Microfluidic Implementation of Ru-Catalyzed Methylation of Amines Using CO2 as Carbon Source

Carbon dioxide chemistry is an area of continuing growth in recent times, due to socioeconomic and environmental reasons. Several methods have now been reported for obtaining N-methylation on primary and secondary amines directly from CO2. We have translated in two microfluidic setups (Slug Flow [SF] and Tube-in-Tube [TiT]) a ruthenium (Ru)-catalyzed process previously reported using a pressure vessel. Here, we demonstrate how the SF approach is more efficient but requires more input to reach a steady state, while the TiT system is less efficient but more tuneable. We have tested these processes on three model amines and two radiopharmaceutical precursors that are routinely used in 11C chemistry. The microfluidic processes tested are also potentially more efficient than the pressure vessel counterpart, in terms of amount of Ru catalyst needed (1% vs. 10%) and projected reaction completion time.