JPH0689016B2 - Method for producing pentaacetylarbutin - Google Patents

Description

TECHNICAL FIELD The present invention relates to a novel method for producing pentaacetylarbutin.

Pentaacetylarbutin is not only an important intermediate in the production of arbutin, but also has useful properties such as an antioxidant effect by itself.

Arbutin has been known for a long time as a compound contained in the natural plant "Urushi", and due to its bactericidal ability, it is a compound included in the Japanese Pharmacopoeia. In addition, recently, it has been used for photographic purposes and has been applied to the cosmetic field by utilizing the bleaching action.

Conventional technical formula [In the formula, Ac represents an acetyl group. ] Acetylated tetraacetylarbutin represented by the formula [In the formula, Ac is the same as above. It is known to obtain pentaacetylarbutin represented by the formula

The above-mentioned raw material, tetraacetylarbutin, has been [In the formula, Ac is the same as above. ] Β-Pentaacetylglucose and hydroquinone represented by the above formula, using a catalyst if necessary, and using, for example, benzene as a solvent [Do
klady Akad.Nauk, SSSR, 86, 333 (1952)], a method using a xylene (MLWolfrom, A.Thompson, "Methods i
n Carbohydrate Chem. ", Vol.II, p211,1963), etc. However, these methods have the drawback that the yield is as low as about 50% or less as shown in Comparative Examples below. There is.

Further, conventionally, after producing tetraacetylarbutin by the above, it was once isolated and then acetylated to produce pentaacetylarbutin, so that the crystallinity of tetraacetylarbutin is not good at the time of isolation and purification of tetraacetylarbutin. Therefore, there is a problem that the loss due to the above is large and the yield of the target pentaacetylarbutin is further reduced. Therefore, conventionally, when producing pentaacetylarbutin from β-pentaacetylglucose, the total yield thereof was extremely low.

Problem to be Solved by the Invention An object of the present invention is to provide a novel and suitable method for producing pentaacetylarbutin, in which the above-mentioned drawbacks of the conventional method are eliminated.

Means for Solving the Problems As a result of intensive studies to obtain pentaacetylarbutin in high yield, the present inventors have found that mono- and / or polyethylene, particularly as a solvent, in the reaction of β-pentaacetylglucose with hydroquinone. When a glycol dialkyl ether is used, it is possible to produce tetraacetylarbutin usually in a high yield of at least 70% or more, and it is possible to produce tetraacetylarbutin and then directly acetylate it directly without isolation. The inventors have found that pentaacetylarbutin to be produced has no loss during the isolation and purification, and that pentaacetylarbutin is usually obtained in a high total yield of at least 80% or more, and has completed the present invention.

That is, in the present invention, β-pentaacetylglucose and hydroquinone are reacted with a mono- and / or polyethylene glycol dialkyl ether as a reaction solvent to produce tetraacetylarbutin, which is then directly acetylated without isolation. The present invention relates to a method for producing pentaacetylarbutin.

In the present invention, it is essential to use mono- and / or polyethylene glycol dialkyl ether as a reaction solvent. Examples of the mono- and / or polyethylene glycol dialkyl ether include those represented by the general formula: R ₁ —O (CH ₂ CH ₂ O) n—R ₂ [wherein R ₁ and R ₂ are the same or different and are an alkyl group having 1 to 4 carbon atoms]. Is shown and n shows the integer of 1-4. ] The one represented by the above formula is preferably used.

Further, as the mono- and / or polyethylene glycol dialkyl ether, in order to allow the reaction to proceed while distilling off the acetic acid by-produced during the reaction, the boiling point of acetic acid (118 ° C / 760 mmHg) is about 20 ° C or higher. Those having a high boiling point are preferable. That is, the boiling point is 140 ° C / 760mmH
It is preferably about g or more.

Particularly suitable mono- and / or polyethylene glycol dialkyl ethers include, for example, ethylene glycol dibutyl ether (C ₄ H ₉ OCH ₂ CH ₂ OC ₄ H ₉ , bp.203.6 ° C / 760 mmHg), diethylene glycol dimethyl ether (CH ₃ -O (CO _{2 CH 2 O) 2 -CH 3} , bp.161 ℃ / 760mmHg), diethylene glycol diethyl ether _{(C 2 H 5 -O (CH} 2 CH 2 O) 2 -C 2 H 5, bp.190 ℃ / 760mmHg), diethylene glycol propyl ether _{(C 3 H 7 -O (CH} 2 CH 2 O) 2 -C 3 H 7, bp.219 ℃ / 760mmHg), diethylene glycol dibutyl ether _{(C 4 H 9 -O (CH} 2 CH 2 O) _{2 -C 4 H 9, bp.254 ℃} / 760mmHg), tetraethylene glycol dimethyl ether _{(CH 3 -O (CH 2 CH} 2 O) 3 -CH 3, bp.276 ℃ / 760mmHg), tetraethylene glycol dibutyl ether ( _{C 4 H 9 -O (CH 2} CH 2 O) 4 -C 4 H 9, bp.330 ℃ / 760mmHg) , etc. It can be mentioned. In the present invention, at least one kind of mono- and / or polyethylene glycol dialkyl ether is used.

Further, in the present invention, β-pentaacetylglucose and hydroquinone are reacted in the above-mentioned specific reaction solvent to produce tetraacetylarbutin, and it is indispensable to perform asylation as it is without isolation. And That is, after the condensation reaction of β-pentaacetylglucose and hydroquinone, acetylation is continued in the same reaction system to give the target pentaacetylarbutin, usually 80%.
It can be obtained in a high yield of at least%. When tetraacetylarbutin is isolated and then acetylated,
As shown in Comparative Examples below, the total yield of pentaacetylarbutin is less than 70%.

The amount of hydroquinone used in the production method of the present invention is β-
The amount is usually 1 time or more, preferably 1.1 to 2.0 times, and particularly preferably 1.2 to 1.7 times the molar amount of pentaacetyl glucose. The amount of the specific reaction solvent used can be selected from a wide range, but β-
It is usually about 0.2 to 10 times by weight, preferably about 0.5 to 5 times by weight, relative to pentaacetyl glucose.
It is preferable that the temperature and pressure of the condensation reaction are usually under a temperature of about 90 to 120 ° C. and under a reduced pressure of about 3 to 150 mmHg. By setting such a reaction temperature and pressure, acetic acid, which is a reaction by-product, can be removed from the reaction system, and the reaction is promoted. The condensation reaction is preferably performed in the presence of a catalyst. Examples of the catalyst that can be used include paratoluene sulfonic acid, zinc chloride, phosphorus oxychloride, sulfuric acid, cation exchange resin, tin tetrachloride and the like, and the amount used is usually 0.05 to 5 of β-pentaacetylglucose. Appropriately about wt%. Further, the reaction time of the condensation reaction is usually appropriate to be about 0.5 to 10 hours.

In the present invention, the reaction mixture in which tetraacetylarbutin is produced by the above condensation reaction is subsequently subjected to an acetylation reaction. The acetylation reaction is performed by adding an acetylating agent such as acetic anhydride and acetic acid chloride to the above reaction mixture,
Usually, it is performed by heating to about 60 to 120 ° C under normal pressure. The amount of the acetylating agent to be used is not particularly limited, but it is preferable that the amount is more than the amount that completely acetylates tetraacetylarbutin and the residual hydroquinone. By acetylating the residual hydroquinone, the effect of further facilitating the purification of the target pentaacetylarbutin can be obtained. In addition, the reaction time of the acetylation reaction is usually appropriate to be about 0.2 to 10 hours.

The target compound pentaacetylarbutin thus obtained can be easily purified by recrystallization, various chromatographies and the like. Pentaacetylarbutin can be easily converted to arbutin by hydrolysis in the usual way.

EFFECTS OF THE INVENTION According to the production method of the present invention, a particularly remarkable effect that the target compound pentaacetylarbutin is usually obtained in a high yield of at least 80% or more is exhibited. Further, since the browning substance, which is a by-product peculiar to the reaction of the sugar derivative, is scarcely produced, the effect of easy purification can be obtained.
In addition, when the acetylating agent is used in an amount of tetraacetylarbutin and the amount that completely acetylates residual hydroquinone, the effect of further facilitating the purification of the target product can be obtained. The reason is that by using the above-mentioned specific reaction solvent, the solubility of the reaction product and the product is good and the reaction is a homogeneous system, the acetic acid by-product can be easily removed from the reaction system, and the isomerization of the product Body rearrangement (transition from β-form to α-form) is extremely small, pentaacetylarbutin is efficiently produced by acetylation as it is after the condensation reaction, and pentaacetylarbutin is more crystalline than tetraacetylarbutin. Is considered to be due to good things.

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to Examples and Comparative Examples.

Example 1 To 39 g (0.1 mol) of β-pentaacetylglucose, 16.5 g (0.15 mol) of hydroquinone, 70 g of diethylene glycol dibutyl ether and 0.5 g of paratoluenesulfonic acid were added, and the mixture was reacted under reduced pressure of 15 mmHg at 110 ° C. for 4 hours. To the obtained reaction mixture, 22 g (0.22 mol) of acetic anhydride was added as it was, and acetylation was carried out at 100 ° C. for 1 hour. After washing with water at room temperature, 140 g of heptane was added to precipitate crystals, and the crystals were recrystallized in an ethyl alcohol solvent to obtain 39 g of pentaacetylarbutin (yield 81%). This is ▲
[Α] ²⁵ _D ▼ = −28.2 ° (acetone). Pentaacetylarbutin had better crystallinity and was easier to purify than tetraacetylarbutin.

Comparative Example 1 β-Pentaacetylglucose 39 g (0.1 mol), hydroquinone 16.5 g (0.15 mol) and xylene (bp.138 ° C / 760 mm)
Hg) 120 g and p-toluenesulfonic acid 0.5 g were added, and 150 m
The mixture was reacted under reduced pressure of mHg at 105 ° C for 4 hours. After washing with water at room temperature,
80 g of xylene was distilled off, and heptane was added thereto to precipitate crystals. When the crystals were recrystallized in an ethyl alcohol solvent, 22.0% of tetraacetylarbutin was obtained.
g (yield 50%) was obtained. 13.6 g of the isolated tetraacetylarbutin was dissolved in 20 ml of acetic anhydride, and 5 g of sodium acetate was added for acetylation. This was poured into water 1 and well stirred, and the obtained crystal was recrystallized from ethyl alcohol to obtain 13.5 g of pentaacetylarbutin (total yield: 47%).
This was ▲ [α] ²⁰ _D ▼ = -27.5 ° (acetone).

Comparative Example 2 Benzene was used as a solvent instead of xylene in Comparative Example 1 to carry out the reaction. Since benzene has a boiling point of 80 ° C / 760 mmHg and is lower than the boiling point of acetic acid, 118 ° C / 760 mmHg, the reaction cannot be performed under reduced pressure, so the reaction was performed under normal pressure. Since the produced acetic acid could not be removed, the reaction did not proceed as much as in the case of xylene, and the yield of tetraacetylarbutin was 47% even when the reaction was carried out for 2 hours which is the optimum reaction time. Using 20.7 g of the isolated tetraacetylarbutin, acetylation and recrystallization were carried out in the same manner as in Comparative Example 1 to obtain 20.2 g of pentaacetylarbutin (total yield 42%). This is ▲ [α] ²⁰ _D ▼ ＝ −27.5
It was at ° (acetone).

Comparative Example 3 To 39 g (0.1 mol) of β-pentaacetylglucose, 16.5 g (0.15 mol) of hydroquinone, 70 g of diethylene glycol dibutyl ether and 0.5 g of paratoluenesulfonic acid were added, and reacted at 110 ° C. for 4 hours under reduced pressure of 15 mmHg. After washing with water at room temperature, 140 g of heptane was added to precipitate crystals. This crystal was recrystallized in an ethyl alcohol solvent to obtain 31.7 g (yield 72%) of tetraacetylarbutin. Using 31.7 g of isolated tetraacetylarbutin, acetylation and recrystallization were carried out in the same manner as in Comparative Example 1 to obtain 31.1 g of pentaacetylarbutin (total yield: 65%). This is ▲ [α]
^The temperature was ²⁰ _D ▼ = −28.2 ° (acetone).

Claims (2)

[Claims] 1. β-Pentaacetylglucose and hydroquinone are reacted with a mono- and / or polyethylene glycol dialkyl ether as a reaction solvent to produce tetraacetylarbutin, which is then acetylated as it is without isolation. A method for producing pentaacetylarbutin, which comprises: 2. The method according to claim 1, wherein the amount of acetylating agent used is such that tetraacetylarbutin and residual hydroquinone are completely acetylated.