1. Sulfanilamide is synthesized through a multi-step process involving the preparation of intermediates like acetanilide, 4-acetamidobenzenesulfonyl chloride, and 4-acetamidobenzenesulfonamide.
2. 4-Acetamidobenzenesulfonyl chloride is obtained through chlorosulfonation of acetanilide using chlorosulfonic acid.
3. 4-Acetamidobenzenesulfonamide is then prepared by reacting 4-acetamidobenzenesulfonyl chloride with aqueous ammonia
1. Sulfanilamide is synthesized through a multi-step process involving the preparation of intermediates like acetanilide, 4-acetamidobenzenesulfonyl chloride, and 4-acetamidobenzenesulfonamide.
2. 4-Acetamidobenzenesulfonyl chloride is obtained through chlorosulfonation of acetanilide using chlorosulfonic acid.
3. 4-Acetamidobenzenesulfonamide is then prepared by reacting 4-acetamidobenzenesulfonyl chloride with aqueous ammonia
1. Sulfanilamide is synthesized through a multi-step process involving the preparation of intermediates like acetanilide, 4-acetamidobenzenesulfonyl chloride, and 4-acetamidobenzenesulfonamide.
2. 4-Acetamidobenzenesulfonyl chloride is obtained through chlorosulfonation of acetanilide using chlorosulfonic acid.
3. 4-Acetamidobenzenesulfonamide is then prepared by reacting 4-acetamidobenzenesulfonyl chloride with aqueous ammonia
1. Sulfanilamide is synthesized through a multi-step process involving the preparation of intermediates like acetanilide, 4-acetamidobenzenesulfonyl chloride, and 4-acetamidobenzenesulfonamide.
2. 4-Acetamidobenzenesulfonyl chloride is obtained through chlorosulfonation of acetanilide using chlorosulfonic acid.
3. 4-Acetamidobenzenesulfonamide is then prepared by reacting 4-acetamidobenzenesulfonyl chloride with aqueous ammonia
Jaro, Iloilo City, Philippines and Medicinal Organic Chemistry - LABORATORY
Activity 8: Preparation of Sulfanilamide
Sulfanilamide is an organic sulfur compound, sulfonamide group and the amino group in the para position of the benzene ring is the first successfully synthesized selectively toxic antimicrobial drugs structurally similar to p-aminobenzoic acid (PABA) with antibacterial property. Competes with PABA for the bacterial enzyme dihydropteroate synthase, thereby preventing the incorporation of PABA into dihydrofolic acid, the immediate precursor of folic acid. The preparation method comprises the steps: 1. adding n-acetylsulfanilyl chloride into ammonium hydroxide, 2. reacting to obtain p-acetamidobenzene sulfamide, 3. adding p-acetamidobenzene sulfamide into sodium hydroxide, 4. hydrolyzing under the alkaline condition to obtain sodium sulfanilamide, 5. reacting the sodium sulfanilamide with hydrochloric acid, 6. directly concentrating under the non-separation condition to obtain the sulfanilamide. Preparation of Aniline via Reduction of Nitrobenzene In this reaction, tin metal serves as the reducing agent and is oxidized to stannic chloride, SnCl4. The crude aniline product is contaminated with unreacted nitrobenzene as well as benzidene and 4-aminophenol formed as byproducts in the reduction. It is purified using a combination of steam distillation and extraction.
Preparation of Acetanilide Aniline can be easily converted to acetanilide by acetylation reaction using acetic anhydride in the presence of sodium acetate to protect the amine functional group from entering into unwanted reactions during the subsequent chlorosulfonation and amination steps. Preparation of 4-Acetamidobenzenesulfonyl Chloride The chlorosulfonyl group can be introduced para to the acetamide group in one step using the electrophilic aromatic substitution reaction known as chlorosulfonation:
The electrophile that initially adds to the ring is probably SO3, forming the sulfonic acid. The initially formed substitution product is the sulfonic acid. Substitution is essentially all para due to combined electronic and steric effects. The sulfonic acid is then converted to 4- acetamidobenzenesulfonyl chloride by reaction with excess chlorosulfonic acid, generating sulfuric acid as the co-product.
Preparation of 4-Acetamidobenzenesulfonamide 4-acetamidobenzenesulfonyl chloride is converted to the corresponding sulfonamide by reaction with aqueous ammonia. This step is carried out immediately after isolating the 4- acetamidosulfonyl chloride to prevent losses due to hydrolysis of the sulfonyl chloride.
Preparation of Sulfanilamide The acetamide group of 4-acetamidobenzenesulfonamide can be hydrolyzed under acidic conditions without affecting the sulfonamide group, which hydrolyzes much more slowly. As a final step, the acidic hydrolysis solution is neutralized with sodium carbonate to isolate sulfanilamide. Figure 4. Schematic representation of the sulfanilamide synthesis
Objectives: 1. Explain the synthetic approach in the preparation of sulfanilamide. 2. Discuss the synthesis of sulfanilamide.
Guide Questions: 1. Discuss briefly the reactants and the product formed in the Synthesis of 4- Acetamidobenzenesulfonyl Chloride. 2. How is 4-Acetamidobenzenesulfonamide obtained? 3. Discuss briefly the Synthesis of Sulfanilamide. 4. Briefly explain why there is a need to maintain the dryness of the apparatus that to be used in the synthesis of p-acetamidobenzene sulfonamide? 5. Why there is a need to add slowly the solid sodium carbonate in the synthesis of p-acetamidobenzene sulfonamide? 6. What is the purpose of solid sodium carbonate to the reaction mixture? 7. In the synthesis of p-amino benzene sulfonamide, a bubble formation is due to the formation of _______? 8. Without protection in the preparation of acetanilide discuss briefly what will happen to the free amine? 9. Draw the sulfonic acid and its derivatives.
