Lanthanide-induced shifts in proton NMR spectra of cyclohexanones

The lanthanide-induced shifts (LIS) of the lanthanide shift reagent (LSR) Eu(FOD)₃ are reported for a large number of cyclohexanones, especially those which are highly substituted. The following compounds were synthesized and characterized: 3-(aryl)-3,5,5-trimethylcyclohexanones, in which aryl = 1-naphthyl, phenyl, o-anisyl, m-anisyl, p-anisyl and p-chlorophenyl. Some analogous compounds were also studied: 3,5,5-trimethylcyclohexanone, 4-tert-butyl-cyclohexanone, 3,3,5,5-tetramethylcyclohexanone 3-(1-naphthyl)5,5-dimethylcyclohexanone and para-tert-butyl-anisole. A method for the regression analysis of the concentration dependence of the LIS of these substrates is developed and reported, and used to derive the limiting incremental LIS (Δ₂) for the LS₂ complex and to evaluate the proton chemical shifts (δ₀) in the absence of LSR. An ‘incremental dilution’ technique was found to be most appropriate to insure constant substrate concentrations, needed to extract both Δ₂ and δ₀. The conformations of the 3-(aryl)-type systems and analogous compounds were studied via LIS and found to conform to:—(i) an axially disposed aryl substituent in the 3,3,5,5-tetra-substituted cyclohexanones and (ii) a flattened chair form of the cyclohexanone ring with distortions in this chair form being an increase in the syn-diaxial (C-3, C-5) substituent distance (C-3 and C-5 substituents still eclipsed). The LIS were fully compatible with these structural assumptions.     

Lanthanide induced 1H and 13C NMR shifts and their use for geometry analysis with alicyclic compounds

Based on computations with conformationally rigid substrates the ambiguities involved in the geometrical analysis of pseudocontact shifts are demonstrated. The minimal agreement factors R and the corresponding lanthanide positions (usually more than one) are extremely dependent upon the chosen structural data for the model substrate and on the errors of the experimental shift values. It is observed, that a difference or improvement of R factors of less than 3% is not significant in most cases. This is so, even on the basis of Ytterbium induced ¹³C shifts, which are found to be more accurate than ¹H shifts and free from contact contributions within the experimental error. Using lanthanide induced shifts some ¹³C signal assignment problems are discussed. The computed minima for five substituted norbornanols indicate a lanthanide position with an L . . . O distance of d = 2·5 Å for the secondary alcohols and an orientation avoiding gauche interactions with the two neighbouring CC bonds. Similar computed results are obtained with five bicyclic ketones, except for an L . . . O distance from 3 to 4 Å increasing with steric hindrance. The particular problems with the analysis of symmetrical compounds like cyclohexyl derivatives are pointed out.     

Lanthanide-ion-induced paramagnetic shifts in NMR spectra in aqueous solutions

Theoretical and Experimental Chemistry -     

NMR stereotopic induced shifts in epimeric mixtures

The proton NMR spectra of epimeric mixtures of menthone ( 1 ), carvomenthone ( 2 ), carquejone ( 3 ), 2,5-dimethyl-1,4-cyclohexanedione ( 4 ) and piqueridione ( 5 ) were studied using the chemical shift reagent Eu(DPM)₃. The results allow quantifications of the epimers and some conformational assignments to be made.     

Effects of methyl substituents on the proton chemical shifts in the NMR spectra of the twenty methyl and ethyl substituted hydrazines. Electronegativity values for hydrazyl groups

The C? H proton NMR spectra of the twenty conceivable methyl and ethyl substituted hydrazines are presented and analyzed with respect to effects on chemical shifts of the C? H protons caused by replacement of hydrogen by methyl and ethyl groups on the C? N? N? C chain. Thirteen different methyl substituent effects and six different ethyl substituent effects are identified and evaluated. Most of the effects are shielding and in accordance with an electron-releasing inductive effect of alkyl groups. A deshielding effect (the ‘C? C bond effect’) is observed when a methyl group replaces the hydrogen on the carbon bearing the hydrogen in focus and primary hydrogen on the carbon bearing the hydrogen in focus and primary hydrogens become secondary, as observed in other systems. On the basis of their effects on the chemical shifts of methyl protons in CH₃X, eighteen different hydrazyl groups (× = ? NR₁NR₂R₃) fall into three classes: I (R₁ = H; R₂, R₃ = H or alkyl); II (R₁ = alkyl; R₂ and/or R₃ = H); III (R₁, R₂ and R₃ = alkyl), with slightly different electronegativities: 2·94, 2·83 and 2·74, respectively.     

Solvent effects in NMR spectra induced by benzene in methyl benzoic esters—IV

NMR solvent effects induced by benzene in methyl substituted benzoic esters can be effectively used in the interpretation of complex NMR spectra. A 1:1 collision complex between solvent and solute is proposed, supported by dilution curve experiments and the geometry of the ‘complex’ is discussed.     

Isotropic chemical shifts in magic-angle spinning NMR spectra of proteins

Here we examine the effect of magic-angle spinning (MAS) rate upon lineshape and observed peak position for backbone carbonyl (C') peaks in NMR spectra of uniformly-(13)C,15N-labeled (U-(13)C,15N) solid proteins. 2D N-C' spectra of U-(13)C,15N microcrystalline protein GB1 were acquired at six MAS rates, and the site-resolved C' lineshapes were analyzed by numerical simulations and comparison to spectra from a sparsely labeled sample (derived from 1,3-(13)C-glycerol). Spectra of the U-(13)C,15N sample demonstrate large variations in the signal-to-noise ratio and peak positions, which are absent in spectra of the sparsely labeled sample, in which most 13C' sites do not possess a directly bonded 13CA. These effects therefore are a consequence of rotational resonance, which is a well-known phenomenon. Yet the magnitude of this effect pertaining to chemical shift assignment has not previously been examined. To quantify these effects in high-resolution protein spectra, we performed exact numerical two- and four-spin simulations of the C' lineshapes, which reproduced the experimentally observed features. Observed peak positions differ from the isotropic shift by up to 1.0 ppm, even for MAS rates relatively far (a few ppm) from rotational resonance. Although under these circumstances the correct isotropic chemical shift values may be determined through simulation, systematic errors are minimized when the MAS rate is equivalent to approximately 85 ppm for 13C. This moderate MAS condition simplifies spectral assignment and enables data sets from different labeling patterns and spinning rates to be used most efficiently for structure determination.     

Carbon-13 NMR spectra of all the isomeric methyl hydroxy- and acetoxyoctadecanoates. Determination of chemical shifts by deuterium isotope effects

Carbon-13 NMR spectra of the 17 isomeric methyl hydroxyoctadecanoates and the corresponding acetate derivatives have been measured and chemical shifts assigned to most carbons. Sixteen specifically deuterated hydroxy esters, and their acetates, were employed to make unambiguous assignments from the deuterium isotope effects on the spectra. When substituents are separated from the ends of the chain by 2–3 methylene groups their effects are largely additive. Long range effects of the hydroxyl group were γ, +0.01; δ, ?0.09; ε, ?0.11; ζ, ?0.06; η, ?0.05; and θ, ?0.04 ppm, and of the acetate group were γ, ?0.20; δ, ?0.20; ε, ?0.16; ζ, ?0.11; η, ?0.08 and θ, ?0.07 ppm, showing that they extend across seven methylene groups.     

Chemical shifts of F19 NMR in spectra of trifluorovinyl compounds

The regularities of the changes of the chemical shift in the F¹⁹ NMR of trifluorovinyl compounds are discussed in this paper. It has been shown that the conditions , where _F ⁰ is the shift of F¹⁹ in tetrafluorethylene (X=F) are satisfied for the chemical shifts of fluorine in compounds. An increase in the electronegativity of X leads to a decrease in the ionic nature of the C-F₃ bond and to a shift toward weak fields. The effect of X on the and shifts is not linked in a specific way to the electronegativity of the X group and is probably determined by the effect of the electric fields on the shielding of the F¹⁹ nucleus. Increments were calculated from the data obtained on the shifts in trifluorovinyl compounds. The method of increments was used for the assignment of the lines in 1, 2-difluoro olefins. This method for the assignment is confirmed by known data. Several cases for the application of the increment method are proposed. The results of spectral measurements of the F¹⁹ NMR in some trifluorovinyl compounds are given in the experimental part.     

New syntheses and13C NMR spectra of the methyl ethers of methyl α-L-arabinopyranoside

A method is described for obtaining the methyl ethers of methyl -L-arabinopyranoside that is based on the partial methylation of methyl -L-arabinopyranoside followed by the liquid chromatography of the methyl ethers. The¹³C NMR spectra of the methyl ethers of methyl -L-arabinopyranoside have been studied.Pacific Ocean Institute of Bioorganic Chemistry, Far Eastern Scientific Center, Academy of Sciences of the USSR, Vladivostok. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 178–181, March–April, 1985.     

Long range substituent-induced chemical shifts in the 13C NMR spectra of N-benzylidenebenzylamines

Carbon-13 chemical shifts for N-benzylidenebenzylamines are affected by substituents up to eleven bonds away from the substituent group. The data correlate well with Hammett constants.     

Stereoelectronic effects on 1H nuclear magnetic resonance chemical shifts in methoxybenzenes

Investigation of all O-methyl ethers of 1,2,3-benzenetriol and 4-methyl-1,2,3-benzenetriol (3-16) by 1H NMR spectroscopy and density-functional calculations disclosed practically useful conformational effects on 1H NMR chemical shifts in the aromatic ring. While the conversion of phenol (2) to anisole (1) causes only small positive changes of 1H NMR chemical shifts (Delta delta < 0.08 ppm) that decrease in the order Hortho > Hmeta > Hpara, the experimental O-methylation induced shifts in ortho-disubstituted phenols are largest for Hpara, Delta delta equals; 0.19 +/- 0.02 ppm (n = 11). The differences are due to different conformational behavior of the OH and OCH3 groups; while the ortho-disubstituted OH group remains planar in polyphenols due to hydrogen bonding and conjugative stabilization, the steric congestion in ortho-disubstituted anisoles outweighs the conjugative effects and forces the Ar-OCH3 torsion out of the ring plane, resulting in large stereoelectronic effects on the chemical shift of Hpara. Conformational searches and geometry optimizations for 3-16 at the B3LYP/6-31G** level, followed by B3LYP/6-311++G(2d,2p) calculations for all low-energy conformers, gave excellent correlation between computed and observed 1H NMR chemical shifts, including agreement between computed and observed chemical shift changes caused by O-methylation. The observed regularities can aid structure elucidation of partly O-methylated polyphenols, including many natural products and drugs, and are useful in connection with chemical shift predictions by desktop computer programs.     

Solvent shifts in the NMR spectra of monomethoxyflavones a comparison of four solvent systems

Nmr chemical shifts of methoxyl protons are reported for the eight monomethoxyflavones in four solvents: deuteriochloroform, benzene, dimethylsulfoxide, and pyridine. Benzene shift data are presented, and Δ values interpreted on the basis of a preferential approach of benzene molecules near the positive end (hetero oxygen atom) of a large pyrone dipole. Pyridine shifts, relative to deuteriochloroform and dimethylsulfoxide, are reported. The Δ values for monomethoxyflavones indicate that only in 2′-methoxyflavone is the shift value positive.