Researchers find green route to pharma compounds

Many industries throughout the world have begun using the non-toxic, environmentally friendly scCO2 as a solvent, replacing harsher volatile organic solvents, such as chlorinated hydrocarbons and chlorofluorocarbons.

Supercritical fluids are gases compressed to a point where they display some of the properties normally associated with liquids. The supercritical fluids have both gas and solvent-like properties that can be tuned through adjustments to pressure and temperature. Their unique properties can then be designed into innovative processes for organic synthesis using modified catalysts.

Carbon dioxide is the most common gas used for supercritical applications. The use of propane, propene and butane has also been studied.

Until now it was not considered possible to make certain classes of molecules in CO2 because it was thought that they would react with it, but the researchers - from the University of Cambridge and the Massachusetts Institute of Technology - have cracked the problem.

Since the 1990s, scCO2 has emerged as an environmentally benign substitute for more conventional solvents used for organic synthesis, such as those that enter the atmosphere from sprays and similar products. Dry cleaners, plastics manufacturers, food producers and various industries involved in the extraction of flavours and fragrances are already using the 'benign' solvent, resulting in more environmentally friendly industrial practices. Using scCO2 as the extractive agent to remove caffeine selectively and leave the flavour of fresh coffee, for example, produces decaffeinated coffee beans.

Although it is a greenhouse gas, scCO2 can be obtained in large quantities as a by-product of fermentation and combustion. The ready availability, coupled with its ease of removal and recycling, makes scCO2 an interesting proposition for synthetic and industrial applications.

Cambridge University's Professor Andrew Holmes, Director of the Melville Laboratory, together with MIT's Professors Rick Danheiser and Jefferson Tester, are among the first to work out how to use scCO2 for reactions without allowing it to react with the reagents.

Prof Holmes said the immediate aim is to help the pharmaceutical industry streamline the drugs manufacturing process with the techniques he and his team have developed.

"We're making molecules of interest to pharmaceutical companies - aromatic amines - which are a key fragment in many neurological drugs. Before it was considered impossible, but we've got preparations of aromatic amine reactions to work in supercritical carbon dioxide."​

Pharmaceutical companies have begun using scCO2 for processing drugs into powder consistently, but the researchers' findings may soon mean that the entire manufacturing process can be integrated, using scCO2 for both synthesis and processing them into powders.

Organic solvents can always react in undesired ways, so an advantage to using this non-toxic supercritical fluid is that it reduces the chances for alternative and less-desired reactions. Another major advantage to using supercritical fluids for organic synthesis is the ability of these physical properties to be tuned simply by a change in pressure and/or temperature.

A patent has been filed on behalf of the work done at Cambridge and MIT, which was funded by the Cambridge-MIT Institute (CMI). The researchers have published their findings in Chemical Communications.

AstraZeneca is one of a number of companies that have supported Professor Holmes' work in scCO2.