CN113336680A - Environment-friendly technological synthesis method of sulfanilamide - Google Patents
Environment-friendly technological synthesis method of sulfanilamide Download PDFInfo
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- CN113336680A CN113336680A CN202110625303.2A CN202110625303A CN113336680A CN 113336680 A CN113336680 A CN 113336680A CN 202110625303 A CN202110625303 A CN 202110625303A CN 113336680 A CN113336680 A CN 113336680A
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- 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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- 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
- C07C303/38—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 sulfanilamide green craft synthesis method, relate to the organic synthesis technical field, said method adopts acetyl amino benzene sulfonyl chloride dry product to take place amination reaction with ammonia under the condition that anhydrous solvent exists; the method has the advantages that: the solvent can be recycled by adjusting the reaction temperature and changing the process method, the yield is improved, the environment-friendly treatment cost is reduced, the reaction condition is mild, the operation is convenient, and the method is suitable for industrial production; the decomposition of the p-acetamido-benzenesulfonyl chloride in water is avoided, the occurrence of side reactions is reduced, and the yield is improved; when the pH value is adjusted in the subsequent treatment, proper acid is used to avoid the generation of mixed high-salinity wastewater; the ammonia gas is used for replacing ammonia water, so that the raw materials are saved, the alkali consumption is reduced by 63%, and various high-salinity 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 to 98.3 percent.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a green technological synthesis method of sulfanilamide.
Background
Sulfanilamide (sulfanilamide) is an organic compound with medicinal value, and is widely used for synthesizing sulfanilamide drugs such as sulfadimidine (SM 2), Sulfisoxazole (SIZ), Sulfadiazine (SD) and the like. The structural formula is as follows:
at present, the preparation method of sulfanilamide is many, and the traditional production process is that wet p-acetamido-benzene sulfonyl chloride and ammonia water are subjected to amination reaction to obtain p-acetamido-benzene sulfonamide, then sodium hydroxide is added, hydrolysis is carried out under an alkaline condition, and finally, the pH is adjusted by hydrochloric acid to obtain sulfanilamide, wherein the reaction formula is as follows:
however, the method hydrolyzes under alkaline conditions, and subsequent treatment generates a large amount of high-salt wastewater containing sodium chloride and sodium acetate, so that the environmental-friendly treatment cost is high.
There are also other preparation methods: adding p-acetamido benzene sulfonyl chloride into ammonia water at the temperature of 15 ℃ by huyanxia, keeping the mixture for 1h after adding, then heating to 50 ℃, keeping the pH value at 8-9, then filtering, washing and drying to obtain a product, wherein the yield is 80.26%, but the method is low; wasley Jan adds p-acetamidobenzenesulfonyl chloride wet product and tetrahydrofuran into ammonia water at 0 ℃, stirs lh at room temperature, removes solvent tetrahydrofuran in the reflux process, then uses ethyl acetate to extract, adds dried Na2SO4 solid into the organic layer to absorb water and filter, and obtains white solid after concentration, the yield is 93%, but the method has higher yield, the process is more complicated, needs to be optimized; gao Ling-Jie added ammonia (0.5M dioxane, 5 equivalents) to p-acetamidobenzenesulfonyl chloride and stirred overnight, after concentration, the residue was dissolved in ethyl acetate, washed with saturated brine and evaporated, and the resulting crude sulfonamide was recrystallized with boiling water at 85% yield, a new process using aqueous ammonia dissolved in dioxane added to the reaction, but dioxane was heavily contaminated and not environmentally friendly.
Although the synthesis route of the compound is improved at a later stage, the following problems still exist: ammonia water is used for generating a large amount of waste water containing ammonium chloride during amination; the used organic solvent has high price and complex process, and is not suitable for industrial production; the subsequent treatment generates sodium chloride high-salinity wastewater when the pH value is adjusted by hydrochloric acid; the method is difficult to select proper process parameters, proper solvents and proper acids to adjust the pH value, reduce the wastewater treatment cost and improve the product yield; the p-acetamido-benzenesulfonyl chloride is seriously decomposed in water, so that the sulfanilamide yield is low, more by-products of the p-aminobenzene sulfonic acid ammonia are generated, the separation is difficult, and the sulfanilamide quality is influenced; the waste water containing sodium chloride and sodium acetate mixed salt is large in amount, high in 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 green process synthesis method of sulfanilamide, which can reduce the cost and the wastewater discharge, has mild reaction conditions, high safety degree, economy and environmental protection and is suitable for industrial production.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
a process for synthesizing sulfanilamide includes such steps as aminating the dried product of acetamido-benzenesulfonyl chloride with ammonia gas in the presence of anhydrous solvent.
The reaction formula is as follows:
a green process synthesis method of sulfanilamide comprises the following specific steps: adding the dry p-acetamidobenzenesulfonyl 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 be 0-15 ℃ in the ammonia gas introduction process, controlling the temperature to be 0-60 ℃ after the ammonia gas is introduced, stirring for reaction for 1-10h, controlling the stirring speed to be 85rpm, and after the stirring reaction is finished, distilling the solvent under reduced pressure under the pressure of-0.08 MPa for recycling in the next batch. And then adding water, cooling to room temperature, filtering to remove ammonium chloride salt, adding alkali into the filter cake, heating to 80-120 ℃, refluxing for 2-10h, dropwise adding acetic acid to adjust the pH value to 6-8, filtering, and performing steam heating drying on filter residues by using fluidized bed drying equipment to obtain the product.
The water content of the p-acetamino-benzenesulfonyl chloride dry 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 p-acetamido-benzenesulfonyl chloride dry product to ammonia gas is 1: 2-6.
The molar ratio of the p-acetamido-benzenesulfonyl chloride dry product to the alkali is 1: 1-5.
Compared with the prior art, the invention has the beneficial effects that:
(1) the green technological synthesis method of sulfanilamide of the invention can recycle the solvent and separate ammonium chloride and acetate by adjusting the reaction temperature and changing the technological method, thereby improving the yield, reducing the environmental protection treatment cost, having mild reaction conditions and convenient operation, and being suitable for industrial production.
(2) The green technological process of synthesizing sulfanilamide has solvent process for selecting dry p-acetamino benzene sulfonyl chloride product to react with ammonia gas during amination, and this can avoid the decomposition of p-acetamino benzene sulfonyl chloride in water, reduce side reaction, raise yield and avoid the production of mixed high salt waste water.
(3) The environment-friendly process synthesis method of sulfanilamide of the invention saves raw materials by replacing ammonia water with ammonia gas, reduces the alkali consumption by 63 percent, and does not generate various high-salinity wastewater.
(4) The green technological synthesis method of sulfanilamide has the advantages of totally closed production in the intermediate process, simple operation, high automation degree and less waste water.
(5) The green technological synthesis method of the sulfanilamide can improve the yield of the sulfanilamide to 96.2% -98.3%.
Detailed Description
In order to more clearly understand the technical features, objects, and effects of the present invention, specific embodiments of the present invention will now be described.
Example 1
Adding 300g (1.28 mol) of ASC (Acetaminobenzenesulfonyl chloride) dry product with the water content of 0 into a 2500ml flask at normal temperature, adding 1500ml of methanol, starting stirring, cooling to 0 ℃, introducing ammonia gas, controlling the flask temperature to 0-15 ℃ in the ammonia gas introduction process, introducing 2.56mol of ammonia gas, controlling the temperature to 10-20 ℃ after the ammonia gas is introduced, stirring for reacting for 6h, controlling the stirring speed to 85prm, and distilling the methanol under the pressure of-0.08 MPa after the stirring reaction is finished, wherein the water content of the ASC dry product is 0, and the methanol is used for recycling in the next batch. Then adding 500ml of water, stirring for dissolving, cooling to room temperature, filtering to remove ammonium chloride solution, adding 213g (1.70mol) of 32% liquid caustic soda into the filter cake, heating to 65 ℃, refluxing for 6h, dropwise adding acetic acid until the pH value is 6-8, separating out the product, filtering to remove sodium acetate salt solution, heating and drying the product by steam by using fluidized bed drying equipment to obtain the product, weighing the product, calculating the yield, wherein the yield is 98.3%.
Example 2
Adding 300g (1.28 mol) of ASC (Acetaminobenzene sulfonyl chloride) dry product with the water content of 0 into a 2500ml flask at normal temperature, adding 1200ml of ethanol, starting stirring, cooling to 0 ℃, introducing ammonia gas, controlling the flask temperature to 0-15 ℃ in the ammonia gas introduction process, introducing 5.12mol of ammonia gas, controlling the temperature to 40-45 ℃ after the ammonia gas is introduced, stirring for reaction for 5h, controlling the stirring speed to 85prm, and distilling the ethanol under the pressure of-0.08 MPa after the stirring reaction is finished, wherein the ethanol is used for recycling in the next batch. Then adding 800ml of water, cooling to room temperature, filtering to remove ammonium chloride solution, adding 159g (1.20mol) of 18% sodium carbonate into the filter cake, heating to 78 ℃, refluxing for 5h, dropwise adding acetic acid until the pH value is 6-8, separating out the product, filtering to remove sodium acetate solution, heating and drying the product by using fluidized bed drying equipment through steam to obtain the product, weighing the product, calculating the yield, wherein the yield is 96.2%.
Example 3
Adding 300g (1.28 mol) of ASC (acetamido benzenesulfonyl chloride) dry product with the water content of 0 into a 2000ml flask at normal temperature, adding 600ml of toluene, starting stirring, cooling to 0 ℃, introducing ammonia gas, controlling the flask temperature to 0-15 ℃ in the ammonia gas introduction process, introducing 7.68mol of ammonia gas, controlling the temperature to 15-20 ℃ after the ammonia gas is introduced, stirring for reaction for 4 hours, controlling the stirring speed to 85prm, distilling the toluene under reduced pressure under the pressure of-0.08 MPa after the stirring reaction is finished, recovering the toluene, and recycling the toluene for next batch. Then adding 300ml of water, cooling to room temperature, filtering to remove ammonium chloride salt solution, adding 198g (1.7mol) of potassium hydroxide with the concentration of 48% into the filter cake, heating to 87 ℃, refluxing for 3h, then dropwise adding acetic acid until the pH value is 6-8, separating out the product, filtering to remove sodium acetate salt solution, heating and drying the product by steam by using fluidized bed drying equipment to obtain the product, weighing the product, and calculating the yield of 97.5%.
Comparative example 1
Adding 300g (1.28 mol) of dry ASC (Acetaminobenzene sulfonyl chloride) with the water content of 0 into a 2500ml flask at normal temperature, adding 1500ml of pure water, starting stirring, cooling to 0 ℃, introducing ammonia gas, controlling the flask temperature to 0-15 ℃ in the ammonia gas introduction process, introducing 2.56mol of ammonia gas, controlling the temperature to 10-20 ℃ after the ammonia gas is introduced, stirring for reaction for 6h, controlling the stirring speed to 85prm, and distilling the pure water under the pressure of-0.08 MPa after the stirring reaction is finished, wherein the pure water is used for recycling in the next batch. Then adding 500ml of water, stirring for dissolving, cooling to room temperature, filtering to remove ammonium chloride solution, adding 213g (1.70mol) of 32% liquid caustic soda into the filter cake, heating to 65 ℃, refluxing for 6h, dropwise adding acetic acid until the pH value is 6-8, separating out the product, filtering to remove sodium acetate solution, heating and drying the product by steam by using fluidized bed drying equipment to obtain the product, weighing the product, calculating the yield, wherein the yield is 80%.
Comparative example 2
Adding 300g (1.28 mol) of dry ASC (Acetaminobenzene sulfonyl chloride) with the water content of 0 into a 2500ml flask at normal temperature, adding 1500ml of methanol, starting stirring, cooling to 0 ℃, then dropwise adding ammonia water, controlling the temperature of the flask to be 0-15 ℃ in the process of dropwise adding ammonia water, dropwise adding 2.56mol of ammonia water, controlling the temperature to be 10-20 ℃ after dropwise adding ammonia water, stirring for reaction for 6h, controlling the stirring speed to be 85prm, and distilling the methanol under the pressure of-0.08 MPa after the stirring reaction is finished, wherein the water content of the ASC is 0, and the methanol is recycled for the next batch. Then adding 500ml of water, stirring for dissolving, cooling to room temperature, filtering to remove ammonium chloride solution, adding 213g (1.70mol) of 32% liquid caustic soda into the filter cake, heating to 65 ℃, refluxing for 6h, dropwise adding acetic acid until the pH value is 6-8, separating out the product, filtering to remove sodium acetate salt solution, heating and drying the product by steam by using fluidized bed drying equipment to obtain the product, weighing the product, calculating the yield, and obtaining the yield of 82%.
All percentages used in the present invention are mass percentages unless otherwise indicated.
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that changes may be made in the embodiments and/or equivalents thereof without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (8)
1. The green technological process of synthesizing sulfanilamide features that dry p-acetamino benzenesulfonyl chloride product is aminated with ammonia gas in the presence of anhydrous solvent.
2. The green technological synthesis method of sulfanilamide according to claim 1, characterized in that the specific steps of the synthesis method are as follows: adding the dry p-acetamidobenzenesulfonyl 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 be 0-15 ℃ in the ammonia gas introduction process, controlling the temperature to be 0-60 ℃ after the ammonia gas is introduced, stirring for reaction for 1-10 hours, controlling the stirring speed to be 85rpm, and after the stirring reaction is finished, distilling the solvent under reduced pressure of-0.08 MPa for recycling in the next batch;
and then adding water, cooling to room temperature, filtering to remove ammonium chloride salt, adding alkali into the filter cake, heating to 80-120 ℃, refluxing for 2-10h, dropwise adding acetic acid to adjust the pH value to 6-8, filtering, and performing steam heating drying on filter residues by using fluidized bed drying equipment to obtain the product.
3. The green technological process of synthesizing sulfanilamide of claim 2, wherein the water content of the dried product of sulfanilamide chloride is 0.
4. The process for the green technological synthesis of sulfanilamide of claim 2, wherein the solvent is one of methanol, ethanol, propanol, toluene, xylene, dichloroethane or DMF.
5. The green process synthesis method of sulfanilamide of claim 2, wherein the base is one of sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate.
6. The green technological process of synthesizing sulfanilamide of claim 2, wherein the molar ratio of the dry product of p-acetamidobenzenesulfonyl chloride to ammonia gas is 1: 2-6.
7. The green technological process of synthesizing sulfanilamide of claim 2, wherein the molar ratio of the dry product of p-acetamidobenzenesulfonyl chloride to the alkali is 1: 1-5.
8. The green process synthesis method of sulfanilamide according to claim 2, characterized in that the yield of sulfanilamide is 96.2% -98.3%.
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- 2021-06-04 CN CN202110625303.2A patent/CN113336680B/en active Active
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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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| CN105237446A (en) * | 2015-08-28 | 2016-01-13 | 苏州市吴赣药业有限公司 | Synthetic method of p-aminobenzenesulfonamide |
| CN108558712A (en) * | 2018-06-20 | 2018-09-21 | 新乡市锦源化工有限公司 | It is a kind of using antifebrin as the method and P-aminobenzene-sulfonamide of Material synthesis high-purity P-aminobenzene-sulfonamide |
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