The Curtius reaction is an important process that involves the rearrangement of an acyl azide to an isocyanate that can then be further trapped by a variety of nucleophiles. We have therefore developed useful methods for conducting these reactions in flow to enable convenient access to a number of molecular scaffolds without the need to isolate potentially hazardous intermediates.

We have prepared an azide-containing monolithic reactor and used it as a flow chemistry device for conducting Curtius rearrangementreactions via acid chloride inputs [1]. We extended the work to the trapping of the intermediate isocyanates with various other nucleophiles [2].

1. Azide monoliths as convenient flow reactors for efficient Curtius rearrangement reactions
M. Baumann, I.R. Baxendale, S.V. Ley, N. Nikbin, C.D. Smith
Org. Biomol. Chem. 2008, 6, 1587-1593

2. A modular flow reactor for performing Curtius rearrangements as a continuous flow process
M. Baumann, I.R. Baxendale, S.V. Ley, N. Nikbin, C.D. Smith, J.P. Tierney
Org. Biomol. Chem. 2008, 6, 1577-1586