CN102030688A - Method for preparing monosodium sulfosuccinate - Google Patents
Method for preparing monosodium sulfosuccinate Download PDFInfo
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- CN102030688A CN102030688A CN2010105519492A CN201010551949A CN102030688A CN 102030688 A CN102030688 A CN 102030688A CN 2010105519492 A CN2010105519492 A CN 2010105519492A CN 201010551949 A CN201010551949 A CN 201010551949A CN 102030688 A CN102030688 A CN 102030688A
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- succinic acid
- sodium salt
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Abstract
The invention provides a method for preparing monosodium sulfosuccinate, which comprises the following steps of: performing hydrolysis reaction on NaOH and monosodium sulfosuccinate; adding concentrated sulfuric acid into the hydrolyzed solution to obtain a coarse product; and desalting the coarse product by using methanol. The molar ratio of the sodium hydroxide to the concentrated sulfuric acid to the monosodium sulfosuccinate is 2.4:1.2:1. The method for preparing the monosodium sulfosuccinate has the characteristics of simple process, low cost and suitability for industrial production.
Description
Technical field
The present invention relates to a kind of method for preparing sulfo-succinic acid list sodium salt.
Background technology
The development research of protein and polypeptide drugs, health-care polypeptide product is a branch active, the most with fastest developing speed in present biological medicine and the healthcare field, along with continually developing of the pharmaceutical use of amino acid derivative and polypeptide, the upstream raw material of polypeptide is had higher requirement.Sulfo-succinic acid list sodium salt is the important intermediate of synthesizing amino acid linker agent, and its structural formula is:
At present, the synthetic method of sulfo-succinic acid list sodium salt has following several:
Welter etc. disclose a kind of method for preparing sulfo-succinic acid list sodium salt in No. the 20060052421st, United States Patent (USP), this method is that sulfo-succinic acid and sodium hydroxide reaction are obtained sulfo-succinic acid list sodium salt, the main drawback of this method is: the price comparison costliness of reaction raw materials sulfo-succinic acid, and be difficult to buy, thereby be unfavorable for suitability for industrialized production.
He Yanli etc. were Chinese Pharmaceutical Journal (2006, the 41st volume, the 17th phase, 1350-1352) reported that another prepares the method for sulfo-succinic acid list sodium salt, this method is that maleic anhydride and sodium bisulfite and sulfurous gas reaction are obtained sulfo-succinic acid list sodium salt, the main drawback of this method is: reaction raw materials sulfurous gas is difficult to buy, and uses inconvenience, thereby is unfavorable for suitability for industrialized production.
Summary of the invention
For overcoming the problems referred to above of the prior art, the invention provides a kind of good operability and the lower-cost method for preparing sulfo-succinic acid list sodium salt.
The technical solution used in the present invention is: a kind of method for preparing sulfo-succinic acid list sodium salt generates sulfo-succinic acid list sodium salt by sulfo-succinic acid dimethyl ester list sodium salt by hydrolysis reaction.
Further, hydrolysis reaction is: under 0 ℃ of-90 ℃ of temperature condition, alkali and sulfo-succinic acid dimethyl ester list sodium salt react.
Further, the alkali that uses in the hydrolysis reaction is preferably NaOH, can certainly be other alkali.
Further, sulfo-succinic acid dimethyl ester list sodium salt may further comprise the steps by the method that hydrolysis reaction generates sulfo-succinic acid list sodium salt: (1) is dissolved in sulfo-succinic acid dimethyl ester list sodium salt in the water, adds NaOH and forms reaction system; (2) above-mentioned solution is remained under 0 ℃ of-90 ℃ of temperature, reacted 4-10 hour; (3) in the solution of step (2) gained, add acid with the NaOH equivalent, obtain containing the thick product of sulfo-succinic acid list sodium salt; (4) described thick product is dissolved in the methyl alcohol, heating removes by filter insolubles, and the mother liquor evaporate to dryness is obtained white solid.
Preferably, the acid of adding in the step (3) is the vitriol oil, also can use strong acid in other.
Further, the molar feed ratio of sodium hydroxide, the vitriol oil and sulfo-succinic acid dimethyl ester list sodium salt is 2.4:1.2:1.
Preferably, hydrolysis reaction carries out under 40 ℃ of-60 ℃ of temperature, and reaction is more complete under this temperature.
Further, the purity of methyl alcohol can obtain than higher yield greater than 90 wt%.
Preferably, in above-mentioned steps (4), the temperature of heating is 40 ℃-60 ℃.
Compared with prior art, the present invention has the following advantages: the method for preparing sulfo-succinic acid list sodium salt of the present invention is the principal reaction raw material with sulfo-succinic acid dimethyl ester list sodium salt, and cost is lower; Reaction conditions gentleness of the present invention, reaction time is short; Technology of the present invention is simple, and operability is good, is fit to suitability for industrialized production.
Embodiment
Below in conjunction with specific embodiment the present invention is described in further detail.
Embodiment 1
In there-necked flask, add 9.2 g sulfo-succinic acid dimethyl ester list sodium salts, and in bottle, add 25 ml water, stir solid is dissolved fully, in above-mentioned solution, add 3.56 g sodium hydroxide; With gained solution under 25 ℃, be hydrolyzed the reaction reach 10 hours; Add the 2.4 ml vitriol oils then in the reaction solution after said hydrolyzed, decompression steamed solvent after question response was finished, and obtained white solid; Add 25 ml methyl alcohol in above-mentioned gained white solid, and institute's formation solution is warmed up to 60 ℃, decompress filter is removed insolubles while hot, with the mother liquor evaporate to dryness that obtains, obtains white solid 3.9 g, and molar yield is 47%.
1
H-NMR?(D
2
O,?500?MHz):?d?=?2.95?(dd,?1H),?3.14?(dd,?1H),?4.25?(dd,?1H)。
Embodiment 2
In there-necked flask, add 9.2 g sulfo-succinic acid dimethyl ester list sodium salts, and in bottle, add 25 ml water, stir solid is dissolved fully, in above-mentioned solution, add 3.56 g sodium hydroxide; With gained solution under 55 ℃, be hydrolyzed the reaction reach 6 hours; Add the 2.4 ml vitriol oils then in the reaction solution after said hydrolyzed, decompression steamed solvent after question response was finished, and obtained white solid; Add 25 ml methyl alcohol in above-mentioned gained white solid, and institute's formation solution is warmed up to 60 ℃, decompress filter is removed insolubles while hot, with the mother liquor evaporate to dryness that obtains, obtains 4.2 g white solids, and molar yield is 56%.
1
H-NMR?(D
2
O,?500?MHz):?d?=2.95?(dd,?1H),?3.14?(dd,?1H),?4.25?(dd,?1H)。
Embodiment 3
In there-necked flask, add 9.2 g sulfo-succinic acid dimethyl ester list sodium salts, and in bottle, add 25 ml water, stir solid is dissolved fully, in above-mentioned solution, add 3.56 g sodium hydroxide; With gained solution under 55 ℃, be hydrolyzed the reaction reach 6 hours; Add the 2.4 ml vitriol oils then in the reaction solution after said hydrolyzed, question response finishes the back decompression and steams solvent, obtains white solid; The methyl alcohol that in above-mentioned gained white solid, adds 25 ml 90%, and institute formation solution is warmed up to 60 ℃, decompress filter is removed insolubles while hot, with the mother liquor evaporate to dryness that obtains, obtains 5.2 g white solids, and molar yield is 70%.
1
H-NMR?(D
2
O,?500?MHz):?d?=2.95?(dd,?1H),?3.14?(dd,?1H),?4.25?(dd,?1H)。
In sum, the method for preparing sulfo-succinic acid list sodium salt of the present invention has not only improved productivity, and has better operability and security; The present invention can satisfy the standard of industrial production aspect, is applicable to suitability for industrialized production; In addition, the present invention can also improve product purity and improve Environmental compatibility.
More than specific embodiment of the present invention is illustrated; but protection content of the present invention is not only limited to above embodiment; in the technical field, the common knowledge of a GPRS just can be carried out diversified change in its technology main idea scope under of the present invention.
Claims (9)
1. method for preparing sulfo-succinic acid list sodium salt is characterized in that: sulfo-succinic acid dimethyl ester list sodium salt generates sulfo-succinic acid list sodium salt by hydrolysis reaction.
2. the method for preparing sulfo-succinic acid list sodium salt according to claim 1 is characterized in that: described hydrolysis reaction reacts for sulfo-succinic acid dimethyl ester list sodium salt and alkali under 0 ℃ of-90 ℃ of temperature condition.
3. the method for preparing sulfo-succinic acid list sodium salt according to claim 2 is characterized in that: the alkali that uses in the described hydrolysis reaction is NaOH.
4. the method for preparing sulfo-succinic acid list sodium salt according to claim 3 is characterized in that may further comprise the steps: (1) is dissolved in sulfo-succinic acid dimethyl ester list sodium salt in the water, adds NaOH and forms reaction system; (2) above-mentioned solution is remained under 0 ℃ of-90 ℃ of temperature, reacted 4-10 hour; (3) in the solution of step (2) gained, add acid with the NaOH equivalent, obtain containing the thick product of sulfo-succinic acid list sodium salt; (4) described thick product is dissolved in the methyl alcohol, heating removes by filter insolubles, and the mother liquor evaporate to dryness is obtained white solid.
5. the method for preparing sulfo-succinic acid list sodium salt according to claim 4 is characterized in that: the acid of adding in the described step (3) is the vitriol oil.
6. the method for preparing sulfo-succinic acid list sodium salt according to claim 5 is characterized in that: the molar feed ratio of described sodium hydroxide, the vitriol oil and sulfo-succinic acid dimethyl ester list sodium salt is 2.4:1.2:1.
7. the method for preparing sulfo-succinic acid list sodium salt according to claim 4 is characterized in that: described hydrolysis reaction carries out under 40 ℃ of-60 ℃ of temperature.
8. the method for preparing sulfo-succinic acid list sodium salt according to claim 4 is characterized in that: the purity of described methyl alcohol is greater than 90 wt%.
9. the method for preparing sulfo-succinic acid list sodium salt according to claim 4 is characterized in that: in described step (4), the temperature of heating is 40 ℃-60 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010551949 CN102030688B (en) | 2010-11-22 | 2010-11-22 | Method for preparing monosodium sulfosuccinate |
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| CN 201010551949 CN102030688B (en) | 2010-11-22 | 2010-11-22 | Method for preparing monosodium sulfosuccinate |
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| CN102030688A true CN102030688A (en) | 2011-04-27 |
| CN102030688B CN102030688B (en) | 2013-01-23 |
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| CN 201010551949 Active CN102030688B (en) | 2010-11-22 | 2010-11-22 | Method for preparing monosodium sulfosuccinate |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060052421A1 (en) * | 2004-09-09 | 2006-03-09 | Eastman Kodak Company | Conjugation agent |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060052421A1 (en) * | 2004-09-09 | 2006-03-09 | Eastman Kodak Company | Conjugation agent |
Non-Patent Citations (2)
| Title |
|---|
| 李成海等: "琥珀酸二辛酯磺酸钠的合成及表面特性", 《广西化工》 * |
| 贺艳丽等: "透明质酸交联剂的合成", 《中国药学杂志》 * |
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Address after: 215011 Jiangsu high tech Zone Suzhou City Binhe Road, No. 1326 Patentee after: Suzhou Hao Fan biological Limited by Share Ltd Address before: 215011 Jiangsu high tech Zone Suzhou City Binhe Road, No. 1326 Patentee before: Suzhou Highfine Biotech Co.,Ltd. |