Conformational analysis for infrared spectroscopy and theoretical calculations of some 2-bromo-2-propyl 2-aryl-acetates, ibuprofen and naproxen analogs

Abstract

Conformational analysis of new para–substituted 2-bromo-2-propyl 2-aryl-acetates (Y = H, OMe, Cl, and NO2) (R1), ibuprofen (R2), and naproxen (R3) analogs using infrared (IR) spectroscopy and theoretical calculations was performed to determine the preferential conformers of these compounds in solvents with increasing polarity (CCl4, CH3Cl, and CH3CN). The aryl-bromo-esters were synthesized via the coupling reactions of 2-bromo-2-methylpropan-1-ol and the corresponding carboxylic acids, with good yields (∼36‒70%). The IR spectra showed that these compounds presented only one conformation, and the experimental data were supported by the theoretical results obtained by density functional theory (DFT) calculations using the 6311+G (2df, 2p) basis set. The calculations revealed that all the studied compounds presented two stable geometric conformations, which agrees with the data obtained experimentally in CCl4. Theses conformers are stabilized by intramolecular hydrogen bonds. However, the orbital interaction calculations using the natural bond orbital (NBO) method showed that the ηO→σ*C-C,ηO→σ*C-O, ηO→σ*C-O and ηO→π*C-O hyper-conjugations are the main interactions that stabilize the conformations. The compounds preferentially adopt the anti-conformation because the steric effect between the gauche bromo and oxygen atoms overrides the hyper-conjugative interactions, in addition to the stabilizing σC-H→ σ*C-Br interactions in the conformers.