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

Author(s)

Abbud Hanna Roque, Ana Carolina ^[1] ; Santos, Daniel de Carvalho ^[1] ; Reginato, Marcelo Mota ^[1] ; Reis, Adriana Karla Cardoso Amorim ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Chem, Rua Prof Arthur Riedel 275, BR-09972270 Diadema - Brazil

• Document type: Journal article
• Source: Journal of Molecular Structure; v. 1233, JUN 5 2021.
• Web of Science Citations: 0

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-o1 and the corresponding carboxylic acids, with good yields (similar to 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 eta(O) -> sigma{*}c-c, eta(O) -> sigma{*}(C-O), eta(O) -> sigma{*}(C-O) and eta(O) -> pi{*}(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 sigma(C-H) -> sigma{*}(C-Br) interactions in the conformers. (C) 2021 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 13/16644-4 - S-nitrosothiols from Aryl-amide and Aryl-pyrimidin-2-ones (thiones) derivatives - potential double inhibitors of HIV-1-PR and renin: synthesis, structural analysis and biological tests
• Grantee: Adriana Karla Cardoso Amorim Reis
• Support Opportunities: Regular Research Grants