Stereochemical and electronic interaction studies of 4′-substituted 2-(phenylselanyl)-2-(ethylsulfinyl)-acetophenones

Abstract

Infrared carbonyl band analysis, supported by B3LYP/6-31+G(d,p) and single-point PCM calculations, natural bond orbital (NBO) analysis and X-ray diffraction were carried out for the diastereoisomers of a selection of 4'-substituted 2-(phenylselanyl)-2-(ethylsulfinyl)-acetophenones bearing the substituents NO2 1a, Br 2a, H 3a, Me 4a and OMe 5a for the CRSR/CSSS enantiomeric pair and Br 2b and Me 4b for the CRSS/CSSR pair. For the gas phase, the theoretical data indicated the existence of three stable conformations for the CRSR series and only two for the CRSS series. For the whole CRSR series 1a-5a, the most stable c1 and the intermediate c2 conformers have similar νCO frequencies, lowered by about 20 cm -1 with respect to the less stable c3. Likewise, the less stable c2 conformers for the CRSS series 2b and 4b exhibit the higher νCO frequencies. The single-point PCM calculations show that the relative abundance of both the less stable c3 CRSR and c2 CRSS conformers, in the gas phase, progressively increases as the dielectric constant of the media increases. The balance between the electrostatic and orbital interactions controls the calculated stability for compounds 1a-5a (CRSR/ CSSS), along with the νCO frequency order of the three conformers.Conversely, the larger stabilisation of the c1 conformer with respect to the c2 one in the

2-[(4-Chlorophenyl)sulfanyl]-2-methoxy-1-phenylethan-1-one: crystal structure and Hirshfeld surface analysis

“…N,Ndiethyl-2-[(4 0 -substituted)phenylthio]acetamides (Vinhato et al, 2013), 1-methyl-3-phenylsulfonyl-2-piperidones (Zukerman-Schpector et al, 2008), 3,3-bis[(4 0 -substituted) phenylsulfanyl]-1-methyl-2-piperidones (Olivato et al, 2013), 2alkylthio-2-alkylsulfinyl-acetophenones and 2-alkylthio-2phenylsulfonyl-acetophenones, 2-alkylsulfinyl-2-alkylsulfonylacetophenones (Distefano et al, 1996), 2-methoxy-2-[(4 0substituted) phenylsulfanyl]-acetophenones (Zukerman-Schpector et al, 2015;Caracelli et al, 2015) and 2-methoxy-2-(phenylselanyl)-(4 0 -substituted)acetophenones (Traesel et al, 2018), utilizing infrared spectroscopy, computational chemistry and X-ray diffraction methods, the title compound (I) was synthesized and characterized. The primary motivation behind this work is the search for selenium/sulfur-containing compounds with anti-inflammatory activity that could be selective COX-2 inhibitors (Cerqueira et al, 2015(Cerqueira et al, , 2017. Molecular docking studies have also been conducted in order to understand the mechanism of inhibition (Baptistini, 2015).…”

Spectroscopic and theoretical studies of some 2‑(methoxy)‑2‑[(4‑substituted)‑phenylsulfanyl]‑(4′‑substituted) acetophenones

“…In particular, these compounds became spectroscopically interesting as the α substituents are expected to compete for the syn-clinal or anti-clinal (gauche) and synperiplanar (cis) geometries with respect to the carbonyl group, due to differences in the orbital and electrostatic interactions that stabilizes the conformers. Finally, this work is an extension of recent conformational studies on the 2-(phenylselanyl)-2-(methoxy)acetophenones, 2-(phenylseleno)-2-(ethylsulfanyl)-acetophenones and their mono-and di-oxygenated derivatives [5][6][7]22].…”

“…Additionally, the quasi-antiperiplanar geometry of the C (3) -S (10) and O (5) -C (6) bonds in the c 3 conformers allows the simultaneous weak interactions σ C3-S10 →σ* O5-C6…”

“…In this context, α-keto thioacetals and their analogues are often used in various synthetic applications, such as in the preparation of complex intermediates [3] and bioactive natural products [4]. With the objective of exploring these themes we have been performing studies in searching for selective cyclooxygenase-2 (COX-2) enzyme inhibitors containing selenium-sulfur atoms [5][6][7], and in molecular docking studies [8] to understand the mechanism of its inhibition. The X-ray crystal and molecular structure of compound (6) was determined, described, and compared with those already published, such as 2-(4chlorophenylsulfanyl)-2-methoxy-1-phenylethanone [9], 2-methoxy-2-(4methylphenylsulfanyl)-1-phenylethanone [10], and 2-methoxy-2-(4methoxyphenylsulfanyl)-1-phenylethanone [11].…”

2-[(4-Bromophenyl)sulfanyl]-2-methoxy-1-phenylethan-1-one: crystal structure, Hirshfeld surface analysis and computational chemistry

“…This was evaluated as a part of on-going studies into the conformational and electronic characteristics of various -thiocarbonyl, -bis-thiocarbonyl and -thio--oxacarbonyl compounds, and their selenium counterparts, employing infrared spectroscopy, computational chemistry and X-ray crystallographic methods (Vinhato et al, 2013;Zukerman-Schpector et al, 2015;Caracelli et al, 2015;Traesel et al, 2018). In particular, the evaluation of the anti-inflammatory activity of what could be selective COX-2 inhibitors (Cerqueira et al, 2017) motivates these investigations, which are supported by molecular docking studies designed to ascertain the mechanism(s) of inhibition (Baptistini, 2015). Subsequently, crystals of the title bromo analogue (I) were obtained: the crystal structure is reported herein along with an analysis of the calculated Hirshfeld surfaces, non-covalent interaction plots (for selected interactions) as well as a computational chemistry study.…”