Sulfanilamide Discovery and Synthesis of the First Antibiotic

An important area of research in the pharmaceutical industry is the discovery and development of new orally active antibiotics to treat bacterial infections. Commonly used antibiotics fall into several important classes, including 3-lactams, the 

Early in the development of sulfa drugs as antibiotics, it was found that p-aminobenzoic acid (PABA, 2), which is now used in sunscreens and sunblocks, inhibits the antibacterial action of sulfanilamide. Since p-aminobenzoic acid and sulfanilamide are structurally similar, this discovery led to the speculation that the two compounds competed with each other in some biological process that was essential for bacterial growth. This speculation was eventually supported by experimentation. p-Aminobenzoic acid is used by bacteria in the synthesis of the essential enzyme cofactor folic acid (3). When sulfanilamide is present, it successfully competes with p-aminobenzoic acid for the active site in the enzyme that 

Reduction of Aromatic Nitro Compounds Preparation of Aniiine (6) 

The procedure for isolating and purifying the aniline formed in this experiment represents an excellent example of how the physical and chemical properties of a component in a mixture of organic substances can be exploited to isolate it without using chromatographic techniques. For example, after completing the procedure for the chemical reduction of nitrobenzene, it is necessary to remove aniline from its principal impurities, which are unchanged nitrobenzene and two by-products, benzidine (12), and 4-aminophenol (13). 

Steam distillation (Secs. 2.16 and 4.5) is a good technique for separating volatile organic compounds from nonvolatile organic and inorganic substances. However, the reaction mixture is acidic, and it must be made basic prior to performing the steam distillation so aniline is present as the free base, and the 4-aminophenol is converted to its water-soluble sodium phenoxide salt. The aniline and nitrobenzene are then removed from the reaction mixture by steam distillation. The nonvolatile salt of 4-aminophenol and the nonvolatile benzidine remain in the aqueous phase. 

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