Conformational Preferences and Pathways for Enantiomerization and Diastereomerization of Benzyl Alcohol. Data Mining and ab Initio Quantum-Mechanical Study

Abstract

The potential energy surface of benzyl alcohol has been explored at the RHF/6-31G* and MP2-(full)/6-31G* levels of ab initio theory. The exo and endo minimum structures and all of the transition-state structures for their enantiomerization and diastereomerization were located. The thermochemical functions were computed, and relative enthalpies and free enthalpies were determined. The computed relative free enthalpy is in excellent agreement with known NMR data. Benzyl alcohol is a highly flexible molecule, which allows for essentially unhindered enantiomerization and diastereomerization of the minima; all pertinent relative energies and free enthalpies are less than 3 kcal/mol, and the entire conformational space about the CC and CO bonds is easily accessible. An examination of the crystallographic record shows a much greater variety of conformations to occur in the solid state as a result of the optimization of intermolecular interactions in the crystals. Data mining shows that the conformations about the CC and CO bonds of all of the CC-staggered and CO-gauche structures are correlated, and consequently, the conformational preferences about the C-O bond greatly deviate from the expected 3-fold barrier. The theoretical study shows the correlation to be instrinsic and offers an explanation. Natural population analysis provides a rational for the relative stabilities of the benzyl alcohol conformations on the basis of the conformation dependence of the effects of electron-electron repulsion between the O-lone pairs and the benzene π-cloud, the charge-charge attraction between the hydroxyl H-atom and the benzene π-density, and the dipole-dipole interaction associated with the CH 2 -C ipso and OH bonds. Our analysis emphasizes the importance of the dipole alignment of the CH 2 -C ipso and OH bond dipole moments.

Understanding benzyl alcohol aggregation by chiral modification: the pairing step

“…The global minima of B are two mirrorimage conformers with both dihedrals synchronized in gauche arrangements with the same sign: G−g− and G+g+ (Fig. 2), in agreement with previous calculations 13, [48][49][50][51][52] and results from rotational spectroscopy 51 . They can interconvert via a shallow barrier of 2.0 kJ mol −1 (B3LYP-D3, zero-point corrected), even down to low conformational temperatures in a jet expansion.…”

Predicting OH stretching fundamental wavenumbers of alcohols for conformational assignment: different correction patterns for density functional and wave-function-based methods

“…Included in the training set are b,gunsaturated alcohols (e.g., phenylmethanol), as the classification of their very weak OHÁ Á Áp interaction is disputed. [51][52][53][54] The derived model from and for transitions of non-hydrogen-bonded conformers is later tested for its performance for hydrogen-bonded species.…”

Rapid assessment of conformational preferences in biaryl and aryl carbonyl fragments

“…As a result, the energy minima for 5 are the planar rotamers. Electronic repulsion between the electron lone pair of the nitrogen in the pyridine and the pi cloud of the phenyl ring [ 20 ] also likely contributes to the higher, meaningful (ΔE > 4kcal/mol) energy increase observed in the CEP of 5 at 90° ( Fig 3D ). This interaction is only present in this system because the orientation of the electron lone pair of the nitrogen for 3- and 4-phenylpyridines (6, 7) is not directed toward the pi electron cloud of their corresponding phenyl rings.…”