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Aspirin (acetylsalicylic acid) is by far the most common type of analgesic, an important class of compounds that relieve pain, and it also lowers abnormally high body temperatures. Aspirin also finds use in reducing inflammation caused by rheumatic fever and rheumatoid arthritis. The manufacture of aspirin is based on the synthesis of salicylic acid from phenol. Reaction of carbon dioxide with sodium phenoxide is an electrophilic aromatic substitution on the ortho, para-directing phenoxy ring. The ortho isomer is steam distilled away from the para isomer. C6H5OH + CO2 → HOC6H4CO2H Salicylic acid reacts easily with acetic anhydride to give aspirin. HOC6H4CO2H + (CH3CO)2O → CH3OCOC6H4CO2H + CH3CO2H In this process, a 500-gallon glass-lined reactor is needed to heat the salicylic acid and acetic anhydride for 2 to 3 hours. The mixture is transferred to a crystallizing kettle and cooled to 3oC. Centrifuging and drying of the crystals yields the bulk aspirin. The excess solution is stored and the acetic acid is recovered to make more acetic anhydride. The irritation of the stomach lining caused by aspirin can be alleviated with the use of mild bases such as sodium bicarbonate, aluminum glycinate, sodium citrate, aluminum hydroxide, or magnesium trisilicate (a trademark for this type of aspirin is Bufferin®). Both phenacetin and the newer replacement acetaminophen are derivatives of p-aminophenol. Although these latter two are analgesics and antipyretics, the aniline-phenol derivatives show little if any anti-inflammatory activity. p-Aminophenol itself is toxic, but acylation of the amino group makes it a convenient drug. A trademark for acetaminophen is Tylenol®. Excedrin® is acetaminophen, aspirin, and caffeine. Acetaminophen is easily synthesized from phenol.