The Reactivity of Ambident Nucleophiles: Marcus Theory or Hard and Soft Acids and Bases Principle?

The model reactions CH X + (NH-CH=O)M ➔ CH -NH-NH═O or NH═CH-O-CH  + MX (M = none, Li, Na, K, Ag, Cu; X = F, Cl, Br) are investigated to demonstrate the feasibility of Marcus theory and the hard and soft acids and bases (HSAB) principle in predicting the reactivity of ambident nucleophiles. The delocalization indices (DI) are defined in the framework of the quantum theory of atoms in molecules (QT-AIM), and are used as the scale of softness in the HSAB principle. To react with the ambident nucleophile NH═CH-O , the carbocation H C from CH X (F, Cl, Br) is actually a borderline acid according to the DI values of the forming C…N and C…O bonds in the transition states (between 0.

O-Regioselective Synthesis with the Silver Salt Method.

The excellent O-regioselectivity of the glycosidation of the ambident 2-O-substituted 5-fluorouracil (5-FU) via the silver salt method is computationally investigated at the MP2/6-311++G(2d,p):DZP//B3LYP/6-31+G(d):DZP level of theory. The reactions studied are those between 1-bromo-1-deoxy-2,3,4,6-tetra--acetyl-α-d-glucopyranose and the silver salts of 5-FU, 2--butyl-5-FU, and 2--benzyl-5-FU. Two pathways are considered as follows: (A) one where the silver and bromide ion do not interact, and (B) another where the silver and bromide ion interact in the transition states.

Theoretical Studies of the Glycosidation of 2-O-Substituted 5-Fluorouracil: N-Regioselective Synthesis with the Phase-Transfer-Catalysis Method.

The observed N-regioselective glycosidation of 2-O-substituted 5-fluorouracil (5-FU) via the phase-transfer-catalysis (PTC) method was investigated computationally. The Gibbs free energy reaction barrier of the N-reaction between the 5-FU anion and 1-bromo-1-deoxy-2,3,4,6-tetra-O-acetyl-α-d-glucopyranose was computed at the MP2/6-311++G(2d,p)//B3LYP/6-31+G* level. The calculated transition states were, in general, quite "loose", with the ambident reaction sites at the N3- or O4-positions on 5-FU located approximately 2.

Towards the accurate and efficient calculation of optical rotatory dispersion using augmented minimal basis sets.

It has been recognized that quantum-chemical predictions of dispersive (nonresonant) chiroptical phenomena are exquisitely sensitive to the periphery of the electronic wavefunction. To further elaborate and potentially exploit this assertion, linear-response calculations of specific optical rotation were performed within the framework of density-functional theory (DFT) by augmenting small basis sets (e.g.

Examination of DFT and TDDFT methods II.

We investigated the isomerization energies for C(8) alkanes (n-octane and 2,2,3,3-tetra-methyl butane) and 1-X-propenes (X = CH(3), F, Cl, Br) and the excited states for tropolone. The recently implemented TDDFT gradients enabled us to optimize the adiabatic excited-state structures and to obtain wave function files for excited-state electron density analyses with 25 functionals. The dispersion interactions had been found to be important for predicting the isomerization energies for n-octane and 2,2,3,3-tetra-methyl butane and for cis- and trans-1-X-propenes (X = CH(3), F, Cl, Br).

Examination of DFT and TDDFT methods I.

We investigated DFT and TDDFT methods in the sense of the molecular orbital (MO) theory and in the framework of the quantum theory of atoms in molecules (QT-AIM). The detailed investigations for the ground state and the pi --> pi* excited state of ethene clarified three aspects about DFT and TDDFT methods: First, the DFT methods included electron correlation effects by directly changing MO energies and MO electron density distributions. Second, MO occupation numbers explained why the delocalization indices (DIs) obtained from DFT wave function files apparently differed from DIs obtained from the conventional correlated wave function files.

Disparate behavior of carbonyl and thiocarbonyl compounds: acyl chlorides vs thiocarbonyl chlorides and isocyanates vs isothiocyanates.

The reaction of benzoyl chloride with methanol catalyzed by pyridine is 9 times more rapid than is the same reaction with thiobenzoyl chloride. The difference in reactivity, as well as the dealkylation reactions that occur when the reaction of thiobenzoyl chloride is catalyzed by bases such as Et(3)N, can be understood in terms of the charge distributions in the intermediate acylammonium ions. The reaction of PhNCO with ethanol occurs at a much higher rate (4.

Intramolecular Nonbonded Attractive Interactions: 1-Substituted Propenes.

Whereas cis-substituted alkenes are normally significantly less stable than the trans-isomers, there is a group of 1-substituted propenes (X = F, OMe, Cl, Br, SMe) where the cis-isomers are the more stable. The calculated structures show that there is steric repulsion with the cis-isomers. However, this is overcome by attractive Coulombic interactions when X = F or OMe and by attractive dispersive interactions when X = Cl or Br.

Optical rotatory dispersion of 2,3-hexadiene and 2,3-pentadiene.

The specific rotation of (P)-2,3-hexadiene (1) was measured as a function of wavelength for the gas phase, the neat liquid, and solutions. There was a surprisingly large difference between the gas phase and condensed phase values. The specific rotation was calculated using B3LYP and CCSD, and the difference in energy between the three low energy conformers was estimated at the G3 level.

Effect of substituents and conformations on the optical rotations of cyclic oxides and related compounds. relationship between the anomeric effect and optical rotation.

The effect of substituents on the specific rotation of substituted cyclic oxides (X = F, Cl, CN, and HCC) and related compounds was studied via geometry optimization at the B3LYP/6-311+G** level followed by calculations of the specific rotation with B3LYP/aug-cc-pVDZ and, when practical, also with B3LYP/aug-cc-pVTZ. In some cases chiral samples were prepared so that the calculated specific rotations could be compared with experimental data. With most compounds there was only a minor effect of the basis set on the specific rotations.

Correlation effects in EOM-CCSD for the excited states: evaluated by AIM localization index (LI) and delocalization index (DI).

We have extended the evaluation and interpretation of QTAIM (quantum theory of atoms in molecules) localization and delocalization indices lambda (LI) and delta (DI) to electronic excited states by studying ground states (at HF and CCSD levels) and excited states (at CIS and EOM-CCSD) of H2C=CH2, HCCH, H2C=O, H2C=S, CO2, CS2, and SO2. These molecules undergo extensive geometrical changes upon the excitation to the valence adiabatic excited singlet state. The importance of Coulomb correlation effects was demonstrated by comparing the LIs and DIs at none-correlated levels (HF and CIS) and those at correlated levels (CCSD and EOM-CCSD).

Sum-over-states calculation of the specific rotations of some substituted oxiranes, chloropropionitrile, ethane, and norbornenone.

A sum-over-states approach has been applied to the calculation of the specific rotations of several substituted oxiranes, 2-chloropropionitrile, and 30 degrees-rotated ethane. In each case, the first few excited states proved to have only a relatively small effect on the calculated specific rotation. It was necessary to use a very large number of excited states in order to achieve convergence with the results of the more direct linear response method.

Permanganate oxidation of alkenes. Substituent and solvent effects. Difficulties with MP2 calculations.

The permanganate oxidation of alkenes has been studied both experimentally and computationally. Transition state structures were located for the reaction of permanganate ion with a variety of monosubstituted alkenes at the B3LYP/6-311++G** level. Although the calculated activation energy for the reaction with ethene was reasonable, the calculated effect of substituents, based on the energies of the reactants, was much larger than that experimentally found.

Chiroptical properties of 2-chloropropionitrile.

(S)-(-)-2-chloropropionitrile has been prepared from (S)-(+)-alanine, and the ORD curves have been obtained in several solvents and in the gas phase. A reaction field extrapolation of the solution data to the gas phase led to an estimated value of [alpha]D = -21 degrees, whereas the interpolated gas phase value is -8 degrees. The specific rotation was found to be temperature dependent in ethylcyclohexane solution over the range 0-100 degrees C.

Conformational effects on optical rotation. 2-Substituted butanes.

The specific rotations of 2-substituted butanes (X = F, Cl, CN, and HCC) were calculated at the B3LYP/aug-cc-pVDZ level as a function of the C-C-C-C torsion angle. The results for the four compounds are remarkably similar, despite large differences in the electronic transition energies. The temperature dependence of the specific rotations for 2-methylbutyronitrile and for 2-chlorobutane was studied to give experimental information about the effect of the torsion angle on the specific rotation.

Comparison of CIS- and EOM-CCSD-calculated adiabatic excited-state structures. Changes in charge density on going to adiabatic excited states.

The CIS and EOM-CCSD adiabatic geometries for the first excited states of a set of small molecules (C2H4, C2H2, H2C=O, H2C=S, CS2, CO2, SO2, NO2) have been calculated using the 6-311++G** basis set to see if the former geometries can be good starting points for optimizations at the latter theoretical level. With most of the molecules, there is fairly good agreement between the results from the two methods, and EOM-CCSD gives good agreement with the available experimental data. A detailed discussion of the lowest-lying singlet excited states in CO2 and CS2 is presented, highlighting the pronounced differences in electronic character and equilibrium structure displayed by these isovalent species.

Conformational energies for 2-substituted butanes.

The conformational free energies for some 2-substituted butanes where X = F, Cl, CN, and CCH were calculated using G3-B3, CBS-QB3, and CCSD(T)/6-311++G(2d,p) as well as other theoretical levels. The above methods gave consistent results with free energies relative to the trans conformers as follows: X = CCH, g+ = 0.77 +/- 0.

Comparison of localization and delocalization indices obtained with Hartree-Fock and conventional correlated methods: effect of Coulomb correlation.

Atomic populations and localization [lambda(A)] and delocalization [delta(A,B)] indices (LIs and DIs) are calculated for a large set of molecules at the Hartree-Fock (HF), MP2, MP4(SDQ), CISD, and QCISD levels with the 6-311++G(2d,2p) basis set. The HF method and the conventional correlation methods [MP2, MP4(SDQ), CISD, and QCISD] yield distinct sets of LIs and DIs. Yet, within the four conventional correlation methods the differences in atomic populations and LIs and DIs are small.

A practical and efficient method to calculate AIM localization and delocalization indices at post-HF levels of theory.

A practical and efficient method is proposed for calculating localization and delocalization indices at post-Hartree-Fock levels, and the method is tested at the CISD/6-311G++(2d, 2p) level for a large set of molecules. Our method, which utilizes wave functions written in the natural molecular orbital format and obtained with GAUSSIAN 94 or GAUSSIAN 98, convincingly extends the concepts established at the HF level.