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Journal of Flow Chemistry
Authors: Giancarlo Pascali, Mariarosaria De Simone, Lidia Matesic, Ivan Greguric and Piero A. Salvadori

Nucleophilic [18F]-fluorination reactions traditionally include a drying step of the labeling agent in order to achieve a successful substitution. This passage extends the time and complexity required for the whole radiotracer production, with increased hardware and detrimental effects on the radioactive recovery of such a short-lived (t ½=109 min) isotope. Because the performance of radiofluorination reactions conducted under microfluidic flow conditions have been demonstrated to be more effective in terms of reaction time and yields, we have tested the tolerance to water present in this specific reaction condition, in view of eliminating the drying step in the process. To this purpose, we tested different substrates selected from typical radiofluorination intermediates. Our results show that water could be tolerated in a microfluidic environment; in particular, we observed a slight decrease in the labeling of aromatic precursors and a significant increase for iodonium salts, whereas the radiochemical yields of the other compounds studied were virtually unchanged. These findings may open the way to the possibility of simpler and faster processes for the production of new 18F-fluorinated positron emission tomography tracers.

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Journal of Flow Chemistry
Authors: Gary Perkins, Omar Khatib, Matthew Peterson, Annukka Kallinen, Tien Pham, Alison Ung, Ivan Greguric and Giancarlo Pascali

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.

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