阅读说明：本技术 一种常压还原制备d,l-泛解酸内酯的方法 (Method for preparing D, L-pantoic acid lactone by normal pressure reduction ) 是由 张玉锋 李斌水 米造吉 何连顺 李克 赵聚波 于 2020-05-19 设计创作，主要内容包括：本发明公开了一种常压还原制备D,L-泛解酸内酯的方法,属于维生素生产技术领域。包括以下步骤(1)乙醛酸于15-35℃下投加有机碱；(2)加异丁醛升温至醛醛缩合反应生成2-羟基-3-甲基-3-甲酰基丁酸；(3)醛醛缩合反应液加还原催化剂,还原反应生成泛解酸；(4)加酸发生分子间脱水环化,生成D,L-泛解酸内酯；(5)将D,L-泛解酸内酯的料液中和、萃取、浓缩蒸馏得D,L-泛解酸内酯产品。本发明在醛醛缩合反应生成2-羟基-3-甲基-3-甲酰基丁酸后,使用还原催化剂,进行常温常压还原反应生成泛解酸；避免使用剧毒品原料和高压氢解等高危工艺,同时避免使用氢解催化剂引入重金属杂质,操作安全。(The invention discloses a method for preparing D, L-pantoic acid lactone by normal pressure reduction, which belongs to the technical field of vitamin production and comprises the following steps of (1) adding organic alkali into glyoxylic acid at 15-35 ℃, (2) adding isobutyraldehyde and heating until aldehyde condensation reaction is carried out to generate 2-hydroxy-3-methyl-3-formylbutyric acid, (3) adding a reduction catalyst into aldehyde condensation reaction liquid to generate pantoic acid by reduction reaction, (4) adding acid to generate intermolecular dehydration cyclization to generate D, L-pantoic acid lactone, and (5) neutralizing, extracting, concentrating and distilling the feed liquid of the D, L-pantoic acid lactone to obtain D, L-pantoic acid lactone products.)

1. A method for preparing D, L-pantoic acid lactone by atmospheric pressure reduction is characterized by comprising the following steps:

(1) adding glyoxylic acid into a reaction device, cooling by a cooling device, and adding organic alkali at 15-35 ℃;

(2) adding isobutyraldehyde into the mixture obtained in the step (1) at the temperature of 15-35 ℃, and heating the mixture to 55-85 ℃ until aldehyde condensation reaction is complete to generate 2-hydroxy-3-methyl-3-formylbutyric acid;

(3) cooling the aldehyde condensation reaction liquid obtained in the step (2) to 15-35 ℃ by a cooling device, adding a reduction catalyst, and carrying out a reduction reaction at the temperature of 15-35 ℃ to generate pantoic acid;

(4) adding an acid solution into the feed liquid containing the pantoic acid in the step (3), and performing intermolecular dehydration cyclization at the temperature of 75-95 ℃ to generate D, L-pantoic acid lactone;

(5) and (3) cooling the feed liquid containing D, L-pantoic acid lactone in the step (4) to 15-35 ℃, adding alkali liquor for neutralization reaction, adding an extraction solvent for extraction, concentrating the organic layer, recovering the extraction solvent, and continuing vacuum concentration and distillation to obtain a D, L-pantoic acid lactone product.

2. The method for preparing D, L-pantoic acid lactone by atmospheric reduction according to claim 1, wherein the organic base is pyridine, piperidine, diethylamine, triethylamine, ethanolamine or triethanolamine.

3. The method for preparing D, L-pantoic acid lactone by atmospheric reduction according to claim 2, wherein the amount of organic base added is 0.2-1.5 times the molar amount of glyoxylic acid.

4. The method for preparing D, L-pantoic acid lactone by atmospheric reduction according to claim 1, wherein the amount of isobutyraldehyde added is 0.95 to 1.25 times the molar amount of glyoxylic acid.

5. The method for preparing D, L-pantoic acid lactone by atmospheric reduction according to claim 1, wherein the reducing catalyst is sodium borohydride or potassium borohydride.

6. The method for preparing D, L-pantoic acid lactone by atmospheric reduction according to claim 5, wherein the amount of the reducing catalyst added is 0.2-1.2 times the molar amount of the glyoxylic acid.

7. The method for preparing D, L-pantoic acid lactone by atmospheric reduction according to claim 1, wherein the acid used in step (4) is sulfuric acid, and the acid is added in an amount to adjust the pH of the feed solution to 0.5-2.

8. The method for preparing D, L-pantoic acid lactone by atmospheric pressure reduction according to claim 1, wherein the base used in step (5) is sodium carbonate solution, sodium bicarbonate solution, ammonia water or sodium hydroxide solution, and the amount of the base added is adjusted to adjust the pH of the feed liquid to 5-8.

9. The method for preparing D, L-pantoic acid lactone by atmospheric reduction according to claim 1, wherein the extraction solvent used in step (5) is acetaldehyde n-butyl ester, ethyl acetate, dichloroethane or toluene.

Technical Field

The invention relates to a preparation method of D, L-pantoic acid lactone, belonging to the technical field of vitamin production.

Background

D-calcium pantothenate refers to D-calcium pantothenate, and has a pharmaceutical name, and is mainly used for feed additives, food additives, and various preparations such as tablets, capsules, oral liquids, granules and the like in the pharmaceutical industry.

Disclosure of Invention

Aiming at the technical problems in the prior art, the invention aims to provide a method for preparing D, L-pantoic acid lactone by normal pressure reduction, which comprises the steps of carrying out normal temperature and normal pressure reduction reaction by using a reduction catalyst after aldehyde condensation reaction generates 2-hydroxy-3-methyl-3-formylbutyric acid, avoiding using highly toxic raw materials, high-pressure hydrogenolysis and other high-risk processes, simultaneously avoiding using a hydrogenolysis catalyst to introduce heavy metal impurities, and having safe operation.

In order to solve the technical problem, the technical scheme adopted by the invention is that the method for preparing D, L-pantoic acid lactone by normal pressure reduction comprises the following steps:

(1) adding glyoxylic acid into a reaction device, cooling by a cooling device, and adding organic alkali at 15-35 ℃;

(2) adding isobutyraldehyde into the mixture obtained in the step (1) at the temperature of 15-35 ℃, and heating the mixture to 55-85 ℃ until aldehyde condensation reaction is complete to generate 2-hydroxy-3-methyl-3-formylbutyric acid;

(3) cooling the aldehyde condensation reaction liquid obtained in the step (2) to 15-35 ℃ by a cooling device, adding a reduction catalyst, and carrying out a reduction reaction at the temperature of 15-35 ℃ to generate pantoic acid;

(4) adding an acid solution into the feed liquid containing the pantoic acid in the step (3), and performing intermolecular dehydration cyclization at the temperature of 75-95 ℃ to generate D, L-pantoic acid lactone;

(5) and (3) cooling the feed liquid containing D, L-pantoic acid lactone in the step (4) to 15-35 ℃, adding alkali liquor for neutralization reaction, adding an extraction solvent for extraction, concentrating the organic layer, recovering the extraction solvent, and continuing vacuum concentration and distillation to obtain a D, L-pantoic acid lactone product.

The organic base is pyridine, piperidine, diethylamine, triethylamine, ethanolamine or triethanolamine; the addition amount of the organic base is 0.2 to 1.5 times of the molar amount of the glyoxylic acid.

The adding amount of the isobutyraldehyde is 0.95 to 1.25 times of the molar weight of the glyoxylic acid.

The reduction catalyst is sodium borohydride or potassium borohydride.

The addition amount of the reduction catalyst is 0.2 to 1.2 times of the molar amount of the glyoxylic acid.

The acid used in the step (4) is sulfuric acid, and the adding amount of the acid is adjusted until the pH value of the feed liquid is 0.5-2.

The alkali used in the step (5) is sodium carbonate solution, sodium bicarbonate solution, ammonia water or sodium hydroxide solution, and the addition amount of the alkali is adjusted until the pH value of the feed liquid is 5-8.

The extraction solvent used in the step (5) is acetaldehyde n-butyl ester, ethyl acetate, dichloroethane or toluene.

The invention has the beneficial effects that:

after aldehyde condensation reaction is carried out to generate 2-hydroxy-3-methyl-3-formyl butyric acid, a reduction catalyst is used to carry out normal-temperature normal-pressure reduction reaction to generate pantoic acid; the method avoids using highly toxic raw materials, high-pressure hydrogenolysis and other high-risk processes, avoids introducing heavy metal impurities by using a hydrogenolysis catalyst, is safe to operate, and reduces the production cost by about 5000 yuan/ton compared with the high-pressure hydrogenolysis reaction. The method has the advantages of easily available raw materials, simple process, easy production operation, low production cost and environmental protection.

Detailed Description

The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.