Syntheses and conformational analyses of mono- and trans-1,4-dialkoxy substituted cyclohexanes—the steric substituent/skeleton interactions

Mono- and trans-1,4-dialkoxy substituted cyclohexanes (alkyl=Me, Et, i-Pr, t-Bu) were prepared using the solvomercuration-demercuration (SM-DM) procedure. The axial?axial and axial,axial?equatorial, equatorial conformational equilibria of the products were studied by low temperature ¹H and ¹³C NMR spectroscopy in CD₂Cl₂. The structures and relative energies of the participating conformers were calculated at both the B3LYP (6-311G^∗//6-311+G^∗) and MP2 (6-311+G^∗//6-311G^∗) levels of theory. In the case of DFT, good correlations of ΔG^o_calcd versus ΔG^o_exptl were obtained. Both the structures and the energy differences of the conformers have been discussed with respect to established models of conformational analysis, viz. steric and hyperconjugative interactions. In addition, ¹J_H,C coupling constants were considered with respect to the hyperconjugation present.     

A quest for triplet silylenes XHSi3 at ab initio and DFT levels (X = H, F, Cl and Br)

Four ground state triplet silylenes are found among 30 possible silylenic XHSi₃ structures (X = H, F, Cl and Br), at seven ab initio and DFT levels including: B3LYP/6-311++G^∗∗, HF/6-311++G^∗∗, MP3/6-311G^∗, MP2/6-311+G^∗∗, MP4(SDTQ)/6-311++G^∗∗, QCISD(T)/6-311++G^∗∗ and CCSD(T)/6-311++G^∗∗. The latter six methods indicate that the triplet states of 3-flouro-1,2,3-trisilapropadienylidene, 1-chloro-1,2,3-trisilapropargylene and 3-chloro-1,2,3-trisilapropargylene are energy minima. These triplets appear more stable than their corresponding singlet states which cannot even exist for showing negative force constants. Also, triplet state of 1-flouro-1,2,3-trisilapropargylene is possibly accessible for being an energy minimum, since its corresponding singlet state is not a real isomer. Some discrepancies are observed between energetic and/or structural results of DFT vs. ab initio data.     

Computational study of keto–enol equilibria of tropolone in gas and aqueous solution phase

Density functional theory calculations employing the B3LYP exchange-correlation functional, as well as Hartree–Fock computations, were performed on 2-hydroxy-2,4,6-cycloheptatrien-1-one (tropolone) and 3,5- and 3,6-cycloheptadiene-1,2-dione in gas and aqueous solution phases in order to determine the equilibrium constant for keto to enol interconversion of the isomers of C₇H₆O₂. Two standard basis sets were used throughout, namely 6-311++G^∗∗ and aug-cc-pVDZ. Solvent effects were modelled using two different self-consistent reaction field approaches – the Onsager dipole and the polarizable continuum models (PCM). In addition, the G3 method was used for calculations on species in the gas phase. Molecular geometries were fully optimized at each model chemistry, and it was found that the two keto isomers are always higher in energy than the enol form. From the results of B3LYP/6-311++G^∗∗ calculations of the difference in Gibbs free energy in the gas phase and using PCM, the relative pK values for the 2-hydroxy-2,4,6-cycloheptatrien-1-one ? 3,5- and 3,6-cycloheptadiene-1,2-dione system are 13.75 (g), 15.78 (g) and 13.05 (aq) and 13.45 (aq), respectively. That equilibrium is tilted almost exclusively in the direction of tropolone is due to resonance stabilization of the enol as a result of aromaticity, and is most easily understood on the basis of elementary Hückel theory.     

Regio- and π-facial selective Lewis acid interceded Diels-Alder reactions of α-dienyl-β-lactams: an indepth analysis

The regio-, diastereo-, and π-facial selective Lewis acid mediated Diels-Alder reactions of cis/trans-3-butadienyl-2-azetidinones with unsymmetrical dienophiles viz. methyl acrylate, dimethyl fumarate, and acrolein leading to the synthesis of diastereomerically pure and biologically potent 1,3,4-trisubstituted-2-azetidinones are reported. Theoretical calculations at HF/6-31G^∗∗ and 6-31G^∗∗/DFT levels have been performed to support the observed π-facial selectivity. The formation of diastereomerically pure ‘endo’ adducts is supported by the X-ray diffraction studies.     

The effect of spiroadamantane substitution on the conformational preferences of N-Me pyrrolidine and N-Me piperidine: a description based on dynamic NMR spectroscopy and ab initio correlated calculations

Dynamic NMR spectroscopy and ab initio correlated calculations revealed that the attachment of a spiroadamantane entity at the C-2 position of N-methylpyrrolidine or N-methylpiperidine induces a severe steric crowding around nitrogen, which changes the conformational space of the heterocycle resulting in: (a) the complete destabilization of the N-Me(eq) conformer in spiranic structures; in contrast the N-Me(eq) conformer corresponds to the global minimum in N-methylpyrrolidine or N-methylpiperidine. The spiroadamantane structure raises the energy of the equatorial conformer because of the severe van der Waals repulsion between the N-Me(eq) group and adamantane C-H bonds. (b) The interconversion between the only populated enantiomeric N-Me(ax) conformers ax→[eq]→ax′; the interconversion eq→ax between N-Me(eq) and N-Me(ax) conformers, which are both populated, is observed in N-methylpyrrolidine or N-methylpiperidine. (c) The raising of ring and nitrogen inversion barriers ax→ts by ∼4-6 kcal mol⁻¹. The dynamic NMR study provides evidence that the most important process required for the enantiomerization between the axial N-Me conformers in spiropiperidine 4 and spiropyrrolidine 5 are different, i.e., a nitrogen inversion in 5 (9.10 kcal mol⁻¹) and a ring inversion in 4 (15.2 kcal mol⁻¹). While an enantiomerization interconverts N-Me axial conformers in spiropiperidine 5 and spiropyrrolidine 4, substitution of the pyrrolidine ring of 5 with a C-Me group effects a diastereomerization between two N-Me axial conformers and reduces effectively the nitrogen inversion barrier according to the protonation experiments and the calculations. In general, all the calculations levels used, i.e., the MM3, B3LYP/6-31+G^∗∗ and MP2/6-311++G^∗∗//B3LYP/6-31+G^∗∗, predict correctly the different stability of the local minima; however only MP2/6-311++G^∗∗//B3LYP/6-31+G^∗∗ was found to be reliable for the calculation of the nitrogen inversion barriers.     

Gomadalactones A, B, and C: novel 3-oxabicyclo[3.3.0]octane compounds in the contact sex pheromone of the white-spotted longicorn beetle, Anoplophora malasiaca

The ether extract of the females of white-spotted longicorn beetle Anoplophora malasiaca showed activity as contact sex pheromone to males. The extract was fractionated, and a pheromonal activity was revealed only when three fractions; n-hexane, n-hexane/EtOAc 9:1, and EtOAc were blended. The relative structures of gomadalactone A, B, and C, three active components isolated from the EtOAc fraction, were determined by spectroscopic studies to be (1S^∗,4R^∗,5S^∗)-5-hydroxy-4-[(E)-7-hydroxy-4-methylhept-3-enyl]-4,8-dimethyl-3-oxabicyclo[3.3.0]octan-7-en-2,6-dione, (1R^∗,4R^∗,5R^∗)-5-hydroxy-4-[(E)-7-hydroxy-4-methylhept-3-enyl]-4,8-dimethyl-3-oxabicyclo[3.3.0]octan-7-en-2,6-dione, and (1S^∗,4R^∗,5S^∗,8S^∗)-5-hydroxy-4-[(E)-7-hydroxy-4-methylhept-3-enyl]-4,8-dimethyl-3-oxabicyclo[3.3.0]octan-2,6-dione, respectively.     

The determination of sulfoxide configuration in six-membered rings using NMR spectroscopy and DFT calculations

Cyclic six-membered ring sulfoxides and sulfones were prepared by a stepwise in situ oxidation of the corresponding sulfides with meta-chloroperbenzoic acid in an NMR tube. The oxidation was followed by NMR spectra and the ¹H and ¹³C NMR data were collected. The geometries of all of the compounds were optimized using the DFT B3LYP/6-31G^∗∗ method and the ¹³C and ¹H NMR chemical shifts were calculated for geometry-optimized structures with the DFT B3LYP/6-31++G^∗∗ method. The calculated ¹³C NMR chemical shifts induced by oxidation (Δδ values) are in very good agreement with the experimental data and can be used to determine the oxidation state of the sulfur atom (-S-, -SO-, -SO₂-). The characteristic differences of the induced oxidation chemical shifts of carbon atoms at the α- and β-position to sulfur were successfully used for distinguishing between the diastereoisomeric sulfoxides.     

A quantum chemical study of tricyclo[3.2.0.0]heptane: a new hypothetical molecule with unusual spatial structure. Similarities and differences with syn- and anti-tricyclo[3.2.0.0]heptanes

HF and MP2 calculations with the 6-31G^∗∗ and 6-311G^∗∗ basis sets for the titled molecules and those at MP2/cc-pVTZ level for the hypothetical tricyclo[3.2.0.0^1,3]heptane indicate that the latter molecule should have a carbon atom with highly unusual configuration strongly departing from the tetrahedral one. Both analysis of vibrational frequencies of this molecules and comparison of its energy with those of known isomeric syn- and anti- tricyclo[3.2.0.0^2,4]heptanes as well as the DFT analysis of its plausible decomposition routes performed at the DFT level indicate that it could be a plausible synthetic target.     

Diastereoselective synthesis of 5-benzylthio- and 5-mercaptohexahydropyrimidin-2-ones

A three-stage diastereoselective synthesis of (4R^∗,5R^∗,6S^∗)-5-mercapto-4-methyl-6-phenylhexahydropyrimidin-2-one has been developed. The first stage involves the formation of 4-hydroxy-5-(4-methoxybenzylthio)-4-methyl-6-phenylhexahydropyrimidin-2-one by the reaction of N-[(phenyl)(tosyl)methyl]urea with the sodium enolate of 1-(4-methoxybenzylthio)propan-2-one. Reduction of the obtained compound by NaBH₄-CF₃COOH and removal of the p-methoxybenzyl protecting group results in the target compound.     

Theoretical calculation of heat of formation for a number of moderate sized fluorinated compounds

Hydrofluorocarbons (HFCs) and hydrofluoroethers (HFEs) are considered to be potential replacements for chlorofluorocarbons (CFCs). The values of heat of formation have been calculated by using both the bond additivity corrected MP2 method (BAC-MP2/6-31G^∗∗) and atom additivity corrected MP2 method (AAC-MP2/6-31G^∗∗) for moderate sized HFCs and HFEs for which the literature values are not available. The reliability of the calculated values by these methods has been examined by comparing them with the values obtained with G2 and G2MP2 methods as well as with the literature values for a set of 42 simpler molecules.     

A DFT study on pyridine-derived N-heterocyclic carbenes

To appreciate the chemistry of N-heterocyclic carbenes (NHCs), eight carbenic tautomers of pyridine (azacyclohexadienylidenes) are studied at B3LYP/AUG-cc-pVTZ//B3LYP/6-31+G^∗ and B3LYP/6-311++G^∗∗//B3LYP/6-31+G^∗ levels of theory. Various thermodynamic parameters are calculated for these minima, along with a kinetic focus on carbene-pyridine tautomerization. Appropriate isodesmic reactions show stabilization energies of 2-azacyclohexa-3,5-dienylidene (1) and 4-azacyclohexa-2,5-dienylidene (6) as 119.4 and 104.1 kcal/mol, rather close to that of the synthesized 1,3-dimethylimidazol-2-ylidene (129.2 kcal/mol). Three different mechanisms are suggested for the tautomerizations including: [1,2]-H shift, [1,4]-H shift, and three sequential [1,2]-H shifts. The calculated energy barrier for [1,2]-H shift of 1 is 44.6 kcal/mol, while the first [1,2]-H shift for the proposed sequential mechanism of 6 requires 65.1 kcal/mol. Three preliminary minimum templates are introduced, which may possess the potential of synthetic consideration: 2,6-di(X)-3,5-dichloro-4-azacyclohexa-2,5-dienylidene for X=Mes, t-Bu, and Ad.     

Synthesis, structure, and photoisomerization of derivatives of 2-(2-quinolyl)-1,3-tropolones prepared by the condensation of 2-methylquinolines with 3,4,5,6-tetrachloro-1,2-benzoquinone

A series of novel derivatives of the 1,3-tropolone (β-tropolone) system—2-(2-quinolyl)-5,6,7-trichloro-1,3-tropolones and 2-(2-quinolyl)-4,5,6,7-tetrachloro-1,3-tropolones have been prepared by the acid-catalyzed reaction of 2-methylquinolines with 3,4,5,6-tetrachloro-1,2-benzoquinone. The molecular structures of two compounds, 2-(4-chloro-6,8-dimethyl-5-nitro-2-quinolyl)-5,6,7-trichloro-1,3-tropolone 8 and 2-(4-chloro-7,8-dimethyl-5-nitro-2-quinolyl)-4,5,6,7-tetrachloro-1,3-tropolone 9, have been determined using X-ray crystallography. According to the performed DFT B3LYP/6-311++G^∗∗ calculations the tautomeric (OH) and (NH) forms of β-tropolones 8 and 9 are nearly energy equivalent, the latter being more stabilized in polar media. Photolysis of 2-(2-quinolyl)-1,3-tropolones in heptane solution leads to the disrotatory electrocyclic rearrangement resulting in the formation of a mixture of E- and Z-isomers of 3-[2(1H)-quinolinylyden]-bicyclo[3.2.0]hept-6-en-2,4-dione derivatives.     

Comparative study of calix[4]arene derivatives: implications for ligand design

The first comparative theoretical study of three parent calix[4]arene analogues (calix[4]arene, thiacalix[4]arene, and homooxacalix[4]arene) has been performed using molecular dynamic simulations and density functional theory (MPWB1K/6-311G^∗∗//B3LYP/6-311G^∗∗) methods. The theoretical observations herein including optimized geometry, polarity, and atomic charge data provide that homooxacalix[4]arene would offer more efficient platform for metal ion recognition compared to thiacalix[4]arene or calix[4]arene.     

A computational approach towards predicting π-facial selectivity in sterically unbiased olefins: an evaluation of the relative importance of electrostatic and orbital effects

Computational studies are presented to show that electrostatic interactions significantly impact the stereochemical outcome in electrophilic addition to a number of sterically unbiased alkenes. Transition states have been located for the reaction of different electrophiles with all the sterically unbiased alkenes studied here and the calculations effectively include interactions involving the σ and σ^∗ orbitals of the newly formed bond. Electrostatic interaction between the substrates and electrophiles was modelled by removing the electrophiles from the transition state geometry and placing the calculated charge at a distance from a selected atom as observed in TS structures. Electrostatic interactions between the electrophiles and the substrate seem to effectively determine the face selectivities in the systems studied and our model calculations indicate that it may not be important to invoke Cieplak type orbital interactions to rationalize the observed face selectivities. The face selectivities predicted for these alkenes and electrophiles with DFT B3LYP/6-31G^∗ and ab initio MP2/6-31G^∗ levels are generally in good agreement.     

1,5-Type nonbonded O?S and S?S interactions in (acylimino) and (thioacylimino)benzothiazoline systems. Crystal structures and theoretical calculations

Intramolecular nonbonded interactions have been observed in the crystalline structures of 6-ethoxy-2-trifluoroacetyliminobenzothiazoline (4) (S?O close contact) and 6-ethoxy-2-trifluorothioacetyliminobenzothiazoline (5) (S?S close contact). Density functional B3LYP/6-311G^∗∗ calculations were performed for all conformers and tautomers of 4 and 5 in order to explain the preference for the S?O and S?S close contact structures. The calculations agree with the observed crystallographic structures only when solvent effects are included via a continuum model, thus showing the importance of the solvent effects to establish the correct relative energies.     

Aromaticity of caffeine,xanthine and the dimethyl xanthines

Xanthine, caffeine and three isomeric dimethyl xanthines (theobromine, theophylline and paraxanthine) are often described as aromatic on various criteria. Here we complete the picture by assessing these molecules for aromaticity on the ring-current criterion. Magnetic response calculations are performed at the B3LYP and CHF/6-31G^∗∗ ipsocentric levels of theory on structures optimised at the B3LYP/6-31G^∗∗ level. All five systems display consistent π-electron ring-currents delocalised around the imidazole moiety in all cases; these are accompanied by localised features on the six-membered rings attributed to nitrogen and oxygen ‘lone-pair’ π-electron circulations. All are therefore aromatic on the magnetic criterion, with a ‘locally delocalised’ ring current in the imidazole moiety, similar to those in the isolated imidazole and methylimidazole molecules.     

A molecular balance to measure the strength of N-H?π hydrogen bonds based on the tautomeric equilibria of C-benzylphenyl substituted NH-pyrazoles

A theoretical (B3LYP/6-31G^∗∗) study of 30 pyrazoles, most of them existing in two tautomeric forms, has been carried out. 3(5)-(2-Benzylphenyl)-5(3)-methyl-1H-pyrazole (11) and 3(5)-(2-benzylbenzylphenyl)-5(3)-phenyl-1H-pyrazole (20) were synthesized from 2-benzoylacetophenone, and their annular tautomeric equilibrium determined. The substituent effects were statistically analyzed and discussed with the help of Hammett substituent constants. In the case of the 5-(2-benzylphenyl) groups, the strength of the N-H?π hydrogen bond depends on the electronic effect of the substituent at position 3.     

Photolysis of open-chain 1,2-diazidoalkenes: generation of 2-azido-2H-azirines, formyl cyanide, and formyl isocyanide

Solutions of several open-chain 1,2-diazidoethenes were photolyzed to yield 2-azido-2H-azirines, which were identified by NMR spectroscopy at low temperature. On prolonged irradiation or warm-up of the NMR solutions, these heterocycles lost a second molecule of nitrogen to be cleaved into two fragments of cyano compounds. In the case of (Z)-2,3-diazidocinnamaldehyde, the formation of formyl cyanide was detected by IR spectroscopy when the photolysis was performed in argon matrix. The latter substance was rearranged to formyl isocyanide on irradiation. This new species was characterized by comparison of its experimental and calculated (B3LYP/6-311+G^∗∗) IR spectrum.     

Carbosilane dendrimers containing peripheral cyclopentadienyl niobium- and tantalum-imido complexes

Anilines Gn-{(C₆H₄)N(SiMe₃)₂}_m, based on simple or dendritic carbosilanes, have been used to synthesized (imido)tantalum compounds Gn-{(C₆H₄)NTaCl₂Cp^∗}_m (1, n = 0, m = 1; 2, n = 1, m = 4; Cp^∗ = η⁵-C₅Me₅), by the reaction with [TaCl₄Cp^∗] and elimination of SiMe₃Cl. (Imido)niobocene compounds of general formula (3-5; n = 0, 1, 2; m = 1, 4, 8, respectively) have been readily prepared from their corresponding half-sandwich complexes Gn-{(C₆H₄)NNbCl₂Cp′}_m by the reaction with m equiv. of LiCp′ (Cp′ = η⁵-C₅H₄SiMe₃). Compounds 1-5 are all found to be exceedingly moisture sensitive, and in the case of the (imido)niobocene materials the hydrolytic reaction selectively leads to the formation of (6). The molecular structure of 6 has been determined by X-ray diffraction studies.     

Regio- and stereoselective cycloadditions of (1Z,4R,5R)-1-arylmethylidene-4-benzoylamino-3-oxo-5-phenylpyrazolidin-1-ium-2-ides to methyl methacrylate

[3+2] Cycloadditions of (1Z,4R^∗,5R^∗)-1-arylmethylidene-4-benzoylamino-3-oxo-5-phenylpyrazolidin-1-ium-2-ides 1a-e to methyl methacrylate gave the 1-CO₂Me regioisomers 3/3′, exclusively, in 1-67% yields. Stereocontrol was dependent on the ortho-substituents at the 1′-aryl group in dipole 1: ortho-unsubstituted dipoles 1a-c gave the major (1R^∗,3R^∗,5R^∗,6R^∗)-isomers 3a-c, whilst ortho-disubstituted dipoles gave the major (1R^∗,3S^∗,5R^∗,6R^∗)-isomers 3′d,e. The structures of cycloadducts were determined by NMR and X-ray diffraction.