Hoffmann Felix

Laboratory notebook entry of Felix Hoffmann, describing his first preparation of aspirin. The initials CD on the page are those of Carl Duisberg. (Courtesy of Bayer A.G., Leverkusen, Germany)... 

Felix Hoffmann did not publish his version of the discovery, nor did he obtain a German patent, since the synthesis had been previously described. Farbenfabriken Bayer did obtain a U.S. Patent2 6 in 1900 which named him as the inventor. Chemical Abstracts reveal no subsequent publications by him, nor is there any record that he was publicly honored for his contribution. However, in 1899, he was appointed director of the pharmaceutical research and marketing division of Bayer. He retired in 19287. 

That s quite a claim for the little pill that was concocted in 1897 by Felix Hoffmann, a chemist working for the Bayer company in Germany. While Hoffmann did synthesize the first commercial sample of acetylsalicylic acid, as aspirin is known generically, he wasn t the first to produce the substance in the laboratory. That honor goes to Karl Friedrich Gerhardt, who, in 1853 at Montpellier University in France, concocted an impure version with an eye towards improving on the effects of salicylic acid, a commonly used painkiller. At the time salicylic acid was extracted from the leaves of the meadowsweet plant and used for the treatment of fevers and pain, particularly of the arthritic variety. But it had to be taken in... 

Pain research is a traditional and well established field within the pharmaceutical industry. Beginning with the isolation of morphine in a small pharmacy by Adam Serturner (1806), the next major breakthrough in pain treatment was achieved by the synthesis of acetylsalicylic acid by Felix Hoffmann in the Bayer Laboratories in Wuppertal (1897). Further outstanding contributions by the pharmaceutical industry were the first fully synthetic opioids pethidine (1939) and methadone (1946). Continued efforts up to now have resulted in many potent and clinically accepted analgesics with reasonable side effects and covering nearly all facets of pain treatment. However, pain treatment is far from being satisfactory in respect to more complex pain states, e.g. neuropathy, visceral pain or migraine. 

Another German chemist, Felix Hoffmann, working for the drug company Bayer, synthesizes a stable form of acetylsalicylic acid, which becomes the major active ingredient in aspirin. 

Felix Hoffmann by Nazis Medicine, 1982, PG synthesis aspirin inhibition of COX)... 

Aspirin, one of the oldest pharmceutical products, has been produced for over a hundred of years [4]. A chemist, Felix Hoffmann, who worked for the Bayer Co. in Elberfeld, Germany, discovered aspirin. He was searching for a medication for pain relief for his father who suffered from the pain of rheumatism. Besides pain relief, physicians have recently found that aspirin helps prevent heart attacks and strokes. 

The well-known drug Aspirin can demonstrate the various stages in the life of a drug substance. It was known since ancient times that the bark and leaves of the willow tree can provide relief from pain and fever. In 1832, the German chemist Piria isolated salicylic acid as the active substance in the plant material. Salicylic acid became the lead substance for further development. Soon a synthetic route was developed that replaced the tedious extraction process. Salicylic acid was used as a pain remedy, but because of its high acidity it had severe side effects when applied orally. In 1887, Felix Hoffmann, a chemist at Bayer AG, realized that the ester form of salicylic acid, acetylsalicylic acid, had fewer side effects and was even more efficacious than the free acid. The Bayer Company marketed the ester under the trade name Aspirin, which soon became the number one selling drug worldwide and is still a synonym for pain relief today. 

But unfortunately salicylic acid attacks the mucous membranes of the mouth and esophagus and causes gastric pain that may be worse than the discomfort it was meant to cure. Felix Hoffmann, a chemist for Friedrich Bayer, a German dye company, reasoned that the corrosive nature of salicylic acid could be altered by addition of an acetyl group and in 1893 the Bayer Company obtained a patent on acetylsalicylic acid, despite the fact that it had been synthesized some forty years previously by Charles Gerhardt. Bayer coined the name Aspirin for their new product to reflect its acetyl nature and its natural occurrence in the Spiraea plant. Over the years they have allowed the term aspirin to fall into the public domain so it is no longer capitalized. The manufacturers of Coke and Sanka work hard to prevent a similar fate befalling their products. 

Then back in Germany in the late 1800s, the father of Felix Hoffmann, a skillful organic chemist, developed painful arthritis. Putting aside his research on dyes, the younger Hoffmann looked for a way to... 

Willow bark has been a remedy for pain and fever for hundreds of years. In the late eighteenth century, scientists isolated the compound in willow bark that is responsible for its effects. They then converted it to a similar compound, salicylic acid, which is even more effective. In the late nineteenth century, a German chemist, Felix Hoffmann, did research to find a pain reliever that would help his father s arthritis, but not cause the nausea that is a side effect of salicylic acid. Because the technologies used to synthesize chemicals had improved, he had a number of more effective ways to work with chemical compounds than the earlier chemists. The compound that he made, acetylsalicylic acid, is known as aspirin. It is still one of the most common pain relievers more than 100 years later. 

In 1834, codeine was isolated from opium by Pierre Jean Robiquet (1780-1840). One year later, Pierre-Joseph Pelletier (1788-1842) and M. Thiboumery discovered thebaine (named after the ancient Egyptian city of Thebes). In 1848, at the University of Giessen, papaverine was extracted from poppy waste by Georg Merck (1825-1873), the son of Heinrich Emanuel Merck. In 1870, Augustus Matthiessen (1831-1870) and Charles R. A. Wright (1844-1894) recognised that codeine is the monomethyl ether of morphine. After the selective methylation of morphine for the preparation of codeine had failed, Felix Hoffmann (1868-1946) tried out in 1897 a selective acetylation, in analogy to the synthesis of aspirin from salicylic acid. [91]... 

Heroin was first synthesised in 1874 by Charles Romley Alder Wright (1844-1894), an English chemist, working at St. Mary s Hospital Medical School in London. However, his invention did not lead to any further developments, until it was more than two decades later independently re-synthesised by Felix Hoffmann. 

Hoffmann s laboratory notebook of August 10,1897. Only a few days later, on August 21 1897, Felix Hoffmann prepared heroin by the double acetylation of morphine. 

Since their discovery during the 1860s, electrophilic aromatic substitution reactions played the dominant role for functionalizations of arenes, and were often the method of choice for the synthesis of substituted arenes. For example, Hermann Kolbe, a student of Friedrich Wohler, devised a synthesis for salicylic acid (7) [13, 14], which set the stage for the industrial preparation of acetylsalicylic acid (ASA, aspirin) (1) by Arthur Eichengriin and Felix Hoffmann at Bayer in 1897 (Scheme 1.2). 

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