Despite the inherent competition between cyclization and linear polymerization, we report the exclusive synthesis of a macrocyclic trimer from 1,2,3,4-tetramethoxybenzene and paraformaldehyde. Dynamic Friedel-Crafts alkylation proceeds solely through linear oligomeric intermediates, which ultimately convert to the cyclic trimer without polymer formation. NMR monitoring tracks this stepwise conversion, and DFT studies identify the cyclic trimer as the thermodynamically favored product among accessible species. This system circumvents the cyclization-polymerization equilibrium, providing insight into the competition mechanism under macrocycle synthesis.
Zhang et al. (Tue,) studied this question.