Ab-Initio MO Study of the Peracid Oxidation of Dimethyl Thiosulfinate

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 α-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 α-disulfoxide. The effect of acids in depressing the reactivity was also demonstrated

Hyperconjugation and the Increasing Bulk of OCOCX₃ Substituents in Trans-1,4-Disubstituted Cyclohexanes Destabilize the Diequatorial Conformer

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 1H 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 ΔG°calcd vs ΔG°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 σC-C/σC-H→σ*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

Theoretical and Electrochemical Analysis of Dissociative Electron Transfers Proceeding through Formation of Loose Radical Anion Species: Reduction of Symmetrical and Unsymmetrical Disulfides

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

Formation and Cleavage of Aromatic Disulfide Radical Anions

The electron transfer (ET) to a series of para-substituted diaryl disulfides, having the general formula (X−C6H4S−)2, has been studied. The X groups were selected as to have a comprehensive variation of the substituent effect, being X = NH2, MeO, H, F, Cl, CO2Et, CN, and NO2. 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° 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 σ*-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 π* character, the actual reduction intermediate (and thus the SOMO) is still a σ*-type radical anion. With the nitro-substituted disulfide, very limited inner reorganization is required and a π*-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 σ increases, which would be in keeping with an increase of both the electronic and solvent reorganization energies

Insights into the Free-Energy Dependence of Intramolecular Dissociative Electron Transfers

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

Evidence for Large Inner Reorganization Energies in the Reduction of Diaryl Disulfides: Toward a Mechanistic Link between Concerted and Stepwise Dissociative Electron Transfers?

Evidence for Large Inner Reorganization Energies in the Reduction of Diaryl Disulfides:  Toward a Mechanistic Link between Concerted and Stepwise Dissociative Electron Transfers

Insights into the Free-Energy Dependence of Intramolecular Dissociative Electron Transfers

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