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 Size and Age of Plants Impact Their Productivity More Than Climate, UA Study Shows
24.07.2014 | University of Arizona

nachricht Diseases of Another Kind
24.07.2014 | University of California - Santa Barbara

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Anzeige

Anzeige

Event News

“Lens on Life” - Artists and Scientists Explore Cell Divison

08.07.2014 | Event News

First International Conference on Consumer Research | ICCR 2014: Early bird deadline July 31, 2014

08.07.2014 | Event News

First evidence for painless atrial fibrillation treatment

04.07.2014 | Event News

 
Latest News

Size and Age of Plants Impact Their Productivity More Than Climate, UA Study Shows

24.07.2014 | Life Sciences

All-Clear for Nonlinear Optical Imaging

24.07.2014 | Health and Medicine

Monitoring Pulse After Stroke May Prevent a Second Stroke

24.07.2014 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>