Fast carbonylation reaction from CO2 using plasma gas/liquid microreactors for radiolabeling applications

Abstract

Carbon-11 is undoubtedly an attractive PET radiolabeling synthon because carbon is present in all biological molecules. It is mainly found under ¹¹CO₂, but the latter being not very reactive, it is necessary to convert it into a secondary precursor. ¹¹CO is an attractive precursor for labeling the carbonyl position through transition-metal mediated carbonylation because of its access to a wide range of functional groups (e.g., amides, ureas, ketones, esters, and carboxylic acids) present in most PET tracer molecules. However, the main limitations of ¹¹CO labeling are the very short half-life of the radioisotope carbon-11 and its low concentration, and the low reactivity and poor solubility of ¹¹CO in commonly used organic solvents. In this work, we show that a possible solution to these limitations is to use microfluidic reactor technology to perform carbonylation reactions, whilst a novel approach to generate CO from CO₂ by plasma is described. The methodology consists of the decomposition of CO₂ into CO by non-thermal DBD plasma at room temperature and atmospheric pressure, followed by the total incorporation of CO thus formed in the gas phase by carbonylation reaction, in less than 2 min of residence time. This “proof of principle” developed in carbon-12 would be further applied in carbon-11. Although considerable advances in ¹¹CO chemistry have been reported in recent years, its application in PET tracer development is still an area of work in progress, because of the lack of commercially available synthesis instruments designed for ¹¹C-carbonylations. To the best of our knowledge, such an innovative and efficient process, combining microfluidics and plasma, allowing the very fast organic synthesis of carbonyl molecules from CO₂ with high yield, in mild conditions, has never been studied.