Unusual conformational preferences of 1,3‐dimethyl‐3‐isopropoxy‐3‐silapiperidine

The conformational analysis of the first representative of the Si‐alkoxy substituted six‐membered Si,N‐heterocycles, 1,3‐dimethyl‐3‐isopropoxy‐3‐silapiperidine, was performed by low‐temperature ¹H and ¹³C NMR spectroscopy and DFT theoretical calculations. In contrast to the expectations from the conformational energies of methyl and alkoxy substituents, the Me_axi‐PrO_eq conformer was found to predominate in the conformational equilibrium in the ratio Me_axi‐PrO_eq : Me_eqi‐PrO_ax of ca. 2 : 1 as from the ¹H and ¹³C NMR study. The thermodynamic parameters obtained by the complete line shape analysis showed that the main contribution to the barrier to ring inversion originates from the entropy term of the free energy of activation. Copyright © 2012 John Wiley & Sons, Ltd.     

4‐Alkyl‐2,2,6,6‐tetramethyl‐1,4,2,6‐oxaazadisilinanes: synthesis,structure, and conformational analysis

4‐Alkyl‐2,2,6,6‐tetramethyl‐1,4,2,6‐oxaazadisilinanes RN[CH₂Si(Me)₂]₂O [R = Me ( 1 ), i‐Pr ( 2 )] were synthesized by two methods which provided good yields up to 84%. Low temperature NMR study of compounds ( 1 ) and ( 2 ) revealed a frozen ring inversion with the energy barriers of 8.5 and 7.7 kcal/mol at 163 and 143 K, respectively, which is substantially lower than that for their carbon analog, N‐methylmorpholine. DFT calculations performed on the example of molecule ( 1 ) showed that N? Me_ax conformer to exist in the sofa conformation with the coplanar fragment C? Si? O? Si? C, and its N? Me_eq conformer in a flattened chair conformation. Copyright © 2009 John Wiley & Sons, Ltd.     

Conformational analysis of 3‐methyl‐3‐silathiane and 3‐fluoro‐3‐methyl‐3‐silathiane

The conformational equilibria of 3‐methyl‐3‐silathiane 5 , 3‐fluoro‐3‐methyl‐3‐silathiane 6 and 1‐fluoro‐1‐methyl‐1‐silacyclohexane 7 have been studied using low temperature ¹³C NMR spectroscopy and theoretical calculations. The conformer ratio at 103 K was measured to be about 5 _ax: 5 _eq = 15:85, 6 _ax: 6 _eq = 50:50 and 7 _ax: 7 _eq = 25:75. The equatorial preference of the methyl group in 5 (0.35 kcal mol^?1) is much less than in 3‐methylthiane 9 (1.40 kcal mol^?1) but somewhat greater than in 1‐methyl‐1‐silacyclohexane 1 (0.23 kcal mol^?1). Compounds 5–7 have low barriers to ring inversion: 5.65 (ax → eq) and 6.0 (eq → ax) kcal mol^?1 ( 5 ), 4.6 ( 6 ), 5.1 (Me_ax → Me_eq) and 5.4 (Me_eq → Me_ax) kcal mol^?1 ( 7 ). Steric effects cannot explain the observed conformational preferences, like equal population of the two conformers of 6 , or different conformer ratio for 5 and 7 . Actually, by employing the NBO analysis, in particular, considering the second order perturbation energies, vicinal stereoelectronic interactions between the Si–X and adjacent C–H, C–S, and C–C bonds proved responsible. Copyright © 2010 John Wiley & Sons, Ltd.     

Conformational analysis of 3,3‐dimethyl‐3‐silathiane, 2,3,3‐trimethyl‐3‐silathiane and 2‐trimethylsilyl‐3,3‐dimethyl‐3‐silathiane—preferred conformers,barriers to ring inversion and substituent effects

The first conformational analysis of 3‐silathiane and its C‐substituted derivatives, namely, 3,3‐dimethyl‐3‐silathiane 1 , 2,3,3‐trimethyl‐3‐silathiane 2 , and 2‐trimethylsilyl‐3,3‐dimethyl‐3‐silathiane 3 was performed by using dynamic NMR spectroscopy and B3LYP/6‐311G(d,p) quantum chemical calculations. From coalescence temperatures, ring inversion barriers ΔG^≠ for 1 and 2 were estimated to be 6.3 and 6.8 kcal/mol, respectively. These values are considerably lower than that of thiacyclohexane (9.4 kcal/mol) but slightly higher than the one of 1,1‐dimethylsilacyclohexane (5.5 kcal/mol). The conformational free energy for the methyl group in 2 (?ΔG° = 0.35 kcal/mol) derived from low‐temperature ¹³C NMR data is fairly consistent with the calculated value. For compound 2 , theoretical calculations give ΔE value close to zero for the equilibrium between the 2 ‐Me_ax and 2 ‐Me_eq conformers. The calculated equatorial preference of the trimethylsilyl group in 3 is much more pronounced (?ΔG° = 1.8 kcal/mol) and the predominance of the 3 ‐SiMe_{3 eq} conformer at room temperature was confirmed by the simulated ¹H NMR and 2D NOESY spectra. The effect of the 2‐substituent on the structural parameters of 2 and 3 is discussed. Copyright © 2010 John Wiley & Sons, Ltd.     

EPR study of radiation-induced radicals in glutaric and amino acid derivatives in solid state

Gamma radiation-induced radicals of 2-methylglutaric acid (2MG), diethyl amino malonate hydrochloride (DEAMHCl), ethyl malonate monoamide have been investigated at room temperature by the electron paramagnetic resonance technique. The type of radicals formed and their room temperature stability were evaluated. Three different radicals have been detected. The free radicals formed in compounds were attributed to the HOOCCH₃?CH₂CH₂ COOH, CH₃?HCO₂CHNH₂COCH₂CH₃ HCl and NH₂COCH₂COO?HCH₃ radicals, respectively. The results were found to be in good agreement with the existing literature data and theoretical predictions conformation.     

Conformations and enthalpies of formation of methylenecyclohexane, 1,4‐dimethylenecyclohexane,cyclohexanone, 4‐methylenecyclohexanone, 1,4‐cyclohexanedione,and their mono‐ and dioxa derivatives by G3(MP2)//B3LYP calculations

A computational study of the stable conformations and gas‐phase enthalpies of formation at 25 °C of the title compounds has been carried out by G3(MP2)//B3LYP calculations. The work stems from our early observations on the thermodynamic and NMR spectroscopic properties of 2‐methylenetetrahydropyran and related compounds suggesting a dominating chair conformation, with poor p–π overlap in the ? O? C?C moiety, for these compounds. Besides computational verification of the chair conformation of 2‐methylenetetrahydropyran, the work was extended to find out the stable conformations of a number of other related compounds and to evaluate the relative stabilities of the various conformers. Another important goal of the work was the estimation of the gas‐phase enthalpies of formation of the present compounds, for which such literature data are scarce. A significant error in the literature value of the enthalpy of formation of methylenecyclohexane was found. Finally, the relative enthalpy levels of the isomeric compounds of this work are discussed. The high thermodynamic stability of the compounds containing an ester functional group, ? O? C?O, relative to the stability of isomeric compounds with an ? O? C?C moiety in place of the ester function, is demonstrated. Copyright © 2009 John Wiley & Sons, Ltd.     

Raman and ab initio study of the conformational isomerism in the 1‐ethyl‐3‐methyl‐imidazolium bis(trifluoromethanesulfonyl)imide ionic liquid

The calculated and experimental Raman spectra of the (EMI⁺)TFSI⁻ ionic liquid, where EMI⁺ is the 1‐ethyl‐3‐methylimidazolium cation and TFSI⁻ the bis(trifluoromethanesulfonyl)imide anion, have been investigated for a better understanding of the EMI⁺ and TFSI⁻ conformational isomerism as a function of temperature. Characteristic Raman lines of the planar (p) and non‐planar (np) EMI⁺ conformers are identified using the reference (EMI⁺)Br⁻ salt. The anion conformer of C₂ symmetry is confirmed to be more stable than the cis (C₁) one by 4.5 ± 0.2 kJ mol⁻¹. At room temperature, the population of trans (C₂) anions and np cations is 75 ± 2% and 87 ± 4%, respectively. Fast cooling quenches a metastable glassy phase composed of mainly C₂ anion conformers and p cation conformers, whereas slow cooling gives a crystalline phase composed of C₁ anion conformers and of np cation conformers. Copyright © 2006 John Wiley & Sons, Ltd.     

N‐σ versus π configuration in mono‐ and bis‐pyrrole and imidazole derivatives of alkaline earth metals

A theoretical study of the preferred N‐σ or π configuration of the mono‐ and bis‐pyrrole and imidazole derivatives of alkaline earth metals has been carried by means of DFT and ab initio methods, up to G2 computational level. The energetic results show that the beryllium derivatives prefer the N‐σ configuration while the calcium ones prefer the π one. In the case of magnesium, both configurations present similar stability. The calculated dissociation enthalpies correspond to the fact that the metallic atom is strongly bonded to the azoles in both configurations. The NBO analysis shows that the systems can be considered as formed by the azolates interacting with the charged metallic atom and thus the Natural Energy Decomposition Analysis (NEDA) indicates that the main attractive force is the electrostatic. Copyright © 2009 John Wiley & Sons, Ltd.     

Anion effect on the conformational equilibrium of sulfamide and its N,N′‐diindolyl derivative: Insights on anion transportation

The relatively high acidity of the sulfamide hydrogens suggests a potential for the development of sulfamide derivatives as novel anion receptors. The interactions of sulfamide with F^?, Cl^?, CH₃COO^?, and H₂PO₄^? anions were spectroscopically (¹H and ¹⁹F NMR) and theoretically (density functional theory) analyzed, and the complexation through hydrogen bonds was confirmed by changes in the NMR signals and theoretical calculations. The replacement of 2 sulfamide hydrogens with indolyl groups yields the N,N′‐diindolylsulfamide ( DIS , N‐1H‐indol‐4‐yl‐N′‐1H‐indol‐7‐ylsulfuric diamide), whose bond rotations allow the interaction of 4 H(N) atoms with anions. The conformational preferences of DIS change upon the presence of anions, but they are practically insensitive to the anion type. According to the quantum theory of atoms in molecules, natural bond orbital analysis, and NMR chemical shifts, as well as to a thermodynamic cycle, the complex with fluoride is the most stable, followed by the oxoanion‐derived models.     

Substituent effect investigation of 3‐(2, 4‐dichlorophenyl)‐1‐(4′‐X‐phenyl)‐2‐propen‐1‐one. Part 1. Correlation analysis of 13C NMR chemical shifts

A series of substituted chlorinated chalcones namely, 3‐(2,4‐dichlorophenyl)‐1‐(4′‐X‐phenyl)‐2‐propen‐1‐one, have been synthesized, X being H, NH₂, OMe, Me, F, Cl, CO₂Et, CN, and NO₂. Dual substituent parameter (DSP) models of ¹³C NMR chemical shift (CS) have revealed that π‐polarization concept could be utilized to explain the reverse field effect at CO, the enhanced substituent field effect at CO, C‐2, and C‐5, and the decreased sensitivity of substituent field effect at C‐6. Chlorine atoms dipole direction at the benzylidene ring either enhances or reduces substituent effect depending on how they couple with the substituent dipole at the probe site. The correlation of ¹³C NMR CS of C‐2, C‐5, and C‐6 with σ and σ indicates that chlorine atoms in the benzylidine ring deplete the ring from charges. Both MSP of Hammett and DSP of Taft ¹³C NMR CS models give similar trends of substituent effects at C‐2, C‐5, and C‐6. However, the former fail to give a significant correlation for CO and C‐6 ¹³C NMR CS. MSP of σ_q and DSP of Taft and Reynolds models significantly correlated ¹³C NMR CS of C_β. MSP of σ_q fails to correlate C‐1′ ¹³C NMR CS. Investigation of ¹³C NMR CS of non‐chlorinated chalcones series: 3‐phenyl‐1‐(4′‐X‐phenyl)‐2‐propen‐1‐one has revealed similar trends of substituent effects as in the chlorinated chalcones series for C‐1′, CO, C_α, and C_β. In contrast, the substituent effect of the non‐chlorinated chalcone series at C‐2, C‐5, and C‐6 did not correlate with any substituent constant. Copyright © 2010 John Wiley & Sons, Ltd.     

DFT,FT‐Raman,FT‐IR and NMR studies of 2‐fluorophenylboronic acid

The experimental and theoretical vibrational spectra of 2‐fluorophenylboronic acid (2fpba) were studied. The Fourier transform Raman and Fourier transform infrared spectra of the 2fpba molecule were recorded in the solid phase. The structural and spectroscopic analysis of the molecule was carried out by using Hartree‐Fock and density functional harmonic calculations. For the title molecule, only one form was found to be the most stable structure, by using B3LYP level with the 6‐31++G(d,p) basis set. Selected experimental bands were assigned and characterized on the basis of the scaled theoretical wavenumbers by their total energy distribution (TED). The ¹H and ¹³C nuclear magnetic resonance (NMR) chemical shifts of the 2fpba molecule were calculated using the Gauge‐Invariant‐ atomic orbital (GIAO) method in DMSO solution using IEF‐PCM model and compared with the experimental data. Finally, geometric parameters, vibrational wavenumbers and chemical shifts were compared with available experimental data of the molecule. Copyright © 2009 John Wiley & Sons, Ltd.     

Vibrational spectroscopy and DFT calculations of di‐amino acid peptides: α‐ and β‐N‐acetyl‐L‐Asp‐L‐Glu in the solid state

Experimental vibrational spectroscopic studies and density functional theory (DFT) calculations of the di‐amino acid peptide derivatives α‐ and β‐N‐acetyl‐L‐Asp‐L‐Glu have been undertaken. Raman and infrared spectra have been recorded for samples in the solid state. DFT simulations were conducted using the B3‐LYP correlation functional and the cc‐pVDZ basis set to determine energy minimized/geometry optimized structures (based on a single isolated molecule in the gaseous state). Normal coordinate calculations have provided vibrational assignments for fundamental modes, including their potential energy distributions. Significant differences are observed between α‐ and β‐N‐acetyl‐L‐Asp‐L‐Glu both in the computed structures and in the vibrational spectra. The combination of experimental and calculated spectra provide an insight into the structural and vibrational spectroscopic properties of di‐amino acid peptide derivatives. Copyright © 2009 John Wiley & Sons, Ltd.     

Unexpected dimerization of 1,3‐dimethyl‐5‐methylenebarbituric acid revealed by a combined experimental and computational study

A comparison of experimental and calculated ¹³C‐nuclear magnetic resonance chemical shifts reveals the molecular structure of a dimer that was obtained by an unexpected dimerization of 1,3‐dimethyl‐5‐methylenebarbituric acid. Furthermore, the puckering angle of the cyclobutane unit linking the six‐membered rings is discussed in detail. The influence of substituents on 1,3‐position of the cyclobutane ring on the puckering angle is demonstrated based on 1,1,3,3‐tetramethylcyclobutane. Copyright © 2015 John Wiley & Sons, Ltd.     

1,1,1‐Trichloro‐3‐(1‐phenethylamino‐ethylidene)‐ pentane‐2,4‐dione—synthesis,spectroscopic, theoretical and structural elucidation

1,1,1‐Trichloro‐3‐(1‐phenethylamino‐ethylidene)‐pentane‐2,4‐dione is spectroscopically and structurally elucidated by means of linear‐polarized IR spectroscopy (IR‐LD) of oriented solids as a colloidal suspension in nematic liquid crystal. Structural information and IR‐spectroscopic assignment are supported by quantum chemical calculations at MP2 and B3LYP level of theory and 6‐311++G** basis set. The geometry is characterized with an inramolecular hydrogen bond of NH^…O?C with length of 2.526 Å and a NHO angle of 140.5(1)°. The NH? C(CH₃)C?C? C?O(CH₃) fragment is nearly flat with a maximal deviation of total planarity of 10.4°. Copyright © 2007 John Wiley & Sons, Ltd.     

Substituent effects on conformational preference in α‐substituted α‐fluorophenylacetic acid methyl ester model systems for chiral derivatizing agents

In connection with study of chiral derivatizing agents (CDAs) for NMR determination of absolute configuration of organic compounds, factors controlling the conformational preference between syn‐ and anti‐forms in α‐substituted α‐fluorophenylacetic acid methyl ester (FC(X)(Ph)COOMe) model systems were theoretically investigated. Substituents X at the stereogenic carbon atom were X = H, C?CH and CH₃, the electronic and steric properties of which were significantly different from each other. The model system with X = C?CH and that with X = CH₃ were found to be possible candidates for fluorine‐containing CDAs. The syn conformation is stable compared with the anti one by 0.7 kcal mol^?1 for the ester with X = C?CH. On the other hand, the anti conformation is stable compared with the syn one by 0.5 kcal mol^?1 for the ester with X = CH₃. Both natural bond orbital (NBO) analysis and deletion of selected orbitals based on the donor–acceptor NBO scheme were adopted for semi‐quantitative estimation of factors responsible for the conformational preference as well as a qualitative inspection of occupied canonical molecular orbitals (MOs). It was shown that [σ–(σ* + π*)(C?O)] and [σ–σ*(Ph) and π(Ph)–σ*] hyperconjugations are the main factors controlling the conformational preferences between the syn and anti conformations. Other types of effects such as electrostatic effects were also investigated. The role of the fluorine atom was also clarified. Copyright © 2009 John Wiley & Sons, Ltd.     

The analysis of pH‐dependent protonated conformers of 1‐hydroxyethylidene‐1,1‐diphosphonic acid by means of FT‐Raman spectroscopy,multivariate curve resolution and DFT modelling

1‐Hydroxyethylidene‐1,1‐diphosphonic acid (HEDP) solutions in the pH range 0.98–13.00 were analysed using FT‐Raman spectroscopy and ³¹P and ²³Na NMR spectroscopy. Vibrational bands for different protonated species were observed in the Raman spectra, whereas only a single NMR signal that shifted with pH was observed for all samples over the entire pH range. No significant shift in the ²³Na NMR signal was observed, confirming that formation of Na⁺(aq) complexes did not take place; hence, no interference with the different protonated forms of HEDP occurred. Vibrational bands were assigned using density functional theory(DFT)‐calculated spectra of the most likely conformers in solution. Multivariate curve resolution was performed on the Raman spectra in the region containing the PO stretching vibrations to determine the number of protonated species formed over the entire pH range. Chemometric analysis compares very favourably with the experimental species distribution diagram which was generated using the reported log K_H values. Copyright © 2009 John Wiley & Sons, Ltd.     

Conformational analysis of 4,4‐dimethyl‐1‐(trifluoromethylsulfonyl)‐1,4‐azasilinane and 2,2,6,6‐tetramethyl‐4‐(trifluoromethylsulfonyl)‐1,4,2,6‐oxazadisilinane

4,4‐Dimethyl‐1‐(trifluoromethylsulfonyl)‐1,4‐azasilinane 1 and 2,2,6,6‐tetramethyl‐4‐(trifluoromethylsulfonyl)‐1,4,2,6‐oxazadisilinane 2 were studied by variable temperature dynamic ¹H, ¹³C, ¹⁹F NMR spectroscopy and theoretical calculations at the DFT (density functional theory) and MP2 (Møller‐Plesset 2) levels of theory. Both kinetic (barriers to ring inversion) and thermodynamic data (frozen conformational equilibria) could be obtained for the two compounds. The computations revealed two minima on the potential energy surface for molecules 1 and 2 corresponding to the rotamers with the CF₃SO₂ group directed ‘inward’ and ‘outward’ the ring, the latter being 0.2–0.4 kcal/mol (for 1 ) and 1.1 kcal/mol (for 2 ) more stable than the former. The vibrational calculations at the DFT and MP2 levels of theory give the values of the free energy difference ΔG^o for the ‘inward’ ‘outward’ equilibrium consistent with those determined from the experimentally measured ratio of the rotamers. The structure of crystalline compound 2 was ascertained by X‐ray diffraction analysis. Copyright © 2011 John Wiley & Sons, Ltd.     

Conformational analysis of N‐phenyl‐ and N‐trifyl‐4,4‐dimethyl‐4‐silathiane 1‐sulfimides

N‐Substituted 4,4‐dimethyl‐4‐silathiane 1‐sulfimides [R = Ph ( 1 ), CF₃ ( 2 )] were studied experimentally by variable temperature dynamic NMR spectroscopy. Low temperature ¹³C NMR spectra of the two compounds revealed the frozen ring inversion process and approximately equal content of the axial and equatorial conformers. Calculations of the 4‐silathiane derivatives 1 , 2 and the model compound [R = Me ( 3 )] as well as their carbon analogs, the similarly N‐substituted thiane 1‐sulfimides [R = Ph ( 4 ), CF₃ ( 5 ), Me ( 6 )] at the DFT/B3LYP/6–311G(d,p) level in the gas phase and in chloroform solution using the PCM model at the same level of theory showed a strong dependence of the relative stability of the conformer on the solvent. The electronegative trifluoromethyl group increases the relative stability of the axial conformer. Copyright © 2010 John Wiley & Sons, Ltd.     

Ring inversion process for a series of 3,5‐dialkyl‐1‐oxa‐3,5‐diazacyclohexanes: 1H DNMR study and semiempirical calculations

The ring inversion process for a series of 3,5‐dialkyl‐1‐oxa‐3,5‐diazacyclohexanes was studied using proton dynamic nuclear magnetic resonance (¹H DNMR) spectroscopy in conjunction with semiempirical calculations. At low temperature, the ring methylene protons decoalesced into two AB spin systems in a 2:1 ratio. Lineshape simulations of the DNMR spectra provided first‐order rate constants for magnetic exchange. The energy barrier for each inversion reaction was calculated from the respective rate constants. In general, as the size of the N‐alkyl group increased, the barrier to ring inversion decreased. A similar trend was seen in semiempirical calculations that modeled the ring inversion process. Copyright © 2010 John Wiley & Sons, Ltd.     

Nitrosation of dialkylhydroxylamines,and computational and NMR investigations of the interconversion of conformational isomers of N‐nitroso‐dimethylhydroxylamine

The effect of acidity upon the rate of nitrosation of N‐benzyl,O‐methylhydroxylamine ( 3 ) in 1:1 (v/v) H₂O/MeOH at 25 °C has been investigated. The pseudo‐first‐order rate constant (k_obs) for loss of HNO₂ as the limiting reagent decreases as [H₃O⁺] increases. This is compatible with two parallel reaction channels (Scheme 2 ). One involves the direct reaction of the free hydroxylamine with HNO₂ (k₁ = 1.4 × 10² dm³ mol^?1 s^?1, 25 °C) and the other involves the reaction of the free hydroxylamine with NO⁺ (k₂ = 5.9 × 10⁹ dm³ mol^?1 s^?1). In contrast, there is only a very slight increase in k_obs with increasing [H₃O⁺] for nitrosation of N,O‐dimethylhydroxylamine ( 4 ) in dilute aqueous solution at 25 °C to give N‐nitroso‐dimethylhydroxylamine, 5 . This also fits a two‐channel mechanism (Scheme 3 ). Again, one involves the nitrosation of the free base by NO⁺ (k₂ = 8 × 10⁹ dm³ mol^?1 s^?1, 25 °C) but the other channel now involves catalysis by chloride (k₃ = 1.3 × 10⁸ dm³ mol^?1 s^?1). Arising from these results, we propose an estimate of pK_a ～ ?5 for protonated nitrous acid, (O = N? OH), which is appreciably different from the literature value of +1.7. The interconversion of cis and trans conformational isomers of 5 has been investigated by temperature‐dependent NMR spectroscopy in CDCl₃, methanol‐d₄, toluene‐d₈ and dimethyl sulfoxide‐d₆. Enthalpies and entropies of reaction and of activation have been determined and compared with computational values obtained at the B3LYP/6‐31G* level of theory. The cis form is slightly more stable at normal temperatures and no solvent effects upon the thermodynamics or kinetics of the conformational equilibrium were predicted computationally or detected experimentally. In addition, key geometric parameters and dipole moments have been calculated for the cis and trans forms, and for the lowest energy transition structure for their interconversion, in the gas phase and in chloroform. These results indicate electronic delocalisation in the ground states of 5 which is lost in the transition structure for their interconversion. Copyright © 2010 John Wiley & Sons, Ltd.