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The Manufacture of Aspirin
The history, synthesis, and industrial manufacture of aspirin (acetylsalicylic
acid) and related compounds will be covered. The differences between
three levels of chemistry -- student laboratory,bench-scale and industrial
scale -- are used to help you understand the intricate interplay
between research chemistry and industrial manufacturing process development.
Areas such as acid-base, solution, and equilibrium chemistry are discussed
for background. Also, the idea of life-cycle analysis will be explained
because of its importance to the various levels of decision-making involved
in pollution prevention as it relates to the aspirin production process.
Finally, the Batch Design Kit tool will be introduced at the end of the
module to show different ways in which decision-making can affect the aspirin
manufacturing process described in this case study, as well
as many other processes.
2.1 Willow Bark: The Precursor
Today, aspirin is a common remedy. Less than one hundred years ago,
however, it was considered a wonder-drug, the newest thing to hit
the stores. Many similar compounds had been produced before and many different
means of producing aspirin have been devised since, but nothing has rivaled
the success of this one synthetic compound. Before undertaking a discussion
of exactly what aspirin is and how it is made, it is important to understand
what it came from. More than 2500 years ago, in approximately 500 BC, Chinese
healers used willow bark as a remedy for many ailments. About 400 BC, Hippocrates,
a Greek often proclaimed as the Father of Medicine, suggested that chewing
willow bark lowered fever and reduced pain. Other accounts such as these
litter the history books. Five hundred years after Hippocrates, in 100
AD, Dioscorides, a Greek physician, prescribed willow bark to reduce inflammation
in his patients. These are the traditional uses of the precursor to aspirin.
Unfortunately, during the middle ages, the benefits of willow bark were
lost to physicians. Though the use of willow bark for its medicinal properties
continued in other parts of the globe. It was forgotten in Europe
was without its benefits for many years.
In the middle of the eighteenth century, Reverend Edward Stone of Oxford
began experimenting with ways to reduce fever. Stone pulverized a pound
of dried willow bark and gave it to fifty feverish people over several
years time. He tried mixing the bark powder into tea, water, or even "small
beer." With few exceptions, the fevers disappeared. This might have seemed
evident but Stone knew nothing of the thousands of years of cases which
preceeded his work. In 1763 The Royal Society of London published Stone's
accounts of the success of willow bark in reducing fever. It would still
be several years before medicine would be able to make wide use of the
bark’s beneficial properties.
In 1828, German chemists isolated the active ingredient in willow bark.
Since the Latin name for the willow tree was salix, the new compound was
named salicin. When crystallized, salicin was appear yellow and bitter-tasting.
Ten years later, a French chemist synthesized a purer compound named
salicylic acid. Salicylic acid would eventually be used as a building block
for many other pharmaceutical compounds including acetylsalicylic acid.
While willow bark was the main source of salicin, several other related
plants were producing similar compounds with almost the same types of medicinal
powers. Over time, scientists were able to isolate several different salicylic
acid derivatives which could be found in nature or more importantly synthesized
in the laboratory. One of the most important of these is sodium salicylate.
Once ingested this compound is transformed to salicylic acid. Unfortunately
for its users, sodium salicylate has the unfortunate side effect of causing
Sodium and methyl salicylate were some of the first salicylates isolated
from natural sources. Today there are several salicylates which are used
commercially. These include: sodium salicylate, magnesium salicylate, choline
salicylate, and choline magnesium salicylate. The most widely used compound,
which when ingested becomes salicylic acid is, of course, acetylsalicylic
Before continuing on with the story of aspirin, it is important to take
a moment and discuss some of the chemistry involved in the isolation process
of salicin and the other salicylates. Earlier, the idea of solubility and
crystallization was mentioned. Now, let us take a closer look at these
ideas and how they are important to the research chemist trying to isolate
a chemical like salicin.