Efficient Synthesis of Multifunctional Chelating Agents Based on Tetraazacycloalkanes

An efficient route has been developed for the synthesis of multifunctional tetraazacycloalkanes (in particular 1,4,7,10‐tetraazacyclotridecane) incorporating an aminomethyl pendant arm on the carbon skeleton. Starting from the appropriate C‐functionalized bisaminal‐protected intermediate, the target macrocycles were easily obtained by means of a step‐by‐step introduction of the desired functional groups onto the free primary amine group, followed by deprotection of the bisaminal intermediates. This straightforward and versatile synthetic approach paves the way for the design of a new family of multifunctional chelators. A straightforward and versatile strategy for the design and synthesis of multifunctional chelating agents based on 1,4,7,10‐tetraazacyclotridecane ([13]aneN4) is reported. The key step in this synthetic route is the use of a C‐aminomethyl‐functionalized bisaminal macrocycle as the starting material.