Journal article
Homogeneous Nucleophilic Radiofluorination and Fluorination with Phosphazene Hydrofluorides
Biomedical Tracers, Radiation Research Division, Risø National Laboratory for Sustainable Energy, Technical University of Denmark1
Radiation Research Division, Risø National Laboratory for Sustainable Energy, Technical University of Denmark2
Risø National Laboratory for Sustainable Energy, Technical University of Denmark3
A series of phosphazenium hydrofluorides, P1tBu⋅[18/19F]HF, P1tOct⋅[18/19F]HF, P2Et⋅[18/19F]HF, and P4tBu⋅[18/19F]HF, was synthesized. The radioactive phosphazenium [18F]hydrofluorides were obtained by the one‐step formation and trapping of gaseous [18F]HF with the respective phosphazene bases. The [19F] isotopomers were prepared from the corresponding phosphazene bases and Et3N⋅3HF.
Under the design of experiment (DoE)‐optimized conditions, P2Et⋅HF and P4tBu⋅HF fluorinated alkyl chlorides, bromides, and pseudohalides in 76–98 % yield, but gave lower yields with iodides and electron‐deficient arenes. DoE models showed that fluorination can be performed in glass vessels, and that the reactivity of P2Et⋅HF and P4tBu⋅HF is dominated by solvent polarity but is insensitive to water to at least 2 equiv.
In contrast, P1tBu⋅HF and P1tOct⋅HF were unstable towards autofluorolysis. DFT calculations were performed to rationalize this finding in terms of diminished steric bulk, higher Parr’s electrophilicity, and chemical hardness of P1RH+. The corresponding radiofluorination reaction gave no valid DoE model but displayed similar substrate scope.
High specific activity and excellent radiochemical yields with various pseudohalides (81–91 %) suggest that the proposed radiofluorination methodology can complement the current [18F]KF/Kryptofix methods, particularly in the areas for which nonpolar reaction conditions are required.
Language: | English |
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Publisher: | WILEY‐VCH Verlag |
Year: | 2011 |
Pages: | 7796-7805 |
ISSN: | 15213765 and 09476539 |
Types: | Journal article |
DOI: | 10.1002/chem.201100458 |
ORCIDs: | Jensen, Andreas Tue Ingemann and Zhuravlev, Fedor |