This meant that by the s it was falling out of favour in the UK. In the search for an alternative, Dr Adams recruited chemist Dr John Nicholson and technician Colin Burrows to help him test the potency of more than chemical compounds. The key was to find a drug that would be well tolerated. From the front room of an old Victorian house in the suburbs of Nottingham, the small team patiently tested and re-tested compounds until they found something worth trying on patients in the clinic.
Dr Adams realised his chances of success were minimal but he and his staff persevered over 10 long years. And he was always prepared to act as guinea pig, testing two or three compounds on himself. That would never be allowed now, he admits, but they were careful to carry out toxicity tests beforehand. During that time, four drugs went to clinical trials and failed before, in , they settled on one called 2- 4-isobutylphenyl propionic acid, later to become ibuprofen.
A patent for ibuprofen was granted to Boots in and it was approved as a prescription drug seven years later. According to Dave McMillan, former head of healthcare development at Boots UK, ibuprofen was an extremely important drug to the company.
It was Boots' number one drug. An incredible 20, tonnes of ibuprofen are now made every year by a range of different companies under many different brand names. There are different forms of it too, including liquid forms specifically designed for children. Dr Adams has been honoured for his research, with an honorary doctorate of science from the University of Nottingham, and two blue plaques from the Royal Society of Chemistry.
He remained with Boots UK for the rest of his career, becoming head of pharmaceutical sciences. What he is most pleased about is that hundreds of millions of people worldwide are now taking the drug he discovered. It was a long road - but a very important one. And it all began with a sore head. Or go unlimited with ACS membership. Chemistry matters. Join us to get the news you need. Don't miss out. Renew your membership, and continue to enjoy these benefits.
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Please enter the following information to continue. As an ACS member you automatically get access to this site. All we need is few more details to create your reading experience. Not you? Sign in with a different account. Need Help? Membership Categories. Regular or Affiliate Member. Graduate Student Member. The synthetic process included a Friedel-Crafts acylation, reduction, chloride substitution, and Grignard reaction.
The products of each step were analyzed using IR and 1H NMR spectroscopy and the final product was additionally confirmed by melting point analysis. Ibuprofen is a nonsteroidal antiinflammatory drug used to relieve pain and reduce swelling, among other common treatments. It was first patented in by the Boots Pure Chemical Company, and was approved as an over-the-counter drug in In , the BHC Company developed a new, sustainable synthesis that halved the number of synthetic steps Scheme 1.
The first step utilized anhydrous hydrogen fluoride as both a catalyst and solvent, which was then recycled and reused. Additionally, the true brilliance behind the BHC method is the reduced amount of unwanted waste due to the generation of only one molecule of water as the byproduct; this, among other factors, have contributed to a genuinely green synthesis. In this report, we describe a five-step synthesis of ibuprofen that mimics the industrial BHC synthesis.
However, our synthesis utilized a chloride substitution, Grignard formation, and Grignard reaction in the final steps as the industrial method, which uses carbon monoxide CO at psi, was avoided due to safety concerns. The synthesis of ibuprofen was accomplished through a five-step process shown in Scheme 2.
Initially, isobutylbenzene 1 and acetic anhydride, were reacted under Friedel-Crafts acylation conditions to create p-isobutylacetophenone 2. Acetic anhydride and AlCl3 formed a lewis acid complex that produced an acylinium ion, which was then attacked by 1 to form p-isobutylacetophenone 2 through electrophilic aromatic substitution. This product was obtained in This shows the appearance of the appropriate ketone functional group.
The 1H NMR spectrum validated the structure of the product. The two doublets integrating to 2 hydrogens at 7. The singlet at 2.
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