A method for isomerizing vitamin a

Abstract

The present application provides a vitamin A isomerization method, by reacting in a specific solvent, so that the vitamin A cis-isomer can be efficiently converted into all-trans vitamin A, in addition, a certain amount of second component solvent is introduced in the reaction system, which greatly improves the conversion rate and selectivity of the isomerization reaction.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of chemical synthesis, in particular to a vitamin A isomerization process. BACKGROUND

[0002] Vitamin A acetate is an important substance in the fields of medicine, cosmetics, food, animal nutrition feed additive, etc., is one of the essential nutrients for human body, and is an indispensable trace element in the growth and development process of children, so many chemical workers have devoted themselves to the synthesis of vitamin A and its derivatives.

[0003] In order to isomerize 11-cis isomer and 9-cis isomer of vitamin A acetate into all-trans structure, there are currently three existing technologies: iodine catalysis, photocatalysis and metal catalysis. However, these three methods have certain defects and deficiencies. Among them, the commonly used catalyst for iodine catalysis is iodide salt, or iodine element is used for catalytic reaction. A large amount of iodine-containing wastewater is generated in this process, which causes serious environmental pollution. The photocatalytic isomerization reaction needs to add a photosensitizer to the system in advance. The presence of the photosensitizer will cause the instability of the structure of vitamin A acetate and bring great difficulty to the subsequent separation process. The commonly used catalytic system for metal catalytic reaction is metal iodide or noble metal catalyst. The comprehensive utilization degree of the catalyst in this process is low, the cost is high, the post-processing steps are complex, and environmental pollution is easy to cause. SUMMARY

[0004] The present application provides a new method for vitamin A isomerization, which realizes efficient conversion of vitamin A cis isomer to all-trans vitamin A without adding additional catalysts, and solves the problems of pollution, poor catalytic efficiency, high cost of using noble metal catalyst and the like in the existing process.

[0005] To achieve the above purpose, the technical scheme adopted by the present application is as follows:

[0006] A new method for vitamin A isomerization, comprising the following steps:

[0007] 1) Under stirring, a certain proportion of solvent and mixed oil containing VA isomers are added to a reaction kettle;

[0008] 2) The reaction kettle is raised to a certain temperature and reacted for a certain time;

[0010] 3) A second component solvent is added to the reaction kettle, and the reaction is continued for a certain time;

[0011] 4) After the reaction is completed, high-purity all-trans VA oil is obtained after post-processing.

[0012] In the present application, preferably, the solvent in step 1) is one or more of toluene, xylene, ethylbenzene and cumene, preferably toluene.

[0012] Preferably, the weight ratio of the solvent to the VA isomer-containing mixed oil (referred to as VA mixed oil) in step 1) is 2-6:1, preferably 3-4:1;

[0013] Preferably, the VA mixed oil in step 1) is prepared by first preparing β-vinylionylidene triphenyl phosphonium salt using β-vinylionyl alcohol and triphenyl phosphine as raw materials, then performing Wittig reaction with 4-acetoxy-2-methyl-but-2-enal, and concentrating the crystallization filtrate obtained after isomerization and crystallization, which is a conventional prior art, wherein the all-trans content is ≤40%, and the total VA content is ≥70%, preferably ≥80%;

[0014] Preferably, the temperature in step 2) is 40-120°C, preferably 60-80°C;

[0015] Preferably, the time in step 2) is 2-12h, preferably 4-6h;

[0016] Preferably, the second component solvent in step 3) is one or more of dichloromethane, dichloroethane and trichloroethane, preferably dichloromethane;

[0017] Preferably, the amount of the second component solvent added in step 3) is 1-20% of the mass of the VA mixed oil, preferably 5-10%;

[0018] Preferably, the reaction temperature in step 3) is 40-120°C, preferably 60-80°C;

[0019] Preferably, the reaction time in step 3) is 1-8h, preferably 3-5h;

[0020] Preferably, the post-treatment method in step 4) is reduced pressure distillation, and the distillation temperature is controlled at 30-60°C, and the pressure is controlled at 0.1-20kPa.

[0021] Preferably, the all-trans VA oil obtained by the above method has a 11-cis isomer content of ≤0.5wt%, and a 9-cis isomer content of ≤0.2wt%.

[0022] Compared with the prior art, the present application has the following outstanding effects:

[0023] 1) In the present application, no additional catalyst is needed to efficiently complete the isomer conversion of vitamin A;

[0024] 2) The post-treatment is simple, and the product can be obtained by simple distillation;

[0025] 3) Compared with the existing process, the present process basically generates no three wastes, greatly reducing the production cost and facilitating industrialized production. DETAILED DESCRIPTION

[0026] It should be noted that the following detailed description is exemplary in nature and is intended to provide further description of the application. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The following detailed description further describes the technical solutions of the present application through specific embodiments. Those skilled in the art should understand that the embodiments are only to help understand the present application and should not be regarded as specific limitations of the present application.

[0027] VA mixed oil source: Wanhua Chemical.

[0028] Example 1

[0029] The present embodiment provides a method for isomerizing vitamin A, comprising the following steps:

[0030] 1) Under stirring, 100 g of VA mixed oil (total purity of VA 87.5%, of which the total content of cis-VA is 47.5%) and 400 g of toluene were added to a reaction kettle and stirred and mixed uniformly;

[0031] 2) After the temperature of the reaction kettle was raised to 80°C, the reaction was kept for 6 h;

[0032] 3) 10 g of dichloromethane was added to the reaction system, and the reaction was continued at the temperature for 3 h;

[0033] 4) After the reaction was completed, the VA oil product was obtained by vacuum concentration (temperature 50°C, pressure 20 kPa).

[0034] The product obtained in Example 1 was tested as follows:

[0035] 1) Yield test: isomerization conversion rate 99.7%, selectivity 99.8%.

[0036] 2) Purity test (HPLC): the total purity of the obtained VA oil was 87.3%, the content of all-trans VA was 87.05%, the content of 11-cis VA was 0.1%, and the content of 9-cis VA was 0.15%.

[0037] Example 2

[0038] 1) Under stirring, 100 g of VA mixed oil (total purity of VA 75%, of which the total content of cis-VA is 45%) and 200 g of xylene were added to a reaction kettle and stirred and mixed uniformly;

[0039] 2) After the temperature of the reaction kettle was raised to 50°C, the reaction was kept for 12 h;

[0040] 3) 2 g of dichloroethane was added to the reaction system, and the reaction was continued at the temperature for 8 h;

[0041] 4) After the reaction, concentrate under reduced pressure (temperature 30°C, pressure 0.1 kPa) to obtain VA oil product.

[0042] The following tests were conducted on the product obtained in Example 2:

[0043] 1) Yield test: isomerization conversion rate 99.6%, selectivity 99.7%.

[0044] 2) Purity test (HPLC): total purity of the obtained VA oil 75%, all-trans VA content 74.68%, 11-cis VA content 0.18%, 9-cis VA content 0.14%.

[0045] Example 3

[0046] 1) Under stirring, add 100 g of VA mixed oil (total purity of VA 80.21%, cis VA content 52.1%) and 600 g of cumene into a reaction kettle, and stir to mix uniformly;

[0047] 2) After raising the temperature of the reaction kettle to 120°C, keep the temperature for 3 h;

[0048] 3) Add 20 g of trichloroethane into the reaction system, and continue to react at the temperature for 1 h;

[0049] 4) After the reaction, concentrate under reduced pressure (temperature 60°C, pressure 20 kPa) to obtain VA oil product.

[0050] The following tests were conducted on the product obtained in Example 3:

[0051] 1) Yield test: isomerization conversion rate 99.8%, selectivity 99.4%.

[0052] 2) Purity test (HPLC): total purity of the obtained VA oil 80.19%, all-trans VA content 80.05%, 11-cis VA content 0.11%, 9-cis VA content 0.03%.

[0053] Comparative Example

[0054] Patent CN100484919C mentions a kind of isomerization mode of double bond in carotenoid, i.e. isomerization occurs in high-boiling-point polar solvent, and the solvent includes glycerol, propylene glycol, glycerol monoacetate, glycerol diacetate or diethylene glycol monoethyl ester; in order to verify the feasibility of isomerization of vitamin A in the solvent system, the following comparative example is made.

[0055] Since vitamin A will undergo ester exchange reaction when heated in polar protic solvents such as glycerol and propylene glycol, isomerization in glycerol and propylene glycol solvents is not feasible, the following comparative example only verifies the other three solvents.

[0056] Example 1

[0057] In a 1000 mL three-necked flask, 300 g of VA mixed oil (total VA purity 87.5%, of which the content of cis-VA is 37.5%) and 700 g of monoacetin were added, the reaction temperature was controlled at 140°C, and the reaction was carried out in the dark under nitrogen for 4 h, then the temperature was lowered to 100°C, and the reaction was continued for 25 h. After the reaction was completed, the VA oil was concentrated. After quantitative determination by liquid chromatography, the purity of the VA oil was 63%, of which the content of cis-isomer was 39.3%. In this reaction system, the conversion of the isomer to all-trans VA could not be completed, and at the same time, due to the long-term high-temperature condition, the all-trans VA deteriorated.

[0058] Example 2

[0059] In a 1000 mL three-necked flask, 300 g of VA mixed oil (total VA purity 87.5%, of which the content of cis-VA is 37.5%) and 700 g of diacetin were added, the reaction temperature was controlled at 140°C, and the reaction was carried out in the dark under nitrogen for 4 h, then the temperature was lowered to 100°C, and the reaction was continued for 25 h. After the reaction was completed, the VA oil was concentrated. After quantitative determination by liquid chromatography, the purity of the VA oil was 72%, of which the content of cis-isomer was 36.3%. In this reaction system, the conversion of the isomer to all-trans VA could not be completed, and at the same time, due to the long-term high-temperature condition, the all-trans VA deteriorated.

[0060] Example 3

[0061] In a 1000 mL three-necked flask, 300 g of VA mixed oil (total VA purity 87.5%, of which the content of cis-VA is 37.5%) and 700 g of diacetin were added, the reaction temperature was controlled at 140°C, and the reaction was carried out in the dark under nitrogen for 4 h, then the temperature was lowered to 100°C, and the reaction was continued for 25 h. After the reaction was completed, the VA oil was concentrated. After quantitative determination by liquid chromatography, the purity of the VA oil was 72%, of which the content of cis-isomer was 36.3%. In this reaction system, the conversion of the isomer to all-trans VA could not be completed, and at the same time, due to the long-term high-temperature condition, the all-trans VA deteriorated.

Claims

1. A method for isomerizing vitamin A, characterized in that, The method comprises the following steps: 1) adding a certain proportion of solvent and mixed oil containing VA isomers into a reaction kettle under stirring; wherein the solvent is one or more of toluene, xylene, ethylbenzene and cumene; 2) raising the reaction kettle to a certain temperature and reacting for a certain time; 3) adding a second component solvent into the reaction kettle and continuing to heat and react for a certain time; 4) obtaining high-purity all-trans VA oil after post-treatment.

2. The isomerization process of claim 1 wherein, In step 1), the total VA content in the mixed oil containing VA isomers is ≥ 70%, and the all-trans content is ≤ 40%.

3. The isomerization process of claim 2, wherein, In step 1), the total VA content in the mixed oil containing VA isomers is ≥ 80%.

4. The isomerization process of claim 1 or 2, wherein, In step 1), the solvent is toluene.

5. The isomerization process according to any one of claims 1 to 3, characterized in that, In step 1), the weight ratio of the solvent to the mixed oil containing VA isomers is 2-6:

1.

6. The isomerization process of claim 1 wherein, In step 2), the certain temperature is 40-120℃, and the certain time is 2-12h.

7. The isomerization process of claim 1 wherein, In step 3), the second component solvent is one or more of dichloromethane, dichloroethane and trichloroethane.

8. The isomerization process of claim 1 or 7, wherein, In step 3), the second component solvent is added in an amount of 1-20% of the mass of the mixed oil containing VA isomers.

9. The isomerization process of claim 1 wherein, In step 3), the reaction temperature is 40-120℃, and the reaction time is 1-8h.

10. The isomeric process of claim 1 wherein, In step 4), the post-treatment method is reduced pressure distillation, the distillation temperature is 30-60℃, and the pressure is 0.1-20kPa.

11. The isomeric process of claim 1 wherein, In the all-trans VA oil, the 11-cis isomer content is ≤ 0.5%, and the 9-cis isomer content is ≤ 0.2%.