Persistent Hydrogen‐Bonded and Non‐Hydrogen‐Bonded Phenoxyl Radicals

Abstract

The production of stable phenoxyl radicals is undoubtedly a synthetic chemical challenge. Yet it is a useful way to gain information on the properties of the biological tyrosyl radicals. Recently, several persistent phenoxyl radicals have been reported, but only limited synthetic variations could be achieved. Herein, we show that the amide-o-substituted phenoxyl radical (i.e. with a salicylamide backbone) can be synthesised in a stable manner, thereby permitting easy synthetic modifications to be made through the amide bond. To study the effect of H-bonding on the properties of the phenolate/phenoxyl radical redox couple, simple H-bonded and non-H-bonded o,p-tBu-protected salicylamidate compounds have been prepared. Their redox properties were examined by cyclic voltammetry and showed a fully reversible one-electron oxidation process to the corresponding phenoxyl radical species. Remarkably, the redox potential appears to be correlated, at least partially, with H-bond strength, as relatively large differences (ca. 300 mV) in the redox potential between H-bonded and non-H-bonded phenolate salts are observed. The corresponding phenoxyl radicals produced electrochemically are persistent at room temperature for at least an hour; their UV/Vis and EPR characterisation is consistent with that of phenoxyl radicals, which makes them excellent models of biological tyrosyl radicals. The analyses of the experimental data coupled with theoretical calculations indicate that both the deviation from planarity of the amide function and intramolecular H-bonding influence the oxidation potential of the phenolate. The latter H-bonding effect appears to be predominantly exerted on the phenolate and not (or only a little) on the phenoxyl radical. Thus, in these systems the H-bonding energy involved in the phenoxyl radical appears to be relatively small.

Conformational Switching of Multi‐Responsive Ferrocenyl‐Phenol Conjugates

“…[13] In the parent phenol H-A OO , the phenolic hydrogen atom forms an intramolecular hydrogen bond (IHB) with the oxygen atom of the amide's carbonyl group (OH···O conformation; Scheme 1, a). [14] Although The combined action of deprotonation and oxidation has also been explored. On the other hand, the deprotonation of H-A OO results in a change from the OH···O bridge to the NH···O IHB to yield the phenolate [A NO ]by inversion of the amide unit to provide an acid/base conformational switch (Scheme 1, a).…”

“…radical [B NO ] · (Scheme 1, b), [14] the ferrocenyl-phenolate [A NO ]displays an even more diverse redox reactivity due to the presence of the ferrocene/ferrocenium redox couple (Scheme 1, a). [13] In addition to the phenoxyl radical valence isomer [Ab NO ] · , the ferrocenium phenolate zwitterion [Aa NO ] · and the ferrocenium iminolate zwitterions [Ac NO ] · and [Ac OO ] · have been identified by IR and EPR spectroscopy as well as by DFT calculations.…”

“…Indeed, photochemical excitation of the phenolate [Aa NO ] · with near-IR light (1040 nm) yields the phenoxyl radical [Ab NO ] · . [14] Furthermore, ferrocenium amides, such as the mixed-valent cation [H-C] +· , are stronger hydrogen-atom donors than neutral ferrocenyl amides. [15] Indeed, phenolates are better hydrogen acceptors than phenoxyl radicals.…”

Unconventional redox properties of hydroquinones with intramolecular OH−N hydrogen bonds

“…This represents a significant development in relation to the much more heavily studied hydrogen-bonded phenols: the one-electron oxidized phenoxyl radical cations have lifetimes of minutes to hours and can only be interrogated spectroscopically. 36,62 In addition, the quinone dication oxidation products are diamagnetic, facilitating their NMR characterization (in contrast with the paramagnetic phenoxyl radical cations). The spectroscopic and structural characterization of the dication quinones reveals that they do not contain intramolecular (NH−O) hydrogen bonds.…”

The effects of intramolecular hydrogen bonding on the reactivity of phenoxyl radicals in model systems

“…There has been considerable interest in developing model systems to better understand the effects of hydrogen bonding on the properties of tyrosyl radicals [17,[30][31][32][33]. Most of these systems incorporate both a phenol and a basic nitrogen atom in a close proximity to facilitate the formation of hydrogen-bonded phenoxyl radical, as shown for C in Scheme 1 [31].…”