Synthesis of organic molecules via spray-drying

Abstract

Confining chemical reactions within microdroplets has attracted significant attention from chemists due to the accelerated reaction rates resulting from the drastically smaller reaction volumes than in standard solutions. Herein we report that, beyond its widespread use for producing dry-powder formulations for industries (e.g. pharmaceuticals and food) via the atomization of microdroplets followed by drying in a hot gas stream, spray-drying can also be employed in organic synthesis. Specifically, we used spray-drying to run three model reactions: a Schiff-base condensation, a Claisen-Schmidt reaction, and acylation of amines, for synthesizing small organic molecules. Our results showcase that, compared to traditional methods, spray-drying can reduce reaction times without compromising (high) yields, paving the way for its use as a scalable method for industrial-scale organic synthesis.

Fig. 1. (a) Schematic (left) and photo (right) of the lab-scale spray-dryer used for the organic reactions. (b) The reactions run with spray-drying.

Fig. 2. (a) Photograph of the spray-dryer after the gram-scale synthesis of paracetamol. (Insets) Photos of the collector after the spray-drying synthesis (top) and of the synthesized paracetamol (bottom). (b) ¹H NMR spectrum of the synthesized paracetamol, corroborating its structure. (c) HPLC chromatogram of the synthesized paracetamol, confirming its purity.