JPS604183B2 - α-tocopherol synthesis method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for synthesizing Q-tocopherol (5,7,8-trimethylcol) represented by the following chemical formula (1).

Tocopherol congeners are naturally occurring such as Q, B, y, 6, etc.6
It is known that seeds exist, but all of them are nuclear 6
It is a substituted chroman with a phenolic hydroxyl group in the position.

It is well known that Q-tocopherol (5,7,8-trimethyltocol) has high vitamin E activity and is widely used in the medical and pharmaceutical fields. Q tocopherol is tocol, 2-methyl-2-(4.8.1
5 of 2-trimethyl-tridecyl)-6-chromanol
・It has methyl groups at the 7 and 8 positions and is the substance with the highest vitamin E activity among tocopherol analogues, but 8-1, y
Non-Q-tocopherols such as - or 6- are substances lacking one or two of these methyl groups.
That is, 8-tocopherol is 5,8-dimethyltocol, y-tocopherol is 7,8-dimethyltocol,
Bi-2 tocopherol is 5,7-dimethyl tocol, and ri-tocopherol is 7-methyl tocol. Also z
Tocopherol [2,5,8-trimethyl-2-(4
・8.12-4.8.12-trimethyltrideca-3.
Unsaturated side chain-chromanol compounds such as 7,11trienyl)-chroman-6-ol] are also considered to be a type of non-Q-tocopherol. *These tocopherols are particularly abundant in vegetable oils, and homologs of 2 and 3 are often mixed together.

The biological activities of these tocopherol analogs differ significantly, and Q tocopherol is known to have the highest vitamin E activity of these tocopherol analogs. However, the proportion of Q tocopherol in vegetable oils that are useful as a resource for these tocopherol analogs is often low; for example, in soybean oil, the content of tocopherol analogs is 10%.
, y tocopherol 60%, 6 tocopherol 30%
It is like %. Therefore, it is extremely necessary and significant to obtain Q-tocopherol with high vitamin E activity by introducing one or two methyl groups into the chroman nucleus of these naturally abundant non-Q-tocopherols. It is.

It is an object of the present invention to convert non-Q-tocopherols with low vitamin E activity into Q-tocopherols with high vitamin E activity, and to carry out this conversion easily and in high yields. The present inventors have conducted extensive research on a method for converting non-Q-tocopherols into Q-tocopherol by introducing a methyl group into the chroman nucleus, and as a result, they have completed the present invention. That is, the present invention is directed to the following general formula (1), where A and B represent hydrogen atoms, or R, R2 and R3 forming a bond with AB represent a hydrogen atom or a methyl group.

However, when R, R2 and R3 are both a methyl group and a hydrogen atom, a non-Q-tocopherol mono or dimethyl tocol alone or a mixture containing two or more thereof is used under catalytic reduction conditions. Q-tocopherol is obtained by reacting it with formaldehyde in the presence of an acid or its derivative.
Raw non-Q tocopherols may be used regardless of their purity.

In nature, non-Q-tocopherols often coexist with Q-tocopherol, but in carrying out the method of the present invention, the coexistence of Q-tocopherol does not hinder the reaction in any way. Therefore, in the method of the present invention, even a crude mixture obtained from vegetable oils can be used satisfactorily as a raw material. Examples of the shelf acid or its derivatives used as a catalyst in the present invention include normal shelf acid; anhydrous shelf acid; metascale acid; pyroscale acid; alkyl shelf acid esters such as methyl shelf acid, ethyl shelf acid, isopropyl shelf acid; phenyl shelf acid; Examples include polyphosphoric acid.

Although the present invention can be carried out without a solvent, aromatic hydrocarbons such as benzene, toluene, and xylene; aliphatic hydrocarbons such as hexane and cyclohexane; alcohols such as methanol, ethanol, and propanol; ethyl ether; Ethers such as isopropyl ether and dioxane;
The reaction can be carried out more smoothly by using harsh acids; ketones such as acetone and methyl ethyl ketone; and organic solvents such as alkyl acid esters such as methyl acid, ethyl acid, and isobutyl acid; Post-processing is advantageous.

In particular, alkyl side acid esters are suitable as solvents because they themselves also act as catalysts. However, the reaction is difficult to proceed in aqueous solvents such as aqueous alcohols, aqueous acetone, and aqueous dioxane.

Examples of formaldehyde used in the present invention include paraformaldehyde, gaseous formaldehyde, and an aqueous formalin solution, but adding paraformaldehyde as a solid to the reaction system is most suitable for smooth reaction. . It is also possible to use an aqueous formalin solution, but in that case, as mentioned above, the reaction is difficult to proceed in a solvent that can be arbitrarily mixed with water, such as acetone or dioxane, so a hydrocarbon solvent that is difficult to mix with water should be selected as the solvent. Should. The catalytic reduction operation in the present invention is preferably carried out at an initial pressure of 30 to 100 k9/ground, particularly 50 kg'
It is preferable that the catalyst be around the following, and as the catalyst to be used, those used in normal catalytic reduction operations, such as nickel-based, palladium-based, platinum-based, etc., can be used. The method of the present invention does not isolate the hydroxymethylated product produced as an intermediate outside the reaction system and moves on to the next operation under reducing conditions, thus avoiding side reactions in the field of unstable hydroxymethylated products. Improvements were observed in the Q-conversion rate and the degree of coloration of the product.

That is, the conventional method of isolating the hydroxymethylated product and then reducing it to obtain Q-tocopherol, such as U.S. Pat. No. 2,640,058 (L.
), the conversion rate of y-tocopherol to Q-tocopherol was at most 75% as a result of additional testing, and the color of the product also showed a red light color. On the other hand, in the method of the present invention, the conversion rate of Q-conversion from y-tocopherol was 97.3%, and the coloring of the product was improved to pale yellow. Therefore, the present invention relates to a method for obtaining Q tocopherol, which has a high commercial value, in a high yield (high arsenicization rate).

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

Example 1 10 days of d-6 tocopherol (purity 95.0%), 5 days of bara formaldehyde, 5 days of regular acid, 5 days of methyl acid
0 and palladium and carbon 500 and 9 were charged into an autoclave, and a catalytic reduction operation was performed for 4 hours under the conditions of an initial pressure of 50 k9/s and 200 qo.

After the reaction is completed, the reaction mixture is filtered, and 50% of benzene is added to the furnace liquid.
was added, washed three times with hot water, and then condensed to obtain 10.4 ml of pale yellow oil. Analysis of this product by gas chromatography did not confirm the presence of 6-tocopherol, a raw material. Also, by the Emery-Engel method, d
The purity of tocopherol was 93.8%. (Q-
(tocopherol conversion rate 97.0%) Example 2 d-6 tocopherol (purity 95%) 10 taparaformaldehyde 5 tapraformaldehyde
5 evening methanol
50 Z Palladium Carbon
9 or more of 500 were reacted according to Example 1.

10.2 hours of pale yellow oil is obtained.

Purity 70.9% Conversion rate 71.9% Example 3 d-6 tocopherol (purity 95%) 10 tapara formaldehyde 5 tap B203
5 evening methanol
50 Z Palladium Carbon
9 or more of 500 were reacted according to Example 1.

10.3 hours of pale yellow oil is obtained.

Purity 94.2% Conversion rate 96.4% Next, Examples 4 to 12 will be described and shown.

However, paraformaldehyde is used as formaldehyde, and the reaction treatment method is carried out in accordance with Example 1.

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Claims (1)

[Claims] 1 The following general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, A and B are hydrogen atoms at the same time, or A
-B means forming a bond, R_1, R_2
and R_3 means a hydrogen atom or a methyl group. However, cases where R_1, R_2 and R_3 are all methyl groups or hydrogen atoms are excluded. ) Mono- or dimethyl tocol alone or 2
A method for synthesizing α-tocopherol represented by the following chemical formula ▲ There are mathematical formulas, chemical formulas, tables, etc. .