We herein report a waste minimization protocol for the
β-azidation
of α,β-unsaturated carbonyl compounds using TMSN3. The selection of the appropriate catalyst (POLITAG-M-F), in combination with the reaction medium, resulted in enhanced
catalytic efficiency and a low environmental footprint. The thermal
and mechanical stability of the polymeric support allowed us to recover
the POLITAG-M-F catalyst for up to 10 consecutive runs.
The CH3CN:H2O azeotrope has a 2-fold positive
effect on the process, increasing the efficiency of the protocol and
minimizing waste generation. Indeed, the azeotropic mixture, used
as a reaction medium and for the workup procedure, was recovered by
distillation, leading to an easy and environmentally friendly procedure
for product isolation in high yield and with a low E-factor. A comprehensive
evaluation of the environmental profile was performed by the calculation
of different green metrics (AE, RME, MRP, 1/SF) and a comparison with
other literature available protocols. A flow protocol was defined
to scale-up the process, and up to 65 mmol of substrates were efficiently
converted with a productivity of 0.3 mmol/min.