Roles of phenol groups and auxiliary ligand of copper(II) complexes with tetradentate ligands in the aerobic oxidation of benzyl alcohol

Article abstract of DOI:10.1039/c7dt01716b

Herein, six copper(ii) complexes with multidentate ligands, [Cu(HL₁)(OAc)(HOAc)] (1), [Cu(HL₂)(OAc)] (2), [Cu(HL₃)(OAc)] (3), [CuL₄(OAc)] (4), [Cu(HL₂)Cl] (5), and [Cu(HL₃)Cl] (6) {H₂L₁ = [bis(3-tert-butyl-2-hydroxybenzyl)](2-pyridylmethyl)amine, H₂L₂ = [(3-tert-butyl-2-hydoxybenzyl)(3-trifluoromethyl-2-hydroxybenzyl) (2-pyridylmethyl)]amine, H₂L₃ = [bis(3-trifluoromethyl-2-hydroxybenzyl)] (2-pyridylmethyl)amine, and HL₄ = [bis(2-pyridylmethyl)] (3-tert-butyl-2-hydroxybenzyl)amine}, are reported. The complexes were characterized by UV-vis spectroscopy, high-resolution mass spectrometry, X-ray single-crystal diffraction analysis and electrochemistry. These copper(ii) complexes have been investigated as catalysts for the aerobic oxidation of benzyl alcohol to benzaldehyde mediated by TEMPO (2,2,6,6-tetramethylpiperidinyl-1-oxyl) radical in water at ambient temperature. Mechanistic investigations have revealed that the phenolate/phenol is involved in the intramolecular proton transfer with a bound substrate in catalysis. Hence, the presence of the trifluoromethyl group on the phenol ring significantly affects the catalysis process since the substituent affects the acidity of phenol, and subsequently, the intramolecular proton transfer from the bound substrate. During catalysis, the dissociation of the auxiliary ligand (Cl^- or OAc^-) occurred in the S_N1 pathway, and it is necessary for the substrate to bind. To complete the catalytic cycle, the cleaved auxiliary ligand rebinds to the metal center to regenerate the catalyst.

Full text of DOI:10.1039/c7dt01716b

View Article Online
View Journal
Dalton
Transactions
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: G. Zhan, W.
Zhong, Z. Wei, Z. Liu and X. Liu, Dalton Trans., 2017, DOI: 10.1039/C7DT01716B.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Volume 45 Number
1 7 January 2016 Pages 1–398
Dalton
Transactions
Accepted Manuscripts are published online shortly after
An international journal of inorganic chemistry
www.rsc.org/dalton
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1477-9226
PAPER
Joseph T. Hupp, Omar K. Farha et al.
Efficient extraction of sulfate from water using
framework
a Zr-metal–organic
rsc.li/dalton

Please do not adjust margins
Dalton Transactions
Page 1 of 13
View Article Online
DOI: 10.1039/C7DT01716B
Journal Name
ARTICLE
The roles of the phenol groups and auxiliary ligand of copper(II)
complexes with tetradentate ligands in aerobic oxidation of
benzyl alcohol
Received 00th January 20xx,
Accepted 00th January 20xx
Guangli Zhan,a Wei Zhong,b Zhenhong Wei,a Zhenzhen Liua and Xiaoming Liu*b
DOI: 10.1039/x0xx00000x
Six copper (II) complexes with multidentate ligands, [Cu(HL1)(OAc)(HOAc)] (1), [Cu(HL2)(OAc)] (2), [Cu(HL3)(OAc)] (3),
[CuL4(OAc)] (4), [Cu(HL2)Cl] (5), [Cu(HL3)Cl] (6), {H2L1 = [bis(3-tert-butyl-2-hydroxybenzyl)](2-pyridylmethyl)amine, H2L2 =
[(3-tert-butyl-2-hydoxybenzyl)(3-trifluoromethyl-2-hydroxybenzyl) (2-pyridylmethyl)]amine, H2L3= [bis(3-trifluoromethyl-2-
hydroxybenzyl)] (2-pyridylmethyl)amine,HL4 = [bis(2-pyridylmethyl)] (3-tert-butyl-2-hydroxybenzyl)amine} are reported.
The complexes were characterized by UV–vis spectroscopy, high resolution mass spectrum, X-ray single crystal diffraction
analysis and electrochemistry.These copper(II) complexes have been investigated as catalysts for the aerobic oxidation of
benzyl alcohol to benzaldehyde mediated by TEMPO (2,2,6,6-tetramethylpiperidinyl-1-oxyl) radical in water under ambient
temperature. Mechanistic investigations revealed that the phenolate / phenol involved intramolecular proton transfer
with bound substrate in catalysis and hence the presence of trifluomethyl group on the phenol ring affects significantly the
catalysis since the substituent affects the acidity of the phenol and then the intramolecular proton transfer from the
bound substrate. In the catalysis, the dissociation of the auxiliary ligand (Cl− or OAc−) occurred in SN1 pathway and it is
necessary for the substrate to bind. To complete the catalytic cycle, the cleaved auxiliary ligand rebinds to the metal
center to regenerate the catalyst.
www.rsc.org/
extensively investigated and some of them showed from moderate
to good catalytic efficiency on oxidation of alcohols to aldehydes.
1. Introduction
The structural and mechanistic revelations of galactose oxidase
(GOase) (Fig. 1 and Scheme S1), a copper enzyme catalyzing
oxidation of an alcohol to corresponding aldehyde by molecular
oxygen, have attracted a great deal of attention in both synthetic
and biological community and initiated great enthusiasm in
mimicking synthetically the mononuclear copper center of the
enzyme in the past decades.1, 2 This is not only because its unique
function of catalyzing aerobic oxidation of primary alcohols to
aldehydes with concomitant reduction of dioxygen to hydrogen
peroxide under physiological conditions, but also due to the
enormous industrial demand for aldehydes, which are ubiquitous
“building blocks” in the synthesis of pharmaceuticals, agrochemicals
and fine chemicals. During the past two decades, enormous
structural and spectroscopic models of GOase have been
developed.3-25 In particular, model complexes derived from
mono(pyridyl)alkylamines,3, 19, 25 bis(pyridyl)alkylamine ligands,9, 20,
Fig. 1 The copper center of the active form of galactose oxidase
(GOase).
Amongst the reported catalytic systems, a catalyst without
requiring TEMPO as a co-catalyst is rare.8, 9, 13, 25 In most cases, the
presence of TEMPO for a catalyst based on either Cu(II) or Cu(I) to
function is a must. Such a system was first reported by Semmelhack
and coworkers in 1984.26 Further development turned out that
either Cu(I) or Cu(II) complexes with ligands of “N,N”/“N,O” donor
set could be efficient catalysts for the aerobic oxidation of various
alcohols.27-30 For example, catalytic systems of the type of
copper/2,2'-bipyridine/TEMPO system developed mainly by
21
triazacyclononanes10, 22-24 and salen ligands5, 8, 12, 15 have been
a.School of Chemistry, Nanchang University, Nanchang, Jiangxi 330031, China.
b.College of Biological, Chemical Sciences and Engineering, Jiaxing University,
Jiaxing, Zhejiang 314001, China. E-mail: xiaoming.liu@mail.zjxu.edu.cn,Tel./Fax:
+86(0)573 83643937.
Electronic Supplementary Information (ESI) available:UV–vis spectra of ligands,
internal standard method with calibration curve, characterization and
crystallographic data of the copper complexes and mechanistic investigation. See:
10.1039/x0xx00000x.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 2 of 13
View Article Online
DOI: 10.1039/C7DT01716B
ARTICLE
Journal Name
Sheldon,31-33 Koskinen34 and Stahl35-38 groups showed efficient
activity, particularly on the aerobic oxidation of aliphatic alcohols.
However, despite considerable efforts have been devoted to this
chemistry, many mechanistic issues remain to be answered. For
example, how the electronic density of the metal center affects the
catalytic efficiency and what is the difference in catalytic
mechanism with / without phenolates as part of the coordinating
sphere? Elucidating these mechanistic issues would have
significance in understanding the catalyzing chemistry and
developing novel catalysts for aerobic oxidation of alcohols.
Furthermore, the reaction performs, in general, in organic solvents,
such as acetonitrile. This is not practically favored due to obvious
reason. By considering its environmental benignity and availability,
water ought to be more favored solvent compared to organic ones.
However, exploring catalytic system operational in water is not well
developed.39, 40
As part of our efforts devoting to the chemistry of C–H bond
activation catalyzed by those base metal complexes, such as iron
and copper, under the inspiration of the catalytic functions of
metalloenzymes, we have been interested in developing novel
ligands and their iron / copper complexes as catalysts for direct
hydroxylation of benzene into phenol using H2O2 as the oxidant.
Our recent work reported a number of Fe(III) / Cu(II) complexes for
Scheme 1 Ligands (H2L1, H2L2,H2L3 and HL4) and their copper(II)
complexes 1–6.
the oxidation.41-43 It has been revealed that the electron density of 2. Experimental
the metal centers correlates well to their catalytic activity. This
2.1 General procedures
electronic effect could be tuned accordingly by modifying the main
Chemicals were purchased from Alfa Aesar and Sigma-Aldrich
ligands and varying auxiliary ones. With this preliminary work and
being inspired by the aerobic oxidation of alcohols catalyzed by
GOase, we are interested in employing multidentate ligands bearing
N and phenolate O coordinating atoms to form Cu(II) complexes
and further exploring their catalytic chemistry of the alcohols
and used without further purification unless otherwise stated.
Most of the organic solvents in this work were purified using
drying agents. UV-vis absorption spectra were measured in the
range from 200 nm to 800 nm on a Thermo Scientific Evolution
201 in acetonitrile. Elemental analyses were performed on an
oxidation. Herein, we report the synthesis, characterization of Elementar Vario MICRO. 1H and 13C NMRspectra were
recorded on Varian 400 MR in CDCl3 or d6-DMSO.The aerobic
oxidation of benzyl alcohol to benzaldehydeat room
temperature in water with ambient air as the oxidant was
monitored and quantitatively analyzed by gas chromatography
(Agilent 7890) with a packed column of Restek capillary SE-54.
copper complexes derived from multidentate ligands, H2L1, H2L2,
H2L3, and HL4 (Scheme 1). All the copper complexes
[Cu(HL1)(OAc)(HOAc)] (1), [Cu(HL2)(OAc)] (2), [Cu(HL3)(OAc)]
(3),[CuL4(OAc)] (4), [Cu(HL2)Cl] (5), [Cu(HL3)Cl] (6) were
characterized by UV-vis spectra, high resolution mass spectrum,
elemental analysis, cyclic voltammetry and single-crystal X-ray
diffraction. These copper(II) complexes have been investigated as
catalysts for the aerobic oxidation of benzyl alcohols to
benzaldehydes mediated by TEMPO radical in water at ambient
temperature. Our results indicated that the catalytic activity varies
greatly. Among these complexes, complex 1 could quantitatively
catalyze the oxidation whereas complex 3 showed extremely low
activity. These variations in catalytic efficiency offer us a good
opportunity to probe how the catalysis is affected by the variation
in the coordination sphere of the catalysts. It turns out that the
catalysis can be tuned by both the phenol / phenolate group(s) and
the auxiliary ligands. Mechanistic investigations suggest that the
penta-coordinated copper(II) complex underwent dissociating /
o
The temperature of the GC column was set at 60 C for 1 min
and then was programmed to 150 oC at the rate of 15 oC min−1.
EPR spectra were recorded at 90 K on a Bruker EMX-10/12
spectrometer operating at 9.7 GHz and a cavity equipped with
a Bruker Aquax liquid sample cell. Electrochemistry was
performed in a gas-tighten three-electrode system in which
avitreous carbondisk (φ = 1 mm) was used as a working
electrode, a carbon strip as counter electrode, and Ag/AgCl
(inner reference solution: 0.45 mol L−1[NnBu4]BF4+ 0.05 mol
L−1[NnBu4]Cl in dichloromethane) against which the potential
of ferrocenium
/ ferrocenecouple is 0.55 V in 0.5
molL−1[NnBu4]BF4indichloromethane as described elsewhere.44,
45
Ferrocene was added as an internal standard after
electrochemical data collection was completed and all
rebinding of the auxiliary ligand. Based on our experimental potentials are quoted against ferrocenium / ferrocene couple
(Fc+/Fc). Crystallographic data of the complexes were collected
evidences and those reported in literatures, a general catalytic
on a Gemini diffractometer with graphite-monochromated
Mo–Kα radiation (λ = 0.71073 Å) or Cu–Kα radiation (λ =
mechanism was proposed.
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 3 of 13
View Article Online
DOI: 10.1039/C7DT01716B
Journal Name
ARTICLE
1.54178 Å or 1.54184 Å). The crystal structures were solved
D as a pale yellow oily liquid (1.98 g, 70%) was analogously
using direct methods in SHELXS program and refined by full- synthesized by using the procedure employed for the
matrix least-squares routines, based on F2, using the SHELXL preparation of
by replacing the 3-tert-butyl-2-
C
package.46 Details of crystal data and structure refinement for hydroxybenzaldehydewith3-trifluoromethyl-2-
these complexes are provided in Table S1. Supplementary hydroxybenzaldehyde (8.11 g, 50 mmol) as the reactant. The
crystallographic data can further be found in CCDC via their product was purified by flash chromatography (eluent:
1
CCDC numbers (1529087–1529090, 1529093 and 1529094 for petroleum ether : ethyl acetate = 3 : 2). H NMR (400 MHz,
complexes
2.2 Synthesis
2.2.1 Preparation of 3-tert-butyl-2-hydroxybenzaldehyde (A)
1
–
6
, respectively).
CDCl3): δ 8.56 (d, J = 4.0 Hz, 1H), 7.65 (t, J = 7.6 Hz, 1H), 7.42 (d,
J = 7.8 Hz, 1H), 7.19 (t, J = 8.7 Hz, 2H), 7.10 (d, J = 7.3 Hz, 1H),
6.79 (t, J = 7.6 Hz, 1H), 4.03 (s, 2H), 3.91 (s, 2H). 13C NMR
To a mixture of 2-tert-butylphenol (7.50 g, 50 mmol) in THF (101MHz,d6-DMSO): δ 158.2, 157.9, 149.4, 137.5, 137.2, 132.9,
(100 mL) were added paraformaldehyde (10.20 g, 337 mmol), 126.1, 125.4, 125.0, 123.3, 122.8, 122.8, 117.9, 53.0, 51.1.
anhydrous magnesium dichloride (7.15 g, 75 mmol) and 2.2.5 Preparation of ligand H2L1
trimethylamine (26.1 mL , 187 mmol). The mixture was then To a solution of 2-(3-tert-butyl-2-hydroxybenzylaminomethyl)
heated to reflux for 12 h under stirring. After being cooled to pyridine (1.35 g, 5 mmol) in MeOH (30 mL) was added 3-tert-
room temperature, the mixture was acidified to pH = 3 with butyl-2-hydroxybenzaldehyde (0.89 g, 5 mmol) and acetic acid
dilute HCl and extracted with ethyl acetate (3×30 mL). The (1eq.). Under ice temperature, sodium cyanotrihydroborate
organic layers were combined, dried with anhydrous (0.95 g, 15 mmol) was further slowly added before the
magnesium sulfate and concentrated under reduced pressure reaction was continuously stirred at ambient temperature for
to give a yellow oily liquid which was purified by flash 24 h. The solvents were removed in vacuum to produce a
chromatography (eluent: petroleum ether). Yield: 7.22 g (81%). residue which was dissolved in water (50 mL). The mixture was
1H NMR (400 MHz, CDCl3): δ 11.79 (d, J = 1.7 Hz, 1 H), 9.87 (s, 1 then extracted with CH2Cl2 (3 × 30 mL). The organic layers were
H), 7.54 (t, J = 12.4 Hz, 1 H), 7.38 (dt, J = 17.9, 9.0 Hz, 1 H), combined, dried with anhydrous magnesium sulfate and
6.99–6.88 (m, 1 H), 1.42 (s, 9 H). 13C NMR (101 MHz, CDCl3): δ concentrated under reduced pressure. The crude product was
197.1, 161.2, 138.2, 134.1, 132.0, 120.6, 119.2, 34.8, 29.2.
purified by flash chromatography (eluent: petroleum ether).
Yield: 1.30 g (60%). 1H NMR (400 MHz, CDCl3): δ 10.74 (s, 2H),
2.2.2 Preparation of 3-trifluoromethyl-2-hydroxybenzyl (B)
B
as a pale yellow solid (4.75 g, 50%) was analogously 8.70 (d, J = 4.3 Hz, 1H), 7.69 (t, J = 7.6 Hz, 1H), 7.32–7.26 (m,
synthesized by using the same procedure employed for the 1H), 7.21 (d, J = 7.6 Hz, 2H), 7.09 (t, J = 7.6 Hz, 1H), 6.95 (d, J =
preparation of by replacing the 2-tert-butylphenolwith 2- 7.3 Hz, 2H), 6.74 (t, J = 7.5 Hz, 2H), 3.83 (d, J = 5.2 Hz, 6H),
A
trifluoromethylphenol (8.11 g, 50 mmol) as the reactant.1H 1.42–1.39 (m, 18H). 13C NMR (101 MHz, CDCl3): δ 157.9, 157.3,
NMR (400 MHz, CDCl3): δ 11.71 (s, 1H), 9.94 (s, 1H), 7.81 (d, J = 149.5, 136.7, 136.6, 126.8, 126.0, 122.7, 122.6, 122.4, 118.3,
7.7 Hz, 1H), 7.75 (dd, J = 7.7, 1.3 Hz, 1H), 7.10 (t, J = 7.7 Hz, 53.1, 52.4, 34.7, 29.6.
1H). 13C NMR (101 MHz, CDCl3): δ 196.2, 159.7, 137.3, 134.0, 2.2.6 Preparation of ligand H2L2
124.2, 121.5, 121.2, 119.2.
2.2.3 Preparation
hydroxybenzylaminomethyl)pyridine (C)
Ligand H2L2 as a white solid (1.56g, 70%) was analogously
(3-tert-butyl-2- synthesized by using the procedure employed for the
preparation of H2L1 by replacing the 3-tert-butyl-2-
of
3-tert-butyl-2-hydroxybenzaldehyde (1.78 g, 10 mmol) was hydroxybenzaldehydewith3-trifluoromethyl-2-
added to a stirred solution of 2-aminomethylpyridine (1.08 g, hydroxybenzaldehyde. The product was purified by flash
10 mmol) in MeOH (30mL). The reaction turned to yellow chromatography (eluent : petroleum ether : ethyl acetate = 10
1
6 h at room : 1). H NMR (400 MHz, CDCl3): δ 8.70 (d, J = 4.3 Hz, 1H), 7.75
immediately and the stirring was continued for 5
−
temperature. Sodium tetrahydroborate (1.15 g, 30 mmol) was (t, J = 7.7 Hz, 1H), 7.50 (d, J = 7.7 Hz, 1H), 7.32 (dd, J = 16.7, 7.0
then slowly added under an ice bath, and the mixture was Hz, 2H), 7.22 (d, J = 7.7 Hz, 1H), 7.15 (d, J = 7.7 Hz, 1H), 6.88 (t,
further stirred at ambient temperature for 12 h. Any volatiles J = 6.7 Hz, 2H), 6.74 (t, J = 7.6 Hz, 1H), 3.86 (s, 2H), 3.81 (d, J =
were removed in vacuum to give a residue which was 8.9 Hz, 4H), 1.40 (s, 9H). 13C NMR (101 MHz, CDCl3): δ 156.4,
dissolved in water (50 mL). The mixture was then extracted 156.1, 154.8, 148.0, 138.0, 137.3, 135.2, 127.9, 126.9, 126.6,
with CH2Cl2 (3× 30 mL). The organic layers were combined, 125.5, 124.3, 123.6, 123.0, 122.8, 121.5, 118.6, 118.5, 57.2,
dried with anhydrous magnesium sulfate and concentrated 54.5, 53.9, 34.8, 29.5.
under reduced pressure. The product (a white solid) was 2.2.7 Preparation of ligand H2L3
purified by flash chromatography (eluent: petroleum ether : To
a
solution
of
2-(3-trifluoromethyl-2-
1
ethyl acetate = 3 : 1). Yield: 2.25 g (83%). H NMR (400 MHz, hydroxybenzylaminomethyl)pyridine (1.41 g, 5 mmol) in MeOH
CDCl3):δ 8.58 (d, J = 3.4 Hz, 1 H), 7.66 (td, J = 7.6, 1.4 Hz, 1 H), (30mL) was added 3-trifluoromethyl-2-hydroxybenzyl (0.95 g,
7.21 (d, J = 7.7 Hz, 3 H), 6.84 (d, J = 6.6 Hz, 1 H), 6.72 (t, J = 7.5 5 mmol) and acetic acid (1eq). Under ice temperature, sodium
Hz, 1 H), 3.99 (s, 2 H), 3.91 (s, 2 H), 1.43 (s, 9 H). 13C NMR (101 cyanotrihydroborate (0.95 g, 15 mmol) was further added
MHz, CDCl3): δ 157.9, 157.3, 149.5, 136.7,136.6, 126.8, 126.0, slowly before the reaction was continuously stirred at ambient
122.7, 122.6, 122.4, 118.3, 53.1, 52.4, 34.7, 29.6.
temperature for 12 h. The solvents were removed in vacuum
2.2.4
Preparation
of
2-(3-trifluoromethyl-2- to produce a residue which was dissolved in water (50 mL).
hydroxybenzylaminomethyl)pyridine (D)
The mixture was then extracted with CH2Cl2 (3 × 30 mL). The
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 4 of 13
View Article Online
DOI: 10.1039/C7DT01716B
ARTICLE
Journal Name
organic layers were combined, dried with anhydrous A solution of CuCl2·2H2O (0.09 g, 0.5 mmol) in methanol (3 mL)
magnesium sulfate and concentrated under reduced pressure. was mixed with a methanol solution (3 mL) of ligand H2L2 (0.22
A white solid was collected by filtration, washed successively g, 0.5 mmol). The reaction turned blue and then a blue
with small amounts of methanol (3 × 10 mL) and dried in precipitate formed gradually. After being stirred at room
vacuum. Yield: 1.71 g (75%). 1H NMR (400 MHz, CDCl3): δ 11.84 temperature for 8 h, the precipitate was collected by filtration,
(s, 2 H), 8.69 (d, J = 4.3 Hz, 1 H), 7.79 (td, J = 7.7, 1.6 Hz, 1 H), washed successively with small amounts of H2O and hexanes,
7.49 (d, J = 7.3 Hz, 2 H), 7.37 (dd, J = 6.8, 5.3 Hz, 1 H), 7.23 (d, J respectively, and then dried in vacuum. Blue crystals of
= 8.6 Hz, 2 H), 7.16 (d, J = 7.8 Hz, 1 H), 6.87 (t, J = 7.6 Hz, 2 H), complex
3.86 (s, 4 H), 3.81 (s, 2 H). 13C NMR (101 MHz,d6-DMSO): δ from methanol/diethyl ether. HRMS (ESI, positive), m/z
155.9, 155.7 148.2, 138.7, 135.0, 126.4, 125.8, 124.8, 124.4, 547.1501 (calcd. for [ 547.1507). Elemental
-Cl+CH3CN]+
(C25H26ClCuF3N2O2·1.5H2O, FW =
542.4862), calc. (%): C, 52.73; H, 5.13; N, 4.92. Found (%): C,
5 (236.0 mg, 87%) were obtained by recrystallization
5
=
123.6, 123.1, 119.1, 56.2, 54.9.
analysis for complex 5
2.2.8 Preparation of ligand HL4
Ligand HL4 as a white solid (0.99 g, 55%) was analogously 52.53; H, 4.64; N, 4.75.
synthesized by using the procedure employed for the Complex was synthesized by using the same procedure
preparation of H2L1 by replacing the 3-tert-butyl-2- employed for the preparation of complex by replacing the
hydroxybenzaldehydewith2-pyridinecarboxaldehyde. The ligand H2L2 with ligand H2L3. Complex (221.7 mg, 80%): HRMS
product was purified by flash chromatography (eluent: (ESI, positive), m/z 559.0771 (calcd. for [
-Cl+CH3CN]+
(C22H17ClCuF6N2O2,
6
5
6
6
=
1
petroleum ether : ethyl acetate = 1 : 1). H NMR (400 MHz, 559.0756). Elemental analysis for complex
6
CDCl3): δ 8.54 (s, 2 H), 7.58 (d, J = 7.4 Hz, 2 H), 7.33 (d, J = 7.2 FW = 554.3764), calc. (%): C, 47.66; H, 3.09; N, 5.05. Found (%):
Hz, 2 H), 7.15 (dd, J = 21.0, 5.5 Hz, 3 H), 6.90 (d, J = 5.7 Hz, 1 H), C, 47.12; H, 3.08; N, 4.78.
6.69 (t, J = 7.3 Hz, 1 H), 3.82 (d, J = 20.2 Hz, 6 H), 1.45 (s, 9 H). 2.3 Catalytic assessment
13C NMR (101 MHz, CDCl3): δ 158.0, 156.4, 149.0, 136.7, 136.6,
A typical procedure is as follows: In a reaction vessel fitted
128.0, 126.2, 123.5, 122.7, 122.2, 118.2, 59.3, 57.7, 34.8, 29.5.
with a water condenser was added benzyl alcohol (0.55 g, 5
2.2.9 Preparation of complexes 1–4
mmol), copper complex (0.015 mmol, 0.3 mol%), K2CO3(1.25
mmol, 2.5 mol%), TEMPO (0.25 mmol, 5 mol%) and finally
water (5 mL). The reaction was carried out at 25 °C for 24 h
under rigorously stirring before it was extracted with ethyl
acetate (3 × 5 mL). The organic layers were combined, dried
over anhydrous Na2SO4 and 0.5mL of 1,2-dichlorobenzene
(138.98 mg / mL) in CH3CN was added to the organic phase as
an internal standard. The products were diluted to 20 mL with
ethyl acetate and analyzed by gas chromatography using the
internal standard method. Quantitative analysis of
benzaldehyde was achieved by establishing their calibration
curve with a linear equations under optimized conditions, AR =
A solution of Cu(CH3COO)2·H2O (0.11 g, 0.55 mmol) in
acetonitrile (5 mL) was mixed with a dichloromethane solution
(3 mL) of ligand H2L1 (0.22 g, 0.5 mmol) and the reaction
turned dark blue. After being stirred at room temperature for
8 h, the solution was centrifuged and the green solid was
washed with H2O followed with hexanes and finally dried in
vacuum. Dark blue crystals of complex
1 (263.6 mg, 86%) were
obtained by recrystallization from dichloromethane/hexanes.
HRMS (ESI, positive), m/z 494.1960 (calcd. for [
HOAc]+
494.1995), 535.2287 (calcd. for
HOAc+CH3CN]+
1
-OAc-
-OAc-
=
[
1
=
535.2260). Elemental analysis for complex 1
0.01716w
where AR is the ratio of the peak areas of the analyte
(benzaldehyde) and the internal standard 1,2-
−
0.1751 (R2 = 0.9988) for benzaldehyde (Fig. S1),
(C32H42CuN2O6, FW = 614.2420), calc. (%): C, 62.57; H, 6.89; N,
4.56. Found (%): C, 62.84; H, 6.89; N, 4.22.
Complexes
procedure employed for the preparation of complex
replacing the ligand H2L1 with ligand H2L2 H2L3 and HL4
respectively. Complex (254.7 mg, 90%): HRMS (ESI, positive),
m/z 588.1378 (calcd. for [ 588.1273), 547.1547 (calcd.
+Na]+
for 547.1508). Elemental analysis for
-OAc+CH3CN]+
complex (C27H29CuN2O4, FW = 566.0802), calc. (%): C, 57.29;
H, 5.16;N, 4.95. Found (%): C, 57.78; H, 4.95; N, 5.09. Complex
(231.2 mg, 80%): HRMS (ESI, positive), m/z 559.0736 (calcd.
for 559.0756). Elemental analysis for
-OAc+CH3CN]+
complex (C24H20CuF6N2O4, FW = 577.9704), calc. (%): C, 49.88;
H, 3.49; N, 4.85. Found (%): C, 49.83; H, 3.43; N, 4.72. Complex
(200.5 mg, 83%): HRMS (ESI, ), m/z 423.1409 (calcd. for [
OAc]+ = 423.1372), 464.1681 (calcd. for [ -OAc+CH3CN]+
464.1637), 905.2899 (calcd. for [2* 905.2877).
-OAc]+
Elemental analysis for complex (C25H29CuN3O3·1.5H2O, FW =
2–
4
were synthesized by using the same
1
by
dichlorobenzene, w (mg) is the mass of the analytes. The yield
of benzaldehyde was calculated as follows: benzaldehyde
(mmol) / benzyl alcohol initially used (mmol) × 100%.
,
,
2
2
=
[2
=
2
3. Results and discussion
3.1 Synthesis of ligands and their copper complexes
3
The multidentate ligands, H2L1, H2L2, H2L3 and HL4, were
[3
=
synthesized by using modified literature procedures with some
modifications (Scheme 2).47, 48 Treatment of ortho-substituted
phenols with paraformaldehyde and MgCl2with the presence
3
4
+
4-
of Et3N under reflux gave substituted salicylaldehydes
in good yields.49 Aldehydes
and reacted furtherwith2-
aminomethylpyridine to form the secondary amines and
respectively. Ligands H2L1 H2L2 H2L3 and HL4 were
subsequently obtained by the reaction of and with
A and B
4
=
A
B
4
=
C
D,
4
,
,
510.0935), calc. (%): C, 58.87; H, 6.32; N, 8.24. Found (%): C,
58.90; H, 6.22; N, 8.20.
C
D
corresponding aldehydes, respectively, employing sodium
cyanoborohydride as reducing reagent in the presence of a
2.2.10 Preparation of complexes 5 and 6
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 5 of 13
Journal Name
View Article Online
DOI: 10.1039/C7DT01716B
ARTICLE
small amount of acetic acid.48 By using the mild reducing agent (Fig. S3), the spectra of these Cu(II) complexes exhibit similar
NaBH3CN under acidic condition, the further reduction of the spectral profiles, displaying a dominating band at ca. 480 nm (ε
aldehydes were inhibited and the reaction yields of the ligands = 800-1300 L mol−1 cm−1) and a less intense shoulder at ca. 700
improved from less than 40% to around 70%. Ligands H2L1 and nm (ε = 100-270 L mol−1 cm−1) (Table S3). Comparison with the
HL4 were prepared in good yield (about 80%).19, 50, 51 However, literature data9, 52 shows that the former band arises from a
the procedure employed in this work avoided N-alkylation of phenolate-to-copper(II) charge transfer (CT) while the latter is
an amine with substituted bromides simplified the reaction.
assigned to d–d transitions.
O
N
H
O
Cu
F
N
F
F
AcO
2
F
F
H2L2
N
O
H
H2L3
F
N
O
H2L1
H
O
Cu(
OAc) —H
2O
Cu
2
O
Cu
N
F
F
AcO
N
OAc
HL4
F
AcO
H
3
1
N
O
N
Cu
AcO
N
4
F
F
N
O
N
O
F
H2L2
H2L3
H
H
CuCl2—2H2O
O
O
Cu
Cu
F
F
F
N
N
F
F
F
Cl
Cl
5
6
Scheme 3 Synthesis of copper complexes
1
–
6.
Scheme 2 Synthesis of ligands H2L1, H2L2, H2L3 and HL4.
The synthetic routes of copper complexes are shown in
Scheme 3. Treatment of Cu(OAc)2·H2O with the four ligands in
the absence of base led to the formation of mononuclear
complexes 1–4, respectively. In complexes 1–3, one of the
phenol groups is not being deprotonated. To examine the
influence of an auxiliary ligand coordinated to the metal center
on the catalytic activity, ligands H2L2 and H2L3 were reacted
respectively with CuCl2·2H2O and mononuclear complexes
5
and 6 formed. Similar to those in complexes 1–3, one of the
phenol groups in these complexes is also not being
deprotonated. For comparison, chloride-bound analogue were
attempted to be prepared by the reaction of ligand H2L1 with
CuCl2·2H2O. But to our biggest surprise, although a complex
analogous to complexes
2 and 3 was obtained, preliminary
result showed that one of the phenol rings was chemically
modified (Fig. S2). This exception makes it an unsuitable
complex for the supposed comparison and we will not discuss
it further in this work.
Fig. 2 UV–Vis absorption spectra of complexes 1–6
(10−4 mol
L−1) in MeCN
Complexes 1–6 are soluble in polar solvents such as MeOH,
DMF and MeCN, and slightly soluble in water. All complexes
were synthesized in decent yields (over 80%) and fully
characterized by UV-vis spectra, high resolution mass
spectrum, elemental analysis, cyclic voltammetry (CV, vide
infra) and X-ray single-crystal diffraction. The UV-vis spectra of
3.2 X-ray crystal structures
Crystals suitable for X-ray diffraction analysis were obtained
upon slow evaporation in methanol / dichloromethane or
methanol / diethyl ether solution. The ellipsoid plots of
complexes 1–6 are depicted in Fig. 3. All the crystallographic
complexes
exception of two intense absorption bands at around 250 and
300 nm deriving from intraligand * and n→ * transitions
1–6 and the ligands are shown in Fig. 2. With the
data are given in Table S1 and selected bonding parameters
are tabulated in Table S2. The geometries around the copper
π
→π
π
center in complexes
2–
6
can be considered as a distorted
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 6 of 13
View Article Online
DOI: 10.1039/C7DT01716B
ARTICLE
Journal Name
square pyramid with “N1N2O1O3”, “N1N2O1Cl1” or “N1N2O1O2”
as the basal plane. The equatorial square plane around the
Cu(II) center in these complexes were formed by one tertiary
amine N1, one pyridine N2 and one phenolato oxygen O1
donors from the ligand, as well as one oxygen O3 from an
acetate anion (complexes
and ) or pyridine N3 (complex
occupied by a non-deprotonated phenol while the other axial
binding site is unoccupied. But complex adopts a distorted
1–
3) or chloride Cl1 (complexes
5
6
4
). The axial positions are
1
octahedral geometry in which the sixth coordinating site is
loosely bound by an acetic acid.
The disparity of the Cu–N bond distances, the one assigned
to Cu–Npyridine (Cu1–N2 and Cu1–N3) being slight shorter than
the bond (Cu1–N1) concerning the tertiary amine N-atoms
(Table S2), is usual and comparable with those reported in the
literatures.25, 43, 53 The distances of Cu1–O2 bond assigned to
Cu–Ophenol in complexes
the Cu1–O1 bonds, reflecting the weak donor capability of the
phenol in these complexes (Table S2). However, complex
1–3, 5 and 6 are over 0.4 Å longer than
1
adopts a octahedral coordination geometry because the
bound acetic acid, as mentioned above, proximity to the
copper center (Cu1⋯O5 bond distance of 2.645 Å) led to a six-
coordinated mode. In this case, the Cu environment will be
defined as “N1N2O1O3” in the equatorial plane and two O-
atoms from the chelating ligand and the acetic acid,
respectively, in the two axial sites. It is noticeable that the
Fig. 3 Crystal structures of complexes
1–6 (most of the
hydrogen atoms and solvent are omitted for clarity) and their
numbering begins from the top-left to the bottom right with
complex 6 as the last one.
Cu1–O2 bond distance (2.637(2) Å) in complex
longer than those observed in complexes
1
is much
and
2,
3
,
5
6,
3.3 Catalytic oxidation of benzyl alcohol to benzyl aldehyde
To optimize the reaction conditions, complex was used as
indicative of very weak coordination between the phenol and
metal center. The distances of Cu–N and other Cu–O bonds are
1
the catalyst. It was found that no catalytic activity could be
observed without TEMPO (Entries 1 and 2, Table 1). In
analogues copper complexes catalytic systems, aerobic
oxidation of benzylic alcohol to benzaldehyde by using air as
similar to those observed in complexes
that in complexes , the auxiliary ligand acetate anion forms
a strong intramolecular hydrogen bond, O2–H2 O4, with the
hydrogen atom of the axial phenol to form a six-member ring,
Fig. 3. In complex
2–6. It is noteworthy
1–3
⋯
3
, further intramolecular hydrogen bond of an oxidant in the absence of TEMPO has been achieved.13, 25 It
the same O atom with one F atom on the axial phenol ring is
observed to form again a six-member ring, Fig. 3. This may
explain why the acetate anion dissociates more difficultly than
was argued that the strong electron-donating effect of the
tert-butyl group can significantly diminishes the ability of the
phenolate ring to delocalize the phenoxy radical during the
catalysis, particularly on the ortho-position of the equatorial
phenolate ring.13, 25, 54 Furthermore, absence of TEMPO means
that the metal center ought to be sufficiently nucleophilic to
activate oxygen. Indeed, there was a report when the copper
center is strongly nucleophilic, good catalytic efficiency could
be also achieved without the addition of TEMPO.55
Cl− as indicated by its conductivity in acetonitrile
(vide
infra). The involvement of F atom in forming intramolecular
hydrogen bond is also observed in complex
3.
6 as shown in Fig.
In addition to the radical, both the base and solvent affect
severely the catalytic reaction as well (Entries 4-12, Table 1).
As shown in Table 1, in aqueous medium, either Cs2CO3 or
K2CO3 gave nearly quantitative yield (Entries 4 and 5, Table 1).
Throughout the investigation, K2CO3 was employed as the
external base by using water as the solvent. To examine
whether the application of an external base depends on the
acidity of the phenol groups, complex
3 which bears a
trifluomethyl group was used as the catalyst under various
basic conditions (Entries 18-22, Table 1). The results show that
both complexes prefer K2CO3 as the external base.
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 7 of 13
View Article Online
DOI: 10.1039/C7DT01716B
Journal Name
ARTICLE
aReaction conditions: solvent(s) (5 mL), benzyl alcohol (5
mmol), catalyst (0.015 mmol), air, K2CO3 (1.25 mmol), TEMPO
(0.25 mmol), 25 oC, 24 h.
Without any ligand, simple copper salts, either (Cu(OAc)2 or
CuCl2), gave quite low yields whereas the addition of bipyridine
can improve significantly the catalysis (Entries 13 and 14; 23
and 24, Table 1). This is attributed to that coordinating the
ligand to the metal center increases its electron density and
hence improves the catalysis. Using (NH4)2S2O8 or (C6H5CO)2O2
to replace TEMPO led to nearly no activity (Entries 15 and 16,
Table 1).
bYields calculated by GC analysis.
cH2O : CH3CN = 1 : 1
dReaction conditions: solvent (5 mL), benzyl alcohol (5 mmol),
catalyst (0.015 mmol), air, K2CO3 (1.25 mmol), TEMPO (0.125
o
mmol), 25 C, 24 h. When TEMPO was changed to 1%, 0.5%
and 0.3%, the yield dropped further to 61%, 39% and 28%,
respectively.
Table 1 Optimizing the reaction conditions for the oxidation of
benzyl alcohol to benzylaldehyde.a
Entry
Catalyst
Base / solvent
K2CO3/H2O
K2CO3/CH3CN
K2CO3/CH3CN
K2CO3/H2O
Cs2CO3/H2O
H2O
Yield (%)b
trace
Under the optimized conditions, the rest of the complexes
were examined for their catalysis on the oxidation of benzyl
alcohol, Table 2. As shown in Table 2, it was found that
1
1
complex
1 exhibited the best catalytic performance among the
2
1
trace
copper complexes. By further analyzing the yields shown in
Table 2, it turns out that there are three factors affecting
significantly the catalytic performance of these complexes, the
substituents on the phenol groups, the auxiliary ligands, and
the number of phenol group. As suggested by the reduction
potentials (Table 2 and Fig. S4), either varying the substituents
on the phenol groups or the number of the phenol group, the
reduction potentials does not change substantially, which
suggests that the two factors do not have much direct
electronic effect on the copper center.
3
1/TEMPO
20 ± 3
96 ± 3
97 ± 1
21 ± 3
26 ± 3
71 ± 1
61 ± 1
trace
4
1/TEMPO
5
1/TEMPO
6
1/TEMPO
7
1/TEMPO
K2CO3/H2O/CH3CN c
KOC4H9/H2O
Et3N/H2O
8
1/TEMPO
However, replacing the acetate with a chloride shifts the
reduction potential positively by about 300 mV. For complex 1,
9
1/TEMPO
no comparison can be made due to lacking of its chloride
analogue as mentioned earlier. However, for the other two
10
11
12
13
14
15
16
17d
18
19
20
21
22
23
24
TEMPO
K2CO3/H2O
Et3N /CH3CN
Et3N /CH2Cl2
K2CO3/H2O
K2CO3/H2O
K2CO3/H2O
K2CO3/H2O
K2CO3/H2O
K2CO3/H2O
Et3N/H2O
pairs, complexes
2 and 5; 3 and 6, this replacement enhanced
1/TEMPO
59 ± 1
15 ± 3
18 ± 1
28 ± 3
7 ± 3
greatly the catalytic activity, Table 2. The observations suggest
that relatively low electron density on the metal center is
beneficial to the catalysis, which is opposite to what we
reported previously in the oxidation of benzene to phenol by
hydrogen peroxide catalyzed by iron or copper complexes, that
1/TEMPO
Cu(OAc)2/TEMPO
CuCl2/TEMPO
1 / (NH4)2S2O8
1 / (C6H5CO)2O2
1/TEMPO
is, complexes with more negative potentials showed better
catalytic activity.42,
43
This may be due to that in the
hydroxylation of benzene, the oxidant binding to the metal
center to generate hydroxyl radical is essential in the catalysis.
In the oxidation of alcohols, substrate binding may be
important since strong Lewis acidity, i. e. low electron density
on the metal center or more positive reduction potential, is an
advantage for this process. The observations indicate also that
although the presence of trifluoromethyl group on the phenol
ring(s) does not affect significantly the electron density on the
metal center, it does drastically decrease the catalytic activity.
Therefore, questions arisen are: How does the trifluoromethyl
group on the phenol ring(s) affect the catalytic activity? What
is the role of the phenol group in the catalysis? How does the
auxiliary ligand correlate to the catalytic activity? There is no
doubt that having answers to these questions might shed
some light on the catalytic mechanism.
6 ± 1
81 ± 2
14 ± 2
11 ± 1
20 ± 5
13 ± 3
33 ± 3
67 ± 4
63 ± 1
3/TEMPO
3/TEMPO
3/TEMPO
KOC4H9/H2O
KOH/H2O
3/TEMPO
3/TEMPO
Cs2CO3/H2O
K2CO3/H2O
K2CO3/H2O
bpy/TEMPO/CuCl2
bpy/TEMPO/Cu(OAc)2
Table 2 Comparison in catalytic activity on the aerobic
oxidation of benzyl alcohol to benzyl aldehyde.a
Complex Auxiliary
Number
Number cEp(Cu2+ Yield(%)b
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 8 of 13
View Article Online
DOI: 10.1039/C7DT01716B
ARTICLE
Journal Name
ligand
of phenol of
group
−
CF3
group
→
Cu+)
dissociate first for the substrate to bind. As shown in Table 1,
complex exhibited enhanced activity in polar solvent. This
1
1
2
3
4
5
6
Acetate
Acetate
Acetate
Acetate
Cl−
2
2
2
1
2
2
0
1
2
0
1
2
−
−
−
−
−
−
1.08
1.05
0.97
1.00
0.67
0.67
96
45
14
70
82
50
±
±
±
±
±
±
3
1
2
1
2
2
solvent-dependent catalytic activity suggests strongly that a
SN1 mechanism may be adopted in the catalysis. To confirm
this, we measured simply their conductivity (Table S4). Indeed,
complexes
5 and 6 show much large conductivity compared to
Cl−
their acetate-bound analogues. The relative difficulty in
dissociation of the acetate from the metal center is in good
agreement with the intramolecular hydrogen bonding
discussed earlier, which may strengthen its coordination to the
copper center to deter its dissociation. For the bound chloride,
no such an intramolecular hydrogen bonding exists. This may
explain their variation in catalytic activity with the auxiliary
aReaction conditions: solvent(s) (5 mL), benzyl alcohol (5
mmol), catalyst (0.015 mmol), air, K2CO3 (1.25 mmol), TEMPO
(0.25 mmol), 25 oC, 24 h.
bYields calculated by GC analysis.
3.4 Mechanistic investigation
It is well known that a phenol radical in the galactose oxidase ligands.
plays an important role in the catalytic oxidation of alcohol by
If the dissociation is a necessary step in the catalysis, to
oxygen.2, 6-9, 48, 56 As the schematic structural view of the metal regenerate the catalyst, the initially cleaved auxiliary ligand
center indicated (Fig. 1), the copper center is surrounded by must undergo rebinding. To confirm this hypothesis, we
two imidazole and two phenol groups. Being inspired by this examined how the catalysis is affected by additionally added
chemistry, we synthesized three tetradentate ligands, H2L1
,
–3
either acetate or chloride by using complex 6 as the catalyst.
which bear two phenol groups and HL4 in which there is only The results are tabulated in Table 3. It is clear that acetate
one phenol group (Scheme 2). The reaction of these ligands affects severely the catalysis while chloride is much less
with Cu(OAc)2 and / or CuCl2 led to complexes 1–6. Since there influential on the catalysis despite the over doubled
have been many reports showing that it is not a must for a concentration of sodium chloride compared to that of sodium
copper complex to possess phenol groups to function as acetate. The addition of chloride would deter the dissociation,
catalysts for the alcohol oxidation,27,
28, 57, 58
it comes to a on one hand, to suppress the activity and on the other hand,
play facilitate the re-binding of the chloride to restore the catalyst.
But the latter effect is off-set by the former one. Therefore, it
question, whether the phenol groups in complexes
such a role of forming a radical at all.
1
–
6
To clarify this, we tuned the ligand by changing the is not surprising that the presence of extra chloride did not
substituents on the phenol ring from C(CH3)3 to CF3 and varied significantly change the activity. However, the presence of
the number of phenol group in the ligand (HL4). As suggested extra acetate exhibited an entirely different scenario in
by the reduction potentials of the complexes (Table 2), the affecting the catalysis. While the added acetate would not
change in substituent exerted weak electronic effect on the substantially exert influence on the dissociation of the chloride
metal center. However, the catalytic activity changed from complex
dramatically with the alterations. When the auxiliary ligand is chloride in the re-binding step to produce presumably species
the same (acetate), the substituent ortho to the phenol group analogous to complex
rather than its parent complex . As
switching from C(CH3)3 to CF3 group decreases the activity shown in Table 2, complex
is much less efficient than
significantly. One CF3 group led to decreases in activity by half. complex
. Therefore, this is in agreement with the observed
6, it competes definitely with the dissociated
3
6
3
6
When both C(CH3)3 groups were replaced by a CF3 group, the catalytic behaviours. Thus, in the catalysis, dissociation and re-
activity decreased by 80%. Reducing the number of phenol binding of the auxiliary ligand are two of the necessary steps.
group in the multidentate ligand (HL4, complex 4), the activity
dropped by about 30%. It is clear that the phenolate / phenol Table 3 Comparison in catalytic activity on the aerobic
groups in the catalysis are not a spectator. Furthermore, the oxidation of benzyl alcohol to benzyl aldehyde by complex
effect is not exerted through altering the electronic density of the presence of various amount of chloride / acetate salt.a
Yield (%)b
the metal center as indicated by their hardly changed
6 in
Entry
Added anion (mmol)
/
reduction potentials.
As we observed before,43 an alcohol can bind to the sixth
1
2
3
4
5
6
7
50
48
31
26
47
42
41
±
±
±
±
±
±
±
2
1
3
1
1
2
1
CH3COONa (0.075 mmol)
CH3COONa (0.225 mmol)
CH3COONa (0.3mmol)
NaCl (0.15 mmol)
NaCl (0.45 mmol)
NaCl (0.75 mmol)
binding
site.
Electronic
spectrally-monitoring
and
electrochemistry indicate substantial change when the
substrate is added, Fig. S5. This is also in agreement with the
EPR evidence (Fig. S6). There is a slight exception for complex
1
which bears a loosely bound acetic acid at its axial position.
aReaction conditions and yield calculations are the same as
those described in Table 1 and TEMPO was employed in each
entry.
This acetic acid ought to dissociate easily in water. Thus for the
substrate binding, there are two possible pathways. The
substrate can approach the metal center at the second axial
position and then the auxiliary ligand dissociates to restore the
preferred five-coordinated mode, that is, SN2 pathway. If SN1
bYields calculated by GC analysis.
pathway is adopted, the auxiliary ligand, OAc− or Cl−
, must
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 9 of 13
Journal Name
View Article Online
DOI: 10.1039/C7DT01716B
ARTICLE
As shown in Table 1, the employment of an appropriate
base can significantly improve the catalysis and K2CO3 / Cs2CO3
are the most suitable ones for the catalysis. In aqueous
medium, these weak bases can maintain
a certain
concentration of OH− in solution. During the catalysis,
deprotonating the substrate is a necessary step and this
explains the essentialness of the base in the catalysis.
However, for complexes 1–3, 5 and 6, they possess a weakly
bound and unprotonated phenol group and hence, it is also
deprotonable in addition to the substrate. Since phenol is
relatively a strong acid whose pKa is about 10 whereas the pKa
value of benzyl alcohol (the substrate) is over 15, the bound
phenol would be first deprotonated to generate its phenolate
form. Subsequently, this phenolate can deprotonate the
bound substrate via intramolecular proton transfer. In other
word, the phenol group may just be an internal base to
facilitate the deprotonation of the bound substrate. Without
such a phenol, an external base will take this role. This explains
why a copper complex without a phenol group works as well.
The presence of the –CF3 group(s) shows no much electronic
effect on the metal center as suggested by the reduction
potentials but decreases very much the catalytic activity of the
copper complexes as shown in Table 2. This may further
strengthen the argument that the phenol maybe act as an
internal base since the basicity of the corresponding phenolate
becomes much weaker due to the strong electron-withdrawing
nature of –CF3 group. By examining the effect of an external
Scheme 4 The proposed catalytic mechanism with the Cu(II)
complexes as the catalyst. For simplicity, its schematic
structure is highly simplified by emphasizing the coordinating
atoms and replacing the rest with wavy lines.
3.5 Oxidation of various alcohols catalyzed by complex 1
To find out whether the complexes catalyze the oxidation of
other alcohols, complex
the optimized reaction conditions. As shown in Table 4,
complex exhibited effective catalytic performance for the
1 was employed as a catalyst under
base on the catalysis of complex
3 (entries 18-22, Table 1), it is
suggested that the decrease in catalytic activity is probably
due to the decrease in the basicity of the phenolate bearing
two –CF3 groups.
1
oxidation of the benzyl alcohol or its analogues. Apparently,
the electronic nature of substituent groups on benzyl alcohols
exerts impact on the catalytic oxidation. In general, aromatic
compounds with electron-donating substituents (Me, OMe, Cl,
Br) (Table 4, entries 1–4) showed high reaction activity
compared to the substrates with electron-withdrawing
substituents (NO2, CF3) (Table 4, entries 6 and 8). The inactivity
may be attributed to their poorer electron donating capability
and binding affinity compared to benzyl alcohol. Bond
That TEMPO binds to a metal center is not unprecedented.
However, in our case, both EPR data and electrochemical
behaviour indicate that the interaction of TEMPO with the
copper (II) center is not significant (Figs. S5 and S6). Quite
likely, TEMPO abstracts one of the H atoms of the methylene
group of the phenylmethanolate (the deprotonated and bound
substrate) to form a ketyl radical. That the reaction yield
decreased when the usage of TEMPO was reduced may further
support the role of TEMPO in the catalysis. Consequently, one
electron transfer from the ketyl radical to Cu(II) occurs to yield
the product aldehyde and a four coordinated Cu(I) species.1, 2,
dissociation energy (BDE) of the
the substituents. But for the C
α −H bond could vary with
H bonds of these substrates,
-C
−
such a change is not significant68 and in this case, it may not
contribute too much to the lowering of the reaction yield.
Moderate product yields could be also obtained for substrates
containing heterocycle or allylic alcohols which are not quite
surprising since somewhat these substrates are analogous to
benzyl alcohol (Table 4, entries 5 and 9). For aliphatic or
secondary alcohols, the complex is almost inactive under the
same conditions (Table 4, entries 10–13). For these alcohols,
59, 60
Then O2 reacts readily with this reduced Cu(I) species to
form supposedly a superoxide which binds to the metal center.
During the process, the metal center is brought back to Cu(II).
Then the bound superoxide is further reduced to peroxide
17, 30, 61
−
(HO2 ) by TEMPOH to regenerate the radical TEMPO.
Finally, to complete the catalytic cycle, the dissociated
auxiliary ligand re-bind to the metal center to restore the
catalyst. Based on the above discussion alongside with those
mechanisms reported in the literatures,2, 30, 38, 62-67 a catalytic
mechanism for the oxidation of benzyl alcohol catalyzed by the
the BDE of the C−H bond may play a significant role. In
addition to this BDE contribution, steric factor may also lead to
the inactivity for secondary alcohols.
complexes (1–6) is depicted in Scheme 4. In this mechanism,
Table 4 Selected alcohols for their aerobic oxidation to
aldehydes or ketones catalyzed by complex 1 a
involving the dissociation of the auxiliary ligand (acetate or
chloride) for the substrate to bind resembles highly the
enzymatic catalysis.
.
Entry
Substrate
Yield(%)b
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 10 of 13
View Article Online
DOI: 10.1039/C7DT01716B
ARTICLE
Journal Name
complexes were fully characterized by a number of analytical
techniques including X-ray single crystal diffraction analysis.
1
99±0.2
99±0.47
92±2
These complexes possess
a
coordinating atmosphere
. Complex
resembling that of the GOase except for complex
1
1
2
3
4
showed the highest catalytic activity with high selectivity
towards the oxidation of benzyl alcohol under the optimized
reaction conditions. Mechanistic investigation allowed us to
propose a catalytic mechanism, which involves the dissociation
/ re-binding of the auxiliary ligand (OAc− or Cl−) in SN1 pathway.
The dissociation and the substrate binding occur likely
concomitantly. In the catalysis, the intramolecular proton
transfer, Step 3 in Scheme 4, may be one of the important
steps. This is indirectly supported by that the presence of the
85±3.5
−
CF3 group weakens the basicity of the phenolate and hence
5
55±4
the intramolecular proton transfer. The phenol group of the
catalysts could act as an internal base to facilitate the
deprotonation of the bound substrate although further
investigation is needed to support such a role for the phenol
group in the catalysis. Acetate affects the catalysis via forming
intramolecular hydrogen bonding with the axial phenol and
decreases the Lewis acidity of the metal center.
6
7
8
51±1.1
37±3.2c/16±4d
46±2.1
Acknowledgements
The authors would like to thank the National Natural Science
Foundation of China (Grant nos. 21571083, 21301071) and the
Government of Zhejiang Province (Qianjiang Professorship for
XL) for supporting this work. We also thank Prof. Yingwu Lin at
the University of South China, Prof. Jihu Su at China University
of Science and Technology and Prof. Jianfeng Li at the
University of Chinese Academy of Sciences for assistance with
the EPR data collection and / or preliminary analysis.
9
45±0.6
10
trace
Notes and references
11
trace
1. M. M. Whittaker and J. W. Whittaker, J. Biol. Chem., 1988,
263, 6074–6080.
2. J. W. Whittaker, Chem. Rev., 2003, 103, 2347–2363.
3. M. M. Whittaker, W. R. Duncan and J. W. Whittaker, Inorg.
Chem., 1996, 35, 382-386.
12
13
Trace/10e
trace
4. O. Das and T. K. Paine, RSC Green Chem. Ser., 2015, 28, 40–
69.
5. C. T. Lyons and T. D. Stack, Coord. Chem. Rev., 2013, 257
528–540.
,
6. F. Thomas, Eur. J. Inorg. Chem., 2007, 2007, 2379–2404.
aReaction conditions and yield calculations were the same as
those described in Table 1.
7. J. W. Whittaker, Arch. Biochem. Biophys., 2005, 433, 227–
239.
bYields calculated by GC-MS analysis.
8. Y. Wang, J. L. DuBois, B. Hedman, K. O. Hodgson and T. D. P.
Stack, Science, 1998, 279, 537–540.
cp-phthalaldehyde.
dp-(Hydroxymethyl)benzaldehyde.
e80 oC.
9. A. Philibert, F. Thomas, C. Philouze, S. Hamman, E. Saint-
Aman and J.-L. Pierre, Chem. Eur. J., 2003, 9, 3803–3812.
10. B. A. Jazdzewski, A. M. Reynolds, P. L. Holland, V. G. Young, S.
Kaderli, A. D. Zuberbühler and W. B. Tolman, J. Biol. Inorg.
4. Conclusions
Chem., 2003, 8, 381–393.
In summary, we have described the synthesis and
11. D. Rokhsana, A. E. Howells, D. M. Dooley and R. K. Szilagyi,
characterization of six bioinspired copper(II) complexes
1–6
Inorg. Chem., 2012, 51, 3513–3524.
derived from four multidentate ligands. All these copper
10 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 11 of 13
Journal Name
View Article Online
DOI: 10.1039/C7DT01716B
ARTICLE
12. R. C. Pratt, C. T. Lyons, E. C. Wasinger and T. D. Stack, J. Am. 39. B.-T. Chen, K. V. Bukhryakov, R. Sougrat and V. O. Rodionov,
Chem. Soc., 2012, 134, 7367–7377. ACS Catal., 2015, , 1313–1317.
13. A. John, M. M. Shaikh and P. Ghosh, Dalton Trans, 2008, 40. B. H. Lipshutz, M. Hageman, J. C. Fennewald, R. Linstadt, E.
5
2815–2824.
Slack and K. Voigtritter, Chem. Commun., 2014, 50, 11378–
11381.
14. S. K. Alamsetti, S. Mannam, P. Mutupandi and G. Sekar,
Chem. Eur. J., 2009, 15, 1086–1090.
41. E. Gu, W. Zhong, H. Ma, B. Xu, H. Wang and X. Liu, Inorg.
Chim. Acta, 2016, 444, 159–165.
15. M. Orio, O. Jarjayes, H. Kanso, C. Philouze, F. Neese and F.
Thomas, Angew. Chem. Int. Ed., 2010, 49, 4989–4992.
16. H. Shi and Y. Yin, Inorg. Chim. Acta, 2014, 421, 446–450.
42. B. Xu, W. Zhong, Z. Wei, H. Wang, J. Liu, L. Wu, Y. Feng and X.
Liu, Dalton Trans, 2014, 43, 15337–15345.
17. E. Safaei, L. Hajikhanmirzaei, B. Karimi, A. Wojtczak, P. Cotič 43. L. Wu, W. Zhong, B. Xu, Z. Wei and X. Liu, Dalton Trans, 2015,
and Y.-I. Lee, Polyhedron, 2016, 106, 153–162. 44, 8013–8020.
18. R. K. Debnath, A. Kalita, P. Kumar, B. Mondal and J. N. 44. X. H. Zeng, Z. M. Li, Z. Y. Xiao, Y. W. Wang and X. M. Liu,
Ganguli, Polyhedron, 2013, 51, 222–227. Electrochem. Commun., 2010, 12, 342–345.
19. D. Zurita, I. Gautier-Luneau, S. Ménage, J.-L. Pierre and E. 45. X. H. Zeng, Z. M. Li and X. M. Liu, Electrochim. Acta, 2010, 55
Saint-Aman, J. Biol. Inorg. Chem., 1997, , 46–55. 2179–2185.
20. S. Itoh, M. Taki, S. Takayama, S. Nagatomo, T. Kitagawa, N. 46. G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr.,
,
2
Sakurada, R. Arakawa and S. Fukuzumi, Angew. Chem. Int.
Ed., 1999, 38, 2774–2776.
2008, 64, 112–122.
47. J.-B. Wang, L.-P. Lu, J.-Y. Liu, H.-l. Mu and Y.-S. Li, J. Mol.
Catal. A: Chem., 2015, 398, 289–296.
21. S. Itoh, S. Takayama, R. Arakawa, A. Furuta, M. Komatsu, A.
Ishida, S. Takamuku and S. Fukuzumi, Inorg. Chem., 1997, 36
,
48. Y. Shimazaki, S. Huth, S. Hirota and O. Yamauchi, Bull. Chem.
Soc. Jpn., 2000, 73, 1187–1195.
1407–1416.
22. A. Sokolowski, H. Leutbecher, T. Weyhermüller, R. Schnepf, 49. N. Gisch, J. Balzarini and C. Meier, J. Med. Chem., 2007, 50
E. Bothe, E. Bill, P. Hildebrandt and K. Wieghardt, J. Biol. 1658–1667.
Inorg. Chem., 1997, , 444–453.
23. J. A. Halfen, B. A. Jazdzewski, S. Mahapatra, L. M. Berreau, E.
,
2
50. Y.-L. Wong, L. H. Tong, J. R. Dilworth, D. K. P. Ng and H. K.
Lee, Dalton Trans., 2010, 39, 4602–4611.
C. Wilkinson, L. Que and W. B. Tolman, J. Am. Chem. Soc., 51. Y.-L. Wong, C.-Y. Mak, H. S. Kwan and H. K. Lee, Inorg. Chim.
1997, 119, 8217–8227. Acta, 2010, 363, 1246–1253.
24. J. A. Halfen, V. G. Young and W. B. Tolman, Angew. Chem. 52. V. Kumar, S. Ghosh, A. K. Saini, S. M. Mobin and B. Mondal,
Int. Ed., 1996, 35, 1687–1690. Dalton Trans, 2015, 44, 19909–19917.
25. F. Thomas, G. Gellon, I. Gautier-Luneau, E. Saint-Aman and 53. N. Berthet, V. Martel-Frachet, F. Michel, C. Philouze, S.
J.-L. Pierre, Angew. Chem., Int. Ed., 2002, 41, 3047–3050.
26. M. F. Semmelhack, C. R. Schmid, D. A. Cortes and C. S. Chou,
J. Am. Chem. Soc., 1984, 106, 3374–3376.
Hamman, X. Ronot and F. Thomas, Dalton Trans., 2013, 42,
8468–8483.
54. Y. Shimazaki, S. Huth, A. Odani and O. Yamauchi, Angew.
Chem. Int. Ed., 2000, 39, 1666–1669.
27. O. Das and T. K. Paine, Dalton Trans, 2012, 41, 11476–11481.
28. B. Xu, J. P. Lumb and B. A. Arndtsen, Angew. Chem. Int. Ed., 55. D. de Bellefeuille, M. Orio, A.-L. Barra, A. Aukauloo, Y.
2015, 54, 4208–4211.
Journaux, C. Philouze, X. Ottenwaelder and F. Thomas, Inorg.
Chem., 2015, 54, 9013–9026.
29. G. Zhang, G. Proni, S. Zhao, E. C. Constable, C. E. Housecroft,
M. Neuburger and J. A. Zampese, Dalton Trans, 2014, 43
,
56. B. A. Jazdzewski and W. B. Tolman, Coord. Chem. Rev., 2000,
12313–12320.
200–202, 633–685.
30. R. Jain, T. J. Gibson, M. S. Mashuta, R. M. Buchanan and C. A. 57. M. M. Hossain and S.-G. Shyu, Adv. Synth. Catal., 2010, 352
Grapperhaus, Dalton Trans., 2016, 45, 18356–18364. 3061–3068.
31. A. Dijksman, I. W. C. E. Arends and R. A. Sheldon, Org. 58. I. Gamba, I. Mutikainen, E. Bouwman, J. Reedijk and S.
Biomol. Chem., 2003, , 3232–3237. Bonnet, Eur. J. Inorg. Chem., 2013, 2013, 115–123.
32. P. Gamez, I. W. C. E. Arends, J. Reedijk and R. A. Sheldon, 59. P. Chaudhuri, M. Hess, T. Weyhermüller and K. Wieghardt,
Chem. Commun., 2003, 2414–2415. Angew. Chem. Int. Ed., 1999, 38, 1095–1098.
33. P. Gamez, I. W. C. E. Arends, R. A. Sheldon and J. Reedijk, 60. D. A. Quist, D. E. Diaz, J. J. Liu and K. D. Karlin, J. Biol. Inorg.
Adv. Synth. Catal., 2004, 346, 805–811. Chem., 2016, 1–36.
34. E. T. Kumpulainen and A. M. Koskinen, Chem. Eur. J., 2009, 61. S. Dharmalingam, E. Koo, S. Yoon and G. Park, Bull. Korean
15, 10901–10911. Chem. Soc., 2014, 35, 715–720.
35. N. J. Hill, J. M. Hoover and S. S. Stahl, J. Chem. Educ., 2013, 62. R. A. Sheldon and I. W. C. E. Arends, Adv. Synth. Catal., 2004,
90, 102–105. 346, 1051–1071.
36. J. M. Hoover, J. E. Steves and S. S. Stahl, Nat. Protocols, 2012, 63. S. E. Allen, R. R. Walvoord, R. Padilla-Salinas and M. C.
,
1
7
, 1161–1166.
37. J. M. Hoover and S. S. Stahl, J. Am. Chem. Soc., 2011, 133
16901–16910.
Kozlowski, Chem. Rev., 2013, 113, 6234–6458.
64. Q. Cao, L. M. Dornan, L. Rogan, N. L. Hughes and M. J.
Muldoon, Chem. Commun., 2014, 50, 4524–4543.
,
38. J. M. Hoover, B. L. Ryland and S. S. Stahl, J. Am. Chem. Soc., 65. B. L. Ryland, S. D. McCann, T. C. Brunold and S. S. Stahl, J.
2013, 135, 2357–2367.
Am. Chem. Soc., 2014, 136, 12166–12173.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 11
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 12 of 13
View Article Online
DOI: 10.1039/C7DT01716B
ARTICLE
Journal Name
66. B. L. Ryland and S. S. Stahl, Angew. Chem. Int. Ed., 2014, 53
,
8824–8838.
67. S. D. McCann and S. S. Stahl, Acc. Chem. Res., 2015, 48
,
1756–1766.
68. X.-M. Zhang, A. J. Fry and F. G. Bordwell, J. Org. Chem., 1996,
61, 4101–4106.
12 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 13 of 13
Dalton Transactions
View Article Online
DOI: 10.1039/C7DT01716B
Graphic Abstract
The mimics assemble structurally the metal center of GOase. The phenol group(s) and
the substituent (R), and the auxiliary ligand (L) of the mimics affect significantly their
catalysis on the aerobic oxidation of benzyl alcohol.