Preparation method of vitamin A acetate

Abstract

The invention provides a preparation method for vitamin A acetate. The preparation method comprises the following steps: carrying out an addition reaction on a C15 phosphonium salt and a C5 aldehyde in the presence of an alkali compound to generate an ylide salt; and subjecting the ylide to a decomposition reaction to obtain the vitamin A acetate, wherein the content of ylide in a reaction system in a reaction process is less than or equal to 0.06 mol / L. According to the preparation method, on the basis of a C15 + C5 Wittig reaction, the content of ylide in the reaction system in the reaction process is controlled, and the vitamin A acetate with high purity, high trans-isomerization selectivity and high yield is obtained. The preparation method is suitable for any-scale reaction and can be carried out in batches and conducted semi-continuously or completely continuously; and the obtained vitamin A acetate is low in chromatic value, good in oxidation resistance and thermal stability, low in deterioration rate, beneficial to long-term stable storage and very good in market competitiveness.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a preparation method of vitamin A acetate. Background technique [0002] Vitamin A acetate (VA acetate) is an important substance used in medicine, cosmetics, food, food supplements, and animal feed additives. It has the functions of maintaining visual function, maintaining the health of epithelial tissue cells, and promoting immunoglobulin synthesis. . Vitamin A acetate has the following three difficulties in storage and use: first, vitamin A acetate has extremely poor antioxidant properties and is easily oxidized and decomposed when exposed to air; second, vitamin A acetate has poor thermal stability , especially in hot summer, the problem of storage is more difficult; third, most commercially available vitamin A acetates are darker in color, with yellowish or reddish crystals, and the color will gradually deepen with time, and few manufacturers can Pro...

AI Technical Summary

Problems solved by technology

This method reduces the use and separation of solvents, but requires the use of highly hazardous reagents such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, or sodium hydride, which require high air and moisture control, and the atomic utilization of the two-step Wittig reagent The rate is lower, both 20%

[0005] CN101219983A discloses an improved preparation method of vitamin A acetate, through the Wittig reaction of carbon pentaphosphonic acid dialkyl ester and 4-acetoxy-2-methyl-2-butene-1 aldehyde as raw material The target product is obtained, and the reaction solvent is a mixture of toluene and pyridine (or methyl-substituted pyridine), so that the reaction is carried out in an environment close to room temperature; however, the method needs to use high-risk reagents such as sodium methylate and sodium ethylate, and The isomer selectivity of the product is poor

In this method, the preparation reaction temperature of the C15 phosphine salt is difficult to control, a large amount of isomer impurities are generated, and the product is difficult to crystallize and separate, resulting in the vitamin A acetate generated by the C15 phosphine salt as a follow-up Wittig reaction raw material containing more tar, and along the way The ratio of trans isomers is 7:3, and the content of trans vitamin A acetate is extremely small, which is not conducive to industrial production

[0007] Overall, the reaction conditions of the Wittig method are relatively harsh, requiring a large amount of organic / inorganic acid-base catalysts, difficult post-treatment, low atom utilization, poor selectivity of the all-trans form in the vitamin A acetate generated after the reaction, and the reaction The elimination and decomposition reaction of intermediates in the process is slow, resulting in the formation of vitamin A acetate doped with more impurities that are difficult to remove due to similar compatibility, which is not conducive to product stability and subsequent crystallization operations

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