CN109134403A - A kind of preparation method of 2-morpholine ethane sulfonic acid - Google Patents
A kind of preparation method of 2-morpholine ethane sulfonic acid Download PDFInfo
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- CN109134403A CN109134403A CN201811129125.9A CN201811129125A CN109134403A CN 109134403 A CN109134403 A CN 109134403A CN 201811129125 A CN201811129125 A CN 201811129125A CN 109134403 A CN109134403 A CN 109134403A
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- morpholine
- sulfonic acid
- ethane sulfonic
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- morpholine ethane
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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Abstract
The present invention relates to ethanesulfonic acid derivative more particularly to a kind of preparation methods of morpholino b acid.A kind of preparation method of 2-morpholine ethane sulfonic acid, by the organic solution of morpholine and chloro ethanesulfonic acid sodium, pH value determination under conditions of being heated to reflux, when pH value drops to 9, it is slowly added into the pH value of sodium methoxide control reaction system, after the reaction was completed, the methanol solution of 2-morpholine ethane sulfonic acid is obtained, after hydrochloric acid solution is added, pH value is adjusted to 5, heat filtering removes sodium chloride, obtains 2-morpholine ethane sulfonic acid solution freezing and crystallizing, and 2-morpholine ethane sulfonic acid is obtained after the crystal of crystallization is centrifugated.
Description
Technical field
The present invention relates to ethanesulfonic acid derivative more particularly to a kind of preparation methods of morpholino b acid.
Background technique
Morpholino b acid is a kind of very important biological buffer, be usually used in the separation of the protoplast of various plants with
Culture.It is readily applicable in perfumed soap and soap, can be used as lime soap dispersant.It is also main detergent active, can replaces
Low-phosphorous or non-phosphate detergent is made in part sodium alkyl benzene sulfonate and sodium tripolyphosphate.
Current conventional synthetic route is that morpholine and sodium vinyl sulfonate are carried out ring-opening reaction, is finally neutralized.Its Central Plains
Expect that price is higher, causes at high cost.And when ring-opening reaction, it is easy to produce by-product, causes reaction efficiency not high, causes finally to produce
Amount of substance is not high.
Summary of the invention
Present invention seek to address that the deficiencies in the prior art, provide a kind of preparation method of 2-morpholine ethane sulfonic acid.The present invention
High production efficiency, cost is lower, and product quality is good.
A kind of preparation method of 2-morpholine ethane sulfonic acid of the present invention is adding the organic solution of morpholine and chloro ethanesulfonic acid sodium
PH value determination is slowly added into sodium methoxide control when pH value drops to 9 under the condition (temperature is controlled at 60-70 DEG C) of heat reflux
The pH value of reaction system obtains the methanol solution of 2-morpholine ethane sulfonic acid after the reaction was completed, after hydrochloric acid solution is added, by pH value tune
For section to 5, heat filtering removes sodium chloride, obtains 2-morpholine ethane sulfonic acid solution freezing and crystallizing, after the crystal of crystallization is centrifugated i.e.
Obtain 2-morpholine ethane sulfonic acid.
A kind of preparation method of 2-morpholine ethane sulfonic acid, the yield of the 2-morpholine ethane sulfonic acid are pure up to 90% or more
Spend >=99% (HPLC).
The water content of a kind of preparation method of 2-morpholine ethane sulfonic acid, the methanol is lower than 1%, the morpholine purity
It is 99.5%.
The mass ratio of a kind of preparation method of 2-morpholine ethane sulfonic acid, the morpholine and organic solvent is 1: 3.
The molal weight ratio of a kind of preparation method of 2-morpholine ethane sulfonic acid, the morpholine and chloro ethanesulfonic acid sodium is
1∶1.1。
The present invention directlys adopt the common morpholine being easy to get, chloro ethanesulfonic acid sodium is raw material, at low cost.Further, since raw material
Structure and product structure are close, and combined coefficient is high, and final product quality is also more preferable.
Specific embodiment
A kind of preparation method of 2-morpholine ethane sulfonic acid of the present invention is adding the organic solution of morpholine and chloro ethanesulfonic acid sodium
PH value determination is slowly added into sodium methoxide control when pH value drops to 9 under the condition (temperature is controlled at 60-70 DEG C) of heat reflux
The pH value of reaction system obtains the methanol solution of 2-morpholine ethane sulfonic acid after the reaction was completed, after hydrochloric acid solution is added, by pH value tune
For section to 5, heat filtering removes sodium chloride, obtains 2-morpholine ethane sulfonic acid solution freezing and crystallizing, after the crystal of crystallization is centrifugated i.e.
Obtain 2-morpholine ethane sulfonic acid.
Embodiment 1
After 200 grams of methanol are added in the there-necked flask of 500ml, 50 grams of morpholines and 116 gram of one water chloro ethanesulfonic acid sodium are added,
There-necked flask is heated to methanol eddy (temperature is controlled at 60-70 DEG C), starts the pH value surveyed in there-necked flask after 30 minutes, works as pH value
When dropping to 9 or so, the mixed liquor for being initially added into sodium methoxide and methanol controls pH value to 9 or so, after reacting 8 hours, passes through TLC
Point the fully reacting of plate analysis morpholine after, start be added dropwise hydrochloric acid to pH value be 5 after, heat filtering desalination cools down there-necked flask
Crystallization, obtains as 2-morpholine ethane sulfonic acid crude product, obtained crude product is dissolved in 80% methanol solution, and adds under heating conditions
After entering 2 grams of decolorizing with activated carbon, obtained 2-morpholine ethane sulfonic acid solution freezing and crystallizing to get to 2-morpholine ethane sulfonic acid monohydrate,
The 2-morpholine ethane sulfonic acid dries to obtain 103 grams of finished product；Yield 92.46%, purity 99.21% (HPLC).
Embodiment 2
After 200 grams of ethyl alcohol are added in the there-necked flask of 500ml, 50 grams of morpholines and 116 gram of one water chloro ethanesulfonic acid sodium are added,
There-necked flask is heated to alcohol reflux (temperature is controlled at 75-85 DEG C), starts the pH value surveyed in there-necked flask after 30 minutes, works as pH value
When dropping to 9 or so, the mixed liquor for being initially added into sodium ethoxide and ethyl alcohol controls pH value to 9 or so, after reacting 8 hours, passes through TLC
Point the fully reacting of plate analysis morpholine after, start be added dropwise hydrochloric acid to pH value be 5 after, heat filtering desalination cools down there-necked flask
Crystallization, obtains as 2-morpholine ethane sulfonic acid crude product, obtained crude product is dissolved in 80% ethanol solution, and adds under heating conditions
After entering 2 grams of decolorizing with activated carbon, obtained 2-morpholine ethane sulfonic acid solution freezing and crystallizing to get to 2-morpholine ethane sulfonic acid monohydrate,
The 2-morpholine ethane sulfonic acid dries to obtain 97 grams of finished product；Yield 87.5%, purity 98.66% (HPLC).
Embodiment 3
After 200 kilograms of methanol are added in the reaction kettle of 500L, 50 kilograms of morpholines and 116 kilogram of one water chloro second sulphur are added
Reaction kettle is heated to methanol eddy (temperature is controlled at 60-70 DEG C), starts the pH value surveyed in reaction kettle after 30 minutes by sour sodium,
When pH value drops to 9 or so, the mixed liquor for being initially added into sodium methoxide and methanol controls pH value to after 9 or so, reaction 8 hours,
After the fully reacting of TLC point plate analysis morpholine, start be added dropwise hydrochloric acid to pH value be 5 after, heat filtering desalination, by reaction kettle into
Row crystallisation by cooling, obtains as 2-morpholine ethane sulfonic acid crude product, obtained crude product is dissolved in 80% methanol solution, and in the item of heating
After 2 kilograms of decolorizing with activated carbon are added under part, obtained 2-morpholine ethane sulfonic acid solution freezing and crystallizing is to get to 2-morpholine ethane sulfonic acid one
Hydrate, the 2-morpholine ethane sulfonic acid dry to obtain 107 kilograms of finished product；Yield 96.05%, purity 99.51% (HPLC).
Embodiment 4
After 800 kilograms of methanol are added in the reaction kettle of 2000L, 200 kilograms of morpholines and 464 kilogram of one water chloro second are added
Reaction kettle is heated to methanol eddy (temperature is controlled at 60-70 DEG C), starts the pH surveyed in reaction kettle after 30 minutes by sodium sulfonate
Value, when pH value drops to 9 or so, the mixed liquor for being initially added into sodium methoxide and methanol controls pH value to 9 or so, reacts 8 hours
Afterwards, after by the fully reacting of TLC point plate analysis morpholine, start be added dropwise hydrochloric acid to pH value be 5 after, heat filtering desalination will react
Kettle carries out crystallisation by cooling, obtains as 2-morpholine ethane sulfonic acid crude product, obtained crude product is dissolved in 80% methanol solution, and heating
Under conditions of 8 kilograms of decolorizing with activated carbon are added after, obtained 2-morpholine ethane sulfonic acid solution freezing and crystallizing is to get to 2- morpholine second sulphur
Sour monohydrate, the 2-morpholine ethane sulfonic acid dry to obtain 420 kilograms of finished product；Yield 94.2%, purity 99.22% (HPLC).
Embodiment 5
After 800 kilograms of methanol are added in the reaction kettle of 2000L, 200 kilograms of morpholines and 422 kilogram of one water chloro second are added
Reaction kettle is heated to methanol eddy (temperature is controlled at 60-70 DEG C), starts the pH surveyed in reaction kettle after 30 minutes by sodium sulfonate
Value, when pH value drops to 9 or so, the mixed liquor for being initially added into sodium methoxide and methanol controls pH value to 9 or so, reacts 8 hours
Afterwards, after by the fully reacting of TLC point plate analysis morpholine, start be added dropwise hydrochloric acid to pH value be 5 after, heat filtering desalination will react
Kettle carries out crystallisation by cooling, obtains as 2-morpholine ethane sulfonic acid crude product, obtained crude product is dissolved in 80% methanol solution, and heating
Under conditions of 8 kilograms of decolorizing with activated carbon are added after, obtained 2-morpholine ethane sulfonic acid solution freezing and crystallizing is to get to 2- morpholine second sulphur
Sour monohydrate, the 2-morpholine ethane sulfonic acid dry to obtain 391 kilograms of finished product；Yield 87.7%, purity 97.03% (HPLC).
Claims (5)
1. a kind of preparation method of 2-morpholine ethane sulfonic acid, it is characterized in that the organic solution of morpholine and chloro ethanesulfonic acid sodium is being added
It is anti-to be slowly added into sodium methoxide control when pH value drops to 9 for the condition of heat reflux, temperature control pH value determination at 60-70 DEG C
The pH value of system is answered, after the reaction was completed, the methanol solution of 2-morpholine ethane sulfonic acid is obtained, hydrochloric acid solution is added, pH value is adjusted to
5, heat filtering removes sodium chloride, obtains 2-morpholine ethane sulfonic acid solution freezing and crystallizing, obtains after the crystal of crystallization is centrifugated
2-morpholine ethane sulfonic acid.
2. a kind of preparation method of 2-morpholine ethane sulfonic acid according to claim 1, which is characterized in that the 2- morpholine second sulphur
The yield of acid is up to 90% or more, HPLC purity >=99%.
3. a kind of preparation method of 2-morpholine ethane sulfonic acid according to claim 1, which is characterized in that the methanol it is aqueous
Amount is lower than 1%, and the morpholine purity is 99.5%.
4. a kind of preparation method of 2-morpholine ethane sulfonic acid according to claim 1 or 3, which is characterized in that the morpholine with
The mass ratio of organic solvent is 1: 3.
5. a kind of preparation method of 2-morpholine ethane sulfonic acid according to claim 1, which is characterized in that the morpholine and chloro
The molal weight ratio of ethanesulfonic acid sodium is 1: 1.1.
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| CN201811129125.9A CN109134403B (en) | 2018-09-27 | 2018-09-27 | Preparation method of 2-morpholine ethanesulfonic acid |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109836399A (en) * | 2017-11-27 | 2019-06-04 | 荆楚理工学院 | A kind of synthetic method of biological buffer-morpholinoethanesulfonic acid |
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| US5792389A (en) * | 1993-10-27 | 1998-08-11 | United States Of America | Water soluble laser dyes |
| US6114337A (en) * | 1998-11-27 | 2000-09-05 | Pugliese; Peter T. | Zwitteronic-fatty acid compounds having anti-inflammatory properties |
| EP1110958A1 (en) * | 1999-12-20 | 2001-06-27 | Ucb, S.A. | Alpha-arylethylpiperazine derivatives as neurokinin antagonists |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109836399A (en) * | 2017-11-27 | 2019-06-04 | 荆楚理工学院 | A kind of synthetic method of biological buffer-morpholinoethanesulfonic acid |
| CN109836399B (en) * | 2017-11-27 | 2021-08-17 | 荆楚理工学院 | Synthetic method of biological buffer-morpholinyl ethanesulfonic acid |
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| CN109134403B (en) | 2022-08-16 |
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Effective date of registration: 20230323 Address after: 425000 West Wulidui Road, Lingling Industrial Park, Lingling District, Yongzhou City, Hunan Province Patentee after: Hunan Hengfei Biopharmaceutical Co.,Ltd. Address before: No. 342, Building B, Phase II, Chemical Zone, Wantian International Building Materials City, Dingziwan Street, Wangcheng District, Changsha City, Hunan Province, 410020 Patentee before: HUNAN HENGTAI CHEMICAL Co.,Ltd. |