Nuclear magnetic resonance of 1,4-benzodiazepines. II Stereochemistry of 1,3-dihydro-2H-1,4-benzodiazepin-2-ones by lanthanide shift reagents

The sterochemistry of some 1,3-dihydro-2H-1,4-benxodiazepin-2-ones, employed as psychotherapeutic agents, is deduced by proton magnetic resonance using the paramagnetic shift reagent Eu(fod)₃. the lanthanide induced shifts are computer simulated on the basis of the geometric parameters of the protons in different model structures, having intermediate conformations between a cycloheptadiene- and a cyclohepatatriene-like system. N-Desmethyldiazepam shows a conformational equilibrium between two pseudoboat forms, while the 1-alkyl substituted derivatives exist, at room temperature, in olny one boat cycloheptatriene-like conformation.     

Application of Lanthanide Shift Reagent to the 1H-NMR Assignments of Acridone Alkaloids

This study investigates the application of the paramagnetic shift reagent tris(dipivaloylmethanato)-europium(III) in NMR spectral studies of permethoxyacridone alkaloids (1–3) and pyranoacridone alkaloids (4–6). The induced chemical shifts (∆δ) of all protons were observed for the same molecule, and were compared to deduce the positions resulting from the distance nearby the Eu(dpm)₃. Assignment of the H-2, H-4 and H-8 of polysubstituted acridones could be distinguished based on the least-squares method of lanthanide-induced shifts plotted against the mole ratios of Eu(dpm)₃ to the substrate. The developed method is not only potentially useful for determining the planar structures of polysubstituted compounds, such as acridones, anthraquinones, xanthones, flavonoids, and phenanthrenes, but also applicable for their stereochemistry.     

Détermination par Résonance Magnétique Nucléaire de la Configuration d'alcools Bicycliques [4.2.0] et Tricycliques [6.4.0.02,7] ou [5.4.0.02,6]

The configuration of various bicyclo[4.2.0]octanols has been established by ¹H NMR spectroscopy, with Eu(dpm)₃ as shift reagent. The intrinsic parameters Δ and K have been obtained and used as structural probes. Moreover, detailed data analysis showed that, contrary to the generally accepted concept, the vicinal coupling constant between trans cyclobutanic protons can be larger than that between cis protons. The chemical shifts obtained by ¹³C NMR spectroscopy are consistent with the proposed structures. The results have been extensively used to determine unambiguously the configuration of tricyclo[6.4.0.0^2,7]dodecanols and tricyclo[5.4.0.0^2,6]undecanol.     

1H- und 13C-NMR-spektroskopische Untersuchungen zur Ladungsverteilung in substituierten 1,3-Dioxan-2-ylium-Salzen

The ¹H and ¹³C NMR spectra of a series of 1,3-dioxan-2-ylium salts substituted at C-2 and C-4, C-5, C-6 have been measured. The atomic charge distribution in 1,3-dioxan- and 1,3-dioxolan-2-ylium cations has been calculated with the MINDO/3 method, leading to a linear correlation between π-charge and ¹³C chemical shift at C-2. The strong C-21-proton downfield shift is caused by the anisotropic influence of the mesomeric cation system. The conformations of substituted 1,3-dioxan-2-ylium cations are discussed.     

Chemical shift reagents in the study of polycyclic alcohols IX—1H NMR spectra of myrtenol and some other primary alcohols

Structure proof of (—)-myrtenol, 3-cyclopentenyl-1-methanol and 5-norbornene-2-endo-methanol has been obtained from their proton magnetic resonance spectra in carbon tetrachloride containing different added amounts of tris(dipivaloylmethanato)europium. For each alcohol, a 1:1 complex structure with Eu(dpm)₃ could be computed, in which the calculated pseudocontact shift effects on all skeleton protons of the ring system were consistent with the observed shift effect values. A considerable contact contribution of opposite sign to that of the pseudocontact part of the effect could be estimated for the methylene protons of the CH₂OH group.     

Conformational Analysis. XIX properties and reactions of 1,3-oxathianes VIII A 1H NMR conformational study of methyl-substituted derivatives

The addition of thioacetic acid to unsaturated alcohols or acids was utilized to obtain mercaptoalkanols which were condensed with suitable carybonyl compounds to prepare 24 methyl-substituted 1,3-oxathianes. The ¹H NMR spectra of the 1,3-oxathiane products were recorded at 60, 100 and/or 300 MHz and fully analysed. The results are best explained by a chair form which is completely staggered in the C-4? C-5? C-6 moiety ψ₄₅ or (ψ₅₆=60±1°). 1,3-Oxathianes having syn-axial 2,4- (and/or 2,6-) methyl-methyl interactions exist appreciably, if not exclusively, in twist forms. The vicinal coupling constants lead to the conformational free energies of axial methyl groups at C-4, ΔG°=7.4±0.4 kJ mol^?1, and at C-5, ΔG°=3.7±0.3 kJ mol^?1, in good agreement with previous estimates. They also show that both r-4,cis-5,trans-6- and r-4,trans-5,trans-6- trimethyl-1,3-oxathianes greatly favour the chiar form where the methyl group at C-4 is axial. The chair-twist energy parameters are reestimated at ΔH°_CT 27.0 kJ mol^?1, ΔS°_CT 11.6J mol^?1K^?1, and ΔG°_CT(298) 23.5 kJ mol^?1 for a 2,5-twist form.     

31P-NMR-Daten heterocyclischer phosphine. Diastereomerenzuordnung an 1,3-Oxa-, 1,3-Aza- und 1,3-thiaphospholanen

The diastereomers of 16 1,3-oxa-, 1,3-aza- and 1,3- thiaphospholanes were assigned by means of the coupling constants ²J(P? C? H) and ³J(P? C? CH₃) and the linewidths of the ³¹P signals and ¹H chemical shifts of CH₃ groups. It is shown that the change in the ³¹P chemical shifts allows the estimation of the relative configuration in these compounds.     

Lanthanide-induced shifts of diastereotopic groups

The chemical shift differences of diastereotopic protons in aliphatic acyclic alcohols, mostly of the type R? CH₂? CR′R″? (CH₂)_nOH, have been investigated. Fairly small amounts of Eu(dpm)₃ cause the spectra of these materials to simplify dramatically; indeed, even diastereotopic protons rather far removed form the hydroxyl group give discrete signals in the presence of the shift reagent. Large shift differences were realized in the γ-protons (n = 1) and the δ-protons (n = 2), particularly if R is bulky and R' and R″ have different steric requirements. Semi-quantitative conformational preferences can be determined from the data obtained.     

NMR-Untersuchungen an Dicyclopentadienderivaten. IV—1-Syn/anti-Epimere von endo-Dicyclopentadienderivaten

The syn/anti-arrangement of some substituents R in position 1 of endo-dicyclopentadiene derivatives is investigated by ¹H-and ¹³C n.m.r. spectroscopy. The HH-coupling constants of the epimeric alcohols 2 and 3 are determined by paramagnetic shift experiments [Eu(fod)₃] and the observed relative paramagnetic shifts ΔEu used for the determination of the configuration. The increasing steric compression in the syn-epimers is well reflected by the ¹H- and ¹³C n.m.r. chemical shifts.     

NMR-Untersuchungen an Dicyclopentadienderivaten: III—Stereochemische Zuordnung von überbrückten endo-Dicyclopentadienderivaten und deren Wagner-Meerwein-Umlagerungs-produkten mit Hilfe der NMR-Spektroskopie

The ¹H n.m.r. spectra of some substituted oxa- and azatetracycloundecanes are studied and selected examples analysed in detail with the aid of spin-spin decoupling and Eu(fod)₃ paramagnetic shift experiments. From the quoted ¹³C n.m.r. spectra the carbon resonances are assigned, using known substituent effects and paramagnetic shift values. The determined paramagnetic shift parameters ΔEu are discussed in respect of their contact and pseudocontact contributions.     

An NMR study of the conformations of certain alcohol derivatives of tricarbonyl(diene)iron compounds: A critique

The initial assignments by Mahler and Pettit of relative configurations of the two racemic diastereomeric tricarbonyl-(trans,trans-3,5-heptadien-2-ol)iron complexes and to the two racemic diastereomeric tricarbonyl-(trans-3,5-hexadien-2-ol)iron complexes are consistent with NMR coupling constants, conformational analysis, previously reported Eu(fod)₃ lanthanide-induced shift data and new Yb(dpm)₃ lanthanide-induced shift data. A detailed discussion shows that, contrary to the claim by Foreman, the lanthanide-induced shift data alone provide no new information regarding the relative configurations of these alcohols.     

Theoretical approach to the out-of-plane deformation of 1,3-disubstituted azulenes

Computational calculations at B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels were employed to analyze the structure and conformation of 1,3-bis(4-bromophenyl)azulene (1), 1,3-bis(2-thienyl)azulene (2), and 1,3-bis(2-pyrrollyl)azulene (3) in order to rationalize the out-of-plane deformation found in the azulene cores of 1 and 2 in the crystalline state, whereas compound 3 shows a totally planar azulene moiety. Our results indicate that 1,3-disubstituted azulenes possess two almost equally stable and easily convertible minimum energy conformers, which differ in the relative orientation of the substituent groups and in the planarity degree of the azulene core. An absolute planarity index (P) is introduced to quantify the out-of-plane distortion found in the azulenes under study. The aromaticity of minimum energy conformers was evaluated by means of geometric (HOMA), magnetic (NICS), and energetic (the frequency of the lowest out-of-plane vibration, ν_min) aromaticity indicators, which suggest that compound 3 possesses the most aromatic azulene core within the group. Calculated molecular dipole moments suggest that the conformation of 1,3-disubstituted azulenes in the crystalline state can be explained in terms of electrostatic intermolecular interactions rather than relative stability of planar and non-planar conformers.     

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.     

[4+2]-Cycloadditionen von 1,2-Dicyanocyclobuten und seine thermische Ringöffnung zum 2,3-Dicyanobutadien-1,3

Facile synthetic routes to 1,2-dicyanocyclobutene ( 3 ), cyclobutene-1,2-dicarboxylic acid ( 56 ) and derivatives thereof are presented, starting from 1,2-dicyanocyclobutane ( 1 ), a commercially available acrylonitrile cyclodimer. The favored mode of [4+2]-cycloadditions of 3 to cyclic dienes with sp³carbon atoms is the endo-addition (above 90% relative yields of adducts with endo-cyclobutane ring). Exo-cycloaddition, however, is preferred by dienes having no sp³-carbon atom (e.g. furane). Cyclisation reactions involving cis-vicinal substituents in [4+ 2]-cycloadducts afford (m.n. 2)-azapropellanes 18 , 74 and 77 . ¹H- and ¹³C-NMR. spectra of the stereoisomeric adducts are discussed in detail. The structures of the furane adducts 14 and 15 were determined by ¹H-NMR. using the shift reagent Eu(dpm)₃. Reactive butadienes 32 , 53 - 55 are obtained in high yield and purity by gasphase thermolysis (380–420°) of the correspondingly substituted cyclobutenes. 2,3-Dicyanobutadiene-l, 3 ( 32 ) gives good yields of [4 + 2]-cycloadducts with strained cycloolefines, moderate yields with vinylethers and non-activated olefins, and no adducts at all with electrophilic dienophiles (8.g. maleic anhydride, fumaronitrile). Thus, reactions of 32 are typical Diels-Alder reactions with ‘inverse electron demand’. Some of these primary [4+2]-cycloadducts ( 38 , 39 and 45 ) were dehydrogenated to new aromatic ortho-dinitriles 46 - 48 .     

A Thermodynamic, 13C NMR,and 17O NMR Study of Isomeric 4,7-Dihydro-1,3-dioxepins and 4,5-Dihydro-1,3-dioxepins

The relative thermodynamic stabilities of 4,7-dihydro-1,3-dioxepin (4,6-dioxacycloheptene, 1a) and 4,5-dihydro-1,3-dioxepin (3,5-dioxacycloheptene, 1b), and of a number of their 2-substituted derivatives, have been determined by base-catalyzed chemical equilibration in DMSO solution. Without exception, the 4,5-dihydro isomer is the dominating species at thermodynamic equilibrium. The relative stability of the b form is promoted by the presence of a single alkyl group on C-2, whereas two alkyl groups on C-2 have an opposite effect. In general, the thermodynamic parameters H _m and _Sm , of isomerization vary unexpectedly with the pattern of substitution at C-2. These trends appear to be derived from significant substituent-induced conformational changes in the b isomer, as suggested by ¹³C and ¹⁷O NMR chemical shift data.     

1H NMR spectra of alkane‐1,3‐diols in benzene: GIAO/DFT shift calculations

The proton nuclear magnetic resonance (NMR) spectra of propane‐1,3‐diol, 2‐methylpropane‐1,3‐diol, 2,2‐dimethylpropane‐1,3‐diol, butane‐1,3‐diol, 3‐methylbutane‐1,3‐diol, pentane‐2,4‐diols (dl and meso), 2‐methylpentane‐2,4‐diol and cyclohexane‐1,3‐diols (cis and trans) in benzene have been analysed. The conformer distribution and the NMR shifts of these diols have been computed on the basis of density functional theory, the solvent being included by means of the integral equation formalism phase continuum model (IEFPCM) implemented in Gaussian 09. Relative Gibbs energies of all conformers are calculated at the Perdew, Burke and Ernzerhof (PBE)0/6‐311 + G(d,p) level, and NMR shifts by the gauge‐including atomic orbital method with the PBE0/6‐311 + G(d,p) geometry and the cc‐pVTZ basis set. Vicinal coupling constants for 1,2‐ and 1,3‐diols are rationalised in terms of relative conformer populations and geometries. The NMR shifts of hydrogen‐bonded protons in individual conformers of alkane‐1,n‐diols show a very rough correlation with the OH?OH distances. The computed overall NMR shifts for CH protons in 1,2‐ and 1,3‐diols are systematically high but correlate very well with the experimental values, with a gradient of 1.07 ± 0.01. Some values for nonequivalent methylene protons in 1,3‐diols are reversed, calculation giving enhanced values for the proton anti to the C? OH bonds. Errors in the NMR shifts computed for the OH protons of nonsymmetrical diols appear to be related to relative populations of conformers where one or other of the OH groups is the donor. Some results based on the second‐order Møller–Plesset approach, the Becke three‐parameter Lee‐Yang‐Parr method and on the IEFPCM solvation model implemented in Gaussian 03 are included. Copyright © 2013 John Wiley & Sons, Ltd.     

Theoretical study of the conformational structure and thermodynamic properties of 5-(4-oxo-1,3-thiazolidine-2-ylidene)-rhodanine and ethyl-5-(4-oxo-1,3-thiazolidine-2-ylidene)-rhodanine-3-acetic acid as acceptor groups of indoline dyes

The quantum chemical DFT method with the B3LYP hybrid functional in 6–31++G(d,p) and 6–311+G(d,p) basis sets is used to calculate the equilibrium geometric parameters of different conformations of 5-(4-oxo-1,3-thiazolidine-2-ylidene)-rhodanine and its substituted form ethyl–5-(4-oxo-1,3-thiazolidine-2-ylidene)-rhodanine-3′-acetic acid applied in the synthesis of indoline and some other sensitizing dyes for solar cells. The thermodynamic parameters of four conformers and their synthesis reactions are calculated. The effect of substituents on the thermodynamic stability of the studied isomers is shown.     

Conformational analysis of 5-substituted 1,3-dioxanes

Quantum-chemical study on the potential energy surface of 5-alkyl- and 5-phenyl-1,3-dioxanes at the RHF/6-31G(d) level of theory revealed two pathways for conformational isomerizations of the equatorial and axial chair conformers. Potential barriers to this process were estimated. The Gibbs conformational energies ΔG° of substituents at C⁵ in the 1,3-dioxane ring were determined on the basis of experimental (¹H NMR) and theoretical vicinal coupling constants, which turned out to be consistent with published data.     

(15N) acetamide in polar solvents: Hindered internal rotation and intermolecular interactions

The ¹H spectrum of (¹⁵N)acetamide has been measured in dimethyl sulphoxide (DMSO), methyl propyl ketone (MPK), 1,3-dioxane, 1,4-dioxane, D₂O, acetonitrile and pyridine-d₅ at various temperature intervals within the range of 278–343 K. From the temperature dependence of the NMR spectra of the amide protons, the free energy of activation, ΔG^≠, for hindered rotation about the central C? N bond was determined by means of total line shape analysis in the four solvents DMSO, MPK and the two dioxanes. Observed values of ΔG^≠ (298 K) (72.7 in DMSO, 70.1 in MPK, 70.0 in 1,3-dioxane and 70.1 kJ mol¹ in 1,4-dioxane) were not very sensitive to the choice of solvent or concentration. The concentration dependence of the internal chemical shift between the amide protons was studied in MPK, D₂O, acetonitrile and pyridine-d₅. The free energy of activation and the internal chemical shift are discussed on the basis of solvent-amide and amide–amide specific hydrogen bonding interactions, and in comparison to the results of molecular orbital calculations.     

Nuclear magnetic resonance and stereochemistry of vincamone

The stereochemistry in solution of vincamone was deduced by proton magnetic resonance using the paramagnetic shifts reagent Eu(fod)₃. The lanthanide induced shift computer simulation suggests that, at room temperature, the indole group is nearly planar, the rings C and E assume the envelope conformation with N-4 and C-16 as flaps, the ring D is in the chair one and the ethyl side chain prefers a trans position with respect to C-15.