Nonempirical study on the potential energy surface of 5-methyl-1,3-dioxane

Quantum-chemical study on the potential energy surface of 5-methyl-1,3-dioxane at the nonempirical RHF//STO-3G, RHF//3-21G, RHF//6-31G(d), RHF//6-31G(d,p), and MP2//6-31G(d,p) levels of theory revealed two energy-equivalent paths of conformational transformation of the equatorial and axial chair conformers. Potential barriers to these processes were estimated. The δG° value for the methyl substituent on C⁵ in 1,3-dioxane ring, determined on the basis of the experimental (NMR) and calculated vicinal 1H-1H coupling constants, was very consistent with published data     

Pathways of conformational isomerization of 4-phenyl-1,3-dioxane

A study of the potential energy surface of 4-phenyl-1,3-dioxane by non-empirical quantum chemical RHF/STO-3G and 6-31G(d) approximations reveals six energetically inequivalent pathways of conformational isomerization of equatorial and axial chair forms.     

Quantum-chemical study of 1,3-dioxane complexes with two water molecules

Methods PM3, RHF/6-31G(d), and MP2/6-31G(d)//RHF/6-31G(d) were used in calculation of the energy of formation of five 1,3-dioxane complexes with two water molecules formed through hydrogen bonds. The study of the conformational properties of the most stable associate revealed two routes of the chair-chair conformation isomerization. It was shown that the difference between the minima on the potential energy surface in this gase increased, and the barriersto the interconversion decreased as compared to the calculated values for the isolated molecule of 1,3-dioxane.     

Conformational analysis of six-membered cyclic carbonates

The conformational isomerization of 2-oxo-1,3-dioxane and its methyl analogs was investigated by means of ab initio RHF//6-31G(d,p) and MP2//6-31G(d,p) quantum-chemical methods. It is shown that in comparison with 1,3-dioxanes the potential energy surface of the mentioned compounds has a fewer number of stationary points and includes two minima corresponding to conformers of sofa or distorted sofa configuration and one maximum corresponding to 2,5-twist form. The value of potential barrier of interconversion of cyclic carbonates is significantly lower than that of the analogously substituted 1,3-dioxanes.     

Quantum-Chemical Study on Positional Selectivity in the Trimethylsilylation and Sulfonation of Pyrrole and <Emphasis Type="Italic">N</Emphasis>-Alkylpyrroles

Positional selectivity (α:β ratio) of electrophilic substitution in pyrrole, N-methylpyrrole, and N-tert-butylpyrrole was analyzed by ab initio [RHF/6-31G(d), MP2/6-31G(d)//RHF/6-31G(d)] and DFT [B3LYP/6-31G(d)] calculations of some σ-complexes derived from the substrates. The results of calculations with the use as model electrophilic species of trimethylsilyl cation [MP2/6-31G(d)//RHF/6-31G(d) and B3LYP/6-31G(d)] and SO₃ molecule [B3LYP/6-31G(d)] instead of proton are fairly consistent with the experimental data, according to which trimethylsilylation of pyrrole and its N-substituted derivatives with trimethylsilyl trifluoromethanesulfonate, as well as sulfonation with pyridine-sulfur trioxide complex, gives the corresponding β-substituted products.     

Computational reexamination of the eclipsed conformation in cis-2-tert-butyl-5-(tert-butylsulfonyl)-1,3-dioxane

The conformational free energy differences, ΔG° values, for the methyl sulfide, methyl sulfoxide, methyl sulfone, tert-butyl sulfide, tert-butyl sulfoxide, and tert-butyl sulfone groups at C(5) in the 1,3-dioxane ring have been calculated at two different levels, B3LYP/6-31G(d) and B3LYP/6-311++G(d,p). There is good agreement between experimental and calculated values, particularly in the case of data obtained at the lower level of theory, B3LYP/6-31G(d). In order to get information that could help understand the nature of the effects present in the molecules of interest, the charge distribution in representative compounds was analyzed by means of the natural bond orbital (NBO) analysis. NBO calculations indicate the existence of substantial negative charges at oxygen and significant positive charge at sulfur. This observation seems to support the argument the existence of electrostatic, attractive interactions between the endocyclic oxygens and the axial sulfonyl group. From the second order perturbation theory analysis of Fock matrix, two σ _C–C → σ*_S–O delocalizing interactions are observed in the methyl-inside conformer of cis-2-tert-butyl-5-(methylsulfonyl)-1,3-dioxane derivative cis-7. These results are in line with anti-periplanar σ _C–C → σ*_S–O hyperconjugative interactions that help stabilize the methyl-inside conformation of cis-7, as previously found by ¹H NMR analysis. By contrast, NBO analysis does not provide evidence for the existence of σ _C–C → σ*_S–O hyperconjugative interactions that might help stabilize the eclipsed tert-butyl—outside conformation previously found in the solid-state crystallographic structure of analog cis-1. Because of the threshold value of the NBO calculations, if present such syn-periplanar stereoelectronic interaction should be less than 0.5 kcal mol^?1. This observation suggests that an anti-periplanar orientation of the interacting orbitals is more effective relatively to the corresponding syn-periplanar orientation.     

Geminal interactions in ClZ(CH3)2X molecules (Z = C, Si, Ge) according to ab initio calculations

The structure and electronic parameters of ClZ(CH₃)₂X molecules (Z = C, Si, Ge, X = CH₃, OCH₃) were calculated by the RHF/6–31G(d) and RHF/6–311G(d,p) methods with full geometry optimization; calculations of ClZ(CH₃)₂OCH₃ molecules were also performed by the RHF/6–31G(d) method with partial geometry optimization. The ³⁵Cl NQR frequencies calculated from the populations of less diffuse 3p constituents of valence p orbitals of chlorine [RHF/6–31G(d)] were in agreement with the experimental values. The ³⁵Cl NQR frequencies for molecules with X = OCH₃ are lower than those for molecules with X = CH₃ (the Z atom being the same), due mainly to direct through-field polarization of the Z-Cl bond, induced by the effect of unshared electron pair of the oxygen atom in the trans position with respect to that bond. The difference in the ³⁵Cl NQR frequencies decreases in going from Z = C to Z = Si, Ge, in parallel with variation of the Z-Cl bond polarization as the size of Z increases.     

A quantum-chemical study of the interaction of the HeT<Superscript>+</Superscript> ion with cycloalkanes and their oxidation products

The RHF/6-311G*(3d), RHF/6-311++G**(3df, 3p) and MP2/6-311G*(3d) ab initio methods were used to calculate the equilibrium structure of the products of the ion-molecular reaction of tritium ion transfer from HeT⁺ to cyclopentane and cyclohexane. Similar reactions with cyclopentanol and cyclopentanone were calculated at the RHF/6-311G*(3d) level. The interaction of HeT⁺ with cycloalkanes was found to produce onium ions with cyclic structures, in which the tritium atom held neighboring methylene groups together. With the alcohol and ketone, not only cyclic but also stabler linear cations could be formed, and the addition of the tritium ion directly to the oxygen atom was possible. The suggestion was made that the chain of tritium ion transfer reactions was the mechanism of the accumulation of tritium by hydrocarbon oxidation products when T₂ was dissolved in mineral oils.     

Conformational Isomerism and Chlorotropy Mechanisms of Chloromethyl- and Trichloromethyldichlorophosphines

³⁵Cl NQR spectroscopy and MP2//RHF/6-31⁺⁺G(d,p) and MNDO-PM3 calculations were used to study the conformational and chlorotropic isomerism of chlorodimethyldichlorophosphine (I) and trichloromethyldichlorophosphine (II). The experimental ³⁵Cl NQR spectrum is in complete accord with the staggered conformation of phosphine II obtained using an RHF/6-31⁺⁺G(d,p) calculation. The rotational barrier of the CCl₃ group is 38.1 kJ/mol. On the other hand, the spectrum of phosphine I is in accord with a gauche conformation, which agrees with experiment only upon taking account of electron correlation (MP2). The ylide and phosphinic chlorotropic isomers for I and II are thermodynamically stable with greater stability found for II. The chlorotropic phosphine–ylide conversion in system I proceeds exclusively through a sigmatropic transition state in qualitative accord with nonempirical and semiempirical calculations. Such a conversion is theoretically possible in system II by means of dissociation of the P⁺—C^– ylide bond.     

Ab initio calculations of complexes of group IVA element tetrachlorides: II. Dynamics of complex formation of GeCl4 with trimethylamine

RHF/6-31G(d) calculations of the system GeCl₄←N(CH₃)₃ were performed with full geometry optimization and at varied Ge←N distance. Mutual approach of the system components is accompanied by their mutual polarization followed by electron density transfer from the H atoms of the donor to the Cl atoms of the acceptor. The C, N, and Ge atoms act merely as conductors of this electron density. The total energy of the system decreases until the Ge←N distance of 3.412 Å is attained; at this distance, however, the complex is not yet formed. The complex formation involves an increase in the energy by 0.213 eV. The applicability of the RHF/6-31G(d) method to studying the trigonal-bipyramidal complex was assessed.     

Conformational analysis of 1,3,2-dioxathiane and its oxides

Computer simulation of the routes of conformational isomerization of 1,3,2-dioxathiane and its Soxides by nonempirical quantum-chemical method RHF/6-31G(d) revealed the main and local minima and transition states of this process. It was shown that the barrier of ring inversion is reduced in going from 1,3,2-dioxathiane to its oxides. The established ΔG ⁰ (300 K) value of S=O group in cyclic sulfite (−15.0 kJ mol⁻¹) is in good agreement with the experimental data.     

Quantum-Chemical Study of Alkyl Carbenium Ions in 100% Sulfuric Acid

A quantum-chemical study of neutral and protonated monoalkyl sulfates RHSO₄and [RH₂SO₄]⁺(where R = CH₃, C₂H₅, iso-C₃H₇, and tert-C₄H₉) is carried out. Calculations are performed using the Hartree–Fock method in the 6-31G** and 6-31++G** basis sets taking into account electron correlation according to the Müller–Plesset perturbation theory MP2/6-31+G*//6-31+G*. Protonated tert-butyl sulfate was also calculated by the DFT B3LYP/6-31++G** method. It was found that monoalkyl sulfates are covalent compounds, and the complete abstraction of alkyl carbenium ions from them has substantial energy cost: 196.4, 161.7, 150.8 and 136.0 kcal/mol, respectively. Protonated methyl and ethyl sulfates are also covalent compounds according to the calculation. They have lower but still high energies of heterolytic dissociation (65.0 and 33.5 kcal/mol, respectively). The energy of R⁺abstraction from protonated isopropyl sulfate is much lower: 23.6 kcal/mol. The main covalent state and the ion–molecular pair, which is a carbenium ion [C(CH₃)₂H]⁺solvated by the H₂SO₄molecule, have about the same energy. The ground state of protonated tert-butyl sulfate corresponds to the ion–molecular complex [C(CH₃)⁺ ₃H₂SO₄] with still lower energy of carbenium ion [C(CH₃)₃]⁺abstraction, which is equal to 10.0 kcal/mol. Calculation according to the DFT B3LYP/6-31++G** method shows the absence of a minimum for the protonated tert-butyl sulfate with a covalent structure on the potential energy surface.     

Synthesis and molecular structure of 3-[5-(quinolin-2-yl)penta-1,4-dien-1-yl]-1,4-benzodioxin-2-one

Acid-catalyzed reaction of 6,10a-dihydroxy-3,4a,7,9-tetra(tert-butyl)-1,2,4a,10a-tetrahydrodibenzo-[b,e][1,4]dioxine-1,2-dione with 4-chloro-2,7,8-trimethylquinoline gave previously unknown 3,6,8-tri-tert-butyl-3-[2-tert-butyl-5-(4-chloro-7,8-dimethylquinolin-2-yl)-4-hydroxy-3-oxopenta-1,4-dien-1-yl]-5-hydroxy-1,4-benzodioxin-2-one whose structure was determined by X-ray analysis. The energy and structure parameters of possible isomers of the product in the gas phase and in solution were estimated by PBE0/6-31G** quantum-chemical calculations.     

Conformational analysis of 1,3-oxathiane

Computer simulation of pathways of conformational isomerization of 1,3-oxathiane molecule carried out with the help of HF/6-31G(d), MP2.6-31G(d)/HF/6-31G(d), and PNE/3z quantum-chemical approximations showed that interconversion between the degenerate in energy chair conformers proceeds through seven independent pathways: directly and via six flexible forms. Potential energy surface contains eight minimum points including chair conformers and enantiomeric pairs of twist forms, and also five transition states, among them different modification of semi-chair, symmetric and unmmetrical boat. Molecular dynamics methods show that flexible forms at room temperature convert into one another and into the chair conformers.     

Ab initio calculations of complexes of tetrachlorides of Group IVA elements: VIII. Structure of SiCl<Subscript>4</Subscript> complexes with hexamethylphosphoric triamide and dynamics of their formation

Quantum-chemical calculations of the systems SiCl₄←OP[N(CH₃)₂]₃ and SiCl₄←2OP[N(CH₃)₂]₃ with complete optimization of their geometry at various Si←O distances were performed by the RHF/6-31G(d) method. The first system was also calculated by the MP2/6-31G(d) method. The calculations of the systems with the complete geometry optimization resulted in trigonal-bipyramidal and trans-octahedral structures, respectively, having energy minima. When the components of the latter system approach each other, first their mutual polarization occurs, and then it is accompanied by electron density transfer from the H and P atoms of the electron-donor molecules to the Cl atoms of the acceptor. The results of the calculation of the trans-octahedral complex agree with the experimental ³⁵Cl NQR data. The electron density of Cl atoms increases upon complex formation, mainly due to an increase in their p _σ electron density.     

Conformational analysis of 2,4,5-trimethyl-1,3,2-dioxaborinane individual stereoisomers

The study of the conformational isomerization of cis- and trans-isomers of 2,4,5-trimethyl-1,3-dioxaborinane I by means of RHF//STO-3G, 3-21G and 6-31G(d) quantumchemical methods led to the conclusion that its route includes equilibrium between sofa conformers with a different steric orientation of substituents at the C-4 and C-5 ring atoms. These conformers are interconverted through the maxima, the conformations of equatorial and axial 2,5-twist-forms. A comparison between experimental ¹H NMR and theoretical vicinal spin-spin coupling constants was used to determine the quantitative conformational composition of stereoisomers and a value of ΔG ⁰ for conformational equilibrium.     

Application of the Blaise reaction: stereoselective synthesis of (4R)-tert-butyl 3-amino-4-trimethylsilyloxy-2-alkenoates from (R)-cyanohydrins

O-Trimethylsilyl protected (R)-cyanohydrins 3 react with Reformatsky reagents from tert-butyl 2-bromoesters 4 and zinc dust (Blaise reaction) to give the corresponding addition products in high yields. Workup with an aqueous solution of NH₄Cl at low temperature gives (4R)-tert-butyl 3-amino-4-trimethylsilyloxy-2-alkenoates (R)-5 without racemization. Hydrogenation of the alkenoates 5 to the corresponding tert-butyl β-amino-γ-hydroxyalkanoates 6, resulting in a mixture of two diastereoisomers, was only possible under special hydrogenation conditions. With HCl in dichloromethane compounds 6 cyclize to the corresponding β-amino-γ-hydroxybutyrolactones 8.     

An improved process for chiron synthesis of the atorvastatin side chain

An improved and practical synthesis of tert-butyl ((4R,6R)-6-aminoethyl-2,2-dimethyl-1,3-dioxan-4-yl)acetate 3 has been developed for supplying this key chiral side-chain of atorvastatin by using a Blaise reaction of (S)-4-chloro-3-((trimethylsilyl)oxy)butanenitrile 7 and the Raney Ni catalyzed hydrogenation of tert-butyl 2-((4R,6R)-6-(-2-oximeethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate 12 as the key steps. This nine-step route from (R)-epichlorohydrin afforded the target compound in 55% overall yield of high chemical and enantiomeric purity.     

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.     

Conformational analysis of 2-methyl-5-nitro-1,3,2-dioxaborinane

Quantum-chemical methods HF/6-31G(d), HF/6-31+G(d), MP2/6-31G(d)//HF/6-31G(d), and MP2/6-31+G(d)//HF/6-31+G(d) were used to investigate the conformational isomerization of 2-methyl-5-nitro-1,3,2-dioxaborinane. It has been shown that a potential energy surface of this compound includes two minima: an axial form of semi-chair and equatorial sofa together with a transition state belonging to the conformation of 2,5-twist-form. A comparison between experimental NMR ¹H and theoretical vicinal coupling constants was used to determine the quantitative conformational composition of cyclic boric acid ester and a value of ΔG ⁰ for nitro group at the ring carbon atom C⁵ in CCl₄ and C₆D₅NO₂ solutions.