A record number of reagents has been made to combine in a single vessel in a reaction scheme devised by a group of German chemists. Because it reduces the need to separate and purify intermediate products, such a scheme could simplify the manufacture of drugs and agrochemicals.
To make complicated molecules, chemists usually have to use a sequence of several separate reactions. In each step, a pair of reagents yields a product, which must be isolated and purified to remove by-products along with any starting material that has remained. The purified intermediate product then becomes one of the reagents in the next step.
However, in what are known as ‘one-pot’ reactions, chemists simply throw three or more ingredients into a reaction vessel. Under appropriate conditions of pressure, temperature and pH, the components then form the desired product.
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Alexander Domling and Ivar Ugi of the University of Munich have raised this technique to new heights. Not for them a one-pot reaction with a mere three or four components: they have devised a reaction involving seven reagents. They say such a system should make it is possible to build a molecule with many chemical groups without isolating the intermediate products.
In the first step of Domling and Ugi’s reaction (see figure), sodium hydrogen sulphide (NaSH) and α-bromoisobutyraldehyde (BrCMe2CHO) reacted to produce HSCMe2CHO. This then reacted with ammonia (NH3) and isobutyraldehyde (Me2CHCHO) to produce a ‘condensation compound’.
Meanwhile, carbon dioxide (CO2) was reacting with methanol (MeOH) to form MeOCO2H, which transferred a proton to the condensation compound. The protonated compound then reacted with MeOCO2– and tert-butylisocyanide (ButNC). In the final step, the product of this reaction rearranged itself and formed the product with a yield of 45 per cent (Angewandte Chemie, International Edition, vol 4, p 563).FIG-mg18803201.jpg
