Synthesis of [c2]Daisy Chains via Mechanochemistry

Mechanochemistry, which uses mechanical force to drive chemical reactions, has emerged as a sustainable alternative to solution-phase synthesis, especially in the context of solvent-free reactions that reduce hazardous waste. Its application to supramolecular chemistry is particularly promising, as it allows high local concentrations and effective molecular recognition in the solid state. One key target in this field is the synthesis of rotaxanes and daisy chains—mechanically interlocked molecules with potential for molecular machines and responsive materials.

The term “daisy chain” has been introduced by Fraser Stoddart and refers to a supramolecular ensemble resulting from the association of self-complementary monomers bearing both a threadable macrocycle (host) and a linear thread (guest). Threading of the macrocycle by the linear fragment of another monomer by intermolecular recognition leads to the formation of either acyclic (a) or cyclic (c) daisy chains.

Jean-François Nierengarten and colleagues, Université de Strasbourg and CNRS, France, have explored the use of mechanochemical conditions to synthesize stoppered [c2]daisy chain rotaxanes based on pillar[5]arene derivatives. These structures involve self-complementary monomers that can interlock through host–guest interactions, forming cyclic dimers. The team focused on the acylation of daisy chain monomers bearing either 11-hydroxy-undecyl or 11-amino-undecyl chains under ball-milling conditions, enabling the introduction of stoppers to lock the interlocked structure. Stoppers prevent the dissociation of the daisy chain assembly.

Their results show that mechanochemical conditions not only support the formation of daisy chain assemblies but also enable successful stopper installation, particularly in systems where solution-phase synthesis fails. While both alcohol- and amine-functionalized monomers yielded stoppered products under solvent-free conditions, only the amine monomer gave comparable results in solution. The success of the alcohol system under mechanochemical conditions highlights the importance of concentration effects in the solid state, allowing otherwise weakly interacting components to form and retain the desired supramolecular architecture.