CN111253289A - Synthetic method of sodium sulfacetamide - Google Patents
Synthetic method of sodium sulfacetamide Download PDFInfo
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- CN111253289A CN111253289A CN202010231821.1A CN202010231821A CN111253289A CN 111253289 A CN111253289 A CN 111253289A CN 202010231821 A CN202010231821 A CN 202010231821A CN 111253289 A CN111253289 A CN 111253289A
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- Prior art keywords
- sulfanilamide
- sulfacetamide
- sodium
- ionic liquid
- mixed solvent
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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
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
Abstract
The invention relates to a synthesis method of sulfacetamide sodium, which is characterized by comprising the following steps: step S1, sequentially adding sulfanilamide and alkaline ionic liquid into a reaction kettle, stirring for 20-30 minutes at the temperature of 100-150 ℃, then dropwise adding acetic anhydride, finishing the dropwise addition within 2-4 hours, then continuously stirring for reaction for 3-6 hours at the temperature of 80-90 ℃, then adding water for dilution, then regulating the pH to 4-5 by hydrochloric acid, standing for 1-3 hours, carrying out suction filtration, adding active carbon into the filtrate, decolorizing for 10-20 minutes at room temperature, and carrying out suction filtration to obtain sulfanilamide acetoyl; and step S2, adding the sulfanilamide prepared in the step S1 and sodium hydroxide into a mixed solvent, stirring at room temperature until the solid is completely dissolved, evaporating the mixed solvent in a water bath, crystallizing, and drying to obtain the sulfanilamide sodium acetate. The synthesis method of the sulfacetamide sodium, disclosed by the invention, has the advantages of high production efficiency, high yield and product purity and low production cost; the alkaline ionic liquid is used as a catalyst and a solvent, so that the conversion rate, the yield and the product purity are improved to a great extent.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a synthesis method of sodium sulfacetamide.
Background
Sulfacetamide Sodium, another name is sulfacetamide Sodium, sulfocetamide Sodium, AlbucidSoluble, SA-Na and the like, white crystalline powder; no smell, slightly bitter taste. It is soluble in water and slightly soluble in ethanol. Can be used for treating eye infection caused by conjunctivitis, keratitis, dacryocystitis, trachoma, and other sensitive bacteria. Sodium sulfacetamide is a common medicine for ophthalmology. It is usually made into 15-30% aqueous solution for eye drop or ointment for ophthalmology, and the product has weak antibacterial effect and is not generally used for oral administration. The product has low toxicity, no irritation to tissue, and low irritation.
With the increase of the market demand and quality requirement of the sodium sulfacetamide, the search for a more appropriate synthesis method is imperative. In the prior art, sulfacetamide sodium is generally synthesized by performing acetylation reaction on sulfanilamide and acetic anhydride to generate a crude sulfacetamide product, then adding hydrochloric acid to adjust the pH value to generate the sulfacetamide, and then reacting with sodium hydroxide to prepare the sulfacetamide sodium. The reaction has low conversion rate and more byproducts, excessive unreacted sulfanilamide needs to be filtered and removed first, and then the pH value of the mother solution is adjusted, and the preparation process has more complicated operation, is not beneficial to improving the product quality and protecting the environment.
The literature: the improved method of the synthesis process of the sodium sulfacetamide is disclosed in Li Zi, Hulunxiang, and students in pharmaceutical profession for experimental teaching of the synthesis process of the sodium sulfacetamide [ J ]. the proceedings of the Guiyang medical college, 2010,35(6): 646-.
Therefore, the synthesis method of the sulfacetamide sodium, which is low in cost, high in yield and high in product purity, is developed, meets the market demand and has a good practical value.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a synthesis method of sulfacetamide sodium, which is simple and easy to implement, has low requirements on equipment and reaction conditions, does not need special equipment and instruments, has high production efficiency, high yield and product purity and low production cost, and has better economic benefit and social benefit.
In order to achieve the purpose, the invention adopts the technical scheme that:
a synthetic method of sodium sulfacetamide is characterized by comprising the following steps:
step S1, sequentially adding sulfanilamide and alkaline ionic liquid into a reaction kettle, stirring for 20-30 minutes at the temperature of 100-150 ℃, then dropwise adding acetic anhydride, finishing the dropwise addition within 2-4 hours, then continuously stirring for reaction for 3-6 hours at the temperature of 80-90 ℃, then adding water for dilution, then regulating the pH to 4-5 by hydrochloric acid, standing for 1-3 hours, carrying out suction filtration, adding active carbon into the filtrate, decolorizing for 10-20 minutes at room temperature, and carrying out suction filtration to obtain sulfanilamide acetoyl;
and step S2, adding the sulfanilamide prepared in the step S1 and sodium hydroxide into a mixed solvent, stirring at room temperature until the solid is completely dissolved, evaporating the mixed solvent in a water bath, crystallizing, and drying to obtain the sulfanilamide sodium acetate.
Preferably, the molar ratio of the sulfanilamide, the basic ionic liquid and the acetic anhydride in the step S1 is 1 (3-5): 1.4.
Preferably, the basic ionic liquid is at least one of 1-ethyl-3-methylimidazole diethyl phosphate, 1-butyl-3-methylimidazole hydroxide and 1-butyl-3-methylimidazole bromide.
Preferably, the mass percentage concentration of the hydrochloric acid is 13-20%.
Preferably, the mass ratio of the sulfacetamide to the sodium hydroxide to the mixed solvent in the step S2 is 1 (2-3) to (40-50).
Preferably, the mixed solvent is ethanol and water according to the mass ratio of 1 (3-5).
Due to the application of the technical scheme, compared with the prior art, the invention has the following advantages: the synthesis method of the sulfacetamide sodium provided by the invention is simple and easy to implement, has low requirements on equipment and reaction conditions, does not need special equipment and instruments, has high production efficiency, high yield and product purity and low production cost, and has better economic and social benefits. The alkaline ionic liquid is used as a catalyst and a solvent, so that the conversion rate, the yield and the product purity are improved to a great extent.
Detailed Description
A synthetic method of sodium sulfacetamide is characterized by comprising the following steps:
step S1, sequentially adding sulfanilamide and alkaline ionic liquid into a reaction kettle, stirring for 20-30 minutes at the temperature of 100-150 ℃, then dropwise adding acetic anhydride, finishing the dropwise addition within 2-4 hours, then continuously stirring for reaction for 3-6 hours at the temperature of 80-90 ℃, then adding water for dilution, then regulating the pH to 4-5 by hydrochloric acid, standing for 1-3 hours, carrying out suction filtration, adding active carbon into the filtrate, decolorizing for 10-20 minutes at room temperature, and carrying out suction filtration to obtain sulfanilamide acetoyl;
and step S2, adding the sulfanilamide prepared in the step S1 and sodium hydroxide into a mixed solvent, stirring at room temperature until the solid is completely dissolved, evaporating the mixed solvent in a water bath, crystallizing, and drying to obtain the sulfanilamide sodium acetate.
Preferably, the molar ratio of the sulfanilamide, the basic ionic liquid and the acetic anhydride in the step S1 is 1 (3-5): 1.4.
Preferably, the basic ionic liquid is at least one of 1-ethyl-3-methylimidazole diethyl phosphate, 1-butyl-3-methylimidazole hydroxide and 1-butyl-3-methylimidazole bromide.
Preferably, the mass percentage concentration of the hydrochloric acid is 13-20%.
Preferably, the mass ratio of the sulfacetamide to the sodium hydroxide to the mixed solvent in the step S2 is 1 (2-3) to (40-50).
Preferably, the mixed solvent is ethanol and water according to the mass ratio of 1 (3-5).
Due to the application of the technical scheme, compared with the prior art, the invention has the following advantages: the synthesis method of the sulfacetamide sodium provided by the invention is simple and easy to implement, has low requirements on equipment and reaction conditions, does not need special equipment and instruments, has high production efficiency, high yield and product purity and low production cost, and has better economic and social benefits. The alkaline ionic liquid is used as a catalyst and a solvent, so that the conversion rate, the yield and the product purity are improved to a great extent.
The invention will be further described with reference to specific examples, but the scope of protection of the invention is not limited thereto:
example 1
Embodiment 1 provides a method for synthesizing sulfacetamide sodium, which is characterized by comprising the following steps:
step S1, sequentially adding sulfanilamide and alkaline ionic liquid into a reaction kettle, stirring for 20 minutes at 100 ℃, then dropwise adding acetic anhydride, finishing dripping within 2 hours, then continuously stirring and reacting for 3 hours at 80 ℃, then adding water for dilution, then adjusting the pH to 4 with hydrochloric acid, standing for 1 hour, carrying out suction filtration, adding activated carbon into the filtrate, decolorizing for 10 minutes at room temperature, and carrying out suction filtration to obtain sulfanilamide acetoyl;
and step S2, adding the sulfanilamide prepared in the step S1 and sodium hydroxide into a mixed solvent, stirring at room temperature until the solid is completely dissolved, evaporating the mixed solvent in a water bath, crystallizing, and drying to obtain the sulfanilamide sodium acetate.
The molar ratio of the sulfanilamide, the basic ionic liquid and the acetic anhydride in the step S1 is 1:3: 1.4.
The alkaline ionic liquid is 1-ethyl-3-methylimidazole diethyl phosphate.
The mass percentage concentration of the hydrochloric acid is 13%.
In the step S2, the mass ratio of the sulfacetamide to the sodium hydroxide to the mixed solvent is 1:2: 40.
The mixed solvent is ethanol and water according to the mass ratio of 1:3.
Example 2
Embodiment 2 provides a method for synthesizing sulfacetamide sodium, which is basically the same as embodiment 1, except that the molar ratio of the sulfanilamide, the basic ionic liquid and the acetic anhydride in the step S1 is 1:3.5: 1.4; the alkaline ionic liquid is 1-butyl-3-methylimidazole hydroxide.
Example 3
Embodiment 3 provides a method for synthesizing sulfacetamide sodium, which is basically the same as embodiment 1, except that the molar ratio of the sulfanilamide, the basic ionic liquid and the acetic anhydride in the step S1 is 1:4: 1.4; the alkaline ionic liquid is brominated 1-butyl-3-methylimidazole.
Example 4
Embodiment 4 provides a method for synthesizing sulfacetamide sodium, which is substantially the same as embodiment 1, except that the molar ratio of the sulfanilamide, the basic ionic liquid and the acetic anhydride in the step S1 is 1:4.5: 1.4; the alkaline ionic liquid is prepared by mixing 1-ethyl-3-methylimidazole diethyl phosphate, 1-butyl-3-methylimidazole hydroxide and 1-butyl-3-methylimidazole bromide according to the mass ratio of 1:3: 2.
Example 5
Embodiment 5 provides a method for synthesizing sulfacetamide sodium, which is basically the same as embodiment 1, except that the molar ratio of the sulfanilamide, the basic ionic liquid and the acetic anhydride in the step S1 is 1:5: 1.4; the alkaline ionic liquid is brominated 1-butyl-3-methylimidazole.
Comparative example 1
Comparative example 1 provides a synthesis method of sodium sulfacetamide which is substantially the same as example 1 except that sodium hydroxide is used instead of the basic ionic liquid.
Comparative example 2
Comparative example 2 provides a synthesis of sodium sulfacetamide, carried out according to conventional synthesis.
In order to further illustrate the beneficial technical effects of each example, statistical techniques were carried out on the yield and product purity of the synthesis method of sodium sulfacetamide in each example 1-5 and comparative example 1-2, and the results are shown in table 1.
TABLE 1
| Test items | Yield of | Purity of the product |
| Unit of | ％ | ％ |
| Example 1 | 98.0 | 99.3 |
| Example 2 | 98.2 | 99.6 |
| Example 3 | 98.5 | 99.7 |
| Example 4 | 98.9 | 99.9 |
| Example 5 | 99.3 | 99.9 |
| Comparative example 1 | 96.3 | 97.5 |
| Comparative example 2 | 96.0 | 96.3 |
As can be seen from table 1, the synthesis of sodium sulfacetamide in examples 1-5 has significantly better yield and product purity than the comparative example.
The above embodiments are merely illustrative of the technical ideas and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the contents of the present invention and implement the present invention, and not to limit the protection scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.
Claims (6)
1. A synthetic method of sodium sulfacetamide is characterized by comprising the following steps:
step S1, sequentially adding sulfanilamide and alkaline ionic liquid into a reaction kettle, stirring for 20-30 minutes at the temperature of 100-150 ℃, then dropwise adding acetic anhydride, finishing the dropwise addition within 2-4 hours, then continuously stirring for reaction for 3-6 hours at the temperature of 80-90 ℃, then adding water for dilution, then regulating the pH to 4-5 by hydrochloric acid, standing for 1-3 hours, carrying out suction filtration, adding active carbon into the filtrate, decolorizing for 10-20 minutes at room temperature, and carrying out suction filtration to obtain sulfanilamide acetoyl;
and step S2, adding the sulfanilamide prepared in the step S1 and sodium hydroxide into a mixed solvent, stirring at room temperature until the solid is completely dissolved, evaporating the mixed solvent in a water bath, crystallizing, and drying to obtain the sulfanilamide sodium acetate.
2. The method for synthesizing sulfacetamide sodium according to claim 1, wherein the molar ratio of the sulfanilamide, the basic ionic liquid and the acetic anhydride in step S1 is 1 (3-5) to 1.4.
3. The method for synthesizing sulfacetamide sodium according to claim 1, characterized in that the basic ionic liquid is at least one of 1-ethyl-3-methylimidazole diethyl phosphate, 1-butyl-3-methylimidazole hydroxide and 1-butyl-3-methylimidazole bromide.
4. The method for synthesizing sulfacetamide sodium according to claim 1, wherein the mass percentage concentration of the hydrochloric acid is 13-20%.
5. The method for synthesizing sulfacetamide sodium according to claim 1, wherein the mass ratio of the sulfacetamide, the sodium hydroxide and the mixed solvent in the step S2 is 1 (2-3) to (40-50).
6. The method for synthesizing sulfacetamide sodium according to claim 1, characterized in that the mixed solvent is ethanol and water according to a mass ratio of 1 (3-5).
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0042182A2 (en) * | 1978-09-05 | 1981-12-23 | Uniroyal Ltd. | Method of making 5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide |
| US20060100460A1 (en) * | 2004-11-10 | 2006-05-11 | Pfizer, Inc. | Substituted N-sulfonylaminobenzyl-2-phenoxyacetamide compounds as VR1 receptor agonists |
| CN103271083A (en) * | 2005-10-07 | 2013-09-04 | 阿拉巴马大学 | Multi-functional ionic liquid compositions |
| CA3013412A1 (en) * | 2016-02-04 | 2016-04-21 | Suzhou M-Conj Biotech Co., Ltd. | Specific conjugation linkers, specific immunoconjugates thereof, methods of making and uses such conjugates thereof |
| CN105884712A (en) * | 2016-05-09 | 2016-08-24 | 中国药科大学 | Compound capable of inhibiting activity of NEDD8 kinase as well as preparation method and pharmaceutical application of compound |
| CN106279034A (en) * | 2016-08-16 | 2017-01-04 | 仇颖莹 | A kind of preparation method of the biphase ionic liquid of modification |
-
2020
- 2020-03-27 CN CN202010231821.1A patent/CN111253289A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0042182A2 (en) * | 1978-09-05 | 1981-12-23 | Uniroyal Ltd. | Method of making 5,6-dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide |
| US20060100460A1 (en) * | 2004-11-10 | 2006-05-11 | Pfizer, Inc. | Substituted N-sulfonylaminobenzyl-2-phenoxyacetamide compounds as VR1 receptor agonists |
| CN103271083A (en) * | 2005-10-07 | 2013-09-04 | 阿拉巴马大学 | Multi-functional ionic liquid compositions |
| CA3013412A1 (en) * | 2016-02-04 | 2016-04-21 | Suzhou M-Conj Biotech Co., Ltd. | Specific conjugation linkers, specific immunoconjugates thereof, methods of making and uses such conjugates thereof |
| CN105884712A (en) * | 2016-05-09 | 2016-08-24 | 中国药科大学 | Compound capable of inhibiting activity of NEDD8 kinase as well as preparation method and pharmaceutical application of compound |
| CN106279034A (en) * | 2016-08-16 | 2017-01-04 | 仇颖莹 | A kind of preparation method of the biphase ionic liquid of modification |
Non-Patent Citations (4)
| Title |
|---|
| ROYCHOWDHURY SUNANDA ET AL: "Synthesis of sulphacetamide sodium by ultrasonic irradiation", 《JOURNAL OF SCIENTIFIC & INDUSTRIAL RESEARCH》 * |
| 何黎琴等: "磺胺醋酰钠合成路线改进", 《安徽化工》 * |
| 李零等: "药学专业学生实验教学磺胺醋酰钠合成工艺的改进", 《贵阳医学院学报》 * |
| 詹长娟等: "磺胺醋酰钠合成工艺的改进", 《应用化工》 * |
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Application publication date: 20200609 |