KryptofixTM 2.2.2 been recognized for decades in the PTC community for its exceptional ability to complex potassium ions even more than crown ethers, but its high cost has historically limited its use to only the most demanding applications to produce very expensive products.
A patent application published this month highlights a compelling case where the performance of KryptofixTM 2.2.2 is justified. In the radiolabeling of a PET imaging agent with fluorine-18, a costly and short-lived isotope, KryptofixTM 2.2.2 plays a critical role in forming a reactive [K⁺·F⁻·cryptand] complex. This is achieved by eluting the F-18 isotope with potassium carbonate and KryptofixTM 2.2.2 in acetonitrile/water, followed by drying at 110 deg C for 10 minutes. The substrate is then introduced, and the nucleophilic fluorination proceeds using stoichiometric [K⁺·F⁻·cryptand] complex at 100 deg C for 10-15 minutes.
This application stands out because the synthetic route avoids the formation of hazardous nitrosamines, which is a major consideration in pharmaceutical synthesis.
The resulting F-18 labeled product exhibited a radiochemical purity of 99% even after 10 hours. This reflects both the chemical stability of the labeled product and the appropriateness of KryptofixTM 2.2.2 as the phase transfer agent (not a catalyst) in this sensitive medical application.
While the patent application did not quantify residual moisture after drying, for example via Karl Fischer titration, such data would be helpful in correlating drying efficiency with labeling yield.
This example reinforces the value of KryptofixTM 2.2.2 in specialized, high-value phase-transfer chemistry where its unique capabilities are crucial.
About Marc Halpern
Dr. Halpern is founder and president of PTC Organics, Inc., the only company dedicated exclusively to developing low-cost high-performance green chemistry processes for the manufacture of organic chemicals using Phase Transfer Catalysis. Dr. Halpern has innovated PTC breakthroughs for pharmaceuticals, agrochemicals, petrochemicals, monomers, polymers, flavors & fragrances, dyes & pigments and solvents. Dr. Halpern has provided PTC services on-site at more than 260 industrial process R&D departments in 37 countries and has helped chemical companies save > $200 million. Dr. Halpern co-authored five books including the best-selling “Phase-Transfer Catalysis: Fundamentals, Applications and Industrial Perspectives” and has presented the 2-day course “Practical Phase-Transfer Catalysis” at 50 locations in the US, Europe and Asia.
Dr. Halpern founded the journal “Industrial Phase-Transfer Catalysis” and “The PTC Tip of the Month” enjoyed by 2,100 qualified subscribers, now beyond 130 issues. In 2014, Dr. Halpern is celebrating his 30th year in the chemical industry, including serving as a process chemist at Dow Chemical, a supervisor of process chemistry at ICI, Director of R&D at Sybron Chemicals and founder and president of PTC Organics Inc. (15 years) and PTC Communications Inc. (20 years). Dr. Halpern also co-founded PTC Interface Inc. in 1989 and PTC Value Recovery Inc. in 1999. His academic breakthroughs include the PTC pKa Guidelines, the q-value for quat accessibility and he has achieved industrial PTC breakthroughs for a dozen strong base reactions as well as esterifications, transesterifications, epoxidations and chloromethylations plus contributed to more than 100 other industrial PTC process development projects.
Dr. Halpern has dedicated his adult life to his family and to phase-transfer catalysis (in that order!).
