阅读说明：本技术 一种d-泛酸钙全合成环保工艺 (Full-synthesis environment-friendly process of D-calcium pantothenate ) 是由 吴江 于 2020-05-14 设计创作，主要内容包括：本发明涉及一种合成D-泛酸钙的成套新工艺。本发明由β-氨基丙酸与氧化钙在水和/或甲醇中合成β-氨基丙酸钙,过滤后,负压蒸干β-氨基丙酸钙溶液中的水和/或甲醇,或过滤后,保持20℃-65℃搅拌结晶8-40小时,再过滤,再过滤的滤饼用甲醇置换滤饼中的母液三次以上,使滤饼中的水份含量小于1%,滤液去掉70%以上溶剂后可套用再过滤步骤。用甲醇浸润β-氨基丙酸钙后,加入D-泛解酸内酯的甲醇溶液,先较低温度反应再回流反应合成D-泛酸钙,再完全蒸去或部分蒸去甲醇,加水溶解过滤,转入喷雾干燥机喷雾干燥出产品D-泛酸钙。产品质量符合行业标准,产品收率比现行工艺水平提高15%-20%。(The invention relates to a complete set of new process for synthesizing D-calcium pantothenate, which comprises the steps of synthesizing β -calcium aminopropionate from β -aminopropionic acid and calcium oxide in water and/or methanol, carrying out negative pressure evaporation on water and/or methanol in β -calcium aminopropionate solution after filtration, keeping the temperature of 20-65 ℃ for stirring and crystallizing for 8-40 hours, carrying out filtration, replacing mother liquor in a filter cake with methanol for more than three times by using a filtered filter cake, ensuring that the water content in the filter cake is less than 1%, removing more than 70% of solvent from the filtrate, then carrying out filtration, infiltrating β -calcium aminopropionate with methanol, adding a methanol solution of D-pantoic acid lactone, carrying out low-temperature reaction and reflux reaction to synthesize the D-calcium pantothenate, completely or partially evaporating the methanol, adding water to dissolve and filter, and transferring to a spray dryer for spray drying to obtain the product D-calcium pantothenate, wherein the product quality meets the industrial standard, and the product yield is improved by 15-20% compared with the existing process level.)

1. A full-synthesis environment-friendly process of D-calcium pantothenate comprises the following steps:

(1) β -preparation of calcium aminopropionate, adding 89 kg (1000 mol) of β -aminopropionic acid into a reaction kettle, adding water and/or methanol accounting for 100-800% of the weight of β -aminopropionic acid, starting stirring, after 10 minutes, dropwise adding 50-1000 ml of 10-80% (volume ratio) sulfuric acid solution, then gradually adding 28-42 kg (500 mol-750 mol) of calcium oxide at the temperature of no more than 45 ℃, stirring for half an hour after adding, heating to 25-100 ℃ for reaction for 2-8 hours, adding 3-8 kg of kieselguhr, heating to boil (not heating when methanol is contained), filtering clear liquid into a steaming drying kettle, cleaning a filtering device and a pipeline by using 100-200 kg of water and/or methanol for two to three times, completely merging a cleaning solution into the steaming drying kettle, starting a steam valve, starting a vacuum unit, starting the steaming kettle for stirring, desolventizing until the water content of β -aminopropionic acid is lower than 10-0%, adding 200 kg of methanol into the steaming drying kettle, or filtering clear liquid into the reaction kettle, keeping the reaction kettle for two to 65-8 hours, filtering a filter cake, and adding filter cake after the filter cake is replaced by more than 70-200 kg of methanol, filtering the filter cake, and adding filter cake after the filter cake is removed by adding 200-200 kg of water and the filter cake after the filter cake is;

(2) preparation of a methanol solution of D-calcium pantothenate: dissolving 120-140 kg of D-pantoic acid lactone (950-1050 mol) in 500 kg of methanol 200-140 kg of methanol, filtering after uniform dissolution (or directly putting D-pantoic acid lactone crystals into a steaming-drying kettle), dropwise adding the D-pantoic acid lactone solution into the stirred steaming-drying kettle within one hour, reacting for 0-30 hours at the temperature of-10 ℃ to 65 ℃, then heating to reflux, and carrying out thermal insulation reflux for 0-8 hours (the sum of the reaction time of the two temperature regions is not less than 1 hour);

(3) preparing and drying the D-calcium pantothenate aqueous solution: and (3) evaporating 30-95% of methanol from the D-calcium pantothenate methanol solution in the step (2) at normal pressure, evaporating the methanol in the D-calcium pantothenate to dryness at micro negative pressure (or directly transferring to the next step without evaporation) until no methanol drips out in a sight glass, adding 1200 kg of water at 0-50 ℃, stirring and dissolving uniformly, filtering to obtain a D-calcium pantothenate aqueous solution, transferring the solution to a spray dryer (or rectifying the methanol firstly) to dry into a D-calcium pantothenate product, cooling the dried gas, and then feeding the gas to a rectifying tower to recover the methanol.

2. The process of claim 1, wherein water and/or methanol is added in an amount of 100-800 wt% β -aminopropionic acid.

3. The process according to claim 1, wherein 50 to 1000 ml of sulfuric acid solution (volume ratio) is added dropwise to 1000 mol of β -aminopropionic acid in an amount of 10 to 80% based on the total amount of the solution.

4. The process of claim 1, wherein the desolventizing step (1) is carried out until the water content of β -calcium aminopropionate is less than 10% -0%.

5. The process according to claim 1, wherein the desolventizing step (1) is carried out until the water content of β -aminopropionic acid calcium is less than 10% -0%, preferably less than 1%.

6. The process according to claim 1, wherein the calcium D-pantothenate is fully synthesized by the following steps: in the step (1), the clear liquid is filtered, crystallized and filtered, and the filter cake is replaced and cleaned for more than three times by methanol until the water content of the filter cake is less than 1% (more than 70% of the water content of the filtrate can be removed for reuse and filtered).

7. The process according to claim 1, wherein the calcium D-pantothenate is fully synthesized by the following steps: in the step (2), the reaction is carried out for 0 to 30 hours at the temperature of between 10 ℃ below zero and 65 ℃, then the temperature is increased to reflux, and the reflux is carried out for 0 to 8 hours under the condition of heat preservation (the sum of the reaction time of the two temperature areas is not less than 1 hour).

8. The process according to claim 1, wherein the molar ratio of D-pantoic acid lactone β -aminopropionic acid in the steps (1) and (2) is 0.95-1.05: 1.00.

9. The process of claim 1, wherein in step (1), the molar ratio of calcium oxide to β -aminopropionic acid is 0.50-0.75: 1.00.

10. The process according to claim 1, wherein the calcium D-pantothenate is fully synthesized by the following steps: in the step (3), the obtained D-calcium pantothenate product can detect inorganic and organic acid radical anions such as chloride ions and/or sulfate ions and/or acetate ions and/or citrate ions.

Technical Field

The invention relates to a full-synthesis environment-friendly process of D-calcium pantothenate, in particular to a complete set of novel process for synthesizing the D-calcium pantothenate, wherein the product yield of the complete set of novel process reaches 100%.

Background

The D-calcium pantothenate is vitamin B5, has a chemical name of (R) - (+) -N- (2, 4-dihydroxy-3, 3-dimethyl-1-oxobutyl) - β -calcium alanine salt and an English name of D- (+) -pantonic acid calcium salt, is used as an important nutrient component, and is widely applied to the fields of feed additives, food additives, medicines and the like;

the synthesis route of D-calcium pantothenate is characterized by that β -aminopropionic acid and calcium oxide are reacted in methyl alcohol to synthesize β -aminopropionic acid calcium, after filtering, D-pantoic acid lactone is added to synthesize D-calcium pantothenate, then the D-calcium pantothenate is separated out by means of low-temp. crystallization, its mother liquor can recover methyl alcohol, calcium, D-pantoic acid lactone and β -aminopropionic acid, and can be returned and used, the recovered or deteriorated material can be used as waste liquor, and can be treated by means of environment-protecting system, and the sulfuric acid and lots of organic solvent can be used in the course of recovery, so that its loss is increased, and its working environment is poor, and the comprehensive utilization rate of main raw material of said process can only be up to 80-85% in industrial production.

Disclosure of Invention

Synthesizing β -calcium aminopropionate from β -aminopropionic acid and calcium oxide in water and/or methanol, evaporating water and/or methanol in β -calcium aminopropionate solution under negative pressure after filtering, or keeping the temperature of 20-65 ℃ after filtering, stirring and crystallizing for 8-40 hours, filtering again, replacing mother liquor in a filter cake with methanol for more than three times to ensure that the water content in the filter cake is less than 1 percent, wherein the filter cake is β -calcium aminopropionate used in the later step, the filtrate can be used in a re-filtering step after removing more than 70 percent of solvent, after β -calcium aminopropionate is soaked in methanol, a methanol solution of D-pantoic acid lactone is added, the mixture is reacted at a lower temperature and then subjected to reflux reaction to synthesize the D-calcium pantothenate, and then the methanol is completely or partially evaporated, the water is added for dissolving, and after filtering, the product D-calcium pantothenate is obtained by spray drying in a spray drier, and is used after rectification of aqueous methanol, and no three wastes are generated in the whole process.

The technical scheme adopted for realizing the above purpose of the invention is as follows: a full-synthesis environment-friendly process of D-calcium pantothenate comprises the following steps:

(1) β -preparation of calcium aminopropionate, adding 89 kg (1000 mol) of β -aminopropionic acid into a reaction kettle, adding water and/or methanol accounting for 100-800% of the weight of β -aminopropionic acid, starting stirring, after 10 minutes, dropwise adding 50-1000 ml of 10-80% (volume ratio) sulfuric acid solution, then gradually adding 28-42 kg (500 mol-750 mol) of calcium oxide at the temperature of no more than 45 ℃, stirring for half an hour after adding, heating to 25-100 ℃ for reaction for 2-8 hours, adding 3-8 kg of kieselguhr, heating to boil (no heating when methanol is contained), filtering clear liquid into a steaming drying kettle, cleaning a filtering device and a pipeline with 100 kg of 200-200 kg of water and/or methanol for two to three times, completely adding a cleaning solution into the steaming drying kettle, starting a steam valve, starting a vacuum unit, starting the steaming kettle for stirring, removing water content from β -25-aminopropionic acid until the water content is less than 10-0%, adding 200 kg of methanol into the steaming drying kettle, filtering to remove water content from the filter cake, filtering the filter cake after the filter cake is replaced by more than 20-40 hours, adding filter cake after the filter cake is replaced by 100-800 kg of 200 kg of methanol, and the filter cake is replaced by the filter cake after the filter cake is removed;

(2) preparation of a methanol solution of D-calcium pantothenate: dissolving 120-140 kg of D-pantoic acid lactone (950-1050 mol) in 500 kg of methanol 200-140 kg of methanol, filtering after uniform dissolution (or directly putting D-pantoic acid lactone crystals into a steaming-drying kettle), dropwise adding the D-pantoic acid lactone solution into the stirred steaming-drying kettle within one hour, reacting for 0-30 hours at the temperature of-10 ℃ to 65 ℃, then heating to reflux, and carrying out thermal insulation reflux for 0-8 hours (and the sum of the reaction time of the two temperature regions is not less than 1 hour);

(3) preparing and drying the D-calcium pantothenate aqueous solution: and (3) evaporating 30-95% of methanol from the D-calcium pantothenate methanol solution in the step (2) at normal pressure, evaporating the methanol in the D-calcium pantothenate to dryness under micro negative pressure (or directly transferring to the next step without evaporation) until no methanol drips out in a sight glass, adding 1200 kg of water at 0-50 ℃, stirring and dissolving uniformly, filtering to obtain a D-calcium pantothenate aqueous solution, and transferring the solution to a spray dryer (or rectifying the methanol firstly) to dry to obtain a D-calcium pantothenate product. Cooling the dried gas, and then recovering the methanol in a rectifying tower.

In the step (1), water and/or methanol with the weight of 100-800 percent of β -aminopropionic acid is added.

In the step (1), 50-1000 ml of sulfuric acid solution with 10-80% (volume ratio) is added dropwise corresponding to 1000 mol of β -aminopropionic acid.

In the step (1), desolventizing is carried out until the water content of β -calcium aminopropionate is lower than 10% -0%, preferably lower than 1%.

In the step (1), the clear liquid is filtered, crystallized and filtered, and the filter cake is replaced and cleaned for more than three times by methanol until the water content of the filter cake is less than 1% (more than 70% of the water content of the filtrate can be removed for reuse and filtered).

In the step (2), the reaction is carried out for 0 to 30 hours at the temperature of between 10 ℃ below zero and 65 ℃, then the temperature is increased to reflux, and the reflux is carried out for 0 to 8 hours under the condition of heat preservation (the sum of the reaction time of the two temperature areas is not less than 1 hour).

In the step (1) and (2), the molar ratio of D-pantolactone to β -aminopropionic acid is 0.95-1.05: 1.00.

In the step (1), the molar ratio of calcium oxide to β -aminopropionic acid is 0.50-0.75: 1.00.

In the step (3), the obtained D-calcium pantothenate product can detect inorganic and organic acid radical anions such as chloride ions and/or sulfate ions and/or acetate ions and/or citrate ions.

Therefore, compared with the prior art, the invention has the following advantages:

1. according to the invention, β -calcium aminopropionate is synthesized in water and/or methanol, and the solvent is completely evaporated after filtration, so that the synthesis of β -calcium aminopropionate is facilitated, the intrinsic safety of production is improved, and the environmental protection pressure is reduced;

2. the process solves the problem that β -calcium aminopropionate is difficult to dry and dehydrate in industrial production;

3. the D-calcium pantothenate product is obtained by a solvent evaporation method, so that the completeness of chemical reaction is ensured, 100% of product yield is also ensured, the industrial production period is greatly shortened, the equipment investment is greatly reduced, and the production energy consumption is greatly reduced;

4. the property of the D-calcium pantothenate is utilized to realize the spray drying of the D-calcium pantothenate aqueous solution;

5. the process introduces a trace amount of 10-80% (volume ratio) sulfuric acid solution when β -calcium aminopropionate is synthesized, so that the filtration difficulty of the system can be greatly reduced, and the yield of β -calcium aminopropionate is indirectly improved;

6. the process has no mother liquor recovery process;

7. the process has no pollution of other three wastes except for ultra-micro filtration of alkaline residues.

The invention is further illustrated with reference to the following examples (the scope of protection includes, but is not limited to, the following examples).

Example 1

(1) β -preparation of calcium aminopropionate by putting 89 kg (1000 mol) of β -aminopropionic acid into a 1000L reaction kettle, adding 300 kg of water, starting stirring, after 10 minutes, dropwise adding 200 ml of 50% (volume ratio) sulfuric acid solution, gradually adding 30 kg (510 mol) of calcium oxide at a temperature of no more than 45 ℃, stirring for half an hour after adding, heating to 50-56 ℃ for reaction for 3 hours, adding 6 kg of diatomite, heating to boiling, filtering clear liquid to 1500L steam-drying kettle, cleaning filtering equipment and a pipeline twice by using 100 kg of water, adding all washing water into the steam-drying kettle, starting a steam valve, starting a vacuum unit, starting the steam-drying kettle for stirring, dehydrating to β -the water content of calcium aminopropionate is 0.98%, and adding 240 kg of methanol into the steam-drying kettle;

(2) preparation of a methanol solution of D-calcium pantothenate: 130 kg (990 mol) of D-pantolactone is dissolved in 440 kg of methanol, and the mixture is filtered after being dissolved evenly. Starting the stirring of the evaporation kettle in the step (1), heating, dropwise adding the D-pantoic acid lactone solution into the evaporation kettle within one hour, and then carrying out heat preservation and reflux for 2 hours;

(3) preparing and drying the D-calcium pantothenate aqueous solution: and (3) evaporating 80% of methanol from the D-calcium pantothenate methanol solution in the step (2) at normal pressure, evaporating the methanol from the D-calcium pantothenate to dryness at micro negative pressure until no methanol drips out of a sight glass, adding 750 kg of water at 30 ℃, stirring and dissolving uniformly, and filtering to obtain a D-calcium pantothenate aqueous solution. The solution is transferred to a spray dryer for drying to obtain the D-calcium pantothenate product. Cooling the dried gas, and then recovering the methanol in a rectifying tower. The product meets the specification by detection, the calcium content is 8.4 percent, the nitrogen content is 5.8 percent, and the specific optical rotation is plus 27.2^oThe drying weight loss is 1.1 percent, the heavy metal content is less than 0.002 percent, and the methanol content is 0.2 percent.