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The conformational equilibria of the cis/trans isomers of some 1,4-di-substituted cyclohexanes (X = OH, OMe, Me, OCOCH3, OCOC(CH3)(3), OCOCCl3, OCOCF3) were calculated at several levels of theory; the best correlation between calculated and experimentally available Delta G(0)s refers to the MP2/6-311 +G*//MP2/6-311G* results. In addition, the hyperconjugative effect of the substituents was studied with the NBO options included in the GAUSSIAN-98 package; a number of interactions between filled NBOs and antibonding orbitals could be considered as most representative for delocalization along the molecules studied. The effect of the substituents on the molecular geometry of the substituted cyclohexanesas well as the partitioning of both hyperconjugative and steric substituent effects on the present conformational equilibria is critically evaluated. Our model [E. Kleinpeter, F. Taddei, J. Mol. Struct. (THEOCHEM) 683 (2004) 29] for interpreting the relative stability of conformers of substituted cyclohexanes could be further verified and its reliability assessed. (c) 2005 Elsevier B.V. All rights reserved

The electron transfer (ET) to a series of para-substituted diaryl disulfides, having the general formula (X-C(6)H(4)S-)(2), has been studied. The X groups were selected as to have a comprehensive variation of the substituent effect, being X = NH(2), MeO, H, F, Cl, CO(2)Et, CN, and NO(2). The reduction was carried out experimentally, using N,N-dimethylformamide as the solvent, and by molecular orbital (MO) ab initio calculations. The ET was studied heterogeneously, by voltammetric reduction and convolution analysis, and homogeneously, by using electrogenerated radical anions as the solution electron donors. The reduction is dissociative, leading to the cleavage of the S-S bond in a stepwise manner. Both experimental approaches led us to estimate the E degrees and the intrinsic barrier values for the formation of the radical anions. Comparison of the independently obtained results allowed obtaining, for the first time, a quantitative description of the correlation between heterogeneous and homogeneous rate constants of ETs associated with significant inner reorganization energy. The experimental outcome was fully supported by the theoretical calculations, which provided information about the disulfide lowest unoccupied MOs (LUMOs) and singly occupied MO (SOMO), the bond dissociation energies, and the most significant structural modifications associated with radical anion formation. With disulfides bearing electron-donating or mildly electron-withdrawing groups, the inner reorganization is particularly large, which reflects the significant stretching of the S-S bond experienced by the molecule upon ET. The process entails formation of loose radical anion species in which the SOMO is heavily localized, as the LUMO, onto the frangible bond. As a consequence of the formation of these sigma-radical anions, the S-S bond energy of the latter is rather small and the cleavage rate constant is very large. With electron-withdrawing groups, the extent of delocalization of the SOMO onto the aryl system increases, leading to a decrease of the reorganization energy for radical anion formation. Interestingly, while the LUMO now has pi character, the actual reduction intermediate (and thus the SOMO) is still a sigma-type radical anion. With the nitro-substituted disulfide, very limited inner reorganization is required and a pi-radical anion initially forms. A nondissociative type intramolecular ET then ensues, leading to the formation of a new radical anion whose antibonding orbital has similar features as those of the SOMO of the other diaryl disulfides. Therefore, independently of the substituent, the actual S-S bond cleavage occurs in a quite similar way along the series investigated. The S-S bond cleavage rate, however, tends to decrease as the Hammett sigma increases, which would be in keeping with an increase of both the electronic and solvent reorganization energies.

The cyclohexyl esters of a series of carboxylic acids, RCO(2)H, spanning a range of electronegativities and quotients of steric hindrance for the R substituent (R=Me, Et, iPr, tBu, CF(3), CH(2)Cl, CHCl(2), CCl(3), CH(2)Br, CHBr(2), and CBr(3)) were prepared. Their conformational equilibria in CD(2)Cl(2) were examined by low-temperature (1)H NMR spectroscopy to study the axial or equatorial orientation of the ester functionality with respect to the adopted chair conformation of the cyclohexane ring. The ab initio and DFT geometry-optimized structures and relative free energies of the axial and equatorial conformers were also calculated at the HF/6-311G**, MP2/6-311G**, and B3LYP/6-31G** levels of theory, both in the gas phase and in solution. In the latter case, a self-consistent isodensity polarized continuum model was employed. Only by including electron correlation in the modeling calculations for the solvated molecules was it possible to obtain a reasonable correlation between DeltaG degrees (calcd) and DeltaG degrees (exp). Both the structures and the free energy differences of the axial and equatorial conformers were evaluated with respect to the factors normally influencing conformational preference, namely, 1,3-diaxial steric interactions in the axial conformer and hyperconjugation. It was assessed that hyperconjugative interactions, sigma(C-C)/sigma(C-H) and sigma*(C-O), together with a steric effect--the destabilization of the equatorial conformer with increasing bulk of the R group--were the determinant factors for the position of the conformational equilibria. Thus, because hyperconjugation is held responsible as the mitigating factor for the anomeric effect in 2-substituted, six-membered saturated heterocyclic rings, and since it is also similarly responsible, at least partly, in these monosubstituted cyclohexanes for a preferential shift towards the axial conformer, the question is therefore raised: can the anomeric effect really be construed as anomalous?

The structures and relative energies of the conformers of the cyclohexyl esters of general formula Cy-XCOCR 3 (X=O; R=H, F, Cl and X=S; R=H, Cl) and Cy-XCR 3 (X=O, S) have been calculated at theoretical levels including HF/6-31G ∗ , HF/6-3l1G ∗∗ , MP2/6-311G ∗∗ , B3LYP/6-311G ∗ and CBS-4M. The different stability of axial and equatorial conformers is analysed as a function of conformational enthalpy (Δ H 0 ), entropy (Δ S 0 ) and free energy (Δ G 0 ) as well. The HF and DFT approaches reproduce the correct higher stability of the equatorial conformers of these molecules while the MP2 treatment inverts this order of stability in the case of X=O. The theoretical results reproduce as well the higher relative stability of the equatorial conformer in the case of X=S relative to those with X=O, yet less satisfactory is the agreement with the trend of experimental results as a function of the different R substituents. The origin of the different stability of the conformers as a function of X and R is discussed in detail; hyperconjugative interactions σ C–C / σ C–H → σ C–X ∗ prove to dominate the position of the conformational equilibria.

The origin of the rotational barrier around the partial C C double bond in substituted ethylenes is discussed with reference to the stabilization of the conformational minimum (GS) and of the rotational transition state (TS). Molecules with different polar character of the double bond were chosen, ranging from ethylene to olefins with strong push–pull character. The enthalpies of hydrogenation, ΔHhydr., and of formation, ΔHf0, of these molecules were employed to obtain the stability of GS; these thermochemical properties were calculated with MO ab-initio theory at HF/6-311G∗∗//HF/6-311G∗∗ and MP2/6-311G∗∗//HF/6-311G∗∗ levels and with CBS-4M model chemistry. The stabilization of TS was derived from the torsional potential for rotation around the C C bond. The lowering of the energy content of GS of substituted ethylenes, referring to ethylene, is accompanied by an even greater stabilization of TS, thus a lowering of the rotational barrier with respect to ethylene is generally found in these molecules.

Internal rotational barriers around the exocyclic partial CC double bond were calculated for a wide group of heterocyclic derivatives as a function of the different structure of the heterocyclic ring and of the nature of heteroatoms, by means of MO abinitio theory. The rotational barriers refer to the two-fold potential energy, V 2 , obtained from single-determinant Hartree–Fock (HF) wave functions and at MP2/6-31G ∗ //HF/6-31G ∗ level of theory. The V 2 values seem to represent homogeneously the rotational barrier in substituted ethylenes with varying polar character of the CC bond, ranging from unpolarized ethylene to molecules having a marked push–pull character, and thus allow the effect of substituents on the height of the barrier to be compared. Sets of parameters quantifying the heteroatom effect of constantly modulating the barrier in the different heterocyclic rings were extracted, and two heteroatoms were found to have an additive effect when acting in the same ring. The difference between the V 2 values and the rotational barriers calculated from the HF energy of the perpendicular conformation is discussed in the light of a qualitative approach based on calculated contributions of singlet excited states to the electronic configuration of the perpendicular conformation.

A theoretical MO ab-initio investigation was carried out on methylenecycloalkanes ( exo -isomer) and methylcycloalkenes ( endo -isomer) bearing electronwithdrawing substituents (CN,COOR) at the exo carbon atom and a pentadiene push–pull structure in the endo isomer. These isomers were found previously to be generated in variable amounts as a function of ring dimension, of the substituents at the exo carbon, and of the push–pull character of the structures. The relative stability of the two isomers was obtained from the total molecular energies at MP2/6-31G ∗ //HF/6-31G ∗ theoretical level taking into account the complex conformational patterns due to several degrees of freedom for internal rotation in these molecules. The results from the theoretical study, carried out also on model compounds of simpler structure and also employing the heats of formation calculated with CBS-4M model chemistry, allow the different effects acting on the relative stability of exo / endo isomers of cyclic compounds to be rationalized.

The rotational barrier for substituted ethylenes was calculated with MO ab initio methods, both in the Hartree–Fock (HF) single determinant scheme and with multiconfigurational self-consistent field (MCSCF) approaches. The HF model affords reliable results only when applied to molecules substituted with strong electron donor groups, assigning a push–pull character to the molecule. The MCSCF approach was employed for calculating rotational barriers in poorly polarized ethylenes not directly amenable to the HF methods; however, this method was found hard to handle for low symmetry molecules with substituents interacting with the double bond. A method is proposed based on the interpolation of the energy of the perpendicular conformation from a Fourier truncated function constructed with HF molecular energies calculated for frozen conformations twisted up to 60°. The application of HF theory for studying internal rotation in substituted ethylenes with poorly polarized character is discussed and an upper limit of 35–40 kcal/mol can be set up for having reliable barriers from the calculated energy of the rotational transition state at this level of theory.

Ab initio MO calculations were carried out in 2-chloro-6-NR2-pyran-4-ones, 2-chloro-6-NR2-thipyran-4-ones and in their protonated forms with the aim of discussing the electronic and structural effects modulating the rotational barriers about the C–N partial double bond measured in previous research. The barriers in these molecules depend on NR2 substituents (pyrrolidino, dimethylamino, piperidino and morpholino groups were examined), on the O/S atoms in the pyranone/thiopyranone rings and differ in neutral and protonated forms. The results of calculations, carried out at different levels of theory (HF/6-31G∗//HF/6-31G∗, HF/6-31G∗∗//HF/6-31G∗∗, B3LYP/6-31G∗∗, MP2/6-31G∗∗/MP2/6-31G∗∗) and simulating the effect of a solvent (self-consistent isodensity polarized continuum model) were employed to analyse the effect of the different molecular fragments on the barrier to internal rotation about the partial C–N double bond. Parallel trends are found for calculated and experimental results as a function of changes in molecular structure even though the calculated barriers for the ions are overestimated.

An MO theoretical ab initio study was performed on 2- exo -methylene push–pull derivatives having as donor groups nitrogen atoms, components of a heterocyclic ring, and as acceptors CN and COOEt groups. Five-, six- and seven-membered ring derivatives were considered. Calculations were also performed on a number of push–pull ethylenes whose experimental properties were reported in the chemical literature in order to test the soundness of the conclusions from theoretical approaches. The physical properties calculated for the latter molecules were compared with known experimental values, in order to check the predictive ability of the theoretical approaches employed. Geometrical features and torsional barriers in solution are satisfactorily reproduced. Results were obtained with different basis sets, second-order Moller–Plesset theory, in order to perform comparisons at different theoretical levels with a view to carrying out calculations in larger molecular systems. The widest range of comparisons between calculated values for the different molecules were carried out at the HF/6-31G ∗ //HF/6-31G ∗ level. The origin of the torsional barrier for isomer interconversion as a function of the electronic properties of these molecules is discussed, in particular by examining the polarized character of the exo double bond. The role of the lone pairs of the nitrogen atoms in the push–pull mechanism is investigated, also in competition with an unsaturated bond within the ring. The different conjugation patterns that can be exploited within these molecules is examined within the donor–acceptor model and Natural Bond Orbital (NBO) theory. Empirical correlations are proposed in order to estimate dipole moments and absorption wavelengths for the family of push–pull olefins.

The energy of the rotational barriers and electronic structure of the transition state in substituted ethylenes are discussed in the light of the results obtained from different theoretical MO ab initio approaches. The 6-31G ∗ basis set at Hartree–Fock (HF) level and with second-order Moller–Plesset perturbation theory (MP2) was employed, critical points were localized through full geometry relaxation and characterized by vibrational analysis. A multiconfigurational approach (MCSCF) with different active spaces was also employed. For alkenes the correct rotational transition state is obtained only from the MCSCF approach, whereas for push–pull olefins the HF approach with correlation corrections at MP2 level provides correct answers for the internal rotation around C(sp 2 )–C(sp 2 ) bonds. The choice is more critical when only acceptor or donor groups are present, especially when change of hybridization occurs at the atoms at the edges of the C–C bond in the critical points.

The S−S bond cleavage of dihydrogen disulfide, HSSH, and of its radical anion was studied theoretically with molecular orbital (MO) ab initio calculations at different levels of theory. The bond dissociation energy obtained from the total molecular energies of the undissociated HSSH and of the HS radicals is close to the best experimental value only with the G2 Moller−Plesset second-order perturbation (MP2) and complete basis set (CBS) methods and underestimated with the multiconfigurational self-consistent field (MCSCF) procedure regardless of the basis set and active space employed. The energy profile of the radical anion as a function of the S−S bond distance displays a minimum at 2.8 A, and the activation energy for the electron transfer was calculated from the crossing of the energy profiles of the neutral molecule and of the radical anion both in the vapor phase and in media of different polarity. Changes in the activation energy of the order of 1 kcal/mol were found when transitions between vibrati...

The potential energy profile for a number of derivatives of benzene substituted with the SiH3, SiH2CH3, and CH2SiX3 (X = H, F, Cl, CH3) groups was calculated at ab initio (HF/6-31G*//HF/6-31G*) level, and the energy barriers were estimated. The rotational barrier is low for the molecules with silicon directly bonded to the phenyl ring, but higher values are found for the CH2SiX3 groups, which depend on X as well. The hyperconjugative effect of the substituents was estimated from the natural bond orbital (NBO) theory of donor acceptor properties: the SiH2CH3 group was found to be electron-acceptor in character, and the CH2SiX3 were found to be electron-donor groups. The rotational barrier of these molecules is mainly determined by hyperconjugation, steric effects being smaller than in the analogous carbon derivatives. The SiH and SiC bonds display an electron-acceptor character of similar magnitude when silicon is attached to the phenyl ring, but the SiC bond has a prevailing donor character when carbon i...

The structural and conformational properties of disulphides R1S-SR2, with R1 = phenil ring (Ph) and R2 = H, Me and Ph and, for a comparison, those of the disulphides with R1,R2 = H,Me were determined with MO ab initio calculations. The level of theory chosen was the 3–21G∗ with full geometry relaxation and electron correlation corrections at a second order Moller-Plesset perturbation scheme (MP2/3-21G∗//MP2/3-21G∗). This choice allowed a comparison of the properties calculated for the molecules containing alkyl and phenyl groups at the same level of theory. All the disulphides examined showed patterns of the potential energy for internal rotation with a minimum conformation of skew type and two maxima, one of cis and one of trans type, with the former representing the higher transition state for internal rotation. The effect of the R group is higher on the cis barrier and the effect of Me and Ph is respectively to increase and decrease the barrier, with respect to RH. The bond energy required for homolitically breaking the bonds (BDE) in these molecules and in the radicals RSS was estimated both from calculated total molecular energies, and from heats of formation of the species involved in the dissociation processes. The BDE's from the ab initio energies were found to have been largely underestimated, which applies to a different extent to the SS, SH and CS bonds. For the SS bond, the BDE's calculated at the level of theory adopted here are proportional to values from experiments or from higher levels of theoretical approaches. For the disulphides with R1,R2 = H,Me, calculations were performed with the sophisticated Gaussian-2 (G2) scheme and the BDE's obtained are very close to the most accurate determinations, showing that a high level of theory is necessary to obtain these quantities at a convenient level of confidence. The origin of the barriers for internal rotation and of the different bond strengths in the molecules and radicals containing the SS bond was analyzed within the natural bond orbital (NBO) description of donor-acceptor interactions.

The mechanism of oxidation of dimethyl thiosulfinate with performic acid was investigated theoretically at MO ab-initio level. Equilibrium geometries and transition states were optimized with two different basis sets (3-21G and 6-31G) and the inclusion of dynamic correlation correction at MP2 level. Along the possible reactions paths three different transition states were characterized, namely, those leading to the formation of the diastereomeric forms (RR/SS or RS/SR) of alpha-disulfoxide and that leading to the thiosulfonate. The calculated values of activation energies and free energies of activation, in the gas phase, fail to reproduce the observed chemoselectivity of oxidation reactions. However, when the formation of reaction clusters, or better, the inclusion of solvent effects (evaluated via SCFR method) is taken into account, one obtains a correct behavior that fits the experimental trend. The reaction path was also analyzed by employing the intrinsic reaction coordinate methodology in order to examine the transitory character of alpha-disulfoxide. The effect of acids in depressing the reactivity was also demonstrated.

The effects governing the barrier for internal rotation in a number of α-substituted toluenes C6H5CH2X (X = Cl, F, CH3, C(CH3)3, CF3, CC13) and α,α-disubstituted toluenes C6H5CHX2 (X = Cl, F) were interpreted using a model which factorizes the energy barrier into three components, namely, 1. a) hyperconjugation, 2. b) electrostatic effects and 3. c) van der Waals interactions. The potential energy profiles for internal rotation of the CH2X and CHX2 rotors were calculated at molecular orbital MO ab initio level with a 6-31G∗ basis set and analysed by means of a truncated Fourier series in the V2 and V4 terms. The hyperconjugative contributions were estimated employing natural bond orbitals (NBO) derived from the 6-31G∗ wave functions in a scheme of acceptor-donor intramolecular interactions. The donor and acceptor hyperconjugative contributions, with respect to the π system of the benzene ring, of each bond constituting the CH2X and CHX2 rotors were found to contribute additively to the hyperconjugative effect of the whole rotating group. Electrostatic effects and van der Waals interactions were tentatively estimated with empirical formulas. The separate contributions of these effects were compared, albeit at a qualitative level, with the total molecular energy and their relative weight discussed. The rotational barriers of benzylchloride and benzalchloride are mainly controlled by hyperconjugative effects. In benzylfluoride and benzalfluoride, the hyperconjugative effects are active to the same extent as in chlorine derivatives but the barrier is mainly controlled by electrostatic effects. In the compounds with bulky X groups (X = C(CH3)3, CF3 and CCl3), hyperconjugation plays a less important role than van der Waals interactions and electrostatic effects, and the relative weight of these effects differs for the substituents examined.

Conformational properties and barriers to internal rotation for the three isomeric picolines mono- bi- and trichlorosubstituted at the methyl group were studied at the theoretical level with ab initio MO calculations. Energy profiles for internal rotation of the chlorinated methyl group were obtained at the 6-31G ∗ level with full molecular geometry relaxation, and the energy of critical points was recalculated at the MP2/6-311G ∗∗ level of theory. The conformational minima and maxima of these derivatives are qualitatively similar to those found for benzene derivatives, yet differences are found in the heights of the barriers to internal rotation and in the presence of two rotational minima or maxima in the molecules with lower rotational symmetry. The origin of the barriers to rotation and of the different energy content of conformational minima is discussed in the light of the natural bond orbital (NBO) approach within the donor-acceptor viewpoint of intramolecular interactions, and electrostatic interactions between the rotating group and the ring.

Reductive electron transfer on the title compounds has been studied theoretically with MO ab initio methods, using the 6-31G* basis set and second-order Moller–Plesset perturbation theory, in order to verify the eventual stability of their radical anion and to analyze the C–Cl bond breaking process both in the neutral molecules and in the anions. The effect of the basis set has been tested at single point energies with the 6-311G** basis set. The geometries of the neutral molecules and radicals formed after bond dissociation are fully relaxed. The energy profiles of the radical anions as a function of the C–Cl bond distance have been found to be dissociative. The energy of activation and the structure of the activated complex have been studied in the forbidden crossing of the energy profiles of the neutral molecule and radical anion. The results show that the activation energy of the process is affected both by the number of chlorine atoms on the methyl group and by the different aromatic ring, yet the energy of reaction is significantly affected only by the number of chlorine atoms. When compared with reduction potentials determined experimentally in a previous work, these activation energies show an excellent linear relationship. The results are discussed in the frame of the Marcus–Hush model of electron transfer and it appears that chloromethyl derivatives of pyridine and benzene do not strictly follow the same reaction mechanism at the end of applying this model.

The potential energy profile of the benzyl chloride radical anion as a function of the CCl bond distance calculated with ab initio MO theory, 6–31G∗ level and molecular relaxation shows a purely dissociative behavior, provided that constraints are dictated to the direction of the departing chloride anion. If the departing anion is allowed complete freedom, a minimum in the energy profile is found corresponding to a molecular complex between the benzyl radical and the chloride anion. This behavior differs from that of the chlorobenzene radical anion, which shows a change of the symmetry of the electronic ground state from 2B1 to 2A1 on elongating the CCl bond distance.

The crystal structures of the title compounds were determined by single crystal X-ray diffraction techniques. The molecule of the Z isomer, which crystallizes in the monoclinic space group C2/c with Z = 4 in a cell of dimensions a = 14.891 (2), b = 10.780(2), c = 8.769(1) Å, β = 97.47(2)°, V = 1395.7(7) Å3 has crystallographic twofold symmetry. The E form crystallizes in the orthorhombic space group Pbca with a = 11.730(1), b = 6.932(1), c = 16.841(1) Å, V = 1369.4(2) Å3 and Z = 4. Its molecules have crystallographically dictated [Formula: see text] symmetry. In both isomers the phenyl rings are roughly perpendicular to the average ethylene plane. The atoms characterizing this plane show significant deviations from planarity in the Z isomer. Marked bond-angle distortions at the ethene carbons of both structures are observed. The 1H and 13C NMR spectra of the compounds were measured and, particularly in the case of the 1H chemical shifts, fall into two quite separate spectral regions. At low temperature, two conformational isomers, those with different relative orientation of the C—Cl bonds of the phenyl rings, are observed in the spectrum of each compound. Keywords: chlorostilbenes, overcrowded molecules. X-ray structure, conformations, NMR spectroscopy.

The conformational equilibrium related to the internal rotation processes occurring in sulphoxides of the type ArCH 2 SOCH 3 (where Ar=2-thienyl, 2-furyl, 2-pyridinyl and (3-methyl)2-pyridinyl rings) were studied with 1 H and 13 C NMR spectroscopy. Proton chemical shifts and long-range coupling constants n J (H,H) were obtained from the iterative analysis of the multiplets and were employed, together with 13 C chemical shifts, long-range n J (C,H) and relaxation parameters (NOE and non-selective T 1 values) to obtain stereochemical relationships between the protons present in these molecules. Conformational predictions at a qualitative level were also derived from total molecular energies calculated with the semi-empirical AM1/MNDO method as a function of internal coordinates. The different approaches converged to indicate that the heterocyclic rings adopt an average orientation similar to the perpendicular orientation of the phenyl ring in benzyl methyl sulphoxide and, as regards rotation around the CH 2 S bond, the prevalent conformer shows that the methyl group is symmetrically oriented with respect to the methylenic protons. The barriers for internal rotation are rather low and the equilibrium between conformers is dependent on the medium properties. Attempts to obtain conformational results were performed for the molecule of omeprazole, an antiulcer drug which contains the ArCH 2 SOR moiety (Ar and R are substituted 2-pyridinyl and 2-benzimidazolyl groups, respectively). With respect to the other compounds examined, the orientation of the Ar ring does not significantly differ and the benzimidazole ring seems to prefer an orientation stereochemically equivalent to that of the methyl group.

Homolytic dissociation energies for different cleavage paths in a number of peroxides peroxyacids and peroxyesters and in the radicals formed from these molecules, were calculated from the total MO ab-initio molecular energies of the chemical species involved in the bond cleavage reactions and compared with experimental values, where known.

Heats of formation ΔHofof a number of peroxyacids RC(O)OOH, peroxyesters RC(O)OOR' and of the radicals RC(O), RC(O)O, RC(O)OO and C(O)OOR', related to possible routes of their thermal decomposition, were estimated by employing empirical approaches. R and R' are a wide set of alkyl and aryl groups. The approaches were based on isodesmic reactions, atom equivalent, group additivity and molecular mechanics (MM2) calculations. Isodesmic reactions and atom equivalent schemes were employed with HF/6-31G∗ ab initio total molecular energies. The MM2 calculations were applied to peroxyacids and peroxyesters and the values of ΔHofobtained were corrected by a constant quantity because they appeared systematically in excess with respect to those obtained by the other approaches. In atom equivalent and group additivity methods, new parameters were evaluated in order to be able to calculate the heats of formation of these molecules. Values of ΔHdgfobtained from the different approaches turn out to be consistent within ±2 kcal mol−1. For the RC(O) radicals with R = H, CH3 C6H5 and CF3, a comparison with values reported in the literature is possible and agreement can be considered satisfactory. For the RC(O)O radicals with R = H, CH3, C6H5, the ΔHof values estimated in this work from isodesmic reactions and atom equivalent approaches are 7–10 kcal mor−1 higher than those reported in the literature. This difference appears to be due to improper evaluation of the total molecular energy with HF/6-31G∗ ab initio calculations for this radical, owing to symmetry breaking in SCF methods. With the heats of formation calculated for peroxyacids, peroxyesters and for the radicals structurally related to these molecules, homolytic dissociation energies for the various bonds were derived and discussed as a function of the structural features of the R and R' groups. Possible routes for the thermal decomposition of the peroxyesters were examined.

The geometrical features relative to the lowest conformational minimum, and absolute and relative energy contents of a number of peroxyacids RC(O)OOH (R = H, CH3, CF3, C6H5) and methyl esters (R = H, CH3, CF3) have been calculated at the ab initio MO level with the 6-31G∗ basis set. For the peroxyacids with R = H and CH3, the most stable conformation obtained from this calculation is of cis type (referring to internal rotation around the O-O bond) and agrees with that found experimentally. This conformation is the most stable one also for the other peroxyacids examined and for the peroxyesters. Poor agreement is, however, found between calculated and experimental geometrical parameters relative to the O-O and O-H bond lengths, and to the OOC and OOH bond angles. Comparison of calculated structural features of peroxyacids with those of the corresponding acids shows that stabilization of the planar cis conformation of the former compounds is due to intramolecular hydrogen bonding. This property influences the energy difference between cis and trans forms, ΔE, which, for the same R, is larger in the peroxyacid than in the peroxyester. The ΔE values increase approximately with the bulk of R. The energy content, conformational features and geometrical parameters of the more stable conformation have been analysed within the same theoretical approach for the radicals RC(O)O, RC(O)OO and C(O)OOR' (R' = H, CH3), formally derived from homolytic bond dissociation of the peroxyacids and peroxyesters examined. The σ(RC(O)O and C(O)OOR') and π (RC(O)OO) characters, atom spin densities and relative stabilities of the conformers of these radicals are discussed.

The geometrical and electronic properties of RSSR, RS(O)SR and RS(O)S(O)R (with RH,CH3) molecules and the energy profile for SS bond cleavage were calculated with ab-initio MO MCSCF wavefunctions at 3–21G* level. The results show that the electronic structure of α—disulphoxides is more likely that of two paired radicals with net spin population localized on the oxygen atoms. Also in terms of bond-length and bond-index the SS bond in α—disulphoxides appears to be much weaker than in the other molecules, as also confirmed by the calculated bond dissociation energy (DE) which turns out much lower than expected for a true SS bond.

The conformational features of a large number of hydroperoxides ROOH and peroxides ROOR′, where R and R′ are alkyl groups of different and increasing size and phenyl rings, including ortho substituted derivatives, were obtained from molecular mechanics calculations by employing a standard package. For the molecules of small molecular size, comparison was carried out with the results of ab initio calculations. Heats of formation were also obtained from molecular mechanics for hydroperoxides and peroxides: The values are, in general, overestimated. For the molecules containing the CF3 group, the calculated values are subject to large errors and heats of formation were obtained from ab initio total energies in the “atom equivalents” scheme. To estimate the homolytic dissociation energies of the different bonds in the peroxide molecules, heats of formation of R·, ·OR, and ·OOR radicals were employed and several of them had to be calculated. Different approaches were employed—molecular mechanics calculations, ab initio energies within the atom equivalent and isodesmic reaction schemes, and Benson's group additivity rule; values consistent within the different calculation methods were chosen for estimating dissociation energies. The bond dissociation energies indicate different trends in these molecules as a function of the nature of the R and R′ groups and the possible electronic effects operating in these molecules are discussed. © 1993 John Wiley & Sons, Inc.

The problem of bond dissociation in hydrogen peroxide and in its monoanion was tackled with the ab initio MCSCF method by employing a triple-zeta (TZP) contracted basis set, augmented by polarization functions. For hydrogen peroxide the calculated energies for homolytic OO and OH bond cleavages are underestimated (by about 12 kcal mol −1 ) with respect to bond dissociation enthalpies obtained from heats of formation. This result seems to arise from not taking dynamical correlation effects properly into account, as emerges from the comparison with the results of MP2/TZP calculations. For the monoanion of hydrogen peroxide the equilibrium geometry turns out to be almost all planar with one hydrogen atom shifted between the oxygen atoms and the unpaired electron mostly localized on the outer oxygen atom. The two processes: H 2 O − 2 (X 2 A) → OH (X 2 Π) + -OH (X 1 ∑ + and H 2 O−1 2 (X 2 A) → O − (X 2 P u + H 2 O(X 1 A 1 ) require 36.15 and 23.82 kcal mol −1 respectively (41.06 and 30.14 kcal mol −1 at MP2/TZP level), and the latter is likely to be the more favoured path in the chemical reactivity of hydrogen peroxide in the presence of electron donating molecules (i.e. Fenton's reagent).

The conformational behaviour in the internal rotation process around the S-S bond was investigated in dimethyl disulphide, dimethyl thiosulphinate and a-dimethyl disulphoxide with the ab initio molecular orbital method at the 6–31 G ∗ atomic orbital basis set level. For each molecule the conformational minima and transition states relative to the internal rotation process were characterized with full geometry relaxation as minima and saddle points. Vibrational analysis of these conformations was carried out and thermodynamic parameters relative to the ground state conformational equilibria and transition states for conformer interconversion were derived. The conformational behaviour of the two diastereoisomers of a-dimethyl disulphoxide was found to be markedly different. An interpretation of the relative stability of ground and transition states was given within two different models of vicinal interactions. A number of calculated structural parameters of these molecules agree with an empirical description of their relative stability, although the seemingly remarkable instability of the a-disulphoxide with respect to the other molecules cannot be predicted with certainty. A multiconfigurational self-consistent field approach applied to the ground state of the corresponding molecules in which the methyl group is substituted with a hydrogen atom shows that in the case of the a-disulphoxide the S-S bond length is much greater than in the other compounds and one excited electronic structure contributes strongly to its ground state electronic structure.

The solid-state crystal and molecular structure of a number of ring-substituted methyl phenyl sulfoxides, containing mainly fluorine substituents, has been obtained by X-ray analysis. The conformation found for the molecules has geometrical features very close to those of the most stable conformer(s) predicted by ab initio molecular orbital calculations. In those compounds without ortho substituents the SO bond is only slightly twisted from being coplanar with the ring plane, while a larger twist is present when both ortho positions are substituted. In the presence of one ortho substituent the SO bond adopts an anti orientation and is almost coplanar with the ring. With the unsymmetrically substituted derivatives two conformers are possible and in the case of ortho substitution the energy difference (18–24 kJ mol–1) is large enough to have crystals only of the lower energy conformer. When the ortho positions are both free, the energy difference is quite low (0.6 kJ mol–1) and both conformers are found in the same crystal.

The fusion of a small, strained ring on a benzene molecule causes remarkable perturbations on the geometry of the latter molecule, perturbations which reduce with increasing number of atoms in the fused ring and become negligible as fusion involves rings larger than five-membered ones. The Cambridge structural database was searched for the experimental geometrical features of compounds containing from three- to ten-membered cycloalkene rings condensed with benzene. MO ab initio calculations at the 3-21 G level were employed for studying the calculated features, i.e. geometries, total energies, enthalpies of formation, strain energies and π-electron distribution, in compounds containing cycloalkenes (from three- to five-membered rings) and related rings with further unsaturation, and in systems related to benzocyclopropene with a heteroatom (oxygen) or a positively charged carbon. The effect of the additional strain, generated in the molecule by the fusion of the two rings, on molecular geometry and π-electron distribution is discussed. Strain, which is highest when a three-membered ring is annellated to the benzene molecule, seems to be the main factor responsible for the geometrical perturbations of these molecules, whereas the π-electron distribution is mainly determined by interactions between the electrons of the atoms or groups at the functions of the annellated ring and those of the benzene π-orbitals.

The 17O chemical shifts and band widths for tert-butyl peresters of ortho-substituted benzoic acids have been measured in benzene solution. Two signals are observed, of different line-width, and that at higher field is broader. The two signals shift to lower field with an increase in the number and size of ortho substituents (methyl and tert-butyl groups were chosen), and the signal at lower field is the one more significantly affected. Correlations with a fair degree of linearity are found for each set of chemical shifts with the twist angle of the carbonyl group from the phenyl plane. Twist angles were calculated from molecular mechanics. From the screening constant estimated theoretically at a semi-empirical level with the Karplus–Pople formula and from line-width arguments based on quadrupole relaxation, it is possible to advance the reasonable conclusion that the signal at lower field of these molecules represents two oxygen nuclei [those of the C(O)–O group] and the other the remaining peroxidic oxygen. For the 2,4,6-tri-But derivative which is solid at room temperature and can be obtained in a suitable crystal form, the crystal and molecular structure has been determined by X-ray diffraction. The structure is built up of one crystallographically independent molecule, affected by statistical disorder due to two alternative orientations of all the tert-butyl groups bonded to the ring. The peroxycarboxyl group is planar and nearly perpendicular (80.8°) to the benzene ring plane.

The potential energy profile for a number of derivatives of benzene substituted with the SiH3, SiH2CH3, and CH2SiX3 (X = H, F, Cl, CH3) groups was calculated at ab initio (HF/6-31G*//HF/6-31G*) level, and the energy barriers were estimated. The rotational barrier is low for the molecules with silicon directly bonded to the phenyl ring, but higher values are found for the CH2SiX3 groups, which depend on X as well. The hyperconjugative effect of the substituents was estimated from the natural bond orbital (NBO) theory of donor acceptor properties: the SiH2CH3 group was found to be electron-acceptor in character, and the CH2SiX3 were found to be electron-donor groups. The rotational barrier of these molecules is mainly determined by hyperconjugation, steric effects being smaller than in the analogous carbon derivatives. The SiH and SiC bonds display an electron-acceptor character of similar magnitude when silicon is attached to the phenyl ring, but the SiC bond has a prevailing donor character when carbon i...

An investigation of the solid-state conformational properties of 3-methylsulphinyl derivatives of furan and 2- and 3-methylsulphinyl derivatives of thiophene, which also contain halogen atoms in the heterocyclic ring, is reported. For 3-iodo-2-(methylsulphinyl)thiophene compound 1 , two crystallographically independent molecules were found in the unit cell, and in 2-bromo-4-iodo-3- (methylsulphinyl)thiophene, compound 5 , a high degree of disorder is present. The sulphur atom of the methylsulphinyl group has a pyramidal structure. The methyl group is highly twisted with respect to the ring plane and the SO bond adopts different orientations in the molecules exam- ined. When only one halogen atom is present in the ring the SO bond is directed to the opposite side of the ring with respect to this atom, yet the relative position of the substituents determines a different twist of this bond with respect to the heterocyclic plane.

The preferred conformations of the methylsulphinyl group bonded to the heterocycles furan and thiophene have been studied with NMR techniques in solution. The presence of one halogen atom ortho to the methylsulphinyl group determines the orientation of the SO bond in the opposite direction with respect to the halogen, and the degree of coplanarity of this bond with the ring depends on the substitution pattern. The higher degree of coplanarity is found when the methylsulphinyl group and the halogen substituent are in position 3 and 4. Two ortho substituents determine structures with large twists of the methylsulphinyl group. The chemical shifts of 1 H, 13 C and 17 O nuclei of the methylsulphinyl group and referred to spectra in solution do not evidence trends of general validity for all the compounds examined as a function of the orientation of the methylsulphinyl group with respect to the ring. Such trends were present in the case of the cor- responding phenyl derivatives. Nevertheless, by examining the behaviour of long-range n J (C,H) coupling constants, involving the carbon nucleus of the methyl group, together with chemical shifts, conclusions regarding the conformational behaviour of these molecules in solution can be derived. Possible perturbations of the equilibrium caused by the polarity of the medium are evidenced as well. The results indicate that in the 2-methylsulphinyl derivatives of furan the S0 bond is preferentially oriented in the O,O-cis direction and significantly twisted from the ring plane, yet the S,O-cis conformer, with a smaller twist, is preferred for the corresponding thiophene derivative. For the 3-methylsulphinyl derivatives, similar behaviour is found for the two hetero- cycles. The molecules consist of an equilibrium mixture of the X,O-cis and X,O-trans conformers, with the latter more abundant and increasing in more polar solvents. For compounds with an iodine atom in position 4, the X,O-cis conformation is the one most preferred in solution.

The ground state conformations and transition states for conformer interconversion in the two isomers of the methylsulphinyl derivatives of furan ( 1 and 2 ) and thiophene ( 3 and 4 ) were identified through a theoretical approach based on ab-initio molecular orbital calculations. Two minima and two transition states were found in the potential energy profiles for all the molecules, but the behaviour of 2-methylsulphinyl furan ( 1 ) differs somewhat from that of the other compounds. The minima correspond to the two orientations of the S0 bond with respect to the heterocyclic heteroatom X (X0 or S), labelled X,O- cis an X,0- trans . The conformer having the S0 bond oriented s-cis with respect to the internal double bond with higher π density (X,0- cis for the 3-methylsulphinyl derivatives and X,0- trans for the 2-methylsulphinyl derivatives) has a twist angle φ (between the S0 bond and the heterocyclic ring) of a few degrees. Larger distortions are present in the conformers with opposite orientation of the S0 bond, and the twist angle has the highest value (φ = 62.8° ) in compound 1. The transition states correspond to the methyl group being nearly coplanar with the heterocyclic ring and this situation seems to be due mostly to a loss of π electron delocalization. More complex is the transition state situation for compound 1 , since a barrier in the potential energy for internal rotation is imposed also by the repulsion between the heterocyclic and sulphinyl oxygen atoms. The conformer populations were estimated from the potential energy expressed as a function of φ by employing a Fourier expansion in the hindered rotor approximation; the populations show that for the 3-methylsulphinyl compounds the X,O- cis form is preferred, although the situation is reversed for the 2-substituted derivatives. An approximate prediction of the behaviour of these molecules in solution was attempted in the framework of the reaction field theory. In solvents of increasing polarity the X,0- cis form becomes progressively more dominant for the 2-methylsulphinyl derivatives, in contrast with the behaviour of 3-methylsulphinyl derivatives which shift to the X,O- trans form. For compound 1 an increase in solvent polarity seems to cause stabilization of a third conformer.

The preferred conformations of the methylsulphinyl group in a number of phenyl methyl sulphoxides substituted in the phenyl ring with one, two or three fluorine atoms have been studied by employing a multinuclear NMR approach. From the 1H, 13C and 17O chemical shifts of the methylsulphinyl group, and the torsional angles obtained either from MO calculations or experimental determinations for a number of the compounds, empirical correlations have been derived which enabled us to extract the preferred orientation of the SO bond or of the methyl group relative to the phenyl ring in all the molecules examined. For a limited number of the compounds, the structure of the preferred conformer is satisfactorily close to the solid-state structure found in an independent study carried out with x-ray diffraction. The twist of the SO bond relative to the phenyl ring changes as a function of the number of ortho substituents, being highest when two substituents are present. The lowest twist, torsional angle nearly zero, was found in ortho-monosubstituted compounds and the SO bond is oriented towards the opposite side with respect to the substituent. Analyses were also carried out of the conformational dependence of long-range nJ(HF) and nJ(CF) coupling constants, where the first nucleus in the parentheses refers to the methylsulphinyl group. The behaviour of these coupling constants as a function of internal rotation around the exocyclic CS bond was derived from semi-empirical INDO MO FPT calculations, and scaled interpolating equations were derived in order to reproduce the experimental results. It thus emerges that 5J(HF), 4J(CF), 5J(CF) and 6J(CF) are conformationally dependent and show, experimentally, significant changes. These parameters can be usefully employed for the conformational analysis of methyl phenyl sulphoxides.

The geometrical structure and thermodynamic properties of the open-chain and cyclic cations formally derived by halogen nucleophilic displacement in 2-chloroethanol, 2-chloroethanethiol and in the corresponding 1,3-propane derivatives were calculated in the MO ab-initio approach with the extended 6-31G ∗ basis set. To set up a comparison between the stability of these cations and that of starting materials, 2-chloroethanol and 2-chloroethanethiol were also examined in the same calculation scheme in order to have a homogeneous conformational description of these two molecules in their ground states. The results show that both in terms of total electronic energy and free-energy content the cyclic ion is more stable than the open form, and this occurs for both the three- and four-membered rings. This stability order is enhanced in the case of the sulphur derivatives. As regards entropy contributions, these do not show appreciable differences in three- and four-membered cyclic ions, at least in comparison with other energy contributions. According to these calculations, the energy required for generating the cations from the starting materials is quite large: of the order of 180 kcal mol − . These reactions thus seem very unlikely to occur, unless ion-pair association and solvation lower the intermediate and transition-state energies. Accordingly, it is rather difficult to give a proper description of the transition state for intra- and intermolecular nucleophilic displacements in these systems and an attempt has been made to obtain a number of approximate conclusions by comparing the stability of intermediate cations. Intramolecular displacements thus appear to be favoured almost to the same extent, when three- and four-membered cyclic intermediates are formed, both entropically and as regards the energy content. Minor effects should thus be involved in decreasing the energy of activation of the process in the case of 1,2-ethane derivatives with respect to the corresponding 1,3-propane derivatives.

The main goal of this communication is to show the utility of empirical approaches combined with mathematical methods in the research regarding the molecular basis of biological chirality. Preparative results (enantiomeric excesses, e.e.) obtained in asymmetric autocatalysis with (AAC) and without (AES) chiral additive were analyzed. Statistical calculations show, that AES (absolute enantioselective synthesis) experiments yield two independent groups of results with prevalence of the R‐ or S‐enantiomer. These are distributed asymmetrically in a second‐order beta distribution. Empirical calculations both on AAC and EAS enable to identify the very low (statistical) e.e.‐s amplified by AES. These initial e.e.‐s show normal distribution. Possible molecular‐level reasons of these results were controlled by quantum chemical MO calculations and compatible mechanism(s) are discussed.

The trans diesters of 1,4-cyclohexanediol with a number of acetic acid analogues, CX3COOH, of varying steric hindrance and polarity (CX3 = Me, Et, iso-Pr, tert-Bu, CF3, CH2Cl, CHCl2, CCl3, CH2Br, CHBr2, CBr3) were synthesized, and the axial, axial/equatorial, equatorial conformational equilibria were studied by low-temperature H-1 NMR spectroscopy in CD2Cl2. The structures and relative energies of the axial, axial and equatorial, equatorial conformers were calculated at both the MP2/6-311G* and the MP2/6-311+G* levels of theory, and it was only by including diffuse functions that a good correlation of Delta G degrees(calcd) vs Delta G(exptl) could be obtained. Both the structures and the energy differences of the axial, axial and equatorial, equatorial conformers are discussed with respect to the established models of conformational analysis, viz., steric 1,3-diaxial and hyperconjugative interactions. Interestingly, the hyperconjugative interactions sigma(C-C)/sigma(C-H)->sigma*(C-O), together with a steric effect which also destabilizes the equatorial, equatorial conformers on increasing bulk of the substituents, proved to dominate the position of the conformational equilibria. In addition, the preference of the axial, axial conformers with respect to their equatorial, equatorial analogues was greater than expected from the conformational energies of the corresponding substituents in the monosubstituted cyclohexyl esters. The reason for this very interesting and unexpected result is also discussed

The dissociative reduction of a series of symmetrical (RSSR, R = H, Me, t-Bu, Ph) and unsymmetrical disulfides (RSSR', R = H, R' = Me and R = Ph, R' = Me, t-Bu) was studied theoretically, by MO ab initio calculations and, for five of them, also experimentally, by convolution voltammetry in N,N-dimethylformamide. The reduction is dissociative but proceeds by a stepwise mechanism entailing the formation of the radical anion species. The electrochemical data led to estimated large intrinsic barriers, in agreement with an unusually large structural modification undergone by the disulfide molecules upon electron transfer. The theoretical results refer to MP2/3-21G*//MP2/3-21G*, MP2/3-21*G*//MP2/3-21G*, CBS-4M, and G2(MP2), the latter approach being used only for the molecules of small molecular complexity. A loose radical-anion intermediate was localized and the dissociation pattern for the relevant bonds analyzed. For all compounds, the best fragmentation pathway in solution is cleavage of the S-S bond. In addition, S-S bond elongation is the major structural modification undergone by the disulfide molecule on its way to the radical anion and eventually to the fragmentation products. The calculated energy of activation for the initial electron transfer was estimated from the crossing of the energy profiles of the neutral molecule and its radical anion (in the form of Morse-like potentials) as a function of the S-S bond length coordinate. The inner intrinsic barrier obtained in this way is in good agreement with that determined by convolution voltammetry, once the solvent effect is taken into account.

To study the relationship between rate and driving force of intramolecular dissociative electron transfers, a series of donor-spacer-acceptor (D-Sp-A) systems has been devised and synthesized. cis-1,4-Cyclohexanedyil and a perester functional group were kept constant as the spacer and acceptor, respectively. By changing the aryl substituents of the phthalimide moiety, which served as the donor, the driving force could be varied by 0.74 eV. X-ray diffraction crystallography and ab initio conformational calculations pointed to D-Sp-A molecules having the cis-(cyclohexane) equatorial(phthalimido)-axial(perester) conformation and the same D/A orientation. The intramolecular dissociative electron-transfer process was studied by electrochemical means in N,N-dimethylformamide, in comparison with thermodynamic and kinetic information obtained with models of the acceptor and the donor. The intramolecular process consists of the electron transfer from the electrochemically generated phthalimide-moiety radical anion to the peroxide functional group. The electrochemical analysis provided clear evidence of a concerted dissociative electron-transfer mechanism, leading to the cleavage of the O-O bond. Support for this mechanism was obtained by ab initio MO calculations, which provided information about the LUMO of the acceptor and the SOMO of the donor. The intramolecular rate constants were determined and compared with the corresponding intermolecular values, the latter data being obtained by using the model molecules. As long as the effective location of the centroid of the donor SOMO does not vary significantly by changing the aryl substituent(s), the intramolecular dissociative electron transfer obeys the same main rules already highlighted for the corresponding intermolecular process. On the other hand, introduction of a nitro group drags the SOMO away from the acceptor, and consequently, the intramolecular rate drops by as much as 1.6 orders of magnitude from the expected value. Therefore, a larger solvent reorganization than for intermolecular electron transfers and the effective D/A distance and thus electronic coupling must be taken into account for quantitative predictions of intramolecular rates.

To estimate the thermochemical properties, bond dissociation energies and atomization energies of sulfur organic derivatives, the complete basis set (CBS) method was employed at the lower computational level (CBS-4) owing to the large molecular size of a number of the molecules chosen. By comparison with experimental values, calculated values of thermochemical properties are subject to error, which increases in line with the increase in molecular complexity. The main source of error affecting the calculated enthalpy of formation stems from the difference between the energy of the molecule and that of the single atoms: the greater the size of the molecule, the greater the accumulation of error. By acting on the empirical correction to the CBS energy and minimizing the error due to the contribution of the single atoms to the dissociation energy a parameter di for each atom i is obtained. Application of these corrections does not greatly affect the heats of formation of the small molecules included in test sets employed for previous comparisons of calculated and experimental values, while there is a great improvement in the case of large molecules, for example, diphenyl disulfide. The mean absolute deviation turns out to be 2.52, which is greater than that obtained in recent reexaminations of model chemistry methods including the G3 and G3(MP3) approaches. The improvement in the results calculated for large molecules, whose heats of formation are calculated with large errors at the CBS-4 level, in comparison also with the CBS-4M version, justify our approach. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 1405–1418, 2000

The structure of a number of 2-exo-methylene substituted quinazolines and benzodiazepines, respectively, 1, 3a,b, 4 ( X=–CN, –COOEt ) and their 2-cyanoimino substituted analogues 2, 3c,d ( X=–CN, –SO 2 C 6 H 4 –Me (p) was completely assigned by the whole arsenal of 1D and 2D NMR spectroscopic methods. The E/Z isomerism at the exo-cyclic double bond was determined by both NMR spectroscopy and confirmed by ab initio quantum chemical calculations; the Z isomer is the preferred one, its amount proved dependent on steric hindrance. Due to the push–pull effect in this part of the molecules the restricted rotation about the partial C2,C11 and C2,N11 double bonds, could also be studied and the barrier to rotation measured by dynamic NMR spectroscopy. The free energies of activation of this dynamic process proved very similar along the compounds studied but being dependent on the polarity of the solvent. Quantum chemical calculations at the ab initio level were employed to prove the stereochemistry at the exo-cyclic partial double bonds of 1–4, to calculate the barriers to rotation but also to discuss in detail both the ground and the transition state of the latter dynamic process in order to better understand electronic, inter- and intramolecular effects on the barrier to rotation which could be determined experimentally. In the cyanoimino substituted compounds 2, 3c,d, the MO ab initio calculations evidence the isomer interconversion to be better described by the internal rotation process than by the lateral shift mechanism.

The vicinal H,H and H,C coupling constants along the Ph–CH 2 AB –CRH M –C X (O)R′ spin system of 5-benzyl substituted hydantoins together with the results of accompanying force field (TRIPOS) and quantum chemical ab initio calculations (GAUSSIAN-94 with atomic basis set of 3-21G type) were employed to report on the rotamer population about the hydantoin C(5)–benzyl substituent bond. The conformation having the phenyl ring folded over the hydantoin ring system proved to be preferred.

The 1 H and 13 C NMR spectra of a series of 3-phenyl-5- exo -methylene-substituted hydantoins were recorded and assigned unequivocally by the various methods of 1D and 2D NMR spectroscopy. Employing the NMR parameters thus obtained, the NOEs between the different protons within the molecules and the results of accompanying semiempirical (AM1 and PM3, respectively) and ab initio (3-21G∗) quantum chemical calculations, the tautomerism, the acidity, the redox potentials, the stereochemistry and the electron density distribution of the hydantoins were studied. In addition, the X-ray crystallographic structure of compound 1r is given and compared with the spectroscopic results.