JPS6035347B2 - Synthesis method of α-tocopherol - Google Patents

Description

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

More specifically, in the presence of an acid condensing agent and an inert solvent, 2
・In the synthesis method of Q-tocopherol, which involves condensing 3,5-trimethylhydroquinone and phytols, zinc chloride and phosphoric acids are used as acid condensing agents, and lower aliphatic hydrogen halide solvents are used as inert solvents. The present invention relates to a method for synthesizing Q-tocopherol, which comprises the following steps. Examples of the lower aliphatic hydrogen halide solvent used in the method of the present invention include dichloromethane, chloroform, carbon tetrachloride, and ethylene dichloride.

In particular, dichloromethane gave more favorable results in terms of purity and yield of the target product. Zinc chloride and phosphoric acids are used as the acid condensing agent in the method of the present invention, and examples of the phosphoric acids include phosphoric acid, poly-IJ phosphoric acid, etc., and the ratio of zinc chloride to phosphoric acids is 1 mole of zinc chloride. 0 phosphoric acids
．． 01 to 0.5 mol is desirable.

The phytols used in the present invention include phytol, isophytol, and their analogs.

In the present invention, the reaction proceeds at room temperature, and operations such as heating to reflux are not necessary.

Further, during the reaction, an organic acid such as acetic acid or propionic acid and zinc dust can be added to the reaction system to facilitate the reaction and improve the yield and quality of the target product. Conventionally, Q
As a method for producing tocopherol, when condensing 2,3,5-trimethylhydroquinoso with phytol and/or isophytol, zinc chloride is used as a condensing agent, and aliphatic compounds such as ligroin, tetralin, benzene, toluene, and xylene are used. A method of heating under reflux in a hydrocarbon solvent is known.

However, since these conventional methods require harsh reaction conditions such as heating under reflux at high temperatures, various undesirable by-products are produced, such as phytagene and its polymers, and reaction products of solvents and phytols. These substances are difficult to remove by purification by distillation, and therefore high yield and high purity Q-tocopherol cannot be obtained. 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 Q-tocopherol is significantly reduced. The present inventors conducted research to eliminate the above-mentioned drawbacks of the conventional Q-tocopherol production method and obtain high-purity Q-tocopherol in high yield. As a result of examining various condensation methods in order to search for a condensation method that does not cause the above-described conditions, the method of the present invention that provides highly pure Q-tocopherol in high yield was discovered.

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 20 to 40 degrees Celsius.

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

When this crude tocopherol is molecularly distilled using a conventional method, it has a purity of 98% or more [National Homilies].
Rally (National Formulary) No. 14
It was measured according to the vitamin E quantitative method using gas chromatography described on pages 758 to 762 of the publication. Good results were obtained in that purified Q tocopherol could be obtained in a yield of 96% or more. It was also confirmed on gas chromatography or thin layer chromatography that the by-products were less refreshing compared to conventional methods. In view of the above, an object of the present invention is to provide Q-tocopherol with higher purity and higher yield than conventional methods.

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

Note that the purity of the target substance Q tocopherol was measured according to the gas chromatography method of the National Homulary No. 14 Test, described above. Example 1 125% of 2,3,5-trimethylhydroquinone, 112% of zinc chloride, 5% of zinc powder, 350% of dichloromethane [
A mixed base of 30 liters of phosphoric acid and 30 liters of phosphoric acid was added, and 245 liters of isophytol (purity 98.1%) was added dropwise over 3 hours at 25 to 30 ounces, followed by condensation for 1 hour at the same temperature.

After the reaction, 50 parts of water was added, zinc chloride was removed, dichloromethane was distilled off at room temperature, and the resulting oil residue (crude Q tocopherol) was dissolved in 300 parts of toluene and 10 parts of methyl ethyl ketone. Washing with water, washing with alkali, and acetylation after washing with water were carried out. After washing with water, the mixture was concentrated to obtain 382.1 kg of Q tocopherol acetate as a pale yellow oil. Purity 96
．． 0%, yield 95.7 This product was subjected to molecular distillation to produce a colorless oily substance (purified Q-tocopheryl acetate) 357.9
An aqueous solution (purity 98.7%) was obtained. Example 2 2,3,5-trimethylhydroquinone 125 times, zinc chloride 112 times, zinc powder 5 times, dichloromethane 450 times,
10 parts of polyphosphoric acid (P.P.A.), 20 parts of acetic acid and 245 parts of isophytol (purity 98.1%) were reacted according to Example 1 to give 348.8 parts of crude Q tocopherol as a clear oil. Obtained.

Purity 95.3%, yield 95.2% This product was subjected to molecular distillation to produce purified Q-tocofe as a pale yellow oily substance. Rule 331.4
An aqueous solution (purity 98.1%) was obtained. Example 3 2,3,5-trimethylhyde.

125 parts of quinone, 112 parts of zinc chloride, 5 parts of zinc powder, 300 parts of dichloromethane, 30 parts of acetic acid, 15 parts of phosphoric acid and 245 parts of isophytol (purity 98.1%) were reacted according to Example 1 to give a pale yellow oil. 382.79 of crude Q-tocopheryl acetate was obtained. Purity: 96.7%, Yield: 96.6% Next, a reference example is given and compared with the present invention.

Reference example 1 125 units of 2,3,5-trimethylhydroquinone, 112 units of zinc chloride, 59 units of zinc powder, 300 units of dichloromethane
, 30% of acetic acid was mixed with a mixture of azaleas, and 245% of isophytol (purity 98.1%) was added dropwise at 25 to 300C over a period of 3 hours, and the mixture was further heated at the same temperature for 1 hour.

Claims (1)

[Claims] 1. A method for producing α-tocopherol by condensing 2,3,5-trimethylhydroquinone and phytols in the presence of an acid condensing agent and an inert solvent, in which zinc chloride is used as the acid condensing agent. and phosphoric acids, and α characterized by using a lower aliphatic hydrogen halide solvent as an inert solvent.
- A method for producing tocopherols. 2. The method for producing α-tocopherol according to claim 1, wherein the lower aliphatic hydrogen halide solvent is a solvent selected from dichloromethane, chloroform, carbon tetrachloride, and ethylene dichloride. 3. The method for producing α-tocopherol according to claim 1, wherein the phosphoric acid is phosphoric acid or polyphosphoric acid. 4. The method for producing α-tocopherol according to claim 1, wherein the phosphoric acid is phosphoric acid, and the lower aliphatic hydrogen halide solvent is dichloromethane.