A copper complex supported by an N2S-tridentate ligand inducing efficient heterolytic O-O bond cleavage of alkylhydroperoxide

Article abstract of DOI:10.1039/c3dt52952e

We have recently reported a copper(ii)-superoxide complex supported by an N₃-tridentate ligand (L^N3), which exhibits a similar structure and reactivity to those of a putative reactive intermediate involved in the catalytic reactions of copper monooxygenases such as peptidylglycine α-hydroxylating monooxygenase (PHM) and dopamine β-monooxygenase (DβM). In this study, we have synthesised and characterised copper complexes supported by a related sulphur-containing ligand (L^N2S) to get insight into the notable electronic effect of the sulphur donor atom in the reaction with cumene hydroperoxide, inducing efficient heterolytic O-O bond cleavage.

Full text of DOI:10.1039/c3dt52952e

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A copper complex supported by an N2S-tridentate
ligand inducing efficient heterolytic O–O bond
cleavage of alkylhydroperoxide†
Cite this: Dalton Trans., 2014, 43,
4871
Tetsuro Tano,a Kaoru Mieda,b Hideki Sugimoto,a Takashi Ogurab and Shinobu Itoh*a
We have recently reported a copper(II)-superoxide complex supported by an N3-tridentate ligand (LN3),
which exhibits a similar structure and reactivity to those of a putative reactive intermediate involved in the
catalytic reactions of copper monooxygenases such as peptidylglycine α-hydroxylating monooxygenase
(PHM) and dopamine β-monooxygenase (DβM). In this study, we have synthesised and characterised
copper complexes supported by a related sulphur-containing ligand (LN2S) to get insight into the notable
electronic effect of the sulphur donor atom in the reaction with cumene hydroperoxide, inducing
efficient heterolytic O–O bond cleavage.
Received 19th October 2013,
Accepted 9th January 2014
DOI: 10.1039/c3dt52952e
www.rsc.org/dalton
Introduction
Copper monooxygenases such as peptidylglycine α-hydroxylat-
ing monooxygenase (PHM), dopamine β-monooxygenase
(DβM) and tyramine β-monooxygenase (TβM) employ two
uncoupled, mononuclear copper sites referred to as CuM and
CuH.1–6 CuM serves as the reaction site for dioxygen activation
and substrate oxygenation, whereas CuH functions as an elec-
tron acceptor from the physiological reductant (ascorbate).
The CuM site is ligated by two histidine imidazoles and one
methionine sulphur (N2S donor set), whereas CuH is co-
ordinated by three histidine imidazoles (N3 donor set).3,4
These coordination environments are somewhat unusual,
since most of the reaction centres of O2-activating copper pro-
teins (type-2 and type-3 Cu proteins) consist of nitrogen rich
donor sets, whereas the large number of electron transfer pro-
teins (type-1 Cu proteins) involve a sulphur-containing ligand
environment.7,8 Thus, such a unique feature of these copper
monooxygenases has long been a target in synthetic bioin-
organic modelling studies.9–20
Fig. 1 Ligand structures.
by a simple N3-ligand LN3 (1-[2-(2-pyridyl)ethyl]-1,5-diaza-
cyclooctane derivatives, Fig. 1) is a unique example, which
exhibits both a similar structural feature (distorted tetrahedral
copper(II) with an end-on superoxide ligand) and a reactivity
(aliphatic hydroxylation) to those of the putative reactive inter-
mediate involved in the enzymatic reactions.26,27 In this study,
we have synthesised and characterised the copper(I) and
copper(II) complexes supported by LN2S (Fig. 1) in order to get
insights into the effects of the sulphur atom on the structure
and reactivity. Ligand LN2S has the same molecular framework
as that of LN3, but one of the alkylamine nitrogen atoms is
replaced by a sulphur atom, allowing us to simply access the
electronic effects of the donor atoms.
So far, a series of mononuclear copper–dioxygen adducts
have been characterised as model compounds of possible reac-
tive intermediates of copper monooxygenases.21–25 Among
them, a mononuclear copper(II)-superoxide complex supported
aDepartment of Material and Life Science, Division of Advanced Science and
Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka,
Suita, Osaka 565-0871, Japan. E-mail: shinobu@mls.eng.osaka-u.ac.jp
bResearch Institute of Picobiology, Graduate School of Life Science, University of
Results and discussion
Synthesis and characterization
Hyogo, 3-2-1 Kouto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan
The ligand LN2S was synthesized in three steps as shown in
Scheme 1. Treatment of 2-(2-aminoethyl)pyridine and
3-chloro-1-propanol in CH3CN gave a bis(3-hydroxypropyl)-
†Electronic supplementary information (ESI) available: Experimental procedures
and characterization details. CCDC 959052–959056. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c3dt52952e
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Fig. 3 UV-vis spectrum of 1N2S (0.5 mM) in acetone at 25 °C. Inset:
cyclic voltammogram of 1N2S (1.0 mM) in acetone containing 0.1 M
TBAPF6; working electrode GC, counter electrode Pt, reference elec-
trode Ag/0.01 M AgNO3, scan rate 50 mV s−1
.
Scheme 1 Ligand synthesis.
Fig. 2 ORTEP drawing of 1N2S showing 50% probability thermal ellip-
soids. Counter anion (PF6−) and hydrogen atoms are omitted for clarity.
Cu(1)–S(1), 2.2028(4) Å; Cu(1)–N(1), 1.9295(13) Å; Cu(1)–N(2), 2.1662(13)
Å; S(1)–Cu(1)–N(1), 163.02(4)°; S(1)–Cu(1)–N(2), 94.37(4)°; N(1)–Cu(1)–
N(2), 102.60(6)°.
Fig. 4 ORTEP drawings of 2N2S·OTf showing 50% probability thermal
ellipsoids. Hydrogen atoms are omitted for clarity. Cu(1)–S(1), 2.2860(15)
Å; Cu(1)–O(1), 2.247(4) Å; Cu(1)–O(4), 2.118(4); Cu(1)–N(1), 2.006(5) Å;
Cu(1)–N(2), 2.040(6) Å; S(1)–Cu(1)–O(1), 84.84(11)°; S(1)–Cu(1)–O(4),
84.78(12)°; S(1)–Cu(1)–N(1), 171.15(16)°; S(1)–Cu(1)–N(2), 90.42(14)°;
O(1)–Cu(1)–O(4), 95.93(15)°; O(1)–Cu(1)–N(1), 92.12(16)°; O(1)–Cu(1)–
N(2), 109.86(17)°; O(4)–Cu(1)–N(1), 87.27(18)°; O(4)–Cu(1)–N(2),
153.25(16)°; N(1)–Cu(1)–N(2), 98.4(2)°.
amine derivative, which was then converted to the dichloro
derivative by the reaction with SOCl2. Ring closure using Na2S
gave the ligand LN2S in a moderate yield.
The copper(I) complex [CuI(LN2S)](PF6) (1N2S) was prepared
by treating LN2S with an equimolar amount of [CuI(CH3CN)4]-
(PF6) in THF. The crystal structure of 1N2S is shown in Fig. 2.
The crystallographic data and the selected bond lengths and
angles of 1N2S are presented in Table S1† and the figure
caption, respectively. 1N2S exhibits
a slightly distorted
reduced CuM, even though the Cu–S distance in 1N2S (2.203 Å)
is slightly shorter than that in the enzyme (2.24 Å).
T-shaped structure ligated by the two nitrogen atoms N(1) and
N(2), and one sulphur atom S(1) of the supporting ligand. The
sum of the three angles around the copper center [∠S(1)–
Cu(1)–N(1), ∠S(1)–Cu(1)–N(2), ∠N(1)–Cu(I)–N(2)] is equal to
360°, indicating that the copper ion and the three donor
atoms exist in the same plane. The copper(I) complex 1N3 sup-
ported by LN3 exhibited a similar T-shaped structure, demon-
strating that the molecular framework of the ligands can
highly stabilise such a three coordinate T-shaped structure of
copper(I).26,27 Although the precise structure of the reduced
enzyme is not known, the EXAFS data have suggested that the
reduced CuM is 3-coordinate, or 4-coordinate with a weakly
bound water molecule, where the CuM–SMet distance is 2.24 Å.4
In this context, 1N2S represents a good structural model of
1N2S showed a relatively intense absorption band at 375 nm
(ε = 1058 M−1 cm−1) ascribable to a CuI to S charge transfer
(MLCT) (Fig. 3), and exhibited a reversible CuI/CuII redox
couple at 0.23 V vs. Ag/AgNO3 in acetone (Fig. 3, inset) that is
higher than that of 1N3 (0.11 V for R = –CH2CH2Ph) under the
same conditions.27
Copper(II) complexes 2N2S·X (X = coordinating counter
anion; Cl, N3, NO2, OTf) were also prepared as the model com-
pounds of resting enzymes in the copper(II) oxidation state.
The crystal structures of 2N2S·Cl, 2N2S·N3, 2N2S·NO2 and
2N2S·OTf have been determined as shown in Fig. S1, S2,† and
Fig. 4. The crystallographic data and the selected bond lengths
and angles are summarised in Tables S2 and S3,† respectively.
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parameters are provided in the figure caption). The structural
feature is quite different from that of the copper(II) complexes
supported by LN3, which enforces the copper(II) center having
a four-coordinate distorted tetrahedral geometry.26,27 Thus, the
replacement of the donor atom from nitrogen to sulphur
resulted in a significant change in the coordination geometry
of the metal center from the four-coordinate distorted tetra-
hedral to the five-coordinate square pyramid or trigonal bipyra-
midal. In this case, Cu–S distance is 2.286 Å, which is longer
than that in the copper(I) complex (2.203 Å). Such an elonga-
tion of the CuII–S bond demonstrates the strong preference of
the CuI–S bond as compared to the CuII–S bond. However, the
CuII–S distance in the model complex (2.286 Å) is much
shorter than that in the resting state (copper(II) oxidation state)
of the enzyme, that is, 2.68 Å, although the coordination geo-
metries are similar to each other.3
Fig. 5 The UV-vis spectrum of 2N2S·OTf (0.25 mM) in acetone, at
−85 °C. λmax = 370 nm (ε = 5520 M−1 cm−1). Inset: an expanded UV-vis
spectrum of 2N2S·OTf (0.60 mM). λmax = 660 nm (ε = 222 M−1 cm−1).
Reactivity
First, the reaction of 1N2S and O2 was examined in acetone at
low temperature (−85 °C). However, no spectral change was
observed. Even at room temperature or in other solvents such
as THF and CH2Cl2, 1N2S showed no reactivity toward O2. This
result is in sharp contrast to the high O2-reactivity of 1N3
,
which gives a mononuclear copper(II)-superoxide complex.26,27
Such a big difference in the O2-reactivity between the two
ligand systems could be attributed to the higher oxidation
potential of 1N2S (0.23 V) as compared to that of 1N3 (0.11 V).
As mentioned above, the Cu–S distance in the enzyme is much
longer, especially in the copper(II) oxidation state, which may
cause the less copper(I)-stabilizing effect of the sulphur donor
atom in the enzymatic system. Therefore, CuM may be able to
activate O2 for the substrate oxygenation reaction even in the
presence of the Met ligand.
On the other hand, 1N2S smoothly reacted with cumene
hydroperoxide (CmOOH) in a 1 : 1 ratio to give CmOH (cumyl
alcohol) as the major product (98%) together with a trace
amount of acetophenone (PhC(O)Me), where CmOOH was
completely consumed (Fig. S3†). In the case of 1N3, on the
other hand, only 44% of CmOH was obtained together with a
small amount of PhC(O)Me (6%), and 50% of CmOOH was
recovered (Fig. S4†). Thus, the stoichiometry in the 1N3 case
was 2 : 1.
We have recently examined the reactivity of a series of
copper complexes using CmOOH as a proof for searching the
O–O breaking pattern in the copper-peroxide adducts.‡29,30 It
has been demonstrated that copper(I) complexes supported by
nitrogen ligands react with CmOOH in a 2 : 1 ratio to induce
the heterolytic O–O bond cleavage of the peroxide to give
CmOH as the major product. In this case, each copper(I)
Fig. 6 The EPR spectrum (EXP, top) of 2N2S·OTf (0.5 mM) in acetone at
−196 °C, and its computer simulation spectrum (SIM, bottom) with the
parameters of g1 = 2.275, g2 = 2.100, g3 = 2.015, A1 = 150 G, A2 = 59 G,
and A3 = 16 G.
All the copper(II) complexes exhibit five-coordinate struc-
tures with τ = 0.01–0.55,28 among which 2N2S·Cl and 2N2S·N3
form coordination polymer chain structures, where the coordi-
nating counter anion (Cl− and N3−) acts as the bridging ligand
(Fig. S1†). On the other hand, 2N2S·OTf and 2N2S·NO2 exhibit a
monomeric structure as shown in Fig. 4 and Fig. S2.† Thus,
the structure and chemical properties were examined using
2N2S·OTf in more detail.
The copper(II) complex 2N2S·OTf exhibits a distorted square
pyramidal structure coordinated by N(1), N(2), S(1) and O(4) in
the equatorial plane and O(1) occupying the axial position (τ =
0.30), which is in accord with the observed ligand field absorp-
tion band at 660 nm (ε = 222 M−1 cm−1, Fig. 5) and a typical
‡It has been reported that the products obtained from a cumylperoxo complex
largely depend on the O–O bond cleavage pattern. If homolytic O–O bond clea-
vage occurs, acetophenone (PhCOMe) is produced from cumyloxyl radical via
β-scission releasing methyl radical (CH3•). In contrast, heterolytic O–O bond clea-
EPR signals of CuII with a tetragonal geometry (Fig. 6, the EPR vage gives cumyl alcohol (CmOH) after oxyanion protonation.36,37
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Fig. 7 The UV-vis spectra of intermediate A (solid line; 1000 s after the
reaction of 1N2S (0.5 mM) with an equimolar amount of CmOOH in
acetone at −85 °C), B (dashed line; 1 h after the reaction), and C (dotted
line; after warming to 30 °C). Inset: expanded spectra at the
400–800 nm region.
Scheme 2
band at 610 cm−1 may be due to the Cu–O stretching
vibration.§31
On the basis of these results, a possible reaction mechan-
ism is proposed in Scheme 2. Association of the copper(I)
complex 1N2S and CmOOH may induce proton-coupled elec-
tron-transfer (PCET) to generate intermediate A, where a
proton of CmOOH is transferred to the sulphur atom and an
electron is transferred from copper(I) to the sulphur atom. In
this case, an empty d orbital of the sulphur atom can accom-
modate the electron provided from copper(I). Then, nucleophi-
lic attack of the sulphur atom to the proximal oxygen leads to
S–O bond formation with concomitant proton migration to the
distal oxygen atom. Eventually, O–O bond heterolytic cleavage
takes place to give intermediate B and CmOH. Then, electronic
rearrangement of B occurs upon warming to give a copper(I)
complex C with an oxygenated ligand.
complex formally acts as a one-electron donor to induce total
two-electron reduction of CmOOH, thus providing the hetero-
lytic cleavage product, CmOH, in a ∼50% yield based on the
copper(I) starting material (stoichiometry of Cu : CmOOH is
2 : 1).30 Thus, 1N3 (N3-donor ligand) giving CmOH in a ∼50%
yield is involved in this category.
In this respect, the reactivity of 1N2S (N2S-donor ligand) is
different, showing the 1 : 1 stoichiometry to give CmOH in a
∼100% yield based on the copper(I) starting material. Such a
unique reactivity of 1N2S can be attributed to the presence of
the sulphur atom. In order to get insight into the effect of the
sulphur atom, the reaction was examined by UV-vis, resonance
Raman and EPR spectra as follows.
Fig. 7 shows the UV-vis spectral change for the reaction of
1N2S and an equimolar amount of CmOOH in acetone. After
about 1000 s, an intermediate A exhibiting characteristic
absorption bands at 336, 465 and 625 nm was developed
(Fig. 7, solid line). This intermediate was gradually converted
to another intermediate B having absorption bands at 336,
415, and 635 nm (Fig. 7, dashed line). When the solution was
warmed to room temperature, the absorption bands in the
visible region disappeared, suggesting formation of a copper(I)
product C (Fig. 7, dotted line). The EPR spectrum of the final
reaction solution was essentially EPR silent, being consistent
with the formation of a copper(I) complex (Fig. S8†).
The sulphoxide ligand LN2SO was obtained nearly quantitat-
ively after the work-up treatment of the reaction mixture with
NH4OH aq (demetalation). The formation of LN2SO was con-
1
firmed by H-NMR, IR and ESI-mass spectra (Fig. S5 and S6,†
also see the Experimental section), and the isotope labeling
experiment using Cm18O2H confirmed that the oxygen atom
incorporated into the ligand originated from the CmOOH used
(Fig. S6†). Oxygenated product LN2SO was not obtained at all in
the reaction of ligand itself and CmOOH under the same
experimental conditions. Although mechanistic details of the
enzymatic reaction remain obscure, such a role of sulphur
Then, the reaction was examined by resonance Raman spec-
trum at the low temperature. As shown in Fig. S5,† isotope-
sensitive Raman bands were observed at 887, 827 and
§The resonance Raman bands due to the C–C–C and C–C–O deformation modes
of the alkylperoxide moiety were also observed at 540, 490 and 436 cm−1 in the
16O-derivative (see Fig. S5†). However, their counterparts in the 18O-derivative
became obscure due to low quality of the spectrum. The two peaks at 887 and
827 cm−1 for the O–O vibration of the 16O-derivative may be Fermi doublet,
which collapsed into one peak at 794 cm−1 in the 18O-derivative. More detailed
examination is required for the complete assignment of the resonance Raman
spectrum.
610 cm−1
, , when
which shifted to 794 and 603 cm−1
18O-labeled CmOOH was employed. The Raman bands at 887
and 827 cm−1 could be attributed to the O–O bond stretching
vibration of a cumylperoxide adduct intermediate A and the
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ligand could be involved in enhancing the O–O bond cleavage recorded with respect to an Ag/AgNO3 (0.01 M) reference
of the peroxide intermediate in the copper monooxygenases.
electrode.
Resonance Raman scattering was excited 441.6 nm from a
He–Cd laser (KIMMON KOHA, K5651R). Resonance Raman
scattering was dispersed by a single polychromator (Ritsu Oyo
Kogaku, MC-100) and was detected by a liquid nitrogen cooled
CCD detector (HORIBA JOBIN YVON, Symphony 1024 × 128
Cryogenic Front Illuminated CCD Detector). The resonance
Raman measurements were carried out using a rotated cylind-
rical cell thermostated at −80 °C or a rotating NMR tube (outer
diameter = 5 mm) thermostated at −40 °C by flashing cold
nitrogen gas. A 135° back-scattering geometry was used.
Conclusions
In summary, copper(I) and copper(II) complexes of the N2S
ligand (LN2S) have been synthesised and characterised in order
to get insights into the effects of the sulphur atom of the Met
ligand in the enzyme active site. Structural examinations have
suggested that the sulphur coordination in the present model
system is stronger than that in the enzymatic system, causing
higher stability of the copper(I) oxidation state toward O2.
Nonetheless, a reactivity study using cumen hydroperoxide has
clearly indicated that the sulphur atom helps in the O–O bond
heterolysis of the peroxide intermediate. Such an effect of
sulphur might be important to facilitate the enzymatic reac-
tions. The present result also suggests that the sulphur atom
of the Met ligand in the enzymatic system can be oxygenated
to sulphoxide during the catalytic cycles. In other words, post-
translational modification of the Met sulphur could occur in
the enzyme active site.
Synthesis
N-(Pyridine-2-yl)ethyl-bis(3-hydroxypropyl)amine. A 200 mL
round-bottom flask was charged with 2-(2-aminoethyl)pyridine
(4.0 g, 33 mmol), 3-chloro-1-propanol (13 g, 0.13 mol), sodium
carbonate (35 g, 0.33 mol), tetrabutylammonium bromide
(∼5 mg), water (70 mL) and CH3CN (70 mL). The mixture was
refluxed for 2 days. The reaction mixture was cooled to room
temperature and extracted with CHCl3 (3 × 50 mL), and the
combined organic fractions were dried over Na2SO4. After
removal of Na2SO4 by filtration, evaporation of the solvent gave
a brown oil, from which the pure product was isolated by
alumina column chromatography (eluent: AcOEt–MeOH =
1
95 : 5) in 70% (6.5 g). H-NMR (CDCl3) δ 1.67 (4 H, pentet, J =
Experimental section
Materials and physical measurements
6.0 Hz, CH2–CH2–CH2), 2.65 (4 H, t, J = 6.0 Hz, N–CH2–CH2–
CH2–OH), 2.82 (2 H, t, J = 7.2 Hz, Py–CH2–CH2–), 3.00 (2 H, t,
The reagents and the solvents used in this study, except the J = 7.2 Hz, Py–CH2–CH2–), 3.61 (4 H, t, J = 5.6 Hz, –CH2–OH),
ligands, cumene hydroperoxide and the copper complexes, 7.15–7.18 (1 H, m, PyH5), 7.20 (1 H, d, J = 7.6 Hz, PyH3), 7.66
were commercial products of the highest available purity and (1 H, td, J = 1.6 Hz and J = 7.2 Hz, PyH4), 8.50 (1 H, d, J =
were further purified by standard methods, if necessary.32 2.4 Hz, PyH6); HRMS (EI+) m/z
= 238.1680, calcd for
Cumene hydroperoxide (CmOOH) used in this study was pre- C13H22N2O2 = 238.1681.
pared by a reported procedure,33 and purified by silica gel
N-(Pyridine-2-yl)ethyl-bis(3-chloropropyl)amine. N-(Pyridine-
column chromatography (eluent: AcOEt–Hexane). 18O-labeled 2-yl)ethyl-bis(3-hydroxypropyl)amine (0.36 g, 1.3 mmol) in
(Cm18O18OH) was synthesized using 18O2 instead of 16O2 by benzene (30 mL) was cooled to 0 °C. At this temperature,
the same procedure.
UV-visible spectra were taken in acetone or in acetonitrile conditions. After an initial exothermal reaction, the mixture
Hewlett Packard 8453 photodiode array spectro- was refluxed for 4 h, then brought down to room temperature
0.5 mL of thionyl chloride was added dropwise under aerobic
on
a
photometer equipped with a Unisoku thermostated cell holder and left to stand overnight. After cooling down again to 0 °C, a
designed for low temperature measurements (USP-203). solution of sodium carbonate (10%) was poured until the pH
1H-NMR spectra were recorded on a JEOL ECS 400 or a Varian became basic. The organic layer was then separated, and dried
UNITY INOVA 600 MHz. ESR spectra were recorded on a over Na2SO4. After removal of Na2SO4 by filtration, evaporation
BRUKER E-500 spectrometer at −196 °C equipped with a vari- of the solvent gave a brown oil, from which the pure product
able temperature cell holder or a JEOL JES-FA100. A MnII- was isolated by alumina column chromatography (eluent:
maker was used as the reference, and experimental error in AcOEt) in 78% (0.28 g). 1H-NMR (CDCl3, 400 MHz) δ 1.84 (4 H,
the EPR parameter is 0.001. Mass spectra were recorded with pentet, J = 6.4 Hz, CH2–CH2–CH2), 2.59 (4 H, t, J = 6.4 Hz,
a JEOL JMS-700T Tandem MS station or a JEOL JMS-700. N–CH2–CH2–CH2–Cl), 2.84 (2 H, t, J = 6.4 Hz, Py–CH2–CH2–),
ESI-MS (electrospray ionization mass spectra) measurements 2.91 (2 H, t, J = 6.4 Hz, Py–CH2–CH2–), 3.46 (4 H, t, J = 6.4 Hz,
were performed on a Mariner ESI-TOF instrument. Cyclic vol- –CH2–Cl), 7.09–7.13 (1 H, m, PyH5), 7.19 (1 H, d, J = 8.0 Hz,
tammetric measurements were performed with a Hokuto PyH3), 7.59 (1 H, td, J = 1.6 Hz and J = 7.6 Hz, PyH4), 8.53 (1 H,
Denko HZ-3000 or HZ-7000 in deaerated solvent containing d, J = 4.8 Hz, PyH6); HRMS (EI+) m/z = 274.1003, calcd for
0.10 M n-Bu4PF6 as a supporting electrolyte. A GC working C13H20Cl2N2 = 274.1004.
(BAS) electrode was polished with BAS polishing alumina
N-(2-(Pyridin-2-yl)ethyl)-1-thia-5-azacyclooctane (LN2S). N-(Pyri-
suspension and rinsed with acetone before use. The counter dine-2-yl)ethyl-bis(3-chloropropyl)amine (0.2 g, 0.55 mmol)
electrode was a platinum wire. The measured potentials were was combined with Na2S (43 mg, 0.55 mmol) in anhydrous
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ethanol (100 mL) and refluxed for 19 h. The ethanol was then room temperature with an acetonitrile–water (40 : 60)
evaporated in vacuo. The residue was taken up with Et2O mixed solvent as the mobile phase at a constant flow rate of
(50 mL) and washed with 5% NaOH aq (20 mL × 3) and then 0.5 mL min−1. The yields of products were determined
water, and dried over Na2SO4. After removal of Na2SO4 by fil- by comparing the integrated peak areas of the products
tration, evaporation of the solvent gave a yellow oil, from with that of the internal standard (anisole) using calibration
which the ligand LN2S was isolated by alumina column chrom- lines.†
atography (eluent: AcOEt) in 52% (67 mg). 1H-NMR (CDCl3,
Hydroxylated ligand (LN2SO). An acetone solution (3.0 mL)
400 MHz) δ 1.81 (4 H, pentet, J = 6.0 Hz, CH2–CH2–CH2), 2.48 of 1N2S (12 mg, 27 μmol) was cooled to −85 °C using a
(4 H, t, J = 6.0 Hz, –CH2–N–CH2–), 2.64 (4 H, t, J = 6.4 Hz, Unisoku thermostated cell holder designed for low tempera-
–CH2–S–CH2–), 2.87–2.94 (4 H, m, Py–CH2–CH2–), 7.10–7.13 ture measurement. Then, an acetone solution of CmOOH
(1 H, m, PyH5), 7.17 (1 H, d, J = 7.6 Hz, PyH3), 7.60 (1 H, td, J = (2 equiv.) was added to the solution under a nitrogen atmos-
2.0 Hz and J = 8.0 Hz, PyH4), 8.54 (1 H, d, J = 5.2 Hz, PyH6); phere. The resulting mixture was stirred for 1 h at −85 °C, and
HRMS (EI+) m/z = 236.1348, calcd for C13H20N2S = 236.1347.
then gradually warmed to room temperature. A mixture of
[CuI(LN2S)](PF6) (1N2S). Since the copper(I) complex is sensi- organic materials was obtained by treating the reaction
tive to air, all the manipulations for the synthesis, crystalliza- mixture with an NH3 aq and subsequent extraction by CHCl3.
tion, and stock solution preparation of the copper(I) complex The combined organic layer was dried over Na2SO4. After
were carried out under a N2 atmosphere inside a glovebox removal of Na2SO4 by filtration, evaporation of the solvent gave
1
(KOREA KIYON KK-011AS, [O2] < 1 ppm).
a yellow oil. H-NMR (400 MHz, CDCl3) δ 2.03 (2 H, pentet, J =
[CuI(CH3CN)](PF6) (24 mg, 64 μmol) was added to a THF 6.0 Hz, CH2–CH2–CH2), 2.18 (2 H, pentet, J = 6.0 Hz, CH2–
solution of LN2S (15 mg, 64 μmol). After stirring the solution CH2–CH2–), 2.62 (2 H, m, –CH2–S–CH2–), 2.74 (2 H, m, –CH2–
for 30 min at room temperature, the insoluble material was S–CH2–) 2.77–2.84 (4 H, m, N–CH2–CH2–), 3.32 (2 H, m, Py–
removed by filtration. Addition of ether (50 mL) to the filtrate CH2–CH2–), 3.50 (2 H, m, Py–CH2–CH2–), 7.16–7.20 (1 H, m,
gave yellow-green solids that were isolated by decantation, PyH5), 7.46–7.51 (1 H, m, PyH3), 7.67 (1 H, td, J = 2.0 Hz and
washed with ether three times, and dried (45% yield, 13 mg). J = 8.0 Hz, PyH4), 8.54 (1 H, d, J = 5.2 Hz, PyH6); HRMS (FAB+)
Single crystals were obtained for the X-ray analysis by vapor m/z = 253.1378, calcd for C13H21N2OS ([LN2SO + H]+) =
diffusion of ether into a THF solution of the complex. FT-IR 253.1375. FT-IR (neat) 1077, 1104 cm−1 (SvO).†
(KBr) 841 cm−1 (PF6−); ESI-MS (pos.) m/z = 299.3, calcd
for [CuI(LN2S)]+ 299.1; Anal. Calcd for [CuI(LN2S)]PF6
X-ray crystal structure determination†
(C13H20CuF6N2PS): C, 35.10; H, 4.53; N, 6.30. Found: C, 35.43;
H, 4.64; N, 6.30.
Each single crystal obtained was mounted on a CryoLoop
(Hampton Research Co.) with a mineral oil, and all data of
X-ray diffraction were collected at −170 °C on a Rigaku R-AXIS--
RAPID diffractometer using filtered Mo-Kα radiation. The
structures were solved by direct methods SIR 92 or SIR 2008
and expanded using Fourier techniques.34,35 The non-hydro-
gen atoms were refined anisotropically by full-matrix least-
squares on F2. The hydrogen atoms were attached at idealized
positions on carbon atoms and were not refined. All structures
in the final stages of refinement showed no movement in the
atom positions. The calculations were performed using Single-
Crystal Structure Analysis Software, version 4.0.
[CuII(LN2S)(OTf)2] (2N2S·OTf). To a CH2Cl2 solution of LN2S
(8.0 mg, 34 μmol) was added CuII(OTf)2 (12 mg, 34 μmol).
After stirring for 5 min, the insoluble material was then
removed by filtration. The filtrate was concentrated to give a
green oily material. Single crystals were obtained for the X-ray
analysis by diffusion of n-hexane into a CH2Cl2 solution of
the green material (74% yield, 15 mg). FT-IR (KBr) 1262, 1170
and 1035 cm−1 (OTf−); ESI-MS (pos.) m/z = 448.1, calcd for
[CuII(LN2S)(OTf)]+ 448.0; Anal. Calcd for CuII(LN2S)(NO2)
(OTf)·0.5H2O (C14H21ClCuF3N3O5.5S2): C, 33.05; H, 3.40; N,
4.71. Found: C, 30.13; H, 3.37; N, 4.68.
Other copper(II) complexes 2N2S·Cl, 2N2S·N3, and 2N2S·NO2
were prepared in a similar manner, as described in the ESI.†
Acknowledgements
Product analysis
This work was supported by a Grant-in-Aid for Scientific
Research on Innovative Areas “Molecular Activation Directed
toward Straightforward Synthesis” (no. 22105007) and
“Stimuli-responsive Chemical Species” (no. 24109015) and a
Grant-in-Aid for Exploratory Research (no. 25620044) from the
Ministry of Education, Culture, Sports, Science and Techno-
logy, Japan.
Decomposition products of cumene hydroperoxide. An
acetone solution (3.0 mL) of 1N2S (0.5 mM) was cooled to
−85 °C, and then an acetone solution of CmOOH (1 equiv.)
was added to the solution under a nitrogen atmosphere. The
resulting mixture was stirred for 1 h at −85 °C. After warming
the solution to room temperature, anisole (0.5 mM) was added
as an internal standard, and then decomposition products
derived from cumene hydroperoxide were analyzed by using a
HPLC system consisting of a Shimadzu 10A series. Reverse
phase chromatography was performed on an ODS column
(Cosmosil 5C18-AR-II, 250 mm × 4.6 mm, Nacalai tesque) at
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