Compounds with bridgehead nitrogen. 44—the conformational analysis of perhydropyrido[1,2-c] [1,3]thiazine

The 270 MHz NMR data on trans- and cis-(H-4a, H-7)-7-ethylperhydropyrido[1,2-c][1,3]thiazine show heavy conformational bias to the trans- and S-inside cis-fused conformations, respectively. Comparison of the ¹³C NMR spectra of these anancomeric systems with the ¹³C NMR spectrum of perhydropyrido[1,2-c][1,3]thiazine indicates a trans-?S-inside cis-conformational equilibrium for the latter compound in CDCl₃ at 25°C, containing ca 75% trans-fused conformer. The ¹³C NMR spectrum of perhydropyrido[1,2-c][1,3]-thiazine at ?75°C showed 64% trans-fused conformer and 36% S-inside cis-conformer.     

Uncovering Key Structural Features of an Enantioselective Peptide‐Catalyzed Acylation Utilizing Advanced NMR Techniques

We report on a detailed NMR spectroscopic study of the catalyst‐substrate interaction of a highly enantioselective oligopeptide catalyst that is used for the kinetic resolution of trans‐cycloalkane‐1,2‐diols via monoacylation. The extraordinary selectivity has been rationalized by molecular dynamics as well as density functional theory (DFT) computations. Herein we describe the conformational analysis of the organocatalyst studied by a combination of nuclear Overhauser effect (NOE) and residual dipolar coupling (RDC)‐based methods that resulted in an ensemble of four final conformers. To corroborate the proposed mechanism, we also investigated the catalyst in mixtures with both trans‐cyclohexane‐1,2‐diol enantiomers separately, using advanced NMR methods such as T₁ relaxation time and diffusion‐ordered spectroscopy (DOSY) measurements to probe molecular aggregation. We determined intramolecular distance changes within the catalyst after diol addition from quantitative NOE data. Finally, we developed a pure shift EASY ROESY experiment using PSYCHE homodecoupling to directly observe intermolecular NOE contacts between the trans‐1,2‐diol and the cyclohexyl moiety of the catalyst hidden by spectral overlap in conventional spectra. All experimental NMR data support the results proposed by earlier computations including the proposed key role of dispersion interaction.     

Conformational Studies of a Six-Membered Phostone

Abstract

Although 1,3,2-dioxaphosphorinanes generally assume chair conformations,¹ there are examples in which the ring adopts the boat or twist-boat form.¹ Recent studies on the synthesis, stereochemistry, and reactivity of 2-alkoxy-2-oxo-1,2-oxaphosphorinanes (phostones) have revealed both cis and trans isomers of 3-(diphenylhydroxymethyl)-2-ethoxy-2-oxo-1,2-axaphosphorinane² to assume a chair conformation in the solid state. In the present work, the conformational properties of cis and trans-3-methoxycarbonyl-2-methoxy-2-oxo-1,2-oxaphosphorinanes were investigated by X-ray analysis, variable temperature ³¹P, ¹H and ¹H{³¹P} NMR spectroscopy, molecular mechanics, and semiempirical calculations. The X-ray crystal structure of the trans isomer revealed a chair dormation with equatorial phosphoryl and carbomethoxy groups. No changes were observed in the ³¹P NMR spectra of either isomer in the temperature range of 183–333 K. A complete set of vicinal J_HH coupling constants was extracted from the ¹H{³¹P} spectra of each isomer taken at five temperatures over the range of 213–293 K and refined by simulation of the spectra. The best-fit analysis of this data using a generalized Karplus equation³ revealed that the conformation of the trans isomer in solution was close to that found in the solid state. This conformation corresponded to the global energy minimum calculated by both molecular mechanics and PM3 semiempirical method. A substantial contribution from an inverted chair conformation of the cis isomer had to be assumed to achieve a reasonable fit of the coupling constants calculated from the generalized Karplus equation.     

Conformational analysis of N,N,N‐Trimethyl‐(3,3‐dimethylbutyl)ammonium iodide by NMR spectroscopy: a sterically hindered trans‐standard

A predominantly trans‐1,2‐disubstituted ethane system – N,N,N‐trimethyl‐(3,3‐dimethylbutyl)ammonium iodide – is of particular interest for conformational analysis, because it contains both an organic and a highly polar substituent, making it soluble and thus applicable to study in a large variety of solvents. The fraction of the trans conformer of this molecule in a wide range of protic and aprotic solvents was determined by the nuclear magnetic resonance proton couplings to be approximately 90%, in contrast to the previously assumed 100%. The consistently strong preference of the trans conformation should establish N,N,N‐trimethyl‐(3,3‐dimethylbutyl)ammonium iodide as a possibly useful ‘trans‐standard’ in conformational analysis, much more so than 1,2‐ditert‐butylethane, which has a poor solubility in many solvents. Copyright © 2013 John Wiley & Sons, Ltd.     

Conformational equilibria in isomeric methylcyclohexanols studied by 13C NMR spectroscopy

The conformational equilibrium constants for isomeric methylcyclohexanols (cis- and trans-1,2-, 1,3- and 1,4-methylcyclohexanols) have been determined from peak area measurements in the completely proton decoupled low temperature ¹³C NMR spectra of the individual conformers. The ¹³C chemical shifts are discussed in terms of the additive model.     

Microstructure of polyisoprene produced by cationic polymerization: NMR spectroscopic study

High-resolution ¹H and ¹³C NMR spectroscopy, including two-dimensional heteronuclear experiments, has been used to study the microstructure of polyisoprene produced by cationic polymerization. It is shown that macromolecules resulting from both regular and inverse additions are predominantly composed of trans-1,4-units, while 1,2- and 3,4-units are present in small amounts. NMR spectra demonstrate the absence of cis-1,4-units in the polymer, whereas broad signals (pedestals) are related to the presence of saturated structures. It is proposed to determine the content of trans-1,4-, 1,2-, and 3,4-units in cationic polyisoprene via the combined measurements of intensities of signals in the olefinic regions of ¹H and ¹³C NMR spectra.     

Conformational analysis of <Emphasis Type="Italic">cis-</Emphasis> and <Emphasis Type="Italic">trans</Emphasis>-isomers of 2,5-dimethyl-1,3-dioxane

The conformational isomerization of cis- and trans-isomers of 2,5-dimethyl-1,3-dioxane was investigated by means of ab initio RHF//6-31G(d) and PBE//ccpVDZ quantum-chemical methods. It has been shown that in comparison with cis-form the potential energy surface of trans-isomer has a less number of stationary points and includes the main minimum belonging to the diequatorial chair form. In the case of cisisomer the main minimum corresponds to the C 2e5a chair form. The values of potentional barriers of conformational isomerization were also determined. On the basis of experimental (NMR ¹H) and theoretical vicinal coupling constants we determine the value ΔG ⁰ of chair-chair inversion for the trans-isomer molecule.     

Reductive Coupling of Halomethylbenzene Derivatives by Nickel and Cobalt

Reduction of benzyl bromide, benzal chloride and benzotrichloride with a commercial nickel powder at 150°C gave bibenzyl, trans-stilbene, and trans-1,2-dichlorostilbene. The reaction intermediates 1,2-dichloro-1,2-diphenylethane for benzal chloride and 1,1,2,2-tetrachloro-1,2-diphenylethane for benzotrichloride were also isolated or detected by NMR spectroscopy. Dehalogenation of these intermediates by the nickel metal or by KI yielded the corresponding trans isomer as the main product. A commercial cobalt powder also reacted with these organic halides leading to similar results. Mechanisms for these reactions are proposed.     

Chemical shift assignment and conformational analysis of monoalkylated acylguanidines

Monoalkylated acylguanidines are important functional groups in many biologically active compounds and additionally applied in coordination chemistry. Yet a straightforward assignment of the individual NH chemical shifts and the acylguanidine conformations is still missing. Therefore, in this study, NMR spectroscopic approaches for the chemical and especially the conformational assignment of protonated monoalkylated acylguanidines are presented. While NOESY and ³J_{H, H} scalar couplings cannot be applied successfully for the assignment of acylguanidines, ⁴J_{H, H} scalar couplings in ¹H,¹H COSY spectra allow for an unambiguous chemical shift and conformational assignment. It is shown that these ⁴J_{H, H} long‐range couplings between individual acylguanidinium NH resonances are observed solely across all‐trans (w) pathways. Already one cis orientation in the magnetisation transfer pathway leads to signal intensities below the actual detection limit and significantly lower than cross‐peaks from ²J_{NH, NH} couplings or chemical exchange. However, it should be noted that also in the case of conformational exchange being fast on the NMR time scale, averaged cross‐peaks from all‐trans ⁴J_{H, H} scalar couplings are detected, which may lead at first glance to an incomplete or even wrong conformational analysis. Copyright © 2010 John Wiley & Sons, Ltd.     

Solid state N and C NMR study of dioxomolybdenum (VI) complexes of Schiff bases derived from trans-1,2-cyclohexanediamine

The ¹³C, ¹⁵N CP MAS NMR and FT-IR spectra of dioxomolybdenum (VI) complexes of trans-N,N′-bis-(R-salicylidene)-1,2-cyclohexanediamine (R=H, R=3,5-diCl, R=3,5-diBr, R=4,6-diOCH₃), trans-N,N′-bis-(2-OH-naphthylidene)-1,2-cyclohexanediamine and trans-N-(salicylidene)-N′-(2-OH-naphthylidene)-1,2-cyclohexanediamine have been measured. Comparative analysis of the NMR and IR spectra of the complexes with those of the corresponding ligands has shown that the complexation of the di-Schiff bases leads to changes in the conformation of the ligands and the charge redistribution. The asymmetric structure and non-planar structure of the complexes have been suggested.     

Synthesis and structural characterization of syndiotactic trans‐1,2 and cis‐1,2 polyhexadienes

The (E) isomer in mixtures of (E) and (Z) 1,3‐hexadiene was polymerized with the system CoCl₂(PⁱPrPh₂)₂‐MAO, a highly active and stereospecific catalyst for the preparation of 1,2 syndiotactic polybutadiene. A new crystalline polymer with a melting point of 109 °C was obtained. The polymer was characterized by IR, NMR (¹³C, ¹H in solution and ¹³C in the solid‐state), X‐ray diffraction, DSC, GPC and it was found to have a trans‐1,2 syndiotactic structure with a 5.18 ± 0.04 Å fiber periodicity. Since only the (E) isomer was polymerized, at the end of the reaction we were able to separate the (Z) isomer, which was ultimately polymerized with CpTiCl₃‐MAO at low temperature, obtaining a low molecular weight, stereoregular polymer that, characterized by IR and NMR methods, was found to exhibit a cis‐1,2 syndiotactic structure, never reported before. Molecular mechanics calculations were carried out on the trans‐1,2 syndiotactic polymer and structural models consistent with the X‐ray diffraction data are proposed. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5339–5353, 2007     

Glass-transition temperature and microstructure of polybutadienes

DSC and NMR are employed to determine the glass-transition temperatures and the structural features of polybutadienes with widely varying configuration isomeric compositions. The dependences of the glass-transition temperature on the contents of cis-1,4-, trans-1,4, and 1,2-units in polybutadiene chains are plotted and discussed. An analysis of the experimental results and the published data suggests that, in the study of the glass-transition-structure relationship, simplified approaches are inapplicable and it is necessary to consider the configurational and conformational geometry of polybutadiene chains.     

Angular dependence of the vicinal interproton spin–spin coupling in silacyclohexanes. The conformational energy term of the methyl group in 1-methyl-1-silacyclohexane

An approximate Karplus-Conroy relationship between the vicinal coupling constants J(H SiCH ) in a silaethane fragment and the corresponding torsional angles τ in silacyclohexanes is proposed. The relationship ³J(H SiCH ) VS τ is asymmetric. The ¹H NMR parameters and conformational features of cis- and trans-3,5-dimethyl-1-silacyclonexane and 3-silabicyclo[3.2.1]octane are discussed, and the conformational energy term for the methyl group in 1-methyl-1-silacyclohexane is found to be approximately 1.45 kJ mole^?1 in favour of the axial position for the methyl group, in good agreement with previously calculated values.     

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.     

Conformational analysis. Part 40: a theoretical and NMR investigation of the conformations of cis‐ and trans‐cyclopentane‐1,3‐diol

The conformations of cis‐ ( 1 ) and trans‐cyclopentane‐1,3‐diol ( 2 ) have been studied by ab initio (Gaussian 98) and molecular mechanics (PCMODEL) calculations and by NMR spectroscopy. The calculations gave two low‐energy conformations for ( 1 ), 1A and 1B , both with axial hydroxyl groups. Two conformations with equatorial hydroxyl groups ( 1C and 1D ) were found but with much higher energy (ca 4.0 kcal mol^?1). Five low‐energy conformers were found for 2 . Four were envelope conformations and one a half‐chair. The complete analysis of the 400 MHz ¹H NMR spectra of 1 in a variety of solvents and 2 in chloroform was performed by extensive decoupling experiments, iterative computer analysis and spectral simulation. This gave all the H,H couplings in the molecule, including in 1 a long‐range ⁴J(H,H) coupling between H‐2cis and H‐4,5cis. The ³J(H,H) couplings were used to determine the conformer populations in these molecules. This was initially achieved using the Haasnoot, de Leeuw and Altona equation. to obtain the conformer couplings. It was found that this equation was not accurate for the C·CH₂·CH₂·C fragment in these molecules and the following equation was derived for this fragment from five‐ and six‐ membered cyclic compounds in fixed conformations: (1) The conformer populations were obtained by calculating the conformer couplings which were then compared with the observed couplings. Compound 1 in benzene solution is an approximately equal mixture of conformers 1A and 1B with small (<4%) amounts of 1C and 1D . In the polar solvents acetone and acetonitrile the populations of 1A and 1B are again equal, with 20% of 1C and <2% of 1D . In 2 the major conformers are 2B and 2D with small amounts of 2C , 2E and 2A . These novel findings are considered with previous data on cyclopentanol and cis‐ and trans‐cyclopentane‐1,2‐diol and it is shown that the axial hydroxyl substituent at the fold of the envelope appears to be a major factor in determining the conformational energies of these compounds. Copyright © 2003 John Wiley & Sons, Ltd.     

A new insight into the mechanism of 1,3‐dienes cationic polymerization. II. Structure of poly(1,3‐pentadiene) synthesized with tBuCl/TiCl4 initiating system

The microstructure of poly(1,3‐pentadiene) synthesized by cationic polymerization of 1,3‐pentadiene with ^tBuCl/TiCl₄ initiating system is analyzed using one‐dimensional‐ and two‐dimensional‐NMR spectroscopy. It is shown that unsaturated part of chain contains only homo and mixed dyads with trans?1,4‐, trans?1,2‐, and cis?1,2‐structures with regular and inverse (head‐to‐head or tail‐to‐tail) enchainment, whereas cis?1,4‐ and 3,4‐units are totally absent. The new quantitative method for the calculation of content of different structural units in poly(1,3‐pentadiene)s based on the comparison of methyl region of ¹³C NMR spectra of original and hydrogenated polymer is proposed. The signals of tert‐butyl head and chloromethyl end groups are identified in a structure of poly(1,3‐pentadiene) chain and the new approaches for the quantitative calculation of number‐average functionality at the α‐ and ω‐end are proposed. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3297–3307     

Studies on the stereochemistry of 1,2,6-trimethyl-4-piperidone

In the effort to create new derivatives of analgesically active spiropiperidines intermediate 1,2,6-trimethyl-4-piperidone was synthesized. The substitution of the skeleton gives rise to configurational as well as conformational isomerism. Despite the symmetry of 1,2,6-trimethyl-4-piperidone two different sets of signals were present in the ¹H and ¹³C NMR spectra. They were supposed to arise from a cis/trans mixture of 1,2,6-trimethyl-4-piperidone. In contrast to this explanation only two signals of the methyl groups and hydrogens at carbon atoms 2 and 6 were observed in the ¹H and ¹³C NMR spectra, normally expecting one for the cis- and two for the trans-isomer. To solve this discrepancy, the kind of isomeric mixture of 1,2,6-trimethyl-4-piperidone leading to the ¹H and ¹³C NMR spectra was examined. Energy differences between chair conformations of both the cis- and the trans-isomer of 1,2,6-trimethyl-4-piperidone and the potential energy surface of the equilibration process of the trans-isomer of 1,2,6-trimethyl-4-piperidone between its chair conformers were determined by quantum chemical calculations. The barrier height of the equilibration process was measured by high and low temperature NMR measurements to confirm the theoretical outcome. The results of all investigations agree nicely and proved a cis-/trans-mixture of 1,2,6-trimethyl-4-piperidone being present at room temperature.     

1,2-Dimethyl-1,2-diphenyidisilane-1,2-diol and its K,Na, and FeII derivatives. Molecular structure of the all-trans-isomer, 2,3,5,6-tetra-methyl-2,3,5,6-tetraphenyl-1,4-dioxa-2,3,5,6-tetrasilacyclohexane

Hydrolysis of 1,2-dimethyl-1,2-diphenyl-1,2-dichlorodisilane yields 1,2-dimethyl-1,2diphenyldisilane-1,2-diol, which undergoes dimerization into stereoisomeric 2,3,5,6-tetramethyl-2,3,5,6-tetraphenyl-1,4-dioxa-2,3,5,6-tetrasilacyclohexanes under the action of H₂SO₄. Pure all-trans-isomer has been isolated and characterized by¹H NMR and IR spectroscopy and X-ray analysis. The reaction of sodium disilanediolate with FeBr₂ results in the formation of 1,2-dimethyl-1,2-diphenyl-4-ferra(ii)-3,5-dioxa-1,2-disilacyclopentane.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2550–2556, October, 1996.     

Deuterium isotope effects on 15N chemical shifts of double Schiff bases in the solid state and solution

The proton transfer equilibrium in a series of double Schiff base derivatives of trans‐1,2‐diaminocyclohexane in solution and the solid state was studied by means of ¹⁵N NMR spectroscopy and analysis of the deuterium isotope effect on the chemical shifts Δ¹⁵N(D). The presence of a proton transfer equilibrium in the N‐2‐hydroxynaphthylidene moieties of the Schiff bases studied in the solid state at room temperature was evidenced. The results confirmed the interrelation of the two hydrogen bonds in double Schiff base derivatives of trans‐1,2‐diaminocyclohexane. Copyright © 2003 John Wiley & Sons, Ltd.     

Characterization of diene polymers. I. Infrared and NMR studies: Nonadditive behavior of characteristic infrared bands

Extinction coefficients of the characteristic infrared bands due to isomeric structural units were measured for polybutadiene and polyisoprene in CS₂ or CCl₄ solutions and were compared with the isomer composition determined by NMR. The NMR signal assignments were made on the basis of the spectra of deutero derivatives of the polymers. In the case of polyisoprene, linear relations were obtained between the extinction coefficients and the isomer contents determined by NMR for the absorption bands at 1385 cm^?1 (characteristic of trans-1,4 units), 1376 cm^?1 (cis-1,4 units), and 889 cm^?1 (3,4 units). However, for the absorption bands at 840 cm^?1 (characteristic of cis-1,4 and trans-1,4 units), isomerized polyisoprenes did not give such a linear relationship. In polybutadiene, the extinction coefficient for the atactic 1,2 units was found to be lower than that of the syndiotactic 1,2 unit. These experimental facts lead to the conclusion that additivity of the extinction coefficients does not always hold for diene polymers. The deviation from the linear relation may be associated with regular sequences of one isomeric conformation in the chain.