Synthesis and reactivity of a (μ-1,1-hydroperoxo)(μ-hydroxo) dicopper(II) complex: Ligand hydroxylation by a bridging hydroperoxo ligand

Article abstract of DOI:10.1021/ja047437h

A new tetradentate tripodal ligand (L3) containing sterically bulky imidazolyl groups was synthesized, where L3 is tris(1-methyl-2-phenyl-4- imidazolylmethyl)amine. Reaction of a bis(μ-hydroxo)dicopper(II) complex, [Cu₂(L3)₂(OH)

Full text of DOI:10.1021/ja047437h

Published on Web 03/11/2005
Synthesis and Reactivity of a
(µ-1,1-Hydroperoxo)(µ-hydroxo)dicopper(II) Complex: Ligand
Hydroxylation by a Bridging Hydroperoxo Ligand
Kyosuke Itoh,† Hideki Hayashi,† Hideki Furutachi,† Takahiro Matsumoto,†
Shigenori Nagatomo,‡ Takehiko Tosha,‡ Shoichi Terada,† Shuhei Fujinami,†
Masatatsu Suzuki,*,† and Teizo Kitagawa‡
Contribution from the Department of Chemistry, Faculty of Science, Kanazawa UniVersity,
Kakuma-machi, Kanazawa 920-1192, Japan, and Center for IntegratiVe Bioscience,
Okazaki National Research Institutes, Myodaiji, Okazaki, 444-8585 Japan
Received May 1, 2004; Revised Manuscript Received January 25, 2005; E-mail: suzuki@cacheibm.s.kanazawa-u.ac.jp
Abstract: A new tetradentate tripodal ligand (L3) containing sterically bulky imidazolyl groups was
synthesized, where L3 is tris(1-methyl-2-phenyl-4-imidazolylmethyl)amine. Reaction of a bis(µ-hydroxo)-
dicopper(II) complex, [Cu2(L3)2(OH)2]2+ (1), with H2O2 in acetonitrile at -40 °C generated a (µ-1,1-
hydroperoxo)dicopper(II) complex [Cu2(L3)2(OOH)(OH)]2+ (2), which was characterized by various
physicochemical measurements including X-ray crystallography. The crystal structure of 2 revealed that
the complex cation has a Cu2(µ-1,1-OOH)(µ-OH) core and each copper has a square pyramidal structure
having an N3O2 donor set with a weak ligation of a tertiary amine nitrogen in the apex. Consequently, one
pendant arm of L3 in 2 is free from coordination, which produces a hydrophobic cavity around the Cu2(µ-
1,1-OOH)(µ-OH) core. The hydrophobic cavity is preserved by hydrogen bondings between the hydro-
peroxide and the imidazole nitrogen of an uncoordinated pendant arm in one side and the hydroxide and
the imidazole nitrogen of an uncoordinated pendant arm in the other side. The hydrophobic cavity significantly
suppresses the H/D and 16O/18O exchange reactions in 2 compared to that in 1 and stabilizes the Cu2(µ-
1,1-OOH)(µ-OH) core against decomposition. Decomposition of 2 in acetonitrile at 0 °C proceeded mainly
via disproportionation of the hydroperoxo ligand and reduction of 2 to [Cu(L3)]+ by hydroperoxo ligand. In
contrast, decomposition of a solid sample of 2 at 60 °C gave a complex having a hydroxylated ligand
[Cu2(L3)(L3-OH)(OH)2]2+ (2-(L3-OH)) as a main product, where L3-OH is an oxidized ligand in which one
of the methylene groups of the pendant arms is hydroxylated. ESI-TOF/MS measurement showed that
complex 2-(L3-OH) is stable in acetonitrile at -40 °C, whereas warming 2-(L3-OH) at room temperature
resulted in the N-dealkylation from L3-OH to give an N-dealkylated ligand, bis(1-methyl-2-phenyl-4-
imidazolylmethyl)amine (L2) in ∼80% yield based on 2, and 1-methyl-2-phenyl-4-formylimidazole (Phim-
CHO). Isotope labeling experiments confirmed that the oxygen atom in both L3-OH and Phim-CHO come
from OOH. This aliphatic hydroxylation performed by 2 is in marked contrast to the arene hydroxylation
reported for some (µ-1,1-hydroperoxo)dicopper(II) complexes with a xylyl linker.
Introduction
cently, the crystal structure of a superoxo-Cu(II)B species has
been reported for PHM.6 This superoxo-Cu(II) or peroxo-
Chemistry of mono- and dicopper complexes having active
oxygen species is of current interest for understanding the
reaction mechanisms of dioxygen activating copper proteins in
biological systems and utilizing metal complexes as oxidation
catalysts. Hydroperoxo-copper(II) species have been proposed
as one of the key intermediates for aliphatic hydroxylation
reactions performed by dopamine â-monooxygenase (DâM) and
peptidylglycine R-hydroxylating enzyme (PHM).1-7 Very re-
copper(II) species generated by the electron transfer from CuA
has been proposed as an active species for H-atom abstraction
from substrate, and the resulting hydroperoxo-copper(II) spe-
cies plays a role for OH transfer to substrate radical.6,7
A
dinuclear (µ-1,1-OOH)Cu(I)Cu(II) species has also been sug-
gested as one possible reaction intermediate for multicopper
oxidases such as laccase.8 Many mononuclear Cu(II)-OOR (R
) H, alkyl, or acyl) complexes have been developed, and they
have provided fundamental insights into the spectroscopic and
† Kanazawa University.
‡ Okazaki National Research Institutes.
(1) Klinman, J. P. Chem. ReV. 1996, 96, 2541-2561.
(2) Evans, J. P.; Ahn, K.; Klinman, J. P. J. Biol. Chem. 2003, 278, 49691-
49698.
(5) Bell, J.; Meskini, R. E.; D′Amato, D.; Mains, R. E.; Eipper, B. A.
Biochemistry 2003, 42, 7133-7142.
(6) Prigge, S. T.; Eipper, B. A.; Mains, R. E.; Amzel, L. M. Science 2004,
304, 864-867.
(3) Prigge, S. T.; Kolhekar, A. S.; Eipper, B. A.; Mains, R. E.; Amzel, L. M.
Science 1997, 278, 1300-1305.
(4) Francisco, W. A.; Blackburn, N. J.; Klinman, J. P. Biochemistry 2003, 42,
1813-1819.
(7) Chen, P.; Solomon, E. I. J. Am. Chem. Soc. 2004, 126, 4991-5000.
(8) Solomon, E. I.; Chen, P.; Metz, M.; Lee, S.-K.; Palmer, A. E. Angew. Chem.,
Int. Ed. 2001, 40, 4570-4590.
9
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J. AM. CHEM. SOC. 2005, 127, 5212-5223
10.1021/ja047437h CCC: $30.25 © 2005 American Chemical Society

Hydroperoxo Dicopper(II) Complex
A R T I C L E S
structural properties.9-21 In addition, oxidation reactions of
various substrates such as (R)2S, (R)2SO, PPh3, cyclohexene,
and cyclohexane have also been reported for some com-
plexes.11,13,17-21 It has been shown that sterically demanding
dinucleating ligands generate dinuclear µ-1,1-hydroperoxo or
acylperoxo-dicopper(II) complexes.22-29 (µ-1,1-Hydroperoxo)-
dicopper(II) species (Cu2-OOH) have been shown to be reactive
for oxo transfer toward nucleophilic substrates such as PPh3
and (R)2S.9,22,27 Furthermore, Cu2-OOH species have been
proposed as reactive intermediates for arene hydroxylation of
m-xylyl linkers of some dicopper complexes.23,28 Karlin and co-
workers suggested the formation of a Cu2-OOH species
generated by the reaction of a dinuclear copper(II) complex
[Cu2LH]4+ 30 with H2O2. The Cu2-OOH species is further
activated by an intermolecular mechanism that involves the
participation of an additional [Cu2LH]4+, leading to the hy-
droxylation of a xylyl linker.23 For a closely related dinucleating
ligand having benzimidazolyl groups instead of pyridyl groups,
Casella and co-workers have also reported the arene hydroxyl-
ation. However, unlike the [Cu2LH]4+ system, double hydroxyl-
ation of a xylyl linker occurs in their complex ([Cu2L]4+). For
this hydroxylation reaction, a Cu2-OOH species has also been
proposed as a reactive intermediate. The hydroxylation has been
suggested to proceed through a direct overlap between the arene
Scheme 1. Synthetic Procedures of Ligands and
(µ-1,1-Hydroperoxo)(µ-hydroxo)dicopper(II) Complexes and
Abbreviations of Complexes
(9) Karlin, K. D.; Zuberbu¨hler, A. D. In Bioinorganic Catalysis, 2nd ed.;
Reedijk, J., Bouwman, E., Eds.; Marcel Dekker: New York, 1999; pp 469-
534.
HOMO and the peroxide σ* component.28 However, the Cu2-
OOH intermediates proposed in the above hydroxylation reac-
tions are not fully characterized. To obtain further insight into
the reactivity of the Cu2-OOH species, it is necessary to
synthesize a reasonably stable complex, which can be character-
ized by various physicochemical measurements and is capable
of arene or aliphatic hydroxylation, although no aliphatic
hydroxylation by Cu(II)2-OOR species has been reported thus
far.
In this study, we synthesized a new sterically hindered
tetradentate tripodal ligand (L3) having a 2-phenylimidazolyl
group as shown in Scheme 1, in which phenyl group is
introduced as a reaction probe and/or a constituent forming a
hydrophobic cavity. The ligand L3 forms a dinuclear bis(µ-
hydroxo)dicopper(II) complex, [Cu2(L3)2(OH)2]2+ (1), which
reacts with H2O2 in acetonitrile at -40 °C to produce a (µ-1,1-
hydroperoxo)(µ-hydroxo)dicopper(II) complex [Cu2(L3)2(OOH)-
(OH)]2+ (2). Complex 2 was spectroscopically and structurally
characterized, and its reactivity was investigated. Decomposition
of 2 in solid state resulted in hydroxylation of the methylene
group of L3. This is the first example of aliphatic hydroxylation
of the supporting ligand by Cu2-OOH species.
(10) Wada, A.; Harata, M.; Hasegawa, K.; Jitsukawa, K.; Masuda, H.; Mukai,
M.; Kitagawa, T.; Einaga, H. Angew. Chem., Int. Ed. 1998, 37, 798-799.
(11) Chen, P.; Fujisawa, K.; Solomon, E. I. J. Am. Chem. Soc. 2000, 122,
10177-10193.
(12) Ohtsu, H.; Itoh, S.; Nagatomo, S.; Kitagawa, T.; Ogo, S.; Watanabe, Y.;
Fukuzumi, S. Chem. Commun. 2000, 1051-1052.
(13) Ohta, T.; Tachiyama, T.; Yoshizawa, K.; Yamabe, T.; Uchida, T.; Kitagawa,
T. Inorg. Chem. 2000, 39, 4358-4369.
(14) Ohtsu, H.; Itoh, S.; Nagatomo, S.; Kitagawa, T.; Ogo, S.; Watanabe, Y.;
Fukuzumi, S. Inorg. Chem. 2001, 40, 3200-3207.
(15) Kodera, M.; Kita, T.; Miura, I.; Nakayama, N.; Kawata, T.; Kano, K.; Hirota,
S. J. Am. Chem. Soc. 2001, 123, 7715-7716.
(16) Osako, T.; Nagatomo, S.; Tachi, Y.; Kitagawa, T.; Itoh, S. Angew. Chem.,
Int. Ed. 2002, 41, 4325-4328.
(17) Fujii, T.; Naito, A.; Yamaguchi, S.; Wada, A.; Funahashi, Y.; Jitsukawa,
K. Nagatomo, S.; Kitagawa, T.; Masuda, H. Chem. Commun. 2003, 2700-
2701.
(18) Yamaguchi, S.; Nagatomo, S.; Kitagawa, T.; Funahashi, Y.; Ozawa, T.;
Jitsukawa, K.; Masuda, H. Inorg. Chem. 2003, 42, 6968-6970.
(19) Kitajima, N.; Katayama, T.; Fujisawa, K.; Iwata, Y.; Morooka, Y. J. Am.
Chem. Soc. 1993, 115, 7872-7873.
(20) Kitajima, N.; Fujisawa, K.; Moro-oka, Y. Inorg. Chem. 1990, 29, 357-
358.
(21) Sanyal, I.; Ghosh, P.; Karlin, K. D. Inorg. Chem. 1995, 34, 3050-3056.
(22) Karlin, K. D.; Ghosh, P.; Cruse, R. W.; Farooq, A.; Gultneh, Y.; Jacobson,
R. R.; Blackburn, N. J.; Strange, R. W.; Zubieta, J. J. Am. Chem. Soc.
1988, 110, 6769-6780.
(23) Cruse, R. W.; Kaderli, S.; Meyer, C. J.; Zuberbu¨hler, A. D.; Karlin, K. D.
J. Am. Chem. Soc. 1988, 110, 5020-5024.
(24) Sorrell, T. N.; Vankai, V. A. Inorg. Chem. 1990, 29, 1687-1692.
(25) Mahroof-Tahir, M.; Murthy, N. N.; Karlin, K. D.; Blackburn, N. J.; Shaikh,
S. N.; Zubieta, J. Inorg. Chem. 1992, 31, 3001-3003.
(26) Root, D. E.; Mahroof-Tahir, M.; Karlin, K. D.; Solomon, E. I. Inorg. Chem.
1998, 37, 4838-4848.
Experimental Section
(27) Murthy, N. N.; Mahroof-Tahir, M.; Karlin, K. D. Inorg. Chem. 2001, 40,
628-635.
Materials. All reagents and solvents were obtained from commercial
sources and used without further purification except for ligand-
recovering experiments and spectroscopic measurements. H218O2 was
prepared by the literature methods.31 Acetonitrile and acetone were dried
over molecular sieves 5A and distilled under N2 atmosphere before
use.
(28) Battaini, G.; Monzani, E.; Perotti, A.; Para, C.; Casella, L.; Santagostini,
L.; Gullotti, M.; Dillinger, R.; Na¨ther, C.; Tuczek, F. J. Am. Chem. Soc.
2003, 125, 4185-4198.
(29) Ghosh, P.; Tyeklar, Z.; Karlin, K. D.; Jacobson, R. R.; Zubieta, J. J. Am.
Chem. Soc. 1987, 109, 6889-6891.
(30) Abbreviations of ligands, used: LH ) R,R′-bis{bis[2-(2-pyridyl)ethyl]-
amino}-m-xylene; L ) R,R′-bis{bis[2-(1′-methyl-2′-benzimidazolyl)ethyl]-
amino}-m-xylene; tpa ) tris(2-pyridylmethyl)amine; bppa ) bis(6-pival-
Syntheses of Ligands. 1-Methyl-2-phenyl-4-formylimidazole (Phim-
CHO). To a suspension of NaH (60% oil dispersion, 5.80 g, 145 mmol)
in 200 mL of dry DMF at 0 °C was added dropwise 2-phenyl-4-
amide-2-pyridylmethyl)(2-pyridylmethyl)amine; La
) N-{2-[(2-bis(2-
pyridylmethyl)aminoethyl)methylamino]ethyl}-2,2-dimethylpropion-
amide; bpba ) bis(2-pyridylmethyl)tert-butylamine; N3S ) 2-bis(6-methyl-
2-pyridylmethyl)amino-1-(phenylthio)ethane; HB(3-tBu-5-iPrpz)3 hydrotris-
(3-tert-butyl-5-isopropylpyrazolyl)borate anion; Py2SSPy2 ) bis{2-[N,N-
bis(2-pyridylethyl)-amino]-1,1-dimethylethyl}disulfide); TPPA ) tris[(6-
phenyl-2-pyridyl)methyl]amine.
(31) Sitter, A. J.; Terner J. J. Labelled Compd. Radiopharm. 1985, 22, 461-
465.
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A R T I C L E S
Itoh et al.
formylimidazole (25.0 g, 145 mmol) with stirring. After evolution of
H2 gas ceased, CH3I (24.7 g, 174 mmol) was slowly added to the
solution with stirring. The resulting solution was stirred for 3 h at 0 °C
and then overnight at room temperature to give a yellow suspension.
After removal of insoluble material by filtration, DMF was removed
under reduced pressure. The residue was suspended in a saturated NaCl
aqueous solution (50 mL) and extracted twice with ethyl acetate (100
mL). The combined extracts were dried over Na2SO4. The solvent was
evaporated under reduced pressure to give a yellow solid, which
contained ca. 30% of an undesirable isomer (1-methyl-2-phenyl-5-
formylimidazole), which was checked by NMR. The solid was finely
powdered and suspended into 200 mL of diethyl ether. The resulting
suspension was stirred overnight to dissolve the undesirable isomer.
Insoluble Phim-CHO was collected by filtration. Yield: 11.9 g (44%).
Anal. Calcd for C11H10N2O: C, 70.95; H, 5.41; N, 15.04%. Found: C,
filtration, chloroform was removed under reduced pressure to give a
pale brown powder, which was used for the subsequent reaction without
purification. Yield: 10.6 g (96%). Anal. Calcd for C22H24N5O0.5: C,
72.11; H, 6.60; N, 19.11%. Found: C, 72.07; H, 6.68; N, 18.89%. 1H
NMR (CDCl3, 400 MHz): δ (ppm) ) 3.67 (6H, s, 1-CH3 of imidazole),
3.86 (4H, s, 4-CH2 of imidazole), 6.90 (2H, s, 5-H of imidazole), 7.37
(2H, t, p-H of phenyl), 7.43 (4H, t, m-H of phenyl), 7.60 (4H, d, o-H
of phenyl). 13C NMR (CDCl3, 100.4 MHz): δ (ppm) ) 34.3 (1-CH3
of imidazole), 46.7 (4-CH2 of imidazole), 119.7 (5-C of imidazole),
128.4 (m-C of phenyl), 128.5 (p-C of phenyl), 128.7 (o-C of phenyl),
130.6 (4-C of imidazole), 140.2 (2-C of imidazole), 147.4 (1-C of
phenyl). GC/MS: tR 22.1 min, m/z (relative intensity): 186 (85), 172
(100), 157 (28). ESI-TOF/MS (CHCl3 solution containing a small
amount of formic acid) m/z: 358.2 (100, [M + 1]+).
Tris(1-methyl-2-phenyl-4-imidazolylmethyl)amine‚1.5H2O (L3).
A THF solution (100 mL) containing L2 (12.8 g, 35.0 mmol), Phim-
CHO (6.52 g, 35.0 mmol), and acetic acid (2.1 g, 35.0 mmol) was
stirred for 5 h. To the resulting solution was added NaBH(OAc)3 (11.2
g, 52.5 mmol), and the suspension was stirred overnight. Then the
solution was made basic by addition of an aqueous NaOH solution,
and THF was removed by reduced pressure. The residue was suspended
in a saturated aqueous NaCl solution (50 mL) and extracted in ethyl
acetate (100 mL) three times. The combined extracts were dried over
Na2SO4. After filtration, ethyl acetate was removed under reduced
pressure to give a white powder. Yield: 14.7 g (76%). Anal. Calcd for
C33H36N7O1.5: C, 71.46; H, 6.54; N, 17.68%. Found: C, 71.40; H, 6.48;
1
71.00; H, 5.39; N, 15.03%. H NMR (CDCl3, 400 MHz): δ (ppm) )
3.81 (3H, s, 1-CH3 of imidazole), 7.47-7.52 (3H, m, m- and p-H of
phenyl), 7.64-7.67 (2H, m, o-H of phenyl), 7.69 (1H, s, 5-H of
imidazole), 9.92 (1H, s, 4-CHO of imidazole). 13C NMR (CDCl3, 100.4
MHz): δ (ppm) ) 34.9 (1-CH3 of imidazole), 128.1 (p-C of phenyl),
128.4 (m-C of phenyl), 128.6 (o-C of phenyl), 129.0 (4-C of imidazole),
129.3 (5-C of imidazole), 140.7 (2-C of imidazole), 149.5 (1-C of
phenyl), 185.6 (4-CHO of imidazole). GC/MS: tR 7.8 min, m/z (relative
intensity): 186 (100), 157 (18), 118 (24). ESI-TOF/MS (CHCl3 solution
containing a small amount of formic acid) m/z: 373.1 (100, [2M +
1]+) 187.1 (35, [M + 1]+).
1
N, 17.21%. H NMR (CDCl3, 400 MHz): δ (ppm) ) 3.62 (9H, s,
Bis(1-methyl-2-phenyl-4-imidazolylmethyl)benzylamine‚H2O (L1).
To a THF solution (100 mL) containing 1-methyl-2-phenyl-4-
formylimidazole (Phim-CHO) (10.24 g, 55.0 mmol) and benzylamine
(5.89 g, 55.0 mmol) was added NaBH(OAc)3 (34.97 g, 165 mmol).
After the suspension was stirred overnight, acetic acid (3.30 g, 55.0
mmol) and another Phim-CHO (10.24 g, 55.0 mmol) was added to the
solution. After being stirred for 6 h, the solution was made basic by
addition of an aqueous NaOH solution. THF was removed under
reduced pressure. To the residue was added a saturated NaCl aqueous
solution (50 mL), and an oily layer separated was extracted twice with
chloroform (100 mL). The combined chloroform extracts were dried
over Na2SO4. After filtration, chloroform was evaporated under reduced
pressure to give a brown oil that was dissolved in an ethyl acetate/
diethyl ether mixture. The solution was allowed to stand overnight to
give a white powder. Yield: 19.2 g (75%). Anal. Calcd for
C29H31N5O: C, 74.81; H, 6.71; N, 15.04%. Found: C, 74.81; H, 6.68;
1-CH3 of imidazole), 3.81 (6H, s, 4-CH2 of imidazole), 7.10 (3H, s,
5-H of imidazole), 7.32 (3H, t, p-H of phenyl), 7.39 (6H, t, m-H of
phenyl), 7.61 (6H, d, o-H of phenyl). 13C NMR (CDCl3, 100.4 MHz):
δ (ppm) ) 34.4 (1-CH3 of imidazole), 51.0 (4-CH2 of imidazole), 121.5
(5-C of imidazole), 128.4 (p-C of phenyl), 128.4 (m-C of phenyl), 128.6
(o-C of phenyl), 130.7 (4-C of imidazole), 138.8 (2-C of imidazole),
146.9 (1-C of phenyl). ESI-TOF/MS (CHCl3 solution containing a small
amount of formic acid) m/z: 528.3 (100, [M + 1]+).
Syntheses of Complexes. Copper(I) and copper(II) complexes were
prepared under N2 atmosphere using Schlenk techniques. Caution:
Perchlorate salts are potentially explosiVe and should be handled with
care.
[Cu2(L3)2(OH)2](CF3SO3)2‚(CH3)2CO‚H2O (1-CF3SO3). To an
acetone solution (20 mL) containing L3 (2.27 g, 4.1 mmol) and
Cu(CF3SO3)2 (1.44 g, 4.0 mmol) was added Et3N (1.67 mL, 12.0 mmol)
with stirring to give a blue powder, which was filtered, washed with
acetone and diethyl ether, and dried in vacuo. Yield: 2.6 g (66%).
Anal. Calcd for C71H76N14Cu2O10F6S2: C, 53.61; H, 4.82; N, 12.33%.
1
N, 15.01%. H NMR (CDCl3, 400 MHz): δ (ppm) ) 3.63 (6H, s,
1-CH3 of imidazole), 3.75 (4H, s, 4-CH2 of imidazole), 3.77 (2H, s,
CH2 of benzyl), 6.96 (2H, s, 5-H of imidazole), 7.20 (1H, t, p-H of
benzyl), 7.30 (2H, t, m-H of benzyl), 7.35-7.40 (6H, m, m- and p-H
of phenyl), 7.45 (2H, d, o-H of benzyl), 7.59 (4H, d, o-H of phenyl).
13C NMR (CDCl3, 100.4 MHz): δ (ppm) ) 34.1 (1-CH3 of imidazole),
51.0 (4-CH2 of imidazole), 57.6 (CH2 of benzyl), 120.6 (5-C of
imidazole), 126.4 (p-C of benzyl), 127.9 (m-C of benzyl), 128.2 (m-
and p-C of phenyl), 128.4 (o-C of phenyl), 128.7 (o-C of benzyl), 130.4
(4-C of imidazole), 138.8 (1-C of benzyl), 139.7 (2-C of imidazole),
146.7 (1-C of phenyl). GC/MS: tR 25.3 min, m/z (relative intensity):
276 (100), 171 (85), 157 (26). ESI-TOF/MS (CHCl3 solution containing
a small amount of formic acid) m/z: 448.2 (100, [M + 1]+).
Bis(1-methyl-2-phenyl-4-imidazolylmethyl)amine‚0.5H2O (L2).
Removal of a benzyl group from L1 was achieved by hydrogenation
using 5% Pd-C and H2. To a methanol solution (100 mL) containing
L1 (13.97 g, 30.0 mmol) and concentrated HCl (10 mL) was added
5% Pd-C (ca. 2 g). H2 gas was introduced into the system, and the
resulting suspension was vigorously stirred for 7 h at 40 °C. After
removal of Pd-C by filtration, the solution was made basic by addition
of an aqueous NaOH solution. The solvent was evaporated under
reduced pressure. The residue was suspended in a saturated aqueous
NaCl solution (50 mL) and extracted by CHCl3 (100 mL) three times.
The combined chloroform extracts were dried over Na2SO4. After
Found: C, 53.57; H, 4.79; N, 12.30%. UV-vis (λmax/nm (ꢀ/M-1 cm-1
)
in acetonitrile at room temperature): 590 (80), 690 (sh). FTIR (KBr,
cm-1): 1585 (CdC, aromatic), 1479 (imidazole), 1407 (imidazole),
1224 (CF3SO3), 1155 (CF3SO3), 1031 (CF3SO3), 638 (CF3SO3). ESI-
TOF/MS (acetonitrile solution at room temperature) m/z: 607.2 [M]2+
.
It was difficult to grow single crystals suitable for X-ray crystallography
by recrystallization from acetone. However, recrystallization from
acetonitrile gave single crystals ([Cu2(L3)2(OH)2](CF3SO3)2‚CH3CN (1-
CF3SO3‚CH3CN)) suitable for X-ray crystallography.
[Cu2(L3)2(OOH)(OH)](CF3SO3)2 (2-CF3SO3). To an acetonitrile
solution (20 mL) containing 1-CF3SO3 (148 mg, 0.093 mmol) at -40
°C was added 30% H2O2 (40 equiv, 372 µL) with stirring to give a
green solution. Diethyl ether was added to the resulting solution to
give olive-green powder, which was collected by filtration and washed
with diethyl ether and dried in vacuo at -40 °C. Although it was
attempted to prepare single crystals suitable for X-ray crystallography
by recrystallization from various solvents, all the attempts were in vain.
However, BPh4 salt prepared by metathesis gave single crystals (vide
infra). UV-vis (λmax/nm (ꢀ/M-1 cm-1) in acetonitrile at -40 °C): 356
(6300) and 580 (240). ESI-TOF/MS (acetonitrile solution at -40 °C)
m/z: 615.2 [M]2+
.
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Hydroperoxo Dicopper(II) Complex
A R T I C L E S
[Cu2(L3)2(OOH)(OH)](BPh4)2‚5(CH3)2CO‚3H2O (2-BPh4). Com-
plex 2-CF3SO3 (ca. 100 mg) was dissolved in a small amount of acetone
at -40 °C, to which was added NaBPh4 (170 mg). The resulting solution
was allowed to stand for a few days at -80 °C to give green crystals
suitable for X-ray crystallography.
were calibrated with indene, and the accuracy of the peak positions of
the Raman bands was (1 cm-1
.
1H NMR spectra were measured with JEOL JNM-LM400. Tetra-
methylsilane was used as an internal standard. Infrared spectra were
obtained by the KBr disk method with a HORIBA FT-200 spectro-
photometer. GC/MS analysis was performed on a Shimadzu GCMS-
QP5050A GC/MS equipped with a fused silica capillary column
(Methyl silicone, 0.32 mm diameter × 25 m, QUADREX corporation).
ESI-TOF/MS spectra were measured with a Micromass LCT spec-
trometer.
[Cu2(L3)2(18O18OH)(OH)](CF3SO3)2 (2-(18O18OH)). This was syn-
thesized by the same method as 2-CF3SO3 except H218O2 was used.
ESI-TOF/MS (acetonitrile solution at -40 °C) m/z: 617.2 [M]2+
.
[Cu2(L1)2(OH)2](CF3SO3)2‚(CH3)2CO‚H2O (3-CF3SO3). To an
acetone solution (10 mL) containing L1 (1.91 g, 4.1 mmol) was added
Cu(CF3SO3)2 (1.44 g, 4.0 mmol). To this solution was added Et3N (1.11
mL, 6.0 mmol), and the resulting solution was stirred for 1 h to afford
pale blue powder, which was collected by filtration, washed with ethanol
and ether, and then dried in vacuo. Yield: 2.4 g (83%). Although it
was attempted to obtain single crystals suitable for X-ray crystallography
by recrystallization from various solvent, all the attempts were in vain.
However, single crystals were obtained as ClO4 salt (vide infra). Anal.
Calcd for C63H68N10Cu2O10F6S2: C, 52.90; H, 4.79; N, 9.79%. Found:
C, 52.80; H, 4.65; N, 9.63%. UV-vis (λmax/nm (ꢀ/M-1 cm-1) in CH3CN
at room temperature): 333 (4000), 680 (110). FTIR (KBr, cm-1): 1714
(acetone CdO), 1589 (CdC, aromatic), 1481 (imidazole), 1409
(imidazole), 1224 (CF3SO3), 1149 (CF3SO3), 1031 (CF3SO3), 636
Ligand Recovery Experiments after Thermal Decomposition of
2-CF3SO3. A solid sample of 2-CF3SO3 (ca. 100 mg) was warmed at
60 °C for 1 h under N2. The resulting solid was dissolved into 100 mL
of acetonitrile in a volumetric flask. A portion (10 mL) was taken up,
and the amount of the complex used was determined by spectro-
photometric determination of copper (vide infra). Identifications and
quantitative analyses of the ligand L3, an N-dealkylated ligand (bis-
(1-methyl-2-phenyl-4-imidazolylmethyl)amine (L2)), and 1-methyl-2-
phenyl-4-formylimidazole (Phim-CHO) were as follows. The remaining
solution was evaporated to dryness under reduced pressure. Demeta-
lation was carried out by the reaction with concentrated aqueous NH4OH
(30 mL), and then ligand and its reaction products were extracted into
chloroform (3 × 20 mL). The reaction products were identified by 1H
(CF3SO3). ESI-TOF/MS (in CH3CN) m/z: 527.2 [M]2+
.
[Cu2(L1)2(OH)2](ClO4)2‚2C2H5CN (3-ClO4‚C2H5CN). This was
prepared by the same method as 3-CF3SO3 except Cu(ClO4)2‚6H2O
was used. Single crystals suitable for X-ray analysis were obtained by
recrystallization from propionitrile.
1
NMR and ESI-TOF/MS, and their amounts were determined by H
NMR by addition of 2,6-dimethyl-p-benzoquinone as an internal
standard. Total amounts of L3 and L2 recovered were more than 91%
for three experiments. Yield of the dealkylated ligand L2 was 79%
based on a dimer for three experiments. Phim-CHO was also recovered,
which was identified by GC/MS and ESI-TOF/MS. Recovery of Phim-
CHO obtained from an 18O-labeled 2-CF3SO3 revealed the presence of
18O. The ESI-TOF/MS spectrum of an acetonitrile solution containing
a decomposed sample at room temperature revealed that the oxygen
atom of Phim-CHO is 18O (almost quantitative), whereas 18O/16O
exchange occurred almost completely after 1 day. It was also found
that ∼60% of 18O was exchanged by 16O during the ligand recovery
experiments mentioned above.
[Cu(L3)]ClO4‚2H2O (5-ClO4). A methanol solution (5 mL) of L3
(0.58 g, 1.05 mmol) was added to a methanol solution (5 mL) of
[Cu(CH3CN)4]ClO4 (0.33 g, 1.0 mmol) to produce a white powder,
which was collected by filtration, washed with ethanol and diethyl ether,
and then dried in vacuo. Yield: 0.46 g (62%). Anal. Calcd for C33H37N7-
CuO6Cl: C, 54.54; H, 5.13; N, 13.49%. Found: C, 54.78; H, 5.15; N,
1
13.10%. H NMR (acetone-d6, 400 MHz): δ (ppm) ) 3.62 (9H, s,
1-CH3 of imidazol), 3.81 (6H, s, 4-CH2 of imidazol), 7.10 (3H, s, 5-H
of imidazol), 7.32 (3H, t, p-H of phenyl), 7.39 (6H, t, m-H of phenyl),
7.61 (6H, d, o-H of phenyl). FTIR (KBr, cm-1): 1579 (CdC, aromatic),
1477 (imidazole), 1405 (imidazole), 1093 (ClO4), 626 (ClO4). ESI-
TOF/MS (acetonitrile solution at room temperature) m/z: 590.2 [M]+.
[Cu(L2)2](ClO4)2‚(CH3)2CO (6-ClO4). Cu(ClO4)2‚6H2O (0.19 g, 0.5
mmol) was dissolved into an acetone solution (5 mL) containing L2
(0.19 g, 0.52 mmol). The resulting blue solution was allowed to stand
under diethyl ether vapor to give blue crystals, which were collected
by filtration, washed with ethanol and diethyl ether, and dried in vacuo.
Yield: 0.25 g (48%). Anal. Calcd for C47H52N10CuO9Cl2: C, 54.52;
H, 5.06; N, 13.53%. Found: C, 54.40; H, 5.17; N, 13.49%. UV-vis
(λmax/nm (ꢀ/M-1 cm-1) in CH3CN at room temperature): 685 (150),
∼850 (120). FTIR (KBr, cm-1): 1704 (acetone CdO), 1594 (CdC,
aromatic), 1477 (imidazole), 1403 (imidazole), 1095 (ClO4), 622 (ClO4).
Thermal decomposition in acetonitrile was carried out as follows.
Typically 2-CF3SO3 (ca. 100 mg) was dissolved in 50 mL of acetonitrile
in a Schlenk tube at 0 °C under N2, and the solution was allowed to
stand for 3 h. After decomposition of the complex, the volume of the
resulting solution was adjusted to 100 mL in a volumetric flask by
addition of acetonitrile. The following procedures are the same as those
described above. Yield of the ligand L3 was more than 92% for three
experiments. A trace amount of a dealkylated ligand (L2) was identified
by GC/MS and ESI-TOF/MS.
Determination of the Concentration of Copper. A typical proce-
dure is as follows. An acetonitrile solution (10 mL) obtained by the
above ligand recovery experiment was diluted by 40 mL of acetonitrile
and ca. 40 mL of H2O, to which was added acetic acid to adjust the
pH to ca. 5. To the resulting solution was added ca. 200 mg of ascorbic
acid and ca. 300 mg of 2,9-dimethyl-1,10-phenanthroline to generate
[Cu(Me2-phen)2]+. The volume of the solution was adjusted to 100
mL by addition of H2O in a volumetric flask. The copper concentration
was determined spectrophotometrically by the absorbance at 455 nm
(the molar extinction coefficient of [Cu(Me2-phen)2]+ under the
conditions is 7800 M-1 cm-1).
ESI-TOF/MS (in CH3CN) m/z: 388.6 [M]2+
.
Physical Measurements. The electronic spectra were measured with
an Otsuka Electronics photodiode array spectrometer MCPD-2000 with
an Otsuka Electronics optical fiber attachment or a Shimadzu diode
array spectrometer Multispec-1500. The temperatures were controlled
with an EYELA low-temperature pair stirrer PSL-1800 for the former
instrument and with a Unisoku thermostated cell holder for the latter
one. The reflectance spectra were obtained with an Otsuka Electronics
photodiode array spectrometer MCPD-2000 with an Otsuka Electronics
optical fiber attachment.
Resonance Raman spectra were obtained with a liquid nitrogen
cooled CCD detector (model LN/CCD-1340 × 400PB, Princeton
Instruments) attached to a 1-m single polychrometor (model MC-
100DG, Ritsu Oyo Kogaku). The 406.7-nm line of a Kr+ laser (model
2060 Spectra Physics) was used as an exciting source. The laser powers
used were ∼10 mW at the sample points. All measurements were
carried out with a spinning cell (1000 rpm) at ∼-40 °C. Raman shifts
Determination of the Amount of Cu(I) Ion in Decomposed
Solution. An acetonitrile solution (20 mL) containing 2-CF3SO3 (ca. 1
mM) was allowed to stand at 0 °C under N2. After 3 h, a portion (5
mL) was taken up, to which was added ca. 20 mL of acetonitrile/water
(1:1) and ca. 50 mg of 2,9-dimethyl-1,10-phenanthroline to generate
[Cu(Me2-phen)2]+. To the resulting solution was added acetic acid to
adjust the pH to ca. 5, and the volume of the solution was adjusted to
50 mL by addition of acetonitrile/water (1:1) in a volumetric flask.
The concentration of copper(I) ion was determined spectrophotometri-
9
J. AM. CHEM. SOC. VOL. 127, NO. 14, 2005 5215

A R T I C L E S
Itoh et al.
Table 1. Crystallographic Data for [Cu2(L3)2(OH)2](CF3SO3)2‚CH3CN (1-CF3SO3‚CH3CN), [Cu2(L3)2(OOH)(OH)](BPh4)2‚5(CH3)2CO‚3H2O
(2-BPh4), and [Cu2(L1)2(OH)2](ClO4)2‚2C2H5CN (3-ClO4‚C2H5CN)
1-CF3SO3
‚
CH3CN
2-BPh4
3-ClO4‚C2H5CN
formula
temp, °C
mol wt
cryst syst
space group
a, Å
b, Å
c, Å
R, deg
â, deg
γ, deg
V, Å3
C70H71O8N15Cu2S2F6
-150
C
-150
2215.36
triclinic
P1h
14.023(5)
15.810(6)
17.194(7)
104.038(7)
101.808(7)
105.329(8)
3416(2)
1
129H144O11N14Cu2B2
C64H70O10N12Cu2Cl2
-150
1365.33
triclinic
P1h
11.163(2)
12.857(2)
13.130(3)
71.78(3)
84.60(3)
64.95(3)
1619.9(7)
1
1555.63
monoclinic
C2/c
23.989(6)
16.678(4)
18.853(5)
105.033(6)
7284(2)
4
Z
2θmax
55.0
3216.00
1.418
55.0
1172.00
1.077
60.7
710.00
1.399
F(000)
D
calcd, g/cm3
abs. coeff, cm-1
No. of reflns colld
No. of indep reflns
No. of refined params
GOF indication
largest peak/hole, e Å-3
Ra
7.21
3.68
23656
8116 (I g 3.00σ(I))
717
1.89
1.19/-0.62
0.088
8.06
18710
6698(I g 3.00σ(I))
406
1.47
1.36/-0.69
0.046
27372
5538 (I g 3.00σ(I))
463
1.70
1.14/-0.64
0.064
b
Rw
0.095
0.133
0.076
2
2
a R ) ∑[|Fo| - |Fc|]/∑|Fo| (I g 3.0σ(I)). b Rw) [∑w(|Fo| - |Fc|)2/∑w|Fo| ]1/2; w ) 1/[σ2(Fo) + p2|Fo| /4] (p ) 0.081 for 1-CF3SO3‚CH3CN, p ) 0.097
for 2-BPh4, and p ) 0.085 for 3-ClO4‚C2H5CN.
cally by the absorbance at 455 nm as described above. Yield of
copper(I) ion was ca. 20% for two experiments.
a full-matrix least-squares method by using the teXsan34 crystallographic
software package (Molecular Structure Corporation). Non-hydrogen
atoms of complex cations and counteranions were refined with
anisotropic displacement parameters. Some non-hydrogen atoms of
solvent molecules were refined with isotropic displacement parameters.
Hydrogen atoms were positioned at calculated positions (0.95 Å). They
were included, but not refined, in the final least-squares cycles.
Crystallographic data are summarized in Table 1. ORTEP views (50%
probability) of the complex cations of 1-CF3SO3‚CH3CN, 2-BPh4, and
3-ClO4‚C2H5CN with full numbering scheme of atoms are shown in
Figure S2, S3, and S4, respectively. Tables of final atomic coordinates,
thermal parameters, and full bond distances and angles are given in
the CIF Supporting Information file.
[Cu2(L3)2(OH)2](CF3SO3)2‚CH3CN (1-CF3SO3‚CH3CN). A single
crystal with approximate dimensions of 0.35 × 0.25 × 0.10 mm3 was
mounted on the tip of a glass rod. The asymmetric unit consists of a
half of a [Cu2(OH)2(L3)2]2+ cation, a trifluoromethanesulfonate anion,
and an acetonitrile molecule with half occupancy. Hydrogen atoms of
acetonitrile were not included in the refinement. The maximum peak
on a final difference Fourier map (1.14 e Å-3) was observed near the
acetonitrile molecule.
[Cu2(L3)2(OOH)(OH)](BPh4)2‚5(CH3)2CO‚3H2O (2-BPh4). A single
crystal with dimensions of 0.25 × 0.18 × 0.05 mm3 was picked up
from a solution by a nylon loop (Hampton Research Co.) on a handmade
cold copper plate mounted inside a liquid N2 Dewar vessel at ca. -80
°C and dipped quickly in liquid nitrogen. Then the crystal was mounted
on a goniometer head in a N2 cryostream. Although the complex cation
has no center of symmetry, analysis revealed the presence of a center
of symmetry due to disorder between the µ-1,1-OOH and µ-OH groups.
The structure was solved by a model in which the bridging OOH ligands
are equally disordered to give a chemically reasonable structure; the
occupancies of O(1) and O(2) were estimated to be 1.0 and 0.5,
respectively. There are one fully occupied and three half-occupied
acetone molecules, and three half-occupied water molecules. The half-
occupied acetone and water molecules were refined isotropically. The
coordinates of the water molecules were fixed at the final least-squares
Dioxygen Evolution Analysis upon Decomposition. An apparatus
used for the experiment is shown in Figure S1a. Acetonitrile (40 mL)
in a vessel (ca. 62 mL) at 0 °C was equilibrated with dry air. After
equilibration, the reading of the oxygen sensor was 18.0 ( 0.1%. The
amount of dioxygen evolved upon decomposition of 2 was calibrated
by injecting the appropriate amounts of O2 gas (0.2, 0.5, 1.0, 1.3, and
1.5 mL) by a pressure-lock syringe through septum, and the oxygen
concentrations were measured after 10 min. A fairly good calibration
line was obtained as seen in Figure S1b. A typical experiment was as
follows. Complex 2 (ca. 60 mg) was quickly placed on a sample holder
from the sample inlet by opening the septum with gentle flowing of
dry air. After the system was closed, a solid sample was dropped into
acetonitrile by pushing the sample plate by a needle. After 10 min,
oxygen concentration was measured. Yield: ca. 40% based on a dimer
for two experiments.
X-ray Crystallography. General Procedures. Data collections were
carried out on a Rigaku/MSC mercury diffractometer with graphite
monochromated Mo KR radiation (λ ) 0.71070 Å). The data were
collected at -150 ( 1 °C to a maximum 2θ value of 55.0° for
1-CF3SO3‚CH3CN and 2-BPh4, and to a maximum 2θ value of 60.7°
for 3-ClO4‚C2H5CN. A total of 720 oscillation images were collected.
The first sweep of data was done using ω scans from -80.0 to 100.0°
in 0.50° step, at ø ) 45.0° and φ ) 0.0°. The second sweep of data
was made using ω scans from -80.0 to 100.0° in 0.50° step, at ø )
45.0° and φ ) 90.0°. Crystal-to-detector distances were 35 mm, and
detector swing angles were 10°. Exposure rates were 24.0, 26.0, and
40.0 s/deg for 1-CF3SO3‚CH3CN, 2-BPh4, and 3-ClO4‚C2H5CN,
respectively. The data were corrected for Lorentz and polarization
effects. Empirical absorption corrections were applied.
The structures were solved by a direct method (SIR92)32 and
expanded using a Fourier technique.33 The structures were refined by
(32) SIR-92: Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A.; Burla,
M. C.; Polidori, G.; Camalli, M. J. Appl. Crystallogr. 1994, 27, 435.
(33) Beurskens, P. T.; Admiraal, G.; Beurskens, G.; Bosman, W. P.; de Gelder,
R.; Israel, R.; Smits, J. M. M. The DIRDIF-94 Program System; Technical
Report of the Crystallography Laboratory; University of Nijmegen:
Nijmegen, The Netherlands, 1994.
(34) teXsan: Crystal Structure Analysis Package; Molecular Structure Corpora-
tion: The Woodlands, TX, 1985 and 1992.
9
5216 J. AM. CHEM. SOC. VOL. 127, NO. 14, 2005

Hydroperoxo Dicopper(II) Complex
A R T I C L E S
Figure 1. ORTEP views (50% probability) of the complex cations of (A) [Cu2(L3)2(OH)2](CF3SO3)2‚CH3CN (1-CF3SO3‚CH3CN), (B) [Cu2(L3)2(OOH)-
(OH)](BPh4)2‚5(CH3)2CO‚3H2O (2-BPh4), and (C) [Cu2(L1)2(OH)2](ClO4)2‚2C2H5CN (3-ClO4‚C2H5CN). Hydrogen atoms are omitted for clarity.
Table 2. Selected Bond Distances and Angles of
cycles. Hydrogen atoms of solvent molecules were not included in the
refinement. The equivalent temperature factors (Ueq’s) of some remote
[Cu2(L3)2(OH)2](CF3SO3)2‚CH3CN (1-CF3SO3‚CH3CN),
[Cu2(L3)2(OOH)(OH)](BPh4)2‚5(CH3)2CO‚3H2O (2-BPh4), and
carbon atoms are large due to the disorder problem, whereas the ratio
Ueq(max)/Ueq(min) of nonsolvent carbons was in the allowable range
(3.4). The maximum peak on a final difference Fourier map (1.19 e
Å-3) was observed near a water molecule.
[Cu2(L1)2(OH)2](ClO4)2‚2C2H5CN (3-ClO4‚C2H5CN). A single
crystal with approximate dimensions of 0.25 × 0.20 × 0.10 mm3 was
picked up from the reaction solution and mounted on top of a glass
fiber. An asymmetric unit consists of a half of a complex cation, a
perchlorate anion, and a propionitrile molecule. The maximum peak
on a final difference Fourier map (1.39 e Å-3) was observed near a
perchlorate anion. Although completeness of the data for 2θmax e 60.7°
is lower (0.82), that for 2θmax e 55.93° is 0.96 and the high refln/
param ratio (16.5) is enough for the sufficient structure quality.
[Cu2(L1)2(OH)2](ClO4)2‚2C2H5CN (3-ClO4‚C2H5CN)
1-CF3SO3
‚
CH3CN
2-BPh4
3-ClO4‚C2H5CN
Bond Distances (Å)
Cu1-N1
Cu1-N2
Cu1-N4
Cu1-O1
Cu1-O1*
Cu1‚‚‚Cu2
O1‚‚‚O2
2.450(4)
1.999(4)
2.017(4)
1.934(3)
1.916(3)
2.927(1)
2.461(5)
2.411(2)
2.012(2)
1.972(2)
1.913(2)
1.930(2)
3.013(2)
1.996(5)
1.997(5))
1.942(4)
1.919(4)
3.072(2)
1.430(9)
Bond Angles (deg)
Cu1-O1-Cu1*
O1-Cu1-O1*
O1-Cu1-N1
Cu1-O1-O2
Cu1*-O1-O2
98.9(1)
81.1(1)
97.7(1)
105.4(2)
103.24(8)
76.76(8)
101.25(7)
74.6(2)
99.4(2)
122.3(4)
131.0(4)
Results and Discussion
Synthesis of Hydroperoxo-Dicopper(II) Complexes
[Cu2(L3)2(OOH)(OH)]2+ (2) and [Cu2(L1)2(OOH)(OH)]2+
Structural Characterization of Complexes 1, 2, and 3.
Figure 1 shows the structures of the complex cations of
1-CF3SO3‚CH3CN (A), 2-BPh4 (B), and 3-ClO4‚C2H5CN (C),
and their selected bond distances and angles are given in Table
2. Complex cations of 1-CF3SO3‚CH3CN and 3-ClO4‚C2H5CN
have a bis(µ-hydroxo)dicopper(II) core, and that of 2-BPh4 has
a (µ-hydroxo)(µ-1,1-hydroperoxo)dicopper(II) core. Unfortu-
nately, the bridging OOH and OH groups in 2-BPh4 are
disordered with each other with 0.5 occupancy for the terminal
oxygen of OOH. Although there is a possibility that the crystals
consist of a mixture of 1 and bis(µ-1,1-hydroperoxo)dicopper(II)
species [Cu2(L3)2(OOH)2]2+, ESI-TOF/MS measurement de-
finitively confirmed the formation of 2 (see ESI-TOF/MS spectra
in Figure S5). Each copper in these three complexes has a square
pyramidal structure having an N3O2 donor set with a weak
ligation of a tertiary amine nitrogen in the apex. Consequently,
one pendant arm of L3 in 1-CF3SO3‚CH3CN and 2-BPh4 is free
from coordination, which produces a hydrophobic cavity around
dicopper(II) core (vide infra). The Cu2(µ-OH)2 and Cu2(µ-1,1-
OOH)(µ-OH) core dimensions of these three complexes (Cu-O
) 1.913-1.942 Å and Cu‚‚‚Cu ) 2.927-3.072 Å) are quite
similar to each other and typical of those of the bis(µ-hydroxo)-
dicopper(II) complexes.
(4). Reaction of
a bis(µ-hydroxo)dicopper(II) complex
([Cu2(L3)2(OH)2]2+ (1)) with H2O2 in acetonitrile at -40 °C
generated a green complex [Cu2(L3)2(OOH)(OH)]2+ (2). The
electronic spectral measurement indicated that more than 5 equiv
of H2O2 is needed for the complete formation of 2. ESI-TOF/
MS spectrum definitively confirmed the formation of 2 (m/z )
615.2, I ) 100% for {Cu2(L3)2(OOH)(OH)}2+ and m/z ) 617.2
for {Cu2(L3)2(18O18OH)(OH)}2+) (see Figure S5). It was also
attempted to synthesize a bis(µ-1,1-hydroperoxo)dicopper(II)
species or a mononuclear hydroperoxo-copper(II) species by
treatment of a large excess of H2O2, whereas no such species
was detected by ESI-TOF/MS. Thus, the present sterically
hindered tetradentate tripodal ligand L3 selectively generates a
(µ-1,1-hydroperoxo)(µ-hydroxo)dicopper(II) complex.
We have also tried to synthesize a (µ-1,1-hydroperoxo)(µ-
hydroxo)dicopper(II) complex having a closely related tridentate
ligand (L1) consisting of two 2-phenylimidazolyl groups
(Scheme 1). Reaction of an acetonitrile solution of a bis(µ-
hydroxo)dicopper(II) complex, [Cu2(L1)2(OH)2]2+ (3) (typically
∼0.1 mM), with 10 equiv of 30% H2O2 at -40 °C generated a
dark blue species. The electronic and Raman measurements
suggested the formation of a hydroperoxo-copper(II) complex
(vide infra). In addition, ESI-TOF/MS measurement showed a
signal at m/z ) 535.2 (I ) 22%) for {Cu2(L1)2(OOH)(OH)}2+
Although detailed discussion about metric parameters of
2-BPh4 may not be warranted due to the disordered problem,
(4) and m/z ) 537.2 for {Cu2(L1)2(18O18OH)(OH)}2+
.
9
J. AM. CHEM. SOC. VOL. 127, NO. 14, 2005 5217

A R T I C L E S
Itoh et al.
Figure 3. Resonance Raman spectra of 2 in acetonitrile at -40 °C prepared
by H216O2 (A) and H218O2 (B) with a 406.7-nm laser excitation. The asterisk
bands are solvent bands, and the spikes are noises.
Figure 2. Space filling model (A) of 2 and ball-and-stick view (B) showing
the hydrogen bondings. Green: copper, red: oxygen, dark blue: nitrogen,
gray: carbon, and light blue: hydrogen. Hydrogen atoms in the space filling
model were placed at the calculated positions, and the C-H bond distances
are set to 1.10 Å.
vibration (ν(O-O)), respectively, by analogy to the features of
a closely related dinuclear complex [Cu2(UN-O)(OOH)]2+
(7).26 Although for 7, νs(Cu-O) vibration was observed at 322
cm-1, no νs(Cu-O) vibration was detected for 2. The band at
1144 cm-1 is tentatively assigned to the overtone of the νas(Cu-
O) vibration. Raman spectra of [Cu2(L1)2(OOH)(OH)]2+ (4) also
the structural features are clear. The Cu(µ-1,1-OOH)(µ-OH) core
is covered by a hydrophobic cavity formed by phenyl groups
and pendant arms (Figure 2A), which is large enough to
accommodate both µ-1,1-hydroperoxo and hydroxo groups
without a significant stereochemical change. Such a large
hydrophobic cavity may be responsible for the disordered
structure. A striking structural feature in 2 is hydrogen bondings
between the hydroperoxide and the imidazole nitrogen of the
uncoordinated pendant arm in one side (N6‚‚‚O2*(H) ) ∼2.7
Å) and between the hydroxide and the imidazole nitrogen of
the uncoordinated pendant arm in the other side (N6*‚‚‚O1(H)
) ∼3.1 Å) (Figures 1B and 2B). Similar hydrogen bondings
between hydroxides and imidazole nitrogens are also present
in 1 (N6‚‚‚O1*(H) ) ∼2.9 Å). Unlike 1 and 2, complex 3
containing the tridentate ligand (L1) has no hydrophobic cavity
(see Figure S4), implying that hydrogen bonding is essential
for the formation of the hydrophobic cavities of 1 and 2.
showed similar features at 562 cm-1
(
16-18∆ ) 23 cm-1), 883
cm-1 16-18∆ ) 50 cm-1), and 1120 cm-1
(
(
16-18∆ ) 40 cm-1
)
as shown in Figure S6. By analogy to the features of 2, they
can be assigned as the Cu-O(OH)-Cu stretching vibration
(νas(Cu-O)), the O-O stretching vibration (ν(O-O)), and the
overtone of the νas(Cu-O) vibration, respectively. The ν(O-
O) values of 4 (883 cm-1) and 7 (892 cm-1) are significantly
higher than that of 2 (868 cm-1). The high ν(O-O) frequency
of 7 has been explained in terms of the direct effect of
protonation to the bridging peroxide.26 The lower energy of the
ν(O-O) vibration of 2 relative to those of 4 and 7 may be in
line with hydrogen bonding which would leave some electron
density on the π* orbital of the peroxo moiety, resulting in the
decrease of the O-O bond order. In contrast, the νas(Cu-O)
Masuda and co-workers reported the first structurally char-
acterized mononuclear hydroperoxo-copper(II) complex having
a tetradentate tripodal ligand containing pivalamido groups
([Cu(bppa)(OOH)]+),10 in which hydrogen bonding between a
coordinated oxygen (proximal oxygen) of hydroperoxide and
two pivalamido NH hydrogens of the supporting ligand is also
present. Although the hydrogen bonding mode of [Cu(bppa)-
(OOH)]+ in which the hydroperoxo ligand acts as a hydrogen
bond acceptor differs from that of 2 in which the hydroperoxo
ligand acts as a hydrogen bond donor, both hydrogen bondings
can contribute the stabilization of the hydroperoxo complexes
(vide infra). Recently, Masuda and co-workers also reported
that the hydrogen bonding between the distal oxygen of
hydroperoxo ligand and amide-hydrogen of the supporting
ligand in [Cu(La)(OOH)]+ where hydroperoxide acts as hydro-
gen bonding acceptor destabilizes the hydroperoxo-Cu(II)
complex.18 Thus, hydrogen bonding plays various roles for
stabilization, destabilization, or activation of hydroperoxo
ligands depending on the hydrogen bonding modes.
frequency of 2 (572 cm-1) is higher than those of 4 (562 cm-1
)
and 7 (506 cm-1), suggesting the stronger donation of the
bridging OOH of 2 compared to those in 4 and 7. This is also
in line with the presence of hydrogen bonding. The ν(O-O)
frequencies of most of the mononuclear copper(II) complexes10-18
reported thus far are in the range 865-835 cm-1 except for
881 cm-1 observed for [Cu(N3S)(OOH)]+.15 The ν(O-O)
frequencies of the dimers are higher than most of the mono-
nuclear complexes, reflecting the stronger electron donation of
the µ-1,1-OOH groups to two copper(II) ions compared to those
of the monodentate OOH groups.
The electronic spectrum of 2 in acetonitrile at -40 °C (Figure
4 and Table 3) showed an intense band at 356 nm (ꢀ ) 6300
M-1 cm-1) and a weak band at 580 nm (ꢀ ) 240 M-1 cm-1
)
with a shoulder at 664 nm (ꢀ ) ∼190 M-1 cm-1), which are
assigned as πσ*(OOH)-to-Cu(II) LMCT26 and d-d transitions,
respectively, by analogy to the features of [Cu2(UN-O)-
(OOH)]2+ (7). Similar spectral features are also observed for 4
(Table 3 and Figure S7). However, the πσ*-to-Cu(II) LMCT
transition energies of 2 and 4 are significantly higher than those
of dinuclear copper(II) complexes having a phenolate bridge
such as 7 (λmas ) 395 nm (ꢀ ) 7000 M-1 cm-1)).22-27 Such a
high transition energy of 2 and 4 could be partly attributable to
a stronger donation of the bridging OOH compared to that in
7. Higher πσ*-to-Cu(II) LMCT transition energy of 4 relative
to that of 2 is not in line with the aforementioned notion given
in Raman spectroscopy that hydrogen bonding in 2 increases
Resonance Raman and UV-Vis Spectroscopies of 2 and
4. The resonance Raman spectrum of [Cu2(L3)2(OOH)(OH)]2+
(2) showed isotope-sensitive bands at 572 cm-1
(
16-18∆ ) 16
16-18
cm-1), 868 cm-1
(
16-18∆ ) 45 cm-1), and 1144 cm-1
(
∆
) 34 cm-1) as shown in Figure 3, and the resonance Raman
and electronic spectral data of some mono- and dinuclear
hydroperoxo-copper(II) complexes are given in Table 3. The
former two bands are assignable to the Cu-O(OH)-Cu
stretching vibration (νas(Cu-O)) and the O-O stretching
9
5218 J. AM. CHEM. SOC. VOL. 127, NO. 14, 2005

Hydroperoxo Dicopper(II) Complex
A R T I C L E S
Table 3. Spectroscopic Data for Mononuclear and Dinuclear Hydroperoxo-Copper(II) Complexes
1
-18
O) (16
-18
1
complexes
UV
−vis
λ
max/nm (
ꢀ
/M-1 cm-
)
ν(O
−
∆),
ν(Cu−
O) (16
∆)
ν
˜/cm-
ref
[Cu2(L3)2(OOH)(OH)]2+ (2)
[Cu2(L1)2(OOH)(OH)]2+ (4)
[Cu2(UN-O)(OOH)]2+ (7)
[Cu2(L)(OOH)]3+
356 (6300), 580 (240), 664 (sh ∼190)
341 (∼7000), 581 (∼170), 770 (sh ∼80)
395 (7000), 645 (660)
342 (12000), 444 (1200), 610 (800)
380 (890), 660 (150), 830 (250)
379 (1700), 668 (170), 828 (200)
350 (3400), 564 (150), 790 (sh 55)
357 (4300), 600 (140)
868 (45), 572 (16)a
883 (50), 562 (23)a
this work
this work
892 (55), 506 (15),a 322 (10)b
26
28
10
17
17
15
11
[Cu(bppa)(OOH)]+
856 (46)
847 (55)
834
881 (49)
[Cu(tpa)(OOH)]+
[Cu(bpba)(OOH)]+
[Cu(N3S)(OOH)]+
[Cu(HB(3-tBu-5-iPrpz)3)(OOH)]+
600 (1540), 830 (∼300)
843 (44), 624 (17)
a νas(Cu-O) vibration. b νs(Cu-O) vibration.
Figure 4. Electronic spectra of (A) 1 and (B) 2 in acetonitrile at -40 °C
and (C) that of a decomposed product of 2 in acetonitrile at room
temperature.
the electron donation of hydroperoxide, suggesting that some
other factor(s) such as stereochemistry around copper(II) ions
seems to be also important. Such a high LMCT transition energy
has been suggested for a dinuclear copper(II) complex
[Cu2(L)(OOH)]3+ (λmax ) 342 nm, ꢀ ) 12000 M-1 cm-1),
which can hydroxylate a xylyl linker.28 A similar absorption
band has also been found in the catalytic cycle of laccase (λmas
) 340 nm (ꢀ ) 4500 M-1 cm-1)), in which a dinuclear Cu(II)(µ-
1,1-OOH)Cu(I) species has been proposed as one of possible
intermediates.8 Thus, the LMCT transitions of dinuclear cop-
per(II) complexes occur in a wide rang depending on stereo-
chemistry around the copper(II) ion and the nature of hydro-
peroxide.
The LMCT of mononuclear hydroperoxo-Cu(II) complexes
are observed in the range 380-350 nm except for that observed
for a tetrahedral [Cu(HB(3-tBu-5-iPrpz)3)(OOH)]+ (λmax ) 600
nm, ꢀ ) 1540 M-1 cm-1).11 Masuda and co-workers suggested
that the LMCT transition energies depend on the stereochemistry
of complexes; transition energies of the square planer and square
pyramidal complexes such as [Cu(bpba)(OOH)]+ 17 and
[Cu(N3S)(OOH)]+ 15 are higher than those of trigonal bi-
pyramidal complexes such as [Cu(bppa)(OOH)]+ 10 and
[Cu(tpa)(OOH)]+.17 The LMCT energies of 2 and 4 are
comparable to those of mononuclear square planer and square
pyramidal copper(II) complexes.
Effect of Hydrophobic Cavity on H/D and 16O/18O
Exchange Reactions of Complexes 1 and 2. It is noted that
the hydrophobic cavity supported by hydrogen bondings sig-
nificantly influences the H/D and 16O/18O exchange reactions
of the bridging hydroxide and/or hydroperoxide in 2. Figure
5A shows the ESI-TOF/MS spectrum of an acetonitrile solution
containing both 1 ({1-(16OH)2}2+) (m/z ) 607.2) and 2 ({2-
(16OH)(16O16OH)}2+) (m/z ) 615.2) at -40 °C (hereafter O
stands for 16O except for 16O/18O). Addition of D2O caused a
rapid H/D exchange from {1-(OH)2}2+ (m/z ) 607.2) to {1-
Figure 5. (A) ESI-TOF/MS spectrum of 1 and 2 in acetonitrile at -40
°C, (B-D) time course of the spectral changes in the presence of D2O,
(B′-D′) that in the {2-(OH)(OOH)}2+ region where the intensities of the
signals (C′ and D′) are magnified for clarity, (E) theoretical isotope pattern
of {2-(OD)(OOH)}2+ or {2-(OH)(OOD)}2+, and (F) a simulated spectrum
of (C′) consisting of {2-(OD)(OOH)}2+ or {2-(OH)(OOD)}2+ (60%), and
{2-(OD)(OOD)}2+ (40%). (B and B′): measured after ∼2 min after addition
of D2O, (C and C′): measured after 4 h, and (D and D′): measured after
12 h,. Sample preparation: (A) a solid sample of 2-CF3SO3 was dissolved
into ∼1 mM acetonitrile solution of 1 (1 mL), and (B) an acetonitrile solution
(∼600 µL) containing ∼20 µL of D2O was mixed with the solution (A).
The concentration of D2O after the solutions are mixed is ∼630 mM.
(OD)2}2+ (m/z ) 608.2) within a few minutes (Figure 5B).
Unlike 1, surprisingly, only one H/D exchange occurred in 2
to generate {2-(OD)(OOH)}2+ or {2-(OH)(OOD)}2+ (m/z )
615.7) as shown in Figure 5, parts B and B′, indicating that the
hydrophobic cavity of 2 prevents a rapid H/D exchange of either
hydroperoxide or hydroxide. For complex 1, a rapid 16O/18O
exchange from {1-(OH)2}2+ (m/z ) 607.2) to {1-(18OH)2}2+
(m/z ) 609.2) was also observed within a few minutes by
reaction of H218O as expected for the substitution-labile cop-
per(II) complexes via either associative or dissociative mech-
anism, whereas no 16O/18O exchange was observed for {2-
(OH)(OOH)}2+ (Figure 6, parts B and B′). Thus the hydrophobic
cavity of 2 has a significant protection effect on the H/D and
16O/18O exchange reactions. We further followed the time
courses of the spectral changes of 2 in the presence of D2O
(Figure 5B-D and B′-D′) and in the presence of H218O (Figure
6B-D and B′-D′). In both cases, the intensities of the signals
of 2 decreased with time (the presence of water accelerated the
decomposition of 2 (vide infra)). In the presence of D2O, the
9
J. AM. CHEM. SOC. VOL. 127, NO. 14, 2005 5219

A R T I C L E S
Itoh et al.
Scheme 2 a
a (A) A ball-and-stick view of 2 showing the C‚‚‚OOOH and H‚‚‚OOOH
distances close to the hydroperoxo group, where hydrogen atoms were
placed at the calculated positions and the C-H bond distances are set to
1.10 Å. (B) and (C) Decomposition products of 2 in acetonitrile at 0 °C
and in solid state at 60 °C.
the other side stabilizes the hydrophobic cavity of 2 compared
to that of 1, and why and how this hydrophobic cavity
suppresses the H/D and 16O/18O exchange reactions. Neverthe-
less, the present results provide fundamental insights into the
control of the ligand exchange reactions of the substitution-
labile complexes by a hydrophobic cavity and the hydrogen
bonding effect on the stability of the hydrophobic cavity. In
addition, this hydrophobic cavity is also responsible for the
enhanced thermal stability of 2 against decomposition compared
to that of [Cu2(L1)2(OOH)(OH)]2+ (4) having no hydrophobic
cavity (vide infra).
Figure 6. (A) ESI-TOF/MS spectrum of 1 and 2 in acetonitrile at -40
°C, (B-D) its time course of the spectral changes in the presence of H218O,
(B′-D′) that in {2-(OH)(OOH)}2+ region where the intensities of the signals
(C′ and D′) are magnified for clarity, (E) theoretical isotope pattern of {2-
(OH)(OOH)}2+, and (F) a simulated spectrum of (C′) consisting of {2-
(OH)(OOH)}2+ (60%) and {2-(18OH)(OOH)}2+ (40%). (B and B′): mea-
sured after ∼2 min after addition of H218O, (C and C′): measured after 4
h, (D and D′): measured after 11 h. Sample preparation: (A) a solid sample
of 2-CF3SO3 was dissolved into ∼1 mM acetonitrile solution of 1 (1 mL),
and (B) an acetonitrile solution (∼600 µL) containing ∼20 µL of H218O
was mixed with the solution (A). The concentration of H218O after the
solutions are mixed is ∼630 mM.
Effect of Hydrophobic Cavity on Thermal Stability of 2
against Decomposition. Unlike 2, [Cu2(L1)2(OOH)(OH)]2+ (4)
has no hydrophobic cavity around the Cu2(µ-1,1-OOH)(µ-OH)
core. It is of interest to compare the relative thermal stabilities
of 2 and 4 against decomposition. We measured the decomposi-
tion rates of 2 and 4 in the presence of water at 0 °C, since an
acetonitrile solution of 4 generated by the reaction of 10 equiv
of 30% H2O2 contains water. Both decomposition reactions of
2 and 4 follow first-order kinetics. Decomposition rate constants
of 2 and 4 in acetonitrile at 0 °C in the presence of 120 equiv
of H2O are 8.0 × 10-4 s-1 and ∼8.2 × 10-2 s-1, respectively
(see Figure S8). Thus, decomposition of 4 is ∼100 times faster
than that of 2. The results clearly indicate that the hydrophobic
cavity supported by hydrogen bonding in 2 significantly
stabilizes the Cu2(µ-1,1-OOH)(µ-OH) core against decomposi-
tion. Such a hydrophobic cavity has also been shown to be
effective for stabilization of the unstable (µ-peroxo)diiron
complexes36 and high-valent bis(µ-oxo)dimetal complexes.37
Reactivity of 2-CF3SO3 in Acetonitrile and in Solid State.
(a) Decomposition of 2-CF3SO3 in Acetonitrile. Since some
Cu(II)2-OOH species have been suggested to be reactive for
aromatic hydroxylation, the reactivity of 2 toward the phenyl
groups that are located in close proximity of the bridging OOH
(Oterminal‚‚‚Cphenyl ) ∼2.7-3.2 Å) as shown in Scheme 2A is
of particular interest. Decomposition of 2 in acetonitrile at 0
°C, however, resulted in no hydroxylation of the phenyl group,
isotope patterns of 2 gradually change with time as shown in
Figure 5, parts C′ and D′, measured after 4 and 12 h, respectively
(cf. the theoretical stick spectrum E). The spectral change
suggests the formation of 2-(OD)(OOD); simulation of the
isotope pattern given in Figure 5F shows that ca. 40% of
conversion to 2-(OD)(OOD) occurs after 12 h.35 Thus the
exchange rates of two hydrogens of hydroperoxide and hydrox-
ide significantly differ due to the hydrophobic cavity supported
by the hydrogen bondings. A similar isotope pattern change in
the 16O/18O exchange reaction of 2 is also seen in Figure 6,
parts C′ and D′, measured after 4 and 11 h, respectively (cf.
theoretical stick spectrum E). Simulation of the isotope pattern
(Figure 6F) also revealed that ca. 40% of the 16O/18O exchange
of hydroxide occurs to generate 2-(18OH)(OOH). The results
indicate that the exchange rate of the hydrogen of either
hydroperoxide or hydroxide and that of the oxygen of hydroxide
are slower than the decomposition rate of 2 and/or the exchange
of these groups may be partly associated with decomposition
of 2. Thus the results clearly demonstrate that the hydrophobic
cavity of 2 is robust and capable of suppressing the H/D and
16O/18O exchange reactions. Such a surprisingly robust hydro-
phobic cavity of 2 seems to be attributable to the stronger
hydrogen bonding effect between the hydroperoxide and the
uncoordinated imidazole nitrogen judging from the structural
comparison of 1 and 2. However, it is not clear at present why
and how the combination of two types of the hydrogen bondings
between the hydroperoxide and the imidazole nitrogen in one
side and between the hydroxide and the imidazole nitrogen in
(36) (a) Hayashi, Y.; Kayatani, T.; Sugimoto, H.; Suzuki, M.; Inomata, K.;
Uehara, A.; Mizutani, Y.; Kitagawa, T.; Maeda, Y. J. Am. Chem. Soc. 1995,
117, 11220-11229. (b) Ookubo, T.; Sugimoto, H.; Nagayama, T.; Masuda,
H.; Sato, T.; Tanaka, K.; Maeda, Y.; Okawa, H.; Hayashi, Y.; Uehara, A.;
Suzuki, M. J. Am. Chem. Soc. 1996, 118, 701-702.
(37) (a) Shiren, K.; Ogo, S.; Fujinami, S.; Hayashi, H.; Suzuki, M.; Uehara, A.;
Watanabe, Y.; Moro-oka, Y. J. Am. Chem. Soc. 2000, 122, 254-262. (b)
Hayashi, H.; Fujinami, S.; Nagatomo, S.; Ogo, S.; Suzuki, M.; Uehara,
A.; Watanabe, Y.; Kitagawa, T. J. Am. Chem. Soc. 2000, 122, 2124-2125.
(35) Prolonged standing for an additional 4 h revealed that further exchange
reaction was still going on. Simulation of the isotope pattern of the spectrum
measured after 16 h revealed that ca. 50% of conversion to 2-(OD)(OOD)
occurs (not shown in Figure 5).
9
5220 J. AM. CHEM. SOC. VOL. 127, NO. 14, 2005

Hydroperoxo Dicopper(II) Complex
A R T I C L E S
but a ligand recovery experiment showed the formation of a
small amount of an N-dealkylated ligand, bis(1-methyl-2-phenyl-
4-imidazolylmethyl)amine (L2), which is generated via hy-
droxylation of a methylene group of L3 (vide infra). It was also
found that dioxygen evolution (ca. 40% based on hydroperoxide)
and reduction of 2 to copper(I) species ([Cu(L3)]+ (5: ca. 20%
based on total copper) were detected, suggesting that the
decomposition involves disproportionation of the hydroperoxo
ligand and reduction of 2 to 5 by the hydroperoxo ligand.38 The
formation of 5 was confirmed by ESI-TOF/MS measurement
(m/z ) 590.2). The reactivity of 5, which was separately
synthesized, with dioxygen under the above experimental
conditions is poor, and no measurable oxidation to copper(II)
complex(es) was detected within the above time scale (a few
hours). Such low dioxygen reactivity of 5 has also been reported
for a closely related copper(I) complex having 6-phenylpyridyl
groups [Cu(TPPA)]+.39 Although decomposition of 2 involves
various pathways as mentioned above, the decomposition
reaction in acetonitrile at 0 °C obeys first-order kinetics with
respect to 2. Addition of water accelerated the decomposition
rate as shown in Figure S9 (kobs ) 6.2 × 10-4 s-1 in acetonitrile,
kobs ) 8.0 × 10-4 s-1 in the presence of 120 equiv of water,
and kobs ) 1.4 × 10-3 s-1 in the presence of 670 equiv of water).
Thus, the decomposition reaction of 2 involves various pathways
such as disproportionation of peroxide, reduction of 2 to
copper(I), and so forth.
In contrast, decomposition of 2 in the presence of excess H2O2
had quite different results; decomposition of 2 in the presence
of 20 equiv of H2O2 in acetonitrile at room temperature gave a
brown solution. The ESI-TOF/MS spectrum of the brown
solution showed a main signal at m/z ) 605.2 (I ) 100%)
assignable to {Cu(L3 + O-H)}+ together with a minor species
having L3 ligand {Cu(L3)(CH3CN)}2+ (m/z ) 605.2) as shown
in Figure S10. An isotope labeling experiment using H218O2
revealed that the oxygen of {Cu(L3 + O-H)}+ comes from
H218O2. The electronic spectrum of the decomposed solution
showed a shoulder at ∼460 nm (ꢀ ≈ 350 M-1 cm-1) and
∼670 nm (ꢀ ≈ 220 M-1 cm-1) as shown in Figure S11, where
ꢀ values are given as a monomer. The spectral feature is
reminiscent of those of various mononuclear phenolato-
copper(II) complexes (λmax ) 450-530 nm (ꢀ ) 2000-500
M-1 cm-1)).40 The combination of ESI-TOF/MS and UV-vis
results suggests the partial hydroxylation of a phenyl group in
L3. The results indicate the formation of some other reactive
species capable of the arene hydroxylation. Further studies are
in progress.
Figure 7. ESI-TOF/MS spectra of 2-(L3-OH) in acetonitrile (A) at -40
°C and (B) at 20 °C. (C and D) ESI-TOF/MS spectra of 2-(L3-OH) obtained
from 2-(OOH) and 2-(18O18OH), respectively. (a) 2-(L3-OH) {Cu2(L3)-
(L3-OH)(OH)2}2+ (m/z ) 615.22), (b) 8 {Cu(L3)(CH3CN)}2+ (m/z )
315.61), (c) 1 {Cu2(L3)2(OH)2}2+ (m/z ) 607.21), (d) 6 {Cu(L2)2}2+ (m/z
) 388.66), (e) {Cu2(L3)(L2)(OH)2}2+ (m/z ) 522.17), (f) {Cu2(L2)2(Phim-
CHO)}2+ (m/z ) 481.70), (g) {Cu(L2)}+ (m/z ) 420.12), (h) {Cu(L3)}+
(m/z ) 590.21). The asterisk (*) is an internal standard signal {(CH3-
(CH2)7)4N}+ (m/z 466.5352).
hydroxylated ligand [Cu2(L3)(L3-OH)(OH)2]2+ (2-(L3-OH)) as
a main product, where L3-OH is an oxidized ligand in which
one of the methylene groups of the pendant arms is hydroxylated
(Scheme 2C). Identification of 2-(L3-OH) was carried out as
follows. The ESI-TOF/MS spectrum of an acetonitrile solution
of 2-(L3-OH) at -40 °C showed a prominent peak at m/z )
615.22 ({Cu2(L3)(L3-OH)(OH)2}2+, I ) 100%) together with
{Cu(L3)(CH3CN)}2+ (8, m/z ) 315.61) as shown in Figure 7A,
the former of which is the same mass number as that of 2.
However, the ESI-TOF/MS spectrum of 2-(L3-OH) obtained
from 2-(18O18OH) showed the presence of only one 18O and no
scrambling with 16O (Figure 7D: m/z ) 616.21), indicating that
2-(L3-OH) has no 18O18OH group and a hydroxide generated
after hydroxylation of the methylene group can be readily
exchanged by adventurous water present in an acetonitrile
solution. The H/D and 16O/18O exchange reactions of 2-(L3-
OH) in acetonitrile at -40 °C showed that 2-(L3-OH) has three
H/D exchangeable hydrogens and only one 16O/18O exchange-
able oxygen (see Figure S12), suggesting that for 2-(L3-OH), a
hydrophobic cavity remains intact and influences the 16O/18O
exchange reaction. Complex 2-(L3-OH) is only stable at low
temperature in acetonitrile. Warming the acetonitrile solution
of 2-(L3-OH) at room temperature caused a drastic spectral
change as shown in Figure 7B. The main m/z ) 615.22 signal
corresponding to 2-(L3-OH) ({Cu2(L3)(L3-OH)(OH)2}2+) dis-
appeared, and a new signal appeared at m/z ) 388.7 as a main
signal, which corresponds to a monomeric copper(II) species
containing two N-dealkylated ligands, bis(1-methyl-2-phenyl-
4-imidazolylmethyl)amine (L2), [Cu(L2)2]2+ (6) together with
other minor species. Formation of [Cu(L2)2]2+ (6) was con-
firmed by comparison with 6 prepared separately. Ligand
recovery experiments confirmed the formation of the N-
dealkylated ligand (L2: yield ) ∼80% based on 2) and
1-methyl-2-phenyl-4-formylimidazole (Phim-CHO). Isotope la-
beling experiment by 2-(18O18OH) showed that the oxygen atom
in Phim-CHO comes from 18O18OH, as mentioned in the
Experimental Section. These experimental results clearly indi-
cate that the hydroxylation occurs at the methylene position,
(b) Decomposition of 2-CF3SO3 in Solid State and Iden-
tification of a Decomposed Complex 2-(L3-OH). Various
unfavorable decomposition reactions occurred simultaneously
in acetonitrile as mentioned above. However, it is expected that
solvent-dependent unfavorable decompositions could be sup-
pressed in the solid state thermolysis. Warming a solid sample
of 2-CF3SO3 at 60 °C for 1 h gave a complex having a
(38) Such a facile reduction of 2 may be partly attributable to strong hydrogen
bonding between the hydroperoxide and the imidazole nitrogen, which
makes the hydroperoxide a stronger reductant. In addition, a proton released
upon reduction neutralizes synchronously the bridging hydroxide, leading
to the stabilization of the copper(I) complex 5.
(39) Chuang, C.-L.; Lim, K.; Chen, Q.; Zubieta, J.; Canary. J. W. Inorg. Chem.
1995, 34, 2562-2568.
(40) See, for example: (a) Itoh, S.; Taki, M.; Fukuzumi, S. Coord. Chem. ReV.
2000, 198, 3-20. (b) Jazdzewski, B. A.; Tolman, W. B. Coord. Chem.
ReV. 2000, 200-202, 633-685.
and 2-(L3-OH) can be formulated as [Cu2(L3)(L3-OH)(OH)2]2+
.
Thus the aliphatic hydroxylation by 2 is in contrast to the arene
9
J. AM. CHEM. SOC. VOL. 127, NO. 14, 2005 5221

A R T I C L E S
Itoh et al.
Scheme 3. Possible Reaction Intermediates
ation in 2 may proceed via intermediate (C) shown in Scheme
3. However, it is difficult to definitively identify the reactive
intermediate from the current data.
It should be noted that some (µ-1,1-hydroperoxo)Cu(II)2
species having xylyl linkers have been proposed to be reactive
for hydroxylation of the xylyl linker as already mentioned.
Casella and co-workers have proposed that the hydroxylation
occurs through a direct overlap between the arene HOMO and
the peroxide σ* component.28 In contrast, no arene hydroxylation
occurred for 2, although 2 has a phenyl group Ph (A) (Scheme
2A) in close proximity of the hydroperoxide and their orienta-
tions seem to be suitable for a direct overlap of those two
orbitals.
Summary
hydroxylation by some (µ-1,1-hydroperoxo)dicopper(II) com-
plexes with a xylyl linker.
We have succeeded in preparation and isolation of a novel
(µ-1,1-hydroperoxo)(µ-hydroxo)dicopper(II) complex 2 by the
reaction of bis(µ-hydroxo)dicopper(II) complex 1 with H2O2
and its structural and spectroscopic characterization. Both Cu2(µ-
OH)2 and Cu2(µ-1,1-OOH)(µ-OH) cores in 1 and 2 are almost
completely covered by the hydrophobic cavities formed by
phenyl groups and uncoordinated pendant arms, which are
preserved by hydrogen bondings. Unusually slow H/D and 16O/
18O exchange reactions were observed for 2, but not for 1,
indicating that the hydrophobic cavity of 2 is capable of
suppressing the H/D and 16O/18O exchange reactions. Although
the origin of such slow exchange reactions due to the hydro-
phobic cavity of 2 is not known at present, the results pro-
vide fundamental insights into the hydrophobic cavity effect
on the ligand exchange reactions of the substitution-labile
complexes and the hydrogen bonding effect on the robustness
of the hydrophobic cavity. It was also found that the hydro-
phobic cavity of 2 significantly enhances the thermal stability
against decomposition compared to 4, which has no hydrophobic
cavity.
Mechanistic Considerations. For regioselective aliphatic
hydroxylation performed by a solid sample of 2, various reactive
intermediates derived from the (µ-1,1-OOH)(µ-OH)Cu(II)2
species may be considered, as shown in Scheme 3A-D. The
homolytic O-O bond cleavage of the hydroperoxide would
•
generate a hydroxy radical OH (A), which is highly reactive
and not selective for various substrates.41 If this is the case,
both the methylene and phenyl groups located in close proximity
of the OOH (Scheme 2A) may be hydroxylated. Since no phenyl
hydroxylation was observed in the solid state thermolysis and
such a homolytic cleavage has been suggested to be energetically
unfavorable,8 this pathway seems unlikely. The heterolytic O-O
bond cleavage is also possible, which could generate a high
valent (µ-hydroxo)(µ-oxo)Cu(III)2 species (B in Scheme 3).
Although such a species has not yet been identified, the
formation of this species may not be excluded in the solid state
thermolysis. Another high valent bis(µ-oxo)Cu(III)2 species (C)
may also be generated by an alternative pathway; displacement
of the hydroxide with the hydroperoxide could lead to the
conversion to (µ-η2:η2-peroxo)Cu(II)2 or trans-(µ-peroxo)Cu(II)2
species, where the synchronous deprotonation from the hydro-
peroxide and the protonation to the hydroxide are needed. The
O-O bond cleavage of the above peroxo complex could produce
a bis(µ-oxo)Cu(III)2 species. Such bis(µ-oxo)Cu(III)2 species
have been shown to be capable of aliphatic hydroxylation of
supporting ligands.9,42 A further possible pathway would be a
direct reaction between an H atom of the methylene group and
Cu(II)2-OOH. The closest H atom of the methylene group is
located within ∼3 Å from both distal and proximal oxygens of
the hydroperoxide (Schemes 2A and 3D). Thus, 2 has the
potential possibility to generate the species having a variety of
reactive oxygen species, which would be consistent with the
observation that 2-(18O18OH) gave only L3-18OH ligand. Since
aliphatic ligand hydroxylation by bis(µ-oxo)dicopper(III) species
has been well-established, the present aliphatic ligand hydroxyl-
The decomposition study of complex 2 provides new insights
into the reactivity of hydroperoxide performed by the (µ-1,1-
hydroperoxo)Cu(II)2 complexes. Decomposition of 2 in aceto-
nitrile resulted in the reduction of 2 to a copper(I) species and
the disproportionation of hydroperoxide probably triggered by
the displacement of the hydroperoxide with solvent or water
molecule, and only a trace amount of ligand oxidation was
observed. In contrast, decomposition of 2 in solid state at 60
°C showed the regioselective hydroxylation of the methylene
group of the pendant arm in ∼80% yield. This is the first
example of the aliphatic hydroxylation of the supporting ligand
by Cu2-OOH species. This behavior is in marked contrast to
those reported for some (µ-1,1-hydroperoxo)Cu(II)2 complexes
capable of the arene hydroxylation. It is noted that decomposi-
tion of 2 in the presence of excess of H2O2 in acetonitrile at
room temperature caused a partial hydroxylation of the phenyl
group of L3 ligand, indicating the formation of some other
reactive species capable of the arene hydroxylation. For fuller
understanding of the reactivity of the (µ-1,1-hydroperoxo)Cu(II)2
species, it is necessary to investigate the details of such
differential reactivities of the (µ-1,1-hydroperoxo)Cu(II)2 species
and the various reactive species derived from the (µ-1,1-
hydroperoxo)Cu(II)2 species.
(41) Ingold K. U.; MacFaul, P. A. In Biomimetic Oxidations Catalyzed by
Transition Metal Complexes; Meunier, B., Ed.; Imperial College Press:
London, 2000; pp 45-89.
(42) See, for example: (a) Tolman, W. B. Acc. Chem. Res. 1997, 30, 227-
237. (b) Que, L., Jr.; Tolman, W. B. Angew. Chem., Int. Ed. 2002, 41,
1114-1137. (c) Itoh, S.; Fukuzumi, S. Bull. Chem. Soc. Jpn. 2002, 75,
2081-2095. (d) Lewis, E. A.; Tolman, W. B. Chem. ReV. 2004, 104, 1047-
1076. (e) Mirica, L. M.; Ottenwaelder, X.; Stack, T. D. Chem. ReV. 2004,
104, 1013-1045. (f) Hatcher, L. Q.; Karlin, K. D. J. Biol. Inorg. Chem.
2004, 9, 669-683.
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5222 J. AM. CHEM. SOC. VOL. 127, NO. 14, 2005

Hydroperoxo Dicopper(II) Complex
A R T I C L E S
Acknowledgment. This work was partly supported by Grants-
in-Aid for Scientific Research from the Ministry of Education,
Science, and Culture, Japan (M.S., H.F., and T.K.).
ESI-TOF/MS spectra of the brown acetonitrile solutions obtained
from decomposition of 2; electronic spectra of 2 and a brown
species obtained after warming at 20 °C; ESI-TOF/MS spectra
of 2-(L3-OH); and X-ray crystallographic files (PDF, CIF) This
material is available free of charge via the Internet at
http://pubs.acs.org.
Supporting Information Available: Twelve figures showing
ORTEP and space-filling views of (1-CF3SO3‚CH3CN), (2-
BPh4), and (3-ClO4‚C2H5CN); ESI-TOF/MS spectrum of 2;
resonance Raman spectra of 4; electronic spectra of 3 and 4;
electronic spectral change for the decomposition of 4 and 2;
JA047437H
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J. AM. CHEM. SOC. VOL. 127, NO. 14, 2005 5223