NMR Coupling Constants Research Articles

Hetero-Diels-Alder reactions of alpha-aryl-beta-monohalo-alpha-nitrosoethylenes: diastereoselective synthesis of 6-substituted 3-aryl-4-halo-5,6-dihydro-4H-1,2-oxazines.

Treatment of alpha-aryl-beta-bromo(or chloro)-alpha-nitrosoethylene, prepared in situ from alpha-monobromo(or chloro)ketoximes and sodium carbonate in ether at rt, with allytrimethylsilane afforded exclusively trans-(4S,6S)- and trans-(4R,6R)-3-aryl-4-halo-6-[(trimethylsilyl)methyl]-5,6-dihydro-4H-1,2-oxazines 10 albeit in low yields. Similar treatment of beta-halo-alpha-nitrosoethylenes with ethyl vinyl ether, however, gave single stereoisomers, i.e., cis-(4S,6S)- and cis-(4R,6R)-6-ethoxy-4-halo-5,6-dihydro-4H-1,2-oxazines 11, in moderate to good yields. The result is in contrast to the reported predominant formation of trans-11a by a radical reaction. On the other hand, similar reactions with tert-butyl vinyl ether at 30 degrees C gave diastereomeric mixtures of cis-(4S,6S)-, cis-(4R,6R)-, trans-(4S,6R)-, and trans-(4R,6S)-6-(tert-butoxy)-4-halo-5,6-dihydro-4H-1,2-oxazines 12. In contrast to compounds 11, the major isomers have (4S,6R) and (4R,6S) configurations. The tendency of a [4 + 2] cycloaddition reaction is consistent with that observed in the Diels-Alder reaction with inverse-electron demand. The stereochemistries of compounds 10-12 were assigned on the basis of the (1)H NMR coupling constants, which were unambiguously determined by the decoupling experiments. All reactions leading to compounds 10-12 proceed with very high regioselectivity. Diastereoselectivity and high regioselectivity are understood in terms of the frontier orbital method. It has been found that cis-12g is isomerized to a mixture of stereoisomers in favor of the trans-isomer in the presence of HClO(4) (72%) in CHCl(3) at rt.

1,2:4,5-Di-O-isopropylidene-β-D-erythro-hexo-2,3-diulo-2,6-pyranose

The crystal structure of title compound, C12H18O6, has been determined using single-crystal data. There are two independent mol­ecules in the asymmetric unit. NMR coupling constants, dihedral angles as well as puckering parameters indicate the 3S0 conformation of the pyran­ose ring in both mol­ecules A and B. The cis-fused 1,3-dioxolane ring in both mol­ecules A and B, adopts an E4 conformation. The second five-membered 1,3-dioxolane ring, in mol­ecule A, has an E2 conformation, whereas in mol­ecule B, this 1,3-dioxolane ring adopts an E4 conformation. Molecules A form a zigzag infinite chain along the b axis with mol­ecules B as side chains. This explains why the displacement ellipsoids of atoms of mol­ecule B are substantially larger than those of mol­ecule A.

NMR analysis of the trisaccharide 2′‐fucosyllactose by heteronuclear trans‐glycosidic coupling constants and molecular simulations

Abstract1H, 13C NMR coupling constants across the glycosidic linkages were measured for the trisaccharide α‐L‐Fucp‐(1→2)‐β‐D‐Galp‐(1→4)‐D‐Glcp from human milk and its reduced analogue α‐L‐Fucp‐(1→2)‐β‐D‐Galp‐(1→4)‐D‐Glucitol employing one‐dimensional multiple‐site 13C excitation experiments. Hadamard spectroscopy and pulsed field gradients were also used with or without band‐selective 1H decoupling during the acquisition period. The experimental scalar coupling constants were compared to those calculated from Langevin dynamics simulations employing different molecular mechanics force fields. An analysis of 3J(C,H) values determined with this NMR technique on di‐ and trisaccharides is also performed. Copyright © 2001 John Wiley & Sons, Ltd.

Complete Prediction of the 1H NMR Spectrum of Organic Molecules by DFT Calculations of Chemical Shifts and Spin–Spin Coupling Constants

1H NMR chemical shifts and coupling constants for several aromatic and aliphatic organic molecules have been calculated with DFT methods. In some test cases (furan, o-dichlorobenzene and n-butyl chloride) the performance of several functionals and basis sets has been analyzed, and the various contributions to spin–spin coupling (Fermi-contact, diamagnetic and paramagnetic spin-orbit) have been evaluated. The latter two components cancel each other, so that the calculation of the contact term only is sufficient for an accurate evaluation of proton–proton couplings. Such calculated values are used to simulate the 1H NMR spectra of organic molecules with complicated spin systems (e.g. naphthalene, o-bromochlorobenzene), obtaining a generally very good agreement with experimental spectra with no prior knowledge of the involved parameters.

Conformational analysis of 2‐bromocyclohexanone. A combined NMR, IR, solvation and theoretical approach

AbstractAn improved method of conformational analysis using 1H and 13C NMR, IR, theoretical calculations and solvation theory is reported for 2‐bromocyclohexanone, used here as a model compound. The solvent dependence of the 3JHH, 1JCH and 1JCD NMR coupling constants and the associated changes in the IR first overtone carbonyl band intensities together with theoretical calculations allow the direct determination of the conformational equilibria without recourse to model compounds. Calculations with the Gaussian 98 program at the HF/6–31 g(d,p) and B3LYP/6–31 + g(d,p) levels together with solvation theory gave the conformer free energy difference (Eeq − Eax) in different solvents. The observed couplings, when analyzed by solvation theory and utilizing DFT geometries, gave a value of Eeq − Eax of 1.15 kcal mol−1 in the vapor phase, decreasing to 0.6 kcal mol−1 in CCl4 and to −0.5 kcal mol−1 in DMSO solution (1 kcal = 4.184 kJ). The axial percentage changes from 74% (in CCl4) to 30% (in DMSO), and these are in good agreement with infrared data (νCO, first overtone), despite the uncertainties of the latter method. The results illustrate the advantages of the joint application of these techniques, which represents an improved approach to the study of the conformational equilibria of substituted cyclohexanones. Copyright © 2001 John Wiley & Sons, Ltd.

Synthesis, solution and solid-state structure of Pd(II), Pt(II), Ir(III) and Zn(II) complexes with 5-pyridyl substituted N-methyl isoxazolidines

Pd(II), Pt(II), Zn(II) and Ir(III) complexes with 5-pyridine substituted N-methyl isoxazolidines (4-(2-methyl-3-phenylisoxazolidin-5-yl)-pyridine ( L 1 ), 2-(2-methyl-3-phenylisoxazolidin-5-yl)-pyridine ( L 2 ), 2-(2-methyl-3-ferrocenylisoxazolidin-5-yl)-pyridine ( L 3 )) have been prepared and characterized by 1H, 13C, and 31P NMR. The configurations of coordinated isoxazolidines have been assigned by the analysis of NMR coupling constants and by nuclear Overhauser measurements through 2D-ROESY experiments. The molecular structures of [Cp*Ir( L 2 )Cl][BPh 4] ( 6) (Cp*-pentamethylcyclopentadienyl) and trans-[PdCl 2( L 3 )PEt 3] ( 8) have been established by means of X-ray crystallography. The crystal structure of 6 consists of piano stool geometry with respect to the Ir(III) center with N, N-bidentate coordinated ligands. The six-membered chelate ring formed by Ir(1), N(1), C(5), C(6), O(1), N(2) possesses a ‘twist-tub’ conformation. The crystal structure of 8 consists of neutral square planar Pd(II) complexes. L 3 is coordinated in a monodentate manner via the pyridine nitrogen atom. The isoxazolidine fragment of both compounds has an envelope conformation. NMR data are consistent with an O, N-bidentate coordination of L 2 for [Zn( L 2 )Cl 2] ( 5), while L 1 act as a monodentate ligand through the nitrogen atom of the pyridine in [Zn( L 1 ) 2Cl 2] ( 4).

Boat conformations: Synthesis, NMR spectroscopy, and molecular dynamics of methyl 4,6- O-benzylidene-3-deoxy-3-phthalimido-α- d-altropyranoside derivatives

Addition of the elements of phthalimide to methyl 2,3-anhydro-4,6- O-benzylidene-α- d-mannopyranoside ( 1) under fusion conditions has yielded methyl 4,6- O-benzylidene-3-deoxy-3-phthalimido-α- d-altropyranoside ( 2). The conformation of the pyranose ring of 2 has been shown to be non-chair by 1H NMR spectroscopy, in contrast to the conformations of related derivatives having smaller substituents at C-3. Molecular dynamics simulations of 2 in explicit chloroform- d solvent have indicated four principal conformational possibilities. Of these, the 7 C 5/ 1 S 5 chair/skew boat form 2d has the lowest potential energy, and is largely consistent with the observed vicinal 1H– 1H NMR coupling constants.

Complete prediction of the 1H NMR spectrum of organic molecules by DFT calculations of chemical shifts and spin-spin coupling constants.

1H NMR chemical shifts and coupling constants for several aromatic and aliphatic organic molecules have been calculated with DFT methods. In some test cases (furan, o-dichlorobenzene and n-butyl chloride) the performance of several functionals and basis sets has been analyzed, and the various contributions to spin-spin coupling (Fermi-contact, diamagnetic and paramagnetic spin-orbit) have been evaluated. The latter two components cancel each other, so that the calculation of the contact term only is sufficient for an accurate evaluation of proton-proton couplings. Such calculated values are used to simulate the 1H NMR spectra of organic molecules with complicated spin systems (e.g. naphthalene, o-bromochlorobenzene), obtaining a generally very good agreement with experimental spectra with no prior knowledge of the involved parameters.

A first comparison of solid state and solution structure of a complex between lanthanum nitrate and 1,9-diaza-18-crown-6.

[figure: see text] The structure of the complex between lanthanum(III)nitrate and 1,9-diaza-18-crown-6 is analyzed with three independent methods. The conformation observed by analysis of vicinal NMR coupling constants in solution agrees with both the one found by a single crystal X-ray study and with simulations by molecular orbital and force field calculations. In the acetonitrile solution, the NMR data show a bent crown conformation with nearly C2v symmetry, which is stable on the NMR time scale.

CD exciton chirality method for determination of the absolute configuration of β‐hydroxy‐α‐amino acid derivatives

The absolute configuration of beta-hydroxy-alpha-amino acids was studied by CD exciton chirality method using 7-diethylaminocoumarin-3-carboxylate as a red-shifted chromophore. The CD spectra of bischromophoric derivatives of (S)-serine and (2S,3R)-threonine methyl esters (2 and 7) were compared with those of acyclic vic-aminoalcohols and diols (3--6 and 8--9). This study indicates that the polar carboxylate group of beta-hydroxy-alpha-amino acids makes them a unique subclass of vic-aminoalcohols. By combining the data of CD and NMR coupling constants, we are able to correlate their preferred conformer B and positive CD to the corresponding absolute configuration.

Modeling of Substituent Effects: Self-Parametrization, a Case of Interdependence of the Coefficients, Illustrated on the Linear Plus Cross-Term Models

The effect of one or several substituents X i on a molecular property f (reaction rate, spectroscopic property, etc.) is often described in terms of substituent parameters λ i (X) depending on the nature X of the substituent, and the position i of substitution. We call self-parametrization the case when the substituents are parameterized by the value λ i (X)=f i (X) of f itself in the molecule monosubstituted by X in position i. On the example of the linear plus cross-term models, we show that self-parametrization implies that the coefficients of the model are interdependent. The theoretical relations between them are given, for equivalent or nonequivalent positions of substitution, and tested on measured acid–base equilibrium constants, and NMR coupling constants.

Interdependence of phosphorus-31–selenium-77 NMR coupling constants in bicyclic phosphorus selenide compounds†

Bicyclic compounds exo,exo-α-P4Se3X2 and exo,exo-α-P4Se3XI (X = CN, NMePh or NPri2) and endo,exo-α-P4Se3(CN)2 have been made in solution and their 31P and 77Se NMR spectra completely analysed. Ab initio calculations of 31P and 77Se NMR shieldings in exo,exo- and endo,exo-α-P4Se3(CN)2 and in exo,exo-α-P4Se3(CN)I confirmed these assignments. In an unsymmetric compound exo,exo-α-P4Se3XI the twelve 31P–77Se NMR coupling constants have values related to those in the corresponding symmetric compounds exo,exo-α-P4Se3X2 and exo,exo-α-P4Se3I2 by simple rules, useful for predicting couplings in exo,exo-α-P4Se3X2 when the spectra of exo,exo-α-P4Se3XI and exo,exo-α-P4Se3I2 have already been analysed.

On the convergence of FPT-DFT calculations of the Fermi contact contribution to NMR coupling constants

Calculations of the Fermi contact term of NMR couplings, JFC(MN), using a single FC perturbation within the Finite Perturbation Theory-DFT frameworks are only reliable if they do not depend either on a) the size of the perturbation, and b) whether the perturbation is placed at the site of the M or N nucleus. In this short communication these two points are addressed by studying the 1JFC(MN) and 2JFC(MN) linear response behavior in a set of small molecules. It is shown how such a linearity depends on the size of the finite perturbation, the basis set employed, and the chosen nucleus site. The dependence of SCF convergence requirements on the size of the perturbation is also discussed. Calculations are carried out employing the B3LYP and B3PW91 hybrid functionals and results are compared with both state-of-the-art calculations and experimental values.

Application of the BIRD sandwich for the rapid and accurate determination of (1)H-(1)H NMR coupling constants in higher order spin systems.

A method is presented that allows for the convenient and reliable determination of (1)H-(1)H NMR coupling constants in higher order or symmetrically coupled spin systems. The method can be applied on any programmable FT-NMR spectrometer and is demonstrated here on micromole quantities of sample in a standard 5-mm NMR tube.

Extracting Residual NMR Coupling Constants From Electrically Aligned Liquids

Molecular alignment by an electric field is used to reintroduce quadrupolar couplings into the nuclear magnetic resonance spectrum of polar liquids. By interleaving a pulsed electric field with rf pulse sequences in a controlled way, spectral simplification is introduced by correlating isotropic chemical shifts with residual anisotropic couplings in a two-dimensional fashion. The success of these experiments is facilitated by combining rapid π rf pulsing with multiple quantum filtration to minimize molecular motion effects on the measured signal. An analysis of the observed coupling constants and their relation to molecular structure are provided.

Quantum Mechanical Conformational Analysis of β-Alanine Zwitterion in Aqueous Solution

The conformational behavior of β-alanine zwitterion in aqueous solution has been investigated by post-Hartree−Fock and density functional methods using the polarizable continuum model (PCM) for the description of the solvent. Our results show that the PCM is able to reproduce the delicate balance between intramolecular hydrogen bridges and preferential solvation of isolated charged groups in determining the overall conformational preferences without any need of explicit solvent molecules. From a methodological point of view, the Hartree−Fock method is not sufficiently reliable for quantitative predictions of conformer equilibria, whereas approaches including electron correlation (DFT, MP2, MP4) perform remarkably well when using medium size basis sets including diffuse functions. Vibrational averaging arising from the torsional motion around the central CC bond leads to vicinal NMR coupling constants (J) in remarkable agreement with experiments when using an extended Karplus-type equation for the torsiona...

Synthesis and fluorine NMR chemical shifts for a series of exo-3,3-difluorotricyclo[3.2.1.0 2,4]octyl derivatives : The Diels–Alder alternative to difluorocarbene additions

The Diels–Alder cycloaddition of 1,2-dihalo-3,3-difluorocyclopropenes 1 to a series of five-membered ring dienes stereoselectively provided the corresponding exo-2,4-dihalo-3,3-difluorotricyclo[3.2.1.0 2,4]oct-6-ene adducts. Removal of the C2, C4 halogens(bromine or chlorine) before or after saturation of the C6, C7 double bond afforded a variety of gem-difluorocyclopropyl derivatives in the analogous tricyclic manifold. The 19F and 1H NMR chemical shifts and coupling constants are listed for each of these tricyclic systems.

MCSCF calculations of NMR spin–spin coupling constant of the HF molecule

The dependence of spin–spin NMR coupling constants on the basis set and electron correlation has been investigated for the hydrogen fluoride using Hartree–Fock (HF-SCF) and multiconfigurational self-consistent field (MCSCF) wave functions. The effect of the size, contraction, and tight s-type, augmented and polarization functions in the basis sets is analyzed. MCSCF wave functions with different number of active orbitals and excited electrons were used within the frozen-core approximation and with all-electron calculations. The correlation effect associated with the core electrons is not negligible. An approximation to determine spin–spin coupling constants at high level of electron correlation and reduced computational cost is applied satisfactorily. The best calculated and estimated 1JFH couplings are 544.20 and 536.63 Hz, respectively, with all electron correlation. Both values agree with the experimental one within the error bars (525±20 Hz).

Preparation, stereochemistry, and cytotoxic activity of the melampolides from Mikania minima.

The semisyntheses of melampolides 1 and 2, previously found in Mikania minima, were carried out in order to confirm their chemical structures and to establish their absolute configurations. Their conformational analyses, performed using molecular mechanics, experimental (1)H NMR coupling constants, and NOE experiments, showed a preferred DU conformer in solution at room temperature. The cytotoxic activities of 1 and 2 against three tumor cell lines were also determined. Conjugated aldehyde 2 showed higher activity than alcohol 1.

Trans-Dichlorobis(triphenylphosphine-P)platinum(II)

Two different crystals (A and B) were used to structurally characterize trans-[PtCl2(PPh3)2] and to study random and systematic errors in derived parameters. The compound is isomorphous with trans-[PdCl2(PPh3)2] and with one of the polymorphs of trans-[PtMeCl(PPh3)2] reported previously. Half-normal probability plot analyses based on A and B show realistic s.u.'s and negligible systematic errors. R.m.s. calculations give very good agreement between A and B, 0.0088 A. Important geometrical parameters are Pt—P = 2.3163 (11) A, Pt—Cl = 2.2997 (11) A, P—Pt—Cl = 87.88 (4) and 92.12 (4)°. Half-normal probability plots and r.m.s. calculations were also used to compare the title compound with the palladium analogue, showing small systematic differences between the compounds. The torsion angles around the Pt—P bond were found to be very similar to those reported for isomorphous complexes, as well as to the torsion angles around the Pt—As bond in trans-[PtCl2(AsPh3)2]. The NMR coupling constants for the title compound are similar to Pt—P coupling constants reported for analogous trans complexes.