Development of Azulene-Based Chromophore for Color-Responsive Self-Assembly Enabled by Flow Chemistry

Azulene has long resisted functionalization owing to the fleeting nature of its lithiated intermediates. Here, we demonstrate that flow microreactors, featuring rapid mixing, short residence times, and precise temperature control, enable controlled generation of these highly reactive species, providing regioselective access to 6- or 1-substituted azulenes in yields of up to 89% under noncryogenic conditions. This methodology allows the synthesis of 6-diethylboryl-1-(pyridin-4-yl)azulene (3), which spontaneously self-assembles into a cyclic trimer (33) via intermolecular B–N coordination. The trimer displays a pronounced blue shift relative to the monomer, while addition of 4-dimethylaminopyridine (DMAP) induces visible red-shifted disassembly into a monomeric DMAP adduct. Notably, this DMAP-driven supramolecular disassembly was monitored in real time using a flow microreactor equipped with in-line UV–vis spectroscopy. These results demonstrate that flow microreactors not only address a long-standing challenge in azulene chemistry but also enable real-time visualization of supramolecular switching, providing a basis for color-responsive functional materials.