Determination of aromaticity indices of thiophene and furan by nuclear magnetic resonance spectroscopic analysis of their phenyl esters

A series of m‐ and p‐substituted phenyl benzoates, 2‐thienoates, and 2‐furoates were prepared and their ¹H and ¹³C nmr spectroscopic characteristics were examined. In general, good correlations were observed between the chemical shift values of protons and carbons of the acyl aromatic rings and the Hammett σ. Plots of the chemical shift values of the carbonyl carbons of the benzoates against those of the 2‐thienoates and 2‐furoates gave an excellent correlation and the values of the slopes are 0.85 and 0.75, respectively, in dimethyl sulfoxide‐d₆ and 0.90 and 0.78, respectively, in chloroform‐d. The values could be considered as a set of aromaticity indices.     

Determination of aromaticity indices of thiophene and furan by nuclear magnetic resonance spectroscopic analysis of their anilides

A series of m‐ and p‐substituted anilides of benzoic acid, 2‐thienoic acid, and 2‐furoic acid were prepared and their ¹H and ¹³C nmr spectroscopic characteristics were examined. In general, good correlations were observed between the chemical shifts of proton and carbon signals of the acyl aromatic rings and the Hammett σ. Plots of the chemical shift values of the carbonyl carbons of the benzanilides against those of the 2‐thienamides and 2‐furamides gave an excellent correlation and the values of the slopes are 0.79 and 0.52, respectively, in dimethyl sulfoxide‐d₆. The slopes could be considered as a set of aromaticity index.     

Quantum chemistry investigation of electronic structure and NMR spectral characteristics for fluorides of dialkylamidosulfoxylic acids and related compounds

The parent (H₂N? S? F) and N,N‐dialkyl‐substituted fluorides of amidosulfoxylic acid (R₂N? S? F, R?Me or R₂N?Morph) as well as the related compounds X? S? F (X?CH₃, OH, F, SiH₃, PH₂, SH, Cl) have been investigated with quantum chemical calculations at the ab initio (MP2) level of approximation. The geometries, electronic structures, molecular orbital (MO) energies and NMR chemical shift values have been calculated to evaluate the role and extent of the polarization and delocalization effects in forming of the high‐field fluorine NMR resonances within the series of interest. The δF magnitudes for all investigated fluorides of amidosulfoxylic acid as well as the δN value calculated for Me₂N? S? F are in the good agreement with the ¹⁹F and ¹⁴N NMR chemical shift values measured experimentally. For the parent compounds, H₂N? S? F and H₂N? SO₂? F, the orientation of principal axes of the magnetic shielding tensors and the corresponding principal σ_ii values along these axes have been qualitatively interpreted basing on the analysis of the MO interactions in the presence of the rotating magnetic field. Copyright © 2009 John Wiley & Sons, Ltd.     

NMR study of O and N,O‐substituted 8‐quinolinol derivatives

The ¹H and ¹³C NMR spectral study of several biologically active derivatives of 8‐quinolinol have been made through extensive NMR studies including homodecoupling and 2D‐NMR experiments such as COSY‐45°, NOESY, and HeteroCOSY. Electron donating resonance and electron withdrawing inductive effect of several groups showed marked changes in chemical shifts of nuclei at the seventh positions of O‐substituted quinolinols (2–15). Although in N‐alkyl, 8‐alkoxyquinolinium halides (16–21), ring A rightly showed low frequency chemical shift values. Copyright © 2013 John Wiley & Sons, Ltd.     

A comparative study between para‐aminophenyl and ortho‐aminophenyl benzothiazoles using NMR and DFT calculations

Ortho‐substituted and para‐substituted aminophenyl benzothiazoles were synthesised and characterised using NMR spectroscopy. A comparison of the proton chemical shift values reveals significant differences in the observed chemical shift values for the NH protons indicating the presence of a hydrogen bond in all ortho‐substituted compounds as compared to the para compounds. The presence of intramolecular hydrogen bond in the ortho amino substituted aminophenyl benzothiazole forces the molecule to be planar which may be an additional advantage in developing these compounds as Alzheimer's imaging agent because the binding to amyloid fibrils prefers planar compounds. The splitting pattern of the methylene proton next to the amino group also showed significant coupling to the amino proton consistent with the notion of the existence of slow exchange and hydrogen bond in the ortho‐substituted compounds. This is further verified by density functional theory calculations which yielded a near planar low energy conformer for all the o‐aminophenyl benzothiazoles and displayed a hydrogen bond from the amine proton to the nitrogen of the thiazole ring. A detailed analysis of the ¹H, ¹³C and ¹⁵N NMR chemical shifts and density functional theory calculated structures of the compounds are described. Copyright © 2014 John Wiley & Sons, Ltd.     

A Photosensitive Liquid Crystal Studied by 14N NMR, 2H NMR,and DFT Calculations

An azobenzene derivative, namely diheptylazobenzene, showing the nematic and smectic A liquid crystalline phases, was investigated by means of a combined approach based on NMR and DFT calculations. ¹⁴N NMR quadrupole‐ and chemical‐shift‐perturbed spectra were acquired in the whole mesophasic range, providing both experimental quadrupolar splittings and chemical shift anisotropy values. On the same mesogen, deuterium labelled at the α‐position of the hydrocarbon chain, ²H NMR quadrupole‐perturbed spectra were recorded. The analysis of these NMR data was performed with the help of ab initio calculations, in vacuo and by taking into account the effect of the anisotropic environment typical of liquid crystals, by using the IEF‐PCM model. The geometry optimizations of the azomesogen in the trans and cis configurations were performed by DFT calculations employing the combination of B3LYP functional with the 6‐311G(d) basis set. The analysis of experimental NMR data was performed by considering the trans configuration as the most populated one and the corresponding quadrupolar tensors and chemical shielding tensors were determined at the DFT level of theory. The main result of this work is the determination of a relatively high and temperature‐dependent molecular biaxiality of the trans state of this azomesogen.     

Adducts of nitrogenous ligands with rhodium(II) tetracarboxylates and tetraformamidinate: NMR spectroscopy and density functional theory calculations

Complexation of tetrakis(μ₂‐N,N'‐diphenylformamidinato‐N,N')‐di‐rhodium(II) with ligands containing nitrile, isonitrile, amine, hydroxyl, sulfhydryl, isocyanate, and isothiocyanate functional groups has been studied in liquid and solid phases using ¹H, ¹³C and ¹⁵N NMR, ¹³C and ¹⁵N cross polarisation–magic angle spinning NMR, and absorption spectroscopy in the visible range. The complexation was monitored using various NMR physicochemical parameters, such as chemical shifts, longitudinal relaxation times T₁, and NOE enhancements. Rhodium(II) tetraformamidinate selectively bonded only unbranched amine (propan‐1‐amine), pentanenitrile, and (1‐isocyanoethyl)benzene. No complexation occurred in the case of ligands having hydroxyl, sulfhydryl, isocyanate, and isothiocyanate functional groups, and more expanded amine molecules such as butan‐2‐amine and 1‐azabicyclo[2.2.2]octane. Such features were opposite to those observed in rhodium(II) tetracarboxylates, forming adducts with all kind of ligands. Special attention was focused on the analysis of Δδ parameters, defined as a chemical shift difference between signal in adduct and corresponding signal in free ligand. In the case of ¹H NMR, Δδ values were either negative in adducts of rhodium(II) tetraformamidinate or positive in adducts of rhodium(II) tetracarboxylates. Experimental findings were supported by density functional theory molecular modelling and gauge independent atomic orbitals chemical shift calculations. The calculation of chemical shifts combined with scaling procedure allowed to reproduce qualitatively Δδ parameters. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis and nuclear magnetic resonance spectroscopic studies of 1‐arylpyrroles

A series of m‐ and p‐substituted 1‐phenyl, 1‐benzyl, 1‐benzoyl, and 1‐(2‐phenylethyl)pyrroles was prepared and their ¹H and ¹³C nmr spectroscopic characteristics were examined. In general, good correlations were observed between the chemical shift values of the β? H and the β? C of pyrroles [except 1‐(2‐phenylethyl)pyrroles] and the Hammettt σ. The observation may be explained in terms of the electronic effects of the substituents which are transmitted through bonds and through space by interaction of the p orbitals between β? Cs of the pyrrole ring and m‐ and p? Cs of the phenyl ring. Substituent constants of 1‐pyrrolyl, 1‐pyrrolylmethyl, and 1‐pyrroloyl groups for the ¹H and ¹³C chemical shifts of phenyl ring are also presented.     

DFT‐GIAO 1H and 13C NMR prediction of chemical shifts for the configurational assignment of 6β‐hydroxyhyoscyamine diastereoisomers

¹H and ¹³C NMR chemical shift calculations using the density functional theory–gauge including/invariant atomic orbitals (DFT–GIAO) approximation at the B3LYP/6‐311G++(d,p) level of theory have been used to assign both natural diastereoisomers of 6β‐hydroxyhyoscyamine. The theoretical chemical shifts of the ¹H and ¹³C atoms in both isomers were calculated using a previously determined conformational distribution, and the theoretical and experimental values were cross‐compared. For protons, the obtained average absolute differences and root mean square (rms) errors for each comparison showed that the experimental chemical shifts of dextrorotatory and levorotatory 6β‐hydroxyhyoscyamines correlated well with the theoretical values calculated for the (3R,6R,2′S) and (3S,6S,2′S) configurations, respectively, whereas for ¹³C atoms the calculations were unable to differentiate between isomers. The nature of the relatively large chemical shift differences observed in nuclei that share similar chemical environments between isomers was asserted from the same calculations. It is shown that the anisotropic effect of the phenyl group in the tropic ester moiety, positioned under the tropane ring, has a larger shielding effect over one ring side than over the other one. Copyright © 2009 John Wiley & Sons, Ltd.     

A 93Nb Solid‐State NMR and Density Functional Theory Study of Four‐ and Six‐Coordinate Niobate Systems

A variable B₀ field static (broadline) NMR study of a large suite of niobate materials has enabled the elucidation of high‐precision measurement of ⁹³Nb NMR interaction parameters such as the isotropic chemical shift (δ_iso), quadrupole coupling constant and asymmetry parameter (C_Q and η_Q), chemical shift span/anisotropy and skew/asymmetry (Ω/Δδ and κ/η_δ) and Euler angles (α, β, γ) describing the relative orientation of the quadrupolar and chemical shift tensorial frames. These measurements have been augmented with ab initio DFT calculations by using WIEN2k and NMR‐CASTEP codes, which corroborate these reported values. Unlike previous assertions made about the inability to detect CSA (chemical shift anisotropy) contributions from Nb^V in most oxo environments, this study emphasises that a thorough variable B₀ approach coupled with the VOCS (variable offset cumulative spectroscopy) technique for the acquisition of undistorted broad (?1/2?+1/2) central transition resonances facilitates the unambiguous observation of both quadrupolar and CSA contributions within these ⁹³Nb broadline data. These measurements reveal that the ⁹³Nb electric field gradient tensor is a particularly sensitive measure of the immediate and extended environments of the Nb^V positions, with C_Q values in the 0 to >80 MHz range being measured; similarly, the δ_iso (covering an approximately 250 ppm range) and Ω values (covering a 0 to approximately 800 ppm range) characteristic of these niobate systems are also sensitive to structural disposition. However, their systematic rationalisation in terms of the Nb? O bond angles and distances defining the immediate Nb^V oxo environment is complicated by longer‐range influences that usually involve other heavy elements comprising the structure. It has also been established in this study that the best computational method(s) of analysis for the ⁹³Nb NMR interaction parameters generated here are the all‐electron WIEN2k and the gauge included projector augmented wave (GIPAW) NMR‐CASTEP DFT approaches, which account for the short‐ and long‐range symmetries, periodicities and interaction‐potential characteristics for all elements (and particularly the heavy elements) in comparison with Gaussian 03 methods, which focus on terminated portions of the total structure.     

N‐arylhexahydropyrimidines. Part 1. Synthesis and 1H NMR characterization of 1,3‐Di and 1,2,3‐trisubstituted derivatives

A series of N‐arylhexahydropyrimidines la‐1 were synthesized by condensation of N‐aryl‐N'‐alkyl‐ (or aryl)‐1,3‐propanediamines 2a‐h with aldehydes. Reactions with formaldehyde proceeded in hydroalcoholic solution, while condensation with aromatic aldehydes required in general the use of activated molecular sieves. ¹H NMR spectra of compounds la‐1 were analyzed and the results correlated with their conforma‐tional features. Derivatives devoid of a 2‐substituent la‐g show fast ring reversal and N‐inversion. The presence of a 2‐aryl group shifts the ring reversal equilibrium towards conformations where the 2‐aryl substituent is equatorial. Differential assignment of axial and equatorial hydrogens in these compounds was made on the basis of coupling constants and chemical shift values. In compound 1k spectral data suggest the axial orientation of the N‐methyl group. Such findings were confirmed in the corresponding NOESY spectrum.     

Consecutive Chemical Activation Steps in the OH‐Initiated Atmospheric Degradation of Isoprene: An Analysis with Coupled Master Equations

The influence of a two‐step chemical activation on 1,5‐H and 1,6‐H shift reactions of hydroxyl‐peroxy radicals formed in the atmospheric photooxidation of isoprene was investigated by means of a master equation analysis. To account for multiple chemical activation processes, three master equations were coupled. The general approach of this coupling is described, and consequences for steady‐state regimes are examined. The specific calculations show that chemical activation has no substantial influence on the rate coefficients of the above‐mentioned reactions under tropospheric conditions. However, it is demonstrated that high‐pressure limits of the thermal rate coefficients instead of the falloff‐corrected values have to be used for kinetic modeling. This is a consequence of the continuous population of the high‐energy part of the isoprene‐OH‐O₂ adduct distribution by the forming reactions under steady‐state conditions. The rate coefficients of the isomerization reactions at T = 298 K were calculated to be k_3a^∞ = 1.5 × 10^?3 s^?1 (1,5‐H‐shift of the 1,2‐isomer) and k_4a^∞ = 6.5 s^?1 (1,6‐H‐shift of the (Z)‐1,4‐isomer). The calculated value of k_4a^∞ is three orders of magnitude larger than a recently reported experimentally observed rate coefficient for the hydrogen shift reactions of the hydroxyl‐peroxy intermediates. It is shown that this discrepancy is in part due to the fact that the experiment does not distinguish between different structural isomers. A comparison of the experimentally determined isotope effect with the calculated value shows a reasonable agreement.     

Deuterium‐induced isotope effects on the 13C chemical shifts of α‐d‐glucose pentaacetate

1,2,3,4,6‐Penta‐O‐acetyl‐α‐d ‐glucopyranose and the corresponding [1‐²H], [2‐²H], [3‐²H], [4‐²H], [5‐²H], and [6,6‐²H₂]‐labeled compounds were prepared for measuring deuterium/hydrogen‐induced effects on ¹³C chemical shift ⁿΔ (DHIECS) values. A conformational analysis of the nondeuterated compound was achieved using density functional theory (DFT) molecular models that allowed calculation of several structural properties as well as Boltzmann‐averaged ¹³C NMR chemical shifts by using the gauge‐including atomic orbital method. It was found that the DFT‐calculated C–H bond lengths correlate with ¹Δ DHIECS. Copyright © 2013 John Wiley & Sons, Ltd.     

Solid‐state NMR studies of 1,3‐imidazolidine‐2‐selenone and some related compounds

Solid‐state cross‐polarization magic angle spinning ¹³C, ⁷⁷Se and ¹⁵N NMR spectra were recorded for 1,3‐imidazolidine‐2‐selenone, its N‐substituted derivatives and some related compounds. The spinning sideband manifold intensities were used to obtain principal values of ¹³C and ⁷⁷Se chemical shift tensors. Large selenium chemical shift anisotropies were observed for these selenones. Copyright © 2003 John Wiley & Sons, Ltd.     

Study of the temperature‐dependent conformational averaging of 1H NMR resonances in vinylcyclopropane through the use of ab initio methodology and Boltzmann statistics

The temperature dependence of the ¹ H NMR resonance of the C‐4 olefinic proton in vinylcyclopropane was investigated through a combination of ab initio calculations and Boltzmann statistics. A torsional energy profile as a function of the 〈?〉 dihedral angle was obtained using HF methodology with a 6–311G** basis set, while the corresponding ¹ H chemical shift profiles for the C‐4 proton were computed using the GIAO approach and either HF, DFT (B3LYP) or MP2 methods at the 6–311G** level of theory. Chemical shifts at different temperatures calculated as canonical ensemble averages in which the different ab initio ¹ H chemical shift profiles and a Boltzmann factor defined by the HF/ 6–311G** energy function are employed reproduce remarkably well the temperature dependence observed experimentally. Attempts to perform a similar study using only the GIAO‐MP2 ¹ H chemical shift profile and 〈?〉 dihedral angle trajectories obtained from molecular dynamics simulations at different temperatures failed to reproduce the experimental trends. This shortcoming was attributed to the inability of the force fields employed, Tripos 6.0 and MMFF94, to reproduce properly the three‐well torsional potential of vinylcyclopropane. The application of both methodologies to the calculation of population‐dependent chemical shifts in other systems is discussed. Copyright © 2002 John Wiley & Sons, Ltd.     

Assignment of Relative Configuration of Desoxypropionates by 1H NMR Spectroscopy: Method Development,Proof of Principle by Asymmetric Total Synthesis of Xylarinic Acid A and Applications

The determination of the relative configuration of 1,3‐dimethyl‐substituted alkyl chains is possible by interpretation of ¹H NMR shift differences. Additionally, assignments are feasible in a variety of deuterated solvents, because the corresponding shift differences are not significantly influenced by the solvent. The trends for Δδ values depending on functional groups adjacent to the stereogenic centers are shown. Based on a thorough comparison with literature data, the relative configuration of natural products can be predicted. For this purpose, we derived an empirical rule for the ranges in which Δδ values usually occur. Furthermore, we were able to proof the validity of our method by the successful prediction of the relative configuration for the polyketide natural product xylarinic acid A, which was confirmed by the asymmetric total synthesis of its enantiomer. Based on the proposed simple analysis of published ¹H NMR data and the determination of the relevant chemical‐shift differences, we predicted the relative configurations of several previously unassigned natural products.     

Synthesis and Bioactivity of Quinoline‐3‐carboxamide Derivatives

Twelve novel substituted 2‐chloroquinoline‐3‐carboxamide derivatives were prepared from acetanilides using the Vilsmeier–Haack reaction, producing 2‐chloro‐3‐carbaldehyde quinolines, followed by oxidation of the 3‐carbaldehyde to the carboxylic acid and coupling this group with various anilines. The structures of the synthesized compounds were confirmed by NMR, mass spectrometry, and single crystal X‐ray diffraction. The chemical shifts of H‐5 and H‐8 were shown to be influenced by the substituent at C‐6. The substituent at C‐6 was also seen to affect the chemical shift of C‐5, C‐7, and C‐8, with C‐5 and C‐7 being more shielded in 5j (F substituted) in comparison with 5g (Cl substituted) and 5d (CH₃ substituted). The compounds showed weak activity in the mM range against Gram‐positive and Gram‐negative bacteria of which 5b , 5d , and 5f showed the best activity with minimum bactericidal concentration values for 5b being 3.79 mM against methicillin‐resistant Staphylococcus aureus and 5d and 5f having minimum bactericidal concentration values of 3.77 and 1.79 mM against S. aureus ATCC 25923, respectively.     

Solid‐state 11B and 13C NMR,IR, and X‐ray crystallographic characterization of selected arylboronic acids and their catechol cyclic esters

Nine arylboronic acids, seven arylboronic catechol cyclic esters, and two trimeric arylboronic anhydrides (boroxines) are investigated using ¹¹B solid‐state NMR spectroscopy at three different magnetic field strengths (9.4, 11.7, and 21.1 T). Through the analysis of spectra of static and magic‐angle spinning samples, the ¹¹B electric field gradient and chemical shift tensors are determined. The effects of relaxation anisotropy and nutation field strength on the ¹¹B NMR line shapes are investigated. Infrared spectroscopy was also used to help identify peaks in the NMR spectra as being due to the anhydride form in some of the arylboronic acid samples. Seven new X‐ray crystallographic structures are reported. Calculations of the ¹¹B NMR parameters are performed using cluster model and periodic gauge‐including projector‐augmented wave (GIPAW) density functional theory (DFT) approaches, and the results are compared with the experimental values. Carbon‐13 solid‐state NMR experiments and spectral simulations are applied to determine the chemical shifts of the ipso carbons of the samples. One bond indirect ¹³C‐¹¹B spin‐spin (J) coupling constants are also measured experimentally and compared with calculated values. The ¹¹B/¹⁰B isotope effect on the ¹³C chemical shift of the ipso carbons of arylboronic acids and their catechol esters, as well as residual dipolar coupling, is discussed. Overall, this combined X‐ray, NMR, IR, and computational study provides valuable new insights into the relationship between NMR parameters and the structure of boronic acids and esters. Copyright © 2012 John Wiley & Sons, Ltd.     

A general chemical shift decomposition method for hyperpolarized 13C metabolite magnetic resonance imaging

Metabolic imaging with hyperpolarized carbon‐13 allows sequential steps of metabolism to be detected in vivo. Potential applications in cancer, brain, muscular, myocardial, and hepatic metabolism suggest that clinical applications could be readily developed. A primary concern in imaging hyperpolarized nuclei is the irreversible decay of the enhanced magnetization back to thermal equilibrium. Multiple methods for rapid imaging of hyperpolarized substrates and their products have been proposed with a multi‐point Dixon method distinguishing itself as a robust protocol for imaging [1‐¹³C]pyruvate. We describe here a generalized chemical shift decomposition method that incorporates a single‐shot spiral imaging sequence plus a spectroscopic sequence to retain as much spin polarization as possible while allowing detection of metabolites that have a wide range of chemical shift values. The new method is demonstrated for hyperpolarized [1‐¹³C]pyruvate, [1‐¹³C]acetoacetate, and [2‐¹³C]dihydroxyacetone. Copyright © 2016 John Wiley & Sons, Ltd.     

The bonding situation in 1,3,2‐diazaphospholene derivatives as studied by solid‐state NMR spectroscopy

The ³¹P chemical shift (CS) tensors of the 1,3,2‐diazaphospholenium cation 1 and the P‐chloro‐1,3,2‐diazaphospholenes 2 and 3 and the ³¹P and ¹⁹F CS tensors of the P‐fluoro‐1,3,2‐diazaphospholene 4 were characterized by solid‐state ³¹P and ¹⁹F NMR studies and quantum chemical model calculations. The computed orientation of the principal axes system of the ³¹P and ¹⁹F CS tensors in the P‐fluoro compound was found to be in good agreement with experimentally derived values obtained from evaluation of P–F dipolar interactions. A comparison of the trends in the chemical shifts of 1 – 4 with further available literature data confirms that the unique high shielding of δ₁₁ in the cation 1 can be related to the effective π‐conjugation in the five‐membered heterocycle, and that a further systematic decrease in δ₁₁ for the P‐halogen derivatives 2 – 4 is attributable to the increased perturbation of the π‐electron distribution by interaction with the halide donor. Copyright © 2002 John Wiley & Sons, Ltd.