JPS59190987A - Preparation of dl-alpha-tocopherol - Google Patents

Abstract

PURPOSE:To obtain the titled compound in high yield, at low temperature, by carrying out the condensation of trimethylhydroquinone with isophytol, etc. in the presence of ethyl acetate as a reaction solvent, using zinc chloride, concentrated hydrochloric acid and acetic acid as the condensation catalyst. CONSTITUTION:The objective dl-alpha-tocopherol is prepared by the condensation reaction of 2,3,5-trimethylhydroquinone with isophytol or phytol preferably at 25-30 deg.C in the presence of ethyl acetate as the reaction solvent, using zinc chloride, concentrated hydrochloric acid (preferably 35-36% concentration) and acetic acid (preferably glacial acetic acid) as the condensation catalyst. If necessary, metallic powder such as metallic zinc, iron, etc. may be added to the reaction system to suppress the generation of colored impurities produced during the reaction. The preferable molar ratio of acetic acid to hydrochloric acid is 1.5-2, that of zinc to trimethylhydroquinone is 0.8-2, and that of acetic acid and hydrochloric acid to zinc chloride is 0.3-0.5.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides α-1
- Concerning a method for producing coferol.

Conventionally, in the production of α-tocopherol, trimedelhydroquinone and isophytol or soybean chloride are combined in the presence of a Friedel-Crafts type acidic catalyst such as zinc chloride, aluminum chloride, or trij-notincline as a condensation catalyst. Many reactions are known to be carried out using organic solvents under heating and reflux.

However, if the reaction is carried out at high temperature under reflux, by-products that are difficult to separate will be produced and the yield will also be reduced.

In this method, JP-A No. 53-144574 uses zinc chloride and hydrochloric acid as condensation catalysts, and in the presence of a halogenated lower aliphatic hydrocarbon solvent such as dichloromethane as a reaction solvent, a comparison is made at room temperature. A method is disclosed that is carried out at extremely low temperatures.

In our follow-up test of the above-mentioned method of JP-A-53-144574, it was found that the reaction progressed even at room temperature to 30"C, the production of by-products was relatively small, and good results were obtained. The amount of α-tocopherol in the product is at most 96
% yield, which was still unsatisfactory.

As a result of intensive research into a method for producing α-tocopherol, the present inventor discovered that by selecting and using a specific catalyst and solvent from among various known catalysts and solvents, the reaction could be carried out at a low temperature. The present invention was achieved by discovering an industrially satisfactory method that allows α-tocopherol to be obtained in a high yield.

That is, the present invention uses zinc chloride, concentrated hydrochloric acid, and acetic acid as a condensation catalyst, and in the presence of ethyl acetate as a reaction solvent.
．． Reacting 5-trimethylhydroquinone with inphytol or efytol.

This is a characteristic method for producing dA'-α-tocopherol.

In the method of the present invention, the condensation catalyst used is zinc chloride in combination with concentrated hydrochloric acid and acetic acid. As concentrated hydrochloric acid, hydrochloric acid with a concentration of 35 to 36% is preferable, and dilute acid has a poor yield. Further, dry enriched hydrogen gas may also be used. As the acetic acid, glacial acetic acid is preferable;
It is used in an amount of 3 moles, preferably 15 to 20 times. In addition, acetic acid and hydrochloric acid are preferably used in an amount of 0.3 to 0.08 mol per 1 mol of zinc chloride.
Use molar amounts.

In the present invention, the reaction temperature can be in the range of room temperature to 30°C. Preferably, the temperature is maintained at 25 to 30°C, and isophytol or phytol is added dropwise to carry out the reaction in an ethyl acetate solvent.

In the method of the present invention, ethyl acetate is used as a solvent, and in the present invention, zinc chloride, acetic acid, and concentrated hydrochloric acid are used together as a condensation catalyst, known solvents such as benzene, 1-toluene, ligroin, and halogenated Even if aliphatic hydrocarbon solvents are used, no effect can be achieved.

Additionally, in order to suppress the coloring impurities generated during the reaction in the production of α-tocopherol, a method is known in which metal powders such as metallic zinc or iron are added and the reaction is carried out in a reducing atmosphere. Perhaps because of the high affinity between the generator hydrogen generated at that time or the metal powder and ethyl acetate, when the metal powder is added to suppress colored by-products and the reaction is carried out, the use of ethyl acetate also has a decolorizing effect. Thick. However, if necessary, a stiff metal powder may be added to the reaction system.

Benefits of the method of the present invention 21. The crude a-1-copherol is
After washing with water and separating the layers, the ethyl acetate oil layer was subjected to distillation to obtain highly purified purified α-tocopherol according to method N.

Examples are shown below.

(5) Example 1 125 g of 2.3.5-trimethylhydroquinone (Q,
082 mol], zinc chloride 1], 2. ? (0,082 mol) glacial acetic acid 1.0,! 7 (0,017 mol), concentrated hydrochloric acid (36% concentration) 1.0 g (0.
Isophytol at ゛C 24.5. ! ? (965% purity,
0080 mol) was added dropwise over 3 hours. Stirring was continued for another 1 hour to cause a ripening reaction and the reaction was completed. The reaction mass was washed with water, and after separation, the ethyl acetate oil layer was desolventized and concentrated using a rotary evaporator. 37. og oily residue (crude α-
Tocopherol) 2 was obtained. GC method (Note-1)
The purity of α-1-copherol was analyzed by
14% (Nfar), theoretical yield 98.1%0
vs.

(Note-1) Based on gas chromatography internal standard method vitamin E determination method (National Homulary Vol. 14 (6)) GC column, 10% silicon SF-301m internal standard substance; l-'l-reacontane comparative example 1 solvent The reaction, post-treatment, and analysis were carried out in exactly the same manner as in Example 1, except that dichloromethane was used instead of ethyl acetate.The results were as follows.

Oily residue after desolvation 35.8.9 GC5 method purity 90.6 wt% Theoretical yield 9B, 1% Comparative Example 2 The procedure was carried out except that only zinc chloride and concentrated hydrochloric acid were used as catalysts and glacial acetic acid was not used. The reaction, post-treatment and analysis were carried out in exactly the same manner as in Example 1. The results were as follows.

Oily residue after desolvation 350g G, C, method purity 89.0wt% theoretical yield
904% Comparative Example 3 A reaction was carried out in the same manner as in Example 1 except that only zinc chloride and glacial acetic acid were used as catalysts and no hydrochloric acid was used. After completion of the reaction, washing with water, separation, and removal of solvent and concentration were carried out in the same manner as in Example 1. However, since a solid substance precipitated in the oily residue, ethyl acetate was added again to make a homogeneous ethyl acetate solution. Perform d-tocopherol in f1'' similar to 1 (
As a result, the cc quantitative analysis was 11. The results were as follows.

Ethyl acetate solution x3o6g G, q method Purity 5.11wt% Theoretical yield
194% Patent applicant Mitsui Toatsu Chemical Co., Ltd.

Claims (2)

[Claims] (1) 2.3.5-1~limethylhy-l-quinone,
By condensing with isophytol or soil, d
l-α ~ dl-α characterized in that when tocopherol is produced, enriched zinc, concentrated hydrochloric acid and acetic acid are used as a condensation catalyst, and the reaction is carried out in the presence of an ethyl acetate reaction solvent.
- A method for producing tocopherol. (2) The method according to claim 1, wherein acetic acid is used 1 to 3 times by mole relative to hydrochloric acid.