15N NMR substituent effects in pyridines and pyrimidines

¹⁵N chemical shifts of 32 substituted pyridines and 19 substituted pyrimidines, together with additional data from the literature, are used to evalute substituent increments, A_i and A_ik, in the respective series. Differential chemical shifts, Δδ(N), correlate with corresponding Δδ(C) values whereby, on the ppm scale, nitrogen shifts are approximately three times more sensitive towards substituents than carbon shifts. The ¹⁵N increments have proven additive and useful for assignment purposes.     

Interpretation of substituent effects on 13C and 15N NMR chemical shifts in 6-substituted purines

A range of purine derivatives modified at position 6 of the basic purine skeleton exhibit a variety of biological activities. Several derivatives are used or tested nowadays for pharmacological treatments. The present work aims to analyze the effects of substituents on the electron distribution in the purine core as reflected by NMR chemical shifts. We collected a comprehensive set of experimental NMR data for a variety of 6-substituted purines (-NH(2), -NHMe, -NMe(2), -OMe, -Me, -CCH, and -CN) and determined the molecular and crystal structures of three derivatives (-NHMe, -CCH, and -CN) by X-ray diffraction. The density-functional methods calibrated in our recent study (Phys. Chem. Chem. Phys., 2010, 12, 5126) have been employed to enable understanding of the substituent-induced changes in the NMR chemical shifts of the atoms in the purine skeleton. Analyses of the nuclear shielding using localized molecular orbitals (LMOs), specifically the natural LMOs (NLMOs) and Pipek-Mezey LMOs, were used to break down the values of the isotropic (13)C and (15)N NMR chemical shifts and the chemical shift tensors into the contributions of the individual LMOs. The experimental and calculated trends in the chemical shift of the N-3 atom correlate nicely with the Hammett constants (σ(para)) and the calculated natural charges on N-3, whereas the contributions of the LMOs to the N-1 and C-6 chemical shifts are found to be more complex.     

The 15N NMR study of silatranes

Various silatrane compounds were studied by means of ¹⁵N NMR spectroscopy. The quantum chemical calculations of some of the compounds were carried out using CNDO/2 method. The following correlations were obtained, i.e., ¹⁵N chemical shifts vary linearly with Taft's polar substituent constants (s) of the substituents R on the silicon atoms, and also with the net charge densities on the nitrogen atoms. From both experimental and theoretical aspects, it could be concluded that the SiN dative bonds in a series of silatrane compounds actually exist.     

Solid state 15N NMR study of 15N enriched melamine-formaldehyde resins

Molecular dynamics and structure of uncured and cured melamine-formaldehyde resins isotopically ¹⁵N enriched at amine sites were studied by solid-state ¹⁵N nuclear magnetic resonance (NMR). Spectra recorded with direct (DP) and cross-polarization (CP) pulse sequences reflect two motionally different regions arising from similar chemical structures. DP spectra of uncured resins at higher temperatures have narrow lines and the detection of slightly different structural units is possible. With increasing crosslinking resonances broaden and overlap and the direct detection of individual signals in cured resins is not possible. On the basis of variable contact time, variable spinning speed, and interrupted decoupling experiments three protonated and one nonprotonated group of signals are identified in the CP spectra for all samples. Short polarization-transfer rates, T_NH, for nonprotonated nitrogen in uncured and lightly cured samples reveal more effective hydrogen bonding in viscous and rubber-like resins compared to the highly cured rigid resins. The rigid portions of the resins exhibit longer T₁ and short T_1ρ relaxation times, while the shorter T₁ times and longer T_1ρ times are associated with the more mobile portion of samples. ©1995 John Wiley & Sons, Inc.     

Experimental and theoretical study of substituent effects of iodonitrobenzenes

The electronic structures and substituent effects of o-, m-, and p-iodonitrobenzene have been studied by ultraviolet photoelectron spectroscopy (UPS). The observed bands were interpreted on the basis of empirical arguments and theoretical calculations. The analysis of electronic effects of the donor/acceptor substituent groups is essential for the reliable assignment of the observed photoelectron spectra. The investigation of pi- and n-orbital ionization potentials enabled us to describe the correlation between substituent effects and the relative reactivities of the iodonitrobenzenes. It was found that the energy order of the pi(2) and n(II) parallel orbitals is reversed as a result of the combined influence of the electron-withdrawing nitro group and the electron-donating iodine atom. Distinct changes of the pi and n bands occur in o-iodonitrobenzene. This characteristic depends on the conjugation between the pi orbitals of the benzene ring and the nitro group and the interaction of in-plane lone pairs of iodine and one of the oxygen atoms of the nitro group in the adjacent position. This might contribute to the high reactivity of o-iodonitrobenzene in a number of reactions.     

NMR chemical shift substituent effects: 2-α-monosubstituted N,N-diethylacetamides

¹H NMR chemical shifts for some α-hetero-substituted N,N-diethylacetamides were recorded. The resonance assignments for the syn- and anti-methylene and -methyl protons have been made unambiguously through their aromatic solvent induced shifts and are opposed to the literture assignments for the N-methylene protons. An empirical relationship between the Charton polar (σ_L) and steric (V) parameters and the α-methylene proton resonances was found. The N-methylene proton chemical shifts also showed a qualitative dependence on the α-substituent electronegativity, while the N-ethyl methyl proton chemical shifts were related to the α-substituent steric effects. The Paulsen and Todt anisotropic model and the more populated rotamers proposed seem to explain the results very well.     

13C and 15N NMR study of acyclic vicinal diastereoisomers. Conformational effects

Conformations of aliphatic diastereoisomers with vicinal asymmetric centers (2,3-disubstituted butanes and 5,6-disubstituted n-decanes) are discussed in terms of their ¹³C and, in some cases, ¹⁵N chemical shifts and spin-lattice relaxation times. Solvent and protonation effects are explained by conformational changes in the isomers.     

A 15N NMR study of some azoles

¹⁵N NMR data are reported for 42 azoles, taken mostly at a standard concentration and in a common solvent (0.5 M dimethyl sulfoxide with a 0.01 M increment of Cr(acac)₃ for each nitrogen atom present). Signal assignments were assisted by comparison with ¹⁴N line widths, the use of ²J(¹⁵N¹H) couplings, and shielding calculations obtained by the INDO/S–SOS approach. The generally large differences in nitrogen-shielding changes permitted rather facile shift assignments.     

A GIAO/DFT study of 1H, 13C and 15N shieldings in amines and its relevance in conformational analysis

The 1H, 13C and 15N absolute shieldings of 13 amines were calculated at the GIAO/B3LYP/6-311++G** level. For some compounds (ethylamine, piperidine and 1-methylpiperidine) two conformations were calculated. The 13C and 15N data could be correctly correlated with experimental chemical shifts, allowing the conformation of 1-methylpiperidine to be established. The 1H NMR absolute shieldings, although less well correlated with delta values, were used to account for the anisotropy effects of the N lone pair.     

Theoretical and experimental study of 15N NMR protonation shifts

A combined theoretical and experimental study revealed that the nature of the upfield (shielding) protonation effect in ¹⁵N NMR originates in the change of the contribution of the sp²‐hybridized nitrogen lone pair on protonation resulting in a marked shielding of nitrogen of about 100 ppm. On the contrary, for amine‐type nitrogen, protonation of the nitrogen lone pair results in the deshielding protonation effect of about 25 ppm, so that the total deshielding protonation effect of about 10 ppm is due to the interplay of the contributions of adjacent natural bond orbitals. A versatile computational scheme for the calculation of ¹⁵N NMR chemical shifts of protonated nitrogen species and their neutral precursors is proposed at the density functional theory level taking into account solvent effects within the supermolecule solvation model. Copyright © 2015 John Wiley & Sons, Ltd.     

15N NMR study of azo-hydrazone tautomerism of 15N-labelled azo dyestuffs

¹⁵N chemical shifts of 3-methyl-1-phenylpyrazole-4,5-dione 4-phenylhydrazone (1), 4-hydroxyazobenzene (2), 2-hydroxy-5-tert-butylazobenzene (3) and 1-phenylazo-2-naphthol (4), monolabelled with ¹⁵N at α-(compounds prepared from ¹⁵N-aniline) and β-positions (compounds prepared from Na¹⁵NO₂), have been measured and the temperature dependence of these chemical shifts followed between 240 and 360 K. For 4, representing a mixture of the azo and hydrazone forms, the hydrazone content has been calculated from the ¹⁵N chemical shifts of both nitrogen atoms at various temperatures. The two calculations gave identical results.     

NMR studies in the heterocyclic series XXIV—1H, 13C and 15N study of 15N labelled indazoles

The ¹⁵N chemical shifts and ¹H? ¹⁵N and ¹³C? ¹⁵N coupling constants of nine monolabelled indazoles were measured and assigned. The experimental values are discussed in terms of the indazolic and iso-indazolic structures, and compared with literature data for other related heterocycles. All the results are consistent with an N-1(H) tautomeric structure for indazole in DMSO-d₆.     

Investigation of substituent effects on the 1H NMR spectra of chalcones

¹H NMR spectra of 26 substituted chalcones (3-aryl-1 phenyl-2-propene-1-ones and 1-aryl-3-phenyl-2-propene-1-ones) have been studied. The chemical shifts of the α and β protons to the carbonyl group were correlated with Hammett s? parameters. To gain information on the effect of the transmission of the resonance and inductive contributions of the substituents on the chemical shifts of H-α and H-β, two parameter correlations with ?? and ?? parameters were also perfomed. The chemical shifts of the aromatic protons of the para-disubstituted benzene ring correlated with the a_i substituent increments.     

Pronounced stereospecificity of 1H, 13C, 15N and 77Se shielding constants in the selenophenyl oximes as shown by NMR spectroscopy and GIAO calculations

In the ¹H and ¹³C NMR spectra of 1‐(2‐selenophenyl)‐1‐alkanone oximes, the ¹H, the ¹³C‐3 and ¹³C‐5 signals of the selenophene ring are shifted by 0.1–0.4, 2.5–3.0 and 5.5–6.0 ppm, respectively, to higher frequencies, whereas those of the ¹³C‐1, ¹³C‐2 and ¹³C‐4 carbons are shifted by 4–5, ～11 and ～1.7 ppm to lower frequencies on going from the E to Z isomer. The ¹⁵N chemical shift of the oximic nitrogen is larger by 13–16 ppm in the E isomer relative to the Z isomer. An extraordinarily large difference (above 90 ppm) between the ⁷⁷Se resonance positions is revealed in the studied oxime isomers, the ⁷⁷Se peak being shifted to higher frequencies in the Z isomer. The trends in the changes of the measured chemical shifts are well reproduced by the GIAO calculations of the ¹H, ¹³C, ¹⁵N and ⁷⁷Se shielding constants in the energy‐favorable conformation with the syn orientation of the? C?N? O? H group relative to the selenophene ring. Copyright © 2009 John Wiley & Sons, Ltd.     

Substituent effects on 15N NMR chemical shifts in selected N-alkylthiohydroxamic acids. A comparative study

The 15N NMR spectra of three N-alkyl-delta-carbomethoxyvalerothiohydroxamic acids (2) and six synthesized N-isopropylbenzothiohydroxamic acids (3) were measured and compared with appropriate spectra of structurally similar hydroxylamines (1), benzohydroxamic acids (4), benzamides (5) and thiobenzamides (6). The analysis of the chemical shifts of the thiohydroxamic acids under investigation indicates that the inductive effect of the hydroxyl group rather than steric hindrance is responsible for non-additivity of the effect of substituents. Additionally, N-hydroxyl diminishes the effect of aromatic ring substituents on the 15N chemical shifts in the thiohydroxamic acids 3 which is approximately half that in the respective thiobenzamides 6. The chemical shift values correlate best with Brown's sigma+ parameter.     

Quantitative 15N NMR spectroscopy

Line intensities in ¹⁵N NMR spectra are strongly influenced by spin-lattice and spin–spin relaxation times, relaxation mechanisms and experimental conditions. Special care has to be taken in using ¹⁵N spectra for quantitative purposes. Quantitative aspects are discussed for the ¹⁵N NMR of molecules with different nitrogen functional groups and also mixtures of nitrogen-containing compounds. It is shown that, in general, quantitative data are obtainable from integration of ¹⁵N lines in proton decoupled ¹⁵N NMR spectra using NOE suppression. Addition of paramagnetic relaxation reagents (PARR) under controlled conditions is frequently needed to accomplish the experiment within reasonable time limits.     

IR and NMR spectral studies of 4-bromo-1-naphthyl chalcones-assessment of substituent effects

Infrared nuCO (cm(-1)) of s-cis and s-trans frequencies and nuclear magnetic resonance chemical shifts delta(1)H (ppm) of H-alpha and H-beta, delta(13)C (ppm) of C-alpha and C-beta data were assigned from their respective spectra of a series of various substituted styryl 4-bromo-1-naphthyl chalcones. These values are correlated with various Hammett substituent constants. From the results of statistical analysis, the effect of substituents can be explained.