Factorial design study to access the 'green' iodocyclization reaction of 2-allylphenols

Iodocyclization of 2-allylphenols is a suitable method to access furans and dihydrofurans with adequate yields. Several methodologies to iodocyclization are reported in the literature; however, since some data about the conditions are conflicting, a more systematic approach is needed to define the best conditions. In this work, we performed a full 22 factorial design to study the influence of solvent (water or EtOH:water (1:9) mixture) and the addition of NaHCO3 in iodine-promoted cyclization of 2-allylphenols. The results have shown water as the best solvent to be employed in the cyclization of liquid 2-allylphenols, and the presence of NaHCO3 leads to lower yields. Several examples of 2-iodomethyl-2,3-dihydrobenzofurans preparations are reported using the optimized conditions; however, high yields are only observed when liquid 2-allylphenols were used.