6-Hy­droxy-2,5,7,8-tetra­methyl-3,4-dihydro-2H-1-benzopyran-2-carbonitrile, from synchrotron data

The crystal structure of the title compound, C14H17NO2, solved and refined against synchrotron diffraction data, contains one formula unit in an asymmetric unit. In the crystal, mol­ecules form right-handed helices located at the 21 screw axis parallel to the a-axis direction, generated by O—H⋯N hydrogen bonding between the hy­droxy group and carbonitrile group of an adjacent mol­ecule

rac-6-Hy­droxy-2,5,7,8-tetra­methyl­chroman-2-carboxamide from synchrotron data

The crystal structure of the title water-soluble analogue of vitamin E, trolox amide, C14H19NO3, solved and refined against synchrotron diffraction data, contains two mol­ecules in the asymmetric unit. In both molecules, the heterocyclic ring is in a half-chair conformation. The crystal packing features a herring-bone pattern generated by N—H⋯O hydrogen bonds between the hy­droxy and amide groups. O—H⋯O hydrogen bonds also occur

Multi-conformer molecules in solutions: an NMR-based DFT/MP2 conformational study of two glucopyranosides of a vitamin E model compound

Overall conformations of both anomeric per-O-acetylated glucosyl derivatives of 2,2,5,7,8-pentamethylchroman- 6-ol were studied in the context of their high flexibility, on the basis of NMR spectra in CDCl3 solution and related DFT calculation results. A few computational protocols were used, including diverse density functional/basis set combinations with a special emphasis on accounting (at various steps of the study) for the impact of intramolecular London-dispersion (LD) effects on geometries and relative Gibbs free energies (ΔGs) of different conformers coexisting in solution. The solvent effect was simulated by an IEF-PCM approach with the UFF radii; its other variants, including the use of the recently introduced IDSCRF radii, were employed for a few compact B3LYP-GD3BJ optimized structures showing one small imaginary vibrational frequency. The advantage of using IDSCRF radii for such purposes was shown. Of the four tested DFT methods, only the application of the B3LYP/6-31+G(d,p) approximation afforded ensembles of 7–8 single forms for which population-average values of computed NMR parameters (δH, δC and some nJHH data) were in close agreement with those measured experimentally; binuclear (δH,C 1 : 1) correlations, rH,C 2 = 0.9998. The associated individual ΔG values, corrected for LD interactions by applying Grimme’s DFT-D3 terms, afforded relative contents of different contributors to the analyzed conformational families in much better agreement with pertinent DFT/NMR-derived populations (i.e., both data sets were found to be practically equal within the limits of estimated errors) than those calculated from dispersion uncorrected ΔGs. All these main findings were confirmed by additional results obtained at the MP2 level of theory. Various other aspects of the study such as the crystal vs. solution structure, gg/gt rotamer ratio, diagnostic (de)shielding effects, dihydrogen C–H⋯H–C contacts, and doubtful applicability of some specialized DFT functionals (M06-2X, ωB97X-D and B3LYP-GD3BJ) for the description of highly flexible molecules are also discussed in detail

2,2,5,7,8-Penta­methyl­chroman-6-yl 2,3,4,6-tetra-O-acetyl-α-d-glucopyran­oside from synchrotron data

The crystal structure of the title compound, C28H38O11, solved and refined against synchrotron diffraction data, contains two formula units in the asymmetric unit. In both mol­ecules, the dihydro­pyran ring along with its methyl substituents is disordered and adopts two alternative half-chair conformations. The occupancy of the major conformers of the two mol­ecules refined to 0.858 (5) and 0.523 (5)

13C CP MAS NMR and DFT Studies of 6-Chromanyl Ethereal Derivatives

Vitamin E consists of a group of compounds including α- β- γ- and δ-tocopherols and α- β- γ- and δ-tocotrienols, containing the chroman-6-ol system. The recognition of the structural and dynamic properties of this system, present in all vitamers, seems to be important for the full explanation of the mechanism of the biological activity of vitamin E. This paper presents results of the structural analysis of the chosen 6-chromanyl ethereal derivatives using experimental (13 C NMR-in solution and solid state, as well as variable temperature experiments; single crystal X-ray diffraction) and theoretical (DFT) methods. For one of the studied compounds, 2,2,5,7,8-pentamethyl-6-((tetrahydro-2H-pyran-2-yl)oxy) chroman, the splitting of some signals was observed in the 13C dynamic NMR spectra. This observation was explained by the application of a conformational analysis and subsequent DFT optimization, followed by the calculation of NMR properties

An X-ray and Natural Bond Orbital (NBO) structural study of α-tocopheryl and 2,2,5,7,8-pentamethylchroman-6-yl succinates

α-Tocopheryl succinate (α-TOS) is a very promising anticancer agent; however, the mechanism of its action and the role of the succinic moiety in biological activity still remains unclear. This paper, presents the first determination of the X-ray structure of α-TOS and 2,2,5,7,8-pentamethylchroman-6-yl succinate (PMCS). The X-ray data indicated high out of planarity deformation of the aryl ring in the chroman-6-ol system. α-TOS and PMCS differed in angle θ value (28.4° vs. 21.5°, respectively) and in their heterocyclic ring conformations: 2-endo-3-exo in PMCS, and 2-endo-3-exo and 2-exo-3-endo in α-TOS. Due to their strong intermolecular hydrogen bonds, both succinates form cyclically repeated dimeric structures in well assembled crystal supramolecular structures.A population analysis of α-tocopherol (α-TOC), 2,2,5,7,8-pentamethylchroman-6-ol (PMC) and their acyl derivatives was performed at B3LYP/6-31G(d,p)/CPCM level of theory using a natural bond orbital (NBO) analysis within the Gaussian 09 program package. For all compounds, relaxed scans were performed along torsion angle γ, and for low-energy conformers the Fukui functions were calculated: electron donor (ƒ−(r)), electron acceptor (ƒ+(r)), free radical (ƒo(r)) and dual descriptor (ƒ2(r)).In general, the differences observed between α-TOC and its acyl derivative structures result from the non-bonding lone pair of the phenolic oxygen and its interaction with aromatic system π electrons. Keywords: α-Tocopheryl succinate, X-ray, Natural Bond Orbital, DFT calculation, Fukui functio