Cláudio F. Tormena

Matrix‐assisted diffusion‐ordered spectroscopy: mixture resolution by NMR using SDS micelles

Diffusion‐ordered spectroscopy (DOSY) is a powerful technique for mixture analysis, but in its basic form it cannot separate the component spectra for species with very similar diffusion coefficients. It has been recently demonstrated that the component spectra of a mixture of isomers with nearly identical diffusion coefficients (the three dihydroxybenzenes) can be resolved using matrix‐assisted DOSY (MAD), in which diffusion is perturbed by the addition of a co‐solute such as a surfactant [R. Evans, S. Haiber, M. Nilsson, G. A. Morris, Anal. Chem. 2009, 81, 4548–4550]. However, little is known about the conditions required for such a separation, for example, the concentrations and concentration ratios of surfactant and solutes. The aim of this study was to explore the concentration range over which matrix‐assisted DOSY using the surfactant SDS can achieve diffusion resolution of a simple model set of isomers, the monomethoxyphenols. The results show that the separation is remarkably robust with respect to both the concentrations and the concentration ratios of surfactant and solutes, supporting the idea that MAD may become a valuable tool for mixture analysis. Copyright

1hJFH coupling in 2-fluorophenol revisited: Is intramolecular hydrogen bond responsible for this long-range coupling?

The present study shows that a hydrogen bond between the OH group and the fluorine atom is not involved in the 1hJFH spin–spin coupling transmission either for 4‐bromo‐2‐fluorophenol or 2‐fluorophenol. In fact, according to a quantum theory of atoms in molecules analysis, no bond critical point is found between O‐H and F moieties. The nature of the transmission mechanism of the Fermi contact term of the 1hJFH spin–spin coupling is studied by analyzing canonical molecular orbitals (see J. Phys. Chem. A 2010, 114, 1044), and it is observed that virtual orbitals play only a quite minor role in its transmission. This is typical of a Fermi contact term transmitted mainly through exchange interactions owing to the overlap of proximate electronic clouds; therefore, it is suggested to identify them as nTSJFH coupling where n stands for the number of formal bonds separating the coupling nuclei. In the cases studied in this work is n = 4. Results presented in this work could provide an interesting rationalization for different experimental signs known in the current literature for proximate JFH couplings. Copyright

The F⋯HO intramolecular hydrogen bond forming five-membered rings hardly appear in monocyclic organofluorine compounds

This paper emphasizes that fluorine atoms in organic molecules need special geometric requirements to experience intramolecular hydrogen bonds (H-bonds). Calculations at the B3LYP/aug-cc-pVDZ theoretical level and using the quantum theory of atoms in molecules applied over a series of monocyclic compounds, which have similar CC(F)–C(OH)C fragments, predict that the F⋯HO intramolecular H-bond does not exist when forming five-membered rings. Indeed, it is shown that the geometric restrictions imposed by the rigid rings are the main reasons in preventing fluorine participating in such a F⋯HO intramolecular H-bond.

Interaction in trans-2-halocyclohexanols — an infrared and theoretical study

Abstract The O–H and C–O stretching frequencies of trans -2-halocyclohexanols in CCl 4 solutions have been measured and theoretical calculations have been performed to elucidate the main interactions, which are responsible for the conformational equilibria in these systems. It can be concluded that hydrogen bonding is predominant for trans -2-fluorocyclohexanol, leading to a stabilization of the eq–eq conformation, while for the chlorine, bromine and iodine derivatives, besides hydrogen bonding, gauche and steric interactions are also present.

Analysis of Canonical Molecular Orbitals to Identify Fermi Contact Coupling Pathways. 1. Through-Space Transmission by Overlap of 31P Lone Pairs

In this work, a new approach to studying coupling pathways for the Fermi contact term of NMR spin-spin coupling constants (SSCCs) is presented. It is based on the known form of propagating the Fermi hole through a canonical molecular orbital (CMO). It requires having an adequate spatial description of the relevant canonical molecular orbitals, which are obtained by expanding CMOs in terms of natural bond orbitals (NBOs). For detecting the relevant contributions of CMOs to a given Fermi contact (FC) pathway, the description of the FC in terms of the triplet polarization propagator (PP) is used. To appreciate the potential of this approach, dubbed FCCP-CMO (Fermi contact coupling pathways-CMO), it is applied to analyze the through-space transmission of the FC term of J(PP) SSCCs by overlap of the P lone pairs. This method can be applied using well-known quantum chemistry software without any further modification, which makes it appealing for use as a complement to SSCC measurements by NMR spectroscopy.

Halogenated six-membered rings: a theoretical approach for substituent effects in conformational analysis

Abstract Studies on the conformational equilibria of a series of dihalosubstituted cyclohexanes ( I ) and halocyclohexanones ( II ) are reported. Theoretical calculations using the B3LYP method and the 6-311+g(d,p) basis set were applied to determine the energy differences (Δ E ) between the conformers of I and II , as well Δ E between the conformers of monohalocyclohexanes, in order to obtain the intramolecular interaction energies, which govern the conformational equilibria of I and II . It is shown that while the intramolecular interactions for 1,3- and 1,4-disubstituted cyclohexanes, as well as for 3- and 4-halocyclohexanones, are due to classical effects (steric and electrostatic), for the 2-halocyclohexanones it becomes evident that orbital interactions between n halo and π ∗ CO drive the equilibria towards the axial conformers. Moreover, the gauche effect seems to be irrelevant for the trans -1,2-dihalocyclohexane equilibria, opposite to several reports from the literature on other trans -1,2-disubstituted cyclohexanes bearing electronegative substituents.

Achieving regio- and stereo-control in the fluorination of aziridines under acidic conditions

We developed an efficient fluorination protocol that converts easily accessible aziridines into β-fluoroamines, which are important motifs in biologically active molecules. In contrast with traditional fluorination approaches, DMPU-HF has shown both higher reactivity and regioselectivity and good functional group tolerance; thus, a wide scope of β-fluoroamines can now be accessed conveniently. The stereochemical behavior of the ring opening depends on the substitution pattern of the aziridine substrate.

1H NMR Spectra. Part 28: Proton chemical shifts and couplings in three-membered rings. A ring current model for cyclopropane and a novel dihedral angle dependence for 3JHH couplings involving the epoxy proton†

The 1H chemical shifts of selected three‐membered ring compounds in CDCl3 solvent were obtained. This allowed the determination of the substituent chemical shifts of the substituents in the three‐membered rings and the long‐range effect of these rings on the distant protons. The substituent chemical shifts of common substituents in the cyclopropane ring differ considerably from the same substituents in acyclic fragments and in cyclohexane and were modelled in terms of a three‐bond (γ)‐effect. For long‐range protons (more than three bonds removed), the substituent effects of the cyclopropane ring were analysed in terms of the cyclopropane magnetic anisotropy and steric effect. The cyclopropane magnetic anisotropy (ring current) shift was modelled by (a) a single equivalent dipole perpendicular to and at the centre of the cyclopropane ring and (b) by three identical equivalent dipoles perpendicular to the ring placed at each carbon atom. Model (b) gave a more accurate description of the 1H chemical shifts and was the selected model. After parameterization, the overall root mean square error for the dataset of 289 entries was 0.068 ppm. The anisotropic effects are significant for the cyclopropane protons (ca 1 ppm) but decrease rapidly with distance. The heterocyclic rings of oxirane, thiirane and aziridine do not possess a ring current. 3JHH couplings of the epoxy ring proton with side‐chain protons were obtained and shown to be dependent on both the H―C―C―H and H―C―C―O orientations. Both density functional theory calculations and a simple Karplus‐type equation gave general agreement with the observed couplings (root mean square error 0.5 Hz over a 10‐Hz range). Copyright

Stereoelectronic interactions and the one-bond C-F coupling constant in sevoflurane.

The conformational preference of the widely utilized anesthetic fluoromethyl-1,1,1,3,3,3-hexafluoro-2-propyl ether (sevoflurane) has been investigated computationally and by NMR spectroscopy. Three conformational minima were located at the B3LYP/aug-cc-pVDZ level, but one is significantly more stable (by ca. 4 kcal/mol) than the other two. This is the case both for gas phase calculations and for solution NMR data. Although the main conformer is stabilized by electron delocalization (n(O) → σ*(C-F)), this type of hyperconjugation was not found to be the main driver for the conformer stabilization in the gas phase and, consequently, for the apparent anomeric effect in sevoflurane. Instead, more classical steric and electrostatic interactions appear to be responsible for the conformational energies. Also the (1)J(CF) coupling constants do not appear to be dominated by hyperconjugation; again, dipolar interactions are invoked instead.

Effect of Electronic Interactions on NMR 1JCF and 2JCF Couplings in cis- and trans-4-t-Butyl-2-fluorocyclohexanones and Their Alcohol Derivatives

In order to study the influence of hyperconjugative, inductive, steric, and hydrogen-bond interactions on (1)J(CF) and (2)J(CF) NMR spin-spin coupling constants (SSCCs), they were measured in cis- and trans-4-t-butyl-2-fluorocyclohexanones and their alcohol derivatives. The four isotropic terms of those SSCCs, Fermi contact (FC), spin dipolar (SD), paramagnetic spin-orbit (PSO), and diamagnetic spin-orbit (DSO), were calculated at the SOPPA(CCSD)/EPR-III level. Significant changes in FC and PSO terms along that series of compounds were rationalized in terms of their transmission mechanisms by employing a qualitative analysis of their expressions in terms of the polarization propagator formalism. The PSO term is found to be sensitive to proximate interactions like steric compression and hydrogen bonding; we describe how it could be used to gauge such interactions. The FC term of (2)J(CF) SSCC in cis-4-t-butyl-2-fluorocyclohexanone is rationalized as transmitted in part by the superposition of the F and O electronic clouds.