Organic Chemists reducing impact on the Environment

Background - Why is this important?


“Green chemistry is not just a mere catch phrase: it is the key to the survival of mankind”
Professor Ryoji Noyori – Nobel Laureate


Green chemistry seeks to reduce chemical related impact on human health and the environment by the use of alternative, environmentally friendly processes and reaction media. 

The selection of solvents, the chemicals used to dissolve substances into a solution, are a key target within Green Chemistry programs. Solvents are a major source of industrial waste in industrial chemical manufacture but careful selection can also increase reaction rates and lower reaction temperatures. Reduction in the quantity of organic solvent used in the synthesis of the drug ViagraTM (Sildenafil Citrate) is a major achievement of Green Chemistry.

Sildenafil Citrate Manufacture

The amount of organic waste produced by the sildenafil citrate processes at various time points

© Peter Dunn: Green Chem. 2004, 6, 43-48

What did the organic chemists do?

Sildenafil Citrate is the active ingredient in two medicines ViagraTM and RevatioTM. ViagraTM is a medicine that probably needs no introduction, in its first year on the market it achieved sales of $1 billion. RevatioTM is an important medicine for the treatment of pulmonary hypertension in adults and children.


Organic chemists working on the ViagraTM synthesis at Pfizer in the UK made some substantial improvements which have resulted in significant environmental benefits. Figure 1 shows the reduction in the quantity of various organic solvents required for the synthesis of sildenafil citrate.1 There was complete elimination of chlorinated and highly volatile solvents such as diethyl ether, methylene chloride, methanol and acetone. This development allowed the original research route to be used for a manufacturing process. One of the immediate changes that was required was the removal of tin (II) chloride from the synthesis. Tin is a heavy metal and a major environmental polluter. The stoichiometric tin reaction was replaced by a catalytic hydrogenation reaction in which water is the only by-product. Catalytic hydrogenations are among the cleanest environmental chemical steps.

Next a whole new synthetic route was invented and this was designed around the philosophy of putting a very clean cyclisation reaction as the final step of the synthesis which ensured very high quality product. 

What is the impact? 

It is estimated that between 1997 and 2013 the new synthesis will eliminate 30,000 tonnes of chemical waste when compared with the optimised medicinal chemistry synthesis.

Manufacture of pregabalin (LyricaTM)


What did the organic chemists do?

An even more convincing example of green chemistry comes from the scale up of the synthesis of pregabalin (LyricaTM), a medicine used to treat neuropathic pain which was launched in the US in 2005 and achieve. Organic chemists developed an enzymatic reaction to introduce a chiral centre in the molecule and then skilfully designed each process step so that both the enzymatic reaction and the other three chemical reactions were all performed in water instead of environmentally harmful solvents. By using nature's own chemical catalyst, a lipase, and water as a solvent, the use of non-renewable organic materials was dramatically reduced. 

What is the impact?

It has been calculated that the enzymatic process used for manufacture of LyricaTM will eliminate more than 3 million tonnes of CO2 emissions compared with the first industrial process. The CO2  savings are the equivalent of taking more than 1,000,000 British cars off the road for a whole year which really shows the benefit of efficient chemistry.

Advances in Green chemistry will continue to offer opportunities to discover and apply new chemistry, to improve the economics of chemical manufacturing and reduce the chemical related environmental impact.


1 P J Dunn, S Galvin and K Hettenbach, Green Chem.2004, 6, 43

Also of interest

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Contact and Further Information

Dr Anne Horan
Programme Manager, Life Sciences
Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge, CB4 0WF
Tel: 01223 432699