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

Abstract

The role of intramolecular hydrogen bonding (HB) on the bond-dissociation enthalpy (BDE) of the phenolic O-H 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(O-H) 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(O-H) 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(O-H) 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(O-H) 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.

A Straightforward Hetero‐Diels–Alder Approach to (2‐ambo,4′R,8′R)‐α/β/γ/δ‐4‐Thiatocopherol

“…The logarithms of the rate constants for H-atom abstraction are known to be inversely proportional to the BDE(O-H)s. The slope and the y-intercept of these plots are dependent on the nature of the abstracting radicals and on the steric crowding around the phenolic OH group, respectively. [30,32,33] In Figure 5 it is shown that 5b-d are on the same line of unhindered phenols, this being consistent with the presence, in ortho position to the OH group, of only one methyl group in 5b,c and with the absence of any substituent in 5d. Compound 5a is near to the line of 2,6-dimethylphenols, as expected from its structure.…”

“…Compound 5a is near to the line of 2,6-dimethylphenols, as expected from its structure. [33] Similarly to natural derivatives, the antioxidant activity of 4-thiatocopherols increases with the number of methyl groups on the aromatic ring. α-4-Thiatocopherol 5a has the lowest BDE(O-H) and is the most active antioxidant (highest k inh ) of the compounds prepared ( Table 1).…”

Antioxidants in Chemistry and Biology

“…Since such intramolecular H bonds have a strength on the order of ∼3 kcal mol −1 , they significantly influence the reactivity of these compounds in apolar solvents. 118 Organochalcogen substituents, besides participating intramolecular H bonding when they are ortho to the -OH, have generally quite complex stereoelectronic properties, as they behave as EW groups in the phenol and as ED groups in the phenoxyl radical, upon rotation with respect to the ring skeleton. A detailed discussion on their stereoelectronic properties and effect on BDE OH and reactivity has been provided.…”

Study the effect of curcumin on hepatic DNA damage in an experimental model of hepatic fibrosis

“…The actual mechanism by which the curcumin works as an antioxidant is still unclear. However, some studies attributed this effect to curcumin content of phenolic hydroxyl groups [27], β-diketone [28], and ortho-alkoxy group [29] in addition to its ability to interact with the thiol group of glutathione and thioredoxin1 [30]. Fu and his group had studied the effect of …”