A R T I C L E S
Wu et al.
pseudo self-exchange reaction between PINO• and 4-Me-NHPI
in acetic acid has kH/kD ) 11.0 (kH ) 677 ( 24 M-1 s-1).18
Reactions of nitroxyl radicals with arylhydroxylamines, how-
ever, exhibit much smaller KIEs, with kH/kD ) 1.5-1.9 at
ambient temperatures (see Table 2 below).13,14
R2NO· + R2NOH f R2NOH + R2NO·
(1)
Hydrogen atom transfer (HAT) has been studied for over a
century6 and is the simplest chemical reaction that involves the
transfer of two particles, a proton and an electron. It can
therefore be considered to be a type of “proton-coupled electron
transfer” (PCET).7,8 HAT is important in combustion and
selective oxidation of alkanes, in the formation and reactivity
of protein-based radicals and reactive oxygen species (ROS),
and many other processes.9 For example, HAT from the double
allylic C-H bond in linoleic acid to the iron(III)-hydroxide
active site in lipoxygenases has received particular attention
because its H/D KIE of up to ∼80 indicates the importance of
tunneling.5a,10 HAT involving nitroxyl radicals and hydroxy-
lamines is important in much of the chemistry of nitroxyl
radicals,11 such as their role as catalysts and cocatalysts in
oxidation of organic substrates.12-15 N-hydroxyphthalimide
(NHPI) has been widely explored as a cocatalyst in Co/Mn-
catalyzed autoxidations of alkylaromatics, with the active species
being the corresponding phthalimide N-oxyl radical (PINO•).16
HAT reactions from benzylic C-H bonds to PINO• in acetic
acid have large deuterium KIEs (17-28 at 298 K)17 and the
We have focused on HAT self-exchange reactions, such as
the nitroxyl/hydroxylamine reactions examined here (eq 1), both
because of their relative simplicity and because of our finding
that the Marcus cross relation usually predicts HAT rate
constants within an order of magnitude or two.19-21 This
treatment is a new approach to understanding HAT rate
constants22 and has been found to hold for both organic reactions
and examples involving transition metal complexes. For in-
stance, the cross relation predicts and explains the inverse
temperature dependence of the rate of HAT from [FeII(H2bip)3]2+
to the stable nitroxyl radical TEMPO• (2,2,6,6-tetramethylpip-
eridine-1-oxyl radical).20 Of the various HAT reactions involv-
ing TEMPO•/TEMPO-H and transition metal complexes that
we have examined,19,20,23,24 the Marcus approach appears to
be least accurate for RuII(acac)2(py-imH) + TEMPO•
f
TEMPO-H and RuIII(acac)2(py-im), which has a large KIE.24b
These results prompted our examination of nitroxyl/hydroxy-
lamine self-exchange reactions; the kinetics of 4-oxo-TEMPO•
plus TEMPO-H were briefly mentioned in a preliminary
communication about the [FeII(H2bip)3]2+ reaction.20
(6) Kochi, J. K. Free Radicals; Wiley: New York, 1973.
(7) (a) Huynh, M. H. V.; Meyer, T. J. Chem. ReV. 2007, 107, 5004. (b)
Meyer, T. J.; Huynh, M. H. V. Inorg. Chem. 2003, 42, 8140. (c)
Hodgkiss, J. M.; Rosenthal, J.; Nocera, D. G. In Hydrogen-Transfer
Reactions; Hynes, J. T.; Klinman, J. P.; Limbach, H.-H.; Schowen,
R. L. Eds.; Wiley-VCH: Weinheim, 2007; Volume 2, pp 503-562.
(d) Stubbe, J.; Nocera, D. G.; Yee, C. S.; Chang, M. C. Y. Chem.
ReV. 2003, 103, 2167. (e) Cukier, R. I.; Nocera, D. G. Annu. ReV.
Phys. Chem. 1998, 49, 337. (f) Partenheimer, W. Catal. Today 1995,
23, 69.
Results
I. Equilibrium Constants. The reaction of 4-oxo-TEMPO•
and TEMPO-H in CD3CN forms an equilibrium mixture with
4-oxo-TEMPO-H and TEMPO• (eq 2), with all four species
observed by 1H NMR spectroscopy. All of the resonances have
been assigned for the paramagnetic and diamagnetic species,
(8) (a) Mayer, J. M. Annu. ReV. Phys. Chem. 2004, 55, 363. (b) Mayer,
J. M.; Rhile, I. J. Biochim. Biophys. Acta 2004, 1655, 51. (c) Mayer,
J. M.; Rhile, I. J.; Larsen, F. B.; Mader, E. A.; Markle, T. F.;
DiPasquale, A. G. Photosynth. Res. 2006, 87, 3. (d) Mayer, J. M.;
Mader, E. A.; Roth, J. P.; Bryant, J. R.; Matsuo, T.; Dehestani, A.;
Bales, B. C.; Watson, E. J.; Osako, T.; Valliant-Saunders, K.; Lam,
W.-H.; Hrovat, D. A.; Borden, W. T.; Davidson, E. R. J. Mol. Catal.
A: Chem. 2006, 251, 24.
(9) (a) Knapp, M. J.; Meyer, M.; Klinman, J. P. In Hydrogen-Transfer
Reactions; Hynes, J. T., Klinman, J. P., Limbach, H.-H., Schowen,
R. L., Eds.; Wiley-VCH: Weinheim, 2007; Volume 4, pp 1241-1284.
(b) Stubbe, J.; van der Donk, W. A. Chem. ReV. 1998, 98, 705. (c)
Halliwell, B.; Gutteridge, J. M. C. Free Radicals in Biology and
Medicine; Oxford University Press: Oxford, 1999.
even though 4-oxo-TEMPO-H has not been isolated. Equilib-
rium is rapidly established (see below) and integration of each
species using Lorentzian line fitting gave K2H,CD3CN ) 4.5 (
(10) (a) Knapp, M. J.; Rickert, K.; Klinman, J. P. J. Am. Chem. Soc. 2002,
124, 3865. (b) Lewis, E. R.; Johansen, E.; Holman, T. R. J. Am. Chem.
Soc. 1999, 121, 1395.
(11) Likhtenshtein, G.; Yamauchi, J.; Nakatsuji, S.; Smirnov, A. I.
Nitroxides: Applications in Chemistry, Biomedicine, and Materials
Science; Wiley-VCH: New York, 2008.
(18) Cai, Y.; Koshino, N.; Saha, B.; Espenson, J. H. J. Org. Chem. 2005,
70, 238.
(19) Roth, J. P.; Yoder, J. C.; Won, T.-J.; Mayer, J. M. Science 2001, 294,
2524.
(12) (a) Sheldon, R. A.; Arends, I. W. C. E. J. Mol. Catal. A: Chem. 2006,
251, 200. (b) Sheldon, R. A.; Arends, I. W. C. E. AdV. Synth. Catal.
2004, 346, 1051. (c) Sheldon, R. A.; Arends, I. W. C. E.; Brink, G.-
J. T.; Dijksman, A. Acc. Chem. Res. 2002, 35, 774. (d) For other
applications of nitroxyl radicals, see refs 5-20 in. Vasbinder, M. J.;
Bakac, A. Inorg. Chem. 2007, 46, 2322.
(20) Mader, E. A.; Larsen, A. S.; Mayer, J. M. J. Am. Chem. Soc. 2004,
126, 8066. H2bip ) 2,2′-bi-1,4,5,6-tetrahydropyrimidine.
(21) Warren, J. J.; Mayer, J. M. manuscript in preparation.
(22) HAT rate constants have traditionally been analyzed using a correlation
of Arrhenius activation energy Ea with enthalpic driving force ∆H
(the Bell-Evans-Polanyi relation), together with “polar effects” and
other influences. (a) Ingold, K. U. In Free Radicals; Kochi, J. K.,
Ed.; Wiley: New York, 1973; Volume 1, p 69ff. (b) Russel, G. A. In
Free Radicals; Kochi, J. K., Ed.; Wiley: New York, 1973; Volume 1,
pp 275-331. (c) O’Neal, H. E.; Benson, S. W. In Free Radicals;
Kochi, J. K., Ed.; Wiley: New York, 1973; Volume 2, p 302ff. (d)
Tedder, J. M. Angew. Chem., Int. Ed. Engl. 1982, 21, 401.
(23) (a) Mader, E. A.; Davidson, E. R.; Mayer, J. M. J. Am. Chem. Soc.
2007, 129, 5153. (b) Mader, E. A.; Manner, V. W.; Markle, T. F.;
Wu, A.; Franz, J. A.; Mayer, J. M. J. Am. Chem. Soc. 2009, 131,
4335–4345.
(13) (a) Kreilick, R. W.; Weissman, S. I. J. Am. Chem. Soc. 1966, 88,
2645. (b) Arick, M. R.; Weissman, S. I. J. Am. Chem. Soc. 1968, 90,
1654.
(14) (a) Malievskii, A. D.; Shapiro, A. B. Kinet. Catal. 2005, 46, 472. (b)
Malievskii, A. D.; Koroteev, S. V.; Shapiro, A. B. Kinet. Catal. 2005,
46, 812. (c) Malievskii, A. D.; Koroteev, S. V.; Gorbunova, N. V.;
Brin, E. F. Kinet. Catal. 1997, 38, 485.
(15) Dijksman, A.; Marino-Gonza´lez, A.; Mairata i Payeras, A.; Arends,
I. W. C. E.; Sheldon, R. A. J. Am. Chem. Soc. 2001, 123, 6826.
(16) Ishii, Y.; Sakaguchi, S.; Iwahama, T. AdV. Synth. Catal. 2001, 343,
393.
(17) (a) Koshino, N.; Saha, B.; Espenson, J. H. J. Org. Chem. 2003, 68,
9364. (b) Koshino, N.; Cai, Y.; Espenson, J. H. J. Phys. Chem. A.
2003, 107, 4262. (c) Amorati, R.; Lucarini, M.; Mugnaini, V.; Pedulli,
G. F. J. Org. Chem. 2003, 68, 1747.
(24) acac ) 2,4-pentanedionato; py-imH ) 2-(2′-pyridyl)imidazole. (a) Wu,
A.; Masland, J.; Swartz, R. D.; Kaminsky, W.; Mayer, J. M. Inorg.
Chem. 2007, 46, 11190. (b) Wu, A.; Mayer, J. M. J. Am. Chem. Soc.
2008, 130, 14745–14754.
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