Redox Chemistry of Selenenic Acids and the Insight It Brings on Transition State Geometry in the Reactions of Peroxyl Radicals

Abstract

The redox chemistry of selenenic acids has been explored for the first time using a persistent selenenic acid, 9-triptyceneselenenic acid (RSeOH), and the results have been compared with those we recently obtained with its lighter chalcogen analogue, 9-triptycenesulfenic acid (RSOH). Specifically, the selenenyl radical was characterized by EPR spectroscopy and equilibrated with a phenoxyl radical of known stability in order to determine the O-H bond dissociation enthalpy of RSeOH (80.9 ± 0.8 kcal/mol): ca. 9 kcal/mol stronger than in RSOH. Kinetic measurements of the reactions of RSeOH with peroxyl radicals demonstrate that it readily undergoes H-atom transfer reactions (e.g., k = 1.7 × 10(5) M(-1) s(-1) in PhCl), which are subject to kinetic solvent effects and kinetic isotope effects similar to RSOH and other good H-atom donors. Interestingly, the rate constants for these reactions are only 18- and 5-fold smaller than those measured for RSOH in PhCl and CH3CN, respectively, despite being 9 kcal/mol less exothermic for RSeOH. IR spectroscopic studies demonstrate that RSeOH is less H-bond acidic than RSOH, accounting for these solvent effects and enabling estimates of the pKas in RSeOH and RSOH of ca. 15 and 10, respectively. Calculations suggest that the TS structures for these reactions have significant charge transfer between the chalcogen atom and the internal oxygen atom of the peroxyl radical, which is nominally better for the more polarizable selenenic acid. The higher than expected reactivity of RSeOH toward peroxyl radicals is the strongest experimental evidence to date for charge transfer/secondary orbital interactions in the reactions of peroxyl radicals with good H-atom donors.

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“…However, due to their high chemical reactivity, these putative reaction intermediates have not been previously isolated in a native selenoprotein [12]. Indeed, selenenic acid has only been detected in a few organic molecules - where a rigid and bulky molecular frame stabilized it - because of its tendency to self-condense and its oxidizing abilities [13, 14]. Consequently, information about the stability of selenenic acids is scarce.…”

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“…The kinh was determined to be 1.7×10 5 M -1 s -1 in a styrene inhibited autoxidation at 30°C in chlorobenzene. 31 While this value is an order of magnitude smaller than in the analogous sulfenic acid (3.0×10 6 M -1 s -1 under the same conditions), 30 it is remarkably large given the 9 kcal/mol difference in O-H bond strength (also considering the kinh for a hydroperoxide is only ~10 3 M -1 s -1 ). 32 Kinetic isotope effects and kinetic solvent effects were also consistent with a formal H-atom transfer mechanism.…”

“…31 Based on the periodic trend of weakening bonds in RO-H > RS-H > RSe-H, we wondered if a selenenic acid would have a weaker O-H bond than a sulfenic acid, which is already considerably weaker than in a hydroperoxide (vide supra). Interestingly, radical equilibration EPR experiments with 2,4,6-tri-tert-butylphenoxyl yielded an O-H BDE of 80.9±0.9 kcal/mol in 9-triptyceneselenenic acid: 9 kcal/mol stronger than the sulfenic acid, and actually more similar to a hydroperoxide (ca.…”

“…86 kcal/mol). 31 We surmised that the longer Se-O bond in the selenenyl radical precludes radical delocalization onto the internal selenium atom (~20%) relative to the sulfur atom in the sulfinyl radical (~50%). 31 …”

“…32 Kinetic isotope effects and kinetic solvent effects were also consistent with a formal H-atom transfer mechanism. 31 To help explain the surprisingly similar reactivity of the sulfenic and selenenic acids towards peroxyl radicals, we undertook a parallel computational investigation. We had previously ascribed the slower-than-expected reactivity of 9-triptycenesulfenic acid (3×10 6 M -1 s -1 vs. 3×10 7 M -1 s -1 derived for α-toluenesulfenic acid) to steric hindrance precluding formation of the preferred syn TS.…”