Crystallographic and Dynamic Aspects of Solid‐State NMR Calibration Compounds: Towards ab Initio NMR Crystallography

The excellent results of dispersion‐corrected density functional theory (DFT‐D) calculations for static systems have been well established over the past decade. The introduction of dynamics into DFT‐D calculations is a target, especially for the field of molecular NMR crystallography. Four ¹³C ss‐NMR calibration compounds are investigated by single‐crystal X‐ray diffraction, molecular dynamics and DFT‐D calculations. The crystal structure of 3‐methylglutaric acid is reported. The rotator phases of adamantane and hexamethylbenzene at room temperature are successfully reproduced in the molecular dynamics simulations. The calculated ¹³C chemical shifts of these compounds are in excellent agreement with experiment, with a root‐mean‐square deviation of 2.0 ppm. It is confirmed that a combination of classical molecular dynamics and DFT‐D chemical shift calculation improves the accuracy of calculated chemical shifts.     

Multiply Borylated Arenes: X‐ray Crystal Structure Analyses and Quantum Chemical Calculations

Optimised synthesis procedures and results of X‐ray single crystal structure analyses for 4‐(dibromoboryl)toluene, 1, 3‐bis(dibromoboryl)benzene, 1, 4‐bis(dibromoboryl)benzene, and 1, 3, 5‐tris(dibromoboryl)benzene are reported. These compounds have also been studied by Hartree‐Fock (HF), density functional theory (DFT), and Mßller‐Plesset second‐order perturbation (MP2) methods in combination with the polarized double‐ζ valence (SVP) and polarized triple‐ζ valence (TZVP) basis sets of Ahlrichs and coworkers. A comparison of the quantum chemical results for optimised geometries and computed NMR chemical shifts with experiment is presented to test the quality of the various methods for this class of compounds. All DFT methods tested yield optimised geometries within the experimental error bars of 3σ for bond lengths, whereas larger deviations among the methods are observed for computed NMR chemical shifts. This calibration recommends the B3LYP/SVP combination as a reliable and computationally efficient level of theory to assess the structures and absolute and relative ¹H‐, ¹³C‐ and ¹¹B NMR shift values of borylated aromatic compounds in future investigations.     

Are there reliable DFT approaches for 13C NMR chemical shift predictions of fullerene C60 derivatives?

The relationships between experimental and theoretical ¹³C NMR chemical shifts of a pristine fullerene C₆₀, monoadducts from [2 + n] cycloaddition (n = 1–3), and one [2 + 1] bis‐adduct are systematically analyzed for the first time by using diverse quantum‐chemical levels of theory. These levels involved B3LYP, B3PW91, B97‐2, mPW1PW91, PBE1PBE, and X3LYP hybrid functionals combined with 3‐21G, 6‐31G, 6‐31G(d), 6‐31G(d,p), 6‐31G(d,2p), LanL2DZ, and SDDAll basis sets. X3LYP/6‐31G approach is determined to have the lowest deviations from the ¹³C NMR experimental data compared to the other methods for all the fullerene compounds (mean absolute error value is 0.856 ppm and root mean squared error value is 1.197 ppm). The highest deviations are characteristic for α (sp² C2/C5/C8/C10) and β (sp² C6/C7/C11/C12) carbon atoms relative to a functionalization site and for those (sp³ C1/C9) directly attached with a side fragment in the [2 + n] monoadducts (n = 1–3). A probable reason of such deviation is that the approaches do not take into account a contribution of paramagnetic ring currents to ¹³C NMR chemical shifts. The results will be useful in design of novel fullerene derivatives and in performing unambiguous ¹³C NMR chemical shift assignments with modern quantum chemistry calculations.     

Theoretical Study of 13C Chemical Shifts Structures of Some ortho-Substituted 3-Anilino-2-nitrobenzo[b]thiophenes and 2-Anilino-3-nitrobenzo[b]thiophenes and Comparison with Experimental

¹³C NMR chemical shifts have been calculated for structures of some substituted 3‐anilino‐2‐nitrobenzo‐[b]thiophenes ( 2 o) and 2‐anilino‐3‐nitrobenzo[b]thiophenes ( 3 o) derivatives containing OH, NH₂, OMe, Me, Et, H, F, Cl and Br. The molecular structures were fully optimized using B3LYP/6‐31G(d,p). The calculation of the ¹³C shielding tensors employed the GAUSSIAN 03 implementation of the gauge‐including atomic orbital (GIAO) and continuous set of gauge transformations (CSGT) by using 6‐311++G(d,p) basis set at density functional levels of theories (DFT). The isotropic and the anisotropy parameters of chemical shielding for all compounds are calculated. The predicted ¹³C chemical shifts are derived from equation δ=δ₀+δ where δ is the chemical shift, δ is the absolute shielding, and δ₀ is the absolute shielding of the standard TMS. Excellent linear relationships have been observed between experimental and calculated ¹³C NMR chemical shifts for all derivatives     

GIAO/DFT studies on 1,2,4‐triazole‐5‐thiones and their propargyl derivatives

Density functional theory (DFT)/Becke–Lee–Yang–Parr (B3LYP) and gauge‐including atomic orbital (GIAO) calculations were performed on a number of 1,2,4‐triazole derivatives, and the optimized structural parameters were employed to ascertain the nature of their predominant tautomers. ¹³C and ¹⁵N NMR chemical shifts of 3‐substituted 1,2,4‐triazole‐5‐thiones and their propargylated derivatives were calculated via GIAO/DFT approach at the B3LYP level of theory with geometry optimization using a 6‐311++G** basis set. A good agreement between theoretical and experimental ¹³C and ¹⁵N NMR chemical shifts could be found for the systems investigated. The data generated were useful in predicting ¹⁵N chemical shifts of all the nitrogen atoms of the triazole ring, some of which could not be obtained in solution state ¹⁵N HMBC/HSQC NMR measurements. The energy profile computed for the dipropargylated derivatives was found to follow the product distribution profile of regioisomers formed during propargylation of 1,2,4‐triazole thiones. Copyright © 2013 John Wiley & Sons, Ltd.     

The determination of sulfoxide configuration in five-membered rings using NMR spectroscopy and DFT calculations

Cyclic five-membered ring sulfoxides and sulfones were prepared by a stepwise in situ oxidation of the corresponding sulfides with meta-chloroperbenzoic acid in an NMR tube. The oxidation was followed by NMR and both ¹H and ¹³C NMR data were collected. The geometries of all of the compounds were optimized using the DFT B3LYP/6-31G⁷ method and the ¹³C and ¹H chemical shifts were calculated for geometry-optimized structures with the DFT B3LYP/6-31++G⁷ method. The calculated ¹³C chemical shifts induced by oxidation (Δδ values) were in very good agreement with the experimental data and could be used to determine the oxidation state of the sulfur atom (–S–, –SO–, –SO₂–). The characteristic differences of the induced oxidation chemical shifts of the carbon atoms in the α-position and β-position to sulfur were successfully used to distinguish between the diastereoisomeric sulfoxides and allowed configuration determination.     

The determination of sulfoxide configuration in six-membered rings using NMR spectroscopy and DFT calculations

Cyclic six-membered ring sulfoxides and sulfones were prepared by a stepwise in situ oxidation of the corresponding sulfides with meta-chloroperbenzoic acid in an NMR tube. The oxidation was followed by NMR spectra and the ¹H and ¹³C NMR data were collected. The geometries of all of the compounds were optimized using the DFT B3LYP/6-31G^∗∗ method and the ¹³C and ¹H NMR chemical shifts were calculated for geometry-optimized structures with the DFT B3LYP/6-31++G^∗∗ method. The calculated ¹³C NMR chemical shifts induced by oxidation (Δδ values) are in very good agreement with the experimental data and can be used to determine the oxidation state of the sulfur atom (-S-, -SO-, -SO₂-). The characteristic differences of the induced oxidation chemical shifts of carbon atoms at the α- and β-position to sulfur were successfully used for distinguishing between the diastereoisomeric sulfoxides.     

Theoretical Studies on the Infrared Vibrational Spectra ,Thermodynamic Properties and Nuclear Magnetic Resonance Spectra for Polynitro-1,3-bishomopentaprismanes

Based on the optimized molecular geometries at the DFT‐B3LYP/6‐31G?? level, IR spectra, thermodynamic functions, as well as ¹³C and ¹H NMR chemical shifts, were obtained and discussed for polynitro‐1,3‐bishomo‐pentaprismanes (PNBPP). The comparison of the calculated IR frequencies and NMR chemical shifts showed considerable agreements with the available experimental results. IR regions, ¹³C and ¹H NMR chemical shifts of PNBPP were assigned. The relationships of the thermodynamic functions with temperature and the number of nitro groups were discussed, and it was found that the latter showed a good group additivity rule. These calculated data and discussions would be helpful for the further study of PNBPP.     

Quantum‐chemical analyses of aromaticity,UV spectra,and NMR chemical shifts in plumbacyclopentadienylidenes stabilized by Lewis bases

We carried out a series of zeroth‐order regular approximation (ZORA)‐density functional theory (DFT) and ZORA‐time‐dependent (TD)‐DFT calculations for molecular geometries, NMR chemical shifts, nucleus‐independent chemical shifts (NICS), and electronic transition energies of plumbacyclopentadienylidenes stabilized by several Lewis bases, (Ph)₂(^tBuMe₂Si)₂C₄PbL₁L₂ (L₁, L₂ = tetrahydrofuran, Pyridine, N‐heterocyclic carbene), and their model molecules. We mainly discussed the Lewis‐base effect on the aromaticity of these complexes. The NICS was used to examine the aromaticity. The NICS values showed that the aromaticity of these complexes increases when the donation from the Lewis bases to Pb becomes large. This trend seems to be reasonable when the 4n‐Huckel rule is applied to the fractional π‐electron number. The calculated ¹³C‐ and ²⁰⁷Pb‐NMR chemical shifts and the calculated UV transition energies reasonably reproduced the experimental trends. We found a specific relationship between the ¹³C‐NMR chemical shifts and the transition energies. As we expected, the relativistic effect was essential to reproduce a trend not only in the ²⁰⁷Pb‐NMR chemical shifts and J[Pb‐C] but also in the ¹³C‐NMR chemical shifts of carbons adjacent to the lead atom. © 2014 Wiley Periodicals, Inc.     

Stereochemical analysis of the 3α‐ and 3β‐hydroxy metabolites of tibolone through NMR and quantum‐chemical investigations. An experimental test of GIAO calculations

The configuration at C‐3 of the 3α‐ and 3β‐hydroxy metabolites of tibolone was studied by extensive application of one‐ and two‐dimensional ¹H and ¹³C NMR spectroscopy combined with molecular modeling performed at the B3LYP/6–31G(d) level. Using HF and DFT GIAO methods, shielding tensors of the two molecules were computed; comparison of the calculated NMR chemical shifts with the experimental values revealed that the density functional methods produced the best results for assigning proton and carbon resonances. Although steroids are relatively large molecules, the present approach appears accurate enough to allow the determination of relative configurations by using calculated ¹³C resonances; the chemical shift of pairs of geminal α/β hydrogen atoms can also be established by using calculated ¹H resonances. Copyright © 2002 John Wiley & Sons, Ltd.     

1H NMR analysis of O‐methyl‐inositol isomers: a joint experimental and theoretical study

Density functional theory (DFT) calculations of ¹H NMR chemical shifts for l ‐quebrachitol isomers were performed using the B3LYP functional employing the 6‐31G(d,p) and 6‐311 + G(2d,p) basis sets. The effect of the solvent on the B3LYP‐calculated NMR spectrum was accounted for using the polarizable continuum model. Comparison is made with experimental ¹H NMR spectroscopic data, which shed light on the average uncertainty present in DFT calculations of chemical shifts and showed that the best match between experimental and theoretical B3LYP ¹H NMR profiles is a good strategy to assign the molecular structure present in the sample handled in the experimental measurements. Among four plausible O‐methyl‐inositol isomers, the l ‐quebrachitol 2a structure was unambiguously assigned based only on the comparative analysis of experimental and theoretical ¹H NMR chemical shift data. The B3LYP infrared (IR) spectrum was also calculated for the four isomers and compared with the experimental data, with analysis of the theoretical IR profiles corroborating assignment of the 2a structure. Therefore, it is confirmed in this study that a combined experimental/DFT spectroscopic investigation is a powerful tool in structural/conformational analysis studies. Copyright © 2012 John Wiley & Sons, Ltd.     

Experimental (FT-IR, FT-Raman, H, C NMR) and theoretical study of alkali metal 2-aminonicotinates

The influence of lithium, sodium, potassium, rubidium and cesium on the electronic system of 2-aminonicotinic acid (2-ANA) was studied by the methods of molecular spectroscopy. The vibrational (FT-IR, FT-Raman) and NMR (¹H and ¹³C) spectra of 2-aminonicotinic acid and its alkali metal salts were recorded. Characteristic shifts and changes in intensities of bands along the metal series were observed. The changes of chemical shifts of protons (¹H NMR) and carbons (¹³C NMR) in the series of studied alkali metal 2-aminonicotinates (2-AN) were observed too.Optimized geometrical structures of the studied compounds were calculated by the B3LYP method using the 6-311++G** basis set. Aromaticity indices, atomic charges, dipole moments and energies were also calculated. The theoretical chemical shifts in ¹H and ¹³C NMR spectra and theoretical wavenumbers and intensities of IR and Raman spectra were determined. The calculated parameters were compared to the experimental characteristics of the studied compounds.     

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.     

The effect of an unsymmetric branched branch on the 13C NMR chemical shifts of main chain carbons in polyethylene

The ¹³C NMR spectra of copolymers of ethylene with 4‐methyl‐1‐hexene and 4‐methyl‐1‐pentene, respectively, were compared. The 4‐methyl‐1‐hexene/ethylene copolymer, which contains an unsymmetric 2‐methylbutyl branch, exhibits two distinct ¹³C NMR peaks for each of the pairwise methylenes spaced one, two, and three carbons from the backbone methine. The chemical shift differences for these pairwise methylenes are 57.4 Hz, 18.7 Hz, and 4.3 Hz, respectively, with chemical shift differences decreasing with increasing distance from the asymmetric carbon. The frequency differences for carbons farther from the branch were not distinguishable. The magnitude of the chemical shift difference also varies with temperature, with the first and second methylene carbon chemical shift differences decreasing with increasing temperature. The third carbon is almost unaffected by temperature variations. In contrast, the 4‐methyl‐1‐pentene/ethylene copolymer exhibits a single peak for each of the pairs of methylenes in the branch's vicinity. This is the first reported observation of a branched branch affecting the chemical shifts of main chain carbons in polyethylene containing short chain branches. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1210–1213, 2000     

13C GIAO DFT calculation as a tool for configuration prediction of N–O group in saturated heterocyclic N‐oxides

Tropane, tropinone, pseudopelletierine and cocaine were oxidized in situ in a nuclear magnetic resonance (NMR) tube providing mixtures of exo/endo N‐oxides. Observed ¹³C chemical shifts were correlated with values calculated by gauge‐including atomic orbitals density functional theory (DFT) OPBE/6‐31G* method using DFT B3LYP/6‐31G* optimized geometries. The same method of ¹³C chemical shift calculation was applied on series of methyl‐substituted 1‐methylpiperidines and their epimeric N‐oxides described in literature. The results show that using this undemanding calculation method enables assignment of configuration of N–O group in N‐epimeric saturated heterocyclic N‐oxides. The approach enables assigning of the configuration with high degree of certainty even if NMR data of only one isomer are available. An improved method of in situ oxidation of starting amines in an NMR tube is also described. Copyright © 2012 John Wiley & Sons, Ltd.     

13C NMR studies of isomeric piperidine derivatives with opiate properties and related compounds

The ¹³C NMR spectra of a series of methyl substituted 3-arylpiperidines and 4-aryl-4-piperidinols and related compounds are reported, and chemical shift data analysed in terms of the configuration and conformation of isomeric pairs. Special attention is given to the γ chemical shift parameter of axial methyl, and the effects of a nitrogen lone pair orbital and hydroxyl or acyloxy group on the chemical shifts of ring and methyl carbons.     

Comparison of GIAO and CSGT for calculating 13C and 15N nuclear magnetic resonance chemical shifts of substituent neutral 5‐aminotetrazole and 5‐nitrotetrazole compounds

The comparison of the gauge‐including atomic orbital (GIAO) and the continuous set of gauge transformation methods for calculating nuclear magnetic chemical shifts (CSs) mainly at density functional levels of theory are presented. Isotropic ¹³ C and ¹⁵ N magnetic CS for 14 compounds of tetrazoles are reported. Compared with establishing a convenient and consistent protocol to be employed for confirming the experimental ¹³ C and ¹⁵ N NMR spectra of tetrazole compounds, different combinations of functionals and basis sets were considered. The most reliable results were obtained at GIAO/B3LYP/aug‐cc‐pVDZ with integral equation formulation for the polarizable continuum model (PCM), which has the smallest root mean square errors and can be used to calculate ¹³ C and ¹⁵ N NMR CS with a very high accuracy for tetrazoles. These results show that the accurately calculated ¹⁵N NMR CS of tetrazoles could be used for the evaluation of the intrinsic relationship between structure and explosive properties. Copyright © 2012 John Wiley & Sons, Ltd.     

13C NMR spectroscopic studies of the behaviors of carbonyl compounds in various solutions

¹³C NMR spectroscopic studies were performed for carbonyl compounds having a hydroxyl group, a carboalkoxy group, an acetoxy group, or a carboxyl group in various solvents with different polarities for observation of their behaviors of ¹³C NMR chemical shifts of carbonyl carbons in solutions. It was found that the chemical shifts of the carbonyl carbons in ¹³C NMR have good correlation with the empirical parameter for solvent polarities, E_T^N, depending on the structures. Inter- or intramolecular hydrogen bonding and dipolar-dipolar interactions appear to play a key role in this observation.     

Comparison of various density functional methods for distinguishing stereoisomers based on computed (1)H or (13)C NMR chemical shifts using diastereomeric penam beta-lactams as a test set

Full (1)H and (13)C NMR chemical shift assignments were made for two sets of penam beta-lactams: namely, the diastereomeric (2S, 5S, 6S)-, (2S, 5R, 6R)-, (2S, 5S, 6R)-, and (2S, 5R, 6S)-methyl 6-(1,3-dioxoisoindolin-2-yl)-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylates (1-4) and (2S, 5R, 6R)-, (2S, 5S, 6R)-, and (2S, 5R, 6S)-6-(1,3-dioxoisoindolin-2-yl)-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acids (6-8). Each penam was then modeled as a family of conformers obtained from Monte Carlo searches using the AMBER* force field followed by IEFPCM/B3LYP/6-31G(d) geometry optimization of each conformer using chloroform solvation. (1)H and (13)C chemical shifts for each conformer were computed at the WP04, WC04, B3LYP, and PBE1 density functional levels as Boltzmann averages of IEFPCM/B3LYP/6-311 + G(2d,p) energies over each family. Comparisons between experimental and theoretical chemical shift data were made using the total absolute error (|Deltadelta| (T)) criterion. For the (1)H shift data, all methods were sufficiently accurate to identify the proper stereoisomers. Computed (13)C shifts were not always successful in identifying the correct stereoisomer, regardless of which DFT method was used. The relative ability of each theoretical approach to discriminate among stereoisomers on the basis of proton shifts was also evaluated.