Shift reagent 1H NMR study of methoxycoumarins

The complete assignment of the proton chemical shifts of coumarin ( 1 ), all monomethoxy derivatives and the six possible dimethoxyl substituted compounds at the aromatic ring was achieved at 60 MHz in a quantitative study utilizing Pr(fod)₃ as the shift reagent. It was found that in addition to the complexation at the lactone carbonyl a second interaction of the lanthanide shift reagent occurs when two methoxyl groups are found in an ortho distribution. The results are discussed in comparison to data published for flavones in the presence of Pr(fod)₃ shift reagent.     

NMR spectral studies: XIII—titanium tetrachloride-induced and lanthanide-induced shifts in the proton NMR spectra of β-lactams

2-Azetidinones which carry a proton each on C-3 and C-4 often pose a problem in the correct assignment of the resonances due to these protons; titanium tetrachloride has been shown to be an effective and reliable n.m.r. shift reagent to differentiate between these two protons on the basis of their different sensitivities to this reagent. A few compounds were also studied with Eu(fod)₃ and Pr(fod)₃ for the sake of confirmation.     

Large lanthanide-induced chemical shifts in cobalt complexes of enethials (α,β-unsaturated thioaldehydes)

Eu(fod)₃-, Yb(fod)₃- and Pr(fod)₃-induced chemical shifts of the ‘thioaldehydic’ protons in enethial ligands complexed to a cobalt cyclopentadienyl group are unusually large and in the same direction (10–30 ppm downfield per mole of shift reagent per mole of substrate). The shifts of the protons induced by Eu(fod)₃ and Pr(fod)₃ in the enethial ligands show an alternation in sign on proceeding away from the sulfur atom. In contrast to the results with the fod reagents, the ytterbium and lanthanum shift reagents Yb(thd)₃ and La(thd)₃ caused only small shifts of protons in the 2-phenylpropenethial ligand. No induced shifts with the Eu or Pr reagents were observed for a cyclopentadienyl cobalt complex of dithioglyoxal. The induced shifts in these enethial complexes may be caused by varying blends of complex formation, contact and pseudocontact shifts. Caution is advised in assigning origins to lanthanide induced shifts in such organometallic systems.     

The conformation of (1R,2S,4R,5S)-2,4-dimethoxybicyclo[3.3.1]nonan-9-one and some related compounds

A mixture of stereoisomers of 2,4-dimethoxybicyclo[3.3.1]nonan-9-one was prepared, separated by column chromatography and characterized by 60 MHz ¹H NMR spectroscopy using Eu(fod)₃. A double chair conformation with axial methoxyl groups is established for (1R,2S,4R,5S)-2,4-dimethoxybicyclo[3.3.1]-nonan-9-one on the basis of the J(12), J(2,H-3 exo) and J(2,3 endo) values and the chemical shifts for H-2(4). The conformation of some related compounds is subsequently inferred.     

Eu(fod)3 binding on the 1H‐NMR spectra of bis(2′‐ethylbenzoate)ethylene glycol podands

The complexing and selective binding constants of Eu(fod)₃ with bis(2′‐ethylbenzoate)ethylene glycol podands having one to four oxyethylene groups was observed on their ¹H‐NMR spectra at 250 MHz and 295 K in CDCl₃. The Eu(fod)₃ interaction displayed the selective binding role of oxygen on H₂C–O–CH₂ backbones with referring the ¹H chemical shifts. The estimated equilibrium constants, K_a, of 1:1 ratio of interactions were in accordance with the Eu(fod)₃ ionic radii to bind the oxygen sites depending on the size and conformation of the esters. Esters having one or two ethyleneoxy groups gave mainly 2:2 complexes using ester sites. The minimum lanthanide‐podand ester distance displayed the maximum stability so that ester with four oxyethylene groups was found to bind the Eu(fod)₃ moderately, whereas ester with three oxyethylene groups showed a large induced chemical shift due to the stability of Eu³⁺ complexes with larger ethyleneoxy groups. Copyright © 2012 John Wiley & Sons, Ltd.     

Constituents of Satureia calamintha. Application of Eu(fod)3 to the assignments of the methyl resonances of triterpenes related to 12-ursene

The n.m.r. spectra of triterpenoids related to 12-ursene have been examined using the shift reagent Eu(fod)₃. The assignment of all the methyl resonances has been achieved for ursolic acid derivatives and the corresponding compounds of the 3-epi series, which have not been investigated previously. The additive shielding effects of various substituents on the methyl resonance frequencies have been deduced from the results.     

NMR–Untersuchungen an Dicyclopentadienderivaten: I—1H-NMR: Anwendung von paramagnetischen Verschiebungsreagenzien (Eu(fod)3) zur Vereinfachung der Spektren exo/endo-isomerer Diole

The determination of the stereochemistry of a series of exo/endo-isomeric dihydro- and tetrahydro-dicyclopentadiene-9.10-diols (exo/exo or endo/endo), using Eu(fod)₃ for separation of the signals in their ¹H n.m.r. spectra, is discussed in detail. The paramagnetic shift values ΔEu determined for half-molar ratios Eu(fod)₃/diol allow an unambiguous stereochemical assignment of the diols with regard to exo/endo isomerism. The ΔEu quantities are correlated with the distance H_i…O-atom (R_i).     

The effects of lanthanide shift reagents on the NMR spectra of diaza-and dithiacyclophanes

The effect of a lanthanide shift reagent Eu(dpm)₃ on the spectra of 3 diazacyclophanes (Ia-c) has been studied together with the effect of a fluorinated shift reagent En(fod)₃d₂₇ on the nmr spectra of three dithiacyclophanes (IIa-c). The shift reagents remove certain unexpected accidental degeneracies in the original spectra and permit the assignment of the peaks in the expanded spectra to the individual methylene groups. The comparison of the chemical shifts for the methylene groups above the aromatic rings with those of related compounds provides evidence of an upfield shift deriving from the aromatic ring current. The synthesis of two new dithiacyclophanes (IIb-c) is reported.     

DNA fragment conformations. I—methods for the assignment of DNA fragment proton resonances. 1H NMR spectra of dApTpGpT and dApCpApTpGpT

A general method for the assignment of DNA fragment proton resonances, especially for the sugar protons, has been presented and used to interpret the 400 MHz proton spectra of dApTpGpT and dApCpApTpGpT in neutral aqueous solution. Only fine splittings of about 3 Hz are observed in the H-2″ resonances, and the total splitting is larger for the H-2′ (≈29 Hz) than for the H-2″ (22–23 Hz) multiplets. The purine and pyrimidine resonances can be distinguished on the basis of the H-2″ and H-2″ chemical shifts. The resonances of the H-2′ and H-2″ protons (above and below the sugar plane, respectively) of dA and dG exhibit chemical shifts of 2.65—2.80 ppm, while those of dC and dT residues are located at higher fields between 1.95 and 2.40 ppm. At high temperature (≥60°C), δH-2′>YδH-2″ for the purine family, while δH-2′ « δH-2″ in the case of the pyrimidine family. Except for the terminal residue, the H-3′ resonances of dA and dG are located at lower fields compared with those of the dC and dT residues. The same is true for the H-4′ resonances. In general δA_1′>δG_1′ and in the case of self complementary duplexes the H-1′ and H-2′ chemical shift variations versus temperature are found to be larger for the dC than for the dT residues.     

Influence of chemical exchange on the temperature dependence of Eu(fod)3-induced shifts

Temperature dependences of the paramagnetic shifts induced by Eu(fod)₃ in ¹H NMR spectra of ethylene oxide in carbon disulphide solution are obtained in the temperature range from +40 to ? 100°C at 100 MHz and from +30 to ?60°C at 60 MHz. The influence of chemical exchange leads to a decrease of the observed paramagnetic shifts with decreasing temperature. It is shown that a modified Swift and Connick equation can be used to describe the observed dependences. Upper limits of the mean lifetimes of the Eu(fod)₃-ethylene oxide adduct are τ_p < 1·7 × 10^?8 s at 14 °C and τ_p < 1 × 10^?8 s at 20 °C, respectively. The corresponding activation energy is equal to V_a = 13·7 kcal/mol.     

Conformational Mobility of Substituted 2-Methoxychalcones under the Action of Lanthanide Shift Reagents

Various lanthanide shift reagents Ln(fod)₃ were found to affect the conformational composition of 2-methoxychalcones. Coordination of Yb(fod)₃ occurs mainly at the carbonyl oxygen atom of the substrate, while Eu(fod)₃ and shift reagents derived from other lanthanides coordinate substituted chalcones as bidentate ligands, giving rise to a secondary tetrachelate with the corresponding change of conformation of the substrate molecule. The possibility for chelation is determined by steric hindrances in the vicinity of the substrate coordination centers and concurrent coordination of other electron-donor groups present in the substrate molecule.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 1, 2005, pp. 51–56.Original Russian Text Copyright © 2005 by Turov, Bondarenko, Tkachuk, Khilya.     

13C NMR spectra of a number of penta- and hexacyclic triterpenoids derived from glycyrrhetic acid

The¹³C NMR spectra of 22 derivatives of 18α- and 18β-glycyrrhetic acids that have been investigated and an assignment of the signals has been made. It has been shown that a modification of the carboxy group of glycyrrhetic acid leads mainly to a change in the chemical shifts of the α-, β-, and γ-carbon atoms of ring E. The assignment of a number of signals has been confirmed by the use of the shift reagent Eu(fod)_s. It has been established that the C₂₈ and C₁₆ signals are the most sensitive to a change in the C₁₈ configuration in the spectra of glycyrrhetic acid derivatives.

     

Conformational analysis of N,N-diisopropylamides by combined use of n.m.r. lanthanide-induced shifts and conformational energy calculations

A new method of conformational analysis has been developed, in which energy minimization calculations are combined with lanthanide-induced shift data. First, exhaustive energy calculations are carried out on the free molecules in order to determine the conformations of lowest energy. Then, the coordinates of all low energy conformations or pairs of conformations are used in the pseudocontact shift equation for lanthanide-induced shifts in order to find which of the theoretically obtained conformation(s) gives the best agreement with experiment. The molecules complexed to the lanthanide shift reagent were N,N-diisopropylformamide (DIPF) and N,N-diisopropylacetamide (DIPA). Two different lanthanide shift reagents were used, Eu(fod)₃

1 Fod is the anion of 1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6-octanedione-d₂₇.

and Pr(fod)₃, in order to check the validity of the method. Proton magnetic resonance spectra were taken at 6 °C in carbon tetrachloride solution. The principal conformation found was different for each amide. DIPF was found to exist as a mixture of I (39 mol%) and II (61 mol%) with Eu(fod)₃, and a mixture of I (37%) and II (63%) with Pr(fod)₃. DIPA was found to exist as a mixture of I (79%) and IV (21%) with Eu(fod)₃ and a mixture of I (87%) and IV (13%) with Pr(fod)₃. For both molecules, the two conformations of lowest computed energy were also the pair which gave the best fit to the lanthanide shift reagent data. The location of the principal magnetic axis of the complex was found to lie between 0° and 14° from the lanthanide atom–oxygen atom bond axis. The technique of combining lanthanide shift reagent data with energy calculations shows great promise in conformational analysis.     

Characterization of di- and trimethoxybenzaldehydes by analysis of deshielding gradients obtained with Eu(fod)3 shift reagent

Eu(fod)₃ shift reagent was used to simplify PMR spectra from isomeric mono-, di and trimethoxybenzaldehydes. Deshielding gradients, obtained by plotting induced shift vs. molar ratio of [Eu(fod)₃]/[substrate] made it possible to assign methoxyl proton signals to the correct positional substituent in polymethoxylated benzaldehydes. Anomalous upfield shifts for the aldehydic protons of 2,6-dimethoxy- and 2,4,6-trimethoxybenzaldehyde were observed with Eu(fod)₃ Various instances of long-range (⁵J) proton coupling between the aldehydic proton and a meta-proton provide insight to the geometry of the substrate in the complexed state with Eu(fod)₃. Di- and trimethoxybenzaldehydes are important precursors for the synthesis of the correspondingly methoxylated amphetamines which are of pharmacological and forensic interest because of abuse and illicit manufacture.     

Mass spectrometry of the paramagnetic nmr shift reagents Eu(fod)3 and Yb(fod)3 and their adducts with propylamine

By means of electron impact mass spectrometry, the occurrence of dimeric (or higher) associates of the lanthanide shift reagents Eu(fod)₃ and Yb(fod)₃ has been demonstrated. Also, the occurrence of 1:1 and 1:2 adducts of Ln(fod)₃ with propylamine was shown.     

Application of 1H NMR?Eu(fod)3?shifted spectra for the determination of the enantiomeric composition and absolute configuration of secondary alcohols,using (−)-ω-camphanic esters

The diastereomeric differences (Δδ) were measured for a series of 11 (?)-ω-camphanic esters of secondary alcohols of known absolute configuration, using ¹H NMR spectroscopy with Eu(fod)₃ as shift reagent. This method is convenient and useful for the measurement of enantiomeric compositions, whereas additional assumptions must be applied in determining the absolute configuration related to the signs of the diastereomeric differences.     

Etude par RMN du proton d'hétérocycles voisins de l'oxazaphospholane-1,3,2. I—La phényl-3 oxo-2 oxathiazolidine-1,3,2

A complete analysis of the ¹H NMR spectrum of the title compound is used for the conformational assignment of the molecule in the C-4—C-5 region. The position of protons is related to the position of the S?O bond with the help of a europium complex Eu(fod)₃. The results obtained are consistent with those found for similar compounds with or without a phosphorus atom.     

Excitation Energy-Transfer Processes in the Sensitization Luminescence of Europium in a Highly Luminescent Complex

The excitation energy transfer (EET) pathways in the sensitization luminescence of Eu^III and the excitation energy migration between the different ligands in [Eu(fod)₃dpbt] [where fod=6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedione and dpbt=2-(N,N-diethylanilin-4-yl)-4,6-bis(3,5-dimethylpyrazol-1-yl)-1,3,5-triazine], exhibiting well-separated fluorescence excitation and phosphorescence bands of the different ligands, were investigated by using time-resolved luminescence spectroscopy for the first time. The data clearly revealed that upon the excitation of dpbt, the sensitization luminescence of Eu^III in [Eu(fod)₃dpbt] was dominated by the singlet EET pathway, whereas the triplet EET pathway involving T₁(dpbt) was inefficient. The energy migration from T₁(dpbt) to T₁(fod) in [Eu(fod)₃dpbt] was not observed. Moreover, upon the excitation of fod, a singlet EET pathway for the sensitization of Eu^III luminescence, including the energy migration from S₁(fod) to S₁(dpbt) was revealed, in addition to the triplet EET pathway involving T₁(fod). Under the excitation of dpbt at 410 nm, [Eu(fod)₃dpbt] exhibited an absolute quantum yield for Eu^III luminescence of 0.59 at 298 K. This work provides a solid and elegant example for the concept that singlet EET pathway could dominate the sensitization luminescence of Eu^III in some complexes.     

Use of silver trifluoroacetate together with lanthanide shift reagents for simplification of 1H NMR spectra of aromatic hydrocarbons

The equimolar mixtures of typical lanthanide shift reagents such as Eu(fod)₃, Pr(fod)₃ or Yb(fod)₃ with silver trifluoroacetate, previously used to induce paramagnetic shifts in the ¹H NMR spectra of alkenes, have been successfully applied to simple aromatic hydrocarbons such as benzene, toluene, ethylbenzene and xylenes. In benzene and p-xylene the signals of all the aromatic protons are shifted identically. In other substituted benzenes the magnitude of the induced shift depends on the distance between the proton and the substituents. In addition, the different behaviour of the signals of the methyl groups in meta-and para-xylene on the addition of the complex shift reagent allows the quantitative analysis of the two xylenes in their mixtures.     

NMR experiments on acetals—XXXIX: Conformational insights through NMR studies at 300 MHz of 2-methyl-4-halogenomethyl-1,3-dioxolanes

NMR spectra of cis- and trans-2-methyl-4-halogeno-methyl-1,3-dioxolanes have been analysed at 300 MHz. Some of the extracted parameters facilitate easy distinction between these 1,3-dioxolanes and the corresponding structurally isomeric 2-Methyl-5-halogeno-1,3-dioxanes. Criteria enabling configurational assignments to be made for the cis-trans isomers of the dioxolane series are tested. The Me-2 group causes an upfield shift (0·2 to 0·3 ppm) of a trans proton at position 5, but the reversed shift for the corresponding cis proton. This competes with, or even overwhelms the effect of the CH₂X-4 substituent, which by virtue of its pronounced preferential rotameric orientation and in comparison with a simple Me-group, has no large upfield effect on the shift of the syn-adjacent proton. Shift criteria and coupling constants J_{H-4, H-5} in cis- and trans derivatives allow further conformational insights into these 1,3-dioxolanes.