Karen D Rojas-Ramírez, Hugo Rojas, Mario A Macías, Diana Becerra, Juan-Carlos Castillo
A Cs2CO3-mediated Rap-Stoermer strategy was developed for the synthesis of functionalized benzo[b]furan derivatives. O-Alkylation of o-hydroxyaryl carbonyl compounds 1 with ethyl α-bromoacetate 2 in acetone at room temperature selectively afforded ethyl 2-(2-carbonylaryloxy)acetates 3 in 70-95% yields, providing experimental evidence for the intermediates involved in the Rap-Stoermer cyclization pathway. Subsequent microwave irradiation in dimethylsulfoxide at 150 °C enabled rapid intramolecular cyclization to furnish ethyl benzo[b]furan-2-carboxylates 4 in 72-94% yields, while alkaline hydrolysis afforded the corresponding benzo[b]furan-2-carboxylic acids 5 in 73-92% yields without chromatographic purification. Single-crystal X-ray diffraction of esters 4c and 4e revealed that subtle rotation of the ethyl ester group gives rise to distinct supramolecular architectures by modifying the preferred hydrogen-bond acceptor atom. Hirshfeld surface, molecular electrostatic potential, and energy framework analyses further demonstrated that weak C-H⋯O interactions govern the crystal packing, whereas dispersion interactions provide the dominant contribution to lattice stabilization. Photophysical studies revealed that fluorescence is restricted to the 6-diethylamino-substituted derivatives. Ester 4d exhibited higher molar absorptivities (ε = 20 646-44160 M-1 cm-1), a more pronounced solvatofluorochromic response (λ em = 368-458 nm), and the highest fluorescence quantum yield (ϕ F = 0.880 in n-hexane), than the corresponding carboxylic acid 5d. Diffuse reflectance spectroscopy and DFT calculations consistently indicated that ester hydrolysis induces only subtle changes in the electronic structure, whereas the 6-diethylamino substituent remains the principal structural feature governing the photophysical behavior of this benzo[b]furan series.