Density Functional Theory Computational Reexamination of the Anomeric Effect in 2‑Methoxy- and 2‑Cyano-1,3-dioxanes and 1,3-Dithianes. Stereoelectronic Interactions Involving the Cyano (CN:) Group Revealed by Natural Bond Orbital (NBO) Analysis

This study reports DFT geometry optimization of the anancomeric (ring conformationally anchored) axial <i>r</i>2-methoxy-<i>trans</i>-4,<i>trans</i>-6-dimethyl- and <i>r</i>-2-cyano-<i>trans</i>-4,<i>trans</i>-6-dimethyl-1,3-dioxanes (<b>1</b>-ax and <b>3</b>-ax, respectively), the equatorial isomers (<b>2</b>-eq and <b>4</b>-eq, respectively), the axial r2-methoxy- and <i>r</i>2-cyano-<i>trans</i>-4,<i>trans</i>-6-dimethyl-1,3-dithianes (<b>5</b>-ax and <b>7</b>-ax, respectively), and the equatorial isomers (<b>6</b>-eq and <b>8</b>-eq, respectively). The computational results reproduce the anomeric effect in <b>1</b>–<b>8</b>, and most importantly, Weinhold’s NBO analysis supports the contribution of n­(X) → σ*­(C–Y) stereoelectronic interactions that stabilize the axial isomers. Furthermore, NBO analysis of delocalization energy <i>E</i>(2) of properly aligned filled/empty orbitals in these isomeric 2-polar-substituted heterocycles reveals that n­(O) → σ*­(C–H_ax) is responsible for the increased charge density at C(2)–H_ax in the equatorial isomers, providing an explanation for the computational observation that very recently led Wiberg, Bailey, Lambert, and Stempel (<i>J. Org. Chem.</i> <b>2018</b>, <i>83</i>, 5242–5255) to discard a potential contribution of n­(X) → σ*­(C–Y) stereoelectronic interactions that stabilize the axial isomers. Interestingly, during the course of this study, two relevant stereoelectronic interactions involving the cyano group were revealed, n­(N) → σ*­(NC–C) and σ­(C(2)–H) → σ*­(C–N)

Theoretical Examination of the S–C–P Anomeric Effect

Three decades after the discovery of a strong S–C–P anomeric effect in 2-diphenylphosphinoyl-1,3-dithiane (<b>1</b>) and 2-trimethylphosphonium-1,3-dithiane (<b>4</b>), its definitive interpretation is still lacking. The present study reports DFT geometry optimizations of <b>1</b>-ax, <b>1</b>-eq, <b>4</b>-ax, and <b>4</b>-eq, which do reproduce the S–C–P anomeric effect in <b>1</b> and <b>4</b>, worth 5.45 and 3.08 kcal/mol, respectively (in chloroform solvent). Weinhold’s NBO analysis supports the existence of dominant n_X → σ*_C–Y stereoelectronic interactions that stabilize the axial conformers

Intrinsic Relative Scales of Electrophilicity and Nucleophilicity

The formulation of the second-order perturbation approach to the stabilization energy of the A–B interacting species due to charge transfer is revisited. Intrinsic (i.e., electronic) theoretical indices for both relative electrophilicity and nucleophilicity are proposed for any electrophile (A)–nucleophile (B) pairs of combining species. By using the new descriptors, an electronic analogue to the Mayr–Patz linear free relationship has been successfully tested in the context of available experimental evidence reported for reactions of primary and secondary amines with benzhydrylium ions

Gas-Phase Acidities and Basicities of Alanines and <i>N</i>‑Benzylalanines by the Extended Kinetic Method

This paper reports an experimental determination of the gas-phase acidities and basicities of <i>N</i>-benzylalanines, in both their α and β forms, by means of the extended kinetic method (EKM). The experimental gas-phase acidity of β-alanine was also determined. Standard ab initio molecular orbital calculations at the G3 level were performed for alanines, and at the G3­(MP2)//B3LYP level for <i>N</i>-benzylalanines. There is a very good agreement between the experimental and the calculated values. The more branched α-amino acids are more acidic and less basic than the linear β-amino acids

Substituent Effects on the Thermochemistry of Thiophenes. A Theoretical (G3(MP2)//B3LYP and G3) Study

Very good linear correlations between experimental and calculated enthalpies of formation in the gas phase (G3­(MP2)//B3LYP and G3) for 48 thiophene derivatives have been obtained. These correlations permit a correction of the calculated enthalpies of formation in order to estimate more reliable “experimental” values for the enthalpies of formation of substituted thiophenes, check the reliability of experimental measurements, and also predict the enthalpies of formation of new thiophenes that are not available in the literature. Moreover, the difference between the enthalpies of formation of isomeric thiophenes with the same substituent in positions 2 and 3 of the ring has been analyzed. Likewise, a comparison of the substituent effect in the thiophene and benzene rings has been established

Thermodynamic and Conformational Study of Proline Stereoisomers

Amino acids play fundamental roles both as building blocks of proteins and as intermediates in metabolism. Proline, one of the 20 natural amino acids, has a primordial function in enzymes, peptide hormones, and proteins. The energetic characterization of these molecules provides information concerning stability and reactivity and has great importance in understanding the activity and behavior of larger molecules containing these structures as fragments. In the present work, parallel experimental and computational studies have been performed. The experimental studies have been based on calorimetric and effusion techniques, from which the enthalpy of formation in the crystalline phase and the enthalpy of sublimation of the sterioisomers l-, d-, and the dl-mixture of proline have been derived. Additionally, vapor pressure measurements have also enabled the determination of the entropies and Gibbs energies of sublimation, at <i>T</i> = 298.15 K. From the former results, the experimental standard (<i>p</i> ^o = 0.1 MPa) molar enthalpies of formation, in the gaseous phase, at <i>T</i> = 298.15 K, of l-proline, d-proline, and dl-proline have been calculated as −388.6 ± 2.3, −391.9 ± 2.0, and −391.5 ± 2.4 kJ·mol^–1, respectively. A computational study at the G3 and G4 levels has been carried out. Conformational analysis has been done and the enthalpy of formation of proline as well as other intrinsic properties such as acidity, basicity, adiabatic ionization enthalpy, electron and proton affinities, and bond dissociation enthalpies have been calculated. There is a very good agreement between calculated and experimental values, when they are available

Thermochemical Insights on the Conformational Energetics of Azepan and Azepan-1-ylacetonitrile

This paper is concerned with computational and experimental thermochemical studies of azepan and azepan-1-ylacetonitrile, molecules whose flexible ring structure provides several conformational forms with low energy barriers among them. The computational study describes the energetic analysis of the six most stable conformers on the potential energy surfaces and the determination of their gas-phase standard enthalpy of formation at the reference temperature of 298.15 K. The same gas-phase enthalpic parameters are also derived from the enthalpies of formation in the liquid phase and the enthalpies of vaporization, at <i>T</i> = 298.15 K, determined experimentally using the combustion calorimetry and the Calvet microcalorimetry techniques, respectively. The experimental data reported in this work for the two titled compounds together with other available in the literature for related molecules enabled the establishment of an increments scheme, providing a reliable approach on the prevision of gas-phase enthalpy of formation of cyclic/acyclic hydrocarbons and amines. Complementary, natural bond orbital (NBO) calculations were also performed, allowing an advance on the analysis of the structural and reactivity behavior of these type of compounds

Isothermal Thermogravimetric Study for Determining Sublimation Enthalpies of Some Hydroxyflavones

The sublimation enthalpies of some hydroxyflavones and one amineflavone were determined with a thermogravimetric device under isothermal conditions. These enthalpies were obtained by measuring the rate of mass loss as a function of temperature. In this methodology, the Clausius–Clapeyron and Langmuir equations were used. The diffusional effect of the gas phase was included in the Langmuir equation. In order to test and validate the experimental methodology, the sublimation enthalpy of three standard materials, anthracene, pyrene, and benzoic acid, were determined. The values obtained are in agreement with the data reported and recommended in the literature. Low uncertainties were obtained in all thermogravimetric measurements. Additionally, by differential scanning calorimetry, the molar fraction, temperature and enthalpy of fusion, and heat capacity of the solid phase were determined for all of the compounds studied. The heat capacities of the gas phase were estimated using computational methods. Isothermal thermogravimetry was applied to study a family of flavones

Rediscovering the Wheel. Thermochemical Analysis of Energetics of the Aromatic Diazines

Thermochemical properties of pyrimidine, pyrazine, and pyridazine have been measured and re-evaluated to provide benchmark quality results. A new internally consistent data set of Δ_f<i>H</i>_m^°(g) has been obtained from combustion calorimetry and vapor pressure measurements. The gas and condensed phase enthalpies of formation of the parent diazines have been re-evaluated, and the results were compared to current theoretical calculations using the highly accurate first-principles methods: G3, G4, CBS-APNO, W1­(RO). Simple “corrected atomization procedures” to derive theoretical Δ_f<i>H</i>_m^°(g) directly from the enthalpies <i>H</i>₂₉₈ have been tested and recommended as an alternative to using the bond separation and isodesmic reaction models for organic cyclic and heterocyclic compounds containing one to three nitrogen atoms

Thermochemistry of Uracils. Experimental and Computational Enthalpies of Formation of 5,6-Dimethyl‑, 1,3,5-Trimethyl‑, and 1,3,5,6-Tetramethyluracils

We describe in the current paper an experimental and computational study of three methylated uracils, in particular, the 5,6-dimethyl-, 1,3,5-trimethyl-, and 1,3,5,6-tetramethyl derivatives. The values of the standard (<i>p</i>⁰ = 0.1 MPa) molar enthalpies of formation in the gas phase at <i>T</i> = 298.15 K have been determined. The energies of combustion were measured by static bomb combustion calorimetry, and from the results obtained, the standard molar enthalpies of formation in the crystalline state at <i>T</i> = 298.15 K were calculated. The enthalpies of sublimation were determined using the transpiration method in a saturated N₂ stream. Values of −(376.2 ± 2.6), −(355.9 ± 3.0), and −(381.7 ± 2.8) kJ·mol^–1 for the gas-phase enthalpies of formation at <i>T</i> = 298.15 K of 5,6-dimethyluracil, 1,3,5-trimethyluracil, and 1,3,5,6-tetramethyluracil, respectively, were obtained from the experimental thermochemical study. An extended theoretical study with the G3 and the G4 quantum-chemical methods has been carried out for all the possible methylated uracils. There is a very good agreement between experimental and calculated enthalpies of formation for the three derivatives studied. A Free–Wilson analysis on G4-calculated enthalpies of formation has been carried out, and the contribution of methylation in the different positions of the uracil ring has been estimated