阅读说明：本技术 一种d-泛解酸内酯的水溶液结晶方法 (Aqueous solution crystallization method of D-pantoic acid lactone ) 是由 段小瑞 汪洪湖 杜斌 李涛 陶勇 于 2019-11-28 设计创作，主要内容包括：本发明涉及一种D-泛解酸内酯的水溶液结晶方法,包括如下步骤：以含有15～23％D-泛解酸内酯的无机盐水溶液为原料,浓缩使其中D-泛解酸内酯的浓度至28～35％,以2～8℃/h的速度降温至0～5℃,保温结晶。本发明提供的方法是以调节D-泛解酸内酯在有无机盐水溶液中的浓度以及控制降温速度而实现结晶,优选适用于以D-泛解酸为原料、采用内酯化工艺制备D-泛解酸内酯所得的混合溶液。该方法具有步骤简单、操作易控、品质较高等特点,是D-泛解酸内酯结晶提纯的一种有效方法。(The invention relates to a method for crystallizing an aqueous solution of D-pantoic acid lactones, which comprises the following steps of taking an inorganic saline solution containing 15-23% of D-pantoic acid lactones as a raw material, concentrating to ensure that the concentration of the D-pantoic acid lactones is 28-35%, cooling to 0-5 ℃ at the speed of 2-8 ℃/h, and carrying out heat preservation and crystallization.)

The aqueous solution crystallization method of D-pantolactone is characterized in that an inorganic saline solution containing 15-23% of D-pantolactone is used as a raw material, concentration is carried out to ensure that the concentration of the D-pantolactone is 28-35%, the temperature is reduced to 0-5 ℃ at the speed of 2-8 ℃/h, and crystallization is carried out under the condition of heat preservation.

2. The method according to claim 1, wherein the aqueous inorganic salt solution containing 15-23% of D-pantoic acid lactone is: d-pantoic acid is used as a raw material, and a mixed solution obtained by preparing D-pantoic acid lactone by adopting a lactonization process.

3. The process according to claim 2, wherein the D-pantoic acid is prepared by resolution using DL-pantoic acid lactone as a raw material, preferably by a biological resolution method.

4. The method of any one of claims 1 to 3 to , wherein the inorganic salts include ammonium sulfate, sodium chloride and ammonium chloride.

5. The method according to any of claims 1 to 4, wherein the mass ratio of D-pantolactone to inorganic salt in the aqueous solution of inorganic salt is 100 (50-75).

6. The method according to claim 1, wherein the concentration is performed under reduced pressure at 55-65 ℃.

7. The method according to claim 1 or 6, wherein the aqueous solution is stirred at a rotation speed of 20-40 r/min during the concentration process.

8. The method according to claim 1 or 7, wherein the aqueous solution is stirred at a rotation speed of 20-40 r/min during the temperature reduction process.

9. The method according to claim 1, wherein the time for the heat-preservation crystallization is 1-3 h.

10. The method of claim 1, comprising the steps of: taking an inorganic salt water solution containing D-pantolactone as a raw material, concentrating under reduced pressure at 58-62 ℃ to ensure that the concentration of the D-pantolactone is 30-32%, stirring at the rotating speed of 28-32 r/min, cooling to 0-2 ℃ at the speed of 6-8 ℃/h, preserving heat, crystallizing for 2h, and filtering and collecting crystals;

the inorganic salt water solution is a mixed solution of D-pantoic acid solution after lactonization, wherein the concentration of D-pantoic acid lactone is 18-22%, and the concentration of inorganic salt is 13-17%.

Technical Field

The invention relates to the field of chemical production, in particular to a crystallization method of D-pantoic acid lactone aqueous solutions.

Background

The D-pantoic acid lactone is white crystalline powder, is very easy to dissolve in methanol and ethanol, and is easy to dissolve in water. Boiling point of 120-122 ℃ and density of 1.165g/cm³Specific rotation (20 ℃ C.) of-45 to-50.8 (C ═ 2.5, water).

D-pantoic acid lactone can be used for producing D-calcium pantothenate, D-panthenol and D-panthenol ethyl ether, and has huge market. For example: the deficiency of calcium D-pantothenate in humans can be manifested by growth arrest, weight loss, sudden death, skin hair disorders, nervous system disorders, disorders of digestive organs, liver dysfunction, influence on antibody formation, and the like. Calcium D-pantothenate is also used as a food additive and a feed additive, plays an important role in the formation of epidermal tissues, is used as an active ingredient in pharmaceutical ingredients, for promoting wound healing and in cosmetics, is an indispensable nutrient for skin health care and beauty, and is also used as an additive for cosmetics, including vitamins such as D-panthenol, D-panthenyl ethyl ether and DL-panthenol, in many foreign countries.

The prior preparation of D-pantolactone generally adopts a chemical or biological resolution method, and the traditional chemical resolution method and the biological resolution method adopt a microbial enzyme method to resolve DL-pantolactone, which becomes important directions of research due to the characteristics of environmental pollution, low toxicity and the like, wherein methods for resolving DL-pantolactone by the microbial enzyme method utilize L-pantolactone producing microorganisms to resolve L-pantolactone in the DL-pantolactone to obtain undecomposed D-configuration pantolactone.

The prior art adopts steps of extracting D-pantoic acid lactone by using an organic solvent and then refining to obtain qualified D-pantoic acid lactone, and has the problems of toxicity and pollution caused by using solvents such as ethyl acetate, dichloromethane, toluene and the like, and complicated steps.

Disclosure of Invention

The invention aims to solve the defects in the prior art and provides aqueous solution crystallization methods which are simple to operate, easy to control and capable of efficiently producing high-quality D-pantolactone crystals.

Specifically, the invention provides a method for crystallizing D-pantolactone in water solution, which comprises the steps of taking inorganic salt water solution containing 15-23% of D-pantolactone as a raw material, concentrating until the concentration of the D-pantolactone is 28-35%, cooling to 0-5 ℃ at the speed of 2-8 ℃/h, and carrying out heat preservation and crystallization.

The concentration of D-pantoic acid lactone refers to the mass volume percentage concentration, namely the gram of D-pantoic acid lactone in each 100ml of aqueous solution. For example, 15 to 23% of D-pantolactone means that the mass of D-pantolactone per 100ml of aqueous solution is 15 to 23 g. For another example, concentration to a concentration of 28 to 35% of D-pantolactone means concentration to a mass of 28 to 35g of D-pantolactone per 100ml of aqueous solution.

The method provided by the invention has the core that the concentration of D-pantoic acid lactone in the inorganic saline solution is controlled and the cooling rate is controlled, so that the D-pantoic acid lactone is efficiently separated out and crystallized, the obtained crystal is large and uniform, the specific rotation degree of the crystallized product D-pantoic acid lactone can reach-45 to-50.5, preferably-49.5 to-50.5, and the method meets the process use standard.

The method provided by the invention is preferably used for preparing the mixed solution of D-pantoic acid lactone by taking D-pantoic acid as a raw material and adopting a lactonization process. The D-pantoic acid can be prepared by taking DL-pantoic acid lactone as a raw material through resolution, and is preferably prepared by adopting a biological resolution method. The crystallization method for the aqueous solution of the inorganic salt containing D-pantolactone provided by the invention is particularly suitable for the product obtained by the process because a large amount of inorganic salt is generated in the mass production process of the process.

The inorganic salts include ammonium sulfate, sodium chloride and ammonium chloride. In the inorganic salt water solution, the mass ratio of D-pantoic acid lactone to inorganic salt is preferably 100: (50-75).

In order to improve the concentration efficiency, the concentration is preferably performed at 55-65 ℃ under reduced pressure. The water solution can be stirred at the rotating speed of 20-40 r/min in the concentration process.

In order to ensure uniform cooling speed so as to efficiently precipitate crystals with excellent quality, the invention preferably stirs the aqueous solution at a rotating speed of 20-40 r/min in the cooling process.

By adopting the method provided by the invention, the thermal insulation crystallization time is about 1-3 h, and large and uniform D-pantolactone crystals can be precipitated, the specific rotation of the crystals obtained by the method provided by the invention can reach-49.5 to-50.5 as , and the quality is excellent.

According to specific preferred schemes, the method comprises the following steps of taking an inorganic saline solution containing D-pantoic acid lactone as a raw material, concentrating under reduced pressure at 58-62 ℃ to ensure that the concentration of the D-pantoic acid lactone is 30-32%, stirring at a rotating speed of 28-32 r/min, cooling to 0-2 ℃ at a speed of 6-8 ℃/h, carrying out heat preservation crystallization for 2h, and carrying out suction filtration to collect crystals;

the inorganic salt water solution is a mixed solution of D-pantoic acid solution after lactonization, wherein the concentration of D-pantoic acid lactone is 18-22%, and the concentration of inorganic salt is 13-17%.

Compared with the prior art, the method provided by the invention is preferably suitable for the solution obtained by performing lactonization on the D-pantoic acid solution obtained by chiral resolution, and the qualified D-pantoic acid lactone can be directly obtained from the inorganic salt water solution of the D-pantoic acid lactone without being extracted by an organic solvent, so that the use of a toxic organic solvent is avoided, the steps are simple, the equipment investment is reduced for production, the production steps are reduced, the cost is saved, the most important is environmental protection and no pollution, and the method actively responds to national policies. The method directly crystallizes the D-pantolactone from the inorganic salt water solution, reduces the working procedures, has easily controlled process and simple and convenient operation, obtains large and uniform crystals of the obtained product, ensures that the specific rotation degree of the crystallized product D-pantolactone can reach-45 to-50.5, preferably reaches-49.5 to-50.5, and meets the process use standard.

Detailed Description

The invention is further illustrated in the following examples, which should not be construed as limiting the invention.

In the following examples, the inorganic salt in the feed solution was composed of ammonium sulfate, sodium chloride, and ammonium chloride.