December 8.Warren et al.Page5.1.2 N-hydroxyphthalimide (NHPI)/phthalimide-N-oxyl radical (PINO)–The PINO radical has been broadly explored in organic free radical oxidations,85,86 especially as a `green’ alternative to the bromide co-catalyst in transition metal-catalyzed autoxidations.87 Flavopiridol site Catalytic oxidations in PINO-containing systems are thought to proceed through a series of H-atom abstraction steps. Despite the wide attention that NHPI/PINO has received, relatively few thermochemical data are available. Koppel and co-workers have determined pKa values for NHPI in water and DMSO,88 and the DMSO value can be used to estimate a pKa in MeCN.89 NHPI is much more acidic than dialkyl hydroxylamines, as would be expected for a phthalimide. There is little consensus between the published electrochemical studies of NHPI. In MeCN in the absence of base, a broad quasi-reversible oxidation is observed at +1.2 V vs. Cp2Fe+/0.90 Addition of pyridine bases caused a shift to much lower potentials, which was attributed to the oxidation of deprotonated NHPI (the NHPI?- couple).90?19293 However, this assignment is unlikely since the pyridine bases used (pKa = 12?6 in MeCN30) are not basic enough to deprotonate NHPI to any great extent (pKa = 23.5 in MeCN, see Table 3). Furthermore, the potentials vary with the strength of the added base, with stronger bases leading to lower potentials ?by roughly 59 mV per unit change in the pyridine pKa, as would be expected for a PCET reaction.90?19293 These data all suggest that the electrochemical process removes 1H+ and 1e- from NHPI, not simply an electron. We estimate, based on the reported electrochemical data extrapolated to pKa(NHPI) = 23.5 (59 mV per pKa), E?NHPI?-) = -0.1 V and BDFE = 84.8 kcal mol-1 in MeCN. Lucarini, Pedulli and co-workers have employed their EPR radical equilibration technique to determine bond strengths (BDEs) of NHPI, substituted NHPI derivatives and other related hydroxylamines.94,95 The BDE of NHPI was determined to be 88.1 kcal mol-1 in tBuOH solvent.94 Later, bond strengths for substituted NHPI derivatives were determined in CH3CN with respect to the parent NHPI, again using the EPR equilibration technique.95 The GGTI298 biological activity reference BDE used in that study was 88.1 kcal mol-1, the BDE of NHPI in tBuOH. However, based on the E?and pKa data for NHPI in MeCN, we conclude that the BDEMeCN of NHPI is 1.2 kcal mol-1 higher than the corresponding BDE in tBuOH. Thus, BDEs for substituted NHPI derivatives have been adjusted upward by 1.2 kcal mol-1 such that they are relative to the BDE of NHPI in MeCN determined here. One of the great advantages of the EPR equilibration technique is that the BDEs are usually very accurate with respect to each other, so that the uncertainty in the absolute BDE is essentially only dependent upon the accuracy of the reference compound BDE. 5.2 Phenols, Hydroquinones, Catechols and Ascorbate This section presents thermochemical data for hydroxylic compounds where the OH group is attached to an unsaturated (sp2) carbon. The redox chemistry of such compounds ?phenols, quinones, ascorbate, etc. ?has been the subject of intense interest for more than a half century. To give just a few examples, PCET reactions of these compounds are integral to biological energy production (e.g. quinone cycling in photosystems I and II and the bc1 complex; tyrosine Z in photosystem II),106?07108 biosynthesis (ribonucleotide reductases),109 antioxidant activity (tocopherols),110,111 and food.December 8.Warren et al.Page5.1.2 N-hydroxyphthalimide (NHPI)/phthalimide-N-oxyl radical (PINO)–The PINO radical has been broadly explored in organic free radical oxidations,85,86 especially as a `green’ alternative to the bromide co-catalyst in transition metal-catalyzed autoxidations.87 Catalytic oxidations in PINO-containing systems are thought to proceed through a series of H-atom abstraction steps. Despite the wide attention that NHPI/PINO has received, relatively few thermochemical data are available. Koppel and co-workers have determined pKa values for NHPI in water and DMSO,88 and the DMSO value can be used to estimate a pKa in MeCN.89 NHPI is much more acidic than dialkyl hydroxylamines, as would be expected for a phthalimide. There is little consensus between the published electrochemical studies of NHPI. In MeCN in the absence of base, a broad quasi-reversible oxidation is observed at +1.2 V vs. Cp2Fe+/0.90 Addition of pyridine bases caused a shift to much lower potentials, which was attributed to the oxidation of deprotonated NHPI (the NHPI?- couple).90?19293 However, this assignment is unlikely since the pyridine bases used (pKa = 12?6 in MeCN30) are not basic enough to deprotonate NHPI to any great extent (pKa = 23.5 in MeCN, see Table 3). Furthermore, the potentials vary with the strength of the added base, with stronger bases leading to lower potentials ?by roughly 59 mV per unit change in the pyridine pKa, as would be expected for a PCET reaction.90?19293 These data all suggest that the electrochemical process removes 1H+ and 1e- from NHPI, not simply an electron. We estimate, based on the reported electrochemical data extrapolated to pKa(NHPI) = 23.5 (59 mV per pKa), E?NHPI?-) = -0.1 V and BDFE = 84.8 kcal mol-1 in MeCN. Lucarini, Pedulli and co-workers have employed their EPR radical equilibration technique to determine bond strengths (BDEs) of NHPI, substituted NHPI derivatives and other related hydroxylamines.94,95 The BDE of NHPI was determined to be 88.1 kcal mol-1 in tBuOH solvent.94 Later, bond strengths for substituted NHPI derivatives were determined in CH3CN with respect to the parent NHPI, again using the EPR equilibration technique.95 The reference BDE used in that study was 88.1 kcal mol-1, the BDE of NHPI in tBuOH. However, based on the E?and pKa data for NHPI in MeCN, we conclude that the BDEMeCN of NHPI is 1.2 kcal mol-1 higher than the corresponding BDE in tBuOH. Thus, BDEs for substituted NHPI derivatives have been adjusted upward by 1.2 kcal mol-1 such that they are relative to the BDE of NHPI in MeCN determined here. One of the great advantages of the EPR equilibration technique is that the BDEs are usually very accurate with respect to each other, so that the uncertainty in the absolute BDE is essentially only dependent upon the accuracy of the reference compound BDE. 5.2 Phenols, Hydroquinones, Catechols and Ascorbate This section presents thermochemical data for hydroxylic compounds where the OH group is attached to an unsaturated (sp2) carbon. The redox chemistry of such compounds ?phenols, quinones, ascorbate, etc. ?has been the subject of intense interest for more than a half century. To give just a few examples, PCET reactions of these compounds are integral to biological energy production (e.g. quinone cycling in photosystems I and II and the bc1 complex; tyrosine Z in photosystem II),106?07108 biosynthesis (ribonucleotide reductases),109 antioxidant activity (tocopherols),110,111 and food.
