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Since no structural theory existed at that time Gerhardt called the compound he obtained "salicylic-acetic anhydride" (wasserfreie Salicylsäure-Essigsäure).When Gerhardt tried to dissolve the solid in a diluted solution of sodium carbonate it immediately decomposed to sodium salts of salicylic and acetic acids.Willow treatments also appeared in Dioscorides's De Materia Medica, and Pliny the Elder's Natural History.

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The Roman encyclopedist Celsus, in his De Medicina of ca.

30 AD, suggested willow leaf extract to treat the four signs of inflammation: redness, heat, swelling and pain.

Inspired by the doctrine of signatures to search for a treatment for agues near the brackish waters that were known to cause it, Stone had tasted the bark of a willow tree in 1758 and noticed an astringency reminiscent of the standard—and expensive—ague cure of Peruvian bark.

He collected, dried, and powdered a substantial amount of willow bark, and over the next five years tested it on a number of people sick with fever and agues.

In his letter, Stone reported consistent success, describing willow extract's effects as identical to Peruvian bark, though a little less potent.

(In fact, the active ingredient of Peruvian bark was quinine, which attacked the infectious cause of malaria, while the active ingredient of willow extract, salicin, relieved the symptoms of malaria but could not cure it.) Stone's letter (mistakenly attributed to Edmund rather than Edward Stone) was printed in Philosophical Transactions, and by the end of the 18th century willow was gaining popularity as an inexpensive substitute for Peruvian bark.in the second half of the nineteenth century, other academic chemists established the compound's chemical structure and devised more efficient methods of synthesis.In 1897, scientists at the drug and dye firm Bayer began investigating acetylsalicylic acid as a less-irritating replacement for standard common salicylate medicines, and identified a new way to synthesize it.In the course of his work on the synthesis and properties of various acid anhydrides, he mixed acetyl chloride with a sodium salt of salicylic acid (sodium salicylate).A vigorous reaction ensued, and the resulting melt soon solidified.Upon taking control of Bayer's overall management in 1890, Duisberg began to expand the company's drug research program.

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