A copper complex bearing a TEMPO moiety as catalyst for the aerobic oxidation of primary alcohols

Article abstract of DOI:10.1039/b802109k

A new bifunctional, triazine-based ligand has been designed with the aim to generate a copper(ii) complex holding a TEMPO (2,2,6,6- tetramethylpiperidinyloxy) moiety. The coordination compound obtained from the ligand 4-(2-(3-(pyridin-2-yl)-1H-pyrazol-1-yl)ethoxy)-6-(4-amino-2,2,6,6- tetramethylpiperidine-1-oxyl)-N,N-diphenyl-1,3,5-triazin-2-amine (pypzt-1) and copper(ii) bromide (i.e. complex 8) is capable of catalysing the selective, aerobic oxidation of benzyl alcohol to 84% of benzaldehyde in 24 h. This galactose oxidase activity of the copper/TEMPO complex is observed as well for the conversion of the non-activated alkyl alcohol octan-1-ol to octanal with a yield of 29% after the same reaction time. The single-crystal X-ray structure of 8 shows that its crystal lattice contains [Cu ^IBr₂]^- anions which appear to be stabilised by means of both anion-π and hydrogen bonding interactions. In addition, the solid state structure of 8 exhibits (lone-pair)-π interactions between the nitrogen atom of an acetonitrile molecule and a triazine ring. The magnetic properties of 8 have been investigated by EPR and magnetic susceptibility measurements.

Full text of DOI:10.1039/b802109k

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/dalton | Dalton Transactions
A copper complex bearing a TEMPO moiety as catalyst for the aerobic
oxidation of primary alcohols†
Zhengliang Lu,a Jose´ Sa´nchez Costa,a Olivier Roubeau,b Ilpo Mutikainen,c Urho Turpeinen,c Simon J. Teat,d
Patrick Gamez*a and Jan Reedijk*a
Received 6th February 2008, Accepted 11th April 2008
First published as an Advance Article on the web 7th May 2008
DOI: 10.1039/b802109k
A new bifunctional, triazine-based ligand has been designed with the aim to generate a copper(II)
complex holding a TEMPO (2,2,6,6-tetramethylpiperidinyloxy) moiety. The coordination compound
obtained from the ligand 4-(2-(3-(pyridin-2-yl)-1H-pyrazol-1-yl)ethoxy)-6-(4-amino-2,2,6,6-
tetramethylpiperidine-1-oxyl)-N,N-diphenyl-1,3,5-triazin-2-amine (pypzt-1) and copper(II) bromide
(i.e. complex 8) is capable of catalysing the selective, aerobic oxidation of benzyl alcohol to 84% of
benzaldehyde in 24 h. This “galactose oxidase activity” of the copper/TEMPO complex is observed as
well for the conversion of the non-activated alkyl alcohol octan-1-ol to octanal with a yield of 29% after
the same reaction time. The single-crystal X-ray structure of 8 shows that its crystal lattice contains
[CuIBr2]− anions which appear to be stabilised by means of both anion–p and hydrogen bonding
interactions. In addition, the solid state structure of 8 exhibits (lone-pair)–p interactions between the
nitrogen atom of an acetonitrile molecule and a triazine ring. The magnetic properties of 8 have been
investigated by EPR and magnetic susceptibility measurements.
metal salts are used.9–15 Especially, a number of [copper/TEMPO]
catalysts have proven to be highly efficient and versatile systems
for the production of a broad range of aldehydes.16–23
Introduction
The selective oxidation of alcohols is an important synthetic trans-
formation in organic chemistry.1,2 In particular, the production of
aldehydes from primary alcohols represents one of the most critical
challenges facing the chemical industry.3 Different methods have
been developed to achieve this chemical conversion. For instance,
an aldehyde is typically obtained by reaction of an alcohol with a
chromium(VI) reagent which is reduced to Cr3+ during the reaction.
However, most of these oxidation procedures involve the use of sto-
ichiometric amounts of toxic salts.4,5 Therefore, the development
of selective and environmentally friendly oxidations catalysed by
transition-metal complexes is a very important and topical area of
contemporary catalysis.6 Several catalytic procedures have been
described,7,8 but some limitations remain that are the chemo-
, regio- and stereoselectivity of the procedures. TEMPO-based
(TEMPO stands for 2,2,6,6-tetramethylpiperidinyloxy) systems
have shown great potential as environmentally benign alternatives
to oxidations where copious amounts of ecologically unfriendly
A few years ago, some of us have reported a [copper(2,2ꢀ-
bipyridine)/TEMPO]-based catalyst capable of selectively con-
verting primary alcohols to the corresponding aldehydes at
room temperature.24,25 Recently, this efficient catalytic system
with bipyridine ligands has been extended to the use of mixed
pyrazole/pyridine ligands.26 The oxidation procedure brings in
the [copper/ligand] catalyst obtained in situ and the TEMPO co-
catalyst as single reagents.25 In the present study, two new ligands
containing one pyrazole and one pyridine donors and holding
a TEMPO moiety have been designed and synthesized. These
bifunctional molecules including both catalyst precursors, i.e. the
ligand to coordinate copper(II) ions and the radical unit, are tested
for the aerobic oxidation of primary alcohols to the corresponding
aldehydic products.
Experimental
General
aLeiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300, RA,
Leiden, The Netherlands. E-mail: reedijk@chem.leidenuniv.nl; Fax: +31
715274671
All chemicals were used as obtained without further purification.
1H and 13C NMR spectra were recorded using a DPX 300 Bruker
(300 MHz) instrument. Chemical shifts are reported in ppm (parts
per million) relative to the solvent peak. Elemental analyses (C,
H, N) were carried out on a Perkin-Elmer 2400 series II analyzer.
FTIR spectra were recorded with a Perkin-Elmer Paragon 1000
FTIR spectrophotometer, equipped with a Golden Gate ATR
device, using the reflectance technique (4000-300 cm−1). ESI mass
analyses were carried out on a Voyager Elite from PerSeptive
Biosystems. X-Band electron paramagnetic resonance (EPR)
measurements were performed on a Bruker EMX spectrometer.
Magnetic susceptibility measurements (5–300 K) were carried out
bUniversite´ Bordeaux 1, CNRS-CRPP, 115 avenue du dr. A. Schweitzer,
33600, Pessac, France
cUniversity of Helsinki, Department of Chemistry, Laboratory of Inorganic
Chemistry, Helsinki, 00014, Finland
dALS, Berkeley Lab, 1 Cyclotron Road, MS2-400, Berkeley, CA, 94720,
USA
† Electronic supplementary information (ESI) available: X-Ray data for
compounds 6a and 6b (Table S1), 7a and 7b (Table S2) and their X-ray
structure representations (Figs. S1–S4); contact distances characterising
the anion–p (Table S3) and the lone pair–p (Table S4) interactions.
CCDC reference numbers 676753–6767657 (6a, 6b, 7a, 7b and 8). For
ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/b802109k
This journal is
The Royal Society of Chemistry 2008
Dalton Trans., 2008, 3567–3573 | 3567
©

View Article Online
using a Quantum Design MPMS-5S SQUID magnetometer at
1000 Oe. Data were corrected for the diamagnetic contributions
estimated from the Pascal constants.27
three times with EtOAc. The combined organic layer was dried
over MgSO4 and the solvent was evaporated under reduced
pressure. The residue was purified by column chromatography to
obtain compound 6a as a colourless solid with a yield of 85%
(0.797 g, 1.7 mmol).
Syntheses
C25H20ClN7O (469.93): calc. C 63.90, H 4.29, N 20.86; found C
64.26, H 4.26, N 20.55%. 1H NMR (300 MHz, CDCl3): d 8.63 (d,
1 H, J = 4.8 Hz), 7.85 (d, 1 H, J = 7.9 Hz), 7.71 (ddd, 1 H, J =
1,5, 7.7 and 7.8 Hz), 7.44–7.17 (m, 12 H), 6.82 (d, 1 H, J = 2 Hz),
4.52 (t, 2 H, J = 5.0 Hz), 4.43 (t, 2 H, J = 5.0 Hz) ppm; 13C
NMR (75 MHz, CDCl3) d 171.3, 170.1, 166.7, 152.0, 149.5, 142.1,
141.6, 136.5, 131.8, 129.2, 127.4, 127.1, 122.4, 120.0, 104.6, 66.6,
Synthesis of the TEMPO-containing ligands pypzt-1 and pypzt-2
and their precursors
2,4-Dichloro-6-diphenylamino{1,3,5}triazine (2). 2 was pre-
pared from 2,4,6-trichloro-1,3,5-triazine (1) and diphenylamine
applying a synthetic procedure described earlier.28
•
50.9 ppm. MS-EI+ (m/z) [M]+ 469.84 (calc. 469.93).
3-(Dimethylamino)-1-(pyridin-2-yl)prop-2-en-1-one (4). 4 was
synthesized by reaction of 2-acetylpyridine (3) with N,N-
dimethylformamide dimethyl acetal, following a procedure used
to prepare a related compound.29 10 g (82.5 mmol) of 2-
acetylpyridine (3) were introduced in a round-bottomed flask.
Then, 18.5 g (155 mmol) of N,N-dimethylformamide dimethyl
acetal were added and the resulting reaction mixture was refluxed
overnight. The dark solution obtained was evaporated to dryness
under reduced pressure. Dark brown crystals of 426 (3.62 g,
33 mmol; yield = 40%) were obtained and washed with hexane
(3 × 100 mL) and with diethyl ether (3 × 100 mL). The 1H NMR
spectrum of compound 4 is identical to that earlier reported.26
The solid-state structure of 6a has been determined by single-
crystal X-ray diffraction and is depicted in Fig. S1 (ESI†).
4-(2-(5-(Pyridin-2-yl)-1H-pyrazol-1-yl)ethoxy)-6-chloro-N,N-
diphenyl-1,3,5-triazin-2-amine (6b). A solution of compound 5b
(0.567 g, 3.0 mmol) in 5 mL of dried THF was added dropwise
to a suspension of NaH (0.16 g, 60% dispersion in mineral oil;
4 mmol) in 20 mL of dried THF. The resulting suspension was
added dropwise to a solution of 2 in (0.951 g, 3.0 mmol) of
40 mL of THF under stirring. After completion of the addition,
the reaction mixture was stirred overnight at room temperature.
The reaction mixture was subsequently diluted with a saturated
aqueous solution of NaCl and the water layer was extracted
three times with EtOAc. The combined organic layer was dried
over MgSO4 and the solvent was evaporated under reduced
pressure. The residue was purified by column chromatography to
obtain compound 6b as a colourless solid with a yield of 81%
(1.13 g, 2.4 mmol).
2-(3-(Pyridin-2-yl)-1H-pyrazol-1-yl)ethanol (5a) and 2-(5-
(pyridin-2-yl)-1H-pyrazol-1-yl) ethanol (5b). 2 g (11.3 mmol) of
4 and 0.912 g (12 mmol) of 2-hydroxyethyl hydrazine were mixed
in a 50 mL round-bottomed flask containing 4 mL of ethanol. The
red reaction mixture was heated to 60 ◦C and stirred for 1 h. After
cooling to room temperature, the resulting crude orange oil was
purified by column chromatography on silica gel. 0.42 g (2.2 mmol,
yield = 20%) of 5a and 1.36 g (7.2 mmol; yield = 63%) of 5b were
collected as orange viscous oils.
C25H20ClN7O (469.93): calc. C 63.90, H 4.29, N 20.86; found
C 63.85, H 4.21, N 21.10%. 1H NMR (300 MHz, CDCl3): d 8.50
(d, 1 H, J = 4.7 Hz), 7.71 (ddd, 1 H, J = 1,6, 7.8 and 7.8 Hz),
7.56 (d, 1 H, J = 7.9 Hz), 7.52 (d, 1 H, J = 1.7 Hz), 7.37 (t,
4 H, J = 7.7 Hz), 7.28–7.18 (m, 7 H), 6.55 (d, 1 H, J = 1.7 Hz),
4.98 (t, 2 H, J = 5.4 Hz), 4.56 (t, 2 H, J = 5.4 Hz) ppm; 13C
NMR (75 MHz, CDCl3) d 171.1, 170.1, 166.7, 149.7, 148.7, 142.3,
141.6, 139.0, 136.8, 129.1, 127.4, 127.0, 123.1, 122.4, 106.8, 67.1,
Data for 5a. 1H NMR (300 MHz, CDCl3): d 8.60 (d, 1 H, J =
4.8 Hz), 7.90 (d, 1 H, J = 7.9 Hz), 7.70 (ddd, 1 H, J = 1,7, 7.7 and
7.8 Hz), 7.49 (d, 1 H, J = 2.3 Hz), 7.10 (ddd, 1 H, J = 1.4, 5.0 and
7.0 Hz), 6.88 (d, 1 H, J = 2.3 Hz), 4.30 (t, 2 H, J = 4.5 Hz), 4.05 (t,
2 H, J = 5.0 Hz) ppm; 13C NMR (75 MHz, CDCl3) d 151.8, 151.5,
149.0, 136.6, 131.7, 122.3, 120.0, 104.1, 61.3, 54.2 ppm. MS-EI+
•
49.2 ppm. MS-EI+ (m/z) [M]+ 469.94 (calc. 469.93).
The solid-state structure of 6b has been determined by single-
crystal X-ray diffraction and is depicted in Fig. S2 (ESI†).
•
(m/z) [M]+ 189.95 (calc. 189.21).
Data for 5b. 1H NMR (300 MHz, CDCl3): d 8.61 (d, 1 H, J =
4.9 Hz), 7.81 (ddd, 1 H, J = 1,6, 7.8 and 7.8 Hz), 7.62 (d, 1 H, J =
7.9 Hz), 7.58 (d, 1 H, J = 1.8 Hz), 7.32 (ddd, 1 H, J = 1.0, 5.0
and 7.5 Hz), 6.57 (d, 1H, J = 1.9 Hz), 4.66 (t, 2 H, J = 4.7 Hz),
4.13 (t, 2 H, J = 4.8 Hz) ppm; 13C NMR (75 MHz, CDCl3) d
148.2, 147.7, 140.8, 137.9, 136.9, 136.5, 122.8, 122.2, 106.0, 61.5,
Ligand pypzt-1 (7a). To a solution of 0.750 g (1.6 mmol) of
compound 6a in 20 mL of THF was added 2 mmol of N,N-
diisopropylethylamine (DiPEA). To this mixture, a solution of
0.31 g (1.8 mmol) of 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl
(4-amino-TEMPO) in 2 mL of THF was added. The resulting
orange solution was refluxed for four days. After the reaction
mixture was cooled down to room temperature, it was diluted
with a saturated aqueous solution of NaCl and the water layer
was extracted three times with EtOAc. The combined organic
solution was dried over MgSO4 and the solvent was evaporated
under reduced pressure. The residue was purified by column
chromatography on silica gel to yield pure pypzt-1 (yield = 81%,
0.785 g, 1.3 mmol). C34H38N9O2 (604.72): calc. C 67.53, H 6.33,
•
51.9 ppm. MS-EI+ (m/z) [M]+ 189.97 (calc. 189.21).
4-(2-(3-(Pyridin-2-yl)-1H-pyrazol-1-yl)ethoxy)-6-chloro-N,N-
diphenyl-1,3,5-triazin-2-amine (6a). A solution of 5a (0.378 g,
2.0 mmol) in 4 mL of dried THF was added dropwise to a
suspension of NaH (0.16 g, 60% dispersion in mineral oil; 4
mmol) in 10 mL of dried THF. The resulting suspension was
added slowly to a solution of 2 (0.666 g, 2.1 mmol) in 20 mL
of THF under stirring. After completion of the addition, the
reaction mixture was stirred overnight at room temperature.
The reaction mixture was subsequently diluted with a saturated
aqueous solution of NaCl and the water layer was extracted
•
N 20.85; found: C 67.46, H 6.38, N 20.35%. MS-EI+ (m/z) [M]+
603.97 (calc. 604.72).
The solid-state structure of pypzt-1 (7a) has been determined by
single-crystal X-ray diffraction and is depicted in Fig. S3 (ESI†).
3568 | Dalton Trans., 2008, 3567–3573
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
Table 1 Crystal
[Cu2(pypzt-1)2Br3(H2O)][CuBr2]·4CH3CN (8)
data
and
structure
refinement
for
Ligand pypzt-2 (7b). To a solution of 0.938 g (2.0 mmol) of
compound 6b in 20 mL of THF was added 4 mmol (0.660 mL) of
DiPEA. To this mixture, a solution of 0.376 g (2.20 mmol) of 4-
amino-TEMPO in 4 mL of THF was added. The resulting solution
was refluxed for four days after which the mixture was cooled to
room temperature. The reaction mixture was subsequently diluted
with a saturated aqueous solution of NaCl and the water layer
was extracted three times with EtOAc. The combined organic
layer was dried over MgSO4 and the solvent was evaporated
under reduced pressure. The solid residue was purified by column
chromatography on silica gel to produce pypzt-2 with a yield of
80% (0.966 g, 1.6 mmol).
Formula
Mr
Crystal size/mm
T/K
C68H78Br3Cu2N18O5·CuBr2·4C2H4N
1981.87
0.05 × 0.13 × 0.13
150(2)
Triclinic, P1 (no. 2)
Orange
¯
Cryst system, space group
Crystal colour
˚
a/A
14.117(2)
17.197(2)
19.668(2)
70.01(2)
77.21(2)
75.18(2)
4290.4(8)
2
1.534
2004
4.408
2.73–28.41
46705 (0.0425)
17521/1010
1.035
0.0668 (0.1712)
0.1037 (0.1896)
1.67 and −1.34
˚
b/A
˚
c/A
a/◦
b/◦
c /◦
C34H38N9O2 (604.72): calc. C 67.53, H 6.33, N 20.85; found:
3
˚
V/A
•
C 67.27, H 6.38, N 20.01%. MS-EI+ (m/z) [M]+ 604.93 (calc.
Z
Dc/g cm−3
604.72).
F(000)
The solid-state structure of pypzt-2 (7b) has been determined by
single-crystal X-ray diffraction and is depicted in Fig. S4 (ESI†).
l/mm−1
h for data collection/◦
Rflns collected (Rint
)
[Cu2(pypzt-1)2Br3(H2O)][CuBr2]·4CH3CN (8). A solution of
CuBr2 (16.8 mg, 0.075 mmol) in 4 mL of acetonitrile was added
to a stirred solution of TEMPO (31 mg, 0.05 mmol) in 6 mL of
acetonitrile. The solution immediately became dark green. After
10 min of stirring, the reaction solution was filtered and the
resulting dark-green filtrate was left unperturbed for the slow
evaporation of the solvent, at room temperature in air. After
two days, dark-orange crystals were obtained which were collected
by filtration (yield 35 mg, based on the ligand, 70%).
Data/params
Goodness of fit on F2
R1 (wR2) [I > 2r(I)]
R1 (wR2) (all data)
−3
˚
Dq/e A
8 − 4CH3CN: calc. C 44.93, H 4.33, N 13.87; found: C 44.69,
H 4.45, N 13.07%. IR (neat): m = 2976, 1584, 1531, 1463, 1441,
1336, 1075, 800, 759, 694, 668, 654, 618, 514, 389 cm−1.
Unfortunately, when this reaction was carried out in the
presence of 1 equiv. of base, a precipitate immediately formed.
Typical catalytic experiment. The oxidation of alcohols was
carried out in air in a 10 mL round-bottom flask equipped with a
magnetic bar. Typically, the alcohols (2.0 mmol) were dissolved in
3 mL of a CH3CN–H2O (2 : 1) solvent mixture. 11.2 mg (0.1 mmol)
of tert-BuOK were added, followed by 22.3 mg (0.1 mmol) of
CuBr2, resulting in a blue-green suspension. The ligand (60.4 mg,
0.1 mmol) was added and the reaction suspension slowly turned
dark-green. Samples of the reaction mixture were taken out
regularly to monitor the reaction by GC.
Structural determinations. Data were collected on an orange
block crystal of 8 on station 11.3.1 of the Advanced Light
˚
Source synchrotron facility (k = 0.7749 A) (for details see ESI†).
The structure was solved by direct methods (SHELXS-97)30 and
refined on F2 (SHELXL-97).31 Crystal and structure refinement
data for 8 are listed in Table 1.
Results and discussion
Syntheses of the TEMPO-containing ligands
The preparation of the bifunctional molecules is based on the
specific chemical properties of 2,4,6-trichloro-1,3,5-triazine (1,
Scheme 1).32 The chloride atoms of 1 can be easily and selectively
substituted by any nucleophilic reagent.33 Thus, the temperature
controlled substitution of each chloride atom of 1 allows the
preparation of triazine derivatives holding up to three different
substituents. The synthetic strategy of the investigation herein
Scheme 1 Synthetic pathway for the preparation of ligands pypzt-1 (7a)
and pypzt-2 (7b).
This journal is
The Royal Society of Chemistry 2008
Dalton Trans., 2008, 3567–3573 | 3569
©

View Article Online
reported is therefore to use 1 as a building block to connect on
one triazine ring both a ligand aimed at coordinating a CuII ion
and a TEMPO unit which is required for the oxidation reaction
to proceed. As is depicted in Scheme 1, the first step of the
synthesis is the reaction of 1 with diphenylamine which produces
2,4-dichloro-6-diphenylamino{1,3,5}triazine (2) with a yield of
55%.28 This step is carried out to “neutralize” one of the three
chloride positions of the ring as only two functional groups
are required for the present study. This position will be used in
future investigations to introduce a third functionality. Next,
the pyrazole/pyridine ligands possessing a nucleophilic group
for their subsequent grafting on the triazine ring are prepared
from 2-acetylpyridine (3). Reaction of 3 with an excess of
N,N-dimethylformamide dimethyl acetal under reflux generates
Scheme 2 Ligands related to pypzt-1 and pypzt-2, respectively, used in
earlier catalytic studies.26
the activities observed are reversed. Indeed, the bidentate ligand
mpypz-2 generates an active copper(II) complex, whereas the
corresponding ligand pypzt-2 shows no activity (Table 2, entries 4
and 2, respectively). In the same way, the bridging ligand pypzt-1
produces an effective copper catalyst, but not mpypz-1 (Table 2,
entries 1 and 3, respectively). In fact, with pypzt-2 (7b) a precipitate
appears which is not observed with pypzt-1 (7a). The same
phenomenon was observed with mpypz-2;26 however, contrary
to pypzt-2, the precipitation of copper species does not quench
the reaction. Most likely, the insoluble polymeric copper species
obtained with mpypz-2 are in equilibrium with soluble, active
ones, which is obviously not the case with pypzt-2. The disparities
between the activities generated by pypzt-1 and mpypz-1 can be
justified by comparable facts. Actually, no precipitation occurs
with pypzt-1 while a precipitate is produced with mpypz-1 (for
which the catalytic activity is quenched after 1 h of reaction time).26
It should be noted that the integration of both a pyridine/pyrazole
ligand and a TEMPO moiety on a single triazine ring allows the
production of a copper catalyst whose activity is equivalent to
that achieved with a pyridine/pyrazole ligand and TEMPO added
separately (Table 2, entries 1 and 4). The copper catalyst obtained
from copper(II) bromide and pypzt-1 is capable of converting 29%
of octan-1-ol (an alkyl alcohol whose oxidation is more difficult
to achieve) to octanal in 24 h (Table 2, entry 5).
3-(dimethylamino)-1-(pyridin-2-yl)prop-2-en-1-one (4) with
a
yield of 40%. The reaction of 4 with 2-hydroxyethyl hydrazine
in ethanol at 60 ◦C produces two pyrazole/pyridine derivatives
with a total yield of 83%. These regioisomers 5a and 5b can be
separated by column chromatography. After deprotonation of
the alcoholic function with sodium hydride, each isomer can
then react with compound 2 in THF at room temperature to
yield 6a (yield = 85%) and 6b (yield = 81%), respectively, as
crystalline materials. The single-crystal X-ray structures of 6a
and 6b are depicted in Fig. S1 and S2 (ESI†), respectively. The
final step consists of reacting the precursors 6a and 6b with
4-amino-TEMPO in THF under reflux during 4 days. This final
reaction leads to the targeted bifunctional molecules pypzt-1 (7a)
and pypzt-2 (7b) whose crystal structures are illustrated in Fig. S3
and S4 (ESI†) , respectively.
Catalytic studies
The good solubility of the complex generated from CuBr2 and
pypzt-1 in acetonitrile has allowed the preparation of single-
crystals of the coordination compound (8).
The two TEMPO-containing ligands pypzt-1 and pypzt-2 have
been tested in the copper-catalysed aerobic oxidation of two
model substrates, i.e. benzyl alcohol and 1-octanol. The catalytic
reactions were performed applying the experimental conditions
described earlier,25 namely using 5 mol% of CuBr2 together
with 5 mol% of the ligand in acetonitrile–water (2 : 1) with
potassium tert-butoxide as basic co-catalyst. The results are listed
in Table 2. The use of pypzt-1 (7a) leads to a conversion of
6% after 1 h and 84% after 24 h, while the use of pypzt-2
(7b) results in catalytically non-active species (Table 2, entries 1
and 2, respectively). For comparison, the catalytic conversions
achieved with the ligands mpypz-1 and mpypz-2 (Scheme 2)26
have been included in Table 2 (entries 3 and 4). Amazingly,
Ligand-field studies
Comparative visible spectroscopy studies of the copper(II) com-
plexes obtained in situ from the ligands mpypz-1, mpypz-2, pypzt-
1 (7a) and pypzt-2 (7b) have been carried out (see ESI†for the
experimental procedure). The spectra recorded are depicted in
Fig. 1. The spectra of 1 : 1 mixtures of Cu–mpypz-1 and Cu–
mpypz-2 in acetonitrile show different features (Fig. 1(A)). With
mpypz-1, a band at 533 nm and a weaker one at 648 nm are
observed. These d–d bands are typical for square-pyramidal CuII
Table 2 [Copper/TEMPO]-catalysed oxidation of benzyl alcohol and octan-1-ol to the corresponding aldehydesa
Conversion (%)
Entry
Alcohol
Ligand used
After 1 h
After 24 h
84b
Ref.
1
2
3
4
5
Benzyl alcohol
Benzyl alcohol
Benzyl alcohol
Benzyl alcohol
Octan-1-ol
pypzt-1
pypzt-2
mpypz-1
mpypz-2
pypzt-1
6
This work
c
c
—
—
—
This work
29d
8
c
26
26
89
29
6
This work
a For the reaction procedure, see Experimental Section. b A conversion of 93% is reached after a reaction time of 30 hours. c No catalytic oxidation was
observed. d The reaction stops after one hour.26
3570 | Dalton Trans., 2008, 3567–3573
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
◦
+
˚
Table 3 Selected bond lengths (A) and angles ( ) for [Cu2(L)2Br3(H2O)]
in 8
Cu1–Br1
Cu1–N11
Cu1–N53
Cu2–Br3
Cu2–N61
Cu2–N3
2.362(1)
2.111(5)
2.066(5)
2.357(1)
2.052(6)
2.007(5)
Cu1–Br2
Cu1–N16
Cu1–O57
Cu2–O100
Cu2–N66
Cu2–O7
2.687(1)
2.011(5)
2.864(5)
2.400(4)
2.021(7)
2.792(5)
Br1–Cu1–Br2
Br1–Cu1–N16
Br2–Cu1–N11
Br2–Cu1–N53
N11–Cu1–N53
Br3–Cu2–O100
Br3–Cu2–N66
O100–Cu2–N61
O100–Cu2–N3
N61–Cu2–N3
93.39(3)
178.67(15)
106.96(15)
113.29(14)
137.3(2)
86.27(12)
167.59(19)
109.5(2)
Br1–Cu1–N11
Br1–Cu1–N53
Br2–Cu1–N16
N11–Cu1–N16
N16–Cu1–N53
Br3–Cu2–N61
Br3–Cu2–N3
O100–Cu2–N66
N61–Cu2–N66
N66–Cu2–N3
101.71(14)
89.90(14)
85.30(14)
78.5(2)
90.8(2)
103.38(19)
92.32(16)
81.4(2)
80.1(3)
92.1(2)
106.47(19)
141.4(2)
Fig. 1 Electronic spectra for 1 : 1 acetonitrile solutions of Cu–ligand
(A and B, top left and right) and for 1 : 1 : 1 acetonitrile solutions of
Cu–ligand–base (C and D, bottom left and right).
complexes. For mpypz-2, the bands at 644 nm and around 480 nm
also suggest a square-pyramidal coordination environment for the
corresponding complex. Comparable spectroscopic characteristics
are noticed with the copper(II) compound generated from pypzt-2
(7b) (Fig. 1(B)), thus indicating that an analogous coordination
geometry. With pypzt-1 (7a), two bands are noted at about 750 and
534 nm which may characterize an octahedral geometry. Upon
addition of base (Fig. 1(C) and (D)), the spectra for mpypz-1 and
7a are not altered while changes are observed for mpypz-2 and 7b.
For mpypz-2, an additional weak band is now detected at 500 nm
and the initial band at 480 nm is shifted to 440 nm. Similarly, for
mpypz-2, three bands are present at 642, 490 and 445 nm.
Electrochemical studies under a variety of conditions resulted
in complicated voltammograms showing the involvement of up to
five different redox species. The cyclic voltammograms are compa-
rable for all four copper/ligand systems. Spectroelectrochemical
investigations would be required to identify these species and are
left for a later paper.
Fig. 2 ORTEP drawing of the cationic part of compound 8. Thermal
ellipsoids are drawn at the 30% probability level. H atoms, lattice solvent
molecules and non-coordinated anions are not shown for clarity.
(Table 3) are typical for such coordination geometry.35 The basal
angles varying from 78.4(2) to 101.72(17)◦ reflect the distortion
which is most likely due to steric hindrance resulting from the
coordination of the triazine ring of the adjacent ligand (nitrogen
atom N53; Fig. 2). In addition, the oxygen atom O57 of this pypzt-
Crystal structure
˚
1 ligand is semi-coordinated to Cu1 (Cu1–O57 2.864(5) A), giving
Single-crystals of a complex prepared from pypzt-1 (7a) and
copper(II) bromide could be obtained. Indeed, the reaction
of 1.5 equiv. of CuBr2 with 1 equiv. of pypzt-1 in acetoni-
trile leads to the formation of orange crystals of [Cu2(pypzt-
1)2Br3(H2O)][CuBr2]·4CH3CN (8) after two days. 8 crystallises
rise to a constrained four-membered coordination unit (including
the atoms Cu1, N53, C52 and O57; Fig. 2). The coordination
geometry around Cu2 is analogous to that of Cu1. Like Cu1, Cu2
is coordinated by a pyrazole/pyridine unit and triazine nitrogen
atom. The coordination sphere of the metal centre is completed by
a bromide anion and a water molecule (Fig. 2). The s5 value for Cu2
is 0.19,34 characterizing a distorted square-pyramidal geometry.
The Cu–N, Cu–Br and Cu–O bond lengths of the CuIIN3BrO
chromophore are in normal ranges.36 The distortion is due to the
coordination of the triazine ring, which generates steric constraints
enhanced by the semi-coordination of the oxygen atom O7 (Cu2–
¯
in the triclinic space group P1. An ORTEP view of compound 8
is depicted in Fig. 2. The crystallographic data for the structural
analysis and the important bond parameters are listed in Tables S1
and S2 (ESI†), respectively. The dinuclear complex is constituted
of two different copper(II) ions characterized by slightly distinct
coordination environments (Fig. 2). The Cu1 atom is pentaco-
ordinated and adopts a distorted square-pyramidal arrangement
(s5 = 0.18).34 The CuIIN3Br2 chromophore is formed by a pyrazole
N atom and a pyridine N atom from one pypzt-1 ligand, two
bromide anions and one N atom from triazine ring belonging
to a second pypzt-1 unit. The Cu–N and Cu–Br bond distances
˚
O7 2.792(5) A; Fig. 2). Furthermore, the axial water molecule
(oxygen atom O100) is hydrogen bonded to the amine nitrogen
atom N21 (N21 · · · O100 3.050(8), N21–H21–O100 175◦; Fig. 2).
The crystal lattice of 8 reveals interesting features. First,
[CuIBr2]− anions are present (Fig. 3). The formation of these
This journal is
The Royal Society of Chemistry 2008
Dalton Trans., 2008, 3567–3573 | 3571
©

View Article Online
The solid line in Fig. 4 corresponds to the theoretical curve
obtained using the above parameters. The poor Curie–Weiss fit
for 8 is indicative of a probable intermolecular antiferromagnetic
super-exchange pathway in this compound. When cooled, the vM
value increases continuously, from 7.46 × 10−3 cm3 mol−1 at 300 K,
to reach a value of 0.46 cm3 mol−1 below 2 K. This behaviour
typically points towards the occurrence of weak antiferromagnetic
interactions at low temperatures.
Fig. 3 Illustrations showing a lattice [CuBr2]− anion and its hydrogen
bonding and anion–p interactions (A, B), and acetonitrile lone pair–tri-
azine ring interactions (C, D).
uncommon copper(I) dibromide ions37,38 is most likely mediated
by the CuII/TEMPO system, thus revealing its redox properties.
The [CuIBr2]− anions appear to be stabilised by means of
supramolecular interactions (Fig. 3(A) and (B)). Indeed, the
bromide atom Br4 of the copper(I) dibromide unit is in contact
with two heteroaromatic rings (labelled as Cg10 and Cg11 in
Fig. 3(A)). These anion–p interactions39,40 are characterised by
Fig. 4 Plots of vMT vs. T (ꢀ) and vM vs. T (ꢁ) for 8. The solid lines are
˚
anion–centroid distances of 3.691(3) A (Cg10 · · · Br4) and 3.781(5)
a fit to the experimental data (see text).
˚
A (Cg11 · · · Br4) and [Br4 axis–ring centroid–ring plane] angles of
82.78(3)◦ (Cg10) and 85.65(3)◦ (Cg11) (see Table S3 (ESI†) for
all [ring atom] · · · Br4 contact distances). In addition, the bromide
atom Br4 is hydrogen-bonded to the water molecule coordinated
The EPR spectrum of an acetonitrile solution of complex 8 at
room temperature shows a broad signal centered at g = 2.054 and
14
a three-line signal with g = 2.003 and A{ N} = 16 G (Fig. 5). No
˚
to Cu2 (the distance O100–H1w · · · Br5 of 3.377(5) A and the
half-field signal was detected. The three-line signal characterises
non-interacting TEMPO moieties.44 In the strong exchange limit
for CuII/nitroxyl radical coupling, the g value for a coordination
compound including copper(II) and n spin-labelled units (L•) can
be estimated using eqn (1).45
O100–H1w–Br5 angle of 138◦ characterise a moderate hydrogen
bonding interaction41).
As is evidenced in Fig. 2, 8 contains two pypzt-1 ligands
and therefore two electron-deficient triazine rings. As mentioned
above, the triazine unit Cg10 (Fig. 3(A)) is involved in anion–p
interactions. Amazingly, the second triazine ring, labelled Cg7
(Fig. 3(C)), is in contact with the nitrogen atom N1S of a
lattice acetonitrile molecule. Such remarkable lone pair–aromatic
interactions42 has been previously observed in the crystal structure
of a zinc(II) complex.43 The present (lone pair)acetonitrile–ptriazine
interaction is characterized by a N1S · · · Cg7 distance of 3.348(11)
•
gobs = (ngL + gCu)/(n + 1)
(1)
For five-coordinated CuIIN3Br2 and CuIIN3BrO chromophores,
g values from 2.10 to 2.15 are expected.35,36 Compound 8 exhibits
one TEMPO unit per copper(II) ion; therefore, the calculated gobs
value is in the range 2.051–2.076. The experimental value of 2.054
◦
˚
A and a [N1S axis–ring centroid–ring plane] angle of 80.16(2)
(see Table S4 (ESI†) for all [ring atom] · · · N1S contact distances).
Physical properties of complex 8
The magnetic properties of 8 have been investigated in some
detail. The vMT and vM vs. T plots (vM is the molar magnetic
susceptibility) are shown in Fig. 4. At room temperature, vMT is
ca. 1.55 cm3 mol−1 K, being consistent with the expected value for
four non-interacting S = 1/2 centers (1.5 cm3 K mol−1 for g =
2). These results show that no interactions between the copper
centres and the TEMPO units are occurring. Upon cooling vMT
remains constant until 60 K where it starts to decrease, illustrating
an antiferromagnetic behaviour. To estimate the magnitude of the
antiferromagnetic coupling, the magnetic susceptibility data were
fitted to the Curie–Weiss law for four interacting S = 1/2 centers
(two CuII ions and two TEMPO radicals). The fitting of the data
gives g = 1.97, h = −3.52 K and R = 2 × 10−4; R symbolizes the
Fig. 5 EPR spectra of complex 8 in acetonitrile solution at room
temperature (top) and at 77 K (bottom).
ꢀ
ꢀ
agreement factor defined as i(vcalc − vobs)2/ i(vobs)2.
3572 | Dalton Trans., 2008, 3567–3573
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
is in good agreement as it is in the expected range. At 77 K, the
three-line signal disappears (Fig. 5) which suggests the occurrence
of intermolecular CuII/TEMPO interactions in the lattice. The
broad signal observed is centered at g = 2.06, which is consistent
with the range value obtained from eqn (1).
In the presence of base, the broad signal corresponding to
the copper(II) species (g = 2.054) disappears which suggests the
formation of dinuclear species.
7 T. Mallat and A. Baiker, Chem. Rev., 2004, 104, 3037–3058.
8 C. Lin, C. Z. Xu, C. G. Xia and Y. H. Feng, Prog. Chem., 2004, 16,
758–765.
9 P. J. Figiel, M. Leskela and T. Repo, Adv. Synth. Catal., 2007, 349,
1173–1179.
10 D. Geisslmeier, W. G. Jary and H. Falk, Monatsh. Chem., 2005, 136,
1591–1599.
11 X. F. Zhao and C. Zhang, Synthesis, 2007, 551–557.
12 N. Jiang and A. J. Ragauskas, J. Org. Chem., 2006, 71, 7087–7090.
13 C. Bolm, A. S. Magnus and J. P. Hildebrand, Org. Lett., 2000, 2, 1173–
1175.
14 I. A. Ansari and R. Gree, Org. Lett., 2002, 4, 1507–1509.
15 W. Adam, C. R. Saha-Moller and P. A. Ganeshpure, Chem. Rev., 2001,
101, 3499–3548.
Concluding remarks
16 S. Mannam, S. K. Alamsetti and G. Sekar, Adv. Synth. Catal., 2007,
349, 2253–2258.
17 S. Striegler, Tetrahedron, 2006, 62, 9109–9114.
18 R. A. Sheldon and I. W. C. E. Arends, J. Mol. Catal. A: Chem., 2006,
251, 200–214.
19 S. Velusamy, A. Srinivasan and T. Punniyamurthy, Tetrahedron Lett.,
2006, 47, 923–926.
20 M. Contel, C. Izuel, M. Laguna, P. R. Villuendas, P. J. Alonso and
R. H. Fish, Chem. Eur. J., 2003, 9, 4168–4178.
21 G. Ragagnin, B. Betzemeier, S. Quici and P. Knochel, Tetrahedron, 2002,
58, 3985–3991.
22 B. Betzemeier, M. Cavazzini, S. Quici and P. Knochel, Tetrahedron
Lett., 2000, 41, 4343–4346.
23 N. Tsubokawa, T. Kimoto and T. Endo, J. Mol. Catal. A: Chem., 1995,
101, 45–50.
24 P. Gamez, I. W. C. E. Arends, R. A. Sheldon and J. Reedijk, Adv. Synth.
Catal., 2004, 346, 805–811.
25 P. Gamez, I. W. C. E. Arends, J. Reedijk and R. A. Sheldon, Chem.
Commun., 2003, 2414–2415.
A new 1,3,5-triazine derivative has been designed to contain both
a binding site for copper(II) ions and a TEMPO sub-unit. The
objective was to obtain a CuII/TEMPO complex able to catalyse a
two-electron oxidation process, namely the oxidation of a primary
alcohol to the corresponding aldehyde (galactose oxidase activity).
Actually, the copper(II) complex obtained by the coordination of
CuII ions to the bifunctional ligand pypzt-1 is able to convert
(as anticipated) benzyl alcohol and octan-1-ol to the aldehydic
products, under mild conditions in air. Moreover, the catalytic
activity observed is analogous to that achieved when a related
ligand (mpypz-2)26 and TEMPO are added as single molecules
to the reaction mixture. Therefore, the incorporation of both the
copper unit and the TEMPO group on a single molecule does
not reduce the catalytic activity. Interestingly, the crystal lattice
of complex 8 reveals the presence of unusual [CuIBr2]− anions
which are involved in hydrogen-bonding and anion–p interactions.
In addition, the solid-state X-ray structure of 8 exhibits only
the second crystallographic evidence of acetonitrile (lone pair)–
triazine (electron-deficient ring) interactions.
New molecules with different spacer lengths between the differ-
ent functional units (ligand or TEMPO moiety) and the triazine
ring are currently investigated. It is expected that an optimal spacer
length will enhance the catalytic activity of the resulting TEMPO
ligand. Indeed, in the present system, the short length of the
spacer connecting the TEMPO unit to the triazine ring prevents its
intramolecular interaction with the copper centre. Moreover, the
third position is now used to anchor the copper/TEMPO catalyst
on a solid support.
26 J. S. Uber, Y. Vogels, D. Van Den Helder, I. Mutikainen, U. Turpeinen,
W. T. Fu, O. Roubeau, P. Gamez and J. Reedijk, Eur. J. Inorg. Chem.,
2007, 4197–4206.
27 O. Kahn, Molecular Magnetism, VCH Publishers, New York,
1993.
28 Z. L. Lu, P. Gamez, I. Mutikainen, U. Turpeinen and J. Reedijk, Cryst.
Growth Des., 2007, 7, 1669–1671.
29 P. Gamez, R. H. Steensma, W. L. Driessen and J. Reedijk, Inorg. Chim.
Acta, 2002, 333, 51–56.
30 G. M. Sheldrick, SHELXS-97 Program for Crystal Structure Determi-
nation, University of Go¨ttingen, Germany, 1997.
31 G. M. Sheldrick, SHELXL-97-2 Program for Crystal Structure Refine-
ment, University of Go¨ttingen, Germany, 1997.
32 P. de Hoog, P. Gamez, W. L. Driessen and J. Reedijk, Tetrahedron Lett.,
2002, 43, 6783–6786.
33 P. Gamez and J. Reedijk, Eur. J. Inorg. Chem., 2006, 29–42.
34 A. W. Addison, T. N. Rao, J. Reedijk, J. van Rijn and G. C. Verschoor,
J. Chem. Soc., Dalton Trans., 1984, 1349–1356.
35 J. Carranza, J. Sletten, C. Brennan, F. Lloret, J. Cano and M. Julve,
Dalton Trans., 2004, 3997–4005.
Acknowledgements
36 Y. Mikata, T. Fujimoto, Y. Sugai and S. Yano, Eur. J. Inorg. Chem.,
The investigations described in this paper were supported by the
Graduate Research School Combination “NRSC Catalysis”, a
joint activity of the graduate research schools NIOK, HRSMC
and PTN. The COST program Action D35/0011 is also kindly
acknowledged.
2007, 1143–1149.
37 W. B. Kim and J. S. Lee, J. Phys. Chem. B, 2003, 107, 9195–9202.
38 P. C. Healy, L. M. Engelhardt, V. A. Patrick and A. H. White, J. Chem.
Soc., Dalton Trans., 1985, 2541–2545.
39 P. Gamez, T. J. Mooibroek, S. J. Teat and J. Reedijk, Acc. Chem. Res.,
2007, 40, 435–444.
40 B. L. Schottel, H. T. Chifotides and K. R. Dunbar, Chem. Soc. Rev.,
2008, 37, 68–83.
41 J. W. Steed and J. L. Atwood, Supramolecular Chemistry, John Wiley
& Sons, Ltd, Chichester, New York, Weinheim, Brisbane, Singapore,
Toronto, 2000.
42 M. Egli and S. Sarkhel, Acc. Chem. Res., 2007, 40, 197–205.
43 T. J. Mooibroek, S. J. Teat, C. Massera, P. Gamez and J. Reedijk, Cryst.
Growth Des., 2006, 6, 1569–1574.
44 M. A. Halcrow, L. M. Rodriguez-Martinez, E. K. Brechin, J. E. Davies,
I. J. Scowen and M. McPartlin, J. Organomet. Chem., 1999, 573, 171–
179.
References
1 R. A. Sheldon, J. Chem. Technol. Biotechnol., 1997, 68, 381–388.
2 S. S. Stahl, Angew. Chem., Int. Ed., 2004, 43, 3400–3420.
3 S. S. Stahl, Science, 2005, 309, 1824–1826.
4 J. March, Advance Organic Chemistry; Reaction, Mechanisms and
Structure, John Wiley & Sons, New York, 4th edn, 1992.
5 Organic Syntheses by Oxidation with Metal Compounds, Plenum, New
York, 1986.
6 R. A. Sheldon, I. W. C. E. Arends, G. J. Ten Brink and A. Dijksman,
Acc. Chem. Res., 2002, 35, 774–781.
45 S. S. Eaton and G. R. Eaton, Coord. Chem. Rev., 1988, 83, 29–72.
This journal is
The Royal Society of Chemistry 2008
Dalton Trans., 2008, 3567–3573 | 3573
©