Key Non-Metal Ingredients for Cu-catalyzed "Click" Reactions in Glycerol: Nanoparticles as Efficient Forwarders

The effect of long‐alkyl‐chain amines in CuI‐assisted azide–alkyne cycloadditions of terminal alkynes with organic azides in glycerol and other environmentally benign solvents (water, ethanol) has been examined. The presence of these additives favors the in situ formation of CuI‐based nanoparticles and results in an increase of the catalytic reactivity. In glycerol, liquid‐phase transmission electron microscopy (TEM) analyses, enabled by the negligible vapor pressure of this solvent, proved that CuI nanoparticles are responsible for the observed catalytic activity. The wide variety of alkynes and azides of which this effect has been investigated (14 combinations) confirms the role played by these additives in Cu‐catalyzed Huisgen cycloadditions. Super amines: The noteworthy reactivity observed in copper‐catalyzed azide–alkyne cycloaddition reactions, with CuI in the presence of long‐chain amines as starting catalytic materials, could be correlated to the in situ formation of CuI nanoparticles. These amines, acting as “super” ingredients, become crucial for accelerating the process, in particular in glycerol medium.