Introduction:

N-acylated aromatic amines (those having an acyl group, RCO- substituted on nitrogen) are important in over-the-counter headache remedies. Over-the-counter drugs are those you may buy without a prescription. Acetanilide, phenacetin, and acetaminophen are mild analgesics and antipyretics and are important, along with aspirin, in many non-prescription drugs.

The discovery that acetanilide was an effective antipyretic came about by accident in 1886. At the University of Strassburg, Professor Kussmaul, of the Department of Internal Medicine, asked two assistants to give naphthalene as a treatment for intestinal worms. Cahn and Hepp, who had been testing naphthalene as a possible vermifuge (an agent that expels worms) by accident, mixed up a bottle of acetanilide and the bottle of naphthalene. The patient’s worms didn’t disappear but his fever did – dramatically. In another instance of serendipity, it was soon in production and remained in use for several years because it was so cheap to produce. However, it had a serious side effect involving the deactivation of some of the hemoglobin in red blood cells. However, restrictions have been placed on its use due to kidney damage in long-term users. The publication of Cahn and Hepp describing their experiments with acetanilide caught the attention of Carl Duisberg, director of research at the Bayer Company in Germany. Duisberg was confronted