JPS6019309B2 - Production method of high purity dl-α-tocopherol - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing dl-Q tocopherol, and more particularly, the present invention relates to a method for producing dl-Q tocopherol. The present invention relates to a method for producing high purity dl-Q tocopherol by.

Conventionally, known methods for producing dl-Q tocopherol include condensation in an organic solvent under a protonic acid catalyst such as p-toluenesulfonic acid, a Lewis acid catalyst such as zinc chloride, or a solid acid catalyst such as silica alumina. ing.

However, when dl-Q-tocopherol is produced by these methods, there is a drawback that by-products are produced.
This created organism could not be removed even after repeated purification treatments. Therefore, in the conventional method, dl-
American National Formulary Standards for Q-Tocopherol Acetate (Natio Tsukuda IFonnula 14ed
It has been nearly impossible to commercially obtain a product with a purity of 96% or higher, as defined in the US Pat. The inventors conducted various studies on methods for producing high-purity dinq-tocopherol, and as a result, they discovered a method for obtaining high-purity dl-Q-tocopherol.

The method of the present invention, as described above, relates to a method of condensing trimethylhydroquinone and phytols in the presence of silica alumina and/or silica gel, zinc chloride and protonic acid. In addition to phytol, the phytols that are one of the raw materials of the present invention include isophytol, halides such as phytyl chloride and phytyl bromide, and alkyl esters such as phytyl acetate and phytyl propionate. Sexual derivatives can also be used. Examples of protonic acids used in the method of the present invention include hydrochloric acid, sulfuric acid, phosphoric acid, p-toluenesulfonic acid, and the like, with hydrochloric acid being particularly preferred. Reaction solvents include aliphatic hydrocarbons such as n-hexane, isooctane, and petroleum ether, aromatic hydrocarbons such as benzene, toluene, and xylene, alicyclic compounds such as cyclohexane and tetralin, and halogenated hydrocarbons such as carbon tetrachloride. , low polarity solvents such as cyclic ethers such as dioxane [Yield rate (2030
) 3 or less], particularly favorable results are obtained. The silica alumina, silica gel and zinc chloride used in carrying out the method of the present invention may be dried by calcination, if necessary.

The amount of silica alumina and/or silica gel used is preferably about the same amount as that of trimethylhydroquinone, and zinc chloride may be used in a catalytic amount. Furthermore, it is preferable to add protonic acid in an amount of about 0.5 to 5.0% of the phytols. Reaction conditions vary depending on the combination of raw materials, solvents and catalysts, but usually 50 to 120 qo
, about 1 to 5 hours is sufficient, but is not particularly limited to these ranges. The reaction product can be purified, for example, by washing the reaction mixture with water, washing with alkali water, dehydrating the solvent, acetylating if necessary, and then performing high vacuum distillation. According to the method of the present invention, crude dl-
High purity dl-Q-tocopheryl acetate can be obtained by simply subjecting Q-tocopherol acetate to two rounds of vacuum distillation, and this method can be said to be commercially extremely advantageous.

In order to show the superiority of the method of the present invention, a comparison with the conventional method is as follows. First, isophytol 25.0 pm,
The resulting dl-
After acetylating Q-tocopherol by a conventional method, 16.5 to 175 qo/8×10-3 leg H was obtained by vacuum distillation.
A fraction of g was collected. The purity was measured by gas chromatography using n-dotriacontane as an internal standard. The test results are shown in Table 1 below. Table 1 Examples will be given to specifically explain the method of the present invention, but the present invention is not limited to the following examples.

Example 1 Trimethylhydroquinone 13.5% to toluene
Silica alumina was dissolved in a nitrogen stream for 13.5 min.
After adding 6.0 mm of zinc chloride and 0.5 mm of concentrated hydrochloric acid (35% hydrochloric acid) and warming the reaction system to 85:00, 25.0 mm of isophytol was added dropwise over about 20 minutes.

After dropping, the mixture was kept at the same temperature for about 4 hours and then released. Next, 100% of toluene is added to the reactants and mixed. Insoluble matter was filtered through a furnace, and the furnace liquid was washed sequentially with a mixture of 3% caustic soda and 1% hydrosulfite soda, water, and saturated saline, and after dehydration over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain dl-Q.
Obtained 37.0 tons of tocopherol (yield 99.8%)
. Next, 25.0 g of the obtained dl-Q-tocopherol was dissolved in 50 g of acetic anhydride, 12.5 g of sodium acetate and 1.25 g of metal zinc powder were added, and 95 to 100 g of dl-Q-tocopherol was dissolved.
Approximately 3. After acetylation by diaphragm, extraction was performed by adding 200% of n-hexane, and the extract was sequentially washed with 1% caustic soda, water, and saturated saline, dried over magnesium sulfate, and extracted with n-hexane. Distillation under reduced pressure yields 26.2 g of crude dl-Q tocopheryl acetate. Next, the obtained crude dl-Q tocopheryl acetate was vacuum distilled, and 16
5-175 pm 0 no 8 x 10-3 ribs Hg classification 20.
Get 5 evenings. The purity of this product is 97.3%, and the distillation yield is 78.0%. Example 2 Trimethylhide.

13.5% of quinone was dispersed over 10% of carbon tetrachloride, 13.5% of silica gel, 6.0% of zinc chloride and 0.5% of concentrated hydrochloric acid (35% hydrochloric acid) were added under a nitrogen stream to reduce the reaction system to 780%.
After flooding with 0.0 ml, 25.0 ml of isophytol was added dropwise over about 2 minutes. After dropping, the mixture was kept at the same temperature for about 4 hours, and then allowed to cool. Add 100 ml of carbon tetrachloride to the reactants and mix.

The insoluble matter was heated in a furnace, and the furnace solution was washed sequentially with a mixture of 3% caustic soda and 1% hydrosulfide soda, water, and saturated saline.
After dehydration over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 36.0 g of dl-Q-tocopherol (yield: 99.
．． 1%, purity 95.3%). Next, 25.0 g of the obtained dl-Q tocopherol was dissolved in 50 g of acetic anhydride,
To this was added 12.5 tons of sodium acetate and 1.5 tons of metal zinc powder.
Add 25 days of heat and heat at 95-100℃ for about 3. After acetylation by performing a periodic process, the desired product was converted into 1-hexane 20
Extract by adding 0'. The extract was washed sequentially with 1% caustic soda, water, and saturated saline, and dried over magnesium sulfate.
The n-hexane was distilled off under reduced pressure to obtain 25.8 g of crude dl-Q-tocopheryl acetate. Then the crude dl-Q obtained
-Vacuum distillation of tocopheryl acetate 165-175
``0/8 x 10-3 plate Hg of 19.6 pieces of real crab were obtained (distillation yield 76.0%, purity 96.8%).

Claims (1)

[Claims] 1. A method for producing high purity dl-α-tocopherol, which comprises condensing trimethylhydroquinone and phytols in the presence of silica alumina and/or silica gel, zinc chloride and protonic acid.