Synthesis, spectroscopic characterization and structural study of 2-isopropenyl-3-methylphenol, carquejiphenol, a carquejol derivative with potential medicinal use

Abstract

In this work, 2-isopropenyl-3-methylphenol, hereafter referred to as carquejiphenol (CARP), a minor component of ?carqueja? essential oil, was synthesized starting from carquejol and characterized by using Fourier Transform infrared (FT-IR) and Raman (FT-Raman) spectroscopies, Ultraviolet?Visible (UV?Visible) spectroscopy, Electron Impact Mass spectrometry (EI-MS), Hydrogen and Carbon Nuclear Magnetic Resonance ( 1 H- and 13 C-NMR) and 2D 1 H? 1 H gCOSY, 1 H? 13 C gHSQC, 1 H? 13 C gHMBC experiments. A very good correlation between the predicted FTIR, FTRaman, UV?visible and 1 H? 13 C-NMR spectra for monomer and dimer of CARP by using theoretical B3LYP/6-31G* and 6-311++G** calculations with the corresponding experimental ones was observed. The solvation energies for CARP were predicted by using both levels of calculations and considering the solvent effects with the polarised continuum and solvation models. The increase in volume in solution supports the H bonds formation due to the presence in its structure of an OH group, as revealed by atoms in molecules (AIM) analysis. A high stability for CARP was found by using natural bond orbital (NBO) and AIM studies, while the investigation of the frontier orbitals reveals that CARP is more reactive than carquejol and N-(3,4-dimethoxybenzyl)-hexadecanamide but less reactive than the sesquiterpene lactone cnicin. The proximity of both the electrophilicy and nucleophilicity index of CARP with those obtained respectively for carquejol and for N-(3,4-dimethoxybenzyl)-hexadecanamide, suggests that CARP could probably present pharmacological properties. The scaled quantum mechanical force field (SQMFF) methodology was used to compute the harmonic force fields and to perform the complete vibrational analysis. In this way, 63 normal modes of vibration were assigned and compared with other terpene substances.