CN113336680B - Green process synthesis method of sulfanilamide - Google Patents
Green process synthesis method of sulfanilamide Download PDFInfo
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- CN113336680B CN113336680B CN202110625303.2A CN202110625303A CN113336680B CN 113336680 B CN113336680 B CN 113336680B CN 202110625303 A CN202110625303 A CN 202110625303A CN 113336680 B CN113336680 B CN 113336680B
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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
- C07C303/36—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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- C—CHEMISTRY; METALLURGY
- 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
- C07C303/36—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
- C07C303/38—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 reaction of ammonia or amines with sulfonic acids, or with esters, anhydrides, or halides thereof
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Abstract
A green process synthesis method of sulfanilamide relates to the technical field of organic synthesis, and the method adopts acetamido benzenesulfonyl chloride dry product to carry out amination reaction with ammonia gas in the presence of anhydrous solvent; the method has the advantages that: the solvent can be recycled by adjusting the reaction temperature and changing the process method, so that the yield is improved, the environmental-friendly treatment cost is reduced, the reaction condition is mild, the operation is convenient, and the method is suitable for industrial production; the water decomposition of the acetamido benzene sulfonyl chloride is avoided, the occurrence of side reaction is reduced, and the yield is improved; the generation of mixed high-salt wastewater is avoided by using proper acid in the subsequent treatment and pH adjustment; the ammonia is used for replacing ammonia water, so that raw materials are saved, the alkali consumption is reduced by 63%, and various high-salt wastewater is not generated; the operation is simple, the automation degree is high, and the waste water is less; can improve the yield of the sulfanilamide to 96.2-98.3 percent.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a green process synthesis method of sulfanilamide.
Background
Sulfanilamide (sulfanilamide) is an organic compound with medicinal value and is widely used for synthesizing sulfanilamide medicines such as sulfadimidine (SM 2), sulfaisoxazole (SIZ), sulfadiazine (SD) and the like. The structural formula is as follows:
the prior sulfanilamide preparation method is many, the traditional production process is that acetamido benzenesulfonyl chloride wet product and ammonia water are subjected to amination reaction to obtain acetamido benzenesulfonamide, then sodium hydroxide is added, hydrolysis is carried out under alkaline conditions, finally hydrochloric acid is used for regulating pH to obtain sulfanilamide, and the reaction formula is as follows:
however, the method is hydrolyzed under alkaline condition, so that a large amount of high-salt wastewater containing sodium chloride and sodium acetate is generated in subsequent treatment, and the environmental-friendly treatment cost is high.
There are other preparation methods: hao Yanxia adding acetamido benzenesulfonyl chloride into ammonia water at 15 ℃, maintaining for 1h after adding, then heating to 50 ℃, maintaining the pH at 8-9, and then filtering, washing and drying to obtain a product with a yield of 80.26%, wherein the yield of the method is lower; adding acetamido benzenesulfonyl chloride wet product and tetrahydrofuran into ammonia water at 0 ℃, stirring for lh at room temperature, removing solvent tetrahydrofuran in the reflux process, extracting by using ethyl acetate, adding dried Na2SO4 solid into an organic layer to absorb water, filtering, concentrating to obtain white solid, and obtaining 93 percent of white solid, wherein the method has higher yield, but the process is complex and needs to be optimized; gao Ling-Jie is a new method of adding ammonia (0.5M dioxane, 5 equivalent) to acetamido benzenesulfonyl chloride, stirring overnight, concentrating, dissolving the residue in ethyl acetate, washing with saturated saline solution, and evaporating, recrystallizing the crude sulfonamide with boiling water, yield 85%, this process adopts ammonia water dissolved in dioxane to add to the reactant, but dioxane pollution is serious, not environment-friendly.
Although the synthetic route of this compound was improved in the latter stage, the following problems still remain: ammonia water is used for generating a large amount of wastewater containing ammonium chloride during amination; the used organic solvent has high price and complex process, and is not suitable for industrial production; the pH value is regulated by hydrochloric acid in the subsequent treatment, and sodium chloride high-salt wastewater is generated; it is difficult to reduce wastewater treatment costs and increase product yields while selecting appropriate process parameters, suitable solvents, suitable acids to adjust pH; the sulfanilamide sulfonyl chloride is severely decomposed in water, so that the sulfanilamide yield is low, the sulfanilamide byproduct is more, the sulfanilamide is difficult to separate, and the quality of the sulfanilamide is influenced; the waste water containing mixed salt of sodium chloride and sodium acetate has large amount, high environmental protection treatment cost and the like.
Disclosure of Invention
In order to solve the technical problems in the prior art, the invention provides a method for synthesizing sulfanilamide by using a green process, which can reduce cost and wastewater discharge, has mild reaction conditions and high safety degree, is economical and environment-friendly, and is suitable for industrial production.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
a green process for synthesizing sulfanilamide features that the dry acetamido-benzenesulfonyl chloride is aminated with ammonia gas in the presence of anhydrous solvent.
The reaction formula is:
a green process synthesis method of sulfanilamide comprises the following specific steps: adding dry acetamido benzenesulfonyl chloride into a reaction kettle at normal temperature, adding a solvent, stirring, cooling to 0 ℃, starting to introduce ammonia gas, controlling the temperature of the flask to 0-15 ℃ in the ammonia gas introducing process, controlling the temperature to 0-60 ℃ after the ammonia gas is introduced, stirring and reacting for 1-10h, controlling the stirring speed to 85rpm, and distilling the solvent under reduced pressure at the pressure of-0.08 MPa after the stirring and reacting are finished for recycling of the next batch. Then adding water, cooling to room temperature, filtering to remove ammonium chloride salt, adding alkali into a filter cake, heating to 80-120 ℃, refluxing for 2-10h, then dripping acetic acid to adjust the PH value to 6-8, filtering, and then using fluidized bed drying equipment to heat and dry filter residues by steam to obtain the product.
The water content of the dry acetamido benzenesulfonyl chloride product is 0.
The solvent is one of methanol, ethanol, propanol, toluene, xylene, dichloroethane or DMF.
The alkali is one of sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate.
The molar ratio of the dry acetamido benzenesulfonyl chloride to ammonia gas is 1:2-6.
The molar ratio of the dry acetamido benzenesulfonyl chloride to the alkali is 1:1-5.
Compared with the prior art, the invention has the beneficial effects that:
(1) According to the synthesis method of the sulfanilamide green process, the reaction temperature is adjusted, the process method is changed, so that the solvent can be recycled, and the ammonium chloride and the acetate are separated, thereby improving the yield, reducing the environmental-friendly treatment cost, and being mild in reaction condition, convenient to operate and suitable for industrial production.
(2) According to the green process synthesis method of the sulfanilamide, a solvent method is adopted in amination, and the dry product of the acetaminophen sulfonyl chloride is selected to react with ammonia gas, so that the water decomposition of the acetaminophen sulfonyl chloride is avoided, the occurrence of side reactions is reduced, the yield is improved, and the generation of mixed high-salt wastewater is avoided by using proper acid in the subsequent treatment and pH adjustment.
(3) According to the green process synthesis method of the sulfanilamide, the ammonia is used for replacing ammonia water, so that raw materials are saved, the alkali consumption is reduced by 63%, and various high-salt wastewater is not generated.
(4) The method for synthesizing the sulfanilamide by the green process has the advantages of complete airtight production in the middle process, simple operation, high automation degree and less wastewater.
(5) The green process synthesis method of the sulfanilamide can improve the yield of the sulfanilamide to 96.2% -98.3%.
Detailed Description
Specific embodiments of the present invention will now be described in order to provide a clearer understanding of the technical features, objects and effects of the present invention.
Example 1
300g (1.28 mol) of ASC (acetamido-benzenesulfonyl chloride) with water content of 0 is added into a 2500ml flask at normal temperature, 1500ml of methanol is added, stirring is started, then the temperature is reduced to 0 ℃ to start ammonia gas introduction, the temperature of the flask is controlled to 0-15 ℃ in the ammonia gas introduction process, 2.56mol of ammonia gas is introduced, after the ammonia gas introduction is finished, the temperature is controlled to 10-20 ℃, stirring is carried out for 6 hours, the stirring speed is controlled to 85prm, and after the stirring reaction is finished, the methanol is distilled out under reduced pressure under the pressure of-0.08 MPa for the next batch for recycling. Then adding 500ml of water, stirring and dissolving, cooling to room temperature, filtering to remove ammonium chloride salt solution, adding 213g (1.70 mol) of liquid alkali with the concentration of 32% into a filter cake, heating to 65 ℃, refluxing for 6 hours, then dropwise adding acetic acid until the pH value is 6-8, separating out a product, filtering to remove sodium acetate salt solution, heating and drying the product by using steam of a fluidized bed drying device to obtain a product, weighing the product, and calculating the yield to obtain the product with the yield of 98.3%.
Example 2
300g (1.28 mol) of ASC (acetamidobenzenesulfonyl chloride) with water content of 0 is added into a 2500ml flask at normal temperature, 1200ml of ethanol is added, stirring is started, then the temperature is reduced to 0 ℃ to start ammonia gas introduction, the temperature of the flask is controlled to 0-15 ℃ in the ammonia gas introduction process, 5.12mol of ammonia gas is introduced, after the ammonia gas introduction is finished, the temperature is controlled to 40-45 ℃, stirring is carried out for 5 hours, the stirring speed is controlled to 85prm, and after the stirring reaction is finished, ethanol is distilled out under reduced pressure under the pressure of-0.08 MPa for recycling of the next batch. Then 800ml of water is added, the temperature is reduced to room temperature, then the ammonium chloride salt solution is removed by filtration, 159g (1.20 mol) of sodium carbonate with the concentration of 18 percent is added into the filter cake, the temperature is raised to 78 ℃, then acetic acid is added dropwise after refluxing for 5 hours until the PH is 6-8, the product is separated out, the sodium acetate salt solution is removed by filtration, the product is obtained after the product is heated and dried by steam through a fluidized bed drying device, the product is weighed, and the yield is calculated to be 96.2 percent.
Example 3
300g (1.28 mol) of ASC (acetamidobenzenesulfonyl chloride) with water content of 0 is added into a 2000ml flask at normal temperature, 600ml of toluene is added, stirring is started, then the temperature is reduced to 0 ℃ to start introducing ammonia, the temperature of the flask is controlled to 0-15 ℃ in the ammonia introducing process, 7.68mol of ammonia is introduced, after the ammonia is introduced, the temperature is controlled to 15-20 ℃, stirring reaction is carried out for 4 hours, the stirring speed is controlled to 85prm, after the stirring reaction is finished, toluene is distilled out under reduced pressure under the pressure of-0.08 MPa to be recycled for the next batch. Then 300ml of water is added, the temperature is reduced to room temperature, the ammonium chloride salt solution is removed by filtration, 198g (1.7 mol) of potassium hydroxide with the concentration of 48 percent is added into the filter cake, the temperature is raised to 87 ℃, then acetic acid is added dropwise after the reflux for 3 hours until the PH is 6-8, the product is separated out, the sodium acetate salt solution is removed by filtration, the product is obtained after the product is heated and dried by steam through a fluidized bed drying device, the product is weighed, and the yield is calculated to be 97.5 percent.
Comparative example 1
300g (1.28 mol) of ASC (acetamido-benzenesulfonyl chloride) with water content of 0 is added into a 2500ml flask at normal temperature, 1500ml of pure water is added, stirring is started, then the temperature is reduced to 0 ℃ to start ammonia gas introduction, the temperature of the flask is controlled to 0-15 ℃ in the ammonia gas introduction process, 2.56mol of ammonia gas is introduced, after the ammonia gas introduction is finished, the temperature is controlled to 10-20 ℃, stirring is carried out for 6 hours, the stirring speed is controlled to 85prm, pure water is distilled out under reduced pressure under the pressure of-0.08 MPa after the stirring reaction is finished, and the ammonia gas is used for the next batch for recycling. Then adding 500ml of water, stirring and dissolving, cooling to room temperature, filtering to remove ammonium chloride salt solution, adding 213g (1.70 mol) of liquid alkali with the concentration of 32% into a filter cake, heating to 65 ℃, refluxing for 6 hours, then dropwise adding acetic acid until the pH value is 6-8, separating out a product, filtering to remove sodium acetate salt solution, heating and drying the product by using steam of a fluidized bed drying device to obtain a product, weighing the product, and calculating the yield to obtain the product with the yield of 80%.
Comparative example 2
300g (1.28 mol) of ASC (p-acetamido benzenesulfonyl chloride) with water content of 0 is added into a 2500ml flask at normal temperature, 1500ml of methanol is added, stirring is started, then ammonia water is added dropwise after the temperature is reduced to 0 ℃, the temperature of the flask is controlled to 0-15 ℃ in the process of adding the ammonia water dropwise, 2.56mol of ammonia water is added dropwise, the temperature is controlled to 10-20 ℃ after the ammonia water is added dropwise, stirring reaction is carried out for 6 hours, the stirring speed is controlled to 85prm, and methanol is distilled out under reduced pressure under the pressure of-0.08 MPa after the stirring reaction is finished for recycling of the next batch. Then adding 500ml of water, stirring and dissolving, cooling to room temperature, filtering to remove ammonium chloride salt solution, adding 213g (1.70 mol) of liquid alkali with the concentration of 32% into a filter cake, heating to 65 ℃, refluxing for 6 hours, then dropwise adding acetic acid until the pH value is 6-8, separating out a product, filtering to remove sodium acetate salt solution, heating and drying the product by using steam of a fluidized bed drying device to obtain a product, weighing the product, and calculating the yield to obtain the product with the yield of 82%.
The percentages used in the present invention are mass percentages unless otherwise indicated.
Finally, it should be noted that: the foregoing description is only a preferred embodiment of the present invention, and the present invention is not limited thereto, but it is to be understood that modifications and equivalents of some of the technical features described in the foregoing embodiments may be made by those skilled in the art, although the present invention has been described in detail with reference to the foregoing embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (1)
1. A green process synthesis method of sulfanilamide is characterized in that the synthesis method specifically comprises the following steps,
adding 300g of acetaminophen sulfonyl chloride with water content of 0 into a 2500ml flask at normal temperature, adding 1500ml of methanol, starting stirring, cooling to 0 ℃ to start introducing ammonia gas, controlling the temperature of the flask to 0-15 ℃ in the ammonia gas introducing process, introducing 2.56mol of ammonia gas, controlling the temperature to 10-20 ℃ after introducing the ammonia gas, stirring for reaction for 6 hours, controlling the stirring speed to 85prm, after the stirring reaction is finished, distilling methanol under the pressure of-0.08 MPa, using for recycling in the next batch, adding 500ml of water for stirring and dissolving, cooling to room temperature, filtering to remove ammonium chloride solution, adding 213g of liquid alkali with concentration of 32%, heating to 65 ℃, refluxing for 6 hours, dripping acetic acid to pH value of 6-8, separating out a product, filtering to remove sodium acetate solution, heating and drying the product by using fluidized bed drying equipment to obtain the product, weighing the product, calculating the yield, and obtaining the product with the yield of 98.3%.
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Patent Citations (5)
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| WO2007029035A2 (en) * | 2005-09-07 | 2007-03-15 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa | Thiophene and thiazole substituted trifluoroethanone derivatives as histone deacetylase (hdac) inhibitors |
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