January 10th, 2018
How Aspirin Works
The role of plant extracts in discovery of medicine is evident from the discovery and subsequent development of aspirin and related non-steroidal anti-inflammatory aids (NSAIDs). Salicylate-containing plant parts such as the bark of the willow tree were widely used to treat pain, fever, and inflammation by early Chinese, Africans, Indians and Americans (Rainsford 4). As early as the fifth century, Hippocrates, considered the father of western medicine, prescribed the juice of willow back tree to relieve fever and calm the pain associated with childbirth (Botting and Botting 499). By mid-19th century, following advancements in chemistry to allow the isolation of ingredients in willow tree bark and other plants such as Salix and Spiraea species that had similar pain and fever-relieving effects, salicylate was implicated as the active ingredient for such effects (Botting and Botting 500). The subsequent synthesis of salicylic acid in Germany in 1860 and its undesirable foul taste and nauseating tendency, led to the search for more palatable preparations. Breakthrough came with the discovery of acetylysalicylate (aspirin), by the German Chemist Felix Hoffman in 1897, in an attempt to relieve his father from arthritis pain (Choubey 3803). Following animal and clinical tests at Bayer, where Hoffman worked, acetylsalicylate was introduced to the market as aspirin in 1899, a name coined from acetyl chloride (“A”), Spiraea ulmaria (“spir”: the source of salicylic acid used in the preparation) and a terminal “in” form used in names of many medications present at the time (Choubey 3803).
What Aspirin is
Aspirin is an Acetyl derivative of salicylic acid that is used for its pain relieving, anti-inflammatory and fever calming effects. The acetyl group is attached to the ortho- position of the benzene ring, to form a disubstituted benzene (that is comprised of a carboxyl substituent at position 1, and an acetyl substituent at position 2; figure 1 below).
In the laboratory, aspirin can be obtained as one of the products of the reaction between salicylic acid (2-hydroxybenzoic acid) and ethanoic anhydride (acetic anhydride) under acidic conditions (phosphoric acid) (Lewis 9). Salicylic acid is obtained from plant extracts, e.g. oil of wintergreen, as methyl 2-hydroxybenzoate, and purified through hydrolysis in the presence of aqueous sodium hydroxide, and subsequent addition of hydrochloric acid to covert the product obtained from hydrolysis, sodium 2-hydroxybenzoate, to salicylic acid (Lewis 7). The reaction between salicylic acid and ethanoic anhydride (fig. 2), which should be performed with dry apparatus since acetic anhydride reacts readily with water, leads to a mixture of aspirin and other compounds (e.g. acetic acid) (Lewis 9). Aspirin can then be separated from the mixture by adding cold water, precipitation under a bath of iced water, and subsequent filtration (Lewis 9). To enhance the purity of the product, recrystallization is performed with deionized water (solvent) by taking advantage of different solubility in the solvent and different melting points among aspirin and the impurities in (Lewis 11-12).