Steric effects and mechanism in the formation of hemi-acetals from aliphatic aldehydes

Some physical properties (pKa, log POW, boiling points) of hexanoic acid 1 (X = COOH) and its seven isomers 2, 3, 4, 5, 6, 7, 8 (X = COOH) are reported. Hexanal 1 (X = CHO) and its seven isomeric aldehydes 2, 3, 4, 5, 6, 7, 8 (X = CHO) are shown to equilibrate, in methanol solution, with their hemi‐acetals. Logarithms of equilibrium constants correlate with values of Es for the isomeric C5H11 substituents, and with logs of relative rates for saponification of the corresponding methyl esters with ρ = 0.52, reflecting the reduced steric demand of hydrogen compared to oxygen in the quaternization of ester and aldehydic carbonyl groups. Rates of equilibration have also been measured in buffered methanol. For hexanal, with a 2:1 Et3N:AcOH buffer, the buffer‐independent contribution is dominated by the methoxide catalysed pathway. Rates in this medium have been determined for isomers 1, 2, 3, 4, 5, 6, 7, 8 (X = CHO), and their logarithms do not correlate with logarithms of equilibrium constants for hemi‐acetal formation or with substituent steric parameters derived from ester formation or saponification, indicating that the steric changes associated with full quaternization of the carbonyl group are not mirrored in the transition structures for hemi‐acetal formation. It is suggested that transition states for hemi‐acetal formation are relatively early so that steric interactions are effectively those between the nucleophile and ground state conformations of the aldehydes. A comparison of the entropies of hemi‐acetal formation with entropies of activation has provided a basis for a suggested transition structure. Comparisons with acid chloride hydrolyses are made. © 2013 The Authors. Journal of Physical Organic Chemistry published by John Wiley & Sons Ltd. Logarithms of equilibrium constants for formation hemi‐acetals of hexanal and its seven isomeric aldehydes correlate well with values of Es for the isomeric C5H11 substituents, and with logs of relative rates for saponification of the corresponding methyl esters. Logarithms of rate constants for hemi‐acetal formation do not, indicating that the steric changes associated with full quaternization of the carbonyl group are not mirrored in the transition structures for hemi‐acetal formation. The reasons for this are discussed.