Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Drug manufacture: Going green with iron

Safe and inexpensive iron catalysts provide a ‘greener’ alternative to typical pharmaceutical production methods

More than one-quarter of all known pharmaceuticals contain the chemical group known as amides: carboxylic acid derivatives derived from ammonia or amines. Most methods for synthesizing amides, however, are inefficient and use hazardous reagents.

New work from Anqi Chen and co-workers at the A*STAR Institute of Chemical and Engineering Sciences in Singapore promises to make amide chemistry more economical and sustainable than before1. The team has uncovered a way to convert aldehydes and amine salts into amides using iron(II) sulfate - a harmless, inexpensive substance as the catalyst to perform this transformation efficiently and with little waste.

Most alternative methods to produce amide molecules use expensive noble metal catalysts such as palladium and ruthenium, which are incompatible with industrial demands for cost-efficiency. Funded by a GlaxoSmithKline (GSK)–Singapore Economic Development Board (EDB) endowment on sustainable drug manufacturing, the researchers investigated a different approach known as ‘direct oxidative amidation’. This method couples an aldehyde and an amine salt in the presence of a catalyst and an oxidant, generating an amide in one step.

Nontoxic and cheap catalysts with sufficient chemical activity for amide transformation are hard to find. To identify an efficient and inexpensive catalyst, the team screened a range of iron compounds and discovered that iron(II) sulfate (see image), a supplement for anemia that costs less than a dollar per kilogram, has strong potential to catalyze amide formation from aldehydes with amine salts.

Apart from the environmentally benign iron catalyst, the transformation uses an inexpensive oxidant known as tert-butyl hydroperoxide and very cheap calcium carbonate, the main composition of limestone, as a base. By combining these inexpensive ingredients together, the researchers achieved excellent amide yields under conditions convenient for both laboratory and industrial operations.
Further experiments revealed the versatility of this amide synthesis. A range of amine salts and aldehydes with different structural and electronic features could be transformed into amides with good-to-excellent yields. Importantly, salts derived from natural amino acids such as valine and proline also underwent oxidative amidation without disrupting their chirality or ‘handedness’ - a critical structural phenomenon for drug molecules and peptides.

The team demonstrated the potential of this iron-catalyzed amidation for drug manufacturing by synthesizing the antiarrhythmic drug N-acetylprocainamide in a one-step procedure that is more efficient than previous multiple-step routes. “This environmentally benign method has significant advantages over conventional techniques,” says Chen, “and we intend to identify pharmaceutical targets where this promising method could bring about significant cost-savings and improved sustainability.”

The A*STAR-affiliated researchers contributing to this research are from the Institute of Chemical and Engineering Sciences

Journal information
Ghosh, S. C., Ngiam, J. S. Y., Chai, C. L. L., Seayad, A. M., Dang, T. T. & Chen, A. Iron-catalyzed efficient synthesis of amides from aldehydes and amine hydrochloride salts. Advanced Synthesis & Catalysis 354, 1407–1412 (2012).

A*STAR Research | Research asia research news
Further information:

More articles from Life Sciences:

nachricht New supercomputer simulations enhance understanding of protein motion and function
24.11.2015 | DOE/Oak Ridge National Laboratory

nachricht Sensor sees nerve action as it happens
24.11.2015 | Duke University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Lactate for Brain Energy

Nerve cells cover their high energy demand with glucose and lactate. Scientists of the University of Zurich now provide new support for this. They show for the first time in the intact mouse brain evidence for an exchange of lactate between different brain cells. With this study they were able to confirm a 20-year old hypothesis.

In comparison to other organs, the human brain has the highest energy requirements. The supply of energy for nerve cells and the particular role of lactic acid...

Im Focus: Laser process simulation available as app for first time

In laser material processing, the simulation of processes has made great strides over the past few years. Today, the software can predict relatively well what will happen on the workpiece. Unfortunately, it is also highly complex and requires a lot of computing time. Thanks to clever simplification, experts from Fraunhofer ILT are now able to offer the first-ever simulation software that calculates processes in real time and also runs on tablet computers and smartphones. The fast software enables users to do without expensive experiments and to find optimum process parameters even more effectively.

Before now, the reliable simulation of laser processes was a job for experts. Armed with sophisticated software packages and after many hours on computer...

Im Focus: Quantum Simulation: A Better Understanding of Magnetism

Heidelberg physicists use ultracold atoms to imitate the behaviour of electrons in a solid

Researchers at Heidelberg University have devised a new way to study the phenomenon of magnetism. Using ultracold atoms at near absolute zero, they prepared a...

Im Focus: Climate Change: Warm water is mixing up life in the Arctic

AWI researchers’ unique 15-year observation series reveals how sensitive marine ecosystems in polar regions are to change

The warming of arctic waters in the wake of climate change is likely to produce radical changes in the marine habitats of the High North. This is indicated by...

Im Focus: Nanocarriers may carry new hope for brain cancer therapy

Berkeley Lab researchers develop nanoparticles that can carry therapeutics across the brain blood barrier

Glioblastoma multiforme, a cancer of the brain also known as "octopus tumors" because of the manner in which the cancer cells extend their tendrils into...

All Focus news of the innovation-report >>>



Event News

Gluten oder nicht Gluten? Überempfindlichkeit auf Weizen kann unterschiedliche Ursachen haben

17.11.2015 | Event News

Art Collection Deutsche Börse zeigt Ausstellung „Traces of Disorder“

21.10.2015 | Event News

Siemens Healthcare introduces the Cios family of mobile C-arms

20.10.2015 | Event News

Latest News

Siemens offers concrete solution portfolio for Industrie 4.0 with Digital Enterprise

24.11.2015 | Trade Fair News

Compact, rugged, three-phase power supplies for worldwide use

24.11.2015 | Trade Fair News

Sensor sees nerve action as it happens

24.11.2015 | Life Sciences

More VideoLinks >>>