Synthesis, structural properties, electrophilic substitution reactions and DFT computational studies of calix[3]benzofurans

Calix[3] benzofuranshave been synthesized by a modified TosMICcoupling reaction, followed by acid treatment and an intramolecular cyclization reaction with TMSI ( trimethylsilyl iodide); X-ray analysis established the structures of two samples, both showing a cone conformation. 1H NMR spectroscopic analyses of the calix[3] benzofuransreveal that they can adopt drastically different conformationsin solution and undergo very fast conformationalchanges relative to the NMR time scale. Calix[3] benzofuran4a exists as two conformers, namely the cone and saddle forms, in a ratio of 83 : 17 at −50 °C. A series of calix[3] benzofuranderivatives was synthesized by electrophilic aromatic substitutions, such as bromination, formylation and acylation, to investigate the influence of the substituents on the conformationsof the calix[3] benzofurans. 1H NMR spectral analyses of the acyl derivatives at room temperature indicated that these macrocycles exist as a mixture of two isomers that are slowly interconverted on the 1H NMR timescale. The conformationalisomers of the calix[3] benzofuransand their derivatives obtained from DFT methods (based on the crystal structure analysis results) were used to estimate the total energies of the different conformations.