Since Sir Geoffrey Wilkinson invented a rhodium catalyst selective for the hydrogenation of cis-alkenes,1 the last several decades have seen an extraordinary rise in the use of precious metal-based catalysts. Soluble forms of palladium, platinum, gold, rhodium, iridium, ruthenium have been made with organic ligands that control the metal, and its environment, to facilitate chemo-, regio-, stereo- and selective chemical transformations. As a result of this, some of these catalysts have found application in the production of complex organic chemicals; but importantly, also because ways have been found to use them efficiently, either through high turnover, or recovery and recycle. Despite this the majority of precious metal catalysts, identified by a large number of academic groups throughout the world, are unusable, even in the high value pharma industry. This is because: the loadings are too high with consequent cost (anything above 0.1mol% is usually uneconomic, whilst most report 1-10mol%); recovery and recycle is frequently impractical. Furthermore these metals are toxic to biological systems with regulations that stipulate drug products must contain <10 ppm quantities.
The increasing global consumption of precious metals has raised international concern over their medium to long-term supply. Whilst by far the largest consumers are the automotive and electronics industries, the pharma industry is involved and needs to adopt sustainable precious metal use policies. This should include some of the Green Chemistry Principles around avoidance, higher efficiency, recovery and recycle.2 The Chem21 project is working to support these aims by evaluating the use of alternative organo-, bio- and base metal catalysts as well as more efficient processes and recovery recycle methods.
The recent Winter Process Conference held by iPRD,3 and organized by Scientific Update had a number of talks from Chem21 collaborators, setting the scene by covering new base-metal catalysts and applications in atom-efficient transformations. Prof. Beller form LIKAT, Rostock spoke, amongst many exciting developments, of new iron catalysts for chemoselective nitroaromatic-reductions;4 Dr Kai Rossen of Sanofi-Aventis spoke of their clean photocatalytic oxidation process in Artemisinin production;5 Prof. Bert Maes of University of Antwerp spoke of their work on the use copper catalysts in aromatic C-H activations;6 I spoke of the Chem21 work done by Dr Andy Wells and Dr John Hayler and others in analyzing the impact of green chemical approaches over the last decade, gaps and areas of future concern including precious metal catalysts.
A paper recently published rather depressingly concludes that finding alternatives to precious metals is unlikely.7 Whilst this may be true regarding the material properties of these metals, with catalyst applications there are already some base metal alternatives and more are being reported every week in what has become an intensive area of research.
A further caution against a knee-jerk response in abandoning precious metals in catalysis, is that their availability follows standard supply and demand economics. As demand outstrips supply and prices increase, new mines become economic and prices can then fall. This recently happened with rhodium that became very expensive until a new gold seam was opened in which there was a higher abundance of the rhodium side-product.8 Despite refining more metals, the conservation of matter laws dictates that they don’t disappear, rather they change form. Consequently more effort needs to be put into identifying methods for recovering metals from catalytic converters, mobile phones and the like. Better still to design such products with recovery in mind. Likewise the community should design methods for catalyst separation and recovery from the outset. Chem21 is working to develop catalyst immobilization methods with partners Reaxa Ltd, and membrane separation methods, Vito Ltd.
To conclude, we should be cautious in redirecting research to sustainable catalysts, not to ignore the amazing progress made in using precious metal catalysts, but to find ways of using these more effectively to make products economically, safely and sustainably. Nevertheless the whole community should welcome the progress being made in new organo-, bio- and base metal catalysts which will give process chemists better alternatives to realize more sustainable and cost effective drug manufacture.
John Blacker – iPRD, University of Leeds
- Osborn, J. A.; Jardine, F. H.; Young, J. F.; Wilkinson, G., Journal of the Chemical Society A, 1711–1732, 1966.
- Kletz, T.A., Chemistry and Industry, 287–292, 1978; Anastas, P. T., Warner, J. C., Green Chemistry Theory and Practice. New York: Oxford University Press, 1998
- www.iprd.leeds.ac.uk; www.chem21.eu/
- R. V. Jagadeesh, A.-E Surkus, H. Junge, M.-M. Pohl, J. Radnik, J. Rabeah, H. Huan, V. Schünemann, A. Brückner, M. Beller, Science, 29 November 2013: 1073-1076
- A. Burgard, M. P. Feth, K. Rossen, EPAppl. 2660234 A1, 20131106
- J. De Houwer, K. Abbaspour Tehrani, B. U. W. Maes, Angew. Chem. Int. Ed. Engl., 51, 2745, 2012
- Recycling of (critical) metals, G. Gunn, C. Hagelüken, Published Online: 27 DEC 2013, DOI: 10.1002/9781118755341.ch3