduced pressure distillation and concentration is 96.2 percent, then 0.657kg/min of absolute ethyl alcohol is introduced into the concentrated solution containing VA palmitate, the VA palmitate is rapidly crystallized and separated out at the temperature of 5 ℃, and the recovery rate of crystals is 95.5 percent. The VA palmitate crystal is stored for 10 days at 10 ℃ in a nitrogen-sealed mode, and the deterioration rate of the VA palmitate crystal is only 0.01%.

Example 3

20g of silicon dioxide is put into 200mL of 15 wt% hydrochloric acid and dipped for 12h at 250 ℃, 100g of polystyrene powder is rapidly added under stirring, the mixture is vigorously stirred and filtered, and the mixture is dried for 12h at 120 ℃ and then ground for standby. Dropwise adding 1mol of potassium sulfide into 500mL of a mixed solvent of butanol and water, wherein the volume ratio of the water to the butanol is 0.5: weighing 50g of the white powder, pouring the white powder into a potassium sulfide solution, stirring the solution at the temperature of 150 ℃ for 16 hours, blowing 250mL/min of nitrogen into the system, heating the system to 450 ℃ under reflux, and stopping introducing the nitrogen. And (3) dropwise adding the prepared 2.0mol/L and 1L of potassium cyanate methanol solution, and controlling the dropwise adding flow rate to ensure that the dropwise adding time is 2.5 h. After the dropwise addition, the obtained solid is filtered and taken out, and is roasted for 10 hours at the temperature of 300 ℃ in the nitrogen atmosphere to obtain the catalyst K₂[email protected]₂。

A normal hexane solution of VA acetate with the mass fraction of 20 wt% is heated to 30 ℃ and then enters from the upper part of a fixed bed reactor at the flow rate of 1.643 kg/min. Palmitic acid was preheated to 30 ℃ and fed at a flow rate of 346g/min from the lower part of the fixed bed reactor. The fixed bed reactor is filled with 5.23g of catalyst, the reaction material is contacted with the filled catalyst on the bed layer, the residence time of the material VA acetic ester in the reactor is 8.2min, and the reaction is carried out at 30 ℃ and the system pressure is 0.03 MPa. After the reaction is finished, the reaction solution is extracted and separated by 0.657kg/min toluene to obtain a product solution, and the content of VA palmitate is 97.63%, the content of vitamin A dimer is 0.23%, the content of succinic acid is 1.26%, and the content of dimethyl ether is 0.88% in liquid phase analysis. The recovery rate of the toluene solvent after reduced pressure distillation and concentration is 96.6 percent, then 0.985kg/min of absolute ethyl alcohol is introduced into the concentrated solution containing the VA palmitate, the VA palmitate is rapidly crystallized and separated out at the temperature of 2 ℃, and the recovery rate of crystals is 98.2 percent. The VA palmitate crystals are stored for 10 days at 10 ℃ in a nitrogen-sealed mode, and the deterioration rate of the VA palmitate crystals is only 0.03%.

Comparative example 1

20g of silicon dioxide are placed in 200mL of 5 wt% hydrochloric acid and are immersed for 2h at 50 ℃, 20g of polystyrene powder is rapidly added while stirring, filtered after vigorous stirring, dried for 5h at 50 ℃ and ground for standby. Dropwise adding 1mol of sodium sulfide into 500mL of a mixed solvent of butanol and water, wherein the volume ratio of the water to the butanol is 0.1: weighing 10g of the solid powder, pouring the solid powder into a sodium sulfide solution, stirring the solution at 50 ℃ for 8 hours, blowing 50mL/min of nitrogen into the system, heating the system to 250 ℃ under reflux, stopping introducing the nitrogen, filtering the mixture, taking out the obtained solid, and roasting the solid at 100 ℃ for 5 hours in a nitrogen atmosphere to obtain a catalyst Na₂[email protected]₂。

A normal hexane solution of VA acetate with the mass fraction of 10 wt% is preheated to 20 ℃ and then enters from the upper part of a fixed bed reactor at the flow rate of 2.46 kg/min. Palmitic acid was preheated to 20 ℃ and fed at a flow rate of 221.2g/min from the lower part of the fixed bed reactor. . The fixed bed reactor is filled with 5.01g of catalyst, the reaction material is contacted with the filled catalyst on the bed layer, the residence time of the material VA acetic ester in the reactor is 2.5min, and the reaction is carried out at 20 ℃ and the system pressure is 0.01 MPa. After the reaction is finished, the reaction solution is extracted and separated by 100mL/min of toluene to obtain a product solution, and the content of VA palmitate is 90.52%, the content of vitamin A dimer is 3.69%, the content of succinic acid is 2.34%, and the content of methyl ether is 3.45% in liquid phase analysis. The recovery rate of the toluene solvent after reduced pressure distillation and concentration is 94.3 percent, then 80mL/min of absolute ethyl alcohol is introduced into the concentrated solution containing the VA palmitate, the VA palmitate is quickly crystallized and separated out at 10 ℃, and the recovery rate of crystals is 90.1 percent. The deterioration rate of the VA palmitate crystal is only 0.03 percent when the 10.0gVA palmitate crystal is stored for 10 days at 10 ℃ in a nitrogen-sealed mode.

Comparative example 2

20g of silica was immersed in 200mL of 5 wt% hydrochloric acid at 50 ℃ for 2 hours, and 20g of polystyrene powder was rapidly put therein with stirring, and after vigorous stirring, a white solid mixture was taken out, dried and ground for use. Weighing 10g of the white powder, pouring the white powder into 500mL of a mixed solvent of butanol and water, wherein the volume ratio of the water to the butanol is 0.1:1, stirring at 50 ℃ for 8h, blowing 50mL/min nitrogen into the system, heating the system to 250 ℃ under reflux, and stopping introducing the nitrogen. And (3) dropwise adding the prepared 0.5mol/L and 1L of potassium ferricyanide methanol solution, and controlling the dropwise adding flow rate to ensure that the dropwise adding time is 1 h. After the dropwise addition, the obtained solid is filtered and taken out, and is roasted for 5 hours at the temperature of 100 ℃ in the nitrogen atmosphere to obtain the catalyst K₃[Fe(CN)₆]@P-SiO₂。

A normal hexane solution of VA acetate with the mass fraction of 10 wt% is preheated to 20 ℃ and then enters from the upper part of a fixed bed reactor at the flow rate of 2.46 kg/min. Palmitic acid was preheated to 20 ℃ and fed at a flow rate of 221.2g/min from the lower part of the fixed bed reactor. The fixed bed reactor was packed with 5.02g of catalyst, the reaction mass was contacted with the packed catalyst on the bed, the feed rate was adjusted to allow the residence time of the mass in the reactor to be 2.5min, and the reaction took place at 20 ℃ and a system pressure of 0.01 MPa. After the reaction is finished, the reaction solution is extracted and separated by 100mL/min of toluene to obtain a product solution, and the content of VA palmitate is 60.25%, the content of vitamin A dimer is 20.35%, the content of succinic acid is 10.27%, and the content of methyl ether is 9.13% in liquid phase analysis. The recovery rate of the toluene solvent after reduced pressure distillation and concentration is 96.6 percent, then 80mL/min of absolute ethyl alcohol is introduced into the concentrated solution containing the VA palmitate, the VA palmitate is quickly crystallized and separated out at 10 ℃, and the recovery rate of crystals is 94.3 percent. The VA palmitate crystals are stored for 10 days at 10 ℃ in a nitrogen-sealed mode, and the deterioration rate of the VA palmitate crystals is 0.05%.

Comparative example 3

A quantity of commercially available solid acid catalyst amberlyst45 was purchased and used for the transesterification reaction, the specific comparative examples being as follows:

VA normal hexane liquid with the mass fraction of 10 wt% is heated to 20 ℃ and then enters from the upper part of the fixed bed reactor at the flow rate of 2.46 kg/min. Palmitic acid was preheated to 20 ℃ and fed at a flow rate of 221.2g/min from the lower part of the fixed bed reactor. The reaction material is contacted with the filled catalyst on the bed layer, 5.12g of the catalyst is filled in the fixed bed reactor, the residence time of the material VA acetic ester in the reactor is 2.5min, and the reaction is carried out at 20 ℃ and the system pressure is 0.01 MPa. After the reaction is finished, the reaction solution is extracted and separated by 0.246kg/min toluene to obtain a product solution, and the content of VA palmitate is 90.28%, the content of vitamin A dimer is 2.59%, the content of succinic acid is 3.79% and the content of methyl ether is 3.34% in liquid phase analysis. The recovery rate of the toluene solvent after reduced pressure distillation and concentration is 96.8 percent, then 0.492kg/min of absolute ethyl alcohol is introduced into the VA palmitate mother liquor, the VA palmitate is crystallized and separated out at 10 ℃, the recovery rate of the crystals is 20.5 percent, the temperature is continuously reduced to 5 ℃, and the yield of the crystals is 75.9 percent. 10.0gVA palmitate crystal is stored for 10 days at 10 ℃ in a nitrogen-sealed mode, and the deterioration rate of the VA palmitate crystal is 1.23%.

As can be seen from the comparative example I, the metal cyanide-free modified solid base catalyst has lower catalytic activity under the same process conditions, which is caused by the fact that the alkalinity of the metal sulfide in the catalyst is too strong and more byproducts are generated; as can be seen from the comparative example two, the solid base catalyst without metal sulfide support does not have a good activity for catalyzing transesterification reaction, since the activity of the solid base is sodium sulfide. As can be seen from the third comparative example, the common solid acid catalyst is adopted to carry out the ester exchange reaction under the same process conditions, the obtained product contains by-products higher than that of the patent, the obtained VA palmitate needs extremely low (about-30 to-10 ℃) crystallization temperature, the deterioration rate under the same process conditions is more than 1%, and the production economic cost is higher.