CN106316869A - Synthesis method of beta-alanine methyl ester salt product - Google Patents
Synthesis method of beta-alanine methyl ester salt product Download PDFInfo
- Publication number
- CN106316869A CN106316869A CN201610684105.2A CN201610684105A CN106316869A CN 106316869 A CN106316869 A CN 106316869A CN 201610684105 A CN201610684105 A CN 201610684105A CN 106316869 A CN106316869 A CN 106316869A
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- Prior art keywords
- beta
- methyl ester
- alanine
- alanine methyl
- solution
- Prior art date
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- UZCXPYDBYUEZCV-UHFFFAOYSA-N methyl 3-aminopropanoate Chemical class COC(=O)CCN UZCXPYDBYUEZCV-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 238000001308 synthesis method Methods 0.000 title abstract 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 57
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims abstract description 50
- 229940000635 beta-alanine Drugs 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000008213 purified water Substances 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims description 20
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 16
- QLAJNZSPVITUCQ-UHFFFAOYSA-N 1,3,2-dioxathietane 2,2-dioxide Chemical compound O=S1(=O)OCO1 QLAJNZSPVITUCQ-UHFFFAOYSA-N 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 13
- 235000011149 sulphuric acid Nutrition 0.000 claims description 11
- 239000001117 sulphuric acid Substances 0.000 claims description 11
- 238000010189 synthetic method Methods 0.000 claims description 10
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 9
- 229910021529 ammonia Inorganic materials 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 238000010992 reflux Methods 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 4
- 238000010792 warming Methods 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- UNKWUIORUPKZBA-UHFFFAOYSA-N methyl 3-aminopropanoate;sulfuric acid Chemical compound OS(O)(=O)=O.COC(=O)CCN UNKWUIORUPKZBA-UHFFFAOYSA-N 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 239000007789 gas Substances 0.000 abstract description 2
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 abstract 1
- 239000000908 ammonium hydroxide Substances 0.000 abstract 1
- 231100000331 toxic Toxicity 0.000 abstract 1
- 230000002588 toxic effect Effects 0.000 abstract 1
- 239000002253 acid Substances 0.000 description 4
- 150000004702 methyl esters Chemical class 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- -1 methyl ester salt Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- WVSBBCCXKUUWGB-ZETCQYMHSA-N COC([C@@H](NCCC)CCO)=O Chemical class COC([C@@H](NCCC)CCO)=O WVSBBCCXKUUWGB-ZETCQYMHSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 230000000680 avirulence Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010959 commercial synthesis reaction Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XPGRZDJXVKFLHQ-UHFFFAOYSA-N hydron;methyl 3-aminopropanoate;chloride Chemical compound Cl.COC(=O)CCN XPGRZDJXVKFLHQ-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- WCYAALZQFZMMOM-UHFFFAOYSA-N methanol;sulfuric acid Chemical compound OC.OS(O)(=O)=O WCYAALZQFZMMOM-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method of a beta-alanine methyl ester salt product, and relates to the technical field of beta-alanine methyl ester salt production. The method includes the following steps of firstly, adding beta-alanine to methyl alcohol to be stirred, and adding concentrated sulfuric acid; secondly, conducting backflow after feeding of concentrated sulfuric acid ends; thirdly, concentrating a methyl alcohol solution of beta-alanine methyl ester salt; fourthly, adding the concentrated solution to purified water to be evenly stirred, adjusting the PH of a water solution of beta-alanine methyl ester salt through ammonium hydroxide, and storing the prepared water solution of beta-alanine methyl ester salt at low temperature. The method has the advantages of being high in yield, easy to operate and easy to control; the method is free of toxic and corrosive gases in the synthesis process, small in environment pollution and beneficial to large-scale production.
Description
Technical field
The present invention relates to the production method technical field of Beta-alanine methyl ester product salt.
Background technology
Methyl lactamine salt is mainly used as medicine intermediate and research reagents, is widely used in molecular biology, pharmacology
Deng scientific research aspect.
Beta-alanine methyl ester salt is highly soluble in water, ethanol, acetone and other organic solvent.At present, the conjunction of Beta-alanine methyl ester salt
One-tenth method complicated condition, need to use a large amount of organic solvent, requires production environment extremely harsh.Meanwhile, the β-the third of commercial synthesis
Propylhomoserin methyl ester salt is mainly Beta-alanine methyl ester hydrochloride, and (chemical formula is C4H9NO2HCl), containing hydrogen chloride in its molecule, tool
There is certain toxicity, be unfavorable for that wide scale security produces.
Summary of the invention
The present invention is directed to above-mentioned the deficiencies in the prior art, it is provided that a kind of Beta-alanine methyl ester product salt synthetic method, adopt
With Beta-alanine, methanol and concentrated sulphuric acid, under the conditions of uniform temperature, synthesize Beta-alanine methosulfate, concentrate afterwards, add water mixed
Close uniformly, yield 90～95%.The technical scheme yield that the present invention provides is high, simple to operate easily controllable, can be used for extensive raw
Produce.
The invention provides the synthetic method of a kind of Beta-alanine methyl ester product salt, comprise the steps:
(1) take after the Beta-alanine of constant weight joins and stir in methanol, under normal temperature condition, be slowly added to concentrated sulphuric acid；
(2), after concentrated sulphuric acid stream adds end, the solution obtained is heated up, refluxes and lowers the temperature；
(3) the Beta-alanine methosulfate methanol solution obtained is concentrated into steams without methanol, i.e. obtain L-glycine methyl ester
Sulfate concentrated solution；
(4) concentrated solution is cooled to 20～23 DEG C, adds purified water and make Beta-alanine methosulfate aqueous solution, and use ammonia
Regulate described solution ph to 0～5, preserve under the conditions of 0～15 DEG C.
Wherein, for ease of controlling, room temperature uses 19～21 DEG C of scopes.Temperature-fall period in step (2) is primarily to just
In L-glycine methyl ester sulfate methanol solution transfer backflow obtained, carry out next step.Step (2) is cooled to 20
～23 DEG C be to prepare in order to next step adds water, temperature adds water in the case of higher and easily causes described L-glycine methyl ester sulphuric acid
The hydrolysis of salt, makes product yield reduce, degradation.Adding water after concentration is to do conversion further, for synthesizing other products
Prepare.
Preferably, in described step (2), it is warming up to 65～68 DEG C, refluxes 6～8 hours, be cooled to 20～25 DEG C.
Preferably, in described step (3), the condition of described concentration is 45 DEG C～50 DEG C, vacuum.
Preferably, in described step (1), described methanol weight is 6～9 times of described L-glycine weight, described dense sulfur
Acid weight is 1～2 times of described Beta-alanine weight.
Preferably, in described step (4), the weight of described purified water is 8～9 times of described Beta-alanine weight.
Preferably, in described step (4), with the ammonia described solution ph of regulation to 2.5, and preserve under the conditions of 7 DEG C.
The technical scheme raw material that the present invention provides includes L-glycine, methanol, concentrated sulphuric acid but it also may have for utilization
The corresponding product of Material synthesis of similar chemical property, as used the isomers of L-glycine to synthesize corresponding methyl ester salt.
Use and have the beneficial effects that produced by technique scheme:
Beta-alanine is placed in methanol to react with concentrated sulphuric acid and generates Beta-alanine methosulfate by the present invention, then by dense
Contracting, molten dilution, ammonia adjust PH thus obtain Beta-alanine methosulfate aqueous solution.The method is simple to operate, easily controllable,
Yield is high, and yield is up to 90～95%.Avirulence, corrosive gas in building-up process, environmental pollution is little, can be used for β the-the third ammonia
The large-scale production of acid methyl ester salt.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is further detailed explanation.
Embodiment one:
Take Beta-alanine 300g and join stirring in 1900g methanol, at 19～21 DEG C, be slowly added to 400g concentrated sulphuric acid.Dense sulfur
After acid stream adds end, it is warming up to 65～68 DEG C, refluxes 8 hours, be cooled to 24 DEG C.By Beta-alanine methosulfate methanol solution
At 45 DEG C, it is concentrated under vacuum condition and steams without methanol.Concentrated solution is down to 22 DEG C, adds purified water 2500ml, adjust with ammonia
Joint Beta-alanine methosulfate solution ph is to 2.5.The Beta-alanine methosulfate aqueous solution 7 DEG C preservation that will prepare.
Obtain Beta-alanine methosulfate aqueous solution 2850ml, methyl ester content 115.7g/L, methyl ester yield 95%.
Embodiment two:
Take Beta-alanine 300g and join stirring in 1900g methanol, at 19～21 DEG C, be slowly added to 400g concentrated sulphuric acid.Dense sulfur
After acid stream adds end, it is warming up to 65～68 DEG C, refluxes 8 hours, be cooled to 23 DEG C.By Beta-alanine methosulfate methanol solution
At 45 DEG C, it is concentrated under vacuum condition and steams without methanol.Concentrated solution is down to 23 DEG C, adds purified water 2500ml, adjust with ammonia
Joint Beta-alanine methosulfate solution ph is to 2.5.The Beta-alanine methosulfate aqueous solution 7 DEG C preservation that will prepare.
Obtain Beta-alanine methosulfate aqueous solution 2850ml, methyl ester content 112g/L, methyl ester yield 92%.
Claims (7)
1. the synthetic method of a Beta-alanine methyl ester product salt, it is characterised in that comprise the steps:
(1) take after the Beta-alanine of constant weight joins and stir in methanol, under normal temperature condition, be slowly added to concentrated sulphuric acid；
(2), after concentrated sulphuric acid stream adds end, the solution obtained is heated up, refluxes and lowers the temperature；
(3) the Beta-alanine methosulfate methanol solution obtained is concentrated into steams without methanol, i.e. obtain Beta-alanine methyl ester
Sulfate concentrated solution.
The synthetic method of Beta-alanine methyl ester product salt the most according to claim 1, it is characterised in that described step
(2) in, it is warming up to 65～68 DEG C, refluxes 6～8 hours, be cooled to 20～25 DEG C.
The synthetic method of Beta-alanine methyl ester product salt the most according to claim 1, it is characterised in that described step (3)
In, the condition of described concentration is 45～50 DEG C, vacuum.
The synthetic method of Beta-alanine methyl ester product salt the most according to claim 1, it is characterised in that described step (1)
In, described methanol weight is 6～9 times of described L-glycine weight, and described concentrated sulphuric acid weight is the 1 of described L-glycine weight
～2 times.
The synthetic method of Beta-alanine methyl ester product salt the most according to claim 1, further comprising the steps of, its feature exists
In, the concentrated solution obtained in described step (3) is cooled to 20～23 DEG C, adds purified water and make Beta-alanine methosulfate
Aqueous solution, and with the ammonia described solution ph of regulation to 0～5, preserve under the conditions of 0～15 DEG C.
The synthetic method of Beta-alanine methyl ester product salt the most according to claim 5, it is characterised in that add described purification
The weight of water is 8～9 times of described Beta-alanine weight.
The synthetic method of Beta-alanine methyl ester product salt the most according to claim 5, it is characterised in that regulate institute with ammonia
State solution ph to 2.5, the L-glycine methyl ester sulfate solution prepared is preserved under the conditions of 7 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610684105.2A CN106316869A (en) | 2016-08-18 | 2016-08-18 | Synthesis method of beta-alanine methyl ester salt product |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610684105.2A CN106316869A (en) | 2016-08-18 | 2016-08-18 | Synthesis method of beta-alanine methyl ester salt product |
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| Publication Number | Publication Date |
|---|---|
| CN106316869A true CN106316869A (en) | 2017-01-11 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610684105.2A Pending CN106316869A (en) | 2016-08-18 | 2016-08-18 | Synthesis method of beta-alanine methyl ester salt product |
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| Country | Link |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110642736A (en) * | 2019-09-23 | 2020-01-03 | 湖北宇阳药业有限公司 | Synthesis method of acetamido-3-methyl chloropropionate |
| CN111019987A (en) * | 2019-12-27 | 2020-04-17 | 江苏诚信药业有限公司 | Preparation method of glutamine dipeptide |
| CN111057732A (en) * | 2019-12-27 | 2020-04-24 | 江苏诚信药业有限公司 | Desalination process in glutamine dipeptide production |
| CN113004160A (en) * | 2021-03-15 | 2021-06-22 | 淮北市博康生物科技有限公司 | Synthetic method of L-serine methyl ester sulfate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0376230A2 (en) * | 1988-12-27 | 1990-07-04 | MITSUI TOATSU CHEMICALS, Inc. | Preparation and isolation of mineral acid salt of an amino methyl ester |
| WO2007074390A2 (en) * | 2005-12-28 | 2007-07-05 | Bakulesh Mafatlal Khamar | Process for preparing rhodanine-3-acetic acid: a key intermediated of epalrestat |
| WO2012025726A1 (en) * | 2010-08-27 | 2012-03-01 | University Of Greenwich | Novel Hybrid Compounds |
-
2016
- 2016-08-18 CN CN201610684105.2A patent/CN106316869A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0376230A2 (en) * | 1988-12-27 | 1990-07-04 | MITSUI TOATSU CHEMICALS, Inc. | Preparation and isolation of mineral acid salt of an amino methyl ester |
| WO2007074390A2 (en) * | 2005-12-28 | 2007-07-05 | Bakulesh Mafatlal Khamar | Process for preparing rhodanine-3-acetic acid: a key intermediated of epalrestat |
| WO2012025726A1 (en) * | 2010-08-27 | 2012-03-01 | University Of Greenwich | Novel Hybrid Compounds |
Non-Patent Citations (3)
| Title |
|---|
| PETER STEUNENBERG等: "Polymerisation of b-alanine through catalytic ester-amide exchange", 《EUROPEAN POLYMER JOURNAL》 * |
| 冯光炷等: "复合氨基酸月桂醇酯的合成及性能", 《郑州工程学院学报》 * |
| 吴建中: "α－L－天门冬酰－L－苯丙氨酸甲酯的合成及应用", 《辽宁化工》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110642736A (en) * | 2019-09-23 | 2020-01-03 | 湖北宇阳药业有限公司 | Synthesis method of acetamido-3-methyl chloropropionate |
| CN111019987A (en) * | 2019-12-27 | 2020-04-17 | 江苏诚信药业有限公司 | Preparation method of glutamine dipeptide |
| CN111057732A (en) * | 2019-12-27 | 2020-04-24 | 江苏诚信药业有限公司 | Desalination process in glutamine dipeptide production |
| CN111057732B (en) * | 2019-12-27 | 2023-11-10 | 江苏诚信药业有限公司 | Desalination process in production of proglutin |
| CN113004160A (en) * | 2021-03-15 | 2021-06-22 | 淮北市博康生物科技有限公司 | Synthetic method of L-serine methyl ester sulfate |
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