A safe and efficient method for the preparation of organic azides under continuous flow

The azide functional group offers the researcher a facile route to the installation of a range of synthetically interesting motifs which include amines, aziridines, 1,4-substituted-123-triazoles and isocyanates. In particular, the [3+2] azide-alkyne cycloaddition (Click chemistry), can be attributed with increasing the popularity of azides with medicinal chemists due to the ease with which biologically active molecules can be constructed with a high degree of structural diversity.
The synthesis of organic azide precursors can however be problematic, owning to the fact the products are thermally unstable materials which readily eliminate N2making them prone to detonation. In addition, the build-up of hydrazoic acid within the headspace of reactors and within the traps of rotary evaporators makes the preparation of this class of compound extremely, particularly when performed at scale.
As a means of developing a safe and efficient technique for the preparation of organic azides, on both a R&D and production scale, the synthesis of an alkyl azide from alkyl mesylates and halides (Cl and Br) was investigated under continuous flow conditions using the inexpensive and readily available reagent NaN5.