CN108129346A - A kind of green synthesis method of D-VB5 calcium - Google Patents
A kind of green synthesis method of D-VB5 calcium Download PDFInfo
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- CN108129346A CN108129346A CN201810030285.1A CN201810030285A CN108129346A CN 108129346 A CN108129346 A CN 108129346A CN 201810030285 A CN201810030285 A CN 201810030285A CN 108129346 A CN108129346 A CN 108129346A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
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Abstract
The invention discloses a kind of green synthesis methods of D calcium pantothenates.A kind of green synthesis method of D calcium pantothenates provided by the invention includes step：Beta Alanine is added in methanol, then adds in calcium source, heating is stirred to react, and filtrate is collected in filtering；Filtrate is cooled down, D pantolactones is then added in, is stirred to react, crystal seed is added in, continues to be stirred to react；Reaction terminates to add in 15-20 DEG C of continuation crystallizations of water, is then filtered, washed, and collects filter cake and filtrate respectively, and filter cake recycles DL pantolactones through drying, filtrate through sour water solution.D calcium pantothenates are prepared for calcium pantothenate in the present invention, and process route is easy to operate, and reaction condition is mild, and safety, environmental protection, raw material is cheap and easy to get, and industrial Applicability is strong, and waste is few, and all raw materials can recycle, and achieve the purpose that clean manufacturing.
Description
Technical field
The present invention relates to medicine and food and feed additive fields, and in particular to a kind of green syt side of D-VB5 calcium
Method.
Background technology
D-VB5 calcium is also known as vitamin B5, is the necessary vitamin of human life activity, and feed can be used as to add
Agent and food additives, market capacity are huge.
In the prior art, the primary synthetic methods of D-VB5 calcium are to be condensed by DL- pantolactones and Beta-alanine calcium, so
By multiple crystallization, qualified D-VB5 calcium is obtained, which is prepared that pantothenic acid calcium contamination is big, and yield is relatively low.
By research and development, D-VB5 calcium is obtained also by microbial fermentation in the prior art, at present, the preparation method is also not
It can carry out industrial amplification production.
The third synthetic method is, using D-VB5 lactone as raw material, is then condensed with Beta-alanine calcium, then through analysis
Crystalline substance obtains D-VB5 calcium.The D-VB5 calcium being prepared at present with the method is relatively low there are content, and Pantothenic acid is larger.
Invention content
The object of the present invention is to provide the green syts of a kind of yield height, product purity height and environmental-friendly D-VB5 calcium
Method.
The present invention is achieved by the following technical solution：
A kind of green synthesis method of D-VB5 calcium includes step：
S1. Beta-alanine is added in methanol, then adds in calcium source, heating is stirred to react, and filtrate is collected in filtering；
S2. filtrate is cooled down, then adds in D-VB5 lactone, be stirred to react, added in crystal seed, continue to be stirred to react；
S3. reaction terminates to add in water-15-- 20 DEG C continuation crystallization, is then filtered, washed, collects filter cake and filtrate respectively,
Filter cake recycles DL- pantolactones through drying, filtrate through sour water solution.
Further, in the green synthesis method of above-mentioned D-VB5 calcium, the calcium source in the step S1 is calcium oxide, carbonic acid
It is one or more in calcium, calcium metal, calcium cationic exchange resin.
Further, in the green synthesis method of above-mentioned D-VB5 calcium, the reaction temperature in the step S1 is 30-50
℃.It is further preferred that the reaction temperature in the step S1 is 30-50 DEG C.
Further, in the green synthesis method of above-mentioned D-VB5 calcium, the organic solvent in the step S1 is dimethyl
The mixing of one or more of sulfoxide, n,N-Dimethylformamide, acetonitrile, the tert-butyl alcohol, methanol, ethyl alcohol.
Further, in the green synthesis method of above-mentioned D-VB5 calcium, the cooling temperature in the step S2 is -10-20
DEG C, the time is stirred to react as 3-6h.It is further preferred that the cooling temperature in the step S2 is -2-2 DEG C, when being stirred to react
Between be 4h.
Further, in the green synthesis method of above-mentioned D-VB5 calcium, in the step S2 continue to be stirred to react when
Between be 12-20h.It is further preferred that continue the time being stirred to react as 16h in the step S2.
Further, in the green synthesis method of above-mentioned D-VB5 calcium, the quality of reaction end plus water in the step S3
Dosage is the 1-5% of inventory.It is further preferred that reaction terminates in the step S3 plus the quality dosage of water is inventory
2%.
Further, in the green synthesis method of above-mentioned D-VB5 calcium, the time for continuing crystallization in the step S3 is 1-
5h.It is further preferred that the time for continuing crystallization in the step S3 is 4h.
It is further preferred that in the green synthesis method of above-mentioned D-VB5 calcium, the drying side of the filter cake in the step S3
Formula is spray drying.Certainly others drying mode is also applied for the present invention, such as be dried under reduced pressure, be spray-dried, forced air drying
Drying means.
Further, in the green synthesis method of above-mentioned D-VB5 calcium, the acid used in sour water solution in the step S3 is
One or more of mixing in hydrochloric acid, sulfuric acid, phosphoric acid, perchloric acid.
D-VB5 calcium is prepared for calcium pantothenate in the present invention, and process route is easy to operate, and reaction condition is mild, safety, ring
It protects, raw material is cheap and easy to get, and industrial Applicability is strong, and waste is few, and all raw materials can recycle, and reach the mesh of clean manufacturing
's.
Specific embodiment
With reference to specific embodiment, the present invention will be further described.The embodiment is only the preferred implementation of the present invention
Example, is not intended to restrict the invention, for those skilled in the art, the present invention can have various changes and change
Change.All within the spirits and principles of the present invention, any modification, equivalent replacement, improvement and so on should be included in the present invention
Protection domain within.In each embodiment parts by weight are referred both to without component number signified in the case of specified otherwise.
Embodiment 1
In reactor, Beta-alanine 71kg, calcium oxide 26.80kg, absolute methanol 426kg are added in.It is to slowly warm up to 33
℃.33 DEG C of temperature control, is stirred to react 1h.Diatomite drainage is added in, continues to be stirred to react 0.5h, is filtered.Filtrate is collected, filtrate is dropped
Temperature adds in D-VB5 lactone 100kg to 2 DEG C.2 DEG C of temperature control is stirred to react 4h, adds in crystal seed 1.0kg, then proceedes to be stirred to react
16h adds in purified water 1.0kg, is then cooled to -15 DEG C.It is filtered after stirring and crystallizing 4h, with absolute methanol solution washing reaction bottle
And filter cake.Filter cake is collected, filter cake is dissolved into 50kg water, it is then spray-dried, obtain white powdery solids
164.77kg。
After above-mentioned methanol mother liquor is evaporated, 6 mole hydrochloride 100kg are added in, then heat to 80 DEG C, 3h is hydrolyzed, then drops
Temperature, with the extraction of ethyl acetate 50kg × 2, merges organic layer to 20 DEG C, is concentrated under reduced pressure into dry, is continuously heating to 160 DEG C, continues to subtract
Pressure distillation, collects 110-120 DEG C of fraction, vacuum degree≤- 0.090Mpa.Obtain glassy yellowish solid 7.5kg.
Embodiment 2
In reactor, Beta-alanine 71kg, calcium oxide 26.80kg, absolute methanol 426kg are added in.It is to slowly warm up to 37
℃.37 DEG C of temperature control, is stirred to react 1h.Diatomite is added in, continues to be stirred to react 0.5h, is filtered.Filtrate is collected, filtrate is cooled down
To -2 DEG C, D-VB5 lactone 100kg is added in.- 2 DEG C of temperature control is stirred to react 4h, adds in crystal seed 1.0kg, then proceedes to be stirred to react
16h adds in purified water 1.0kg, is then cooled to -20 DEG C.It is filtered after stirring and crystallizing 4h, with absolute methanol solution washing reaction bottle
And filter cake.Filter cake is collected, filter cake is dissolved into 50kg water, it is then spray-dried, obtain white powdery solids
164.77kg。
After above-mentioned methanol mother liquor is evaporated, 6 mole hydrochloride 100kg are added in, then heat to 90 DEG C, 3h is hydrolyzed, then drops
Temperature, with the extraction of ethyl acetate 50kg × 2, merges organic layer to 20 DEG C, is concentrated under reduced pressure into dry, is continuously heating to 150 DEG C, continues to subtract
Pressure distillation, collects 110-120 DEG C of fraction, vacuum degree≤- 0.090Mpa.Obtain glassy yellowish solid 7.7kg.
Embodiment 3
In reactor, Beta-alanine 71kg, calcium oxide 26.80kg, absolute methanol 426kg are added in.It is to slowly warm up to 45
℃.45 DEG C of temperature control, is stirred to react 1h.Diatomite is added in, continues to be stirred to react 0.5h, is filtered.Filtrate is collected, is cooled the filtrate to
10 DEG C, add in D-VB5 lactone 100kg.10 DEG C of temperature control is stirred to react 4h, adds in crystal seed 1.0kg, then proceedes to be stirred to react
12h adds in purified water 1.0kg, is then cooled to -15 DEG C.Stirring and crystallizing 4h.It filters, with absolute methanol solution washing reaction bottle
And filter cake.Filter cake is collected, filter cake is dissolved into 50kg water, it is then spray-dried, obtain white powdery solids
164.77kg。
After above-mentioned methanol mother liquor is evaporated, 6 mole hydrochloride 100kg are added in, then heat to 90 DEG C, 3h is hydrolyzed, then drops
Temperature, with the extraction of ethyl acetate 50kg × 2, merges organic layer to 20 DEG C, is concentrated under reduced pressure into dry, is continuously heating to 160 DEG C, continues to subtract
Pressure distillation, collects 110-120 DEG C of fraction, vacuum degree≤- 0.090Mpa.Obtain glassy yellowish solid 7.6kg.
Claims (10)
1. a kind of green synthesis method of D-VB5 calcium, which is characterized in that including step：
S1. Beta-alanine is added in methanol, then adds in calcium source, heating is stirred to react, and filtrate is collected in filtering；
S2. filtrate is cooled down, then adds in D-VB5 lactone, be stirred to react, added in crystal seed, continue to be stirred to react；
S3. reaction, which terminates to add at water-15-- 20 DEG C, continues crystallization, is then filtered, washed, collects filter cake and filtrate, filter respectively
Cake recycles DL- pantolactones through drying, filtrate through sour water solution.
2. the green synthesis method of D-VB5 calcium according to claim 1, which is characterized in that
Calcium source in the step S1 is one or more in calcium oxide, calcium carbonate, calcium metal, calcium cationic exchange resin.
3. the green synthesis method of D-VB5 calcium according to claim 1, which is characterized in that
Reaction temperature in the step S1 is 30-50 DEG C.
4. the green synthesis method of D-VB5 calcium according to claim 1, which is characterized in that
Organic solvent in the step S1 is dimethyl sulfoxide (DMSO), n,N-Dimethylformamide, acetonitrile, the tert-butyl alcohol, methanol, ethyl alcohol
One or more of mixing.
5. the green synthesis method of D-VB5 calcium according to claim 1, which is characterized in that
Cooling temperature in the step S2 is -10-20 DEG C, is stirred to react the time as 3-6h.
6. the green synthesis method of D-VB5 calcium according to claim 5, which is characterized in that
Continue the time being stirred to react as 12-20h in the step S2.
7. the green synthesis method of D-VB5 calcium according to claim 1, which is characterized in that
The 1-5% that reaction terminates in the step S3 plus the quality dosage of water is inventory.
8. the green synthesis method of D-VB5 calcium according to claim 1, which is characterized in that
The time for continuing crystallization in the step S3 is 1-5h.
9. the green synthesis method of D-VB5 calcium according to claim 1, which is characterized in that
The drying mode of filter cake in the step S3 is spray drying.
10. the green synthesis method of D-VB5 calcium according to claim 1, which is characterized in that
The acid used in sour water solution in the step S3 is hydrochloric acid, one or more of mixing in sulfuric acid, phosphoric acid, perchloric acid.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109970586A (en) * | 2019-04-29 | 2019-07-05 | 安徽安力肽生物科技有限公司 | A kind of preparation method of Beta- Alanine calcium salt |
| CN110845307A (en) * | 2019-11-28 | 2020-02-28 | 安徽泰格生物科技有限公司 | Method for recovering D-calcium pantothenate mother liquor |
| CN111518861A (en) * | 2020-05-14 | 2020-08-11 | 吴江 | Novel process for preparing D-calcium pantothenate |
| CN111807980A (en) * | 2019-11-28 | 2020-10-23 | 安徽泰格生物科技有限公司 | Crystallization method of D-calcium pantothenate |
| CN112457181A (en) * | 2020-12-11 | 2021-03-09 | 黄冈美丰化工科技有限公司 | Synthesis method of D-calcium pantothenate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU403670A1 (en) * | 1971-05-24 | 1973-10-26 | METHOD OF OBTAINING D-CALCIUM PANTOTENATE | |
| CN1765877A (en) * | 2005-10-24 | 2006-05-03 | 浙江大学宁波理工学院 | D-calcium pantothenate synthesis method |
| CN101948402A (en) * | 2010-08-20 | 2011-01-19 | 新发药业有限公司 | Method for preparing D-calcium pantothenate |
-
2018
- 2018-01-12 CN CN201810030285.1A patent/CN108129346A/en active Pending
Patent Citations (3)
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|---|---|---|---|---|
| SU403670A1 (en) * | 1971-05-24 | 1973-10-26 | METHOD OF OBTAINING D-CALCIUM PANTOTENATE | |
| CN1765877A (en) * | 2005-10-24 | 2006-05-03 | 浙江大学宁波理工学院 | D-calcium pantothenate synthesis method |
| CN101948402A (en) * | 2010-08-20 | 2011-01-19 | 新发药业有限公司 | Method for preparing D-calcium pantothenate |
Non-Patent Citations (1)
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| 任怡: "D-泛酸钙的合成工艺研究", 《中国优秀硕士学位论文全文数据库 工程科技I辑》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109970586A (en) * | 2019-04-29 | 2019-07-05 | 安徽安力肽生物科技有限公司 | A kind of preparation method of Beta- Alanine calcium salt |
| CN110845307A (en) * | 2019-11-28 | 2020-02-28 | 安徽泰格生物科技有限公司 | Method for recovering D-calcium pantothenate mother liquor |
| CN111807980A (en) * | 2019-11-28 | 2020-10-23 | 安徽泰格生物科技有限公司 | Crystallization method of D-calcium pantothenate |
| CN111518861A (en) * | 2020-05-14 | 2020-08-11 | 吴江 | Novel process for preparing D-calcium pantothenate |
| CN111518861B (en) * | 2020-05-14 | 2022-05-03 | 安徽泰格生物科技有限公司 | Novel process for preparing D-calcium pantothenate |
| CN112457181A (en) * | 2020-12-11 | 2021-03-09 | 黄冈美丰化工科技有限公司 | Synthesis method of D-calcium pantothenate |
| CN112457181B (en) * | 2020-12-11 | 2023-08-29 | 黄冈美丰化工科技有限公司 | Synthesis method of D-calcium pantothenate |
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