JPS6046114B2 - Production method of α-tocopherol - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing alpha-tocopherol.

More specifically, when producing α-tocopherol by condensing 2.3.5-trimethylhydroquinone and phytol, zinc chloride and hydrochloric acid are used as acidic condensing agents, and a halogenated lower aliphatic hydrocarbon solvent is used as a reaction solvent. The present invention relates to a method for producing alpha-tocopherol, which comprises using the method of producing alpha-tocopherol. Examples of the oxidized lower aliphatic hydrocarbon solvent used in the method of the present invention include dichloromethane, chloroform, carbon tetrachloride, and ethylene dichloride.

Zinc chloride and hydrochloric acid are used as acidic condensing agents.
Examples of hydrochloric acid include concentrated hydrochloric acid (36% concentration) and dry hydrochloric acid gas. The ratio of hydrochloric acid to zinc chloride is 0.01 to 0.01 to 1 mole of zinc chloride.
A desirable amount is about 5 molar amount, especially about 0.2 molar amount. In addition, examples of the phytols that can be used include phytol, isophytol, and analogous compounds thereof.
In the present invention, the reaction proceeds even at a low temperature of room temperature to about 30°C.

Additionally, during the reaction, an organic acid such as acetic acid or propionic acid, and a metal such as zinc powder or tin powder are added to the reaction system, either alone or in combination, to smooth the reaction and improve the yield and quality of the target product. be able to. Conventionally, as a method for producing α-tocopherol, when condensing 2,3,5-trimethylhydroquinone with phytol and/or isophytol, zinc chloride is used as a condensing agent, and ligroin, tetralin, benzene, toluene, xylene, etc. A method of heating under reflux in an aliphatic hydrocarbon solvent is known.

However, in these conventional methods, harsh reaction conditions such as heating under reflux at high temperatures are essential, and therefore, for example, lydadiene and its polymers, reaction products of solvents and phytols, etc. Undesirable by-products of the species are formed, which are difficult to remove by distillative purification operations, and therefore it is not possible to obtain high yields and high purity alpha-tocopherols.
Therefore, in order to eliminate these drawbacks, it is conceivable to simply carry out the reaction at a relatively low temperature, but at low temperatures the progress of the reaction is low and the yield of α-tocopherol is significantly reduced. Research has been carried out to obtain α-tocopherol at a relatively low temperature and with a high yield. A method for obtaining α-tocopherol by reacting with phytol or isophytol in a reaction solvent such as toluene, n-hexane, or dioxane at 60 to 80°C has been reported (Japanese Patent Publication No. 45-2
1835).

This method is said to have a reaction completion rate (yield) of 99% or more, but the measurement of the content of α-tocopherol in the reaction product, which is the basis of the numerical calculation, is performed using redox methods such as the Emery-Engel method. Substances (impurities) that behave similarly to α-tocopherol in the Emery-Engel method in the reaction product are also measured as α-tocopherol, and the actual yield is The yield is 90% when measured using the more selective gas chromatography method described below.
% or less (molecular distillation purified product). Furthermore, the presence of impurities that were difficult to purify and remove was observed on the gas chromatograph and thin layer chromatograph. The present inventors conducted research to remove the above-mentioned drawbacks of the conventional method for producing alpha-tocopherol and obtain high-yield alpha-tocopherol of high purity. As a result of examining various condensation methods in order to find a condensation method that does not produce the product, the present invention has been found to provide highly purified α-tocopherol in high yield.

The advantage of the method of the present invention is that when carrying out the condensation reaction, there is no need to perform heating under reflux at a high temperature, and the reaction proceeds almost quantitatively under mild temperature conditions of room temperature to 30°C.

As a result, the generation of by-products due to the harsh reaction conditions of the conventional method was minimal, and crude α-tocopherol could be obtained at a high yield of 95% or more.

This crude α-tocopherol was molecularly distilled according to a conventional method, with a purity of 98% or more [NatiOnalFOrmulary, Vol. 1, No. 75]
It was measured according to the vitamin E quantitative method using gas chromatography described on pages 8-762. Good results were obtained in that purified α-tocopherol could be obtained in a yield of 96% or more.
It was also confirmed on a gas chromatograph or thin layer chromatograph that there was less contamination by by-products compared to conventional methods. As described above, an object of the present invention is to provide α-tocopherol with higher purity and higher yield than conventional methods.

Next, the present invention will be explained with reference to examples.

The purity of the target α-tocopherol was measured in accordance with the gas chromatography method described in the National Homillery, Vol. 1, mentioned above. Example 1 2,3,5-trimethylhydroquinone - 125 g 1 zinc chloride 112 g 1 dichloromethane 350
Mix and stir 10 g of glacial acetic acid and 10 ml of concentrated hydrochloric acid (36%) at 25-30°C to prepare 245 g of isophytol (
(purity 98.1%) was added dropwise over a period of 3 hours, followed by further stirring at the same temperature for 1 hour.

After the reaction was completed, 50 ml of water was added, zinc chloride was removed, and dichloromethane was distilled off under normal pressure. The resulting oily residue (crude α-tocopherol) was dissolved in 300 ml of toluene and 100 ml of methyl ethyl ketone. After washing with water, alkaline washing, and water washing. After acetylation, washing with water, and concentration, 386.1 g of α-tocopherol was obtained as a pale yellow oil. Purity 96.0%,
Yield: 96.2% This product was subjected to molecular distillation to produce a colorless oily substance (
Purified α-tocopherol) 357.9g (purity 98.7
%), yield 92.0% Example 2 125 g of 2,3,5-trimethylhydroquinone, 112 g of zinc chloride, 2 g of dry hydrochloric acid gas (absorbed and dissolved in dichloromethane in advance and added to the reaction system), 1 g of dichloromethane, 350 ml, 11 10 ml of glacial acetic acid. Mix and stir and add isophytol (purity 98.1%) 2 at 18-20℃.
45 g was added dropwise over 6 hours.

Hereinafter, each reaction was carried out according to Example 1. 381.8g pale yellow crude α-tocopheryl acetate (purity 96.1%)
) was obtained. This product was purified by molecular distillation to obtain 360.2 g (purity 98.7%) of α-tocopheryl acetate. Yield: 92.6% Next, the superiority of the method of the present invention will be further demonstrated by comparing the method of the present invention with the conventional method.

Claims (1)

[Claims] 1. When producing α-tocopherol by condensing 2,3,5-trimethylhydroquinone and phytols, it is recommended to use a halogenated lower aliphatic hydrocarbon solvent with zinc chloride and hydrochloric acid as an acidic condensing agent and a reaction solvent. Characteristic method for producing α-tocopherol.