Dl-alpha tocopherol acetate preparation method

Abstract

The present invention relates to a dl-alpha tocopherol acetate preparation method, wherein trimethyl hydroquinone diethyl ester or trimethyl hydroquinone-4-ethyl ester is adopted as a raw material, Bronsted acid and Lewis acid are adopted as catalysts, the raw material and phytol or isophytol or a phytol derivative are directly subjected to a condensation reaction in an ester solvent to obtain the product dl-alpha tocopherol acetate or an intermediate dl-alpha tocopherol, wherein the intermediate dl-alpha tocopherol is subjected to further esterification to obtain the product dl-alpha tocopherol acetate. According to the present invention, the process route is simple, the production cost is reduced, the quality of the obtained product is good, the yield is high, and the method is suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to a method for preparing dl-alpha tocopheryl acetate by using trimethylhydroquinone diethyl ester or trimethylhydroquinone-1-ethyl ester as a raw material for condensation reaction, wherein trimethylhydroquinone diethyl ester is used as a raw material for condensation reaction The reaction directly obtains dl-alpha tocopheryl acetate product, trimethylhydroquinone-1-ethyl ester is used as raw material for condensation reaction to obtain dl-alpha tocopherol, and further esterification reaction obtains dl-alpha tocopheryl acetate product. Background technique [0002] As a kind of organic matter necessary to maintain human life activities, vitamins are also important active substances to maintain human health. They play an important role in the processes of human growth, metabolism, development, and reproduction. Among them, vitamin E is a fat-soluble vitamin. An important component of the cell membrane, which mainly plays an anti-...

AI Technical Summary

Problems solved by technology

[0009] These reactions have the following defects: 1) the synthesis of raw material trimethylhydroquinone is more complex than trimethylhydroquinone monoester or trimethylhydroquinone diester, and the cost is higher; 2) raw material trimethylhydroquinone is unstable and easy It is oxidized and difficult to store; 3) The raw material trimethylhydroquinone has certain toxicity and exists in the state of light solid powder, which is easy to float in the air or adsorbed on the human body, and will cause great harm to human skin, respiratory tract, etc. irritating, thereby bringing a certain environmental impact and occupational disease risk to actual production; 4) The dl-α tocopherol obtained by the reaction is easily oxidized, and generally needs to be esterified to obtain dl-α tocopherol acetate, and the process is more complicated. At the same time, the esterification reaction must consume a certain amount of acetic acid or acetic anhydride and energy, etc.

[0010] There are also some synthetic processes that select trimethylhydroquinone esters (including trimethylhydroquinone monoester or trimethylhydroquinone diester) as raw materials. Although the above-mentioned defects can be overcome to a certain extent, there are certain disadvantages, among which Trimethylhydroquinone-4-ester ( R 4 The group is a group such as hydrogen or methyl) due to the F-C reaction (the reaction site is located at the 1st and 6th positions on the benzene ring), there are no factors that limit the reaction such as steric hindrance and group activity, so the reaction is relatively easy to carry out, and can also dl-alpha tocopheryl acetate can be directly obtained, but due to certain limitations in the selection of raw materials, only trimethylhydroquinone-4-ester can be selected, and trimethylhydroquinone-4-ester is mainly derived from trimethylhydroquinone Enzymatic hydrolysis of quinone diesters and other reactions, such reactions are more complicated and costly

[0011] Trimethylhydroquinone diester ( R 5 , R 6 The group is a group such as hydrogen or methyl) or trimethylhydroquinone-1-ester ( R 7 group is a group such as hydrogen or methyl) as a raw material, the synthesis process is relatively immature, because the No. 1 position on the benzene ring in the structure of trimethylhydroquinone diester or trimethylhydroquinone-1-ester is esterified There are limiting factors such as steric hindrance and group activity in participating in the F-C reaction, the reactivity of raw materials is small, the process reaction degree disclosed in most documents is small, the reaction yield is low, and the quality of the obtained product is poor

[0014] In the DE10011402 patent, it is mentioned that directly use trimethylhydroquinone diethyl ester to react with isophytol, and use a polar solvent (such as acetic acid) as the reaction medium. This method mainly utilizes the polar solvent acetic acid to dissolve the catalyst so as to facilitate subsequent recovery and mechanical application, and Solvents such as acetic acid are not easy to decompose, and the loss is small, but trimethylhydroquinone diethyl ester is not easy to remove the ethyl carboxyl group in polar solvents such as acetic acid, thereby hindering the formation of the product dl-α tocopherol or dl-α by cyclization with isophytol Tocopherol acetate, resulting in low process yield, and because it is difficult to separate acetic acid and water in the industry, the water content in the mechanically applied catalyst will continue to accumulate, resulting in the failure of the late catalyst and the inability to catalyze the condensation reaction

[0015] EP02025989 patent states that trimethylhydroquinone-4-ethyl ester is reacted with isophytol or phytol, the solvent is an aprotic organic solvent, and the catalyst only uses a sulfonic acid catalyst or a basic catalyst to finally obtain dl-α tocopherol Acetate, this invention technology is limited to trimethylhydroquinone-4-ethyl ester to raw material, has certain limitation, simultaneously in sulfonic acid catalyst or basic catalyst, condensation reaction is also more difficult, causes product yield relatively Low, yield 10.2~81.9%

[0016] Patent EP03000493 / EP03024288 uses a special catalyst to catalyze the reaction of trimethylhydroquinone-4-ethyl ester with phytol, isophytol or (iso)phytol derivatives to obtain dl-α tocopheryl acetate, in which the catalyst is made of noble metal or rare earth Metal compounds, the raw material is also limited to trimethylhydroquinone-4-ethyl ester, there are limitations, the catalyst leads to higher process costs, and the reaction temperature is high, the process is slightly complicated

[0017] EP04013713 patent also uses trimethylhydroquinone-4-ester (including esters such as ethyl ester and propyl ester) to react with isophytol, phytol or (iso)phytol derivatives, and the catalyst is a salt compound containing rare metals , wherein the raw material is limited to trimethylhydroquinone-4-ester, the condensation reaction is required to be carried out under a certain pressure, the reaction conditions are relatively complicated, and the selection of catalysts leads to higher process costs

[0018] EP01104141.5 patent uses appropriate biological esterase to convert trimethylhydroquinone diethyl ester into trimethylhydroquinone-4-ethyl ester, then purify and then carry out subsequent corresponding F-C reaction condensation to obtain dl-α growth For phenol acetate, the appropriate cost of biological esterase will greatly increase the process cost. In order to ensure the activity of biological esterase, the requirements for enzymatic hydrolysis and separation process are relatively high, and the process route is relatively complicated

[0019] Chinese patent CN201110198791 uses a one-pot method to react trimethylhydroquinone diethyl ester with isophytol. The process first uses lower aliphatic alcohols to perform transesterification with trimethylhydroquinone diethyl ester under acid catalysis to obtain trimethylhydroquinone diethyl ester. Hydroquinone, then reclaim lower fatty alcohol and the acetic acid lower fatty acid ester that produces, obtain trimethylhydroquinone solid, then carry out follow-up condensation reaction and esterification reaction to obtain dl-alpha tocopheryl acetate, this method has certain defects : Trimethylhydroquinone is easily oxidized in the process of reclaiming lower fatty alcohols and fatty acid esters; trimethylhydroquinone is solid in the process of reclaiming lower fatty alcohols and esters, which is difficult to realize in actual industrial production; transesterification is difficult to complete, Lead to lower final product yield, poor product quality, etc.

[0020] The literature technologies disclosed above all have certain defects. Among them, some synthesis processes are relatively complicated and costly. Some processes obtain poor product quality and low yield. Some processes also have relatively high process conditions. Large-scale production has certain advantages. limitations, etc.

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