Page 125 - Chemical and process design handbook

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ASPIRIN

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.
C H OH + CO → HOC H CO H
6 5 2 6 4 2
Salicylic acid reacts easily with acetic anhydride to give aspirin.

HOC H CO H + (CH CO) O → CH OCOC H CO H + CH CO H
6 4 2 3 2 3 6 4 2 3 2
In this process, a 500-gallon glass-lined reactor is needed to heat the sal-
icylic acid and acetic anhydride for 2 to 3 hours. The mixture is transferred
o
to a crystallizing kettle and cooled to 3 C. 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 glyci-
nate, sodium citrate, aluminum hydroxide, or magnesium trisilicate (a
®
trademark for this type of aspirin is Bufferin ).
Both phenacetin and the newer replacement acetaminophen are deriv-
atives of p-aminophenol. Although these latter two are analgesics and
antipyretics, the aniline-phenol derivatives show little if any antiinflam-
matory 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 aceta-
minophen, aspirin, and caffeine. Acetaminophen is easily synthesized
from phenol.

See Salicylic Acid.

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