Substituent effects on 13C chemical shifts of ketenimines: a GIAO/HF and DFT study

GIAO/HF and DFT methods were utilized to predict the ¹³C chemical shifts of substituted ketenimines. GIAO HF/6–311+G(2d,p) and B3LYP/6–311+G(2d,p) methods were applied on the optimized B3LYP/6–31G(d) geometries and ¹³C chemical shifts of C_α and C_β of substituted ketenimines were correlated with group electronegativities. HF and DFT calculations indicated that increasing substituent group electronegativity leads to increasing chemical shift of C_β of substituted ketenimines, whereas the C_α values decrease. Copyright © 2003 John Wiley & Sons, Ltd.     

Influence of the H/F replacement on the homoaromaticity of homotropylium ion: a GIAO/DFT theoretical study

The problem of homoaromaticity in mono-, di- and polyfluorinated- homotropylium cations is addressed by the B3LYP/6-311++G** DFT method. The energetic, structural and magnetic criteria are used for this purpose. They convincingly show that the ground state equilibrium species are aromatic, or in other words that the homoaromaticity is preserved by the (poly)fluorination. In contrast, a considerable decrease in the aromatic stabilization is observed in the transition structures (TS). According to the NICS(0) index, they vary form strongly antiaromatic, via weakly and non-aromatic to slightly aromatic transition states. However, the hierarchy of the aromaticity in fluorinated homotropylium ions predicted by NICS(0) is completely unrelated to that obtained by using the energy criterion assuming a kinetic definition of aromaticity. On the other hand the latter is closely related to geometric parameters of the equilibrium and transition structures.     

GIAO/DFT evaluation of 13C NMR chemical shifts of selected acetals based on DFT optimized geometries

DFT/B3LYP calculations of the ground-state conformation of eight cyclic and acyclic acetals are presented and compared with experimental data. Results of single-point GIAO/DFT calculations at five different levels of theory show that isotropic shieldings need to be empirically scaled to achieve agreement with experimental chemical shifts. Statistical evaluation of data indicates that the most accurate prediction of 13C chemical shifts is achieved at the MPW1PW91/6-311G** level of theory. An empirical equation describing the relationship between delta values and shielding constants is postulated. This equation has been applied to the non-chair ground-state conformation of the six-membered acetonide and to the conformationally flexible benzodioxonine derivative. The agreement observed between the experimental and predicted chemical shifts shows that calculations at the MPW1PW91/6-311G** level of theory are adequate for addressing questions of conformation.     

A H, C and N NMR spectroscopic and GIAO DFT study of ethyl 5-oxo-2-phenyl-4-(2-phenylhydrazono)-4,5-dihydro-1H-pyrrole-3-carboxylate

¹⁵N-Labelled ethyl 5-oxo-2-phenyl-4-(2-phenylhydrazono)-4,5-dihydro-1H-pyrrole-3-carboxylate was synthesized by azo-coupling of diazotized aniline (using Na¹⁵NO₂ , 99% ¹⁵N) with ethyl 4,5-dihydro-5-oxo-2-phenyl-(1H)-pyrrole-3-carboxylate. The product was formed as a tautomeric hydrazone mixture as confirmed by ¹³C and ¹⁵N chemical shifts, and was obtained as a mixture of E and Z isomers according to ⁿJ(¹⁵N, ¹³C). A comparison of the ¹H NMR data with GIAO DFT calculations enabled determination of the configuration of the carboxy ester group in both isomers.     

1H NMR spectra of alcohols and diols in chloroform: DFT/GIAO calculation of chemical shifts

Proton nuclear magnetic resonance (NMR) shifts of aliphatic alcohols in chloroform have been computed on the basis of density functional theory, the solvent being included by the integral‐equation‐formalism polarisable continuum model of Gaussian 09. Relative energies of all conformers are calculated at the Perdew, Burke and Ernzerhof (PBE)0/6‐311+G(d,p) level, and NMR shifts by the gauge‐including atomic orbital method with the PBE0/6‐311+G(d,p) geometry and the cc‐pVTZ basis set. The 208 computed CH proton NMR shifts for 34 alcohols correlate very well with the experimental values, with a gradient of 1.00 ± 0.01 and intercept close to zero; the overall root mean square difference (RMSD) is 0.08 ppm. Shifts for CH protons of diols in chloroform are well correlated with the theoretical values for (isotropic) benzene, with similar gradient and intercept (1.02 ± 0.01, ?0.13 ppm), but the overall RMSD is slightly higher, 0.12 ppm. This approach generally gives slightly better results than the CHARGE model of Abraham et al. The shifts of unsaturated alcohols in benzene have been re‐examined with Gaussian 09, but the overall fit for CH protons is not improved, and OH proton shifts are worse. Shifts of vinyl protons in alkenols are systematically overestimated, and the correlation of computed shifts against the experimental data for unsaturated alcohols follows a quadratic equation. Splitting the 20 compounds studied into two sets, and applying empirical scaling based on the quadratic for the first set to the second set, gives an RMSD of 0.10 ppm. A multi‐standard approach gives a similar result. Copyright © 2014 John Wiley & Sons, Ltd.     

A 1H, 13C and 15N NMR study in solution and in the solid state of six N-substituted pyrazoles and indazoles

Three N-substituted pyrazoles and three N-substituted indazoles [1-(4-nitrophenyl)-3,5-dimethylpyrazole (1), 1-(2,4-dinitrophenyl)-3,5-dimethylpyrazole (2), 1-tosyl-pyrazole (3), 1-p-chlorobenzoylindazole (4), 1-tosylinda-zole (5) and 2-(2-hydroxy-2-phenylethyl)-indazole (6)] have been studied by NMR spectroscopy in solution (1H, 13C, 15N) and in the solid state (13C, 15N). The chemical shifts have been compared with GIAO/DFT calculated absolute shieldings. Some discrepancies have been analyzed.     

1H NMR spectra of alcohols in hydrogen bonding solvents: DFT/GIAO calculations of chemical shifts

Proton nuclear magnetic resonance (NMR) shifts of aliphatic alcohols in hydrogen bonding solvents have been computed on the basis of density functional theory by applying the gauge‐including atomic orbital method to geometry‐optimized alcohol/solvent complexes. The OH proton shifts and hydrogen bond distances for methanol or ethanol complexed with pyridine depend very much on the functional employed and very little on the basis set, provided it is sufficiently large to give the correct quasi‐linear hydrogen bond geometry. The CH proton shifts are insensitive to both the functional and the basis set. NMR shifts for all protons in several alcohol/pyridine complexes are calculated at the Perdew, Burke and Ernzerhof PBE0/cc‐pVTZ//PBE0/6‐311 + G(d,p) level in the gas phase. The results correlate with the shifts for the pyridine‐complexed alcohols, determined by analysing data from the NMR titration of alcohols against pyridine. More pragmatically, computed shifts for a wider range of alcohols correlate with experimental shifts in neat pyridine. Shifts for alcohols in dimethylsulfoxide, based on the corresponding complexes in the gas phase, correlate well with the experimental values, but the overall root mean square difference is high (0.23 ppm), shifts for the OH, CH OH and other CH protons being systematically overestimated, by averages of 0.42, 0.21 and 0.06 ppm, respectively. If the computed shifts are corrected accordingly, a very good correlation is obtained with a gradient of 1.00 ± 0.01, an intercept of 0.00 ± 0.02 ppm and a root mean square difference of 0.09 ppm. This is a modest improvement on the result of applying the CHARGE programme to a slightly different set of alcohols. Some alcohol complexes with acetone and acetonitrile were investigated both in the gas phase and in a continuum of the relevant solvent. Copyright © 2015 John Wiley & Sons, Ltd.     

Theoretical and experimental 13C and 15N NMR investigation of guanylhydrazones in solution

Experimental and theoretical ¹⁵N and ¹³C NMR data for the three nitrobenzaldehyde guanylhydrazones are reported. The theoretical data were obtained using sequential molecular dynamics/quantum mechanics methodology for the calculation of flexible molecules in a condensed phase, followed by the use of the GIAO/DFT method with the 6–311G** basis set. The experimental ¹⁵N chemical shifts for the guanylhydrazones are compared with the calculated shifts. Copyright © 2003 John Wiley & Sons, Ltd.     

Ab Initio (GIAO) Calculations of Absolute Nuclear Shieldings for Representative Compounds Containing 1(2)H, 6(7)Li, 11B, 13C, 14(15)N, 17O, 19F, 29Si, 31P, 33S,and 35Cl Nuclei

Two kinds of ab initio calculations (B3LYP and HF) using the GIAO approach have been carried out for fifteen H, three Li, three B, eleven C, seven N, nine O, four F, three Si, four P, six S and five Cl containing derivatives. The calculated absolute nuclear shieldings have been compared with experimental absolute values (either measured or estimated from relative chemical shifts) when available or with relative chemical shifts (¹¹B, ³⁵Cl). The correlations range from good to excellent and only three compounds (PN, P₂H₂, SO₂) deviate significantly.     

Association of symmetrical alkane diols with pyridine: DFT/GIAO calculation of 1H NMR chemical shifts

Proton nuclear magnetic resonance (NMR) shifts of the free diol and of its 1 : 1 and 1 : 2 hydrogen‐bonded complexes with pyridine have been computed for five symmetrical alkane diols on the basis of density functional theory, by applying the gauge‐including atomic orbital method to geometry‐optimized conformers. For certain conformers, intramolecular OH ···OH interactions, evidenced by high NMR OH proton shifts, are further enhanced on going from the free diol to the corresponding 1 : 1 diol/pyridine complex. This is confirmed by atoms‐in‐molecules and non‐covalent interaction plots. The computed OH and CH proton shifts for the diol and the two complexes correlate well with values obtained by analysing data from the NMR titration of the diols in benzene against pyridine. Shift values for the diols in neat pyridine are calculated by weighting the shifts of the various protons in the three forms (free diol, 1 : 1 and 1 : 2 diol/pyridine complexes) according to the experimentally determined association constants. The results are in good agreement with those observed, and after empirical scaling, the root mean square difference is 0.18 ppm. Copyright © 2016 John Wiley & Sons, Ltd.     

Structural study of oxalamide compounds: H, C, and DFT calculations

The conformational properties of some N-alkyl, N,N′-dialky, and tetraalkyloxalamides have been investigated, in vacuo and in solvent using DFT methods at the B3LYP/6-31G^∗∗ computational level. Special emphasis has been given on oxalamides with substituents of the type -CH₂CH₂OH. In oxalamides with the N-H group (N-alkyl and N,N′-dialky), the most stable conformations are those in which the oxalamide moiety adopts a planar s-trans arrangement and the amide bonds are trans. A different situation appears in the case of tetraalkyloxalamides, in which the oxalamide moiety always adopts a skewed arrangement and there are conformations with similar energy. A careful study of ¹³C and ¹H NMR spectra together with theoretical calculations (GIAO method) allowed the assignment of the signals of these conformers. The presence of the -CH₂CH₂OH chain produces numerous rotamers. The most stable rotamers, in vacuo, are those with strong intramolecular hydrogen bonds, however in solvent, hydrogen bonds are not crucial to establish the most stable specie and depend on the solvent used.     

Substituent effects on scalar J(13C, 13C) couplings in pyrimidines. An experimental and DFT study

One- two- and three 13C, 13C (n = 1, 2, 3) scalar couplings, (n)J(C,C) in a set of pyrimidine derivatives were studied both experimentally at natural abundance and theoretically by their DFT calculation of all four contributions. Trends of non-contact terms are discussed and substituent effects are rationalized, comparing some of them with the corresponding values in benzene and pyridine. Although substituent effects on non-contact terms are relatively important, the whole trend is dominated by the Fermi contact term. According to the current literature, substituent effects on 1J(C,C) couplings in benzene derivatives are dominated by the inductive effect, which, apparently, is also the case in nitrogen heteroaromatic compounds. However, some differences observed in this work for substituent effects on 1J(C,C) couplings in pyrimidine derivatives suggest that in the latter type of compounds substituent effects can be affected by the orientation of the ring nitrogen lone pairs.     

Complete 1H, 13C and 15N NMR assignment of tirapazamine and related 1,2,4-benzotriazine N-oxides

1H, 13C and 15N NMR measurements (1D and 2D including 1H--15N gs-HMBC) have been carried out on 3-amino-1, 2,4-benzotriazine and a series of N-oxides and complete assignments established. N-Oxidation at any position resulted in large upfield shifts of the corresponding N-1 and N-2 resonances and downfield shifts for N-4 with the exception of the 3-amino-1,2,4-benzotriazine 1-oxide in which a small upfield shift of N-4 was observed. Density functional GIAO calculations of the 15N and 13C chemical shifts [B3LYP/6-31G(d)//B3LYP/6-311+G(2d,p)] gave good agreement with experimental values confirming the assignments. The combination of 13C and 15N NMR provides an unambiguous method for assigning the 1H and 13C resonances of N-oxides of 1,2,4-benzotriazines.     

1H, 13C and 15N NMR spectra of ciprofloxacin

1H NMR assignment, including the values of delta(H) and J(H,H) for the cyclopropane moiety, and 13C NMR and 15N NMR spectral data for ciprofloxacin are presented.     

Conformational analysis of cis‐3, 5‐dioxa‐bicyclo[5.4.0]undecane and its 4‐substituted derivatives by DNMR,molecular modeling,and GIAO/DFT methods

Temperature‐dependent ¹H and ¹³C‐NMR spectra of the title compounds are presented. Coalescence effects are discussed and assigned to dynamic process—the interconversion of bicyclic system. The free energies of activation covered the range 39–52 kJ/mol. The dioxepane ring adopts twist‐chair (TC) conformation. GIAO/DFT calculation of isotropic shieldings for the set of low‐energy conformations showed that only one conformer is present at 298 K in solution that matched well with experimental data. Copyright © 2010 John Wiley & Sons, Ltd.     

A C and N experimental NMR and theoretical study of the structure of linear primary aliphatic amines and ammonium salts: from C1 to C18

Eighteen aliphatic linear amines, from methylamine to stearylamine, have been experimentally studied by NMR and theoretically calculated at the GIAO/B3LYP/6-311++G(d,p) level. A partial exploration of their conformation has been carried out, mainly to determine the effect on the chemical shifts. In solution and for neutral amines, ¹⁵N chemical shifts indicate a mixture of two conformations. In the solid state (CPMAS NMR) only the subset of solid amines has been studied (from C14 to C18). The ¹⁵N signals of the corresponding ammonium salts in the solid state depend on the counteranions, Cl⁻ and CF₃CO₂⁻, a result that is theoretically proven.     

A multinuclear 1H, 13C, and 15N magnetic resonance study of ten 4-nitropyridine N-oxides

The ¹H, ¹³C, and ¹⁵N NMR chemical shifts of ten 4-nitropyridine N-oxide derivatives are assigned. The shielding of the pyridine ring nitrogen is sensitive to ring substitution through inductive effects, steric effects by ortho-substituents, and the possibility for electron delocalisation (resonance energy). In solution, 3-ethylnitrosoamino-4-nitropyridine N-oxide has two tautomers. The proposed reason is the steric crowding between vicinal 4-nitro and 3-ethylnitrosoamino groups, causing a disturbance to amino nitrogen that can delocalize its lone pair to the oxygen atom of the nitroso group.     

1H, 13C and 15N NMR assignments of phenazopyridine derivatives

Phenazopyridine hydrochloride (1), a drug in clinical use for many decades, and some derivatives were studied by one- and two-dimensional (1)H, (13)C and (15)N NMR methodology. The assignments, combined with DFT calculations, reveal that the preferred protonation site of the drug is the pyridine ring nitrogen atom. The chemoselective acetylation of phenazopyridine (2) and its influence on the polarization of the azo nitrogen atoms were evidenced by the (15)N NMR spectra. Molecular calculations of the phenazopyridines 2-4 show that the pyridine and phenyl groups are oriented in an antiperiplanar conformation with intramolecular hydrogen bonding between the N-b atom and the C-2 amino group preserving the E-azo stereochemistry.