JPS5929636A - Preparation of optically active tartaric acid - Google Patents

Abstract

PURPOSE:To obtain optically active tartaric acid in high yield and optical purity, by resolving (+ or -)-tartaric acid optically with optically active alpha-amino-epsilon-caprolactam as a resolving agent. CONSTITUTION:One mole (+ or -)-tartaric acid is reacted with 2 molar equivalents optically active alpha-amino-epsilon-caprolactam in water or a mixed solvent of water with a water-soluble organic solvent, preferably a mixed solvent of water with methanol and 2-propanol, under heating to form a diastereomer salt, which is then cooled to deposit slightly soluble diastereomer salt. The deposited diastereomer salt is then separated and converted into a free acid. The conversion of the salt into the free acid is effectively carried out by passing the aqueous solution through an ion exchange resin column. (+)-alpha-Amino-epsilon-caprolactam is used as the resolving agent to deposit (+)-tartrate as a slightly soluble salt. If (-)-alpha-amino- epsilon-caprolactam is used, (-)-tartrate is deposited as the slightly soluble salt.

Description

[Detailed description of the invention] The present invention relates to a method for producing optically active tartaric acid.

(e) - Some methods for producing optically active tartaric acid by optical resolution of tartaric acid are already known, but they have drawbacks such as low product yield or optical purity, and resolving agents are expensive and difficult to obtain. Therefore, it was desired to establish a new optical resolution method.

From this point of view, the present inventors have made extensive studies to establish a new optical resolution method for (e)-tartaric acid, and as a result, they have arrived at the present invention, which is highly effective.

That is, the present invention allows optically active α-amino-ε-caprolactam to act on (e)-tartaric acid to form a diastereomeric salt, and utilizes the solubility difference between ←)-tartrate and ←)-tartrate. The present invention provides a method for producing optically active tartaric acid, which comprises separating the two, and then converting the salt into the free acid.

After separation, the optically active tartrate can be converted to a free acid by any suitable method similar to the conventional method for converting a carboxylate to a carboxylic acid. In particular, a method using an ion exchange resin is particularly preferred.

The optically active α-amino-ε-caprolactam used as a resolving agent in the present invention can be any dextrorotatory or levorotatory compound.

The amount of optically active α-amino-ε-caprolactam to be used is theoretically preferably 2 molar equivalents per mol of ←)-tartaric acid in order to resolve (→-tartaric acid with high purity).

The production of diastereomeric salts from (g)-tartaric acid and optically active α-amino-ε-caprolactam is carried out in a solution system, and the solvents used at this time are water, water and a water-soluble organic solvent. There are mixed solvents such as water-alcohol mixed solvent, among which water-methanol-
A mixed solvent of 2-propertool is preferred.

The reaction for producing diastereomeric salts is usually carried out under heating, for example at ω to 70°C. It is preferable to allow the reaction to cool gradually to room temperature. In this way, sparingly soluble diastereomeric salts precipitate. , When (→-α-amino-ε-caglolactam is used as a resolving agent, 0-)-tartaric acid 2(→-α-amino-ε-caglolactam salt precipitates as a sparingly soluble salt, and ←)-tartaric acid 2(→- α-amino-ε-caglolactam salt remains in the mother liquor. On the other hand, when ←)-α-amino-ε-caprolactam is used as a resolving agent, ←)-tartaric acid 2(→-α-amino-ε-caglolactam salt remains as a sparingly soluble salt. Precipitate, (→
-Tartaric acid・2←)-α-amino-ε-caprolactam salt remains in the mother liquor.

After separating the sparingly soluble diastereomeric salts thus precipitated, by converting all of the salts into free acids, (→ or ←)
- Tartaric acid is obtained.

The conversion of the salt to the free acid can be carried out in accordance with the conventional method for obtaining carboxylic acids from carboxylic acid salts, but it is extremely efficient when the aqueous solution is passed through a column of ion exchange resins, especially strong ion exchange resins. optically active tartaric acid can be obtained.

The salt in the mother liquor is also converted into the free acid in the same manner as described above after being separated from the solvent by evaporation to dryness or the like.

In this way, optically active tartaric acid can be produced with low yield and high optical purity. In addition, the optically active α-amino-ε-caprolactam used as a resolving agent in the present invention is a readily available compound that is produced in large quantities as a precursor for the production of L-') gin using an enzymatic method. be. Therefore, it can be said that the method of the present invention is an excellent method suitable for implementation on an industrial scale.

Next, the present invention will be explained in more detail based on Examples. The present invention is not limited in any way by these Examples.

Example 1゜←)-Tartaric acid [hereinafter abbreviated as (!:)-1) 5.00
r(33,3mno l) (→-α-amino-ε-
Caglolactam [hereinafter abbreviated as (g)-■] 8.5
Add 4t (66.6mmol)k and add 97% water! was added and heated to dissolve. Add 4 methanol to this solution.
After the mixture was completely added and stirred, 45 ml of 2-propanol was added, gently stirred, and left overnight at room temperature. By filtering the precipitated crystals, 8.17f of Hiro(+)-r.2(+)-11 salt was obtained. This diastereomeric salt 5.0 (l
After heating and dissolving the mixture in 3 liters of water, 40 liters of methanol was added thereto, gently stirred, and left at room temperature overnight.

In order to treat the precipitated crystals, (→-I・2(→
-■ Salt 3.63F was obtained. (→- in (e)-I used)
The yield for ■ is 31.5 87.6%, (α) +64.2° (CO,5
, MeOH), m, p.

35 202-203℃, N analysis value 13.79%, C□6
The analysis value as H3oO8N4 is 13.78%. This diastereomeric salt 1.0305f (2,535mmo
0.3673 f(
2,447 toxins (30.5 mol) f were obtained. Yield 96.5%, Ca)
+11.23°89 6- (C1,0, H2O), optical purity 67.6%.

Example 2゜The fractionated crystallization mother liquor first prepared in Example 1 was dried under reduced pressure, a part of it was dissolved in water, and added to an ion exchange resin (Amberlite 1R120B, H type). The eluate was dried under reduced pressure to obtain ←)-1.

blood.

Example 3 Add ←)-H8,09f (63,1 mmol) to (i=)-15,00f (33,3 mmol),
Water 9m7! was added and heated to dissolve. After adding 90 mm of methanol to this solution and stirring, 45 mm of 2-propanol was added, gently stirred, and left overnight at room temperature.

By filtering all the precipitated crystals, (→-■・2(→
-■ 6.46f of salt was obtained. This diastereomeric salt5.
After heating and dissolving 00 tons in 3 ml of water, add 40 tons of methanol.
After adding m1 and stirring gently, the mixture was left at room temperature overnight.

By filtering the precipitated crystals, ←)-I・2←)
-II salt 3.8 (l) was obtained. This diastereomeric salt 2
．． 0ff 20rnl of methanol heated to 60-70℃ after dissolving in 2ml of water! After adding and stirring,
It was left at room temperature overnight.

By filtering the precipitated crystals, (→−■・2(−
)-11 salt 1.39f was obtained. (g)-I used (
The yield for →−■ is 33.5% to 50.4%. [α] 76.2° (C1,1, H
2O), m, p.

35 212.5-213.0°C. This diastereomeric salt 0
．． 77669 (1,910 mmol) was dissolved in 5 portions of water and mixed with ion exchange resin (Amberlite 1R120).
0.2824 f (1,882wn
ol) 31.0 total obtained. Yield 98.5%. [α) −16,7°
(C1,0°89 H2, optical purity 100chi.

-23°

Claims (2)

[Claims] (1) (e) - Tartaric acid is reacted with optically active α-amino-ε-caprolactam to form diastereomeric salts, and the difference in solubility of the salts is utilized (→-tartrate and ←)-
A method for producing optically active tartaric acid, which comprises separating the tartrate and then converting the salt into free acid. (2) The method according to claim 1, characterized in that the conversion of the salt into the free acid is carried out using an ion exchange resin.