Steric Effects in Isolated Molecules: Gas‐Phase Basicity of Methyl‐Substituted Acetophenones

Abstract

The energies of 14 methyl‐substituted acetophenones and of their protonated forms were calculated within the framework of the density functional theory at the B3LYP/6‐311+G(d,p) level. The gas‐phase basicities of some members of this series were measured using Fourier transform ion cyclotron resonance mass spectrometry in order to complete the known data. The protonated forms exist in two configurations differing in the position of the hydrogen atom; their equilibrium depends strongly on the substitution pattern. Taking into account all conformational equilibria, the experimental and calculated basicities agreed to within 2.7 kJ mol–1. Substituent effects were tentatively resolved into polar and steric contributions by comparing the corresponding ortho and para derivatives. The steric effect of the ortho‐methyl groups defined in this way has a clear physical meaning proven by several correlations; it destabilizes the neutral acetophenone molecules but destabilizes the cations even more. Hence it is base‐weakening relative to the steric effect on the acidity of substituted benzoic acids, which is acid‐strengthening. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Thermochemical Considerations of Metal Enolates

“…These results were explained in terms of steric hindrance of the products-the enolate appears not that much more strained than the parent ketone that also has a trigonal carbon attached to the substituted phenyl ring 79 . By contrast, the alkoxide addition product is expected to have considerable strain arising from a substituted ring bonded to a quaternary carbon, as is found in the structurally related o-t-butyltoluene 80 which is strained by ca 25 kJ mol −1 relative to its m-and p-isomers.…”

Substituent Effects of the Alkyl Groups: Polarity vs. Polarizability

“…Protonation of the carbonyl group at the two sterically different positions was observed in acetophenone derivatives [40] but not in other ketones.…”

“…In our opinion the failure of electrostatic models is mainly in the assumed fixed position of the charges. [32,34] In Equations (3) and (4) one must assume that the positive charge is more localized and situated nearer to the polarizable medium but in any case the electrostatic calculation is a very rough approximation.…”

“…In contradistinction to Figure 1, we encounter in Figure 2 the problem of variable conformation. The actual energies of 1, 2, 3 are given by the Boltzmann distribution of all conformers but the minimum-energy conformation need not be the same in the ionic forms 2 and 3 as in the parent molecules 1: changes of conformation (configuration) with ionization [39,40] or with solvation [41] may affect markedly the acidobasic properties. For evaluating just the substituent effects we kept the same conformation in the corresponding species 1, 2 and 3, even when another conformation could coexist.…”

Calorimetric study of 2′-methylacetophenone and 4′-methylacetophenone

“…Small [1] studied the photoenolization of 2 0 -methylacetophenone to clarify the process of hydrogen abstraction from the c position. Also, some studies based on acid-base properties in solution of methyl-substituted acetophenones were made in order to elucidate the steric effects of ortho substituents on their basicities [2]. Keto-enol isomerisation of gas-phase 2 0 -methylacetophenone has been the subject of a study made by Giroldo and Riveros [3].…”