Spray-drying investigated as a speedy method for synthesising small organic molecules

Scientists in Spain have shown that spray-drying equipment can be used to perform three common organic reactions. The researchers behind the work suggest that spray-drying could prove to be a faster and more sustainable alternative to traditional techniques for synthesising numerous small organic molecules at scale.

Spray-drying is widely used in the pharmaceutical and food industries, usually to make dry powders from liquids, using hot gas. Daniel Maspoch, of the Catalan Institute of Nanoscience and Nanotechnology, explains that using aerosols in synthetic organic chemistry isn’t new, but that he and his colleagues were inspired to explore the limits of such techniques by recent findings that microdroplets can speed up chemical reactions. Here, surface area is thought to play an influential role, alongside the physical effects of evaporation.

The approach explored by Maspoch and colleagues sees chemical reactions take place in microdroplets before the liquid is evaporated in a stream of hot air, leaving the final product behind as a dry powder. As well as being faster than traditional batch-based methods, another benefit of the approach is that the resulting molecules are synthesised with a high purity, eliminating the need for a separate purification step, which can be time and solvent intensive.

Moreover, by using techniques that are already used in industry, there’s a clear path for scaling the concept up. ‘Scaling it up is a big deal because it means this method could be used to manufacture medicines and other chemicals faster and more efficiently,’ explains Maspoch.

To test their concept, the team performed three types of reaction – Schiff-base condensations, Claisen–Schmidt reactions and amine acylations – and made eight different compounds. In particular, the team showed that they could make paracetamol (also known as acetaminophen) in a single, continuous step and when scaling it up from the milligram to gram-scale they maintained a purity of 98% and a yield of 85%.

Ryan Bain, a chemist with the Bureau of Alcohol, Tobacco, Firearms and Explosives in the US, describes the work as ‘a turning point’ and says ‘it’s no longer going to be just the pure synthetic chemists and mass spectrometrists that are going to have access to this technology.’

Maspoch says the method’s ‘impact could be huge’ for the pharmaceutical and chemical industries. His team now plan to test and optimise this process for more reactions, and to make the process even more efficient.