Showing papers by "José Elguero published in 2012"
TL;DR: In this paper, the authors provide a summary of the present knowledge of axial chirality in heteroaromatic compounds and present methods used to study atropisomerism, from X-ray diffraction to theoretical calculations.
Abstract: The chapter “Atropisomerism and axial chirality in heteroaromatic compounds” provides a summary of the present knowledge of this important topic. The structure of the chapter is: first a detailed description of the methods used to study atropisomerism, from X-ray diffraction to theoretical calculations (14 items), then the application to different compounds according to the nature of the central bond. Rotation about a C–C bond (5–5, 5–6 and 6–6 rings), rotation about a C–N bond (azoles, oxo- and thioxo-five-membered rings, azines), rotation about an N–N bond (5–5, 5–6 and 6–6 rings), rotation about ortho-ortho’-linked compounds, rotation about N-metal bonds, multiple rotations, to end with axial chiral synthesis. In conclusion, a phenomenon that was discovered in 1922 for diphenic acids and that was extended to heterocycles in 1931 by Adams shows eighty years later to be very active, being expected to grow in importance because it is related to asymmetric synthesis, to materials and to biological properties.
87 citations
TL;DR: A clear cooperativity is found between these two noncovalent interactions, since the intermolecular HB between the two imidazole molecules in the dimer-BeX2 complex becomes much stronger than in the isolated dimer, whereas the beryllium bond becomes also stronger in theDimer- beX2complex.
Abstract: The mutual influence between beryllium bonds and inter- or intramolecular hydrogen bonds (HBs) has been investigated at the B3LYP/6-311++G(3df,2p) level of theory, using the complexes between imidazole dimer and malonaldehyde with BeH2 and BeF2 as suitable model systems. Imidazole and its dimer form very strong beryllium bonds with both BeH2 and BeF2, accompanied by a significant geometry distortion of the Lewis acid. More importantly, we have found a clear cooperativity between these two noncovalent interactions, since the intermolecular HB between the two imidazole molecules in the dimer-BeX2 complex becomes much stronger than in the isolated dimer, whereas the beryllium bond becomes also stronger in the dimer-BeX2 complex, with respect to that found in the imidazole-BeX2 complex. The effects of beryllium bonds are also dramatic on the strength of intramolecular HBs. Depending on to which center the BeX2 is attached, the intramolecular HB becomes much stronger or much weaker. The first situation is found when the beryllium derivative is attached to the HB donor, whereas the second occurs if it is attached to the HB acceptor. The first effect can be so strong as to produce a spontaneous proton transfer, as it is actually the case of the malonaldehyde-BeF2 complex.
79 citations
TL;DR: An extension of the harmonic oscillator model of aromaticity (HOMA) model to systems with carbon-boron bonds is presented in this article, where parameters were estimated using experimental and theoretical bond lengths.
Abstract: An extension of the harmonic oscillator model of aromaticity (HOMA) model to systems with carbon–boron bonds is presented Model parameters were estimated using experimental and theoretical bond lengths It is shown that both approaches produce very similar HOMA models In the second part of the article, the aromaticity levels of several model compounds containing carbon–boron bonds are calculated using the previously obtained parameters The results of these calculations are compared with those provided by other aromaticity indices The aromaticity of boron-containing compounds is also compared with the aromaticity of analogous compounds containing carbon and nitrogen
35 citations
TL;DR: In this paper, a survey of the Cambridge Crystallographic database reveals that there are 17 1H-indazoles forming dimers (7), trimers (4), and catemers or chains (6).
Abstract: A survey of the Cambridge Crystallographic Database reveals that there are 17 1H-indazoles forming dimers (7), trimers (4) and catemers or chains (6). Amongst the catemers there is one centrosymmetric compound and five non-centrosymmetric ones that crystallize in chiral helices, either M or P, including indazole itself, whose structure has been determined anew. An explanation will be provided for how an achiral molecule crystallizes in a chiral space group. The second part of the paper is devoted to the use of Vibrational Circular Dichroism (VCD) for determining the absolute configuration of a crystal of indazole. This previously needs the complete assignment of its IR and Raman spectra in solution and in the solid-state based on B3LYP/6-31G(d) calculations of indazole dimers and trimers, which are already chiral.
31 citations
TL;DR: In this paper, the theoretical study of the aromaticity of a series of carbocycles (benzene, cyclohexane, bent and planar cyclooctatetraene) and their didehydro forms (arynes and hetarynes) is presented.
28 citations
TL;DR: The reaction mechanism of the hemiacetal formation from formaldehyde and methanol has been studied theoretically at the B3LYP/6-311++G(d,p) level and it has been found that structural rearrangements represent an important energetic penalty during the activation process.
Abstract: The reaction mechanism of the hemiacetal formation from formaldehyde and methanol has been studied theoretically at the B3LYP/6-311++G(d,p) level. In addition to the study of the reaction between the isolated reactants, three different kinds of catalysis have been explored. The first one examines the use of assistants, especially bridging water molecules, in the proton transfer process. The second one attempts to increase the local electrophilicity of the carbon atom in formaldehyde with the presence of a Bronsted acid (H(+) or H(3)O(+)). The last one considers the combined effect of both catalytic strategies. The reaction force, the electronic chemical potential, and the reaction electronic flux have been characterized for the reaction path in each case. In general, it has been found that structural rearrangements represent an important energetic penalty during the activation process. The barriers for the reactions catalyzed by Bronsted acids show a high percentage of electronic reorganization contribution. The catalytic effects for the reactions assisted by water molecules are due to a reduction of the strain in the transition state structures. The reaction that includes both acid catalysis and proton assistance transfer shows the lowest energy barrier (25.0 kJ mol(-1)).
28 citations
27 citations
TL;DR: G3B3 calculations on the most stable minima indicate that the α-furanose configuration is the moststable for both D-erythrose and D-threose.
26 citations
TL;DR: Surprisingly, although both series of compounds exhibit the same bonding arrangements, they follow opposite stability trends and the expected increase of the interaction energies with the number of fluorine substituents is only observed in the acetylene series.
Abstract: The complexes formed by CuF with CC double and triple bonds have been studied at the MP2 and CCSD(T) computational levels. The interaction of CuF with acetylene, ethylene and their fluoro derivatives is very strong, with interaction energies close to those of conventional covalent bonds. Hence, these complexes could be actually viewed as a new kind of metallocycles, with significantly strong Cu–C linkages. All electronic indexes analyzed by means of the AIM, ELF and NBO formalisms, indicate that the strength of the interaction should increase with the number of fluorine substituents in both series of compounds. Surprisingly, however, although both series of compounds exhibit the same bonding arrangements, they follow opposite stability trends and the expected increase of the interaction energies with the number of fluorine substituents is only observed in the acetylene series. The reason for this unexpected behavior is once more associated with the effects triggered by the distortion of the interacting subunits. Deformation not only has a direct energetic cost but dramatically affects the intrinsic properties of the interacting systems.
22 citations
TL;DR: The structure of glibenclamide, an important antidiabetic drug, has been studied both in solution and in the solid state by a combination of NMR spectroscopy and theoretical calculations and the possibility of a tautomerization under melting to afford a desmotrope was rejected.
Abstract: The structure of glibenclamide, 5-chloro-N-(2-{4-[(cyclohexylamino)carbonyl] aminosulfonyl}phenyl) ethyl)-2-methoxybenzamide, an important antidiabetic drug, has been studied both in solution and in the solid state by a combination of NMR spectroscopy and theoretical calculations. The possibility that glibenclamide suffers a tautomerization under melting to afford a desmotrope was rejected.
20 citations
TL;DR: The biological activity of newly synthesized compounds at the androgen receptor, along with a series of structural analogs, was determined and provides the basis for preliminary qualitative structure-activity relationship analysis.
Abstract: We report the conformational analysis of a series of 3-hydroxy-N′-((naphthalen-2-yl)methylene)naphthalene-2-carbohydrazides. This class of compounds has recently been reported as androgen receptor (AR)-coactivator disruptors for potential application in prostate cancer therapy. Definition of the E/Z isomerism around the imine linker group (hydrazide) is significant from a mechanistic point of view. A detailed study using theoretical calculations coupled with experimental techniques has allowed us determine an initial preference for the E isomer. The biological activity of newly synthesized compounds at the androgen receptor, along with a series of structural analogs, was determined and provides the basis for preliminary qualitative structure–activity relationship analysis.
TL;DR: In this article, the three parent NH-benzazoles, benzimidazole, indazole and benzotriazole were studied theoretically at the B3LYP/6-311++G(d,p) level.
Abstract: The three parent NH-benzazoles, benzimidazole, indazole and benzotriazole, have been studied theoretically at the B3LYP/6-311++G(d,p) level. Optimized geometries have been compared with those obtained by X-ray crystallography, energies with studies about tautomerism, acidbase properties with pKas, and chemical shifts with those reported in the literature. As aromaticity probe, Schleyer's Nuclear Independent Chemical Shifts (NICS) were used and represented in two 3D isosurfaces of the electron density.
TL;DR: In this paper, a theoretical study of FCCF(HF)n complexes, with n = 1 and 2, was carried out by means of ab initio computational methods and the indirect spin-spin coupling constants were calculated at the CCSD/aug-cc-pVTZ-J computational level.
TL;DR: In this article, the authors report a theoretical study of three hypothetical possible six-membered rings that contain the N = S −S −S = N motif carried out at the MP2/aug-cc-pVDZ level.
Abstract: The sulfur electronic structure allows for the existence of hypervalent molecules that were discussed as early as 1939 by Schomaker and Pauling. In the present paper, we report a theoretical study of three hypothetical possible six-membered rings that contain the –N=S–S=N– motif carried out at the MP2/aug-cc-pVDZ level. Three minima have been found, of which two of them are six-membered rings with all covalent bonds. Since they do not have a planar structure, we have calculated the aromaticity index NICS through the symmetry axis perpendicular to the mid-plane and at various points in space. Benzene, cyclohexane, and 1,2,5-thiadiazole have served as points of comparison.
TL;DR: The proton tautomerism of pyrazole-4-carboxylic acid (PCA) has been studied by a combination of CPMAS and ²H NMR spectroscopy and relaxometry as discussed by the authors.
Abstract: The proton tautomerism of pyrazole-4-carboxylic acid (PCA) has been studied by a combination of
¹⁵N CPMAS and ²H NMR spectroscopy and relaxometry. Down to 250 K, PCA forms a hydrogen
bonded ribbon where adjacent carboxylic and pyrazole groups are linked by an OH···N and an
O···HN hydrogen bond, forming either the tautomeric state A or B. Down to about 250 K, the
tautomerism is fast on the NMR timescale and degenerate, corresponding to a phase exhibiting
dynamic proton disorder. At lower temperatures, a transition to an ordered phase is observed with
localized protons, assigned to an all-syn conformation adopting the sequence of tautomeric states
..ABABA.. The longitudinal ¹⁵N relaxation times T₁ of PCA-¹⁵N₂ have been measured at 9.12 MHz
(2.1 T). Because of the low field, a chemical shift anisotropy mechanism could be neglected, and
the data were analyzed in terms of a dipolar ¹H-¹⁵N relaxation mechanism, yielding the rate
constants kHH. The rate constants kHD and kDD were obtained from the measurement and analysis of
the ²H T₁ values of PCA-¹⁵N₁ -d₀.₉ and PCA-¹⁵N₁ -d₀.₁ measured at 46.03 MHz. Within the margin
of error, no kinetic isotope effects could be detected, in contrast to previous results reported for
the very fast tautomerism of solid benzoic acid dimers and the much slower tautomerism of solid
3,5-diphenyl-4-brompyrazole (DPBrP) dimers. The Arrhenius curves of all three systems were
simulated using the Bell–Limbach tunneling model. Evidence for a major heavy atom motion for
the tautomerism of PCA is obtained, associated with small angle reorientation of PCA molecules around the molecular axis. The observed proton order-disorder transition and the mechanism of the
observed rate process are discussed in terms of a coupling of adjacent tautomeric states.
TL;DR: A theoretical study of acidity and hydrogen bond acceptor properties of tetrahedric phosphine oxide derivatives have been carried out by means of MP2 computational methods as mentioned in this paper, and the results obtained for the mentioned complexes have been compared with the analogous ones of trimethylphosphine oxide.
TL;DR: In this paper, the structure of the main tautomeric form of 8-hydroxy carbostyril has been established using NMR, X-ray and DSC.
TL;DR: A theoretical study of the hemiacetal formation reaction between methanol and CX3CHO has been carried out using density functional theory and Becke, three-parameter, Lee-Yang-Parr/6-311++G(d,p) computational methods as discussed by the authors.
TL;DR: In this article, an azo derivative of 1H-pyrazole was chosen to study the information obtained from different techniques for determining the structure of a non-crystalline compound in the solid-state and in solution.
TL;DR: A protocol for the enantioselective synthesis of the three stereoisomers of 1,1′-binaphthalene-2,2′-diyl)bis(2,3,2-trifluoroethanol) and their characterization and these compounds, that combine axial and central chirality, might present interesting properties for enantiorecognition.
TL;DR: In this paper, the structure of three fluorinated NH-indazolinones, two oxo derivatives and one 3-hydroxyindazole, has been determined by 13C and 15N solid state NMR.
TL;DR: Theoretical calculations at the B3LYP/6-31G(d) level have been carried out on the isomerization of cyclic-tri-glycine into the corresponding tri-cyclol.
Abstract: Theoretical calculations at the B3LYP/6-31G(d) level have been carried out on the isomerization of cyclic-tri-glycine into the corresponding tri-cyclol. The results confirmed that the cyclol hypothesis was untenable both from a thermodynamic as well as from a kinetic point of view.
TL;DR: In this paper, MP2/aug'-cc-pVTZ calculations have been carried out to determine the structures and binding energies of binary complexes formed by HBO with a series of small molecules A.
TL;DR: A closer look at Davidson's text reveals that most of the structures were correctly drawn the only exception being guanosine represented in the enol form as discussed by the authors, which is the case of the double helix.
Abstract: J D Watson in his book, The Double Helix, blamed J N Davidson’s text The biochemistry of nucleic acids for Watson initially using the wrong formulae of the nitrogenous bases in his and F Crick’s quest for the DNA structure A closer look at Davidson’s text, however, reveals that most of the structures were correctly drawn the only exception being guanosine represented in the enol form
TL;DR: In this paper, the authors showed that the title compound exists mainly as an OH⋯N tautomer in solution, and compared the experimental chemical shifts of 4,4-dimethyl-7-pentyl-2,4dihydrochromeno[4,3-c ]pyrazol-9-ol with absolute shieldings calculations performed using the GIAO approximation.
TL;DR: The conclusion of these studies is that a slow tautomerism between 1H‐ and 2H‐tetrazoles cannot explain the experimental observations reported recently in the literature.
Abstract: The structure of 5-(2,6-dimethylphenoxy)-1H- and 2H-tetrazoles together with those of 5-(2,6-diisopropyl-phenoxy)-1H and 2H-tetrazoles have been theoretically studied including absolute shieldings and energies. The conclusion of these studies is that a slow tautomerism between 1H- and 2H-tetrazoles cannot explain the experimental observations reported recently in the literature.