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A cheaper and cleaner way of producing drugs to combat conditions such as obesity and Alzheimer’s is in sight.

Prof. Joost Reek and PhD candidate Paweł Dydio of the University of Amsterdam (UvA) have found a way of very selectively converting a vinyl benzene to a β-aldehyde, a compound commonly used in the pharmaceutical and fine chemical industries. The results of the study have been published online as ‘Very Important Paper’ in the scitific journal Angewandte Chemie International Edition. The study will appear in print later this year.

Special form of hydroformylation

The new reaction is a special form of hydroformylation, a process by which carbon monoxide and hydrogen can be added to a carbon-carbon double bond. A rhodium ion is used in this reaction as a catalyst: all molecules bind to the rhodium ion, react there and are released once the reaction has taken place. There are two possible products: depending on which side of the double bond the carbon monoxide is positioned, the α-or the β-aldehyde is formed.

In some cases, the reaction has a clear preference for one of these two products. This is, for example, the case with vinyl benzene: hydroformylation leads almost exclusively to the creation of the α-aldehyde. This is unfortunate, because it is often the β-aldehyde that is needed for processes such as producing drugs.

Solution to hydroformylation problem

Reek and Dydio have found a solution to this problem: they combine a special 'auxiliary molecule’ to the catalyst that holds onto the vinyl benzene, as it were, during hydroformylation. As a result, only one side of the double bond is directed to the rhodium ion allowing the carbon monoxide molecule to bind to that side. That is exactly the opposite side to where the aldehyde would normally be created.

The newly developed catalytic process is very interesting for industrial applications: it operates between 25-120 degrees and is above all very active, so a less active catalyst is needed. Because no α-aldehyde is created, the reaction  also creates less waste than previously and it is easy to isolate the product. This discovery is also useful for various other molecules, as a result of which different drugs could be produced in a cleaner and cheaper way in the future.

Publication Details

Paweł Dydio and Joost N. H. Reek. Supramolecular Control of Selectivity in Hydroformylation of Vinyl Arenes: Easy Access to Valuable b Aldehyde Intermediates. Angewandte Chemie International Edition (2013, 52).