Figure 1. (a) Schematic set-up of the packed-bed resin-N3 flow device. (b) Azidation of benzyl chloride with resin-N3at different temperatures and different runs, with 0.1 ml/min flow rate. The plot reports the conversion obtained when the resin-N3 was reused three times, the total volume of benzyl chloride passed through the resin bed at the optimized conditions was 18 mL (6 mL per each use). This resulted in a total production of 2,6-difluorobenzyl azide of 3.0 g at 80°C (average conversion 99.5 ± 0.4%) and 2.5 g at 65°C (average conversion 82.6 ± 3.1%).
For the second reaction, Cu-bis(oxazoline) loaded cross-linked polymersomes were employed as a nanosized reactor and separator. These functionalized polymersomes were successfully applied previously for a Cu (II) catalyzed cyclopropanation reaction at r.t. in a batch reactor,17 but were never exploited before in a CuAAC reaction toward the synthesis of pharmaceuticals. The objective of introducing polymersomes in this microflow process was to integrate the two-step synthetic procedure into one step, and to protect the Cu (I) catalyst, positioned in the bilayer membrane from undesired interactions with the azide ion.