Visualization and quantification of anisotropic effects on the H NMR spectra of 1,3-oxazino[4,3-a]isoquinolines—indirect estimates of steric compression

The anisotropic effects of the phenyl, α- and β-naphthyl moieties in four series of 1,3-oxazino[4,3-a]isoquinolines on the ¹H chemical shifts of the isoquinoline protons were calculated by employing the Nucleus Independent Chemical Shift (NICS) concept and visualized as anisotropic cones by a through-space NMR shielding grid. The signs and extents of these spatial effects on the ¹H chemical shifts of the isoquinoline protons were compared with the experimental ¹H NMR spectra. The differences between the experimental δ (¹H)/ppm values and the calculated anisotropic effects of the aromatic moieties are discussed in terms of the steric compression that occurs in the compounds studied.     

Ring current and anisotropy effects on OH chemical shifts in resonance-assisted intramolecular H-bonds

Ring current effects on resonance-assisted and intramolecularly bridged hydrogen bond protons for 10-hydroxybenzo[h]quinoline 1 and a number of related compounds were calculated and the through-space NMR shieldings (TSNMRS) obtained hereby visualized as iso-chemical-shielding surfaces (ICSS) of various size and direction. These calculations revealed that this through-space effect is comparably large (up to 2?ppm) dependent on the position of the intramolecularly bridged OH proton, and therefore, contribute considerably to the chemical shift of the latter making it questionable to use δ(OH)/ppm in the estimation of intramolecular hydrogen bond strength without taking this into account. Furthermore, the anisotropy effects of additional groups on the aromatic moiety (e.g. the carbonyl group in salicylaldehyde or in o-hydroxyacetophenone of ca. 0.6?ppm deshielding) should also be considered. These through-space effects need to be taken into account when using OH chemical shifts to estimate hydrogen bond strength.     

FICA,a new chiral derivatizing agent for determining the absolute configuration of secondary alcohols by 19F and 1H NMR spectroscopies

Optically active 1-fluoroindan-1-carboxylic acid (FICA) was designed and prepared as its methyl ester for determining the absolute configuration of chiral molecules by both ¹H and ¹⁹F NMR spectroscopies. Enantiomerically pure isomers of FICA methyl esters (FICA Me esters) were obtained by chromatographic separation using HPLC with a Daicel Chiralcel OJ-H column. The absolute configuration of the (+)-FICA Me ester was deduced to be (S) by X-ray crystallographic analysis of the (+)-FICA amide of (R)-α-phenethylamine. Both enantiomers were derived to the diastereomeric esters of chiral secondary alcohols by an ester exchange reaction. In the ¹H NMR spectra, the signs of Δδ_H (δ_R ? δ_S) were consistent on each side of the FICA molecular plane. Therefore, the concept of the modified Mosher’s method could be successfully applied to the FICA-based procedure. Moreover, the consistency in the signs of Δδ_F (δ_R ? δ_S) values suggests that the FICA method would be reliable in assigning the absolute configurations of secondary alcohols based on ¹⁹F NMR spectroscopy.     

Synthesis, complete NMR assignments, and NOE versus GIAO data assisted ab initio modelling the overall conformations of amide 3,4′-diquinolinyl sulfides in solution. Another approach to analysis of flexible systems

Two isomeric amide sulfides 3 and 4 were prepared by the treatment of 6-substituted thioquinanthrene (2) with sodium methoxide and methyl iodide. Product structures were determined by ¹H and ¹³C NMR spectroscopy in solution, including 2D experiments HSQC and HMBC at 11.75 T. The time-averaged conformations were elucidated, based on best fitting the measured data δ_C and δ_H to those computed by the ab initio GIAO NMR method at the HF/6-31G^* level. All used input molecular models had been pre-selected before in the light of NOE experimental data. Excellent two-nuclear linear correlations δ_C,H^exp vs. δ_C,H^calc were achieved (R>0.999). Spatial orientations of the ring substituents [SMe and, especially, of C(O)NMe₂] in both isomers were considered to rationalise the NMR spectra of these and other related amide systems. A protocol for the three-step conformational analysis is described in detail.     

Microscopic structures of ionic liquids 1-ethyl-3-methylimidazolium tetrafluoroborate in water probed by the relative chemical shift

The relative chemical shifts (Δδ) were put forward to investigate the microscopic structure of 1-ethyl-3-methyl-imidazolium tetrafluoroborate (EmimBF₄) during the dilution process with water. The concentration-dependent Δδ _{(C2)H–(C4)H}, Δδ _{(C2)H–(C5)H} and Δδ _{(C4)H–(C5)H} were analyzed. The results reveal that the variations of the microscopic structures of three aromatic protons are inconsistent. The strength of the H-bond between water and three aromatic protons follows the order: (C2)H…O > (C4)H…O > (C5)H…O. The concentration-dependent Δδ _{(C6)H–(C7)H} and Δδ _{(C6)H–(C8)H} indicate the formation of the H-bonds of (C_alkyl)H…O is impossible, and more water is located around (C6)H than around (C7)H or (C8)H. The concentration-dependent Δδ _{(C2)H–(C4)H} and Δδ _{(C2)H–(C5)H} both increase rapidly when x _water > 0.9 or so, suggesting the ionic pairs of EmimBF₄ are dissociated rapidly. The turning points of concentration-dependent Δδ _{(C2)H–(C4)H} and Δδ _{(C2)H–(C5)H} indicate that some physical properties of the EmimBF₄/water mixtures also change at the corresponding concentration point. The microscopic structures of EmimBF₄ in water could be clearly detected by the relative chemical shifts.     

Anisotropic effect of the nitrate anion—manifestation of diamagnetic proton chemical shifts in the H NMR spectra of NO3 coordinated complexes

The anisotropic effect of the planar nitrate anion NO₃⁻ has been ab initio calculated employing the Nucleus-Independent Chemical Shift (NICS) concept of von Ragué Schleyer and visualized as Iso-Chemical-Shielding Surfaces (ICSSs) of various (de)shieldings. Complexation-induced shifts in the ¹H NMR spectra of nitrate/metal complexes or nitrate/receptor supramolecules can be separated now into anisotropic influences of the suitably coordinated nitrate anions and effects originating from differential sources.     

Chemical shifts as a novel measure of interactions between two binding sites of symmetric dialkyldimethylammonium bromides to α-cyclodextrin

Complex formation of α-cyclodextrin (α-CD) with decyltrimethylammonium (DeTAB), N,N-dioctyldimethylammonium (DOAB), and N,N-didecyldimethylammonium bromides (DDeAB) was investigated by proton NMR spectroscopy. Analysis of chemical shifts yielded macroscopic 1:1 and 1:2 binding constants (K₁ and K₂) and chemical shift differences (Δδ_SD and Δδ_SD2) for the 1:1 and 1:2 complexes of DeTAB, DOAB, and DDeAB with α-CD. The K₁ and K₂ values of DDeAB were quantitatively explained on the basis of the assumption that the microscopic 1:1 binding constant of DDeAB is identical to the observed K₁ value of DeTAB. The K₂ value of DDeAB was also explained in terms of its observed K₁ value and the independent binding of two alkyl chains. Furthermore, the Δδ_SD and Δδ_SD2 values for protons of DDeAB and α-CD were quantitatively explained on the basis of the assumption that the geometry of the decyl group of DDeAB in an α-CD cavity is identical to that of DeTAB. The Δδ_SD value was also explicable on the basis of the same geometric assumption and the observed Δδ_SD2 value for this system. Similar results were obtained for the 1:1 and 1:2 DOAB-α-CD complexes.     

Structural examination of some polychlorinated 2-phenoxyphenols by 1H and 13C nuclear magnetic resonance

Carbon-13 NMR spectra of some polychlorinated 2-phenoxyphenols have been obtained. The substituent chemical shifts obtained by varying the chlorine substitution pattern of one ring are very similar to those reported for the corresponding diphenyl ethers. Thus, the replacement of a 2-chlorine atom by a hydroxyl group only induces minor shielding changes at the adjacent aryl moiety and the ¹³C chemical shift changes are mainly determined by the preferred conformations governed by the steric demand of the ortho substituents. An ¹H NMR/IR study revealed an equilibrium between intermolecular aggregates and intramolecular OH…π species in the concentration interval 2-0.005 M. Any hydrogen bonding effects on ¹³C NMR shieldings are, therefore, minor compared to shielding variations caused by steric perturbations.     

Structure, configuration, conformation and quantification of the push-pull effect of 2-alkylidene-4-thiazolidinones and 2-alkylidene-4,5-fused bicyclic thiazolidine derivatives

Structures of a series of push-pull 2-alkylidene-4-thiazolidinones and 2-alkylidene-4,5-fused bicyclic thiazolidine derivatives were optimized at the B3LYP/6-31G(d) level of theory in the gas phase and discussed with respect to configurational and conformational stability. Employing the GIAO method, ¹³C NMR chemical shifts of the C-2, C-2′, C-4 and C-5 atoms were calculated at the same level of theory in the gas phase and with inclusion of solvent, and compared with experimental data. Push-pull effect of all compounds was quantified by means of the quotient π^∗/π, length of the partial double bond, ¹³C NMR chemical shift difference (Δδ_CC) and ¹H NMR chemical shifts of olefinic protons. The effect of bromine on donating and accepting ability of other substituents of the push-pull CC double bond is discussed, too.     

A DFT study of the geometric,magnetic NMR chemical shifts and optical rotation properties of Tröger’s bases

A DFT computational study of Tröger’s bases and related compounds (TBs) has been used to satisfactorily explain their geometry (including the flexibility aspect), the ¹H NMR chemical shifts of the endo/exo protons and their optical properties. The Cambridge Structural Database has been searched to collect 34 structures of TBs that have been analyzed with respect to the folding angle ϕ. The GIAO approach has been used to calculate the absolute shieldings of TB and a quinoline analogue providing an explanation for the dependence of the relative position of the endo/exo protons on the structure of the TBs. Finally, the specific rotations of several molecules related to TBs have been calculated at the B3LYP/6-311++G(2s,2p) level. The [α]_D values are strongly dependent on relatively small structural variations.     

Benzyne − an acetylene- or cumulene-like electronic structure?

The spatial magnetic properties, through-space NMR shieldings (TSNMRS), of benzyne 1 and analogues (benzene 2, 1,2,3-cyclohexatriene 3, cyclohexen-3-yne 4, cyclohexen-4-yne 5, cyclohexyne 6) have been calculated using the GIAO perturbation method employing the nucleus independent chemical shift (NICS) concept and visualized as iso-chemical-shielding surfaces (ICSS) of various size and direction. The TSNMRS values could be employed to compare the diatropic ring current effects of benzene and benzyne, and, when compared with the spatial magnetic properties of the analogues, to answer the question whether the benzyne electronic structure is more acetylene- or cumulene-like, supported by structural data and δ(¹³C)/ppm values.     

Is the term “Carbene” justified for remote N-heterocyclic carbenes (r-NHCs) and abnormal N-heterocyclic carbenes (aNHCs/MICs)?

The spatial magnetic properties, through-space NMR shieldings (TSNMRS), of typical N-heterocyclic carbenes NHCs, r-NHCs, a-NHCs and MICs have been calculated using the GIAO perturbation method employing the nucleus independent chemical shift (NICS) concept and visualized as iso-chemical-shielding surfaces (ICSS) of various size and direction. Prior to that both structures and ¹³C chemical shifts were calculated and in case of isolated carbenes the computed δ(¹³C)/ppm values compared (as a quality criterion for obtained structures) with the experimental ones. The TSNMRS values of the studied carbenes, which are in mesomeric equilibrium with zwitterionic (ylide/betaine/mesoionic) resonance contributors, are employed to qualify and quantify the present electronic structure and if the term carbene is still justified to denote the compounds studied. The results, thus obtained from spatial magnetic properties (TSNMRS), are compared with the geometry of the compounds, the corresponding WIBERG's bond index values, and the ¹³C chemical shifts especially of the carbene electron-deficient centre.     

1H NMR spectra. Part 29§: proton chemical shifts and couplings in esters—the conformational analysis of methyl γ‐butyrolactones

The ¹H NMR spectra of 35 cyclic and acyclic esters are analysed to give the ¹H chemical shifts and couplings. The substituent chemical shifts of the ester group were analysed using three‐bond (γ) effects for near protons and the electric field, magnetic anisotropy and steric effect of the ester group for more distant protons. The electric field is calculated from the partial atomic charges on the O?C = O atoms, and the asymmetric magnetic anisotropy of the carbonyl group acts at the midpoint of the C = O bond. The values of the anisotropies Δχ_parl and Δχ_perp were for the aliphatic esters 10.35 and ?18.84 and for the conjugated esters 7.33 and ?15.75 (×10^?6 ų/molecule). The oxygen steric coefficients found were 104.4 (aliphatic C = O), 45.5 (aromatic C = O) and 16.0 (C–O) (×10^?6 Å⁶/molecule). After parameterisation, the overall RMS error for the data set of 280 entries was 0.079 ppm. The strongly coupled ¹H NMR spectra of the 2‐methyl, 3‐methyl and 4‐methyl γ‐butyrolactones were analysed and the methyl conformational equilibrium obtained from the observed couplings. The observed versus calculated density functional theory (DFT) ΔG(ax‐eq) was 1.0 (1.01), 0.34 (0.54) and 0.65 (0.71) kcal/mol res. The shielding effect of a methyl cis to a proton in the five‐membered lactone rings is ?0.40 ±0.05 ppm and deshielding trans effect 0.12 ±0.05 ppm, which is common to both five and six membered rings. The cis/trans isomerism in the vinyl esters methyl acrylate, crotonate and methacrylate and methyl furoate was examined using the ¹H chemical shifts. The calculated shifts of both the cis and trans isomers were in good agreement with the observed shifts. Copyright © 2012 John Wiley & Sons, Ltd.     

1H NMR spectra part 31: 1H chemical shifts of amides in DMSO solvent

The ¹H chemical shifts of 48 amides in DMSO solvent are assigned and presented. The solvent shifts Δδ (DMSO‐CDCl₃) are large (1–2 ppm) for the NH protons but smaller and negative (?0.1 to ?0.2 ppm) for close range protons. A selection of the observed solvent shifts is compared with calculated shifts from the present model and from GIAO calculations. Those for the NH protons agree with both calculations, but other solvent shifts such as Δδ(CHO) are not well reproduced by the GIAO calculations. The ¹H chemical shifts of the amides in DMSO were analysed using a functional approach for near ( ≤ 3 bonds removed) protons and the electric field, magnetic anisotropy and steric effect of the amide group for more distant protons. The chemical shifts of the NH protons of acetanilide and benzamide vary linearly with the π density on the αN and βC atoms, respectively. The C=O anisotropy and steric effect are in general little changed from the values in CDCl₃. The effects of substituents F, Cl, Me on the NH proton shifts are reproduced. The electric field coefficient for the protons in DMSO is 90% of that in CDCl₃. There is no steric effect of the C=O oxygen on the NH proton in an NH…O=C hydrogen bond. The observed deshielding is due to the electric field effect. The calculated chemical shifts agree well with the observed shifts (RMS error of 0.106 ppm for the data set of 257 entries). Copyright © 2014 John Wiley & Sons, Ltd.     

An experimental/theoretical approach to determine the optical purity and the absolute configuration of endo- and exo-norborn-5-en-2-ol using mandelate derivatives

The O-acetylmandelates and mandelates of endo- and exo-norborn-5-en-2-ol were prepared, both as a mixture and also as separate diastereomers. ¹H NMR spectroscopy of these derivatives was efficiently used to determine the enantiomeric ratios and to predict the absolute configuration of the alcohols. Theoretical calculations were performed to locate the predominant conformations of the mandelate derivatives and GIAO ¹H NMR Boltzmann-weighted average chemical shifts were computed, correctly reproducing the experimental δ and Δδ values.     

Quantitative determination of mebeverine HCl by NMR chemical shift migration

Quantitative ¹H NMR spectroscopic methods are not frequently reported, but current NMR instrumentation allows ready access to such data. Mebeverine HCl is an attractive molecule for NMR spectroscopy teaching purposes as it possesses a variety of simple but significant functional groups; we fully assign its ¹H and ¹³C NMR spectra. Using mebeverine HCl, we show that concentration changes, in water as a solvent, can lead to significant changes in the ¹H chemical shifts of non-exchangeable aromatic protons and to a lesser extent to aromatic methoxy protons. An important observation is that different protons migrate to different extents as the concentration of the solute is varied, and thus the ¹H NMR spectra are concentration-dependent across a useful range. This chemical shift variation of selected protons was therefore analyzed and applied in the quantitative determination of mebeverine HCl in a medicine (Colofac IBS) formulated as a tablet. Self-association phenomena in water could account for these observed chemical shift migration effects as shown by determining the hydrodynamic radius from the modified form of the Stokes-Einstein equation, and thence the apparent hydrodynamic volume, V_H, for mebeverine HCl in D₂O solution which is 10-fold greater than that seen in either CDCl₃ or CD₃OD.     

Structural correlations for 1H, 13C and 15N NMR coordination shifts in Au(III), Pd(II) and Pt(II) chloride complexes with lutidines and collidine

¹H, ¹³C and ¹⁵N NMR studies of gold(III), palladium(II) and platinum(II) chloride complexes with dimethylpyridines (lutidines: 2,3‐lutidine, 2,3lut; 2,4‐lutidine, 2,4lut; 3,5‐lutidine, 3,5lut; 2,6‐lutidine, 2,6lut) and 2,4,6‐trimethylpyridine (2,4,6‐collidine, 2,4,6col) having general formulae [AuLCl₃], trans‐[PdL₂Cl₂] and trans‐/cis‐[PtL₂Cl₂] were performed and the respective chemical shifts (δ^1H, δ^13C, δ^15N) reported. The deshielding of protons and carbons, as well as the shielding of nitrogens was observed. The ¹H, ¹³C and ¹⁵N NMR coordination shifts (Δ^1H_coord, Δ^13C_coord, Δ^15N_coord; Δ_coord = δ_complex ? δ_ligand) were discussed in relation to some structural features of the title complexes, such as the type of the central atom [Au(III), Pd(II), Pt(II)], geometry (trans‐ or cis‐), metal‐nitrogen bond lengths and the position of both methyl groups in the pyridine ring system. Copyright © 2010 John Wiley & Sons, Ltd.     

Effect of proton irradiation on structure and optical property of PTFE film

Effects of protons on chemical structure and optical properties of polytetrafluoroethylene (PTFE) film were investigated in the energy range of 60 to 170 keV to simulate the effects of space proton irradiation environment. The results show that for PTFE film irradiated with protons, the change in C_1s spectrum, along with those in F_1s and the FT‐IR spectrum after irradiation, demonstrates that two processes take place simultaneously. One is substitution in which carbon to fluorine bonds can be broken by the protons and some positions of fluorine are occupied by active protons; the other is the carbonification, which results in the change of surface color and an increase of carbon percentage on the irradiated surface. For the PTFE film irradiated with 150 keV protons, the spectral absorbance ΔA_λ in the wavelengths longer than 300 nm increase unmonotonously with proton fluence, and an abnormally recovery decrease of the ΔA_λ with the increase of fluence in the range of 5×10¹³ cm^?2 to 10¹⁵ cm^?2 is observed. The change of the ΔA_λ could be related to the competition of the carbonification and the substituting effect. The carbonification increases the ΔA_λ, while the substituting increases the amorphousness amount, leading to an increase in the transparency of the film. In addition, the creation of radicals can also contribute to the increase in absorbance. Copyright © 2003 John Wiley & Sons, Ltd.     

Intramolecular interactions in nitroamines studied by 1H, 13C, 15N and 17O NMR spectral and quantum chemical methods

¹H, ¹³C, ¹⁵N and ¹⁷O NMR chemical shifts are used for the characterization of the intramolecular interactions in several nitramines of the Me₂N-G-NO₂ type. The charge of lone electron pair of the amino group in N,N-dimethylnitramine, N,N-dimethyl-2-nitroethenamine, N,N-dimethyl-p-nitroaniline, 4-nitro-β-dimethylaminostyrene, 4-N,N-dimethylamino-β-nitrostyrene, 4-(N,N-dimethylamino)-4′-nitrobiphenyl, and 4-(N,N-dimethylamino)-4′-nitrostilbene is transferred not only to the nitro oxygens, but also to the vinylene and benzene carbons of the G spacer and to N-methyl carbons as well. Decreased nuclear shielding is found to be qualitatively related to the decreased atomic charge around a nucleus. This finding was further verified and quantified by comparison of the NMR data with those obtained by ab initio quantum chemical calculations. ¹⁷O NMR chemical shift changes seem to be more significant when the interacting NMe₂ and NO₂ groups are separated by a short spacer. On the other hand, ¹⁵N NMR chemical shifts suggest that a decrease of the charge at the amino nitrogen is not related to the length of the spacer alone. A lack of the linear dependence between the ¹⁷O_nitro and ¹⁵N_amino chemical shifts suggests that the charge lost by the amino nitrogen was only partially gained by the oxygens in the nitro group. The increased shieldings of the aryl carbons in 4-(N,N-dimethylamino)-4′-nitrobiphenyl indicate that atoms of the p,p-biphenylene spacer also gain some charge originating from the amino nitrogen. ³ J _H,H spin–spin coupling constant shows that among different vinylene compounds, the charge transfer to the nitro group is practically effective only in N,N-dimethyl-2-nitroethenamine where the bond between the vinylene carbons is significantly of low order by character. The calculated Natural Population Analysis (NPA) data confirms that except the nitro oxygens, other atoms that receive the negative charge lost by NMe₂ in the compounds studied are the aryl and N-methyl carbons.