Curtius Reactions

Curtius Reactions in Flow

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