[¹¹C]Carbonyl Difluoride—a New and Highly Efficient [¹¹C]Carbonyl Group Transfer Agent

Abstract

Herein, the synthesis and use of [ 11 C]carbonyl difluoride for labeling heterocycles with [ 11 C]carbonyl groups in high molar activity is described. A very mild single-pass gasphase conversion of [ 11 C]carbon monoxide into [ 11 C]carbonyl difluoride over silver(II) fluoride provides easy access to this new synthon in robust quantitative yield for labeling a broad range of cyclic substrates, for example, imidazolidin-2-ones, thiazolidin-2-ones, and oxazolidin-2-ones. Labeling reactions may utilize close-to-stoichiometric precursor quantities and short reaction times at room temperature in a wide range of solvents while also showing high water tolerability. The overall radiosynthesis protocol is both simple and reproducible. The required apparatus can be constructed from widely available parts and is therefore well suited to be automated for PET radiotracer production. We foresee that this straightforward method will gain wide acceptance for PET radiotracer syntheses across the radiochemistry community.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Phosgene‐Free Carbonyl Insertion: Hot Advances in 11C‐Chemistry

“…Jakobsson et al . describe a new carbonyl group transfer agent, [ 11 C]carbonyl difluoride [9] . Using a standard reaction, [ 11 C]CO 2 is reduced to [ 11 C]CO by passing over solid‐phase molybdenum at 875 °C.…”

Highlight selection of radiochemistry and radiopharmacy developments by editorial board

“…In order to expand carbon-11 radiochemical space it is important to develop novel 11 C-synthons that can be produced with simple, reliable, high-yield and robust procedures. Jacobsson and colleagues describe the efficient radiosynthesis of [ 11 C]carbonyl difluoride starting from [ 11 C]CO 2 using a two-step gas-phase procedure (Jakobsson et al, 2020 ). In the first instance, [ 11 C]CO 2 harvested from the cyclotron target is converted by a well–known procedure to [ 11 C]CO by passage over a heated (875 °C) column filled with molybdenum (See Fig.…”

Broad Scope and High‐Yield Access to Unsymmetrical Acyclic [11C]Ureas for Biomedical Imaging from [11C]Carbonyl Difluoride

“…We recently reported a straightforward and efficient synthesis of a new labelling agent, [ 11 C]carbonyl difluoride, from cyclotron-produced [ 11 C]carbon dioxide by on-line conversion into [ 11 C]carbon monoxide and then passage over silver(II) fluoride. [16] In this method, [ 11 C]carbonyl difluoride is produced reliably in useful overall radiochemical yield and with high nocarrier-added (NCA) molar activity (> 200 GBq/μmol). This new labelling agent has been shown to be very effective for 11 Ccarbonylation reactions giving intracyclic ureas, as especially exemplified by the synthesis of a β-adrenergic receptor imaging agent, [ 11 C](S)-CGP12177.…”

“…This new labelling agent has been shown to be very effective for 11 Ccarbonylation reactions giving intracyclic ureas, as especially exemplified by the synthesis of a β-adrenergic receptor imaging agent, [ 11 C](S)-CGP12177. [16] Here we aimed to further explore NCA [ 11 C]carbonyl difluoride as a labelling agent for acyclic ureas, especially unsymmetrical ureas.…”