Aspirin, acetylsalicylic acid (ASA), 2-acetyloxybenzoic acid
Who?
Felix Hoffman (1868–1946)
He has long been credited with the first pure synthesis, but it could likely have been a team effort. The chemist Arthur Eichengrün (1867–1949), who was imprisoned in the Theresienstadt concentration camp in 1944, later claimed to have been the true driving force behind the development of aspirin. According to him, Hoffmann followed his instructions, and without his insistence, Heinrich Dreser (1860–1924), another Bayer scientist, would have discarded the substance. However, Eichengrün’s claim is not supported by any written sources and remains controversial [1,2].
When?
On August 10, 1897
How?
Salicylic acid is treated with acetic anhydride.
Figure 1. Acetylation of salicylic acid.
Very Short History of Aspirin
In 1883, Carl Duisburg (1861–1935) joined Bayer, then known as “Farbenfabriken vorm. Friedr. Bayer & Co”, and established a major research laboratory in Wuppertal-Elberfeld in 1891, setting new standards in industrial research. Under his leadership, Bayer released its first drug, phenacetin, in 1887 and introduced 48 medicines by 1902.
Felix Hoffmann, who earned his Ph.D. in 1893 under Eugen Bamberger (1857–1932) in Munich, Germany, joined Bayer in 1894 and was tasked with acetylating various substances to make them less toxic as part of a systematic search for useful drugs.
On 10 August 1897, he succeeded in synthesizing and crystallizing acetylsalicylic acid, which would later be called aspirin. Eleven days later, on 21 August 1897, Felix Hoffmann produced diacetylmorphine, which would later be called heroin. [3,4] Heroin was the first drug to be marketed, while aspirin was not pursued initially, as it seemed less promising. At first, it was believed that the only side effects of heroin were sexual aversion and constipation. You can read more about this in “The Misjudgment of Heroin” [4].
Salicylic Acid
The pain-relieving and fever-reducing properties of willow bark have been known since ancient times. Much later, these properties were attributed to salicylic acid, which occurs in the form of its methyl ester in essential oils and as a plant hormone in the leaves, flowers, and roots of various plants, where it helps defend against pathogens. This compound is converted to salicylic acid in the body.
Figure 2. Paths leading to the discovery [3].
In 1859, Hermann Kolbe (1818–1884) determined its chemical structure and synthesized it, and in 1874, the Heyden Company near Dresden, Germany, began producing and selling synthetic salicylic acid, which was cheaper than the extract from willow bark or other plants. However, salicylic acid irritated the stomach and was not tolerated by some patients. The knowledge of these side effects associated with salicylic acid initially made aspirin seem less attractive as well.
Figure 3. Bottle with aspirin, 1899. (© Bayer AG; from Bayer Archives; CC BY-SA 3.0)
Aspirin
The Aspirin trademark was registered for acetylsalicylic acid with the Imperial Patent Office in Berlin, Germany, on March 6, 1899. Aspirin was originally sold as a powder in a bottle. The name is made up of “A” for acetyl, “spir” from the plant Spiraea ulmaria (meadowsweet), from which salicin is extracted, and “in” was a common ending for medicines at the time.
Aspirin continues to be a popular drug with uses far beyond those originally envisioned. It is probably Bayer’s best-known drug.
Where?
in Wuppertal-Elberfeld, Germany, in the laboratory of the “Farbenfabriken vorm. Friedr. Bayer & Co.”.
Figure 4. Bayer’s Central Scientific Laboratory in Wuppertal-Elberfeld in 1891. © Bayer AG
Original building?
Old brick buildings from this period still stand on the site which is still Bayer today, which can be overlooked by the Wuppertal Suspension Railway.
Figure 5. View of the Elberfeld site at the end of the 19th century. © Bayer AG
Brief History of the Elberfeld Site
The Elberfeld site was the company’s headquarters from 1878 to 1912, but it became too small for further expansion. In 1891 Bayer therefore acquired the alizarin red factory of Dr. Carl Leverkus & Sons north of Cologne, before purchasing additional land along the Rhine River. Beginning in 1895, Bayer systematically expanded this site according to plans drawn up by Carl Duisberg, the company’s Chairman of the Board of Management from 1912 to 1925. Leverkusen became the company’s headquarters in 1912.
References
[1] Elisabeth Vaupel, Arthur Eichengrün—Tribute to a Forgotten Chemist, Entrepreneur, and German Jew, Angew. Chem. Int. Ed. 2005, 44(22), 3344–3355. https://doi.org/10.1002/anie.200462959
[2] Ulrich Chaussy, Arthur Eichengrün. Der Mann, der alles erfinden konnte, nur nicht sich selbst, Verlag Herder, Freiburg im Breisgau, Germany, 2023. ISBN: 978-3-451-39216-0
[3] K. C. Nicolaou, Tamsyn Montagnon, Molecules that Changed the World, Wiley-VCH, Weinheim, Germany, 2008. ISBN-13: 978-3527309832
[4] V. Koester, The Misjudgment of Heroin, ChemistryViews 2024. https://doi.org/10.1002/chemv.202400057
