Jorge L. Jios

17O NMR spectroscopy of 1‐(2‐hydroxyphenyl)‐3‐ naphthylpropane‐1,3‐diones. Influences of keto–enol tautomerism and substituents†

The 17O NMR data of 10 of the title compounds were assigned and interpreted in terms of keto–enol tautomerism, substituent effects and mesomeric structures. Copyright

SYNTHESIS OF SUBSTITUTED FLAVONES AND ARYLCHROMONES USING Ρ AND Si KEGGIN HETEROPOLYACIDS AS CATALYSTS

A simple and clean procedure for the preparation of functionalized flavones and chromones using commercial Keggin heteropolyacid in acetonitrile medium is described for the cyclization of l-(2hydroxyaiyl)-3-aryl-l,3-propanodiones. Sixteen examples are reported, yields ranging in 60-91%; five substituted 2-naphthyIchromones are prepared for the first time. Introduction Compounds containing the chromone skeleton (4//-benzopyran-4-one) are widely distributed in the plant kingdom; they constitute a group of compounds in the flavonoid family (1). These compounds have multiple biological properties, for example anti-inflammatory, antibacterial, antitumor (2), antioxidant (3), anti HIV (4), vasodilator, antiviral, antiallergic (5) and neuroprotective . Some flavonoids inhibit the histamine release from human basophils and rat mast cells (6). Moreover, it is known that some flavonoids have antifeedant activity against some phytophagous insects and a Coptotermes sp. subterranean termite (7, 8). The importance of flavones and their derivatives has led to the development of various methods for their synthesis; for example the Kostanecki-Robinson strategy (9a), from chalcones (9b), or via the Baker-Venkataraman rearrangement to 1,3-diaryl 1,3diketones (9c, 10). The latter compounds give 2-arylchromones on cyclocondensation. Different media have been employed for performing it, for example using excess of sulfuric acid in glacial acetic acid (11, 12); cationic exchange resins in isopropanol (13) glacial acetic acid-anhydrous sodium acetate or aqueous potassium carbonate (14). Greener procedures have been recently described, for example using CuCI2 in ethanol and microwave irradiation (2). Environmental pollution is a usual drawback caused from the use of common acid catalysts like sulfuric, phosphoric, hydrofluoric acids, or boron trifluoride; frequently corrosion problems appear (15). Nevertheless, it is possible avoid them by using an insoluble acid, for example a heteropolyacid (ΗΡΑ) as catalyst HP As are useful solid catalysts because of their superacidic properties (16); catalysis by HP As or some of their derivatives is a field of increasing importance worldwide. There is a great activity in basic research as well as in developing of technological processes involving them (17-19). Varied reactions are currently catalyzed by HPAs, being important dehydration (20), cyclization (15), esterification (21), amine oxidation and olefin epoxidation (22). HPAs are widely applicable in production of fine chemicals (23). Heteropolycompounds with Keggintype primary structure are polynuclear complexes mainly composed by Mo, W or V as polyatoms (M) and P, Si or Ge as central atoms (X). The Keggin structure involves a central tetrahedron X04 surrounded by 12 octahedra M06 . Keggin catalysts could be either multi-electron oxidants or strong acids, with an acid strength higher than that of the classical mineral acids. These properties can be controlled by a proper choice of the heteroatom and polyatoms (15).

Hydrogen Bonds, Tautomers, and Conformation in 2-Hydroxyphenyl 2-hydroxy-2-(β-naphthyl)vinyl Ketone

Single crystal X-ray diffraction and IR spectroscopy have been used to study the conformation of 2-hydroxyphenyl 2-hydroxy-2-(α-naphthyl)vinyl ketone in solid state. It was found that one of the two possible enol tautomeric forms is stabilized in the crystal. The 1-hydroxy-3-oxo-1,3-propenylene moiety, O=C—CH=C—OH, shows a strong intramolecular H bond with a definite character of reasonance-assisted hydrogen bond in spite of being in competition with ring intermolecular hydrogen bonds. The comparison of the present results with solution NMR data indicates that the molecular geometry in solid state and in solution are similar.

A structural, spectroscopic and theoretical study of an o-vanillin Schiff base derivative involved in enol-imine and keto-amine tautomerism

The potassium salt of the Schiff base obtained by condensation of 2-hydroxy-3-methoxybenzaldehyde (o-vanillin) and 2-aminoethanesulfonic acid (taurine) in a methanol potassium hydroxide solution was characterized by crystallographic, spectroscopic and DFT methods. The compound crystallizes in the monoclinic C2/c space group with a = 37.539(4), b = 5.9129(4), c = 26.321(5) A, β = 121.10(2)° and Z = 8 molecules per unit cell. The crystallographic data reveal that two different anionic molecules, which constitute a tautomeric pair, coexist in the crystal. This finding is supported by FTIR, Raman and electronic measurements in methanol solution. The main crystallographic differences between the bonding structures occur along the shortest chemical path linking the oxygen and the nitrogen atom of the OH and CN group. Both tautomeric forms are stabilized by strong O–H⋯N and N–H⋯O intramolecular hydrogen bonds. Optimized geometrical parameters and calculated spectroscopic features obtained by DFT calculations show a very good agreement with the experimental data. Moreover, 1H NMR, 13C NMR and electronic measurements in DMSO solution show the prevalence of the enol-imine tautomer in this solvent.

A detailed experimental and theoretical study of two novel substituted trifluoromethylchromones. The influence of the bulky bromine atom on the crystal packing.

The new 3-methyl-2-trifluoromethylchromone (1) and 3-bromomethyl-2-trifluoromethylchromone (2) compounds were synthesized and characterized by vibrational (IR, Raman), UV-Vis and NMR ((1)H, (13)C and (19)F) spectroscopy and MS spectrometry. The crystal structures of 1 and 2 were determined by X-ray diffraction methods. Both compounds crystallize in the monoclinic P21/c space group with Z=4 molecules per unit cell. The structures were solved from 1423 (1) and 1856 (2) reflections with I>2σ (I) and refined by full-matrix least-squares to agreement R1-values of 0.0403 (1) and 0.0554 (2). Because of π-bonding delocalization, the organic molecular skeletons are planar and the molecular bonding structures can be described by formally single, double and resonant bonds. In 2, the CF3 group revealed a strong rotational disorder around the CCF3 bond, which could be explained in terms of four split positions with about uniform angular distribution. The vibrational, electronic and NMR, spectra were discussed and assigned with the assistance of DFT calculations.

The role of non-covalent interactions in some 2-trifluoromethylchromones in the solid state

The intermolecular interactions in the solid state and the spectroscopic vibrational, electronic and NMR properties of new 3-methyl-substituted-2-trifluoromethylchromone derivatives with –CN (1), –NO2 (2), –OH (3) and –NH2 (4) groups were discussed with the assistance of DFT calculations. The crystal structures of compounds 1–3 were determined by X-ray diffraction showing molecular ribbons for compounds 1 and 2, and dimers via O–H⋯OC hydrogen bonds for 3. Hirshfeld surfaces and the corresponding fingerprint plots, as well as the electrostatic potentials mapped on the surfaces revealed C–H⋯O and C–H⋯F hydrogen bonds, and π⋯π stacking as the main cooperative driving forces for building supramolecular architectures in all compounds. The C–H⋯π and CO⋯π interactions also contribute to stabilizing the crystal structures of 1 and 2. A further analysis of Hirshfeld surfaces was performed using the enrichment ratio as a new descriptor to determine the likelihood of chemical species to establish specific interactions in the molecular packing. The lattice energies of the crystal structures and several intermolecular contacts present in different molecular pairs were also quantified. Molecular docking studies showed the interaction of the title compounds with the catalytic site of PLA2 (PDB code 2QOG) from Crotalus durissus terrificus, and suggested that the investigated compounds could inhibit toxic effects of snake venom.

Relationships between Kováts retention indices and molecular descriptors of 1-(2-hydroxy)-3-arylpropane-1,3-diones.

Experimental and theoretical results for retention index of a set of 20 beta-diketones are given. The quantitative structure-chromatographic retention relationships (QSRR) theory is employed and six molecular descriptors are chosen to compute the fitting polynomials. Multiple regression analysis yields satisfactory results when one resorts to several variables equations, instead of computing just one-variable formulae. Average absolute deviations from experimental results are rather low, which seems to point out the suitability of the present approach.

One-pot synthesis of ferrocenyl-pyrimidones using a recyclable molibdosilicic H4SiMo12O40 heteropolyacid

A series of ferrocene-containing dihydropyrimidines (DHPs) were prepared by the one-pot Biginelli reaction of formylferrocene, 1,3-dicarbonyl component and urea/thiourea. The reaction was catalyzed by a commercial Keggin heteropolyacid (H4SiMo12O40) as a safe, clean and recyclable catalyst. Three different synthetic protocols were examined in order to improve the yields of the reaction and to elucidate its mechanism. Intermediates of the competitive Knoevenagel reaction were also isolated. The methodology is operationally simple and provides access to highly substituted dihydropyrimidines containing ferrocene in very good yields. The catalyst can be used and recycled without appreciable loss of the catalytic activity.

New thiourea and urea derivatives containing trifluoromethyl- and bis-triflouromethyl-4H-chromen-3-yl substituents

ABSTRACT Two new thiourea (1) and urea (2) derivatives, substituted with 2-trifluoromethyl-4H-chromen-3-yl moieties at defined positions, were obtained by convenient synthetic methodologies. The pure compounds were studied in solid state by vibrational spectroscopy (FT-IR and Raman) and in solution by NMR and UV–Vis spectroscopy. The crystal structure of the urea derivative (compound 2) was also determined by X-ray diffraction. The crystal packing is governed by N–H···O intramolecular interactions of moderate strength in a self-assembled dimer of the terminal amide fragment (C(=O)–NH2). Hirshfeld surface and 2D-fingerprint plots were also performed to characterise the role in the packing stabilisation of all contacts, including weak C–H···F hydrogen bonds and π–π stacking interactions. For both compounds, the tentative assignment of vibrational and electronic spectra was assisted by theoretical calculations. Besides, to evaluate the influence on the pharmacokinetic and pharmacodynamic properties of molecules with –CF3 groups, the anti-microbial activity of the title compounds was tested against the standard strains of various Gram-positive and Gram-negative organisms with noteworthy antimicrobial effect over Staphylococcus aureus, Klebsiella pneumoniae and Salmonella typhi. GRAPHICAL ABSTRACT

Aryl Naphthoates: A Conformational Analysis Supported by Single-Crystal X-Ray Diffraction

The conformational study by X-ray diffraction of 12 aroyl esters of ortho-acetyl phenols is reported. The data are supported by theoretical calculations and described in terms of co-planarity, intramolecular steric interference, and intermolecular contacts. The observed hindrance was correlated with the C=O stretching vibration values in infrared spectroscopy.