JPS5844671B2 - Alpha-tocophero-Renoseizouhou - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an improved method for producing α-tocopherol, more specifically, it involves condensing trimethylhydroquinone with phytols in the presence of stannic chloride and at least one protonic acid. Regarding the method.

Conventionally, the method for producing α-tocopherol is a method using zinc chloride and acidic potassium sulfate (Japanese Patent Publication No. 45, No. 2314).
6), a method using zinc chloride and hydrogen halide (Japanese Patent Publication No. 45-21835), a method using submerged chloride and a nitro compound (Japanese Patent Publication No. 47-22574), a method using boron trifluoride and an acid (Japanese Patent Publication No. 47-22574), (Japanese Patent Publication No. 47-8821), method using phytyl chloride and acid (Japanese Patent Publication No. 48-8821)
48872), a method using an inorganic solid acid (Japanese Unexamined Patent Publication No. 48872),
9-42672), a method using iron, iron chloride and hydrogen chloride (Japanese Unexamined Patent Publication No. 47-14176), and a method using tin chloride and hydrogen chloride gas (Japanese Unexamined Patent Publication No. 45-21712).

However, α-tocopherol obtained by these production methods has isomers as by-products as impurities, and it is impossible to completely remove these isomers even by high-vacuum distillation, so it is not possible to achieve high purity. There is a drawback that the product cannot be obtained.

For example, in the case of sulfuric acid, a large amount of impurities in the low boiling point category and high boiling point category are produced as by-products, and in the case of zinc chloride and acidic potassium sulfate or tin chloride and hydrogen chloride gas, impurities in the low boiling point category are also produced as by-products.

When zinc or salt chloride is used, it is difficult to completely recover it, even though the zinc itself and the cadmium contained therein are pollutants.

In order to overcome these drawbacks, the present inventor conducted various studies on catalysts and came up with the invention of a method for producing α-tocopherol with high purity and without the risk of causing pollution.

According to the findings of the present inventor, it is estimated that the production of α-tocophenol by a Lewis acid and protonic acid mixed catalyst system involves first the dehydration condensation of trimethylhydroquinone and phytol by the Lewis acid, and then the cyclization reaction by the protonic acid. be done.

The isomers (impurities) observed in gas chromatography are thought to be mainly caused by isomerization of phytols by protic acids.

This is because when only a protonic acid (for example, sulfuric acid) is used, the ratio of isomers increases, and even in a combination of a Lewis acid and a protonic acid, adding the protonic acid and the Lewis acid in that order increases the isomer ratio. This can be seen from the increase.

Therefore, when producing high-purity α-tocopherol, it is appropriate to first condense it with trimethylhydroquinone using a suitable Lewis acid catalyst and then carry out the cyclization reaction.

It is desirable to use a catalyst that does not cause isomerization of phytols as the Lewis acid, and using a large amount of protic acid causes an increase in isomers. It is necessary to make it happen.

As a result of further various studies based on these points of view, the present inventor found that the use of stannic chloride as the Lewis acid and p-toluenesulfonic acid, methanesulfonic acid, acidic potassium sulfate, and sodium chloride as the protonic acid is optimal. It was found that good results could be obtained.

That is, the method of the present invention uses stannic chloride and protonic acid as a catalyst in producing α-tocopherol by condensing phytols and trimethylhydroquinone in the presence of a solvent.

Phytols, which are one of the starting materials of the present invention, include:
Phytol, inphytol, its halides such as phytyl chloride, or its alkyl esters such as phytyl acetate, etc. may be used, and as the protonic acid which is one of the composite catalysts, p-toluenesulfonic acid, methanesulfonic acid, trifluoro Examples include organic acids such as acetic acid, sodium or potassium hydrogen sulfate, inorganic acids such as sulfuric acid, or salts thereof, and especially at least one selected from methanesulfonic acid, p-toluenesulfonic acid, sodium or potassium hydrogen sulfate. When this compound is used, almost no isomers are produced and the yield is extremely high.Also, the quantitative ratio of the composite catalyst is approximately 0.1 to equimole of stannic chloride to 1 mole of trinotylhydroquinone. It is most effective when the protonic acid is used in an amount of about 0.01 to 0.1 mol, that is, the stannic chloride is used in an amount of about 5 to 30 times the protonic acid.

The amount of the mixed acid condensing agent used varies depending on the required reaction time, and if a shorter time is required, the amount of the acid condensing agent may be increased, but the maximum value is preferably equimolar to trimethylhydroquinone. .

Solvents used in the present invention include n-hexane, n-
Aliphatic hydrocarbons such as hebutane, isopropyl ether,
Examples include ethers such as tetrahydrofuran and dioxane, aromatic hydrocarbons such as benzene, toluene, and xylene, esters such as ethyl acetate and butyl acetate, and carboxylic acids such as acetic acid and propionic acid. The solvent is not limited to these exemplified compounds as long as it is an inert solvent.

Next, in one embodiment of the present invention, a mixture of trimethylhydroquinone and an inert solvent, stannic chloride, and at least one protonic acid is heated and refluxed, and Infitol is added dropwise. Once complete, heat and reflux for a sufficient time to form alpha-tocopherol.

The order of addition can be changed in the reaction operation, and the most effective method is to add phytols and then protonic acid to trimethylhydroquinone, stannic chloride, and an inert solvent.

Furthermore, the stannic chloride used in the present invention can be precipitated and recovered as a salt by adding a base such as triethylamine or pyridine after the completion of the reaction.

The α-tocopherol obtained by the method of the present invention has only traces of impurities, and is crude α-tocopherol with a purity of 95% or more, and by distillation, the purity can be increased to 99%.
It is possible to increase the coloring even further, and almost no coloring is observed.

Furthermore, the stannic chloride used as a catalyst can be easily quantitatively recovered as a precipitate by adding a base such as triethylamine or pyridine, as mentioned above, so it is extremely excellent in terms of preventing pollution. .

First, we will compare the results obtained with the present invention and other methods.
Shown in the table.

In addition, the results of gas chromatography analysis are shown in Figures 1 to 4.
As shown in the figure.

In addition, the purity before distillation in the above table was determined by gas chromatography.

The product of the conventional method was pale yellow in color, whereas the product of the present invention was colorless.

Example 1 30 g of trimethylhydroquinone and 10 g of stannic chloride
g was suspended in 40rfLl of ethyl acetate, and the temperature was adjusted to 50~
The temperature is raised to 60° C., 60 g of infitol and 0.5 g of p-toluenesulfonic acid are added, and the mixture is refluxed for 3 hours.

After cooling the reaction solution, it is washed with alkali and water in sequence, and the solvent is distilled off.

86 g of crude α-tocopherol is obtained as a yellow oil (yield 99%).

The purity of this product by the cerium sulfate method is 96.4%, and the purity by gas chromatography is 95.8%.
%.

Crude α-tocopherol was purified by vacuum distillation, b, po
, 63180 to 200°C.

78 g of dl-α-tocopherol are obtained as a yellow transparent viscous oil (yield 90%').

The purity of this product by the cerium sulfate method is 99.9%, and the purity by gas chromatography is 99.6%.
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Example 2 Trimethylhydroquinone 30,9, stannic chloride log
and 0.5 g of methanesulfonic acid are suspended in 50 ml of isopropyl ether, the temperature is raised to 50-60' and 60 g of infitol are added.

After refluxing for 4 hours, the reaction solution was returned to room temperature and 15 g of pyridine was added.

The generated precipitate was filtered, and the same procedure as in Example 1 was carried out to obtain crude α.
- Obtain 85 g of Tocoferano L' (yield 98%).

The purity of this product by the cerium sulfate method is 97.0%, and the purity by gas chromatography is 95.3.
%.

Example 3 Infitol 60,9. 10 g of stannic chloride, 30 g of trimethylhydroquinone and potassium hydrogen sulfate i, o
, y are suspended in 60rrLl of n-hexane and refluxed for 4 hours.

Hereinafter, in the same manner as in Example 2, crude α-tocopherol 85
g (yield 98%).

The purity of this product by the cerium sulfate method is 96.8%, and the purity by gas chromatography is 95.4%.
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Example 4 60 g of phytol, 10 g of stannic chloride and 30 g of trimethylhydroquinone are suspended in 50 ml of ethyl acetate, the temperature is raised to 60-70°C and 1.
Add 0g.

After refluxing for 3 hours, 84 g of crude α-tocopherol was obtained in the same manner as in Example 1 (yield 97%).

The purity of this product by the cerium sulfate method is 96.0 or more, and the purity by gas chromatography is 95.2.
%.

Example 5 64 g of phytyl chloride, 7 g of stannic chloride, 30 p of trimethylhydroquinone and 1.0 g of p-toluenesulfonic acid are suspended in 40 ml of toluene and refluxed for 2.5 hours.

Hereinafter, in the same manner as in Example 1, crude α-tocopherol 82
g (95% yield).

The purity of this product by the cerium sulfate method is 95.9%, and the purity by gas chromatography is 95.0%.
It is.

Example 6 69 g of phytyl acetate, 12.9 g of stannic chloride, and 30.9 g of trimethylhydroquinone were suspended in 150 ml of toluene, heated to 50-60°C, added with 1.2 ml of p-toluenesulfonic acid, and further stirred for 4 hours. Heat to reflux.

Hereinafter, 92 g of crude α-tocopherol was prepared in the same manner as in Example 2.
(yield 96%).

The purity of this product by the cerium sulfate method is 97.1%, and the purity by gas chromatography is 95.4.
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[Brief explanation of drawings]

FIG. 1 is a gas chromatograph of α-tocopherol acetate obtained by the sulfuric acid method, and FIG. 2 is a gas chromatograph of α-tocopherol acetate obtained by the zinc chloride and acidic potassium sulfate method. Figure 3 is a gas chromatograph of α-tocopherol acetate obtained by the stannic chloride and hydrogen chloride gas method, and Figure 4 is a gas chromatograph of α-tocopherol acetate obtained by the stannic chloride and p-toluenesulfonic acid method. - Gas chromatograph of tocopherol acetate.

Claims (1)

[Claims] 1. When producing α-tocopherol by condensing trimethylhydroquinone and phytols, a specific Lewis acid consisting of stannic chloride, protonic acid, methanesulfonic acid, p-toluenesulfonic acid, and sulfuric acid aqueous alkali metal salt is used. A method for producing α-tocopherol, characterized by using a composite catalyst in combination with a compound of