JPS6045195B2 - Method for producing dl-α-tocopherol - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing d-1-α-tocopherol, and more specifically, in condensing trimethylhydroquinone and phytol, a metal chelate sulfonic acid resin having Lewis acid activity ( (hereinafter referred to as metal chelate resin), high purity d, I-α
The goal is to obtain tocopherol.

The conventional method for producing d.1-α-tocopherol is to react trimethylhydroquinone and phytols in an organic solvent under a protonic acid catalyst such as p-toluenesulfonic acid or sulfuric acid, or a composite catalyst of a Lewis acid and a protonic acid. Condensation methods are commonly practiced.

With carprotonic acid catalysts, d・1-α is generally obtained.
One drawback is that the purity of the tocopherol is low. Furthermore, in order to obtain a purity of d·1-α-tocopherol, a composite catalyst of a Lewis acid and a protonic acid must be used. However, since Lewis acids generally contain many metal halide compounds, their use is currently limited due to post-reaction treatment and contamination of heavy metals into products. Also, a method is known in which a cation exchange resin is used for the purpose of easily separating the catalyst from the product, but this method has the drawback that the catalyst is insoluble and the catalyst activity is extremely low.
As a result of various studies to solve these conventional drawbacks, the present inventors have achieved the object of the present invention by carrying out the condensation reaction between trimethylhydroquinone and phytol in the presence of a metal chelate resin. This is what we discovered.

According to the findings of the present inventors, it is presumed that the reaction in the method of the present invention proceeds by the mechanism shown below. (
1) Polymer-(SO3H)nfMC1n→J
Polymer-(SO3)nM+nHC1↑(3)P
OlyrTler-(SO3H)n+MCln→POl
yTTler-(SO3)RIM+NHCl↑ (M represents a metal atom, n represents an integer) In other words, as is clear from the above formula, the present invention uses a metal chelate resin as a medium during the reaction to form a homogeneous complex of a Lewis acid and a protonic acid. It acts as a catalyst and, after the reaction, is recovered as a heterogeneous solid substance that is insoluble in solvents.

Therefore, the method of the present invention has the advantage that it can be expected to have the same effect as the combination using a homogeneous catalyst. In fact, the purity and yield of d·1-α-monotocopherol synthesized using the metal chelate resin of the present invention show no decrease at all compared to when the corresponding Lewis acid is used. The phytyl halide used in the method of the present invention includes phytyl chloride, phytyl bromide and the like.

Examples of resins used for metal chelate resins include sulfonic acid resins such as Amperlite IR-121 (manufactured by Organo Co., Ltd.), Amperlyst XN-1004 (manufactured by Organo Co., Ltd.), and Amperlyst 15 (manufactured by Organo Co., Ltd.). Among them, Amperlyst 15 is the most excellent in terms of heat and solvent stability. Iron is the metal atom in metal chelate resin. zinc. tin. aluminum. indium. potassium. It has Lewis acid activity through ion exchange with titanium, etc. Benzene is the solvent. toluene. Aromatic compounds such as xylene. Isopropyl luteal. Tetrahydrofuran. Ether solvents such as dioxane, and other acetonitrile. Ethyl acetate. Dimethylformamide. All solvents used in general organic reactions, such as dimethyl sulfoxide, can be used, but considering the repeated reuse of the catalyst, they are relatively inefficient.
Active benzene. Preference is given to using toluene.
The amount of metal chelate resin used is 0.1 to 2. A small amount may be sufficient, and the amount may be increased as appropriate. The method for preparing the metal chelate resin used in the present invention is to first dissolve the metal halide in an organic solvent, then add an equivalent amount (exchange volume) of the resin to the metal halide, and leave it at room temperature for 10 to 2 minutes. , can be adjusted by filtering and drying.

It was confirmed by atomic absorption spectrum that the obtained metal chelate resin contained a theoretical amount of 7 metal ions. Next, to specifically explain the method of the present invention, the most common method is to first put a solvent into a reaction vessel, then add trimethylhydroquinone, stir and dissolve it, and then gradually add metal chelate resin and then phytyl halide. However, it is of course not limited to this method. The metal chelate resin added to the reaction system can be filtered off after the reaction is completed and, if dried, can be reused in the next reaction. Also, the reaction conditions are not determined depending on the combination of raw materials, metal chelate resin, and solvent, but usually a reaction time of about 1 to 3 hours at 70 to 8σC is sufficient, but there are no conditions that are particularly limited. There isn't. The reaction product is treated and distilled using a conventional method.
Determine purity by GLC. As is clear from the reaction mechanism described above, the purpose of the method of the present invention can be sufficiently achieved with a metal chelate resin alone, but it is necessary to include a catalytic amount of a protonic acid such as p-toluenesulfonic acid or methanesulfonic acid in the reaction system. This allows the reaction to proceed smoothly.

According to the method of the present invention, during the reaction, the catalyst acts as a homogeneous system using the metal chelate resin as a medium, and after the reaction is completed, the metal chelate resin can be easily removed from the reaction system by means such as filtration. This method has various advantages such as increasing the speed, preventing metal chelate resin from being mixed into the product, and allowing the metal chelate resin to be reused as it is in the next reaction.

EXAMPLES Next, the present invention will be described with reference to examples to further illustrate the present invention, but the present invention is not limited to the following examples.

Example 1 Trimethylhydroquinone 30.4y (0.2 mol),
62.8y (0.2 mol) of phytyl chloride and 30fI of zinc chelate resin are added to 200ml of benzene, and the mixture is heated under reflux for 3 hours.

After the reaction, the metal chelate resin was filtered off, the filtrate was washed with 10% sodium hydroxide and saturated saline, and then distilled (Bp.2O
O~210℃/0.1? Hg) to obtain the desired product [yield: 73y1, yield: 85%, purity: 97.4% (GLC)].
Note that the metal chelate resin that has been filtered and dried can be used again as it is in the next reaction.

Reference Example Preparation of zinc chelate resin 13.6y (0.1 mol) of zinc chloride was mixed with 100% of ethyl acetate.
m1, then Amperlyst 15 (H type) (4
．． 3-4.6m1q1y) Add 60y.

Hydrogen chloride is actively generated, but it remains at room temperature for 1
Leave it overnight. The produced zinc chelate resin is filtered through a glass filter, thoroughly washed and dried with ethyl acetate and then acetone to remove generated hydrogen chloride and excess zinc chloride (yield: 62 f1). Note that other metal chelate resins can also be prepared in exactly the same manner.

Example 2 Trimethylhydroquinone 30.4f (0.2 mol),
Predetermined amounts of phytyl halide, metal chelate resin 30y and p-toluenesulfonic acid 0.3y (a) shown in Table 1.
002 mol) was added to 200 mt of benzene and heated under reflux for 3 hours.

After the reaction, the same treatment as in Example 1 was carried out to obtain d●1-α-tocopherol. Next, the filtered metal chelate resin was used repeatedly to carry out the reaction, and the results are shown in Table 1. Example 3 Trimethylhydroquinone 30.4f (0.2 mol),
Phytyl bromide 73.8f (0.2 mol), zinc chelate resin 30y and p-toluenesulfonic acid 0.3
Add f1 (0.002 mol) to 200 mt of benzene and heat under reflux for 2 hours.

After the reaction, the same procedure as in Example 1 was carried out to obtain d-1-α-tocopherol 76y (yield: 88.4%, purity: 98.2%).
). Example 4 Trimethylhydroquinone 30.4g (4). 2 moles)
62.8 g (0.2 mol) of phytyl chloride and:
Add 30 ml of tin chelate resin and 100 mt of acetonitrile, and heat to reflux for 1 hour.

After the reaction, d-1-α-tocopherol y was obtained by processing in the same manner as in Examples (yield: 82.6%, purity: 99.0%). Example 5 30.4 g of trimethylhydroquinone (0.2 mol) 73.8 fI (0.2 mol) of methyl bromide, 40 y of aluminum chelate resin and 0.0 mol of trimethylhydroquinone
．． 1f (0.001 mol) to isopropyl ether 1T
Add to ILL and heat to reflux for 3 hours.

After the reaction, it is treated in the same manner as in Example 1 to obtain d-1-α-tocopherol 65y (yield 75.6%, purity 94.1%).
Example 6 Trimethylhydroquinone 30.4y (a).
2 mol), 5 predetermined amounts of phytols, 30 y of metal chelate resin, and 0.3 mol (0.00 mol) of p-toluenesulfonic acid.
2 mol) was added to 200 ml of solvent and heated under reflux for 3 hours.

Claims (1)

[Claims] 1 d. characterized in that the bonding of trimethylhydroquinone and phytyl halide is carried out in the presence of a metal chelate sulfonic acid resin having Lewis acid activity.
Method for producing l-α-tocopherol.