JPH0262552B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Conventionally, the compound of formula () is produced by thermally decomposing chelidonic acid obtained by dehydration condensation of two molecules of diethyl oxalate and one molecule of acetone in the presence of a base, followed by cyclization. A method of synthesizing by eliminating one molecule of carbon and an improved method thereof are known.

However, the first stage of synthesis of chelidonic acid requires strict non-aqueous operations, and the second stage of decarboxylation requires high temperatures. It is difficult to say that it is necessarily a preferable manufacturing method.

The present inventors have conducted various studies on the stereospecific decomposition reactions of uronic acids, which are six-carbon pyran-type carboxylic acid derivatives like comanic acid (), in the presence of a basic compound in acetic anhydride. ，
It has been found that comanic acid () can be obtained with high selectivity by treating 3,4-tetra-O-acetyl-β-D-glucuronic acid () under relatively mild reaction conditions.

D-glucuronic acid is an oxidized form of D-glucose at the 6-position, and is widely available in nature. It is industrially produced from acacia resin, which contains a particularly large amount, and is one of the easiest to obtain among uronic acids. I can say it.

Regarding the production of 1,2,3,4-tetra-O-acetyl-β-D-glucuronic acid, we have discovered a selective synthesis method using commercially available D-glucuronic acid as a starting material, and the present invention The method can be said to be useful as a method for producing comanic acid ().

The reaction is carried out by heating a compound of formula () in acetic anhydride in the presence of a base.

As the basic compound used in the method of the present invention, organic basic compounds such as pyridine and triethylamine are suitable.

The ratio of the basic compound used to the compound of the above formula () is not particularly limited as long as it is at least twice the molar ratio.

The reaction is carried out in acetic anhydride, but acetic acid may also coexist in acetic anhydride.

The reaction temperature is suitably 50 to 100°C, and the reaction time is preferably 3 to 25 hours.

Note that the product is produced in the form of a salt with the basic compound used. Therefore, appropriate treatment is required depending on the type of base used. For example, when pyridine is used, the compound of the formula () can be obtained as a crystal by treating under reduced pressure at 30 to 35°C to remove pyridine. When using triethylamine, ion exchange is required, and ion exchange is performed using an acidic ion exchange resin such as DOWEX50WX2.
Crystals of the compound of formula () can be obtained.

Next, the method of the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto.

Example 1 0.4 g of the compound of formula () was mixed with 6 ml of acetic anhydride and 0.6
Dissolve in 1 ml of pyridine and stir at 100°C for 16 hours to react.

The resulting solution is concentrated under reduced pressure, treated with activated carbon with ethanol, and concentrated again under reduced pressure. The precipitated crystals were washed with benzene and dried under reduced pressure to obtain crystals of r-pyrone-2-carboxylic acid () in a yield of 73.5%. If recrystallization is necessary, perform it with ethanol.

Example 2 0.2 g of the compound of formula () was mixed with 3 ml of acetic anhydride and 1
Dissolved in ml acetic acid and 0.3 ml pyridine and incubated at 100 °C for 25
Stir for an hour and allow to react.

The resulting solution is concentrated under reduced pressure, treated with activated carbon in ethanol, and concentrated again under reduced pressure. When the obtained crystals are washed with benzene and dried under reduced pressure, the desired crystals of the compound of formula () are obtained.
Obtained with a yield of 83.7%.

Example 3 0.2 g of the compound of formula () was mixed with 3 ml of acetic anhydride and 0.3
ml of triethylamine and stirred at 50°C for 16 hours to react.

After concentrating the obtained solution under reduced pressure, the soluble portion was extracted with benzene, and the solution was made into an aqueous solution.
After ion exchange with DOWEX50W-X2 (H) and concentration under reduced pressure, crystals of r-pyrone-2-carboxylic acid () were obtained with a yield of 90.0%.

Example 4 30 ml of acetic anhydride and 6 ml of triethylamine are added to 2 g of the compound of formula (), and the mixture is reacted at 100°C for 5 hours with stirring. After concentrating the resulting solution under reduced pressure, 20 ml of water is added and insoluble matter is separated. This aqueous solution was subjected to ion exchange using a DOWEX, 50WX2 (H type) column, and water was removed under reduced pressure to obtain 0.75 g (yield: 96.9%) of comanic acid () crystals.

Claims (1)

[Scope of Claims] 1. Using 1,2,3,4-tetra-O-acetyl-β-D-glucuronic acid represented by the formula K0314 as a starting material, the reaction is carried out in acetic anhydride in the presence of a basic compound. A method for producing comanic acid represented by formula K0315, characterized by: