Hydrogen-Atom Transfer Reactions from ortho-Alkoxy-Substituted Phenols: An Experimental Approach

Graphical Abstract

Deceptively simple: Joint results obtained by EPR and IR spectroscopies and inhibited autoxidation studies allow an explanation, on quantitative grounds, of the factors determining the H-atom donating abilities of 2-alkoxyphenols (see graphic; blue: 2-methoxyphenol, red: cyclic phenol).

Abstract

Deceptively simple: Joint results obtained by EPR and IR spectroscopies and inhibited autoxidation studies allow an explanation, on quantitative grounds, of the factors determining the H-atom donating abilities of 2-alkoxyphenols (see graphic; blue: 2-methoxyphenol, red: cyclic phenol).

The role of intramolecular hydrogen bonding (HB) on the bond-dissociation enthalpy (BDE) of the phenolic OH and on the kinetics of H-atom transfer to peroxyl radicals (k_inh) of several 2-alkoxyphenols was experimentally quantified by the EPR equilibration technique and by inhibited autoxidation studies. These compounds can be regarded as useful models for studying the H-atom abstraction from 2-OR phenols, such as many lignans, reduced coenzyme Q and curcumin. The effects of the various substituents on the BDE(OH) of 2-methoxy, 2-methoxy-4-methyl, 2,4-dimethoxyphenols versus phenol were measured in benzene solution as −1.8; −3.7; −5.4 kcal mol⁻¹, respectively. In the case of polymethoxyphenols, significant deviations from the BDE(OH) values predicted by the additive effects of the substituents were found. The logarithms of the k_inh constants in cumene were inversely related to the BDE(OH) values, obeying a linear Evans–Polanyi plot with the same slope of other substituted phenols and a y-axis intercept slightly smaller than that of 2,6-dimethyl phenols. In the cases of phenols having the 2-OR substituent included in a five-membered condensed ring (i.e, compounds 9–11), both conformational isomers in which the OH group points toward or away from the oxygen in position 2 were detected by FTIR spectroscopy and the intramolecular HB strength was thus estimated. The contribution to the BDE(OH) of the ortho-OR substituent in 9, corrected for intramolecular HB formation, was calculated as −5.6 kcal mol⁻¹. The similar behaviour of cyclic and non-cyclic ortho-alkoxy derivatives clearly showed that the preferred conformation of the OMe group in ortho-methoxyphenoxyl radicals is that in which the methyl group points away from the phenoxyl oxygen, in contrast to the geometries predicted by DFT calculations.