Tuning Antiaromaticity through meso-Substituent Orientation in Core-Modified Isophlorins

Antiaromaticity is a fundamental concept in organic chemistry that significantly influences the properties of cyclic π-conjugated systems. This study systematically investigates the effect of meso-substituents on the antiaromaticity of dithiadioxaisophlorins (S2O2Iphs), stable isophlorin derivatives with strong antiaromatic character. We synthesized two new S2O2Iphs derivatives with 3,5-bis(trifluoromethyl)phenyl and 5-cyanothien-2-yl substituents alongside the previously reported pentafluorophenyl-substituted analogue. Notably, a derivative with sterically demanding 2,6-dichlorophenyl substituents could not be isolated despite detection by mass spectrometry, highlighting the delicate balance required between electronic stabilization and steric effects. Through comprehensive analysis using ¹H NMR spectroscopy, UV/vis absorption spectroscopy, and multiple computational approaches (NICS, GIMIC, HOMA/HOMAc, and AV1245/AVmin), we demonstrate that the steric bulkiness of meso-substituents predominantly determines their tilt angle relative to the isophlorin macrocycle, critically influencing antiaromaticity. Bulkier substituents maintain larger tilt angles, preserving stronger antiaromaticity, while less bulky groups allow greater π-conjugation with the macrocycle, thereby reducing antiaromaticity. These findings provide valuable guidance for designing functional antiaromatic materials with tunable electronic properties.