OF SYNTHESIS SULFANILAMIDE FROM ACETANILIDE
I. Introduction.
Sulfanilamide is one of a group of chemotherapeutic agents commonly referred to as Sulfa drugs discovered in the 1930's. Sulfa drugs were the first synthetic compounds found to be effective against such grave bacterial infections as meningitis, pneumonia and blood poisoning, and saved thousand of lives in World War II (1939-1945). The following are formulas of sulfanilamide and several related Sulfa drugs.
O H2N S NH2 O Sulfanilamide
H2N
O H S N O Sulfathiazole
S
H2N
O H S N O Sulfadiazine
N
N
N
Although Sulfa drugs represented a medical breakthrough at the time, their toxicity and other side-effects have presented difficulties for extended continued usage. Today, safer and more powerful antibiotics such as penicillin and tetracycline are available, but some Sulfa drugs are still being used in the treatment of meningitis and urinary tract infections. The activity of the sulfa drugs has been extensively studied and can be explained in the following manner. Microorganisms have to synthesize folic acid to grow, sulfanilamide inhibits the formation of folic acid and the bacteria ceases to grow and dies. Humans must supply folic acid in their diet because they cannot synthesize it and the Sulfa drugs do not interfere in a specific human metabolic step. One of the steps in the synthesis of folic acid is the incorporation of para-aminobenzoic acid (PABA) into the folic acid molecule by attaching PABA to a pteridine molecule. The following are the formulas for folic acid and PABA.
FOLIC ACID H2N N N OH C O Pteridine segment p-Aminobenzoic acid segment CH2 N N H N H N C
para-Aminobenzoic acid
O CH2 OH CH2 CH C O HO Glutamic acid segment
O H2N C OH
The structure of sulfanilamide resembles that of PABA in that both have the "amino-phenyl" segment on one end. The enzyme responsible for attaching the PABA to the pteridine recognizes only the "amino-phenyl" group segment of either molecule and and mistakenly attaches the sulfanilamide instead of PABA. The next step, involving the formation of an amide linkage (on the opposite end of the phenyl ring) between the carboxyl group of the PABA segment and the amino group of glutamic acid cannot proceed, ergo, no folic acid is formed and bacterial growth is stunted. II. Nomenclature. Sulfanilamide is the common name...
SULFANAM