CN112479937A - 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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- CN112479937A CN112479937A CN202011357994.4A CN202011357994A CN112479937A CN 112479937 A CN112479937 A CN 112479937A CN 202011357994 A CN202011357994 A CN 202011357994A CN 112479937 A CN112479937 A CN 112479937A
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- C07—ORGANIC CHEMISTRY
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- 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
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
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Abstract
The invention discloses a preparation method of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid, which comprises the following steps: dissolving trihydroxymethyl aminomethane and 1, 2-dihaloethane in a solvent, heating and raising the temperature to reflux reaction while stirring, and controlling the pH value of the solution to be more than or equal to 7.0 to obtain a first intermediate reaction solution; adding sodium sulfite into the first intermediate reaction liquid, heating to raise the temperature to reflux reaction under the action of a catalyst to obtain a second intermediate reaction liquid; and cooling and filtering the second intermediate reaction liquid, adding cation exchange resin, adsorbing, desolventizing and crystallizing to obtain the 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid. The invention adopts a two-step one-pot method for synthesis, has high reaction yield, simple and convenient post-treatment process and good product purity, and simultaneously overcomes the problems of low yield or three wastes caused by using 2-halogenated ethanesulfonic acid.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid.
Background
2- [ [ tris (hydroxymethyl) methyl group]Amino group]Ethanesulfonic acid, a biological buffer of the sulfamate type, the molecular structural formula of which is
2- [ [ tris (hydroxymethyl) methyl group]Amino group]Ethanesulfonic acid has found wide applications in tissue culture, vaccine production, research on cationic efficacy, bacterial culture, cryopreservation of tissues, virus identification, storage of blood proteins, fungal protoplast culture, electron microscopy, and techniques for separation of biological materials. In addition, it is worth trying to use in diagnostic medicine, clinical chemistry, and the like.
The amphoteric ion buffer of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid is one of the products with important application value of the buffer salt, and is used in a plurality of biochemical processes. However, the synthesis of such products has not been reported publicly at present.
Through deep research, the related production process in China is found, 2-haloethylsulfonic acid is used as a raw material and reacts with chloride or bromide to synthesize a target product, but under the reaction condition of the 2-haloethylsulfonic acid, if the chloride reacts with the chloride, the product may not be obtained or the yield is low due to the problems of the related properties of the chloride; the use of bromide to react with the bromide causes problems of increased cost and generation of a large amount of three wastes in practical application although the yield is improved to a certain extent.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a preparation method of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid, which adopts a two-step one-pot method for synthesis, takes trihydroxymethyl aminomethane as a raw material, reacts with 1, 2-dihaloethane, and then reacts with sodium sulfite to finally obtain a target product, and the method has the advantages of high reaction yield, simple post-treatment process and good product purity, and simultaneously overcomes the problems of low yield or three wastes caused by using 2-halogenated ethanesulfonic acid.
The invention is realized by adopting the following technical scheme:
a preparation method of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid comprises the following steps:
s1: dissolving trihydroxymethyl aminomethane and 1, 2-dihaloethane in a solvent, heating and raising the temperature to reflux reaction while stirring, and controlling the pH value of the solution to be more than or equal to 7.0 to obtain a first intermediate reaction solution;
s2: adding sodium sulfite into the first intermediate reaction liquid obtained in the step S1, heating and raising the temperature to reflux reaction under the action of a catalyst to obtain a second intermediate reaction liquid;
s3: and (4) cooling and filtering the second intermediate reaction liquid obtained in the step (S2), adding cation exchange resin, adsorbing, and performing desolventizing and crystallization treatment to obtain the 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid.
Further, in step S1, the pH of the solution was controlled to 7.0 or more by dropwise addition of an aqueous NaOH solution having a concentration of 6 mol/L.
Further, in step S1, the time of the reflux reaction is 4h to 5 h.
Further, the 1, 2-dihaloethane is one or more of 1, 2-dibromoethane, 1, 2-dichloroethane, 1, 2-diiodoethane, 2-chloro-1-bromoethane, 1-chloro-2-iodoethane and 1-bromo-2-iodoethane.
Further, in step S1, the solvent is water.
Further, the molar ratio of the trihydroxymethylaminomethane to the 1, 2-dihaloethane is 1.01 to 1.1: 1. preferably, the molar ratio of the trihydroxymethylaminomethane to the 1, 2-dihaloethane is 1.05: 1.
further, in step S2, the catalyst is copper powder.
Further, in step S2, the reflux reaction time is 16h-17 h.
Further, the molar ratio of the sodium sulfite to the 1, 2-dihaloethane is 1.2-1.5: 1. preferably, the molar ratio of the sodium sulfite to the 1, 2-dihaloethane is 1.5: 1.
further, the cation exchange resin is styrene gel type strong acid cation resin or acrylic gel type weak acid cation resin. In other embodiments, the cation exchange resin may also be one of phenolic gel type strong acid cation resin, epoxy gel type strong acid cation resin, vinylpyridine gel type strong acid cation resin, and urea-formaldehyde gel type strong acid cation resin.
Compared with the prior art, the invention has the beneficial effects that:
the invention adopts a two-step one-pot synthesis method, takes trihydroxymethyl aminomethane as a raw material, reacts with 1, 2-dihaloethane, and then reacts with sodium sulfite to finally obtain a target product, the yield of the reaction is high, the post-treatment process is simple and convenient, the product purity is good, and the problems of low yield or three wastes caused by using 2-halogenated ethanesulfonic acid are solved.
Detailed Description
The present invention is further described below with reference to specific embodiments, and it should be noted that, without conflict, any combination between the embodiments or technical features described below may form a new embodiment.
The invention provides a 2- [ [ tri (hydroxymethyl) methyl group]Amino group]The synthesis route of the preparation method of the ethanesulfonic acid is as follows:
wherein R is-C (HOCH)2)3，X1、X2Is halogen.
Specifically, the preparation method of the 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid comprises the following steps:
s1: dissolving trihydroxymethyl aminomethane and 1, 2-dihaloethane in water, heating and raising the temperature to reflux reaction under stirring, controlling the pH value of the solution to be more than or equal to 7.0 by dropwise adding a 6mol/L NaOH aqueous solution, and obtaining a first intermediate reaction solution after the reflux reaction is carried out for 4-5 hours;
s2: adding sodium sulfite into the first intermediate reaction liquid obtained in the step S1, heating and raising the temperature to reflux reaction under the action of a catalyst, wherein the reflux reaction time is 16-17 h, and obtaining a second intermediate reaction liquid;
s3: and (4) cooling and filtering the second intermediate reaction liquid obtained in the step (S2), adding cation exchange resin, adsorbing, and performing desolventizing and crystallization treatment to obtain the 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid.
Wherein the 1, 2-dihaloethane is one or more of 1, 2-dibromoethane, 1, 2-dichloroethane, 1, 2-diiodoethane, 2-chloro-1-bromoethane, 1-chloro-2-iodoethane and 1-bromo-2-iodoethane; the molar ratio of the trihydroxymethylaminomethane to the 1, 2-dihaloethane is 1.01-1.1: 1; the molar ratio of the sodium sulfite to the 1, 2-dihaloethane is 1.2-1.5: 1. preferably, the molar ratio of the trihydroxymethylaminomethane to the 1, 2-dihaloethane is 1.05: 1; the molar ratio of the sodium sulfite to the 1, 2-dihaloethane is 1.5: 1.
the catalyst is, but not limited to, copper powder, and the addition amount of the copper powder is 2.4-2.7% of the weight of sodium sulfite.
The cation exchange resin is but not limited to a styrene gel type strong acid cation resin or an acrylic gel type weak acid cation resin. In other embodiments, the cation exchange resin may also be one of phenolic gel type strong acid cation resin, epoxy gel type strong acid cation resin, vinylpyridine gel type strong acid cation resin, and urea-formaldehyde gel type strong acid cation resin. Since the cation exchange resin contains a large amount of strongly acidic groups such as sulfonic acid group-SO3H, or weakly acidic groups, e.g. carboxyl-COOH, readily dissociates H in solution+. After the resin is dissociated, the negative charge groups contained in the bulk can adsorb and combine other cations in the solution, and the two reactions lead to H in the resin+Exchange with cations in the solution.
In one embodiment, the step S3 specifically includes:
and (3) cooling the second intermediate reaction liquid obtained in the step (S2), filtering the catalyst and insoluble impurities, adding cation exchange resin, adsorbing, filtering and separating to obtain mother liquor, then carrying out reduced pressure desolventizing, removing the solvent to obtain a viscous liquid, adding ethanol while the liquid is hot, stirring and dispersing for 1 hour, and filtering to obtain the 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid.
The reaction yield in the preparation steps is high, the total reaction yield can reach 87 percent at most, the post-treatment process is simple and convenient, the product purity is good, and the problems of low yield or three wastes caused by using 2-halogenated ethanesulfonic acid are solved.
The following are specific examples of the present invention, and raw materials, equipment, and the like used in the following examples can be obtained by purchasing, unless otherwise specified.
Example 1
Adding 143.4g (1mol) of 2-chloro-1-bromoethane and 127.5g (1.05mol) of tris (hydroxymethyl) aminomethane into 400mL of water, heating to reflux under stirring, monitoring the pH value of the reaction in the reaction process, controlling the pH value of the reaction solution to be not less than 7.0 by dropwise adding NaOH aqueous solution (6.0M), supplementing 200mL of water after refluxing for 4 hours, then adding 190g of sodium sulfite and 5g of copper powder catalyst, refluxing for 16 hours, then cooling, filtering the catalyst and insoluble impurities, adding cation exchange resin, adsorbing, filtering and separating to obtain mother liquor, removing the solvent under reduced pressure to obtain viscous liquid, finally adding 400mL of ethanol while hot, stirring and dispersing for 1 hour, filtering to obtain 199g of white solid, namely 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid, wherein the yield is about 87%, the purity by chromatography was 99%.
Example 2
Adding 143.4g (1mol) of 2-chloro-1-bromoethane and 122.4g (1.01mol) of tris (hydroxymethyl) aminomethane into 400mL of water, heating to reflux under stirring, monitoring the pH value of the reaction in the reaction process, controlling the pH value of the reaction solution to be not less than 7.0 by dropwise adding NaOH aqueous solution (6.0M), supplementing 200mL of water after refluxing for 4 hours, then adding 190g of sodium sulfite and 5g of copper powder catalyst, refluxing for 16 hours, then cooling, filtering the catalyst and insoluble impurities, adding cation exchange resin, adsorbing, filtering and separating to obtain a mother solution, removing the solvent under reduced pressure to obtain a viscous liquid, finally adding 400mL of ethanol while hot, stirring and dispersing for 1 hour, filtering to obtain 185g of white solid, namely 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid, wherein the yield is about 81.6%, the purity by chromatography was 99%.
In the above embodiments, each material is not limited to the above-mentioned components, and each material may also be other single components described in the present invention, and the content of each component is not limited to the above-mentioned content, and the content of each material may also be a combination of other component contents described in the present invention, and will not be described again here.
The above embodiments are only preferred embodiments of the present invention, and the protection scope of the present invention is not limited thereby, and any insubstantial changes and substitutions made by those skilled in the art based on the present invention are within the protection scope of the present invention.
Claims (10)
1. A preparation method of 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid is characterized by comprising the following steps:
s1: dissolving trihydroxymethyl aminomethane and 1, 2-dihaloethane in a solvent, heating and raising the temperature to reflux reaction while stirring, and controlling the pH value of the solution to be more than or equal to 7.0 to obtain a first intermediate reaction solution;
s2: adding sodium sulfite into the first intermediate reaction liquid obtained in the step S1, heating and raising the temperature to reflux reaction under the action of a catalyst to obtain a second intermediate reaction liquid;
s3: and (4) cooling and filtering the second intermediate reaction liquid obtained in the step (S2), adding cation exchange resin, adsorbing, and performing desolventizing and crystallization treatment to obtain the 2- [ [ tri (hydroxymethyl) methyl ] amino ] ethanesulfonic acid.
2. The process for preparing 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid according to claim 1, wherein the pH of the solution is controlled to 7.0 or more by dropwise addition of an aqueous NaOH solution having a concentration of 6mol/L in step S1.
3. The process for preparing 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid according to claim 1, wherein the reflux reaction time in step S1 is 4-5 h.
4. The process for the preparation of 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid according to claim 1, characterized in that the 1, 2-dihaloethane is one or a combination of more of 1, 2-dibromoethane, 1, 2-dichloroethane, 1, 2-diiodoethane, 2-chloro-1-bromoethane, 1-chloro-2-iodoethane, 1-bromo-2-iodoethane.
5. The process for preparing 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid according to claim 1, wherein in step S1, the solvent is water.
6. The process for the preparation of 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid according to claim 1, characterized in that the molar ratio of trihydroxymethylaminomethane to the 1, 2-dihaloethane is from 1.01 to 1.1: 1.
7. the process for preparing 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid according to claim 1, wherein in step S2, the catalyst is copper powder.
8. The process for preparing 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid according to claim 1, wherein the reflux reaction time in step S2 is 16-17 h.
9. The process for the preparation of 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid according to claim 1, characterized in that the molar ratio of sodium sulfite to 1, 2-dihaloethane is from 1.2 to 1.5: 1.
10. the process for preparing 2- [ [ tris (hydroxymethyl) methyl ] amino ] ethanesulfonic acid according to claim 1, wherein the cation exchange resin is a styrenic gel type strong acid cation resin or an acrylic gel type weak acid cation resin.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114478325A (en) * | 2022-02-14 | 2022-05-13 | 罗长青 | Preparation method of N, N-bis (2-hydroxyethyl) -2-aminoethanesulfonic acid |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4481150A (en) * | 1980-12-08 | 1984-11-06 | Nippon Paint Co., Ltd. | Process for preparing hydroxyalkylaminosulfonic acids |
| 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 |
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2020
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4481150A (en) * | 1980-12-08 | 1984-11-06 | Nippon Paint Co., Ltd. | Process for preparing hydroxyalkylaminosulfonic acids |
| 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 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114478325A (en) * | 2022-02-14 | 2022-05-13 | 罗长青 | Preparation method of N, N-bis (2-hydroxyethyl) -2-aminoethanesulfonic acid |
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Inventor after: Cao Lihui Inventor after: Ma Fengming Inventor after: Yuan Yongkun Inventor before: Cao Lihui Inventor before: Ma Fengming Inventor before: Yuan Yongkun |