CN114394918B - Preparation method of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid - Google Patents
Preparation method of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid Download PDFInfo
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- CN114394918B CN114394918B CN202210062719.2A CN202210062719A CN114394918B CN 114394918 B CN114394918 B CN 114394918B CN 202210062719 A CN202210062719 A CN 202210062719A CN 114394918 B CN114394918 B CN 114394918B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
- C07C303/22—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof from sulfonic acids, by reactions not involving the formation of sulfo or halosulfonyl groups; from sulfonic halides by reactions not involving the formation of halosulfonyl groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/42—Separation; Purification; Stabilisation; Use of additives
- C07C303/44—Separation; Purification
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Abstract
The application provides a preparation method of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid, which comprises the following steps of S1: carrying out addition reaction on sodium vinylsulfonate and tris (hydroxymethyl) aminomethane in the solution to generate a 2- ((tris (hydroxymethyl) methyl) amino) ethanesulfonic acid sodium solution; s2: removing sodium ions from the solution obtained in the step S1 through a strong acid ion exchange resin to obtain a 2- ((tri (hydroxymethyl) methyl) amino) ethanesulfonic acid solution; s3: the solution obtained in the step S2 is decompressed and distilled to remove water, and then is recrystallized by an organic solvent to obtain the product 2- ((tris (hydroxymethyl) methyl) amino) ethanesulfonic acid. The preparation method provided by the application has the advantages of simple process operation, repeated use after the exchange treatment of the strong acid ion exchange resin, safety, environmental protection, high reaction yield and high product purity. Avoid the salification problem caused by using halogenated substance halogenated ethyl sulfonic acid or 1, 2-dihalogenated ethane, and can be used for industrial production.
Description
Technical Field
The application relates to the technical field of organic synthesis, in particular to a preparation method of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid.
Background
2- ((tri (hydroxymethyl) methyl) amino) ethanesulfonic acid is a sulfamate biological buffer and has wide application in tissue culture, vaccine production, blood protein storage, biological substance separation and other aspects.
Through literature review, the related synthesis process is found, one is that the catalyst is prepared by reflux reaction of 2-haloethyl sulfonic acid serving as a raw material and tris (hydroxymethyl) aminomethane; and a preparation method of 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid, which is disclosed in patent CN112479937A, wherein 1, 2-dihaloethane is taken as a raw material, and is reacted with tris (hydroxymethyl) aminomethane in a reflux manner and then reacted with sodium sulfite in the presence of a catalyst to finally obtain a target product. In the two processes, the halide is used as a raw material, residual halogen acid exists in the reaction, salt is formed with the product, and the halogen acid is very difficult to remove in practical application. In view of the above, the present application proposes a method for preparing 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid.
Disclosure of Invention
The application aims to provide a preparation method of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid, which has the advantages of simple and convenient process operation, safety, environmental protection, high reaction yield and high product purity.
A method for preparing 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid, comprising the steps of:
s1: carrying out addition reaction on sodium vinylsulfonate and tris (hydroxymethyl) aminomethane in the solution to generate a 2- ((tris (hydroxymethyl) methyl) amino) ethanesulfonic acid sodium solution;
s2: removing sodium ions from the solution obtained in the step S1 through a strong acid ion exchange resin to obtain a 2- ((tri (hydroxymethyl) methyl) amino) ethanesulfonic acid solution;
s3: the solution obtained in the step S2 is decompressed and distilled to remove water, and then is recrystallized by an organic solvent to obtain the product 2- ((tris (hydroxymethyl) methyl) amino) ethanesulfonic acid.
Further, the reaction solvent in the step S1 is water.
Further, in the step S1, the reaction feeding molar ratio of the tris (hydroxymethyl) aminomethane to the sodium vinylsulfonate is 1.0-1.5:1.0.
further, the reaction temperature of the step S1 is 80-140 ℃.
Further, the reaction time of the step S1 is 24-72h.
Further, the amount of the strongly acidic ion exchange resin is 1.5 to 3.0L per mol of sodium vinylsulfonate.
Further, the organic solvent in the step S3 is methanol or ethanol.
The application has the advantages that:
in the preparation method of 2- ((tri (hydroxymethyl) methyl) amino) ethanesulfonic acid, sodium vinylsulfonate (or an aqueous solution thereof) is used as a raw material to react with tris (hydroxymethyl) aminomethane, and the obtained reaction solution is subjected to sodium ion removal through strong acid ion exchange resin to generate the product 2- ((tri (hydroxymethyl) methyl) amino) ethanesulfonic acid. The process is simple and convenient to operate, can be repeatedly used after the strong acid ion exchange resin is subjected to exchange treatment, is safe and environment-friendly, and has high reaction yield and high product purity. Avoid the salification problem caused by using halogenated substance halogenated ethyl sulfonic acid or 1, 2-dihalogenated ethane, and can be used for industrial production.
Drawings
FIG. 1 is an equation for a method of preparation provided by the present application;
FIG. 2 is an infrared spectrum of the product obtained in example 1 of the present application.
Detailed Description
The application will be further illustrated with reference to the following specific embodiments, which are intended to illustrate the application and not to limit it further.
The application adopts the following technical scheme to solve the technical problems: the application provides a preparation method of 2- ((tri (hydroxymethyl) methyl) amino) ethanesulfonic acid, which takes sodium vinylsulfonate as a raw material, reacts with tris (hydroxymethyl) aminomethane, and the generated 2- ((tri (hydroxymethyl) methyl) amino) ethanesulfonic acid sodium is subjected to sodium ion removal through a strong acid ion exchange resin to generate 2- ((tri (hydroxymethyl) methyl) amino) ethanesulfonic acid.
The method specifically comprises the following steps:
s1: carrying out addition reaction on sodium vinylsulfonate and tris (hydroxymethyl) aminomethane in the solution to generate a 2- ((tris (hydroxymethyl) methyl) amino) ethanesulfonic acid sodium solution;
s2: removing sodium ions from the solution obtained in the step S1 through a strong acid ion exchange resin to obtain a 2- ((tri (hydroxymethyl) methyl) amino) ethanesulfonic acid solution;
s3: the solution obtained in the step S2 is decompressed and distilled to remove water, and then is recrystallized by an organic solvent to obtain the product 2- ((tris (hydroxymethyl) methyl) amino) ethanesulfonic acid.
Wherein, the reaction solvent in the step S1 is water; further, in the step S1, the reaction feeding molar ratio of the tris (hydroxymethyl) aminomethane to the sodium vinylsulfonate is 1.0-1.5:1.0, preferably the reaction charge mole ratio is 1.0-1.3:1.0; the reaction temperature in the step S1 is 80-140 ℃, and the preferable reaction temperature is 90-130 ℃; the reaction time of the step S1 is 24-72h, and the preferable reaction time is 36-48h; the dosage of the strong acid ion exchange resin is 1.5-3.0L per mol of sodium vinylsulfonate; the organic solvent in the step S3 is methanol or ethanol.
The following is a description of specific examples:
example 1
Example 1 provides a process for the preparation of 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid comprising the steps of: 520 g (1 mol) of 25% aqueous solution of sodium vinylsulfonate and 133 g (1.1 mol) of tris (hydroxymethyl) aminomethane are added into a 1000 ml four-port bottle, stirring is started, the stirring speed is 50-60 r/min, the reactant is heated under normal pressure, and water is continuously distilled out along with the increase of the temperature of the materials;
when the temperature of the reactant reaches 130 ℃, reflux is changed, and stirring reflux reaction is carried out for 48 hours under the temperature; after the reaction was completed, the reaction mixture was cooled to room temperature and passed through a strongly acidic ion exchange resin (1.5 liter). After the materials pass through the resin, washing the materials to the resin by using 1 liter of water;
combining the materials and the washing water solution, and concentrating under reduced pressure at 70-80deg.C until the materials become thick paste;
cooling to 40deg.C, adding ethanol (200 g), heating to reflux, and refluxing for 1 hr; cooling to room temperature, precipitating crystals, and filtering; the resulting product was air dried at 60℃or vacuum dried.
193 g of white crystalline product were finally obtained, with a yield of 84.2% calculated on sodium vinylsulfonate.
Through detection, the infrared spectrogram is consistent with the standard substance.
Melting point: 222-225 ℃;
the content is as follows: 99.20%;
moisture content: 0.07%;
heavy metal: <5ppm;
ultraviolet absorbance (33% aqueous solution, w/w) 290nm:0.050;
solubility (33% aqueous solution, w/w): colorless and transparent.
Example 2
Example 2 provides a process for the preparation of 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid comprising the steps of: 520 g (1 mol) of 25% aqueous solution of sodium vinylsulfonate and 145 g (1.2 mol) of tris (hydroxymethyl) aminomethane are added into a 1000 ml four-port bottle, stirring is started, the stirring speed is 50-60 r/min, the reactant is heated under normal pressure, and water is continuously distilled out along with the rise of the temperature of the material;
when the temperature of the reactant reaches 130 ℃, reflux is changed, and stirring reflux reaction is carried out for 48 hours under the temperature; after the reaction was completed, the reaction mixture was cooled to room temperature and passed through a strongly acidic ion exchange resin (1.5 liter). After the materials pass through the resin, washing the materials to the resin by using 1 liter of water;
combining the materials and the washing water solution, and concentrating under reduced pressure at 70-80deg.C until the materials become thick paste;
cooling to 40deg.C, adding ethanol (200 g), heating to reflux, and refluxing for 1 hr; cooling to room temperature, precipitating crystals, and filtering; the resulting product was air dried at 60℃or vacuum dried.
194 g of white crystalline product are finally obtained, with a yield of 84.6% calculated on sodium vinylsulfonate.
Through detection, the infrared spectrogram is consistent with the standard substance.
Melting point: 223-225 ℃;
the content is as follows: 99.25%;
moisture content: 0.08%;
heavy metal: <5ppm;
ultraviolet absorbance (33% aqueous solution, w/w) 290nm:0.056;
solubility (33% aqueous solution, w/w): colorless and transparent.
Finally, it should be noted that: the above embodiments are only for illustrating the present application and not for limiting the technical solution described in the present application; it will be understood by those skilled in the art that the present application may be modified or equivalents; all technical solutions and modifications thereof that do not depart from the spirit and scope of the present application are intended to be included in the scope of the appended claims.
Claims (1)
1. A process for the preparation of 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid, comprising the steps of:
adding 520 g of 25% aqueous solution of sodium vinylsulfonate into a 1000 ml four-port bottle, adding 133 g of tris (hydroxymethyl) aminomethane, starting stirring, heating the reactant at the stirring speed of 50-60 r/min under normal pressure, and continuously steaming out water along with the increase of the temperature of the material;
when the temperature of the reactant reaches 130 ℃, reflux is changed, and stirring reflux reaction is carried out for 48 hours under the temperature; after the reaction was completed, the reaction mixture was cooled to room temperature and passed through 1.5 liters of a strongly acidic ion exchange resin; after the materials pass through the resin, washing the materials to the resin by using 1 liter of water; combining the materials and the washing water solution, and concentrating under reduced pressure at 70-80deg.C until the materials become thick paste;
cooling to 40 ℃, adding 200 g of ethanol, heating to reflux, and refluxing for 1 hour; cooling to room temperature, precipitating crystals, and filtering; the obtained product is dried by blowing at 60 ℃ or vacuum;
or (b)
Adding 520 g of 25% aqueous solution of sodium vinylsulfonate into a 1000 ml four-port bottle, adding 145 g of tris (hydroxymethyl) aminomethane, starting stirring, heating the reactant at the stirring speed of 50-60 r/min under normal pressure, and continuously steaming out water along with the increase of the temperature of the material;
when the temperature of the reactant reaches 130 ℃, reflux is changed, and stirring reflux reaction is carried out for 48 hours under the temperature; after the reaction was completed, the reaction mixture was cooled to room temperature and passed through 1.5 liters of a strongly acidic ion exchange resin; after the materials pass through the resin, washing the materials to the resin by using 1 liter of water; combining the materials and the washing water solution, and concentrating under reduced pressure at 70-80deg.C until the materials become thick paste;
cooling to 40 ℃, adding 200 g of ethanol, heating to reflux, and refluxing for 1 hour; cooling to room temperature, precipitating crystals, and filtering; the resulting product was air dried at 60℃or vacuum dried.
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| CN202210062719.2A CN114394918B (en) | 2022-01-19 | 2022-01-19 | Preparation method of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid |
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| CN202210062719.2A CN114394918B (en) | 2022-01-19 | 2022-01-19 | Preparation method of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2066245A (en) * | 1979-07-30 | 1981-07-08 | Nippon Paint Co Ltd | Process for preparing hydroxyalkylaminosulphonic acids |
| CN1250161A (en) * | 1998-09-29 | 2000-04-12 | 松下电器产业株式会社 | Glucose sensor |
| CN101845003A (en) * | 2010-01-29 | 2010-09-29 | 华东理工大学 | N-tris (hydroxymethyl) methyl-3-aminopropanesulfonic acid compound and preparation method thereof |
| CN103919792A (en) * | 2008-08-22 | 2014-07-16 | 瑞立普萨公司 | Crosslinked Cation Exchange Polymers, Compositions And Use In Treating Hyperkalemia |
| CN112209858A (en) * | 2020-10-16 | 2021-01-12 | 湖南韵邦生物医药有限公司 | Preparation method of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid |
-
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- 2022-01-19 CN CN202210062719.2A patent/CN114394918B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2066245A (en) * | 1979-07-30 | 1981-07-08 | Nippon Paint Co Ltd | Process for preparing hydroxyalkylaminosulphonic acids |
| CN1250161A (en) * | 1998-09-29 | 2000-04-12 | 松下电器产业株式会社 | Glucose sensor |
| CN103919792A (en) * | 2008-08-22 | 2014-07-16 | 瑞立普萨公司 | Crosslinked Cation Exchange Polymers, Compositions And Use In Treating Hyperkalemia |
| CN101845003A (en) * | 2010-01-29 | 2010-09-29 | 华东理工大学 | N-tris (hydroxymethyl) methyl-3-aminopropanesulfonic acid compound and preparation method thereof |
| CN112209858A (en) * | 2020-10-16 | 2021-01-12 | 湖南韵邦生物医药有限公司 | Preparation method of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid |
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