Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Drug manufacture: Going green with iron

01.02.2013
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:
http://www.a-star.edu.sg
http://www.researchsea.com

More articles from Life Sciences:

nachricht Biology in a twist -- deciphering the origins of cell behavior
31.03.2015 | National University of Singapore

nachricht Speech dynamics are coded in the left motor cortex
31.03.2015 | Universitätsmedizin Göttingen - Georg-August-Universität

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Experiment Provides the Best Look Yet at 'Warm Dense Matter' at Cores of Giant Planets

In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...

Im Focus: Energy-autonomous and wireless monitoring protects marine gearboxes

The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.

As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...

Im Focus: 3-D satellite, GPS earthquake maps isolate impacts in real time

Method produced by UI researcher could improve reaction time to deadly, expensive quakes

When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.

Im Focus: Atlantic Ocean overturning found to slow down already today

The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe. 

Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...

Im Focus: Robot inspects concrete garage floors and bridge roadways for damage

Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.

From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Conference On Regenerative Medicine 2015: Registration And Abstract Submission Now Open

25.03.2015 | Event News

University presidents from all over the world meet in Hamburg

19.03.2015 | Event News

10. CeBiTec Symposium zum Big Data-Problem

17.03.2015 | Event News

 
Latest News

Biology in a twist -- deciphering the origins of cell behavior

31.03.2015 | Life Sciences

Wrapping carbon nanotubes in polymers enhances their performance

31.03.2015 | Materials Sciences

Research Links Two Millennia of Cyclones, Floods, El Niño

31.03.2015 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>